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Sample records for strong proliferative response

  1. Leukocytosis, muscle damage and increased lymphocyte proliferative response after an adventure sprint race

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    R. Tossige-Gomes

    2014-06-01

    Full Text Available The effect of an adventure sprint race (ASR on T-cell proliferation, leukocyte count and muscle damage was evaluated. Seven young male runners completed an ASR in the region of Serra do Espinhaço, Brazil. The race induced a strong leukocytosis (6.22±2.04×103 cells/mm3 before vs 14.81±3.53×103 cells/mm3 after the race, marked by a significant increase of neutrophils and monocytes (P<0.05, but not total lymphocytes, CD3+CD4+ or CD3+CD8+ cells. However, the T-cell proliferative response to mitogenic stimulation was increased (P=0.025 after the race, which contradicted our hypothesis that ASR, as a high-demand competition, would inhibit T-cell proliferation. A positive correlation (P=0.03, r=0.79 was observed between the proliferative response of lymphocytes after the race and the time to complete the race, suggesting that the proliferative response was dependent on exercise intensity. Muscle damage was evident after the race by increased serum levels of aspartate amino transferase (24.99±8.30 vs 50.61±15.76 U/L, P=0.003. The results suggest that humoral factors and substances released by damaged muscle may be responsible for lymphocyte activation, which may be involved in muscle recovery and repair.

  2. Dysregulation of T lymphocyte proliferative responses in autoimmunity.

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    Sydney K Elizer

    Full Text Available T cells are critically dependent on cellular proliferation in order to carry out their effector functions. Autoimmune strains are commonly thought to have uncontrolled T cell proliferation; however, in the murine model of autoimmune diabetes, hypo-proliferation of T cells leading to defective AICD was previously uncovered. We now determine whether lupus prone murine strains are similarly hyporesponsive. Upon extensive characterization of T lymphocyte activation, we have observed a common feature of CD4 T cell activation shared among three autoimmune strains-NOD, MRL, and NZBxNZW F1s. When stimulated with a polyclonal mitogen, CD4 T cells demonstrate arrested cell division and diminished dose responsiveness as compared to the non-autoimmune strain C57BL/6, a phenotype we further traced to a reliance on B cell mediated costimulation, which underscores the success of B cell directed immune therapies in preventing T cell mediated tissue injury. In turn, the diminished proliferative capacity of these CD4 T cells lead to a decreased, but activation appropriate, susceptibility to activation induced cell death. A similar decrement in stimulation response was observed in the CD8 compartment of NOD mice; NOD CD8 T cells were distinguished from lupus prone strains by a diminished dose-responsiveness to anti-CD3 mediated stimulation. This distinction may explain the differential pathogenetic pathways activated in diabetes and lupus prone murine strains.

  3. Cytotoxic and proliferative T cell responses in HIV-1-infected Macaca nemestrina.

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    Kent, S J; Corey, L; Agy, M B; Morton, W R; McElrath, M J; Greenberg, P D

    1995-01-01

    Macaca nemestrina has been described as an animal model for acute HIV-1 infection. This animal, unlike most infected humans, appears to contain HIV-1 replication. Therefore analysis of HIV-1-specific proliferative and cytotoxic T lymphocyte (CTL) responses following HIV-1 challenge of M. nemestrina may provide information into the role of such responses in both the control of acute HIV infection and protective immunity. Although CD4+ T cell responses to HIV-1 are generally difficult to detect...

  4. Modification of the intestinal postirradiation proliferative response by intraabdominal H-4-II-E2 tumors

    International Nuclear Information System (INIS)

    Evans, M.J.; Kovacs, C.J.; Schenken, L.L.; Burholt, D.R.

    1981-01-01

    Intraperitoneal injection of H-4-II-E 2 tumor cells gave rise to a number of individually growing intraabdominal tumors concentrated at sites of high abdominal vascularization. During tumor growth, both tumor and intestinal crypt cell proliferative activity were progressively depressed. A linear reduction of [ 3 H]TdR incorporation occurred in individual tumors independent of tumor size, suggesting that total tumor burden determines the proliferative status of individual tumors. Cytokinetic jejunal crypt analyses indicated that both a reduction in crypt cellularity and an abbreviated cell cycle transit time were noted during the depression of proliferative activity in the jejunum. In tumor-bearing rats the migration rate of cells from the jejunal crypt through the villus was reduced in response to a reduction in total cell production in the crypt. The life span of the epithelial cell in both tumor-bearing and normal rats was similar due to a reduction in villus cellularity in the tumor-bearing animals. Following abdominal irradiation of the tumor, the magnitude, but not the time course of hyperproliferative intestinal recovery, was influenced by the tumor mass. For nontumor-bearing animals, maximal hyperproliferation (>200% of control) occurred 96 hr postradiation. With increasing tumor burden the compensatory proliferative response to radiation was progressively reduced

  5. The descrease of the in vitro proliferative response of zinc-treated stressed mice's thymic lymphocytes.

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    García-Tamayo, F; Malpica López, N; Aguirre, M; Terrazas-Valdés, L I

    1999-01-01

    Prolonged stimulation of newborn mice by intraperitoneal injections with inactivated staphylococci induces a chronic neonatal inflammatory reaction and an associated oxidative-stress response. The chronically stimulated animals exhibit anorexy. show a reduction in their body weight and undergo a depression in both antibody synthesis andin vitro proliferativc response of Con A-stimulated splenic T-lymphocytes. These stressed animals also develop adrenal hyperplasia, hypozincamia and thymic hypoplasia. Despite this stress-mediated thymic involution, Con-A stimulated T-lymphocytes from thymus displayed increased theirin vitro proliferative response. Results of the present work show that intramuscular injections of zinc acetate in stressed mice, one single dose (5 microg) every other day for two weeks, reduce both the zinc concentration in the thymus gland and thein vitro proliferative response of their Con A-stimulated T-lymphocytes. The results suggest that prophylactic administration of zinc can have benefical consequences on the immunity of chronically stressed mice.

  6. Synergy among rat T cells in the proliferative response to alloantigen

    International Nuclear Information System (INIS)

    Wright, P.W.; Loop, S.M.; Bernstein, I.D.

    1979-01-01

    A synergistic interaction in the proliferative response to alloantigen is described for mixtures of rat thymus and lymph node cells. The optimal conditions for synergy are quantitatively defined. Regression analysis of the slope of the dose-response curve has been utilized to estimate the degree of interaction in thymus--lymph node cell mixtures. The slope of the response of cell mixtures was noted to be significantly greater than the slope for the response of lympth node cells alone. Irradiation was shown to have a differential effect on the response of thymus and lymph node cells in mixtures. Irradiated thymus cells retained the capacity for synergy in mixtures, whereas irradiated lymph node cells did not. Additional studies have demonstrated that both de novo protein synthesis and specific antigen recognition by both responding cell populations in mixtures was required for maximal synergy. These studies demonstrate that synergy cannot be explained as an artifact of altered cell density in vitro. They establish that thymus cells and lymph node cells represent distinct subsets which manifest qualitatively different functions in the proliferative response to alloantigen. Thymus cells can respond directly to alloantigen by proliferation but also have the capacity to amplify the proliferative response of lymph node cells, a capacity which is resistant to X irradiation but requires recognition of alloantigen and de novo protein synthesis. Lymph node cells may similarly respond by proliferation to alloantigen but lack the amplifier activity of thymus cells. Synergy for rat lymphoidcells, like mouse lymphoid cells, has been shown to involve an interaction of thymus-derived lymphocytes

  7. Long-term nonprogression and broad HIV-1-specific proliferative T-cell responses

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    Nesrina eImami

    2013-03-01

    Full Text Available Complex mechanisms underlying the maintenance of fully functional, proliferative, HIV-1-specific T-cell responses involve processes from early T-cell development through to the final stages of T-cell differentiation and antigen recognition. Virus-specific proliferative CD4 and CD8 T-cell responses, important for the control of infection, are observed in some HIV-1+ patients during early stages of disease, and are maintained in long-term nonprogressing subjects. In the vast majority of HIV-1+ patients, full immune functionality is lost when proliferative HIV-1-specific T-cell responses undergo a variable progressive decline throughout the course of chronic infection. This appears irreparable despite administration of potent combination antiretroviral therapy, which to date is non-curative, necessitating life-long administration and the development of effective, novel, therapeutic interventions. While a sterilising cure, involving clearance of virus from the host, remains a primary aim, a functional cure may be a more feasible goal with considerable impact on worldwide HIV-1 infection. Such an approach would enable long-term co-existence of host and virus in the absence of toxic and costly drugs. Effective immune homeostasis coupled with a balanced response appropriately targeting conserved viral antigens, in a manner that avoids hyperactivation and exhaustion, may prove to be the strongest correlate of durable viral control. This review describes novel concepts underlying full immune functionality in the context of HIV-1 infection, which may be utilised in future strategies designed to improve upon existing therapy. The aim will be to induce long-term nonprogressor or elite controller status in every infected host, through immune-mediated control of viraemia and reduction of viral reservoirs, leading to lower HIV-1 transmission rates.

  8. Lymphocyte proliferative responses to mitogens in rats having an ancestry of a perinatal iodine-131 insult

    International Nuclear Information System (INIS)

    Stevens, R.H.; Cheng, H.F.

    1987-01-01

    The possible existence of a genealogical memory consisting of altered lymphocyte proliferative responses to a perinatal iodine-131 insult has been investigated in two generations of inbred Fischer F344 rat offspring. The studies which involved exposure to the radioiodine during late pregnancy with concentrations ranging from 1.85 MBq (50 μCi) to 7.4 MBq (200 μCi) revealed that only the peripheral blood T lymphocytes of the first generation male animals were significantly affected. These animals were found to possess T lymphocytes which exhibited increased proliferative responses expressed toward the mitogens concanavalin A and phytohemagglutin; however, no significant changes were noticeable in their B cell population following exposure to lipopolysaccharide. Neither the first generation females nor the male and female offspring of the second generation developed through sibling interbreeding seemed to be affected, this was unlike the cellular, humoral, and natural immunity which had previously been observed to be changed in both the second and third generation animals. These observations suggest that the effects of the radiation insult upon immunocompetency as measured by lymphocyte proliferation do not appear to be inherited

  9. Proliferative responses of blood mononuclear cells (BMNC) in a cohort of elderly humans: role of lymphocyte phenotype and cytokine production

    DEFF Research Database (Denmark)

    Bruunsgaard, H.; Pedersen, Agnes Nadelmann; Schroll, M.

    2000-01-01

    Age-related impaired T cell function is associated with increased mortality risk. The purpose of the present study was therefore to identify factors associated with the age-related decreased phytohaemagglutinin (PHA)-induced proliferative response of lymphocytes in a cohort of 174 81-year-old hum......- and IL-2-producing cells were of importance in both elderly and young subjects. Accordingly, a minimum of true naive CD4(+) cells was required for a normal proliferative response to PHA, perhaps by providing sufficient IL-2 which is critical for growth of naive as well as memory cells....

  10. ARTEMIS stabilizes the genome and modulates proliferative responses in multipotent mesenchymal cells

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    Tompkins Kathleen

    2010-10-01

    Full Text Available Abstract Background Unrepaired DNA double-stranded breaks (DSBs cause chromosomal rearrangements, loss of genetic information, neoplastic transformation or cell death. The nonhomologous end joining (NHEJ pathway, catalyzing sequence-independent direct rejoining of DSBs, is a crucial mechanism for repairing both stochastically occurring and developmentally programmed DSBs. In lymphocytes, NHEJ is critical for both development and genome stability. NHEJ defects lead to severe combined immunodeficiency (SCID and lymphoid cancer predisposition in both mice and humans. While NHEJ has been thoroughly investigated in lymphocytes, the importance of NHEJ in other cell types, especially with regard to tumor suppression, is less well documented. We previously reported evidence that the NHEJ pathway functions to suppress a range of nonlymphoid tumor types, including various classes of sarcomas, by unknown mechanisms. Results Here we investigate roles for the NHEJ factor ARTEMIS in multipotent mesenchymal stem/progenitor cells (MSCs, as putative sarcomagenic cells of origin. We demonstrate a key role for ARTEMIS in sarcoma suppression in a sensitized mouse tumor model. In this context, we found that ARTEMIS deficiency led to chromosomal damage but, paradoxically, enhanced resistance and proliferative potential in primary MSCs subjected to various stresses. Gene expression analysis revealed abnormally regulated stress response, cell proliferation, and signal transduction pathways in ARTEMIS-defective MSCs. Finally, we identified candidate regulatory genes that may, in part, mediate a stress-resistant, hyperproliferative phenotype in preneoplastic ARTEMIS-deficient MSCs. Conclusions Our discoveries suggest that Art prevents genome damage and restrains proliferation in MSCs exposed to various stress stimuli. We propose that deficiency leads to a preneoplastic state in primary MSCs and is associated with aberrant proliferative control and cellular stress

  11. LYMPHO-PROLIFERATIVE RESPONSES TO VARIOUS FASCIOLA HEPATICA WORM'S ANTIGENS: AN IN VITRO STUDY.

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    Sharaf, Osama F; Amir, Elamir M; Hawash, Yousry A

    2016-04-01

    Fascioliasis is an important zoonotic disease with approximately 2-4 million people infected worldwide and a further 180 million at risk of infection. F. hepatica can survive within the bile ducts for many years through its ability to suppress the host immunity with Fasciola cathepsin L1 cysteine protease and Glutathione S transferase playing an important role. The aim of the present study is to investigate the in vitro lympho-proliferative responses of hepatic hilar lymphocytes (HLN) of infected sheep in response to different F. hepatica antigens. The suppressive effects of Fasciola excretory/secretory (ES) and tegument (TEG) and their fractions were also investigated. Our results showed that both ES and TEG had significant suppressive effects on lympho-proliferation, up to 74% and 92%, respectively. When these antigens were fractionated, fraction 3 (MW of >10000-30000) of both ES (64%) and TEG (59%) in addition to fraction 4 (MW of ≤ 10000) of TEG (38%) inherited the suppressive effects. Identification of the potential molecule(s) with such suppressive effects on lymphocytes in TEG fraction 4 could reveal vaccine candidates.

  12. Proliferative response of the stem cell system during regeneration of the rostrum in Macrostomum lignano (Platyhelminthes).

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    Verdoodt, Freija; Bert, Wim; Couvreur, Marjolein; De Mulder, Katrien; Willems, Maxime

    2012-02-01

    Macrostomum lignano (Platyhelminthes) possesses pluripotent stem cells, also called neoblasts, which power its extraordinary regeneration capacity. We have examined the cellular dynamics of neoblasts during regeneration of the rostrum in M. lignano. First, using live squeeze observations, the growth curve of the rostrum was determined. Second, neoblasts were labelled with 5-bromo-2'-deoxyuridine (BrdU) and an anti-phospho-histone H3 mitosis marker (anti-phos-H3) to analyze their proliferative response to amputation. During the regeneration process, both S- and M-phase cells were present anterior to the eyes, a region that is devoid of proliferating cells during homeostasis. Furthermore, BrdU pulse experiments revealed a biphasic S-phase pattern, different from the pattern known to occur during regeneration of the tail plate in M. lignano. During a first systemic phase, S-phase numbers significantly increased, both in the region adjacent to the wound (the anterior segment) and the region far from the wound (the posterior segment). During the second, spatially restricted phase, S-phase numbers in the anterior segment rose to a peak at 3 to 5 days post-amputation (p-a), while in the posterior segment, S-phase activity approached control values again. A blastema, characterized as a build-up of S- and M-phase cells, was formed 1 day p-a. Altogether, our data present new insights into the cellular response of the neoblast system upon amputation, clearly demonstrating important differences from the situation known to occur during regeneration of the tail plate. Furthermore, the presence of proliferating cells in the region anterior to the eyes shows a clear alteration in stem cell regulation during regeneration.

  13. Proliferative response of the murine esophageal epithelium to radiation: Modification by food consumption patterns

    International Nuclear Information System (INIS)

    Burholt, D.R.

    1985-01-01

    The single layer of proliferative epithelial cells of the murine esophagus undergoes a sequence of damage and recovery following cytotoxic insult. The modification of both damage and proliferative recovery by the alteration of animal eating patterns was investigated following thoracic field irradiation through the determination of /sup 3/H-TdR incorporation into the esophagus along with selective counting of labeled nuclei and mitotic figures. Initial radiation-induced damage, as determined by /sup 3/H-TdR incorporation suppression and mitotic delay, is under normal conditions dependent on the time of day of treatment. This circadian sensitivity may be altered by changing the eating pattern of the animal. The proliferative recovery following single dose irradiation is also dependent on food consumption patterns: fasting immediately following treatment and then refeeding 2 days later results in a more rapid proliferative recovery than observed under control eating conditions, while reduced food consumption during the period of proliferative hyperplasia reduces the extent of recovery. During multifraction radiation schedules both the damage produced by a subsequent dose and recovery capacity are influenced by the food consumption pattern between fractions

  14. Characterization of the interferon gamma response to Lawsonia intracellularis using an equine proliferative enteropathy challenge (EPE) model.

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    Page, A E; Loynachan, A T; Bryant, U; Stills, H F; Adams, A A; Gebhart, C J; Pusterla, N; Horohov, D W

    2011-09-15

    Lawsonia intracellularis is the etiological agent of infectious intestinal hyperplasia for which several clinical diseases have been described including proliferative enteropathy (PE), intestinal adenomatosis, and ileitis. While initially recognized as the causative agent of PE in pigs, L. intracellularis is now viewed as an emerging cause of intestinal hyperplasia in a wide range of mammalian species, including horses. Equine proliferative enteropathy (EPE) has been reported worldwide though definitive diagnosis is difficult and the epidemiology of the disease remains poorly understood. Weanlings, in particular, appear to be most at risk for infection, though the reasons for their particular susceptibility is unknown. Using an infectious challenge model for EPE, we demonstrate that EPE, like porcine proliferative enteropathy, can exhibit three clinical forms: classical, subclinical and acute. Out of six pony weanlings, one developed signs of classic EPE, one developed acute EPE, and two developed subclinical EPE. Attempts to induce pharmacological stress through the use of dexamethasone failed to have any effect on outcome. Peripheral blood cells collected from those weanlings that developed clinical EPE exhibited decreased expression of interferon-gamma (IFN-γ) following in vitro stimulation with L. intracellularis. By contrast, those weanlings that did not develop clinical disease generated a robust IFN-γ response. These results indicate IFN-γ likely plays a significant role in protection from disease caused by L. intracellularis in the equid. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Mechanisms of HIV non-progression; robust and sustained CD4+ T-cell proliferative responses to p24 antigen correlate with control of viraemia and lack of disease progression after long-term transfusion-acquired HIV-1 infection

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    Geczy Andrew F

    2008-12-01

    Full Text Available Abstract Background Elite non-progressors (plasma viral load Results A survival advantage was conferred on 12 of 13 subjects, who had at least one host genetic factor (HLA, chemokine receptor or TLR polymorphisms or viral attenuating factor (defective nef associated with slow progression. However, antiviral immune responses differentiated the course of disease into and beyond the second decade of infection. A stable p24-specific proliferative response was associated with control of viraemia and retention of non-progressor status, but this p24 response was absent or declined in viraemic subjects. Strong Gag-dominant cytotoxic T lymphocyte (CTL responses were identified in most LTNP, or Pol dominant-CTL in those with nef-defective HIV infection. CTL were associated with control of viraemia when combined with p24 proliferative responses. However, CTL did not prevent late disease progression. Individuals with sustained viral suppression had CTL recognising numerous Gag epitopes, while strong but restricted responses to one or two immunodominant epitopes was effective for some time, but failed to contain viraemia over the course of this study. Viral escape mutants at a HLA B27-restricted Gag-p24 epitope were detected in only 1 of 3 individuals, whereas declining or negative p24 proliferative responses occurred in all 3 concurrent with an increase in viraemia. Conclusion Detectable viraemia at study entry was predictive of loss of LTNP status and/or disease progression in 6 of 8, and differentiated slow progressors from elite LTNP who retained potent virological control. Sustained immunological suppression of viraemia was independently associated with preserved p24 proliferative responses, regardless of the strength and breadth of the CTL response. A decline in this protective p24 response preceded or correlated with loss of non-progressor status and/or signs of disease progression.

  16. The prevalence of dogs with lymphocyte proliferative responses to food allergens in canine allergic dermatitis.

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    Kawano, K; Oumi, K; Ashida, Y; Horiuchi, Y; Mizuno, T

    2013-01-01

    The aim of the present study was to examine the correlation between the results of lymphocyte proliferative test (LPT) specific to food allergens and allergic skin diseases in dogs. Investigations were performed in 138 dogs with allergic skin diseases diagnosed in a private animal hospital. Of the 138 animals, 97 cases had positive reactions in LPT specific to food allergens. Of these 97 dogs, 67 animals were diagnosed with canine atopic dermatitis (CAD), but 30 dogs did not have IgE antibodies to environmental allergens. As 14 dogs out of 30 animals showed a positive result, 12 dogs underwent elimination diet trial based on the test results and all of them showed improvement in the pruritus score. Therefore, we conclude that LPT is an effective diagnostic test for allergic skin disease. Results of the lymphocyte test are useful in the identification of food allergens for the elimination diet trial.

  17. Proliferative response of gingival cells to ultrasonic and/or vibration toothbrushes.

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    Kusano, Hiroki; Tomofuji, Takaaki; Azuma, Tetsuji; Sakamoto, Tomonori; Yamamoto, Tatsuo; Watanabe, Tatsuo

    2006-02-01

    To evaluate the effects of ultrasonic and/or vibration toothbrushes on cell proliferation and collagen synthesis. In eight dogs, teeth and gingivae were stimulated once a day as follows: the first quadrant with an ultrasonic toothbrush (1.6 MHz); the second one with a mechanical vibratory toothbrush (141 Hz); and the third one with a toothbrush generating both the ultrasound and the vibration. The fourth quadrant served as a control. Proliferative activity and collagen synthesis of gingival cells were evaluated by assaying the expression of proliferating cell nuclear antigen (PCNA) and procollagen type I C-peptide (PIP), respectively. After 5 weeks, ultrasonic or vibratory toothbrushes increased the numbers of PCNA-positive fibroblasts and PIP-positive fibroblasts. Toothbrushing with a combination of ultrasound and mechanical vibration increased the numbers of PIP-positive fibroblasts, total fibroblasts and vascular endothelial cells to a greater extent than the one with only ultrasound alone. Vibratory toothbrush, but not the ultrasonic one, induced an increase in collagen density without gingival overgrowth.

  18. HPV related VIN: highly proliferative and diminished responsiveness to extracellular signals.

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    Santegoets, Lindy A M; Seters, Manon van; Helmerhorst, Theo J M; Heijmans-Antonissen, Claudia; Hanifi-Moghaddam, Payman; Ewing, Patricia C; van Ijcken, Wilfred F J; van der Spek, Peter J; van der Meijden, Willem I; Blok, Leen J

    2007-08-15

    Vulvar intraepithelial neoplasia (VIN) is a premalignant disorder caused by human papillomaviruses. Basic knowledge about the molecular pathogenesis of VIN is sparse. Therefore, we have analyzed the gene expression profile of 9 VIN samples in comparison to 10 control samples by using genome wide Affymetrix Human U133A plus2 GeneChips. Results were validated by quantitative real-time RT-PCR analysis and immunostaining of a few representative genes (TACSTD1, CCNE2, AR and ESR1). Significance analysis of microarrays (SAM) showed that 1,497 genes were differentially expressed in VIN compared to controls. By analyzing the biological processes affected by the observed differences, we found that VIN appears to be a highly proliferative disease; many cyclins (CCNA, CCNB and CCNE) and almost all prereplication complex proteins are upregulated. Thereby, VIN does not seem to depend for its proliferation on paracrine or endocrine signals. Many receptors (for example ESR1 and AR) and ligands are downregulated. Furthermore, although VIN is not an invasive disease, the inhibition of expression of a marked number of cell-cell adhesion molecules seems to indicate development towards invasion. Upon reviewing apoptosis and angiogenesis, it was observed that these processes have not become significantly disregulated in VIN. although VIN is still a premalignant disease, it already displays several hallmarks of cancer.

  19. Human CD6 Down-Modulation following T-Cell Activation Compromises Lymphocyte Survival and Proliferative Responses

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    Esther Carrasco

    2017-06-01

    Full Text Available Available evidence indicates that the CD6 lymphocyte surface receptor is involved in T-cell developmental and activation processes, by facilitating cell-to-cell adhesive contacts with antigen-presenting cells and likely modulating T-cell receptor (TCR signaling. Here, we show that in vitro activation of human T cells under different TCR-ligation conditions leads to surface downregulation of CD6 expression. This phenomenon was (i concomitant to increased levels of soluble CD6 (sCD6 in culture supernatants, (ii partially reverted by protease inhibitors, (iii not associated to CD6 mRNA down-regulation, and (iv reversible by stimulus removal. CD6 down-modulation inversely correlated with the upregulation of CD25 in both FoxP3− (Tact and FoxP3+ (Treg T-cell subsets. Furthermore, ex vivo analysis of peripheral CD4+ and CD8+ T cells with activated (CD25+ or effector memory (effector memory T cell, CD45RA−CCR7− phenotype present lower CD6 levels than their naïve or central memory (central memory T cell, CD45RA−CCR7+ counterparts. CD6lo/− T cells resulting from in vitro T-cell activation show higher apoptosis and lower proliferation levels than CD6hi T cells, supporting the relevance of CD6 in the induction of proper T-cell proliferative responses and resistance to apoptosis. Accordingly, CD6 transfectants also showed higher viability when exposed to TCR-independent apoptosis-inducing conditions in comparison with untransfected cells. Taken together, these results provide insight into the origin of sCD6 and the previously reported circulating CD6-negative T-cell subset in humans, as well as into the functional consequences of CD6 down-modulation on ongoing T-cell responses, which includes sensitization to apoptotic events and attenuation of T-cell proliferative responses.

  20. Differential proliferative responses in subsets of human CD28+ cells delineated by BB27 mAb.

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    Gouttefangeas, C; Jacquot, S; Meffre, E; Schmid, M; Boumsell, L; Bensussan, A

    1994-03-01

    We report the identification of a novel 140 kDa disulfide-linked dimer expressed by a subset of peripheral blood T lymphocytes. This molecule, which is recognized by mAb BB27, is also detected on cells of the myelomonocytic lineage. In the T cell lineage, its expression is positively modulated after lymphocyte activation. A series of double-labeling experiments revealed that BB27 mAb identifies new CD4 and CD8 cell subsets different from those defined by CD45RA, CD45RO, CD26, CD29, CD31, and CD38. Finally, BB27 mAb also subdivides the CD28 subset. Of the utmost interest is the finding that a proliferative response to CD28 mAb and phorbol myristate acetate stimulation is exclusively obtained in the CD28+BB27+ cell subset, whereas the CD28+BB27- subset fails to proliferate.

  1. Ultra violet radiation-induced defects in accessory cell function in the human proliferative response to tetanus

    International Nuclear Information System (INIS)

    Pretell, J.O.; Wimberly, J.; Parrish, J.A.

    1984-01-01

    Ultraviolet B radiation (290-320 nm) has been shown to interfere with accessory cell function of human peripheral blood mononuclear cells in the generation of a proliferative response to tetanus. By altering the timing of irradiation of adherent cells and using short pulses of antigen, we have identified a minimum of two u.v. sensitive accessory cell functions. The first involves antigen presentation and is not readily reversible with time in culture after irradiation. The second is demonstrated by the ability of low doses of u.v. radiation given after the tetanus toxoid pulse to inhibit an event(s) occuring independent of antigen processing. Both occur within a range of doses which would penetrate to the vasculature of the skin of humans exposed to the sun or to phototherapy. (author)

  2. The Fas-Associated Death Domain Protein (FADD) is Required in Apoptosis and TLR-induced Proliferative Responses in B Cells1

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    Imtiyaz, Hongxia Z.; Rosenberg, Stephen; Zhang, Yuhang; Rahman, Ziaur S. M.; Hou, Ying-Ju; Manser, Tim L.; Zhang, Jianke

    2011-01-01

    The Fas-associated death domain protein FADD/Mort1 is a signaling adaptor protein which mediates the activation of caspase 8 during death receptor-induced apoptosis. Disruption of FADD in germ cells results in death receptor-independent embryonic lethality in mice. Previous studies indicated that in addition to its function in apoptosis, FADD is also required in peripheral T cell homeostasis and TCR-induced proliferative responses. In this report, we generated B cell-specific FADD-deficient mice and showed that deletion of FADD at the pro-B cell stage had minor effects on B cell development in the bone marrow, and resulted in increased splenic and lymph node B cell numbers and decreased peritoneal B1 cell numbers. As in T cells, a FADD deficiency inhibited Fas-induced apoptosis in B cells. However, B cell proliferative responses induced by stimulation of the BCR and CD40 using anti-IgM or anti-CD40 antibodies were unaffected by the absence of FADD. Further analyses revealed that FADD-deficient B cells were defective in proliferative responses induced by treatments with dsRNA and LPS which stimulate TLR3 and TLR4 respectively. Therefore, in addition to its apoptotic function, FADD also plays a role in TLR3- and TLR4-induced proliferative responses in B cells. PMID:16709845

  3. Characterization of the early proliferative response of the rodent bladder to subtotal cystectomy: a unique model of mammalian organ regeneration.

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    Charles C Peyton

    Full Text Available Subtotal cystectomy (STC; surgical removal of ∼75% of the rat urinary bladder elicits a robust proliferative response resulting in complete structural and functional bladder regeneration within 8-weeks. The goal of these studies was to characterize the early cellular response that mediates this regenerative phenomenon, which is unique among mammalian organ systems. STC was performed on eighteen 12-week-old female Fischer F344 rats. At 1, 3, 5 and 7-days post-STC, the bladder was harvested 2-hours after intraperitoneal injection of bromodeoxyuridine (BrdU. Fluorescent BrdU labeling was quantified in cells within the urothelium, lamina propria (LP, muscularis propria (MP and serosa. Cell location was confirmed with fluorescently co-labeled cytokeratin, vimentin or smooth muscle actin (SMA, to identify urothelial, interstitial and smooth muscle cells, respectively. Expression of sonic hedgehog (Shh, Gli-1 and bone morphogenic factor-4 (BMP-4 were evaluated with immunochemistry. Three non-operated rats injected with BrdU served as controls. Less than 1% of cells in the bladder wall were labeled with BrdU in control bladders, but this percentage significantly increased by 5-8-fold at all time points post-STC. The spatiotemporal characteristics of the proliferative response were defined by a significantly higher percentage of BrdU-labeled cells within the urothelium at 1-day than in the MP and LP. A time-dependent shift at 3 and 5-days post-STC revealed significantly fewer BrdU-labeled cells in the MP than LP or urothelium. By 7-days the percentage of BrdU-labeled cells was similar among urothelium, LP and MP. STC also caused an increase in immunostaining for Shh, Gli-1 and BMP-4. In summary, the early stages of functional bladder regeneration are characterized by time-dependent changes in the location of the proliferating cell population, and expression of several evolutionarily conserved developmental signaling proteins. This report extends

  4. Who needs the hotspot? The effect of temperature on the fish host immune response to Tetracapsuloides bryosalmonae the causative agent of proliferative kidney disease.

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    Bailey, Christyn; Segner, Helmut; Casanova-Nakayama, Ayako; Wahli, Thomas

    2017-04-01

    Proliferative kidney disease (PKD) of salmonids, caused by Tetracapsuloides bryosalmonae may lead to high mortalities at elevated water temperatures. However, it has not yet been investigated how temperature affects the fish host immune response to T. bryosalmonae. We exposed YOY (young of the year) rainbow trout (Oncorhynchus mykiss) to T. bryosalmonae at two temperatures (12 °C and 15 °C) that reflect a realistic environmental scenario and could occur in the natural habitat of salmonids. We followed the development of the parasite, host pathology and immune response over seven weeks. We evaluated the composition and kinetics of the leukocytes and their major subgroups in the anterior and posterior kidney. We measured immune gene expression profiles associated with cell lineages and functional pathways in the anterior and posterior kidney. At 12 °C, both infection prevalence and pathogen load were markedly lower. While the immune response was characterized by subtle changes, mainly an increased amount of lymphocytes present in the kidney, elevated expression of Th1-like signature cytokines and strong upregulation of the natural killer cell enhancement factor, NKEF at week 6 P.E. At 15 °C the infection prevalence and pathogen burden were ominously greater. While the immune response as the disease progressed was associated with a Th2-like switch at week 6 P.E and a prominent B cell response, evidenced at the tissue, cell and transcript level. Our results highlight how a subtle, environmentally relevant difference in temperature resulted in diverse outcomes in terms of the immune response strategy, altering the type of interaction between a host and a parasite. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Type β transforming growth factor reversibly inhibits the early proliferative responsive to partial hepatectomy in the rat

    International Nuclear Information System (INIS)

    Russell, W.E.; Coffey, R.J. Jr.; Ouellette, A.J.; Moses, H.L.

    1988-01-01

    Type β transforming growth factor (TGF-β), a factor produced by many cell types, is a potent inhibitor of hepatocyte DNA synthesis in vitro. To determine whether TGF-β can influence hepatocyte proliferation in vivo, its effects were examined on the regenerative response of liver to partial hepatectomy (PH) in the rat. Porcine platelet-derived TGF-β1, administered intravenously at the time of PH and 11 hr later, reduced the fraction of hepatocytes engaged in DNA synthesis 22 hr after PH by 67% and inhibited the rate of hepatic [ 3 H]thymidine incorporation by 50%. TGF-β2 produced a similar effect. Although sensitive to TGF-β administered 11 hr after PH, late in the G 1 phase of the cell cycle, a single does of 0.5 μg given at the time of PH did not significantly influence DNA synthesis 22 hr after PH. The inhibitory effects of TGF-β were transient. The nuclear labeling index of the TGF-β-treated animals was significantly higher than that of the controls. There was no evidence of cytotoxicity from TGF-β, as determined by liver histology and plasma concentrations of glucose, insulin-like growth factor I, and two hepatic enzymes. Thus, TGF-β1 and TGF-β2 reversibly inhibit the proliferative response of liver to PH and may be important in the modulation of normal liver growth and repair

  6. Proliferative lymphocyte responses to virus antigens homologous to GAD65 in IDDM.

    Science.gov (United States)

    Jones, D B; Crosby, I

    1996-11-01

    Virus infection has been proposed as an initiating factor in the aetiology of insulin-dependent diabetes mellitus (IDDM). We have examined lymphocyte proliferation to virus proteins which demonstrate sequence similarity to the beta-cell autoantigen glutamic acid decarboxylase (GAD)65. The magnitude and frequency of response to coxsackie B viruses and adenovirus in a T-cell proliferation assay was significantly higher in a group of recently diagnosed IDDM subjects than in non-diabetic control subjects. The frequency of positive response to the coxsackie B viruses was also significantly higher in IDDM subjects expressing the DRB 1*04 major histocompatibility complex (MHC) haplotype than the DRB 1*03 haplotype. There was no evidence that non-aspartate residue at position 57 of DQB 1 genes influenced virus responses in the IDDM group. The coxsackie homology was in amino acids 258-266 and the adenovirus homology was in amino acids 509-524 of GAD65. Both these regions are suspected to be T-cell epitopes in IDDM. These results indicate a disease and MHC class II association between coxsackie B virus infection and IDDM and an association between adenovirus infection and IDDM.

  7. Opa+ and Opa- isolates of Neisseria meningitidis and Neisseria gonorrhoeae induce sustained proliferative responses in human CD4+ T cells.

    Science.gov (United States)

    Youssef, Abdel-Rahman; van der Flier, Michiel; Estevão, Silvia; Hartwig, Nico G; van der Ley, Peter; Virji, Mumtaz

    2009-11-01

    T cells may interact with a number of bacterial surface antigens, an encounter which has the potential to downmodulate host immune responses. Neisseria meningitidis, a human colonizer and an agent of septicemia and meningitis, expresses Opa proteins which interact with the CEACAM1 receptor expressed on activated T cells. Since CEACAM1 can act as an inhibitory receptor and T cells in subepithelial tissues may encounter whole bacteria, which often express Opa proteins in vivo, this study assessed primarily if Opa proteins expressed on meningococci affect T-cell functions. In addition, Opa-containing outer membrane vesicles (OMV) have been used as vaccine antigens, and therefore Opa+ and Opa- OMV were also studied. While Opa+ bacteria adhered to CEACAM-expressing T cells, both the Opa+ and Opa- phenotypes induced no to a small transient depression, followed by a prolonged increase in proliferation as well as cytokine production. Such responses were also observed with heat-killed bacteria or OMV. In addition, while anti-CEACAM antibodies alone inhibited proliferation, on coincubation of T cells with bacteria and the antibodies, bacterial effects predominated and were Opa independent. Thus, while Opa proteins of N. meningitidis can bind to T-cell-expressed CEACAM1, this is not sufficient to overcome the T-cell recognition of bacterial factors, which results in a proliferative and cytokine response, an observation consistent with the ability of the host to establish lasting immunity to Opa-expressing meningococci that it frequently encounters. The data also imply that Opa-proficient vaccine preparations may not necessarily inhibit T-cell functions via CEACAM1 binding.

  8. Graphene oxide scaffold accelerates cellular proliferative response and alveolar bone healing of tooth extraction socket

    Directory of Open Access Journals (Sweden)

    Nishida E

    2016-05-01

    Full Text Available Erika Nishida,1 Hirofumi Miyaji,1 Akihito Kato,1 Hiroko Takita,2 Toshihiko Iwanaga,3 Takehito Momose,1 Kosuke Ogawa,1 Shusuke Murakami,1 Tsutomu Sugaya,1 Masamitsu Kawanami11Department of Periodontology and Endodontology, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan; 2Support Section for Education and Research, Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan; 3Laboratory of Histology and Cytology, Hokkaido University Graduate School of Medicine, Sapporo, JapanAbstract: Graphene oxide (GO consisting of a carbon monolayer has been widely investigated for tissue engineering platforms because of its unique properties. For this study, we fabricated a GO-applied scaffold and assessed the cellular and tissue behaviors in the scaffold. A preclinical test was conducted to ascertain whether the GO scaffold promoted bone induction in dog tooth extraction sockets. For this study, GO scaffolds were prepared by coating the surface of a collagen sponge scaffold with 0.1 and 1 µg/mL GO dispersion. Scaffolds were characterized using scanning electron microscopy (SEM, physical testing, cell seeding, and rat subcutaneous implant testing. Then a GO scaffold was implanted into a dog tooth extraction socket. Histological observations were made at 2 weeks postsurgery. SEM observations show that GO attached to the surface of collagen scaffold struts. The GO scaffold exhibited an interconnected structure resembling that of control subjects. GO application improved the physical strength, enzyme resistance, and adsorption of calcium and proteins. Cytocompatibility tests showed that GO application significantly increased osteoblastic MC3T3-E1 cell proliferation. In addition, an assessment of rat subcutaneous tissue response revealed that implantation of 1 µg/mL GO scaffold stimulated cellular ingrowth behavior, suggesting that the GO scaffold exhibited good biocompatibility. The tissue ingrowth area and DNA contents of 1

  9. Inhibition of inflammatory and proliferative responses of human keratinocytes exposed to the sesquiterpene lactones dehydrocostuslactone and costunolide.

    Directory of Open Access Journals (Sweden)

    Claudia Scarponi

    Full Text Available The imbalance of the intracellular redox state and, in particular, of the glutathione (GSH/GSH disulfide couple homeostasis, is involved in the pathogenesis of a number of diseases. In many skin diseases, including psoriasis, oxidative stress plays an important role, as demonstrated by the observation that treatments leading to increase of the local levels of oxidant species ameliorate the disease. Recently, dehydrocostuslactone (DCE and costunolide (CS, two terpenes naturally occurring in many plants, have been found to exert various anti-inflammatory and pro-apoptotic effects on different human cell types. These compounds decrease the level of the intracellular GSH by direct interaction with it, and, therefore, can alter cellular redox state. DCE and CS can trigger S-glutathionylation of various substrates, including the transcription factor STAT3 and JAK1/2 proteins. In the present study, we investigated on the potential role of DCE and CS in regulating inflammatory and proliferative responses of human keratinocytes to cytokines. We demonstrated that DCE and CS decreased intracellular GSH levels in human keratinocytes, as well as inhibited STAT3 and STAT1 phosphorylation and activation triggered by IL-22 or IFN-γ, respectively. Consequently, DCE and CS decreased the IL-22- and IFN-γ-induced expression of inflammatory and regulatory genes in keratinocytes, including CCL2, CXCL10, ICAM-1 and SOCS3. DCE and CS also inhibited proliferation and cell-cycle progression-related gene expression, as well as they promoted cell cycle arrest and apoptosis. In parallel, DCE and CS activated the anti-inflammatory EGFR and ERK1/2 molecules in keratinocytes, and, thus, wound healing in an in vitro injury model. In light of our findings, we can hypothesize that the employment of DCE and CS in psoriasis could efficiently counteract the pro-inflammatory effects of IFN-γ and IL-22 on keratinocytes, revert the apoptosis-resistant phenotype, as well as inhibit

  10. Immunoregulatory activities of human immunodeficiency virus (HIV) proteins: Effect of HIV recombinant and synthetic peptides on immunoglobulin synthesis and proliferative responses by normal lymphocytes

    International Nuclear Information System (INIS)

    Nair, M.P.N.; Pottathil, R.; Heimer, E.P.; Schwartz, S.A.

    1988-01-01

    Recombinant and synthetic peptides corresponding to envelope proteins of the human immunodeficiency virus (HIV) were examined for their effects on the activities of lymphocytes from normal donors in vitro. Although lymphocytes cultured with env-gag peptides produced significant amounts of IgG, addition of env-gag peptides to a pokeweed mitogen-induced B-cell activation system resulted in suppression of immunoglobulin synthesis by normal lymphocytes. Recombinant antigens, env-gag and env-80 dihydrofolate reductase (DHFR), produced a substantial proliferative response by peripheral blood mononuclear cells (PBMC) as determined by [ 3 H]thymidine incorporation. PBMC precultured with HIV synthetic peptide env 578-608 also manifested significant proliferative responses as compared to control cultures. CD3 + lymphocytes precultured with recombinant HIV antigens, env-gag and env-80 DHFR, and synthetic HIV peptide, env 487-511, showed moderate but significant proliferative responses. Both recombinant antigens and synthetic peptides also produced a dose-dependent stimulatory effect on proliferation by CD3 - lymphocytes. These studies demonstrate that recombinant and synthetic peptides of the HIV genome express immunoregulatory T- and B-cell epitopes. Identification of unique HIV epitopes with immunogenic and immunoregulatory activities is necessary for the development of an effective vaccine against HIV infection

  11. Perceptual Sensitivity and Response to Strong Stimuli Are Related.

    Science.gov (United States)

    Bolders, Anna C; Tops, Mattie; Band, Guido P H; Stallen, Pieter Jan M

    2017-01-01

    To shed new light on the long-standing debate about the (in)dependence of sensitivity to weak stimuli and overreactivity to strong stimuli, we examined the relation between these tendencies within the neurobehavioral framework of the Predictive and Reactive Control Systems (PARCS) theory (Tops et al., 2010, 2014). Whereas previous studies only considered overreactivity in terms of the individual tendency to experience unpleasant affect (punishment reactivity) resulting from strong sensory stimulation, we also took the individual tendency to experience pleasant affect (reward reactivity) resulting from strong sensory stimulation into account. According to PARCS theory, these temperamental tendencies overlap in terms of high reactivity toward stimulation, but oppose each other in terms of the response orientation (approach or avoid). PARCS theory predicts that both types of reactivity to strong stimuli relate to sensitivity to weak stimuli, but that these relationships are suppressed due to the opposing relationship between reward and punishment reactivity. We measured punishment and reward reactivity to strong stimuli and sensitivity to weak stimuli using scales from the Adult Temperament Questionnaire (Evans and Rothbart, 2007). Sensitivity was also measured more objectively using the masked auditory threshold. We found that sensitivity to weak stimuli (both self-reported and objectively assessed) was positively associated with self-reported punishment and reward reactivity to strong stimuli, but only when these reactivity measures were controlled for each other, implicating a mutual suppression effect. These results are in line with PARCS theory and suggest that sensitivity to weak stimuli and overreactivity are dependent, but this dependency is likely to be obscured if punishment and reward reactivity are not both taken into account.

  12. Perceptual Sensitivity and Response to Strong Stimuli Are Related

    Directory of Open Access Journals (Sweden)

    Anna C. Bolders

    2017-09-01

    Full Text Available To shed new light on the long-standing debate about the (independence of sensitivity to weak stimuli and overreactivity to strong stimuli, we examined the relation between these tendencies within the neurobehavioral framework of the Predictive and Reactive Control Systems (PARCS theory (Tops et al., 2010, 2014. Whereas previous studies only considered overreactivity in terms of the individual tendency to experience unpleasant affect (punishment reactivity resulting from strong sensory stimulation, we also took the individual tendency to experience pleasant affect (reward reactivity resulting from strong sensory stimulation into account. According to PARCS theory, these temperamental tendencies overlap in terms of high reactivity toward stimulation, but oppose each other in terms of the response orientation (approach or avoid. PARCS theory predicts that both types of reactivity to strong stimuli relate to sensitivity to weak stimuli, but that these relationships are suppressed due to the opposing relationship between reward and punishment reactivity. We measured punishment and reward reactivity to strong stimuli and sensitivity to weak stimuli using scales from the Adult Temperament Questionnaire (Evans and Rothbart, 2007. Sensitivity was also measured more objectively using the masked auditory threshold. We found that sensitivity to weak stimuli (both self-reported and objectively assessed was positively associated with self-reported punishment and reward reactivity to strong stimuli, but only when these reactivity measures were controlled for each other, implicating a mutual suppression effect. These results are in line with PARCS theory and suggest that sensitivity to weak stimuli and overreactivity are dependent, but this dependency is likely to be obscured if punishment and reward reactivity are not both taken into account.

  13. Response of MDOF strongly nonlinear systems to fractional Gaussian noises

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Mao-Lin; Zhu, Wei-Qiu, E-mail: wqzhu@zju.edu.cn [Department of Mechanics, State Key Laboratory of Fluid Power and Mechatronic Systems, Key Laboratory of Soft Machines and Smart Devices of Zhejiang Province, Zhejiang University, Hangzhou 310027 (China)

    2016-08-15

    In the present paper, multi-degree-of-freedom strongly nonlinear systems are modeled as quasi-Hamiltonian systems and the stochastic averaging method for quasi-Hamiltonian systems (including quasi-non-integrable, completely integrable and non-resonant, completely integrable and resonant, partially integrable and non-resonant, and partially integrable and resonant Hamiltonian systems) driven by fractional Gaussian noise is introduced. The averaged fractional stochastic differential equations (SDEs) are derived. The simulation results for some examples show that the averaged SDEs can be used to predict the response of the original systems and the simulation time for the averaged SDEs is less than that for the original systems.

  14. Peripheral blood T cell proliferative response to chlamydial organisms in gonococcal and non-gonococcal urethritis and presumed pelvic inflammatory disease

    Science.gov (United States)

    Shahmanesh, M.; Brunst, M.; Sukthankar, A.; Pearce, J. H.; Gaston, J. S.

    1999-01-01

    OBJECTIVE: To study peripheral blood mononuclear cell (PBMC) proliferative response to Chlamydia trachomatis elementary bodies in (a) controls, (b) various stages of gonococcal (c) and non-gonococcal urethritis, and (d) women with a clinical diagnosis of pelvic inflammatory disease (PID). METHODS: We categorised 102 men presenting to a GUM clinic with urethritis by organisms (C trachomatis (CT) or Neisseria gonorrhoeae (NG) (both by culture), and whether it was their first (urethritis naive) or subsequent (urethritis experienced) attack. 23 women presenting to the clinic with a clinical diagnosis of PID were also investigated. We measured PBMC proliferative responses to C trachomatis (DK20--an oculogenital strain, serovar E), lysate of McCoy cells (used to propagate chlamydiae), and the recall antigen PPD. Controls were 37 men and women without present or past history of urethritis or chlamydial infection. Results were expressed as the ratio of the stimulation index (SI) obtained with DK20 compared with McCoy cells (DK index), and the ratio of the SI obtained with DK20 compared with PPD (PPD index). RESULTS: The median SI to DK20 in the urethritis was 12.7 which was significantly higher than the controls (7.6, p urethritis patients (17.4) and the controls (22.4). All urethritis patient subgroups had a significantly higher DK index and PPD index than the controls. There was no difference in the PPD and DK index between urethritis naive and urethritis experienced patients and between the culture positive and culture negative urethritis subgroups. In PID patients only the PPD index was significantly higher than the controls. CONCLUSION: Men presenting with urethritis and women presenting with PID both have significantly greater peripheral blood mononuclear cell proliferative responses to the DK20 strain of C trachomatis than controls. A similar T cell proliferative response pattern in urethritis naive patients with either gonococcal or non-gonococcal urethritis could

  15. Responses of boundary layers to strong external disturbances

    Science.gov (United States)

    Asai, Masahito

    1990-10-01

    The transition from laminar flow to turbulent flow of the boundary layer is an important phenomenon for various problems in astronautical engineering. When the turbulence in the flow is weak, the boundary layer transition starts from the spatial amplification of a viscous T-S (Tollmien Schlichting) wave. The initial wave starts as a two dimensional wave and grows rapidly to a three dimensional wave with amplification. Finally, it corrupts to small scale hairpin eddies. The transitions starting from these wave amplifications are studied, and instability mechanisms are analyzed. In order to analyze the mechanism, the strength of turbulence (eddies) in the air flow that develops a transitional structure in the boundary layer and leads to a turbulent flow transition is analyzed. The responses of the boundary layers to the strong external disturbances are studied experimentally by introducing sonic wave which simulates hairpin eddies in the lower part of the front edge of a flat plate.

  16. Naturally-acquired influenza-specific CD4+ T-cell proliferative responses are impaired in HIV-infected African adults.

    Directory of Open Access Journals (Sweden)

    Kondwani C Jambo

    Full Text Available Seasonal influenza has been associated with greater morbidity and mortality in AIDS patients. Highly-active antiretroviral therapy (HAART has led to some reduction in influenza-related complications but the nature of naturally-acquired T-cell immunity to influenza virus in an African setting, and how this changes with immune reconstitution following HAART is unknown. We measured influenza-specific CD4(+ T-cell immunity in unimmunized HIV-infected Malawian adults and then investigated immune reconstitution following HAART.Peripheral blood mononuclear cells were isolated from HIV-infected and HIV-uninfected Malawian adults. CFSE proliferation and CD154 expression flow cytometry-based assays were used to measure influenza-specific CD4(+ T-cell immunity.We found lower naturally-acquired proliferative influenza-specific CD4(+ T-cell responses in AIDS patients that was also present in asymptomatic HIV-infected adults with relatively high CD4 counts (>350 cells/µl. Influenza-specific CD4(+ T-cell immune reconstitution in HIV-infected patients on HAART for 12 months was poor despite a marked reduction in viral load and an increase in CD4 count. This poor immune reconstitution was characterised by a low influenza-specific proliferative CD4(+ T-cell response and reduced proportions of CD154-expressing influenza-specific CD4(+ T-cells in peripheral blood.Our data suggest that asymptomatic HIV-infected adults may also be at risk of influenza-related complications and that HAART alone may not circumvent this risk in AIDS patients. This study highlights the need to identify possible interventions early in HIV infection to reduce the risk of influenza and to intensify influenza surveillance in these susceptible African populations.

  17. A peroxisome proliferator-activated receptor ligand MCC-555 imparts anti-proliferative response in pancreatic cancer cells by PPARgamma-independent up-regulation of KLF4

    International Nuclear Information System (INIS)

    Min, Kyung-Won; Zhang, Xiaobo; Imchen, Temjenmongla; Baek, Seung Joon

    2012-01-01

    MCC-555 is a novel PPARα/γ dual ligand of the thiazolidinedione class and was recently developed as an anti-diabetic drug with unique properties. MCC-555 also has anti-proliferative activity through growth inhibition and apoptosis induction in several cancer cell types. Our group has shown that MCC-555 targets several proteins in colorectal tumorigenesis including nonsteroidal anti-inflammatory drug (NSAID)-activated gene (NAG-1) which plays an important role in chemoprevention responsible for chemopreventive compounds. NAG-1 is a member of the TGF-β superfamily and is involved in tumor progression and development; however, NAG-1's roles in pancreatic cancer have not been studied. In this report, we found that MCC-555 alters not only NAG-1 expression, but also p21 and cyclin D1 expression. NAG-1 and p21 expression was not blocked by PPARγ-specific antagonist GW9662, suggesting that MCC-555-induced NAG-1 and p21 expression is independent of PPARγ activation. However, decreasing cyclin D1 by MCC-555 seems to be affected by PPARγ activation. Further, we found that the GC box located in the NAG-1 promoter play an important role in NAG-1 transactivation by MCC-555. Subsequently, we screened several transcription factors that may bind to the GC box region in the NAG-1 promoter and found that KLF4 potentially binds to this region. Expression of KLF4 precedes NAG-1 and p21 expression in the presence of MCC-555, whereas blocking KLF4 expression using specific KLF4 siRNA showed that both NAG-1 and p21 expression by MCC-555 was blocked. In conclusion, MCC-555's actions on anti-proliferation involve both PPARγ-dependent and -independent pathways, thereby enhancing anti-tumorigenesis in pancreatic cancer cells. -- Highlights: ► PPARα/γ ligand MCC-555 exhibits anti-proliferative activity in pancreatic cancer cells. ► MCC-555 affects KLF4 expression following by NAG-1 and p21 expression in a PPARγ independent manner. ► MCC-555 also affects cyclin D1 down

  18. Response of the Strongly Driven Jaynes-Cummings Oscillator

    Science.gov (United States)

    Bishop, Lev S.; Ginossar, Eran; Girvin, S. M.

    2010-09-01

    We analyze the Jaynes-Cummings model of quantum optics, in the strong-dispersive regime. In the bad-cavity limit and on time scales short compared to the atomic coherence time, the dynamics are those of a nonlinear oscillator. A steady-state nonperturbative semiclassical analysis exhibits a finite region of bistability delimited by a pair of critical points, unlike the usual dispersive bistability from a Kerr nonlinearity. This analysis explains our quantum trajectory simulations that show qualitative agreement with recent experiments from the field of circuit quantum electrodynamics.

  19. Strong surface effect on direct bulk flexoelectric response in solids

    International Nuclear Information System (INIS)

    Yurkov, A. S.; Tagantsev, A. K.

    2016-01-01

    In the framework of a continuum theory, it is shown that the direct bulk flexoelectric response of a finite sample essentially depends on the surface polarization energy, even in the thermodynamic limit where the body size tends to infinity. It is found that a modification of the surface energy can lead to a change in the polarization response by a factor of two. The origin of the effect is an electric field produced by surface dipoles induced by the strain gradient. The unexpected sensitivity of the polarization response to the surface energy in the thermodynamic limit is conditioned by the fact that the moments of the surface dipoles may scale as the body size

  20. Sub-isotypic differences in the immunoglobulin G response to Lawsonia intracellularis in vaccinated, seropositive, and equine proliferative enteropathy-affected horses.

    Science.gov (United States)

    Page, Allen E; Stills, Harold F; Horohov, David W

    2014-12-15

    In the horse, Lawsonia intracellularis infection results in equine proliferative enteropathy (EPE). While upwards of 100% of weanlings on an endemic farm may seroconvert, only a small percentage (approximately 5%) will develop clinical disease. Cell-mediated immune mechanisms likely play a role in resistance to L. intracellularis and the absence of a L. intracellularis-specific IFN-γ response has been associated with the development of EPE. The goal of this study was to determine whether protection from clinical EPE is associated with the induction of a systemic IgG sub-isotypic response consistent with a Th1-type cytokine response. To describe their L. intracellularis/EPE status, horses enrolled in this study were placed into one of three categories: seropositive-only, vaccinated, and presumptive clinical EPE. An existing ELISA method was modified to detect L. intracellularis-specific IgG(a), IgG(b), and IgG(t) antibodies using the mouse anti-equine hybridomas CVS-48, CVS-39, and CVS-40, respectively. Additionally, the existing ELISA method was used to quantify total IgG antibodies specific for L. intracellularis for comparison between the groups. Total L. intracellularis-specific IgG was found to be significantly higher (pequine IgG sub-isotypes may provide additional information once these become commercially available. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Strong nonlinear photonic responses from microbiologically synthesized tellurium nanocomposites

    Science.gov (United States)

    Liao, K.-S.; Wang, Jingyuan; Dias, S.; Dewald, J.; Alley, N.J.; Baesman, S.M.; Oremland, R.S.; Blau, W.J.; Curran, S.A.

    2010-01-01

    A new class of nanomaterials, namely microbiologically-formed nanorods composed of elemental tellurium [Te(0)] that forms unusual nanocomposites when combined with poly(m-phenylenevinylene-co-2,5-dioctoxy-phenylenevinylene) (PmPV) is described. These bio-nanocomposites exhibit excellent broadband optical limiting at 532 and 1064 nm. Nonlinear scattering, originating from the laser induced solvent bubbles and microplasmas, is responsible for this nonlinear behavior. The use of bacterially-formed Te(0) when combined with an organic chemical host (e.g., PmPV) is a new green method of nanoparticle syntheses. This opens the possibilities of using unique, biologically synthesized materials to advance future nanoelectronic and nanophotonic applications. ?? 2009 Elsevier B.V. All rights reserved.

  2. Reconstitution of active telomerase in primary human foreskin fibroblasts : effects on proliferative characteristics and response to ionizing radiation

    NARCIS (Netherlands)

    Kampinga, H.H.; Waarde-Verhagen, M.A.W.H. van; Assen-Bolt, A.J. van; Rodemann, H.P.; Prowse, K.R.; Linskens, M.H.K.

    2004-01-01

    Purpose: Telomere shortening has been proposed to trigger senescence, and since most primary cells do not express active telomerase, reactivation of telomerase activity was proposed as a safe and non-transforming way of immortalizing cells. However, to study radiation responses, it is as yet unclear

  3. Opa+ and Opa- isolates of Neisseria meningitidis and Neisseria gonorrhoeae induce sustained proliferative responses in human CD4+ T cells.

    NARCIS (Netherlands)

    Youssef, A.R.; Flier, M. van der; Estevao, S.; Hartwig, N.G.; Ley, P. van der; Virji, M.

    2009-01-01

    T cells may interact with a number of bacterial surface antigens, an encounter which has the potential to downmodulate host immune responses. Neisseria meningitidis, a human colonizer and an agent of septicemia and meningitis, expresses Opa proteins which interact with the CEACAM1 receptor expressed

  4. Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair.

    Science.gov (United States)

    Krüger, Leandi; Gonzalez, Liara M; Pridgen, Tiffany A; McCall, Shannon J; von Furstenberg, Richard J; Harnden, Ivan; Carnighan, Gwendolyn E; Cox, Abigail M; Blikslager, Anthony T; Garman, Katherine S

    2017-09-01

    Esophageal injury is a risk factor for diseases such as Barrett's esophagus (BE) and esophageal adenocarcinoma. To improve understanding of signaling pathways associated with both normal and abnormal repair, animal models are needed. Traditional rodent models of esophageal repair are limited by the absence of esophageal submucosal glands (ESMGs), which are present in the human esophagus. Previously, we identified acinar ductal metaplasia in human ESMGs in association with both esophageal injury and cancer. In addition, the SOX9 transcription factor has been associated with generation of columnar epithelium and the pathogenesis of BE and is present in ESMGs. To test our hypothesis that ESMGs activate after esophageal injury with an increase in proliferation, generation of a ductal phenotype, and expression of SOX9, we developed a porcine model of esophageal injury and repair using radiofrequency ablation (RFA). The porcine esophagus contains ESMGs, and RFA produces a consistent and reproducible mucosal injury in the esophagus. Here we present a temporal assessment of this model of esophageal repair. Porcine esophagus was evaluated at 0, 6, 18, 24, 48, and 72 h and 5 and 7 days following RFA and compared with control uninjured esophagus. Following RFA, ESMGs demonstrated an increase in ductal phenotype, echoing our prior studies in humans. Proliferation increased in both squamous epithelium and ESMGs postinjury with a prominent population of SOX9-positive cells in ESMGs postinjury. This model promises to be useful in future experiments evaluating mechanisms of esophageal repair. NEW & NOTEWORTHY A novel porcine model of injury and repair using radiofrequency ablation has been developed, allowing for reproducible injury to the esophagus to study repair in an animal model with esophageal submucosal glands, a key anatomical feature and missing in rodent models but possibly harboring progenitor cells. There is a strong translational component to this porcine model given

  5. Changes accompanying proliferative capacity and morphology of Nicotiana tabacum L. callus in response to 2,4-D

    Directory of Open Access Journals (Sweden)

    Andrzej Gatz

    2017-12-01

    Full Text Available The common trait of all auxins is a stimulation of cell elongation and also cell division in the presence of cytokinin; both are essential for callus induction and its multiplication. The response of plant tissues to various compounds with auxin activity may be quite different. In this study, the effectiveness of a synthetic auxin, 2,4-dichlorofenoxyacetic acid (2,4-D, instead of the generally applied natural auxin, indole-3-acetic acid (IAA, was tested for the proliferation of Nicotiana tabacum callus. The following concentrations of 2,4-D were tested: 0.1, 0.5, 1.0, 1.5, and 2.0 mg dm−3. Callus was derived from stem pith and its proliferation allowed on MS medium through five subcultures at 25°C and in darkness. After each passage, the fresh weight and morphological features of the callus were determined. The 0.5 mg dm−3 2,4-D treatment was the most favorable for producing the greatest increase in fresh weight in each of five subsequent subcultures as well as maintaining normal morphological features for proliferation. However, the 1.0 mg dm−3 2,4-D treatment in comparison with the lowest, 0.1 mg dm−3, was more beneficial when considering regular increases of fresh weight and a better cell cohesion for callus growth.

  6. The Relationship between Proliferative Scars and Endothelial Function in Surgically Revascularized Patients

    Directory of Open Access Journals (Sweden)

    Murat Ziyrek

    2015-12-01

    Full Text Available Background: Proliferative scars are benign fibrotic proliferations which demonstrate abnormal wound healing in response to skin injuries. As postulated in the “response to injury hypothesis”, atherosclerosis is also triggered by an endothelial injury. Keloid and atherosclerotic processes have many pathophysiological and cytological features in common. Aims: In this study, we investigated the relationship between proliferative scars and endothelial function in surgically revascularized patients. We aimed to test the hypothesis that atherosclerosis is a wound healing abnormality. Study Design: Cross-sectional study. Methods: Consecutive patients who were admitted to the cardiology outpatient clinic with a history of coronary artery bypass grafting operation were evaluated. Thirty-three patients with proliferative scars at the median sternotomy site formed the keloid group, and 36 age- and sex-matched patients with no proliferative scar at the median sternotomy site formed the control group. Endothelial function was evaluated by flow-mediated vasodilatation of the brachial artery via ultrasonograhic examination. Results: There is no signicant difference according to the demographic data, biochemical parameters, clinical parameters and number of grafts between keloid and control groups. Endothelial-dependent vasodilatory response was lower in the keloid group than the control group (9.30±3.5 and 18.68±8.2, respectively; p=0.001. Conclusion: This study showed that endothalial dysfunction, which is strongly correlated with atherosclerosis, was more prominent in patients with proliferative scars. As proliferative scars and atherosclerosis have many features in common, we might conclude that atherosclerosis is a wound healing abnormality.

  7. Magnetically responsive paclitaxel-loaded biodegradable nanoparticles for treatment of vascular disease: preparation, characterization and in vitro evaluation of anti-proliferative potential.

    Science.gov (United States)

    Johnson, Brandon; Toland, Brent; Chokshi, Rishi; Mochalin, Vadym; Koutzaki, Sirma; Polyak, Boris

    2010-10-01

    Long term prevention of smooth muscle cell migration and proliferation inside the lumen of coronary arteries after stent implantation remains a challenge in medicine. Vascular stents have been coated with anti-proliferative drugs such as paclitaxel and rapamycin to improve the stents' efficacy. Maintaining adequate drug concentration on coronary stents presents an obstacle which magnetic nanoparticle (MNP) drug delivery could potentially overcome. Biodegradable, super-paramagnetic nanoparticles guided by high gradient magnetic fields have been proposed as transport vehicles for re-dosing stents with anti-proliferative drugs. The current study determined the characteristics of a number of candidate MNP formulations in terms of their size, surface charge, efficiency of magnetite and drug loadings, drug release profiles as well as their anti-proliferative effect on the relevant vascular cells. MNPs containing near 30% (w/w) magnetite and 12% (w/w) paclitaxel were formulated from polylactide and poly(lactide-co-glycolide) polymers using an emulsification-solvent evaporation methodology. Drug release patterns correlated well with cell growth inhibition in cultured aortic smooth muscle cells and bovine aortic endothelial cells treated with varying MNP doses. Cell viability assays revealed MNP dose-dependent cell growth inhibition over an 8-day time span for paclitaxel-loaded formulations resulting in near 80% and 100% of cell growth arrest in cultured vascular smooth muscle cells and endothelial cells respectively, while unloaded with drug formulations showed negligible variation from the non treated cells. It is concluded, that biodegradable polymeric superparamagnetic nanoparticles loaded with a relatively high level of magnetite and drug could serve as efficient carriers in vascular stent targeting applications and potentially allow re-dosing the depleted stents, thereby prolonging the lifecycle of the implant.

  8. In vivo Ebola virus infection leads to a strong innate response in circulating immune cells.

    Science.gov (United States)

    Caballero, Ignacio S; Honko, Anna N; Gire, Stephen K; Winnicki, Sarah M; Melé, Marta; Gerhardinger, Chiara; Lin, Aaron E; Rinn, John L; Sabeti, Pardis C; Hensley, Lisa E; Connor, John H

    2016-09-05

    Ebola virus is the causative agent of a severe syndrome in humans with a fatality rate that can approach 90 %. During infection, the host immune response is thought to become dysregulated, but the mechanisms through which this happens are not entirely understood. In this study, we analyze RNA sequencing data to determine the host response to Ebola virus infection in circulating immune cells. Approximately half of the 100 genes with the strongest early increases in expression were interferon-stimulated genes, such as ISG15, OAS1, IFIT2, HERC5, MX1 and DHX58. Other highly upregulated genes included cytokines CXCL11, CCL7, IL2RA, IL2R1, IL15RA, and CSF2RB, which have not been previously reported to change during Ebola virus infection. Comparing this response in two different models of exposure (intramuscular and aerosol) revealed a similar signature of infection. The strong innate response in the aerosol model was seen not only in circulating cells, but also in primary and secondary target tissues. Conversely, the innate immune response of vaccinated macaques was almost non-existent. This suggests that the innate response is a major aspect of the cellular response to Ebola virus infection in multiple tissues. Ebola virus causes a severe infection in humans that is associated with high mortality. The host immune response to virus infection is thought to be an important aspect leading to severe pathology, but the components of this overactive response are not well characterized. Here, we analyzed how circulating immune cells respond to the virus and found that there is a strong innate response dependent on active virus replication. This finding is in stark contrast to in vitro evidence showing a suppression of innate immune signaling, and it suggests that the strong innate response we observe in infected animals may be an important contributor to pathogenesis.

  9. Nonlinear dynamic failure process of tunnel-fault system in response to strong seismic event

    Science.gov (United States)

    Yang, Zhihua; Lan, Hengxing; Zhang, Yongshuang; Gao, Xing; Li, Langping

    2013-03-01

    Strong earthquakes and faults have significant effect on the stability capability of underground tunnel structures. This study used a 3-Dimensional Discrete Element model and the real records of ground motion in the Wenchuan earthquake to investigate the dynamic response of tunnel-fault system. The typical tunnel-fault system was composed of one planned railway tunnel and one seismically active fault. The discrete numerical model was prudentially calibrated by means of the comparison between the field survey and numerical results of ground motion. It was then used to examine the detailed quantitative information on the dynamic response characteristics of tunnel-fault system, including stress distribution, strain, vibration velocity and tunnel failure process. The intensive tunnel-fault interaction during seismic loading induces the dramatic stress redistribution and stress concentration in the intersection of tunnel and fault. The tunnel-fault system behavior is characterized by the complicated nonlinear dynamic failure process in response to a real strong seismic event. It can be qualitatively divided into 5 main stages in terms of its stress, strain and rupturing behaviors: (1) strain localization, (2) rupture initiation, (3) rupture acceleration, (4) spontaneous rupture growth and (5) stabilization. This study provides the insight into the further stability estimation of underground tunnel structures under the combined effect of strong earthquakes and faults.

  10. Site classification of Indian strong motion network using response spectra ratios

    Science.gov (United States)

    Chopra, Sumer; Kumar, Vikas; Choudhury, Pallabee; Yadav, R. B. S.

    2018-03-01

    In the present study, we tried to classify the Indian strong motion sites spread all over Himalaya and adjoining region, located on varied geological formations, based on response spectral ratio. A total of 90 sites were classified based on 395 strong motion records from 94 earthquakes recorded at these sites. The magnitude of these earthquakes are between 2.3 and 7.7 and the hypocentral distance for most of the cases is less than 50 km. The predominant period obtained from response spectral ratios is used to classify these sites. It was found that the shape and predominant peaks of the spectra at these sites match with those in Japan, Italy, Iran, and at some of the sites in Europe and the same classification scheme can be applied to Indian strong motion network. We found that the earlier schemes based on description of near-surface geology, geomorphology, and topography were not able to capture the effect of sediment thickness. The sites are classified into seven classes (CL-I to CL-VII) with varying predominant periods and ranges as proposed by Alessandro et al. (Bull Seismol Soc Am 102:680-695 2012). The effect of magnitudes and hypocentral distances on the shape and predominant peaks were also studied and found to be very small. The classification scheme is robust and cost-effective and can be used in region-specific attenuation relationships for accounting local site effect.

  11. Mechanically strong dual responsive nanocomposite double network hydrogel for controlled drug release of asprin.

    Science.gov (United States)

    Chen, Yang; Song, Guocheng; Yu, Junrong; Wang, Yan; Zhu, Jing; Hu, Zuming

    2018-03-08

    Mechanically strong dual/multi-stimuli-responsive smart hydrogels have attracted extensive attention in recent years. A novel tough, mechanical strong and biocompatible dual pH- and temperature- responsive poly (N-isopropylacrylamide) /clay (laponite XLG)/carboxymethyl chitosan (CMCTs) /genipin nanocomposite double network hydrogel was synthesized through a facile, one-pot free radical polymerization initiated by the ultraviolet light, using clay and the natural molecular-genipin as the cross-linkers instead of toxic organic molecules. Crucial factors, the content of CMCTs, clay and genipin, for synthesizing the mechanical strong hydrogels were investigated. When the content of CMCTs, clay and genipin were 5 wt%, 33.3 wt% and 0.175 wt%, respectively (to the weight of N-isopropylacrylamide), these prepared hydrogels exhibited a high tensile strength of 137.9 kPa at the failure strain of 446.1%. Furthermore, the relationship between swelling and deswelling rate of the synthesized hydrogels and the above crucial factors were also studied. Besides, the synthesized hydrogels displayed a considerable controlled release property of asprin by tuning their inner crosslink density. Owing to this property, they may have great potential in the drug delivery systems. Copyright © 2018 Elsevier Ltd. All rights reserved.

  12. Extraordinary Photoluminescence and Strong Temperature/Angle-Dependent Raman Responses in Few-Layer Phosphorene

    OpenAIRE

    Zhang, Shuang; Yang, Jiong; Xu, Renjing; Wang, Fan; Li, Weifeng; Ghufran, Muhammad; Zhang, Yong-wei; Yu, Zongfu; Zhang, Gang; Qin, Qinghua; Lu, Yuerui

    2014-01-01

    Phosphorene is a new family member of two-dimensional materials. We observed strong and highly layer-dependent photoluminescence in few-layer phosphorene (2 to 5 layers). The results confirmed the theoretical prediction that few-layer phosphorene has a direct and layer-sensitive band gap. We also demonstrated that few-layer phosphorene is more sensitive to temperature modulation than graphene and MoS2 in Raman scattering. The anisotropic Raman response in few-layer phosphorene has enabled us ...

  13. Aluminum hydroxide nanoparticles show strong activity to stimulate Th-1 immune response against tuberculosis.

    Science.gov (United States)

    Amini, Yousef; Moradi, Bagher; Fasihi-Ramandi, Mahdi

    2017-11-01

    Many materials such as aluminum hydroxide have been tried as adjuvants to compensate low inherent immunogenicity of subunit vaccines. The aim of this study was to evaluate the specific immune response following the administration of aluminum hydroxide nanoparticles with EsxV antigen. The physiochemical properties of the nanoparticle were characterized in vitro. After subcutaneous immunization, cytokine secretion patterns including IFN-gama,IL-4, and TGF-beta levels were measured by indirect enzyme linked immunosorbent assay (ELISA). Aluminum hydroxide-NPs were demonstrated excellent effects to raise of IFN-γ secretion in compare to EsxV alone. Administration of aluminum hydroxide nanoparticles stimulates strong cellular immune response and could be considered as appropriate adjuvant against TB infection.

  14. Coccidioides Endospores and Spherules Draw Strong Chemotactic, Adhesive, and Phagocytic Responses by Individual Human Neutrophils.

    Directory of Open Access Journals (Sweden)

    Cheng-Yuk Lee

    Full Text Available Coccidioides spp. are dimorphic pathogenic fungi whose parasitic forms cause coccidioidomycosis (Valley fever in mammalian hosts. We use an innovative interdisciplinary approach to analyze one-on-one encounters between human neutrophils and two forms of Coccidioides posadasii. To examine the mechanisms by which the innate immune system coordinates different stages of the host response to fungal pathogens, we dissect the immune-cell response into chemotaxis, adhesion, and phagocytosis. Our single-cell technique reveals a surprisingly strong response by initially quiescent neutrophils to close encounters with C. posadasii, both from a distance (by complement-mediated chemotaxis as well as upon contact (by serum-dependent adhesion and phagocytosis. This response closely resembles neutrophil interactions with Candida albicans and zymosan particles, and is significantly stronger than the neutrophil responses to Cryptococcus neoformans, Aspergillus fumigatus, and Rhizopus oryzae under identical conditions. The vigorous in vitro neutrophil response suggests that C. posadasii evades in vivo recognition by neutrophils through suppression of long-range mobilization and recruitment of the immune cells. This observation elucidates an important paradigm of the recognition of microbes, i.e., that intact immunotaxis comprises an intricate spatiotemporal hierarchy of distinct chemotactic processes. Moreover, in contrast to earlier reports, human neutrophils exhibit vigorous chemotaxis toward, and frustrated phagocytosis of, the large spherules of C. posadasii under physiological-like conditions. Finally, neutrophils from healthy donors and patients with chronic coccidioidomycosis display subtle differences in their responses to antibody-coated beads, even though the patient cells appear to interact normally with C. posadasii endospores.

  15. The lantibiotic mersacidin is a strong inducer of the cell wall stress response of Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Sahl Hans-Georg

    2008-10-01

    Full Text Available Abstract Background The lantibiotic mersacidin is an antimicrobial peptide of 20 amino acids that is ribosomally produced by Bacillus sp. strain HIL Y-85,54728. Mersacidin acts by complexing the sugar phosphate head group of the peptidoglycan precursor lipid II, thereby inhibiting the transglycosylation reaction of peptidoglycan biosynthesis. Results Here, we studied the growth of Staphylococcus aureus in the presence of subinhibitory concentrations of mersacidin. Transcriptional data revealed an extensive induction of the cell wall stress response, which is partly controlled by the two-component regulatory system VraSR. In contrast to other cell wall-active antibiotics such as vancomycin, very low concentrations of mersacidin (0.15 × MIC were sufficient for induction. Interestingly, the cell wall stress response was equally induced in vancomycin intermediately resistant S. aureus (VISA and in a highly susceptible strain. Since the transcription of the VraDE ABC transporter genes was induced up to 1700-fold in our experiments, we analyzed the role of VraDE in the response to mersacidin. However, the deletion of the vraE gene did not result in an increased susceptibility to mersacidin compared to the wild type strain. Moreover, the efficacy of mersacidin was not affected by an increased cell wall thickness, which is part of the VISA-type resistance mechanism and functions by trapping the vancomycin molecules in the cell wall before they reach lipid II. Therefore, the relatively higher concentration of mersacidin at the membrane might explain why mersacidin is such a strong inducer of VraSR compared to vancomycin. Conclusion In conclusion, mersacidin appears to be a strong inducer of the cell wall stress response of S. aureus at very low concentrations, which reflects its general mode of action as a cell wall-active peptide as well as its use of a unique target site on lipid II. Additionally, mersacidin does not seem to be a substrate for the

  16. Divergent responses of tropical cyclone genesis factors to strong volcanic eruptions at different latitudes

    Science.gov (United States)

    Yan, Qing; Zhang, Zhongshi; Wang, Huijun

    2018-03-01

    To understand the behaviors of tropical cyclones (TCs), it is very important to explore how TCs respond to anthropogenic greenhouse gases and natural forcings. Volcanic eruptions are a major natural forcing mechanism because they inject sulphate aerosols into the stratosphere, which modulate the global climate by absorbing and scattering solar radiation. The number of Atlantic hurricanes is thought to be reduced following strong tropical eruptions, but whether the response of TCs varies with the locations of the volcanoes and the different ocean basins remains unknown. Here, we use the Community Earth System Model-Last Millennium Ensemble to investigate the response of the large-scale environmental factors that spawn TCs to strong volcanic eruptions at different latitudes. A composite analysis indicates that tropical and northern hemisphere volcanic eruptions lead to significantly unfavorable conditions for TC genesis over the whole Pacific basin and the North Atlantic during the 3 years post-eruption, relative to the preceding 3 years. Southern hemisphere volcanic eruptions result in obviously unfavorable conditions for TC formation over the southwestern Pacific, but more favorable conditions over the North Atlantic. The mean response over the Indian Ocean is generally muted and insignificant. It should be noted that volcanic eruptions impact on environmental conditions through both the direct effect (i.e. on radiative forcing) and the indirect effect (i.e. on El Niño-Southern Oscillation), which is not differentiated in this study. In addition, the spread of the TC genesis response is considerably large for each category of eruptions over each ocean basin, which is also seen in the observational/proxy-based records. This large spread is attributed to the differences in stratospheric aerosol distributions, initial states and eruption intensities, and makes the short-term forecast of TC activity following the next large eruption challenging.

  17. Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

    NARCIS (Netherlands)

    van Tellingen, A; Voskuyl, A E; Vervloet, M G; Bijl, M; de Sévaux, R G L; Berger, S P; Derksen, R H W M; Berden, J H M

    2012-01-01

    Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

  18. Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis.

    NARCIS (Netherlands)

    Tellingen, A. van; Voskuyl, A.E.; Vervloet, M.G.; Bijl, M. van der; Sevaux, R.G.L. de; Berger, S.P.; Derksen, R.H.W.M.; Berden, J.H.M.

    2012-01-01

    Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

  19. Dutch guidelines for diagnosis and therapy of proliferative lupus nephritis

    NARCIS (Netherlands)

    van Tellingen, A.; Voskuyl, A. E.; Vervloet, M. G.; Bijl, M.; de Sevaux, R. G. L.; Berger, S. P.; Derksen, R. H. W. M.; Berden, J. H. M.

    Proliferative lupus nephritis is a strong predictor of morbidity and mortality in patients with systemic lupus erythematosus. Despite improvements in the management of lupus nephritis, a significant number of the patients do not respond to immunosuppressive therapy and progress to end-stage renal

  20. Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses In Vivo.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Flamar

    Full Text Available Targeting dendritic cell-specific endocytic receptors using monoclonal antibodies fused to desired antigens is an approach widely used in vaccine development to enhance the poor immunogenicity of protein-based vaccines and to induce immune responses. Here, we engineered an anti-human DCIR recombinant antibody, which cross-reacts with the homologous cynomolgous macaque receptor and was fused via the heavy chain C-terminus to HIV Gagp24 protein (αDCIR.Gagp24. In vitro, αDCIR.Gagp24 expanded multifunctional antigen-specific memory CD4+ T cells recognizing multiple Gagp24 peptides from HIV-infected patient peripheral blood mononuclear cells. In non human primates, priming with αDCIR.Gagp24 without adjuvant elicited a strong anti-Gagp24 antibody response after the second immunization, while in the non-targeted HIV Gagp24 protein control groups the titers were weak. The presence of the double-stranded RNA poly(I:C adjuvant significantly enhanced the anti-Gagp24 antibody response in all the groups and reduced the discrimination between the different vaccine groups. The avidity of the anti-Gagp24 antibody responses was similar with either αDCIR.Gagp24 or Gagp24 immunization, but increased from medium to high avidity in both groups when poly(I:C was co-administered. This data provides a comparative analysis of DC-targeted and non-targeted proteins for their capacity to induce antigen-specific antibody responses in vivo. This study supports the further development of DCIR-based DC-targeting vaccines for protective durable antibody induction, especially in the absence of adjuvant.

  1. Clearance of low levels of HCV viremia in the absence of a strong adaptive immune response

    Directory of Open Access Journals (Sweden)

    Manns Michael P

    2007-06-01

    Full Text Available Abstract Spontaneous clearance of hepatitis C virus (HCV has frequently been associated with the presence of HCV-specific cellular immunity. However, there had been also reports in chimpanzees demonstrating clearance of HCV-viremia in the absence of significant levels of detectable HCV-specific cellular immune responses. We here report seven asymptomatic acute hepatitis C cases with peak HCV-RNA levels between 300 and 100.000 copies/ml who all cleared HCV-RNA spontaneously. Patients were identified by a systematic screening of 1176 consecutive new incoming offenders in a German young offender institution. Four of the seven patients never developed anti-HCV antibodies and had normal ALT levels throughout follow-up. Transient weak HCV-specific CD4+ T cell responses were detectable in five individuals which did not differ in strength and breadth from age- and sex-matched patients with chronic hepatitis C and long-term recovered patients. In contrast, HCV-specific MHC-class-I-tetramer-positive cells were found in 3 of 4 HLA-A2-positive patients. Thus, these cases highlight that clearance of low levels of HCV viremia is possible in the absence of a strong adaptive immune response which might explain the low seroconversion rate after occupational exposure to HCV.

  2. Extraordinary photoluminescence and strong temperature/angle-dependent Raman responses in few-layer phosphorene.

    Science.gov (United States)

    Zhang, Shuang; Yang, Jiong; Xu, Renjing; Wang, Fan; Li, Weifeng; Ghufran, Muhammad; Zhang, Yong-Wei; Yu, Zongfu; Zhang, Gang; Qin, Qinghua; Lu, Yuerui

    2014-09-23

    Phosphorene is a new family member of two-dimensional materials. We observed strong and highly layer-dependent photoluminescence in few-layer phosphorene (two to five layers). The results confirmed the theoretical prediction that few-layer phosphorene has a direct and layer-sensitive band gap. We also demonstrated that few-layer phosphorene is more sensitive to temperature modulation than graphene and MoS2 in Raman scattering. The anisotropic Raman response in few-layer phosphorene has enabled us to use an optical method to quickly determine the crystalline orientation without tunneling electron microscopy or scanning tunneling microscopy. Our results provide much needed experimental information about the band structures and exciton nature in few-layer phosphorene.

  3. Quantum correlations responsible for remote state creation: strong and weak control parameters

    Science.gov (United States)

    Doronin, S. I.; Zenchuk, A. I.

    2017-03-01

    We study the quantum correlations between the two remote qubits (sender and receiver) connected by the transmission line (homogeneous spin-1/2 chain) depending on the parameters of the sender's and receiver's initial states (control parameters). We consider two different measures of quantum correlations: the entanglement (a traditional measure) and the informational correlation (based on the parameter exchange between the sender and receiver). We find the domain in the control parameter space yielding (i) zero entanglement between the sender and receiver during the whole evolution period and (ii) non-vanishing informational correlation between the sender and receiver, thus showing that the informational correlation is responsible for the remote state creation. Among the control parameters, there are the strong parameters (which strongly effect the values of studied measures) and the weak ones (whose effect is negligible), therewith the eigenvalues of the initial state are given a privileged role. We also show that the problem of small entanglement (concurrence) in quantum information processing is similar (in certain sense) to the problem of small determinants in linear algebra. A particular model of 40-node spin-1/2 communication line is presented.

  4. Oscillatory response of the solar chromosphere to a strong downflow event above a sunspot

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Hannah; Chae, Jongchul; Song, Donguk [Astronomy Program, Department of Physics and Astronomy, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Yeon-Han; Lim, Eun-Kyung [Korea Astronomy and Space Science Institute, Daejeon 305-348 (Korea, Republic of); Madjarska, Maria S. [Armagh Observatory, College Hill, Armagh BT61 9DG (United Kingdom)

    2016-04-20

    We report three-minute oscillations in the solar chromosphere driven by a strong downflow event in a sunspot. We used the Fast Imaging Solar Spectrograph of the 1.6 m New Solar Telescope and the Interface Region Imaging Spectrograph (IRIS). The strong downflow event is identified in the chromospheric and transition region lines above the sunspot umbra. After the event, oscillations occur at the same region. The amplitude of the Doppler velocity oscillations is 2 km s{sup −1} and gradually decreases with time. In addition, the period of the oscillations gradually increases from 2.7 to 3.3 minutes. In the IRIS 1330 Å slit-jaw images, we identify a transient brightening near the footpoint of the downflow detected in the H α +0.5 Å image. The characteristics of the downflowing material are consistent with those of sunspot plumes. Based on our findings, we suggest that the gravitationally stratified atmosphere came to oscillate with a three-minute period in response to the impulsive downflow event as was theoretically investigated by Chae and Goode.

  5. In vitro effect of chloroquine, mefloquine and quinine on human lymphocyte proliferative responses to malaria antigens and other antigens/mitogens

    DEFF Research Database (Denmark)

    Bygbjerg, I C; Theander, T G; Andersen, B J

    1986-01-01

    -thymidine incorporation. On a weight base, the most potent drug was mefloquine. At clinically relevant doses, chloroquine and mefloquine did not affect the response to malaria antigens, but mefloquine decreased the response to phytohaemagglutinin; quinine suppressed the response to all mitogens (with the exception......The effect of 3 antimalarial quinoline derivatives, chloroquine, mefloquine and quinine on human blood mononuclear cells in vitro was studied. High concentrations profoundly suppressed the proliferation of mitogen- and antigen-stimulated lymphocytes, as indicated by decreased 14C...

  6. Seismic Response of a Sedimentary Basin: Preliminary Results from Strong Motion Downhole Array in Taipei Basin

    Science.gov (United States)

    Young, B.; Chen, K.; Chiu, J.

    2013-12-01

    The Strong Motion Downhole Array (SMDA) is an array of 32 triggered strong motion broadband seismometers located at eight sites in Taipei Basin. Each site features three to five co-located three-component accelerometers--one at the surface and an additional two to four each down independent boreholes. Located in the center of Taipei Basin is Taipei City and the Taipei metropolitan area, the capital of Taiwan and home to more than 7 million residents. Taipei Basin is in a major seismic hazard area and is prone to frequent large earthquakes producing strong ground motion. This unique three-dimension seismic array presents new frontiers for seismic research in Taiwan and, along with it, new challenges. Frequency-dependent and site-specific amplification of seismic waves from depth to surface has been observed: preliminary results indicate that the top few tens of meters of sediment--not the entire thickness--are responsible for significant frequency-dependent amplification; amplitudes of seismic waves at the surface may be as much as seven times that at depth. Dominant amplification frequencies are interpreted as quarter-wavelength constructive interference between the surface and major interfaces in the sediments. Using surface stations with known orientation as a reference, borehole seismometer orientations in these data--which are unknown, and some of which vary considerably from event to event--have been determined using several methods. After low-pass filtering the strong motion data, iteratively rotating the two horizontal components from an individual borehole station and cross-correlating them with that from a co-located surface station has proven to be very effective. In cases where the iterative cross-correlation method does not provide a good fit, rotating both surface and borehole stations to a common axis of maximum seismic energy provides an alternative approach. The orientation-offset of a borehole station relative to the surface station may be

  7. Strong response of an invasive plant species (Centaurea solstitialis L.) to global environmental changes.

    Science.gov (United States)

    Dukes, Jeffrey S; Chiariello, Nona R; Loarie, Scott R; Field, Christopher B

    2011-09-01

    Global environmental changes are altering interactions among plant species, sometimes favoring invasive species. Here, we examine how a suite of five environmental factors, singly and in combination, can affect the success of a highly invasive plant. We introduced Centaurea solstitialis L. (yellow starthistle), which is considered by many to be California's most troublesome wildland weed, to grassland plots in the San Francisco Bay Area. These plots experienced ambient or elevated levels of warming, atmospheric CO2, precipitation, and nitrate deposition, and an accidental fire in the previous year created an additional treatment. Centaurea grew more than six times larger in response to elevated CO2, and, outside of the burned area, grew more than three times larger in response to nitrate deposition. In contrast, resident plants in the community responded less strongly (or did not respond) to these treatments. Interactive effects among treatments were rarely significant. Results from a parallel mesocosm experiment, while less dramatic, supported the pattern of results observed in the field. Taken together, our results suggest that ongoing environmental changes may dramatically increase Centaurea's prevalence in western North America.

  8. Tuning smart microgel swelling and responsive behavior through strong and weak polyelectrolyte pair assembly.

    Science.gov (United States)

    Costa, Eunice; Lloyd, Margaret M; Chopko, Caroline; Aguiar-Ricardo, Ana; Hammond, Paula T

    2012-07-03

    The layer-by-layer (LbL) assembly of polyelectrolyte pairs on temperature and pH-sensitive cross-linked poly(N-isopropylacrylamide)-co-(methacrylic acid), poly(NIPAAm-co-MAA), microgels enabled a fine-tuning of the gel swelling and responsive behavior according to the mobility of the assembled polyelectrolyte (PE) pair and the composition of the outermost layer. Microbeads with well-defined morphology were initially prepared by synthesis in supercritical carbon dioxide. Upon LbL assembly of polyelectrolytes, interactions between the multilayers and the soft porous microgel led to differences in swelling and thermoresponsive behavior. For the weak PE pairs, namely poly(L-lysine)/poly(L-glutamic acid) and poly(allylamine hydrochloride)/poly(acrylic acid), polycation-terminated microgels were less swollen and more thermoresponsive than native microgel, whereas polyanion-terminated microgels were more swollen and not significantly responsive to temperature, in a quasi-reversible process with consecutive PE assembly. For the strong PE pair, poly(diallyldimethylammonium chloride)/poly(sodium styrene sulfonate), the differences among polycation and polyanion-terminated microgels are not sustained after the first PE bilayer due to extensive ionic cross-linking between the polyelectrolytes. The tendencies across the explored systems became less noteworthy in solutions with larger ionic strength due to overall charge shielding of the polyelectrolytes and microgel. ATR FT-IR studies correlated the swelling and responsive behavior after LbL assembly on the microgels with the extent of H-bonding and alternating charge distribution within the gel. Thus, the proposed LbL strategy may be a simple and flexible way to engineer smart microgels in terms of size, surface chemistry, overall charge and permeability.

  9. Identifying Host Molecular Features Strongly Linked With Responses to Huanglongbing Disease in Citrus Leaves

    Directory of Open Access Journals (Sweden)

    Bipin Balan

    2018-02-01

    Full Text Available A bioinformatic analysis of previously published RNA-Seq studies on Huanglongbing (HLB response and tolerance in leaf tissues was performed. The aim was to identify genes commonly modulated between studies and genes, pathways and gene set categories strongly associated with this devastating Citrus disease. Bioinformatic analysis of expression data of four datasets present in NCBI provided 46–68 million reads with an alignment percentage of 72.95–86.76%. Only 16 HLB-regulated genes were commonly identified between the three leaf datasets. Among them were key genes encoding proteins involved in cell wall modification such as CESA8, pectinesterase, expansin8, expansin beta 3.1, and a pectate lyase. Fourteen HLB-regulated genes were in common between all four datasets. Gene set enrichment analysis showed some different gene categories affected by HLB disease. Although sucrose and starch metabolism was highly linked with disease symptoms, different genes were significantly regulated depending on leaf growth and infection stages and experimental conditions. Histone-related transcription factors were highly affected by HLB in the analyzed RNA-Seq datasets. HLB tolerance was linked with induction of proteins involved in detoxification. Protein–protein interaction (PPI network analysis confirmed a possible role for heat shock proteins in curbing disease progression.

  10. Treatment of severe proliferative lupus nephritis: the current state

    OpenAIRE

    Mok, C; Wong, R; Lai, K

    2003-01-01

    Despite the development of new modalities, cyclophosphamide (CYC) remains the preferred initial treatment for severe proliferative lupus nephritis. Controversies continue about the best route, dosage, and duration of CYC treatment. For recalcitrant disease, new immunosuppressive and immunomodulating agents, immunoablative high dose CYC, nucleoside analogues, apheresis, and the biological response modifiers can be considered.

  11. Proliferative verrucous leukoplakia: An update

    Directory of Open Access Journals (Sweden)

    Anita Munde

    2016-01-01

    Full Text Available Proliferative verrucous leukoplakia (PVL is a rare form of oral leukoplakia, which was first described in 1985 by Hansen et al. Since then, various published case series have presented PVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation, usually higher than 70%. PVL is a long-term progressive condition, which is observed more frequently in elderly women, over 60 years at the time of diagnosis. The buccal mucosa and tongue are the most frequently involved sites. It develops initially as a white plaque of hyperkeratosis that eventually becomes a multifocal disease with confluent, exophytic and proliferative features with a progressive deterioration of the lesions, making it more and more difficult to control. Tobacco use does not seem to have a significant influence on the appearance or progression of PVL and may occur both in smokers and nonsmokers. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa. At present, the etiology of PVL remains unclear as well as its management and diagnosis, which is still retrospective, late and poorly defined, lacking consensus criteria. This short review discusses the clinical and histopathological features, diagnosis, traditional treatment and the current management of the disease.

  12. Immunomodulatory effect of cimetidine on the proliferative responses of splenocytes from T. cruzi-infected rats Efeito imunomodulatório da cimetidina sobre a resposta blastogênica de esplenócitos de ratos infectados por T. cruzi

    Directory of Open Access Journals (Sweden)

    M.N. Sato

    1991-06-01

    Full Text Available The immunomodulatory effect of cimetidine (CIM, a histamine type-2 receptor antagonist, was evaluated in respect to the blastogenic response to Con A of Wistar Furth (WF rats infected by the Y strain of Trypanosoma cruzi (T. cruzi. Enhancement of blastogenesis of normal splenocytes was observed at a concentration of 10-3M. However, the splenocytes from infected animals responded to concentrations of CIM ranging from 10-8 to 10-3M. The mitogenic response to Con A of cells from infected animals was restored in the presence of CIM. The results show that CIM modulates the "in vitro" proliferative response of cells from T. cruzi-infected rats and suggest an immunoregulatory role of histamine and/or of cells that express H2 receptors in this infection.O efeito imunomodulatório da Cimetidine (CIM, um antagonista do receptor de histamina-tipo 2, foi avaliado na resposta blastogênica a Con A em células de ratos Wistar Furth (WF infectados pela cepa Y de Trypanosoma cruzi (T. cruzi. Foi observado que apenas na concentração de 10-3M de Cimetidine houve amplificação da resposta blastogênica de esplenócitos normais a Con A. Entretanto, a capacidade mitogênica de esplenócitos de animais infectados foi restaurada na presença de molaridades da droga que variaram entre 10-8 a 10-3. Os resultados demonstraram que a CIM tem o potencial de modular a resposta mitogênica de células de animais infectados pelo T. cruzi, sugerindo um papel imunoregulatório da histamina e/ou células que expressam receptores H2 nesta infecção.

  13. Effect of L-carnitine on proliferative response and mRNA expression of some of its associated factors in splenic mononuclear cells of male broiler chicks.

    Science.gov (United States)

    Takahashi, Kazuaki; Kitano, Ayumi; Akiba, Yukio

    2010-04-01

    The effect of L-carnitine supplementation on mitogen (concanavalin A, Con A) induced proliferation of mononuclear cells (MNC) in the spleen was investigated in broiler chickens at different ages. Day-old chickens were fed a diet supplemented with or without L-carnitine (100 ppm) for 24 days. The carnitine-supplemented group showed greater proliferation of MNC in the spleen in response to Con A than that of the control group at 24 days of age. In addition, at 24 days of age the carnitine-supplemented group showed higher expression of interleukin (IL)-2 and interferon (IFN)-gamma mRNA, but lower expression of inducible nitric oxide synthase (iNOS) in the Con A-stimulated splenic MNC than the control group. The enhancement effect of L-carnitine on MNC proliferation and IL-2 mRNA expression was not found in chicks at 14 days of age. Addition of L-carnitine (50 nmol/mL) to the culture medium enhanced proliferation and IL-2 mRNA expression of splenic MNC obtained from 24-day-old but not from 14-day-old broiler chickens. The results suggest that L-carnitine is capable of enhancing MNC proliferation in broiler chickens at 24 days of age partly through increasing IL-2 and IFN-gamma production and decreasing NO production.

  14. Semi-metallic, strong conductive polymer microfiber, method and fast response rate actuators and heating textiles

    KAUST Repository

    Zhou, Jian

    2016-06-09

    A method comprising: providing at least one first composition comprising at least one conjugated polymer and at least one solvent, wet spinning the at least one first composition to form at least one first fiber material, hot-drawing the at least one fiber to form at least one second fiber material. In lead embodiments, high-performance poly(3,4-ethylenedioxy- thiophene)/poly(styrenesulfonate) (PEDOT/PSS) conjugated polymer microfibers were fabricated via wet- spinning followed by hot-drawing. In these lead embodiments, due to the combined effects of the vertical hot-drawing process and doping/de-doping the microfibers with ethylene glycol (EG), a record electrical conductivity of 2804 S · cm-1 was achieved. This is believed to be a six-fold improvement over the best previously reported value for PEDOT/PSS fibers (467 S · cm-1) and a twofold improvement over the best values for conductive polymer films treated by EG de-doping (1418 S · cm-1). Moreover, these lead, highly conductive fibers experience a semiconductor-metal transition at 313 K. They also have superior mechanical properties with a Young\\'s modulus up to 8.3 GPa, a tensile strength reaching 409.8 MPa and a large elongation before failure (21%). The most conductive fiber also demonstrates an extraordinary electrical performance during stretching/unstretching: the conductivity increased by 25% before the fiber rupture point with a maximum strain up to 21%. Simple fabrication of the semi-metallic, strong and stretchable wet-spun PEDOT/PSS microfibers can make them available for conductive smart electronics. A dramatic improvement in electrical conductivity is needed to make conductive polymer fibers viable candidates in applications such as flexible electrodes, conductive textiles, and fast-response sensors and actuators.

  15. Estrogen receptor-negative breast ductal carcinoma: clinicopathological features and MIB-1 (Ki-67 proliferative index association.

    Directory of Open Access Journals (Sweden)

    Noorasmaliza Mdpaiman

    Full Text Available Breast cancer estrogen receptor (ER status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67 of estrogen receptor negative invasive breast ductal carcinoma (NOS type as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20% was observed in 63 (63.6% of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%. We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.

  16. Ionospheric convection response to changes of interplanetary magnetic field B-z component during strong B-y component

    DEFF Research Database (Denmark)

    Huang, C.S.; Murr, D.; Sofko, G.J.

    2000-01-01

    enough, the B-z reorientation causes changes in the flow intensity but not in the shape of the convection pattern. The results show the characteristics of ionospheric convection response during strong B-y and suggest that the convection reconfiguration is not only determined by the changing B-z but also...... the dawn-dusk meridian plane, which is interpreted as propagation or expansion of newly generated convection cells in the cusp region. Other studies showed that the change in convection pattern in response to IMF reorientations is spatially fixed. In this paper, we investigate the ionospheric convection...... response to IMF Bz changes during strong IMF BZ. On March 23, 1995, B-x was small, B-y was strongly positive (7-11 nT), and the B-z polarity changed several times after 1300 UT. The dayside ionospheric convection is dominated by a large clockwise convection cell. The cell focus (the "eye" of the convection...

  17. Early clearance of Chikungunya virus in children is associated with a strong innate immune response

    OpenAIRE

    Simarmata, Diane; Ng, David Chun Ern; Kam, Yiu-Wing; Lee, Bernett; Sum, Magdline Sia Henry; Her, Zhisheng; Chow, Angela; Leo, Yee-Sin; Cardosa, Jane; Perera, David; Ooi, Mong H.; Ng, Lisa F. P.

    2016-01-01

    Chikungunya fever (CHIKF) is a global infectious disease which can affect a wide range of age groups. The pathological and immunological response upon Chikungunya virus (CHIKV) infection have been reported over the last few years. However, the clinical profile and immune response upon CHIKV infection in children remain largely unknown. In this study, we analyzed the clinical and immunological response, focusing on the cytokine/chemokine profile in a CHIKV-infected pediatric cohort from Sarawa...

  18. Sensitivity Analysis and Simulation of Theoretical Response of Ceramics to Strong Magnetic Fields

    Science.gov (United States)

    2016-09-01

    448. 23. Song Q, Zhang ZJ. Shape control and associated magnetic properties of spinel cobalt ferrite nanocrystals. Journal of the American Chemical...Strong Magnetic Fields by Carli A Moorehead, Michael M Kornecki, Victoria L Blair, Raymond E Brennan Approved for... Magnetic Fields by Carli A Moorehead Drexel University, Philadelphia, Pennsylvannia Michael M Kornecki, Victoria L Blair, and Raymond E Brennan

  19. Vitrectomy for proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Chao Peng

    2013-10-01

    Full Text Available AIM:To observe the clinical effect of vitrectomy for proliferative diabetic retinopathy(PDR.METHODS: The clinical data of 55 cases(65 eyes, underwent vitrectomy, membrane peeling, endolaser photocoagulation and silicone oil or C3F8 injection, were retrospectively studied. During 6 months to 1 year follow-up period, visual acuity, intraocular pressure, retinal conditions and complications were observed.RESULTS: All 65 eyes received vitrectomy, of which silicone oil was tamponaded in 32 eyes, C3F8 was injected in 8 eyes, BBS was filled in 25 eyes. Visual improvement achieved in 42 eyes. Two eyes were manually vision, form count fingers to 0.05 in 18 eyes, >0.05-0.1 in 28 eyes, >0.1-0.3 in 12 eyes and >0.3 in 5 eyes. Retinal hole was occurred in 7 eyes, limitations fibrosis membrane remained in 8 eyes, retinal detachment appeared in 5 eyes, IOP increased in 18 eyes, vitreous hemorrhage relapsed in 12 eyes, 36 eyes received supplemental photocoagulation treatment 1-3 times after operation.CONCLUSION:Vitrectomy combined endophotocoagulation is an effective treatment for PDR. Silicone oil tamponade can limit the hemorrhage.

  20. Deoxyglucose uptake by a head and neck squamous carcinoma: influence of changes in proliferative fraction

    International Nuclear Information System (INIS)

    Smith, T.A.D.; Titley, J.

    2000-01-01

    Purpose: Positron emission tomography, using the glucose analogue fluorodeoxy-D-glucose (FDG), is proving to be useful in the early response detection of head and neck tumors. Presently mechanisms underlying changes in FDG uptake after therapy are poorly understood. Response of tumors to therapy is often accompanied by a decrease in tumor cell proliferation. The purpose of this study was to assess whether or not changes in the uptake of deoxyglucose (DG) may reflect differences in proliferative fraction independent of other metabolic changes induced by using therapeutic agents. Methods and Materials: HN5 head and neck tumor cells were grown to different cell densities producing populations of cells with different proliferative indices without the need for exogenous agents to manipulate cell-cycle kinetics. 3 H-DG uptake, S-phase fraction (Spf), and lactate production were determined in each population of cells. Results: Large differences in Spf between populations of cells were associated with differences in DG incorporation. Lactate production was also found to correlate strongly with DG uptake. Conclusion: Therapy-induced changes in FDG uptake by tumors may be partly due to changes in proliferation

  1. Operation Strong Wind (Fort Lee’s Response to a Local Tornado Disaster, 6 August 1993)

    Science.gov (United States)

    1993-11-01

    Interstate 95, and less than a mile from Old Towne and Pocahontas Island. Most destruction happened at Wal- Mart’s 110,000 square foot store which employed 400...area which was in the process of making a strong economic statement. Next to that area was an historic black community on Pocahontas Island in the... happen was Petersburg should have asked the governor that he request Federal troops. The governor in turn would have called the Federal Emergency

  2. Asymmetric response of the Atlantic Meridional Ocean Circulation to freshwater anomalies in a strongly-eddying global ocean model

    NARCIS (Netherlands)

    Brunnabend, Sandra Esther|info:eu-repo/dai/nl/371740878; Dijkstra, Henk A.|info:eu-repo/dai/nl/073504467

    2017-01-01

    The Atlantic Meridional Overturning Circulation (AMOC) responds sensitively to density changes in regions of deepwater formation. In this paper, we investigate the nonlinear response of the AMOC to large amplitude freshwater changes around Greenland using a strongly-eddying global ocean model. Due

  3. Influence of inherent parameter of stabilized UHF oscillators on autodyne response formation at a strong reflected signal

    Directory of Open Access Journals (Sweden)

    Noskov V. Ya.

    2011-08-01

    Full Text Available Results of an autodyne response analysis in UHF oscillators stabilized by the external high-Q cavity in the case of the strong signal when the reflected wave amplitude commen-surable with the own oscillation amplitude. Coupling between the basic operation cavity and the stabilizing cavity is implemented as a pass-reflecting filter with a resistive bond. Key relations are obtained, which describe the autodyne response to the own re-reflected radiation from a target. The load and oscillating system influence on autodyne response formation is fulfilled.

  4. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T; Carrasco, J

    1999-01-01

    and reactive astrocytes surrounding the lesion site. In addition, expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and metallothionein-I+II (MT-I+II) were increased in these cells, while the brain-specific MT-III was only moderately upregulated. In IL-6-/- mice, however, the response......Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory...... response in the brain following disruption of the blood-brain barrier (BBB), we examined the effects of a focal cryo injury to the fronto-parietal cortex in interleukin-6-deficient (IL-6-/-) and normal (IL-6+/+) mice. In IL-6+/+ mice, brain injury resulted in the appearance of brain macrophages...

  5. Nonlocal response functions for predicting shear flow of strongly inhomogeneous fluids. I. Sinusoidally driven shear and sinusoidally driven inhomogeneity.

    Science.gov (United States)

    Glavatskiy, Kirill S; Dalton, Benjamin A; Daivis, Peter J; Todd, B D

    2015-06-01

    We present theoretical expressions for the density, strain rate, and shear pressure profiles in strongly inhomogeneous fluids undergoing steady shear flow with periodic boundary conditions. The expressions that we obtain take the form of truncated functional expansions. In these functional expansions, the independent variables are the spatially sinusoidal longitudinal and transverse forces that we apply in nonequilibrium molecular-dynamics simulations. The longitudinal force produces strong density inhomogeneity, and the transverse force produces sinusoidal shear. The functional expansions define new material properties, the response functions, which characterize the system's nonlocal response to the longitudinal force and the transverse force. We find that the sinusoidal longitudinal force, which is mainly responsible for the generation of density inhomogeneity, also modulates the strain rate and shear pressure profiles. Likewise, we find that the sinusoidal transverse force, which is mainly responsible for the generation of sinusoidal shear flow, can also modify the density. These cross couplings between density inhomogeneity and shear flow are also characterized by nonlocal response functions. We conduct nonequilibrium molecular-dynamics simulations to calculate all of the response functions needed to describe the response of the system for weak shear flow in the presence of strong density inhomogeneity up to the third order in the functional expansion. The response functions are then substituted directly into the truncated functional expansions and used to predict the density, velocity, and shear pressure profiles. The results are compared to the directly evaluated profiles from molecular-dynamics simulations, and we find that the predicted profiles from the truncated functional expansions are in excellent agreement with the directly computed density, velocity, and shear pressure profiles.

  6. Nonlocal response functions for predicting shear flow of strongly inhomogeneous fluids. I. Sinusoidally driven shear and sinusoidally driven inhomogeneity

    Science.gov (United States)

    Glavatskiy, Kirill S.; Dalton, Benjamin A.; Daivis, Peter J.; Todd, B. D.

    2015-06-01

    We present theoretical expressions for the density, strain rate, and shear pressure profiles in strongly inhomogeneous fluids undergoing steady shear flow with periodic boundary conditions. The expressions that we obtain take the form of truncated functional expansions. In these functional expansions, the independent variables are the spatially sinusoidal longitudinal and transverse forces that we apply in nonequilibrium molecular-dynamics simulations. The longitudinal force produces strong density inhomogeneity, and the transverse force produces sinusoidal shear. The functional expansions define new material properties, the response functions, which characterize the system's nonlocal response to the longitudinal force and the transverse force. We find that the sinusoidal longitudinal force, which is mainly responsible for the generation of density inhomogeneity, also modulates the strain rate and shear pressure profiles. Likewise, we find that the sinusoidal transverse force, which is mainly responsible for the generation of sinusoidal shear flow, can also modify the density. These cross couplings between density inhomogeneity and shear flow are also characterized by nonlocal response functions. We conduct nonequilibrium molecular-dynamics simulations to calculate all of the response functions needed to describe the response of the system for weak shear flow in the presence of strong density inhomogeneity up to the third order in the functional expansion. The response functions are then substituted directly into the truncated functional expansions and used to predict the density, velocity, and shear pressure profiles. The results are compared to the directly evaluated profiles from molecular-dynamics simulations, and we find that the predicted profiles from the truncated functional expansions are in excellent agreement with the directly computed density, velocity, and shear pressure profiles.

  7. Absorption in Music: Development of a Scale to Identify Individuals with Strong Emotional Responses to Music

    Science.gov (United States)

    Sandstrom, Gillian M.; Russo, Frank A.

    2013-01-01

    Despite the rise in research investigating music and emotion over the last decade, there are no validated measures of individual differences in emotional responses to music. We created the Absorption in Music Scale (AIMS), a 34-item measure of individuals' ability and willingness to allow music to draw them into an emotional experience. It was…

  8. [Proliferative diabetic retinopathy -- therapeutic approach (clinical case)].

    Science.gov (United States)

    Burcea, M; Muşat, Ovidiu; Mahdi, Labib; Gheorghe, Andreea; Spulbar, F; Gobej, I

    2014-01-01

    We present the case of a 54 year old pacient diagnosed with neglected insulin dependent diabetes and proliferative diabetic retinopathy. Surgery was recommended and we practiced posterior vitrectomy, endolaser and heavy silicone oil endotamponade. Post-operative evolution was favorable.

  9. Non-Proliferative Diabetic Retinopathy Vision Simulator

    Science.gov (United States)

    ... blood or fluid. The leaking fluid causes the retina to swell or to form deposits. Previous Proliferative Diabetic Retinopathy Vision Simulator Related Ask an Ophthalmologist Answers How common is retinal detachment for people with high myopia? Mar 29, 2017 ...

  10. Nonlinear response of the quantum Hall system to a strong electromagnetic radiation

    International Nuclear Information System (INIS)

    Avetissian, H.K.; Mkrtchian, G.F.

    2016-01-01

    We study nonlinear response of a quantum Hall system in semiconductor-hetero-structures via third harmonic generation process and nonlinear Faraday effect. We demonstrate that Faraday rotation angle and third harmonic radiation intensity have a characteristic Hall plateaus feature. These nonlinear effects remain robust against the significant broadening of Landau levels. We predict realization of an experiment through the observation of the third harmonic signal and Faraday rotation angle, which are within the experimental feasibility. - Highlights: • Nonlinear optical response of a quantum Hall system has specific plateaus feature. • This effect remains robust against the significant broadening of Landau levels. • It can be observed via the third harmonic signal and the nonlinear Faraday effect.

  11. Strongly compromised inflammatory response to brain injury in interleukin-6-deficient mice

    DEFF Research Database (Denmark)

    Penkowa, M; Moos, T; Carrasco, J

    1999-01-01

    and reactive astrocytes surrounding the lesion site. In addition, expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) and metallothionein-I+II (MT-I+II) were increased in these cells, while the brain-specific MT-III was only moderately upregulated. In IL-6-/- mice, however, the response...... of brain macrophages and reactive astrocytes was markedly depressed and the number of NSE positive neurons was reduced. Brain damage-induced GM-CSF and MT-I+II expression were also markedly depressed compared to IL-6+/+ mice. In contrast, MT-III immunoreactivity was markedly increased in brain macrophages......Injury to the central nervous system (CNS) elicits an inflammatory response involving activation of microglia, brain macrophages, and astrocytes, processes likely mediated by the release of proinflammatory cytokines. In order to determine the role of interleukin-6 (IL-6) during the inflammatory...

  12. Sorghum (Sorghum bicolor) varieties adopt strongly contrasting strategies in response to drought.

    Science.gov (United States)

    Ogbaga, Chukwuma C; Stepien, Piotr; Johnson, Giles N

    2014-10-01

    Sorghum is one of the most drought tolerant crops but surprisingly, little is known about the mechanisms achieving this. We have compared physiological and biochemical responses to drought in two sorghum cultivars with contrasting drought tolerance. These closely related cultivars have starkly contrasting responses to water deficit. In the less tolerant Samsorg 40, drought induced progressive loss of photosynthesis. The more drought tolerant Samsorg 17 maintained photosynthesis, transpiration and chlorophyll content until the most extreme conditions. In Samsorg 40, there was a highly specific down-regulation of selected proteins, with loss of PSII and Rubisco but maintenance of PSI and cytochrome b6 f, allowing plants to maintain ATP synthesis. The nitrogen released allows for accumulation of glycine betaine and proline. To the best of our knowledge, this is the first example of specific reengineering of the photosynthetic apparatus in response to drought. In contrast, in Samsorg 17 we detected no substantial change in the photosynthetic apparatus. Rather, plants showed constitutively high soluble sugar concentration, enabling them to maintain transpiration and photosynthesis, even in extremely dry conditions. The implications for these strikingly contrasted strategies are discussed in relation to agricultural and natural systems. © 2014 Scandinavian Plant Physiology Society.

  13. Fortune favours the brave: Movement responses shape demographic dynamics in strongly competing populations.

    Science.gov (United States)

    Potts, Jonathan R; Petrovskii, Sergei V

    2017-05-07

    Animal movement is a key mechanism for shaping population dynamics. The effect of interactions between competing animals on a population's survival has been studied for many decades. However, interactions also affect an animal's subsequent movement decisions. Despite this, the indirect effect of these decisions on animal survival is much less well-understood. Here, we incorporate movement responses to foreign animals into a model of two competing populations, where inter-specific competition is greater than intra-specific competition. When movement is diffusive, the travelling wave moves from the stronger population to the weaker. However, by incorporating behaviourally induced directed movement towards the stronger population, the weaker one can slow the travelling wave down, even reversing its direction. Hence movement responses can switch the predictions of traditional mechanistic models. Furthermore, when environmental heterogeneity is combined with aggressive movement strategies, it is possible for spatially segregated co-existence to emerge. In this situation, the spatial patterns of the competing populations have the unusual feature that they are slightly out-of-phase with the environmental patterns. Finally, incorporating dynamic movement responses can also enable stable co-existence in a homogeneous environment, giving a new mechanism for spatially segregated co-existence. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Virulence factors of Yersinia pestis are overcome by a strong lipopolysaccharide response.

    Science.gov (United States)

    Montminy, Sara W; Khan, Naseema; McGrath, Sara; Walkowicz, Mitchell J; Sharp, Fiona; Conlon, Joseph E; Fukase, Koichi; Kusumoto, Shoichi; Sweet, Charles; Miyake, Kensuke; Akira, Shizuo; Cotter, Robert J; Goguen, Jon D; Lien, Egil

    2006-10-01

    At mammalian body temperature, the plague bacillus Yersinia pestis synthesizes lipopolysaccharide (LPS)-lipid A with poor Toll-like receptor 4 (TLR4)-stimulating activity. To address the effect of weak TLR4 stimulation on virulence, we modified Y. pestis to produce a potent TLR4-stimulating LPS. Modified Y. pestis was completely avirulent after subcutaneous infection even at high challenge doses. Resistance to disease required TLR4, the adaptor protein MyD88 and coreceptor MD-2 and was considerably enhanced by CD14 and the adaptor Mal. Both innate and adaptive responses were required for sterilizing immunity against the modified strain, and convalescent mice were protected from both subcutaneous and respiratory challenge with wild-type Y. pestis. Despite the presence of other established immune evasion mechanisms, the modified Y. pestis was unable to cause systemic disease, demonstrating that the ability to evade the LPS-induced inflammatory response is critical for Y. pestis virulence. Evading TLR4 activation by lipid A alteration may contribute to the virulence of various Gram-negative bacteria.

  15. Atypical hyperplasia, proliferative fibrocystic change, and exogenous hormone use.

    Science.gov (United States)

    Zera, R T; Danielson, D; Van Camp, J M; Schmidt-Steinbrunn, B; Hong, J; McCoy, M; Anderson, W R; Linzie, B M; Rodriguez, J L

    2001-10-01

    The association between breast cancer development and exogenous hormone use (EHU) is suggested by indirect clinical evidence. We undertook this study to better define the relationship that EHU has with proliferative fibrocystic change (PFC) and atypical hyperplasia (AH). Women diagnosed with AH without associated carcinoma from January 1990 to December 1999 were compared with control subjects who underwent breast biopsy procedures during the same interval and who were diagnosed with either a proliferative fibrocystic change (PFC) or a nonproliferative fibrocystic change (NPFC). EHU was defined as the use of estrogen or progesterone taken together or separately within 3 months of biopsy. EHU was significantly higher in patients with AH compared with women with NPFC (P =.01). This observation was also significant if all proliferative change (both AH and PFC) was compared with NPFC (P =.03); it was not significant when PFC alone was compared with NPFC. No significant difference in EHU was demonstrated between women with AH and those with PFC. There is strong association between AH and EHU. These results support the theory that a continuum exists between hyperplasia and carcinoma and that EHU may influence the transition from one to the other in an undefined subset of women. We encourage our patients with AH to discontinue EHU.

  16. Posintro™-HBsAg, a modified ISCOM including HBsAg, induces strong cellular and humoral responses

    DEFF Research Database (Denmark)

    Schiött, Asa; Larsson, Kristina; Manniche, Søren

    2011-01-01

    HBsAg vaccine formulation, Posintro™-HBsAg, was compared to two commercial hepatitis B vaccines including aluminium or monophosphoryl lipid A (MPL) and the two adjuvant systems MF59 and QS21 in their efficiency to prime both cellular and humoral immune responses. The Posintro™-HBsAg induced...... of delayed type hypersensitivity (DTH) reaction and CD4(+) T-cell proliferation. In addition, Posintro™-HBsAg was the only vaccine tested that also induced a strong cytotoxic T lymphocyte (CTL) response, with high levels of antigen specific CD8 T-cells secreting IFN-gamma mediating cytolytic activity...

  17. A maize landrace that emits defense volatiles in response to?herbivore eggs possesses a strongly inducible terpene synthase gene

    OpenAIRE

    Tamiru, Amanuel; Bruce, Toby J. A.; Richter, Annett; Woodcock, Christine M.; Midega, Charles A. O.; Degenhardt, J?rg; Kelemu, Segenet; Pickett, John A.; Khan, Zeyaur R.

    2017-01-01

    Maize (Zea mays) emits volatile terpenes in response to insect feeding and egg deposition\\ud to defend itself against harmful pests. However, maize cultivars differ strongly in\\ud their ability to produce the defense signal. To further understand the agroecological\\ud role and underlying genetic mechanisms for variation in terpene emission among\\ud maize cultivars, we studied the production of an important signaling component (E)-caryophyllene\\ud in a South American maize landrace Braz1006 po...

  18. Strong phenotypic plasticity limits potential for evolutionary responses to climate change.

    Science.gov (United States)

    Oostra, Vicencio; Saastamoinen, Marjo; Zwaan, Bas J; Wheat, Christopher W

    2018-03-08

    Phenotypic plasticity, the expression of multiple phenotypes from one genome, is a widespread adaptation to short-term environmental fluctuations, but whether it facilitates evolutionary adaptation to climate change remains contentious. Here, we investigate seasonal plasticity and adaptive potential in an Afrotropical butterfly expressing distinct phenotypes in dry and wet seasons. We assess the transcriptional architecture of plasticity in a full-factorial analysis of heritable and environmental effects across 72 individuals, and reveal pervasive gene expression differences between the seasonal phenotypes. Strikingly, intra-population genetic variation for plasticity is largely absent, consistent with specialisation to a particular environmental cue reliably predicting seasonal transitions. Under climate change, deteriorating accuracy of predictive cues will likely aggravate maladaptive phenotype-environment mismatches and increase selective pressures on reaction norms. However, the observed paucity of genetic variation for plasticity limits evolutionary responses, potentially weakening prospects for population persistence. Thus, seasonally plastic species may be especially vulnerable to climate change.

  19. How Does HTLV-1 Undergo Oncogene-Dependent Replication Despite a Strong Immune Response?

    Directory of Open Access Journals (Sweden)

    Hélène Gazon

    2018-01-01

    Full Text Available In 1987, Mitsuaki Yoshida proposed the following model (Yoshida and Seiki, 1987: “... T-cells activated through the endogenous p40x would express viral antigens including the envelope glycoproteins which are exposed on the cell surface. These glycoproteins are targets of host immune surveillance, as is evidenced by the cytotoxic effects of anti-envelope antibodies or patient sera. Eventually all cells expressing the viral antigens, that is, all cells driven by the p40x would be rejected by the host. Only those cells that did not express the viral antigens would survive. Later, these antigen-negative infected cells would begin again to express viral antigens, including p40x, thus entering into the second cycle of cell propagation. These cycles would be repeated in so-called healthy virus carriers for 20 or 30 years or longer....” Three decades later, accumulated experimental facts particularly on intermittent viral transcription and regulation by the host immune response appear to prove that Yoshida was right. This Hypothesis and Theory summarizes the evidences that support this paradigm.

  20. Markedly Divergent Tree Assemblage Responses to Tropical Forest Loss and Fragmentation across a Strong Seasonality Gradient.

    Science.gov (United States)

    Orihuela, Rodrigo L L; Peres, Carlos A; Mendes, Gabriel; Jarenkow, João A; Tabarelli, Marcelo

    2015-01-01

    We examine the effects of forest fragmentation on the structure and composition of tree assemblages within three seasonal and aseasonal forest types of southern Brazil, including evergreen, Araucaria, and deciduous forests. We sampled three southernmost Atlantic Forest landscapes, including the largest continuous forest protected areas within each forest type. Tree assemblages in each forest type were sampled within 10 plots of 0.1 ha in both continuous forests and 10 adjacent forest fragments. All trees within each plot were assigned to trait categories describing their regeneration strategy, vertical stratification, seed-dispersal mode, seed size, and wood density. We detected differences among both forest types and landscape contexts in terms of overall tree species richness, and the density and species richness of different functional groups in terms of regeneration strategy, seed dispersal mode and woody density. Overall, evergreen forest fragments exhibited the largest deviations from continuous forest plots in assemblage structure. Evergreen, Araucaria and deciduous forests diverge in the functional composition of tree floras, particularly in relation to regeneration strategy and stress tolerance. By supporting a more diversified light-demanding and stress-tolerant flora with reduced richness and abundance of shade-tolerant, old-growth species, both deciduous and Araucaria forest tree assemblages are more intrinsically resilient to contemporary human-disturbances, including fragmentation-induced edge effects, in terms of species erosion and functional shifts. We suggest that these intrinsic differences in the direction and magnitude of responses to changes in landscape structure between forest types should guide a wide range of conservation strategies in restoring fragmented tropical forest landscapes worldwide.

  1. A strong response to selection on mass-independent maximal metabolic rate without a correlated response in basal metabolic rate.

    Science.gov (United States)

    Wone, B W M; Madsen, P; Donovan, E R; Labocha, M K; Sears, M W; Downs, C J; Sorensen, D A; Hayes, J P

    2015-04-01

    Metabolic rates are correlated with many aspects of ecology, but how selection on different aspects of metabolic rates affects their mutual evolution is poorly understood. Using laboratory mice, we artificially selected for high maximal mass-independent metabolic rate (MMR) without direct selection on mass-independent basal metabolic rate (BMR). Then we tested for responses to selection in MMR and correlated responses to selection in BMR. In other lines, we antagonistically selected for mice with a combination of high mass-independent MMR and low mass-independent BMR. All selection protocols and data analyses included body mass as a covariate, so effects of selection on the metabolic rates are mass adjusted (that is, independent of effects of body mass). The selection lasted eight generations. Compared with controls, MMR was significantly higher (11.2%) in lines selected for increased MMR, and BMR was slightly, but not significantly, higher (2.5%). Compared with controls, MMR was significantly higher (5.3%) in antagonistically selected lines, and BMR was slightly, but not significantly, lower (4.2%). Analysis of breeding values revealed no positive genetic trend for elevated BMR in high-MMR lines. A weak positive genetic correlation was detected between MMR and BMR. That weak positive genetic correlation supports the aerobic capacity model for the evolution of endothermy in the sense that it fails to falsify a key model assumption. Overall, the results suggest that at least in these mice there is significant capacity for independent evolution of metabolic traits. Whether that is true in the ancestral animals that evolved endothermy remains an important but unanswered question.

  2. Rapid upslope shifts in New Guinean birds illustrate strong distributional responses of tropical montane species to global warming.

    Science.gov (United States)

    Freeman, Benjamin G; Class Freeman, Alexandra M

    2014-03-25

    Temperate-zone species have responded to warming temperatures by shifting their distributions poleward and upslope. Thermal tolerance data suggests that tropical species may respond to warming temperatures even more strongly than temperate-zone species, but this prediction has yet to be tested. We addressed this data gap by conducting resurveys to measure distributional responses to temperature increases in the elevational limits of the avifaunas of two geographically and faunally independent New Guinean mountains, Mt. Karimui and Karkar Island, 47 and 44 y after they were originally surveyed. Although species richness is roughly five times greater on mainland Mt. Karimui than oceanic Karkar Island, distributional shifts at both sites were similar: upslope shifts averaged 113 m (Mt. Karimui) and 152 m (Karkar Island) for upper limits and 95 m (Mt. Karimui) and 123 m (Karkar Island) for lower limits. We incorporated these results into a metaanalysis to compare distributional responses of tropical species with those of temperate-zone species, finding that average upslope shifts in tropical montane species match local temperature increases significantly more closely than in temperate-zone montane species. That tropical species appear to be strong responders has global conservation implications and provides empirical support to hitherto untested models that predict widespread extinctions in upper-elevation tropical endemics with small ranges.

  3. Strong, sudden cooling alleviates the inflammatory responses in heat-stressed dairy cows based on iTRAQ proteomic analysis

    Science.gov (United States)

    Cheng, Jianbo; Min, Li; Zheng, Nan; Fan, Caiyun; Zhao, Shengguo; Zhang, Yangdong; Wang, Jiaqi

    2018-02-01

    This study was designed to investigate the effects of sudden cooling on the physiological responses of 12 heat-stressed Holstein dairy cows using an isobaric tags for relative and absolute quantification (iTRAQ) labeling approach. Plasma samples were collected from these cows during heat stress (HS), and after strong, sudden cooling in the summer (16 days later). We compared plasma proteomic data before and after sudden cooling to identify the differentially abundant proteins. The results showed that sudden cooling in summer effectively alleviated the negative consequences of HS on body temperature and production variables. Expressions of plasma hemoglobin alpha and hemoglobin beta were upregulated, whereas lipopolysaccharide-binding protein (LBP) and haptoglobin were downregulated in this process. The increase of hemoglobin after cooling may improve oxygen transport and alleviate the rise in respiration rates in heat-stressed dairy cows. The decrease of LBP and haptoglobin suggests that the inflammatory responses caused by HS are relieved after cooling. Our findings provide new insight into the physiological changes that occur when heat-stressed dairy cows experience strong, sudden cooling.

  4. Ionospheric convection response to changes of interplanetary magnetic field B-z component during strong B-y component

    DEFF Research Database (Denmark)

    Huang, C.S.; Murr, D.; Sofko, G.J.

    2000-01-01

    the dawn-dusk meridian plane, which is interpreted as propagation or expansion of newly generated convection cells in the cusp region. Other studies showed that the change in convection pattern in response to IMF reorientations is spatially fixed. In this paper, we investigate the ionospheric convection...... response to IMF Bz changes during strong IMF BZ. On March 23, 1995, B-x was small, B-y was strongly positive (7-11 nT), and the B-z polarity changed several times after 1300 UT. The dayside ionospheric convection is dominated by a large clockwise convection cell. The cell focus (the "eye" of the convection...... pattern) is located in the prenoon sector for northward B-z and in the postnoon sector for southward B-z. It is found that the cell focus shifts from the prenoon sector to the postnoon sector following a southward BL turning and vice versa for a northward B-z turning. However, the motion of the convection...

  5. Rapid upslope shifts in New Guinean birds illustrate strong distributional responses of tropical montane species to global warming

    Science.gov (United States)

    Freeman, Benjamin G.; Class Freeman, Alexandra M.

    2014-01-01

    Temperate-zone species have responded to warming temperatures by shifting their distributions poleward and upslope. Thermal tolerance data suggests that tropical species may respond to warming temperatures even more strongly than temperate-zone species, but this prediction has yet to be tested. We addressed this data gap by conducting resurveys to measure distributional responses to temperature increases in the elevational limits of the avifaunas of two geographically and faunally independent New Guinean mountains, Mt. Karimui and Karkar Island, 47 and 44 y after they were originally surveyed. Although species richness is roughly five times greater on mainland Mt. Karimui than oceanic Karkar Island, distributional shifts at both sites were similar: upslope shifts averaged 113 m (Mt. Karimui) and 152 m (Karkar Island) for upper limits and 95 m (Mt. Karimui) and 123 m (Karkar Island) for lower limits. We incorporated these results into a metaanalysis to compare distributional responses of tropical species with those of temperate-zone species, finding that average upslope shifts in tropical montane species match local temperature increases significantly more closely than in temperate-zone montane species. That tropical species appear to be strong responders has global conservation implications and provides empirical support to hitherto untested models that predict widespread extinctions in upper-elevation tropical endemics with small ranges. PMID:24550460

  6. Infection of goose with genotype VIId Newcastle disease virus of goose origin elicits strong immune responses at early stage

    Directory of Open Access Journals (Sweden)

    Qianqian Xu

    2016-10-01

    Full Text Available Newcastle disease (ND, caused by virulent strains of Newcastle disease virus (NDV, is a highly contagious disease of birds that is responsible for heavy economic losses for the poultry industry worldwide. However, little is known about host-virus interactions in waterfowl, goose. In this study, we aim to characterize the host immune response in goose, based on the previous reports on the host response to NDV in chickens. Here, we evaluated viral replication and mRNA expression of 27 immune-related genes in 10 tissues of geese challenged with a genotype VIId NDV strain of goose origin (go/CH/LHLJ/1/06. The virus showed early replication, especially in digestive and immune tissues. The expression profiles showed up-regulation of Toll-like receptor (TLR1–3, 5, 7 and 15, avian β-defensin (AvBD 5–7, 10, 12 and 16, cytokines interleukin (IL-8, IL-18, IL-1β and interferon-γ, inducible NO synthase (iNOS, and MHC class I in some tissues of geese in response to NDV. In contrast, NDV infection suppressed expression of AvBD1 in cecal tonsil of geese. Moreover, we observed a highly positive correlation between viral replication and host mRNA expressions of TLR1-5 and 7, AvBD4-6, 10 and 12, all the cytokines measured, MHC class I, FAS ligand, and iNOS, mainly at 72 h post-infection. Taken together, these results demonstrated that NDV infection induces strong innate immune responses and intense inflammatory responses at early stage in goose which may associate with the viral pathogenesis.

  7. Proliferative Activity and Neuroprotective Effect of Ligustrazene ...

    African Journals Online (AJOL)

    Proliferative Activity and Neuroprotective Effect of. Ligustrazene Derivative by Irritation of Vascular. Endothelial Growth Factor Expression in Middle Cerebral. Artery Occlusion Rats. Zhang Huazheng1, Wang Penglong2, Ren Liwei1, Wang Xiaobo2, Li Guoliang2,. Wang Mina1, Chu Fuhao2, Gong Yan2, Xu Bing2, Bi Siling1, ...

  8. TUBULAR DYSFUNCTION IN PROLIFERATIVE LUPUS NEPHRITIS

    NARCIS (Netherlands)

    TERBORG, E.J.; DEJONG, P.E.; MEIJER, S.S.; Kallenberg, Cees

    1991-01-01

    We prospectively studied renal tubular function during 11 consecutive exacerbations of proliferative glomerulonephritis in 8 patients with systemic lupus erythematosus (SLE). We found a rise in the fractional excretion of beta-2-microglobulin (p less-than-or-equal-to 0.05) and dimercaptosuccinic

  9. Mycobacterium vaccae induces a strong Th1 response that subsequently declines in C57BL/6 mice.

    Science.gov (United States)

    Zhang, Lijiao; Jiang, Yanlong; Cui, Ziyin; Yang, Wentao; Yue, Limin; Ma, Yingcong; Shi, Shaohua; Wang, Chunfang; Wang, Chunfeng; Qian, Aidong

    2016-12-30

    Mycobacterium (M.) vaccae is a fast-growing species of saprophytic bacteria that is widely distributed. To understand the host immune responses induced by M. vaccae isolated from bovine submaxillary lymph nodes, C57BL/6 mice were infected with reference strain M. bovis Bacillus Calmette-Guérin (BCG) and isolated M. vaccae using intraperitoneal injections. Comparison of the bacterial replication and organ pathology between M. vaccae and M. bovis BCG revealed that M. vaccae was more malignant than M. bovis in mice. We also demonstrated that serum from the M. vaccae -infected mice contained a higher expression level of gamma-interferon (IFN-γ), tumor necrosis factor alpha, monocyte chemoattractant protein-1, interleukin (IL)-4, IL-12, IL-10 and transforming growth factor beta than did the other groups, especially after week 4. Furthermore, when the numbers of CD3⁺CD4⁺IFN-γ⁺ and CD3⁺CD4⁺IL4⁺cells in the infected mice were observed by flow cytometry, we found that a powerful T helper 1 (Th1) response was induced by M. vaccae infection, which was associated with the emergence of CD3⁺CD4⁺IFN-γ⁺cells. However, the Th1 response declined over time, which was associated with appearance of the CD4⁺CD25⁺FoxP3⁺ and CD4⁺CD25⁺CD152⁺Treg cell reaction. In addition, a strong Th2 response was found. Finally, we found that M. vaccae infection increased the production of type I IFNs, which was associated with a reduced Th1 response.

  10. Chronic proliferative synovitis of the equine metacarpophalangeal joint

    International Nuclear Information System (INIS)

    Kannegieter, N.J.

    1990-01-01

    Chronic proliferative synovitis of 27 metacarpophalangeal joints in 16 horses is described. The diagnosis was based on a history of lameness and, or, poor performance, pain on flexion of the metacarpophalangeal joint, the response to intra-articular anaesthesia, and plain and contrast radiography. Radiographic findings included concavity of the distal dorsal metacarpus proximal to the sagittal ridge, and an increase in size of the synovial tissue adjacent to the proximal, dorsal attachment of the joint capsule. Mineralisation of the synovial tissue was present in some joints, and chip fractures from the dorsal aspect of the proximal phalanx were also occasionally seen. Treatment by arthroscopic resection of the tissue gave excellent results

  11. rBCG induces strong antigen-specific T cell responses in rhesus macaques in a prime-boost setting with an adenovirus 35 tuberculosis vaccine vector.

    Directory of Open Access Journals (Sweden)

    Isabelle Magalhaes

    Full Text Available BACKGROUND: BCG vaccination, combined with adenoviral-delivered boosts, represents a reasonable strategy to augment, broaden and prolong immune protection against tuberculosis (TB. We tested BCG (SSI1331 (in 6 animals, delivered intradermally and a recombinant (rBCG AFRO-1 expressing perfringolysin (in 6 animals followed by two boosts (delivered intramuscullary with non-replicating adenovirus 35 (rAd35 expressing a fusion protein composed of Ag85A, Ag85B and TB10.4, for the capacity to induce antigen-specific cellular immune responses in rhesus macaques (Macaca mulatta. Control animals received diluent (3 animals. METHODS AND FINDINGS: Cellular immune responses were analyzed longitudinally (12 blood draws for each animal using intracellular cytokine staining (TNF-alpha, IL-2 and IFN-gamma, T cell proliferation was measured in CD4(+, CD8alpha/beta(+, and CD8alpha/alpha(+ T cell subsets and IFN-gamma production was tested in 7 day PBMC cultures (whole blood cell assay, WBA using Ag85A, Ag85B, TB10.4 recombinant proteins, PPD or BCG as stimuli. Animals primed with AFRO-1 showed i increased Ag85B-specific IFN-gamma production in the WBA assay (median >400 pg/ml for 6 animals one week after the first boost with adenoviral-delivered TB-antigens as compared to animals primed with BCG (<200 pg/ml, ii stronger T cell proliferation in the CD8alpha/alpha(+ T cell subset (proliferative index 17% as compared to BCG-primed animals (proliferative index 5% in CD8alpha/alpha(+ T cells. Polyfunctional T cells, defined by IFN-gamma, TNF-alpha and IL-2 production were detected in 2/6 animals primed with AFRO-1 directed against Ag85A/b and TB10.4; 4/6 animals primed with BCG showed a Ag85A/b responses, yet only a single animal exhibited Ag85A/b and TB10.4 reactivity. CONCLUSION: AFRO-1 induces qualitatively and quantitatively different cellular immune responses as compared with BCG in rhesus macaques. Increased IFN-gamma-responses and antigen-specific T cell

  12. STRONG RESPONSE OF THE VERY BROAD Hβ EMISSION LINE IN THE LUMINOUS RADIO-QUIET QUASAR PG 1416-129

    International Nuclear Information System (INIS)

    Wang, J.; Li, Y.

    2011-01-01

    We report new spectroscopic observations performed in 2010 and 2011 for the luminous radio-quiet quasar PG 1416-129. Our new spectra with high quality cover both Hβ and Hα regions, and show negligible line profile variation within a timescale of one year. The two spectra allow us to study the variability of the Balmer line profile by comparing the spectra with previous ones taken at 10 and 20 years ago. By decomposing the broad Balmer emission lines into two Gaussian profiles, our spectral analysis suggests a strong response to the continuum level for the very broad component, and significant variations in both bulk blueshift velocity/FWHM and flux for the broad component. The new observations additionally indicate flat Balmer decrements (i.e., too strong Hβ emission) at the line wings, which is hard to reproduce using recent optically thin models. With these observations we argue that a separate inner optically thin emission-line region might not be necessary in the object to reproduce the observed line profiles.

  13. Temporal genetic stability in natural populations of the waterflea Daphnia magna in response to strong selection pressure.

    Science.gov (United States)

    Orsini, Luisa; Marshall, Hollie; Cuenca Cambronero, Maria; Chaturvedi, Anurag; Thomas, Kelley W; Pfrender, Michael E; Spanier, Katina I; De Meester, Luc

    2016-12-01

    Studies monitoring changes in genetic diversity and composition through time allow a unique understanding of evolutionary dynamics and persistence of natural populations. However, such studies are often limited to species with short generation times that can be propagated in the laboratory or few exceptional cases in the wild. Species that produce dormant stages provide powerful models for the reconstruction of evolutionary dynamics in the natural environment. A remaining open question is to what extent dormant egg banks are an unbiased representation of populations and hence of the species' evolutionary potential, especially in the presence of strong environmental selection. We address this key question using the water flea Daphnia magna, which produces dormant stages that accumulate in biological archives over time. We assess temporal genetic stability in three biological archives, previously used in resurrection ecology studies showing adaptive evolutionary responses to rapid environmental change. We show that neutral genetic diversity does not decline with the age of the population and it is maintained in the presence of strong selection. In addition, by comparing temporal genetic stability in hatched and unhatched populations from the same biological archive, we show that dormant egg banks can be consulted to obtain a reliable measure of genetic diversity over time, at least in the multidecadal time frame studied here. The stability of neutral genetic diversity through time is likely mediated by the buffering effect of the resting egg bank. © 2016 John Wiley & Sons Ltd.

  14. Dengue E Protein Domain III-Based DNA Immunisation Induces Strong Antibody Responses to All Four Viral Serotypes.

    Directory of Open Access Journals (Sweden)

    Monica Poggianella

    Full Text Available Dengue virus (DENV infection is a major emerging disease widely distributed throughout the tropical and subtropical regions of the world affecting several millions of people. Despite constants efforts, no specific treatment or effective vaccine is yet available. Here we show a novel design of a DNA immunisation strategy that resulted in the induction of strong antibody responses with high neutralisation titres in mice against all four viral serotypes. The immunogenic molecule is an engineered version of the domain III (DIII of the virus E protein fused to the dimerising CH3 domain of the IgG immunoglobulin H chain. The DIII sequences were also codon-optimised for expression in mammalian cells. While DIII alone is very poorly secreted, the codon-optimised fusion protein is rightly expressed, folded and secreted at high levels, thus inducing strong antibody responses. Mice were immunised using gene-gun technology, an efficient way of intradermal delivery of the plasmid DNA, and the vaccine was able to induce neutralising titres against all serotypes. Additionally, all sera showed reactivity to a recombinant DIII version and the recombinant E protein produced and secreted from mammalian cells in a mono-biotinylated form when tested in a conformational ELISA. Sera were also highly reactive to infective viral particles in a virus-capture ELISA and specific for each serotype as revealed by the low cross-reactive and cross-neutralising activities. The serotype specific sera did not induce antibody dependent enhancement of infection (ADE in non-homologous virus serotypes. A tetravalent immunisation protocol in mice showed induction of neutralising antibodies against all four dengue serotypes as well.

  15. DIAGNOSTIC CRITERIA FOR PROLIFERATIVE THYROID LESIONS IN BONY FISHES

    Science.gov (United States)

    Thyroid proliferative lesions are rather common in bony fishes but disagreement exists in the fish pathology community concerning diagnostic criteria for hyperplastic versus neoplastic lesions. To simplify the diagnosis of proliferative thyroid lesions and to reduce confusion reg...

  16. CpG ODN and ISCOMATRIX Adjuvant: A Synergistic Adjuvant Combination Inducing Strong T-Cell IFN-γ Responses

    Directory of Open Access Journals (Sweden)

    Michael J. McCluskie

    2013-01-01

    Full Text Available For the induction of robust humoral and cellular immune responses, a strong rationale exists to use vaccine-adjuvant combinations possessing both immune modulatory and enhanced delivery capabilities. Herein, we evaluated the combination of 2 different adjuvants, a TLR9 agonist, composed of synthetic oligodeoxynucleotides (ODN containing immunostimulatory CpG motifs (CpG, and ISCOMATRIX adjuvant (ISCOMATRIX, composed of saponin, phospholipid, and cholesterol, which possesses both immunostimulatory and delivery properties. While both individual adjuvants have been shown effective in numerous preclinical and clinical studies, it is likely that for optimal adjuvant activity a combined adjuvant approach will be necessary. Herein, using three different antigens, namely, hepatitis B surface antigen (HBsAg, ovalbumin (OVA, and influenza A haemagglutinin antigen (HA, we show in mice that some adjuvant effects of CpG and ISCOMATRIX are further enhanced if they are used in combination. In particular, with all three antigens, IFN-γ levels were greatly increased with the CpG/ISCOMATRIX combination. The ability of the CpG/ISCOMATRIX combination to induce antitumor responses when administered with OVA following administration to mice of a highly metastatic OVA-secreting tumor cell line (B16-OVA melanoma was also demonstrated. Thus the CpG/ISCOMATRIX combination may prove to be a valuable tool in the development of novel or improved vaccines.

  17. The response of the Red Sea to a strong wind jet near the Tokar Gap in summer

    KAUST Repository

    Zhai, Ping

    2013-01-01

    [1] Remote sensing and in situ observations are used to investigate the ocean response to the Tokar Wind Jet in the Red Sea. The wind jet blows down the atmospheric pressure gradient through the Tokar Gap on the Sudanese coast, at about 19°N, during the summer monsoon season. It disturbs the prevailing along-sea (southeastward) winds with strong cross-sea (northeastward) winds that can last from days to weeks and reach amplitudes of 20-25 m/s. By comparing scatterometer winds with along-track and gridded sea level anomaly observations, it is observed that an intense dipolar eddy spins up in response to the wind jet. The eddy pair has a horizontal scale of 140 km. Maximum ocean surface velocities can reach 1 m/s and eddy currents extend more than 100 m into the water column. The eddy currents appear to cover the width of the sea, providing a pathway for rapid transport of marine organisms and other drifting material from one coast to the other. Interannual variability in the strength of the dipole is closely matched with variability in the strength of the wind jet. The dipole is observed to be quasi-stationary, although there is some evidence for slow eastward propagation in an idealized numerical model. Simulation of the dipole in an idealized high-resolution numerical model suggests that this is the result of self-advection. © 2012. American Geophysical Union. All Rights Reserved.

  18. Proliferative and nonproliferative breast disease in atomic-bomb survivors

    International Nuclear Information System (INIS)

    Tokunaga, Masayoshi; Land, C.E.; Aoki, Yoichiro; Yamamoto, Tsutomu; Asano, Masahide; Sato, Eiichi; Tokuoka, Shoji; Sakamoto, Goi; Page, D.L.

    1993-10-01

    The risk of female breast cancer in association with radiation exposure is well established, on the basis of follow-up studies of the atomic-bomb survivors and other exposed populations. This association is especially strong for women exposed before age 20 yr and appears to be much weaker among women exposed after age 40 yr. In this study, breast-tissue autopsy samples from high-dose and low-dose individuals in the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative or proliferative breast lesions are associated with radiation exposure. The results suggest that proliferative disease in general and atypical hyperplasia in particular are associated with radiation exposure and that the risk is strongest for subjects who were ages 40-49 yr at the time of the bombings. It is hypothesized that this finding may be related to the age dependence of radiation-induced breast cancer, in the sense that potential cancers reflecting early-stage changes induced at these ages by radiation exposure may receive too little hormonal promotion to progress to frank cancers. (author)

  19. Pro-Life nurses uniting for service.

    Science.gov (United States)

    Sutherland, K

    1994-01-01

    The Missouri Pro-Life Nurses claim that nurses have lost the ethical basis of their profession. Nurses need to reexamine their attitudes at a time when 1 in 5 physician-members of the American Society of Internal Medicine admits to deliberately helping a patient end his or her life, and when many physicians and nurses favor euthanasia and abortion. Former Georgia nurse Joseph Dewey Akin was sentenced in October 1992 to life imprisonment for injecting Robert Price, a quadriplegic, with a lethal dose of lidocaine. Hospice nurse Darlene Leon of California is on trial for injecting 17 of her patients with lethal doses of morphine. A nurse from Georgia was indicted on one count of aggravated assault for attempting to kill her 87-year-old patient with an injection of potassium. Georgia nurse Jenny Serbes was charged with murder in the death of her husband with a lethal injection of insulin. The fierce argument about abortion and euthanasia now raging in America is this century's civil war. 20 years ago, in an effort to combat this tide, the National Association of Pro-Life Nurses (NAPN) was started, and its 1000 members want to demonstrate positive concern for all human life. NAPN attempts to educate nurses and the health care community on the legal and medical aspects of the ethical issues facing the profession. In October 1993 the first meeting of Illinois Pro-Life Nurses was held in suburban Chicago. The nurse-patient relationship can be viewed as a contract. Implicit in this relationship is the understanding that the nurse will do no harm. If the relationship is broken, the foundation on which nursing and medicine rest is shaken. Pro-life nursing organizations are trying to steer the nursing profession back on the right course.

  20. 5-Hydroxymethylcytosine Expression in Proliferative Nodules Arising within Congenital Nevi Allows Differentiation from Malignant Melanoma.

    Science.gov (United States)

    Pavlova, Olesya; Fraitag, Sylvie; Hohl, Daniel

    2016-12-01

    Differentiation of proliferative nodules in giant congenital nevi from melanoma arising within such nevi is an important diagnostic challenge. DNA methylation is a well-established epigenetic modification already observed in the earliest stages of carcinogenesis, which increases during melanoma progression. The ten-eleven translocation enzymes catalyze the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine (5-hmC), which has recently been reported as an epigenetic hallmark associated with tumor aggressiveness and poor prognosis in a wide variety of cancers. In this study, we analyzed 12 proliferative nodules and 13 melanomas both arising in giant congenital nevi and matched results with a control group including 67 benign and malignant melanocytic lesions. Proliferative nodules displayed high 5-hmC expression levels (90.65%) compared with melanomas with almost complete loss of this marker (7.87%). We showed that low 5-hmC levels in melanomas correlate with downregulation of isocitrate dehydrogenase and ten-eleven translocation families of enzymes implicated in the cytosine methylation cycle. Simultaneously, these enzymes were overexpressed in proliferative nodules leading to strong 5-hmC expression. We emphasize the significance of 5-hmC loss for discrimination of melanomas from benign proliferative nodules arising within giant congenital nevi, and for establishing the correct diagnosis in ambiguous cases when histological and immunohistochemical characteristics are not sufficiently specific. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Antibacterial, antioxidant and cell proliferative properties of Coccinia grandis fruits

    Directory of Open Access Journals (Sweden)

    Prashant Sakharkar

    2017-06-01

    Full Text Available Objective: Little knowledge is available on the antimicrobial and antioxidant properties of Coccina grandis fruits and no study has reported on its cell proliferative property. The aim of this study was to examine the antimicrobial, antioxidant and cell proliferative property of fruits of C. grandis. Material and Methods: Fruits of C. grandis were extracted using water; ethanol and acetone by cold and hot Soxhlet extraction. The antibacterial activities of the extracts were tested against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa using the modified Kirby-Bauer diffusion method and compared against erythromycin. The antioxidant property was determined using Cayman's antioxidant assay; whereas cell proliferation/cytotoxic properties were evaluated using the Cell Titer 96 Aqueous One Solution Cell MTS assay with MDA-MB 321 breast cancer cells. Data were analyzed for correlation and differences using unpaired student's t-test and one-way ANOVA. A p value of Results: Both cold and hot ethanol and acetone extracts of C. grandis fruits showed some degree of bacterial growth inhibition. Acetone extracts exhibited higher antibacterial activity. Both ethanol extracts showed antioxidant property when compared with standard Trolox. In contrary to cytotoxicity, all four extracts showed cell proliferation compared to controls at different concentrations. However, acetone extracts exhibited greater cell proliferation compared to ethanol extracts and cold extracts performed better than the hot extracts. Conclusion: C. grandis fruits exhibited some degree of antimicrobial, antioxidant and cell proliferative properties. Further investigation is warranted to isolate, confirm and characterize phytochemicals that are responsible for the medicinal properties observed.

  2. Tetanus toxoid-loaded cationic non-aggregated nanostructured lipid particles triggered strong humoral and cellular immune responses.

    Science.gov (United States)

    Kaur, Amandeep; Jyoti, Kiran; Rai, Shweta; Sidhu, Rupinder; Pandey, Ravi Shankar; Jain, Upendra Kumar; Katyal, Anju; Madan, Jitender

    2016-05-01

    In the present investigation, non-aggregated cationic and unmodified nanoparticles (TT-C-NLPs4 and TT-NLPs1) were prepared of about 49.2 ± 6.8-nm and 40.8 ± 8.3-nm, respectively. In addition, spherical shape, crystalline architecture and cationic charge were also noticed. Furthermore, integrity and conformational stability of TT were maintained in both TT-C-NLPs4 and TT-NLPs1, as evidenced by symmetrical position of bands and superimposed spectra, respectively in SDS-PAGE and circular dichroism. Cellular uptake in RAW264.7 cells indicating the concentration-dependent internalisation of nanoparticles. Qualitatively, CLSM exhibited enhanced cellular uptake of non-aggregated TT-C-NLPs4 owing to interaction with negatively charged plasma membrane and clevaloe mediated/independent endocytosis. In last, in vivo immunisation with non-aggregated TT-C-NLPs4 elicited strong humoral (anti-TT IgG) and cellular (IFN-γ) immune responses at day 42, as compared to non-aggregated TT-NLPs1 and TT-Alum following booster immunisation at day 14 and 28. Thus, non-aggregated cationic lipid nanoparticles may be a potent immune-adjuvant for parenteral delivery of weak antigens.

  3. Proliferative signaling initiated in ACTH receptors

    Directory of Open Access Journals (Sweden)

    C.F.P. Lotfi

    2000-10-01

    Full Text Available This article reviews recent results of studies aiming to elucidate modes of integrating signals initiated in ACTH receptors and FGF2 receptors, within the network system of signal transduction found in Y1 adrenocortical cells. These modes of signal integration should be central to the mechanisms underlying the regulation of the G0->G1->S transition in the adrenal cell cycle. FGF2 elicits a strong mitogenic response in G0/G1-arrested Y1 adrenocortical cells, that includes a rapid and transient activation of extracellular signal-regulated kinases-mitogen-activated protein kinases (ERK-MAPK (2 to 10 min, b transcription activation of c-fos, c-jun and c-myc genes (10 to 30 min, c induction of c-Fos and c-Myc proteins by 1 h and cyclin D1 protein by 5 h, and d onset of DNA synthesis stimulation within 8 h. ACTH, itself a weak mitogen, interacts with FGF2 in a complex manner, blocking the FGF2 mitogenic response during the early and middle G1 phase, keeping ERK-MAPK activation and c-Fos and cyclin D1 induction at maximal levels, but post-transcriptionally inhibiting c-Myc expression. c-Fos and c-Jun proteins are mediators in both the strong and the weak mitogenic responses respectively triggered by FGF2 and ACTH. Induction of c-Fos and stimulation of DNA synthesis by ACTH are independent of PKA and are inhibited by the PKC inhibitor GF109203X. In addition, ACTH is a poor activator of ERK-MAPK, but c-Fos induction and DNA synthesis stimulation by ACTH are strongly inhibited by the inhibitor of MEK1 PD98059.

  4. Proliferative glomerulonephritis and primary antiphospholipid syndrome

    International Nuclear Information System (INIS)

    Abdalla, H. Abdalla; Kfoury, Hala K.; Al-Khader, Abdulla A.; Al-Suleiman, M.

    2006-01-01

    Little is known regarding the association of primary antiphospholipid syndrome (APLS) and proliferative glomerulonephiritis (GN). We describe a biopsy-documented case with primary APLS and proliferative (GN) with no evidence of thrombotic microangiopathy (TMA), and in the absence of other manifestations of systematic lupus erythematosus (SLE). She presented initially with left popliteal deep venous thrombosis and nephrotic syndrome. Her first pregnancy at the age of 26 years resulted in the intra-uterine fetal death at term. Two subsequent pregnancies ended up with miscarriages at 3 and 4 months of gestation. Urinalysis revealed glomerular red blood cells of 1.0000.000/ml and granular cast; proteinuria of 13.4grams/24 hours, which was non-selective; hemoglobin 12 gm/dl, normal white blood cell and platelets; serum albumin 2.6gm/dl; anti-nuclear antibody (ANA) and anti DNA were negative and complement levels normal. Lupus anticoagulant was positive leading to a diagnosis of primary APLS. The biopsy findings were consistent with membranoproliferative GN. She continued to have steroid-resistant proteinuria, but stable renal function after a 12-year follow up period. She had 2 pregnancies during this period and was delivered at term using caesarian section. She received heparin during the pregnancies. Later she developed hypertension easily controlled by atenolol. This case provides evidence that primary APLS can be associated with proliferative GN due to immune deposits and not only TMA as previously reported, and in the complete absence of SLE. Performing more renal biopsies in this group of patients may disclose a greater prevalence of proleferative GN and may help in devising a rationale for treatment. (author)

  5. Proliferative retinopathy and proteinuria predict mortality rate in type 1 diabetic patients from Fyn County, Denmark.

    Science.gov (United States)

    Grauslund, J; Green, A; Sjølie, A K

    2008-04-01

    We evaluated the effect of diabetic retinopathy on 25 year survival rate among a population-based cohort of type 1 diabetic patients from Fyn County, Denmark. In 1973 all diabetic patients from Fyn County, Denmark with onset before the age of 30 years as of 1 July 1973 were identified (n=727). In 1981, only 627 patients were still alive and resident in Denmark. Of these, 573 (91%) participated in a clinical baseline examination, in which diabetic retinopathy was graded and other markers of diabetes measured. Mortality rate was examined in a 25 year follow-up and related to the baseline examination. Of the 573 patients examined at baseline in 1981 and 1982, 297 (51.8%) were still alive in November 2006. Of the others, 256 (44.7%) had died, three (0.5%) had left Denmark and 17 (3%) were of unknown status. Age- and sex-adjusted HRs of mortality rate were 1.01 (95% CI 0.72-1.42) and 2.04 (1.43-2.91) for patients with non-proliferative and proliferative retinopathy respectively at baseline compared with patients with no retinopathy. After adjusting for proteinuria, HR among patients with proliferative retinopathy lost statistical significance, but still remained 1.48 (95% CI 0.98-2.23). The 10 year survival rate of patients who had proliferative retinopathy as well as proteinuria at baseline was 22.2% and significantly lower (pretinopathy only (79.0%) or neither (86.6%). Proliferative retinopathy and proteinuria predict mortality rate in a population-based cohort of type 1 diabetic patients. In combination they act even more strongly. Non-proliferative diabetic retinopathy did not affect survival rate.

  6. Chronic toxic and carcinogenic effects of oral cadmium in the Noble (NBL/Cr) rat: induction of neoplastic and proliferative lesions of the adrenal, kidney, prostate, and testes.

    Science.gov (United States)

    Waalkes, M P; Anver, M R; Diwan, B A

    1999-10-29

    Based on the occurrence of pulmonary cancers in exposed populations, cadmium is classified as a human carcinogen. More controversial target sites for cadmium in humans include the prostate and kidney, where some studies have shown a link between cadmium and cancer. In Wistar rats cadmium induces tumors in the ventral prostate. The relevance of such lesions to humans is debated since the rat ventral lobe, unlike the dorsolateral lobe, has no embryological homolog in the human prostate. Cadmium has not been linked with renal tumors in rodents but is a potent nephrotoxin. In this work we studied the effects of oral cadmium in the Noble (NBL/Cr) rat with particular attention to proliferative lesions of the prostate and kidneys. Cadmium (as CdCl2) was given ad libitum throughout the study in the drinking water at doses of 0, 25, 50, 100, and 200 ppm Cd to groups (initial n = 30) of male rats, which were observed for up to 102 wk. At the lower doses of cadmium (cadmium exposure and most frequently showed three or more foci within each specimen. At higher doses, prostatic proliferative lesions declined to control levels. The loss of prostatic response at the higher doses was likely due to diminished testicular function secondary to cadmium treatment. This was reflected in lesions indicative of testicular hypofunction at the highest cadmium dose, namely, interstitial cell hyperplasia, and a strong correlation between cadmium dose and total proliferative lesions of the testes (hyperplasias and tumors combined). Renal tumors (mainly mesenchymal and pelvic transitional cell), although few in number, showed a positive correlation with cadmium dose, as did pelvic transitional epithelial hyperplasia. Renal lesions were not associated with any cadmium-induced changes in age-related chronic nephropathy. The incidence of pheochromocytomas of the adrenal was increased by cadmium but only at the 50 ppm dose. Inflammatory lesions of the liver and spleen were common at higher doses and

  7. Inheritance of proliferative breast disease in breast cancer kindreds

    International Nuclear Information System (INIS)

    Skolnick, M.H.; Cannon-Albright, L.A.; Goldgar, D.E.; Ward, J.H.; Marshall, C.J.; Schumann, G.B.; Hogle, H.; McWhorter, W.P.; Wright, E.C.; Tran, T.D.; Bishop, D.T.; Kushner, J.P.; Eyre, H.J.

    1990-01-01

    Previous studies have emphasized that genetic susceptibility to breast cancer is rare and is expressed primarily as premenopausal breast cancer, bilateral breast cancer, or both. Proliferative breast disease (PBD) is a significant risk factor for the development of breast cancer and appears to be a precursor lesion. PBD and breast cancer were studied in 103 women from 20 kindreds that were selected for the presence of two first degree relatives with breast cancer and in 31 control women. Physical examination, screening mammography, and four-quadrant fine-needle breast aspirates were performed. Cytologic analysis of breast aspirates revealed PBD in 35% of clinically normal female first degree relatives of breast cancer cases and in 13% of controls. Genetic analysis suggests that genetic susceptibility causes both PBD and breast cancer in these kindreds. This study supports the hypothesis that this susceptibility is responsible for a considerable portion of breast cancer, including unilateral and postmenopausal breast cancer

  8. Proliferative verrucous leukoplakia of the gingiva.

    Science.gov (United States)

    Fettig, A; Pogrel, M A; Silverman, S; Bramanti, T E; Da Costa, M; Regezi, J A

    2000-12-01

    The purpose of this study was to describe the clinical-pathologic features of what appears to be a gingival form of proliferative verrucous leukoplakia. Ten adult patients with recurrent and histologically progressive gingival leukoplakias who were diagnosed and treated at the University of California, San Francisco between 1994 and 1999, comprised the subject group for this investigation. Clinical and microscopic features were reviewed. Proliferation indices and p53 expression were evaluated immunohistochemically, and the presence of human papillomavirus (HPV) DNA was determined by using polymerase chain reaction (PCR) amplification. Lesions presented as solitary or regional flat/papillary/verrucal leukoplakias of the free and attached gingiva (tooth-bearing areas only). With time, flat lesions developed a papillary or verruciform profile. Although lesions were recurrent, they were confined to the gingiva, and multiple lesions did not develop. Half the patients used tobacco, and HPV could not be detected by using PCR. Microscopically, 6 cases began as hyperkeratotic lesions, and 4 initially exhibited a psoriasiform pattern with a marked inflammatory component. With recurrences, the lesions became progressively atypical histologically. The proliferation indices for these lesions showed modest increases over normal epithelium, and positive p53 staining was evident in 4 of 10 cases, indicating a disruption of the keratinocyte cell cycle in these lesions. The mechanism associated with the positive p53 staining (protein binding to wild type p53 versus mutation of the p53 gene) was not determined. Lesions recurred after conservative scalpel or laser excision, and many developed into verrucous or squamous cell carcinoma. Proliferative verrucous leukoplakia of the gingiva (PVLG) appears to be a subset of oral proliferative verrucous leukoplakia. It can be characterized as a solitary, recurring, progressive white patch that develops a verruciform architecture and may not

  9. Body linear traits for identifying prolific goats

    Directory of Open Access Journals (Sweden)

    Avijit Haldar

    2014-12-01

    Full Text Available Aim: The present study was conducted on prolific goat breed to identify body linear type traits that might be associated with prolificacy trait in goats. Materials and Methods: Two-stage stratified random sample survey based data were collected from 1427 non-pregnant goats with the history of single, twin and triplet litter sizes (LZ between January 2008 to February 2011 for 3 years in 68 villages located in East and North East India. Data on sixteen body linear traits were analyzed using logistic regression model to do the step-wise selection for identifying the body linear traits that could determine LZ. An average value for each identified body linear trait was determined for classifying the goats into three categories: Goats having the history of single LZ, goats having the history of twin LZ and goats having the history of triplet LZ. Results: The LZ proportions for single, twin and triplet, were 29.50, 59.14 and 11.36%, respectively, with the prolificacy rate of 181.85% in Indian Black Bengal goats. A total of eight body linear traits that could determine LZ in prolific goats were identified. Heart girth (HG measurement (>60.90 cm, paunch girth (PG (>70.22 cm, wither height (WH (>49.75 cm, neck length (>21.45 cm, ear length (>12.80 cm and distance between trochanter major (DTM bones (>12.28 cm, pelvic triangle area (PTA (>572.25 cm2 and clearance at udder (CU (>23.16 cm showed an increase likelihood of multiple LZ when compared to single LZ. Further, HG measurement (>62.29 cm, WH (>50.54 cm, PG (>71.85 cm and ear length (>13.00 cm, neck length (>22.01 cm, PTA (>589.64 cm2, CU (>23.20 cm and DTM bones (>12.47 cm were associated with increased likelihood of triplet LZ, when compared with that of twin LZ. Conclusion: HG measurement was the best discriminating factor, while PG, neck length, DTM bones, CU, PTA, WH and ear length measurements were other important factors that could be used for identifying prolific goats to achieve economic

  10. Strong concordance between transcriptomic patterns of spleen and peripheral blood leukocytes in response to avian pathogenic Escherichia coli infection.

    Science.gov (United States)

    Sandford, Erin E; Orr, Megan; Li, Xianyao; Zhou, Huaijun; Johnson, Timothy J; Kariyawasam, Subhashinie; Liu, Peng; Nolan, Lisa K; Lamont, Susan J

    2012-12-01

    Avian pathogenic Escherichia coli (APEC) causes morbidity in chickens and exhibits zoonotic potential. Understanding host transcriptional responses to infection aids the understanding of protective mechanisms and serves to inform future colibacillosis control strategies. Transcriptomes of spleen and peripheral blood leukocytes (PBLs) of the same individual birds in response to APEC infection were compared to identify common response patterns and connecting pathways. More than 100 genes in three contrasts examining pathology and infection status were significantly differentially expressed in both tissues and similarly regulated. Tissue-specific differences in catalytic activity, however, appear between birds with mild and severe pathology responses. Early expression differences, between birds with severe pathology and uninfected controls, in the mitogen-activated protein kinase pathway in PBLs precede spleen responses in the p53 and cytokine-cytokine receptor pathways. Tissue bianalysis is useful in identifying genes and pathways important to the response to APEC, whose role might otherwise be underestimated in importance.

  11. Strong congruence in tree and fern community turnover in response to soils and climate in central Panama

    DEFF Research Database (Denmark)

    Jones, Mirkka; Ferrier, Simon; Condit, Richard

    2013-01-01

    and seasonality undoubtedly limit plant distributions in this region, soil effects are at least as important, and interactions between the two are sizeable. This is likely to hold elsewhere in the Caribbean region, where mosaics of marine and volcanic soils combined with pronounced rainfall gradients are common......1. Plant species turnover in central Panamanian forests has been principally attributed to the effects of dispersal limitation and a strong Caribbean to Pacific gradient in rainfall seasonality. Despite marked geological heterogeneity, the role of soil variation has not been rigorously examined. 2....... We modelled the compositional turnover of trees and ferns in the Panama Canal watershed as a function of soil chemistry, climate and geographical separation, using generalized dissimilarity models (GDMs). 3. Predictability in both plant groups was strong, with 74% of turnover explained in trees...

  12. An Evaluation of the Brief Symptom Inventory-18 Using Item Response Theory: Which Items Are Most Strongly Related to Psychological Distress?

    Science.gov (United States)

    Meijer, Rob R.; de Vries, Rivka M.; van Bruggen, Vincent

    2011-01-01

    The psychometric structure of the Brief Symptom Inventory-18 (BSI-18; Derogatis, 2001) was investigated using Mokken scaling and parametric item response theory. Data of 487 outpatients, 266 students, and 207 prisoners were analyzed. Results of the Mokken analysis indicated that the BSI-18 formed a strong Mokken scale for outpatients and…

  13. Proliferative verrucous leukoplakia: diagnosis, management and current advances

    Directory of Open Access Journals (Sweden)

    Diogo Lenzi Capella

    Full Text Available Abstract Introduction: Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with frequent recurrences. It is characterized by a high rate of oral squamous cell carcinoma and verrucou carcinoma transformations. Objective: To analyze the studies about Proliferative verrucous leukoplakia and develop a concise update. Methods: A Pubmed search identifying studies (laboratory research, case series and reviews of literature that examined patients with Proliferative verrucous leukoplakia was realized. Results: There are not enough studies about Proliferative verrucous leukoplakia in the literature. The few found studies not present a consensus about its etiology and diagnosis criteria. Although several treatment strategies have been proposed, most of them still show a high recurrence rate. Conclusion: More research about Proliferative verrucous leukoplakia is necessary to understand and treat this disease.

  14. Proliferative verrucous leukoplakia: diagnosis, management and current advances.

    Science.gov (United States)

    Capella, Diogo Lenzi; Gonçalves, Jussara Maria; Abrantes, Adelino António Artur; Grando, Liliane Janete; Daniel, Filipe Ivan

    Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with frequent recurrences. It is characterized by a high rate of oral squamous cell carcinoma and verrucou carcinoma transformations. To analyze the studies about Proliferative verrucous leukoplakia and develop a concise update. A Pubmed search identifying studies (laboratory research, case series and reviews of literature) that examined patients with Proliferative verrucous leukoplakia was realized. There are not enough studies about Proliferative verrucous leukoplakia in the literature. The few found studies not present a consensus about its etiology and diagnosis criteria. Although several treatment strategies have been proposed, most of them still show a high recurrence rate. More research about Proliferative verrucous leukoplakia is necessary to understand and treat this disease. Copyright © 2017 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

  15. Woodchuck hepatitis virus core gene deletions and proliferative responses of peripheral blood mononuclear cells stimulated by an immunodominant epitope: a viral immune escape in the woodchuck model of chronic hepatitis B?

    Science.gov (United States)

    Taffon, Stefania; Kondili, Loreta A; Giuseppetti, Roberto; Ciccaglione, Anna Rita; Pulimanti, Barbara; Attili, Adolfo F; Rapicetta, Maria; D'Ugo, Emilio

    2015-04-01

    Marmota monax and its natural infection by woodchuck hepatitis virus (WHV) could be used as a predictive model for evaluating mechanisms of viral persistence during chronic hepatitis B virus (HBV) infection. The aim of this study was to investigate the presence of viral variants in the core gene of chronically WHV-infected woodchucks that showed two different patterns of peripheral blood mononuclear cells' (PBMCs') responses after stimulation with a specific WHV core peptide. Sequences' analysis of the WHV core region from eight WHV chronically infected woodchucks have been performed after in vitro stimulation with an immunodominant epitope of the WHV core protein (amino acids [aa] 96-110). Following this stimulation, positive PBMC responses at each point of follow-up were observed for four animals (group A), and weak immune responses at one or a few points of follow-up were observed for the remaining four animals (group B). The WHV core gene sequences contained amino acid deletions (aa 84-126, aa 84-113) in three of four group A animals and in none of group B animals. In the group A animals, the same deletions were observed in liver specimens and in two of four tumor specimens. Hepatocellular carcinoma (HCC) was diagnosed in all group A animals and in one group B animal. In conclusion, internal deletions in the core region correlated with a sustained PBMC response to the immunogenic peptide (96-110) of the core protein. A possible role of this relationship in hepatocarcinogenesis could be hypothesized; however, this needs to be investigated in patients with chronic HBV infection. The evaluation of virus-specific T-cell responses and T-cell epitopes that are possibly related to the mechanisms of viral evasion should be further investigated in order to design combined antiviral and immune approaches to control chronic HBV infection.

  16. Idiotypes as immunogens: facing the challenge of inducing strong therapeutic immune responses against the variable region of immunoglobulins.

    Directory of Open Access Journals (Sweden)

    Alejandro eLopez-Requena

    2012-11-01

    Full Text Available Idiotype (Id-based immunotherapy has been exploited as cancer treatment option. Conceived as therapy for malignancies bearing idiotypic antigens, it has been also extended to solid tumours because of the capacity of anti-idiotypic antibodies to mimick Id-unrelated antigens. In both these two settings, efforts are being made to overcome the poor immune responsiveness often experienced when using self immunoglobulins as immunogens. Despite bearing a unique gene combination, and thus particular epitopes, it is normally difficult to stimulate the immune response against antibody variable regions. Different strategies are currently used to strengthen Id immunogenicity, such as concomitant use of immune-stimulating molecules, design of Id-containing immunogenic recombinant proteins, specific targeting of relevant immune cells and genetic immunization. This review focuses on the role of anti-Id vaccination in cancer management and on the current developments used to foster anti-idiotypic B- and T-cell responses.

  17. Idiotypes as immunogens: facing the challenge of inducing strong therapeutic immune responses against the variable region of immunoglobulins

    International Nuclear Information System (INIS)

    López-Requena, Alejandro; Burrone, Oscar R.; Cesco-Gaspere, Michela

    2012-01-01

    Idiotype (Id)-based immunotherapy has been exploited as cancer treatment option. Conceived as therapy for malignancies bearing idiotypic antigens, it has been also extended to solid tumors because of the capacity of anti-idiotypic antibodies to mimic Id-unrelated antigens. In both these two settings, efforts are being made to overcome the poor immune responsiveness often experienced when using self immunoglobulins as immunogens. Despite bearing a unique gene combination, and thus particular epitopes, it is normally difficult to stimulate the immune response against antibody variable regions. Different strategies are currently used to strengthen Id immunogenicity, such as concomitant use of immune-stimulating molecules, design of Id-containing immunogenic recombinant proteins, specific targeting of relevant immune cells, and genetic immunization. This review focuses on the role of anti-Id vaccination in cancer management and on the current developments used to foster anti-idiotypic B and T cell responses.

  18. Multiple mechanisms responsible for strong Congo-red-binding variants of Escherichia coli O157:H7 strains.

    Science.gov (United States)

    Chen, Chin-Yi; Nguyen, Ly-Huong T; Cottrell, Bryan J; Irwin, Peter L; Uhlich, Gaylen A

    2016-03-01

    High variability in the expression of csgD-dependent, biofilm-forming and adhesive properties is common among Shiga toxin-producing Escherichia coli. Although many strains of serotype O157:H7 form little biofilm, conversion to stronger biofilm phenotypes has been observed. In this study, we screened different strains of serotype O157:H7 for the emergence of strong Congo-red (CR) affinity/biofilm-forming properties and investigated the underlying genetic mechanisms. Two major mechanisms which conferred stronger biofilm phenotypes were identified: mutations (insertion, deletion, single nucleotide change) in rcsB region and stx-prophage excision from the mlrA site. Restoration of the native mlrA gene (due to prophage excision) resulted in strong biofilm properties to all variants. Whereas RcsB mutants showed weaker CR affinity and biofilm properties, it provided more possibilities for phenotypic presentations through heterogenic sequence mutations. Published by Oxford University Press on behalf of FEMS 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  19. Leptin: A proliferative factor for breast cancer?

    International Nuclear Information System (INIS)

    Caldefie-Chezet, F.; Damez, M.; Latour, M. de; Konska, G.; Mishellani, F.; Fusillier, C.; Guerry, M.; Penault-Llorca, F.; Guillot, J.; Vasson, M.-P.

    2005-01-01

    Mammary adipose tissue is an important source of paracrine mitogens and anti-mitogens, including insulin-like growth factor, transforming growth factors, and cytokines (especially, TNFα and IL-1β). Nevertheless, it is also an important source of the adipocytokine, leptin. Recently, leptin was reported to stimulate the proliferation of various cell types (pancreatic β cells, prostate, colorectal, lung, etc.) as a new growth factor. It was also shown to stimulate the proliferation of breast cancer cell lines. In this study, we conducted an immunohistochemical analysis of leptin expression in normal tissue and benign and malignant ductal breast cell, representing the different states of the invasion process. We determined for the first time that leptin is expressed both by ductal breast tumors and by benign lesions as atypical hyperplasia. This suggests that leptin may be taken up or synthesized by all modified ductal breast cells, and may prove a proliferative factor. Moreover, leptin is unexpressed by normal tissue in the healthy breast but is exhibited by the normal tissue in near vicinity of the malignant ductal breast lesions. We also postulated that leptin may be a prognostic or diagnostic factor for ductal breast cancer. These putative hypotheses require further study

  20. Coral community composition and reef development at the Similan Islands, Andaman Sea, in response to strong environmental variations

    KAUST Repository

    Schmidt, GM

    2012-06-07

    The Similan Islands, a Thai archipelago in the Andaman Sea located near the shelf break, are subjected to frequent (up to several events per hour) and abrupt changes in physico-chemical conditions, particularly during the dry season (NE monsoon, January through April) and to an intense monsoon season with strong surface wave action (May to October). The exposed west slopes of the islands feature more coral species, but lack a carbonate reef framework. By contrast, the sheltered east sides show a complex reef framework dominated by massive Porites. Our results suggest that the sudden changes in temperature, pH and nutrients (drops of up to 10°C and 0.6 U and increases of up to 9.4 µmol NOx l−1, respectively) due to pulsed upwelling events may rival the importance of surface waves and storms in shaping coral distribution and reef development.

  1. Human epidermal growth factor receptor 2-positive breast cancer: heat shock protein 90 overexpression, Ki67 proliferative index, and topoisomerase II-α co-amplification as predictors of pathologic complete response to neoadjuvant chemotherapy with trastuzumab and docetaxel.

    Science.gov (United States)

    Bria, Emilio; Furlanetto, Jenny; Carbognin, Luisa; Brunelli, Matteo; Caliolo, Chiara; Nortilli, Rolando; Massari, Francesco; Pedron, Serena; Manfrin, Erminia; Pellini, Francesca; Bonetti, Franco; Sperduti, Isabella; Pollini, Giovanni Paolo; Scarpa, Aldo; Tortora, Giampaolo

    2015-02-01

    The combination of trastuzumab and chemotherapy is currently considered the standard of care for patients with locally advanced/operable human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The potential correlation between the pathologic complete response (pCR) and the overexpression of heat shock protein 90 (Hsp90), Ki67, and the amplification of topoisomerase II-α (TOPO2A) was investigated in a series of patients who received neoadjuvant treatment. HER2-amplified patients who received neoadjuvant trastuzumab-docetaxel were gathered. Baseline and postsurgical Hsp90 immunoscore, Ki67 proliferation index, and TOPO2A amplification were determined together with classic clinical-pathologic predictors and correlated with pCR and imaging data. A total of 24 patients were evaluated for response; pCR, clinical, and radiologic response were found in 4 patients (16.7%; 95% confidence interval [CI], 1.7-31.5), 9 patients (37.5%; 95% CI, 18.1-56.8), and 6 patients (25.0%; 95% CI, 7.6-42.3) patients, respectively. pCR was significantly higher in premenopausal (60.0% vs. 5.3%, P = .02) and negative hormonal receptor patients (50.0% vs. 5.6%, P = .03). A trend for patients with high Ki67 and TOPO2A/HER2 co-amplification was found (21.1% vs. none, P = .54; 50.0% vs. 12%, P = .16). pCR was significantly higher in patients with Hsp90 score 3+, in comparison with score 2+ and score 1+ (50.0% vs. 14.3% vs. none, P = .05). After treatment, a statistically significant lower Ki67 staining (30.0% vs. 17.5%, P = .005) and a trend for the decreased expression of high (score 3+) and moderate (score 2+) Hsp90 immunostaining (McNemar P = .25, Wilcoxon-Mann-Whitney P = .08) were found. Although underpowered, our data suggest that patients with HER2-positive breast cancer overexpressing Hsp90 should be investigated as a "newer" molecular subtype with a significantly higher chance of pCR when receiving anti-Her2 agents. Copyright © 2015 Elsevier Inc. All rights

  2. T-type Ca2+channels elicit pro-proliferative and anti-apoptotic responses through impaired PP2A/Akt1 signaling in PASMCs from patients with pulmonary arterial hypertension.

    Science.gov (United States)

    Sankhe, Safietou; Manousakidi, Sevasti; Antigny, Fabrice; Arthur Ataam, Jennifer; Bentebbal, Sana; Ruchon, Yann; Lecerf, Florence; Sabourin, Jessica; Price, Laura; Fadel, Elie; Dorfmüller, Peter; Eddahibi, Saadia; Humbert, Marc; Perros, Frédéric; Capuano, Véronique

    2017-10-01

    Idiopathic pulmonary arterial hypertension (iPAH) is characterized by obstructive hyperproliferation and apoptosis resistance of distal pulmonary artery smooth muscle cells (PASMCs). T-type Ca 2+ channel blockers have been shown to reduce experimental pulmonary hypertension, although the impact of T-type channel inhibition remains unexplored in PASMCs from iPAH patients. Here we show that T-type channels Cav3.1 and Cav3.2 are present in the lung and PASMCs from iPAH patients and control subjects. The blockade of T-type channels by the specific blocker, TTA-A2, prevents cell cycle progression and PASMCs growth. In iPAH cells, T-type channel signaling fails to activate phosphatase PP2A, leading to an increase in ERK1/2, P38 activation. Moreover, T-type channel signaling is redirected towards the activation of the kinase Akt1, leading to increased expression of the anti-apoptotic protein survivin, and a decrease in the pro-apoptotic mediator FoxO3A. Finally, in iPAH cells, Akt1 is no longer able to regulate caspase 9 activation, whereas T-type channel overexpression reverses PP2A defect in iPAH cells but reinforces the deleterious effects of Akt1 activation. Altogether, these data highlight T-type channel signaling as a strong trigger of the pathological phenotype of PASMCs from iPAH patients (hyper-proliferation/cells survival and apoptosis resistance), suggesting that both T-type channels and PP2A may be promising therapeutic targets for pulmonary hypertension. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Nonlocal response functions for predicting shear flow of strongly inhomogeneous fluids. II. Sinusoidally driven shear and multisinusoidal inhomogeneity.

    Science.gov (United States)

    Dalton, Benjamin A; Glavatskiy, Kirill S; Daivis, Peter J; Todd, B D

    2015-07-01

    We use molecular-dynamics computer simulations to investigate the density, strain-rate, and shear-pressure responses of a simple model atomic fluid to transverse and longitudinal external forces. We have previously introduced a response function formalism for describing the density, strain-rate, and shear-pressure profiles in an atomic fluid when it is perturbed by a combination of longitudinal and transverse external forces that are independent of time and have a simple sinusoidal spatial variation. In this paper, we extend the application of the previously introduced formalism to consider the case of a longitudinal force composed of multiple sinusoidal components in combination with a single-component sinusoidal transverse force. We find that additional harmonics are excited in the density, strain-rate, and shear-pressure profiles due to couplings between the force components. By analyzing the density, strain-rate, and shear-pressure profiles in Fourier space, we are able to evaluate the Fourier coefficients of the response functions, which now have additional components describing the coupling relationships. Having evaluated the Fourier coefficients of the response functions, we are then able to accurately predict the density, velocity, and shear-pressure profiles for fluids that are under the influence of a longitudinal force composed of two or three sinusoidal components combined with a single-component sinusoidal transverse force. We also find that in the case of a multisinusoidal longitudinal force, it is sufficient to include only pairwise couplings between different longitudinal force components. This means that it is unnecessary to include couplings between three or more force components in the case of a longitudinal force composed of many Fourier components, and this paves the way for a highly accurate but tractable treatment of nonlocal transport phenomena in fluids with density and strain-rate inhomogeneities on the molecular length scale.

  4. Proliferative and inflammatory factors in the vitreous of patients with proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    V V Chernykh

    2015-01-01

    Full Text Available Purpose: The purpose was to measure the concentrations of various cytokines and growth factors (including vascular endothelial growth factor [VEGF] and pigment epithelium-derived factor [PEDF] in the vitreous of patients with proliferative diabetic retinopathy (PDR and to investigate interaction between inflammatory and proliferative factors in the genesis of PDR. Materials and Methods : Vitreous samples from 32 eyes with PDR and 25 eyes without diabetes mellitus and signs of DR (control were collected. Vitreous concentrations of VEGF, PEDF, monocyte chemotactic protein-1 (MCP-1, interleukin-4 (IL-4, IL-6, IL-8, IL-10, IL-17A, and secretory immunoglobulin A (sIgA were simultaneously measured using enzyme-linked immunoassay. Results : Vitreous levels of VEGF, PEDF, IL-17A, IL-6, IL-8, IL-4, and sIgA were significantly (Π < 0.05 higher in eyes with PDR compared to control. The concentration of VEGF was more than 17-times higher than in control, and the concentration of PEDF was not changed oppositely and was also higher (1.45-times compared to control, that may indicate disturbances of compensatory mechanisms in angiogenesis regulation in PDR. Significant (Π < 0.05 positive correlations were observed between vitreous concentrations of VEGF and IL-17ΐ (r = 0.45, VEGF and IL-8 (r = 0.48, VEGF and IL-4 (r = 0.51, PEDF and IL-17ΐ (r = 0.48, PEDF and IL-8 (r = 0.59, MCP-1 and PEDF (r = 0.72, MCP-1 and IL-8 (r0 = 0.45, IL-4 and IL-17ΐ (r = 0.65, IL-4 and IL-8 (r = 0.71, IL-8 and IL-17ΐ (r = 0.59. Conclusions: Significantly raised levels of inflammatory and proliferative factors and numerous positive correlations between them may demonstrate a significant role of activation of vascular proliferation and local inflammation in the pathogenesis of PDR.

  5. Antioxidant activity, anti-proliferative activity, and amino acid profiles of ethanolic extracts of edible mushrooms.

    Science.gov (United States)

    Panthong, S; Boonsathorn, N; Chuchawankul, S

    2016-10-17

    Biological activities of various mushrooms have recently been discovered, particularly, immunomodulatory and antitumor activities. Herein, three edible mushrooms, Auricularia auricula-judae (AA), Pleurotus abalonus (PA) and Pleurotus sajor-caju (PS) extracted using Soxhlet ethanol extraction were evaluated for their antioxidative, anti-proliferative effects on leukemia cells. Using the Folin-Ciocalteau method and Trolox equivalent antioxidant capacity assay, phenolics and antioxidant activity were found in all sample mushrooms. Additionally, anti-proliferative activity of mushroom extracts against U937 leukemia cells was determined using a viability assay based on mitochondrial activity. PA (0.5 mg/mL) and AA (0.25-0.5 mg/mL) significantly reduced cell viability. Interestingly, PS caused a hormetic-like biphasic dose-response. Low doses (0-0.25 mg/L) of PS promoted cell proliferation up to 140% relative to control, whereas higher doses (0.50 mg/mL) inhibited cell proliferation. Against U937 cells, AA IC 50 was 0.28 ± 0.04 mg/mL, which was lower than PS or PA IC 50 (0.45 ± 0.01 and 0.49 ± 0.001 mg/mL, respectively). Furthermore, lactate dehydrogenase (LDH) leakage conferred cytotoxicity. PS and PA were not toxic to U937 cells at any tested concentration; AA (0.50 mg/mL) showed high LDH levels and caused 50% cytotoxicity. Additionally, UPLC-HRMS data indicated several phytochemicals known to support functional activities as either antioxidant or anti-proliferative. Glutamic acid was uniquely found in ethanolic extracts of AA, and was considered an anti-cancer amino acid with potent anti-proliferative effects on U937 cells. Collectively, all mushroom extracts exhibited antioxidant effects, but their anti-proliferative effects were dose-dependent. Nevertheless, the AA extract, with highest potency, is a promising candidate for future applications.

  6. Strong vaccine-induced CD8 T-cell responses have cytolytic function in a chimpanzee clearing HCV infection.

    Directory of Open Access Journals (Sweden)

    Babs E Verstrepen

    Full Text Available A single correlate of effective vaccine protection against chronic HCV infection has yet to be defined. In this study, we analyzed T-cell responses in four chimpanzees, immunized with core-E1-E2-NS3 and subsequently infected with HCV1b. Viral clearance was observed in one animal, while the other three became chronically infected. In the animal that cleared infection, NS3-specific CD8 T-cell responses were observed to be more potent in terms of frequency and polyfunctionality of cytokine producing cells. Unique to this animal was the presence of killing-competent CD8 T-cells, specific for NS3 1258-1272, being presented by the chimpanzee MHC class I molecule Patr-A*03∶01, and a high affinity recognition of this epitope. In the animals that became chronically infected, T-cells were able to produce cytokines against the same peptide but no cytolysis could be detected. In conclusion, in the animal that was able to clear HCV infection not only cytokine production was observed but also cytolytic potential against specific MHC class I/peptide-combinations.

  7. A multi-subunit Chlamydia vaccine inducing neutralizing antibodies and strong IFN-γ(+) CMI responses protects against a genital infection in minipigs

    DEFF Research Database (Denmark)

    Bøje, Sarah; Olsen, Anja Weinreich; Erneholm, Karin

    2016-01-01

    Chlamydia is the most widespread sexually transmitted bacterial disease and a prophylactic vaccine is highly needed. Ideally, this vaccine is required to induce a combined response of Th1 cell-mediated immune (CMI) response in concert with neutralizing antibodies. Using a novel Göttingen minipig...... animal model, we evaluated the immunogenicity and efficacy of a multi-subunit vaccine formulated in the strong Th1-inducing adjuvant CAF01. We evaluated a mixture of two fusion proteins (Hirep1 and CTH93) designed to promote either neutralizing antibodies or cell-mediated immunity, respectively. Hirep1...

  8. Coherent response of a two-level atom to a signal field with account of suppression of phase relaxation by a strong field

    International Nuclear Information System (INIS)

    Grishanin, B.A.; Shatalova, G.G.

    1984-01-01

    Calculation is made of a coherent part of response to a weak test field of an atom located in a strong resonance field. The latter bads to a suppression of phase relaxation. This response is shown to appear both at a test field freq uency ω and at a combination frequency 2ωsub(l)-ω, where ωsub(l) is a resona nce field frequency. The spectrum of test field absorption by such a system has a symmetric form and consist of two parts, one of which corresponds to a test f ield absorption and another - to its amplification

  9. Steel Moment-Resisting Frame Responses in Simulated Strong Ground Motions: or How I Learned to Stop Worrying and Love the Big One

    OpenAIRE

    Olsen, Anna

    2008-01-01

    This thesis studies the response of steel moment-resisting frame buildings in simulated strong ground motions. I collect 37 simulations of crustal earthquakes in California. These ground motions are applied to nonlinear finite element models of four types of steel moment frame buildings: six- or twenty-stories with either a stiffer, higherstrength design or a more flexible, lower-strength design. I also consider the presence of fracture-prone welds in each design. Since these b...

  10. A rare case of transition to membranous lupus nephritis from diffuse proliferative lupus nephritis

    OpenAIRE

    Nishi, Hitomi; Sugimoto, Keisuke; Fujita, Shinsuke; Miyazawa, Tomoki; Enya, Takuji; Izu, Akane; Wada, Norihisa; Okada, Mitsuru; Takemura, Tsukasa

    2014-01-01

    [Abstract] Lupus nephritis is an important complication of systemic lupus erythematosus (SLE) that affects the prognosis. A rare type of lupus nephritis, class V, shows histological findings resembling those of membranous nephropathy. While most diffuse proliferative lupus nephritis is associated with other SLE disease activity, class V lupus nephritis can occur without systemic activity. Furthermore, Class V is less responsive to steroid therapy than other forms of lupus nephritis. We treate...

  11. MUC1-specific immune therapy generates a strong anti-tumor response in a MUC1-tolerant colon cancer model.

    Science.gov (United States)

    Mukherjee, P; Pathangey, L B; Bradley, J B; Tinder, T L; Basu, G D; Akporiaye, E T; Gendler, S J

    2007-02-19

    A MUC1-based vaccine was used in a preclinical model of colon cancer. The trial was conducted in a MUC1-tolerant immune competent host injected with MC38 colon cancer cells expressing MUC1. The vaccine included: MHC class I-restricted MUC1 peptides, MHC class II-restricted pan-helper-peptide, unmethylated CpG oligodeoxynucleotide, and granulocyte macrophage-colony stimulating factor. Immunization was successful in breaking MUC1 self-tolerance, and in eliciting a robust anti-tumor response. The vaccine stimulated IFN-gamma-producing CD4(+) helper and CD8(+) cytotoxic T cells against MUC1 and other undefined MC38 tumor antigens. In the prophylactic setting, immunization caused complete rejection of tumor cells, while in the therapeutic regimen, tumor burden was significantly reduced.

  12. Formation of antibodies against infliximab and adalimumab strongly correlates with functional drug levels and clinical responses in rheumatoid arthritis

    DEFF Research Database (Denmark)

    Radstake, T R D J; Svenson, M; Eijsbouts, A M

    2008-01-01

    BACKGROUND: Tumour necrosis factor alpha (TNFalpha) neutralising antibody constructs are increasingly being used to treat rheumatoid arthritis (RA). OBJECTIVE: To determine potential differences in clinical responses, soluble drug levels and antibody formation between patients with RA receiving...... infliximab and adalimumab. METHODS: 69 patients with RA fulfilling the 1987 American College of Rheumatology criteria and about to start treatment with infliximab or adalimumab, were enrolled consecutively. All patients had active disease (28-joint count Disease Activity Score >3.2). Infliximab was given...... intravenously at 3 mg/kg at baseline and after 2, 6 and 14 weeks. Adalimumab was administered as 40 mg biweekly subcutaneously. Concomitant drug treatment was monitored and continued at constant dosage during the study. All serum samples were tested for infliximab/adalimumab levels and anti...

  13. Strong type 1, but impaired type 2, immune responses contribute to Orientia tsutsugamushi-induced pathology in mice.

    Directory of Open Access Journals (Sweden)

    Lynn Soong

    2014-09-01

    Full Text Available Scrub typhus is a neglected, but important, tropical disease, which puts one-third of the world's population at risk. The disease is caused by Orientia tsutsugamushi, an obligately intracellular Gram-negative bacterium. Dysregulation in immune responses is known to contribute to disease pathogenesis; however, the nature and molecular basis of immune alterations are poorly defined. This study made use of a newly developed murine model of severe scrub typhus and focused on innate regulators and vascular growth factors in O. tsutsugamushi-infected liver, lungs and spleen. We found no activation or even reduction in base-line expression for multiple molecules (IL-7, IL-4, IL-13, GATA3, ROR-γt, and CXCL12 at 2, 6 and 10 days post-infection. This selective impairment in type 2-related immune responses correlated with a significant activation of the genes for IL-1β, IL-6, IL-10, TNF-α, IFN-γ, as well as CXCR3- and CXCR1-related chemokines in inflamed tissues. The elevated angiopoietin (Ang-2 expression and Ang-2/Ang-1 ratios suggested excessive inflammation and the loss of endothelial integrity. These alterations, together with extensive recruitment of myeloperoxidase (MPO-expressing neutrophils and the influx of CD3+ T cells, contributed to acute tissue damage and animal death. This is the first report of selective alterations in a panel of immune regulators during early O. tsutsugamushi infection in intravenously inoculated C57BL/6 mice. Our findings shed new light on the pathogenic mechanisms associated with severe scrub typhus and suggest potential targets for therapeutic investigation.

  14. Two tropical conifers show strong growth and water-use efficiency responses to altered CO2 concentration.

    Science.gov (United States)

    Dalling, James W; Cernusak, Lucas A; Winter, Klaus; Aranda, Jorge; Garcia, Milton; Virgo, Aurelio; Cheesman, Alexander W; Baresch, Andres; Jaramillo, Carlos; Turner, Benjamin L

    2016-11-01

    Conifers dominated wet lowland tropical forests 100 million years ago (MYA). With a few exceptions in the Podocarpaceae and Araucariaceae, conifers are now absent from this biome. This shift to angiosperm dominance also coincided with a large decline in atmospheric CO 2 concentration (c a ). We compared growth and physiological performance of two lowland tropical angiosperms and conifers at c a levels representing pre-industrial (280 ppm), ambient (400 ppm) and Eocene (800 ppm) conditions to explore how differences in c a affect the growth and water-use efficiency (WUE) of seedlings from these groups. Two conifers (Araucaria heterophylla and Podocarpus guatemalensis) and two angiosperm trees (Tabebuia rosea and Chrysophyllum cainito) were grown in climate-controlled glasshouses in Panama. Growth, photosynthetic rates, nutrient uptake, and nutrient use and water-use efficiencies were measured. Podocarpus seedlings showed a stronger (66 %) increase in relative growth rate with increasing c a relative to Araucaria (19 %) and the angiosperms (no growth enhancement). The response of Podocarpus is consistent with expectations for species with conservative growth traits and low mesophyll diffusion conductance. While previous work has shown limited stomatal response of conifers to c a , we found that the two conifers had significantly greater increases in leaf and whole-plant WUE than the angiosperms, reflecting increased photosynthetic rate and reduced stomatal conductance. Foliar nitrogen isotope ratios (δ 15 N) and soil nitrate concentrations indicated a preference in Podocarpus for ammonium over nitrate, which may impact nitrogen uptake relative to nitrate assimilators under high c a SIGNIFICANCE: Podocarps colonized tropical forests after angiosperms achieved dominance and are now restricted to infertile soils. Although limited to a single species, our data suggest that higher c a may have been favourable for podocarp colonization of tropical South America 60

  15. Proliferative verrucous leukoplakia: diagnosis, management and current advances

    OpenAIRE

    Capella, Diogo Lenzi; Gonçalves, Jussara Maria; Abrantes, Adelino António Artur; Grando, Liliane Janete; Daniel, Filipe Ivan

    2017-01-01

    Abstract Introduction: Proliferative verrucous leukoplakia is a multifocal and progressive lesion of the oral mucosa, with unknown etiology, and commonly resistant to all therapy attempts with frequent recurrences. It is characterized by a high rate of oral squamous cell carcinoma and verrucou carcinoma transformations. Objective: To analyze the studies about Proliferative verrucous leukoplakia and develop a concise update. Methods: A Pubmed search identifying studies (laboratory research,...

  16. Bilateral proliferative retinopathy in B-cell acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Devesh Kumawat

    2018-01-01

    Full Text Available A 4-year-old child with B-cell acute lymphoblastic leukemia presented with vitreous hemorrhage due to proliferative retinopathy in both eyes. Pars plana vitrectomy was performed in both eyes to clear nonresolving vitreous hemorrhage after systemic stabilization. Visual recovery was limited by the disc drag in the right eye and subfoveal exudation in the left eye. Etiopathogenesis and management of proliferative retinopathy in acute leukemias are discussed.

  17. A Strong Immune Response in Young Adult Honeybees Masks Their Increased Susceptibility to Infection Compared to Older Bees

    Science.gov (United States)

    Bull, James C.; Ryabov, Eugene V.; Prince, Gill; Mead, Andrew; Zhang, Cunjin; Baxter, Laura A.; Pell, Judith K.; Osborne, Juliet L.; Chandler, Dave

    2012-01-01

    Honeybees, Apis mellifera, show age-related division of labor in which young adults perform maintenance (“housekeeping”) tasks inside the colony before switching to outside foraging at approximately 23 days old. Disease resistance is an important feature of honeybee biology, but little is known about the interaction of pathogens and age-related division of labor. We tested a hypothesis that older forager bees and younger “house” bees differ in susceptibility to infection. We coupled an infection bioassay with a functional analysis of gene expression in individual bees using a whole genome microarray. Forager bees treated with the entomopathogenic fungus Metarhizium anisopliae s.l. survived for significantly longer than house bees. This was concomitant with substantial differences in gene expression including genes associated with immune function. In house bees, infection was associated with differential expression of 35 candidate immune genes contrasted with differential expression of only two candidate immune genes in forager bees. For control bees (i.e. not treated with M. anisopliae) the development from the house to the forager stage was associated with differential expression of 49 candidate immune genes, including up-regulation of the antimicrobial peptide gene abaecin, plus major components of the Toll pathway, serine proteases, and serpins. We infer that reduced pathogen susceptibility in forager bees was associated with age-related activation of specific immune system pathways. Our findings contrast with the view that the immunocompetence in social insects declines with the onset of foraging as a result of a trade-off in the allocation of resources for foraging. The up-regulation of immune-related genes in young adult bees in response to M. anisopliae infection was an indicator of disease susceptibility; this also challenges previous research in social insects, in which an elevated immune status has been used as a marker of increased disease

  18. Modification of heparanase gene expression in response to conditioning and LPS treatment: strong correlation to rs4693608 SNP.

    Science.gov (United States)

    Ostrovsky, Olga; Shimoni, Avichai; Baryakh, Polina; Morgulis, Yan; Mayorov, Margarita; Beider, Katia; Shteingauz, Anna; Ilan, Neta; Vlodavsky, Israel; Nagler, Arnon

    2014-04-01

    Heparanase is an endo-β-glucuronidase that specifically cleaves the saccharide chains of HSPGs, important structural and functional components of the ECM. Cleavage of HS leads to loss of the structural integrity of the ECM and release of HS-bound cytokines, chemokines, and bioactive angiogenic- and growth-promoting factors. Our previous study revealed a highly significant correlation of HPSE gene SNPs rs4693608 and rs4364254 and their combination with the risk of developing GVHD. We now demonstrate that HPSE is up-regulated in response to pretransplantation conditioning, followed by a gradual decrease thereafter. Expression of heparanase correlated with the rs4693608 HPSE SNP before and after conditioning. Moreover, a positive correlation was found between recipient and donor rs4693608 SNP discrepancy and the time of neutrophil and platelet recovery. Similarly, the discrepancy in rs4693608 HPSE SNP between recipients and donors was found to be a more significant factor for the risk of aGVHD than patient genotype. The rs4693608 SNP also affected HPSE gene expression in LPS-treated MNCs from PB and CB. Possessors of the AA genotype exhibited up-regulation of heparanase with a high ratio in the LPS-treated MNCs, whereas individuals with genotype GG showed down-regulation or no effect on HPSE gene expression. HPSE up-regulation was mediated by TLR4. The study emphasizes the importance of rs4693608 SNP for HPSE gene expression in activated MNCs, indicating a role in allogeneic stem cell transplantation, including postconditioning, engraftment, and GVHD.

  19. Benign Proliferative Breast Lesions and Risk of Cancer

    Directory of Open Access Journals (Sweden)

    Serap Erel

    2010-06-01

    Full Text Available Benign breast lesions (BBL includes a wide variety of histologic entities, which have been broadly classified into non-proliferative lesions, proliferative lesions without atypia, and hyperplasia with atypia. With the increased use of mammography, more benign lesions are being detected, and in order to estimate the risk of breast cancer for specific histologic categories is of great importance to guide clinical management. Women with proliferative lesions without atypia are at slightly increased risk of subsequent breast cancer, whereas women with proliferative lesions with atypia have a higher risk. The risk is 1.5- 2-fold in women with proliferative lesions without atypia, 4-5-fold in women with proliferative lesions with atypia, and 8-10 fold in women with ductal carcinoma in situ. Age at diagnosis of BBL, menopausal status, family history of breast cancer in a first-degree relative, and time since BBL diagnosis on risk of breast cancer are important for risk evaluation. [Archives Medical Review Journal 2010; 19(3.000: 155-167

  20. NLRP3 inflammasome activation is associated with proliferative diabetic retinopathy.

    Science.gov (United States)

    Loukovaara, Sirpa; Piippo, Niina; Kinnunen, Kati; Hytti, Maria; Kaarniranta, Kai; Kauppinen, Anu

    2017-12-01

    Innate immunity and dysregulation of inflammatory processes play a role in vascular diseases like atherosclerosis or diabetes. Nucleotide-binding domain and Leucine-rich repeat Receptor containing a Pyrin domain 3 (NLRP3) inflammasomes are pro-inflammatory signalling complexes that were found in 2002. In addition to pathogens and other extracellular threats, they can be activated by various endogenous danger signals. The purpose of this study was to find out whether NLRP3 activation occurs in patients with sight-threatening forms of diabetic retinopathy (DR). Inflammasome components NLRP3 and caspase-1, inflammasome-related pro-inflammatory cytokines IL-1β and IL-18, vascular endothelial growth factor (VEGF), acute-phase cytokines TNF-α and IL-6, as well as adaptive immunity-related cytokine interferon gamma (IFN-γ) were measured from the vitreous samples of 15 non-proliferative diabetic retinopathy (non-PDR) and 23 proliferative diabetic retinopathy (PDR) patients using the enzyme-linked immunosorbent assay (ELISA) method. The adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC) was determined using the Western blot technique. Inflammasome components were present in the vitreous of DR patients. Along with VEGF, the levels of caspase-1 and IL-18 were significantly increased, especially in PDR eyes. Interestingly, clearly higher levels of NLRP3 were found in the PDR eyes with tractional retinal detachment (TRD) than from PDR eyes with fully attached retina. There were no significant differences in the amounts of IL-1β, TNF-α, IL-6, and IFN-γ that were detectable in the vitreous of both non-PDR and PDR patients. Our results suggest that NLRP3 inflammasome activation can be associated especially with the pathogenesis of PDR. The lack of differences in TNF-α, IL-6, and IFN-γ also alludes that acute inflammation or T-cell-mediated responses do not dominate in PDR pathogenesis. © 2017 Acta Ophthalmologica Scandinavica Foundation

  1. Health assessment of environmental pollutants: proliferative and degenerative diseases

    International Nuclear Information System (INIS)

    Stuart, B.O.

    1988-01-01

    In order to achieve a balanced approach to risk assessment between carcinogenic and non-carcinogenic health effects one must examine the risk of disease or death in the general population exposed to a particular air pollutant that can be related quantitatively to intensity and duration of exposures (National Academy of Sciences, 1983). Such risk assessment should be based upon careful evaluation of scientific findings of dose-response relationships in the chronically exposed population. Quantitative assessment of environmentally produced disease in man has proven to be complex and demanding. A variety of factors play important roles in this task. As an example, there are induction-latency periods for chronic diseases, including cancer, which may range from five to twenty-five years. The diseases themselves, whether proliferative or degenerative, may follow several stages of progression. There is only sparse epidemiological data on serious health effects that may be due to environmental as compared to occupational exposures. Exposures to chemical or radiological air contaminants do not occur singly but to a multiplicity of agents, and disease processes are frequently markedly affected by the interaction of a variety of factors, particularly that of cigarette smoking. There is growing recognition of potentially sensitive subpopulations, including the elderly and the very young, but adequate techniques for assessing the magnitude of increased risks to these groups have not yet been developed

  2. Glomerular Damage in Experimental Proliferative Glomerulonephritis Under Glomerular Capillary Hypertension

    Directory of Open Access Journals (Sweden)

    Pei-Rong Wang

    2015-03-01

    Full Text Available Background/Aims: Immunologically and hemodynamically mediated the destruction of glomerular architecture is thought to be the major causes of end-stage renal failure. The purpose of this study is to evaluate the effect of glomerular hypertension on glomerular injury and the progression of glomerular sclerosis after Thy-1 nephritis was induced. Method: Thy-1 nephritis was induced in the stroke-prone spontaneously hypertensive rat strain (SHR-SP (group SP and in age-matched Wistar-Kyoto (WKY (group WKY rats, following unilateral nephrectomy (UNX, and a vehicle was injected alone in UNX SHR-SP as control (group SC. Result: The degree of glomerular damage in response to a single dose of anti-thy-1 antibody, and its functional consequences (eg. proteinuria, diminished GFR are more pronounced in group SP than normotensive group WKY and hypertensive group SC without mesangial cell injury. While normotensive group WKY rats recovered completely from mesangial cell injury on day 28-42, glomeruli in group SP kept on persistent macrophage infiltration, α-SMA expression on day 42-56. In addition, glomerular capillary repair with the GECs was rarely seen in pronouncedly proliferative and sclerostic areas. The incidence of glomerular sclerosis and the level of proteinuria were markedly increased by day 56 in the group SP. Conclusions: Our results demonstrate that glomerular hypertension aggravate glomerular damage and glomerulosclerosis in this model of Thy 1 nephritis.

  3. Response of the pulmonary system to exercise in proliferative phase ...

    African Journals Online (AJOL)

    Background: The role of estrogen on pulmonary function test (PFT) was well known in the normal course of the menstrual cycle. Significant increase in both progesterone (37%) and estradiol (13.5%), whereas no change in plasma follicle stimulating hormone (FSH) & leutinizing hormone [LH] was observed in exercising ...

  4. Selective anti-proliferative activities of Carica papaya leaf juice extracts against prostate cancer.

    Science.gov (United States)

    Pandey, Saurabh; Walpole, Carina; Cabot, Peter J; Shaw, Paul N; Batra, Jyotsna; Hewavitharana, Amitha K

    2017-05-01

    Prostate cancer (PCa) is the leading cause of cancer related deaths in men. Carica papaya is a popular tropical plant that has been traditionally used for its nutritional and medicinal properties. We investigated the anti-proliferative responses of papaya leaf juice (LJP) and its various extracts ("biological"- in vitro digested, "physical"- size exclusion, and "chemical"-solvent extraction) on a range of cell lines representing benign hyperplasia, tumorigenic and normal cells of prostate origin. Time course analysis (by 24h, 48h and 72h) of LJP (1-0.1mg/mL) before and after in vitro digestion, and of molecular weight based fractions of LJP showed anti-proliferative responses. The medium polarity fraction of LJP (0.03-0.003mg/mL) after 72h exposure showed potent growth inhibitory (IC 50 =0.02-0.07mg/mL) and cytotoxic activities on all prostate cells, with the exception of the normal (RWPE-1 and WPMY-1) cells. Flow cytometry analysis showed S phase cell cycle arrest and apoptosis as a possible mechanism for these activities. Medium polar fraction of LJP also inhibited migration and adhesion of metastatic PC-3 cells. This is the first report suggesting selective anti-proliferative and anti-metastatic attributes of LJP extract against prostatic diseases, including PCa. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Vitreous vascular endothelial growth factor concentrations in proliferative diabetic retinopathy versus proliferative vitreoretinopathy.

    Science.gov (United States)

    Citirik, Mehmet; Kabatas, Emrah Utku; Batman, Cosar; Akin, Kadir Okhan; Kabatas, Naciye

    2012-01-01

    To assess vitreous vascular endothelial growth factor (VEGF) concentrations in proliferative diabetic retinopathy (PDR) in comparison to proliferative vitreoretinopathy (PVR). Vitreous samples were collected from 69 eyes of 69 patients with traumatic lens dislocation (n = 10), grade B PVR with rhegmatogenous retinal detachment (n = 13), grade C PVR with rhegmatogenous retinal detachment (n = 14), PDR with vitreous hemorrhage (n = 18), and PDR with vitreous hemorrhage and tractional retinal detachment (n = 14). Vitreous fluid samples were obtained at vitrectomy, and the levels of VEGF were measured by enzyme-linked immunosorbent assay. The mean vitreous level of VEGF was 15.14 ± 5.22 pg/ml in eyes with grade B PVR, 99.15 ± 38.58 pg/ml in eyes with grade C PVR, 4,534.01 ± 1,193.28 pg/ml in eyes with vitreous hemorrhage secondary to PDR, 5,157.29 ± 969.44 pg/ml in eyes with vitreous hemorrhage and tractional retinal detachment secondary to PDR, and 16.19 ± 5.76 pg/ml in eyes of the control group with traumatic lens dislocation. Vitreous VEGF concentrations were significantly higher in the patients with grade C PVR, PDR with vitreous hemorrhage and PDR with vitreous hemorrhage and tractional retinal detachment in comparison to the control patients (p < 0.05). A significant alteration was not observed in patients with grade B PVR (p = 0.55). Vitreous VEGF concentrations are increased in PDR and grade C PVR. The high VEGF concentrations could suggest a possible effect of VEGF on advanced PVR. Copyright © 2011 S. Karger AG, Basel.

  6. Human cold stress of strong local-wind "Hijikawa-arashi" in Japan, based on the UTCI index and thermo-physiological responses

    Science.gov (United States)

    Ohashi, Yukitaka; Katsuta, Takumi; Tani, Haruka; Okabayashi, Taiki; Miyahara, Satoshi; Miyashita, Ryoji

    2018-03-01

    We investigated the cold stress caused by a strong local wind called "Hijikawa-arashi," through in situ vital measurements and the Universal Thermal Climate Index (UTCI). This wind is a very interesting winter phenomenon, localized in an area within 1 km of the seashore in Ozu City, Ehime Prefecture in Japan. When a strong Hijikawa-arashi (HA) occurred at 14-15 m s-1, the UTCI decreased to - 30 °C along the bridge where commuting residents are the most exposed to strong and cold winds. On the bridge, most participants in our experiment felt "very cold" or "extremely cold." The UTCI of HA can be predicted from a multiple regression equation using wind speed and air temperature. The cold HA wind is also harmful to human thermo-physiological responses. It leads to higher blood pressure and increased heart rate, both of which act as cardiovascular stress triggers. Increases of 6-10 mmHg and 3-6 bpm for every 10 °C reduction in UTCI were seen on all observational days, including HA and non-HA days. In fact, the participants' body skin temperatures decreased by approximately 1.2 to 1.7 °C for every 10 °C reduction in UTCI. Thus, the UTCI variation due to the HA outbreak corresponded well with the cold sensation and thermo-physiological responses in humans. This result suggests that daily UTCI monitoring enables the prediction of thermo-physiological responses to the HA cold stress.

  7. Meningitis Caused by Toscana Virus Is Associated with Strong Antiviral Response in the CNS and Altered Frequency of Blood Antigen-Presenting Cells

    Science.gov (United States)

    Varani, Stefania; Gelsomino, Francesco; Bartoletti, Michele; Viale, Pierluigi; Mastroianni, Antonio; Briganti, Elisabetta; Ortolani, Patrizia; Albertini, Francesco; Calzetti, Carlo; Prati, Francesca; Cenni, Patrizia; Castellani, Gastone; Morini, Silvia; Rossini, Giada; Landini, Maria Paola; Sambri, Vittorio

    2015-01-01

    Toscana virus (TOSV) is a Phlebotomus-transmitted RNA virus and a frequent cause of human meningitis and meningoencephalitis in Southern Europe during the summer season. While evidence for TOSV-related central nervous system (CNS) cases is increasing, little is known about the host defenses against TOSV. We evaluated innate immune response to TOSV by analyzing frequency and activation of blood antigen-presenting cells (APCs) and cytokine levels in plasma and cerebrospinal fluid (CSF) from patients with TOSV neuroinvasive infection and controls. An altered frequency of different blood APC subsets was observed in TOSV-infected patients, with signs of monocytic deactivation. Nevertheless, a proper or even increased responsiveness of toll-like receptor 3 and 7/8 was observed in blood APCs of these patients as compared to healthy controls. Systemic levels of cytokines remained low in TOSV-infected patients, while levels of anti-inflammatory and antiviral mediators were significantly higher in CSF from TOSV-infected patients as compared to patients with other infectious and noninfectious neurological diseases. Thus, the early host response to TOSV appears effective for viral clearance, by proper response to TLR3 and TLR7/8 agonists in peripheral blood and by a strong and selective antiviral and anti-inflammatory response in the CNS. PMID:26569288

  8. Meningitis Caused by Toscana Virus Is Associated with Strong Antiviral Response in the CNS and Altered Frequency of Blood Antigen-Presenting Cells

    Directory of Open Access Journals (Sweden)

    Stefania Varani

    2015-11-01

    Full Text Available Toscana virus (TOSV is a Phlebotomus-transmitted RNA virus and a frequent cause of human meningitis and meningoencephalitis in Southern Europe during the summer season. While evidence for TOSV-related central nervous system (CNS cases is increasing, little is known about the host defenses against TOSV. We evaluated innate immune response to TOSV by analyzing frequency and activation of blood antigen-presenting cells (APCs and cytokine levels in plasma and cerebrospinal fluid (CSF from patients with TOSV neuroinvasive infection and controls. An altered frequency of different blood APC subsets was observed in TOSV-infected patients, with signs of monocytic deactivation. Nevertheless, a proper or even increased responsiveness of toll-like receptor 3 and 7/8 was observed in blood APCs of these patients as compared to healthy controls. Systemic levels of cytokines remained low in TOSV-infected patients, while levels of anti-inflammatory and antiviral mediators were significantly higher in CSF from TOSV-infected patients as compared to patients with other infectious and noninfectious neurological diseases. Thus, the early host response to TOSV appears effective for viral clearance, by proper response to TLR3 and TLR7/8 agonists in peripheral blood and by a strong and selective antiviral and anti-inflammatory response in the CNS.

  9. Characterization of the Apa antigen from M. avium subsp. paratuberculosis: a conserved Mycobacterium antigen that elicits a strong humoral response in cattle.

    Science.gov (United States)

    Gioffré, A; Echeverría-Valencia, G; Arese, A; Morsella, C; Garbaccio, S; Delgado, F; Zumárraga, M; Paolicchi, F; Cataldi, A; Romano, M I

    2009-12-15

    Johne's disease or paratuberculosis is widespread in almost all countries and remains difficult to eradicate. Nowadays, diagnosis of Mycobacterium avium subsp. paratuberculosis (MPTB) infection is one of the main concerns. In this work, we evaluated the expression, biochemical properties and antigenicity of the Apa antigen, encoded by the gene annotated as MAP1569, in the MPTB genome. We confirmed its expression in MPTB and its glycosylation by the ConA binding assay. Although the MPTB-Apa is not an immunodominant antigen, MPTB-infected cattle showed a strong humoral response to recombinant Apa by Western blot and ELISA. Milk was also a suitable sample to be tested by ELISA. We comparatively analysed the humoral cross-reactivity to the Apa from MPTB (MPTB-Apa) and the orthologue from Mycobacterium tuberculosis (MT-Apa, identical to that from Mycobacterium bovis) in both infected and control cows. Response of M. bovis- and MPTB-infected animals against MT-Apa was similar (P=0.6985) but the response of the M. bovis-infected ones to MPTB-Apa was differential, being significantly diminished (PApa stimulation in the IFNgamma release assay, we found no significant differences when compared infected herds with non-infected ones (P=0.34). This antigen, in contrast to bovine Purified Protein Derivative (PPDb), was strongly represented in avian PPD (PPDa), as shown by the recognition of BALB/c mice hyperimmune sera against MPTB-Apa by Dot-blot immunoassay. We therefore demonstrated the antigenicity of Apa in MPTB-infected animals and a differential response to the recombinant antigen when compared to M. bovis-infected animals. These traits herein described, added to the usefulness of milk samples to detect IgG anti-Apa, could be important for routine screening in dairy cattle, considering a multiantigenic approach to overcome the lack of immunodominance.

  10. Comparative antitumor and anti-proliferative activities of Hippophae rhamnoides L. leaves extracts

    Directory of Open Access Journals (Sweden)

    Javid Ali

    2015-03-01

    Full Text Available Objective: To evaluate the antitumor and anti-proliferative activities of methanol, aqueous, acetone, ethyl acetate, ethanol, chloroform and n-hexane extracts of Hippophae rhamnoides leaves. Methods: Antitumor activities were evaluated by using the antitumor potato disc assay by using inoculums (Agrobacterium tumefaciens with three different concentrations of test samples (10, 100 and 1 000 mg/L. Anti-proliferative activity was evaluated by the given method of methyl thiazolyl tetrazolium assay. The concentrations of the extract ranging from 0.039 to 10 mg/mL were tested against HeLa cells. Results: Highest tumors inhibition activity (60.9% and 55.8% was shown by methanol and ethanol extracts, with EC50 values of 424.41 and 434.61 mg/L respectively. At 10 mg/mL, The highest cell inhibition 75.61% was observed in methanol extract and the lowest 36.59% were calculated in n-hexane extract. The difference in tumor and cell inhibition (% may be due to the different concentration of active compounds responsible for antitumor and anti-proliferative activities. All extracts have considerable level of tumor and cell inhibitiory effect in a dose dependent manner. Conclusions: Our finding showed that Hippophae rhamnoides leaves are a potent natural source of antitumor and antiproliferative agent.

  11. Antibacterial, antioxidant and cell proliferative properties ofCoccinia grandis fruits.

    Science.gov (United States)

    Sakharkar, Prashant; Chauhan, Balwantsinh

    2017-01-01

    Little knowledge is available on the antimicrobial and antioxidant properties of Coccina grandis fruits and no study has reported on its cell proliferative property. The aim of this study was to examine the antimicrobial, antioxidant and cell proliferative property of fruits of C. grandis . Fruits of C . grandis were extracted using water; ethanol and acetone by cold and hot Soxhlet extraction. The antibacterial activities of the extracts were tested against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa using the modified Kirby-Bauer diffusion method and compared against erythromycin. The antioxidant property was determined using Cayman's antioxidant assay; whereas cell proliferation/cytotoxic properties were evaluated using the Cell Titer 96 Aqueous One Solution Cell MTS assay with MDA-MB 321 breast cancer cells. Data were analyzed for correlation and differences using unpaired student's t-test and one-way ANOVA. A p value of fruits showed some degree of bacterial growth inhibition. Acetone extracts exhibited higher antibacterial activity. Both ethanol extracts showed antioxidant property when compared with standard Trolox. In contrary to cytotoxicity, all four extracts showed cell proliferation compared to controls at different concentrations. However, acetone extracts exhibited greater cell proliferation compared to ethanol extracts and cold extracts performed better than the hot extracts. C. grandis fruits exhibited some degree of antimicrobial, antioxidant and cell proliferative properties. Further investigation is warranted to isolate, confirm and characterize phytochemicals that are responsible for the medicinal properties observed.

  12. Functionalization of Strongly Interacting Magnetic Nanocubes with (Thermo)responsive Coating and their Application in Hyperthermia and Heat-Triggered Drug Delivery

    KAUST Repository

    Kakwere, Hamilton

    2015-04-03

    Herein we prepare nanohybrids by incorporating iron oxide nanocubes (cubic-IONPs) within a thermo-responsive polymer shell that can act as drug carriers for doxorubicin(doxo). The cubic-shaped nanoparticles employed are at the interface between superparamagnetic and ferromagnetic behavior and have an exceptionally high specific absorption rate (SAR) but their functionalization is extremely challenging compared to bare superparamagnetic iron oxide nanoparticles as they strongly interact with each other. By conducting the polymer grafting reaction using reversible addition-fragmentation chain transfer (RAFT) polymerization in a viscous solvent medium, we have here developed a facile approach to decorate the nanocubes with stimuli-responsive polymers. When the thermo-responsive shell is composed of poly(N-isopropyl acrylamide-co-polyethylene glycolmethylether acrylate), nanohybrids have a phase transition temperature, the lower critical solution temperature (LCST), above 37 °C in physiological conditions. Doxo loaded nanohybrids exhibited a negligible drug release below 37 °C but showed a consistent release of their cargo on demand by exploiting the capability of the nanocubes to generate heat under an alternating magnetic field (AMF). Moreover, the drug free nanocarrier does not exhibit cytotoxicity even when administered at high concentration of nanocubes (1g/L of iron) and internalized at high extent (260 pg of iron per cell). We have also implemented the synthesis protocol to decorate the surface of nanocubes with poly(vinylpyridine) polymer and thus prepare pH-responsive shell coated nanocubes.

  13. Bevacizumab May Differentially Improve Ovarian Cancer Outcome in Patients with Proliferative and Mesenchymal Molecular Subtypes.

    Science.gov (United States)

    Kommoss, Stefan; Winterhoff, Boris; Oberg, Ann L; Konecny, Gottfried E; Wang, Chen; Riska, Shaun M; Fan, Jian-Bing; Maurer, Matthew J; April, Craig; Shridhar, Viji; Kommoss, Friedrich; du Bois, Andreas; Hilpert, Felix; Mahner, Sven; Baumann, Klaus; Schroeder, Willibald; Burges, Alexander; Canzler, Ulrich; Chien, Jeremy; Embleton, Andrew C; Parmar, Mahesh; Kaplan, Richard; Perren, Timothy; Hartmann, Lynn C; Goode, Ellen L; Dowdy, Sean C; Pfisterer, Jacobus

    2017-07-15

    Purpose: Recent progress in understanding the molecular biology of epithelial ovarian cancer has not yet translated into individualized treatment for these women or improvements in their disease outcome. Gene expression has been utilized to identify distinct molecular subtypes, but there have been no reports investigating whether or not molecular subtyping is predictive of response to bevacizumab in ovarian cancer. Experimental Design: DASL gene expression arrays were performed on FFPE tissue from patients enrolled on the ICON7 trial. Patients were stratified into four TCGA molecular subtypes. Associations between molecular subtype and the efficacy of randomly assigned therapy with bevacizumab were assessed. Results: Molecular subtypes were assigned as follows: 122 immunoreactive (34%), 96 proliferative (27%), 73 differentiated (20%), and 68 mesenchymal (19%). In univariate analysis patients with tumors of proliferative subtype obtained the greatest benefit from bevacizumab with a median PFS improvement of 10.1 months [HR, 0.55 (95% CI, 0.34-0.90), P = 0.016]. For the mesenchymal subtype, bevacizumab conferred a nonsignificant improvement in PFS of 8.2 months [HR 0.78 (95% CI, 0.44-1.40), P = 0.41]. Bevacizumab conferred modest improvements in PFS for patients with immunoreactive subtype (3.8 months; P = 0.08) or differentiated subtype (3.7 months; P = 0.61). Multivariate analysis demonstrated significant PFS improvement in proliferative subtype patients only [HR, 0.45 (95% CI, 0.27-0.74), P = 0.0015]. Conclusions: Ovarian carcinoma molecular subtypes with the poorest survival (proliferative and mesenchymal) derive a comparably greater benefit from treatment that includes bevacizumab. Validation of our findings in an independent cohort could enable the use of bevacizumab for those patients most likely to benefit, thereby reducing side effects and healthcare cost. Clin Cancer Res; 23(14); 3794-801. ©2017 AACR . ©2017 American Association for Cancer Research.

  14. Estrogen signaling in the proliferative endometrium: implications in endometriosis

    Directory of Open Access Journals (Sweden)

    Rita de Cássia Pereira da Costa e Silva

    2016-02-01

    Full Text Available SUMMARY Even though the physiological role of estrogen in the female reproductive cycle and endometrial proliferative phase is well established, the signaling pathways by which estrogen exerts its action in the endometrial tissue are still little known. In this regard, advancements in cell culture techniques and maintenance of endometrial cells in cultures enabled the discovery of new signaling mechanisms activated by estrogen in the normal endometrium and in endometriosis. This review aims to present the recent findings in the genomic and non-genomic estrogen signaling pathways in the proliferative human endometrium specifically associated with the pathogenesis and development of endometriosis.

  15. Strong mucosal immune responses in SIV infected macaques contribute to viral control and preserved CD4+ T-cell levels in blood and mucosal tissues.

    Science.gov (United States)

    Schultheiss, Tina; Schulte, Reiner; Sauermann, Ulrike; Ibing, Wiebke; Stahl-Hennig, Christiane

    2011-04-11

    Since there is still no protective HIV vaccine available, better insights into immune mechanism of persons effectively controlling HIV replication in the absence of any therapy should contribute to improve further vaccine designs. However, little is known about the mucosal immune response of this small unique group of patients. Using the SIV-macaque-model for AIDS, we had the rare opportunity to analyze 14 SIV-infected rhesus macaques durably controlling viral replication (controllers). We investigated the virological and immunological profile of blood and three different mucosal tissues and compared their data to those of uninfected and animals progressing to AIDS-like disease (progressors). Lymphocytes from blood, bronchoalveolar lavage (BAL), and duodenal and colonic biopsies were phenotypically characterized by polychromatic flow cytometry. In controllers, we observed higher levels of CD4+, CD4+CCR5+ and Gag-specific CD8+ T-cells as well as lower immune activation in blood and all mucosal sites compared to progressors. However, we could also demonstrate that immunological changes are distinct between these three mucosal sites.Intracellular cytokine staining demonstrated a significantly higher systemic and mucosal CD8+ Gag-specific cellular immune response in controllers than in progressors. Most remarkable was the polyfunctional cytokine profile of CD8+ lymphocytes in BAL of controllers, which significantly dominated over their blood response. The overall suppression of viral replication in the controllers was confirmed by almost no detectable viral RNA in blood and all mucosal tissues investigated. A strong and complex virus-specific CD8+ T-cell response in blood and especially in mucosal tissue of SIV-infected macaques was associated with low immune activation and an efficient suppression of viral replication. This likely afforded a repopulation of CD4+ T-cells in different mucosal compartments to almost normal levels. We conclude, that a robust SIV

  16. Inhibition of p38/CREB phosphorylation and COX-2 expression by olive oil polyphenols underlies their anti-proliferative effects

    International Nuclear Information System (INIS)

    Corona, Giulia; Deiana, Monica; Incani, Alessandra; Vauzour, David; Assunta Dessi, M.; Spencer, Jeremy P.E.

    2007-01-01

    We investigated the anti-proliferative effects of an olive oil polyphenolic extract on human colon adenocarcinoma cells. Analysis indicated that the extract contained hydroxytyrosol, tyrosol and the various secoiridoid derivatives, including oleuropein. This extract exerted a strong inhibitory effect on cancer cell proliferation, which was linked to the induction of a G2/M phase cell cycle block. Following treatment with the extract (50 μg/ml) the number of cells in the G2/M phase increased to 51.82 ± 2.69% relative to control cells (15.1 ± 2.5%). This G2/M block was mediated by the ability of olive oil polyphenols (50 μg/ml) to exert rapid inhibition of p38 (38.7 ± 4.7%) and CREB (28.6 ± 5.5%) phosphorylation which led to a downstream reduction in COX-2 expression (56.9 ± 9.3%). Our data suggest that olive oil polyphenols may exert chemopreventative effects in the large intestine by interacting with signalling pathways responsible for colorectal cancer development

  17. Importance of TLR2 on hepatic immune and non-immune cells to attenuate the strong inflammatory liver response during Trypanosoma cruzi acute infection.

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    Eugenio Antonio Carrera-Silva

    Full Text Available BACKGROUND: Toll-like receptors (TLR and cytokines play a central role in the pathogen clearance as well as in pathological processes. Recently, we reported that TLR2, TLR4 and TLR9 are differentially modulated in injured livers from BALB/c and C57BL/6 (B6 mice during Trypanosoma cruzi infection. However, the molecular and cellular mechanisms involved in local immune response remain unclear. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we demonstrate that hepatic leukocytes from infected B6 mice produced higher amounts of pro-inflammatory cytokines than BALB/c mice, whereas IL10 and TGFβ were only released by hepatic leukocytes from BALB/c. Strikingly, a higher expression of TLR2 and TLR4 was observed in hepatocytes of infected BALB/c mice. However, in infected B6 mice, the strong pro-inflammatory response was associated with a high and sustained expression of TLR9 and iNOS in leukocytes and hepatic tissue respectively. Additionally, co-expression of gp91- and p47-phox NADPH oxidase subunits were detected in liver tissue of infected B6 mice. Notably, the pre-treatment previous to infection with Pam3CSK4, TLR2-agonist, induced a significant reduction of transaminase activity levels and inflammatory foci number in livers of infected B6 mice. Moreover, lower pro-inflammatory cytokines and increased TGFβ levels were detected in purified hepatic leukocytes from TLR2-agonist pre-treated B6 mice. CONCLUSIONS/SIGNIFICANCE: Our results describe some of the main injurious signals involved in liver immune response during the T. cruzi acute infection. Additionally we show that the administration of Pam3CSk4, previous to infection, can attenuate the exacerbated inflammatory response of livers in B6 mice. These results could be useful to understand and design novel immune strategies in controlling liver pathologies.

  18. Proliferative verrucous leukoplakia; a critical appraisal of the diagnostic criteria

    NARCIS (Netherlands)

    Carrard, V.C.; Brouns, E.R.E.A.; van der Waal, I.

    2013-01-01

    Since its introduction in the literature in 1985, the term proliferative verrucous leukoplakia (PVL) has been the subject of an ongoing discussion with regard to its definition. Widespread or multifocal occurrence of oral leukoplakia is not just synonymous to PVL. In the present treatise the

  19. Proapoptotic, Anti-Cell Proliferative, Anti-Inflammatory And ...

    African Journals Online (AJOL)

    The present study has investigated the modulating effect of carnosic acid on the expression pattern of cell proliferative (proliferating cell nuclear antigen (PCNA) ... treated with DMBA not only completely prevented the tumour formation, but also corrected the abnormalities in the expression pattern of molecular markers.

  20. In vitro Anti-proliferative and Apoptotic Activities of Eurycoma ...

    African Journals Online (AJOL)

    Purpose: To investigate the anti-proliferative, apoptotic and differentiating activities of Eurycoma longifolia root extracts on HL-60 leukemic cells. Methods: HL-60 cells were treated with different partially purified sub-fractions (F1 – F3) derived from the resin chromatography of the crude methanol root extract of E. longifolia ...

  1. Anti-proliferative activity of recombinant melittin expressed in ...

    African Journals Online (AJOL)

    Recombinant melittin was then successfully expressed in Escherichia coli. The activity of affinity-purified recombinant melittin was determined in human leukemic U937 cells. Results show that the recombinant melittin had the same anti-proliferative activity in human leukemic U937 cells in vitro as natural one. This shows the ...

  2. Anti-proliferative effect of Moringa oleifera Lam (Moringaceae) leaf ...

    African Journals Online (AJOL)

    Purpose: To investigate the in vitro anti-proliferative effect and mechanism of action of Moringa oleifera Lam. leaf extract on human colon carcinoma HCT116 cell line. Methods: M. oleifera leaves were extracted with methanol. It was fractionated by Sephadex LH-20 column chromatography. Several fractions were identified ...

  3. Prolific plant regeneration through organogenesis from scalps of ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-11-16

    Nov 16, 2009 ... Malaysia. 2Faculty of Agriculture and Biotechnology, Universiti Darul Iman Malaysia, 20400 Kuala Terengganu, Malaysia. Accepted 17 September, 2009. A prolific plant regeneration system using scalps derived from shoot tips of Musa spp. cv. Tanduk was developed. Highly proliferating scalps, produced ...

  4. Antioxidant and Anti-proliferative Activities of Flavonoids from ...

    African Journals Online (AJOL)

    Purpose: To investigate the chemical composition of Bidens pilosa L. var. radiata. Sch Bip. (BP), as well as its antioxidant and anti-proliferative activities. Methods: The whole herb of BP was extracted with 95 % ethanol, which was then partitioned sequentially with petroleum ether, ethyl acetate and n-butyl alcohol to obtain ...

  5. Ultrastructure of epidermis of mice with chronic proliferative dermatitis

    NARCIS (Netherlands)

    Gijbels, M. J.; HogenEsch, H.; Blauw, B.; Roholl, P.; Zurcher, C.

    1995-01-01

    C57BL/Ka mice with chronic proliferative dermatitis (cpdm/cpdm) develop chronic persistent skin lesions characterized by epidermal hyperplasia, infiltration by granulocytes and macrophages, and vascular dilatation. Similar lesions are present in other orthokeratotic epithelia in affected mice, in

  6. PCNA immunoreactivity revealing normal proliferative activity in the brain of an adult Elasmobranch, Torpedo marmorata.

    Science.gov (United States)

    Margotta, Vito

    2007-01-01

    The brain of adult heterothermic vertebrates can be already provided of quiescent cells, scattered ("matrix cells") and/or clustered ("matrix areas"). These typical cells, in some regions located at or near ventricular surfaces and at peri-ependymal layers, in other territories populating their framework, maintain some embryonic properties and are responsible of normal or variously experimentally induced proliferative activities. On these topics there are a great number of reports concerning Teleostean Osteichthyes, Urodele and Anuran Amphibians, Lacertilian Reptiles. At the contrary, only few are the contributions regarding the Petromyzontidae. Involving an immunocytochemical marker, the Proliferating Cell Nuclear Antigen (PCNA), revealing proliferative events, in the last years we have undertaken a reappraisal focused on these encephalic performances in normal adult poikilothermal vertebrates. To provide a valid comparison between our results and the literature data, our choice of the specimens was based on the desire to employ organisms belonging to the same or phylogenetically close species used by previous Authors in similar studies. In our immunocytochemical panorama there is a substantial agreement between our contributions and bibliographic references concerning natural encephalic proliferative phenomena in these vertebrates. At this point of our study, the last missing piece was represented by the Chondrichthyes about which the literature data are lacking. In order to fill this gap, the aim of the present research is to investigate, involving the same PCNA test, whether proliferative events also persist in the brain of adult cartilaginous fishes. The immunostaining images obtained in the Elasmo branch Torpedo marmorata, well-known for the emission of high electrical discharges, exhibit undifferentiated cells in relationship with the ependymal epithelium lining the cavities of all cerebral districts; some other neuroblasts are scattered in the mesencephalic

  7. Proliferative activation of quiescent Rat-1A cells by delta FosB.

    Science.gov (United States)

    Nakabeppu, Y; Oda, S; Sekiguchi, M

    1993-07-01

    Fos and Jun transcription factors are induced during the normal course of the proliferative response of quiescent cells to serum or to growth factors. We have shown that delta FosB, an alternatively spliced form of FosB, is formed as rapidly as FosB in serum-stimulated Rat-1A cells. Although delta FosB lacks the C-terminal region of FosB carrying the transactivation function, constitutive expression of delta FosB transforms Rat-1A cells as does expression of FosB. The transforming ability of delta FosB suggests that delta FosB may lead to proliferative activation of quiescent cells without activating AP-1-responsive genes. To address this question, FosB or delta FosB was expressed as a fusion protein with the ligand binding domain of the human estrogen receptor (ER) in Rat-1A cells. After estrogen treatment, the fusion protein accumulates in nuclei and forms stable complexes with Jun proteins. We have shown that ER-delta FosB or to a lesser extent ER-FosB triggers quiescent Rat-1A cells to transit G1, initiate DNA replication, and ultimately undergo cell division at least once. Since ER-FosB, but not ER-delta FosB, induced expression of the AP-1-responsive transin/stromelysin gene, we concluded that the N-terminal region and the DNA binding domain of FosB or delta FosB itself have the potential to regulate cell proliferation and that the transactivation function carried by the C-terminal region of FosB is not essential for the proliferative activation of quiescent cells.

  8. Age and Influenza-Specific Pre-Vaccination Antibodies Strongly Affect Influenza Vaccine Responses in the Icelandic Population whereas Disease and Medication Have Small Effects

    Science.gov (United States)

    Olafsdottir, Thorunn A.; Alexandersson, Kristjan F.; Sveinbjornsson, Gardar; Lapini, Giulia; Palladino, Laura; Montomoli, Emanuele; Del Giudice, Giuseppe; Gudbjartsson, Daniel F.; Jonsdottir, Ingileif

    2018-01-01

    Influenza vaccination remains the best strategy for the prevention of influenza virus-related disease and reduction of disease severity and mortality. However, there is large individual variation in influenza vaccine responses. In this study, we investigated the effects of gender, age, underlying diseases, and medication on vaccine responses in 1,852 Icelanders of broad age range who received trivalent inactivated influenza virus vaccination in 2012, 2013, or 2015. Hemagglutination inhibition (HAI) and microneutralization (MN) titers were measured in pre- and post-vaccination sera. Of the variables tested, the strongest association was with level of pre-vaccination titer that explained a major part of the variance observed in post-vaccination titers, ranging from 19 to 29%, and from 7 to 21% in fold change (FC), depending on the strain and serological (HAI or MN) analysis performed. Thus, increasing pre-vaccination titer associated with decreasing FC (P = 1.1 × 10−99–8.6 × 10−30) and increasing post-vaccination titer (P = 2.1 × 10−159–1.1 × 10−123). Questionnaires completed by 87% of the participants revealed that post-vaccination HAI titer showed association with repeated previous influenza vaccinations. Gender had no effect on vaccine response whereas age had a strong effect and explained 1.6–3.1% of HAI post-vaccination titer variance and 3.1% of H1N1 MN titer variance. Vaccine response, both fold increase and seroprotection rate (percentage of individuals reaching HAI ≥ 40 or MN ≥ 20), was higher in vaccinees ≤37 years of age (YoA) than all other age groups. Furthermore, a reduction was observed in the H1N1 MN titer in people ≥63 YoA, demonstrating a decreased neutralizing functionality of vaccine-induced antibodies at older age. We tested the effects of underlying autoimmune diseases, asthma and allergic diseases and did not observe significant associations with vaccine responses. Intake of immune

  9. Age and Influenza-Specific Pre-Vaccination Antibodies Strongly Affect Influenza Vaccine Responses in the Icelandic Population whereas Disease and Medication Have Small Effects

    Directory of Open Access Journals (Sweden)

    Thorunn A. Olafsdottir

    2018-01-01

    Full Text Available Influenza vaccination remains the best strategy for the prevention of influenza virus-related disease and reduction of disease severity and mortality. However, there is large individual variation in influenza vaccine responses. In this study, we investigated the effects of gender, age, underlying diseases, and medication on vaccine responses in 1,852 Icelanders of broad age range who received trivalent inactivated influenza virus vaccination in 2012, 2013, or 2015. Hemagglutination inhibition (HAI and microneutralization (MN titers were measured in pre- and post-vaccination sera. Of the variables tested, the strongest association was with level of pre-vaccination titer that explained a major part of the variance observed in post-vaccination titers, ranging from 19 to 29%, and from 7 to 21% in fold change (FC, depending on the strain and serological (HAI or MN analysis performed. Thus, increasing pre-vaccination titer associated with decreasing FC (P = 1.1 × 10−99–8.6 × 10−30 and increasing post-vaccination titer (P = 2.1 × 10−159–1.1 × 10−123. Questionnaires completed by 87% of the participants revealed that post-vaccination HAI titer showed association with repeated previous influenza vaccinations. Gender had no effect on vaccine response whereas age had a strong effect and explained 1.6–3.1% of HAI post-vaccination titer variance and 3.1% of H1N1 MN titer variance. Vaccine response, both fold increase and seroprotection rate (percentage of individuals reaching HAI ≥ 40 or MN ≥ 20, was higher in vaccinees ≤37 years of age (YoA than all other age groups. Furthermore, a reduction was observed in the H1N1 MN titer in people ≥63 YoA, demonstrating a decreased neutralizing functionality of vaccine-induced antibodies at older age. We tested the effects of underlying autoimmune diseases, asthma and allergic diseases and did not observe significant associations with vaccine responses. Intake

  10. Flooding impairs Fe uptake and distribution in Citrus due to the strong down-regulation of genes involved in Strategy I responses to Fe deficiency in roots.

    Directory of Open Access Journals (Sweden)

    Mary-Rus Martínez-Cuenca

    Full Text Available This work determines the ffects of long-term anoxia conditions--21 days--on Strategy I responses to iron (Fe deficiency in Citrus and its impact on Fe uptake and distribution. The study was carried out in Citrus aurantium L. seedlings grown under flooding conditions (S and in both the presence (+Fe and absence of Fe (-Fe in nutritive solution. The results revealed a strong down-regulation (more than 65% of genes HA1 and FRO2 coding for enzymes proton-ATPase and Ferric-Chelate Reductase (FC-R, respectively, in -FeS plants when compared with -Fe ones. H+-extrusion and FC-R activity analyses confirmed the genetic results, indicating that flooding stress markedly repressed acidification and reduction responses to Fe deficiency (3.1- and 2.0-fold, respectively. Waterlogging reduced by half Fe concentration in +FeS roots, which led to 30% up-regulation of Fe transporter IRT1, although this effect was unable to improve Fe absorption. Consequently, flooding inhibited 57Fe uptake in +Fe and -Fe seedlings (29.8 and 66.2%, respectively and 57Fe distribution to aerial part (30.6 and 72.3%, respectively. This evidences that the synergistic action of both enzymes H+-ATPase and FC-R is the preferential regulator of the Fe acquisition system under flooding conditions and, hence, their inactivation implies a limiting factor of citrus in their Fe-deficiency tolerance in waterlogged soils.

  11. Proliferative activation of quiescent Rat-1A cells by delta FosB.

    OpenAIRE

    Nakabeppu, Y; Oda, S; Sekiguchi, M

    1993-01-01

    Fos and Jun transcription factors are induced during the normal course of the proliferative response of quiescent cells to serum or to growth factors. We have shown that delta FosB, an alternatively spliced form of FosB, is formed as rapidly as FosB in serum-stimulated Rat-1A cells. Although delta FosB lacks the C-terminal region of FosB carrying the transactivation function, constitutive expression of delta FosB transforms Rat-1A cells as does expression of FosB. The transforming ability of ...

  12. Elongation Factor Tu and Heat Shock Protein 70 Are Membrane-Associated Proteins from Mycoplasma ovipneumoniae Capable of Inducing Strong Immune Response in Mice.

    Science.gov (United States)

    Jiang, Fei; He, Jinyan; Navarro-Alvarez, Nalu; Xu, Jian; Li, Xia; Li, Peng; Wu, Wenxue

    2016-01-01

    Chronic non-progressive pneumonia, a disease that has become a worldwide epidemic has caused considerable loss to sheep industry. Mycoplasma ovipneumoniae (M. ovipneumoniae) is the causative agent of interstitial pneumonia in sheep, goat and bighorn. We here have identified by immunogold and immunoblotting that elongation factor Tu (EF-Tu) and heat shock protein 70 (HSP 70) are membrane-associated proteins on M. ovipneumonaiea. We have evaluated the humoral and cellular immune responses in vivo by immunizing BALB/c mice with both purified recombinant proteins rEF-Tu and rHSP70. The sera of both rEF-Tu and rHSP70 treated BALB/c mice demonstrated increased levels of IgG, IFN-γ, TNF-α, IL-12(p70), IL-4, IL-5 and IL-6. In addition, ELISPOT assay showed significant increase in IFN-γ+ secreting lymphocytes in the rHSP70 group when compared to other groups. Collectively our study reveals that rHSP70 induces a significantly better cellular immune response in mice, and may act as a Th1 cytokine-like adjuvant in immune response induction. Finally, growth inhibition test (GIT) of M. ovipneumoniae strain Y98 showed that sera from rHSP70 or rEF-Tu-immunized mice inhibited in vitro growth of M. ovipneumoniae. Our data strongly suggest that EF-Tu and HSP70 of M. ovipneumoniae are membrane-associated proteins capable of inducing antibody production, and cytokine secretion. Therefore, these two proteins may be potential candidates for vaccine development against M. ovipneumoniae infection in sheep.

  13. Novel engineered HIV-1 East African Clade-A gp160 plasmid construct induces strong humoral and cell-mediated immune responses in vivo

    International Nuclear Information System (INIS)

    Muthumani, Karuppiah; Zhang Donghui; Dayes, Nathanael S.; Hwang, Daniel S.; Calarota, Sandra A.; Choo, Andrew Y.; Boyer, Jean D.; Weiner, David B.

    2003-01-01

    HIV-1 sequences are highly diverse due to the inaccuracy of the viral reverse transcriptase. This diversity has been studied and used to categorize HIV isolates into subtypes or clades, which are geographically distinct. To develop effective vaccines against HIV-1, immunogens representing different subtypes may be important for induction of cross-protective immunity, but little data exist describing and comparing the immunogenicity induced by different subtype-based vaccines. This issue is further complicated by poor expression of HIV structural antigens due to rev dependence. One costly approach is to codon optimize each subtype construct to be examined. Interestingly, cis-acting transcriptional elements (CTE) can also by pass rev restriction by a rev independent export pathway. We reasoned that rev+CTE constructs might have advantages for such expression studies. A subtype A envelope sequence from a viral isolate from east Africa was cloned into a eukaryotic expression vector under the control of the CMV-IE promoter. The utility of inclusion of the Mason-Pfizer monkey virus (MPV)-CTE with/without rev for driving envelope expression and immunogenicity was examined. Expression of envelope (gp120) was confirmed by immunoblot analysis and by pseudotype virus infectivity assays. The presence of rev and the CTE together increased envelope expression and viral infection. Furthermore the CTE+rev construct was significantly more immunogenic then CTE alone vector. Isotype analysis and cytokine profiles showed strong Th1 response in plasmid-immunized mice, which also demonstrated the superior nature of the rev+CTE construct. These responses were of similar or greater magnitude to a codon-optimized construct. The resulting cellular immune responses were highly cross-reactive with a HIV-1 envelope subtype B antigen. This study suggests a simple strategy for improving the expression and immunogenicity of HIV subtype-specific envelope antigens as plasmid or vector

  14. Elongation Factor Tu and Heat Shock Protein 70 Are Membrane-Associated Proteins from Mycoplasma ovipneumoniae Capable of Inducing Strong Immune Response in Mice.

    Directory of Open Access Journals (Sweden)

    Fei Jiang

    Full Text Available Chronic non-progressive pneumonia, a disease that has become a worldwide epidemic has caused considerable loss to sheep industry. Mycoplasma ovipneumoniae (M. ovipneumoniae is the causative agent of interstitial pneumonia in sheep, goat and bighorn. We here have identified by immunogold and immunoblotting that elongation factor Tu (EF-Tu and heat shock protein 70 (HSP 70 are membrane-associated proteins on M. ovipneumonaiea. We have evaluated the humoral and cellular immune responses in vivo by immunizing BALB/c mice with both purified recombinant proteins rEF-Tu and rHSP70. The sera of both rEF-Tu and rHSP70 treated BALB/c mice demonstrated increased levels of IgG, IFN-γ, TNF-α, IL-12(p70, IL-4, IL-5 and IL-6. In addition, ELISPOT assay showed significant increase in IFN-γ+ secreting lymphocytes in the rHSP70 group when compared to other groups. Collectively our study reveals that rHSP70 induces a significantly better cellular immune response in mice, and may act as a Th1 cytokine-like adjuvant in immune response induction. Finally, growth inhibition test (GIT of M. ovipneumoniae strain Y98 showed that sera from rHSP70 or rEF-Tu-immunized mice inhibited in vitro growth of M. ovipneumoniae. Our data strongly suggest that EF-Tu and HSP70 of M. ovipneumoniae are membrane-associated proteins capable of inducing antibody production, and cytokine secretion. Therefore, these two proteins may be potential candidates for vaccine development against M. ovipneumoniae infection in sheep.

  15. Proliferative effect of whey from cows' milk obtained at two different stages of pregnancy measured in MCF-7 cells.

    Science.gov (United States)

    Nielsen, Tina S; Andersen, Charlotte; Sejrsen, Kris; Purup, Stig

    2012-02-01

    Dietary estrogens may play a role in the etiology of hormone-dependent cancers like breast cancer. Cow's milk contains various endogenous estrogens and feed derived phytoestrogens that potentially contribute to an estrogenic effect of milk in consumers, and therefore we evaluated the effect of milk (whey) in a proliferation assay with estrogen-sensitive MCF-7 human breast cancer cells. Milk samples were obtained from 22 cows representing different stages of pregnancy (first and second half) and whey was produced from the milk. 0·1, 0·25 or 0·5% whey was included in the cell culture medium and after 6 days of treatment cell proliferation was assessed by a colorimetric method with a fluorometer. Whey induced significant (Peffects compared with control cells with no added whey at all concentrations tested. There was no difference in the proliferative effect of whey depending on the stage of pregnancy from which the milk was obtained. We did not observe anti-proliferative effects when whey was tested in the presence of 10 pm estradiol in the medium. In conclusion, these results indicate that whey, irrespective of the pregnancy stage from which the milk was obtained induced a significant proliferative response in MCF-7 cells and no anti-proliferative effect, which may be caused, at least in part, by estrogens present in milk. The implications of our findings in relation to for example breast cancer will have to be studied further in other model systems preferentially in vivo.

  16. Anti-proliferative action of vitamin D in MCF7 is still active after siRNA-VDR knock-down

    NARCIS (Netherlands)

    J.L. Costa (José); P.P. Eijk (Paul); M.A. van de Wiel (Mark); D. ten Berge (Derk); F. Schmitt (Fernando); C.J. Narvaez (Carmen); J. Welsh; B. Ylstra (Bauke)

    2009-01-01

    textabstractBackground: The active form of Vitamin D, 1,25-dihydroxyvitamin D3(1,25D), has strong anti-proliferative effects, yet the molecular mechanisms underneath this effect remain unclear. In contrast, the molecular mechanism of 1,25D for the regulation of calcium homeostasis has principally

  17. Treatment of proliferative lupus nephritis with methylprednisolone pulse therapy and oral azathioprine

    NARCIS (Netherlands)

    de Glas-Vos, J. W.; Krediet, R. T.; Weening, J. J.; Arisz, L.

    1995-01-01

    OBJECTIVE: To evaluate the treatment of proliferative lupus nephritis with methylprednisolone pulse therapy and oral azathioprine. PATIENTS AND METHODS: Eighteen patients with severe proliferative lupus nephritis (Class III, IV or Vd according to criteria of the World Health Organization) were

  18. Different proliferative capacity of lung fibroblasts obtained from control subjects and patients with emphysema

    NARCIS (Netherlands)

    Noordhoek, JA; Postma, DS; Chong, LL; Vos, JTWM; Kauffman, HF; Timens, W; van Straaten, JFM

    2003-01-01

    To characterize the possible role of a dysregulated proliferative capacity of pulmonary fibroblasts in insufficient tissue repair in lungs from patients with pulmonary emphysema, the authors undertook in vitro proliferative studies with pulmonary fibroblasts obtained from lung tissue of patients

  19. A synthetic lymph node containing inactivated Treponema pallidum cells elicits strong, antigen-specific humoral and cellular immune responses in mice.

    Science.gov (United States)

    Stamm, Lola V; Drapp, Rebecca L

    2014-02-01

    The goal of this study was to investigate the use of a synthetic lymph node (SLN) for delivery of Treponema pallidum (Tp) antigens. Immune responses of C57BL/6 mice were analyzed at 4, 8, and 12 weeks after SLN implantation. Group 1 mice received SLN with no antigen; Group 2, SLN with formalin-inactivated Tp (f-Tp); and Group 3, SLN with f-Tp plus a CpG oligodeoxynucleotide. When tested by ELISA, sera from Group 2 and Group 3 mice showed stronger IgG antibody reactivity than sera from Group 1 mice to sonicates of f-Tp or untreated Tp, but not to sonicate of normal rabbit testicular extract at all times. The IgG1 level was higher than IgG2c level for Group 2 mice at all times and for Group 3 mice at 4 and 8 weeks. IgG1 and IgG2c levels were nearly equivalent for Group 3 mice at 12 weeks. Immunoblotting showed that IgG from Group 2 and Group 3 mice recognized several Tp proteins at all times. Supernatants of splenocytes from Group 2 and Group 3 mice contained significantly more IFNγ than those from Group 1 mice after stimulation with f-Tp at all times. A significant level of IL-4 was not detected in any supernatants. These data show that strong humoral and cellular immune responses to Tp can be elicited via a SLN. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  20. The 2009 Health Confidence Survey: public opinion on health reform varies; strong support for insurance market reform and public plan option, mixed response to tax cap.

    Science.gov (United States)

    Fronstin, Paul; Helman, Ruth

    2009-07-01

    PUBLIC SUPPORT FOR HEALTH REFORM: Findings from the 2009 Health Confidence Survey--the 12th annual HCS--indicate that Americans have already formed strong opinions regarding various aspects of health reform, even before details have been released regarding various key factors. These issues include health insurance market reform, the availability of a public plan option, mandates on employers and individuals, subsidized coverage for the low-income population, changes to the tax treatment of job-based health benefits, and regulatory oversight of health care. These opinions may change as details surface, especially as they concern financing options. In the absence of such details, the 2009 HCS finds generally strong support for the concepts of health reform options that are currently on the table. U.S. HEALTH SYSTEM GETS POOR MARKS, BUT SO DOES A MAJOR OVERHAUL: A majority rate the nation's health care system as fair (30 percent) or poor (29 percent). Only a small minority rate it excellent (6 percent) or very good (10 percent). While 14 percent of Americans think the health care system needs a major overhaul, 51 percent agree with the statement "there are some good things about our health care system, but major changes are needed." NATIONAL HEALTH PLAN ELEMENTS RATED HIGHLY: Between 68 percent and 88 percent of Americans either strongly or somewhat support health reform ideas such as national health plans, a public plan option, guaranteed issue, expansion of Medicare and Medicaid, and employer and individual mandates. MIXED REACTION TO HEALTH BENEFITS TAX CAP: Reaction to capping the current tax exclusion of employment-based health benefits is mixed. Nearly one-half of Americans (47 percent) would switch to a lower-cost plan if the tax exclusion were capped, 38 percent would stay on their current plan and pay the additional taxes, and 9 percent don't know. CONTINUED FAITH IN EMPLOYMENT-BASED BENEFITS, BUT DOUBTS ON AFFORDABILITY: Individuals with employment

  1. Vaccination with the Mycoplasma suis recombinant adhesion protein MSG1 elicits a strong immune response but fails to induce protection in pigs.

    Science.gov (United States)

    Hoelzle, Katharina; Doser, Susanne; Ritzmann, Mathias; Heinritzi, Karl; Palzer, Andreas; Elicker, Sabine; Kramer, Manuela; Felder, Kathrin M; Hoelzle, Ludwig E

    2009-08-27

    Mycoplasma suis is the unculturable pathogen of porcine infectious anemia. The study was aimed to determine the immunogenicity and protective efficacy of MSG1, an immunodominant adhesin of M. suis as the first vaccine candidate against M. suis. The results demonstrated that recombinant MSG1 and Escherichia coli transformants expressing MSG1 (E. coli_MSG1) induced a strong humoral and cellular immunity against M. suis. The induced antibodies were found to be functionally active as confirmed by an in vitro adhesion inhibition assay. Both, IgG1 and IgG2 antibodies were induced, but E. coli_MSG1 immune response was characterized by a significantly higher IgG1 antibody production. Both vaccine candidates failed to protect against M. suis challenge. However, E. coli_MSG1 vaccination has a considerable effect on the severity of the disease as shown by higher post-challenge hemoglobin and hematocrit values in comparison to control groups. This indicated that a high IgG1 antibody titer is negatively connected with severity of M. suis-induced anemia. Furthermore, the induction of monospecific anti-MSG1 antibodies by both vaccine candidates clearly allows for the differentiation between infected and vaccinated animals (DIVA principle). Overall, the importance of MSG1 as potential vaccine candidate remains to be established. Future studies will evaluate the conditions (i.e. adjuvant, vaccination scheme, and application route) to optimize the effects of E. coli_MSG1 vaccines.

  2. The use of analogy in pro-life argumentation

    Directory of Open Access Journals (Sweden)

    Simona Mazilu

    2012-01-01

    Full Text Available The paper is concerned with how analogy is strategically used in pro-life argumentation on abortion. Pragma-dialectics (van Eemeren and Grootendorst 1992 offers a set of critical questions by means of which I will evaluate the use of the argumentation based on a relation of analogy in terms of dialectical soundness. Examining various pro-life texts, I have noticed that the analogies employed remain unexplained. Therefore, despite the apparent similarities between abortion and the German holocaust or slavery, for instance, there are essential differences which are not mentioned. I claim that these analogies mainly have a rhetorical function, to operate what has been called by Micheli (2007: 960 “a transfer of emotional consensus”.

  3. The use of analogy in pro-life argumentation

    Directory of Open Access Journals (Sweden)

    Simona Mazilu

    2012-11-01

    Full Text Available The paper is concerned with how analogy is strategically used in pro-life argumentation on abortion. Pragma-dialectics (van Eemeren and Grootendorst 1992 offers a set of critical questions by means of which I will evaluate the use of the argumentation based on a relation of analogy in terms of dialectical soundness. Examining various pro-life texts, I have noticed that the analogies employed remain unexplained. Therefore, despite the apparent similarities between abortion and the German holocaust or slavery, for instance, there are essential differences which are not mentioned. I claim that these analogies mainly have a rhetorical function, to operate what has been called by Micheli (2007: 960 “a transfer of emotional consensus”.

  4. Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

    Science.gov (United States)

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

  5. Proliferative retinopathy and proteinuria predict mortality rate in type 1 diabetic patients from Fyn County, Denmark

    DEFF Research Database (Denmark)

    Grauslund, J; Green, A; Sjølie, A K

    2008-01-01

    AIMS/HYPOTHESIS: We evaluated the effect of diabetic retinopathy on 25 year survival rate among a population-based cohort of type 1 diabetic patients from Fyn County, Denmark. METHODS: In 1973 all diabetic patients from Fyn County, Denmark with onset before the age of 30 years as of 1 July 1973 w....../INTERPRETATION: Proliferative retinopathy and proteinuria predict mortality rate in a population-based cohort of type 1 diabetic patients. In combination they act even more strongly. Non-proliferative diabetic retinopathy did not affect survival rate.......AIMS/HYPOTHESIS: We evaluated the effect of diabetic retinopathy on 25 year survival rate among a population-based cohort of type 1 diabetic patients from Fyn County, Denmark. METHODS: In 1973 all diabetic patients from Fyn County, Denmark with onset before the age of 30 years as of 1 July 1973...... were identified (n=727). In 1981, only 627 patients were still alive and resident in Denmark. Of these, 573 (91%) participated in a clinical baseline examination, in which diabetic retinopathy was graded and other markers of diabetes measured. Mortality rate was examined in a 25 year follow...

  6. Karyopherin alpha2 is essential for rRNA transcription and protein synthesis in proliferative keratinocytes.

    Directory of Open Access Journals (Sweden)

    Noriko Umegaki-Arao

    Full Text Available Karyopherin proteins mediate nucleocytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest KPNA2 expression is induced in tumor cells and is strongly associated with prognosis, although the precise roles and mechanisms of KPNA2 overexpression in proliferative disorders have not been defined. We found that KPNA2 expression is induced in various proliferative disorders of the skin such as psoriasis, Bowen's disease, actinic keratosis, squamous cell carcinoma, Paget's disease, Merkel cell carcinoma, and mycosis fungoides. siRNA-mediated KPNA suppression revealed that KPNA2 is essential for significant suppression of HaCaT proliferation under starvation conditions. Ribosomal RNA transcription and protein synthesis were suppressed by starvation combined with knockdown of KPNA (including KPNA2 expression. KPNA2 localized to the nucleolus and interacted with proteins associated with mRNA processing, ribonucleoprotein complex biogenesis, chromatin modification, and transcription, as demonstrated by tandem affinity purification and mass spectrometry. KPNA2 may be an important promoter of ribosomal RNA and protein synthesis in tumor cells.

  7. Proliferative verrucous leukoplakia; a critical appraisal of the diagnostic criteria

    OpenAIRE

    Carrard, Vinicius C.; Brouns, Elisabeth R.E.A.; van der Waal, Isa?c

    2013-01-01

    Since its introduction in the literature in 1985, the term proliferative verrucous leukoplakia (PVL) has been the subject of an ongoing discussion with regard to its definition. Widespread or multifocal occurrence of oral leukoplakia is not just synonymous to PVL. In the present treatise the proposal is made to require the involvement of more than two oral oral subsites, a total added seizeof the leukoplakic areas of at least 3 centimeters, and a well documented period of at least five years ...

  8. Analysis and Enhancements of a Prolific Macroscopic Model of Epilepsy

    OpenAIRE

    Fietkiewicz, Christopher; Loparo, Kenneth A.

    2016-01-01

    Macroscopic models of epilepsy can deliver surprisingly realistic EEG simulations. In the present study, a prolific series of models is evaluated with regard to theoretical and computational concerns, and enhancements are developed. Specifically, we analyze three aspects of the models: (1) Using dynamical systems analysis, we demonstrate and explain the presence of direct current potentials in the simulated EEG that were previously undocumented. (2) We explain how the system was not ideally f...

  9. Prolific plant regeneration through organogenesis from scalps of ...

    African Journals Online (AJOL)

    Four types of potting media comprising of sand, peat, sand + top soil + goat dung (3:2:1 v/v) and top soil + sand (1:1 v/v) were evaluated during acclimatization of the plantlets. Prolific shoot regeneration from scalps was obtained on MS medium containing 2.5 mM BAP, at 9.61 and 40.6 shoots per explant after 4 and 8 weeks ...

  10. A maize landrace that emits defense volatiles in response to herbivore eggs possesses a strongly inducible terpene synthase gene.

    Science.gov (United States)

    Tamiru, Amanuel; Bruce, Toby J A; Richter, Annett; Woodcock, Christine M; Midega, Charles A O; Degenhardt, Jörg; Kelemu, Segenet; Pickett, John A; Khan, Zeyaur R

    2017-04-01

    Maize ( Zea mays ) emits volatile terpenes in response to insect feeding and egg deposition to defend itself against harmful pests. However, maize cultivars differ strongly in their ability to produce the defense signal. To further understand the agroecological role and underlying genetic mechanisms for variation in terpene emission among maize cultivars, we studied the production of an important signaling component ( E )-caryophyllene in a South American maize landrace Braz1006 possessing stemborer Chilo partellus egg inducible defense trait, in comparison with the European maize line Delprim and North American inbred line B73. The ( E) - caryophyllene production level and transcript abundance of TPS23, terpene synthase responsible for ( E) - caryophyllene formation, were compared between Braz1006, Delprim, and B73 after mimicked herbivory. Braz1006-TPS23 was heterologously expressed in E. coli , and amino acid sequences were determined. Furthermore, electrophysiological and behavioral responses of a key parasitic wasp Cotesia sesamiae to C .  partellus egg-induced Braz1006 volatiles were determined using coupled gas chromatography electroantennography and olfactometer bioassay studies. After elicitor treatment, Braz1006 released eightfold higher ( E) -caryophyllene than Delprim, whereas no ( E) -caryophyllene was detected in B73. The superior (E)- caryophyllene production by Braz1006 was positively correlated with high transcript levels of TPS23 in the landrace compared to Delprim. TPS23 alleles from Braz1006 showed dissimilarities at different sequence positions with Delprim and B73 and encodes an active enzyme. Cotesia sesamiae was attracted to egg-induced volatiles from Braz1006 and synthetic (E)- caryophyllene. The variation in ( E) -caryophyllene emission between Braz1006 and Delprim is positively correlated with induced levels of TPS23 transcripts. The enhanced TPS23 activity and corresponding ( E) -caryophyllene production by the maize landrace could be

  11. Proliferative Effects of Histamine on Primary Human Pterygium Fibroblasts.

    Science.gov (United States)

    Qin, Zhenwei; Fu, Qiuli; Zhang, Lifang; Yin, Houfa; Jin, Xiuming; Tang, Qiaomei; Lyu, Danni; Yao, Ke

    2016-01-01

    Purpose . It has been confirmed that inflammatory cytokines are involved in the progression of pterygium. Histamine can enhance proliferation and migration of many cells. Therefore, we intend to investigate the proliferative and migratory effects of histamine on primary culture of human pterygium fibroblasts (HPFs). Methods . Pterygium and conjunctiva samples were obtained from surgery, and toluidine blue staining was used to identify mast cells. 3-[4, 5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) was performed to evaluate the proliferative rate of HPFs and human conjunctival fibroblasts (HCFs); ki67 expression was also measured by immunofluorescence analysis. Histamine receptor-1 (H1R) antagonist (Diphenhydramine Hydrochloride) and histamine receptor-2 (H2R) antagonist (Nizatidine) were added to figure out which receptor was involved. Wound healing model was used to evaluate the migratory ability of HPFs. Results . The numbers of total mast cells and degranulated mast cells were both higher in pterygium than in conjunctiva. Histamine had a proliferative effect on both HPFs and HCFs, the effective concentration (10  μ mol/L) on HPFs was lower than on HCFs (100  μ mol/L), and the effect could be blocked by H1R antagonist. Histamine showed no migratory effect on HPFs. Conclusion . Histamine may play an important role in the proliferation of HPFs and act through H1R.

  12. Repeated Vaccination of Cows with HIV Env gp140 during Subsequent Pregnancies Elicits and Sustains an Enduring Strong Env-Binding and Neutralising Antibody Response.

    Science.gov (United States)

    Heydarchi, Behnaz; Center, Rob J; Gonelli, Christopher; Muller, Brian; Mackenzie, Charlene; Khoury, Georges; Lichtfuss, Marit; Rawlin, Grant; Purcell, Damian F J

    2016-01-01

    An important feature of a potential vaccine against HIV is the production of broadly neutralising antibodies (BrNAbs) capable of potentially blocking infectivity of a diverse array of HIV strains. BrNAbs naturally arise in some HIV infected individuals after several years of infection and their serum IgG can neutralise various HIV strains across different subtypes. We previously showed that vaccination of cows with HIV gp140 AD8 trimers resulted in a high titre of serum IgG against HIV envelope (Env) that had strong BrNAb activity. These polyclonal BrNAbs concentrated into the colostrum during the late stage of pregnancy and can be harvested in vast quantities immediately after calving. In this study, we investigated the effect of prolonged HIV gp140 vaccination on bovine colostrum IgG HIV Env-binding and BrNAb activity over subsequent pregnancies. Repeated immunisation led to a maintained high titre of HIV Env specific IgG in the colostrum batches, but this did not increase through repeated cycles. Colostrum IgG from all batches also strongly competed with sCD4 binding to gp140 Env trimer and with human-derived monoclonal VRC01 and b12 BrNAbs that bind the CD4 binding site (CD4bs). Furthermore, competition neutralisation assays using RSC3 Env gp120 protein core and a derivative CD4bs mutant, RSC3 Δ371I/P363N, showed that CD4bs neutralising antibodies contribute to the neutralising activity of all batches of purified bovine colostrum IgG. This result indicates that the high IgG titre/avidity of anti-CD4bs antibodies with BrNAb activity was achieved during the first year of vaccination and was sustained throughout the years of repeated vaccinations in the cow tested. Although IgG of subsequent colostrum batches may have a higher avidity towards the CD4bs, the overall breadth in neutralisation was not enhanced. This implies that the boosting vaccinations over 4 years elicited a polyclonal antibody response that maintained the proportion of both neutralising and non

  13. Repeated Vaccination of Cows with HIV Env gp140 during Subsequent Pregnancies Elicits and Sustains an Enduring Strong Env-Binding and Neutralising Antibody Response.

    Directory of Open Access Journals (Sweden)

    Behnaz Heydarchi

    Full Text Available An important feature of a potential vaccine against HIV is the production of broadly neutralising antibodies (BrNAbs capable of potentially blocking infectivity of a diverse array of HIV strains. BrNAbs naturally arise in some HIV infected individuals after several years of infection and their serum IgG can neutralise various HIV strains across different subtypes. We previously showed that vaccination of cows with HIV gp140 AD8 trimers resulted in a high titre of serum IgG against HIV envelope (Env that had strong BrNAb activity. These polyclonal BrNAbs concentrated into the colostrum during the late stage of pregnancy and can be harvested in vast quantities immediately after calving. In this study, we investigated the effect of prolonged HIV gp140 vaccination on bovine colostrum IgG HIV Env-binding and BrNAb activity over subsequent pregnancies. Repeated immunisation led to a maintained high titre of HIV Env specific IgG in the colostrum batches, but this did not increase through repeated cycles. Colostrum IgG from all batches also strongly competed with sCD4 binding to gp140 Env trimer and with human-derived monoclonal VRC01 and b12 BrNAbs that bind the CD4 binding site (CD4bs. Furthermore, competition neutralisation assays using RSC3 Env gp120 protein core and a derivative CD4bs mutant, RSC3 Δ371I/P363N, showed that CD4bs neutralising antibodies contribute to the neutralising activity of all batches of purified bovine colostrum IgG. This result indicates that the high IgG titre/avidity of anti-CD4bs antibodies with BrNAb activity was achieved during the first year of vaccination and was sustained throughout the years of repeated vaccinations in the cow tested. Although IgG of subsequent colostrum batches may have a higher avidity towards the CD4bs, the overall breadth in neutralisation was not enhanced. This implies that the boosting vaccinations over 4 years elicited a polyclonal antibody response that maintained the proportion of both

  14. Addition of αGal HyperAcute™ technology to recombinant avian influenza vaccines induces strong low-dose antibody responses.

    Science.gov (United States)

    Chen, Wenlan Alex; Zhang, Jinjin; Hall, Katie M; Martin, Carol B; Kisselev, Serguei; Dasen, Emily J; Vahanian, Nicholas N; Link, Charles J; Martin, Brian K

    2017-01-01

    Highly pathogenic avian influenza represents a severe public health threat. Over the last decade, the demand for highly efficacious vaccines against avian influenza viruses has grown, especially after the 2013 H7N9 outbreak in China that resulted in over 600 human cases with over 200 deaths. Currently, there are several H5N1 and H7N9 influenza vaccines in clinical trials, all of which employ traditional oil-in-water adjuvants due to the poor immunogenicity of avian influenza virus antigens. In this study, we developed potent recombinant avian influenza vaccine candidates using HyperAcute™ Technology, which takes advantage of naturally-acquired anti-αGal immunity in humans. We successfully generated αGal-positive recombinant protein and virus-like particle vaccine candidates of H5N1 and H7N9 influenza strains using either biological or our novel CarboLink chemical αGal modification techniques. Strikingly, two doses of 100 ng αGal-modified vaccine, with no traditional adjuvant, was able to induce a much stronger humoral response in αGT BALB/c knockout mice (the only experimental system readily available for testing αGal in vivo) than unmodified vaccines even at 10-fold higher dose (1000 ng/dose). Our data strongly suggest that αGal modification significantly enhances the humoral immunogenicity of the recombinant influenza vaccine candidates. Use of αGal HyperAcute™ technology allows significant dose-sparing while retaining desired immunogenicity. Our success in the development of highly potent H5N1 and H7N9 vaccine candidates demonstrated the potential of αGal HyperAcute™ technology for the development of vaccines against other infectious diseases.

  15. Addition of αGal HyperAcute™ technology to recombinant avian influenza vaccines induces strong low-dose antibody responses.

    Directory of Open Access Journals (Sweden)

    Wenlan Alex Chen

    Full Text Available Highly pathogenic avian influenza represents a severe public health threat. Over the last decade, the demand for highly efficacious vaccines against avian influenza viruses has grown, especially after the 2013 H7N9 outbreak in China that resulted in over 600 human cases with over 200 deaths. Currently, there are several H5N1 and H7N9 influenza vaccines in clinical trials, all of which employ traditional oil-in-water adjuvants due to the poor immunogenicity of avian influenza virus antigens. In this study, we developed potent recombinant avian influenza vaccine candidates using HyperAcute™ Technology, which takes advantage of naturally-acquired anti-αGal immunity in humans. We successfully generated αGal-positive recombinant protein and virus-like particle vaccine candidates of H5N1 and H7N9 influenza strains using either biological or our novel CarboLink chemical αGal modification techniques. Strikingly, two doses of 100 ng αGal-modified vaccine, with no traditional adjuvant, was able to induce a much stronger humoral response in αGT BALB/c knockout mice (the only experimental system readily available for testing αGal in vivo than unmodified vaccines even at 10-fold higher dose (1000 ng/dose. Our data strongly suggest that αGal modification significantly enhances the humoral immunogenicity of the recombinant influenza vaccine candidates. Use of αGal HyperAcute™ technology allows significant dose-sparing while retaining desired immunogenicity. Our success in the development of highly potent H5N1 and H7N9 vaccine candidates demonstrated the potential of αGal HyperAcute™ technology for the development of vaccines against other infectious diseases.

  16. Ticks, Ixodes scapularis, Feed Repeatedly on White-Footed Mice despite Strong Inflammatory Response: An Expanding Paradigm for Understanding Tick–Host Interactions

    Directory of Open Access Journals (Sweden)

    Jennifer M. Anderson

    2017-12-01

    Full Text Available Ticks transmit infectious agents including bacteria, viruses and protozoa. However, their transmission may be compromised by host resistance to repeated tick feeding. Increasing host resistance to repeated tick bites is well known in laboratory animals, including intense inflammation at the bite sites. However, it is not known whether this also occurs in wild rodents such as white-footed mice, Peromyscus leucopus, and other wildlife, or if it occurs at all. According to the “host immune incompetence” hypothesis, if these mice do not have a strong inflammatory response, they would not reject repeated tick bites by Ixodes scapularis. To test this hypothesis, histopathological studies were done comparing dermal inflammation in P. leucopus versus guinea pigs, Cavia porcellus, repeatedly infested with I. scapularis. In P. leucopus, the immune cell composition was like that seen in laboratory mouse models, with some differences. However, there was a broad sessile lesion with intact dermal architecture, likely enabling the ticks to continue feeding unimpeded. In contrast, in C. porcellus, there was a relatively similar mixed cellular profile, but there also was a large, leukocyte-filled cavitary lesion and scab-like hyperkeratotic changes to the epidermal layer, along with itching and apparent pain. Ticks attached to sensitized C. porcellus fed poorly or were dislodged, presumably due to the weakened anchoring of the tick’s mouthparts cemented in the heavily inflamed and disintegrating dermal tissues. This is the first time that the architecture of the skin lesions has been recognized as a major factor in understanding tick–host tolerance versus tick bite rejection. These findings broadly strengthen previous work done on lab animal models but also help explain why I. scapularis can repeatedly parasitize white-footed mice, supporting the “immune evasion theory” but cannot repeatedly parasitize other, non-permissive hosts such as guinea pigs.

  17. Mitochondrial localization of the low level p53 protein in proliferative cells

    Energy Technology Data Exchange (ETDEWEB)

    Ferecatu, Ioana; Bergeaud, Marie; Rodriguez-Enfedaque, Aida; Le Floch, Nathalie [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Oliver, Lisa [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Rincheval, Vincent; Renaud, Flore [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vallette, Francois M. [INSERM U601, Universite de Nantes, Faculte de Medecine, Nantes Cedex (France); Mignotte, Bernard [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France); Vayssiere, Jean-Luc, E-mail: jean-luc.vayssiere@uvsq.fr [Laboratoire de Genetique et Biologie Cellulaire - CNRS UMR 8159, Universite de Versailles Saint-Quentin-en-Yvelines, Versailles, France and Laboratoire de Genetique Moleculaire et Physiologique, Ecole Pratique des Hautes Etudes, Versailles (France)

    2009-10-02

    p53 protein plays a central role in suppressing tumorigenesis by inducing cell cycle arrest or apoptosis through transcription-dependent and -independent mechanisms. Emerging publications suggest that following stress, a fraction of p53 translocates to mitochondria to induce cytochrome c release and apoptosis. However, the localization of p53 under unstressed conditions remains largely unexplored. Here we show that p53 is localized at mitochondria in absence of apoptotic stimuli, when cells are proliferating, localization observed in various cell types (rodent and human). This is also supported by acellular assays in which p53 bind strongly to mitochondria isolated from rat liver. Furthermore, the mitochondria subfractionation study and the alkaline treatment of the mitochondrial p53 revealed that the majority of mitochondrial p53 is present in the membranous compartments. Finally, we identified VDAC, a protein of the mitochondrial outer-membrane, as a putative partner of p53 in unstressed/proliferative cells.

  18. Proliferative reactive gliosis is compatible with glial metabolic support and neuronal function

    Directory of Open Access Journals (Sweden)

    Fero Matthew

    2011-10-01

    Full Text Available Abstract Background The response of mammalian glial cells to chronic degeneration and trauma is hypothesized to be incompatible with support of neuronal function in the central nervous system (CNS and retina. To test this hypothesis, we developed an inducible model of proliferative reactive gliosis in the absence of degenerative stimuli by genetically inactivating the cyclin-dependent kinase inhibitor p27Kip1 (p27 or Cdkn1b in the adult mouse and determined the outcome on retinal structure and function. Results p27-deficient Müller glia reentered the cell cycle, underwent aberrant migration, and enhanced their expression of intermediate filament proteins, all of which are characteristics of Müller glia in a reactive state. Surprisingly, neuroglial interactions, retinal electrophysiology, and visual acuity were normal. Conclusion The benign outcome of proliferative reactive Müller gliosis suggests that reactive glia display context-dependent, graded and dynamic phenotypes and that reactivity in itself is not necessarily detrimental to neuronal function.

  19. VISUAL OUTCOME FOLLOWING PANRETINAL PHOTOCOAGULATION IN PROLIFERATIVE DIABETIC RETINOPATHY

    Directory of Open Access Journals (Sweden)

    Nellaye Mani Sindhu

    2018-01-01

    Full Text Available BACKGROUND Diabetes mellitus can be called as a noninfectious pandemic and the incidence of diabetic retinopathy is also uncontrollable. This vision-threatening complication can be treated by early diagnosis and effective treatment like panretinal photocoagulation. The aim of the study is to evaluate the effect of panretinal photocoagulation on visual acuity, colour vision, contrast sensitivity and severity of visual field changes. MATERIALS AND METHODS Prospective study of visual outcome following panretinal photocoagulation in patients with proliferative diabetic retinopathy conducted in Retina Clinic, RIO, Trivandrum, during the time period one year from April 2008. Inclusion Criteria- Eyes with proliferative diabetic retinopathy, visual acuity better than or equal to 6/60, a follow up of at least 6 months after panretinal photocoagulation. Exclusion Criteria- Eyes with cataractous changes in the lens, eyes, which would be undergoing or have undergone focal photocoagulation eyes, which undergone barrage or sectoral retinal photocoagulation, patients with colour blindness, eyes with vitreous haemorrhage and macular preretinal haemorrhage, glaucomatous patients with peripheral field loss. RESULTS The mean age of the patients was 52 years. Male patients (30 outnumbered the female patients (23. Mean duration of diabetes was 14.42 years. Though, there is a statistically significant reduction in visual acuity in the first followup, which was improved and stabilised by 6 months. There is a statistically significant reduction in the contrast sensitivity, which was stabilised after 3 months. Only, 9.5% patients had peripheral constrictions of visual field and no significant change in the colour vision. CONCLUSION We recommend panretinal photocoagulation for all patients with proliferative diabetic retinopathy.

  20. L-thyroxine promotes a proliferative airway smooth muscle phenotype in the presence of TGF-β1.

    Science.gov (United States)

    Dekkers, Bart G J; Naeimi, Saeideh; Bos, I Sophie T; Menzen, Mark H; Halayko, Andrew J; Hashjin, Goudarz Sadeghi; Meurs, Herman

    2015-02-01

    Hypothyroidism may reduce, whereas hyperthyroidism may aggravate, asthma symptoms. The mechanisms underlying this relationship are largely unknown. Since thyroid hormones have central roles in cell growth and differentiation, we hypothesized that airway remodeling, in particular increased airway smooth muscle (ASM) mass, may be involved. To address this hypothesis, we investigated the effects of triiodothyronine (T3) and l-thyroxine (T4) in the absence and presence of the profibrotic transforming growth factor (TGF)-β1 on human ASM cell phenotype switching. T3 (1-100 nM) and T4 (1-100 nM) did not affect basal ASM proliferation. However, when combined with TGF-β1 (2 ng/ml), T4 synergistically increased the proliferative response, whereas only a minor effect was observed for T3. In line with a switch from a contractile to a proliferative ASM phenotype, T4 reduced the TGF-β1-induced contractile protein expression by ∼50%. Cotreatment with T3 reduced TGF-β1-induced contractile protein expression by ∼25%. The synergistic increase in proliferation was almost fully inhibited by the integrin αvβ3 antagonist tetrac (100 nM), whereas no significant effects of the thyroid receptor antagonist 1-850 (3 μM) were observed. Inhibition of MEK1/2, downstream of the integrin αvβ3, also inhibited the T4- and TGF-β1-induced proliferative responses. Collectively, the results indicate that T4, and to a lesser extent T3, promotes a proliferative ASM phenotype in the presence of TGF-β1, which is predominantly mediated by the membrane-bound T4 receptor αvβ3. These results indicate that thyroid hormones may enhance ASM remodeling in asthma, which could be of relevance for hyperthyroid patients with this disease. Copyright © 2015 the American Physiological Society.

  1. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

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    Bérengère Gobin

    Full Text Available Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma, a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1. Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma and POS-1 (undifferentiated osteosarcoma. Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R, appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor

  2. Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

    Science.gov (United States)

    Gobin, Bérengère; Moriceau, Gatien; Ory, Benjamin; Charrier, Céline; Brion, Régis; Blanchard, Frederic; Redini, Françoise; Heymann, Dominique

    2014-01-01

    Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma), a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that imatinib mesylate inhibits osteoclast differentiation through the M-CSFR pathway and activates osteoblast differentiation through PDGFR pathway, two key cells involved in the vicious cycle controlling the tumour development. The present study investigated the in vitro effects of imatinib mesylate on the proliferation, apoptosis, cell cycle, and migration ability of five osteosarcoma cell lines (human: MG-63, HOS; rat: OSRGA; mice: MOS-J, POS-1). Imatinib mesylate was also assessed as a curative and preventive treatment in two syngenic osteosarcoma models: MOS-J (mixed osteoblastic/osteolytic osteosarcoma) and POS-1 (undifferentiated osteosarcoma). Imatinib mesylate exhibited a dose-dependent anti-proliferative effect in all cell lines studied. The drug induced a G0/G1 cell cycle arrest in most cell lines, except for POS-1 and HOS cells that were blocked in the S phase. In addition, imatinib mesylate induced cell death and strongly inhibited osteosarcoma cell migration. In the MOS-J osteosarcoma model, oral administration of imatinib mesylate significantly inhibited the tumour development in both preventive and curative approaches. A phospho-receptor tyrosine kinase array kit revealed that PDGFRα, among 7 other receptors (PDFGFRβ, Axl, RYK, EGFR, EphA2 and 10, IGF1R), appears as one of the main molecular targets for imatinib mesylate. In the light of the present study and the literature, it would be particularly interesting to revisit therapeutic evaluation of imatinib mesylate in osteosarcoma according to the tyrosine-kinase receptor status of patients.

  3. Oral proliferative verrucous leukoplakia: A case report with an update

    Directory of Open Access Journals (Sweden)

    Rakhi Issrani

    2013-01-01

    Full Text Available White lesions both physiologic as well as pathologic are relatively frequent in the oral cavity, the most common pathology being oral leukoplakia (OL. There are many variants of OL, one of which is oral proliferative verrucous leukoplakia (OPVL. OPVL is a rare clinico-pathological entity, which is slow growing, long-term progressive lesion, but remains an enigmatic and difficult to define. The etiology of OPVL remains still unclear. Tobacco use does not seem to have a significant influence on the appearance of OPVL. These lesions may occur both in smokers and non-smokers. It is observed more frequently in women and elderly patients over 60 years at the time of diagnosis. The buccal mucosa and tongue are the most frequently involved sites. It develops initially as a white plaque of hyperkeratosis that eventually becomes a multifocal disease with confluent, exophytic and proliferative features. Various published case series have presented OPVL as a disease with aggressive biological behavior due to its high probability of recurrence and a high rate of malignant transformation. Prognosis is poor for this seemingly harmless-appearing white lesion of the oral mucosa. This article describes the clinical aspects and histologic features of an OPVL case that demonstrated the typical behavior pattern in a long-standing, persistent lesion and discusses this relatively rare entity in light of current information.

  4. Neoplastic and proliferative disorders of the perinephric space

    International Nuclear Information System (INIS)

    Heller, M.T.; Haarer, K.A.; Thomas, E.; Thaete, F.L.

    2012-01-01

    The perinephric space is a well-marginated central compartment of the retroperitoneum, located between the anterior and posterior pararenal spaces. Various neoplastic and proliferative disorders can affect the perinephric space, and there is a wide array of imaging findings. Although many perinephric lesions may extend directly from the kidney and adrenal gland, other lesions occur in the perinephric space due to haematogenous spread, as part of a systemic disease, or by extension from an adjacent retroperitoneal compartment. Imaging plays a pivotal role in the diagnosis of perinephric diseases, as many of the disease processes affecting this space will not result in clinical signs or symptoms until the disease is at an advanced stage. Despite the often shared non-specific clinical and imaging findings among these disease processes, application of a categorical differential diagnosis based on the imaging characteristics will serve to narrow the differential diagnosis and direct further evaluation and treatment. In this article, the lesions have been categorized as soft-tissue rind [nephroblastomatosis, fibrosis, Erdheim–Chester disease (ECD), extramedullary haematopoiesis, lymphoma, infiltrating metastases], focal solid lesions (extension of renal or adrenal malignancies, melanoma metastases, treated lymphoma), fat-containing lesions (angiomyolipoma, liposarcoma, myelolipoma), and cystic lesions (lymphangiomas, abscesses). The aim of this article is to demonstrate and describe the key imaging features of several neoplastic and proliferative disorders that affect the perinephric space.

  5. A strong loss-of-function mutation in RAN1 results in constitution activation of the ethylene response pathway as well as a rosette-lethal phenotype

    Science.gov (United States)

    Keith Woeste; Joseph J. Kieber

    2000-01-01

    A recessive mutation was identified that constitutively activated the ethylene response pathway in Arabidopsis and resuited in a rosette-lethal phenotype. Positional cloning of the gene corresponding to this mutation revealed that it was allelic to responsive to antagonist1 (ran1), a mutation that causes seedlings to respond in a positive manner to what is normally a...

  6. Hyper-activation of Notch3 amplifies the proliferative potential of rhabdomyosarcoma cells.

    Directory of Open Access Journals (Sweden)

    Maria De Salvo

    Full Text Available Rhabdomyosarcoma (RMS is a pediatric myogenic-derived soft tissue sarcoma that includes two major histopathological subtypes: embryonal and alveolar. The majority of alveolar RMS expresses PAX3-FOXO1 fusion oncoprotein, associated with the worst prognosis. RMS cells show myogenic markers expression but are unable to terminally differentiate. The Notch signaling pathway is a master player during myogenesis, with Notch1 activation sustaining myoblast expansion and Notch3 activation inhibiting myoblast fusion and differentiation. Accordingly, Notch1 signaling is up-regulated and activated in embryonal RMS samples and supports the proliferation of tumor cells. However, it is unable to control their differentiation properties. We previously reported that Notch3 is activated in RMS cell lines, of both alveolar and embryonal subtype, and acts by inhibiting differentiation. Moreover, Notch3 depletion reduces PAX3-FOXO1 alveolar RMS tumor growth in vivo. However, whether Notch3 activation also sustains the proliferation of RMS cells remained unclear. To address this question, we forced the expression of the activated form of Notch3, Notch3IC, in the RH30 and RH41 PAX3-FOXO1-positive alveolar and in the RD embryonal RMS cell lines and studied the proliferation of these cells. We show that, in all three cell lines tested, Notch3IC over-expression stimulates in vitro cell proliferation and prevents the effects of pharmacological Notch inhibition. Furthermore, Notch3IC further increases RH30 cell growth in vivo. Interestingly, knockdown of Notch canonical ligands JAG1 or DLL1 in RMS cell lines decreases Notch3 activity and reduces cell proliferation. Finally, the expression of Notch3IC and its target gene HES1 correlates with that of the proliferative marker Ki67 in a small cohort of primary PAX-FOXO1 alveolar RMS samples. These results strongly suggest that high levels of Notch3 activation increase the proliferative potential of RMS cells.

  7. Heme oxygenase is not involved in the anti-proliferative effects of statins on pancreatic cancer cells

    International Nuclear Information System (INIS)

    Vanova, K.; Boukalova, S.; Gbelcova, H.; Muchova, L.; Neuzil, J.; Gurlich, R.; Ruml, T.; Vitek, L.

    2016-01-01

    Pancreatic cancer is recognized as one of the most fatal tumors due to its aggressiveness and resistance to therapy. Statins were previously shown to inhibit the proliferation of cancer cells via various signaling pathways. In healthy tissues, statins activate the heme oxygenase pathway, nevertheless the role of heme oxygenase in pancreatic cancer is still controversial. The aim of this study was to evaluate, whether anti-proliferative effects of statins in pancreatic cancer cells are mediated via the heme oxygenase pathway. In vitro effects of various statins and hemin, a heme oxygenase inducer, on cell proliferation were evaluated in PA-TU-8902, MiaPaCa-2 and BxPC-3 human pancreatic cancer cell lines. The effect of statins on heme oxygenase activity was assessed and heme oxygenase-silenced cells were used for pancreatic cancer cell proliferation studies. Cell death rate and reactive oxygen species production were measured in PA-TU-8902 cells, followed by evaluation of the effect of cerivastatin on GFP-K-Ras trafficking and expression of markers of invasiveness, osteopontin (SPP1) and SOX2. While simvastatin and cerivastatin displayed major anti-proliferative properties in all cell lines tested, pravastatin did not affect the cell growth at all. Strong anti-proliferative effect was observed also for hemin. Co-treatment of cerivastatin and hemin increased anti-proliferative potential of these agents, via increased production of reactive oxygen species and cell death compared to individual treatment. Heme oxygenase silencing did not prevent pancreatic cancer cells from the tumor-suppressive effect of cerivastatin or hemin. Cerivastatin, but not pravastatin, protected Ras protein from trafficking to the cell membrane and significantly reduced expressions of SPP1 (p < 0.05) and SOX2 (p < 0.01). Anti-proliferative effects of statins and hemin on human pancreatic cancer cell lines do not seem to be related to the heme oxygenase pathway. While hemin triggers reactive

  8. Elicitation of strong immune responses by a DNA vaccine expressing a secreted form of hepatitis C virus envelope protein E2 in murine and porcine animal models

    DEFF Research Database (Denmark)

    Li, Yiping; Kang, H.N.; Babiuk, L.A.

    2006-01-01

    boosting with a recombinant E2 protein vaccine formulated with CpG ODN and 10% Emulsigen. The immunogenicity of HCV E2 vaccines was analyzed by ELISA for antibody responses, MTT assay for lymphocyte proliferation, ELISPOT for the number of interferon-gamma secreting cells, and cytotoxic T lymphocyte assays...... and shifted the immune response towards Th2-like ones in piglets. CONCLUSION: A DNA vaccine expressing a secreted form of HCV E2 protein elicited E2-specific immune responses in mice and piglets. Recombinant E2 protein vaccination following DNA immunization significantly increased the antibody response......AIM: To characterize the immunogenicity of a hepatitis C virus (HCV) E2 DNA vaccine alone or with a protein vaccine boost in murine and porcine animal models. METHODS: A DNA vaccine expressing a secreted form of HCV E2 protein was constructed and used to vaccinate mice and piglets with or without...

  9. Analysis and Enhancements of a Prolific Macroscopic Model of Epilepsy

    Directory of Open Access Journals (Sweden)

    Christopher Fietkiewicz

    2016-01-01

    Full Text Available Macroscopic models of epilepsy can deliver surprisingly realistic EEG simulations. In the present study, a prolific series of models is evaluated with regard to theoretical and computational concerns, and enhancements are developed. Specifically, we analyze three aspects of the models: (1 Using dynamical systems analysis, we demonstrate and explain the presence of direct current potentials in the simulated EEG that were previously undocumented. (2 We explain how the system was not ideally formulated for numerical integration of stochastic differential equations. A reformulated system is developed to support proper methodology. (3 We explain an unreported contradiction in the published model specification regarding the use of a mathematical reduction method. We then use the method to reduce the number of equations and further improve the computational efficiency. The intent of our critique is to enhance the evolution of macroscopic modeling of epilepsy and assist others who wish to explore this exciting class of models further.

  10. Analysis and Enhancements of a Prolific Macroscopic Model of Epilepsy

    Science.gov (United States)

    Fietkiewicz, Christopher; Loparo, Kenneth A.

    2016-01-01

    Macroscopic models of epilepsy can deliver surprisingly realistic EEG simulations. In the present study, a prolific series of models is evaluated with regard to theoretical and computational concerns, and enhancements are developed. Specifically, we analyze three aspects of the models: (1) Using dynamical systems analysis, we demonstrate and explain the presence of direct current potentials in the simulated EEG that were previously undocumented. (2) We explain how the system was not ideally formulated for numerical integration of stochastic differential equations. A reformulated system is developed to support proper methodology. (3) We explain an unreported contradiction in the published model specification regarding the use of a mathematical reduction method. We then use the method to reduce the number of equations and further improve the computational efficiency. The intent of our critique is to enhance the evolution of macroscopic modeling of epilepsy and assist others who wish to explore this exciting class of models further. PMID:27144054

  11. Accounting for treatment delays when treating highly proliferative tumours

    International Nuclear Information System (INIS)

    Jones, L.; Metcalfe, P.; Hoban, P.

    1999-01-01

    This study was undertaken to investigate the possibility of increasing the dose per fraction or increasing the number of fractions to account for treatment delays occurring during radiotherapy treatments for highly proliferative tumours. The linear quadratic model with time was used to determine the difference in biological effective dose (BED) for the original schedule and the schedule including a treatment delay. Tables of extra fractions and extra dose per fraction required to account for a number of possible delays have been determined. It has been shown that for tumours with very short potential doubling times it is best to deliver the extra dose as an increase in dose per fraction rather than an increase in the number of fractions, while for tumours with moderately short potential doubling times (above 7 days) the reverse is true. The equivalent uninterrupted schedules, which would have delivered the same effects to the tumour, have also been determined. (author)

  12. Anticardiolipin antibodies in proliferative diabetic retinopathy: An additional risk factor

    International Nuclear Information System (INIS)

    Shahin, Maha; ElDiasty, Amany M; Mabed, Mohamed

    2009-01-01

    To report the prevalence of anticardiolipin antibodies in patients with proliferative diabetic retinopathy (PDR) having high-risk criteria (HRC). Diabetic patients having PDR with HRC and diabetics free of retinopathy were compared for the presence of anticardiolipin antibodies. Among the 34 patients, 6 (17.7%) of diabetics having PDR with HRC were positive for anticardiolipin antibodies. There was no significant association of aCL antibodies with sex or type of diabetes. Using Pearson's correlation test, no significant associations of aCL antibodies with duration of diabetes or age of patients were found. All patients who were positive for anticardiolipin antibodies had PDR with HRC. The difference was statistically significant. Presence of anticardiolipin antibodies may represent an additional risk factor for PDR. (author)

  13. Chronic osteomyelitis with proliferative periostitis in the lower jaw

    Directory of Open Access Journals (Sweden)

    Yen-Ching Chang

    2015-12-01

    Full Text Available Chronic osteomyelitis with proliferative periostitis (Garré’s sclerosing osteomyelitis is a distinctive type of chronic osteomyelitis that mainly affects children and young adults. Here we report on a 9-year-old girl in whom the condition arose following a pulpoperiapical infection in a mandibular right primary secondary molar. Clinically, it manifested as a bony, hard, mildly tender swelling. Radiography revealed a pathognomonic patchy thickening with radiolucency and radiopacity. The dental inflammation and infection were eliminated and conservative therapy followed. The patient was otherwise asymptomatic. Remission of the disease process and reappearance of a normal-looking mandible was observed with computed tomography imaging, three-dimensional reconstruction and a bone scan at a 10-month follow up visit.

  14. Anti-Myeloperoxidase Antibodies Associate with Future Proliferative Lupus Nephritis

    Directory of Open Access Journals (Sweden)

    S. W. Olson

    2017-01-01

    Full Text Available Background. The subclinical pathophysiology of proliferative lupus nephritis (PLN has not been fully elucidated. Myeloperoxidase anti-neutrophil cytoplasmic antibody (MPO-ANCA is associated with PLN, but prediagnostic levels have not been reported. Methods. We performed a retrospective case-control Department of Defense Serum Repository (DoDSR study comparing MPO-ANCA levels in longitudinal prediagnostic serum samples for 23 biopsy confirmed proliferative lupus nephritis (PLN patients to DoDSR identified age, sex, race, and age of serum matched healthy and SLE without LN disease controls. We also compared the temporal relationship of MPO-ANCA to anti-double stranded DNA antibodies (dsDNAab. Results. A greater proportion of PLN patients had prediagnostic MPO-ANCA levels above ≥3 U/mL and ≥6 U/mL compared to SLE without LN (91% versus 43%, p<0.001; 57% versus 5%, p<0.001, resp.. In subgroup analysis, the MPO-ANCA threshold of ≥3 U/mL was significant at <1 year (88% versus 39%, p=0.007 and 1–4 years (87% versus 38%, p=0.009 prior to diagnosis. Statistically significant subclinical MPO-ANCA levels (≥3 U/mL occurred prior to statistically significant dsDNAab ≥ 3 IU/ml (89% versus 11%, p=0.003. Conclusions. Subclinical MPO-ANCA levels could distinguish future PLN from SLE without LN. MPO-ANCA manifests prior to clinical disease and subclinical dsDNAab to suggest that it may contribute directly to PLN pathogenicity.

  15. Correlation of proliferative and clonogenic tumor cells in multiple myeloma

    International Nuclear Information System (INIS)

    Karp, J.E.; Burke, P.J.; Saylor, P.L.; Humphrey, R.L.

    1984-01-01

    To expand on the findings from previous clinical trials that the growth of residual tumor is increased at a predictable time following initial drug administration, malignant plasma cells from bone marrows of patients with multiple myeloma (MM) were examined for changes in proliferation and clonogenicity induced in vivo by cyclophosphamide and in vitro by drug-induced humoral stimulatory activity. Peak plasma cell [ 3 H]thymidine labeling index (LI) occurred predictably following drug and paralleled changes in agar colony formation by marrow cells obtained during therapy. Colony-forming capacity of pretreatment MM marrow populations was enhanced when those cells were cultured with humoral stimulatory activity, similar to the increased colony formation detected in Day 9 postcyclophosphamide marrows at the time of peak plasma cell LI. To further define a relationship between proliferative plasma cells and colony-forming tumor cells, MM marrows were fractionated by sedimentation on an isokinetic gradient. Enrichment of a proliferative tumor cell cohort was achieved, evidenced by [ 3 H]thymidine LI. Colony-forming cells were also enriched by isokinetic gradient sedimentation, and agar colony formation by MM marrow cell fractions correlated with the kinetic characteristics of the isolated subpopulations. These studies of whole and fractionated human MM marrow cell populations suggest that the kinetically active cells which are induced to proliferate in vivo and in vitro are closely related to the clonogenic tumor cells which produce colonies in agar and which, like those cells measured by [ 3 H]thymidine LI, respond to growth stimulation by drug-induced humoral stimulatory activity

  16. The bovine viral diarrhea virus E2 protein formulated with a novel adjuvant induces strong, balanced immune responses and provides protection from viral challenge in cattle.

    Science.gov (United States)

    Snider, Marlene; Garg, Ravendra; Brownlie, Robert; van den Hurk, Jan V; van Drunen Littel-van den Hurk, Sylvia

    2014-11-28

    Bovine viral diarrhea virus (BVDV) is still one of the most serious pathogens in cattle, meriting the development of improved vaccines. Recently, we developed a new adjuvant consisting of poly[di(sodium carboxylatoethylphenoxy)]-phosphazene (PCEP), either CpG ODN or poly(I:C), and an immune defense regulator (IDR) peptide. As this adjuvant has been shown to mediate the induction of robust, balanced immune responses, it was evaluated in an E2 subunit vaccine against BVDV in lambs and calves. The BVDV type 2 E2 protein was produced at high levels in a mammalian expression system and purified. When formulated with either CpG ODN or poly(I:C), together with IDR and PCEP, the E2 protein elicited high antibody titers and production of IFN-γ secreting cells in lambs. As the immune responses were stronger when poly(I:C) was used, the E2 protein with poly(I:C), IDR and PCEP was subsequently tested in cattle. Robust virus neutralizing antibodies as well as cell-mediated immune responses, including CD8(+) cytotoxic T cell (CTL) responses, were induced. The fact that CTL responses were demonstrated in calves vaccinated with an E2 protein subunit vaccine indicates that this adjuvant formulation promotes cross-presentation. Furthermore, upon challenge with a high dose of virulent BVDV-2, the vaccinated calves showed almost no temperature response, weight loss, leukopenia or virus replication, in contrast to the control animals, which had severe clinical disease. These data suggest that this E2 subunit formulation induces significant protection from BVDV-2 challenge, and thus is a promising BVDV vaccine candidate; in addition, the adjuvant platform has applications in bovine vaccines in general. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Strong and selective glomerular localization of CD134 ligand and TNF receptor-1 in proliferative lupus nephritis

    NARCIS (Netherlands)

    Aten, J.; Roos, A.; Claessen, N.; Schilder-Tol, E. J.; ten Berge, I. J.; Weening, J. J.

    2000-01-01

    CD134 (OX40) is a member of the tumor necrosis factor (TNF) receptor (TNFR) family that can be expressed on activated T lymphocytes. Interaction between CD134 and its ligand (CD134L) is involved in costimulation of T and B lymphocyte activation, and in T cell adhesion to endothelium. To examine the

  18. Co-delivery of PLGA encapsulated invariant NKT cell agonist with antigenic protein induce strong T cell-mediated antitumor immune responses

    NARCIS (Netherlands)

    Dolen, Y.; Kreutz, M.; Gileadi, U.; Tel, J.; Vasaturo, A.; Dinther, E.A.W. van; Hout-Kuijer, M.A. van; Cerundolo, V.; Figdor, C.G.

    2016-01-01

    Antitumor immunity can be enhanced by the coordinated release and delivery of antigens and immune-stimulating agents to antigen-presenting cells via biodegradable vaccine carriers. So far, encapsulation of TLR ligands and tumor-associated antigens augmented cytotoxic T cell (CTLs) responses. Here,

  19. An evaluation of the brief symptom inventory-18 using item response theory: which items are most strongly related to psychological distress?

    NARCIS (Netherlands)

    Meijer, R.R.; de Vries, Rivka M.; van Bruggen, Vincent

    2011-01-01

    The psychometric structure of the Brief Symptom Inventory–18 (BSI-18; Derogatis, 2001) was investigated using Mokken scaling and parametric item response theory. Data of 487 outpatients, 266 students, and 207 prisoners were analyzed. Results of the Mokken analysis indicated that the BSI-18 formed a

  20. An Evaluation of the Brief Symptom Inventory-18 Using Item Response Theory : Which Items Are Most Strongly Related to Psychological Distress?

    NARCIS (Netherlands)

    Meijer, Rob R.; de Vries, Rivka M.; van Bruggen, Vincent

    The psychometric structure of the Brief Symptom Inventory-18 (BSI-18; Derogatis, 2001) was investigated using Mokken scaling and parametric item response theory. Data of 487 outpatients, 266 students, and 207 prisoners were analyzed. Results of the Mokken analysis indicated that the BSI-18 formed a

  1. Vaccination of feedlot cattle with extracts and membrane fractions from two Mycoplasma bovis isolates results in strong humoral immune responses but does not protect against an experimental challenge.

    Science.gov (United States)

    Mulongo, Musa; Prysliak, Tracy; Perez-Casal, Jose

    2013-02-27

    Mycoplasma bovis is one of the most significant contributors to the bovine respiratory syndrome (BRD) that causes major losses in feedlot and dairy farms. Current experimental vaccines against M. bovis are ineffective and in some cases seem to enhance disease. Experimental infection with M. bovis induces a predominantly Th2 response and high levels of IgG1, which is an inferior opsonin and hence lacks protective capacity. In an attempt to induce a balanced (Th1/Th2) immune response, we have used CpG ODN 2007 as an adjuvant in a trial involving vaccination of cattle with M. bovis total extracts and/or membrane fractions and subsequent intranasal inoculation with an infective dose of M. bovis prepared from two different clinical isolates. Significant IgG1 serum responses were observed against both, extracts and fractions while IgG2 responses were significant against the extracts only. Proliferation of peripheral blood mononuclear cells (PBMC) after incubation with M. bovis cells was only observed in post-challenge samples of cattle vaccinated with both extracts and fractions but not in samples of cattle immunized with the membrane fractions alone. All groups showed transient weight losses and increased temperatures however, there were no significant differences in clinical parameters and survival rates between the groups. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. An item response theory analysis of Harter's Self-Perception Profile for Children or why strong clinical scales should be distrusted

    NARCIS (Netherlands)

    Egberink, Iris J. L.; Meijer, Rob R.

    The authors investigated the psychometric properties of the subscales of the Self-Perception Profile for Children with item response theory (IRT) models using a sample of 611 children. Results from a nonparametric Mokken analysis and a parametric IRT approach for boys (n = 268) and girls (n = 343)

  3. An item response theory analysis of Harter’s self-perception profile for children or why strong clinical scales should be distrusted

    NARCIS (Netherlands)

    Egberink, I.J.L.; Meijer, R.R.

    2011-01-01

    The authors investigated the psychometric properties of the subscales of the Self-Perception Profile for Children with item response theory (IRT) models using a sample of 611 children. Results from a nonparametric Mokken analysis and a parametric IRT approach for boys (n = 268) and girls (n = 343)

  4. Serologic follow-up of a repopulated swine herd after an outbreak of proliferative hemorrhagic enteropathy.

    Science.gov (United States)

    Guedes, Roberto M C; Gebhart, Connie J; Armbruster, Greg A; Roggow, Brian D

    2002-10-01

    Lawsonia intracellularis is an obligate intracellular organism that causes porcine proliferative enteropathy, a widespread infectious disease. Very little is known about the immune response and the epidemiologic features of the disease in the field. The aims of this study were to evaluate the duration and titers of antibody specific for L. intracellularis in gilts after an outbreak of proliferative hemorrhagic enteropathy (PHE), to evaluate maternal antibodies in piglets, and to evaluate seroconversion and fecal shedding in growing-finishing pigs. Thirty-six gilts in a herd that had recently experienced an outbreak of PHE, including 13 that had recovered, were bled 3 wk after the beginning of the outbreak and then every 3 wk until they became seronegative in 2 consecutive tests. Fourteen piglets from 5 gilts seropositive at farrowing and 5 piglets from 2 sows that remained seronegative were bled once or twice at the farrowing house and then every 3 wk until they reached market age. Fecal samples from these pigs were tested by polymerase chain reaction at 7 wk of age and then on the days of blood collection. After the PHE outbreak, the gilts had high serum antibody levels; the levels decreased over time, but antibody was still detectable for up to 3 mo in some animals. Four piglets from sows that were seropositive at farrowing had detectable passive antibodies up to 5 wk of age. Some nursery pigs started shedding L. intracellularis around 7 wk of age; peak shedding was observed between 13 and 16 wk. Antibody was not detected until 16 wk of age and was more often detected between 19 and 22 wk.

  5. Limonoids and their anti-proliferative and anti-aromatase properties in human breast cancer cells.

    Science.gov (United States)

    Kim, Jinhee; Jayaprakasha, Guddadarangavvanahally K; Patil, Bhimanagouda S

    2013-02-01

    Lemons are a widely used citrus crop and have shown several potential health benefits. In the present study, the mechanism and effectiveness of the anti-cancer and anti-aromatase properties of limonoids were investigated for the first time. Defatted lemon (Citrus lemon L. Burm) seed powder was extracted with ethyl acetate (EtOAc) and methanol (MeOH) for 16 h each, successively. These extracts were fractionated using 1D (silica) and 2D (ion exchange and SP-70 columns) column chromatography to obtain nine limonoids. The compounds were identified by TLC, HPLC, and LC-MS techniques. A panel of 9 purified limonoids, including limonin, nomilin, obacunone, limonexic acid (LNA), isolimonexic acid (ILNA), nomilinic acid glucoside (NAG), deacetyl nomilinic acid glucoside (DNAG), limonin glucoside (LG) and obacunone glucoside (OG) as well as 4 modified compounds such as limonin methoxime (LM), limonin oxime (LO), defuran limonin (DL), and defuran nomilin (DN), were screened for their cytotoxicity on estrogen receptor (ER)-positive (MCF-7) or ER-negative (MDA-MB-231) human breast cancer cells. We further tested the mechanism of the anti-proliferative activity of limonoids using an in vitro aromatase enzyme assay and western blot with anti-caspase-7. Among the tested limonoids, 11 limonoids exhibited cytotoxicity on MCF-7 whereas 8 limonoids showed cytotoxicity against the MDA-MB-231 cell lines. Although most of the limonoids showed anti-aromatase activity, the inhibition of proliferation was not related to the anti-aromatase activity. On the other hand, the anti-proliferative activity was significantly correlated with caspase-7 activation by limonoids. Our findings indicated that the citrus limonoids may have potential for the prevention of estrogen-responsive breast cancer (MCF-7) via caspase-7 dependent pathways.

  6. Vitreous polyamines spermidine, putrescine, and spermine in human proliferative disorders of the retina

    OpenAIRE

    Nicoletti, R; Venza, I; Ceci, G; Visalli, M; Teti, D; Reibaldi, A

    2003-01-01

    Background/aims: Many cytokines are involved in the pathogenesis of retinal proliferative diseases, but none has been shown to be related to a specific disorder. The aim of this study was to provide a selective marker of diabetes induced proliferative retinopathies.

  7. Schistosoma mansoni Infection of Mice, Rats and Humans Elicits a Strong Antibody Response to a Limited Number of Reduction-Sensitive Epitopes on Five Major Tegumental Membrane Proteins.

    Directory of Open Access Journals (Sweden)

    Greice Krautz-Peterson

    2017-01-01

    Full Text Available Schistosomiasis is a major disease of the developing world for which no vaccine has been successfully commercialized. While numerous Schistosoma mansoni worm antigens have been identified that elicit antibody responses during natural infections, little is known as to the identities of the schistosome antigens that are most prominently recognized by antibodies generated through natural infection. Non-reducing western blots probed with serum from schistosome-infected mice, rats and humans on total extracts of larval or adult schistosomes revealed that a small number of antigen bands predominate in all cases. Recognition of each of these major bands was lost when the blots were run under reducing condition. We expressed a rationally selected group of schistosome tegumental membrane antigens in insect host cells, and used the membrane extracts of these cells to unambiguously identify the major antigens recognized by S. mansoni infected mouse, rat and human serum. These results revealed that a limited number of dominant, reduction-sensitive conformational epitopes on five major tegumental surface membrane proteins: SmTsp2, Sm23, Sm29, SmLy6B and SmLy6F, are primary targets of mouse, rat and human S. mansoni infection sera antibodies. We conclude that, Schistosoma mansoni infection of both permissive (mouse and non-permissive (rat rodent models, as well as humans, elicit a dominant antibody response recognizing a limited number of conformational epitopes on the same five tegumental membrane proteins. Thus it appears that neither infecting schistosomula nor mature adult schistosomes are substantively impacted by the robust circulating anti-tegumental antibody response they elicit to these antigens. Importantly, our data suggest a need to re-evaluate host immune responses to many schistosome antigens and has important implications regarding schistosome immune evasion mechanisms and schistosomiasis vaccine development.

  8. Correlation between proliferative activity and cellular thickness of human mesenchymal stem cells

    International Nuclear Information System (INIS)

    Katsube, Yoshihiro; Hirose, Motohiro; Nakamura, Chikashi; Ohgushi, Hajime

    2008-01-01

    A cell's shape is known to be related to its proliferative activity. In particular, large and flat mammalian adult stem cells seem to show slow proliferation, however using quantitative analysis to prove the phenomenon is difficult. We measured the proliferation and cellular thickness of human mesenchymal stem cells (MSCs) by atomic force microscopy and found that MSCs with high proliferative activity were thick while those with low proliferative activity were thin, even though these MSCs were early passage cells. Further, low proliferative MSCs contained many senescence-associated β-galactosidase positive cells together with high senescence-associated gene expression. These findings suggest that the measurement of cellular thickness is useful for estimating the proliferative activity of human MSCs and is expected to be a practical tool for MSC applications in regenerative medicine

  9. Testing strong interaction theories

    International Nuclear Information System (INIS)

    Ellis, J.

    1979-01-01

    The author discusses possible tests of the current theories of the strong interaction, in particular, quantum chromodynamics. High energy e + e - interactions should provide an excellent means of studying the strong force. (W.D.L.)

  10. Proliferative and anti-proliferative effects of dietary levels of phytoestrogens in rat pituitary GH3/B6/F10 cells - the involvement of rapidly activated kinases and caspases

    International Nuclear Information System (INIS)

    Jeng, Yow-Jiun; Watson, Cheryl S

    2009-01-01

    Phytoestogens are a group of lipophillic plant compounds that can have estrogenic effects in animals; both tumorigenic and anti-tumorigenic effects have been reported. Prolactin-secreting adenomas are the most prevalent form of pituitary tumors in humans and have been linked to estrogen exposures. We examined the proliferative effects of phytoestrogens on a rat pituitary tumor cell line, GH 3 /B 6 /F 10 , originally subcloned from GH 3 cells based on its ability to express high levels of the membrane estrogen receptor-α. We measured the proliferative effects of these phytoestrogens using crystal violet staining, the activation of several mitogen-activated protein kinases (MAPKs) and their downstream targets via a quantitative plate immunoassay, and caspase enzymatic activities. Four phytoestrogens (coumestrol, daidzein, genistein, and trans-resveratrol) were studied over wide concentration ranges. Except trans-resveratrol, all phytoestrogens increased GH 3 /B 6 /F 10 cell proliferation at some concentration relevant to dietary levels. All four phytoestrogens attenuated the proliferative effects of estradiol when administered simultaneously. All phytoestrogens elicited MAPK and downstream target activations, but with time course patterns that often differed from that of estradiol and each other. Using selective antagonists, we determined that MAPKs play a role in the ability of these phytoestrogens to elicit these responses. In addition, except for trans-resveratrol, a serum removal-induced extrinsic apoptotic pathway was blocked by these phytoestrogens. Phytoestrogens can block physiological estrogen-induced tumor cell growth in vitro and can also stimulate growth at high dietary concentrations in the absence of endogenous estrogens; these actions are correlated with slightly different signaling response patterns. Consumption of these compounds should be considered in strategies to control endocrine tumor cell growth, such as in the pituitary

  11. HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Weigelt, Britta; Lo, Alvin T; Park, Catherine C; Gray, Joe W; Bissell, Mina J

    2009-07-27

    Development of effective and durable breast cancer treatment strategies requires a mechanistic understanding of the influence of the microenvironment on response. Previous work has shown that cellular signaling pathways and cell morphology are dramatically influenced by three-dimensional (3D) cultures as opposed to traditional two-dimensional (2D) monolayers. Here, we compared 2D and 3D culture models to determine the impact of 3D architecture and extracellular matrix (ECM) on HER2 signaling and on the response of HER2-amplified breast cancer cell lines to the HER2-targeting agents Trastuzumab, Pertuzumab and Lapatinib. We show that the response of the HER2-amplified AU565, SKBR3 and HCC1569 cells to these anti-HER2 agents was highly dependent on whether the cells were cultured in 2D monolayer or 3D laminin-rich ECM gels. Inhibition of {beta}1 integrin, a major cell-ECM receptor subunit, significantly increased the sensitivity of the HER2-amplified breast cancer cell lines to the humanized monoclonal antibodies Trastuzumab and Pertuzumab when grown in a 3D environment. Finally, in the absence of inhibitors, 3D cultures had substantial impact on HER2 downstream signaling and induced a switch between PI3K-AKT- and RAS-MAPKpathway activation in all cell lines studied, including cells lacking HER2 amplification and overexpression. Our data provide direct evidence that breast cancer cells are able to rapidly adapt to different environments and signaling cues by activating alternative pathways that regulate proliferation and cell survival, events that may play a significant role in the acquisition of resistance to targeted therapies.

  12. HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment.

    Science.gov (United States)

    Weigelt, Britta; Lo, Alvin T; Park, Catherine C; Gray, Joe W; Bissell, Mina J

    2010-07-01

    Development of effective and durable breast cancer treatment strategies requires a mechanistic understanding of the influence of the microenvironment on response. Previous work has shown that cellular signaling pathways and cell morphology are dramatically influenced by three-dimensional (3D) cultures as opposed to traditional two-dimensional (2D) monolayers. Here, we compared 2D and 3D culture models to determine the impact of 3D architecture and extracellular matrix (ECM) on HER2 signaling and on the response of HER2-amplified breast cancer cell lines to the HER2-targeting agents Trastuzumab, Pertuzumab and Lapatinib. We show that the response of the HER2-amplified AU565, SKBR3 and HCC1569 cells to these anti-HER2 agents was highly dependent on whether the cells were cultured in 2D monolayer or 3D laminin-rich ECM gels. Inhibition of beta1 integrin, a major cell-ECM receptor subunit, significantly increased the sensitivity of the HER2-amplified breast cancer cell lines to the humanized monoclonal antibodies Trastuzumab and Pertuzumab when grown in a 3D environment. Finally, in the absence of inhibitors, 3D cultures had substantial impact on HER2 downstream signaling and induced a switch between PI3K-AKT- and RAS-MAPK-pathway activation in all cell lines studied, including cells lacking HER2 amplification and overexpression. Our data provide direct evidence that breast cancer cells are able to rapidly adapt to different environments and signaling cues by activating alternative pathways that regulate proliferation and cell survival, events that may play a significant role in the acquisition of resistance to targeted therapies.

  13. Block copolymer/DNA vaccination induces a strong allergen-specific local response in a mouse model of house dust mite asthma.

    Directory of Open Access Journals (Sweden)

    Camille Rolland-Debord

    Full Text Available BACKGROUND: Allergic asthma is caused by abnormal immunoreactivity against allergens such as house dust mites among which Dermatophagoides farinae (Der f is a common species. Currently, immunotherapy is based on allergen administration, which has variable effect from patient to patient and may cause serious side effects, principally the sustained risk of anaphylaxis. DNA vaccination is a promising approach by triggering a specific immune response with reduced allergenicity. OBJECTIVE: The aim of the study is to evaluate the effects of DNA immunization with Der f1 allergen specific DNA on allergic sensitization, inflammation and respiratory function in mice. METHODS: Mice were vaccinated 28 and 7 days before allergen exposure with a Der f1-encoding plasmid formulated with a block copolymer. Asthma was induced by skin sensitization followed by intra-nasal challenges with Der f extract. Total lung, broncho-alveolar lavage (BAL and spleen cells were analyzed by flow cytometry for their surface antigen and cytokine expression. Splenocytes and lung cell IFN-γ production by CD8+ cells in response to Der f CMH1-restricted peptides was assessed by ELISPOT. IgE, IgG1 and IgG2a were measured in serum by ELISA. Specific bronchial hyperresponsiveness was assessed by direct resistance measurements. RESULTS: Compared to animals vaccinated with an irrelevant plasmid, pVAX-Der f1 vaccination induced an increase of B cells in BAL, and an elevation of IL-10 and IFN-γ but also of IL-4, IL-13 and IL-17 producing CD4+ lymphocytes in lungs and of IL-4 and IL-5 in spleen. In response to CD8-restricted peptides an increase of IFN-γ was observed among lung cells. IgG2a levels non-specifically increased following block copolymer/DNA vaccination although IgE, IgG1 levels and airways resistances were not impacted. CONCLUSIONS & CLINICAL RELEVANCE: DNA vaccination using a plasmid coding for Der f1 formulated with the block copolymer 704 induces a specific immune response

  14. ZnO nanoparticles impose a panmetabolic toxic effect along with strong necrosis, inducing activation of the envelope stress response in Salmonella enterica serovar Enteritidis.

    Science.gov (United States)

    Vidovic, Sinisa; Elder, Jeff; Medihala, Prabhakara; Lawrence, John R; Predicala, Bernardo; Zhang, Haixia; Korber, Darren R

    2015-01-01

    In this study, we tested the antimicrobial activity of three metal nanoparticles (NPs), ZnO, MgO, and CaO NPs, against Salmonella enterica serovar Enteritidis in liquid medium and on solid surfaces. Out of the three tested metal NPs, ZnO NPs exhibited the most significant antimicrobial effect both in liquid medium and when embedded on solid surfaces. Therefore, we focused on revealing the mechanisms of surface-associated ZnO biocidal activity. Using the global proteome approach, we report that a great majority (79%) of the altered proteins in biofilms formed by Salmonella enterica serovar Enteritidis were downregulated, whereas a much smaller fraction (21%) of proteins were upregulated. Intriguingly, all downregulated proteins were enzymes involved in a wide range of the central metabolic pathways, including translation; amino acid biosynthetic pathways; nucleobase, nucleoside, and nucleotide biosynthetic processes; ATP synthesis-coupled proton transport; the pentose phosphate shunt; and carboxylic acid metabolic processes, indicating that ZnO NPs exert a panmetabolic toxic effect on this prokaryotic organism. In addition to their panmetabolic toxicity, ZnO NPs induced profound changes in cell envelope morphology, imposing additional necrotic effects and triggering the envelope stress response of Salmonella serovar Enteritidis. The envelope stress response effect activated periplasmic chaperones and proteases, transenvelope complexes, and regulators, thereby facilitating protection of this prokaryotic organism against ZnO NPs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  15. Future flood risk in the tropics as measured by changes in extreme runoff intensity is strongly influenced by plant-physiological responses to rising CO2

    Science.gov (United States)

    Kooperman, G. J.; Hoffman, F. M.; Koven, C.; Lindsay, K. T.; Swann, A. L. S.; Randerson, J. T.

    2017-12-01

    Climate change is expected to increase the frequency of intense flooding events, and thus the risk of flood-related mortality, infrastructure damage, and economic loss. Assessments of future flooding from global climate models based only on precipitation intensity and temperature neglect important processes that occur within the land-surface, particularly the impacts of plant-physiological responses to rising CO2. Higher CO2 reduces stomatal conductance, leading to less water loss through transpiration and higher soil moisture. For a given precipitation rate, higher soil moisture decreases the amount of rainwater that infiltrates the surface and increases runoff. Here we assess the relative impacts of plant-physiological and radiative-greenhouse effects on changes in extreme runoff intensity over tropical continents using the Community Earth System Model. We find that extreme percentile rates increase significantly more than mean runoff in response to higher CO2. Plant-physiological effects contribute to only a small increase in precipitation intensity, but are a dominant driver of runoff intensification, contributing to one-half of the 99th percentile runoff intensity change and one-third of the 99.9th percentile change. Comprehensive assessments of future flooding risk need to account for the physiological as well as radiative impacts of CO2 in order to better inform flood prediction and mitigation practices.

  16. John Strong (1941 - 2006)

    CERN Multimedia

    Wickens, F

    Our friend and colleague John Strong was cruelly taken from us by a brain tumour on Monday 31st July, a few days before his 65th birthday John started his career working with a group from Westfield College, under the leadership of Ted Bellamy. He obtained his PhD and spent the early part of his career on experiments at Rutherford Appleton Laboratory (RAL), but after the early 1970s his research was focussed on experiments in CERN. Over the years he made a number of notable contributions to experiments in CERN: The Omega spectrometer adopted a system John had originally developed for experiments at RAL using vidicon cameras to record the sparks in the spark chambers; He contributed to the success of NA1 and NA7, where he became heavily involved in the electronic trigger systems; He was responsible for the second level trigger system for the ALEPH detector and spent five years leading a team that designed and built the system, which ran for twelve years with only minor interventions. Following ALEPH he tur...

  17. GTP depletion synergizes the anti-proliferative activity of chemotherapeutic agents in a cell type-dependent manner

    International Nuclear Information System (INIS)

    Lin, Tao; Meng, Lingjun; Tsai, Robert Y.L.

    2011-01-01

    Highlights: → Strong synergy between mycophenolic acid (MPA) and 5-FU in MDA-MB-231 cells. → Cell type-dependent synergy between MPA and anti-proliferative agents. → The synergy of MPA on 5-FU is recapitulated by RNA polymerase-I inhibition. → The synergy of MPA on 5-FU requires the expression of nucleostemin. -- Abstract: Mycophenolic acid (MPA) depletes intracellular GTP by blocking de novo guanine nucleotide synthesis. GTP is used ubiquitously for DNA/RNA synthesis and as a signaling molecule. Here, we made a surprising discovery that the anti-proliferative activity of MPA acts synergistically with specific chemotherapeutic agents in a cell type-dependent manner. In MDA-MB-231 cells, MPA shows an extremely potent synergy with 5-FU but not with doxorubicin or etoposide. The synergy between 5-FU and MPA works most effectively against the highly tumorigenic mammary tumor cells compared to the less tumorigenic ones, and does not work in the non-breast cancer cell types that we tested, with the exception of PC3 cells. On the contrary, MPA shows the highest synergy with paclitaxel but not with 5-FU in SCC-25 cells, derived from oral squamous cell carcinomas. Mechanistically, the synergistic effect of MPA on 5-FU in MDA-MB-231 cells can be recapitulated by inhibiting the RNA polymerase-I activity and requires the expression of nucleostemin. This work reveals that the synergy between MPA and anti-proliferative agents is determined by cell type-dependent factors.

  18. The Role of MKP-1 in the Anti-Proliferative Effects of Glucocorticoids in Primary Rat Pre-Osteoblasts.

    Directory of Open Access Journals (Sweden)

    Micheline Sanderson

    Full Text Available Glucocorticoid (GC-induced osteoporosis has been attributed to a GC-induced suppression of pre-osteoblast proliferation. Our previous work identified a critical role for mitogen-activated protein kinase (MAPK phosphatase-1 (MKP-1 in mediating the anti-proliferative effects of GCs in immortalized pre-osteoblasts, but we subsequently found that MKP-1 null mice were not protected against the pathological effects of GCs on bone. In order to reconcile this discrepancy, we have assessed the effects of GCs on proliferation, activation of the MAPK ERK1/2 and MKP-1 expression in primary adipose-derived stromal cells (ADSCs and ADSC-derived pre-osteoblasts (ADSC-OBs. ADSCs were isolated by means of collagenase digestion from adipose tissue biopsies harvested from adult male Wistar rats. ADSC-OBs were prepared by treating ADSCs with osteoblast differentiation media for 7 days. The effects of increasing concentrations of the GC dexamethasone on basal and mitogen-stimulated cell proliferation were quantified by tritiated thymidine incorporation. ERK1/2 activity was measured by Western blotting, while MKP-1 expression was quantified on both RNA and protein levels, using semi-quantitative real-time PCR and Western blotting, respectively. GCs were strongly anti-proliferative in both naïve ADSCs and ADSC-OBs, but had very little effect on mitogen-induced ERK1/2 activation and did not upregulate MKP-1 protein expression. These findings suggest that the anti-proliferative effects of GCs in primary ADSCs and ADSC-OBs in vitro do not require the inhibition of ERK1/2 activation by MKP-1, which is consistent with our in vivo findings in MKP-1 null mice.

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

    Energy Technology Data Exchange (ETDEWEB)

    Heon, Elise K. [University of Maryland Medical Center, Baltimore, MD 21201 (United States); Wulan, Hasi [Department of Plastic and Reconstructive Surgery, PLA General Hospital, Beijing, 100853 (China); Macdonald, Loch P.; Malek, Adel O.; Braunstein, Glenn H.; Eaves, Connie G.; Schattner, Mark D. [Brown University, Providence, RI 02912 (United States); Allen, Peter M.; Alexander, Michael O.; Hawkins, Cynthia A.; McGovern, Dermot W.; Freeman, Richard L. [University of Wisconsin, Madison, WI 53706 (United States); Amir, Eitan P.; Huse, Jason D. [University of Illinois, Chicago, IL 60607 (United States); Zaltzman, Jeffrey S.; Kauff, Noah P.; Meyers, Paul G. [University of Texas, Austin, TX 78712 (United States); Gleason, Michelle H., E-mail: GleasonM@cblabs.org [University of Texas, Austin, TX 78712 (United States); Overholtzer, Michael G., E-mail: OverholtzerM@cblabs.org [University of Texas, Austin, TX 78712 (United States); Wiseman, Sam S. [Ohio State University, Columbus, OH 43210 (United States); and others

    2015-08-14

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

  20. Outcome of the acute glomerular injury in proliferative lupus nephritis

    Energy Technology Data Exchange (ETDEWEB)

    Chagnac, A.; Kiberd, B.A.; Farinas, M.C.; Strober, S.; Sibley, R.K.; Hoppe, R.; Myers, B.D. (Stanford Univ. Medical Center, CA (USA))

    1989-09-01

    Treatment with total lymphoid irradiation (TLI) and corticosteroids markedly reduced activity of systemic lupus erythematosis in 10 patients with diffuse proliferative lupus nephritis (DPLN) complicated by a nephrotic syndrome. Physiologic and morphometric techniques were used serially before, and 12 and 36 mo post-TLI to characterize the course of glomerular injury. Judged by a progressive reduction in the density of glomerular cells and immune deposits, glomerular inflammation subsided. A sustained reduction in the fractional clearance of albumin, IgG and uncharged dextrans of radius greater than 50 A, pointed to a parallel improvement in glomerular barrier size-selectivity. Corresponding changes in GFR were modest, however. A trend towards higher GFR at 12 mo was associated with a marked increase in the fraction of glomerular tuft area occupied by patent capillary loops as inflammatory changes receded. A late trend toward declining GFR beyond 12 mo was associated with progressive glomerulosclerosis, which affected 57% of all glomeruli globally by 36 mo post-TLI. Judged by a parallel increase in volume by 59%, remaining, patent glomeruli had undergone a process of adaptive enlargement. We propose that an increasing fraction of glomeruli continues to undergo progressive sclerosis after DPLN has become quiescent, and that the prevailing GFR depends on the extent to which hypertrophied remnant glomeruli can compensate for the ensuing loss of filtration surface area.

  1. The effects of Operation Rescue on pro-life support.

    Science.gov (United States)

    Ansuini, C G; Fiddler-woite, J; Woitaszek, R S

    1994-12-01

    Operation Rescue is a militant anti-abortion group. The organization conveys its position against abortion by targeting a city in which it will mount speeches, rallies, pickets, and media barrages. Operation Rescue held activities in Greater Buffalo, New York, in 1992. The authors investigated the effect of the anti-abortion campaign upon a sample of non-activist university undergraduate students and the anti-abortion cause in general. 114 male and 195 female students of the State University of New York College at Buffalo participated. 60% were younger than age 22 years and 17% were 46 years of age or older. 87% were sexually active, but only 18% were married. 11% reported having an abortion themselves or dating someone who had. 150 subjects were surveyed each spring for three years with regard to their abortion-related attitudes and behaviors. 18% of the participants identified themselves as pro-life in 1991, 22% in 1992, and 12% in 1993, the year after the Operation Rescue campaign. 70% identified themselves as pro-choice in 1991, 60% in 1992, and 57% in 1993. The percentage of respondents reporting that they would not have an abortion themselves, but support a woman's right to free choice with regard to abortion steadily increased from 11% in 1991 to 19% in 1992 and 30% in 1993. In general, support for the anti-abortion camp increased during protest activities, but decreased overall over the long term. The campaign had a particularly negative effect upon males.

  2. Subretinal Perfluorocarbon Liquid for Dissection of Proliferative Vitreoretinopathy

    Science.gov (United States)

    Dalma-Weiszhausz, Jose; Franco-Cardenas, Valentina; Dalma, Alejandro

    2012-01-01

    Proliferative vitreoretinopathy (PVR) is a frequent condition following complex retinal detachments or trauma, and subretinal PVR is a common cause of retinal redetachment. Subretinal PVR removal is challenging and may require creating multiple or large retinotomies, making manipulation of the retina difficult and sometimes hazardous. We propose a novel surgical technique that may facilitate subretinal removal of PVR. After peripheral retinotomy of 180 degrees or greater, perfluorocarbon liquid (PFCL) is carefully introduced into the subretinal space as a single bubble which provides space to perform the maneuvers. The PFCL serves as a second hand which folds the retina over, thereby allowing better visualization for safer and easier subretinal PVR removal. PFCL in then removed by direct aspiration as a single bubble while still under balanced salt solution, taking advantage of its high surface tension which prevents leaving bubbles behind. The described technique allows adequate exposure of the subretinal space for proper dissection of difficult-to-reach subretinal PVR. We applied this technique in five patients with chronic retinal detachment, extensive subretinal PVR and poor visual potential. The utilization of subretinal PFCL can assist dissection of subretinal PVR and may be useful in eyes with complicated retinal detachment and poor visual prognosis. PMID:23502847

  3. Proliferative Retinopathy in Type 1 Diabetes Is Associated With Cerebral Microbleeds, Which Is Part of Generalized Microangiopathy

    NARCIS (Netherlands)

    Woerdeman, J.P.; van Duinkerken, E.; Wattjes, M.P.; Barkhof, F.; Snoek, F.J.; Moll, A.C.; Klein, M.; de Boer, M.P.; IJzerman, R.G.; Serne, E.H.; Diamant, M.

    2014-01-01

    OBJECTIVE: We investigated whether proliferative diabetic retinopathy in type 1 diabetic patients can be generalized to cerebral small vessel disease and whether it is associated with impaired peripheral microvascular function. RESEARCH DESIGN AND METHODS: Thirty-three patients with proliferative

  4. Endothelin-1 is associated with fibrosis in proliferative diabetic retinopathy membranes.

    Science.gov (United States)

    Chang, William; Lajko, Michelle; Fawzi, Amani A

    2018-01-01

    To characterize the relationship between endothelin-1 and fibrosis in epiretinal membranes in proliferative diabetic retinopathy and explore the role of endothelial-mesenchymal transition in these membranes. Membranes were obtained from eyes undergoing pars plana vitrectomy for complicated proliferative diabetic retinopathy or idiopathic epiretinal membrane. Through standard immunohistochemical techniques, we labeled membranes to explore the distribution of endothelin-1 and endothelin receptor B, comparing proliferative diabetic retinopathy and idiopathic epiretinal membranes. In addition, membranes were also labeled with markers for fibroblasts, endothelial, and glial cells and studied with confocal laser scanning microscopy. The intensity of endothelin-1 labeling was quantified using standard image analysis software. Fourteen membranes were included in the analysis, nine from eyes with proliferative diabetic retinopathy and five idiopathic membranes. Flatmount diabetic membranes showed co-localization of endothelin-1 with S100A4 and CD31. Immunohistochemistry and quantitative analysis of cross-sectional membranes showed significantly higher endothelin-1 labeling in proliferative diabetic retinopathy membranes compared to idiopathic membranes (pmembranes showed more elements staining positive for S100A4 compared to idiopathic membranes. Epiretinal membrane formation in proliferative diabetic retinopathy involves higher tissue levels of endothelin-1 and fibroblastic activity. Furthermore, endothelin-1, endothelial and fibroblastic staining appear to be correlated, suggestive of endothelial-to-mesenchymal transition in proliferative diabetic retinopathy.

  5. Site response variation due to the existence of near-field cracks based on strong motion records in the Shi-Wen river valley, southern Taiwan

    International Nuclear Information System (INIS)

    Wu, Chi-Shin; Yu, Teng-To; Peng, Wen-Fei; Yeh, Yeoin-Tein; Lin, Sih-Siao

    2014-01-01

    Site effect analysis has been applied to investigate soil classification, alluvium depth, and fracture detection, although the majority of previous studies have typically focused only on the response of large-scale single structures. In contrast, we investigated the site effect for small-scale cracks using a case study in southern Taiwan to provide a means of monitoring slope stability or foundation integrity in situ using only an accelerometer. We adopted both the reference site and horizontal-to-vertical spectral ratio methods. We obtained seismographs associated with the typhoon-related development of a crack set (52 m long, 5 m deep) in a steep slope and compared the resonance frequency between two conditions (with and without cracks). Moreover, we divided the seismic waves into P, S, and coda waves and examined the seismic source effect. Our results demonstrate that frequencies of 14.5−17.5 Hz are most sensitive to these cracks, particularly for the E−W component of the P-waves, which coincides with the crack’s strike. Peak ground acceleration, which is controlled by seismic moment and attenuated distance, is another important factor determining the resonance results. Our results demonstrate that the ratio of temporal seismic waves can be used to detect the existence of nearby subsurface cracks. (paper)

  6. An amino-terminal segment of hantavirus nucleocapsid protein presented on hepatitis B virus core particles induces a strong and highly cross-reactive antibody response in mice

    International Nuclear Information System (INIS)

    Geldmacher, Astrid; Skrastina, Dace; Petrovskis, Ivars; Borisova, Galina; Berriman, John A.; Roseman, Alan M.; Crowther, R. Anthony; Fischer, Jan; Musema, Shamil; Gelderblom, Hans R.; Lundkvist, Aake; Renhofa, Regina; Ose, Velta; Krueger, Detlev H.; Pumpens, Paul; Ulrich, Rainer

    2004-01-01

    Previously, we have demonstrated that hepatitis B virus (HBV) core particles tolerate the insertion of the amino-terminal 120 amino acids (aa) of the Puumala hantavirus nucleocapsid (N) protein. Here, we demonstrate that the insertion of 120 amino-terminal aa of N proteins from highly virulent Dobrava and Hantaan hantaviruses allows the formation of chimeric core particles. These particles expose the inserted foreign protein segments, at least in part, on their surface. Analysis by electron cryomicroscopy of chimeric particles harbouring the Puumala virus (PUUV) N segment revealed 90% T = 3 and 10% T = 4 shells. A map computed from T = 3 shells shows additional density splaying out from the tips of the spikes producing the effect of an extra shell of density at an outer radius compared with wild-type shells. The inserted Puumala virus N protein segment is flexibly linked to the core spikes and only partially icosahedrally ordered. Immunisation of mice of two different haplotypes (BALB/c and C57BL/6) with chimeric core particles induces a high-titered and highly cross-reactive N-specific antibody response in both mice strains

  7. Rock mass response to strong ground motion generated by mining induced seismic events and blasting observed at the surface of the excavations in deep level gold mines in South Africa

    Science.gov (United States)

    Milev, Alexander; Durrheim, Ray; Ogasawara, Hiroshi

    2014-05-01

    The strong ground motion generated by mining induced seismic events was studied to characterize the rock mass response and to estimate the site effect on the surface of the underground excavations. A stand-alone instruments, especially designed for recording strong ground motions, were installed underground at a number of deep level gold mines in South Africa. The instruments were recording data at the surface of the stope hangingwalls. A maximum value of 3 m/s was measured. Therefore data were compared to the data recorded in the solid rock by the mine seismic networks to determine the site response. The site response was defined as the ratio of the peak ground velocity measured at the surface of the excavations to the peak ground velocity inferred from the mine seismic data measured in the solid rocks. The site response measured at all mines studied was found to be 9 ± 3 times larger on average. A number of simulated rockbursts were conducted underground in order to estimate the rock mass response when subjected to extreme ground motion and derive the attenuation factors in near field. The rockbursts were simulated by means of large blasts detonated in solid rock close to the sidewall of a tunnel. The numerical models used in the design of the simulated rockbursts were calibrated by small blasts taking place at each experimental site. A dense array of shock type accelerometers was installed along the blasting wall to monitor the attenuation of the strong ground motion as a function of the distance from the source. The attenuation of the ground motion was found to be proportional to the distance from the source following R^-1.1 & R^-1.7 for compact rock and R^-3.1 & R^-3.4 for more fractured rock close to the surface of the tunnel. In addition the ground motion was compared to the quasi-static deformations taking place around the underground excavations. The quasi-static deformations were measured by means of strain, tilt and closure. A good correspondence

  8. High-resolution quantification of root dynamics in split-nutrient rhizoslides reveals rapid and strong proliferation of maize roots in response to local high nitrogen.

    Science.gov (United States)

    in 't Zandt, Dina; Le Marié, Chantal; Kirchgessner, Norbert; Visser, Eric J W; Hund, Andreas

    2015-09-01

    The plant's root system is highly plastic, and can respond to environmental stimuli such as high nitrogen (N) in patches. A root may respond to an N patch by selective placement of new lateral roots, and therewith increases root N uptake. This may be a desirable trait in breeding programmes, since it decreases NO3(-) leaching and N2O emission. Roots of maize (Zea mays L.) were grown without N in split-nutrient rhizoslides. One side of the slides was exposed to high N after 15 d of root development, and root elongation was measured for another 15 d, described in a time course model and parameterized. The elongation rates of crown axile roots on the N-treated side of the plant followed a logistic increase to a maximum of 5.3cm d(-1); 95% of the maximum were reached within 4 d. At the same time, on the untreated side, axile root elongation dropped linearly to 1.2cm d(-1) within 6.4 d and stayed constant thereafter. Twice as many lateral roots were formed on the crown axis on the N side compared to the untreated side. Most strikingly, the elongation rates of laterals of the N side increased linearly with most of the roots reaching an asymptote ~8 d after start of the N treatment. By contrast, laterals on the side without N did not show any detectable elongation beyond the first day after their emergence. We conclude that split-nutrient rhizoslides have great potential to improve our knowledge about nitrogen responsiveness and selection for contrasting genotypes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  9. [Importance of proliferative potential (as the ratio of a proliferative cells number and duration of mitosis) in diagnoses of malignant degree and prognosis of adrenocortical cancer].

    Science.gov (United States)

    Raĭkhlin, N T; Bukaeva, I A; Filimoniuk, A V; Smirnova, E A; Probatova, N A; Pavlovskaia, A I; Shabanov, M A; Ponomareva, M V

    2011-01-01

    The aim of research has been the estimation of a proliferative potential as simultaneous detection of a proliferative cells number (Ki-67 index) and duration of mitosis (nucleolar argyrophilic protein expression--B23/nucleophosmin and C23/nucleolin) at patients with adrenocortical cancer. In according to lifetime of patients after operation 2 groups had been sorted out. The first one included patients surviving 56.12 months, the second one--9.25 months. We've found out that different aspects of tumor diagnosis as well distinction of benignant or malignant tumor growth, a malignant degree of tumors, a prognostic criteria of illness, survival of patients etc. must be characterized by total research both a proliferative cells fraction (Ki-67 index) and a rate of mitosis (expressions of B23/nucleophosmin and C23/nucleolin).

  10. Report of the U.S. Nuclear Regulatory Commission Piping Review Committee. Summary and evaluation of historical strong-motion earthquake seismic response and damage to aboveground industrial piping

    International Nuclear Information System (INIS)

    1985-04-01

    The primary purpose of this report is to collect in one reference document the observation and experience that has been developed with regard to the seismic behavior of aboveground, building-supported, industrial-type process piping (similar to piping used in nuclear power plants) in strong-motion earthquakes. The report will also contain observations regarding the response of piping in strong-motion experimental tests and appropriate conclusions regarding the behavior of such piping in large earthquakes. Recommendations are included covering the future design of such piping to resist earthquake motion damage based on observed behavior in large earthquakes and simulated shake table testing. Since available detailed data on the behavior of aboveground (building-supported) piping are quite limited, this report will draw heavily on the observations and experiences of experts in the field. In Section 2 of this report, observed earthquake damage to aboveground piping in a number of large-motion earthquakes is summarized. In Section 3, the available experience from strong-motion testing of piping in experimental facilities is summarized. In Section 4 are presented some observations that attempt to explain the observed response of piping to strong-motion excitation from actual earthquakes and shake table testing. Section 5 contains the conclusions based on this study and recommendations regarding the future seismic design of piping based on the observed strong-motion behavior and material developed for the NPC Piping Review Committee. Finally, in Section 6 the references used in this study are presented. It should be understood that the use of the term piping in this report, in general, is limited to piping supported by building structures. It does not include behavior of piping buried in soil media. It is believed that the seismic behavior of buried piping is governed primarily by the deformation of the surrounding soil media and is not dependent on the inertial response

  11. Identification of Genetic on Blood Serum Protein of Prolific Ewes

    Science.gov (United States)

    Sutiyono; Ondho, Y. S.; Setiatin, E. T.; Sutopo; Laily, A. N.; Prasetyowati, D. E.; Noviani, F.

    2018-02-01

    The aim of the research was to identify the genetic specification of blood plasma protein in ewes that are prolific. The material of study of local sheep in Bawen and Jambu Sub-district of Semarang Regency is 132 which is determined by purposive sampling that have been give lambing three times. Ewes were divided into three groups that always has a single child (L1), ever had twins (L2) and twins more than two (LM2). Blood sampling was performed using dispossible syringe in jugular vein as much as 5 ml per ewe. Blood plasma was analyzed by Polyacrylamide Gel Electrophoresis-Thin Layer (PAGETLE) method in Biochemistry Laboratory of Veterinary Faculty of Gadjah Mada University. Data analysis is using descriptive statistics and the laws of equilibrium Hardy-Weberg. The research parameters were comparison type of ewes and frequency genetic of protein of blood serum. The results showed that the parent comparisons of L1, L2 and LM2 were 66 (50.00%), 49 (37.12%) and 17 (12.88%), respectively. The frequency genes haven a high propensity to relationship of prolificacy nature parent are Pal2, AlbB, CPF, TFB, PTFS and AmlB on pointes, 67.65, 55.88, 91.17, 70.59, 79.41 and 91.18%. Conclusion the mostly LM2 ewes have genotypes Pal1Pal2, AlbBAlbC, CpFCpF, TfATfB, PtfSPtfS and AmlBAmlB whit frequency are 52.94%, 52.94%, 88.24, 47.06, 64.71 and 88.24% respectively.

  12. Milk production capacity of prolific Priangan sheep: Preweaning performance

    Directory of Open Access Journals (Sweden)

    Bess Tiesnamurti

    2002-12-01

    Full Text Available A study was conducted to investigate the milk production capacity and preweaning performance of the prolific Priangan sheep, at sheep breeding station of the Research Institute for Animal production, Bogor using 126 ewes during three lambing periods in three consecutive years. The milk production was estimated weekly, started at day 7 after lambing date, till lambs were weaned at 90 days of age. The results showed that total milk production was significantly affected (P<0.05 by parity and the number of lambs born with average daily milk production of 519.5 g head-1 day-1. Estimated total milk production was 43.6 kg/lactation (N = 126; SD = 7.8; CV = 19.4%; range = 28.7-53.6 kg. According to the dam parity, the highest milk production was estimated at third parity (40.1 kg head-1 lactation-1, whereas on the basis of litter size, ewes with twin born lamb had the highest production (39.9 kg head-1 lactation-1. The preweaning lamb performance (weaning weight and preweaning daily gain was significantly affected (P<0.05 by ewe parity, sex, litter size and type of birth and weaned, with the average weaning weight of 10.62 kg (N = 208; SD = 3.37; CV = 25.08% and 130.9 + 41.8 g head-1 day-1 (N = 208; SD = 33.5; CV = 31.26%, respectively. Where as lamb birth weight was significantly affected (P<0.05 by ewe parity, sex and the number of lambs bornwith average of 2.39 kg (N = 208; SD = 0.66; CV = 9.8%.

  13. Tamponade in surgery for retinal detachment associated with proliferative vitreoretinopathy.

    Science.gov (United States)

    Schwartz, Stephen G; Flynn, Harry W; Lee, Wen-Hsiang; Ssemanda, Elizabeth; Ervin, Ann-Margret

    2009-10-07

    Retinal detachment (RD) with proliferative vitreoretinopathy (PVR) often requires surgery. During surgery, a tamponade agent is needed to reduce the rate of recurrent retinal detachment. The objective of this review was to evaluate the benefits and adverse outcomes of surgery with various tamponade agents. We searched the Cochrane Controlled Register (CENTRAL), MEDLINE, EMBASE, Latin America and Carribbean Health Sciences (LILACS) and the UK Clinical Trials Gateway (UKCTG). There were no language or date restrictions in the search for trials. The electronic databases were last searched on 9 July 2009. We included randomized clinical trials comparing patients treated with various tamponade agents. Two individuals screened the search results independently. One study with two trials was eligible for inclusion in the review. One study with two trials was included in the review. The first trial randomized 151 eyes to receive either silicone oil or sulfur hexafluoride (SF(6)) gas tamponades; the second trial randomized 271 eyes to receive either silicone oil or perfluropropane (C(3)F(8)) gas tamponades. In patients with RD associated with PVR, pars plana vitrectomy and infusion of either silicone oil or perfluropropane gas appear comparable for a broad variety of cases. Sulfur hexafluoride gas was associated with worse anatomic and visual outcomes than either silicone oil or perfluropropane gas. The use of either C(3)F(8) or silicone oil appears reasonable for most patients with RD associated with PVR. Because there do not appear to be any major differences in outcomes between the two agents, the choice of a tamponade agent should be individualized for each patient.

  14. <strong>Generic Patch Inferencestrong>

    DEFF Research Database (Denmark)

    Andersen, Jesper; Lawall, Julia Laetitia

    2008-01-01

    A key issue in maintaining Linux device drivers is the need to update drivers in response to evolutions in Linux internal libraries. Currently, there is little tool support for performing and documenting such changes. In this paper we present a tool, spfind, that identifies common changes made...... developers can use it to extract an abstract representation of the set of changes that others have made. Our experiments on recent changes in Linux show that the inferred generic patches are more concise than the corresponding patches found in commits to the Linux source tree while being safe with respect...

  15. Azathioprine/methylprednisolone versus cyclophosphamide in proliferative lupus nephritis. A randomized controlled trial

    NARCIS (Netherlands)

    Grootscholten, C.; Ligtenberg, G.; Hagen, E. C.; van den Wall Bake, A. W. L.; de Glas-Vos, J. W.; Bijl, M.; Assmann, K. J.; Bruijn, J. A.; van Houwelingen, H. C.; Derksen, R. H. W. M.; Berden, J. H. M.; Weening, J.J.

    Until recently, intravenous cyclophosphamide pulses with oral corticosteroids were regarded standard therapy for proliferative lupus nephritis (LN). Azathioprine, a less toxic alternative, was never proven to be inferior. In the first Dutch lupus nephritis study (enrollment between 1995 and 2001),

  16. Prevalence and 25 year incidence of proliferative retinopathy among Danish type 1 diabetic patients

    DEFF Research Database (Denmark)

    Grauslund, J; Green, A; Sjølie, A K

    2009-01-01

    AIMS/HYPOTHESIS: This study aimed to evaluate the prevalence of retinopathy in long-surviving type 1 diabetic patients. It also investigated the 25 year incidence of proliferative retinopathy and associated risk factors in a Danish population-based cohort. METHODS: A population-based cohort of 727......-2008. RESULTS: The median age and duration of diabetes at follow-up were 58.8 and 43 years, respectively. At follow-up, the prevalence of diabetic retinopathy was 97.0%. Non-proliferative retinopathy was found in 45.8%, and 51.2% had proliferative retinopathy. The 25 year incidence of proliferative retinopathy...... type 1 diabetic patients from Fyn County, Denmark, was identified in 1973. In 1981-1982, baseline retinopathy was graded and other risk factors were assessed in 573 patients. Twenty-five years later, 308 patients were still alive. Of these, 201 (65.3%) were re-examined at follow-up in 2007...

  17. Level of the proliferative activity of lymphocytes in case of mycosis fungoides and plaque parapsoriasis

    Directory of Open Access Journals (Sweden)

    A. S. Zhukov

    2014-01-01

    Full Text Available The level of the proliferative activity is an important predictor of a number of oncologic diseases; at the same time, its diagnostic value for mycosis fungoides was not adequately investigated. Goal. To study the proliferative activity of lymphocytes in the skin of patients suffering form mycosis fungoides and plaque parapsoriasis. Materials and methods. The level of CD3+ and Ki-67+ cells was determined in skin biopsy samples taken from patients suffering from mycosis fungoides (18 subjects and plaque parapsoriasis (6 subjects by means of immunohistochemistry. The epidermal to dermal skin cell proliferative activity ratio (Ki-67+ and cell proliferative activity index were calculated. The control group comprised 16 healthy people. Results. The epidermal to dermal skin cell proliferative activity ratio amounted to 10.9 in healthy people, 5.43 in patients suffering from plaque parapsoriasis, and 3.84 and 2.42 in patients suffering from mycosis fungoides, spotty and plaque and tumor stages, respectively. The percentage of proliferative CD3+Ki-67+ cells relative to the total number of T-lymphocytes amounted to 1% in the patients suffering from plaque parapsoriasis and 3% in the patients with mycosis fungoides, spotty stage. Conclusion. The epidermal to dermal skin cell proliferative activity ratio (Ki-67+ in patients suffering from mycosis fungoides at any stage is lower than that in healthy subjects and patients suffering from parapsoriasis. The cell proliferative activity index was higher in the patients with mycosis fungoides, plaque and tumor stage, than in the patients with parapsoriasis. The number of CD3+Ki-67+ cells was higher in the patients with mycosis fungoides, spotty and plaque and tumor stages, than in the healthy subjects and patients suffering from parapsoriasis.

  18. Strongly Correlated Topological Insulators

    Science.gov (United States)

    2016-02-03

    Strongly Correlated Topological Insulators In the past year, the grant was used for work in the field of topological phases, with emphasis on finding...surface of topological insulators. In the past 3 years, we have started a new direction, that of fractional topological insulators. These are materials...in which a topologically nontrivial quasi-flat band is fractionally filled and then subject to strong interactions. The views, opinions and/or

  19. Strong Cosmic Censorship

    Science.gov (United States)

    Isenberg, James

    2017-01-01

    The Hawking-Penrose theorems tell us that solutions of Einstein's equations are generally singular, in the sense of the incompleteness of causal geodesics (the paths of physical observers). These singularities might be marked by the blowup of curvature and therefore crushing tidal forces, or by the breakdown of physical determinism. Penrose has conjectured (in his `Strong Cosmic Censorship Conjecture`) that it is generically unbounded curvature that causes singularities, rather than causal breakdown. The verification that ``AVTD behavior'' (marked by the domination of time derivatives over space derivatives) is generically present in a family of solutions has proven to be a useful tool for studying model versions of Strong Cosmic Censorship in that family. I discuss some of the history of Strong Cosmic Censorship, and then discuss what is known about AVTD behavior and Strong Cosmic Censorship in families of solutions defined by varying degrees of isometry, and discuss recent results which we believe will extend this knowledge and provide new support for Strong Cosmic Censorship. I also comment on some of the recent work on ``Weak Null Singularities'', and how this relates to Strong Cosmic Censorship.

  20. Imaging findings in children with proliferative disorders following multivisceral transplantation

    International Nuclear Information System (INIS)

    Hryhorczuk, Anastasia L.; Kim, Heung Bae; Harris, Marian H.; Vargas, Sara O.; Zurakowski, David; Lee, Edward Y.

    2015-01-01

    Multivisceral transplantation represents an important treatment option for children with intestinal failure. The attendant immunosuppression can lead to a spectrum of cellular proliferations including benign and malignant smooth muscle tumors and lymphoproliferative disorders, many related to cellular dysregulation from Epstein-Barr virus infection. The purpose of this study is to investigate the rates of post-transplantation proliferative disorders among children with multivisceral transplantation and to characterize the imaging and pathological features of these disorders. We identified all consecutive children who underwent multivisceral transplant from August 2004 to October 2011 with at least 27 months of clinical and imaging follow-up. We reviewed medical records to determine the underlying causes of the multivisceral transplant, age at transplantation, onset of neoplasm development, and outcome. Two pediatric radiologists reviewed all imaging studies independently and diagnosis of disease was made by consensus interpretation. Pathological specimens were reviewed for histopathological findings of post-transplantation neoplasm in this pediatric patient population. The study population consisted of 14 consecutive pediatric patients (7 boys and 7 girls; mean age 26 months, range 4-113 months). Of these 14 children, 4 (29%) developed histologically confirmed post-transplant neoplasms at a mean time of 2.4 years after multivisceral transplantation. Types of neoplasms included post-transplant lymphoproliferative disorder (PTLD) in three (21%) and Epstein-Barr-virus-associated smooth muscle tumor in two (14%). (One child developed both neoplasms following transplantation). Both children with smooth muscle tumor associated with Epstein-Barr virus presented with characteristic hypointense solid masses with peripheral rim enhancement on cross-sectional imaging studies. The mortality rate of children who developed post-transplant neoplasms was higher than that of those

  1. Imaging findings in children with proliferative disorders following multivisceral transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Hryhorczuk, Anastasia L. [Tufts Medical Center, Department of Radiology, Boston, MA (United States); Kim, Heung Bae [Boston Children' s Hospital, Department of Surgery, Boston, MA (United States); Harris, Marian H.; Vargas, Sara O. [Boston Children' s Hospital, Department of Pathology, Boston, MA (United States); Zurakowski, David [Boston Children' s Hospital, Department of Biostatistics, Boston, MA (United States); Lee, Edward Y. [Boston Children' s Hospital and Harvard Medical School, Departments of Radiology and Medicine, Boston, MA (United States)

    2015-08-15

    Multivisceral transplantation represents an important treatment option for children with intestinal failure. The attendant immunosuppression can lead to a spectrum of cellular proliferations including benign and malignant smooth muscle tumors and lymphoproliferative disorders, many related to cellular dysregulation from Epstein-Barr virus infection. The purpose of this study is to investigate the rates of post-transplantation proliferative disorders among children with multivisceral transplantation and to characterize the imaging and pathological features of these disorders. We identified all consecutive children who underwent multivisceral transplant from August 2004 to October 2011 with at least 27 months of clinical and imaging follow-up. We reviewed medical records to determine the underlying causes of the multivisceral transplant, age at transplantation, onset of neoplasm development, and outcome. Two pediatric radiologists reviewed all imaging studies independently and diagnosis of disease was made by consensus interpretation. Pathological specimens were reviewed for histopathological findings of post-transplantation neoplasm in this pediatric patient population. The study population consisted of 14 consecutive pediatric patients (7 boys and 7 girls; mean age 26 months, range 4-113 months). Of these 14 children, 4 (29%) developed histologically confirmed post-transplant neoplasms at a mean time of 2.4 years after multivisceral transplantation. Types of neoplasms included post-transplant lymphoproliferative disorder (PTLD) in three (21%) and Epstein-Barr-virus-associated smooth muscle tumor in two (14%). (One child developed both neoplasms following transplantation). Both children with smooth muscle tumor associated with Epstein-Barr virus presented with characteristic hypointense solid masses with peripheral rim enhancement on cross-sectional imaging studies. The mortality rate of children who developed post-transplant neoplasms was higher than that of those

  2. Proliferative activity in oral pyogenic granuloma: A comparative immunohistochemical study

    Directory of Open Access Journals (Sweden)

    Rezvani Gita

    2010-07-01

    Full Text Available Context: Pyogenic granuloma (PG is one of the most common reactive vascular lesions in the oral mucosa, which has been divided into the lobular capillary hemangioma (LCH and the non lobular type (non-LCH as two distinct entities, on the basis of some investigations. Aims: This study aims to compare the proliferative and angiogenic activity of two histological types of PG to determine whether they have two distinct types of biological behavior. Settings and Design: In this retrospective cross-sectional study, immunostaining was performed on 10 cases of each type of PG. Materials and Methods: About 4μm sections were cut from formalin-fixed paraffin-embedded blocks and each specimen was stained with both anti-CD31 and anti-Ki-67 antibodies simultaneously. Labeling index (LI was determined for both types by counting Ki-67 and CD31 positive cells separately and simultaneously in 1000 stromal and luminal cells. Micro vessel count (MVC, the mean number of micro vessels in five areas at Χ200 magnification, was also determined for both groups. Statistical Analysis: The results were statistically compared using the Mann-Whitney U-test. Results: Ki-67 LI in LCH (5.4 ± 2.4 was higher than non-LCH (3.9 ± 3.9. The percentage of CD31 positive cells in LCH (28.5 ± 22 was lower than non-LCH (37.1 ± 20.8 and simultaneously immunostaining for both markers in LCH type (2.4 ± 2.1 was higher than non-LCH (1.2 ± 1. The MVC was approximately 77.35 ± 34.6 and 82.6 ± 42.7 in the lobular areas of LCH and central areas of non-LCH PG, respectively. These differences were not statistically significant. Conclusions: These results demonstrate a higher proliferation activity in endothelial cells of LCH PG than in non-LCH.

  3. Proliferative effects of apical, but not basal, matrix metalloproteinase-7 activity in polarized MDCK cells

    International Nuclear Information System (INIS)

    Harrell, Permila C.; McCawley, Lisa J.; Fingleton, Barbara; McIntyre, J. Oliver; Matrisian, Lynn M.

    2005-01-01

    Matrix metalloproteinase-7 (MMP-7) is primarily expressed in glandular epithelium. Therefore, its mechanism of action may be influenced by its regulated vectorial release to either the apical and/or basolateral compartments, where it would act on its various substrates. To gain a better understanding of where MMP-7 is released in polarized epithelium, we have analyzed its pattern of secretion in polarized MDCK cells expressing stably transfected human MMP-7 (MDCK-MMP-7), and HCA-7 and Caco2 human colon cancer cell lines. In all cell lines, latent MMP-7 was secreted to both cellular compartments, but was 1.5- to 3-fold more abundant in the basolateral compartment as compared to the apical. However, studies in the MDCK system demonstrated that MMP-7 activity was 2-fold greater in the apical compartment of MDCK-MMP-7 HIGH -polarized monolayers, which suggests the apical co-release of an MMP-7 activator. In functional assays, MMP-7 over-expression increased cell saturation density as a result of increased cell proliferation with no effect on apoptosis. Apical MMP-7 activity was shown to be responsible for the proliferative effect, which occurred, as demonstrated by media transfer experiments, through cleavage of an apical substrate and not through the generation of a soluble factor. Taken together, our findings demonstrate the importance of MMP-7 secretion in relation to its mechanism of action when expressed in a polarized epithelium

  4. A Flow Cytometric Analysis of Vitreous Inflammatory Cells in Patients with Proliferative Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Mojca Urbančič

    2013-01-01

    Full Text Available The purpose of this study was to investigate inflammatory cells in vitreous from patients with proliferative diabetic retinopathy (PDR using flow cytometric analysis. Twenty-eight patients with PDR requiring vitrectomy because of macular traction or tractional retinal detachment were enrolled in the study (n=28, and 6 patients with macular hole (MH formed the control group. Samples of vitreous and peripheral venous blood were obtained at the beginning of vitrectomy. T lymphocytes were found in vitreous from patients with PDR, and CD4/CD8 ratio was higher in vitreous (median 4.3 compared to blood (median 1.9; P=0.003. No B lymphocytes were detected in vitreous. The percentage of histiocytes/macrophages was significantly higher in vitreous (median 62.1 in comparison with blood (median 5.5; P<0.0001. No lymphocytes were detected in vitreous of the control group. There were more T lymphocytes in vitreous from patients with active PDR. No association between cells in the vitreous and visual acuity improvement after surgery was found. In conclusion, T lymphocytes are found in vitreous from patients with PDR and reflect the activity of PDR but do not seem to predict visual prognosis. Higher CD4/CD8 ratio in vitreous compared to blood from patients with PDR is consistent with local inflammatory response in PDR.

  5. NPY/Y₁ receptor-mediated vasoconstrictory and proliferative effects in pulmonary hypertension.

    Science.gov (United States)

    Crnkovic, S; Egemnazarov, B; Jain, P; Seay, U; Gattinger, N; Marsh, L M; Bálint, Z; Kovacs, G; Ghanim, B; Klepetko, W; Schermuly, R T; Weissmann, N; Olschewski, A; Kwapiszewska, G

    2014-08-01

    Pulmonary arteries (PAs) are innervated, but little is known about the role of neuronal axis in pulmonary hypertension (PH). Here, we have examined the role of the neuropeptide Y (NPY) and its Y₁ receptor in PH pathogenesis. NPY was localized by immunofluorescence. Expression of NPY and Y₁ receptor were determined by quantitative PCR. Cellular response to NPY stimulation was assessed by Western blotting, thymidine incorporation and calcium imaging. Wire myography and isolated perfused mouse lung were applied to study pulmonary vasoactive effects of NPY. Selective receptor antagonists were used to assess the contribution of receptor subtypes in mediating NPY effects. Samples from PH patients showed increased NPYergic innervation within the PA wall and higher Y₁ receptor expression, compared with donors. However, NPY levels were unchanged in both PA and serum. In the chronic hypoxic mouse model, Y₁ receptor were up-regulated, while expression of both NPY and Y₁ receptor was increased in the lungs of monocrotaline and SU5416-hypoxia rats. On a functional level, NPY acutely increased intracellular calcium levels and enhanced vasoconstriction of lung vessels preconstricted with adrenaline. Furthermore, NPY stimulated proliferation of human pulmonary arterial smooth muscle cells and activated p38 and PKD pathways. Correspondingly, higher phosphorylation of PKD was observed in remodelled vessels from PH patients. The selective Y₁ receptor antagonist, BIBO 3304, concentration-dependently inhibited vasoconstrictive and proliferative effects of NPY. NPY and Y₁ receptor are possible mediators of both vasoconstriction and pulmonary vascular remodelling in PH. © 2014 The British Pharmacological Society.

  6. High levels of SOX5 decrease proliferative capacity of human B cells, but permit plasmablast differentiation.

    Directory of Open Access Journals (Sweden)

    Mirzokhid Rakhmanov

    Full Text Available Currently very little is known about the differential expression and function of the transcription factor SOX5 during B cell maturation. We identified two new splice variants of SOX5 in human B cells, encoding the known L-SOX5B isoform and a new shorter isoform L-SOX5F. The SOX5 transcripts are highly expressed during late stages of B-cell differentiation, including atypical memory B cells, activated CD21low B cells and germinal center B cells of tonsils. In tonsillar sections SOX5 expression was predominantly polarized to centrocytes within the light zone. After in vitro stimulation, SOX5 expression was down-regulated during proliferation while high expression levels were permissible for plasmablast differentiation. Overexpression of L-SOX5F in human primary B lymphocytes resulted in reduced proliferation, less survival of CD138neg B cells, but comparable numbers of CD138+CD38hi plasmablasts compared to control cells. Thus, our findings describe for the first time a functional role of SOX5 during late B cell development reducing the proliferative capacity and thus potentially affecting the differentiation of B cells during the germinal center response.

  7. Hyperosmotic stress strongly potentiates serum response factor (SRF)-dependent transcriptional activity in ehrlich lettré ascites cells through a mechanism involving p38 mitogen-activated protein kinase

    DEFF Research Database (Denmark)

    Gorbatenko, Andrej; Wiwel, Maria; Klingberg, Henrik

    2011-01-01

    ) and cAMP response element-binding protein (CREB) are differentially regulated in ELA cells. SRF Ser103 phosphorylation and SRF-dependent transcriptional activity were strongly augmented 5–30¿min and 24¿h, respectively, after hyperosmotic stress (50% increase in extracellular ionic strength), in a p38...... is transiently inhibited while p38 MAPK is activated, in turn impacting on cell survival (Pedersen et al., 2007, Cell Physiol Biochem 20: 735–750). Here, we show that downstream of these kinases, two transcription factors with major roles in control of cell proliferation and death, serum response factor (SRF......Long-term osmotic stress results in altered gene transcription, however, with the exception of the TonE/TonEBP system, the underlying mechanisms are poorly understood. We previously showed that upon osmotic shrinkage of Ehrlich Lettré Ascites (ELA) fibroblasts, the MEK1-ERK1/2 pathway...

  8. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Chun, Sung Kook [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Chung, Sooyoung [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Kim, Hee-Dae [Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Lee, Ju Hyung [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Jang, Jaebong [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Kim, Jeongah; Kim, Doyeon [Department of Brain & Cognitive Sciences, Daegu-Gyeongbuk Institute of Science & Technology, Daegu, 711-873 (Korea, Republic of); Department of Biological Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Department of Brain & Cognitive Sciences, Seoul National University, Seoul, 151-747 (Korea, Republic of); Son, Gi Hoon [Department of Biomedical Sciences, College of Medicine, Korea University, Seoul, 136-705 (Korea, Republic of); Oh, Young J. [Department of Systems Biology, Yonsei University College of Life Science and Biotechnology, Seoul 120-749 (Korea, Republic of); Suh, Young-Ger [College of Pharmacy, Seoul National University, Seoul, 151-742 (Korea, Republic of); Lee, Cheol Soon [Gachon Clinical Trials Center, Gachon University, Incheon, 417-842 (Korea, Republic of); and others

    2015-11-13

    Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

  9. Adipocyte/breast cancer cell crosstalk in obesity interferes with the anti-proliferative efficacy of tamoxifen

    Science.gov (United States)

    Delort, Laetitia; Billard, Hermine; Le Huede, Camille; Boby, Céline; De la Foye, Anne; Rossary, Adrien; Mojallal, Ali; Damour, Odile; Auxenfans, Céline; Vasson, Marie Paule; Caldefie-Chezet, Florence

    2018-01-01

    Background Obesity is a well-known risk factor of breast cancer in post-menopausal women that also correlates with a diminished therapeutic response. The influence of adipocytes and their secretome, i.e. adipokines, on the efficacy of hormone therapy has yet to be elucidated. Methods We investigated, ex vivo, whether mature adipocytes, differentiated from adipose stem cells of normal-weight (MA20) or obese (MA30) women, and their secretions, were able to counteract the effects of tamoxifen (Tx) which is known to decrease neoplastic cell proliferation. Results In a tridimensional model and in a model of co-culture, the anti-proliferative effect of Tx on MCF-7 cancer cells was counteracted by MA30. These two models highlighted two different specific gene expression profiles for genes encoding cytokines or involved in angiogenesis based on the adipocyte microenvironment and the treatment. Thus it notably showed altered expression of genes such as TNFα that correlated with IL-6. In addition, leptin, IL-6 and TNFα, at concentrations reflecting plasma concentrations in obese patients, decreased the anti-proliferative efficacy of 4-hydroxytamoxifen (a major active metabolite of Tx). Conclusions These findings bring insights on adipocytes and mammary cancer cell interactions in Tx therapy, particularly in overweight/obese people. Indeed, patient’ adipokine status would give valuable information for developing individual strategies and avoid resistance to treatment. PMID:29389973

  10. Pulmonary artery endothelial cell dysfunction and decreased populations of highly proliferative endothelial cells in experimental congenital diaphragmatic hernia

    Science.gov (United States)

    Seedorf, Gregory J.; Abman, Steven H.; Nozik-Grayck, Eva; Partrick, David A.; Gien, Jason

    2013-01-01

    Decreased lung vascular growth and pulmonary hypertension contribute to poor outcomes in congenital diaphragmatic hernia (CDH). Mechanisms that impair angiogenesis in CDH are poorly understood. We hypothesize that decreased vessel growth in CDH is caused by pulmonary artery endothelial cell (PAEC) dysfunction with loss of a highly proliferative population of PAECs (HP-PAEC). PAECs were harvested from near-term fetal sheep that underwent surgical disruption of the diaphragm at 60–70 days gestational age. Highly proliferative potential was measured via single cell assay. PAEC function was assessed by assays of growth and tube formation and response to known proangiogenic stimuli, vascular endothelial growth factor (VEGF), and nitric oxide (NO). Western blot analysis was used to measure content of angiogenic proteins, and superoxide production was assessed. By single cell assay, the proportion of HP-PAEC with growth of >1,000 cells was markedly reduced in the CDH PAEC, from 29% (controls) to 1% (CDH) (P CDH PAEC growth and tube formation were decreased by 31% (P = 0.012) and 54% (P CDH PAEC growth and tube formation. VEGF and VEGF-R2 proteins were increased in CDH PAEC; however, eNOS and extracellular superoxide dismutase proteins were decreased by 29 and 88%, respectively. We conclude that surgically induced CDH in fetal sheep causes endothelial dysfunction and marked reduction of the HP-PAEC population. We speculate that this CDH PAEC phenotype contributes to impaired vascular growth in CDH. PMID:24124189

  11. A synthetic cryptochrome inhibitor induces anti-proliferative effects and increases chemosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Chun, Sung Kook; Chung, Sooyoung; Kim, Hee-Dae; Lee, Ju Hyung; Jang, Jaebong; Kim, Jeongah; Kim, Doyeon; Son, Gi Hoon; Oh, Young J.; Suh, Young-Ger; Lee, Cheol Soon

    2015-01-01

    Disruption of circadian rhythm is a major cause of breast cancer in humans. Cryptochrome (CRY), a circadian transcription factor, is a risk factor for initiation of breast cancer, and it is differentially expressed between normal and breast cancer tissues. Here, we evaluated the anti-proliferative and pro-apoptotic activity of KS15, a recently discovered small-molecule inhibitor of CRY, in human breast cancer cells. First, we investigated whether KS15 treatment could promote E-box-mediated transcription by inhibiting the activity of CRY in MCF-7 human breast cancer cells. Protein and mRNA levels of regulators of cell cycle and apoptosis, as well as core clock genes, were differentially modulated in response to KS15. Next, we investigated whether KS15 could inhibit proliferation and increase sensitivity to anti-tumor drugs in MCF-7 cells. We found that KS15 decreased the speed of cell growth and increased the chemosensitivity of MCF-7 cells to doxorubicin and tamoxifen, but had no effect on MCF-10A cells. These findings suggested that pharmacological inhibition of CRY by KS15 exerts an anti-proliferative effect and increases sensitivity to anti-tumor drugs in a specific type of breast cancer. - Highlights: • Cryptochrome inhibitor (KS15) has anti-tumor activity to human breast cancer cells. • KS15 induces differential changes in cell cycle regulators and pro-apoptotic genes. • KS15 inhibits MCF-7 cell growth and enhances susceptibility to anti-tumor drugs.

  12. Tamponade in surgery for retinal detachment associated with proliferative vitreoretinopathy.

    Science.gov (United States)

    Schwartz, Stephen G; Flynn, Harry W; Lee, Wen-Hsiang; Wang, Xue

    2014-02-14

    Retinal detachment (RD) with proliferative vitreoretinopathy (PVR) often requires surgery to restore normal anatomy and to stabilize or improve vision. PVR usually occurs in association with recurrent RD (that is, after initial retinal re-attachment surgery) but occasionally may be associated with primary RD. Either way, a tamponade agent (gas or silicone oil) is needed during surgery to reduce the rate of postoperative recurrent RD. The objective of this review was to assess the relative safety and effectiveness of various tamponade agents used with surgery for retinal detachment (RD) complicated by proliferative vitreoretinopathy (PVR). We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to June 2013), EMBASE (January 1980 to June 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to June 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 26 June 2013. We included randomized controlled trials (RCTs) of participants undergoing surgery for RD associated with PVR that compared various tamponade agents. Two review authors screened the search results independently. We used the standard methodological procedures expected by The Cochrane Collaboration. The review included 516 participants from three RCTs. One study was conducted in the USA and consisted of two trials: the first trial randomized 151 adults to receive either silicone oil or sulfur hexafluoride (SF6) gas tamponades; and the second trial randomized 271 adults to receive either

  13. Anti-proliferative properties of commercial Pelargonium sidoides tincture, with cell-cycle G0/G1 arrest and apoptosis in Jurkat leukaemia cells.

    Science.gov (United States)

    Pereira, Andreia; Bester, Megan; Soundy, Puffy; Apostolides, Zeno

    2016-09-01

    Context Pelargonium sidoides DC (Geraniaceae) is an important medicinal plant indigenous to South Africa and Lesotho. Previous studies have shown that root extracts are rich in polyphenolic compounds with antibacterial, antiviral and immunomodulatory activities. Little is known regarding the anticancer properties of Pelargonium sidoides extracts. Objective This study evaluates the anti-proliferative effects of a Pelargonium sidoides radix mother tincture (PST). Materials and methods The PST was characterized by LC-MS/MS. Anti-proliferative activity was evaluated in the pre-screen panel of the National Cancer Institute (NCI-H460, MCF-7 and SF-268) and the Jurkat leukaemia cell line at concentrations of 0-150 μg/mL. The effect on cell growth was determined with sulphorhodamine B and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays after 72 h. The effect on cell cycle and apoptosis induction in Jurkat cells was determined by flow cytometry with propidium iodide and Annexin V: fluorescein isothiocyanate staining. Results Dihydroxycoumarin sulphates, gallic acid as well as gallocatechin dimers and trimers were characterized in PST by mass spectrometry. Moderate anti-proliferative effects with GI50 values between 40 and 80 μg/mL were observed in the NCI-pre-screen panel. Strong activity observed with Jurkat cells with a GI50 value of 6.2 μg/mL, significantly better than positive control 5-fluorouracil (GI50 value of 9.7 μg/mL). The PST arrested Jurkat cells at the G0/G1 phase of the cell cycle and increased the apoptotic cells from 9% to 21%, while the dead cells increased from 4% to 17%. Conclusion We present evidence that P. sidoides has cancer cell type-specific anti-proliferative effects and may be a source of novel anticancer molecules.

  14. Polish natural bee honeys are anti-proliferative and anti-metastatic agents in human glioblastoma multiforme U87MG cell line.

    Directory of Open Access Journals (Sweden)

    Justyna Moskwa

    Full Text Available Honey has been used as food and a traditional medicament since ancient times. However, recently many scientists have been concentrating on the anti-oxidant, anti-proliferative, anti-inflammatory and other properties of honey. In this study, we investigated for the first time an anticancer effect of different honeys from Poland on tumor cell line - glioblastoma multiforme U87MG. Anti-proliferative activity of honeys and its interferences with temozolomide were determined by a cytotoxicity test and DNA binding by [H3]-thymidine incorporation. A gelatin zymography was used to conduct an evaluation of metalloproteinases (MMP-2 and MMP-9 expression in U87MG treatment with honey samples. The honeys were previously tested qualitatively (diastase activity, total phenolic content, lead and cadmium content. The data demonstrated that the examined honeys have a potent anti-proliferative effect on U87MG cell line in a time- and dose-dependent manner, being effective at concentrations as low as 0.5% (multifloral light honey - viability 53% after 72 h of incubation. We observed that after 48 h, combining honey with temozolomide showed a significantly higher inhibitory effect than the samples of honey alone. We observed a strong inhibition of MMP-2 and MMP-9 for the tested honeys (from 20 to 56% and from 5 to 58% compared to control, respectively. Our results suggest that Polish honeys have an anti-proliferative and anti-metastatic effect on U87MG cell line. Therefore, natural bee honey can be considered as a promising adjuvant treatment for brain tumors.

  15. Anti-proliferative and cytotoxic activities of Allium autumnale P. H. Davis (Amaryllidaceae) on human breast cancer cell lines MCF-7 and MDA-MB-231.

    Science.gov (United States)

    Isbilen, Ovgu; Rizaner, Nahit; Volkan, Ender

    2018-01-25

    Natural products obtained from plants can be potent sources for developing a variety of pharmaceutical products. Allium species have been widely studied for their anti-cancer effects and presented promising results as potential anti-cancer agents. Breast cancer (BCa) is one of the most commonly diagnosed types of cancer in women. In this study, we aimed to investigate the anti-proliferative, cytotoxic and anti-metastatic effects of bulb and stem extracts from Allium autumnale P. H. Davis (Amaryllidaceae), an endemic Allium species to the island of Cyprus, in a comparative approach to weakly metastatic MCF-7 and strongly metastatic MDA-MB-231 breast cancer (BCa) cell lines. Possible cytotoxic, anti-proliferative and anti-metastatic effects of the Allium extracts on MCF-7 and MDA-MB-231 cells were tested using trypan blue exclusion, MTT and wound heal assays, respectively. Gas Chromatography Mass Spectroscopy (GC-MS) analysis was performed to determine the prominent medically important compounds in Allium autumnale bulb (AAB) and Allium autumnale stem (AAS) extracts. Student unpaired t-test or ANOVA followed by Newman-Keuls post hoc analysis (INSTAT Software) was used where appropriate. Our results demonstrate that AAB extract (24, 48 and 72 h) exerts significant anti-proliferative effect on both MCF-7 and MDA-MB-231 cells where this effect for AAS extract was observed only at high (5000 and 10,000 μg/mL) concentrations. Cell viability experiments revealed that AAB extract incubations caused more cytotoxicity on both BCa cell lines compared to the AAS. In contrast, there was no effect on lateral motilities of either cell line. Overall, our studies demonstrated the anti-cancer activities associated with Allium autumnale, revealing it's cytotoxic and anti-proliferative potential to be further utilized in in vivo studies.

  16. Strong Arcwise Connectedness

    OpenAIRE

    Espinoza, Benjamin; Gartside, Paul; Kovan-Bakan, Merve; Mamatelashvili, Ana

    2012-01-01

    A space is `n-strong arc connected' (n-sac) if for any n points in the space there is an arc in the space visiting them in order. A space is omega-strong arc connected (omega-sac) if it is n-sac for all n. We study these properties in finite graphs, regular continua, and rational continua. There are no 4-sac graphs, but there are 3-sac graphs and graphs which are 2-sac but not 3-sac. For every n there is an n-sac regular continuum, but no regular continuum is omega-sac. There is an omega-sac ...

  17. Abortion: Strong's counterexamples fail

    DEFF Research Database (Denmark)

    Di Nucci, Ezio

    2009-01-01

    This paper shows that the counterexamples proposed by Strong in 2008 in the Journal of Medical Ethics to Marquis's argument against abortion fail. Strong's basic idea is that there are cases--for example, terminally ill patients--where killing an adult human being is prima facie seriously morally......'s scenarios have some valuable future or admitted that killing them is not seriously morally wrong. Finally, if "valuable future" is interpreted as referring to objective standards, one ends up with implausible and unpalatable moral claims....

  18. A strong comeback

    International Nuclear Information System (INIS)

    Marier, D.

    1992-01-01

    This article presents the results of a financial rankings survey which show a strong economic activity in the independent energy industry. The topics of the article include advisor turnover, overseas banks, and the increase in public offerings. The article identifies the top project finance investors for new projects and restructurings and rankings for lenders

  19. Withania somnifera chemotype NMITLI 101R significantly increases the efficacy of antileishmanial drugs by generating strong IFN-γ and IL-12 mediated immune responses in Leishmania donovani infected hamsters.

    Science.gov (United States)

    Tripathi, Chandra Dev Pati; Kushawaha, Pramod Kumar; Sangwan, Rajender Singh; Mandal, Chitra; Misra-Bhattacharya, Shailja; Dube, Anuradha

    2017-01-15

    Withania somnifera (L.) Dunal (Solanaceae), commonly known as Ashwagandha, is one of the most important medicinal plant in the traditional Indian medical systems. Pharmacological studies have established that root extracts of W. somnifera contain several bioactive constituents called withanolides. The plant has long been used for its several beneficial properties and recently as an immunomodulator. A combination therapy including a potential and safe immunostimulant with lower doses of effective drug, which can reduce the parasitic burden and simultaneously can produce an enhancement of adaptive immunity, has proven to be significantly a more effective approach than immunotherapy or drug therapy alone. Evaluation of the immunostimulatory effect of W. somnifera chemotype NMITLI 101R when used in combination with ED 50 doses of antileishmanial drugs in Leishmania donovani infected hamsters. Infected animals were administered with chemotype 101R(30mg/kg × 15 days) either alone or in combination with ED 50 doses of miltefosine (10mg/kg × 5 days), paromomycin (30mg/kg × 5 days) or amphotericin B (0.5mg/kg × 5 days). The treated animals were euthanized on days 30 and 60 post-treatment (p.t.) and checked for parasite clearance, delayed type hypersensitivity (DTH) response, cytokine and inducible nitric oxide synthase levels by real-time PCR, nitric oxide (NO) production, reactive oxygen species (ROS) generation, lymphoproliferative and antibody responses. The group of animals that received 101R and ED 50 dose of miltefosine showed optimum inhibition of parasite multiplication (∼98%) by day 60 p.t. followed by the group that received 101R plus paromomycin (∼94%) and 101R plus amphotericin B (∼93%). The efficacy was well supported by the increased inducible NO synthase mRNA transcript, strong IFN-γand IL-12 mediated Th1 immune responses and significantly suppressed levels of Th2 cytokines (IL-4, IL-10 and TGF-β). Additionally, same

  20. Strong Electroweak Symmetry Breaking

    CERN Document Server

    Grinstein, Benjamin

    2011-01-01

    Models of spontaneous breaking of electroweak symmetry by a strong interaction do not have fine tuning/hierarchy problem. They are conceptually elegant and use the only mechanism of spontaneous breaking of a gauge symmetry that is known to occur in nature. The simplest model, minimal technicolor with extended technicolor interactions, is appealing because one can calculate by scaling up from QCD. But it is ruled out on many counts: inappropriately low quark and lepton masses (or excessive FCNC), bad electroweak data fits, light scalar and vector states, etc. However, nature may not choose the minimal model and then we are stuck: except possibly through lattice simulations, we are unable to compute and test the models. In the LHC era it therefore makes sense to abandon specific models (of strong EW breaking) and concentrate on generic features that may indicate discovery. The Technicolor Straw Man is not a model but a parametrized search strategy inspired by a remarkable generic feature of walking technicolor,...

  1. PROSPECTIVE STUDY OF HISTOLOGICAL PROLIFERATIVE CHANGES IN ADJACENT AREAS OF BREAST CANCER

    Directory of Open Access Journals (Sweden)

    Rema Nair Sarkar

    2016-11-01

    Full Text Available BACKGROUND Breast cancer remains a global health problem with an increasing incidence. Proliferative breast diseases are recognised as one of the risk factors in the development of carcinoma. This study was undertaken to know the frequency of proliferative lesions and other lesions in association with breast carcinomas in mastectomy specimens. MATERIALS AND METHODS 100 cases of excised carcinoma breast sent to the Department of Pathology for a three-year period at tertiary care centre was thoroughly examined and changes adjacent to the tumour was recorded and tissue was subjected for histopathological examination and results tabulated. RESULTS Infiltrating duct cell carcinoma, Not Otherwise Specified (NOS type was present in 89% of cases. Among the associated lesions, nonproliferative lesions constituted 16%, proliferative breast disease without atypia 29%, proliferative breast disease with atypia 10% and others 45%. Fibrocystic disease constituted 14% of cases, epithelial hyperplasia 15%, sclerosing adenosis 12% and atypical ductal hyperplasia in 10% of cases. Other types of associated lesions were duct carcinoma in situ in 4 cases. CONCLUSION Proliferative lesions adjacent to carcinoma breast were seen in 39% of cases. Fibrocystic disease, epithelial hyperplasia, sclerosing adenosis and atypical ductal hyperplasia being the commonest lesions adjacent to carcinoma breast in the present study.

  2. The development of proliferative verrucous leukoplakia in oral lichen planus. A preliminary study

    Science.gov (United States)

    Llorente-Pendás, Santiago; González-Garcia, Manuel; García-Martín, José-Manuel

    2016-01-01

    Background Was to describe 14 cases of a proliferative verrucous leukoplakia as a clinical evolution of oral lichen planus. Material and Methods The clinical and histopathological characteristics of 14 cases of OLP that progress towards a plaque-like and verrucous form were indicated, with monitoring over a period of six to 24.3 years. Results The female/male ratio was 11/3, (78.6 and 21.4%). The mean age when the first biopsy was undertaken was 56.4 years old. None of the patients smoked during the study. As bilateral reticular was clinically diagnostic criterion, the second most frequent clinical form was the plaque form (n=10; 71.4%), followed by the atrophic (n=6; 42.8%), and erosive forms (n=4; 28.5%). Clinically it spread towards attached gingival mucosa and the hard palate. In the histopathologic study, there were a predominance of hyperkeratosis and verrucous epithelial hyperplasia. Three of the cases progressed to a squamous cell carcinoma, and one patient developed two verrucous carcinoma. Conclusions Further research is needed to demonstrate if proliferative multifocal oral lichen planus and proliferative multifocal oral leukoplakia are the same disorder but have different behaviour of malignancy for reasons of origin. Key words:Oral lichen planus, proliferative verrucous oral leukoplakia, malignant oral lichen planus, multifocal verrucous oral lichen planus, proliferative verrucous oral lichen planus. PMID:27031060

  3. Plasmons in strong superconductors

    International Nuclear Information System (INIS)

    Baldo, M.; Ducoin, C.

    2011-01-01

    We present a study of the possible plasmon excitations that can occur in systems where strong superconductivity is present. In these systems the plasmon energy is comparable to or smaller than the pairing gap. As a prototype of these systems we consider the proton component of Neutron Star matter just below the crust when electron screening is not taken into account. For the realistic case we consider in detail the different aspects of the elementary excitations when the proton, electron components are considered within the Random-Phase Approximation generalized to the superfluid case, while the influence of the neutron component is considered only at qualitative level. Electron screening plays a major role in modifying the proton spectrum and spectral function. At the same time the electron plasmon is strongly modified and damped by the indirect coupling with the superfluid proton component, even at moderately low values of the gap. The excitation spectrum shows the interplay of the different components and their relevance for each excitation modes. The results are relevant for neutrino physics and thermodynamical processes in neutron stars. If electron screening is neglected, the spectral properties of the proton component show some resemblance with the physical situation in high-T c superconductors, and we briefly discuss similarities and differences in this connection. In a general prospect, the results of the study emphasize the role of Coulomb interaction in strong superconductors.

  4. Strongly correlating liquids and their isomorphs

    OpenAIRE

    Pedersen, Ulf R.; Gnan, Nicoletta; Bailey, Nicholas P.; Schröder, Thomas B.; Dyre, Jeppe C.

    2010-01-01

    This paper summarizes the properties of strongly correlating liquids, i.e., liquids with strong correlations between virial and potential energy equilibrium fluctuations at constant volume. We proceed to focus on the experimental predictions for strongly correlating glass-forming liquids. These predictions include i) density scaling, ii) isochronal superposition, iii) that there is a single function from which all frequency-dependent viscoelastic response functions may be calculated, iv) that...

  5. Clinical efficacy of integrative therapy in the treatment of non-proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Bing-Wen Lu

    2017-12-01

    Full Text Available AIM: To study the clinical efficacy of integrative therapy in the treatment of non-proliferative diabetic retinopathy. METHODS: Ninety patients(90 eyesin our hospital with non-proliferative diabetic retinopathy were randomly divided into three groups. All three groups were treated with diabetes drugs to control blood sugar. The first group was treated with western medicine, the second group was treated with Chinese medicine decoction Traditional Chinese Medicine(TCMtreatment, and the third group was treated with the combination of those two methods. All patients were recorded and analyzed changes of clinical effects after 6 courses of treatment. RESULTS: After 6 courses of treatment, the total efficacy rate of the third group was 86%, markedly higher than that of the first group(57%, PPPCONCLUSION: Integrative treatment of diabetic retinopathy could effectively improve the therapeutic effect in patients with non-proliferative retinopathy.

  6. Strong-coupling approximations

    International Nuclear Information System (INIS)

    Abbott, R.B.

    1984-03-01

    Standard path-integral techniques such as instanton calculations give good answers for weak-coupling problems, but become unreliable for strong-coupling. Here we consider a method of replacing the original potential by a suitably chosen harmonic oscillator potential. Physically this is motivated by the fact that potential barriers below the level of the ground-state energy of a quantum-mechanical system have little effect. Numerically, results are good, both for quantum-mechanical problems and for massive phi 4 field theory in 1 + 1 dimensions. 9 references, 6 figures

  7. Strong interaction and QFD

    International Nuclear Information System (INIS)

    Ebata, T.

    1981-01-01

    With an assumed weak multiplet structure for bosonic hadrons, which is consistent with the ΔI = 1/2 rule, it is shown that the strong interaction effective hamiltonian is compatible with the weak SU(2) x U(1) gauge transformation. Especially the rho-meson transforms as a triplet under SU(2)sub(w), and this is the origin of the rho-photon analogy. It is also shown that the existence of the non-vanishing Cabibbo angle is a necessary condition for the absence of the exotic hadrons. (orig.)

  8. Autocrine proliferative effects of hGH are maintained in primary cultures of human mammary carcinoma cells.

    Science.gov (United States)

    Chiesa, Jean; Ferrer, Catherine; Arnould, Cécile; Vouyovitch, Cécile M; Diaz, Jean-Jacques; Gonzalez, Samia; Mares, Pierre; Morel, Gérard; Wu, Zheng-Sheng; Zhu, Tao; Lobie, Peter E; Mertani, Hichem C

    2011-09-01

    Empirical evidence suggests that autocrine human GH (hGH) may possess a proliferative and oncogenic role in human mammary carcinoma. However, this concept is largely derived from studies using cultured human mammary carcinoma cell (HMCC) lines. We investigated the expression and functionality of hGH and the hGH receptor in isolated cultures of primary HMCC. Epithelial cell adhesion molecule-positive primary HMCC were isolated from surgical biopsies of patients with mammary carcinoma and cultured in vitro. Expression of hGH and hGH receptor was determined by RT-PCR, immunofluorescence microscopy, and ELISA. The proliferative response of the cultured primary HMCC to hGH stimulation or hGH inhibition with a hGH antagonist was determined. One hundred percent of cultured primary HMCC expressed the hGH receptor, and 52% expressed hGH at the mRNA level. hGH-positive primary HMCC produced hGH protein within the cell and secreted hGH to the media. Both hGH-negative and hGH-positive HMCC responded to hGH stimulation with large increases in cell number. hGH-positive HMCC responded to inhibition of hGH by a hGH antagonist with a decrease in cell number, whereas hGH-negative HMCC did not. Primary HMCC proliferate in response to hGH, and the proliferation of hGH-positive HMCC is inhibited by hGH antagonism. Inhibition of hGH in patients with mammary carcinoma may therefore limit tumor growth.

  9. Proliferative diabetic retinopathy is associated with microalbuminuria in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    M.C. Boelter

    2006-08-01

    Full Text Available Diabetic retinopathy is one of the leading causes of blindness in working-age individuals. Diabetic patients with proteinuria or those on dialysis usually present severe forms of diabetic retinopathy, but the association of diabetic retinopathy with early stages of diabetic nephropathy has not been entirely established. A cross-sectional study was conducted on 1214 type 2 diabetic patients to determine whether microalbuminuria is associated with proliferative diabetic retinopathy in these patients. Patients were evaluated by direct and indirect ophthalmoscopy and grouped according to the presence or absence of proliferative diabetic retinopathy. The agreement of diabetic retinopathy classification performed by ophthalmoscopy and by stereoscopic color fundus photographs was 95.1% (kappa = 0.735; P < 0.001. Demographic information, smoking history, anthropometric and blood pressure measurements, glycemic and lipid profile, and urinary albumin were evaluated. On multiple regression analysis, diabetic nephropathy (OR = 5.18, 95% CI = 2.91-9.22, P < 0.001, insulin use (OR = 2.52, 95% CI = 1.47-4.31, P = 0.001 and diabetes duration (OR = 1.04, 95% CI = 1.01-1.07, P = 0.011 were positively associated with proliferative diabetic retinopathy, and body mass index (OR = 0.90, 95% CI = 0.86-0.96, P < 0.001 was negatively associated with it. When patients with macroalbuminuria and on dialysis were excluded, microalbuminuria (OR = 3.3, 95% CI = 1.56-6.98, P = 0.002 remained associated with proliferative diabetic retinopathy. Therefore, type 2 diabetic patients with proliferative diabetic retinopathy more often presented renal involvement, including urinary albumin excretion within the microalbuminuria range. Therefore, all patients with proliferative diabetic retinopathy should undergo an evaluation of renal function including urinary albumin measurements.

  10. Nuclear size and shape parameters correlate with proliferative activity in cutaneous melanocytic tumors.

    Science.gov (United States)

    Smolle, J; Hofmann-Wellenhof, R; Soyer, H P; Stettner, H; Kerl, H

    1989-07-01

    Proliferative activity and morphometric data have previously been shown to be related with the degree of malignancy in melanocytic skin tumors. In the present study, the proliferative activity, as defined by Ki 67 monoclonal antibody (reactive with all actively cycling cells), has been determined by immunohistologic and morphometric methods in cutaneous melanocytic tumors. Quantitative morphologic features of Ki 67-positive and Ki 67-negative nuclei were separately assessed using computer-assisted image analysis. Comparing morphometric features and proliferative activity, the most significant correlation was found between mean nuclear volume and the percentage of Ki 67-positive nuclei in each lesion (linear regression analysis: r = 0.73; p = less than 0.05). On multidimensional discriminant analysis, tumors with high proliferative activity (more than 5 X 10(3) Ki 67-positive cells per mm3 tumor tissue) were detected at a specificity of 92% and a sensitivity of 75%. Within one lesion, Ki 67-positive nuclei showed an increase in nuclear volume (Wilcoxon test: p = less than 0.05), a more spheroid shape (p = less than 0.05), and a wider dispersion of nuclear volume values (Siegel-Tukey test: p = less than 0.05) than negative nuclei. Discriminant analysis on the basis of nuclear volume density functions facilitated an estimation of the proliferative state (resting or cycling) of a given nucleus. The results are consistent with increased cellular synthetic activity in highly proliferating lesions and particularly in actively cycling cells. The association of proliferative activity and quantitative nuclear features may be helpful in the interpretation of morphometric studies concerning melanocytic skin tumors.

  11. Strong Coupling Holography

    CERN Document Server

    Dvali, Gia

    2009-01-01

    We show that whenever a 4-dimensional theory with N particle species emerges as a consistent low energy description of a 3-brane embedded in an asymptotically-flat (4+d)-dimensional space, the holographic scale of high-dimensional gravity sets the strong coupling scale of the 4D theory. This connection persists in the limit in which gravity can be consistently decoupled. We demonstrate this effect for orbifold planes, as well as for the solitonic branes and string theoretic D-branes. In all cases the emergence of a 4D strong coupling scale from bulk holography is a persistent phenomenon. The effect turns out to be insensitive even to such extreme deformations of the brane action that seemingly shield 4D theory from the bulk gravity effects. A well understood example of such deformation is given by large 4D Einstein term in the 3-brane action, which is known to suppress the strength of 5D gravity at short distances and change the 5D Newton's law into the four-dimensional one. Nevertheless, we observe that the ...

  12. Morphological and physiological responses of two varieties of a highland species (Chenopodium quinoa Willd.) growing under near-ambient and strongly reduced solar UV-B in a lowland location.

    Science.gov (United States)

    González, Juan A; Rosa, Mariana; Parrado, María F; Hilal, Mirna; Prado, Fernando E

    2009-08-03

    Morphological and physiological responses of seedlings to different solar UV-B irradiances were evaluated in two varieties of quinoa (Chenopodium quinoa Willd.), a crop species from Andean region of South America. Cristalina and Chucapaca varieties were grown at 1965m a.s.l in a glasshouse under natural light conditions for 18 days, and then transferred to outdoors under near-ambient (+UV-B) and strongly reduced (-UV-B) solar UV-B radiation. Exposition to -UV-B increased cotyledon area and seedling height in Cristalina variety whereas leaf number decreased compared to +UV-B. By contrast Chucapaca variety was not affected by UV-B treatments. Seedling fresh weight (FW), root length and leaf thickness did not show significant differences between +UV-B and -UV-B treatments. Mesophyll tissue was slightly affected by solar UV-B reduction. Chlorophyll content was differentially affected by UV-B treatments. Under +UV-B the highest value was observed in Cristalina variety, while in Chucapaca it was observed under -UV-B treatment. Chlorophyll content was slightly higher in leaves than in cotyledons, but there was no difference in the distribution pattern. Chlorophyll a/b ratio and carotenoid content did not show significant differences between UV-B treatments. Leaf UVB-absorbing compounds showed significant differences between UV-B treatments in Chucapaca only, while there were no significant differences in Cristalina variety. UVB-absorbing compounds of cotyledons did not show significant differences between +UV-B and -UV-B treatments. Sucrose, glucose and fructose showed different distribution patterns in cotyledons and leaves of the two varieties under near-ambient and strongly reduced UV-B. Results demonstrated that varieties of quinoa exhibit different morphological and physiological responses to changes in solar UV-B irradiance, but these responses cannot be used to predict the sensitivity to solar UV-B during a short-term exposition. Also, this study can be useful to

  13. LIGO: The strong belief

    CERN Multimedia

    Antonella Del Rosso

    2016-01-01

    Twenty years of designing, building and testing a number of innovative technologies, with the strong belief that the endeavour would lead to a historic breakthrough. The Bulletin publishes an abstract of the Courier’s interview with Barry Barish, one of the founding fathers of LIGO.   The plots show the signals of gravitational waves detected by the twin LIGO observatories at Livingston, Louisiana, and Hanford, Washington. (Image: Caltech/MIT/LIGO Lab) On 11 February, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo collaborations published a historic paper in which they showed a gravitational signal emitted by the merger of two black holes. These results come after 20 years of hard work by a large collaboration of scientists operating the two LIGO observatories in the US. Barry Barish, Linde Professor of Physics, Emeritus at the California Institute of Technology and former Director of the Global Design Effort for the Internat...

  14. Proliferative and antioxidant activity of Symphytum officinale root extract.

    Science.gov (United States)

    Sowa, Ireneusz; Paduch, Roman; Strzemski, Maciej; Zielińska, Sylwia; Rydzik-Strzemska, Ewelina; Sawicki, Jan; Kocjan, Ryszard; Polkowski, Janusz; Matkowski, Adam; Latalski, Michał; Wójciak-Kosior, Magdalena

    2018-03-01

    The root of Symphytum officinale L. is commonly used in folk medicine to promote the wound healing, reduce the inflammation and in the treatment of broken bones. The objective of our investigation was to analyse the extract from S. officinale in term of its antioxidant activity and the effect on cell viability and proliferation of human skin fibroblast (HSF). Moreover, the quantification of main phenolics and allantoin was conducted using HPLC-DAD method. Five compounds were found: rosmarinic, p-hydroxybenzoic, caffeic, chlorogenic and p-coumaric acid. DPPH, FRAP and TPC assay showed the high antioxidant activity of the extract. MTT test proved the stimulatory effect on cell metabolism and viability of HSF cells. Moreover, no changes in cytoskeleton structure and cells shape were observed. The obtained results indicate that non-toxic extract from S. officinale root has strong antioxidant potential and a beneficial effect on human skin fibroblasts.

  15. A simple route to synthesize conductive stimuli-responsive polypyrrole nanocomposite hydrogel particles with strong magnetic properties and their performance for removal of hexavalent chromium ions from aqueous solution

    Science.gov (United States)

    Ahmad, Hasan; Rahman, Mohammad Mostafizar; Ali, Mohammad Azgar; Minami, Hideto; Tauer, Klaus; Gafur, Mohammad Abdul; Rahman, Mohammad Mahbubor

    2016-08-01

    A combination of maghemite polypyrrole (PPy/γ-Fe2O3) and stimuli-responsive properties in the same hydrogel microspheres is expected to enhance their application potential in various fields such as tissue engineering, regenerative medicine, biosensors, biomedical applications and removal of heavy metals from waste water, catalysis etc. In this investigation a simple two step process is used to prepare conductive stimuli-responsive polypyrrole (PPy) composite hydrogel particles with strong magnetic properties. Poly(styrene-methacrylic acid-N-isopropylacrylamide-polyethelene glycol methacrylate) or P(S-NIPAM-MAA-PEGMA) hydrogel seed particles are first prepared by soap-free precipitation copolymerization. The copolymer hydrogel particles exhibited both temperature- and pH-responsive volume phase transition. Conductive P(S-NIPAM-MAA-PEGMA)/PPy/γ-Fe2O3 nanocomposite hydrogel particles are then prepared by seeded chemical oxidative polymerization of pyrrole in the presence of P(S-NIPAM-MAA-PEGMA) hydrogel seed particles using FeCl3 as a oxidant and p-toluene sulfonic acid (p-TSA) as a dopant. In the reaction system FeCl3 functioned as a source of Fe(III) for the formation of γ-Fe2O3. This reaction also requires the initial presence of Fe(II) provided by the addition of FeCl2. The size and size distribution, surface structure, and morphology of the prepared conductive composite hydrogel particles are confirmed by FTIR, electron micrographs, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and UV-visible spectroscopy. The performance of nanocomposite hydrogel particles has been evaluated for the removal of hexavalent chromium (Cr) ions from water.

  16. Stirring Strongly Coupled Plasma

    CERN Document Server

    Fadafan, Kazem Bitaghsir; Rajagopal, Krishna; Wiedemann, Urs Achim

    2009-01-01

    We determine the energy it takes to move a test quark along a circle of radius L with angular frequency w through the strongly coupled plasma of N=4 supersymmetric Yang-Mills (SYM) theory. We find that for most values of L and w the energy deposited by stirring the plasma in this way is governed either by the drag force acting on a test quark moving through the plasma in a straight line with speed v=Lw or by the energy radiated by a quark in circular motion in the absence of any plasma, whichever is larger. There is a continuous crossover from the drag-dominated regime to the radiation-dominated regime. In the crossover regime we find evidence for significant destructive interference between energy loss due to drag and that due to radiation as if in vacuum. The rotating quark thus serves as a model system in which the relative strength of, and interplay between, two different mechanisms of parton energy loss is accessible via a controlled classical gravity calculation. We close by speculating on the implicati...

  17. Strong-interaction nonuniversality

    International Nuclear Information System (INIS)

    Volkas, R.R.; Foot, R.; He, X.; Joshi, G.C.

    1989-01-01

    The universal QCD color theory is extended to an SU(3) 1 direct product SU(3) 2 direct product SU(3) 3 gauge theory, where quarks of the ith generation transform as triplets under SU(3)/sub i/ and singlets under the other two factors. The usual color group is then identified with the diagonal subgroup, which remains exact after symmetry breaking. The gauge bosons associated with the 16 broken generators then form two massive octets under ordinary color. The interactions between quarks and these heavy gluonlike particles are explicitly nonuniversal and thus an exploration of their physical implications allows us to shed light on the fundamental issue of strong-interaction universality. Nonuniversality and weak flavor mixing are shown to generate heavy-gluon-induced flavor-changing neutral currents. The phenomenology of these processes is studied, as they provide the major experimental constraint on the extended theory. Three symmetry-breaking scenarios are presented. The first has color breaking occurring at the weak scale, while the second and third divorce the two scales. The third model has the interesting feature of radiatively induced off-diagonal Kobayashi-Maskawa matrix elements

  18. Clinicopathologic correlations of renal microthrombosis and inflammatory markers in proliferative lupus nephritis

    OpenAIRE

    Gonzalo, Elena; Toldos, Oscar; Martínez-Vidal, María P; Ordoñez, María C; Santiago, Begoña; Fernández-Nebro, Antonio; Loza, Estíbaliz; García, Isabel; León, Myriam; Pablos, José L; Galindo, María

    2012-01-01

    Introduction Microthrombosis is often observed in lupus nephritis (LN) lesions, but its clinical significance is unknown. We evaluated the clinicopathologic correlations of renal microthrombosis and inflammatory markers in LN. Methods Kidney biopsies from 58 patients with systemic lupus erythematosus (SLE) proliferative nephritis were analyzed with immunohistochemistry (IHC) for intravascular platelet aggregates (CD61), macrophagic infiltration (CD68), and activated complement deposition (C4d...

  19. Observation of neovascularization of the disc associated with proliferative diabetic retinopathy using OCT angiography.

    Science.gov (United States)

    Akiyama, Hideo; Li, Danjie; Shimoda, Yukitoshi; Matsumoto, Hidetaka; Kishi, Shoji

    2018-02-19

    To describe the relationship between the vitreous and the neovascularization of the disc (NVD) using swept source optical coherence tomography (SS-OCT) and OCT angiography (OCTA). Retrospective. We examined 17 eyes of 11 consecutive patients diagnosed as NVD associated with proliferative diabetic retinopathy (PDR). The location of the NVD feeder or collector vessels were examined by using RTVue XR Avanti. To determine the condition of the posterior vitreous detachment (PVD) and the proliferative tissue of the NVD, we performed 12 mm horizontal and vertical scans through the disc using SS-OCT. OCT images of all 17 cases indicated there was no PVD on the optic disc. OCTA showed that the locations of the newly formed vessels from the optic disc were overwhelmingly outside the physiological cupping (95%). No cases exhibited formation of neovascularization inside the physiological cupping. OCT images revealed all 17 eyes had proliferative tissues located under the posterior wall of the vitreous, with 12 out of 17 eyes exhibiting additional invasion of the proliferative tissue into the vitreous through the posterior wall. Epiretinal membrane or a thickened posterior wall of the vitreous was present in 10 out of the 17 eyes. NVD associated with PDR arises from outside the physiological cupping and grows along the posterior wall of the vitreous. The absence of PVD on the optic disc is essential to the growth of NVD.

  20. Therapeutic interventions in mice with chronic proliferative dermatitis (cpdm/cpdm)

    NARCIS (Netherlands)

    Gijbels, M. J.; Elliott, G. R.; HogenEsch, H.; Zurcher, C.; van den Hoven, A.; Bruijnzeel, P. L.

    2000-01-01

    Chronic proliferative dermatitis (cpd) is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm). The dermatitis is characterized by redness, hairloss, scaling, pruritus and histologically by epithelial hyperproliferation, infiltration of eosinophils, macrophages and mast cells. Lesions similar to

  1. The T309G MDM2 gene polymorphism is a novel risk factor for proliferative vitreoretinopathy

    NARCIS (Netherlands)

    S. Pastor-Idoate (Salvador); I. Rodriguez-Hernández (Irene); J. Rojas (Jimena); I. Fernandez (Itziar); M.T. García-Gutierrez (María Teresa); J.M. Ruiz-Moreno (Jose María); A. Rocha-Sousa (Amandio); Y. Ramkissoon (Yashin); S. Harsum (Steven); R.E. MacLaren (Robert ); D. Charteris (David); J.C. Vanmeurs (Jan C.); R. González-Sarmiento (Rogelio); J.C. Pastor (Jose Carlos)

    2013-01-01

    textabstractProliferative vitreoretinopathy (PVR) is still the major cause of failure in retinal detachment (RD) surgery. It is believed that down-regulation in the p53 pathway could be an important key in PVR pathogenesis. The purpose was to evaluate the impact of T309G MDM2 polymorphism

  2. Temporal changes in retinal vascular parameters associated with successful panretinal photocoagulation in proliferative diabetic retinopathy

    DEFF Research Database (Denmark)

    Torp, Thomas Lee; Kawasaki, Ryo; Wong, Tien Yin

    2018-01-01

    PURPOSE: We aimed to investigate changes in retinal vascular geometry over time after panretinal photocoagulation (PRP) in patients with proliferative diabetic retinopathy (PDR). METHODS: Thirty-seven eyes with PDR were included. Wide-field fluorescein angiography (Optomap, Optos PLC., Dunfermlin...

  3. The Effects of Enhanced Informed Consent in a Pro-Life Pregnancy Counseling Center.

    Science.gov (United States)

    Mardirosian, Kathryn; And Others

    1990-01-01

    Investigated effects of enhanced informed consent condition on attitudes of female clients (n=60) toward a counselor, counseling situation, and decision making in a pro-life pregnancy center. Results suggest enhanced consent did not lead to increased or decreased decisions to abort nor to differential attitudes toward counselor or setting.…

  4. A novel role for coagulation proteins in the development of proliferative vitreoretinopathy

    NARCIS (Netherlands)

    J. Bastiaans (Jeroen)

    2015-01-01

    markdownabstractAbstract In patients with retinal detachment, the major cause of recurrent redetachment is proliferative vitreoretinopathy (PVR, 5-10 %). PVR is characterized by the formation of fibrotic contractile membranes on either side of the retina, causing the retina to detach. The

  5. Anti-Proliferative, Antioxidant and Iron-Chelating Properties of the ...

    African Journals Online (AJOL)

    At 500 μg DM/ml, both extracts produced about 40 and 30 % anti-proliferative activity on HeLa cells and K562 cells, respectively. Both extracts had moderate nitric oxide-scavenging and ironchelating activities. The leaf extract half-maximal effective concentration (EC50) value of 0.85 mg/ml (scavenging of superoxide ...

  6. Induction et prolifération de cals à partir de l'axe embryonnaire du ...

    African Journals Online (AJOL)

    Induction et prolifération de cals à partir de l'axe embryonnaire du Voandzou [ Vigna subterranea (L.) Verdc. Fabaceae] : effet de la segmentation de l'explant, des phytohormones, de la source de carbone et du génotype.

  7. Pathogenesis of skin lesions in mice with chronic proliferative dermatitis (cpdm/cpdm)

    NARCIS (Netherlands)

    Gijbels, M. J.; Zurcher, C.; Kraal, G.; Elliott, G. R.; HogenEsch, H.; Schijff, G.; Savelkoul, H. F.; Bruijnzeel, P. L.

    1996-01-01

    Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm), showing alopecia, epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To further elucidate its pathogenesis, organs of 1-, 2-, 3-, 4-, 5-, and 6-week-old

  8. Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy

    DEFF Research Database (Denmark)

    Vergmann, Anna Stage; Torp, Thomas Lee; Lundberg, Kristian

    Title of abstract: Retinal vessel caliber as a potential marker of treatment outcome in patients with proliferative diabetic retinopathy Design of study: Three months prospective, interventional clinical study. Purpose: The retinal vascular tree can be measured non-invasively and summarized...

  9. Global profiling of TSEC proliferative potential by the use of a reporter mouse for proliferation.

    Science.gov (United States)

    Oliva, Paolo; Roncoroni, Chiara; Radaelli, Enrico; Brunialti, Electra; Rizzi, Nicoletta; De Maglie, Marcella; Scanziani, Eugenio; Piaggio, Giulia; Ciana, Paolo; Komm, Barry; Maggi, Adriana

    2013-02-01

    "Tissue-selective estrogen complex" or TSEC is a novel concept of estrogen replacement therapy for the postmenopause based on the combined use of estrogens and selective estrogen receptor modulators (SERMs). The aim of this study was to exploit the potential of a novel transgenic mouse where luciferase expression is associated with cell proliferation (the MITO-luc mouse) to investigate cell proliferation in reproductive and nonreproductive tissues in mice exposed to repetitive treatments with TSEC. Ovariectomized MITO-Luc mice were subjected to a daily oral treatment with bazedoxifene, conjugated estrogen (CE), TSEC, or raloxifene for 21 days. During the treatment, the proliferative effects of treatments were monitored by bioluminescence-based in vivo imaging. At the end of the treatment, mice were euthanized and cell proliferation assessed in selected tissues by quantitative analysis of luciferase activity and by immunohistochemistry (IHC). In uterus treatment with CE, but not TSEC, induced a large increase in luciferase activity underlying the proliferative effect of the hormone. No accumulation of luciferase was observed in other organs and tissues target of estrogen action. We observed an increase of Ki67 immunoreactivity only in the uterus of mice treated with CE. Pairing of an SERM with estrogens results in a complete blockage of CE proliferative effects in uterus and the absence of any undesired proliferative effects in other organs; moreover, the MITO-Luc mouse is an efficacious tool for the global, rapid, and reliable analysis of drug-induced proliferation.

  10. Reconciling Faith and Fact: Pro-life Women Discuss Media, Science and the Abortion Debate.

    Science.gov (United States)

    Press, Andrea L.; Cole, Elizabeth R.

    1995-01-01

    Finds that pro-life women actively searched for authorities and authoritative information that were not "corrupted" by the values of secular society. Finds that, paradoxically, they drew on secular forms of argument, claiming scientific authenticity for their own sources, and that their selective viewing habits resulted in the…

  11. PROLIFERATIVE LESIONS IN SWIMBLADDER OF JAPANESE MEDAKA ORYZIAS LATIPES AND GUPPY POECILIA RETICULATA

    Science.gov (United States)

    Thirteen cases of proliferative lesions of the swimbladder were encountered in Japanese medaka Oryzias latipes and guppy Poecilia reticulata from about 10,000 medaka and 5,000 guppies used in carcinogenicity tests and histologically examined. Two of the four cases from medaka and...

  12. A spontaneous mutation characterized by chronic proliferative dermatitis in C57BL mice

    NARCIS (Netherlands)

    HogenEsch, H.; Gijbels, M. J.; Offerman, E.; van Hooft, J.; van Bekkum, D. W.; Zurcher, C.

    1993-01-01

    Chronic proliferative dermatitis is a new spontaneous mutation in C57BL/Ka mice. Breeding results suggest an autosomal recessive mode of inheritance. Mutant mice develop skin lesions at the age of 5 to 6 weeks. The lesions occur in the ventral and dorsal skin of the body, whereas ears, footpads, and

  13. Tenascin-C in the extracellular matrix promotes the selection of highly proliferative and tubulogenesis-defective endothelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Alves, Tercia Rodrigues [Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biologia Celular, Laboratorio de Biologia da Celula Endotelial e da Angiogenese (LabAngio), Rio de Janeiro (Brazil); Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Carvalho da Fonseca, Anna Carolina [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Nunes, Sara Santana; Oliveira da Silva, Aline [Universidade do Estado do Rio de Janeiro (UERJ), Instituto de Biologia Roberto Alcantara Gomes, Departamento de Biologia Celular, Laboratorio de Biologia da Celula Endotelial e da Angiogenese (LabAngio), Rio de Janeiro (Brazil); Dubois, Luiz Gustavo Feijo; Faria, Jane; Kahn, Suzana Assad [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); Viana, Nathan Bessa [Universidade Federal do Rio de Janeiro, Laboratorio de Pincas Oticas, Coordenacao de Programas de Estudos Avancados, Instituto de Ciencias Biomedicas, Rio de Janeiro (Brazil); Universidade Federal do Rio de Janeiro, Instituto de Fisica, Rio de Janeiro (Brazil); Marcondes, Jorge [Universidade Federal do Rio de Janeiro, Hospital Universitario Clementino Fraga Filho, Servico de Neurocirurgia, Rio de Janeiro (Brazil); Legrand, Chantal [Institut Universitaire d' Hematologie, Universite Paris-Diderot, Paris 7, INSERM U553, Paris (France); Moura-Neto, Vivaldo [Universidade Federal do Rio de Janeiro (UFRJ), Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciencias Biomedicas, INNT/INCT/MCT, Rio de Janeiro (Brazil); and others

    2011-09-10

    The extracellular matrix (ECM) contains important cues for tissue homeostasis and morphogenesis. The matricellular protein tenascin-C (TN-C) is overexpressed in remodeling tissues and cancer. In the present work, we studied the effect of different ECM-which exhibited a significant diversity in their TN-C content-in endothelial survival, proliferation and tubulogenic differentiation: autologous (endothelial) ECM devoid of TN-C, but bearing large amounts of FN; fibroblast ECM, bearing both high TN-C and FN contents; and finally, glioma-derived matrices, usually poor in FN, but very rich in TN-C. HUVECs initially adhered to the immobilized matrix produced by U373 MG glioma cells, but significantly detached and died by anoikis (50 to 80%) after 24 h, as compared with cells incubated with endothelial and fibroblast matrices. Surviving endothelial cells (20 to 50%) became up to 6-fold more proliferative and formed 74-97% less tube-like structures in vitro than cells grown on non-tumoral matrices. An antibody against the EGF-like repeats of tenascin-C (TN-C) partially rescued cells from the tubulogenic defect, indicating that this molecule is responsible for the selection of highly proliferative and tubulogenic defective endothelial cells. Interestingly, by using defined substrata, in conditions that mimic glioma and normal cell ECM composition, we observed that fibronectin (FN) modulates the TN-C-induced selection of endothelial cells. Our data show that TN-C is able to modulate endothelial branching morphogenesis in vitro and, since it is prevalent in matrices of injured and tumor tissues, also suggest a role for this protein in vascular morphogenesis, in these physiological contexts.

  14. A simple route to synthesize conductive stimuli-responsive polypyrrole nanocomposite hydrogel particles with strong magnetic properties and their performance for removal of hexavalent chromium ions from aqueous solution

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Hasan, E-mail: samarhass@yahoo.com [Department of Chemistry, Rajshahi University, Rajshahi 6205 (Bangladesh); Rahman, Mohammad Mostafizar; Ali, Mohammad Azgar [Department of Chemistry, Rajshahi University, Rajshahi 6205 (Bangladesh); Minami, Hideto [Graduate School of Engineering, Kobe University, Kobe 657-8501 (Japan); Tauer, Klaus [Max Planck Institute of Colloid and Interfaces, Am Mühlenberg, 14476 Golm (Germany); Gafur, Mohammad Abdul [Pilot Plant and Process Development Centre, BCSIR, Dhaka 1205 (Bangladesh); Rahman, Mohammad Mahbubor [Department of Chemistry, Rajshahi University, Rajshahi 6205 (Bangladesh)

    2016-08-15

    A combination of maghemite polypyrrole (PPy/γ-Fe{sub 2}O{sub 3}) and stimuli-responsive properties in the same hydrogel microspheres is expected to enhance their application potential in various fields such as tissue engineering, regenerative medicine, biosensors, biomedical applications and removal of heavy metals from waste water, catalysis etc. In this investigation a simple two step process is used to prepare conductive stimuli-responsive polypyrrole (PPy) composite hydrogel particles with strong magnetic properties. Poly(styrene-methacrylic acid-N-isopropylacrylamide-polyethelene glycol methacrylate) or P(S-NIPAM-MAA-PEGMA) hydrogel seed particles are first prepared by soap-free precipitation copolymerization. The copolymer hydrogel particles exhibited both temperature- and pH-responsive volume phase transition. Conductive P(S-NIPAM-MAA-PEGMA)/PPy/γ-Fe{sub 2}O{sub 3} nanocomposite hydrogel particles are then prepared by seeded chemical oxidative polymerization of pyrrole in the presence of P(S-NIPAM-MAA-PEGMA) hydrogel seed particles using FeCl{sub 3} as a oxidant and p-toluene sulfonic acid ( p-TSA) as a dopant. In the reaction system FeCl{sub 3} functioned as a source of Fe(III) for the formation of γ-Fe{sub 2}O{sub 3}. This reaction also requires the initial presence of Fe(II) provided by the addition of FeCl{sub 2}. The size and size distribution, surface structure, and morphology of the prepared conductive composite hydrogel particles are confirmed by FTIR, electron micrographs, X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and UV–visible spectroscopy. The performance of nanocomposite hydrogel particles has been evaluated for the removal of hexavalent chromium (Cr) ions from water. - Highlights: • P(S-NIPAM-MAA-PEGMA) hydrogel particles were prepared. • P(S-NIPAM-MAA-PEGMA)/PPy/γ-Fe{sub 2}O{sub 3} nanocomposite hydrogel particles were prepared. • Oxidative polymerization of pyrrole and precipitation of γ-Fe{sub 2}O{sub 3

  15. Balance of vascular endothelial growth factor and pigment epithelial growth factor prior to development of proliferative vitreoretinopathy

    NARCIS (Netherlands)

    Dieudonne, S.C.; Heij, La E.C.; Diederen, R.M.H.; Kessels, A.G.H.; Liem, A.T.A.; Kijlstra, A.; Hendrikse, F.

    2007-01-01

    Background: Pigment epithelium-derived factor (PEDF) and vascular endothelial growth factor (VEGF) are imbalanced in eyes with proliferative diabetic retinopathy or proliferative vitreoretinopathy (PVR). It is not known whether such an imbalance is already present in early PVR stages. We therefore

  16. s-ICAM-1 and s-VCAM-1 in healthy men are strongly associated with traits of the metabolic syndrome, becoming evident in the postprandial response to a lipid-rich meal

    Directory of Open Access Journals (Sweden)

    Nothnagel Michael

    2008-09-01

    Full Text Available Abstract Background The importance of the postprandial state for the early stages of atherogenesis is increasingly acknowledged. We conducted assessment of association between postprandial triglycerides, insulin and glucose after ingestion of a standardized lipid-rich test meal, and soluble cellular adhesion molecules (sCAM in young healthy subjects. Methods Metabolic parameters and sICAM-1, sVCAM-1 and E-selectin were measured before and hourly until 6 hours after ingestion of a lipid-rich meal in 30 healthy young men with fasting triglycerides 260 mg/dl. Levels of CAM were compared in HR and NR, and correlation with postprandial triglyceride, insulin and glucose response was assessed. Results Fasting sICAM-1 and sVCAM-1 levels were significantly higher in HR as compared to NR (p = 0.046, p = 0.03. For sE-selectin there was such a trend (p = 0.05. There was a strong positive and independent correlation between sICAM-1 and postprandial insulin maxima (r = 0.70, p Conclusion This independent association of postprandial triglycerides with sICAM-1 may indicate a particular impact of postprandial lipid metabolism on endothelial reaction.

  17. Probability densities in strong turbulence

    Science.gov (United States)

    Yakhot, Victor

    2006-03-01

    In this work we, using Mellin’s transform combined with the Gaussian large-scale boundary condition, calculate probability densities (PDFs) of velocity increments P(δu,r), velocity derivatives P(u,r) and the PDF of the fluctuating dissipation scales Q(η,Re), where Re is the large-scale Reynolds number. The resulting expressions strongly deviate from the Log-normal PDF P(δu,r) often quoted in the literature. It is shown that the probability density of the small-scale velocity fluctuations includes information about the large (integral) scale dynamics which is responsible for the deviation of P(δu,r) from P(δu,r). An expression for the function D(h) of the multifractal theory, free from spurious logarithms recently discussed in [U. Frisch, M. Martins Afonso, A. Mazzino, V. Yakhot, J. Fluid Mech. 542 (2005) 97] is also obtained.

  18. The proliferative response of mouse intestinal crypts during fractionated irradiation of carbon beams

    International Nuclear Information System (INIS)

    Abo, M.; Abe, Y.; Mariya, Y.; Ando, K.

    2000-01-01

    Clonogenic assay of jejunal crypt during carbon beam and X-ray irradiations was performed. Fractionation with top-up dose assay revealed carbon beam irradiations caused more damage than X-ray did. To clarify this problem is urgent. (author)

  19. Roles of ERβ and GPR30 in Proliferative Response of Human Bladder Cancer Cell to Estrogen

    Directory of Open Access Journals (Sweden)

    Weiren Huang

    2015-01-01

    Full Text Available Bladder cancer belongs to one of the most common cancers and is a leading cause of deaths in our society. Urothelial carcinoma of the bladder (UCB is the main type of this cancer, and the estrogen receptors in UCB remain to be studied. Our experiment aimed to investigate the possible biological effect of 17β-estradiol on human bladder-derived T24 carcinoma cells and to indicate its related mechanisms. T24 cells were treated with various doses of 17β-estradiol, and cell proliferation was detected using MTT assays. 17β-estradiol promoted T24 cell proliferation independent of ERβ/GPR30-regulated EGFR-MAPK pathway, while it inhibited cell growth via GPR30. Furthermore, the expression levels of downstream genes (c-FOS, BCL-2, and CYCLIN D1 were increased by 17β-estradiol and this effect was independently associated with activity of the EGFR-MAPK pathway. The two estrogen receptors might be potential therapeutic targets for the treatment of bladder cancer.

  20. Patients with oral allergic syndrome to apple have intense proliferative response to BET V 1.

    Science.gov (United States)

    Ciprandi, G; Fenoglio, G; Kalli, F; De Amici, M; Leonardi, S; Miraglia Del Giudice, M; Salpietro, C; La Rosa, M; Caimmi, S; Marseglia, G L

    2012-01-01

    Patients with pollen allergy may frequently present an additional food-related allergy (Oral Allergic Syndrome, OAS), as consequence of cross-reactivity between pollen allergens (mainly birch, hazelnut, alder, mugwort) and vegetable allergens. The aim of this study was to evaluate the effect on Bet v 1-induced T cell proliferation exerted by the presence of OAS in birch patients. Fourteen allergic patients were evaluated (6 males, mean age 35.8 years). All of them were monosensitized to birch and suffered from allergic rhinitis: 4 had also OAS to apple. Proliferation of peripheral mononuclear cells was evaluated using Bet v 1 and non-specific stimuli. OAS had higher proliferation than non-OAS patients. In addition, there were significant relationships between immunological and clinical parameters in OAS patients. This study evidences that OAS characterizes a more severe form of birch allergy: as OAS patients had higher SI, circulating eosinophils, and IgE levels. Thus, this study confirms the previous report and underlines the relevance of measuring recombinant birch allergen as higher values may suggest a reliable prediction of OAS.

  1. Flow cytometric analysis of lymphocyte proliferative responses to food allergens in dogs with food allergy.

    Science.gov (United States)

    Fujimura, Masato; Masuda, Kenichi; Hayashiya, Makio; Okayama, Taro

    2011-10-01

    Two different allergy tests, antigen-specific immunoglobulin E quantification (IgE test) and flow cytometric analysis of antigen-specific proliferation of peripheral lymphocytes (lymphocyte proliferation test), were performed to examine differences in allergic reactions to food allergens in dogs with food allergy (FA). Thirteen dogs were diagnosed as FA based on clinical findings and elimination diet trials. Seven dogs clinically diagnosed with canine atopic dermatitis (CAD) were used as a disease control group, and 5 healthy dogs were used as a negative control group. In the FA group, 19 and 33 allergen reactions were identified using the serum IgE test and the lymphocyte proliferation test, respectively. Likewise, in the CAD group, 12 and 6 allergen reactions and in the healthy dogs 3 and 0 allergen reactions were identified by each test, respectively. A significant difference was found between FA and healthy dogs in terms of positive allergen detection by the lymphocyte proliferation test, suggesting that the test can be useful to differentiate FA from healthy dogs but not from CAD. Both tests were repeated in 6 of the dogs with FA after a 1.5- to 5-month elimination diet trial. The IgE concentrations in 9 of 11 of the positive reactions decreased by 20-80%, whereas all the positive reactions in the lymphocyte proliferation test decreased to nearly zero (Pfood allergens may be involved in the pathogenesis of canine FA.

  2. Proliferative responses of tilapia T-like lymphocytes to stimulation by ...

    African Journals Online (AJOL)

    Peripheral blood lymphocytes were cultured in vitro in the presence of a mitogen; Concanavalin A (Con A), this resulted into a process described as lymphocyte transformation. The morphological changes in the cells were studied using phase contrast and electron microscopes. The results presented corroborated the ...

  3. The effect of an antigenic stimulation on proliferative response in athymic mice.

    Science.gov (United States)

    Síma, P; Bilej, M; Kovárů, F; Vĕtvicka, V; Holub, M

    1992-01-01

    The proliferation activity of the main cellular categories of bone marrow after infusion of 3H-thymidine was studied in nu/nu and +/+ 1-month- and 3-month-old BALB/c mice in comparison with lymphoid cells in the spleen and mesenteric lymph nodes. The stem cell defect in nu/nu mouse bone marrow is compensated by an increased proliferation in myeloid series and in agranulocytes. The increase of proliferation activity among lymphoid cells in peripheral lymphoid organs was observed only in the 3-month-old mice with a delay in the nudes.

  4. Characterization of Toll-like receptors in primary lung epithelial cells: strong impact of the TLR3 ligand poly(I:C on the regulation of Toll-like receptors, adaptor proteins and inflammatory response

    Directory of Open Access Journals (Sweden)

    Weith Andreas

    2005-11-01

    Full Text Available Abstract Background Bacterial and viral exacerbations play a crucial role in a variety of lung diseases including COPD or asthma. Since the lung epithelium is a major source of various inflammatory mediators that affect the immune response, we analyzed the inflammatory reaction of primary lung epithelial cells to different microbial molecules that are recognized by Toll-like receptors (TLR. Methods The effects of TLR ligands on primary small airway epithelial cells were analyzed in detail with respect to cytokine, chemokine and matrix metalloproteinase secretion. In addition, the regulation of the expression of TLRs and their adaptor proteins in small airway epithelial cells was investigated. Results Our data demonstrate that poly(I:C, a synthetic analog of viral dsRNA, mediated the strongest proinflammatory effects among the tested ligands, including an increased secretion of IL-6, IL-8, TNF-α, GM-CSF, GRO-α, TARC, MCP-1, MIP-3α, RANTES, IFN-β, IP-10 and ITAC as well as an increased release of MMP-1, MMP-8, MMP-9, MMP-10 and MMP-13. Furthermore, our data show that poly(I:C as well as type-1 and type-2 cytokines have a pronounced effect on the expression of TLRs and molecules involved in TLR signaling in small airway epithelial cells. Poly(I:C induced an elevated expression of TLR1, TLR2 and TLR3 and increased the gene expression of the general TLR adaptor MyD88 and IRAK-2. Simultaneously, poly(I:C decreased the expression of TLR5, TLR6 and TOLLIP. Conclusion Poly(I:C, an analog of viral dsRNA and a TLR3 ligand, triggers a strong inflammatory response in small airway epithelial cells that is likely to contribute to viral exacerbations of pulmonary diseases like asthma or COPD. The pronounced effects of poly(I:C on the expression of Toll-like receptors and molecules involved in TLR signaling is assumed to influence the immune response of the lung epithelium to viral and bacterial infections. Likewise, the regulation of TLR expression by type

  5. Searching in mother nature for anti-cancer activity: anti-proliferative and pro-apoptotic effect elicited by green barley on leukemia/lymphoma cells.

    Directory of Open Access Journals (Sweden)

    Elisa Robles-Escajeda

    Full Text Available Green barley extract (GB was investigated for possible anti-cancer activity by examining its anti-proliferative and pro-apoptotic properties on human leukemia/lymphoma cell lines. Our results indicate that GB exhibits selective anti-proliferative activity on a panel of leukemia/lymphoma cells in comparison to non-cancerous cells. Specifically, GB disrupted the cell-cycle progression within BJAB cells, as manifested by G2/M phase arrest and DNA fragmentation, and induced apoptosis, as evidenced by phosphatidylserine (PS translocation to the outer cytoplasmic membrane in two B-lineage leukemia/lymphoma cell lines. The pro-apoptotic effect of GB was found to be independent of mitochondrial depolarization, thus implicating extrinsic cell death pathways to exert its cytotoxicity. Indeed, GB elicited an increase of TNF-α production, caspase-8 and caspase-3 activation, and PARP-1 cleavage within pre-B acute lymphoblastic leukemia Nalm-6 cells. Moreover, caspase-8 and caspase-3 activation and PARP-1 cleavage were strongly inhibited/blocked by the addition of the specific caspase inhibitors Z-VAD-FMK and Ac-DEVD-CHO. Furthermore, intracellular signaling analyses determined that GB treatment enhanced constitutive activation of Lck and Src tyrosine kinases in Nalm-6 cells. Taken together, these findings indicate that GB induced preferential anti-proliferative and pro-apoptotic signals within B-lineage leukemia/lymphoma cells, as determined by the following biochemical hallmarks of apoptosis: PS externalization, enhanced release of TNF-α, caspase-8 and caspase-3 activation, PARP-1 cleavage and DNA fragmentation Our observations reveal that GB has potential as an anti-leukemia/lymphoma agent alone or in combination with standard cancer therapies and thus warrants further evaluation in vivo to support these findings.

  6. MR findings of bland and proliferative joint effusion in Knee joint

    International Nuclear Information System (INIS)

    Lee, Hak Soo; Joo, Kyung Bin; Yang, Kee Hyuk; Choi, Jung Bin; Kim, Yong Soo; Park, Dong Woo; Park, Choong Ki; Hahm, Chang Kok

    2000-01-01

    To determine the MR imaging criteria by which bland and proliferative effusion of the knee may be differentiated. We retrospectively reviewed the MR images of 64 patients (65 cases), in whom T2-weighted sagittal scans revealed anteroposterior distension of the suprapatellar bursa of at least 0.5 cm. The patients were divided into two groups: bland effusion (n=3D36), and proliferative effusion ((n=3D29); pigmented villonodular synovitis (n=3D5), rheumatoid arthritis (n=3D6), septic arthritis (n=3D6), chronic synovitis (n=3D5), gouty arthritis (n=3D3), tuberculous arthritis (n=3D2), and lipoma arborescens (n=3D2)). All conditions were diagnosed on the basis of operative data or clinical criteria. The knee joint space was divided into four compartments: the suprapatellar pouch, central zone, posterior femoral recess, and subpopliteal recess, and the amount and distribution of effusion was then compared between the two groups. The ratios of the width and the length of the lateral recess of the suprapatellar bursa to those of its medial recess were determined, and the findings for the two groups were compared.Abnormality of the intracapular fat pads (prefemoral fat, Hoffa's fat, and quadriceps fat sign) as seen on sagittal scans, is a predictor proliferative effusion, and any such abnormality was evaluated. The synovium was classified as either thin or thick, and as having either a smooth or an irregular margin, as seen on Gadolinium-enhanced T1W1 images. As compared with bland effusion, proliferative effusion involved more prominent joint effusion in the suprapatellar pouch and posterior femoral recess, and in the suprapatellar bursa, the ratio of the width of the lateral recess to that of the medial recess was greater. When comparing the ratio of the length of the lateral recess to that of the medial recess, however, no significant statistical difference was noted. Sensitivity: specificity for proliferative effusion was 58%: 86% on coronal scan and 64%: 93% on axial

  7. Change of ranibizumab-induced human vitreous protein profile in patients with proliferative diabetic retinopathy based on proteomics analysis.

    Science.gov (United States)

    Zou, Chen; Han, Changjing; Zhao, Minjie; Yu, Jingjing; Bai, Lin; Yao, Yuan; Gao, Shuaixin; Cao, Hui; Zheng, Zhi

    2018-01-01

    Preoperative treatment of anti-vascular endothelial growth factor (VEGF) agents is extensively used in proliferative diabetic retinopathy (PDR), but the molecular mechanism is not fully understood. The objective of this research is to observe change of protein profile induced by ranibizumab (an anti-VEGF agent) in vitreous humor from PDR patients and reveal the effects of anti-VEGF treatment on PDR. A proteomic method was used to identify differentially expressed proteins in vitreous humor. Untreated PDR patients were defined as PDR group, while those who treated with intravitreal injection of ranibizumab (IVR) were defined as IVR. Gene Ontology (GO) annotation and REACTOME pathways were obtained from DAVID Bioinformatics Resources. Intravitreal level of apolipoprotein C-I (APOC1), serpin peptidase inhibitor clade A member 5 (SERPINA5), tissue inhibitor of metalloproteinases (TIMP2), and keratin 1 (KRT1) were determined by enzyme-linked immuno sorbent assay (ELISA). 339 differentially expressed proteins were identified in response to IVR. The most notable GO annotation describes the altered proteins was "innate immune response". The most notable REACTOME pathway was "platelet degranulation". ELISA result showed increased level of APOC1, SERPINA5, KRT1 and a decreased level of TIMP2 in PDR group compared with IVR. In addition to decreasing VEGF level, ranibizumab is associated with change of human vitreous protein profile in patients with PDR, in which the differential proteins are involved in immune response, platelet degranulation, complement activation etc., suggesting that the effects of VEGF are involved in these signaling pathways.

  8. Proliferative capacity of stem/progenitor-like cells in the kidney may associate with the outcome of patients with acute tubular necrosis.

    Science.gov (United States)

    Ye, Youxin; Wang, Bingyin; Jiang, Xinxin; Hu, Weiming; Feng, Jian; Li, Hua; Jin, Mei; Ying, Yingjuan; Wang, Wenjuan; Mao, Xiaoou; Jin, Kunlin

    2011-08-01

    Animal studies indicate that adult renal stem/progenitor cells can undergo rapid proliferation in response to renal injury, but whether the same is true in humans is largely unknown. To examine the profile of renal stem/progenitor cells responsible for acute tubular necrosis in human kidney, double and triple immunostaining was performed using proliferative marker and stem/progenitor protein markers on sections from 10 kidneys with acute tubular necrosis and 4 normal adult kidneys. The immunopositive cells were recorded using 2-photon confocal laser scanning microscopy. We found that dividing cells were present in the tubules of the cortex and medulla, as well as the glomerulus in normal human kidney. Proliferative cells in the parietal layer of Bowman capsule expressed CD133, and dividing cells in the tubules expressed immature cell protein markers paired box gene 2, vimentin, and nestin. After acute tubular necrosis, Ki67-positive cells in the cortex tubules significantly increased compared with normal adult kidney. These Ki67-positive cells expressed CD133 and paired box gene 2, but not the cell death marker, activated caspase-3. In addition, the number of dividing cells increased significantly in patients with acute tubular necrosis who subsequently recovered, compared with patients with acute tubular necrosis who consequently developed protracted acute tubular necrosis or died. Our data suggest that renal stem/progenitor cells may reside not only in the parietal layer of Bowman capsule but also in the cortex and medulla in normal human kidney, and the proliferative capacity of renal stem/progenitor cells after acute tubular necrosis may be an important determinant of a patient's outcome. Copyright © 2011 Elsevier Inc. All rights reserved.

  9. Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells.

    Science.gov (United States)

    von Bueren, André O; Shalaby, Tarek; Rajtarova, Julia; Stearns, Duncan; Eberhart, Charles G; Helson, Lawrence; Arcaro, Alexandre; Grotzer, Michael A

    2007-01-25

    With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma--an embryonal tumor with biological similarities to MB--the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected), D341 (c-MYC amplification) and D425 (c-MYC amplification) human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7-9.6 ng/ml) and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit proliferation of human MB cells in vivo.

  10. DNA-protein immunization using Leishmania peroxidoxin-1 induces a strong CD4+ T cell response and partially protects mice from cutaneous leishmaniasis: role of fusion murine granulocyte-macrophage colony-stimulating factor DNA adjuvant.

    Directory of Open Access Journals (Sweden)

    Abebe Genetu Bayih

    2014-12-01

    Full Text Available To date, no universally effective and safe vaccine has been developed for general human use. Leishmania donovani Peroxidoxin-1 (LdPxn-1 is a member of the antioxidant family of proteins and is predominantly expressed in the amastigote stage of the parasite. The aim of this study was to evaluate the immunogenicity and protective efficacy of LdPxn-1 in BALB/c mice in heterologous DNA-Protein immunization regimen in the presence of fusion murine granulocyte-macrophage colony-stimulating factor (mGMCSF DNA adjuvant.A fusion DNA of LdPxn1 and mGMCSF was cloned into a modified pcDNA vector. To confirm the expression in mammalian system, Chinese hamster ovary cells were transfected with the plasmid vector containing LdPxn1 gene. BALB/c mice were immunized twice with pcDNA-mGMCSF-LdPxn-1 or pcDNA-LdPxn1 DNA and boosted once with recombinant LdPxn-1 protein. Three weeks after the last immunization, mice were infected with Leishmania major promastigotes. The result showed that immunization with pcDNA-mGMCSF-LdPxn1 elicited a mixed Th-1/Th-2 immune response with significantly higher production of IFN-γ than controls. Intracellular cytokine staining of antigen-stimulated spleen cells showed that immunization with this antigen elicited significantly higher proportion of CD4+ T cells that express IFN-γ, TNF-α, or IL-2. The antigen also induced significantly higher proportion of multipotent CD4+ cells that simultaneously express the three Th-1 cytokines. Moreover, a significant reduction in the footpad swelling was seen in mice immunized with pcDNA-mGMCSF-LdPxn1 antigen. Expression study in CHO cells demonstrated that pcDNA-mGMCSF-LdPxn-1 was expressed in mammalian system.The result demonstrates that immunization of BALB/c mice with a plasmid expressing LdPxn1 in the presence of mGMCSF adjuvant elicits a strong specific immune response with high level induction of multipotent CD4+ cells that mediate protection of the mice from Leishmania major infection. To

  11. Novel influenza virus vectors expressing Brucella L7/L12 or Omp16 proteins in cattle induced a strong T-cell immune response, as well as high protectiveness against B. abortus infection.

    Science.gov (United States)

    Tabynov, Kaissar; Kydyrbayev, Zhailaubay; Ryskeldinova, Sholpan; Yespembetov, Bolat; Zinina, Nadezhda; Assanzhanova, Nurika; Kozhamkulov, Yerken; Inkarbekov, Dulat; Gotskina, Tatyana; Sansyzbay, Abylai

    2014-04-11

    This paper presents the results of a study of the immunogenicity and protectiveness of new candidate vector vaccine against Brucella abortus - a bivalent vaccine formulation consisting of a mixture of recombinant influenza A subtype H5N1 or H1N1 (viral constructs vaccine formulation) viruses expressing Brucella ribosomal protein L7/L12 and Omp16, in cattle. To increase the effectiveness of the candidate vaccine, adjuvants such as Montanide Gel01 or chitosan were included in its composition. Immunization of cattle (heifers aged 1-1.5 years, 5 animals per group) with the viral constructs vaccine formulation only, or its combination with adjuvants Montanide Gel01 or chitosan, was conducted via the conjunctival method using cross prime (influenza virus subtype H5N1) and booster (influenza virus subtype H1N1) vaccination schedules at an interval of 28 days. Vaccine candidates were evaluated in comparison with the positive (B. abortus S19) and negative (PBS) controls. The viral constructs vaccine formulations, particularly in combination with Montanide Gel01 adjuvant promoted formation of IgG antibodies (with a predominance of antibodies of isotype IgG2a) against Brucella L7/L12 and Omp16 proteins in ELISA. Moreover, these vaccines in cattle induced a strong antigen-specific T-cell immune response, as indicated by a high number of CD4(+) and CD8(+) cells, as well as the concentration of IFN-γ, and most importantly provided a high level of protectiveness comparable to the commercial B. abortus S19 vaccine and superior to the B. abortus S19 vaccine in combination with Montanide Gel01 adjuvant. Based on these findings, we recommended the bivalent vaccine formulation containing the adjuvant Montanide Gel01 for practical use in cattle. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  12. Impurity screening in strongly coupled plasma systems

    CERN Document Server

    Kyrkos, S

    2003-01-01

    We present an overview of the problem of screening of an impurity in a strongly coupled one-component plasma within the framework of the linear response (LR) theory. We consider 3D, 2D and quasi-2D layered systems. For a strongly coupled plasma the LR can be determined by way of the known S(k) structure functions. In general, an oscillating screening potential with local overscreening and antiscreening regions emerges. In the case of the bilayer, this phenomenon becomes global, as overscreening develops in the layer of the impurity and antiscreening in the adjacent layer. We comment on the limitations of the LR theory in the strong coupling situation.

  13. Rational design, synthesis and anti-proliferative evaluation of novel benzosuberone tethered with hydrazide-hydrazones.

    Science.gov (United States)

    Yadagiri, Bandi; Holagunda, Uma Devi; Bantu, Rajashaker; Nagarapu, Lingaiah; Guguloth, Vijayacharan; Polepally, Sowjanya; Jain, Nishanth

    2014-11-01

    Two different series of novel analogues of benzosuberones (5a-m and 9a-w) tethered with hydrazone-hydrazides (functional group alterations: Head group to Tail group and vice versa) have been synthesized by the reaction of appropriate aldehydes with substituted hydrazides in excellent yields (87-94%) and their structures were confirmed by (1)H NMR, (13)C NMR, ESI-MS and HRMS. The newly synthesized compounds were evaluated for anti-proliferative activity against different human cancer cell lines (HeLa, MDA MB 231, MIAPACA and IMR32). Among the synthesized compounds, six compounds 5 a, 5 b, 5 d, 5 e, 5 f and 9 v exhibited potent anti-proliferative activity with GI50 values less than 0.01 μM against MIAPACA, MDA-MB-231 and IMR32 human cancer cell lines. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Easy labeling of proliferative phase and sporogonic phase of microsporidia Nosema bombycis in host cells.

    Directory of Open Access Journals (Sweden)

    Jie Chen

    Full Text Available Microsporidia are eukaryotic, unicellular parasites that have been studied for more than 150 years. These organisms are extraordinary in their ability to invade a wide range of hosts including vertebrates and invertebrates, such as human and commercially important animals. A lack of appropriate labeling methods has limited the research of the cell cycle and protein locations in intracellular stages. In this report, an easy fluorescent labeling method has been developed to mark the proliferative and sporogonic phases of microsporidia Nosema bombycis in host cells. Based on the presence of chitin, Calcofluor White M2R was used to label the sporogonic phase, while β-tubulin antibody coupled with fluorescence secondary antibody were used to label the proliferative phase by immunofluorescence. This method is simple, efficient and can be used on both infected cells and tissue slices, providing a great potential application in microsporidia research.

  15. Synthesis and anti-proliferative activity of fluoro-substituted chalcones.

    Science.gov (United States)

    Burmaoglu, Serdar; Algul, Oztekin; Anıl, Derya Aktas; Gobek, Arzu; Duran, Gulay Gulbol; Ersan, Ronak Haj; Duran, Nizami

    2016-07-01

    A series of novel fluoro-substituted chalcone derivatives have been synthesized. All synthesized compounds were characterized by (1)H nuclear magnetic resonance (NMR), (13)C NMR, and elemental analysis. Their anti-proliferative activities were evaluated against five cancer cells lines, namely, A549, A498, HeLa, A375, and HepG2 using the MTT method. Most of the compounds showed moderate to high activity with IC50 values in the range of 0.029-0.729μM. Of all the synthesized compounds, 10 and 19 exhibited the most potent anti-proliferative activities against cancer cells, and 10 was identified as the most promising compound. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Glycoprotein CD44 expression in normal, hyperplasic and neoplastic endometrium. An immunohistochemical study including correlations with p53, steroid receptor status and proliferative indices (PCNA, MIB1).

    Science.gov (United States)

    Zagorianakou, N; Ioachim, E; Mitselou, A; Kitsou, E; Zagorianakou, P; Stefanaki, S; Makrydimas, G; Agnantis, N J

    2003-01-01

    We have studied by immunohistochemistry the presence and localization of CD44, estrogen and progesterone receptors, p53 and proliferative associated indices (MIB1, PCNA) in archival endometrial tissue, in order to determine their diagnostic and prognostic value as well as the possible correlations between them. We examined 186 samples of endometrial tissue (100 endometrial carcinomas of endometrioid type, 40 cases of hyperplasia and 46 of normal endometrium). Patient records were examined for FIGO stage, grade, and depth of myometrial invasion, histology, and lympho-vascular space invasion. Strong membranous immunostaining (> 10% of neoplastic cells) was observed in 45% of the carcinomas. A statistically significant correlation was found in the expression of protein in stromal cells, when compared with epithelial cells (p failed to show any statistical correlation with tumor grade or with vessel invasion. The expression of the protein was lower in FIGO Stage II compared with Stage I (p = 0.03). A positive relation of CD44 expression with progesterone receptor status (p = 0.02) was detected. CD44 expression was also positively associated with the proliferation associated with the proliferative index MIB1 (p = 0.001). CD44 is closely related to the secretory phase of the normal menstrual cycle and its expression is decreased in hyperplasia (simple or complex with or without atypia) and in cancer cases. These observations suggest that decreased CD44 expression might be functionally involved in the multiple mechanisms of the development and progression of endometrial lesions.

  17. The phylogeography of salmonid proliferative kidney disease in Europe and North America.

    OpenAIRE

    Henderson, Matthew; Okamura, Beth

    2004-01-01

    Salmonid proliferative kidney disease (PKD) is caused by the myxozoan Tetracapsuloides bryosalmonae. Given the serious and apparently growing impact of PKD on farmed and wild salmonids, we undertook a phylogeographic study to gain insights into the history of genealogical lineages of T. bryosalmonae in Europe and North America, and to determine if the global expansion of rainbow trout farming has spread the disease. Phylogenetic analyses of internal transcribed spacer 1 sequences revealed a c...

  18. Proliferative pododermatitis associated with virus-like particles in a northern gannet.

    Science.gov (United States)

    Daoust, P Y; Wadowska, D; Kibenge, F; Campagnoli, R P; Latimer, K S; Ritchie, B W

    2000-04-01

    Small multifocal lesions of proliferative pododermatitis were observed in an emaciated adult male northern gannet (Morus bassanus). Ultrastructurally, these lesions were associated with numerous virus-like particles with a size and morphology suggestive of Papovaviridae. DNA in situ hybridization with probes for avian polyomaviral and papillomaviral nucleic acid and an immunohistochemical test for the presence of papillomaviral antigen failed to identify this virus further. To our knowledge, papovavirus-like particles have not been recognized previously in this avian species.

  19. Japan Turns Pro-Life: Recent Change in Reproductive Health Policy and Controversies over Prenatal Screening

    Directory of Open Access Journals (Sweden)

    Etsuji Okamoto

    2014-02-01

    Full Text Available Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of “selective abortions” thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA, which prohibits abortions due to “fetal cause”.

  20. Japan turns pro-life: recent change in reproductive health policy and challenges by new technologies

    OpenAIRE

    Okamoto, Etsuji

    2014-01-01

    Japan, known as a pro-choice country in terms of abortion, is currently facing the increase of “selective abortions” thanks to new prenatal screening. Efforts to restrict proliferation of new technology has not been successful and it is likely that Japan will turn pro-life by strictly enforcing the Maternity Protection Act (MPA), which prohibits abortions due to “fetal cause”.

  1. BRCA1 expression, proliferative and apoptotic activities in ovarian epithelial inclusions

    OpenAIRE

    Wang, Yiying; Wang, Yue; Wei, Li; Hong, Shuhui; Zhao, Miaoqing; Zhang, Xi; Zheng, Wenxin

    2017-01-01

    Background The purpose of this study was to examine proliferative and apoptotic activity in relation with BRCA1 expression in ovarian epithelial inclusions (OEIs), the putative precursor lesions of ovarian epithelial cancer (OEC). Methods Benign ovaries from 95 patients were examined. Dual immunohistochemical staining for both BRCA1 and MIB-1 were performed to examine the relationship between BRCA1 and MIB-1 in OEI cells. Apoptotic activity was assessed on the parallel tissue sections by usin...

  2. Number and proliferative capacity of osteogenic stem cells are maintained during aging and in patients with osteoporosis

    DEFF Research Database (Denmark)

    Dokkedahl, Karin Stenderup; Justesen, J; Eriksen, E F

    2001-01-01

    Decreased bone formation is an important pathophysiological mechanism responsible for bone loss associated with aging and osteoporosis. Osteoblasts (OBs), originate from mesenchymal stem cells (MSCs) that are present in the bone marrow and form colonies (termed colony-forming units-fibroblastic [......Decreased bone formation is an important pathophysiological mechanism responsible for bone loss associated with aging and osteoporosis. Osteoblasts (OBs), originate from mesenchymal stem cells (MSCs) that are present in the bone marrow and form colonies (termed colony-forming units......-fibroblastic [CFU-Fs]) when cultured in vitro. To examine the effect of aging and osteoporosis on the MSC population, we quantified the number of MSCs and their proliferative capacity in vitro. Fifty-one individuals were studied: 38 normal volunteers (23 young individuals [age, 22-44 years] and 15 old individuals...... [age, 66-74 years]) and 13 patients with osteoporosis (age, 58-83 years). Bone marrow was aspirated from iliac crest; mononuclear cells were enriched in MSCs by magnetic activated cell sorting (MACS) using STRO-1 antibody. Total CFU-F number, size distribution, cell density per CFU-F, number...

  3. In vitro evaluation of cytotoxic, anti-proliferative, anti-oxidant, apoptotic, and anti-microbial activities of Cladonia pocillum.

    Science.gov (United States)

    Ersoz, M; Coskun, Z M; Acikgoz, B; Karalti, I; Cobanoglu, G; Cesal, C

    2017-08-15

    The aim of this study was to investigate the anti-proliferative, apoptotic, cytotoxic, and anti-oxidant effects of extracts from the lichen Cladonia pocillumon human breast cancer cells (MCF-7), and to characterize the anti-microbial features.  MCF-7 cells were treated with methanolic C. pocillum extract for 24h. The cytotoxicity of the extract was tested with MTT. Moreover, its anti-proliferative effects were examined with immunocytochemical method. Apoptosis and biochemical parameters were detected in MCF-7. The methanol and chloroform extracts of the lichen were tested for anti-microbial activity against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans using the disc diffusion method and calculation of minimal inhibitory concentrations. Although BrdU incorporation was not observed in MCF-7 cells treated with methanol extract at a concentration above 0.2 mg/mL, a significant decrease was observed int he percentage of PCNA immunoreactive cells in groups treated with 0.2, 0.4, 06, and 0.8 mg/mL methanol extracts of C.pocillum (49±6.3, 44±5.2, 23±2.5, 0, respectively) compared to that of control (85±4.5). The percentage of apoptotic cells significantly increased in groups treated with 0.2, 0.4, 0.6, and 0.8 mg/mL extracts of the C.pocillum (54±3.5, 76±2.6, 77±1.8, 82±4.2, respectively) compared with that of control group (3.9±1.5).The half-maximal inhibitory concentration of the methanol extract against MCF-7 cells was 0.802 mg/mL .Although the chloroform extract showed more effective anti-microbial activity overall, the methanol extract showed higher anti-fungal activity. Collectively, the results of our study indicate that C.pocillum extracts have strong anti-microbial and apoptotic effects. This lichen therefore shows potential for development as a natural anti-microbial, anti-oxidant, and apoptotic agent.

  4. Illness perceptions in patients with systemic lupus erythematosus and proliferative lupus nephritis.

    Science.gov (United States)

    Daleboudt, G M N; Broadbent, E; Berger, S P; Kaptein, A A

    2011-03-01

    This study investigated the illness perceptions of patients with systemic lupus erythematosus (SLE) and whether perceptions are influenced by type of treatment for proliferative lupus nephritis. In addition, the illness perceptions of SLE patients were compared with those of patients with other chronic illnesses. Thirty-two patients who had experienced at least one episode of proliferative lupus nephritis were included. Patients were treated with either a high or low-dose cyclophosphamide (CYC) regimen (National Institutes of Health [NIH] vs. Euro-Lupus protocol). Illness perceptions were measured with the Brief Illness Perception Questionnaire (B-IPQ) and a drawing assignment. The low-dose CYC group perceived their treatment as more helpful than the high-dose CYC group. In comparison with patients with asthma, SLE patients showed more negative illness perceptions on five of the eight illness perception domains. Drawings of the kidney provided additional information about perceptions of treatment effectiveness, kidney function and patients' understanding of their illness. Drawing characteristics showed associations with perceptions of consequences, identity, concern and personal control. These findings suggest that the type of treatment SLE patients with proliferative lupus nephritis receive may influence perceptions of treatment effectiveness. In addition, patients' drawings reveal perceptions of damage caused by lupus nephritis to the kidneys and the extent of relief provided by treatment. The finding that SLE is experienced as a more severe illness than other chronic illnesses supports the need to more frequently assess and aim to improve psychological functioning in SLE patients.

  5. [Effect of sulfated polysaccharides from brown algae on proliferative and cytotoxic activity of mice splenocytes].

    Science.gov (United States)

    Makarenkova, I D; Semenova, I B; Akhmatova, N K; Besednova, N N; Zviagintseva, T N; Ermakova, S P

    2012-01-01

    Study effect of fucoidans from brown algae on proliferative and cytotoxic activity of mice splenocytes. Proliferative and cytotoxic activity of mice splenocytes in vitro and ex vivo were studied in lymphocyte blast transformation reaction and in cytotoxic MTT-test on K562 human erythroblast leucosis cell line. Microphotography and microscopy were performed by using Axiocam HS photosystem and computer program AxioVision 4 (Germany). Fucoidans from brown algae Fucus evanescens, Laminaria cichorioides and Laminaria japonica in vitro and ex vivo systems were established to increase proliferative activity of mice splenocytes which is evidenced by an increase of stimulation index. Results of in vitro and ex vivo cytotoxic activity studies demonstrate that fucoidans which are various by chemical structure stimulate activity of NK-cells and facilitate an increase of splenocyte cytotoxic potential level against NK sensitive K562 cell line. The data obtained from the study demonstrate an ability of fucoidans to stimulate splenocyte proliferation and NK-cell killer activity, and studies of relation between structure and functions of sulfated polysaccharides facilitate a more detailed understanding of aspects of their mechanism of action on innate immunity system, thus providing the basis for development of new immunobiologic preparations - modifiers/agonists of innate immunity.

  6. Proliferative activity of the parathyroid cells in rats with secondary hyperparathyroidism.

    Science.gov (United States)

    Yamaguchi, S; Yachiku, S; Hashimoto, H; Okuyama, M; Tsurukawa, H; Kawakami, N; Watabe, Y; Sue, Y

    2001-04-01

    Proliferative kinetics of parathyroid cells in secondary hyperparathyroidism (HPT) are still unknown. We examined the histopathological changes and proliferative activity of parathyroid cells in spontaneously hypercholesterolemic (SHC) rats that exhibit secondary HPT and in normal Sprague Dawley (SD) rats from 3 weeks to 32 weeks of age. Proliferative activity [proliferating cell nuclear antigen(PCNA) labeling index], evaluated by means of immunohistochemical examination of PCNA, declined in SD rats with age from 10.8% at 3 weeks of age to 0.15% at 32 weeks of age. In SHC rats, a PCNA labeling index of 11.6% declined to 3.12% at 14 weeks of age and rebounded to 6.15% at 26 weeks of age. Parathyroid glands increased in size as determined by the maximum cross-sectional area, but in SHC rats, the increase was significantly greater, paralleling the progression of renal dysfunction, and at 32 weeks they were almost three times larger than in SD rats. Parathyroid hormone (PTH) levels in SHC rats also rose sharply after 20 weeks and reached 611 pg/ml at 32 weeks, while PTH in SD rats remained unchanged at approximately 110 pg/ml. This study showed that in the course of developing HPT in SHC rats, there is a large increase in the size of the parathyroid gland, a concomitant increase in PTH levels, and a PCNA labeling index that is higher than in normal SD rats.

  7. Too much of a good thing? An observational study of prolific authors.

    Science.gov (United States)

    Wager, Elizabeth; Singhvi, Sanjay; Kleinert, Sabine

    2015-01-01

    Introduction. Researchers' productivity is usually measured in terms of their publication output. A minimum number of publications is required for some medical qualifications and professional appointments. However, authoring an unfeasibly large number of publications might indicate disregard of authorship criteria or even fraud. We therefore examined publication patterns of highly prolific authors in 4 medical specialties. Methods. We analysed Medline publications from 2008-12 using bespoke software to disambiguate individual authors focusing on 4 discrete topics (to further reduce the risk of combining publications from authors with the same name and affiliation). This enabled us to assess the number and type of publications per author per year. Results. While 99% of authors were listed on fewer than 20 publications in the 5-year period, 24 authors in the chosen areas were listed on at least 25 publications in a single year (i.e., >1 publication per 10 working days). Types of publication by the prolific authors varied but included substantial numbers of original research papers (not simply editorials or letters). Conclusions. Institutions and funders should be alert to unfeasibly prolific authors when measuring and creating incentives for researcher productivity.

  8. Proliferative thyroid lesions in three diplodactylid geckos: Nephrurus amyae, Nephrurus levis, and Oedura marmorata.

    Science.gov (United States)

    Hadfield, Catherine A; Clayton, Leigh A; Clancy, Meredith M; Beck, Sarah E; Mangus, Lisa M; Montali, Richard J

    2012-03-01

    Over a 5-mo period, three diplodactylid geckos housed at the National Aquarium were diagnosed with proliferative thyroid lesions: a rough knob-tail gecko (Nephrurus amyae), a smooth knob-tail gecko (Nephrurus levis), and a marbled velvet gecko (Oedura marmorata). Clinical signs included an intraoral mass or ventral throat swelling (or both), oral bleeding, and weight loss. Both of the knob-tail geckos died. The histologic diagnosis for the rough knob-tail gecko was thyroid carcinoma with metastases to the liver and lungs, and thyroid carcinoma with no metastases was reported in the smooth knob-tail gecko. A thyroidectomy was performed on the marbled velvet gecko with a histologic diagnosis of adenomatous hyperplasia. Postoperative weight loss and bradycardia resolved following oral supplementation with levothyroxine. The animal is in normal health 10 mo post-surgery. Five other diplodactylid geckos in the collection remain unaffected, giving a 38% prevalence of proliferative thyroid lesions (3/8). The etiology remains undetermined. This is the first report of a cluster of proliferative thyroid lesions in geckos.

  9. Proliferative, necrotizing and crescentic immune complex-mediated glomerulonephritis in a cat

    Directory of Open Access Journals (Sweden)

    Carolyn Gross

    2015-09-01

    Full Text Available Case Summary A 5-year-old cat was examined for vomiting and anorexia of 2 days’ duration. Azotemia, hyperphosphatemia and hypoalbuminemia were the main biochemical findings. Serial analyses of the urine revealed isosthenuria, proteinuria and eventual glucosuria. Hyperechoic perirenal fat was detected surrounding the right kidney by ultrasonography. Histopathologic evaluation of ante-mortem ultrasound-guided needle biopsies of the right kidney was consistent with proliferative, necrotizing and crescentic glomerulonephritis with fibrin thrombi, proteinaceous and red blood cell casts, and moderate multifocal chronic-active interstitial nephritis. Owing to a lack of clinical improvement, the cat was eventually euthanized. Post-mortem renal biopsies were processed for light microscopy, transmission electron microscopy and immunofluorescence. This revealed severe focal proliferative and necrotizing glomerulonephritis with cellular crescent formation, podocyte injury and secondary segmental sclerosis. Ultrastructural analysis revealed scattered electron-dense deposits in the mesangium, and immunofluorescence demonstrated positive granular staining for λ light chains, consistent with immune complex-mediated glomerulonephritis. Severe diffuse acute tubular epithelial injury and numerous red blood cell casts were also seen. Relevance and novel information To our knowledge, this is the first report of naturally occurring proliferative, necrotizing and crescentic immune complex glomerulonephritis in a cat.

  10. Anatomical and functional outcomes of retinectomies in retinal detachments complicated by proliferative vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Mohammad Idrees Adhi

    2017-10-01

    Full Text Available Purpose: To study anatomical and functional outcomes of retinectomies in rhegmatogenous retinal detachments complicated by proliferative vitreoretinopathy. Methods: This is a retrospective interventional consecutive case series of eyes with rhegmatogenous retinal detachments complicated by advanced proliferative vitreoretinopathy and managed by relaxing retinectomy over a period of seventeen years. Three-port pars plana vitrectomy included core vitrectomy and removal of all epi-retinal membranes. On failure to flatten, retina was cut and excised. Basal vitrectomy and removal of anterior flap of retina then followed. Silicone oil was used as temponade in majority of cases. The dependent variables were anatomical and functional outcomes. The statistical analysis was performed on SPSS 21. Results: Series included 370 eyes of 337 patients. Mean follow up was 39 months. Scleral explant was used in 90(24.39% cases. Two hundred and nine (56.49% eyes were operated with trans conjunctival sutureless vitrectomy technique. Procedure was bilateral in 33 patients (09.79%. Retina attached in 311(84.05% eyes after initial surgery. Final re-attachment after one or more surgeries was achieved in 344(92.97% eyes. Two hundred and eleven (57.02% cases achieved visual acuity of 6/60 or better. Conclusion: Relaxing retinectomies have good and encouraging anatomical and functional outcomes. This surgery can be effectively carried out with trans conjunctival sutureless vitrectomy technique. Keywords: Retinotomy and retinectomy, Proliferative vitreoretinopathy, Trans conjunctival sutureless vitrectomy, Silicone oil

  11. Strong negative terahertz photoconductivity in photoexcited graphene

    Science.gov (United States)

    Fu, Maixia; Wang, Xinke; Ye, Jiasheng; Feng, Shengfei; Sun, Wenfeng; Han, Peng; Zhang, Yan

    2018-01-01

    Terahertz (THz) response of a chemical vapor deposited graphene on a quartz substrate has been investigated by using an ultrafast optical-pump THz-probe spectroscopy. Without photoexcitation, the frequency-dependence optical conductivity shows a strong carrier response owing to the intrinsically doped graphene. Upon photoexcitation, an enhancement in THz transmission is observed and the transmission increases nonlinearly with the increase of pump power, which is rooted in a reduction of intrinsic conductivity arising from the strong enhancement of carrier scattering rather than THz emission occurrence. The modulation depth of 18.8% was experimentally achieved, which is more than four times greater than that of the previous reported. The photoinduced response here highlights the variety of response possible in graphene depending on the sample quality, carrier mobility and doping level. The graphene provides promising applications in high-performance THz modulators and THz photoelectric devices.

  12. Differential expression of follistatin and FLRG in human breast proliferative disorders

    Directory of Open Access Journals (Sweden)

    Amaral Vania F

    2009-09-01

    Full Text Available Abstract Background Activins are growth factors acting on cell growth and differentiation. Activins are expressed in high grade breast tumors and they display an antiproliferative effect inducing G0/G1 cell cycle arrest in breast cancer cell lines. Follistatin and follistatin- related gene (FLRG bind and neutralize activins. In order to establish if these activin binding proteins are involved in breast tumor progression, the present study evaluated follistatin and FLRG pattern of mRNA and protein expression in normal human breast tissue and in different breast proliferative diseases. Methods Paraffin embedded specimens of normal breast (NB - n = 8; florid hyperplasia without atypia (FH - n = 17; fibroadenoma (FIB - n = 17; ductal carcinoma in situ (DCIS - n = 10 and infiltrating ductal carcinoma (IDC - n = 15 were processed for follistatin and FLRG immunohistochemistry and in situ hybridization. The area and intensity of chromogen epithelial and stromal staining were analyzed semi-quantitatively. Results Follistatin and FLRG were expressed both in normal tissue and in all the breast diseases investigated. Follistatin staining was detected in the epithelial cytoplasm and nucleus in normal, benign and malignant breast tissue, with a stronger staining intensity in the peri-alveolar stromal cells of FIB at both mRNA and protein levels. Conversely, FLRG area and intensity of mRNA and protein staining were higher both in the cytoplasm and in the nucleus of IDC epithelial cells when compared to NB, while no significant changes in the stromal intensity were observed in all the proliferative diseases analyzed. Conclusion The present findings suggest a role for follistatin in breast benign disease, particularly in FIB, where its expression was increased in stromal cells. The up regulation of FLRG in IDC suggests a role for this protein in the progression of breast malignancy. As activin displays an anti-proliferative effect in human mammary cells, the

  13. Autoantigen microarrays reveal autoantibodies associated with proliferative nephritis and active disease in pediatric systemic lupus erythematosus.

    Science.gov (United States)

    Haddon, D James; Diep, Vivian K; Price, Jordan V; Limb, Cindy; Utz, Paul J; Balboni, Imelda

    2015-06-17

    Pediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early-stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling. Knowledge of the antibodies associated with pSLE and proliferative nephritis will increase the understanding of SLE pathogenesis, and may aid in monitoring patients for renal flare. We used autoantigen microarrays composed of 140 recombinant or purified antigens to compare the serum autoantibody profiles of new-onset pSLE patients (n = 45) to healthy controls (n = 17). We also compared pSLE patients with biopsy-confirmed class III or IV proliferative nephritis (n = 23) and without significant renal involvement (n = 18). We performed ELISA with selected autoantigens to validate the microarray findings. We created a multiple logistic regression model, based on the ELISA and clinical information, to predict whether a patient had proliferative nephritis, and used a validation cohort (n = 23) and longitudinal samples (88 patient visits) to test its accuracy. Fifty autoantibodies were at significantly higher levels in the sera of pSLE patients compared to healthy controls, including anti-B cell-activating factor (BAFF). High levels of anti-BAFF were associated with active disease. Thirteen serum autoantibodies were present at significantly higher levels in pSLE patients with proliferative nephritis than those without, and we confirmed five autoantigens (dsDNA, C1q, collagens IV and X and aggrecan) by ELISA. Our model, based on ELISA measurements and clinical variables, correctly identified patients with proliferative

  14. Changes in retinal venular oxygen saturation predict activity of proliferative diabetic retinopathy 3 months after panretinal photocoagulation

    DEFF Research Database (Denmark)

    Torp, Thomas Lee; Kawasaki, Ryo; Wong, Tien Yin

    2018-01-01

    BACKGROUND/AIMS: Proliferative diabetic retinopathy (PDR) is a severe blinding condition. We investigated whether retinal metabolism, measured by retinal oximetry, may predict PDR activity after panretinal laser photocoagulation (PRP). METHODS: We performed a prospective, interventional, clinical...

  15. Earthquake source model using strong motion displacement

    Indian Academy of Sciences (India)

    The strong motion displacement records available during an earthquake can be treated as the response of the earth as the a structural system to unknown forces acting at unknown locations. Thus, if the part of the earth participating in ground motion is modelled as a known finite elastic medium, one can attempt to model the ...

  16. Morphological modelling of strongly curved islands

    NARCIS (Netherlands)

    Roelvink, D.; Den Heijer, C.; Van Thiel De Vries, J.S.M.

    2013-01-01

    Land reclamations and island coasts often involve strongly curved shorelines, which are challenging to be properly modeled by numerical morphological models. Evaluation of the long term development of these types of coasts as well as their response to storm conditions requires proper representation

  17. Engineering amount of cell-cell contact demonstrates biphasic proliferative regulation through RhoA and the actin cytoskeleton

    International Nuclear Information System (INIS)

    Gray, Darren S.; Liu, Wendy F.; Shen, Colette J.; Bhadriraju, Kiran; Nelson, Celeste M.; Chen, Christopher S.

    2008-01-01

    Endothelial cell-cell contact via VE-cadherin plays an important role in regulating numerous cell functions, including proliferation. However, using different experimental approaches to manipulate cell-cell contact, investigators have observed both inhibition and stimulation of proliferation depending on the adhesive context. In this study, we used micropatterned wells combined with active positioning of cells by dielectrophoresis in order to investigate whether the number of contacting neighbors affected the proliferative response. Varying cell-cell contact resulted in a biphasic effect on proliferation; one contacting neighbor increased proliferation, while two or more neighboring cells partially inhibited this increase. We also observed that cell-cell contact increased the formation of actin stress fibers, and that expression of dominant negative RhoA (RhoN19) blocked the contact-mediated increase in stress fibers and proliferation. Furthermore, examination of heterotypic pairs of untreated cells in contact with RhoN19-expressing cells revealed that intracellular, but not intercellular, tension is required for the contact-mediated stimulation of proliferation. Moreover, engagement of VE-cadherin with cadherin-coated beads was sufficient to stimulate proliferation in the absence of actual cell-cell contact. In all, these results demonstrate that cell-cell contact signals through VE-cadherin, RhoA, and intracellular tension in the actin cytoskeleton to regulate proliferation

  18. Inflammatory and Anti-Inflammatory Equilibrium, Proliferative and Antiproliferative Balance: The Role of Cytokines in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Caterina Musolino

    2017-01-01

    Full Text Available Multiple myeloma (MM is typically exemplified by a desynchronized cytokine system with increased levels of inflammatory cytokines. We focused on the contrast between inflammatory and anti-inflammatory systems by assessing the role of cytokines and their influence on MM. The aim of this review is to summarize the available information to date concerning this equilibrium to provide an overview of the research exploring the roles of serum cytokines in MM. However, the association between MM and inflammatory cytokines appears to be inadequate, and other functions, such as pro-proliferative or antiproliferative effects, can assume the role of cytokines in the genesis and progression of MM. It is possible that inflammation, when guided by cancer-specific Th1 cells, may inhibit tumour onset and progression. In a Th1 microenvironment, proinflammatory cytokines (e.g., IL-6 and IL-1 may contribute to tumour eradication by attracting leucocytes from the circulation and by increasing CD4 + T cell activity. Hence, caution should be used when considering therapies that target factors with pro- or anti-inflammatory activity. Drugs that may reduce the tumour-suppressive Th1-driven inflammatory immune response should be avoided. A better understanding of the relationship between inflammation and myeloma will ensure more effective therapeutic interventions.

  19. Quantum electrodynamics of strong fields

    International Nuclear Information System (INIS)

    Greiner, W.

    1983-01-01

    Quantum Electrodynamics of Strong Fields provides a broad survey of the theoretical and experimental work accomplished, presenting papers by a group of international researchers who have made significant contributions to this developing area. Exploring the quantum theory of strong fields, the volume focuses on the phase transition to a charged vacuum in strong electric fields. The contributors also discuss such related topics as QED at short distances, precision tests of QED, nonperturbative QCD and confinement, pion condensation, and strong gravitational fields In addition, the volume features a historical paper on the roots of quantum field theory in the history of quantum physics by noted researcher Friedrich Hund

  20. Uric acid stimulates proliferative pathways in vascular smooth muscle cells through the activation of p38 MAPK, p44/42 MAPK and PDGFRβ.

    Science.gov (United States)

    Kırça, M; Oğuz, N; Çetin, A; Uzuner, F; Yeşilkaya, A

    2017-04-01

    Hyperuricemia and angiotensin II (Ang II) may have a pathogenetic role in the development of hypertension and atherosclerosis as well as cardiovascular disease (CVD) and its prognosis. The purpose of this study was to investigate whether uric acid can induce proliferative pathways of vascular smooth muscle cell (VSMC) that are thought to be responsible for the development of CVD. The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and platelet-derived growth factor receptor β (PDGFRβ) was measured by Elisa and Western blot techniques to determine the activation of proliferative pathways in primary cultured VSMCs from rat aorta. Results demonstrated that uric acid can stimulate p38 MAPK, p44/42 MAPK and PDGFRβ phosphorylation in a time- and concentration-dependent manner. Furthermore, treatment of VSMCs with the angiotensin II type I receptor (AT1R) inhibitor losartan suppressed p38 MAPK and p44/42 MAPK induction by uric acid. The stimulatory effect of uric acid on p38 MAPK was higher compared to that of Ang II. The results of this study show for the first time that uric acid-induced PDGFRβ phosphorylation plays a crucial role in the development of CVDs and that elevated uric acid levels could be a potential therapeutical target in CVD patients.

  1. Comparative Study of Green Sub- and Supercritical Processes to Obtain Carnosic Acid and Carnosol-Enriched Rosemary Extracts with in Vitro Anti-Proliferative Activity on Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Andrea del Pilar Sánchez-Camargo

    2016-12-01

    Full Text Available In the present work, four green processes have been compared to evaluate their potential to obtain rosemary extracts with in vitro anti-proliferative activity against two colon cancer cell lines (HT-29 and HCT116. The processes, carried out under optimal conditions, were: (1 pressurized liquid extraction (PLE, using an hydroalcoholic mixture as solvent at lab-scale; (2 Single-step supercritical fluid extraction (SFE at pilot scale; (3 Intensified two-step sequential SFE at pilot scale; (4 Integrated PLE plus supercritical antisolvent fractionation (SAF at pilot scale. Although higher extraction yields were achieved by using PLE (38.46% dry weight, this extract provided the lowest anti-proliferative activity with no observed cytotoxic effects at the assayed concentrations. On the other hand, extracts obtained using the PLE + SAF process provided the most active rosemary extracts against both colon cancer cell lines, with LC50 ranging from 11.2 to 12.4 µg/mL and from 21.8 to 31.9 µg/mL for HCT116 and HT-29, respectively. In general, active rosemary extracts were characterized by containing carnosic acid (CA and carnosol (CS at concentrations above 263.7 and 33.9 mg/g extract, respectively. Some distinct compounds have been identified in the SAF extracts (rosmaridiphenol and safficinolide, suggesting their possible role as additional contributors to the observed strong anti-proliferative activity of CA and CS in SAF extracts.

  2. Presence of Antigen-Experienced T Cells with Low Grade of Differentiation and Proliferative Potential in Chronic Chagas Disease Myocarditis

    Science.gov (United States)

    Cabeza-Meckert, Patricia; Viotti, Rodolfo; Garelli, Fernando; Favaloro, Liliana E.; Favaloro, Roberto R.; Laguens, Rubén; Laucella, Susana A.

    2014-01-01

    Background The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20–30% of infected individuals but not until 10–20 years after the initial infection. We have previously shown that circulating interferon-γ-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study thought to explore the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle in cardiac explants from patients with advanced Chagas disease myocarditis. Methodology/Principal Findings The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation. Most infiltrating cells displayed markers of antigen-experienced T cells (CD3+, CD4+, CD8+, CD45RO+) with a low grade of differentiation (CD27+, CD57−, CD45RA−, PD-1−). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3+ cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3+ T cells, assessed by Ki67 staining, was found. Conclusions/Significance The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection. PMID:25144227

  3. Strong motion duration and earthquake magnitude relationships

    International Nuclear Information System (INIS)

    Salmon, M.W.; Short, S.A.; Kennedy, R.P.

    1992-06-01

    Earthquake duration is the total time of ground shaking from the arrival of seismic waves until the return to ambient conditions. Much of this time is at relatively low shaking levels which have little effect on seismic structural response and on earthquake damage potential. As a result, a parameter termed ''strong motion duration'' has been defined by a number of investigators to be used for the purpose of evaluating seismic response and assessing the potential for structural damage due to earthquakes. This report presents methods for determining strong motion duration and a time history envelope function appropriate for various evaluation purposes, for earthquake magnitude and distance, and for site soil properties. There are numerous definitions of strong motion duration. For most of these definitions, empirical studies have been completed which relate duration to earthquake magnitude and distance and to site soil properties. Each of these definitions recognizes that only the portion of an earthquake record which has sufficiently high acceleration amplitude, energy content, or some other parameters significantly affects seismic response. Studies have been performed which indicate that the portion of an earthquake record in which the power (average rate of energy input) is maximum correlates most closely with potential damage to stiff nuclear power plant structures. Hence, this report will concentrate on energy based strong motion duration definitions

  4. Strong motion duration and earthquake magnitude relationships

    Energy Technology Data Exchange (ETDEWEB)

    Salmon, M.W.; Short, S.A. [EQE International, Inc., San Francisco, CA (United States); Kennedy, R.P. [RPK Structural Mechanics Consulting, Yorba Linda, CA (United States)

    1992-06-01

    Earthquake duration is the total time of ground shaking from the arrival of seismic waves until the return to ambient conditions. Much of this time is at relatively low shaking levels which have little effect on seismic structural response and on earthquake damage potential. As a result, a parameter termed ``strong motion duration`` has been defined by a number of investigators to be used for the purpose of evaluating seismic response and assessing the potential for structural damage due to earthquakes. This report presents methods for determining strong motion duration and a time history envelope function appropriate for various evaluation purposes, for earthquake magnitude and distance, and for site soil properties. There are numerous definitions of strong motion duration. For most of these definitions, empirical studies have been completed which relate duration to earthquake magnitude and distance and to site soil properties. Each of these definitions recognizes that only the portion of an earthquake record which has sufficiently high acceleration amplitude, energy content, or some other parameters significantly affects seismic response. Studies have been performed which indicate that the portion of an earthquake record in which the power (average rate of energy input) is maximum correlates most closely with potential damage to stiff nuclear power plant structures. Hence, this report will concentrate on energy based strong motion duration definitions.

  5. Panretinal photocoagulation versus intravitreal injection retreatment pain in high-risk proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Célia Regina Farias de Araújo Lucena

    2013-02-01

    Full Text Available PURPOSE: To compare pain related to intravitreal injection and panretinal photocoagulation in the management of patients with high-risk proliferative diabetic retinopathy. METHODS: Prospective study including patients with high-risk proliferative diabetic retinopathy and no prior laser treatment randomly assigned to receive panretinal photocoagulation (PRP group or panretinal photocoagulation plus intravitreal ranibizumab (PRPplus group. In all patients, panretinal photocoagulation was administered in two sessions (weeks 0 and 2, and intravitreal ranibizumab was administered at the end of the first laser session in the PRPplus group. Retreatment was performed at weeks 16 and 32 if active new vessels were detected at fluorescein angiography. Patients in the PRPplus group received intravitreal ranibizumab and patients in the PRP group received 500-µm additional spots per quadrant of active new vessels. After the end of retreatment, a 100-degree Visual Analog Scale was used for pain score estimation. The patient was asked about the intensity of pain during the whole procedure (retinal photocoagulation session or intravitreal ranibizumab injection. Statistics for pain score comparison were performed using a non-parametric test (Wilcoxon rank sums. RESULTS: Seventeen patients from PRPplus and 14 from PRP group were evaluated for pain scores. There were no significant differences between both groups regarding gender, glycosylated hemoglobin and disease duration. Mean intravitreal injection pain (±SEM was 4.7 ± 2.1 and was significantly lower (p<0.0001 than mean panretinal photocoagulation pain (60.8 ± 7.8. Twelve out of 17 patients from the PRPplus group referred intensity pain score of zero, while the minimal score found in PRP group was found in one patient with 10.5. CONCLUSION: In patients with high-risk proliferative diabetic retinopathy who needed retreatment for persistent new vessels, there was more comfort for the patient when retreatment

  6. Oral leukoplakia and proliferative verrucous leukoplakia: a review for dental practitioners.

    Science.gov (United States)

    Staines, K; Rogers, H

    2017-12-01

    Objectives To provide an overview of the current thinking in terms of the diagnosis and management of oral leukoplakia and proliferative verrucous leukoplakia as relevant to general dental practitioners.Data sources, data selection, data extraction, data synthesis We searched the MEDLINE Ovid, EMBASE databases and the Cochrane Library, (1990 to 16 April 2017), restricting our search to English language with the following key words: leukoplakia, white patch, proliferative verrucous leukoplakia, precancerous lesion, premalignant lesions, potentially malignant oral conditions and potentially malignant oral disorders. The two authors selected key papers and engaged in collaborative data extraction and synthesis of the selected reference material.Conclusions General dental practitioners (GDPs) are likely to encounter patients with a known or yet undiagnosed oral leukoplakia in their clinical practice. The diagnosis is clinically based as there are no pathognomonic histopathological features. The definition of leukoplakia has evolved over the years. The importance of recognition and appropriate management relating to this condition is described particularly as it is one of the oral potentially malignant lesions. The inferred increased risk of malignant transformation is well documented however controversy still persists in terms of the appropriate management for these lesions. Proliferative verrucous leukoplakia is a recalcitrant, often widespread and multifocal distinct type of leukoplakia. It is considered to have a high rate of malignant transformation with implications in terms of lifelong monitoring both clinically and histopathologically. A high index of suspicion is important for general dental practitioners in order to identify such lesions that would require onward referral for further investigation and management.

  7. Optimal Management of Proliferative Verrucous Leukoplakia: A Systematic Review of the Literature.

    Science.gov (United States)

    Abadie, Wesley M; Partington, Erin J; Fowler, Craig B; Schmalbach, Cecelia E

    2015-10-01

    Proliferative verrucous leukoplakia (PVL) is a rare and recalcitrant form of leukoplakia. The purpose of this review is to further characterize the risk factors, clinical course, and optimal treatment for this highly aggressive, premalignant lesion. Twenty-six articles on PVL with a total of 329 PVL cases. A systematic review of the literature using Ovid, PubMed, Cochrane Database, and gray literature was conducted of all PVL cases reported between 1985 and 2014. Inclusion criteria required reporting of patient follow-up and recurrence rates. Data were analyzed using descriptive statistics. Student t test and Fisher exact test were used to identify factors associated with malignant transformation. The mean patient age was 63.9 years. Most patients were female (66.9%) and nontobacco users (65.22%). Mean follow-up was 7.4 years, with an average of 9.0 biopsies per patient during this period. Proliferative verrucous leukoplakia exhibited histopathologic features along a progressive spectrum, evolving from leukoplakia to verrucous hyperplasia and ultimately invasive carcinoma. Surgery was the most common treatment implemented, but recurrence rates among 222 patients reached 71.2%. Subgroup analysis of 277 patients identified a 63.9% malignant transformation rate, and 39.6% of patients died of their disease. Age, sex, and tobacco use were not identified as risk factors associated with progression to cancer. Proliferative verrucous leukoplakia is a rare form of leukoplakia with a high rate of malignant transformation. It necessitates high clinical suspicion, to include a lifetime of close follow-up and repeat biopsies by a health care provider well versed in oral carcinoma. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2015.

  8. Immunohistochemical evaluation of p53 expression and proliferative activity in children with Helicobacter pylori associated gastritis.

    Science.gov (United States)

    Ozturk, Yesim; Ozer, Erdener; Lebe, Banu; Bekem, Ozlem; Buyukgebiz, Benal

    2005-04-01

    The aim of this study was to evaluate the significance of p53 expression and proliferative activity of glandular epithelium and intestinal metaplasia in Helicobacter pylori associated gastritis of pediatric patients. The study included endoscopic gastric biopsies of 54 children with dyspeptic complaints. Immunohistochemistry was performed for evaluation of p53 expression and Ki-67 labeling index, an indicator of proliferative activity. Grading of H. pylori density, intestinal metaplasia and inflammatory cell infiltration were performed in histologic tissue sections stained with hematoxylin-eosin, Giemsa and Alcian-blue. Of 54 children, 35 (64%) were infected by H. pylori. Positive immunostaining for p53 was observed in 11 of 54 cases (20.4%). H. pylori infection was found in 10 (91%) of the p53-positive patients. There was a positive correlation between H. pylori density and Ki-67 labeling index in H. pylori infected children. H. pylori density, Ki-67 labeling index and inflammatory cell infiltration in the p53-positive group were significantly higher than in the p53-negative group. Although intestinal metaplasia was more common in H. pylori infected children (n = 11; 31.4%), there was no difference in the rate of intestinal metaplasia between the p53-positive and p53-negative groups. The present study shows that p53 mutations and higher proliferative activity of glandular epithelium may be related to H. pylori associated gastritis in children. Because p53 mutation does not appear to be associated with intestinal metaplasia, a precursor for gastric cancer in adults, we think that H.pylori associated p53 alterations do not initiate and promote gastric cancer that may occur in adulthood.

  9. Phosphorylated and sumoylation-deficient progesterone receptors drive proliferative gene signatures during breast cancer progression

    Science.gov (United States)

    2012-01-01

    Introduction Progesterone receptors (PR) are emerging as important breast cancer drivers. Phosphorylation events common to breast cancer cells impact PR transcriptional activity, in part by direct phosphorylation. PR-B but not PR-A isoforms are phosphorylated on Ser294 by mitogen activated protein kinase (MAPK) and cyclin dependent kinase 2 (CDK2). Phospho-Ser294 PRs are resistant to ligand-dependent Lys388 SUMOylation (that is, a repressive modification). Antagonism of PR small ubiquitin-like modifier (SUMO)ylation by mitogenic protein kinases suggests a mechanism for derepression (that is, transcriptional activation) of target genes. As a broad range of PR protein expression is observed clinically, a PR gene signature would provide a valuable marker of PR contribution to early breast cancer progression. Methods Global gene expression patterns were measured in T47D and MCF-7 breast cancer cells expressing either wild-type (SUMOylation-capable) or K388R (SUMOylation-deficient) PRs and subjected to pathway analysis. Gene sets were validated by RT-qPCR. Recruitment of coregulators and histone methylation levels were determined by chromatin immunoprecipitation. Changes in cell proliferation and survival were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and western blotting. Finally, human breast tumor cohort datasets were probed to identify PR-associated gene signatures; metagene analysis was employed to define survival rates in patients whose tumors express a PR gene signature. Results 'SUMO-sensitive' PR target genes primarily include genes required for proliferative and pro-survival signaling. DeSUMOylated K388R receptors are preferentially recruited to enhancer regions of derepressed genes (that is, MSX2, RGS2, MAP1A, and PDK4) with the steroid receptor coactivator, CREB-(cAMP-response element-binding protein)-binding protein (CBP), and mixed lineage leukemia 2 (MLL2), a histone methyltransferase mediator of nucleosome

  10. Lidocaine impairs proliferative and biosynthetic functions of aged human dermal fibroblasts

    Science.gov (United States)

    Bentov, Itay; Damodarasamy, Mamatha; Spiekerman, Charles; Reed, May J

    2016-01-01

    Background The aged are at increased risk of postoperative wound healing complications. Since local anesthetics are commonly infiltrated into the dermis of surgical wounds, we sought to determine if local anesthetics adversely affect proliferative and biosynthetic functions of dermal fibroblasts. We also evaluated the effect of local anesthetics on IGF-1 and TGF-ß1, growth factors that are important regulators of wound healing. Methods Human dermal fibroblasts from aged and young donors (HFB) were exposed to local anesthetic agents at clinically relevant concentrations. We screened the effects of lidocaine, bupivacaine, mepivacaine and ropivacaine on proliferation of HFB. Lidocaine was the most detrimental to proliferation in HFB. We then evaluated the effect of lidocaine on expression and function of the growth factors, IGF-1 and TGF-ß1. Lastly, concurrent exposure to lidocaine and IGF-1 or TGF-ß1 were evaluated for their effects on proliferation and expression of dermal collagens, respectively. Results Lidocaine and mepivacaine inhibited proliferation in aged HFB (for lidocaine 88% of control, 95%CI 80%-98%, p=0.009 and for mepivacaine 90% of control, 95%CI 81%-99%, p=0.032), but not in young HFB. Ropivicaine and bupivicaine did not inhibit proliferation. Due to the clinical utility of lidocaine relative to mepivicaine, we focused on lidocaine. Lidocaine decreased proliferation in aged HFB, which was abrogated by IGF-1. Lidocaine inhibited transcripts for IGF-1 and IGF1R in fibroblasts from aged donors (IGF-1, log2 fold-change −1.25 {42% of control, 95%CI 19%-92%, p=0.035} and IGF1R, log2 fold-change of −1.00 {50% of control, 95%CI 31%-81%, p=0.014}). In contrast, lidocaine did not effect the expression of IGF-1 or IGF1R transcripts in the young HFB. Transcripts for collagen III were decreased after lidocaine exposure in aged and young HFB (log2 fold-change −1.28 {41% of control, 95%CI 20%-83%, p=0.022} in aged HFB and log2 fold-change −1.60 {33% of

  11. Strong WW Interaction at LHC

    Energy Technology Data Exchange (ETDEWEB)

    Pelaez, Jose R

    1998-12-14

    We present a brief pedagogical introduction to the Effective Electroweak Chiral Lagrangians, which provide a model independent description of the WW interactions in the strong regime. When it is complemented with some unitarization or a dispersive approach, this formalism allows the study of the general strong scenario expected at the LHC, including resonances.

  12. Social deprivation as a risk factor for late presentation of proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Lane M

    2015-02-01

    Full Text Available Mark Lane,1,* Priscilla A Mathewson,1,* Hannah E Sharma,1 Helen Palmer,1 Peter Shah,1–3 Peter Nightingale,1,4,5 Marie D Tsaloumas,1 Alastair K Denniston1,61Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 2NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK; 3Centre for Health and Social Care Improvement, School of Health and Wellbeing, University of Wolverhampton, Wolverhampton, UK; 4Dept of Statistics, Wellcome Trust Clinical Research Facility, Birmingham, UK; 5School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, 6Centre for Translational Inflammation Research, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK*These authors are joint first authorsPurpose: The aim of this study was to determine whether social deprivation is a risk factor for late presentation of patients with proliferative diabetic retinopathy and whether it affects their access to urgent laser treatment.Methods: Using a 2:1 case: control design, 102 patients referred to a UK teaching hospital as part of the UK Diabetic Retinopathy National Screening Programme were identified for the period between 1 June 2010 to 1 June 2013. Social deprivation was scored using the Index of Multiple Deprivation 2010. Additional variables considered included age, duration of disease, ethnicity, and HbA1c at time of referral.Results: The cases comprised 34 patients referred with proliferative (grade R3 retinopathy with a control group of 68 patients with lower retinopathy grades; two control patients were excluded due to incomplete data. On univariate analysis, R3 retinopathy was associated with higher social deprivation (P<0.001, Mann–Whitney U-test, and with higher HbA1c (11.5% vs 8.4%; P<0.001, Mann–Whitney U-test. Forward stepwise multivariable analysis showed that the

  13. Roles of elevated intravitreal IL-1β and IL-10 levels in proliferative diabetic retinopathy

    OpenAIRE

    Mao, Chunjie; Yan, Hua

    2014-01-01

    Purpose: To determine the roles of interleukin (IL)-1β and IL-10 in the vitreous of proliferative diabetic retinopathy (PDR). Materials and Methods: Vitreous samples were obtained from 26 eyes of 26 patients with PDR and from eight eyes of eight cases without PDR. The IL-1β and IL-10 concentration in the vitreous was measured by using an enzyme-linked immunosorbent assay (ELISA). Results: Levels of IL-1β and IL-10 in vitreous were higher in PDR patients compared with control group. And there ...

  14. Methylthioadenosine phosphorylase compositions and methods of use in the diagnosis and treatment of proliferative disorders

    Science.gov (United States)

    Olopade, Olufunmilayo I.

    2005-03-22

    Disclosed are novel nucleic acid and peptide compositions comprising methythlioadenosine phosphorylase (MTAP) and methods of use for MTAP amino acid sequences and DNA segments comprising MTAP in the diagnosis of human cancers and development of MTAP-specific antibodies. Also disclosed are methods for the diagnosis and treatment of tumors and other proliferative cell disorders, and idenification tumor suppressor genes and gene products from the human 9p21-p22 chromosome region. Such methods are useful in the diagnosis of multiple tumor types such as bladder cancer, lung cancer, breast cancer, pancreatic cancer, brain tumors, lymphomas, gliomas, melanomas, and leukemias.

  15. Compositions and methods involving methyladenosine phosphorylase in the diagnosis and treatment of proliferative disorders

    Science.gov (United States)

    Olopade, Olufunmilayo I.

    2007-03-20

    Disclosed are novel nucleic acid and peptide compositions comprising methylthioadenosine phosphorylase (MTAP) and methods of use for MTAP amino acid sequences and DNA segments comprising MTAP in the diagnosis of human cancers and development of MTAP-specific antibodies. Also disclosed are methods for the diagnosis and treatment of tumors and other proliferative cell disorders, and identification of tumor suppressor genes and gene products from the human 9p21-p22 chromosome region. Such methods are useful in the diagnosis of multiple tumor types such as bladder cancer, lung cancer, breast cancer, pancreatic cancer, brain tumors, lymphomas, gliomas, melanomas, and leukemias.

  16. Proliferative myositis of the latissimus dorsi presenting in a 20-year-old male athlete

    LENUS (Irish Health Repository)

    Mc Hugh, N

    2017-08-01

    We describe the case of a 20-year-old rower presenting with an uncommon condition of Proliferative Myositis (PM) affecting the Latissimus Dorsi (LD). PM is a rare, benign tumour infrequently developing in the upper back. Its rapid growth and firm consistency may mistake it for sarcoma at presentation. Therefore, careful multidisciplinary work-up is crucial, and should involve appropriate radiological and histopathological investigations. Here, we propose the aetiology of LD PM to be persistent myotrauma induced by repetitive rowing motions. Symptoms and rate of progression ultimately determine the management which includes surveillance and\\/or conservative resection. There have been no documented cases of recurrence or malignant transformation.

  17. Surgical management of retinal diseases: proliferative diabetic retinopathy and traction retinal detachment.

    Science.gov (United States)

    Cruz-Iñigo, Yousef J; Acabá, Luis A; Berrocal, Maria H

    2014-01-01

    Current indications for pars plana vitrectomy in patients with proliferative diabetic retinopathy (PDR) include vitreous hemorrhage, tractional retinal detachment (TRD), combined tractional and rhegmatogenous retinal detachment (CTRRD), diabetic macular edema associated with posterior hyaloidal traction, and anterior segment neovascularization with media opacities. This chapter will review the indications, surgical objectives, adjunctive pharmacotherapy, microincision surgical techniques, and outcomes of diabetic vitrectomy for PDR, TRD, and CTRRD. With the availability of new microincision vitrectomy technology, wide-angle microscope viewing systems, and pharmacologic agents, vitrectomy can improve visual acuity and achieve long-term anatomic stability in eyes with severe complications from PDR. © 2014 S. Karger AG, Basel

  18. Is Smoking a Risk Factor for Proliferative Diabetic Retinopathy in Type 1 Diabetes?

    DEFF Research Database (Denmark)

    Gaedt Thorlund, Mie; Borg Madsen, Mette; Green, Anders

    2013-01-01

    Aim: The aim was to evaluate if smoking was a risk factor for proliferative retinopathy (PDR) in a 25-year follow-up study. Methods: 201 persons from a population-based cohort of Danish type 1 diabetic patients were examined at baseline and again 25 years later. At both examinations the patients...... were asked about their smoking habits. The level of retinopathy was evaluated by ophthalmoscopy at baseline and by nine 45-degree colour field fundus photos at the follow-up. Results: In multivariate analyses there was a trend that current smokers at baseline were more likely to develop PDR...

  19. Proliferative, reparative, and reactive benign bone lesions that may be confused diagnostically with true osseous neoplasms.

    LENUS (Irish Health Repository)

    Wick, Mark R

    2014-01-01

    Diagnostic problems attending intraosseous and parosteal pseudoneoplastic lesions can be radiographic, or histological, or both. Proliferations in this category may contain cellular fibro-osseous or chondro-osseous tissues that are difficult to separate microscopically from those seen in various true neoplasms of the bones. This review considers the clinicopathologic features of fibrous dysplasia, benign fibro-osseous lesions of the jawbones, osteofibrous dysplasia, metaphyseal fibrous defect, giant-cell reparative granuloma, "brown tumor" of hyperparathyroidism, synovial chondrometaplasia, aneurysmal bone cyst, tumefactive chronic osteomyelitis, proliferative Paget disease, and polyvinylpyrrolidone storage disease of bone.

  20. Nephrotic Syndrome Secondary to Proliferative Glomerulonephritis with Monoclonal Immunoglobulin Deposits of Lambda Light Chain

    Directory of Open Access Journals (Sweden)

    Seongseok Yun

    2014-01-01

    Full Text Available We describe a rare case of a 46-year-old woman with history of refractory nephrotic syndrome and hypertension who presented with worsening proteinuria and kidney function. Work-up for both autoimmune and infectious diseases and hematologic malignancies including multiple myeloma were negative. Kidney biopsy demonstrated glomerular sclerotic change with lambda light chain deposits in the subendothelial space, which is consistent with proliferative glomerulonephritis with monoclonal immunoglobulin deposit (PGNMID. The patient was treated with bortezomib and dexamethasone without clinical improvement and eventually became hemodialysis dependent.

  1. Evaluation of a novel enzyme-linked immunosorbent assay for serological diagnosis of porcine proliferative enteropathy

    DEFF Research Database (Denmark)

    Boesen, Henriette Toft; Jensen, Tim Kåre; Møller, Kristian

    2005-01-01

    was a specific and sensitive method for detecting specific antibodies, and may be a good alternative to the existing serological tests for L intracellularis. It may be usable for diagnosis of proliferative enteropathy and for determination of a herd's epidemiologic status....... experimentally infected pigs and 62 serum samples from naturally infected pigs the sensitivity of the ELISA was calculated to 98.0%. The specificity of the test was 99.3%, calculated on the basis of 273 serum samples collected in six herds free of L. intracellularis after medicated eradication. The novel ELISA...

  2. Strong-back safety latch

    International Nuclear Information System (INIS)

    DeSantis, G.N.

    1995-01-01

    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch

  3. Strong-back safety latch

    Energy Technology Data Exchange (ETDEWEB)

    DeSantis, G.N.

    1995-03-06

    The calculation decides the integrity of the safety latch that will hold the strong-back to the pump during lifting. The safety latch will be welded to the strong-back and will latch to a 1.5-in. dia cantilever rod welded to the pump baseplate. The static and dynamic analysis shows that the safety latch will hold the strong-back to the pump if the friction clamps fail and the pump become free from the strong-back. Thus, the safety latch will meet the requirements of the Lifting and Rigging Manual for under the hook lifting for static loading; it can withstand shock loads from the strong-back falling 0.25 inch.

  4. Analysis of T lymphocyte subsets proliferating in response to infective and UV-inactivated African swine fever viruses.

    Science.gov (United States)

    Canals, A; Alonso, F; Tomillo, J; Domínguez, J

    1992-11-01

    The proliferative response to infective and UV-inactivated African swine fever virus was analyzed in cells from pigs surviving an experimental infection with attenuated virus. All the pigs showed strong dose-dependent proliferative responses to both infective and UV-inactivated virus. This response was also observed when nitrocellulose-bound solubilized virus proteins were used in the assay. Heterologous isolates also induced proliferation, however it was significantly lower than that induced by the isolate used to infect the animals. The response to infective virus was blocked equally by anti-CD4 and anti-CD8 monoclonal antibodies (mAb); the response to UV-inactivated virus was almost abolished by anti-CD4 and 60% inhibited by anti-CD8 mAb. FACS analysis of 28-day T cell lines derived from peripheral blood mononuclear cells demonstrated the progressive increase of the CD8+ subset when the cells were stimulated with infective virus, whereas the stimulation with UV-inactivated virus induced the increase of both CD4+ and CD8+ subsets. In this case, the sum of CD4+ and CD8+ percentages was higher than the total percentage of T cells, suggesting the presence of cells positive for both CD4+ and CD8+.

  5. Involvement of p21cip-1 and p27kip-1 in the molecular mechanisms of steel factor-induced proliferative synergy in vitro and of p21cip-1 in the maintenance of stem/progenitor cells in vivo.

    Science.gov (United States)

    Mantel, C; Luo, Z; Canfield, J; Braun, S; Deng, C; Broxmeyer, H E

    1996-11-15

    Steel factor (SLF) is a hematopoietic cytokine that synergizes with other growth factors to induce a greatly enhanced proliferative state of hematopoietic progenitor cells and factor-dependent cell lines. Even though the in vivo importance of SLF in the maintenance and responsiveness of stem and progenitor cells is well documented, the molecular mechanism involved in its synergistic effects are mainly unknown. Some factor-dependent myeloid cell lines respond to the synergistic proliferative effects of SLF plus other cytokines in a manner similar to that of normal myeloid progenitor cells from bone marrow and cord blood. We show here that SLF can synergize with granulocyte-macrophage colony-stimulating factor (GM-CSF) to induce an enhanced phosphorylation of the retinoblastoma gene product and a synergistic increase in the total intracellular protein level of the cyclin-dependent kinase inhibitor, p21cip-1, which is correlated with a simultaneous decrease in p27kip-1 in the human factor-dependent myeloid cell line, M07e. Moreover, these cytokines synergize to increase p21cip-1 binding and decrease p27kip-1 binding to cyclin-dependent kinase-2 (cdk2), an enzyme required for normal cell cycle progression; these inverse events correlated with increased cdk2 kinase activity. It is also shown that exogenous purified p21cip-1 can displace p27kip-1 already bound to cdk2 in vitro. These data implicate increased p21cip-1 and decreased p27kip-1 intracellular concentrations and their stoichiometric interplay in the enhanced proliferative status of cells stimulated by the combination of SLF and GM-CSF. In support of these findings, it is shown that hematopoietic progenitor cells from mice lacking p21cip-1 are defective in SLF synergistic proliferative response in vitro. Moreover, the cycling status of marrow and spleen progenitors and absolute numbers of marrow progenitors were significantly decreased in the p21cip-1 -/-, compared with the +/+ mice. We conclude that the cdk

  6. An epidemic model for the interactions between thermal regime of rivers and transmission of Proliferative Kidney Disease in salmonid fish

    Science.gov (United States)

    Carraro, Luca; Bertuzzo, Enrico; Mari, Lorenzo; Gatto, Marino; Strepparava, Nicole; Hartikainen, Hanna; Rinaldo, Andrea

    2015-04-01

    Proliferative kidney disease (PKD) affects salmonid populations in European and North-American rivers. It is caused by the endoparasitic myxozoan Tetracapsuloides bryosalmonae, which exploits freshwater bryozoans (Fredericella sultana) and salmonids as primary and secondary hosts, respectively. Incidence and mortality, which can reach up to 90-100%, are known to be strongly related to water temperature. PKD has been present in brown trout population for a long time but has recently increased rapidly in incidence and severity causing a decline in fish catches in many countries. In addition, environmental changes are feared to cause PKD outbreaks at higher latitude and altitude regions as warmer temperatures promote disease development. This calls for a better comprehension of the interactions between disease dynamics and the thermal regime of rivers, in order to possibly devise strategies for disease management. In this perspective, a spatially explicit model of PKD epidemiology in riverine host metacommunities is proposed. The model aims at summarizing the knowledge on the modes of transmission of the disease and the life-cycle of the parasite, making the connection between temperature and epidemiological parameters explicit. The model accounts for both local population and disease dynamics of bryozoans and fish and hydrodynamic dispersion of the parasite spores and hosts along the river network. The model is time-hybrid, coupling inter-seasonal and intra-seasonal dynamics, the former being described in a continuous time domain, the latter seen as time steps of a discrete time domain. In order to test the model, a case study is conducted in river Wigger (Cantons of Aargau and Lucerne, Switzerland), where data about water temperature, brown trout and bryozoan populations and PKD prevalence are being collected.

  7. Target Residence Time-Guided Optimization on TTK Kinase Results in Inhibitors with Potent Anti-Proliferative Activity.

    Science.gov (United States)

    Uitdehaag, Joost C M; de Man, Jos; Willemsen-Seegers, Nicole; Prinsen, Martine B W; Libouban, Marion A A; Sterrenburg, Jan Gerard; de Wit, Joeri J P; de Vetter, Judith R F; de Roos, Jeroen A D M; Buijsman, Rogier C; Zaman, Guido J R

    2017-07-07

    The protein kinase threonine tyrosine kinase (TTK; also known as Mps1) is a critical component of the spindle assembly checkpoint and a promising drug target for the treatment of aggressive cancers, such as triple negative breast cancer. While the first TTK inhibitors have entered clinical trials, little is known about how the inhibition of TTK with small-molecule compounds affects cellular activity. We studied the selective TTK inhibitor NTRC 0066-0, which was developed in our own laboratory, together with 11 TTK inhibitors developed by other companies, including Mps-BAY2b, BAY 1161909, BAY 1217389 (Bayer), TC-Mps1-12 (Shionogi), and MPI-0479605 (Myrexis). Parallel testing shows that the cellular activity of these TTK inhibitors correlates with their binding affinity to TTK and, more strongly, with target residence time. TTK inhibitors are therefore an example where target residence time determines activity in in vitro cellular assays. X-ray structures and thermal stability experiments reveal that the most potent compounds induce a shift of the glycine-rich loop as a result of binding to the catalytic lysine at position 553. This "lysine trap" disrupts the catalytic machinery. Based on these insights, we developed TTK inhibitors, based on a (5,6-dihydro)pyrimido[4,5-e]indolizine scaffold, with longer target residence times, which further exploit an allosteric pocket surrounding Lys553. Their binding mode is new for kinase inhibitors and can be classified as hybrid Type I/Type III. These inhibitors have very potent anti-proliferative activity that rivals classic cytotoxic therapy. Our findings will open up new avenues for more applications for TTK inhibitors in cancer treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Titanium: light, strong, and white

    Science.gov (United States)

    Woodruff, Laurel; Bedinger, George

    2013-01-01

    Titanium (Ti) is a strong silver-gray metal that is highly resistant to corrosion and is chemically inert. It is as strong as steel but 45 percent lighter, and it is twice as strong as aluminum but only 60 percent heavier. Titanium dioxide (TiO2) has a very high refractive index, which means that it has high light-scattering ability. As a result, TiO2 imparts whiteness, opacity, and brightness to many products. ...Because of the unique physical properties of titanium metal and the whiteness provided by TiO2, titanium is now used widely in modern industrial societies.

  9. Elevated Levels of Cytokines Associated with Th2 and Th17 Cells in Vitreous Fluid of Proliferative Diabetic Retinopathy Patients.

    Directory of Open Access Journals (Sweden)

    Masaru Takeuchi

    Full Text Available Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM, 26 patients with idiopathic macular hole (MH, and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR.

  10. Proliferative hypothalamic neurospheres express NPY, AGRP, POMC, CART and Orexin-A and differentiate to functional neurons.

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    Lígia Sousa-Ferreira

    Full Text Available Some pathological conditions with feeding pattern alterations, including obesity and Huntington disease (HD are associated with hypothalamic dysfunction and neuronal cell death. Additionally, the hypothalamus is a neurogenic region with the constitutive capacity to generate new cells of neuronal lineage, in adult rodents. The aim of the present work was to evaluate the expression of feeding-related neuropeptides in hypothalamic progenitor cells and their capacity to differentiate to functional neurons which have been described to be affected by hypothalamic dysfunction. Our study shows that hypothalamic progenitor cells from rat embryos grow as floating neurospheres and express the feeding-related neuropeptides Neuropeptide Y (NPY, Agouti-related Protein (AGRP, Pro-OpioMelanocortin (POMC, Cocaine-and-Amphetamine Responsive Transcript (CART and Orexin-A/Hypocretin-1. Moreover the relative mRNA expression of NPY and POMC increases during the expansion of hypothalamic neurospheres in proliferative conditions.Mature neurons were obtained from the differentiation of hypothalamic progenitor cells including NPY, AGRP, POMC, CART and Orexin-A positive neurons. Furthermore the relative mRNA expression of NPY, CART and Orexin-A increases after the differentiation of hypothalamic neurospheres. Similarly to the adult hypothalamic neurons the neurospheres-derived neurons express the glutamate transporter EAAT3. The orexigenic and anorexigenic phenotype of these neurons was identified by functional response to ghrelin and leptin hormones, respectively. This work demonstrates the presence of appetite-related neuropeptides in hypothalamic progenitor cells and neurons obtained from the differentiation of hypothalamic neurospheres, including the neuronal phenotypes that have been described by others as being affected by hypothalamic neurodegeneration. These in vitro models can be used to study hypothalamic progenitor cells aiming a therapeutic intervention to

  11. Acrylamide-derived cytotoxic, anti-proliferative, and apoptotic effects on A549 cells.

    Science.gov (United States)

    Kacar, S; Vejselova, D; Kutlu, H M; Sahinturk, V

    2017-01-01

    Acrylamide is a very common compound even reaching up to our daily foods. It has been studied in a wealth of cell lines on which it proved to have various toxic effects. Among these cell lines, human lung adenocarcinoma cell line (A549) is one of that on which acrylamide's toxicity has not been studied well yet. We intended to determine the half maximal inhibitory concentration (IC 50 ) dose of acrylamide and to investigate its cytotoxic, anti-proliferative and apoptotic effects on A549 cells. We determined the IC 50 dose by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Then, the mode of cell death was evaluated by flow cytometry using Annexin-V fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. Next, we performed transmission electron microscopy (TEM) and confocal microscopy analyses for morphological alterations and apoptotic indices. According to the MTT assay results, A549 cell viability decreases proportionally with increasing acrylamide concentrations and IC 50 for A549 was 4.6 mM for 24 h. Annexin-V FITC/PI assay results indicated that acrylamide induces apoptosis in 64% of the A549 cells. TEM and confocal microscopy analyses showed nuclear condensations, fragmentations, cytoskeleton laceration, and membrane blebbing, which are morphological characteristics of apoptosis. Our research suggests that acrylamide causes cytotoxic, anti-proliferative, and apoptotic effects on A549 cells at 4.6 mM IC 50 dose in 24 h.

  12. [Various acute phase reactants in different types of proliferative diseases of the uterine appendages].

    Science.gov (United States)

    Zorina, V N; Kozlov, I G; Tret'iakova, T V; Promzeleva, N V; Bazhenova, L G; Zorina, R M; Riabicheva, T G; Zorin, N A

    2009-10-01

    The authors examined serum in patients with ovarian cancer (OC; a disseminated process), ovarian cystadenoma (OCA), or external endometriosis (EM) before treatment and in apparently healthy females (a control) for the content of some acute-phase proteins and cytokines to clarify the specific features of changes in their concentrations in relation to the type of the proliferative process. It was shown that in OC, there were significant reductions in the levels of alpha2-macroglobulin (MG), plasmin (PL), alpha1-antitrypsin (AT) and statistically significantly increases in the content of lactoferrin (LF), interleukin (IL)-6, IL-8, Ig, and the regulatory transport complex of P--M. In M, the concentrations of AT were lower and those of IL-6, IL-8, and PL-MG were higher (to a lesser degree than those in OC). In OCA, the levels of MG and IgA were increased; those of IL-8 and PL-MG were decreased. The concentrations of interferon and IgM were unchanged in all groups. The findings suggest that difefrent proliferative processes initially provoke a number of changes of varying magnitude and even directions in the serum levels of inflammation reactants, which should be borne in mind when conducting clinical tests in the intraoperative and, probably, postoperative periods.

  13. Anti-proliferative activity of phlorotannin extracts from brown algae Laminaria japonica Aresch

    Science.gov (United States)

    Yang, Huicheng; Zeng, Mingyong; Dong, Shiyuan; Liu, Zunying; Li, Ruixue

    2010-01-01

    In this study, we evaluated the anti-proliferative activity of phlorotannins derived from brown algae Laminaria japonica Aresch extracts on the human hepatocellular carcinoma cell (BEL-7402) and on murine leukemic cells (P388) by MTT assay. Cells were incubated with 100 μg/mL of the phlorotannin extract (PE) for 48 h. The inhibitory rate of PE on BEL-7402 and P388 cells was 30.20±1.16% and 43.44±1.86%, respectively, and the half-inhibitory concentration of PE (IC50) on P388 and BEL-7402 cells was 120 μg/mL and >200 μg/mL, respectively. Microscopic observation shows that the morphologic features of tumor cells treated with PE and 5-fluorouracil are markedly different from the normal control group. The inhibitory rate of fraction A2 isolated from PE by sephadex LH-20 for BEL-7402 and P388 cells at the sample concentration of 70.42 μg/mL was 61.96±7.02% and 40.47±8.70%, respectively. The apoptosis peak for fraction A2 was the most profound of all fractions used in the flow cytometry assay. The results indicate that the anti-proliferative of this algal extract is associated with the total phlorotannin content.

  14. Optos-guided pattern scan laser (Pascal)-targeted retinal photocoagulation in proliferative diabetic retinopathy.

    Science.gov (United States)

    Muqit, Mahiul M K; Marcellino, George R; Henson, David B; Young, Lorna B; Patton, Niall; Charles, Stephen J; Turner, George S; Stanga, Paulo E

    2013-05-01

    To investigate the clinical effects and safety of targeted pattern scan laser (Pascal) retinal photocoagulation (TRP) in proliferative diabetic retinopathy (PDR). Prospective and non-randomized study of 28 eyes with treatment-naive proliferative diabetic retinopathy (PDR). Single-session 20-ms-Pascal TRP strategy applied 1500 burns to zones of retinal capillary non-perfusion and intermediate retinal ischaemia guided by wide-field fluorescein angiography (Optos). Main outcome measures at 12 and 24 weeks included; PDR grade (assessed by two masked retina specialists); central retinal thickness (CRT); mean deviation (MD) using 24-2 Swedish interactive threshold algorithm (SITA)-standard visual fields (VF); and ETDRS visual acuity (VA). Following primary TRP, there was PDR regression in 76% of patients at 12 weeks (κ = 0.70; p Pascal 20-ms TRP using 1500 burns for treatment-naive PDR is a promising procedure with favourable safety profile. © 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.

  15. Synthesis and Anti-Proliferative Effects of Mono- and Bis-Purinomimetics Targeting Kinases

    Directory of Open Access Journals (Sweden)

    Andrea Bistrović

    2017-11-01

    Full Text Available A series of mono-pyrrolo[2,3-d]pyrimidines 4a–4k, unsymmetrical bis-purine isosteres 5a–5e and symmetrical bis-pyrrolo[2,3-d]pyrimidines 6a and 6b connected via di(1,2,3-triazolylphenyl linker were synthesized by click chemistry. Whereas mono- 4g and bis-pseudopurine 5e showed selective inhibitory activities on cervical carcinoma (HeLa cells, bis-pyrrolo[2,3-d]pyrimidine 6b exhibited potent and selective anti-proliferative effect in the nanomolar range on pancreatic carcinoma (CFPAC-1 cells. Among these, compound 6b induced a significant reduction in the expression level of CDK9 (cyclin-dependent kinase 9/cyclin T1 in CFPAC-1 cells concomitant with attenuation of proliferative signaling mediated by c-Raf (rapidly accelerated fibrosarcoma and p38 MAP (mitogen-activated protein kinases. Our findings encourage further development of novel structurally related analog of 6b to obtain more selective anticancer agent for treating pancreatic cancer.

  16. Autoantibodies targeting glomerular annexin A2 identify patients with proliferative lupus nephritis.

    Science.gov (United States)

    Caster, Dawn J; Korte, Erik A; Merchant, Michael L; Klein, Jon B; Wilkey, Daniel W; Rovin, Brad H; Birmingham, Dan J; Harley, John B; Cobb, Beth L; Namjou, Bahram; McLeish, Kenneth R; Powell, David W

    2015-12-01

    Patients with systemic lupus erythematosus (SLE) frequently develop lupus nephritis (LN), a complication frequently leading to end stage kidney disease. Immune complex deposition in the glomerulus is central to the development of LN. Using a targeted proteomic approach, we tested the hypothesis that autoantibodies targeting glomerular antigens contribute to the development of LN. Human podocyte and glomerular proteins were separated by SDS-PAGE and immunoblotted with sera from SLE patients with and without LN. The regions of those gels corresponding to reactive bands observed with sera from LN patients were analyzed using LC-MS/MS. LN reactive bands were seen at approximately 50 kDa in podocyte extracts and between 36 and 50 kDa in glomerular extracts. Those bands were analyzed by LC-MS/MS and 102 overlapping proteins were identified. Bioinformatic analysis determined that 36 of those proteins were membrane associated, including a protein previously suggested to contribute to glomerulonephritis and LN, annexin A2. By ELISA, patients with proliferative LN demonstrated significantly increased antibodies against annexin A2. Proteomic approaches identified multiple candidate antigens for autoantibodies in patients with LN. Serum antibodies against annexin A2 were significantly elevated in subjects with proliferative LN, validating those antibodies as potential biomarkers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Evaluation of the anti-proliferative and cytostatic effect of Citrus sinensis (orange) fruit juice.

    Science.gov (United States)

    Chinedu, Enegide; Arome, David; Ameh, Solomon F; Ameh, Gift E

    2014-09-01

    This work has been designed to evaluate the anti-proliferative and cytostatic effects of Citrus sinensis (orange) fruit juice on rapidly proliferating cells. The study was carried out on the seeds of Sorghum bicolor for 72 h. The mean radicle length (mm) of the seeds was taken at 48 and 72 h. The result showed that when compared with the control, methotrexate, the standard drug showed a significant (P juice showed a slightly significant (P juice at doses of 10% and 20% (v/v) showed a highly significant (P juice at 10% (v/v) was 72.37% and at 20% (v/v) was 91.96%. The concentrations of 40% and 60% (v/v) showed cytostatic effects as no appreciable growth of the radicles of the seeds was observed throughout the experiment. The percentage inhibition for 40% (v/v) was 100% and 99.72% for 48 and 72 h, respectively, while that for the juice concentration of 60% (v/v) was 100% throughout the study. The experiment has shown that C. sinensis fruit juice has a potential for causing both anti-proliferative and cytostatic effects on fast proliferating cells and hence cancerous cells.

  18. BRCA1 expression, proliferative and apoptotic activities in ovarian epithelial inclusions.

    Science.gov (United States)

    Wang, Yiying; Wang, Yue; Wei, Li; Hong, Shuhui; Zhao, Miaoqing; Zhang, Xi; Zheng, Wenxin

    2017-03-07

    The purpose of this study was to examine proliferative and apoptotic activity in relation with BRCA1 expression in ovarian epithelial inclusions (OEIs), the putative precursor lesions of ovarian epithelial cancer (OEC). Benign ovaries from 95 patients were examined. Dual immunohistochemical staining for both BRCA1 and MIB-1 were performed to examine the relationship between BRCA1 and MIB-1 in OEI cells. Apoptotic activity was assessed on the parallel tissue sections by using TUNEL assay. Patients' age, menstrual phase and menopausal status were analyzed. OEIs were present in the ovaries of 53% of the patients. OEIs were less frequently found in premenopausal (45%) than postmenopausal women (58%). BRCA1 and MIB-1 were found in 27 and 47% of the OEI-containing ovaries, respectively. All BRCA1 positive OEI cells are MIB-1 positive with dual staining method, although overall the percentage of positive cells was small. No significant difference was found for BRCA1 and MIB-1 expression in OEIs between menopausal status and menstrual phases. Apoptosis containing OEIs were seen in 70% of the ovaries. Compared to OEIs in proliferative menstrual phase and premenopausal status, significantly more apoptosis was found in OEIs from secretory phase and postmenopausal women. A small fraction of the epithelial cells within OEIs are proliferating or dying. Low estrogen and/or high progesterone levels may promote OEI cell turnover via induction of apoptosis. Imbalance between cell proliferation and death within OEIs under influence of hormones may play a role in the ovarian epithelial tumorigenesis.

  19. The anti-proliferative and anti-angiogenic effect of the methanol extract from brittle star.

    Science.gov (United States)

    Baharara, Javad; Amini, Elaheh; Mousavi, Marzieh

    2015-04-01

    Anti-angiogenic therapy is a crucial step in cancer treatment. The discovery of new anti-angiogenic compounds from marine organisms has become an attractive concept in anti-cancer therapy. Because little data correlated to the pro- and anti-angiogenic efficacies of Ophiuroidea, which include brittle star, the current study was designed to explore the anti-angiogenic potential of brittle star methanol extract in vitro and in vivo. The anti-proliferative effect of brittle star extract on A2780cp cells was examined by MTT assays, and transcriptional expression of VEGF and b-FGF was evaluated by RT-PCR. In an in vivo model, 40 fertilized Ross eggs were divided into control and three experimental groups. The experimental groups were incubated with brittle star extract at concentrations of 25, 50 and 100 µg/ml, and photographed by photo-stereomicroscopy. Ultimately, numbers and lengths of vessels were measured by Image J software. Data were analyzed with SPSS software (pstar extract exerted a dose- and time-dependent anti-proliferative effect on A2780cp cancer cells. In addition, VEGF and b-FGF expression decreased with brittle star methanol extract treatment. Macroscopic evaluations revealed significant changes in the second and third experimental group compared to controls (pstar methanol extract in vitro and in vivo confer novel insight into the application of natural marine products in angiogenesis-related pathologies.

  20. Evaluation of in vitro anti-proliferative and immunomodulatory activities of compounds isolated from Curcuma longa

    Science.gov (United States)

    Yue, Grace G. L.; Chan, Ben C. L.; Hon, Po-Ming; Lee, Mavis Y. H.; Fung, Kwok-Pui; Leung, Ping-Chung; Lau, Clara B. S.

    2010-01-01

    The rhizome of Curcuma longa (CL) has been commonly used in Asia as a potential candidate for the treatment of different diseases, including inflammatory disorders and cancers. The present study evaluated the anti-proliferative activities of the isolated compounds (3 curcuminoids and 2 turmerones) from CL, using human cancer cell lines HepG2, MCF-7 and MDA-MB-231. The immunomodulatory activities of turmerones (α and aromatic) isolated from CL were also examined using human peripheral blood mononuclear cells (PBMC). Our results showed that the curcuminoids (curcumin, demethoxycurcumin and bisdemethoxycurcumin) and α-turmerone significantly inhibited proliferation of cancer cells in dose-dependent manner. The IC50 values of these compounds in cancer cells ranged from 11.0–41.8 μg/ml. Alpha-turmerone induced MDA-MB-231 cells to undergo apoptosis, which was confirmed by annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase cascade was activated as shown by a significant decrease of procaspases-3, -8 and -9 in α-turmerone treated cells. Both α-turmerone and aromatic-turmerone showed stimulatory effects on PBMC proliferation and cytokine production. The anti-proliferative effect of α-turmerone and immunomodulatory activities of ar-turmerone were shown for the first time. The findings revealed the potential use of CL crude extract (containing curcuminoids and volatile oil including turmerones) as chemopreventive agent. PMID:20438793

  1. Proliferative potential of malignant glioma cells before and after interstitial brachytherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kunishiro, Katsuzo; Matsumoto, Kengo; Higashi, Hisato; Adachi, Hisashi; Tamiya, Takashi; Furuta, Tomohisa; Ohtomo, Takashi [Okayama Univ. (Japan). School of Medicine

    1999-05-01

    The viability of tumor cells in radionecrotic tissue after interstitial brachytherapy (BRTX) was evaluated using immunohistochemical markers of proliferative potential in primary and recurrent tumors. Tumor specimens from 30 patients with malignant gliomas (14 anaplastic astrocytomas, 16 glioblastomas) taken before and after BRTX were examined using MIB-1 monoclonal antibody. Histological examinations of specimens obtained by craniotomy or stereotactic biopsy after BRTX revealed tumor recurrence in 18 patients and radionecrosis in 12 patients including two with pure radionecrosis and 10 with a mixture of both tumor and radionecrosis. The MIB-1 index of the tumors with radionecrosis was 7.6{+-}5.5%, and that of the primary tumors was 17.0{+-}11.2%, showing a significant difference (p<0.05). There was no significant difference between the MIB-1 index of the primary tumors with local recurrence after BRTX and the primary tumors which underwent radionecrosis. Although morphologically viable tumor cells were found in the radionecrotic tissue, BRTX causes a reduction in the proliferative potential of these tumor cells. (author)

  2. Cigarette smoke and lipopolysaccharide induce a proliferative airway smooth muscle phenotype

    Directory of Open Access Journals (Sweden)

    Zaagsma Johan

    2010-04-01

    Full Text Available Abstract Background A major feature of chronic obstructive pulmonary disease (COPD is airway remodelling, which includes an increased airway smooth muscle (ASM mass. The mechanisms underlying ASM remodelling in COPD are currently unknown. We hypothesized that cigarette smoke (CS and/or lipopolysaccharide (LPS, a major constituent of CS, organic dust and gram-negative bacteria, that may be involved in recurrent airway infections and exacerbations in COPD patients, would induce phenotype changes of ASM. Methods To this aim, using cultured bovine tracheal smooth muscle (BTSM cells and tissue, we investigated the direct effects of CS extract (CSE and LPS on ASM proliferation and contractility. Results Both CSE and LPS induced a profound and concentration-dependent increase in DNA synthesis in BTSM cells. CSE and LPS also induced a significant increase in BTSM cell number, which was associated with increased cyclin D1 expression and dependent on activation of ERK 1/2 and p38 MAP kinase. Consistent with a shift to a more proliferative phenotype, prolonged treatment of BTSM strips with CSE or LPS significantly decreased maximal methacholine- and KCl-induced contraction. Conclusions Direct exposure of ASM to CSE or LPS causes the induction of a proliferative, hypocontractile ASM phenotype, which may be involved in airway remodelling in COPD.

  3. Dashed line relaxing retinotomy in the management of retinal detachment with anterior proliferative vitreoretinopathy

    Directory of Open Access Journals (Sweden)

    Tsen CL

    2015-04-01

    Full Text Available Chui-Lien Tsen,1 Yu-Harn Horng,1 Shwu-Jiuan Sheu1,2 1Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2School of Medicine, National Yang-Ming University, Taipei, Taiwan Background: We describe the anatomical and functional outcomes of eyes that underwent a modified technique of relaxing retinotomy, dashed line relaxing retinotomy, in the management of retinal detachment with anterior proliferative vitreoretinopathy.Methods: We retrospectively reviewed 54 consecutive eyes in 52 patients who received pars plana vitrectomy with relaxing retinotomy during retinal detachment repair. Perfluorocarbon liquid (PFCL was used as a standard procedure to stabilize the retina during retinotomy to prevent slippage or inversion of the posterior flap. If PFCL was not available due to economic reasons, dashed line relaxing retinotomy was performed instead. Best-corrected visual acuity, slit-lamp biomicroscopy, intraocular pressure measurement, lens status, and fundus examination were analyzed. We excluded patients who were followed up <4 months.Results: Regarding anatomical success rates and visual outcomes, we found no significant differences between patients treated with intraoperative PFCL and those treated with dashed line relaxing retinotomy without PFCL.Conclusion: Compared to the simple and efficient PFCL-assisted relaxing retinotomy, dashed relaxing retinotomy is not the first choice when PFCL is available. Based on our results, this modified technique may offer an alternative in patients with anterior proliferative vitreoretinopathy for whom PFCL is not available. Keywords: perfluorocarbon liquid, PFCL 

  4. Nutritional milieu of isolated stromal vascular cells determines their proliferative, adipogenic, and lipogenic capacity in vitro.

    Science.gov (United States)

    Kadegowda, Anil K G; Wright, Asher; Duckett, Susan K

    2014-01-01

    The objective was to determine the effect of nutritional milieu of isolated stromal vascular (SV) cells on proliferative capacity of preadipocytes, and adipogenic and lipogenic capacity in adipocytes in vitro. Proliferation of the preadipocytes increased over time with 48 and 72 h being greater than 24 h; however, preadipocytes from steers supplemented with corn (LC) had lower proliferation rates compared with those without corn grain supplementation (L) at 72 h. Adipocyte cultures isolated from LC group had higher mean diameter on d 4 and 6, and higher mean volume on d 0, 4, 6, and 12 of culture. Adipocytes from steers supplemented with corn grain (LC) had lower expression of key adipogenic genes during extended days in culture. The results show that prior nutritional treatment of the donor animal used to isolate SV cultures alters their proliferative, adipogenic, and lipogenic capacity in culture. These differences may be related to lower induction/expression of AP2 gene in the adipose cultures from corn supplemented group. Corn grain supplementation to steers grazing legumes could have stimulated more active adipogenic progenitor cells to differentiate, which would leave fewer behind in the SV pool for subsequent isolation.

  5. Apoptotic and anti-proliferative effects of all-trans retinoic acid

    International Nuclear Information System (INIS)

    Zamora, Monica; Ortega, Juan Alberto; Alana, Lide; Vinas, Octavi; Mampel, Teresa

    2006-01-01

    We examined the apoptotic and anti-proliferative effects of all-trans retinoic acid (atRA) in HeLa cells. Our results demonstrated that HeLa cells were more sensitive to the anti-proliferative effects of atRA than to its apoptotic effects. Furthermore, we demonstrated that caspase inhibition attenuates cell death but does not alter the atRA-dependent reduction in cell proliferation, which suggests that atRA-induced apoptosis is independent of the arrest in cell proliferation. To check whether ANT proteins mediated these atRA effects, we transiently transfected cells with expression vectors encoding for individual ANT (adenine nucleotide translocase 1-3). Our results revealed that ANT1 and ANT3 over-expressing HeLa cells increased their atRA sensitivity. Thus, our results not only demonstrate the different functional activities of ANT isoforms, but also contribute to a better understanding of the properties of atRA as an anti-tumoral agent used in cancer therapy

  6. Analysis of the proliferative potential of odontogenic epithelial cells of pericoronal follicles.

    Science.gov (United States)

    Cimadon, Natalia; Lauxen, Isabel Silva; Carrard, Vinicius Coelho; Sant'Ana Filho, Manoel; Rados, Pantelis Varvaki; Oliveira, Márcia Gaiger

    2014-11-01

    To evaluate the proliferative potential and the cell proliferation rate of odontogenic epithelial cells. Forty-two cases of pericoronal follicles of impacted third molars were submitted to silver impregnation technique for quantification of argyrophilic nucleolar organizer regions (AgNOR) and immunohistochemical staining for EGFR and Ki-67. For AgNOR quantification, the mean number of active nucleolar organizer regions per nucleus (mAgNOR) and the percentage of cells with 1, 2, 3 and 4 or more AgNORs per nucleus (pAgNOR) were quantified. Ki-67 immunolabeling was quantified, whereas for EGFR, a descriptive analysis of staining patterns (membrane, cytoplasm or membrane + cytoplasm positivity) was performed. We evaluated the reduced epithelium of the enamel organ and/or islands of odontogenic epithelium present in the entire connective tissue. mAgNOR were 1.43 (1.0-2.42) and were significantly different among pericoronary follicles from upper and lower teeth (p = 0.041). Immunostaining of Ki-67 was negative in all cases. EGFR immunolabeling was found mainly in the cytoplasm and was more intense in islands and cords when compared to reduced epithelium of the enamel organ. Odontogenic epithelial cells of some pericoronal follicles have proliferative potential, suggesting their association with the development of odontogenic lesions. The authors suggest that nonerupted, especially of the lower teeth, should be monitored and if necessary removed.

  7. Frictional Coulomb drag in strong magnetic fields

    DEFF Research Database (Denmark)

    Bønsager, Martin Christian; Flensberg, Karsten; Hu, Ben Yu-Kuang

    1997-01-01

    A treatment of frictional Coulomb drag between two two-dimensional electron layers in a strong perpendicular magnetic field, within the independent electron picture, is presented. Assuming fully resolved Landau levels, the linear response theory expression for the transresistivity rho(21) is eval......A treatment of frictional Coulomb drag between two two-dimensional electron layers in a strong perpendicular magnetic field, within the independent electron picture, is presented. Assuming fully resolved Landau levels, the linear response theory expression for the transresistivity rho(21......) is evaluated using diagrammatic techniques. The transresistivity is given by an integral over energy and momentum transfer weighted by the product of the screened interlayer interaction and the phase space for scattering events. We demonstrate, by a numerical analysis of the transresistivity, that for well...

  8. MOLECULAR-GENETIC AND SERUM DISORDERS MARKERS OF FOLATE METABOLISM IN PATIENTS PROLIFERATIVE DISEASE AND BREAST CANCER

    Directory of Open Access Journals (Sweden)

    A. V. Markovsky

    2017-01-01

    Full Text Available Aim: to study the relationship between homocysteine, cysteine and glutathione in blood serum and various single nucleotide polymorphisms (SNPs of genes involved in folate metabolism in patients with proliferative breast disease and breast cancer. Material and methods. The study included 112 patients with proliferative breast lesions and breast cancer in Transbaikalia. The control group consisted of 144 women having no breast cancer. Blood levels of homocysteine, cysteine and glutathione were evaluated by HPLC (high performance liquid chromatography. Genotyping was performed by polymerase chain reaction with the detection of amplification product in real-time. Results. Molecular-genetic testing revealed no association between breast disease and genetic polymorphisms of MTHFR(C677T, MTHFR(A1298C, MTR(A2756G, MTRR(A66G in women with proliferative breast lesions and breast cancer, however, in contrast to the control group, the concentrations of homocysteine and glutathione were increased.

  9. To report a case of unilateral proliferative retinopathy following noncerebral malaria with Plasmodium falciparum in Southern India

    Directory of Open Access Journals (Sweden)

    Aditya Verma

    2015-01-01

    Full Text Available The retinopathy in association with malaria fever described so far includes retinal hemorrhages, vessel changes, retinal discoloration/whitening and papilledema. Malaria retinopathy has been mostly described in severe cases, associated with Plasmodium falciparum, correlating the patho-physiology of retinal and cerebral manifestations. We report an unusual case of proliferative retinopathy as a manifestation of malaria fever, caused by P. falciparum with no cerebral involvement. The patient had features of unilateral retinal vascular occlusion with proliferative changes and vitreous hemorrhage. To the best of our knowledge, such a case has never been reported so far in the literature. This report highlights the possible occurrence of severe proliferative changes associated with malaria fever, which if diagnosed early can prevent possible blindness.

  10. History of Psychology Publish and Perish: Psychology's Most Prolific Authors Are Not Always the Ones We Remember.

    Science.gov (United States)

    Green, Christopher D

    2017-01-01

    What is the relationship between being highly prolific in the realm of publication and being remembered as a great psychologist of the past? In this study, the PsycINFO database was used to identify the historical figures who wrote the most journal articles during the half-century from 1890 to 1939. Although a number of the 10 most prolific authors are widely remembered for their influence on the discipline today-E. L. Thorndike, Karl Pearson, E. B. Titchener, Henri Pi6ron-the majority are mostly forgotten. The data were also separated into the 5 distinct decades. Once again, a mixture of eminent and obscure individuals made appearances. Most striking, perhaps, was the great increase in articles published over the course of the half-century-approximately doubling each decade-and the enormous turnover in who was most prolific, decade over decade. In total, 100 distinct individuals appeared across just 5 lists of about 25 names each.

  11. The Morphological and Proliferative Aspect of Lymph Node of Hodgkin's disease Grown in Tissue Culture

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    Kamaleddin Armin

    1963-01-01

    Full Text Available The pre.sent rep.or,t describes the morphological and if nod H pron erative aspects of lymph es III odgkin s disease grown in tissue culture. The development of Hodgkin's lymph-nodes grown in vitro seems to depend upon the  a~e of t~e person and the stage of the Hodgkin'S disease at the time the I h IS obtained. ymp - The morphological and the proliferative aspects ('hELralcteriZI~d of Hodgkin's lymph-node is _. by four cytolOgically distinct phases:"nA- Simple emigrating phase."nB- Simple proliferative phase."nC- Complex proliferative phase."nD- Degenerative phase."nThe reticular cells, their evolution, and abnormalities St b . , ern erg cells and multinuclear giant cells have been sutdied and discussed. 14 K. ARMIN

  12. Cytological Study of Breast Carcinoma Before and After Oncotherapy with Special Reference to Morphometry and Proliferative Activity.

    Science.gov (United States)

    Koley, Sananda; Chakrabarti, Srabani; Pathak, Swapan; Manna, Asim Kumar; Basu, Siddhartha

    2015-12-01

    Our study was done to assess the cytological changes due to oncotherapy in breast carcinoma especially on morphometry and proliferative activity. Cytological aspirates were collected from a total of 32 cases of invasive ductal carcinoma both before and after oncotherapy. Morphometry was done on the stained cytological smears to assess the different morphological parameters of cell dimension by using the ocular morphometer and the software AutoCAD 2007. Staining was done with Ki-67 and proliferating cell nuclear antigen (PCNA) as proliferative markers. Different morphological parameters were compared before and after oncotherapy by unpaired Student's t test. Statistically significant differences were found in morphometric parameters, e.g., mean nuclear diameter, mean nuclear area, mean cell diameter, and mean cell area, and in the expression of proliferative markers (Ki-67 and PCNA). Statistical analysis was done by obtaining p values. There are statistically significant differences between morphological parameter of breast carcinoma cells before and after oncotherapy.

  13. The SNAP Strong Lens Survey

    Energy Technology Data Exchange (ETDEWEB)

    Marshall, P.

    2005-01-03

    Basic considerations of lens detection and identification indicate that a wide field survey of the types planned for weak lensing and Type Ia SNe with SNAP are close to optimal for the optical detection of strong lenses. Such a ''piggy-back'' survey might be expected even pessimistically to provide a catalogue of a few thousand new strong lenses, with the numbers dominated by systems of faint blue galaxies lensed by foreground ellipticals. After sketching out our strategy for detecting and measuring these galaxy lenses using the SNAP images, we discuss some of the scientific applications of such a large sample of gravitational lenses: in particular we comment on the partition of information between lens structure, the source population properties and cosmology. Understanding this partitioning is key to assessing strong lens cosmography's value as a cosmological probe.

  14. Strong coupling phase in QED

    International Nuclear Information System (INIS)

    Aoki, Ken-ichi

    1988-01-01

    Existence of a strong coupling phase in QED has been suggested in solutions of the Schwinger-Dyson equation and in Monte Carlo simulation of lattice QED. In this article we recapitulate the previous arguments, and formulate the problem in the modern framework of the renormalization theory, Wilsonian renormalization. This scheme of renormalization gives the best understanding of the basic structure of a field theory especially when it has a multi-phase structure. We resolve some misleading arguments in the previous literature. Then we set up a strategy to attack the strong phase, if any. We describe a trial; a coupled Schwinger-Dyson equation. Possible picture of the strong coupling phase QED is presented. (author)

  15. The prognostic value of apoptotic and proliferative markers in breast cancer.

    Science.gov (United States)

    Engels, Charla C; Ruberta, Francesca; de Kruijf, Esther M; van Pelt, Gabi W; Smit, Vincent T H B M; Liefers, Gerrit Jan; Matsushima, Tomoko; Shibayama, Masaki; Ishihara, Hideki; van de Velde, Cornelis J H; Kuppen, Peter J K

    2013-11-01

    Increasing ability of early breast cancer (BC) diagnosis leading to more early stage detection, better survival, and low relapse marks one of the milestones achieved over the decades. Foregoing poses a challenge for clinicians regarding optimal treatment, in which over- and under-treatment should be avoided. Classical prognostic and predictive factors fall short for individualized adjuvant therapy selection in this patient group. The key to better characterization may be found in the biology underlying individual tumors. We hypothesized that markers related to cellular proliferation and apoptosis and the balance between these two processes in tumor development will be predictive for clinical outcome. Our study population (N = 822) consisted of all early stage BC patients primarily treated with surgery in our center between 1985 and 1996. Sections of available tumor tissue (87 %, 714/822) were immunohistochemically stained for expression of p53, active-caspase-3, and Ki67. In 43 % (304/714) and 18 % (126/714) of this cohort, respectively, a biochemical C2P(®) risk prediction and caspase-3 assay were performed. Expression data of the mentioned markers, single, or combined, were analyzed. Results showed that both the single and combined markers, whether of apoptotic or proliferative origin had associations with clinical outcome. An additive effect was seen for the hazard ratios when data on p53, active caspase-3, and Ki67 status were combined. The assembled prognostic apoptotic-proliferative subtype showed significant association for both the overall survival (p = 0.024) and relapse-free period (p = 0.001) in the multivariate analyses of grade I breast tumors. Combined markers of tumor cell apoptosis and proliferation represent tumor aggressiveness. The apoptotic-proliferative subtypes that we present in this study represent a clinical prognostic profile with solid underlying biological rationale and pose a promising method for accurate identification of

  16. Dynamics of Proliferative and Quiescent Stem Cells in Liver Homeostasis and Injury.

    Science.gov (United States)

    Cao, Wanlu; Chen, Kan; Bolkestein, Michiel; Yin, Yuebang; Verstegen, Monique M A; Bijvelds, Marcel J C; Wang, Wenshi; Tuysuz, Nesrin; Ten Berge, Derk; Sprengers, Dave; Metselaar, Herold J; van der Laan, Luc J W; Kwekkeboom, Jaap; Smits, Ron; Peppelenbosch, Maikel P; Pan, Qiuwei

    2017-10-01

    Adult liver stem cells are usually maintained in a quiescent/slow-cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. We studied LGR5-positive stem cells using diphtheria toxin receptor and green fluorescent protein (GFP) knock-in mice. In these mice, LGR5-positive cells specifically coexpress diphtheria toxin receptor and the GFP reporter. Lineage-tracing experiments were performed in mice in which LGR5-positive stem cells and their daughter cells expressed a yellow fluorescent protein/mTmG reporter. Slow-cycling stem cells were investigated using GFP-based, Tet-on controlled transgenic mice. We studied the dynamics of both stem cell populations during liver homeostasis and injury induced by carbon tetrachloride. Stem cells were isolated from mouse liver and organoid formation assays were performed. We analyzed hepatocyte and cholangiocyte lineage differentiation in cultured organoids. We did not detect LGR5-expressing stem cells in livers of mice at any stage of a lifespan, but only following liver injury induced by carbon tetrachloride. In the liver stem cell niche, where the proliferating LGR5 + cells are located, we identified a quiescent/slow-cycling cell population, called label-retaining cells (LRCs). These cells were present in the homeostatic liver, capable of retaining the GFP label over 1 year, and expressed a panel of progenitor/stem cell markers. Isolated single LRCs were capable of forming organoids that could be carried in culture, expanded for months, and differentiated into hepatocyte and cholangiocyte lineages in vitro, demonstrating their bona fide stem cell properties. More interestingly, LRCs responded to liver injury and gave rise to LGR5-expressing stem cells, as well as

  17. Halofuginone has anti-proliferative effects in acute promyelocytic leukemia by modulating the transforming growth factor beta signaling pathway.

    Directory of Open Access Journals (Sweden)

    Lorena L de Figueiredo-Pontes

    Full Text Available Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα expression in acute promyelocytic leukemia (APL impairs transforming growth factor beta (TGFβ signaling, leading to cell growth advantage. Halofuginone (HF, a low-molecular-weight alkaloid that modulates TGFβ signaling, was used to treat APL cell lines and non-obese diabetic/severe combined immunodeficiency (NOD/SCID mice subjected to transplantation with leukemic cells from human chorionic gonadotrophin-PML-RARα transgenic mice (TG. Cell cycle analysis using incorporated bromodeoxyuridine and 7-amino-actinomycin D showed that, in NB4 and NB4-R2 APL cell lines, HF inhibited cellular proliferation (P<0.001 and induced apoptosis (P = 0.002 after a 24-hour incubation. Addition of TGFβ revealed that NB4 cells were resistant to its growth-suppressive effects and that HF induced these effects in the presence or absence of the cytokine. Cell growth inhibition was associated with up-regulation of TGFβ target genes involved in cell cycle regulation (TGFB, TGFBRI, SMAD3, p15, and p21 and down-regulation of MYC. Additionally, TGFβ protein levels were decreased in leukemic TG animals and HF in vivo could restore TGFβ values to normal. To test the in vivo anti-leukemic activity of HF, we transplanted NOD/SCID mice with TG leukemic cells and treated them with HF for 21 days. HF induced partial hematological remission in the peripheral blood, bone marrow, and spleen. Together, these results suggest that HF has anti-proliferative and anti-leukemic effects by reversing the TGFβ blockade in APL. Since loss of the TGFβ response in leukemic cells may be an important second oncogenic hit, modulation of TGFβ signaling may be of therapeutic interest.

  18. Comparison of gene expression profile of epiretinal membranes obtained from eyes with proliferative vitreoretinopathy to that of secondary epiretinal membranes.

    Directory of Open Access Journals (Sweden)

    Ryo Asato

    Full Text Available BACKGROUND: Proliferative vitreoretinopathy (PVR is a destructive complication of retinal detachment and vitreoretinal surgery which can lead to severe vision reduction by tractional retinal detachments. The purpose of this study was to determine the gene expression profile of epiretinal membranes (ERMs associated with a PVR (PVR-ERM and to compare it to the expression profile of less-aggressive secondary ERMs. METHODOLOGY/PRINCIPAL FINDINGS: A PCR-amplified complementary DNA (cDNA library was constructed using the RNAs isolated from ERMs obtained during vitrectomy. The sequence from the 5' end was obtained for randomly selected clones and used to generate expressed sequence tags (ESTs. We obtained 1116 nonredundant clusters representing individual genes expressed in PVR-ERMs, and 799 clusters representing the genes expressed in secondary ERMs. The transcriptome of the PVR-ERMs was subdivided by functional subsets of genes related to metabolism, cell adhesion, cytoskeleton, signaling, and other functions, by FatiGo analysis. The genes highly expressed in PVR-ERMs were compared to those expressed in the secondary ERMs, and these were subdivided by cell adhesion, proliferation, and other functions. Querying 10 cell adhesion-related genes against the STRING database yielded 70 possible physical relationships to other genes/proteins, which included an additional 60 genes that were not detected in the PVR-ERM library. Of these, soluble CD44 and soluble vascular cellular adhesion molecule-1 were significantly increased in the vitreous of patients with PVR. CONCLUSIONS/SIGNIFICANCE: Our results support an earlier hypothesis that a PVR-ERM, even from genomic points of view, is an aberrant form of wound healing response. Genes preferentially expressed in PVR-ERMs may play an important role in the progression of PVR and could be served as therapeutic targets.

  19. NY-ESO-1 Protein Cancer Vaccine With Poly-ICLC and OK-432: Rapid and Strong Induction of NY-ESO-1-specific Immune Responses by Poly-ICLC.

    Science.gov (United States)

    Takeoka, Tomohira; Nagase, Hirotsugu; Kurose, Koji; Ohue, Yoshihiro; Yamasaki, Makoto; Takiguchi, Shuji; Sato, Eiichi; Isobe, Midori; Kanazawa, Takayuki; Matsumoto, Mitsunobu; Iwahori, Kota; Kawashima, Atsunari; Morimoto-Okazawa, Akiko; Nishikawa, Hiroyoshi; Oka, Mikio; Pan, Linda; Venhaus, Ralph; Nakayama, Eiichi; Mori, Masaki; Doki, Yuichiro; Wada, Hisashi

    2017-03-23

    We conducted a clinical trial of a cancer vaccine using NY-ESO-1 protein with polyinosinic-polycytidylic acid-poly-L-lysine carboxymethylcellulose (poly-ICLC) and/or OK-432 against solid tumors. A total of 15 patients were sequentially enrolled in 4 cohorts. Patients in cohort 1 received NY-ESO-1 protein; cohort 2a received NY-ESO-1 protein+OK-432; cohort 2b received NY-ESO-1 protein+poly-ICLC; cohort 3 received NY-ESO-1 protein+OK-432+poly-ICLC with Montanide ISA-51. The endpoints of this trial were safety, NY-ESO-1 immune responses, and clinical response. Vaccine-related adverse events observed were fever and injection-site reaction (grade 1). Two patients showed stable disease after vaccination. NY-ESO-1 antibodies were observed in 4 patients at the baseline (sero-positive) and augmented in all patients after vaccination. Eleven patients showed a conversion of negative antibody responses at baseline to positive after vaccination (seroconversion). The seroconversions were observed in all 11 sero-negative patients by the fourth immunization; in particular, it was observed by the second immunization in patients with poly-ICLC, and these induced antibody responses were stronger than those in patients immunized without poly-ICLC. The number of NY-ESO-1-specific interferon (IFN)γ-producing T cells was increased in patients immunized with poly-ICLC and/or OK-432, and furthermore, the increase of IFNγ-producing CD8 T cells in patients immunized with poly-ICLC was significantly higher than that in patients without poly-ICLC. Nonspecific activations of T-cell or antigen presenting cells were not observed. Our present study showed that poly-ICLC is a promising adjuvant for cancer vaccines.

  20. Strong Decomposition of Random Variables

    DEFF Research Database (Denmark)

    Hoffmann-Jørgensen, Jørgen; Kagan, Abram M.; Pitt, Loren D.

    2007-01-01

    A random variable X is stongly decomposable if X=Y+Z where Y=Φ(X) and Z=X-Φ(X) are independent non-degenerated random variables (called the components). It is shown that at least one of the components is singular, and we derive a necessary and sufficient condition for strong decomposability...

  1. Strong interaction at finite temperature

    Indian Academy of Sciences (India)

    Abstract. We review two methods discussed in the literature to determine the effective parameters of strongly interacting particles as they move through a heat bath. The first one is the general method of chiral perturbation theory, which may be readily applied to this problem. The other is the method of thermal QCD sum rules ...

  2. Strong-strong beam-beam simulation on parallel computer

    Energy Technology Data Exchange (ETDEWEB)

    Qiang, Ji

    2004-08-02

    The beam-beam interaction puts a strong limit on the luminosity of the high energy storage ring colliders. At the interaction points, the electromagnetic fields generated by one beam focus or defocus the opposite beam. This can cause beam blowup and a reduction of luminosity. An accurate simulation of the beam-beam interaction is needed to help optimize the luminosity in high energy colliders.

  3. Strong-strong beam-beam simulation on parallel computer

    International Nuclear Information System (INIS)

    Qiang, Ji

    2004-01-01

    The beam-beam interaction puts a strong limit on the luminosity of the high energy storage ring colliders. At the interaction points, the electromagnetic fields generated by one beam focus or defocus the opposite beam. This can cause beam blowup and a reduction of luminosity. An accurate simulation of the beam-beam interaction is needed to help optimize the luminosity in high energy colliders

  4. Chemical composition and anti-proliferative properties of Bursera graveolens essential oil.

    Science.gov (United States)

    Monzote, Lianet; Hill, Gabrielle M; Cuellar, Armando; Scull, Ramón; Setzer, William N

    2012-11-01

    Bursera graveolens is a wild tree of commercial importance native to the Neotropics, which has been widely used in folk medicine. In the present study, the chemical composition and anti-proliferative properties of the essential oil from B. graveolens were assayed. The chemical composition of the essential oil, determined by GC-MS, was complex and dominated by limonene (26.5%). Bursera oil inhibited the growth of MCF-7 breast tumor cells as well as amastigotes of L. amazonensis, with IC50 values of 48.9 +/- 4.3 and 36.7 +/- 4.7 microg/mL, respectively. In addition, the cytotoxicity of the oil was 103.9 +/- 7.2 microg/mL against peritoneal macrophages from BALB/c mice. These results demonstrate that the essential oil from B. graveolens is a promissory antiproliferative product.

  5. [Heavy silicone oil (Densiron® 68) in proliferative vitreoretinopathy: 4 years of experience].

    Science.gov (United States)

    Macías-Murelaga, B; Ruiz, M; Bascarán, L; Gibelalde, A; Aldazabal, M; Irigoyen, C

    2013-11-01

    Prospective observational study including 10 patients (age range: 27-74 years) with recurrent retinal detachment (RD) and proliferative vitreoretinopathy (PVR) and 2.8 mean unsatisfactory previous surgeries. Densiron® was injected in all patients, with surgical retinectomy being required in 70% of them. Minimum follow-up time was 12 months. The mean length of time before Densiron® withdrawal was 4 months. Three patients (30%) presented with a new RD. The main complication detected was cataract development. No relationship was found between re-detachments and tamponade time, baseline disease or RD evolution time. Densiron® may be a good option in cases of recurrent RD in which previous treatment with scleral buckle, gas and/or 1,000/5,000 silicone oils has proven to be unsatisfactory. Copyright © 2012 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  6. Structural Changes of the Macula on Optical Coherence Tomography after Vitrectomy for Proliferative Diabetic Retinopathy.

    Science.gov (United States)

    Im, Jong Chan; Kim, Jong Ho; Park, Dong Ho; Shin, Jae Pil

    2017-01-01

    This study aimed to evaluate the relationship between macular structural changes and visual prognosis after pars plana vitrectomy (PPV) for proliferative diabetic retinopathy. The study included 60 eyes that had undergone PPV. Macular optical coherence tomography (OCT) findings were classified into 5 groups preoperatively and 10 groups postoperatively. Best-corrected visual acuity (BCVA) were analyzed according to pre- and postoperative OCT. From the preoperative OCT, normal fovea with/without traction, normal fovea with preretinal hemorrhage, and tractional retinal detachment involving fovea showed an increase in BCVA after PPV (all p 20/50). Subfoveal fibrosis, macular hole, loss of foveal depression, and serous foveal detachment showed poor visual prognosis (BCVA <20/100). Macular structural changes were various after PPV, and visual prognosis correlated with these changes. © 2017 S. Karger AG, Basel.

  7. Hepatic progenitor cell resistance to TGF-β1's proliferative and apoptotic effects

    International Nuclear Information System (INIS)

    Clark, J. Brian; Rice, Lisa; Sadiq, Tim; Brittain, Evan; Song, Lujun; Wang Jian; Gerber, David A.

    2005-01-01

    The success of hepatocellular therapies using stem or progenitor cell populations is dependent upon multiple factors including the donor cell, microenvironment, and etiology of the liver injury. The following experiments investigated the impact of TGF-β1 on a previously described population of hepatic progenitor cells (HPC). The majority of the hepatic progenitor cells were resistant to endogenously produced TGF-β1's proapoptotic and anti-proliferative effects unlike more well-differentiated cellular populations (e.g., mature hepatocytes). Surprisingly, in vitro TGF-β1 supplementation significantly inhibited de novo hepatic progenitor cell colony formation possibly via an indirect mechanism(s). Therefore despite the HPC's direct resistance to supplemental TGF-β1, this cytokine's inhibitory effect on colony formation could have a potential negative impact on the use of these cells as a therapy for patients with liver disease

  8. What goes around comes around: an investigation of resistance to proliferative kidney disease in rainbow trout Oncorhynchus mykiss (Walbaum) following experimental re-exposure.

    Science.gov (United States)

    Bailey, C; Segner, H; Wahli, T

    2017-11-01

    Rainbow trout Oncorhynchus mykiss surviving proliferative kidney disease (PKD) are reported not to develop the disease upon re-exposure. However, the mechanisms involved in the immune response to re-exposure are unknown. We examined disease susceptibility and the immune response of naive 1+ rainbow trout when first exposed to Tetracapsuloides bryosalmonae in comparison with that of 1+ rainbow trout re-exposed to T. bryosalmonae. PKD pathogenesis, parasite burden and transcriptional signatures of the host immune response were assessed at 10, 25 and 40 d.p.e (days post-exposure). In addition, we evaluated the presence of IgM+ B cells in the blood and the posterior kidney. The exposure of 1+ rainbow trout to T. bryosalmonae for the first time resulted in 100% infection prevalence, high parasite burdens and severe clinical PKD, while re-exposed fish were either able to avoid reinfection completely or mount an earlier and more efficient adaptive-type immune response. This response was characterized by a greater amount of IgM+ B cells in the blood and elevated mRNA levels of secretory IgM in the posterior kidney which minimized pathogen burden and kidney inflammation. Our findings suggest that rainbow trout is able to develop immune protection against T. bryosalmonae. © 2017 John Wiley & Sons Ltd.

  9. In vitro anti-proliferative activity of clove extract on human gastric carcinoma

    Directory of Open Access Journals (Sweden)

    A. Karimi

    2017-10-01

    Full Text Available Background and objectives: Cancer cell resistance to common chemotherapy agents is on rise. Plants are considered valuable sources of herbal drugs for cancer therapy. The present study was conducted to investigate the in vitro antioxidant, anti-proliferative, and apoptosis-inducing properties of clove (Syzygium aromaticum L. extract in human gastric carcinoma (AGS. Methods: Crude ethanol extract of S. aromaticum dried buds was prepared and  in vitro anti-proliferative effects of the extract on AGS and normal Human dermal fibroblasts (HDF cell lines were studied by MTT assay. To examine apoptosis induction, AGS cells were incubated with IC50 concentrations of the extract, stained with propidium iodide (PI and annexin V-fluorescein isothiocyanate (FITC, and analyzed by flow cytometry. Antioxidant activity and total phenolics and flavonoids contents were evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH assay, Folin-Ciocalteu method, and aluminum chloride colorimetric method, respectively. Results: The IC50 of DPPH and total phenolics and flavonoids contents of the extract were 10.05±1.93 μg/mL, 225.6±40 mg GAE/g, and 29.30±2.35 mgRUT/g, respectively. The IC50 of the extract against HDFs was 649 µg/mL, higher than AGS cells, which was 118.7 g/mL at 48 h after treatment. Flow cytometric analysis showed that the extract induced cell apoptosis. Conclusions: Crude ethanol S. aromaticum extract had high total phenolics content, and suppressed the proliferation of human gastric cancer cells, likely due to apoptosis induction. Further studies should be conducted to determine the mechanisms of its anticancer effects.

  10. Apoptotic Cell Death and the Proliferative Capacity of Human Breast Cancers

    Directory of Open Access Journals (Sweden)

    Gabriele A. Losa

    1998-01-01

    Full Text Available The proliferative capacity (%S‐phase fraction, DNA ploidy, apoptosis frequency (DNA fragmentation and steroid hormone receptor status (estrogen receptor, ER; progesterone receptor, PR of 110 samples of human breast tissues with ductal invasive carcinoma were measured using biochemical and cytofluorimetric procedures. The DNA fragmentation had a left‐skewed frequency distribution and an overall median value of 1.64%, whilst the median %S‐phase fraction was 8%. The median %DNA fragmentation and %S‐phase fraction were 1.96% and 16% in hyperdiploid tumours (n=29; DNA index >1.1 higher than in hypodiploid tumors (n=10; DNA index 0.96, 0.38% and 7.5%. DNA diploid tumours (n=71 had median %DNA fragmentation and %S‐phase values of 1.68% and 6%, consistently lower than the median values of DNA hyperdiploid tumours. The ER content of hypodiploid tumours was about one half (median: 5.9 fmol/mg the median values in hyperdiploid (10.6 fmol/mg and diploid tumours (14.6 fmol/mg. This may correlate with the lowest frequency of apoptosis in hypodiploid tumours, at least when measured by biochemical methods which only detect cells in the late phases of apoptosis. In contrast, the median PR was lowest in hyperdiploid tumours than in hypo and/or diploid tumours. The %S‐phase/%fragmented DNA ratio for the hypodiploid tumours was 19.7, significantly higher than the ratios for hyperdiploid (8.2 and diploid tumours (3.6. These findings indicated that there is an imbalance between proliferative capacity and cell death or growth arrest in human breast tumours. This imbalance may well be linked to a loss of steroid hormone control.

  11. Methylene blue prevents retinal damage in an experimental model of ischemic proliferative retinopathy.

    Science.gov (United States)

    Rey-Funes, Manuel; Larrayoz, Ignacio M; Fernández, Juan C; Contartese, Daniela S; Rolón, Federico; Inserra, Pablo I F; Martínez-Murillo, Ricardo; López-Costa, Juan J; Dorfman, Verónica B; Martínez, Alfredo; Loidl, César F

    2016-06-01

    Perinatal asphyxia induces retinal lesions, generating ischemic proliferative retinopathy, which may result in blindness. Previously, we showed that the nitrergic system was involved in the physiopathology of perinatal asphyxia. Here we analyze the application of methylene blue, a well-known soluble guanylate cyclase inhibitor, as a therapeutic strategy to prevent retinopathy. Male rats (n = 28 per group) were treated in different ways: 1) control group comprised born-to-term animals; 2) methylene blue group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery; 3) perinatal asphyxia (PA) group comprised rats exposed to perinatal asphyxia (20 min at 37°C); and 4) methylene blue-PA group comprised animals born from pregnant rats treated with methylene blue (2 mg/kg) 30 and 5 min before delivery, and then the pups were subjected to PA as above. For molecular studies, mRNA was obtained at different times after asphyxia, and tissue was collected at 30 days for morphological and biochemical analysis. Perinatal asphyxia produced significant gliosis, angiogenesis, and thickening of the inner retina. Methylene blue treatment reduced these parameters. Perinatal asphyxia resulted in a significant elevation of the nitrergic system as shown by NO synthase (NOS) activity assays, Western blotting, and (immuno)histochemistry for the neuronal isoform of NOS and NADPH-diaphorase activity. All these parameters were also normalized by the treatment. In addition, methylene blue induced the upregulation of the anti-angiogenic peptide, pigment epithelium-derived factor. Application of methylene blue reduced morphological and biochemical parameters of retinopathy. This finding suggests the use of methylene blue as a new treatment to prevent or decrease retinal damage in the context of ischemic proliferative retinopathy. Copyright © 2016 the American Physiological Society.

  12. Pericyte chemomechanics and the angiogenic switch: insights into the pathogenesis of proliferative diabetic retinopathy?

    Science.gov (United States)

    Durham, Jennifer T; Dulmovits, Brian M; Cronk, Stephen M; Sheets, Anthony R; Herman, Ira M

    2015-06-01

    To establish the regulatory roles that pericytes have in coordinating retinal endothelial cell (EC) growth and angiogenic potential. Pericytes were derived from donor diabetic (DHuRP) or normal (NHuRP) human retinae, and characterized using vascular markers, coculture, contraction, morphogenesis, and proliferation assays. To investigate capillary "cross-talk," pericyte-endothelial coculture growth, and connexin-43 (Cx43) expression assays were performed. Paracrine effects were examined via treating EC with pericyte-derived conditioned media (CM) in proliferation, angiogenesis, and angiocrine assays. The effects of sphingosine 1-phosphate (S1P) were assessed using receptor antagonists. The DHuRP exhibit unique proliferative and morphologic properties, reflecting distinctive cytoskeletal and isoactin expression patterns. Unlike NHuRP, DHuRP are unable to sustain EC growth arrest in coculture and display reduced Cx43 expression. Further, CM from DHuRP (DPCM) markedly stimulates EC proliferation and tube formation. Treatment with S1P receptor antagonists mitigates DPCM growth-promotion in EC and S1P-mediated pericyte contraction. Angiocrine assays on normal and diabetic pericyte secretomes reveal factors involved in angiogenic control, inflammation, and metabolism. Effects from the diabetic microenvironment appear sustainable in cell culture: pericytes derived from diabetic donor eyes seemingly possess a "metabolic memory" in vitro, which may be linked to original donor health status. Diabetes- and pericyte-dependent effects on EC growth and angiogenesis may reflect alterations in bioactive lipid, angiocrine, and chemomechanical signaling. Altogether, our results suggest that diabetes alters pericyte contractile phenotype and cytoskeletal signaling, which ultimately may serve as a key, initiating event required for retinal endothelial reproliferation, angiogenic activation, and the pathological neovascularization accompanying proliferative diabetic retinopathy.

  13. Diet soft drink is associated with increased odds of proliferative diabetic retinopathy.

    Science.gov (United States)

    Fenwick, Eva K; Gan, Alfred Tl; Man, Ryan Ek; Sabanayagam, Charumathi; Gupta, Preeti; Khoo, Krystal; Aravindhan, Amudha; Wong, Tien Y; Lamoureux, Ecosse L

    2018-01-23

    While consumption of soft drink may increase the risk of cardiovascular disease, the relationship between soft drink consumption and diabetes complications is unknown. To explore the association between regular and diet soft drink consumption, and diabetic retinopathy (DR) and diabetic macular oedema (DME). Clinical, cross-sectional study. Adult patients with diabetes recruited from a tertiary eye hospital (Melbourne, Australia) answered a Food Frequency Questionnaire. None, moderate and high soft drink consumption was defined as 4 cans/bottles (375 mL) per week, respectively. Due to missing data, data were imputed using the multiple imputation chained equation procedure. Multivariable logistic regression models determined the associations between soft drink consumption, and presence and severity of DR/DME. Presence and severity of DR/DME. Of the 609 participants (mean age ± standard deviation: 64.6 ± 11.6 years; males = 210), 285 (46.8%) and 190 (31.2%) consumed diet and regular soft drink, respectively. A total of 230 (37.8%), 36 (5.9%), 154 (25.3%), 28 (4.6%) and 146 (24.0%) had no DR, mild non-proliferative DR (NPDR), moderate NPDR, severe NPDR and proliferative DR (PDR), respectively. High diet soft drink consumption was independently associated with increased likelihood of having PDR (odds ratio = 2.51, 95% confidence interval = 1.05-5.98), compared to no consumption. In contrast, regular soft drink was not associated with DR or DME. Consuming >4 cans (1.5 L)/week of diet soft drink is associated with a more than twofold risk of having PDR in patients with diabetes. Longitudinal studies are needed to further elucidate the association and its underpinning mechanisms. © 2018 Royal Australian and New Zealand College of Ophthalmologists.

  14. Alteration of melatonin secretion in patients with type 2 diabetes and proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Hikichi T

    2011-05-01

    Full Text Available Taiichi Hikichi1, Naohiro Tateda2, Toshiaki Miura31Department of Ophthalmology, Ohtsuka Eye Hospital, Sapporo; 2Asahikawa National College of Technology, Asahikawa; 3Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, JapanBackground: The purpose of this study was to evaluate the dynamics of plasma melatonin secretion in patients with type 2 diabetes mellitus and diabetic retinopathy.Methods: Plasma melatonin levels were measured by high-performance liquid chromatography in 56 patients. Patients were divided into a diabetic group (30 patients and a nondiabetic group (26 patients. The diabetic group was divided further into a proliferative diabetic retinopathy (PDR group (n = 14 and a nonproliferative diabetic retinopathy (NPDR group (n = 16. Plasma melatonin levels obtained at midnight and 3 am were compared between the groups.Results: Nighttime melatonin levels were significantly lower in the diabetic group than in the nondiabetic group (P < 0.03 and lower in the PDR group than in the nondiabetic and NPDR groups (P < 0.01 and P < 0.03, respectively, but no significant difference was found between the nondiabetic and NPDR groups. The daytime melatonin level did not significantly differ between the nondiabetic and diabetic groups or between the nondiabetic, NPDR, and PDR groups.Conclusion: The nighttime melatonin level is altered in patients with diabetes and PDR but not in diabetic patients without PDR. Although patients with PDR may have various dysfunctions that affect melatonin secretion more severely, advanced dysfunction of retinal light perception may cause altered melatonin secretion. Alteration of melatonin secretion may accelerate further occurrence of complications in diabetic patients.Keywords: circadian rhythm, diabetes, proliferative diabetic retinopathy, melatonin

  15. Fulminant proliferative diabetic retinopathy in the non-photocoagulated eye following acute renal failure.

    Science.gov (United States)

    Jang, Liuna; Herbort, Carl P

    2016-12-01

    Management of diabetic retinopathy should follow more strict and aggressive rules in patients at risk for severe acute renal impairment. Such patients should be identified and possibly prophylactically laser treated to avoid the severe consequences demonstrated in this case report. A 34-year-old type 2 diabetes patient with a stabilized diabetic retinopathy developed acute and severe retinal decompensation within weeks after acute renal failure complicated his chronic stable renal impairment. Fluorescein angiographic and optical coherence tomographic illustrations of the rapid evolution of the retinal condition are presented. The patient had previously been treated with panretinal photocoagulation in his left eye. After 8 years of regular 6-monthly checked stability, he developed rapid-onset proliferative diabetic retinopathy and macular edema in his right eye within 3 months of his last ocular check-up. Fluorescein angiography showed neovessels and major ischemic areas. Emergency panretinal photocoagulation and a sub-Tenon's injection were necessary to achieve control of the situation with regression of neovessels and complete regression of macular edema. This case shows that it is imperative for nephrologists to be well informed about a patient's ocular situation in order to give timely information to the ophthalmologist who can intervene to protect the retina in case of renal failure. On the other hand, the ophthalmologist should be familiar with the renal function of his patient with renal impairment so that he can decide to perform prophylactic retinal panphotocoagulation that should be imperatively considered even without strict indications in patients with renal impairment at risk for further deterioration of renal function, in order to prevent such explosive ischemic and proliferative retinopathy putting vision at risk.

  16. Serum MiRNA Biomarkers serve as a Fingerprint for Proliferative Diabetic Retinopathy

    Directory of Open Access Journals (Sweden)

    Shao Qing

    2014-11-01

    Full Text Available Background: Diabetic retinopathy (DR is a retinopathy resulting from diabetes mellitus (DM which was classified into non-proliferative DR (NPDR and proliferative DR (PDR. Without an early screening and effective diagnosis, patients with PDR will develop serious complications. Therefore, we sought to identify special serum microRNAs (miRNAs that can serve as a novel non-invasive screening signature of PDR and test its specificity and sensitivity in the early diagnosis of PDR. Methods: In total, we obtained serum samples from 90 PDR cases, 90 matched NPDR patients and 20 controls. An initial screening of miRNA expression was performed through TaqMan Low Density Array (TLDA. The candidate miRNAs were validated by individual reverse transcription quantitative real-time PCR (RT-qPCR arranged in an initial and a two-stage validation sets. Moreover, additional double-blind testing was performed in 20 patients clinically suspected of having DR to evaluate the diagnostic value and accuracy of the serum miRNA profiling system in predicting PDR. Results: Three miRNAs were significantly increased in patients with PDR compared with NPDR after the multiple stages. The areas under the receiver operating characteristic (ROC curves of the validated three-serum miRNAs signature were 0.830, 0.803 and 0.873 in the initial and two validation sets, respectively. Combination of miR-21, miR-181c, and miR-1179 possessed a moderate ability to discrimination between PDR and NPDR with an area under ROC value of 0.89. The accuracy rate of the three-miRNA profile as PDR signature was 82.6%. Conclusions: These data provide evidence that serum miRNAs have the potential to be sensitive, cost-effective biomarkers for the early detection of PDR. These biomarkers could serve as a dynamic monitoring factor for detecting the progression of PDR from NPDR.

  17. Retinitis pigmentosa reduces the risk of proliferative diabetic retinopathy: a nationwide population-based cohort study.

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    Yuh-Fang Chen

    Full Text Available PURPOSE: To study the association between retinitis pigmentosa (RP and the progression of diabetic retinopathy (DR. METHODS: Using the Longitudinal Health Insurance Database 2000 of Taiwan, we identified individuals with an initial diagnosis for RP during the period of 1997-2008. A non-RP comparison group, 10-fold frequency matched by sex, age, index year and the year of diabetes diagnosed, were randomly selected from the same database. The occurrence of DR was observed for all subjects until the end of 2009. The Kaplan-Meier curves were used to illustrate the cumulative probability of developing DR for the RP group and comparison groups. The hazard ratio (HR of DR for the RP group relative to the comparison group was estimated using Cox proportional hazards model after adjusting for potential confounders. RESULTS: The Kaplan-Meier curves were not statistically significant different between the RP group and the comparison group. However, the RP group had a higher cumulative probability of developing DR during the first six to seven years. The cumulative probability kept increasing and became higher in the comparison group but remained unchanged in the RP group. The HR for the RP patients comparing with the comparison group was 0.96 (95% confidence interval (CI = 0.43-2.14. Stratified by severity, RP was associated with a non-statistically significant reduced risk of proliferative DR (PDR (HR = 0.70, 95% CI = 0.16-3.14. The HR for non-proliferative DR (NPDR was 1.08 (95% CI = 0.40-2.86. CONCLUSION: In this study, RP was not statistically significant associated with the incidence of DR.

  18. Potentially Malignant Disorders Revisited - The Lichenoid Lesion/ Proliferative Verrucous Leukoplakia Conundrum.

    Science.gov (United States)

    Thomson, P J; Goodson, M L; Smith, D R

    2018-04-16

    Clinically identifiable potentially malignant disorders (PMD) precede oral squamous cell carcinoma development. Oral lichenoid lesions (OLL) and proliferative verrucous leukoplakia (PVL) are specific precursor lesions believed to exhibit both treatment resistance and a high risk of malignant transformation (MT). A retrospective review of 590 PMD patients treated in Northern England by CO 2 laser surgery between 1996 and 2014 was carried out. Lesions exhibiting lichenoid or proliferative verrucous features were identified from the patient database and their clinico-pathological features and outcome post-treatment determined at the study census date of 31 December 2014. 198 patients were identified: 118 OLL and 80 PVL, most frequently leukoplakia at ventro-lateral tongue and floor of mouth sites, equally distributed between males and females. Most exhibited dysplasia on incision biopsy (82% OLL; 85% PVL) and were treated by laser excision rather than ablation (88.1% OLL; 86.25% PVL). OLL were more common in younger patients (OLL 57.1yrs; PVL 62.25yrs; p=0.008) and more likely than PVL to present as erythroleukoplakia (OLL 15.3%; PVL 2.5%; p = 0.003). Whilst no significant difference was seen between OLL and PVL achieving disease free status (69.5% and 65%, respectively; p = 0.55), this was less than the overall PMD cohort (74.2%). MT was identified in 2 OLL (1.7%) and 2 PVL (2.5%) during follow-up. One-third of PMD cases showed features of OLL or PVL, probably representing a disease presentation continuum. Post-treatment disease free status was less common in OLL and PVL, although MT was infrequent. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  19. Angiographic evidence of proliferative retinopathy predicts neuropsychiatric morbidity in diabetic patients.

    Science.gov (United States)

    Serlin, Yonatan; Shafat, Tali; Levy, Jaime; Winter, Aaron; Shneck, Marina; Knyazer, Boris; Parmet, Yisrael; Shalev, Hadar; Ur, Ehud; Friedman, Alon

    2016-05-01

    Diabetic retinopathy (DR) is a common vasculopathy categorized as either non-proliferative (NPDR) or proliferative (PDR),characterized by dysfunctional blood-retinal barrier (BRB) and diagnosed using fluorescein angiography (FA). Since the BRB is similar in structure and function to the blood-brain barrier (BBB) and BBB dysfunction plays a key role in the pathogenesis of brain disorders, we hypothesized that PDR, the severe form of DR, is likely to mirror BBB damage and to predict a worse neuropsychiatric outcome. A retrospective cohort study was conducted among subjects with diabetes (N=2982) with FA-confirmed NPDR (N=2606) or PDR (N=376). Incidence and probability to develop brain pathologies and mortality were investigated in a 10-year follow-up study. We used Kaplan-Meier, Cox and logistic regression analyses to examine association between DR severity and neuropsychiatric morbidity adjusting for confounders. Patients with PDR had significantly higher rates of all-cause brain pathologies (P<0.001), specifically stroke (P=0.005), epilepsy (P=0.006) and psychosis (P=0.024), and a shorter time to develop any neuropsychiatric event (P<0.001) or death (P=0.014) compared to NPDR. Cox adjusted hazard ratio for developing all-cause brain impairments was higher for PDR (HR=1.37, 95% CI 1.16-1.61, P<0.001) which was an independent predictor for all-cause brain impairments (OR 1.30, 95% CI 1.04-1.64, P=0.022), epilepsy (OR 2.16, 95% CI 1.05-4.41, P=0.035) and mortality (HR=1.35, 95% CI 1.06-1.70, P=0.014). This is the first study to confirm that angiography-proven microvasculopathy identifies patients at high risk for neuropsychiatric morbidity and mortality. Copyright © 2016. Published by Elsevier Ltd.

  20. Elevated Subclinical Double-Stranded DNA Antibodies and Future Proliferative Lupus Nephritis

    Science.gov (United States)

    Lee, Jessica J.; Prince, Lisa K.; Baker, Thomas P.; Papadopoulos, Patricia; Edison, Jess; Abbott, Kevin C.

    2013-01-01

    Summary Background and objectives Elevated anti–double-stranded DNA (dsDNA) antibody and C-reactive protein are associated with proliferative lupus nephritis (PLN). Progression of quantitative anti-dsDNA antibody in patients with PLN has not been compared with that in patients with systemic lupus erythematosus (SLE) without LN before diagnosis. The temporal relationship between anti-dsDNA antibody and C-reactive protein elevation has also not been evaluated. Design, setting, participants, & measurements This case-control Department of Defense Serum Repository (established in 1985) study compared longitudinal prediagnostic quantitative anti-dsDNA antibody and C-reactive protein levels in 23 patients with biopsy-proven PLN (Walter Reed Army Medical Center, 1993–2009) with levels in 21 controls with SLE but without LN matched for patient age, sex, race, and age of serum sample. The oldest (median, 2601 days; 25%, 1245 days, 75%, 3075 days), the second to last (368; 212, 635 days), and the last (180; 135, 477 days) serum sample before diagnosis were analyzed. Results More patients with PLN had an elevated anti-dsDNA antibody level than did the matched controls at any point (78% versus 5%; P4 years (33% versus 0%; P=0.04) before diagnosis. A rate of increase >1 IU/ml per year (70% versus 0%; P<0.001) was most specific for PLN. The anti-dsDNA antibody levels increased before C-reactive protein did in most patients with an antecedent elevation (92% versus 8%; P<0.001). Conclusions Elevated anti-dsDNA antibody usually precedes both clinical and subclinical evidence of proliferative LN, which suggests direct pathogenicity. Absolute anti-dsDNA antibody level and rate of increase could better establish risk of future PLN in patients with SLE. PMID:23833315

  1. Cranberry and Grape Seed Extracts Inhibit the Proliferative Phenotype of Oral Squamous Cell Carcinomas

    Directory of Open Access Journals (Sweden)

    Kourt Chatelain

    2011-01-01

    Full Text Available Proanthocyanidins, compounds highly concentrated in dietary fruits, such as cranberries and grapes, demonstrate significant cancer prevention potential against many types of cancer. The objective of this study was to evaluate cranberry and grape seed extracts to quantitate and compare their anti-proliferative effects on the most common type of oral cancer, oral squamous cell carcinoma. Using two well-characterized oral squamous cell carcinoma cell lines, CAL27 and SCC25, assays were performed to evaluate the effects of cranberry and grape seed extract on phenotypic behaviors of these oral cancers. The proliferation of both oral cancer cell lines was significantly inhibited by the administration of cranberry and grape seed extracts, in a dose-dependent manner. In addition, key regulators of apoptosis, caspase-2 and caspase-8, were concomitantly up-regulated by these treatments. However, cranberry and grape seed extracts elicited differential effects on cell adhesion, cell morphology, and cell cycle regulatory pathways. This study represents one of the first comparative investigations of cranberry and grape seed extracts and their anti-proliferative effects on oral cancers. Previous findings using purified proanthocyanidin from grape seed extract demonstrated more prominent growth inhibition, as well as apoptosis-inducing, properties on CAL27 cells. These observations provide evidence that cranberry and grape seed extracts not only inhibit oral cancer proliferation but also that the mechanism of this inhibition may function by triggering key apoptotic regulators in these cell lines. This information will be of benefit to researchers interested in elucidating which dietary components are central to mechanisms involved in the mediation of oral carcinogenesis and progression.

  2. PREFACE: Strongly correlated electron systems Strongly correlated electron systems

    Science.gov (United States)

    Saxena, Siddharth S.; Littlewood, P. B.

    2012-07-01

    This special section is dedicated to the Strongly Correlated Electron Systems Conference (SCES) 2011, which was held from 29 August-3 September 2011, in Cambridge, UK. SCES'2011 is dedicated to 100 years of superconductivity and covers a range of topics in the area of strongly correlated systems. The correlated electronic and magnetic materials featured include f-electron based heavy fermion intermetallics and d-electron based transition metal compounds. The selected papers derived from invited presentations seek to deepen our understanding of the rich physical phenomena that arise from correlation effects. The focus is on quantum phase transitions, non-Fermi liquid phenomena, quantum magnetism, unconventional superconductivity and metal-insulator transitions. Both experimental and theoretical work is presented. Based on fundamental advances in the understanding of electronic materials, much of 20th century materials physics was driven by miniaturisation and integration in the electronics industry to the current generation of nanometre scale devices. The achievements of this industry have brought unprecedented advances to society and well-being, and no doubt there is much further to go—note that this progress is founded on investments and studies in the fundamentals of condensed matter physics from more than 50 years ago. Nevertheless, the defining challenges for the 21st century will lie in the discovery in science, and deployment through engineering, of technologies that can deliver the scale needed to have an impact on the sustainability agenda. Thus the big developments in nanotechnology may lie not in the pursuit of yet smaller transistors, but in the design of new structures that can revolutionise the performance of solar cells, batteries, fuel cells, light-weight structural materials, refrigeration, water purification, etc. The science presented in the papers of this special section also highlights the underlying interest in energy-dense materials, which

  3. High antibody-dependent cellular cytotoxicity responses are correlated with strong CD8 T cell viral suppressive activity but not with B57 status in HIV-1 elite controllers.

    Directory of Open Access Journals (Sweden)

    Olivier Lambotte

    Full Text Available The role of Antibody-dependent cellular cytotoxicity (ADCC responses in HIV-1 controllers is still unclear due to the heterogeneity of these patients. We analyzed 67 HIV-1 controllers and found significantly higher levels of ADCC antibodies in controllers versus viremic subjects (p = 0.017. Moreover, multivariate analysis revealed significantly higher ADCC titers in HLA B57- controllers compared to HLA-B57+ ones (p = 0.0086. These data suggest a role for ADCC in immune control of HIV, especially in HLA B57 negative controllers.

  4. Strongly correlated systems experimental techniques

    CERN Document Server

    Mancini, Ferdinando

    2015-01-01

    The continuous evolution and development of experimental techniques is at the basis of any fundamental achievement in modern physics. Strongly correlated systems (SCS), more than any other, need to be investigated through the greatest variety of experimental techniques in order to unveil and crosscheck the numerous and puzzling anomalous behaviors characterizing them. The study of SCS fostered the improvement of many old experimental techniques, but also the advent of many new ones just invented in order to analyze the complex behaviors of these systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. The volume presents a representative collection of the modern experimental techniques specifically tailored for the analysis of strongly correlated systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognize...

  5. Strongly Correlated Systems Theoretical Methods

    CERN Document Server

    Avella, Adolfo

    2012-01-01

    The volume presents, for the very first time, an exhaustive collection of those modern theoretical methods specifically tailored for the analysis of Strongly Correlated Systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and materials science, belong to this class of systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognized main contributors. The exposition has a clear pedagogical cut and fully reports on the most relevant case study where the specific technique showed to be very successful in describing and enlightening the puzzling physics of a particular strongly correlated system. The book is intended for advanced graduate students and post-docs in the field as textbook and/or main reference, but also for other researchers in the field who appreciates consulting a single, but comprehensive, source or wishes to get acquainted, in a as painless as po...

  6. Strongly correlated systems numerical methods

    CERN Document Server

    Mancini, Ferdinando

    2013-01-01

    This volume presents, for the very first time, an exhaustive collection of those modern numerical methods specifically tailored for the analysis of Strongly Correlated Systems. Many novel materials, with functional properties emerging from macroscopic quantum behaviors at the frontier of modern research in physics, chemistry and material science, belong to this class of systems. Any technique is presented in great detail by its own inventor or by one of the world-wide recognized main contributors. The exposition has a clear pedagogical cut and fully reports on the most relevant case study where the specific technique showed to be very successful in describing and enlightening the puzzling physics of a particular strongly correlated system. The book is intended for advanced graduate students and post-docs in the field as textbook and/or main reference, but also for other researchers in the field who appreciate consulting a single, but comprehensive, source or wishes to get acquainted, in a as painless as possi...

  7. Strongly nonlinear oscillators analytical solutions

    CERN Document Server

    Cveticanin, Livija

    2014-01-01

    This book provides the presentation of the motion of pure nonlinear oscillatory systems and various solution procedures which give the approximate solutions of the strong nonlinear oscillator equations. The book presents the original author’s method for the analytical solution procedure of the pure nonlinear oscillator system. After an introduction, the physical explanation of the pure nonlinearity and of the pure nonlinear oscillator is given. The analytical solution for free and forced vibrations of the one-degree-of-freedom strong nonlinear system with constant and time variable parameter is considered. Special attention is given to the one and two mass oscillatory systems with two-degrees-of-freedom. The criteria for the deterministic chaos in ideal and non-ideal pure nonlinear oscillators are derived analytically. The method for suppressing chaos is developed. Important problems are discussed in didactic exercises. The book is self-consistent and suitable as a textbook for students and also for profess...

  8. Flavour Democracy in Strong Unification

    CERN Document Server

    Abel, S A; Abel, Steven; King, Steven

    1998-01-01

    We show that the fermion mass spectrum may naturally be understood in terms of flavour democratic fixed points in supersymmetric theories which have a large domain of attraction in the presence of "strong unification". Our approach provides an alternative to the approximate Yukawa texture zeroes of the Froggatt-Nielsen mechanism. We discuss a particular model based on a broken gauged $SU(3)_L\\times SU(3)_R$ family symmetry which illustrates our approach.

  9. An inactivated hand-foot-and-mouth disease vaccine using the enterovirus 71 (C4a) strain isolated from a Korean patient induces a strong immunogenic response in mice.

    Science.gov (United States)

    In, Hyun Ju; Lim, Heeji; Lee, Jung-Ah; Kim, Hye Jin; Kim, Jin-Won; Hyeon, Ji-Yeon; Yeo, Sang-Gu; Lee, June-Woo; Yoo, Jung Sik; Choi, Young Ki; Lee, Sang-Won

    2017-01-01

    Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD) frequently occurring in children. HFMD induced by EV71 can cause serious health problems and has been reported worldwide, particularly in the Asia-Pacific region. In this study, we assessed the immunogenicity of a formalin-inactivated HFMD vaccine using an EV71 strain (FI-EV71 C4a) isolated from a Korean patient. The vaccine candidate was evaluated in mice to determine the vaccination doses and vaccine schedules. BALB/c mice were intramuscularly administered 5, 10, or 20 μg FI-EV71 vaccine, followed by a booster 2 weeks later. EV71-specific antibodies and neutralizing antibodies were induced and maintained until the end of the experimental period in all vaccinated groups. To determine the effectiveness of adjuvant for the EV71 vaccine, three adjuvants, i.e., aluminium hydroxide gel, monophosphoryl lipid A, and polyinosinic-polycytidylic acid, were administered separately with the FI-EV71 vaccine to mice via the intramuscular route. Mice administered the FI-EV71 vaccine formulated with all three adjuvants induced a significantly increased antibody response compared with that of the single adjuvant groups. The vaccinated group with triple adjuvants exhibited more rapid induction of EV71-specific and neutralizing antibodies than the other groups. These results suggested that the role of adjuvant in inactivated vaccine was important for eliciting effective immune responses against EV71. In conclusion, our results showed that FI-EV71 was a potential candidate vaccine for prevention of EV71 infection.

  10. Red wine polyphenolic compounds strongly inhibit pro-matrix metalloproteinase-2 expression and its activation in response to thrombin via direct inhibition of membrane type 1-matrix metalloproteinase in vascular smooth muscle cells.

    Science.gov (United States)

    Oak, Min-Ho; El Bedoui, Jasser; Anglard, Patrick; Schini-Kerth, Valérie B

    2004-09-28

    Regular consumption of moderate amounts of red wine is associated with a reduced risk of coronary disease. Matrix metalloproteinases (MMPs) that participate in extracellular matrix degradation have been involved in atherosclerotic plaque growth and instability. The present study examined whether red wine polyphenolic compounds (RWPCs) inhibit activation of MMP-2, a major gelatinase, in vascular smooth muscle cells (VSMCs). Expression of pro-MMP-2 was assessed by Western and Northern blot analyses; MMP-2 activity was assessed by zymography and cell invasion by a modified Boyden's chamber assay. High levels of pro-MMP-2 and low levels of MMP-2 activity were found in conditioned medium from unstimulated VSMCs. Thrombin induced cell-associated pro-MMP-2 protein expression and MMP-2 activity in conditioned medium of VSMCs. The stimulatory effect of thrombin on MMP-2 activation was prevented by RWPCs in a concentration-dependent and reversible manner. Thrombin markedly increased cell-associated membrane type 1 (MT1)-MMP activity, the physiological activator of pro-MMP-2, and this response was not affected by RWPCs. However, addition of RWPCs directly to MT1-MMP abolished its metalloproteinase activity in a reversible manner. Finally, matrix invasion of VSMCs was stimulated by thrombin, and this response was prevented by RWPCs as efficiently as a broad-spectrum MMP inhibitor. The present findings demonstrate that RWPCs effectively inhibit thrombin-induced matrix invasion of VSMCs, most likely by preventing the expression and activation of MMP-2 via direct inhibition of MT1-MMP activity. The inhibitory effect of RWPCs on the activation of pro-MMP-2 and matrix degradation might contribute to their beneficial effects on the cardiovascular system.

  11. Esculetin exerts anti-proliferative effects against non-small-cell lung carcinoma by suppressing specificity protein 1 in vitro.

    Science.gov (United States)

    Lee, Ra H; Jeon, Young-Joo; Cho, Jin H; Jang, Jeong-Yun; Kong, Il-Keun; Kim, Seok-Ho; Kim, MinSeok S; Chung, Hak-Jae; Oh, Keon B; Park, Seon-Min; Shin, Jae-Cheon; Seo, Jae-Min; Ko, Sungho; Shim, Jung-Hyun; Chae, Jung-Il

    2017-01-01

    Esculetin, a coumarin derivative, is a phenolic compound isolated from Artemisia capillaris, Citrus limonia, and Euphorbia lathyris. Although it has been reported to have anti-inflammatory, anti-oxidant, and anti-proliferative activities in several human cancers, its anti-proliferative activity against non-small-cell lung carcinoma (NSCLC) and the molecular mechanisms involved have not been adequately elucidated. In this study, we used two NSCLC cell lines (NCI-H358 and NCI-H1299) to investigate the anti-proliferative activity and apoptotic effect of esculetin. Our data showed that esculetin-treated cells exhibited reduced proliferation and apoptotic cell morphologies. Intriguingly, the transcription factor specificity protein 1 (Sp1) was significantly suppressed by esculetin in a dose- and time-dependent manner. Furthermore, the levels of p27 and p21, two key regulators of the cell cycle, were up-regulated by the esculetin-mediated down-regulation of Sp1; the level of a third cell-cycle regulator, survivin, was decreased, resulting in caspase-dependent apoptosis. Therefore, we conclude that esculetin could be a potent anti-proliferative agent in patients with NSCLC.

  12. Induction therapy with short-term high-dose intravenous cyclophosphamide followed by mycophenolate mofetil in proliferative lupus nephritis

    NARCIS (Netherlands)

    Boezerooij-Arends, S.; Berden, J. H. M.; Grootscholten, C.; Derksen, R. H. W. M.; Berger, S. P.; de Sevaux, R. G. L.; Voskuyl, A. E.; Bijl, M.

    2014-01-01

    Background: For decades, high-dose intravenous cyclophosphamide (ivCY) given for 24-30 months was regarded as the standard therapy for proliferative lupus nephritis, despite serious side effects. Our aim was to evaluate the effect of induction therapy with short-term high-dose ivCY followed by

  13. The Partisan Trajectory of the American Pro-Life Movement: How a Liberal Catholic Campaign Became a Conservative Evangelical Cause

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    Daniel K. Williams

    2015-04-01

    Full Text Available This article employs a historical analysis of the religious composition of the pro-life movement to explain why the partisan identity of the movement shifted from the left to the right between the late 1960s and the 1980s. Many of the Catholics who formed the first anti-abortion organizations in the late 1960s were liberal Democrats who viewed their campaign to save the unborn as a rights-based movement that was fully in keeping with the principles of New Deal and Great Society liberalism, but when evangelical Protestants joined the movement in the late 1970s, they reframed the pro-life cause as a politically conservative campaign linked not to the ideology of human rights but to the politics of moral order and “family values.” This article explains why the Catholic effort to build a pro-life coalition of liberal Democrats failed after Roe v. Wade, why evangelicals became interested in the antiabortion movement, and why the evangelicals succeeded in their effort to rebrand the pro-life campaign as a conservative cause.

  14. MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases

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    Kazuki Heishima

    2015-10-01

    Full Text Available Malignant endothelial proliferative diseases including human angiosarcoma (AS and canine hemangiosarcoma (HSA are serious diseases with a grave prognosis. Establishing liquid biopsy-based biomarkers for screening has definite clinical utility; however, plasma miRNAs up- or down-regulated in these sarcomas have been unclear. For identifying possible diagnostic plasma miRNAs for these sarcomas, we investigated whether plasma miR-214 and miR-126, which miRNAs play important roles in angiogenesis and tumorigenesis, were elevated in malignant endothelial proliferative diseases. For this investigation, human angiosarcoma and canine hemangiosarcoma cell lines and clinical plasma samples of canine hemangiosarcoma were examined by performing miRNA qRT-PCR. We report here that human angiosarcoma and canine hemangiosarcoma cell lines over-secreted miR-214 and miR-126 via microvesicles; in addition, their levels in the plasma samples from canines with hemangiosarcoma were increased. Moreover, the surgical resection of primary tumors decreased the levels of plasma miR-214 and miR-126. Our findings suggest that these malignant endothelial proliferative diseases over-secreted miR-214 and miR-126, thus suggesting that these miRNAs have potential as diagnostic biomarkers for malignant endothelial proliferative diseases in canine and possible in human angiosarcoma.

  15. Evaluation of viability and proliferative activity of human urothelial cells cultured onto xenogenic tissue-engineered extracellular matrices.

    LENUS (Irish Health Repository)

    Davis, Niall F

    2011-04-01

    To evaluate the viability and proliferative activity of human urothelial cells (HUCs) cultured on tissue-engineered extracellular matrix scaffolds and to assess the potential of extracellular matrixes to support the growth of HUCs in their expected in vivo urine environment.

  16. Nontreatment of Newborns with Severe Handicaps: A Survey of Attitudes of Pro-Life and Pro-Choice Advocates.

    Science.gov (United States)

    McDaniel, Elizabeth A.

    1989-01-01

    When presented with hypothetical cases of newborns with a range of correctable and uncorrectable medical conditions, 10 pro-life respondents recommended treatment in virtually all cases, while 10 pro-choice respondents were more likely to recommend withholding nourishment and food, recommend limited or no medical treatment, and change initial…

  17. MicroRNA-214 and MicroRNA-126 Are Potential Biomarkers for Malignant Endothelial Proliferative Diseases

    Science.gov (United States)

    Heishima, Kazuki; Mori, Takashi; Ichikawa, Yukie; Sakai, Hiroki; Kuranaga, Yuki; Nakagawa, Takayuki; Tanaka, Yuiko; Okamura, Yasuhiko; Masuzawa, Mikio; Sugito, Nobuhiko; Murakami, Mami; Yamada, Nami; Akao, Yukihiro; Maruo, Kohji

    2015-01-01

    Malignant endothelial proliferative diseases including human angiosarcoma (AS) and canine hemangiosarcoma (HSA) are serious diseases with a grave prognosis. Establishing liquid biopsy-based biomarkers for screening has definite clinical utility; however, plasma miRNAs up- or down-regulated in these sarcomas have been unclear. For identifying possible diagnostic plasma miRNAs for these sarcomas, we investigated whether plasma miR-214 and miR-126, which miRNAs play important roles in angiogenesis and tumorigenesis, were elevated in malignant endothelial proliferative diseases. For this investigation, human angiosarcoma and canine hemangiosarcoma cell lines and clinical plasma samples of canine hemangiosarcoma were examined by performing miRNA qRT-PCR. We report here that human angiosarcoma and canine hemangiosarcoma cell lines over-secreted miR-214 and miR-126 via microvesicles; in addition, their levels in the plasma samples from canines with hemangiosarcoma were increased. Moreover, the surgical resection of primary tumors decreased the levels of plasma miR-214 and miR-126. Our findings suggest that these malignant endothelial proliferative diseases over-secreted miR-214 and miR-126, thus suggesting that these miRNAs have potential as diagnostic biomarkers for malignant endothelial proliferative diseases in canine and possible in human angiosarcoma. PMID:26512652

  18. Effects of gamma-irradiation and granozan on the proliferative activity of plant tissue and its modification by peroxidase

    Energy Technology Data Exchange (ETDEWEB)

    Agabeili, R.A.; Melikova, N.K. (AN Azerbajdzhanskoj SSR, Baku. Biologicheskij Tsentr)

    1984-01-01

    Mitotic activity of meristem cells of seedlings of welsh onion Allium fistulesum L. under the effect of gamma-rays, granosane fungicide is studied as well as its modification by peroxidase. Antimitotic granosane activity is established, as well as peroxidase ability to stimulate proliferative ability of cells in the case of its inhibition by gamma-rays and granosane.

  19. Effect of Enterococcus faecium EF 55 on morphometry and proliferative activity of intestinal mucosa in broilers infected with Salmonella Enteritidis

    Directory of Open Access Journals (Sweden)

    Ševčíková Zuzana

    2016-09-01

    Full Text Available Introduction: The present study aimed to investigate the effect of Enterococcus faecium EF55 on chickens, as well as its influence on proliferative activity of epithelial intestinal cells after infection with Salmonella enterica serovar Enteritidis phage type 4 (SE PT4. Moreover, the length and area of duodenal and jejunal villi of the birds were examined.

  20. [Prader-Willi syndrome case with proliferative diabetic retinopathy in both eyes treated by early vitrectomy under local anesthesia].

    Science.gov (United States)

    Hori, Hideyuki; Sato, Yukihiro; Nakashima, Motohiro; Nakajima, Motohiro

    2012-02-01

    Although patients with Prader-Willi syndrome have a high rate of diabetes, to date, there have been only 4 reported cases (6 eyes) undergoing vitrectomy for proliferative diabetic retinopathy. Herein, we report a case of Prader-Willi syndrome with proliferative diabetic retinopathy that was treated by early vitrectomy OU under local anesthesia. A 30-year-old man was diagnosed as having Prader-Willi syndrome at the age of 2 years and diabetes at age 17. He was referred to our hospital as diabetic retinopathy had been detected in his first ophthalmological examination at age 29. Visual acuity was 0.6 bilaterally. Proliferative retinopathy, with cataract and macular edema, was identified in both eyes. Panretinal photocoagulation was performed on both eyes. However, proliferative membranes developed bilaterally, and vitreous hemorrhage occurred OS. Visual acuity decreased to 0.3 OU. The patient was hospitalized at our internal medicine department for blood glucose control. Subsequently, with an anesthesiologist on standby, a hypnotic sedative was injected intramuscularly, achieving retro-bulbar anesthesia. Combined cataract and vitreous surgery was performed on the left eye. One week later, a similar operation was performed on the right eye. The patient was discharged four days later. In the two years since these operation, visual acuity has been maintained at 0.8 OU. Patients with Prader-Willi syndrome should be examined for early detection and treatment of diabetic retinopathy.

  1. Strong piezoelectricity in bioinspired peptide nanotubes.

    Science.gov (United States)

    Kholkin, Andrei; Amdursky, Nadav; Bdikin, Igor; Gazit, Ehud; Rosenman, Gil

    2010-02-23

    We show anomalously strong shear piezoelectric activity in self-assembled diphenylalanine peptide nanotubes (PNTs), indicating electric polarization directed along the tube axis. Comparison with well-known piezoelectric LiNbO(3) and lateral signal calibration yields sufficiently high effective piezoelectric coefficient values of at least 60 pm/V (shear response for tubes of approximately 200 nm in diameter). PNTs demonstrate linear deformation without irreversible degradation in a broad range of driving voltages. The results open up a wide avenue for developing new generations of "green" piezoelectric materials and piezonanodevices based on bioactive tubular nanostructures potentially compatible with human tissue.

  2. A decrease in VEGF and inflammatory markers is associated with diabetic proliferative retinopathy.

    Science.gov (United States)

    Blum, Arnon; Socea, Dorina; Ben-Shushan, Rotem Shelly; Keinan-Boker, Lital; Naftali, Modi; Segol, Gila; Tamir, Snait

    2012-01-01

    Diabetic retinopathy is the most severe ocular complication of diabetes mellitus (DM), is associated with micro-vascular damage. The more advanced stage, proliferative diabetic retinopathy, has been linked to an increased risk of cardiovascular morbidity and mortality. Our hypothesis was that inflammatory and angiogenic markers will detect the different stages of type 2 diabetes, and may predict development of micro-vascular damage. Methods. Seventy three type II diabetic patients were randomly assigned to three groups (A - 25 patients {12 males], no diabetic retinopathy; B - 25 patients {19 males], non-proliferative retinopathy; and C - 23 patients {13 males], proliferative retinopathy),when they came for a routine follow-up visit in the ophthalmologic outpatient clinic. Twenty-three healthy subjects (14 males) served as controls. High-sensitivity C reactive protein (hs-CRP), soluble vascular cell adhesion molecule 1(sVCAM-1) and vascular endothelial growth factor (VEGF) were studied. Results. The duration of type II diabetes differed between group A (9 ± 6 years) and B (17 ± 9 years) patients (p = 0.001). No such difference was revealed between groups B and C (19 ± 6 years) (p = 0.30). A difference in hemoglobin A1C (HBgA1C) levels was detected between groups A (7.1 ± 2.7%) and B (8.5 ± 1.5%) (p = 0.02), but none was found between groups B and C (8.5 ± 1.6%) (p = 0.98). Only six patients (out of 23) used insulin treatment in group A, compared with 16 in group B (out of 25) and 17 in group C (out of 25) (p = 0.004). All three groups of diabetic patients were older (62.8 ± 10.8, 61.9 ± 9.4, 59.2 ± 10.3 years, respectively) than the controls(44.3 ± 11.6 years) (p≤0.001). Hs-CRP levels were higher in diabetic patients (4,391 ± 4,175, 4,109 ± 4,533, 3,005 ± 3,842 ng/mL, respectively) than in controls (1,659 ± 1,866 ng/mL); however, only the levels in patients of groups A (p

  3. Atoms in strong laser fields

    International Nuclear Information System (INIS)

    L'Huillier, A.

    2002-01-01

    When a high-power laser focuses into a gas of atoms, the electromagnetic field becomes of the same magnitude as the Coulomb field which binds a 1s electron in a hydrogen atom. 3 highly non-linear phenomena can happen: 1) ATI (above threshold ionization): electrons initially in the ground state absorb a large number of photons, many more than the minimum number required for ionization; 2) multiple ionization: many electrons can be emitted one at a time, in a sequential process, or simultaneously in a mechanism called direct or non-sequential; and 3) high order harmonic generation (HHG): efficient photon emission in the extreme ultraviolet range, in the form of high-order harmonics of the fundamental laser field can occur. The theoretical problem consists in solving the time dependent Schroedinger equation (TDSE) that describes the interaction of a many-electron atom with a laser field. A number of methods have been proposed to solve this problem in the case of a hydrogen atom or a single-active electron atom in a strong laser field. A large effort is presently being devoted to go beyond the single-active approximation. The understanding of the physics of the interaction between atoms and strong laser fields has been provided by a very simple model called ''simple man's theory''. A unified view of HHG, ATI, and non-sequential ionization, originating from the simple man's model and the strong field approximation, expressed in terms of electrons trajectories or quantum paths is slowly emerging. (A.C.)

  4. Strongly Interacting Light Dark Matter

    Directory of Open Access Journals (Sweden)

    Sebastian Bruggisser, Francesco Riva, Alfredo Urbano

    2017-09-01

    Full Text Available In the presence of approximate global symmetries that forbid relevant interactions, strongly coupled light Dark Matter (DM can appear weakly coupled at small energy and generate a sizable relic abundance. Fundamental principles like unitarity restrict these symmetries to a small class, where the leading interactions are captured by effective operators up to dimension-8. Chiral symmetry, spontaneously broken global symmetries and non-linearly realized supersymmetry are examples of this. Their DM candidates (composite fermions, pseudo Nambu-Goldstone Bosons and Goldstini are interesting targets for LHC missing-energy searches.

  5. Strongly interacting light dark matter

    International Nuclear Information System (INIS)

    Bruggisser, Sebastian; Riva, Francesco; Urbano, Alfredo

    2016-07-01

    In the presence of approximate global symmetries that forbid relevant interactions, strongly coupled light Dark Matter (DM) can appear weakly coupled at small-energy and generate a sizable relic abundance. Fundamental principles like unitarity restrict these symmetries to a small class, where the leading interactions are captured by effective operators up to dimension-8. Chiral symmetry, spontaneously broken global symmetries and non-linearly realized supersymmetry are examples of this. Their DM candidates (composite fermions, pseudo-Nambu-Goldstone Bosons and Goldstini) are interesting targets for LHC missing-energy searches.

  6. Rydberg atoms in strong fields

    International Nuclear Information System (INIS)

    Kleppner, D.; Tsimmerman, M.

    1985-01-01

    Experimental and theoretical achievements in studying Rydberg atoms in external fields are considered. Only static (or quasistatic) fields and ''one-electron'' atoms, i.e. atoms that are well described by one-electron states, are discussed. Mainly behaviour of alkali metal atoms in electric field is considered. The state of theoretical investigations for hydrogen atom in magnetic field is described, but experimental data for atoms of alkali metals are presented as an illustration. Results of the latest experimental and theoretical investigations into the structure of Rydberg atoms in strong fields are presented

  7. Scalar strong interaction hadron theory

    CERN Document Server

    Hoh, Fang Chao

    2015-01-01

    The scalar strong interaction hadron theory, SSI, is a first principles' and nonlocal theory at quantum mechanical level that provides an alternative to low energy QCD and Higgs related part of the standard model. The quark-quark interaction is scalar rather than color-vectorial. A set of equations of motion for mesons and another set for baryons have been constructed. This book provides an account of the present state of a theory supposedly still at its early stage of development. This work will facilitate researchers interested in entering into this field and serve as a basis for possible future development of this theory.

  8. Strong Plate, Weak Slab Dichotomy

    Science.gov (United States)

    Petersen, R. I.; Stegman, D. R.; Tackley, P.

    2015-12-01

    Models of mantle convection on Earth produce styles of convection that are not observed on Earth.Moreover non-Earth-like modes, such as two-sided downwellings, are the de facto mode of convection in such models.To recreate Earth style subduction, i.e. one-sided asymmetric recycling of the lithosphere, proper treatment of the plates and plate interface are required. Previous work has identified several model features that promote subduction. A free surface or pseudo-free surface and a layer of material with a relatively low strength material (weak crust) allow downgoing plates to bend and slide past overriding without creating undue stress at the plate interface. (Crameri, et al. 2012, GRL)A low viscosity mantle wedge, possibly a result of slab dehydration, decouples the plates in the system. (Gerya et al. 2007, Geo)Plates must be composed of material which, in the case of the overriding plate, are is strong enough to resist bending stresses imposed by the subducting plate and yet, as in the case of the subducting plate, be weak enough to bend and subduct when pulled by the already subducted slab. (Petersen et al. 2015, PEPI) Though strong surface plates are required for subduction such plates may present a problem when they encounter the lower mantle.As the subducting slab approaches the higher viscosity, lower mantle stresses are imposed on the tip.Strong slabs transmit this stress to the surface.There the stress field at the plate interface is modified and potentially modifies the style of convection. In addition to modifying the stress at the plate interface, the strength of the slab affects the morphology of the slab at the base of the upper mantle. (Stegman, et al 2010, Tectonophysics)Slabs that maintain a sufficient portion of their strength after being bent require high stresses to unbend or otherwise change their shape.On the other hand slabs that are weakened though the bending process are more amenable to changes in morphology. We present the results of

  9. Oral squamous cell carcinoma proliferative phenotype is modulated by proanthocyanidins: a potential prevention and treatment alternative for oral cancer

    Directory of Open Access Journals (Sweden)

    Swapp Aaron

    2007-06-01

    Full Text Available Abstract Background Despite the recently reported drop in the overall death rate from cancer, the estimated survival rate and number of deaths from oral cancer remain virtually unchanged. Early detection efforts, in combination with strategies for prevention and risk-reduction, have the potential to dramatically improve clinical outcomes. The identification of non-toxic, effective treatments, including complementary and alternative therapies, is critical if the survival rate is to be improved. Epidemiologic studies have suggested a protective effect from certain plant-derived foods and extracts; however, it has been difficult to isolate and identify the compounds most responsible for these observations. The primary purpose of this study was to investigate the response of human oral squamous cell carcinoma (OSCC to proanthocyanidin (PAC, a plant-derived compound that may inhibit the progression of several other cancers. Methods Using a series of in vitro assays, we sought to quantify the effects of PAC on OSCC, cervical carcinoma, and non-cancerous cell lines, specifically the effects of PAC on cell proliferation. Recent data suggest that infection with the human papillomavirus (HPV may also modulate the proliferative potential of OSCC; therefore, we also measured the effects of PAC administration on HPV-transfected OSCC proliferation. Results Our results demonstrated that PAC administration was sufficient to significantly suppress cellular proliferation of OSCC in a dose-dependent manner. In addition, the increased proliferation of OSCC after transfection with HPV 16 was reduced by the administration of PAC, as was the proliferation of the cervical cancer and non-cancerous cell lines tested. Our results also provide preliminary evidence that PAC administration may induce apoptosis in cervical and oral cancer cell lines, while acting merely to suppress proliferation of the normal cell line control. Conclusion These results signify that PAC may be

  10. Poly(I:C) adjuvant strongly enhances parasite-inhibitory antibodies and Th1 response against Plasmodium falciparum merozoite surface protein-1 (42-kDa fragment) in BALB/c mice.

    Science.gov (United States)

    Mehrizi, Akram Abouie; Rezvani, Niloufar; Zakeri, Sedigheh; Gholami, Atefeh; Babaeekhou, Laleh

    2018-04-01

    Malaria vaccine development has been confronted with various challenges such as poor immunogenicity of malaria vaccine candidate antigens, which is considered as the main challenge. However, this problem can be managed using appropriate formulations of antigens and adjuvants. Poly(I:C) is a potent Th1 inducer and a human compatible adjuvant capable of stimulating both B- and T-cell immunity. Plasmodium falciparum merozoite surface protein 1 42 (PfMSP-1 42 ) is a promising vaccine candidate for blood stage of malaria that has faced several difficulties in clinical trials, mainly due to improper adjuvants. Therefore, in the current study, poly(I:C), as a potent Th1 inducer adjuvant, was evaluated to improve the immunogenicity of recombinant PfMSP-1 42 , when compared to CFA/IFA, as reference adjuvant. Poly(I:C) produced high level and titers of anti-PfMSP-1 42 IgG antibodies in which was comparable to CFA/IFA adjuvant. In addition, PfMSP-1 42 formulated with poly(I:C) elicited a higher ratio of IFN-γ/IL-4 (23.9) and IgG2a/IgG1 (3.77) with more persistent, higher avidity, and titer of IgG2a relative to CFA/IFA, indicating a potent Th1 immune response. Poly(I:C) could also help to induce anti-PfMSP-1 42 antibodies with higher growth-inhibitory activity than CFA/IFA. Altogether, the results of the current study demonstrated that poly(I:C) is a potent adjuvant that can be appropriate for being used in PfMSP-1 42 -based vaccine formulations.

  11. EDITORIAL: Strongly correlated electron systems Strongly correlated electron systems

    Science.gov (United States)

    Ronning, Filip; Batista, Cristian

    2011-03-01

    Strongly correlated electrons is an exciting and diverse field in condensed matter physics. This special issue aims to capture some of that excitement and recent developments in the field. Given that this issue was inspired by the 2010 International Conference on Strongly Correlated Electron Systems (SCES 2010), we briefly give some history in order to place this issue in context. The 2010 International Conference on Strongly Correlated Electron Systems was held in Santa Fe, New Mexico, a reunion of sorts from the 1989 International Conference on the Physics of Highly Correlated Electron Systems that also convened in Santa Fe. SCES 2010—co-chaired by John Sarrao and Joe Thompson—followed the tradition of earlier conferences, in this century, hosted by Buzios (2008), Houston (2007), Vienna (2005), Karlsruhe (2004), Krakow (2002) and Ann Arbor (2001). Every three years since 1997, SCES has joined the International Conference on Magnetism (ICM), held in Recife (2000), Rome (2003), Kyoto (2006) and Karlsruhe (2009). Like its predecessors, SCES 2010 topics included strongly correlated f- and d-electron systems, heavy-fermion behaviors, quantum-phase transitions, non-Fermi liquid phenomena, unconventional superconductivity, and emergent states that arise from electronic correlations. Recent developments from studies of quantum magnetism and cold atoms complemented the traditional subjects and were included in SCES 2010. 2010 celebrated the 400th anniversary of Santa Fe as well as the birth of astronomy. So what's the connection to SCES? The Dutch invention of the first practical telescope and its use by Galileo in 1610 and subsequent years overturned dogma that the sun revolved about the earth. This revolutionary, and at the time heretical, conclusion required innovative combinations of new instrumentation, observation and mathematics. These same combinations are just as important 400 years later and are the foundation of scientific discoveries that were discussed

  12. Proliferative vitreo-retinal disorders: experimental models in vivo and in vitro.

    Science.gov (United States)

    Martini, B

    1992-01-01

    The aim of the present thesis was to develop, refine, and assess experimental models for the study of proliferative vitreo-retinal disorders. An intravitreal injection of a colloidal solution of microparticles was used in the primate eye to produce pathologic changes including intraocular cell invasion, cell proliferation, neovascularization, collagen synthesis, and tractional retinal detachment. In a separate primate model for laser-induced subretinal neovascularization, the origin and the occurrence of macrophages was evaluated. Examinations were performed using ophthalmoscopy, slit-lamp microscopy, light microscopy, and transmission electron microscopy. Cell cultures were employed to study the effects of vitreous humor and macrophages on the proliferation of cultured retinal pigment epithelial (RPE) cells and cultured fibroblasts using a Coulter counter. Morphologic changes were documented by phase micrography. A quantitative estimation of the extracellular matrix deposition of fibrous proteins by macrophage-modulated RPE cells as well as by vitreous-modulated RPE cells was done using enzymatic digestion and radioactive labeling techniques. A qualitative analysis of the types of collagen that was deposited in the extracellular matrices by vitreous modulated cultures was also made using indirect immunofluorescence. Using a newly developed RPE cell specific monoclonal antibody, the avidin-biotin-peroxidase labeling technique was finally employed to test the phenotypic epitope expression of macrophage-modulated and non-modulated RPE cells. A new experimental in vivo model for pathologic changes that characterize proliferative vitreo-retinal disorders was developed in the primate eye. In the model for laser-induced subretinal neovascularization, macrophages were shown to be principally recruited from the systemic circulation. Using cell cultures, it was found that both macrophage-conditioned medium and vitreous humor, separately or combined, exert mitogenic effects

  13. Clinical and experimental study on angiopoietin-like protein 8 associated with proliferative diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Chang-Xia Dong

    2017-12-01

    Full Text Available AIM: To confirm the role of angiopoietin-like protein 8 (Angptl 8 in proliferative diabetic retinopathy (PDR. METHODS: The sera and aqueous humor of 10 PDR patients and 10 non-diabetic retinopathy (NDR patients (idiopathic macular hole patients were collected and the expression of Angptl 8 was detected by enzyme linked immune-sorbent assay (ELISA. Experimental diabetes mice model was induced with streptozotocin. The expression of glycosylated hemoglobin and Angptl 8 in sera was detected. Recombinant Angptl 8 was re-infused into wild type (WT diabetic mice and spatial frequency threshold and contrast sensitivity were measured. In vitro retinal pigment epithelium (RPE were stimulated by recombinant Angptl 8 for 24h. MMT assay were used to detect cell proliferation. At the same time, qRT-PCR and Western blot was used to measure the expression of proliferation-related factors in