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Sample records for cells persist years

  1. Memory T cell responses targeting the SARS coronavirus persist up to 11 years post-infection.

    Science.gov (United States)

    Ng, Oi-Wing; Chia, Adeline; Tan, Anthony T; Jadi, Ramesh S; Leong, Hoe Nam; Bertoletti, Antonio; Tan, Yee-Joo

    2016-04-12

    Severe acute respiratory syndrome (SARS) is a highly contagious infectious disease which first emerged in late 2002, caused by a then novel human coronavirus, SARS coronavirus (SARS-CoV). The virus is believed to have originated from bats and transmitted to human through intermediate animals such as civet cats. The re-emergence of SARS-CoV remains a valid concern due to the continual persistence of zoonotic SARS-CoVs and SARS-like CoVs (SL-CoVs) in bat reservoirs. In this study, the screening for the presence of SARS-specific T cells in a cohort of three SARS-recovered individuals at 9 and 11 years post-infection was carried out, and all memory T cell responses detected target the SARS-CoV structural proteins. Two CD8(+) T cell responses targeting the SARS-CoV membrane (M) and nucleocapsid (N) proteins were characterized by determining their HLA restriction and minimal T cell epitope regions. Furthermore, these responses were found to persist up to 11 years post-infection. An absence of cross-reactivity of these CD8(+) T cell responses against the newly-emerged Middle East respiratory syndrome coronavirus (MERS-CoV) was also demonstrated. The knowledge of the persistence of SARS-specific celullar immunity targeting the viral structural proteins in SARS-recovered individuals is important in the design and development of SARS vaccines, which are currently unavailable. PMID:26954467

  2. Analysis of 30 patients with persistent or recurrent squamous cell carcinoma of the cervix within one year after concurrent chemoradiotherapy

    International Nuclear Information System (INIS)

    To investigate the recurrence sites, risk factors, and prognosis of patients with persistent or recurrent squamous cell carcinoma (SCC) of the cervix within one year after undergoing concurrent chemoradiotherapy (CCRT). Clinical data of 30 patients with persistent or recurrent SCC of the cervix within one year after CCRT between July 2006 and July 2011 were analyzed retrospectively. These data were compared with those of 35 SCC cases with no signs of recurrence after complete remission. These 35 patients were treated during the same period (between 2006 and 2011) and selected randomly. Among these 30 patients, 25 exhibited distant metastases of which 14 were observed within 6 months after CCRT. Univariate analysis showed higher incidence of pelvic or para-aortic lymphadenectasis and SCC-ag >10 ng/mL in the group with persistent or recurrent disease before treatment (P<0.01). Multivariate analysis by logistic regression revealed that the pre-therapeutic pelvic or para-aortic lymph node enlargement and SCC-ag >10 ng/mL were the independent risk factors. Palliative chemotherapy was the main treatment option for patients with persistent or recurrent disease. The 2-year survival rate was 21.7%, and the median survival time was 17 months. Patients with persistent or recurrent SCC of the cervix after CCRT exhibited a high rate of distant metastasis with poor prognosis. The pre-therapeutic pelvic or para-aortic lymph node enlargement and SCC-ag >10 ng/mL were identified as the independent risk factors for persistent or recurrent SCC within 1 year after CCRT

  3. Persistence of T-cell immune response induced by two acellular pertussis vaccines in children five years after primary vaccination.

    Science.gov (United States)

    Palazzo, Raffaella; Carollo, Maria; Bianco, Manuela; Fedele, Giorgio; Schiavoni, Ilaria; Pandolfi, Elisabetta; Villani, Alberto; Tozzi, Alberto E; Mascart, Françoise; Ausiello, Clara M

    2016-01-01

    The resurgence of pertussis suggests the need for greater efforts to understand the long-lasting protective responses induced by vaccination. In this paper we dissect the persistence of T memory responses induced by primary vaccination with two different acellular pertussis (aP) vaccines, hexavalent Hexavac® vaccine (Hexavac) (Sanofi Pasteur MSD) and Infanrix hexa® (Infanrix) (Glaxo-SmithKline Biologicals). We evaluated magnitude and duration of T-cell responses to pertussis toxin (PT) by measuring T-cell proliferation, cytokines (IL-2 and IFNγ) production and memory subsets in two groups of children 5 years after primary vaccination. Some of the enrolled children received only primary vaccination, while others had the pre-school boost dose. Positive T-cell responses to PT were detected in 36% of children. Percentage of responsive children, T-cell proliferation and CD4IL-2+ cells were significantly higher in the children primed with Hexavac than in those who received Infanrix vaccine. No major effects of the boost on PT-specific proliferation were observed. Overall, our data documented a persistence of T-cell memory against PT in a minor fraction of children 5 years after primary vaccination. The different responses induced by Hexavac and Infanrix vaccine could rely on differences in PT inactivation process or excipients/adjuvants formulations.

  4. Protective Antigen-Specific Memory B Cells Persist Years after Anthrax Vaccination and Correlate with Humoral Immunity

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    Lori Garman

    2014-08-01

    Full Text Available Anthrax Vaccine Adsorbed (AVA generates short-lived protective antigen (PA specific IgG that correlates with in vitro toxin neutralization and protection from Bacillus anthracis challenge. Animal studies suggest that when PA-specific IgG has waned, survival after spore challenge correlates with an activation of PA-specific memory B cells. Here, we characterize the quantity and the longevity of AVA-induced memory B cell responses in humans. Peripheral blood mononuclear cells (PBMCs from individuals vaccinated ≥3 times with AVA (n = 50 were collected early (3–6 months, n = 27 or late after their last vaccination (2–5 years, n = 23, pan-stimulated, and assayed by ELISPOT for total and PA-specific memory B cells differentiated into antibody secreting cells (ASCs. PA-specific ASC percentages ranged from 0.02% to 6.25% (median: 1.57% and did not differ between early and late post-vaccination individuals. PA-specific ASC percentages correlated with plasma PA-specific IgG (r = 0.42, p = 0.03 and toxin neutralization (r = 0.52, p = 0.003 early post vaccination. PA-specific ASC percentages correlated with supernatant anti-PA both early (r = 0.60, p = 0.001 and late post vaccination (r = 0.71, p < 0.0001. These data suggest PA-specific memory B cell responses are long-lived and can be estimated after recent vaccination by the magnitude and neutralization capacity of the humoral response.

  5. Severe acute respiratory syndrome coronavirus persistence in Vero cells

    Institute of Scientific and Technical Information of China (English)

    Gustavo Palacios; Omar Jabado; Neil Renwick; Thomas Briese; W. Ian Lipkin

    2005-01-01

    Background Several coronaviruses establish persistent infections in vitro and in vivo, however it is unknown whether persistence is a feature of the severe acute respiratory syndorme coronavirus (SARS-CoV) life cycle. This study was conducted to investigate viral persistence.Methods We inoculated confluent monolayers of Vero cells with SARS-CoV at a multiplicity of infection of 0.1 TCID50 and passaged the remaining cells every 4 to 8 days for a total of 11 passages. Virus was titrated at each passage by limited dilution assay and nucleocapsid antigen was detected by Western blot and immunofluoresence assays. The presence of viral particles in passage 11 cells was assessed by electron microscopy. Changes in viral genomic sequences during persistent infection were examined by DNA sequencing. Results Cytopathic effect was extensive after initial inoculation but diminished with serial passages. Infectious virus was detected after each passage and viral growth curves were identical for parental virus stock and virus obtained from passage 11 cells. Nucleocapsid antigen was detected in the majority of cells after initial inoculation but in only 10%-40% of cells at passages 2-11. Electron microscopy confirmed the presence of viral particles in passage 11 cells. Sequence analysis at passage 11 revealed fixed mutations in the spike (S) gene and ORFs 7a-8b but not in the nucleocapsid (N) gene. Conclusions SARS-CoV can establish a persistent infection in vitro. The mechanism for viral persistence is consistent with the formation of a carrier culture whereby a limited number of cells are infected with each round of virus replication and release. Persistence is associated with selected mutations in the SARS-CoV genome. This model may provide insight into SARS-related lung pathology and mechanisms by which humans and animals can serve as reservoirs for infection.

  6. Asymmetric cell division: a persistent issue?

    OpenAIRE

    Aakre, Christopher D.; Laub, Michael T.

    2012-01-01

    Heterogeneity within a clonal population of cells can increase survival in the face of environmental stress. In a recent issue of Science, Aldridge et al. (2012) demonstrate that cell division in mycobacteria is asymmetric, producing daughter cells that differ in size, growth rate, and susceptibility to antibiotics.

  7. Persistence Factors Associated with First-Year Engineering Technology Learners

    Science.gov (United States)

    Christe, Barbara

    2015-01-01

    Engineering technology learners are understudied group that comprise the "T" of the science, technology, engineering, and mathematics disciplines. Attrition from engineering technology majors is a profound and complex challenge, as substantially less than half of students who begin an engineering technology major persist through the…

  8. DNA-crosslinker cisplatin eradicates bacterial persister cells.

    Science.gov (United States)

    Chowdhury, Nityananda; Wood, Thammajun L; Martínez-Vázquez, Mariano; García-Contreras, Rodolfo; Wood, Thomas K

    2016-09-01

    For all bacteria, nearly every antimicrobial fails since a subpopulation of the bacteria enter a dormant state known as persistence, in which the antimicrobials are rendered ineffective due to the lack of metabolism. This tolerance to antibiotics makes microbial infections the leading cause of death worldwide and makes treating chronic infections, including those of wounds problematic. Here, we show that the FDA-approved anti-cancer drug cisplatin [cis-diamminodichloroplatinum(II)], which mainly forms intra-strand DNA crosslinks, eradicates Escherichia coli K-12 persister cells through a growth-independent mechanism. Additionally, cisplatin is more effective at killing Pseudomonas aeruginosa persister cells than mitomycin C, which forms inter-strand DNA crosslinks, and cisplatin eradicates the persister cells of several pathogens including enterohemorrhagic E. coli, Staphylococcus aureus, and P. aeruginosa. Cisplatin was also highly effective against clinical isolates of S. aureus and P. aeruginosa. Therefore, cisplatin has broad spectrum activity against persister cells. Biotechnol. Bioeng. 2016;113: 1984-1992. © 2016 Wiley Periodicals, Inc. PMID:26914280

  9. Interaction of Staphylococcus aureus persister cells with the host when in a persister state and following awakening

    Science.gov (United States)

    Mina, Elin G.; Marques, Cláudia N. H.

    2016-01-01

    Persister cells, a tolerant cell sub-population, are commonly associated with chronic and recurrent infections. However, little is known about their ability to actually initiate or establish an infection, become virulent and cause pathogenicity within a host. Here we investigated whether Staphylococcus aureus persister cells initiate an infection and are recognized by macrophages, while in a persister cell status, and upon awakening due to exposure to cis-2-decenoic acid (cis-DA). Our results show that S. aureus persister cells are not able to initiate infections in A. thaliana and present significantly reduced virulence towards C. elegans compared to total populations. In contrast, awakened S. aureus persister cells are able to initiate infections in A. thaliana and in C. elegans albeit, with lower mortality than total population. Furthermore, exposure of S. aureus persister cells to cis-DA led to a loss of tolerance to ciprofloxacin, and an increase of the bacterial fluorescence to levels found in total population. In addition, macrophage engulfment of persister cells was significantly lower than engulfment of total population, both before and following awakening. Overall our findings indicate that upon awakening of a persister population the cells regain their ability to infect hosts despite the absence of an increased immune response. PMID:27506163

  10. Ferritinophagy drives uropathogenic Escherichia coli persistence in bladder epithelial cells.

    Science.gov (United States)

    Bauckman, Kyle A; Mysorekar, Indira U

    2016-05-01

    Autophagy is a cellular recycling pathway, which in many cases, protects host cells from infections by degrading pathogens. However, uropathogenic Escherichia coli (UPEC), the predominant cause of urinary tract infections (UTIs), persist within the urinary tract epithelium (urothelium) by forming reservoirs within autophagosomes. Iron is a critical nutrient for both host and pathogen, and regulation of iron availability is a key host defense against pathogens. Iron homeostasis depends on the shuttling of iron-bound ferritin to the lysosome for recycling, a process termed ferritinophagy (a form of selective autophagy). Here, we demonstrate for the first time that UPEC shuttles with ferritin-bound iron into the autophagosomal and lysosomal compartments within the urothelium. Iron overload in urothelial cells induces ferritinophagy in an NCOA4-dependent manner causing increased iron availability for UPEC, triggering bacterial overproliferation and host cell death. Addition of even moderate levels of iron is sufficient to increase and prolong bacterial burden. Furthermore, we show that lysosomal damage due to iron overload is the specific mechanism causing host cell death. Significantly, we demonstrate that host cell death and bacterial burden can be reversed by inhibition of autophagy or inhibition of iron-regulatory proteins, or chelation of iron. Together, our findings suggest that UPEC persist in host cells by taking advantage of ferritinophagy. Thus, modulation of iron levels in the bladder may provide a therapeutic avenue to controlling UPEC persistence, epithelial cell death, and recurrent UTIs.

  11. Persistent inflammation and endothelial activation in HIV-1 infected patients after 12 years of antiretroviral therapy.

    Directory of Open Access Journals (Sweden)

    Frederikke F Rönsholt

    Full Text Available OBJECTIVE: The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART. METHODS: Inflammation and endothelial activation were assessed by measuring levels of immunoglobulins, β2-microglobulin, interleukin (IL 8, tumor necrosis factor α (TNFα, vascular cell adhesion molecule-1 (sVCAM-1, intercellular adhesion molecule-1 (sICAM-1, sE-Selectin, and sP-Selectin. RESULTS: HIV infected patients had higher levels of β2-microglobulin, IL-8, TNFα, and sICAM-1 than uninfected controls, and HIV infected patients lacked correlation between platelet counts and sP-Selectin levels found in uninfected controls. CONCLUSION: Discrete signs of systemic and vascular inflammation persist even after very long term cART.

  12. A Study of Single Mothers' Experience of Persistence at a Four-Year Public University

    Science.gov (United States)

    Hayes Nelson, Geraldine

    2009-01-01

    The overall purpose of this study was to uncover and describe the barriers that low-income, single mothers between the ages of 17-24 experience and the strategies they adopt in their efforts to persist through year one to year three of college at a four-year public university. Adult education scholarship has shed light on the obstacles to college…

  13. Persistent, triple-virus co-infections in mosquito cells

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    Malasit Prida

    2010-01-01

    Full Text Available Abstract Background It is known that insects and crustaceans can carry simultaneous, active infections of two or more viruses without showing signs of disease, but it was not clear whether co-infecting viruses occupied the same cells or different cells in common target tissues. Our previous work showed that successive challenge of mosquito cell cultures followed by serial, split-passage resulted in stabilized cultures with 100% of the cells co-infected with Dengue virus (DEN and an insect parvovirus (densovirus (DNV. By addition of Japanese encephalitis virus (JE, we tested our hypothesis that stable, persistent, triple-virus co-infections could be obtained by the same process. Results Using immunocytochemistry by confocal microscopy, we found that JE super-challenge of cells dually infected with DEN and DNV resulted in stable cultures without signs of cytopathology, and with 99% of the cells producing antigens of the 3 viruses. Location of antigens for all 3 viruses in the triple co-infections was dominant in the cell nuclei. Except for DNV, this differed from the distribution in cells persistently infected with the individual viruses or co-infected with DNV and DEN. The dependence of viral antigen distribution on single infection or co-infection status suggested that host cells underwent an adaptive process to accommodate 2 or more viruses. Conclusions Individual mosquito cells can accommodate at least 3 viruses simultaneously in an adaptive manner. The phenomenon provides an opportunity for genetic exchange between diverse viruses and it may have important medical and veterinary implications for arboviruses.

  14. Effect of surface treatments of titanium on amphotericin B-treated Candida albicans persister cells

    OpenAIRE

    Tsang, CSP; Tang, DYK

    2010-01-01

    Although persister cells in Candida albicans biofilm may contribute to its increased resistance to antifungal drugs, little information is available on the formation of Candida persister cells on titanium surfaces. The effect of different surface treatments of Ti on persister cells was determined in the present study. Titanium discs were surface-treated by three different methods (Group A - polishing, Group B - sandblasting followed by acid-etching, and Group C - sandblasting alone). Persiste...

  15. Smoking increases oral HPV persistence among men: 7-year follow-up study.

    Science.gov (United States)

    Kero, K; Rautava, J; Syrjänen, K; Willberg, J; Grenman, S; Syrjänen, S

    2014-01-01

    Persistent high-risk human papillomavirus (HR-HPV) infection is the key event in the progression of HPV lesions, and more data are urgently needed on asymptomatic oral HPV infections in men. Asymptomatic fathers-to-be (n = 131, mean age 28.9 years) were enrolled in the cohort, sampled by serial oral scrapings at baseline and at 2-month, 6-month, 12-month, 24-month, 36-month, and 7-year follow-up visits to accomplish persistent and cleared HPV infections. HPV genotyping was performed using nested PCR and Multimetrix® assay. Covariates of persistent and cleared oral HPV infections were analysed using generalised estimating equation (GEE) and Poisson regression. Altogether, 17 HPV genotypes were detected in male oral mucosa point prevalence, varying from 15.1 % to 31.1 %. Genotype-specific HPV persistence was detected in 18/129 men the mean persistence time ranging from 6.0 to 30.7 months. History of genital warts decreased (p = 0.0001; OR = 0.41, 95 % CI 0.33-0.51) and smoking increased (p = 0.033, OR = 1.92, 95 % CI 1.05-3.50) the risk of persistent species 7/9 HPV infections. Of the 74 HPV-positive men, 71.6 % cleared their infection actuarial and crude clearance times, varying between 1.4 and 79.6 months. No independent predictors were identified for species 7/9 clearance. At the last follow-up-visit, 50.1 % of the fathers had oral mucosal changes, correlating only with smoking (p = 0.046). To conclude, most of the persisting oral infections in males were caused by HPV16. Smoking increased while previous genital warts decreased oral HR-HPV persistence. No predictors of HR-HPV clearance were disclosed.

  16. Persistent photovoltage in methylammonium lead iodide perovskite solar cells

    Directory of Open Access Journals (Sweden)

    A. Baumann

    2014-08-01

    Full Text Available We herein perform open circuit voltage decay (OCVD measurements on methylammonium lead iodide (CH3NH3PbI3 perovskite solar cells to increase the understanding of the charge carrier recombination dynamics in this emerging technology. Optically pulsed OCVD measurements are conducted on CH3NH3PbI3 solar cells and compared to results from another type of thin-film photovoltaics, namely, the two reference polymer–fullerene bulk heterojunction solar cell devices based on P3HT:PC60BM and PTB7:PC70BM blends. We observe two very different time domains of the voltage transient in the perovskite solar cell with a first drop on a short time scale that is similar to the decay in the studied organic solar cells. However, 65%–70% of the maximum photovoltage persists on much longer timescales in the perovskite solar cell than in the organic devices. In addition, we find that the recombination dynamics in all time regimes are dependent on the starting illumination intensity, which is also not observed in the organic devices. We then discuss the potential origins of these unique behaviors.

  17. Spatial but not verbal cognitive deficits at age 3 years in persistently antisocial individuals.

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    Raine, Adrian; Yaralian, Pauline S; Reynolds, Chandra; Venables, Peter H; Mednick, Sarnoff A

    2002-01-01

    Previous studies have repeatedly shown verbal intelligence deficits in adolescent antisocial individuals, but it is not known whether these deficits are in place prior to kindergarten or, alternatively, whether they are acquired throughout childhood. This study assesses whether cognitive deficits occur as early as age 3 years and whether they are specific to persistently antisocial individuals. Verbal and spatial abilities were assessed at ages 3 and 11 years in 330 male and female children, while antisocial behavior was assessed at ages 8 and 17 years. Persistently antisocial individuals (N = 47) had spatial deficits in the absence of verbal deficits at age 3 years compared to comparisons (N = 133), and also spatial and verbal deficits at age 11 years. Age 3 spatial deficits were independent of social adversity, early hyperactivity, poor test motivation, poor test comprehension, and social discomfort during testing, and they were found in females as well as males. Findings suggest that early spatial deficits contribute to persistent antisocial behavior whereas verbal deficits are developmentally acquired. An early-starter model is proposed whereby early spatial impairments interfere with early bonding and attachment, reflect disrupted right hemisphere affect regulation and expression, and predispose to later persistent antisocial behavior.

  18. Late-onset persistent retinal microvascular changes after bone marrow transplantation: 3-year follow-up

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    Muccioli Cristina

    2002-01-01

    Full Text Available Purpose: To describe a case of persistent retinopathy after bone marrow transplantation in the absence of radiation therapy. Methods: Case Report. Results: A 42 year-old man developed bilateral visual loss 15 months after receiving a bone marrow transplant for acute leukemia. The patient was treated with a high dose of cyclosporin A and oral corticosteroids. No radiation therapy was given. Late-onset, multiple, bilateral cotton-wool spots developed 15 months after the bone marrow transplantation and still persist. After three years other cotton-wool spots arose in the absence of any immunosuppressive therapy. Conclusions: Bone marrow transplantation microvasculopathy of the retina may be related to certain combinations of chemotherapy drugs or immunosuppression itself and may persist in the absence of these immunosuppressive drugs.

  19. Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice.

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    Wu, Xudong; Indzhykulian, Artur A; Niksch, Paul D; Webber, Roxanna M; Garcia-Gonzalez, Miguel; Watnick, Terry; Zhou, Jing; Vollrath, Melissa A; Corey, David P

    2016-01-01

    Members of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group. We then characterized mice lacking functional Trpm2, Pkd2, Pkd2l1, Pkd2l2 and Pkd1l3, using scanning electron microscopy, auditory brainstem response, permeant dye accumulation, and single-cell electrophysiology. In all of these TRP-deficient mice, and in double and triple knockouts, mechanotransduction persisted. Together with published studies, these results argue against the participation of any of the 33 mouse TRP channels in hair cell transduction. PMID:27196058

  20. Hair-Cell Mechanotransduction Persists in TRP Channel Knockout Mice.

    Directory of Open Access Journals (Sweden)

    Xudong Wu

    Full Text Available Members of the TRP superfamily of ion channels mediate mechanosensation in some organisms, and have been suggested as candidates for the mechanotransduction channel in vertebrate hair cells. Some TRP channels can be ruled out based on lack of an inner ear phenotype in knockout animals or pore properties not similar to the hair-cell channel. Such studies have excluded Trpv4, Trpa1, Trpml3, Trpm1, Trpm3, Trpc1, Trpc3, Trpc5, and Trpc6. However, others remain reasonable candidates. We used data from an RNA-seq analysis of gene expression in hair cells as well as data on TRP channel conductance to narrow the candidate group. We then characterized mice lacking functional Trpm2, Pkd2, Pkd2l1, Pkd2l2 and Pkd1l3, using scanning electron microscopy, auditory brainstem response, permeant dye accumulation, and single-cell electrophysiology. In all of these TRP-deficient mice, and in double and triple knockouts, mechanotransduction persisted. Together with published studies, these results argue against the participation of any of the 33 mouse TRP channels in hair cell transduction.

  1. 20 Years of persistent identifiers - Which systems are here to stay?

    Science.gov (United States)

    Klump, Jens; Huber, Robert; Lehnert, Kerstin

    2016-04-01

    Web-based persistent identifiers have been around for more than 20 years, a period long enough to start observing patterns of success and failure. Persistent identifiers were invented to address challenges arising from the distributed and disorganised nature of the internet, which not only allowed new technologies to emerge, it also made it difficult to maintain a persistent record of science. Persistent identifiers now allow unambiguous identification of resources on the net. The expectations were that persistent identifiers would lead to greater accessibility, transparency and reproducibility of research results. Over the past two decades a number of persistent identifier systems have been built, one of them being Digital Object Identifiers (DOI). While DOI were originally invented by the publishing industry, they quickly became an established way for the identification of research resources. At first, these resources referred to scholarly literature and related resources. Other identifier systems, some of them using DOI as an example, were developed as grass-roots efforts by the scientific community. The concept of using persistent identifiers has since been expanded to other, non-textual resources, like datasets (DOI, EPIC) and geological specimens (IGSN), and more recently to authors and contributors of scholarly works (ORCID), and to software and instruments. A common witticism states that "a great thing about standards is that there are so many to choose from." Setting up identifier systems is technically trivial. The real challenge lies in creating a governance system for the respective identifiers. Which systems will stand the test of time? Drawing on data from the Registry of Research Data Repositories (re3data.org) and our own experience in the field, this presentation looks at the history and adoption of existing identifier systems and how this gives us some indications towards factors influencing sustainability of these systems.

  2. Absence of Amphotericin B-Tolerant Persister Cells in Biofilms of Some Candida Species▿

    OpenAIRE

    Al-Dhaheri, Rawya S.; Douglas, L. Julia

    2008-01-01

    Biofilms and planktonic cells of five Candida species were surveyed for the presence of persister (drug-tolerant) cell populations after exposure to amphotericin B. None of the planktonic cultures (exponential or stationary phase) contained persister cells. However, persisters were found in biofilms of one of two strains of Candida albicans tested and in biofilms of Candida krusei and Candida parapsilosis, but not in biofilms of Candida glabrata or Candida tropicalis. These results suggest th...

  3. Analytical cell adhesion chromatography reveals impaired persistence of metastatic cell rolling adhesion to P-selectin.

    Science.gov (United States)

    Oh, Jaeho; Edwards, Erin E; McClatchey, P Mason; Thomas, Susan N

    2015-10-15

    Selectins facilitate the recruitment of circulating cells from the bloodstream by mediating rolling adhesion, which initiates the cell-cell signaling that directs extravasation into surrounding tissues. To measure the relative efficiency of cell adhesion in shear flow for in vitro drug screening, we designed and implemented a microfluidic-based analytical cell adhesion chromatography system. The juxtaposition of instantaneous rolling velocities with elution times revealed that human metastatic cancer cells, but not human leukocytes, had a reduced capacity to sustain rolling adhesion with P-selectin. We define a new parameter, termed adhesion persistence, which is conceptually similar to migration persistence in the context of chemotaxis, but instead describes the capacity of cells to resist the influence of shear flow and sustain rolling interactions with an adhesive substrate that might modulate the probability of extravasation. Among cell types assayed, adhesion persistence to P-selectin was specifically reduced in metastatic but not leukocyte-like cells in response to a low dose of heparin. In conclusion, we demonstrate this as an effective methodology to identify selectin adhesion antagonist doses that modulate homing cell adhesion and engraftment in a cell-subtype-selective manner.

  4. Architecture, persistence and dissolution of a 20 to 45 year old trichloroethene DNAPL source zone

    Science.gov (United States)

    Rivett, Michael O.; Dearden, Rachel A.; Wealthall, Gary P.

    2014-12-01

    A detailed field-scale investigation of processes controlling the architecture, persistence and dissolution of a 20 to 45 year old trichloroethene (TCE) dense non-aqueous phase liquid (DNAPL) source zone located within a heterogeneous sand/gravel aquifer at a UK industrial site is presented. The source zone was partially enclosed by a 3-sided cell that allowed detailed longitudinal/fence transect monitoring along/across a controlled streamtube of flow induced by an extraction well positioned at the cell closed end. Integrated analysis of high-resolution DNAPL saturation (Sn) (from cores), dissolved-phase plume concentration (from multilevel samplers), tracer test and permeability datasets was undertaken. DNAPL architecture was determined from soil concentration data using partitioning calculations. DNAPL threshold soil concentrations and low Sn values calculated were sensitive to sorption assumptions. An outcome of this was the uncertainty in demarcation of secondary source zone diffused and sorbed mass that is distinct from trace amounts of low Sn DNAPL mass. The majority of source mass occurred within discrete lenses or pools of DNAPL associated with low permeability geological units. High residual saturation (Sn > 10-20%) and pools (Sn > 20%) together accounted for almost 40% of the DNAPL mass, but only 3% of the sampled source volume. High-saturation DNAPL lenses/pools were supported by lower permeability layers, but with DNAPL still primarily present within slightly more permeable overlying units. These lenses/pools exhibited approximately linearly declining Sn profiles with increasing elevation ascribed to preferential dissolution of the uppermost DNAPL. Bi-component partitioning calculations on soil samples confirmed that the dechlorination product cDCE (cis-dichloroethene) was accumulating in the TCE DNAPL. Estimated cDCE mole fractions in the DNAPL increased towards the DNAPL interface with the uppermost mole fraction of 0.04 comparable to literature

  5. Architecture, persistence and dissolution of a 20 to 45 year old trichloroethene DNAPL source zone.

    Science.gov (United States)

    Rivett, Michael O; Dearden, Rachel A; Wealthall, Gary P

    2014-12-01

    A detailed field-scale investigation of processes controlling the architecture, persistence and dissolution of a 20 to 45year old trichloroethene (TCE) dense non-aqueous phase liquid (DNAPL) source zone located within a heterogeneous sand/gravel aquifer at a UK industrial site is presented. The source zone was partially enclosed by a 3-sided cell that allowed detailed longitudinal/fence transect monitoring along/across a controlled streamtube of flow induced by an extraction well positioned at the cell closed end. Integrated analysis of high-resolution DNAPL saturation (Sn) (from cores), dissolved-phase plume concentration (from multilevel samplers), tracer test and permeability datasets was undertaken. DNAPL architecture was determined from soil concentration data using partitioning calculations. DNAPL threshold soil concentrations and low Sn values calculated were sensitive to sorption assumptions. An outcome of this was the uncertainty in demarcation of secondary source zone diffused and sorbed mass that is distinct from trace amounts of low Sn DNAPL mass. The majority of source mass occurred within discrete lenses or pools of DNAPL associated with low permeability geological units. High residual saturation (Sn>10-20%) and pools (Sn>20%) together accounted for almost 40% of the DNAPL mass, but only 3% of the sampled source volume. High-saturation DNAPL lenses/pools were supported by lower permeability layers, but with DNAPL still primarily present within slightly more permeable overlying units. These lenses/pools exhibited approximately linearly declining Sn profiles with increasing elevation ascribed to preferential dissolution of the uppermost DNAPL. Bi-component partitioning calculations on soil samples confirmed that the dechlorination product cDCE (cis-dichloroethene) was accumulating in the TCE DNAPL. Estimated cDCE mole fractions in the DNAPL increased towards the DNAPL interface with the uppermost mole fraction of 0.04 comparable to literature laboratory

  6. H. pylori exploits and manipulates innate and adaptive immune cell signaling pathways to establish persistent infection

    Directory of Open Access Journals (Sweden)

    Arnold Isabelle C

    2011-11-01

    Full Text Available Abstract Persistent infection with the gastric bacterial pathogen Helicobacter pylori causes gastritis and predisposes carriers to a high gastric cancer risk, but has also been linked to protection from allergic, chronic inflammatory and autoimmune diseases. In the course of tens of thousands of years of co-existence with its human host, H. pylori has evolved elaborate adaptations that allow it to persist in the hostile environment of the stomach in the face of a vigorous innate and adaptive immune response. For this review, we have identified several key immune cell types and signaling pathways that appear to be preferentially targeted by the bacteria to establish and maintain persistent infection. We explore the mechanisms that allow the bacteria to avoid detection by innate immune cells via their pattern recognition receptors, to escape T-cell mediated adaptive immunity, and to reprogram the immune system towards tolerance rather than immunity. The implications of the immunomodulatory properties of the bacteria for the prevention of allergic and auto-immune diseases in chronically infected individuals are also discussed.

  7. Antibody persistence six years after two doses of combined hepatitis A and B vaccine.

    Science.gov (United States)

    Burgess, Margaret A; McIntyre, Peter B; Hellard, Margaret; Ruff, Tilman A; Lefevre, Inge; Bock, Hans L

    2010-03-01

    Persistent immunity to hepatitis A and hepatitis B antibodies six years after vaccination of adolescents (aged 12-15 years) with a combined hepatitis A and B (HAB) vaccine following a 0, 6 month or a 0, 12 month schedule was assessed. Yearly (Year-2-6) serum samples were tested for anti-HAV and anti-HBs using EIA. Subjects with anti-HBs concentrations vaccine dose approximately 12 months after Year-6. Blood samples were collected pre-booster and 1 month post-booster to assess booster response. 240 subjects were vaccinated in the study; at Year-6, data were available from 88 subjects. At that time 84.8% (39/46; 0, 6 month) and 92.9% (39/42; 0, 12 month) of subjects had anti-HBs concentrations > or = 10 mIU/mL. All but one of the 14 boosted subjects responded to the additional HBV vaccine dose with anti-HBs concentrations > or = 100 mIU/mL. All seroconverted subjects who returned at Year-6 were seropositive for anti-HAV. Simplification, reduced number of doses and similar long-term persistence of immunity make the 0, 6 month and 0, 12 month schedule preferable for immunization against HAV/HBV in this population.

  8. Establishment of persistent foot-and-mouth disease virus (FMDV) infection in MDBK cells.

    Science.gov (United States)

    Kopliku, Lela; Relmy, Anthony; Romey, Aurore; Gorna, Kamila; Zientara, Stephan; Bakkali-Kassimi, Labib; Blaise-Boisseau, Sandra

    2015-10-01

    In addition to acute infection and disease, foot-and-mouth disease virus (FMDV) can cause persistent infection in ruminants. Such "carrier" animals represent a potential risk for FMDV transmission to susceptible animals. However, the mechanisms and the factors that determine FMDV persistence remain unknown. We describe here the establishment of FMDV type O persistent infection in a bovine epithelial cell line (Madin-Darby bovine kidney; MDBK). Preliminary experiments to assess the permissivity of MDBK cells to FMDV O infection revealed an unusual pattern of infection: after the initial phase of acute cell lysis, new monolayers formed within 48-72 h post-infection. We found that some cells survived cytolytic infection and subsequently regrew, thereby demonstrating that this bovine cell line can be persistently infected with FMDV type O. Further evidence that MDBK cells were persistently infected with FMDV includes: (i) detection of viral RNA in cells as well as in cell culture supernatants, (ii) detection of viral antigens in the cells by immunofluorescence analysis, and (iii) production of infectious viral particles for up to 36 cell passages. Furthermore, preliminary sequence analysis of persistent virus revealed a single nucleotide substitution within the VP1 coding region, resulting in the V50A amino acid substitution. This bovine model of FMDV persistence holds promise for the investigation of the viral and cellular molecular determinants that promote FMDV persistence.

  9. Toxin YafQ increases persister cell formation by reducing indole signalling.

    Science.gov (United States)

    Hu, Ying; Kwan, Brian W; Osbourne, Devon O; Benedik, Michael J; Wood, Thomas K

    2015-04-01

    Persister cells survive antibiotic and other environmental stresses by slowing metabolism. Since toxins of toxin/antitoxin (TA) systems have been postulated to be responsible for persister cell formation, we investigated the influence of toxin YafQ of the YafQ/DinJ Escherichia coli TA system on persister cell formation. Under stress, YafQ alters metabolism by cleaving transcripts with in-frame 5'-AAA-G/A-3' sites. Production of YafQ increased persister cell formation with multiple antibiotics, and by investigating changes in protein expression, we found that YafQ reduced tryptophanase levels (TnaA mRNA has 16 putative YafQ cleavage sites). Consistently, TnaA mRNA levels were also reduced by YafQ. Tryptophanase is activated in the stationary phase by the stationary-phase sigma factor RpoS, which was also reduced dramatically upon production of YafQ. Tryptophanase converts tryptophan into indole, and as expected, indole levels were reduced by the production of YafQ. Corroborating the effect of YafQ on persistence, addition of indole reduced persistence. Furthermore, persistence increased upon deleting tnaA, and persistence decreased upon adding tryptophan to the medium to increase indole levels. Also, YafQ production had a much smaller effect on persistence in a strain unable to produce indole. Therefore, YafQ increases persistence by reducing indole, and TA systems are related to cell signalling.

  10. Superior T memory stem cell persistence supports long-lived T cell memory

    Science.gov (United States)

    Lugli, Enrico; Dominguez, Maria H.; Gattinoni, Luca; Chattopadhyay, Pratip K.; Bolton, Diane L.; Song, Kaimei; Klatt, Nichole R.; Brenchley, Jason M.; Vaccari, Monica; Gostick, Emma; Price, David A.; Waldmann, Thomas A.; Restifo, Nicholas P.; Franchini, Genoveffa; Roederer, Mario

    2013-01-01

    Long-lived memory T cells are able to persist in the host in the absence of antigen; however, the mechanism by which they are maintained is not well understood. Recently, a subset of human T cells, stem cell memory T cells (TSCM cells), was shown to be self-renewing and multipotent, thereby providing a potential reservoir for T cell memory throughout life. However, their in vivo dynamics and homeostasis still remain to be defined due to the lack of suitable animal models. We identified T cells with a TSCM phenotype and stem cell–like properties in nonhuman primates. These cells were the least-differentiated memory subset, were functionally distinct from conventional memory cells, and served as precursors of central memory. Antigen-specific TSCM cells preferentially localized to LNs and were virtually absent from mucosal surfaces. They were generated in the acute phase of viral infection, preferentially survived in comparison with all other memory cells following elimination of antigen, and stably persisted for the long term. Thus, one mechanism for maintenance of long-term T cell memory derives from the unique homeostatic properties of TSCM cells. Vaccination strategies designed to elicit durable cellular immunity should target the generation of TSCM cells. PMID:23281401

  11. Persistence Increases in the Absence of the Alarmone Guanosine Tetraphosphate by Reducing Cell Growth.

    Science.gov (United States)

    Chowdhury, Nityananda; Kwan, Brian W; Wood, Thomas K

    2016-02-03

    Most bacterial cells are stressed, and as a result, some become tolerant to antibiotics by entering a dormant state known as persistence. The key intracellular metabolite that has been linked to this persister state is guanosine tetraphosphate (ppGpp), the alarmone that was first linked to nutrient stress. In Escherichia coli, ppGpp redirects protein production during nutrient stress by interacting with RNA polymerase directly and by inhibiting several proteins. Consistently, increased levels of ppGpp lead to increased persistence; but, the mechanism by which elevated ppGpp translates into persistence has not been determined. Hence, we explored persistence in the absence of ppGpp so that the underlying mechanism of persister cell formation could be explored. We found that persister cells still form, although at lower levels, in the absence of ppGpp. Additionally, the toxin/antitoxin systems that we investigated (MqsR, MazF, GhoT, and YafQ) remain able to increase persistence dramatically in the absence of ppGpp. By overproducing each E. coli protein from the 4287 plasmid vectors of the ASKA library and selecting for increased persistence in the absence of ppGpp (via a relA spoT mutant), we identified five new proteins, YihS, PntA, YqjE, FocA, and Zur, that increase persistence simply by reducing cell growth.

  12. Characteristics of type I Gaucher disease associated with persistent thrombocytopenia after treatment with imiglucerase for 4-5 years.

    Science.gov (United States)

    Hollak, Carla E M; Belmatoug, Nadia; Cole, J Alexander; Vom Dahl, Stephan; Deegan, Patrick B; Goldblatt, Jack; Rosenbloom, Barry; van Dussen, Laura; Tylki-Szymańska, Anna; Weinreb, Neal J; Zimran, Ari; Cappellini, Maria Domenica

    2012-08-01

    The characteristics of Gaucher disease (GD) associated with persistent thrombocytopenia despite imiglucerase enzyme therapy in type 1 GD (GD1) were investigated by retrospective analysis of International Collaborative Gaucher Group (ICGG) Registry data. The study involved 1016 GD1 patients with an intact spleen for whom date of diagnosis, therapy initiation, and platelet counts were known, and who received continuous imiglucerase therapy for 4 to 5 years. These patients were stratified by last platelet count: ≥ 120 × 10(9) /l (n = 772); ≥ 100 to <120 × 10(9) /l (n = 94); ≥ 80 to <100 × 10(9) /l (n = 80); and <80 × 10(9) /l (n = 70; 20 with <60 × 10(9) /l) and characterized by initial and cumulative average imiglucerase dose, body mass index, platelet count, anaemia, hepatomegaly, splenomegaly, and skeletal assessments at baseline and after 4-5 years of therapy. Statistically significant associations were found between persistent thrombocytopenia and baseline platelet count (<80 × 10(9) /l), splenomegaly, and anaemia (all P < 0·0001). After 4-5 years, statistically significant associations were found with splenomegaly (P < 0·0001), anaemia (P < 0·0001), white blood cell count (P = 0·049), hepatomegaly (P = 0·004) and bone pain (P = 0·035). Exponential platelet decay in relation to splenomegaly suggests that platelets increase only when spleen volume decreases substantially. PMID:22640238

  13. Persistence of Natural Killer (NK cell lymphocytosis with hyposplenism without development of leukaemia

    Directory of Open Access Journals (Sweden)

    Khan Sujoy

    2005-09-01

    Full Text Available Abstract Background Natural killer (NK cell lymphocytosis usually has an indolent course and can progress into massive lymphocytosis with development of cytopenias and neoplastic diseases. NK-cells usually express one or more "NK-associated" antigens (CD16, CD56, CD57. Reactive expansions are seen in autoimmune diseases, viral infections, solid tumours and non-Hodgkin's lymphoma. Case presentation We report a lady with a benign clinical course over 10 years and persistent CD8+/CD3-/CD57+/CD16+ LGL proliferation with presence of Howell-Jolly bodies (functional hyposplenism, an association not previously described. Conclusion We discuss the possible causes of clonal expansion and conclude that this may be part of the spectrum of immune dysregulation associated with NK-cell lymphocytosis.

  14. Career Development among First-Year College Students: College Self-Efficacy, Student Persistence, and Academic Success

    Science.gov (United States)

    Wright, Stephen L.; Jenkins-Guarnieri, Michael A.; Murdock, Jennifer L.

    2013-01-01

    The present study investigates the career development of college student persistence decisions through the theoretical lens of social cognitive career theory (SCCT). Specifically, the authors sought to understand the potential role of college self-efficacy in first-year student persistence and academic success at a medium size university. Using a…

  15. Rapid Elimination of the Persistent Synergid through a Cell Fusion Mechanism

    KAUST Repository

    Maruyama, Daisuke

    2015-05-01

    In flowering plants, fertilization-dependent degeneration of the persistent synergid cell ensures one-on-one pairings of male and female gametes. Here, we report that the fusion of the persistent synergid cell and the endosperm selectively inactivates the persistent synergid cell in Arabidopsis thaliana. The synergid-endosperm fusion causes rapid dilution of pre-secreted pollen tube attractant in the persistent synergid cell and selective disorganization of the synergid nucleus during the endosperm proliferation, preventing attractions of excess number of pollen tubes (polytubey). The synergid-endosperm fusion is induced by fertilization of the central cell, while the egg cell fertilization predominantly activates ethylene signaling, an inducer of the synergid nuclear disorganization. Therefore, two female gametes (the egg and the central cell) control independent pathways yet coordinately accomplish the elimination of the persistent synergid cell by double fertilization. Two female gametes (the egg cell and the central cell) in flowering plants coordinately prevent attractions of excess number of pollen tubes via two mechanisms to inactivate persistent synergid cell. © 2015 Elsevier Inc.

  16. Dual-Reporter Mycobacteriophages (Φ2DRMs) Reveal Preexisting Mycobacterium tuberculosis Persistent Cells in Human Sputum

    Science.gov (United States)

    Jain, Paras; Weinrick, Brian C.; Kalivoda, Eric J.; Yang, Hui; Munsamy, Vanisha; Vilcheze, Catherine; Weisbrod, Torin R.; Larsen, Michelle H.; O’Donnell, Max R.; Pym, Alexander

    2016-01-01

    ABSTRACT Persisters are the minor subpopulation of bacterial cells that lack alleles conferring resistance to a specific bactericidal antibiotic but can survive otherwise lethal concentrations of that antibiotic. In infections with Mycobacterium tuberculosis, such persisters underlie the need for long-term antibiotic therapy and contribute to treatment failure in tuberculosis cases. Here, we demonstrate the value of dual-reporter mycobacteriophages (Φ2DRMs) for characterizing M. tuberculosis persisters. The addition of isoniazid (INH) to exponentially growing M. tuberculosis cells consistently resulted in a 2- to 3-log decrease in CFU within 4 days, and the remaining ≤1% of cells, which survived despite being INH sensitive, were INH-tolerant persisters with a distinct transcriptional profile. We fused the promoters of several genes upregulated in persisters to the red fluorescent protein tdTomato gene in Φ2GFP10, a mycobacteriophage constitutively expressing green fluorescent protein (GFP), thus generating Φ2DRMs. A population enriched in INH persisters exhibited strong red fluorescence, by microscopy and flow cytometry, using a Φ2DRM with tdTomato controlled from the dnaK promoter. Interestingly, we demonstrated that, prior to INH exposure, a population primed for persistence existed in M. tuberculosis cells from both cultures and human sputa and that this population was highly enriched following INH exposure. We conclude that Φ2DRMs provide a new tool to identify and quantitate M. tuberculosis persister cells.

  17. Long-term persistence of T cell memory to HBsAg after hepatitis B vaccination

    Institute of Scientific and Technical Information of China (English)

    Ru-Xiang Wang; Greet J. Boland; Jan van Hattum; Gijsbert C. de Gast

    2004-01-01

    AIM: To determine if the T cell memory to HBsAg can persist for a long time after hepatitis B (HB) vaccination.METHODS: Thirty one vaccine recipients who were healthcare workers (18 females and 13 males aged 34-58 years) from Utrecht University Hospital, Netherlands, and had previously Received a standard course of vaccination for hepatitis B were investigated and another 9 unvaccinated healthy volunteers from the same hospital were used as the control. Blood samples were taken just before the experiment to test serum anti-HBs levels and the subjects were classified into different groups according to their serum titers of anti-HBs and vaccination history. Their peripheral blood mononuclear cells (pBrvMc) were isolated from freshly heparinized venous blood and the proliferative response of Tlymphocytes to the recombinant hepatitis B surface antigen(HBsAg) was investigated.RESULTS: Positive serum anti-HBs was found in 61.3%(19/31) vaccine recipients and a significant in vitro lymphocyte proliferative response to recombinant HBsAg was observed in all the vaccinees with positive anti-HBs. Serum anti-HBs level ≤10 IU/L was found in 38.7% (12/31)subjects. In this study, we specially focused on lymphocyte proliferative response to recombinant HBsAg in those vaccine recipients with serum anti-HBsAg less than 10 IU/L.Most of them had Received a standard course of vaccination about 10 years before. T lymphocyte proliferative response was found positive in 7 of the 12 vaccine recipients. These results confirmed that HBsAg-specific memory T cells remained detectable in the circulation for a long time after vaccination, even when serum anti-HBs level had been undetectable.CONCLUSION: The T cell memory to HBsAg can persist for at least 10 years after HB vaccination. Further booster injection is not necessary in healthy responders to HB vaccine.

  18. Persistent Effect of Vitamin D Supplementation on Musculoskeletal Parameters in Adolescents One Year After Trial Completion.

    Science.gov (United States)

    Ghazal, Nisrine; Al-Shaar, Laila; Maalouf, Joyce; Nabulsi, Mona; Arabi, Asma; Choucair, Mahmoud; Tamim, Hani; Mahfoud, Ziad; El-Hajj Fuleihan, Ghada

    2016-07-01

    We showed a beneficial effect of vitamin D supplementation on musculoskeletal parameters in adolescent girls in a 1-year, randomized, double-blinded placebo-controlled trial (RCT). Our objective for this study was to investigate the residual effect of vitamin D supplementation on bone mineral content (BMC), bone mineral density (BMD), at the lumbar spine and hip, lean mass, and height, 1 year after trial completion. We performed post hoc analyses in 167 adolescents, 86 girls and 81 boys, age 13.9 ± 2 years, who received vitamin D or placebo during the trial, and continued into the follow-up trial. Musculoskeletal parameters were measured at baseline, 12 months (intervention), and 24 months (follow-up). ANOVA and t tests were used to compare results between the placebo group and the merged vitamin D arms (200 or 2000 IU/day), by gender. Baseline characteristics were comparable between treatment groups at entry into the extension. Girls who had received vitamin D during the trial, had significantly larger hip BMC increments compared to those assigned to placebo, at 24 months compared to study entry, but not 24 compared to 12 months, which persisted in adjusted analyses. There were no significant differences in bone mass changes between treatment groups in boys, at 24 months compared to 12 months or to baseline. The beneficial effect of vitamin D supplementation on hip bone mass, achieved in girls during the trial, persisted 1 year after trial completion. These net cumulative increments, 1 year after discontinuation of supplementation, may have important implications on optimizing peak bone mass accretion in adolescent girls. © 2016 American Society for Bone and Mineral Research. PMID:26841085

  19. Virus-host interactions in persistently FMDV-infected cells derived from bovine pharynx

    Science.gov (United States)

    Foot-and-mouth disease virus (FMDV) produces a disease in cattle characterized by vesicular lesions and a persistent infection with asymptomatic low-level production of virus. Here we describe the establishment of a persistently infected primary cell culture derived from bovine pharynx tissue (PBPT)...

  20. Historical data reveal 30-year persistence of benthic fauna associations in heavily modified waterbody

    Directory of Open Access Journals (Sweden)

    Ruth Callaway

    2016-08-01

    Full Text Available Baseline surveys form the cornerstone of coastal impact studies where altered conditions, for example through new infrastructure development, are assessed against a temporal reference state. They are snapshots taken before construction. Due to scarcity of relevant data prior to baseline surveys long-term trends can often not be taken into account. Particularly in heavily modified waterbodies this would however be desirable to control for changes in anthropogenic use over time as well as natural ecological variation. Here, the benthic environment of an industrialized embayment was investigated (Swansea Bay, Wales, UK where it is proposed to build a tidal lagoon that would generate marine renewable energy from the tidal range. Since robust long-term baseline data was not available, the value of unpublished historical benthos information from 1984 by a regional water company was assessed with the aim to improve certainty about the persistence of current benthic community patterns. A survey of 101 positions in 2014 identified spatially discrete benthic communities with areas of high and low diversity. Habitat characteristics including sediment properties and the proximity to a sewage outfall explained 17-35% of the variation in the community structure. Comparing the historical information from 1984 with 2014 revealed striking similarity in the benthic communities between those years, not just in their spatial distribution but also to a large extent in the species composition. The 30-year-old information confirmed spatial boundaries of discrete species associations and pinpointed a similar diversity hotspot. A group of five common species was found to be particularly persistent over time (Nucula nitidosa, Spisula elliptica, Spiophanes bombyx, Nephtys hombergii, Diastylis rathkei. According to the Infauna Quality Index (IQI linked to the EU Water Framework Directive (WFD the average ecological status for 2014 was ‘moderate’, but eleven samples

  1. Persistence of artificial sweeteners in a 15-year-old septic system plume

    Science.gov (United States)

    Robertson, W. D.; Van Stempvoort, D. R.; Solomon, D. K.; Homewood, J.; Brown, S. J.; Spoelstra, J.; Schiff, S. L.

    2013-01-01

    SummaryGroundwater contamination from constituents such as NO3-, often occurs where multiple sources are present making source identification difficult. This study examines a suite of major ions and trace organic constituents within a well defined septic system plume in southern Ontario, Canada (Long Point site) for their potential use as wastewater tracers. The septic system has been operating for 20 years servicing a large, seasonal-use campground and tritium/helium age dating indicates that the 200 m long monitored section of the plume is about 15 years old. Four parameters are elevated along the entire length of the plume as follows; the mean electrical conductivity value (EC) in the distal plume zone is 926 μS/cm which is 74% of the mean value below the tile bed, Na+ (14.7 mg/L) is 43%, an artificial sweetener, acesulfame (12.1 μg/L) is 23% and Cl- (71.5 mg/L) is 137%. EC and Cl- appear to be affected by dispersive dilution with overlying background groundwater that has lower EC but has locally higher Cl- as result of the use of a dust suppressant (CaCl2) in the campground. Na+, in addition to advective dilution, could be depleted by weak adsorption. Acesulfame, in addition to the above processes could be influenced by increasing consumer use in recent years. Nonetheless, both Na+ and acesulfame remain elevated throughout the plume by factors of more than 100 and 1000 respectively compared to background levels, and are strong indicators of wastewater impact at this site. EC and Cl- are less useful because their contrast with background values is much less (EC) or because other sources are present (Cl-). Nutrients (NO3-, NH4+, PO43-, K+) and pathogens (Escherichia coli) do not persist in the distal plume zone and are less useful as wastewater indicators here. The artificial sweetener, acesulfame, has persisted at high concentrations in the Long Point plume for at least 15 years (and this timing agrees with tritium/helium-3 dating) and this compound likely

  2. Persistent Polyclonal B Cell Lymphocytosis B Cells Can Be Activated through CD40-CD154 Interaction

    Directory of Open Access Journals (Sweden)

    Emmanuelle Dugas-Bourdages

    2014-01-01

    Full Text Available Persistent polyclonal B cell lymphocytosis (PPBL is a rare disorder, diagnosed primarily in adult female smokers and characterized by an expansion of CD19+CD27+IgM+ memory B cells, by the presence of binucleated lymphocytes, and by a moderate elevation of serum IgM. The clinical course is usually benign, but it is not known whether or not PPBL might be part of a process leading to the emergence of a malignant proliferative disorder. In this study we sought to investigate the functional response of B cells from patients with PPBL by use of an optimal memory B cell culture model based on the CD40-CD154 interaction. We found that the proliferation of PPBL B cells was almost as important as that of B cells from normal controls, resulting in high immunoglobulin secretion with in vitro isotypic switching. We conclude that the CD40-CD154 activation pathway is functional in the memory B cell population of PPBL patients, suggesting that the disorder may be due to either a dysfunction of other cells in the microenvironment or a possible defect in another B cell activation pathway.

  3. Extensive cell heterogeneity during persistent infection with foot-and-mouth disease virus.

    OpenAIRE

    de la Torre, J C; Martínez-Salas, E; J. Díez; Domingo, E

    1989-01-01

    Coevolution of viruses and the host cells occurred in BHK-21 cell cultures persistently infected with foot-and-mouth disease virus (FMDV) (J. C. de la Torre, E. Martínez-Salas, J. Diez, A. Villaverde, F. Gebauer, E. Rocha, M. Dávila, and E. Domingo, J. Virol. 62:2050-2058, 1988). In the present report we provide evidence of an extreme phenotypic heterogeneity of the cells, which was generated in the course of persistence. A total of 248 stable cell clones isolated from FMDV carrier cultures a...

  4. Emergence and Persistence of Collective Cell Migration on Small Circular Micropatterns

    CERN Document Server

    Segerer, Felix J; Alberola, Alicia Piera; Frey, Erwin; Rädler, Joachim O

    2015-01-01

    The spontaneous formation of vortices is a hallmark of collective cellular activity. Here, we study the onset and persistence of coherent angular motion (CAMo) as a function of the number of cells $N$ confined in circular micropatterns. We find that the persistence of CAMo increases with $N$ but exhibits a pronounced discontinuity accompanied by a geometric rearrangement of cells to a configuration containing a central cell. Computer simulations based on a generalized Potts model reproduce the emergence of vortex states and show in agreement with experiment that their stability depends on the interplay of spatial arrangement and internal polarization of neighboring cells. Hence, the distinct migrational states in finite size

  5. Epidemiology of frequent attenders: a 3-year historic cohort study comparing attendance, morbidity and prescriptions of one-year and persistent frequent attenders

    Directory of Open Access Journals (Sweden)

    ter Riet Gerben

    2009-01-01

    Full Text Available Abstract Background General Practitioners spend a disproportionate amount of time on frequent attenders. So far, trials on the effect of interventions on frequent attenders have shown negative results. However, these trials were conducted in short-term frequent attenders. It would be more reasonable to target intervention at persistent frequent attenders. Typical characteristics of persistent frequent attenders, as opposed to 1-year frequent attenders and non-frequent attenders, may generate hypotheses regarding modifiable factors on which new randomized trials may be designed. Methods We used the data of all 28,860 adult patients from 5 primary healthcare centers. Frequent attenders were patients whose attendance rate ranked in the (age and sex adjusted top 10 percent during 1 year (1-year frequent attenders or 3 years (persistent frequent attenders. All other patients on the register over the 3-year period were referred to as non-frequent attenders. The lists of medical problems coded by the GP using the International Classification of Primary Care (ICPC were used to assess morbidity. First, we determined which proportion of 1-year frequent attenders was still a frequent attender during the next two consecutive years and calculated the GPs' workload for these patients. Second, we compared morbidity and number of prescriptions for non-frequent attenders, 1-year frequent attenders and persistent frequent attenders. Results Of all 1-year frequent attenders, 15.4% became a persistent frequent attender equal to 1.6% of all patients. The 1-year frequent attenders (3,045; 10.6% were responsible for 39% of the face-to-face consultations; the 470 patients who would become persistent frequent attenders (1.6% were responsible for 8% of all consultations in 2003. Persistent frequent attenders presented more social problems, more psychiatric problems and medically unexplained physical symptoms, but also more chronic somatic diseases (especially diabetes

  6. Cell motility as persistent random motion: Theories from experiments

    DEFF Research Database (Denmark)

    Selmeczi, D.; Mosler, S.; Hagedorn, P.H.;

    2005-01-01

    Experimental time series for trajectories of motile cells may contain so much information that a systematic analysis will yield cell-type- specific motility models. Here we demonstrate how, using human keratinocytes and fibroblasts as examples. The two resulting models reflect the cells' differen...

  7. Foxp3+ regulatory T cells control persistence of viral CNS infection.

    Directory of Open Access Journals (Sweden)

    Dajana Reuter

    Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

  8. Persistent Associations between Maternal Prenatal Exposure to Phthalates on Child IQ at Age 7 Years.

    Directory of Open Access Journals (Sweden)

    Pam Factor-Litvak

    Full Text Available Prior research reports inverse associations between maternal prenatal urinary phthalate metabolite concentrations and mental and motor development in preschoolers. No study evaluated whether these associations persist into school age.In a follow up of 328 inner-city mothers and their children, we measured prenatal urinary metabolites of di-n-butyl phthalate (DnBP, butylbenzyl phthalate (BBzP, di-isobutyl phthalate (DiBP, di-2-ethylhexyl phthalate and diethyl phthalate in late pregnancy. The Wechsler Intelligence Scale for Children, 4th edition was administered at child age 7 years and evaluates four areas of cognitive function associated with overall intelligence quotient (IQ.Child full-scale IQ was inversely associated with prenatal urinary metabolite concentrations of DnBP and DiBP: b = -2.69 (95% confidence interval [CI] = -4.33, -1.05 and b = -2.69 (95% CI = -4.22, -1.16 per log unit increase. Among children of mothers with the highest versus lowest quartile DnBP and DiBP metabolite concentrations, IQ was 6.7 (95% CI = 1.9, 11.4 and 7.6 (95% CI = 3.2, 12.1 points lower, respectively. Associations were unchanged after control for cognition at age 3 years. Significant inverse associations were also seen between maternal prenatal metabolite concentrations of DnBP and DiBP and child processing speed, perceptual reasoning and working memory; DiBP and child verbal comprehension; and BBzP and child perceptual reasoning.Maternal prenatal urinary metabolite concentrations measured in late pregnancy of DnBP and DiBP are associated with deficits in children's intellectual development at age 7 years. Because phthalate exposures are ubiquitous and concentrations seen here within the range previously observed among general populations, results are of public health significance.

  9. Human memory T cells with a naive phenotype accumulate with aging and respond to persistent viruses.

    Science.gov (United States)

    Pulko, Vesna; Davies, John S; Martinez, Carmine; Lanteri, Marion C; Busch, Michael P; Diamond, Michael S; Knox, Kenneth; Bush, Erin C; Sims, Peter A; Sinari, Shripad; Billheimer, Dean; Haddad, Elias K; Murray, Kristy O; Wertheimer, Anne M; Nikolich-Žugich, Janko

    2016-08-01

    The number of naive T cells decreases and susceptibility to new microbial infections increases with age. Here we describe a previously unknown subset of phenotypically naive human CD8(+) T cells that rapidly secreted multiple cytokines in response to persistent viral antigens but differed transcriptionally from memory and effector T cells. The frequency of these CD8(+) T cells, called 'memory T cells with a naive phenotype' (TMNP cells), increased with age and after severe acute infection and inversely correlated with the residual capacity of the immune system to respond to new infections with age. CD8(+) TMNP cells represent a potential new target for the immunotherapy of persistent infections and should be accounted for and subtracted from the naive pool if truly naive T cells are needed to respond to antigens. PMID:27270402

  10. Persistence of Breakage in Specific Chromosome Bands 6 Years after Acute Exposure to Oil

    Science.gov (United States)

    Francés, Alexandra; Hildur, Kristin; Barberà, Joan Albert; Rodríguez-Trigo, Gema; Zock, Jan-Paul; Giraldo, Jesús; Monyarch, Gemma; Rodriguez-Rodriguez, Emma; de Castro Reis, Fernanda; Souto, Ana; Gómez, Federico P.; Pozo-Rodríguez, Francisco; Templado, Cristina; Fuster, Carme

    2016-01-01

    Background The identification of breakpoints involved in chromosomal damage could help to detect genes involved in genetic disorders, most notably cancer. Until now, only one published study, carried out by our group, has identified chromosome bands affected by exposure to oil from an oil spill. In that study, which was performed two years after the initial oil exposure in individuals who had participated in clean-up tasks following the wreck of the Prestige, three chromosomal bands (2q21, 3q27, 5q31) were found to be especially prone to breakage. A recent follow-up study, performed on the same individuals, revealed that the genotoxic damage had persisted six years after oil exposure. Objectives To determine whether there exist chromosome bands which are especially prone to breakages and to know if there is some correlation with those detected in the previous study. In addition, to investigate if the DNA repair problems detected previously persist in the present study. Design Follow-up study performed six years after the Prestige oil spill. Setting Fishermen cooperatives in coastal villages. Participants Fishermen highly exposed to oil spill who participated in previous genotoxic study six years after the oil. Measurements Chromosome damage in peripheral lymphocytes. For accurate identification of the breakpoints involved in chromosome damage of circulating lymphocytes, a sequential stain/G-banding technique was employed. To determine the most break-prone chromosome bands, two statistical methods, the Fragile Site Multinomial and the chi-square tests (where the bands were corrected by their length) were used. To compare the chromosome lesions, structural chromosome alterations and gaps/breaks between two groups of individuals we used the GEE test which takes into account a possible within-individual correlation. Dysfunctions in DNA repair mechanisms, expressed as chromosome damage, were assessed in cultures with aphidicolin by the GEE test. Results Cytogenetic

  11. Persistent photovoltage in methylammonium lead iodide perovskite solar cells

    OpenAIRE

    Baumann, A.; Tvingstedt, K.; Heiber, M. C.; Väth, S.; C. Momblona; H. J. Bolink; Dyakonov, V.

    2014-01-01

    We herein perform open circuit voltage decay (OCVD) measurements on methylammonium lead iodide (CH3NH3PbI3) perovskite solar cells to increase the understanding of the charge carrier recombination dynamics in this emerging technology. Optically pulsed OCVD measurements are conducted on CH3NH3PbI3 solar cells and compared to results from another type of thin-film photovoltaics, namely, the two reference polymer–fullerene bulk heterojunction solar cell devices based on P3HT:PC60BM and PTB7:PC70...

  12. Keeping It in the Family: ATRX Loss Promotes Persistent Sister Telomere Cohesion in ALT Cancer Cells.

    Science.gov (United States)

    Roake, Caitlin M; Artandi, Steven E

    2015-09-14

    In this issue of Cancer Cell, Ramamoorthy and Smith report that cancer cells that maintain their chromosome ends through alternative lengthening of telomeres (ALT) display persistent sister telomere cohesion. This delayed resolution of sister telomere cohesion depends upon the loss of ATRX and its histone-sequestering function and is associated with increased recombination between sister telomeres. PMID:26373274

  13. Persistence of 10-year old Exxon Valdez oil on Gulf of Alaska beaches: The importance of boulder-armoring

    Energy Technology Data Exchange (ETDEWEB)

    Irvine, G.V. [United States Geological Survey , Anchorage, AK (United States); Mann, D.H. [University of Alaska, Fairbanks, AK (United States). Institute of Arctic Biology; Short, J.W. [National Oceanic and Atmospheric Administration, Juneau, AK (United States). Auke Bay Fisheries Laboratory

    2006-09-15

    Oil stranded as a result of the 1989 Exxon Valdez spill has persisted for >10 years at study sites on Gulf of Alaska shores distant from the spill's origin. These sites were contaminated by 'oil mousse', which persists in these settings due to armoring of underlying sediments and their included oil beneath boulder. The boulder-armored beaches that we resampled in 1999 showed continued contamination by subsurface oil, despite their exposure to moderate to high wave energies. Significant declines in surface oil cover occurred at all study sites. In contrast, mousse has persisted under boulders in amounts similar to what was present in 1994 and probably in 1989. Especially striking is the general lack of weathering of this subsurface oil over the last decade. Oil at five of the six armored-beach sites 10 years after the spill is compositionally similar to 11-day old Exxon Valdez oil. Analysis of movements in the boulder-armor that covers the study beaches reveals that only minor shifts have occurred since 1994, suggesting that over the last five, and probably over the last 10 years, boulder-armors have remained largely unmoved at the study sites. These findings emphasize the importance of particular geomorphic parameters in determining stranded oil persistence. Surface armoring, combined with stranding of oil mousse, results in the unexpectedly lengthy persistence of only lightly to moderately weathered oil within otherwise high-energy wave environments. (author)

  14. Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore.

    Science.gov (United States)

    Harenberg, Anke; Begue, Sarah; Mamessier, Audrey; Gimenez-Fourage, Sophie; Ching Seah, Ching; Wei Liang, Ai; Li Ng, Jun; Yun Toh, Xue; Archuleta, Sophia; Wilder-Smith, Annelies; Shek, Lynette P; Wartel-Tram, Anh; Bouckenooghe, Alain; Lang, Jean; Crevat, Denis; Caillet, Catherine; Guy, Bruno

    2013-11-01

    To characterize the cell mediated immunity (CMI) induced by the investigational CYD tetravalent dengue vaccine (TDV), we developed a whole-blood, intracellular cytokine staining (ICS) assay and a multiplex assay, each requiring 3 mL of blood. We assessed CMI before and 28 d after a first and third injection of CYD-TDV and one year after the third injection in a subset of 80 adolescents and adults enrolled in a phase II trial in Singapore (ClinicalTrial.gov NCT NCT00880893). CD4/IFNγ/TNFα responses specific to dengue NS3 were detected before vaccination. Vaccination induced YF-17D-NS3-specific CD8/IFNγ responses, without significant TNFα, and a CYD-specific Th1/Tc1 cellular response in all participants, which was characterized by predominant IFNγ secretion compared with TNFα, associated with low level IL-13 secretion in multiplex analysis of peripheral blood mononuclear cells (PBMC) supernatants after restimulation with each the CYD vaccine viruses. Responses were directed mainly against CYD-4 after the first vaccination, and were more balanced against all four serotypes after the third vaccination. The same qualitative profile was observed one year after the third vaccination, with approximately 2-fold lower NS3-specific responses, and 3-fold lower serotype-specific cellular responses. These findings confirm previous observations regarding both the nature and specificity of cellular responses induced by CYD-TDV, and for the first time demonstrate the persistence of cellular responses after one year. We also established the feasibility of analyzing CMI with small blood samples, allowing such analysis to be considered for pediatric trials.

  15. The in vivo activation of persistent nanophosphors for optical imaging of vascularization, tumours and grafted cells

    Science.gov (United States)

    Maldiney, Thomas; Bessière, Aurélie; Seguin, Johanne; Teston, Eliott; Sharma, Suchinder K.; Viana, Bruno; Bos, Adrie J. J.; Dorenbos, Pieter; Bessodes, Michel; Gourier, Didier; Scherman, Daniel; Richard, Cyrille

    2014-04-01

    Optical imaging for biological applications requires more sensitive tools. Near-infrared persistent luminescence nanoparticles enable highly sensitive in vivo optical detection and complete avoidance of tissue autofluorescence. However, the actual generation of persistent luminescence nanoparticles necessitates ex vivo activation before systemic administration, which prevents long-term imaging in living animals. Here, we introduce a new generation of optical nanoprobes, based on chromium-doped zinc gallate, whose persistent luminescence can be activated in vivo through living tissues using highly penetrating low-energy red photons. Surface functionalization of this photonic probe can be adjusted to favour multiple biomedical applications such as tumour targeting. Notably, we show that cells can endocytose these nanoparticles in vitro and that, after intravenous injection, we can track labelled cells in vivo and follow their biodistribution by a simple whole animal optical detection, opening new perspectives for cell therapy research and for a variety of diagnosis applications.

  16. Antibody persistence and immune memory 4 years post-vaccination with combined hepatitis A and B vaccine in adults aged over 40 years.

    Science.gov (United States)

    Chlibek, Roman; von Sonnenburg, Frank; Van Damme, Pierre; Smetana, Jan; Tichy, Petr; Gunapalaiah, Bhavyashree; Leyssen, Maarten; Jacquet, Jeanne-Marie

    2011-01-01

    Persistence of immune response was assessed in adults aged >40 years (N = 596) following primary vaccination with combined hepatitis A/B vaccine or concomitant monovalent hepatitis A and B vaccines. Anti-hepatitis A virus antibody responses persisted for at least 4 years regardless of the vaccine used, with anti-hepatitis B surface antibody responses higher and more sustained in subjects who received the combined hepatitis A/B vaccine. Response rates to an additional dose of the same vaccine(s) used for priming were high.

  17. The role of monocyte-lineage cells in human immuno-deficiency virus persistence: mechanisms and progress

    Institute of Scientific and Technical Information of China (English)

    WU Li

    2011-01-01

    Human immunodeficiency virus type 1 (HIV-1) persistence is a major barrier to the successful treatment and eradication of acquired immunodeficiency syndrome (AIDS). In addition to resting CD4+ T cells, a significant long-lived compartment of HIV-1 infection in vivo includes blood monocytes and tissue macrophages. Studying HIV-1 persistence in monocyte-lineage cells is critical because these cells are important HIV-1 target cells in vivo. Monocyte-lineage cells, including monocytes, dendritic cells (DCs) and macrophages, play a significant role in HIV-1 infection and transmission. These cells have been implicated as viral reservoirs that facilitate HIV-1 latency and persistence. A better understanding of HIV-1 interactions with monocyte-lineage cells can potentially aid in the development of new approaches for intervention. This minireview highlights the latest advances in understanding the role of monocyte-lineage cells in HIV-1 persistence and emphasizes new insights into the mechanisms underlying viral persistence.

  18. Impact of Noncognitive Factors on First-Year Academic Performance and Persistence of NCAA Division I Student Athletes

    Science.gov (United States)

    Ting, Siu-Man Raymond

    2009-01-01

    SAT scores and noncognitive factors (acquired knowledge in a field, community service, positive self-concept, and preference for long-term goals) were found to be related to academic performance and persistence among 1st-year NCAA Division I student athletes (N = 109). Implications for college counselors and future research directions are…

  19. Use it or lose it: establishment and persistence of T cell memory

    Directory of Open Access Journals (Sweden)

    Katherine eKedzierska

    2012-11-01

    Full Text Available Pre-existing T cell memory provides substantial protection against viral, bacterial and parasitic infections. The generation of protective T cell memory constitutes a primary goal for cell-mediated vaccines, thus understanding the mechanistic basis of memory development and maintenance are of major importance. The widely accepted idea that T cell memory pools are directly descended from the effector populations has been challenged by recent reports that provide evidence for the early establishment of T cell memory and suggest that the putative memory precursor T cells do not undergo full expansion to effector status. Moreover, it appears that once the memory T cells are established early in life, they can persist for the lifetime of an individual. This is in contrast to the reported waning of naïve T cell immunity with age. Thus, in the elderly, immune memory that was induced at an early age may be more robust than recently induced memory, despite the necessity for long persistence. The present review discusses the mechanisms underlying the early establishment of immunological memory and the subsequent persistence of memory T cell pools in animal models and humans.

  20. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

    Directory of Open Access Journals (Sweden)

    Nuriban Valero-Pacheco

    Full Text Available The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs, have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

  1. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine

    Science.gov (United States)

    Villasís-Keever, Miguel Ángel; Núñez-Valencia, Adriana; Boscó-Gárate, Ilka; Lozano-Dubernard, Bernardo; Lara-Puente, Horacio; Espitia, Clara; Alpuche-Aranda, Celia; Bonifaz, Laura C.; Arriaga-Pizano, Lourdes; Pastelin-Palacios, Rodolfo; Isibasi, Armando; López-Macías, Constantino

    2016-01-01

    The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans. PMID:26919288

  2. Antibody Persistence in Adults Two Years after Vaccination with an H1N1 2009 Pandemic Influenza Virus-Like Particle Vaccine.

    Science.gov (United States)

    Valero-Pacheco, Nuriban; Pérez-Toledo, Marisol; Villasís-Keever, Miguel Ángel; Núñez-Valencia, Adriana; Boscó-Gárate, Ilka; Lozano-Dubernard, Bernardo; Lara-Puente, Horacio; Espitia, Clara; Alpuche-Aranda, Celia; Bonifaz, Laura C; Arriaga-Pizano, Lourdes; Pastelin-Palacios, Rodolfo; Isibasi, Armando; López-Macías, Constantino

    2016-01-01

    The influenza virus is a human pathogen that causes epidemics every year, as well as potential pandemic outbreaks, as occurred in 2009. Vaccination has proven to be sufficient in the prevention and containment of viral spreading. In addition to the current egg-based vaccines, new and promising vaccine platforms, such as cell culture-derived vaccines that include virus-like particles (VLPs), have been developed. VLPs have been shown to be both safe and immunogenic against influenza infections. Although antibody persistence has been studied in traditional egg-based influenza vaccines, studies on antibody response durations induced by VLP influenza vaccines in humans are scarce. Here, we show that subjects vaccinated with an insect cell-derived VLP vaccine, in the midst of the 2009 H1N1 influenza pandemic outbreak in Mexico City, showed antibody persistence up to 24 months post-vaccination. Additionally, we found that subjects that reported being revaccinated with a subsequent inactivated influenza virus vaccine showed higher antibody titres to the pandemic influenza virus than those who were not revaccinated. These findings provide insights into the duration of the antibody responses elicited by an insect cell-derived pandemic influenza VLP vaccine and the possible effects of subsequent influenza vaccination on antibody persistence induced by this VLP vaccine in humans.

  3. Persistent pulmonary interstitial emphysema in a case of Langerhans cell histiocytosis

    Directory of Open Access Journals (Sweden)

    Pooja Abbey

    2014-01-01

    Full Text Available We present the case of a 10-month-old boy with multisystem Langerhans cell histiocytosis showing thin-walled lung cysts along with computed tomography (CT evidence of persistent pulmonary interstitial emphysema (PPIE, in the absence of pneumothorax or pneumomediastinum. Follow-up CT performed after 6 months demonstrated complete resolution of interstitial emphysema.

  4. Persistent pulmonary interstitial emphysema in a case of Langerhans cell histiocytosis

    OpenAIRE

    Pooja Abbey; Mahender K Narula; Rama Anand; Jagdish Chandra

    2014-01-01

    We present the case of a 10-month-old boy with multisystem Langerhans cell histiocytosis showing thin-walled lung cysts along with computed tomography (CT) evidence of persistent pulmonary interstitial emphysema (PPIE), in the absence of pneumothorax or pneumomediastinum. Follow-up CT performed after 6 months demonstrated complete resolution of interstitial emphysema.

  5. Factors associated with persistence of red blood cell antibodies in woman after pregnancies complicated by fetal alloimmune haemolytic disease treated with intrauterine transfusions.

    Science.gov (United States)

    Verduin, Esther P; Brand, Anneke; van de Watering, Leo M G; Claas, Frans H J; Oepkes, Dick; Lopriore, Enrico; Doxiadis, Ilias I N; Schonewille, Henk

    2015-02-01

    Red blood cell (RBC) antibodies can persist for decades or decrease quickly to undetectable levels. Antibody persistence has not been systematically studied. Women whose children are treated with intrauterine transfusions (IUT) for haemolytic disease of the fetus (HDFN) often produce additional antibodies, which can be evoked by the intrauterine transfusion or by fetomaternal haemorrhage during the procedure. Factors associated with persistence of both the antibodies responsible for HDFN and additional antibodies were studied in 260 women whose children were treated with IUT between 1988 and 2008. They possessed 499 (205 anti-D and 294 non-D) antibodies after the last IUT. After a median follow-up of 8·7 years, all 260 antibodies primarily responsible for HDFN had persisted. Additional antibodies directed against antigens of the children persisted in 70·6%, and in 32·3% if they were not child-specific (P < 0·001). Antibodies induced by irradiated IUT persisted in only 7·1%. Multivariate analyses showed that non-HDFN antibody persistence was dependent on the antibody titre and specificity. In conclusion, persistence of antibodies mainly depends on antibody strength and specificity. Difference between fetal or non-fetal immunogens suggests maintenance of antigenic stimulation possibly by long-term fetomaternal chimerism. PMID:25244566

  6. Previously Homeschooled College Freshmen: Their First Year Experiences and Persistence Rates

    Science.gov (United States)

    Saunders, Mary K.

    2010-01-01

    Utilizing survey research on the entire 2004-2005 freshmen class of a private, interdenominational Christian college (n = 261), this study examined the social experiences and persistence rates of college freshmen who were homeschooled prior to attending higher education, and compared this group to college freshmen who were educated in a classroom…

  7. Three-Year Course of Cannabis Dependence and Prediction of Persistence

    NARCIS (Netherlands)

    P. van der Pol; N. Liebregts; R. de Graaf; D.J. Korf; W. van den Brink; M. van Laar

    2015-01-01

    Aims: To examine the course and the predictors of the persistence of cannabis dependence. Methods: Through cannabis outlets and chain referral, a prospective enriched community cohort of 207 young adults (aged 18-30) with DSM-IV cannabis dependence at baseline (T0) was formed and followed-up after 1

  8. Microrefugia and species persistence in the Galápagos highlands: a 26,000-year paleoecological perspective.

    Science.gov (United States)

    Collins, Aaron F; Bush, Mark B; Sachs, Julian P

    2013-01-01

    The Galápagos Islands are known to have experienced significant drought during the Quaternary. The loss of mesophytic upland habitats has been suggested to underlie the relatively lower endemism of upland compared with lowland plant assemblages. A fossil pollen record spanning the last 26,000 years from an upland bog on Santa Cruz Island, revealed the persistent presence of highland pollen and spore types during the last glacial maximum and a millennial-scale series of droughts in the mid Holocene. The absence of lowland taxa and presence of mesic taxa led to the conclusion that the highland flora of the Galápagos persisted during both these periods. The resiliency of the highland flora of the Galápagos to long-term drought contradicts an earlier hypothesis that an extinction of highland taxa occurred during the last glacial maximum and that rapid Holocene speciation created the modern plant assemblage within the last 10,000 years. Based on the palynological data, we suggest that, even during the height of glacial and Holocene droughts, cool sea-surface temperatures and strong trade-wind activity would have promoted persistent ground level cloudiness that provided the necessary moisture inputs to maintain microrefugia for mesophytic plants. Although moist conditions were maintained, the lack of precipitation caused the loss of open water habitat during such events, and accounts for the known extinctions of species such as Azolla sp., and Elatine sp., while other moisture dependent taxa, i.e., Cyathea weatherbyana, persisted.

  9. 25 YEARS OF EPIDERMAL STEM CELLS

    OpenAIRE

    Ghadially, Ruby

    2011-01-01

    This is a chronicle of concepts in the field of epidermal stem cell biology and a historic look at their development over time. The last 25 years have seen the evolution of epidermal stem cell science, from first fundamental studies to a sophisticated science. The study of epithelial stem cell biology was aided by the ability to visualize the distribution of stem cells and their progeny through lineage analysis studies. The excellent progress we have made in understanding epidermal stem cell ...

  10. Rapid cell variation can determine the establishment of a persistent viral infection.

    OpenAIRE

    Martín-Hernández, Ana M.; Carrillo, Elisa C.; Sevilla, Noemí; Domingo, Esteban

    1994-01-01

    Evidence for a mechanism of initiation of viral persistence in which the cell, and not the virus, plays a critical role has been obtained using the important animal pathogen foot-and-mouth disease virus (FMDV). We have developed a virulence assay consisting of quantification of the ability of virus to kill cells and of cells to divide in the presence of virus and to initiate a carrier state. Cells were cured of FMDV at early times following a cytolytic infection of BHK-21 monolayers with FMDV...

  11. Persistent posttetanic depression at cerebellar parallel fiber to Purkinje cell synapses.

    Directory of Open Access Journals (Sweden)

    Astrid Bergerot

    Full Text Available Plasticity at the cerebellar parallel fiber to Purkinje cell synapse may underlie information processing and motor learning. In vivo, parallel fibers appear to fire in short high frequency bursts likely to activate sparsely distributed synapses over the Purkinje cell dendritic tree. Here, we report that short parallel fiber tetanic stimulation evokes a ∼7-15% depression which develops over 2 min and lasts for at least 20 min. In contrast to the concomitantly evoked short-term endocannabinoid-mediated depression, this persistent posttetanic depression (PTD does not exhibit a dependency on the spatial pattern of synapse activation and is not caused by any detectable change in presynaptic calcium signaling. This persistent PTD is however associated with increased paired-pulse facilitation and coefficient of variation of synaptic responses, suggesting that its expression is presynaptic. The chelation of postsynaptic calcium prevents its induction, suggesting that post- to presynaptic (retrograde signaling is required. We rule out endocannabinoid signaling since the inhibition of type 1 cannabinoid receptors, monoacylglycerol lipase or vanilloid receptor 1, or incubation with anandamide had no detectable effect. The persistent PTD is maximal in pre-adolescent mice, abolished by adrenergic and dopaminergic receptors block, but unaffected by adrenergic and dopaminergic agonists. Our data unveils a novel form of plasticity at parallel fiber synapses: a persistent PTD induced by physiologically relevant input patterns, age-dependent, and strongly modulated by the monoaminergic system. We further provide evidence supporting that the plasticity mechanism involves retrograde signaling and presynaptic diacylglycerol.

  12. T Cell Memory in the Context of Persistent Herpes Viral Infections

    Directory of Open Access Journals (Sweden)

    Nicole Torti

    2012-07-01

    Full Text Available The generation of a functional memory T cell pool upon primary encounter with an infectious pathogen is, in combination with humoral immunity, an essential process to confer protective immunity against reencounters with the same pathogen. A prerequisite for the generation and maintenance of long-lived memory T cells is the clearance of antigen after infection, which is fulfilled upon resolution of acute viral infections. Memory T cells play also a fundamental role during persistent viral infections by contributing to relative control and immuosurveillance of active replication or viral reactivation, respectively. However, the dynamics, the phenotype, the mechanisms of maintenance and the functionality of memory T cells which develop upon acute/resolved infection as opposed to chronic/latent infection differ substantially. In this review we summarize current knowledge about memory CD8 T cell responses elicited during α-, β-, and γ-herpes viral infections with major emphasis on the induction, maintenance and function of virus-specific memory CD8 T cells during viral latency and we discuss how the peculiar features of these memory CD8 T cell responses are related to the biology of these persistently infecting viruses.

  13. Montelukast, a leukotriene receptor antagonist, for the treatment of persistent asthma in children aged 2 to 5 years

    DEFF Research Database (Denmark)

    Knorr, B; Franchi, L M; Bisgaard, H;

    2001-01-01

    BACKGROUND: The greatest prevalence of asthma is in preschool children; however, the clinical utility of asthma therapy for this age group is limited by a narrow therapeutic index, long-term tolerability, and frequency and/or difficulty of administration. Inhaled corticosteroids and inhaled...... cromolyn are the most commonly prescribed controller therapies for young children with persistent asthma, although very young patients may have difficulty using inhalers, and dose delivery can be variable. Moreover, reduced compliance with inhaled therapy relative to orally administered therapy has been....... To our knowledge, this represents the first large, multicenter study to address the effects of a leukotriene receptor antagonist in children younger than 5 years of age with persistent asthma, as well as one of the few asthma studies that incorporated end points validated for use in preschool children...

  14. Pilot study of a cell phone-based exercise persistence intervention post-rehabilitation for COPD

    OpenAIRE

    Nguyen, Huong Q.; Gill, Dawn P; Wolpin, Seth; Steele, Bonnie G; Benditt, Joshua O.

    2009-01-01

    Objective To determine the feasibility and efficacy of a six-month, cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease (COPD) following pulmonary rehabilitation. Methods Participants who completed a two-week run-in were randomly assigned to either MOBILE-Coached (n = 9) or MOBILE-Self-Monitored (n = 8). All participants met with a nurse to develop an individualized exercise plan, were issued a pedometer and exercise booklet, and instruct...

  15. Microrefugia and species persistence in the Galápagos highlands: a 26,000-year paleoecological perspective.

    Science.gov (United States)

    Collins, Aaron F; Bush, Mark B; Sachs, Julian P

    2013-01-01

    The Galápagos Islands are known to have experienced significant drought during the Quaternary. The loss of mesophytic upland habitats has been suggested to underlie the relatively lower endemism of upland compared with lowland plant assemblages. A fossil pollen record spanning the last 26,000 years from an upland bog on Santa Cruz Island, revealed the persistent presence of highland pollen and spore types during the last glacial maximum and a millennial-scale series of droughts in the mid Holocene. The absence of lowland taxa and presence of mesic taxa led to the conclusion that the highland flora of the Galápagos persisted during both these periods. The resiliency of the highland flora of the Galápagos to long-term drought contradicts an earlier hypothesis that an extinction of highland taxa occurred during the last glacial maximum and that rapid Holocene speciation created the modern plant assemblage within the last 10,000 years. Based on the palynological data, we suggest that, even during the height of glacial and Holocene droughts, cool sea-surface temperatures and strong trade-wind activity would have promoted persistent ground level cloudiness that provided the necessary moisture inputs to maintain microrefugia for mesophytic plants. Although moist conditions were maintained, the lack of precipitation caused the loss of open water habitat during such events, and accounts for the known extinctions of species such as Azolla sp., and Elatine sp., while other moisture dependent taxa, i.e., Cyathea weatherbyana, persisted. PMID:24348520

  16. Microrefugia and species persistence in the Galápagos highlands: A 26,000-year paleoecological perspective.

    Directory of Open Access Journals (Sweden)

    Aaron F Collins

    2013-12-01

    Full Text Available The Galápagos Islands are known to have experienced significant drought during the Quaternary. The loss of mesophytic upland habitats has been suggested to underlie the relatively lower endemism of upland compared with lowland plant assemblages. A fossil pollen record spanning the last 26,000 years from an upland bog on Santa Cruz Island, revealed the persistent presence of highland pollen and spore types during the last glacial maximum and a millennial-scale series of droughts in the mid Holocene. The absence of lowland taxa and presence of mesic taxa led to the conclusion that the highland flora of the Galápagos persisted during both these periods. The resiliency of the highland flora of the Galápagos to long-term drought contradicts an earlier hypothesis that an extinction of highland taxa occurred during the last glacial maximum and that rapid Holocene speciation created the modern plant assemblage within the last 10,000 years. Based on the palynological data, we suggest that, even during the height of glacial and Holocene droughts, cool sea-surface temperatures and strong trade-wind activity would have promoted persistent ground level cloudiness that provided the necessary moisture inputs to maintain microrefugia for mesophytic plants. Although moist conditions were maintained, the lack of precipitation caused the loss of open water habitat during such events, and accounts for the known extinctions of species such as Azolla sp., and Elatine sp., while other moisture dependent taxa, i.e. Cyathea weatherbyana, persisted.

  17. Effect of clpP and clpC deletion on persister cell number in Staphylococcus aureus.

    Science.gov (United States)

    Springer, Matthew T; Singh, Vineet K; Cheung, Ambrose L; Donegan, Niles P; Chamberlain, Neal R

    2016-08-01

    Staphylococcus aureus is responsible for a wide variety of infections that include superficial skin and soft tissue infections, septicaemia, central nervous system infections, endocarditis, osteomyelitis and pneumonia. Others have demonstrated the importance of toxin-antitoxin (TA) modules in the formation of persisters and the role of the Clp proteolytic system in the regulation of these TA modules. This study was conducted to determine the effect of clpP and clpC deletion on S. aureus persister cell numbers following antibiotic treatment. Deletion of clpP resulted in a significant decrease in persister cells following treatment with oxacillin and erythromycin but not with levofloxacin and daptomycin. Deletion of clpC resulted in a decrease in persister cells following treatment with oxacillin. These differences were dependent on the antibiotic class and the CFU ml-1 in which the cells were treated. Persister revival assays for all the bacterial strains in these studies demonstrated a significant delay in resumption of growth characteristic of persister cells, indicating that the surviving organisms in this study were not likely due to spontaneous antibiotic resistance. Based on our results, ClpP and possibly ClpC play a role in persister cell formation or maintenance, and this effect is dependent on antibiotic class and the CFU ml-1 or the growth phase of the cells.

  18. An electron microscopic study of MDBK cells persistently infected with Newcastle disease virus.

    Science.gov (United States)

    McNulty, M S; Gowans, E J; Louza, A C; Fraser, G

    1977-01-01

    Ultrastructural examination of a line of MDBK cells persistently infected with Newcastle disease virus (MDBKpi cells) revealed the presence of cytoplasmic aggregates of both smooth and granular nucleocapsids. Only granular nucleocapsids aligned under modified areas of plasma membrane and were incorporated into virus particles. On the grounds of morphogenesis, there was no apparent explanation for the persistent, not-cytocidal nature of the infection. Both nuclear and cytoplasmic aggregates of smooth nucleocapsids were present in MDBKpi cells which had been held without subculture for between 40 and 130 days (aged MDBKpi cells). Modified areas of plasma membrane with associated alignment of nucleocapsids were not present in aged MDBKpi cells, and neither budding nor released virus particles were observed, indicating a block in virus maturation. It is suggested that the granular material coating granular nucleocapsids allows them to interact with modified areas of plasma membrane, thereby inducing virus budding. A deficiency of this material, as apparently occurs in aged MDBKpi cells, would therefore cause a block in virus maturation. The nature of this granular material is discussed, and we suggest that it consists of M protein.

  19. Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Yan Nan; Shin, Hyun-Jin; Joo, Hyun-Yoo; Park, Eun-Ran; Kim, Su-Hyeon; Hwang, Sang-Gu [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Park, Sang Jun; Kim, Chun-Ho [Laboratory of Tissue Engineering, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of); Lee, Kee-Ho, E-mail: khlee@kirams.re.kr [Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706 (Korea, Republic of)

    2014-01-17

    Highlights: •HAS2 may be a promising target for the radiosensitization of human cancer. •HAS2 is elevated (up to ∼10-fold) in irradiated radioresistant and -sensitive cancer cells. •HAS2 knockdown sensitizes cancer cells to radiation. •HAS2 knockdown potentiates irradiation-induced DNA damage and apoptotic death. •Thus, the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. -- Abstract: Hyaluronan synthase 2 (HAS2), a synthetic enzyme for hyaluronan, regulates various aspects of cancer progression, including migration, invasion and angiogenesis. However, the possible association of HAS2 with the response of cancer cells to anticancer radiotherapy, has not yet been elucidated. Here, we show that HAS2 knockdown potentiates irradiation-induced DNA damage and apoptosis in cancer cells. Upon exposure to radiation, all of the tested human cancer cell lines exhibited marked (up to 10-fold) up-regulation of HAS2 within 24 h. Inhibition of HAS2 induction significantly reduced the survival of irradiated radioresistant and -sensitive cells. Interestingly, HAS2 depletion rendered the cells to sustain irradiation-induced DNA damage, thereby leading to an increase of apoptotic death. These findings indicate that HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage, further suggesting that the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. Thus, HAS2 could potentially be targeted for therapeutic interventions aimed at radiosensitizing cancer cells.

  20. Persistence of Multidrug-Resistant Acinetobacter baumannii Isolates Harboring blaOXA-23 and bap for 5 Years.

    Science.gov (United States)

    Sung, Ji Youn; Koo, Sun Hoe; Kim, Semi; Kwon, Gye Cheol

    2016-08-28

    The emergence and dissemination of carbapenemase-producing Acinetobacter baumannii isolates have been reported worldwide, and A. baumannii isolates harboring blaOXA-23 are often resistant to various antimicrobial agents. Antimicrobial resistance can be particularly strong for biofilm-forming A. baumannii isolates. We investigated the genetic basis for carbapenem resistance and biofilm-forming ability of multidrug-resistant (MDR) clinical isolates. Ninety-two MDR A. baumannii isolates were collected from one university hospital located in the Chungcheong area of Korea over a 5-year period. Multiplex PCR and DNA sequencing were performed to characterize carbapenemase and bap genes. Clonal characteristics were analyzed using REP-PCR. In addition, imaging and quantification of biofilms were performed using a crystal violet assay. All 92 MDR A. baumannii isolates involved in our study contained the blaOXA-23 and bap genes. The average absorbance of biomass in Bap-producing strains was much greater than that in non-Bap-producing strains. In our study, only three REP-PCR types were found, and the isolates showing type A or type B were found more than 60 times among unique patients during the 5 years of surveillance. These results suggest that the isolates have persisted and colonized for 5 years, and biofilm formation ability has been responsible for their persistence and colonization.

  1. Persistent Inflammation and Endothelial Activation in HIV-1 Infected Patients after 12 Years of Antiretroviral Therapy

    DEFF Research Database (Denmark)

    Rönsholt, Frederikke F; Ullum, Henrik; Katzenstein, Terese L;

    2013-01-01

    The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART).......The study investigated markers of inflammation and endothelial activation in HIV infected patients after 12 years of successful combination antiretroviral treatment (cART)....

  2. Persistence of immunoglobulin M or immunoglobulin G antibody responses to Borrelia burgdorferi 10-20 years after active Lyme disease.

    Science.gov (United States)

    Kalish, R A; McHugh, G; Granquist, J; Shea, B; Ruthazer, R; Steere, A C

    2001-09-15

    The interpretation of serological results for patients who had Lyme disease many years ago is not well defined. We studied the serological status of 79 patients who had had Lyme disease 10-20 years ago and did not currently have signs or symptoms of active Lyme disease. Of the 40 patients who had had early Lyme disease alone, 4 (10%) currently had IgM responses to Borrelia burgdorferi, and 10 (25%) still had IgG reactivity to the spirochete, as determined by a 2-test approach (enzyme-linked immunosorbent assay and Western blot). Of the 39 patients who had had Lyme arthritis, 6 (15%) currently had IgM responses and 24 (62%) still had IgG reactivity to the spirochete. IgM or IgG antibody responses to B. burgdorferi may persist for 10-20 years, but these responses are not indicative of active infection.

  3. Persistence and Adaptation in Immunity: T Cells Balance the Extent and Thoroughness of Search.

    Directory of Open Access Journals (Sweden)

    G Matthew Fricke

    2016-03-01

    Full Text Available Effective search strategies have evolved in many biological systems, including the immune system. T cells are key effectors of the immune response, required for clearance of pathogenic infection. T cell activation requires that T cells encounter antigen-bearing dendritic cells within lymph nodes, thus, T cell search patterns within lymph nodes may be a crucial determinant of how quickly a T cell immune response can be initiated. Previous work suggests that T cell motion in the lymph node is similar to a Brownian random walk, however, no detailed analysis has definitively shown whether T cell movement is consistent with Brownian motion. Here, we provide a precise description of T cell motility in lymph nodes and a computational model that demonstrates how motility impacts T cell search efficiency. We find that both Brownian and Lévy walks fail to capture the complexity of T cell motion. Instead, T cell movement is better described as a correlated random walk with a heavy-tailed distribution of step lengths. Using computer simulations, we identify three distinct factors that contribute to increasing T cell search efficiency: 1 a lognormal distribution of step lengths, 2 motion that is directionally persistent over short time scales, and 3 heterogeneity in movement patterns. Furthermore, we show that T cells move differently in specific frequently visited locations that we call "hotspots" within lymph nodes, suggesting that T cells change their movement in response to the lymph node environment. Our results show that like foraging animals, T cells adapt to environmental cues, suggesting that adaption is a fundamental feature of biological search.

  4. The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells.

    Directory of Open Access Journals (Sweden)

    Conrad von Schubert

    Full Text Available The protozoan parasite Theileria inhabits the host cell cytoplasm and possesses the unique capacity to transform the cells it infects, inducing continuous proliferation and protection against apoptosis. The transforming schizont is a multinucleated syncytium that resides free in the host cell cytoplasm and is strictly intracellular. To maintain transformation, it is crucial that this syncytium is divided over the two daughter cells at each host cell cytokinesis. This process was dissected using different cell cycle synchronization methods in combination with the targeted application of specific inhibitors. We found that Theileria schizonts associate with newly formed host cell microtubules that emanate from the spindle poles, positioning the parasite at the equatorial region of the mitotic cell where host cell chromosomes assemble during metaphase. During anaphase, the schizont interacts closely with host cell central spindle. As part of this process, the schizont recruits a host cell mitotic kinase, Polo-like kinase 1, and we established that parasite association with host cell central spindles requires Polo-like kinase 1 catalytic activity. Blocking the interaction between the schizont and astral as well as central spindle microtubules prevented parasite segregation between the daughter cells during cytokinesis. Our findings provide a striking example of how an intracellular eukaryotic pathogen that evolved ways to induce the uncontrolled proliferation of the cells it infects usurps the host cell mitotic machinery, including Polo-like kinase 1, one of the pivotal mitotic kinases, to ensure its own persistence and survival.

  5. Human T cell aging and the impact of persistent viral infections

    Directory of Open Access Journals (Sweden)

    Tamas eFulop

    2013-09-01

    Full Text Available Aging is associated with a dysregulation of the immune response, loosely termed immunosenescence. Each part of the immune system is influenced to some extent by the aging process. However, adaptive immunity seems more extensively affected and among all participating cells it is the T cells that are most altered. There is a large body of experimental work devoted to the investigation of age-associated differences in T cell phenotypes and functions in young and old individuals, but few longitudinal studies in humans actually delineating changes at the level of the individual. In most studies, the number and proportion of late-differentiated T cells, especially CD8+ T cells, is reported to be higher in the elderly than in the young. Limited longitudinal studies suggest that accumulation of these cells is a dynamic process and does indeed represent an age-associated change. Accumulations of such late-stage cells may contribute to the enhanced systemic pro-inflammatory milieu commonly seen in older people. We do not know exactly what causes these observed changes, but an understanding of the possible causes is now beginning to emerge. A favored hypothesis is that these events are at least partly due to the effects of the maintenance of essential immune surveillance against persistent viral infections, notably Cytomegalovirus (CMV, which may exhaust the immune system over time. It is still a matter of debate as to whether these changes are compensatory and beneficial or pathological and detrimental to the proper functioning of the immune system and whether they impact longevity. Here, we will review present knowledge of T cell changes with aging and their relation to chronic viral and possibly other persistent infections.

  6. The persistence of predictors of wellbeing among refugee youth eight years after resettlement in Melbourne, Australia.

    Science.gov (United States)

    Correa-Velez, Ignacio; Gifford, Sandra M; McMichael, Celia

    2015-10-01

    This short report assesses the predictors of subjective health and happiness among a cohort of refugee youth over their first eight years in Australia. Five waves of data collection were conducted between 2004 (n = 120) and 2012-13 (n = 51) using mixed methods. Previous schooling, self-esteem, moving house in the previous year, a supportive social environment, stronger ethnic identity and perceived discrimination were significant predictors of wellbeing after adjusting for demographic and pre-migration factors. When compared with a previous analysis of this cohort over their first three years of settlement, experiences of social exclusion still have a significant impact on wellbeing eight years after arriving in Australia. This study contributes to mounting evidence in support of policies that discourage discrimination and promote social inclusion and cultural diversity and which underpin the wellbeing of resettled refugee youth. PMID:26310592

  7. Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist.

    Science.gov (United States)

    Damond, Nicolas; Thorel, Fabrizio; Moyers, Julie S; Charron, Maureen J; Vuguin, Patricia M; Powers, Alvin C; Herrera, Pedro L

    2016-01-01

    Glucagon secretion dysregulation in diabetes fosters hyperglycemia. Recent studies report that mice lacking glucagon receptor (Gcgr(-/-)) do not develop diabetes following streptozotocin (STZ)-mediated ablation of insulin-producing β-cells. Here, we show that diabetes prevention in STZ-treated Gcgr(-/-) animals requires remnant insulin action originating from spared residual β-cells: these mice indeed became hyperglycemic after insulin receptor blockade. Accordingly, Gcgr(-/-) mice developed hyperglycemia after induction of a more complete, diphtheria toxin (DT)-induced β-cell loss, a situation of near-absolute insulin deficiency similar to type 1 diabetes. In addition, glucagon deficiency did not impair the natural capacity of α-cells to reprogram into insulin production after extreme β-cell loss. α-to-β-cell conversion was improved in Gcgr(-/-) mice as a consequence of α-cell hyperplasia. Collectively, these results indicate that glucagon antagonism could i) be a useful adjuvant therapy in diabetes only when residual insulin action persists, and ii) help devising future β-cell regeneration therapies relying upon α-cell reprogramming. PMID:27092792

  8. iPS Cells 10 Years Later.

    Science.gov (United States)

    2016-09-01

    In 2006, Takahashi and Yamanaka reported the breakthrough discovery of induction of pluripotent stem cells from fibroblasts by a combination of defined factors. Ten years later, Cell editor João Monteiro brings together Shinya Yamanaka and Hans Schöler, one the original reviewers of the landmark study, to revisit the history behind the paper and its long-lasting legacy. PMID:27610558

  9. No evidence of persistent parvovirus B19 viremia among Iranian patients with HIV after a 1-year follow-up.

    Science.gov (United States)

    Aghakhani, Arezoo; Mohraz, Minoo; Azadmanesh, Kayhan; Moayedi-Nia, Saeedeh; Kazemimanesh, Monireh; Mamishi, Setareh; Banifazl, Mohammad; Ramezani, Amitis

    2016-05-01

    Recent studies have demonstrated that, in common with other latent viruses, parvovirus B19 infection can be controlled by the host immune response but may persist in some places such as the bone marrow. Persistent B19 infection has been found in both immunocompetent and immunocompromised individuals, such as patients infected with human immunodeficiency virus (HIV). However, there is limited data regarding long-term B19 viremia in HIV patients. In this study, we investigated virological and hematological findings, and also the clinical outcome, of seven cases of HIV/B19 coinfection (confirmed by PCR) after one year. These cases were provided from a previous study on patients with HIV infection that found B19 DNA in 13 cases. Seven of these 13 patients were available after 1 year, and we retested them for B19 viremia and B19-specific antibodies. B19 IgG was tested by ELISA, and B19 DNA was assessed by nested PCR. Anemia was not observed in these cases. All subjects had cleared viremia, but B19 IgG seroconversion occurred in two cases. No significant changes in CD4 and hemoglobin occurred. The results of this study indicate that B19 infection in HIV patients is a subtle infection and that B19 viremia is not a long-term event. PMID:26860911

  10. Genetic relationship of lactation persistency with milk yield, somatic cell score, reproductive traits, and longevity in Slovak Holstein cattle

    OpenAIRE

    Strapáková, Eva; Candrák, Juraj; Strapák, Peter

    2016-01-01

    The objective of this study was to estimate the breeding values (BVs) of lactation persistency, the test day of milk yield, the somatic cell score, reproductive traits (calving interval, days open), longevity in Slovak Holstein dairy cattle. BVs were used for the detection of relationships among the persistency of lactation and other selected traits. Data for the estimation of BVs of milk production and somatic cell score were collected from 855 240 cows. BVs for reproductive t...

  11. Blood Patch Pleurodesis in the Treatment of Persistant Air Leakage in Langerhans Cell Histiocytosis; A Case Report

    Directory of Open Access Journals (Sweden)

    Ayse Baccioglu

    2013-08-01

    Full Text Available Pulmonary langerhans cell histiocytosis is a rare reactive disorder with unclear pathogenesis. 16-year-old male patient complained about shortness of breath induced with exercise, non-productive cough, and intermittent chest pain for one year. Pulmonary function tests were in restrictive nature. There were multiple air cysts in lung parenchyma smaller than one cm and minimal pneumothorax on the left hemithorax in high resolution computed tomography of thorax. There was no hypoxemia in arterial blood gas analysis, and no pulmonary hypertension in echocardiography. Pulmonary langerhans cell histiocytosis was diagnosed with clinical features and typical radiographic appearance. Existence of multisystem langerhans cell histiocytosis was excluded thorough a detailed history, comprehensive physical examination, and baseline radiographic, blood and urine tests. He was recommended to quit smoking and close follow-up was planned. A tube thoracostomy was performed for left sided total pneumothorax one month later, and %u201Cblood patch%u201D pleurodesis was done due to persistent air leakage with a successful outcome. As far as we know this is the first case report of pulmonary langerhans cell histiocytosis who was treated with autologous blood pleurodesis in the literature.

  12. Prenatal exposure to persistent organochlorine pollutants is associated with high insulin levels in 5-year-old girls

    DEFF Research Database (Denmark)

    Tang-Péronard, Jeanett L.; Heitmann, Berit L.; Jensen, Tina K.;

    2015-01-01

    BACKGROUND: Several persistent organochlorine pollutants (POPs) possess endocrine disrupting abilities, thereby potentially leading to an increased risk of obesity and metabolic diseases, especially if the exposure occurs during prenatal life. We have previously found associations between prenatal......-year-old children, thus possibly mediating the association with overweight and obesity at 7 years of age. METHODS: The analyses were based on a prospective Faroese Birth Cohort (n=656), recruited between 1997 and 2000. Major POPs, polychlorinated biphenyls (PCBs), p...... to girls in the lowest quartile. No significant associations were observed with leptin, or among boys. A mediating effect of insulin or leptin on later obesity was not observed. CONCLUSION: These findings suggest, that for girls, prenatal exposure to POPs may play a role for later development of metabolic...

  13. Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection.

    Science.gov (United States)

    Lang, P A; Meryk, A; Pandyra, A A; Brenner, D; Brüstle, A; Xu, H C; Merches, K; Lang, F; Khairnar, V; Sharma, P; Funkner, P; Recher, M; Shaabani, N; Duncan, G S; Duhan, V; Homey, B; Ohashi, P S; Häussinger, D; Knolle, P A; Honke, N; Mak, T W; Lang, K S

    2015-01-01

    During virus infection and autoimmune disease, inflammatory dendritic cells (iDCs) differentiate from blood monocytes and infiltrate infected tissue. Following acute infection with hepatotropic viruses, iDCs are essential for re-stimulating virus-specific CD8(+) T cells and therefore contribute to virus control. Here we used the lymphocytic choriomeningitis virus (LCMV) model system to identify novel signals, which influence the recruitment and activation of iDCs in the liver. We observed that intrinsic expression of Toso (Faim3, FcμR) influenced the differentiation and activation of iDCs in vivo and DCs in vitro. Lack of iDCs in Toso-deficient (Toso(-/-)) mice reduced CD8(+) T-cell function in the liver and resulted in virus persistence. Furthermore, Toso(-/-) DCs failed to induce autoimmune diabetes in the rat insulin promoter-glycoprotein (RIP-GP) autoimmune diabetes model. In conclusion, we found that Toso has an essential role in the differentiation and maturation of iDCs, a process that is required for the control of persistence-prone virus infection. PMID:25257173

  14. Pilot study of a cell phone-based exercise persistence intervention post-rehabilitation for COPD

    OpenAIRE

    Nguyen, Huong Q.; Gill, Dawn P; Seth Wolpin; et al.

    2009-01-01

    Huong Q Nguyen1, Dawn P Gill1, Seth Wolpin1, Bonnie G Steele2, Joshua O Benditt11University of Washington, seattle, WA, USA; 2VA Puget Sound Health Care System, Seattle, WA, USAObjective: To determine the feasibility and efficacy of a six-month, cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease (COPD) following pulmonary rehabilitation.Methods: Participants who completed a two-week run-in were randomly assigned to either MOBILE...

  15. Persistent infections of fish cell lines by paramyxovirus isolates from Chinook salmon (Oncorhynchus tschawytscha)

    Science.gov (United States)

    Lannan, C.N.

    1989-01-01

    We have reported the isolation of a paramyxovirus from stocks of adult chinook salmon (Oncorhynchus tshawytscha) returning to coastal rivers of Oregon, USA (Winton et al 1985). The isolates were obtained from kidney and spleen tissues using the chinook salmon embryo cell line, CHSE-214. Initial cytopathic effect (CPE) was slow to develop, requiring 28 days incubation at 18°C. The virus replicated in CHSE-214, chum heart (CHH-1), kokanee ovary (K0-6), coho salmon embryo (CSE-119), and fathead minnow (FHM) cell lines where it produced a lytic type of CPE.The virus was stable at pH 3-11 and iodo-deoxyuridine did not inhibit wiral replication. Infectivity was lost after treatment with chloroform indicating the presence of essential lipids. The density of virions in CsCl was 1.2 g/ml. The virus hemagglutinated cells of 11 of 14 species of birds, mammals, and fish tested. Electron microscopy of infected cells revealed enveloped particles 125-250 nm in dia. containing coiled nucleocapsids and examination of freon-treated virions showed the nucleocapsid was a helix approximately 18 nm in dia. and > 1000 nm in length (Winton et al 1985).In addition to causing hemagglutination, members of the Paramyxoviridae are known for the ability to establish persistent infections of cell lines (Choppin and Compans 1975). The purpose of this study was to determine if the paramyxovirus isolates from salmon were able to establish persistent infections in fish cell lines and to study the nature of the infection.

  16. An examination of the impact of a first year experience course on STEM persistence

    Science.gov (United States)

    Welchert, Tammy S.

    A review of STEM literature indicates that increased attention is being paid to STEM initiatives particularly with K-12 teachers and programs designed to foster interest in STEM fields at the secondary education level, both of which feed the STEM pipeline. The President of the United States, Barack Obama, Presidents of Higher Education Institutions, and an increased global awareness of the shortfall of workers in the STEM pipeline are driving the increased attention. Recognition that an inability to meet STEM workforce demands may jeopardize the position of the United States as a world leader is significant. The purpose of this study was to examine the impact of a first year experience course, Biology 115: First Year Seminar, specifically with regards to academic performance and retention, and to evaluate how the impact changes when course instruction was delivered in a 16-week versus an 8-week model. Three sample groups (N = 596) consisting of first time college freshmen declared as biology majors from 2005-2012 at the University of Missouri-Kansas City were selected for participation. Data was collected from student's high school and college transcripts and college applications by the Office of Institutional Research. A three phase analysis including descriptive statistics and t-tests, principle component analysis, and binary logistic regression were performed using a hierarchical model informed by Alexander Astins' Input-Environment-Output model. The majority of students were female, residents of the State of Missouri, and White. Analysis results indicated that students enrolled in the Biology 115 course earned higher grade point averages, were in better academic standing, and were retained at a higher level than the control group. Additionally, students enrolled in the course in the 8-Week model earned higher grade point averages and had higher retention from Year 1 to Year 2 and retention as biology majors over the 16-week model.

  17. Scrapie Agent (Strain 263K) Can Transmit Disease via the Oral Route after Persistence in Soil over Years

    Science.gov (United States)

    Groschup, Martin H.; Peters, Rainer; Beekes, Michael; Terytze, Konstantin

    2007-01-01

    The persistence of infectious biomolecules in soil constitutes a substantial challenge. This holds particularly true with respect to prions, the causative agents of transmissible spongiform encephalopathies (TSEs) such as scrapie, bovine spongiform encephalopathy (BSE), or chronic wasting disease (CWD). Various studies have indicated that prions are able to persist in soil for years without losing their pathogenic activity. Dissemination of prions into the environment can occur from several sources, e.g., infectious placenta or amniotic fluid of sheep. Furthermore, environmental contamination by saliva, excrements or non-sterilized agricultural organic fertilizer is conceivable. Natural transmission of scrapie in the field seems to occur via the alimentary tract in the majority of cases, and scrapie-free sheep flocks can become infected on pastures where outbreaks of scrapie had been observed before. These findings point to a sustained contagion in the environment, and notably the soil. By using outdoor lysimeters, we simulated a contamination of standard soil with hamster-adapted 263K scrapie prions, and analyzed the presence and biological activity of the soil-associated PrPSc and infectivity by Western blotting and hamster bioassay, respectively. Our results showed that 263K scrapie agent can persist in soil at least over 29 months. Strikingly, not only the contaminated soil itself retained high levels of infectivity, as evidenced by oral administration to Syrian hamsters, but also feeding of aqueous soil extracts was able to induce disease in the reporter animals. We could also demonstrate that PrPSc in soil, extracted after 21 months, provides a catalytically active seed in the protein misfolding cyclic amplification (PMCA) reaction. PMCA opens therefore a perspective for considerably improving the detectability of prions in soil samples from the field. PMID:17502917

  18. Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy.

    Directory of Open Access Journals (Sweden)

    Libin Rong

    2009-10-01

    Full Text Available Although potent combination therapy is usually able to suppress plasma viral loads in HIV-1 patients to below the detection limit of conventional clinical assays, a low level of viremia frequently can be detected in plasma by more sensitive assays. Additionally, many patients experience transient episodes of viremia above the detection limit, termed viral blips, even after being on highly suppressive therapy for many years. An obstacle to viral eradication is the persistence of a latent reservoir for HIV-1 in resting memory CD4(+ T cells. The mechanisms underlying low viral load persistence, slow decay of the latent reservoir, and intermittent viral blips are not fully characterized. The quantitative contributions of residual viral replication to viral and the latent reservoir persistence remain unclear. In this paper, we probe these issues by developing a mathematical model that considers latently infected cell activation in response to stochastic antigenic stimulation. We demonstrate that programmed expansion and contraction of latently infected cells upon immune activation can generate both low-level persistent viremia and intermittent viral blips. Also, a small fraction of activated T cells revert to latency, providing a potential to replenish the latent reservoir. By this means, occasional activation of latently infected cells can explain the variable decay characteristics of the latent reservoir observed in different clinical studies. Finally, we propose a phenomenological model that includes a logistic term representing homeostatic proliferation of latently infected cells. The model is simple but can robustly generate the multiphasic viral decline seen after initiation of therapy, as well as low-level persistent viremia and intermittent HIV-1 blips. Using these models, we provide a quantitative and integrated prospective into the long-term dynamics of HIV-1 and the latent reservoir in the setting of potent antiretroviral therapy.

  19. Fifty years of dielectrophoretic cell separation technology

    Science.gov (United States)

    Hughes, Michael P.

    2016-01-01

    In 1966, Pohl and Hawk [Science 152, 647–649 (1966)] published the first demonstration of dielectrophoresis of living and dead yeast cells; their paper described how the different ways in which the cells responded to an applied nonuniform electric field could form the basis of a cell separation method. Fifty years later, the field of dielectrophoretic (DEP) cell separation has expanded, with myriad demonstrations of its ability to sort cells on the basis of differences in electrical properties without the need for chemical labelling. As DEP separation enters its second half-century, new approaches are being found to move the technique from laboratory prototypes to functional commercial devices; to gain widespread acceptance beyond the DEP community, it will be necessary to develop ways of separating cells with throughputs, purities, and cell recovery comparable to gold-standard techniques in life sciences, such as fluorescence- and magnetically activated cell sorting. In this paper, the history of DEP separation is charted, from a description of the work leading up to the first paper, to the current dual approaches of electrode-based and electrodeless DEP separation, and the path to future acceptance outside the DEP mainstream is considered. PMID:27462377

  20. Persistent oral health disparity in 12-year-old Hispanics: a cross-sectional study

    OpenAIRE

    Elias-Boneta, Augusto R.; Toro, Milagros J; Rivas-Tumanyan, Sona; Murillo, Margarita; Orraca, Luis; Encarnacion, Angeliz; Cernigliaro, Dana; Toro-Vizcarrondo, Carlos; Psoter, Walter J.

    2016-01-01

    Background Dental caries is the most prevalent chronic illness worldwide. In the US dental caries has been described as a “silent epidemic”, affecting 58.2 % of 12–15 year-olds, particularly in minority and immigrant groups. Caries is associated with complex yet preventable biological and behavioral factors such as dental plaque and diet, as well as social determinants of health. In developed nations, a higher risk caries has been associated with populations of low socio-economic status (SES)...

  1. Persistence of Neutralizing Antibody Against Dengue Virus 2 After 70 Years from Infection in Nagasaki.

    Science.gov (United States)

    Ngwe Tun, Mya Myat; Muta, Yoshihito; Inoue, Shingo; Morita, Kouichi

    2016-01-01

    This study aimed to investigate the duration of humoral immune responses to dengue virus (DENV) infection in Japanese who experienced acute febrile illness with hemorrhagic manifestations 70 years ago, when an epidemic of dengue occurred in Nagasaki, Japan, from 1942 to 1944. A Japanese volunteer requested serological diagnosis of DENV infection in 2014 and donated blood sample to measure the antibody titer against DENV by antiflavi IgG indirect ELISA, focus reduction neutralization test, and plaque reduction neutralization test. The serum sample of the volunteer was positive in flavi IgG ELISA and it indicated primary infection. In the neutralization test, the highest neutralizing titer was ≥218 for DENV-2. We report here the existence of DENV-specific antibodies in the serum of a person after 70 years from infection. Published reports indicated that DENV-1 was responsible for the 1942-1944 outbreak in Nagasaki. However, our data suggested that DENV-2 also played a role in this Nagasaki dengue epidemic. PMID:27493841

  2. Isolated oestrogen deficiency in male 30-year-old: persistent growth plates with severe osteopenia

    International Nuclear Information System (INIS)

    Full text: A 31-year-old male presented with right rib pain and generalised skeletal symptoms. He has a past history of multiple fractures following trauma. No history of childhood fractures. Asthma (No steroids). A product of a consanguineous marriage, he has one child aged 7. Examination showed 178.6cm male with normal sexual characteristics. No abnormality detected apart from tenderness over right ribs. Bone scan showed active growth plates and right and left rib fractures. X-rays demonstrated a bone age of 15 1/2 - 16 yrs and a compression fracture of L2. His bone mineral density is severely reduced. Metabolic investigations revealed Testosterone 27.4 nmol (N 11-35), oestradiol < 70 pmol/L, ultrasensitive assay 14 and 17 pmol/L (consistent with 8-year-old male), LH N, FSH N, 46 XY Karyotype. Alkaline phosphatase. 148 (N<120), Normal glucose tolerance test. This patient illustrates a very rare condition of oestrogen deficiency in a male, probably due to aromatase deficiency. This enzyme converts testosterone to oestradiol. It illustrates the role of oestrogen in fusing growth plates and maintaining bone mass in males with otherwise normal androgen levels. A similar clinical picture can result from an oestrogen receptor abnormality. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  3. Beijing fifteen years on: the persistence of barriers to gender mainstreaming in health policy.

    Science.gov (United States)

    Payne, Sarah

    2011-01-01

    In 2010, fifteen years after the Beijing declaration on women's rights, the UN Commission on the Status of Women met to review progress in gender mainstreaming. Reports on gender equality by member states revealed differences in the degree of change achieved in this period, while highlighting common barriers to gender mainstreaming. The same barriers have long been identified by academics and activists, but prove remarkably resistant to strategies to address gender inequalities. This paper reviews approaches to gender mainstreaming in the context of health policy, and suggests that a model of the obstacles to gender mainstreaming, which identifies barriers as essentially pragmatic, conceptual, or political in origin, might enable a more explicit discussion of the factors underlying this resistance and the ways in which they might be challenged. PMID:22292172

  4. Beijing fifteen years on: the persistence of barriers to gender mainstreaming in health policy.

    Science.gov (United States)

    Payne, Sarah

    2011-01-01

    In 2010, fifteen years after the Beijing declaration on women's rights, the UN Commission on the Status of Women met to review progress in gender mainstreaming. Reports on gender equality by member states revealed differences in the degree of change achieved in this period, while highlighting common barriers to gender mainstreaming. The same barriers have long been identified by academics and activists, but prove remarkably resistant to strategies to address gender inequalities. This paper reviews approaches to gender mainstreaming in the context of health policy, and suggests that a model of the obstacles to gender mainstreaming, which identifies barriers as essentially pragmatic, conceptual, or political in origin, might enable a more explicit discussion of the factors underlying this resistance and the ways in which they might be challenged.

  5. Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence.

    Directory of Open Access Journals (Sweden)

    Cameron R Cunningham

    2016-01-01

    Full Text Available Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections.

  6. Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence.

    Science.gov (United States)

    Cunningham, Cameron R; Champhekar, Ameya; Tullius, Michael V; Dillon, Barbara Jane; Zhen, Anjie; de la Fuente, Justin Rafael; Herskovitz, Jonathan; Elsaesser, Heidi; Snell, Laura M; Wilson, Elizabeth B; de la Torre, Juan Carlos; Kitchen, Scott G; Horwitz, Marcus A; Bensinger, Steven J; Smale, Stephen T; Brooks, David G

    2016-01-01

    Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV) to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs) during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I) then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections. PMID:26808628

  7. Identification of a stable molecular signature in mammary tumor endothelial cells that persists in vitro

    Science.gov (United States)

    Xiao, Lin; Harrell, J. Chuck; Perou, Charles M.; Dudley, Andrew C.

    2013-01-01

    Long-term, in vitro propagation of tumor-specific endothelial cells (TEC) allows for functional studies and genome-wide expression profiling of clonally-derived, well-characterized subpopulations. Using a genetically engineered mouse model (GEMM) of mammary adenocarcinoma, we have optimized an isolation procedure and defined growth conditions for long-term propagation of mammary TEC. The isolated TEC maintain their endothelial specification and phenotype in culture. Furthermore, gene expression profiling of multiple TEC subpopulations revealed striking, persistent overexpression of several candidate genes including Irx2 and Zfp503 (transcription factors), Alcam and Cd133 (cell surface markers), Ccl4 and neurotensin (Nts) (angiocrine factors), and Gpr182 and Cnr2 (G protein-coupled receptors, GPCRs). Taken together, we have developed an effective method for isolating and culture-expanding mammary TEC, and uncovered several new TEC-selective genes whose overexpression persists even after long-term in vitro culture. These results suggest that the tumor microenvironment may induce changes in vascular endothelium in vivo that are stably transmittable in vitro. PMID:24257808

  8. Persistent cell migration and adhesion rely on retrograde transport of β(1) integrin.

    Science.gov (United States)

    Shafaq-Zadah, Massiullah; Gomes-Santos, Carina S; Bardin, Sabine; Maiuri, Paolo; Maurin, Mathieu; Iranzo, Julian; Gautreau, Alexis; Lamaze, Christophe; Caswell, Patrick; Goud, Bruno; Johannes, Ludger

    2016-01-01

    Integrins have key functions in cell adhesion and migration. How integrins are dynamically relocalized to the leading edge in highly polarized migratory cells has remained unexplored. Here, we demonstrate that β1 integrin (known as PAT-3 in Caenorhabditis elegans), but not β3, is transported from the plasma membrane to the trans-Golgi network, to be resecreted in a polarized manner. This retrograde trafficking is restricted to the non-ligand-bound conformation of β1 integrin. Retrograde trafficking inhibition abrogates several β1-integrin-specific functions such as cell adhesion in early embryonic development of mice, and persistent cell migration in the developing posterior gonad arm of C. elegans. Our results establish a paradigm according to which retrograde trafficking, and not endosomal recycling, is the key driver for β1 integrin function in highly polarized cells. These data more generally suggest that the retrograde route is used to relocalize plasma membrane machinery from previous sites of function to the leading edge of migratory cells.

  9. Quantitative analysis of the acute and long-term CD4(+) T-cell response to a persistent gammaherpesvirus

    DEFF Research Database (Denmark)

    Christensen, Jan Pravsgaard; Doherty, P C

    1999-01-01

    The murine gammaherpesvirus 68 (MHV-68) replicates in respiratory epithelial cells, where it establishes a persistent, latent infection limited predominantly to B lymphocytes. The virus-specific CD4(+) T-cell response in C57BL/6 mice challenged intranasally with MHV-68 is detected first in the me......The murine gammaherpesvirus 68 (MHV-68) replicates in respiratory epithelial cells, where it establishes a persistent, latent infection limited predominantly to B lymphocytes. The virus-specific CD4(+) T-cell response in C57BL/6 mice challenged intranasally with MHV-68 is detected first...... were initially CD62Llow, with >80% maintaining that phenotype for the next 14 months. The overall conclusion is that MHV-68-specific CD4(+) T cells remain activated (CD62Llow) and at a stable frequency in the face of persistent infection....

  10. Persistence of side population cells with high drug efflux capacity in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM:To investigate the persistence of side population (SP) cells in pancreatic cancer and their role and mechanism in the drug resistance.METHODS:The presentation of side population cells in pancreatic cancer cell line PANC-1 and its proportion change when cultured with Gemcitabine,was detected by Hoechst 33342 staining and FACS analysis.The expression of ABCB1 and ABCG2 was detected by realtime PCR in either SP cells or non-SP cells.RESULTS:SP cells do exist in PANC-1,with a median of 3.3% and a range of 2.1-8.7%.After cultured with Gemcitabine for 3 d,the proportion of SP cells increased significantly(3.8% ± 1.9%,10.7% ± 3.7%, t = 4.616,P = 0.001 < 0.05).ABCB1 and ABCG2 expressed at higher concentrations in SP as compared with non-SP cells (ABCBI: 1.15 ± 0.72, 5.82 ± 1.16, t = 10.839,P = 0.000 < 0.05; ABCG2:1.16 ± 0.75,5.48 ± 0.94,t = 11.305,P = 0.000 < 0.05),which may contribute to the efflux of fluorescent staining and drug resistance.CONCLUSION:SP cells with inherently high resistance to chemotherapeutic agents do exist in pancreatic cancers,which may be candidate cancer stem cells contributing to the relapse of the tumor.

  11. In vivo safety and persistence of endoribonuclease gene-transduced CD4+ T cells in cynomolgus macaques for HIV-1 gene therapy model.

    Directory of Open Access Journals (Sweden)

    Hideto Chono

    Full Text Available BACKGROUND: MazF is an endoribonuclease encoded by Escherichia coli that specifically cleaves the ACA sequence of mRNA. In our previous report, conditional expression of MazF in the HIV-1 LTR rendered CD4+ T lymphocytes resistant to HIV-1 replication. In this study, we examined the in vivo safety and persistence of MazF-transduced cynomolgus macaque CD4+ T cells infused into autologous monkeys. METHODOLOGY/PRINCIPAL FINDINGS: The in vivo persistence of the gene-modified CD4+ T cells in the peripheral blood was monitored for more than half a year using quantitative real-time PCR and flow cytometry, followed by experimental autopsy in order to examine the safety and distribution pattern of the infused cells in several organs. Although the levels of the MazF-transduced CD4+ T cells gradually decreased in the peripheral blood, they were clearly detected throughout the experimental period. Moreover, the infused cells were detected in the distal lymphoid tissues, such as several lymph nodes and the spleen. Histopathological analyses of tissues revealed that there were no lesions related to the infused gene modified cells. Antibodies against MazF were not detected. These data suggest the safety and the low immunogenicity of MazF-transduced CD4+ T cells. Finally, gene modified cells harvested from the monkey more than half a year post-infusion suppressed the replication of SHIV 89.6P. CONCLUSIONS/SIGNIFICANCE: The long-term persistence, safety and continuous HIV replication resistance of the mazF gene-modified CD4+ T cells in the non-human primate model suggests that autologous transplantation of mazF gene-modified cells is an attractive strategy for HIV gene therapy.

  12. The Native Bee Fauna of Carlinville, Illinois, Revisited After 75 Years: a Case for Persistence

    Directory of Open Access Journals (Sweden)

    Wallace E. LaBerge

    2001-06-01

    Full Text Available As a follow-up to the observations of Charles Robertson from 1884 to 1916, we revisited the Carlinville, Illinois, area between 18 August 1970 and 13 September1972 to sample and identify bee species (Hymenoptera: Apoidea. We concentrated on collecting nonparasitic bees (and excluded Apis and Bombus visiting 24 plant species that bloomed at various times of the year, and upon which Charles Robertson found many bee species. For example, we collected most intensively on spring-blooming Claytonia virginica and fall-blooming Aster pilosus, upon which Robertson reported 58 and 90 bee visitors, respectively. Bees were also collected on an opportunistic basis at some other plants. We updated the species names used by Robertson for revisions and synonymies. This paper summarizes a comparison of the two collections, made about 75 years apart at the same small geographic location. The study considers 214 valid bee species that Robertson collected plus an additional 14 species found by us but not by Robertson. Of these 214, we collected 140 species. The absence of most of the remaining 74 species that we did not collect can be explained by examining their plant preferences. Robertson did not record 47 of these 74 species on the 24 plant species where we collected intensively, and he observed 19 more species on only one or two of the 24 plant species. Additionally, he observed 21 of them on only one of the 441 plants he studied. Of the bee species found by Robertson on the 24 plant species, we collected 82% on the same plant species. The land uses and land cover on Macoupin County's 225,464 ha (558,080 acres, which bear directly on the type and availability of habitat for bees and their host plants, varied considerably over two centuries. For example, in the early 1800s, land cover was about 73% prairie and 27% forest. The estimated 59,792 ha (148,000 acres of forested land in 1820 diminished to 24,644 ha (61,000 acres by 1924. It then grew to 34,340 ha (85

  13. Persistence of antibodies 3 years after booster vaccination of adults with combined acellular pertussis, diphtheria and tetanus toxoids vaccine.

    Science.gov (United States)

    Weston, Wayde; Messier, Marc; Friedland, Leonard R; Wu, Xiangfeng; Howe, Barbara

    2011-11-01

    The duration of protection after vaccination with reduced antigen content diphtheria, tetanus and acellular pertussis vaccines (Tdap) is not known. Long-term post-vaccination serological data will help to improve understanding of the duration of humoral immunity and guide vaccination policy for the timing of repeat dose administration. The persistence of antibodies to Tdap antigens was measured 3 years after vaccination of adults 19-64 years of age with one of 2 Tdap vaccines (Boostrix(®), GlaxoSmithKline Biologicals; Tdap-B: or Adacel(®), Sanofi Pasteur; Tdap-A). In both groups, geometric mean concentrations for antibodies to diphtheria, tetanus, and pertussis vaccine antigens were decreased at year 3 relative to levels observed 1 month and 1 year following vaccination, but remained higher than pre-vaccination levels. Seroprotection rates for diphtheria and tetanus remained high for both Tdap vaccines (for diphtheria, 96.9% and 97.8% for the Tdap-B and Tdap-A groups, respectively; for tetanus, 98.1% and 99.6%, respectively).

  14. Coevolution of cells and viruses in a persistent infection of foot-and-mouth disease virus in cell culture.

    OpenAIRE

    de la Torre, J C; Martínez-Salas, E; Diez, J; Villaverde, A; Gebauer, F; Rocha, E.; Dávila, M; Domingo, E

    1988-01-01

    Virus and cells evolve during serial passage of cloned BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV). These carrier cells, termed C1-BHK-Rc1 (J.C. de la Torre, M. Dávila, F. Sobrino, J. Ortín, and E. Domingo, Virology 145:24-35, 1985), become constitutively resistant to the parental FMDV C-S8c1. Curing of late-passage C1-BHK-Rc1 cells of FMDV by ribavirin treatment (J.C. de la Torre, B. Alarcón, E. Martínez-Salas, L. Carrasco, and E. Domingo, J. Virol. 61:233-235...

  15. Gene flow persists millions of years after speciation in Heliconius butterflies

    Directory of Open Access Journals (Sweden)

    Kronforst Marcus R

    2008-03-01

    Full Text Available Abstract Background Hybridization, or the interbreeding of two species, is now recognized as an important process in the evolution of many organisms. However, the extent to which hybridization results in the transfer of genetic material across the species boundary (introgression remains unknown in many systems, as does the length of time after initial divergence that the species boundary remains porous to such gene flow. Results Here I use genome-wide genotypic and DNA sequence data to show that there is introgression and admixture between the melpomene/cydno and silvaniform clades of the butterfly genus Heliconius, groups that separated from one another as many as 30 million generations ago. Estimates of historical migration based on 523 DNA sequences from 14 genes suggest unidirectional gene flow from the melpomene/cydno clade into the silvaniform clade. Furthermore, genetic clustering based on 520 amplified fragment length polymorphisms (AFLPs identified multiple individuals of mixed ancestry showing that introgression is on-going. Conclusion These results demonstrate that genomes can remain porous to gene flow very long after initial divergence. This, in turn, greatly expands the evolutionary potential afforded by introgression. Phenotypic and species diversity in a wide variety of organisms, including Heliconius, have likely arisen from introgressive hybridization. Evidence for continuous gene flow over millions of years points to introgression as a potentially important source of genetic variation to fuel the evolution of novel forms.

  16. A 1-year-old boy with persistent, generalized eruption. Urticaria pigmentosa.

    Science.gov (United States)

    Mir, Adnan; Chamlin, Sarah L

    2014-01-01

    A healthy 1-year-old boy born at full term after an uncomplicated pregnancy presented to the dermatology clinic for a widespread eruption with gradual onset since 3 months of age. He was otherwise well, afebrile, feeding well, and gaining weight appropriately. The child was overall asymptomatic, though some of his lesions occasionally became red and pruritic. His mother noticed that after mild illnesses, he was more prone to these flares. She denied flushing, vomiting, diarrhea, respiratory distress, and irritability. He was meeting all developmental milestones and started walking at 11 months of age. The remainder of his review of systems was unremarkable, and family history was noncontributory. Physical exam revealed a well-appearing, well-nourished, playful, and interactive toddler. There were innumerable discrete and coalescing pink-brown macules and papules concentrated on the trunk and extending onto the proximal upper and lower extremities bilaterally, as well as the neck and lower face. Stroking the lesions quickly led to development of erythematous edematous wheals. There was no hepatosplenomegaly, and the lymph node exam was unremarkable.

  17. [Persistent diarrhea

    Science.gov (United States)

    Andrade, J A; Moreira, C; Fagundes Neto, U

    2000-07-01

    INTRODUCTION: Persistent diarrhea has high impact on infantile morbidity and mortality rates in developing countries. Several studies have shown that 3 to 20% of acute diarrheal episodes in children under 5 years of age become persistent. DEFINITION: Persistent diarrhea is defined as an episode that lasts more than 14 days. ETIOLOGY: The most important agents isolated in persistent diarrhea are: Enteropathogenic E. coli (EPEC), Salmonella, Enteroaggregative E. coli (EAEC), Klebisiella and Cryptosporidium. CLINICAL ASPECTS: In general, the clinical characteristics of patients with persistent diarrhea do not change with the pathogenic agent. Persistent diarrhea seems to represent the final result of a several insults a infant suffers that predisposes to a more severe episode of diarrhea due to a combination of host factors and high rates of enviromental contamination. Therefore, efforts should be made to promptly treat all episodes of diarrhea with apropriate follow-up. THERAPY: The aim of the treatment is to restore hydroelectrolytic deficits and to replace losses until the diarrheal ceases. It is possible in the majority of the cases, using oral rehydration therapy and erly an appropriate type of diet. PREVENTION: It is imperative that management strategies also focus on preventive aspects. The most effective diarrheal prevention strategy in young infants worldwide is promotion of exclusive breast feeding. PMID:14676915

  18. Long-term persistence with injectable therapy in relapsing-remitting multiple sclerosis: an 18-year observational cohort study.

    Directory of Open Access Journals (Sweden)

    Simon Zhornitsky

    Full Text Available Disease modifying therapies (DMTs reduce the frequency of relapses and accumulation of disability in multiple sclerosis (MS. Long-term persistence with treatment is important to optimize treatment benefit. This long-term, cohort study was conducted at the Calgary MS Clinic. All consenting adults with relapsing-remitting MS who started either glatiramer acetate (GA or interferon-β 1a/1b (IFN-β between January 1st, 1996 and July 1st, 2011 were included. Follow-up continued to February 1st, 2014. Time-to-discontinuation of the initial and subsequently-prescribed DMTs (switches was analysed using Kaplan-Meier survival analyses. Group differences were compared using log-rank tests and multivariable Cox regression models. Analysis included 1471 participants; 906 were initially prescribed GA and 565 were initially prescribed IFN-β. Follow-up information was available for 87%; 29 (2% were lost to follow-up and 160 (11% moved from Southern Alberta while still using DMT. Median time-to-discontinuation of all injectable DMTs was 11.1 years. Participants with greater disability at treatment initiation, those who started treatment before age 30, and those who started between 2006 and 2011 were more likely to discontinue use of all injectable DMTs. Median time-to-discontinuation of the initial DMT was 8.6 years. Those initially prescribed GA remained on treatment longer. Of 610 participants who discontinued injectable DMT, 331 (54% started an oral DMT, or a second-line DMT, or resumed injectable DMT after 90 days. Persistence with injectable DMTs was high in this long-term population-based study. Most participants who discontinued injectable DMT did not remain untreated. Further research is required to understand treatment outcomes and outcomes after stopping DMT.

  19. Evolution of the persistence of snow over Sierra Nevada Mountain (southern, Spain) in the last 55 years

    Science.gov (United States)

    Pimentel, Rafael; José Pérez-Palazón, María; Herrero, Javier; José Polo, María

    2016-04-01

    Snow plays a crucial role in mountainous areas, not only as water resources for human supply, irrigation and energy production, but also for the ecosystem, flora and fauna, over these areas. Sierra Nevada Mountains, southern Spain, constitutes a rich reservoir of endemic wildlife species, and it is considered the most important center of biodiversity in the wester Mediterranean region. The highest regions of the range were declared UNESCO Biosphere Reserve, Natural and National Parks. Climate trends over the last decades put a lot of pressure on both snowfall occurrence and snow persistence; this poses a risk for biodiversity and has led to its inclusion in the Global Change Observatory Network. This work quantifies the evolution of the persistence of snow over the Sierra Nevada area during the last fifty-five years (1960-2015) as a basis to assess the vulnerability of its ecosystem services. For this, the spatial distribution of the annual number of days with snow, SDS, was analyzed over a study area of 4583 km2 (140-3479 m.a.s.l.), which comprises the head of the five basins in these mountains. The following indicator variables were studied over the whole area and each one of the five head regions identified: 1) the trend of SDS; 2) the annual area where SDS exceeded selected percentiles in its distribution; and 3) the annual minimum altitude where SDS exceeded those percentiles. SDS was obtained during the study period by means of the snow module in WiMMed (Watershed Integrated Model in Mediterranean Environment), a physically-based hydrological model developed, calibrated and validated in the area; the model is based on an energy-mass balance over the snowpack that is spatially distributed through the use of depletion curves, and is operational at hourly and daily scales. A general decreasing trend of SDS (0.25 days year-1) was found over the whole study area for the study period. This value is higher in the more humid basins (0.45 and 0.41 days year-1) than in

  20. Regulatory T cell suppressive potency dictates the balance between bacterial proliferation and clearance during persistent Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Tanner M Johanns

    Full Text Available The pathogenesis of persistent infection is dictated by the balance between opposing immune activation and suppression signals. Herein, virulent Salmonella was used to explore the role and potential importance of Foxp3-expressing regulatory T cells in dictating the natural progression of persistent bacterial infection. Two distinct phases of persistent Salmonella infection are identified. In the first 3-4 weeks after infection, progressively increasing bacterial burden was associated with delayed effector T cell activation. Reciprocally, at later time points after infection, reductions in bacterial burden were associated with robust effector T cell activation. Using Foxp3(GFP reporter mice for ex vivo isolation of regulatory T cells, we demonstrate that the dichotomy in infection tempo between early and late time points is directly paralleled by drastic changes in Foxp3(+ Treg suppressive potency. In complementary experiments using Foxp3(DTR mice, the significance of these shifts in Treg suppressive potency on infection outcome was verified by enumerating the relative impacts of regulatory T cell ablation on bacterial burden and effector T cell activation at early and late time points during persistent Salmonella infection. Moreover, Treg expression of CTLA-4 directly paralleled changes in suppressive potency, and the relative effects of Treg ablation could be largely recapitulated by CTLA-4 in vivo blockade. Together, these results demonstrate that dynamic regulation of Treg suppressive potency dictates the course of persistent bacterial infection.

  1. Halogenated Phenazines that Potently Eradicate Biofilms, MRSA Persister Cells in Non-Biofilm Cultures, and Mycobacterium tuberculosis.

    Science.gov (United States)

    Garrison, Aaron T; Abouelhassan, Yasmeen; Kallifidas, Dimitris; Bai, Fang; Ukhanova, Maria; Mai, Volker; Jin, Shouguang; Luesch, Hendrik; Huigens, Robert W

    2015-12-01

    Conventional antibiotics are ineffective against non-replicating bacteria (for example, bacteria within biofilms). We report a series of halogenated phenazines (HP), inspired by marine antibiotic 1, that targets persistent bacteria. HP 14 demonstrated the most potent biofilm eradication activities to date against MRSA, MRSE, and VRE biofilms (MBEC = 0.2-12.5 μM), as well as the effective killing of MRSA persister cells in non-biofilm cultures. Frontline MRSA treatments, vancomycin and daptomycin, were unable to eradicate MRSA biofilms or non-biofilm persisters alongside 14. HP 13 displayed potent antibacterial activity against slow-growing M. tuberculosis (MIC = 3.13 μM), the leading cause of death by bacterial infection around the world. HP analogues effectively target persistent bacteria through a mechanism that is non-toxic to mammalian cells and could have a significant impact on treatments for chronic bacterial infections.

  2. Pilot study of a cell phone-based exercise persistence intervention post-rehabilitation for COPD

    Directory of Open Access Journals (Sweden)

    Huong Q Nguyen

    2009-08-01

    Full Text Available Huong Q Nguyen1, Dawn P Gill1, Seth Wolpin1, Bonnie G Steele2, Joshua O Benditt11University of Washington, seattle, WA, USA; 2VA Puget Sound Health Care System, Seattle, WA, USAObjective: To determine the feasibility and efficacy of a six-month, cell phone-based exercise persistence intervention for patients with chronic obstructive pulmonary disease (COPD following pulmonary rehabilitation.Methods: Participants who completed a two-week run-in were randomly assigned to either MOBILE-Coached (n = 9 or MOBILE-Self-Monitored (n = 8. All participants met with a nurse to develop an individualized exercise plan, were issued a pedometer and exercise booklet, and instructed to continue to log their daily exercise and symptoms. MOBILE-Coached also received weekly reinforcement text messages on their cell phones; reports of worsening symptoms were automatically flagged for follow-up. Usability and satisfaction were assessed. Participants completed incremental cycle and six minute walk (6MW tests, wore an activity monitor for 14 days, and reported their health-related quality of life (HRQL at baseline, three, and six months.Results: The sample had a mean age of 68 ± 11 and forced expiratory volume in one second (FEV1 of 40 ± 18% predicted. Participants reported that logging their exercise and symptoms was easy and that keeping track of their exercise helped them remain active. There were no differences between groups over time in maximal workload, 6MW distance, or HRQL (p > 0.05; however, MOBILE-Self-Monitored increased total steps/day whereas MOBILE-Coached logged fewer steps over six months (p = 0.04.Conclusions: We showed that it is feasible to deliver a cell phone-based exercise persistence intervention to patients with COPD post-rehabilitation and that the addition of coaching appeared to be no better than self-monitoring. The latter finding needs to be interpreted with caution since this was a purely exploratory study.Trial registration: Clinical

  3. Persistent STAT3 Activation in Colon Cancer Is Associated with Enhanced Cell Proliferation and Tumor Growth

    Directory of Open Access Journals (Sweden)

    Florian M. Corvinus

    2005-06-01

    Full Text Available Colorectal carcinoma (CRC is a major cause of morbidity and mortality in Western countries. It has so far been molecularly defined mainly by alterations of the Wnt pathway. We show here for the first time that aberrant activities of the signal transducer and activator of transcription STAT3 actively contribute to this malignancy and, thus, are a potential therapeutic target for CRC. Constitutive STAT3 activity was found to be abundant in dedifferentiated cancer cells and infiltrating lymphocytes of CRC samples, but not in non-neoplastic colon epithelium. Cell lines derived from malignant colorectal tumors lost persistent STAT3 activity in culture. However, implantation of colon carcinoma cells into nude mice resulted in restoration of STAT3 activity, suggesting a role of an extracellular stimulus within the tumor microenvironment as a trigger for STAT activation. STAT3 activity in CRC cells triggered through interleukin-6 or through a constitutively active STAT3 mutant promoted cancer cell multiplication, whereas STAT3 inhibition through a dominant-negative variant impaired IL-6-driven proliferation. Blockade of STAT3 activation in CRCderived xenograft tumors slowed down their development, arguing for a contribution of STAT3 to colorectal tumor growth.

  4. Role of denileukin diftitox in the treatment of persistent or recurrent cutaneous T-cell lymphoma

    Directory of Open Access Journals (Sweden)

    Frederick Lansigan

    2010-02-01

    Full Text Available Frederick Lansigan1, Diane M Stearns1, Francine Foss21Hematology/Oncology, Norris Cotton Cancer Center, Dartmouth Hitchcock Medical Center, Lebanon, NH, USA; 2Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, CT, USAAbstract: Denileukin diftitox (Ontak® is indicated for the treatment of patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL, a rare lymphoproliferative disorder of the skin. Denileukin diftitox was the first fusion protein toxin approved for the treatment of a human disease. This fusion protein toxin combines the IL2 protein with diphtheria toxin, and targets the CD25 subunit of the IL2 receptor, resulting in the unique delivery of a cytocidal agent to CD-25 bearing T-cells. Historically, immunotherapy targeting malignant T-cells including monoclonal antibodies has been largely ineffective as cytocidal agents compared to immunotherapy directed against B-cells such as rituximab. This review will summarize the development of denileukin diftitox, its proposed mechanism of action, the pivotal clinical trials that led to its FDA approval, the improvements in quality of life, and the common toxicities experienced during the treatment of patients with CTCL. CTCL is often a chronic progressive lymphoma requiring the sequential use of treatments such as retinoids, traditional chemotherapy, or biological response modifiers. The incorporation of the immunotoxin denileukin diftitox into the sequential or combinatorial treatment of CTCL will also be addressed.Keywords: denileukin diftitox, cutaneous T-cell lymphoma, fusion protein toxin

  5. Establishment of Functional B Cell Memory Against Parvovirus B19 Capsid Proteins May be Associated With Resolution of Persistent Infection

    OpenAIRE

    Corcoran, A; Crowley, B.; Dewhurst, C.; Pizer, B L; Doyle, Sean

    2006-01-01

    Parvovirus B19 (B19) infection can occur during acute lymphoblastic leukemia and persistent viral infection can occur despite intravenous immunoglobulin administration. Here, evidence is presented that resolution of persistent B19 infection in an acute lymphoblastic leukemia patient may be associated with the simultaneous strengthening of antigen-specific B cell memory against the B19 capsid protein VP2 and diminution in the memory response against the B19 non-structural protein 1 (NS1). Dete...

  6. Upon oxidative stress, the antiapoptotic Hsp60/procaspase-3 complex persists in mucoepidermoid carcinoma cells

    Directory of Open Access Journals (Sweden)

    C Campanella

    2009-08-01

    Full Text Available Hsp60, a mitochondrial chaperonin highly conserved during evolution, has been found elevated in the cytosol of cancer cells, both in vivo and in vitro, but its role in determining apoptosis during oxidative stress (OS has not yet been fully elucidated. The aim of the present work was to study the effects of OS on Hsp60 levels and its interactions with procaspase- 3 (p-C3 and p53 in tumor cells. NCI-H292 (mucoepidermoid carcinoma cells were exposed to various concentrations of hydrogen peroxide (H2O2 for 24 hours. Cell viability was determined by Trypan blue and MTT assays. DNA damage was assessed by the Comet assay, and apoptosis was measured by the AnnexinV cytofluorimetric test. Exposure to increasing concentrations of H2O2 resulted in a reduction of cell viability, DNA damage, and early apoptotic phenomena. Hsp60, p-C3, p53, and p21 were assessed by Western blotting and immunocytochemistry before and after OS. Hsp60 and p-C3 were present before and after OS induction. Immunoprecipitation experiments showed an Hsp60/p-C3 complex before OS that persisted after it, while an Hsp60/p53 complex was not detected in either condition. The presence of wild type (wt p53 was confirmed by RT-PCR, and p21 detection suggested p53 activation after OS. We postulate that, although OS may induce early apoptosis in NCI-H292 cells, Hsp60 exerts an anti-apoptotic effect in these cells and, by extension, it may do so in other cancer cells.

  7. Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection

    Directory of Open Access Journals (Sweden)

    Laura M. Snell

    2016-09-01

    Full Text Available Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and persistent virus infection, demonstrating an unrecognized suppressive function for PD-L1 in virus infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control persistent viral infection.

  8. Overcoming CD4 Th1 Cell Fate Restrictions to Sustain Antiviral CD8 T Cells and Control Persistent Virus Infection.

    Science.gov (United States)

    Snell, Laura M; Osokine, Ivan; Yamada, Douglas H; De la Fuente, Justin Rafael; Elsaesser, Heidi J; Brooks, David G

    2016-09-20

    Viral persistence specifically inhibits CD4 Th1 responses and promotes Tfh immunity, but the mechanisms that suppress Th1 cells and the disease consequences of their loss are unclear. Here, we demonstrate that the loss of CD4 Th1 cells specifically leads to progressive CD8 T cell decline and dysfunction during viral persistence. Therapeutically reconstituting CD4 Th1 cells restored CD4 T cell polyfunctionality, enhanced antiviral CD8 T cell numbers and function, and enabled viral control. Mechanistically, combined interaction of PD-L1 and IL-10 by suppressive dendritic cell subsets inhibited new CD4 Th1 cells in both acute and persistent virus infection, demonstrating an unrecognized suppressive function for PD-L1 in virus infection. Thus, the loss of CD4 Th1 cells is a key event leading to progressive CD8 T cell demise during viral persistence with important implications for restoring antiviral CD8 T cell immunity to control persistent viral infection.

  9. [Recurrent cystitis and vaginitis: role of biofilms and persister cells. From pathophysiology to new therapeutic strategies].

    Science.gov (United States)

    Graziottin, A; Zanello, P P; D'Errico, G

    2014-10-01

    Recurrent vaginitis and cystitis are a daily challenge for the woman and the physician. The recurrence worsens the symptoms' severity, increases comorbidities, both pelvic (provoked vestibulodynia, bladder pain syndrome, levator ani hyperactivity, introital dyspareunia, obstructive constipation, chronic pelvic pain) and cerebral (neuroinflammation and depression), increases health costs, worsens the quality of life. Antibiotics increase the risk of bacterial resistences and devastate the ecosystems: intestinal, vaginal and mucocutaneous. Pathogenic biofilms are the (still) neglected etiology of recurrences. Biofilms are structured communities of bacteria and yeasts, protected by a self-produced polymeric matrix adherent to a living or inert structures, such as medical devices. Biofims can be intra or extracellular. Pathogens live in a resting state in the deep biofilm layers as "persister cells", resistant to antibiotics and host defences and ready to re-attack the host. The paper updates the evidence on biofilms and introduces new non-antibiotic strategies of preventing and modulating recurrent vaginitis and cystitis. PMID:25245998

  10. Anti-aquaporin-4 autoantibodies in systemic lupus erythematosus persist for years and induce astrocytic cytotoxicity but not CNS disease.

    Science.gov (United States)

    Alexopoulos, Harry; Kampylafka, Eleni I; Fouka, Penelope; Tatouli, Ioanna; Akrivou, Sofia; Politis, Panagiotis K; Moutsopoulos, Haralampos M; Tzioufas, Athanasios G; Dalakas, Marinos C

    2015-12-15

    Anti-aquaporin-4 autoantibodies are specific for the neuromyelitis optica spectrum disorders (NMOSD) and they have also been described in patients with systemic lupus erythematosus (SLE) with neurological signs consistent with NMOSD. Our objective was to test for the presence and pathogenicity of anti-AQP4 antibodies in SLE patients without neurological disease. Sera from 89 non-CNS-SLE patients were screened for anti-AQP4 autoantibodies. Two of the 89 patients were positive. Archived samples dating back 11 years were also positive. A brain and spinal cord MRI did not reveal any NMOSD-compatible lesions. An in vitro cytotoxicity assay showed that either sera or purified IgG from these patients induced a complement-mediated damage in cultured astrocytes comparable to antibodies obtained from typical NMO patients. We conclude that AQP4-antibodies can be present in SLE patients and persist for many years, without concurrent clinical or radiological NMOSD signs. It is unclear why the anti-AQP4 antibodies did not induce CNS disease.

  11. Enhanced propagation of fish nodaviruses in BF-2 cells persistently infected with snakehead retrovirus (SnRV).

    Science.gov (United States)

    Nishizawa, Toyohiko; Kokawa, Yuki; Wakayama, Takako; Kinoshita, Shinichi; Yoshimizu, Mamoru

    2008-03-01

    Fish nodaviruses are causative agents of viral nervous necrosis causing high mortality in cultured marine fishes around the world. The first successful isolation of fish nodavirus was made with SSN-1 cells, which are persistently infected with snakehead retrovirus (SnRV). In the present study, a BF-2 cell line persistently infected with SnRV (PI-BF-2) was established to evaluate the influence of SnRV on the production of fish nodavirus. The PI-BF-2 cells were slightly more slender than BF-2 cells, but no difference was observed in propagation rate between both cell lines. No difference was observed in production of SnRV between PI-BF-2 and SSN-1 cell lines. Although both PI-BF-2 and BF-2 cell lines showed no cytopathic effect (CPE) after inoculation of striped jack nervous necrosis virus (SJNNV) and redspotted grouper nervous necrosis virus (RGNNV), these fish nodaviruses could be amplified in BF-2 cells, and moreover, production of fish nodaviruses in the PI-BF-2 cell line was more than 40 times higher than in BF-2 cells. Thus, it was concluded that BF-2 cell permissiveness to fish nodaviruses was enhanced by persistent infection with SnRV. Furthermore, homologous cDNA to genomic RNA of SJNNV was detected from both PI-BF-2 and SSN-1 cell lines persistently infected with SnRV. The amount of nodavirus cDNA in SJNNV-inoculated PI-BF-2 cells was clearly lower than that in SJNNV-inoculated SSN-1 cells.

  12. Evaluation of the persistence of functional and biological respiratory health effects in clean-up workers 6 years after the Prestige oil spill.

    NARCIS (Netherlands)

    Zock, J.P.; Rodríguez-Trigo, G.; Rodríguez-Rodríguez, E.; Souto-Alonso, A.; Espinosa, A.; Pozo-Rodríguez, F.; Gómez, F.P.; Fuster, C.; Castaño-Vinyals, G.; Antó, J.M.; Barberà, J.A.

    2014-01-01

    Fishermen who had participated in clean-up activities of the Prestige oil spill showed increased bronchial responsiveness and higher levels of respiratory biomarkers 2years later. We aimed to evaluate the persistence of these functional and biological respiratory health effects 6years after clean-up

  13. Evolution of the persistence of snow over Sierra Nevada Mountain (southern, Spain) in the last 55 years

    Science.gov (United States)

    Pimentel, Rafael; José Pérez-Palazón, María; Herrero, Javier; José Polo, María

    2016-04-01

    Snow plays a crucial role in mountainous areas, not only as water resources for human supply, irrigation and energy production, but also for the ecosystem, flora and fauna, over these areas. Sierra Nevada Mountains, southern Spain, constitutes a rich reservoir of endemic wildlife species, and it is considered the most important center of biodiversity in the wester Mediterranean region. The highest regions of the range were declared UNESCO Biosphere Reserve, Natural and National Parks. Climate trends over the last decades put a lot of pressure on both snowfall occurrence and snow persistence; this poses a risk for biodiversity and has led to its inclusion in the Global Change Observatory Network. This work quantifies the evolution of the persistence of snow over the Sierra Nevada area during the last fifty-five years (1960-2015) as a basis to assess the vulnerability of its ecosystem services. For this, the spatial distribution of the annual number of days with snow, SDS, was analyzed over a study area of 4583 km2 (140-3479 m.a.s.l.), which comprises the head of the five basins in these mountains. The following indicator variables were studied over the whole area and each one of the five head regions identified: 1) the trend of SDS; 2) the annual area where SDS exceeded selected percentiles in its distribution; and 3) the annual minimum altitude where SDS exceeded those percentiles. SDS was obtained during the study period by means of the snow module in WiMMed (Watershed Integrated Model in Mediterranean Environment), a physically-based hydrological model developed, calibrated and validated in the area; the model is based on an energy-mass balance over the snowpack that is spatially distributed through the use of depletion curves, and is operational at hourly and daily scales. A general decreasing trend of SDS (0.25 days year‑1) was found over the whole study area for the study period. This value is higher in the more humid basins (0.45 and 0.41 days year‑1

  14. Persistent DNA Damage in Spermatogonial Stem Cells After Fractionated Low-Dose Irradiation of Testicular Tissue

    Energy Technology Data Exchange (ETDEWEB)

    Grewenig, Angelika; Schuler, Nadine; Rübe, Claudia E., E-mail: claudia.ruebe@uks.eu

    2015-08-01

    Purpose: Testicular spermatogenesis is extremely sensitive to radiation-induced damage, and even low scattered doses to testis from radiation therapy may pose reproductive risks with potential treatment-related infertility. Radiation-induced DNA double-strand breaks (DSBs) represent the greatest threat to the genomic integrity of spermatogonial stem cells (SSCs), which are essential to maintain spermatogenesis and prevent reproduction failure. Methods and Materials: During daily low-dose radiation with 100 mGy or 10 mGy, radiation-induced DSBs were monitored in mouse testis by quantifying 53 binding protein 1 (53BP-1) foci in SSCs within their stem cell niche. The accumulation of DSBs was correlated with proliferation, differentiation, and apoptosis of testicular germ cell populations. Results: Even very low doses of ionizing radiation arrested spermatogenesis, primarily by inducing apoptosis in spermatogonia. Eventual recovery of spermatogenesis depended on the survival of SSCs and their functional ability to proliferate and differentiate to provide adequate numbers of differentiating spermatogonia. Importantly, apoptosis-resistant SSCs resulted in increased 53BP-1 foci levels during, and even several months after, fractionated low-dose radiation, suggesting that surviving SSCs have accumulated an increased load of DNA damage. Conclusions: SSCs revealed elevated levels of DSBs for weeks after radiation, and if these DSBs persist through differentiation to spermatozoa, this may have severe consequences for the genomic integrity of the fertilizing sperm.

  15. Predictors of Persistence in Girls with Attention-Deficit/Hyperactivity Disorder Results from an 11-year Controlled Follow-up Study

    Science.gov (United States)

    Biederman, Joseph; Petty, Carter R.; O’Connor, Katherine B.; Hyder, Laran L.; Faraone, Stephen V.

    2011-01-01

    Objective This study sought to examine the age-dependent persistence of attention-deficit/hyperactivity disorder (ADHD) and its predictors in a large sample of girls with and without ADHD followed prospectively for 11 years into young adulthood. Method Participants were girls with (N=96) and without (N=91) ADHD 6 –17 years old at the baseline assessment (mean age 11 years) and 15–30 years old at the follow-up assessment (mean: 22 years). Participants were comprehensively and blindly assessed with structured diagnostic interviews and assessments of cognitive, social, school, and family functioning. Results At the 11-year follow-up, 33.3% met full criteria for ADHD, 29.2% showed partial persistence of the disorder, 10.4% had impaired functioning and 4.2% were remitted but treated (77.1% of the sample). Predictors of persistence were psychiatric comorbidity, family history of psychopathology, and family and school functioning at baseline. Conclusion These long-term, prospective, follow-up findings extend to girls findings that ADHD is persistent over the long term and can be predicted from psychosocial adversity and psychiatric comorbidity ascertained 11 years earlier. PMID:22097933

  16. Overweight in Infancy : Which Pre- and Perinatal Factors Determine Overweight Persistence or Reduction? A Birth Cohort Followed for 11 Years

    NARCIS (Netherlands)

    van Rossem, Lenie; Wijga, Alet H.; Brunekreef, Bert; de Jongste, Johan C.; Kerkhof, Marjan; Postma, Dirkje S.; Gehring, Ulrike; Smit, Henriette A.

    2014-01-01

    Background: A considerable proportion of children with early-life overweight attain a normal weight. To recognize infants at risk of persistent overweight, we compared early-life factors of children with a longitudinal pattern of persistent overweight to children with a pattern of overweight in earl

  17. Relation of Persistent Depressive Symptoms to Coronary Artery Calcification in Women Aged 46 to 59 Years.

    Science.gov (United States)

    Janssen, Imke; Powell, Lynda H; Matthews, Karen A; Jasielec, Mateusz S; Hollenberg, Steven M; Bromberger, Joyce T; Sutton-Tyrrell, Kim; Everson-Rose, Susan A

    2016-06-15

    Depressive disorders have been associated with cardiovascular disease (CVD), but the impact of depression on early atherogenesis has not been well described, particularly in women and minorities. The relation between repeated episodes of high depressive symptoms and coronary calcium (CAC) is unknown in women at midlife when depression is common. Participants in the Study of Women's Health Across the Nation Heart study were assessed annually for depressive symptoms (Center for Epidemiological Studies Depression Scale [CES-D scale]) over 5 years before CAC assessment and classified as high (CES-D ≥16) or not. CAC, measured by computed tomography, was analyzed as a categorical variable using cumulative logit partial proportional odds models. In these middle-aged women free of CVD and diabetes (194 black, 334 white), high depressive symptoms over 5 years were common; 19% had 1, 9% had 2, and 11% experienced ≥3 episodes. CAC was low; 54% had no CAC, 25% had scores from 0 to 10, and 21% had CAC ≥10 Agatston score. After adjusting for CVD risk factors, women with ≥3 episodes were twice as likely to have significant CAC (≥10 Agatston units) than women with no depressive episodes (odds ratio 2.20, 95% confidence interval 1.13 to 4.28, p = 0.020) with no difference by race. Women with 1 or 2 episodes did not differ from women with no episodes. In conclusion, in healthy women aged 46 to 59 years without clinical CVD or diabetes, persistent depressive symptoms were significantly associated with elevated CAC scores, suggesting that they are more likely to have pathophysiological and behavioral effects on the development of subclinical CVD than does a single episode of elevated depressive symptoms. PMID:27138181

  18. Effect of input multiplicity on the establishment of simian virus 40 persistent infections in rhesus monkey kidney cells.

    Science.gov (United States)

    Norkin, L C

    1977-12-01

    Monolayer cultures of LLC-MK2 rhesus monkey kidney cells become persistently infected with simian virus 40 after infection at input multiplicities of 100, 10, or 1 plaque-forming unit per cell. After 3 weeks, all cells of the cultures infected at a multiplicity of 1 plaque-forming unit per cell produced the simian virus 40 T antigen. In contrast, 8 to 11 weeks elapsed before all the cells in the cultures infected at a multiplicity of 100 plaque-forming units per cell produced T antigen. Defective interfering particles and interferon production were not evident during this time.

  19. CD4+ T Cells Expressing PD-1, TIGIT and LAG-3 Contribute to HIV Persistence during ART

    Science.gov (United States)

    Fromentin, Rémi; Bakeman, Wendy; Lawani, Mariam B.; Khoury, Gabriela; Hartogensis, Wendy; DaFonseca, Sandrina; Killian, Marisela; Epling, Lorrie; Hoh, Rebecca; Sinclair, Elizabeth; Hecht, Frederick M.; Bacchetti, Peter; Deeks, Steven G.; Lewin, Sharon R.; Sékaly, Rafick-Pierre; Chomont, Nicolas

    2016-01-01

    HIV persists in a small pool of latently infected cells despite antiretroviral therapy (ART). Identifying cellular markers expressed at the surface of these cells may lead to novel therapeutic strategies to reduce the size of the HIV reservoir. We hypothesized that CD4+ T cells expressing immune checkpoint molecules would be enriched in HIV-infected cells in individuals receiving suppressive ART. Expression levels of 7 immune checkpoint molecules (PD-1, CTLA-4, LAG-3, TIGIT, TIM-3, CD160 and 2B4) as well as 4 markers of HIV persistence (integrated and total HIV DNA, 2-LTR circles and cell-associated unspliced HIV RNA) were measured in PBMCs from 48 virally suppressed individuals. Using negative binomial regression models, we identified PD-1, TIGIT and LAG-3 as immune checkpoint molecules positively associated with the frequency of CD4+ T cells harboring integrated HIV DNA. The frequency of CD4+ T cells co-expressing PD-1, TIGIT and LAG-3 independently predicted the frequency of cells harboring integrated HIV DNA. Quantification of HIV genomes in highly purified cell subsets from blood further revealed that expressions of PD-1, TIGIT and LAG-3 were associated with HIV-infected cells in distinct memory CD4+ T cell subsets. CD4+ T cells co-expressing the three markers were highly enriched for integrated viral genomes (median of 8.2 fold compared to total CD4+ T cells). Importantly, most cells carrying inducible HIV genomes expressed at least one of these markers (median contribution of cells expressing LAG-3, PD-1 or TIGIT to the inducible reservoir = 76%). Our data provide evidence that CD4+ T cells expressing PD-1, TIGIT and LAG-3 alone or in combination are enriched for persistent HIV during ART and suggest that immune checkpoint blockers directed against these receptors may represent valuable tools to target latently infected cells in virally suppressed individuals. PMID:27415008

  20. Distinguishing the early-onset/persistent and adolescence-onset antisocial behavior types: from birth to 16 years.

    Science.gov (United States)

    Aguilar, B; Sroufe, L A; Egeland, B; Carlson, E

    2000-01-01

    Moffitt's theory regarding two types of adolescent antisocial behavior was investigated using a prospective, longitudinal study of normal and abnormal development in a primarily low socioeconomic status, ethnically diverse sample. Results supported the presence of an early-onset/persistent (EOP) group and an adolescence-onset (AO) group. Groups were most reliably and significantly distinguished by indices of socioemotional history within the first 3 years, but no significant differences were found on early measures of temperament or neuropsychological functioning. EOPs scored significantly lower than other groups on measures of neuropsychological functioning only during late childhood and adolescence, suggesting that the declines in verbal functioning that have been so reliably found in this and other samples of early-starting antisocial adolescents are progressive and consequent to adverse experience. In adolescence, AOs were significantly more likely to report high levels of internalizing symptoms and life stress, suggesting that AO antisocial behavior is not a benign phenomenon. Implications of these findings for etiologic theories of adolescent antisocial behavior are discussed. PMID:10847620

  1. Cell-cell contact viral transfer contributes to HIV infection and persistence in astrocytes

    OpenAIRE

    Luo, Xiaoyu; He, Johnny J.

    2014-01-01

    Astrocytes are the most abundant cells in the central nervous system and play important roles in HIV/neuroAIDS. Detection of HIV proviral DNA, RNA and early gene products but not late structural gene products in astrocytes in vivo and in vitro indicates that astrocytes are susceptible to HIV infection albeit in a restricted manner. We as well as others have shown that cell-free HIV is capable of entering CD4− astrocytes through human mannose receptor-mediated endocytosis. In this study, we to...

  2. Postembryonic Nephrogenesis and Persistence of Six2-Expressing Nephron Progenitor Cells in the Reptilian Kidney.

    Directory of Open Access Journals (Sweden)

    Troy Camarata

    Full Text Available New nephron formation (nephrogenesis ceases in mammals around birth and is completely absent in adults. In contrast, postembryonic nephrogenesis is well documented in the mesonephric kidneys of fishes and amphibians. The transient mesonephros in reptiles (including birds and mammals is replaced by the metanephros during embryogenesis. Thus, one may speculate that postembryonic nephrogenesis is restricted to the mesonephric kidney. Previous reports have suggested the metanephros of non-avian reptiles (hereafter reptiles may continually form nephrons throughout life. We investigated the presence of adult nephrogenesis in reptiles by examining adult kidneys from several species including Trachemys scripta, Chrysemys picta, Boa constrictor, Tupinambis tegu, Anolis carolinensis, and Alligator mississipiensis among others. We found that all major reptilian groups (Testudines, Crocodylia, and Squamates showed the presence of adult nephrogenesis. The total amount of nephrogenesis varied greatly between species with turtles displaying the highest density of nephrogenesis. In contrast, we were unable to detect adult nephrogenesis in monotremes, and in the iguanid A. carolinensis. Nephron progenitor cells express the transcription factor Six2, which in mammals, becomes downregulated as the progenitor cell population is exhausted and nephrogenesis ends. Using the alligator as a model, we were able to detect Six2-positive cap mesenchyme cells in the adult kidney, which spatially correlated with areas of nephrogenesis. These results suggest that the metanephric kidney of reptiles has maintained the ability to continually grow new nephrons during postembryonic life, a process lost early in mammalian evolution, likely due to the persistence of a Six2-expressing progenitor cell population.

  3. Holliday junction-containing DNA structures persist in cells lacking Sgs1 or Top3 following exposure to DNA damage

    DEFF Research Database (Denmark)

    Mankouri, Hocine W; Ashton, Thomas M; Hickson, Ian D

    2011-01-01

    The Sgs1-Rmi1-Top3 "dissolvasome" is required for the maintenance of genome stability and has been implicated in the processing of various types of DNA structures arising during DNA replication. Previous investigations have revealed that unprocessed (X-shaped) homologous recombination repair (HRR......) intermediates persist when S-phase is perturbed by using methyl methanesulfonate (MMS) in Saccharomyces cerevisiae cells with impaired Sgs1 or Top3. However, the precise nature of these persistent DNA structures remains poorly characterized. Here, we report that ectopic expression of either of two heterologous...... to RusA or GEN1(1-527), demonstrating specificity of these HJ resolvases for MMS-induced X-structures in vivo. These data suggest that the X-structures persisting in cells with impaired Sgs1 or Top3 contain HJs. Furthermore, we demonstrate that Sgs1 directly promotes X-structure removal, because the...

  4. Prospects for dendritic cell vaccination in persistent infection with hepatitis C virus

    OpenAIRE

    Gowans, Eric J.; Jones, Kathryn L.; Bharadwaj, Mandvi; Jackson, David C.

    2004-01-01

    Although hepatitis C virus (HCV) is classified in the Hepacivirus genus in the family Flaviviridae, it is unlike most of the other members of this family due to its propensity to cause persistent infections. This persistent infection eventually results in chronic liver disease, cirrhosis and hepatocellular carcinoma in a proportion of infected individuals. It has been difficult to examine correlates of clearance or persistence because most acute phase HCV infections are subclinical or result ...

  5. Persistent DNA damage-induced premature senescence alters the functional features of human bone marrow mesenchymal stem cells.

    Science.gov (United States)

    Minieri, Valentina; Saviozzi, Silvia; Gambarotta, Giovanna; Lo Iacono, Marco; Accomasso, Lisa; Cibrario Rocchietti, Elisa; Gallina, Clara; Turinetto, Valentina; Giachino, Claudia

    2015-04-01

    Human mesenchymal stem cells (hMSCs) are adult multipotent stem cells located in various tissues, including the bone marrow. In contrast to terminally differentiated somatic cells, adult stem cells must persist and function throughout life to ensure tissue homeostasis and repair. For this reason, they must be equipped with DNA damage responses able to maintain genomic integrity while ensuring their lifelong persistence. Evaluation of hMSC response to genotoxic insults is of great interest considering both their therapeutic potential and their physiological functions. This study aimed to investigate the response of human bone marrow MSCs to the genotoxic agent Actinomycin D (ActD), a well-known anti-tumour drug. We report that hMSCs react by undergoing premature senescence driven by a persistent DNA damage response activation, as hallmarked by inhibition of DNA synthesis, p21 and p16 protein expression, marked Senescent Associated β-galactosidase activity and enlarged γH2AX foci co-localizing with 53BP1 protein. Senescent hMSCs overexpress several senescence-associated secretory phenotype (SASP) genes and promote motility of lung tumour and osteosarcoma cell lines in vitro. Our findings disclose a multifaceted consequence of ActD treatment on hMSCs that on the one hand helps to preserve this stem cell pool and prevents damaged cells from undergoing neoplastic transformation, and on the other hand alters their functional effects on the surrounding tissue microenvironment in a way that might worsen their tumour-promoting behaviour.

  6. Persistence of Fall 1988 Math 310, Math 12 & Math 13 Students through Transfer Level Math over Four Academic Years (Fall 1988-Spring 1992). Research Report #269.

    Science.gov (United States)

    Kangas, Jon; Ma, Tony

    A study was conducted at Evergreen Valley College (EVC) and San Jose City College (SJCC) to determine persistence rates over 4 academic years for students with no previous college experience who entered arithmetic (Math 310), beginning algebra (Math 12), and intermediate algebra (Math 13) courses in fall 1988. The study sought to determine…

  7. Persistence of Fall 1988 ENGL 330/335 Students through Transfer Level English (1A) over Four Academic Years (Fall 1988-Spring 1992). Research Report #267.

    Science.gov (United States)

    Kangas, Jon; Ma, Tony

    In fall 1992, a study was conducted at Evergreen Valley College (EVC) and San Jose City College (SJCC), in California, to measure the persistence rate of fall 1988 developmental English students (ENGL 330 at EVC; ENGL 335 at SJCC) through transfer level English (1A) over 4 academic years. Results of the study included the following: (1) of the 152…

  8. Persistence of Fall 1988 ENGL 321 & ENGL 322 Students through Transfer Level English (1A) over Four Academic Years (Fall 1988-Spring 1992). Research Report #268.

    Science.gov (United States)

    Kangas, Jon; Ma, Tony

    In fall 1992, a study was conducted at Evergreen Valley College (EVC) and San Jose City College (SJCC), in California, to measure the persistence rate over 4 academic years of students with no previous college experience who entered into a fundamentals of reading course (English 321) and an introduction to college reading course (English 322) in…

  9. Prevalence, incidence rates and persistence of contact allergy and allergic contact dermatitis in The Odense Adolescence Cohort Study: a 15-year follow-up

    DEFF Research Database (Denmark)

    Mortz, C. G.; Bindslev-Jensen, C.; Andersen, Klaus Ejner

    2013-01-01

    BACKGROUND: A cohort of 1501 unselected 8th grade schoolchildren was established 15 years ago with the aim to follow the course of contact allergy and allergic contact dermatitis (ACD) from school age into adult life. To date no studies have evaluated incidence rates and persistence of contact...

  10. Students' Persistence and Academic Success in a First-Year Professional Bachelor Program: The Influence of Students' Learning Strategies and Academic Motivation

    Directory of Open Access Journals (Sweden)

    Gert Vanthournout

    2012-01-01

    Full Text Available The present study explores whether students' learning strategies and academic motivation predict persistence and academic success in the first year of higher education. Freshmen students in a professional bachelor program in teacher education were questioned on their learning strategy use and motivation at the start and at the end of the academic year. Students' learning strategies were assessed using the inventory of learning styles-SV. Motivation was measured using scales from the self-regulation questionnaire and the academic motivation scale. Gender and students' prior education were incorporated as control variables. Logistic regression analyses and general linear modelling were applied to predict persistence and academic success, respectively. In each case a stepwise approach in data analysis was used. Results on persistence indicate that lack of regulation and amotivation at the start of the year are significant predictors. For academic success, results showed that relating and structuring, lack of regulation, and lack of motivation at the end of the year are meaningful predictors. Overall, our study demonstrates that learning strategies and motivation have a moderate explanatory value regarding academic success and persistence, and that these effects remain even after controlling for the influence of background variables.

  11. The Inhaled Steroid Treatment As Regular Therapy in Early Asthma (START) study 5-year follow-up: effectiveness of early intervention with budesonide in mild persistent asthma

    DEFF Research Database (Denmark)

    Busse, William W; Pedersen, Søren; Pauwels, Romain A;

    2008-01-01

    BACKGROUND: The Inhaled Steroid Treatment as Regular Therapy in Early Asthma (START) study enrolled 7241 patients aged 5 to 66 years with recent-onset, mild persistent asthma to assess early intervention with the inhaled corticosteroid budesonide on long-term asthma control. OBJECTIVE: The open-l...

  12. Land Deformation at the Thessaloniki - Giannitsa Plain (Greece) Deduced from 20- years Radar Observations using Persistent Scatterers Techniques

    Science.gov (United States)

    Svigkas, N.; Papoutsis, I.; Loupasakis, K.; Kiratzi, A. A.; Kontoes, C.

    2015-12-01

    We present the detected deformation and interpret the results in the light of ground-truth hydrological data, for the Thessaloniki-Giannitsa plain, the largest deltaic plain in Greece, encircled by Mounts Vermio, Paiko and Pieria. The contemporary morphology was gradually developed from the tectonic variations of the upper Pleistocene. The area has been subjected to many changes due to both natural causes and to human intervention. ERS-1, 2 and Envisat data provided from the European Space Agency were analysed to produce a time-series analysis based on Persistent Scatterer techniques. The mass processing of the 81 satellite images led to the creation of more than 250 Interferograms. The broader area of interest consists primarily of agricultural lands, leading to limited Interferometric coherence, and therefore careful Interferogram filtering and phase unwrapping of the input stack was crucial for reliable velocity generation. Our results show a strong deformation signal in regions of significant lifelines, as the railway and road network. Moreover, the satellite imagery revealed two significantly deforming sites: Kalochori and Sindos. The broader Kalochori region, the locus of the industrial activity of the city of Thessaloniki, is located below sea level. Both sites are suffering from land subsidence for more than 50 years, with several marine invasions reported in the past. Interestingly enough the two datasets -that represent two decades- show a reversed deformation pattern: The period in-between 1993 to 2000 is characterized by subsidence up to 34 mm/y, whereas from 2002 to 2010 there is an uplifting trend (more than 20 mm/yr). This result is crosschecked with hydrogeological data; the interpretation depicts that at Kalochori and Sindos the human factor (i.e. over pumping) is the dominant driver of these surface displacements. Although this was an assumption of previous studies, here we present for the first time, systematic proof that the detected uplift of

  13. Responsiveness of a patient in a persistent vegetative state after a coma to weekly injections of autologous activated immune cells: a case report

    Directory of Open Access Journals (Sweden)

    Fellerhoff Barbara

    2012-01-01

    Full Text Available Abstract Introduction An 82-year-old Caucasian woman had remained in a persistent vegetative state after a coma of seven months duration, which occurred after a stroke with hemiplegia, nine years previously. The persistent vegetative state could be reversed in part by weekly injections with activated immune cells. After therapy, our patient responded to commands in addition to regaining spontaneous movements of both arms and the ability to swallow. This is the first report on the treatment with activated immune cells of a patient in a persistent vegetative state after a coma. Case presentation An 82-year-old Caucasian woman presented with a persistent vegetative state subsequent to a coma. She retained respiratory and autonomic functions. As contact was not possible, physiotherapy was passive. Her skin was yellowish, and our patient did not move by herself. Vomiting repeatedly resulted from tube feeding. After a once-weekly treatment with activated immune cells sampled from our patient's blood and activated in vitro, several of her functions gradually returned. Our patient opened her eyes in the requested direction and turned her head toward people entering the room. She 'supported' nursing efforts, as the nurse noted a loss of spastic motions. The strength in both her arms returned, and she spontaneously moved her arm on the side experiencing hemiplegia. After three months, our patient could stick out her tongue upon demand. Finally, the swallow reflexes of our patient started to return. However, tube feeding was continued, and our patient died after aspiration of vomit following a feeding. Conclusion The success of treatment with autologous activated immune cells in this patient may have resulted from the production of neuroactive substances, such as neurotrophin-3 and brain-derived neurotrophic factor, by activated immune cells. The deterioration of our patient could be reversed, as demonstrated by the restoration of motor strength in her

  14. DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

    Science.gov (United States)

    Habibovic, Aida; Hristova, Milena; Heppner, David E.; Danyal, Karamatullah; Ather, Jennifer L.; Janssen-Heininger, Yvonne M.W.; Irvin, Charles G.; Poynter, Matthew E.; Lundblad, Lennart K.; Dixon, Anne E.; Geiszt, Miklos

    2016-01-01

    Chronic inflammation with mucous metaplasia and airway remodeling are hallmarks of allergic asthma, and these outcomes have been associated with enhanced expression and activation of EGFR signaling. Here, we demonstrate enhanced expression of EGFR ligands such as amphiregulin as well as constitutive EGFR activation in cultured nasal epithelial cells from asthmatic subjects compared with nonasthmatic controls and in lung tissues of mice during house dust mite–induced (HDM-induced) allergic inflammation. EGFR activation was associated with cysteine oxidation within EGFR and the nonreceptor tyrosine kinase Src, and both amphiregulin production and oxidative EGFR activation were diminished by pharmacologic or genetic inhibition of the epithelial NADPH oxidase dual oxidase 1 (DUOX1). DUOX1 deficiency also attenuated several EGFR-dependent features of HDM-induced allergic airway inflammation, including neutrophilic inflammation, type 2 cytokine production (IL-33, IL-13), mucous metaplasia, subepithelial fibrosis, and central airway resistance. Moreover, targeted inhibition of airway DUOX1 in mice with previously established HDM-induced allergic inflammation, by intratracheal administration of DUOX1-targeted siRNA or pharmacological NADPH oxidase inhibitors, reversed most of these outcomes. Our findings indicate an important function for DUOX1 in allergic inflammation related to persistent EGFR activation and suggest that DUOX1 targeting may represent an attractive strategy in asthma management.

  15. Persistent oxidative stress in human neural stem cells exposed to low fluences of charged particles

    Directory of Open Access Journals (Sweden)

    Janet E. Baulch

    2015-08-01

    Full Text Available Exposure to the space radiation environment poses risks for a range of deleterious health effects due to the unique types of radiation encountered. Galactic cosmic rays are comprised of a spectrum of highly energetic nuclei that deposit densely ionizing tracks of damage along the particle trajectory. These tracks are distinct from those generated by the more sparsely ionizing terrestrial radiations, and define the geometric distribution of the complex cellular damage that results when charged particles traverse the tissues of the body. The exquisite radiosensitivity of multipotent neural stem and progenitor cells found within the neurogenic regions of the brain predispose the central nervous system to elevated risks for radiation induced sequelae. Here we show that human neural stem cells (hNSC exposed to different charged particles at space relevant fluences exhibit significant and persistent oxidative stress. Radiation induced oxidative stress was found to be most dependent on total dose rather than on the linear energy transfer of the incident particle. The use of redox sensitive fluorogenic dyes possessing relative specificity for hydroxyl radicals, peroxynitrite, nitric oxide (NO and mitochondrial superoxide confirmed that most irradiation paradigms elevated reactive oxygen and nitrogen species (ROS and RNS, respectively in hNSC over a 1 week interval following exposure. Nitric oxide synthase (NOS was not the major source of elevated nitric oxides, as the use of NOS inhibitors had little effect on NO dependent fluorescence. Our data provide extensive evidence for the capability of low doses of charged particles to elicit marked changes in the metabolic profile of irradiated hNSC. Radiation induced changes in redox state may render the brain more susceptible to the development of neurocognitive deficits that could affect an astronaut’s ability to perform complex tasks during extended missions in deep space.

  16. Persistent oxidative stress in human neural stem cells exposed to low fluences of charged particles.

    Science.gov (United States)

    Baulch, Janet E; Craver, Brianna M; Tran, Katherine K; Yu, Liping; Chmielewski, Nicole; Allen, Barrett D; Limoli, Charles L

    2015-08-01

    Exposure to the space radiation environment poses risks for a range of deleterious health effects due to the unique types of radiation encountered. Galactic cosmic rays are comprised of a spectrum of highly energetic nuclei that deposit densely ionizing tracks of damage along the particle trajectory. These tracks are distinct from those generated by the more sparsely ionizing terrestrial radiations, and define the geometric distribution of the complex cellular damage that results when charged particles traverse the tissues of the body. The exquisite radiosensitivity of multipotent neural stem and progenitor cells found within the neurogenic regions of the brain predispose the central nervous system to elevated risks for radiation induced sequelae. Here we show that human neural stem cells (hNSC) exposed to different charged particles at space relevant fluences exhibit significant and persistent oxidative stress. Radiation induced oxidative stress was found to be most dependent on total dose rather than on the linear energy transfer of the incident particle. The use of redox sensitive fluorogenic dyes possessing relative specificity for hydroxyl radicals, peroxynitrite, nitric oxide (NO) and mitochondrial superoxide confirmed that most irradiation paradigms elevated reactive oxygen and nitrogen species (ROS and RNS, respectively) in hNSC over a 1 week interval following exposure. Nitric oxide synthase (NOS) was not the major source of elevated nitric oxides, as the use of NOS inhibitors had little effect on NO dependent fluorescence. Our data provide extensive evidence for the capability of low doses of charged particles to elicit marked changes in the metabolic profile of irradiated hNSC. Radiation induced changes in redox state may render the brain more susceptible to the development of neurocognitive deficits that could affect an astronaut's ability to perform complex tasks during extended missions in deep space. PMID:25800120

  17. Students' Persistence and Academic Success in a First-Year Professional Bachelor Program: The Influence of Students' Learning Strategies and Academic Motivation

    OpenAIRE

    Gert Vanthournout; David Gijbels; Liesje Coertjens; Vincent Donche; Peter Van Petegem

    2012-01-01

    The present study explores whether students' learning strategies and academic motivation predict persistence and academic success in the first year of higher education. Freshmen students in a professional bachelor program in teacher education were questioned on their learning strategy use and motivation at the start and at the end of the academic year. Students' learning strategies were assessed using the inventory of learning styles-SV. Motivation was measured using scales from the self-regu...

  18. ECTOPIC PANCREATIC, GASTRIC, AND SMALL INTESTINE TI SSUE IN AN UMBILICAL POLYP, CAUSING PERSISTENT UMBILICAL DISCH ARGE IN A 2 YEAR OLD CHILD – A RARE CASE REPORT

    Directory of Open Access Journals (Sweden)

    Sangeeta

    2013-01-01

    Full Text Available ABSTRACT: Umbilical polyps, containing vestigial remnants of th e omphalomesentric duct, are a rare cause of persistent umbilical discharge in th e paediatric age group, as compared to omphalitis or umbilical granulomas. However, umbilic al polyps need to be investigated thoroughly to ensure complete resection and to rule out extension into the abdominal cavity. Further, such umbilical polyps may cause complication s due to the presence of ectopic tissues inside them. The present case is the first reported c ase of three tissue types, viz. Pancreatic, Gastric, and Small Intestinal tissues, being present ectopically in an umbilical polyp, which had caused persistent umbilical discharge with severe lo cal excoriation and ulceration in a 2 year old child. CONCLUSION Umbilical polyps with ectopic tissues can lead to se vere complications if not treated properly, and should be ruled out in all cases of persistent umbilical discharge in the paediatric age group.

  19. Stochastic anomaly of methylome but persistent SRY hypermethylation in disorder of sex development in canine somatic cell nuclear transfer

    Science.gov (United States)

    Jeong, Young-Hee; Lu, Hanlin; Park, Chi-Hun; Li, Meiyan; Luo, Huijuan; Kim, Joung Joo; Liu, Siyang; Ko, Kyeong Hee; Huang, Shujia; Hwang, In Sung; Kang, Mi Na; Gong, Desheng; Park, Kang Bae; Choi, Eun Ji; Park, Jung Hyun; Jeong, Yeon Woo; Moon, Changjong; Hyun, Sang-Hwan; Kim, Nam Hyung; Jeung, Eui-Bae; Yang, Huanming; Hwang, Woo Suk; Gao, Fei

    2016-01-01

    Somatic cell nuclear transfer (SCNT) provides an excellent model for studying epigenomic reprogramming during mammalian development. We mapped the whole genome and whole methylome for potential anomalies of mutations or epimutations in SCNT-generated dogs with XY chromosomal sex but complete gonadal dysgenesis, which is classified as 78, XY disorder of sex development (DSD). Whole genome sequencing revealed no potential genomic variations that could explain the pathogenesis of DSD. However, extensive but stochastic anomalies of genome-wide DNA methylation were discovered in these SCNT DSD dogs. Persistent abnormal hypermethylation of the SRY gene was observed together with its down-regulated mRNA and protein expression. Failure of SRY expression due to hypermethylation was further correlated with silencing of a serial of testis determining genes, including SOX9, SF1, SOX8, AMH and DMRT1 in an early embryonic development stage at E34 in the XYDSD gonad, and high activation of the female specific genes, including FOXL2, RSPO1, CYP19A1, WNT4, ERα and ERβ, after one postnatal year in the ovotestis. Our results demonstrate that incomplete demethylation on the SRY gene is the driving cause of XYDSD in these XY DSD dogs, indicating a central role of epigenetic regulation in sex determination. PMID:27501986

  20. Stochastic anomaly of methylome but persistent SRY hypermethylation in disorder of sex development in canine somatic cell nuclear transfer.

    Science.gov (United States)

    Jeong, Young-Hee; Lu, Hanlin; Park, Chi-Hun; Li, Meiyan; Luo, Huijuan; Kim, Joung Joo; Liu, Siyang; Ko, Kyeong Hee; Huang, Shujia; Hwang, In Sung; Kang, Mi Na; Gong, Desheng; Park, Kang Bae; Choi, Eun Ji; Park, Jung Hyun; Jeong, Yeon Woo; Moon, Changjong; Hyun, Sang-Hwan; Kim, Nam Hyung; Jeung, Eui-Bae; Yang, Huanming; Hwang, Woo Suk; Gao, Fei

    2016-01-01

    Somatic cell nuclear transfer (SCNT) provides an excellent model for studying epigenomic reprogramming during mammalian development. We mapped the whole genome and whole methylome for potential anomalies of mutations or epimutations in SCNT-generated dogs with XY chromosomal sex but complete gonadal dysgenesis, which is classified as 78, XY disorder of sex development (DSD). Whole genome sequencing revealed no potential genomic variations that could explain the pathogenesis of DSD. However, extensive but stochastic anomalies of genome-wide DNA methylation were discovered in these SCNT DSD dogs. Persistent abnormal hypermethylation of the SRY gene was observed together with its down-regulated mRNA and protein expression. Failure of SRY expression due to hypermethylation was further correlated with silencing of a serial of testis determining genes, including SOX9, SF1, SOX8, AMH and DMRT1 in an early embryonic development stage at E34 in the XY(DSD) gonad, and high activation of the female specific genes, including FOXL2, RSPO1, CYP19A1, WNT4, ERα and ERβ, after one postnatal year in the ovotestis. Our results demonstrate that incomplete demethylation on the SRY gene is the driving cause of XY(DSD) in these XY DSD dogs, indicating a central role of epigenetic regulation in sex determination. PMID:27501986

  1. Is bacterial persistence a social trait?

    Directory of Open Access Journals (Sweden)

    Andy Gardner

    Full Text Available The ability of bacteria to evolve resistance to antibiotics has been much reported in recent years. It is less well-known that within populations of bacteria there are cells which are resistant due to a non-inherited phenotypic switch to a slow-growing state. Although such 'persister' cells are receiving increasing attention, the evolutionary forces involved have been relatively ignored. Persistence has a direct benefit to cells because it allows survival during catastrophes-a form of bet-hedging. However, persistence can also provide an indirect benefit to other individuals, because the reduced growth rate can reduce competition for limiting resources. This raises the possibility that persistence is a social trait, which can be influenced by kin selection. We develop a theoretical model to investigate the social consequences of persistence. We predict that selection for persistence is increased when: (a cells are related (e.g. a single, clonal lineage; and (b resources are scarce. Our model allows us to predict how the level of persistence should vary with time, across populations, in response to intervention strategies and the level of competition. More generally, our results clarify the links between persistence and other bet-hedging or social behaviours.

  2. Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein

    OpenAIRE

    Wyss-Fluehmann, Gaby; Zurbriggen, Andreas; Vandevelde, Marc; Plattet, Philippe

    2010-01-01

    The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target ce...

  3. Loss of B7-H1 expression by recipient parenchymal cells leads to expansion of infiltrating donor CD8+ T cells and persistence of GVHD

    Science.gov (United States)

    Li, Xiaofan; Deng, Ruishu; He, Wei; Liu, Can; Wang, Miao; Young, James; Meng, Zhipeng; Du, Chantal; Huang, Wendong; Chen, Lieping; Chen, Yuan-Zhong; Martin, Paul; Forman, Stephen; Zeng, Defu

    2013-01-01

    Previous experimental studies have shown that acute graft-versus-host disease (GVHD) is associated with two waves of donor CD8+ T cell expansion. In the current studies, we used in vivo bioluminescent imaging (BLI), in vivo BrdU-labeling, and three different experimental GVHD systems to show that B7-H1 expression by recipient parenchymal cells controls the second wave of alloreactive donor CD8+ T cell expansion and the associated second phase of GVHD. Loss of B7-H1 expression by parenchymal cells during the course of GVHD was associated with persistent proliferation of donor CD8+ T cells in GVHD target tissues and continued tissue injury, whereas persistent expression of B7-H1 expression by parenchymal cells led to reduced proliferation of donor CD8+ T cells in GVHD target tissues and resolution of GVHD. These studies demonstrate that parenchymal cell expression of B7-H1 is required for tolerizing infiltrating T cells and preventing the persistence of GVHD. Our results suggest that therapies designed to preserve or restore expression of B7-H1 expression by parenchymal tissues in the recipient could prevent or ameliorate GVHD in humans. PMID:22156590

  4. Curing of foot-and-mouth disease virus from persistently infected cells by ribavirin involves enhanced mutagenesis

    International Nuclear Information System (INIS)

    BHK-21 cells persistently infected with foot-and-mouth disease virus (FMDV) can be cured of virus by treatment with the antiviral nucleoside analogue ribavirin. To study whether the process involved an increase in the number of mutations in the mutant spectrum of the viral population, viral genomes were cloned from persistently infected cells treated or untreated with ribavirin. An increase of up to 10-fold in mutation frequencies associated with ribavirin treatment was observed in the viral genomes from the treated cultures as compared with parallel, untreated cultures. To address the possible mechanisms of enhanced mutagenesis, we investigated the mutagenic effects of ribavirin together with guanosine, and mycophenolic acid in the presence or absence of guanosine. Changes in the intracellular nucleotide concentrations were determined for all treatments. The results suggest that the increased mutation frequencies were not dependent on nucleotide pool imbalances or due to selection of preexisting genomes but they were produced by a mutagenic action of ribavirin

  5. Associations between Exposure to Persistent Organic Pollutants in Childhood and Overweight up to 12 Years Later in a Low Exposed Danish Population

    DEFF Research Database (Denmark)

    Tang-Péronard, Jeanett L; Jensen, Tina K; Andersen, Helle R;

    2015-01-01

    BACKGROUND: Persistent organic pollutants (POPs) have metabolic disrupting abilities and are suggested to contribute to the obesity epidemic. We investigated whether serum concentrations of POPs at 8-10 years of age were associated with subsequent development of overweight at age 14-16 and 20...... children aged 8-10 years (n = 509). Information on BMI z-scores, waist circumference and % body fat were collected at clinical examinations at ages 8-10, 14-16 and 20-22 years. Multiple linear regression analyses were performed taking potential confounders into account. RESULTS: Overall, POP serum...

  6. Persistence of Vancomycin Resistance in Multiple Clones of Enterococcus faecium Isolated from Danish Broilers 15 Years after the Ban of Avoparcin

    DEFF Research Database (Denmark)

    Bortolaia, Valeria; Mander, Manuela; Jensen, Lars Bogø;

    2015-01-01

    The occurrence and diversity of vancomycin-resistant Enterococcus faecium (VREF) were investigated in 100 Danish broiler flocks 15 years after the avoparcin ban. VREF occurred in 47 flocks at low fecal concentrations detectable only by selective enrichment. Vancomycin resistance was prevalently...... associated with a transferable nontypeable plasmid lineage occurring in multiple E. faecium clones. Coselection of sequence type 842 by tetracycline use only partly explained the persistence of vancomycin resistance in the absence of detectable plasmid coresistance and toxin-antitoxin systems....

  7. Controlling Persister and Biofilm Cells of Gram-Negative Bacteria with a New 1,3,5-Triazine Derivative

    Directory of Open Access Journals (Sweden)

    Ali Adem Bahar

    2015-10-01

    Full Text Available Infections caused by multidrug-resistant bacteria have been on the rise. This important issue presents a great challenge to the healthcare system and creates an urgent need for alternative therapeutic agents. As a potential solution to this problem, antimicrobial peptides (AMPs have attracted increasing attention due to their broad spectrum of targeted microbes. However, most AMPs are expensive to synthesize, have relatively high cytotoxicity to mammalian cells, and are susceptible to proteolytic degradation. In order to overcome these limitations, novel synthetic AMPs are desired. Using 1,3,5-triazine (TN as a template, several combinatorial libraries with varying cationic charge and lipophilicity were designed and screened by the Kallenbach lab. From this screening, TN-5 was identified as a potent lead. In the present study, this compound was tested for its antimicrobial activities on Escherichia coli and Pseudomonas aeruginosa. In addition to regular planktonic cells, the effects on biofilms and persister cells (metabolically inactive and antibiotic tolerant subpopulation were also investigated. TN-5 was found to have a minimum inhibitory concentration (MIC of 12.8 μM for both species and kill regular planktonic cells of both species dose dependently. TN-5 is also effective against persister cells of both E. coli and P. aeruginosa. The killing of biofilm cells of the mucoid P. aeruginosa PDO300 was enhanced by alginate lyase.

  8. A four-year follow-up controlled study of stress response and symptom persistence in Brazilian children and adolescents with attention deficit disorder and hyperactivity (ADHD).

    Science.gov (United States)

    Palma, Sonia Maria Motta; Natale, Ana Carolina Motta Palma; Calil, Helena Maria

    2015-12-15

    This study evaluated children and adolescents with Attention Deficit Disorder andHyperactivity Disorder (ADHD), reassessing them at a four-year follow-up. Their cortisol response to a stress stimulus was measured twice. ADHD symptom persistence, development of comorbidities, and psychostimulant usage were also reassessed. The initial sample consisted of 38 ADHD patients and 38 healthy controls, age ranging 6-14. At the follow-up, there were 37 ADHD patients and 22 healthy controls, age ranging 10-18. ADHD was classified as persistent if the patients fulfilled all DSM IV criteria for syndromic or subthreshold or had functional impairment. Salivary cortisol samples were collected prior to the application of a cognitive stressor (Continuous Performance Test - CPT), and at three time intervals afterwards at baseline and at the follow-up. Their reassessment showed that 75% had persistent symptoms, psychiatric comorbidities (oppositional defiant and behavioral disorders), functional and academic impairement. Only seven patients were on medication. The ADHD group's cortisol levels were lower than those measured four years earlier, but cortisol concentrations were similar for both ADHD and control groups at the four-year follow-up. The cortisol results suggest that HPA axis reactivity could be a marker differentiating ADHD from ADHD with comorbidities.

  9. Persistent donor cell gene expression among human induced pluripotent stem cells contributes to differences with human embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Zhumur Ghosh

    Full Text Available Human induced pluripotent stem cells (hiPSCs generated by de-differentiation of adult somatic cells offer potential solutions for the ethical issues surrounding human embryonic stem cells (hESCs, as well as their immunologic rejection after cellular transplantation. However, although hiPSCs have been described as "embryonic stem cell-like", these cells have a distinct gene expression pattern compared to hESCs, making incomplete reprogramming a potential pitfall. It is unclear to what degree the difference in tissue of origin may contribute to these gene expression differences. To answer these important questions, a careful transcriptional profiling analysis is necessary to investigate the exact reprogramming state of hiPSCs, as well as analysis of the impression, if any, of the tissue of origin on the resulting hiPSCs. In this study, we compare the gene profiles of hiPSCs derived from fetal fibroblasts, neonatal fibroblasts, adipose stem cells, and keratinocytes to their corresponding donor cells and hESCs. Our analysis elucidates the overall degree of reprogramming within each hiPSC line, as well as the "distance" between each hiPSC line and its donor cell. We further identify genes that have a similar mode of regulation in hiPSCs and their corresponding donor cells compared to hESCs, allowing us to specify core sets of donor genes that continue to be expressed in each hiPSC line. We report that residual gene expression of the donor cell type contributes significantly to the differences among hiPSCs and hESCs, and adds to the incompleteness in reprogramming. Specifically, our analysis reveals that fetal fibroblast-derived hiPSCs are closer to hESCs, followed by adipose, neonatal fibroblast, and keratinocyte-derived hiPSCs.

  10. Differential effects of the persistent DDT metabolite methylsulfonyl-DDE in nonstimulated and LH-stimulated neonatal porcine Leydig cells.

    Science.gov (United States)

    Castellanos, Cesilie Granum; Sørvik, Irene Beate; Tanum, Marte Bruu; Verhaegen, Steven; Brandt, Ingvar; Ropstad, Erik

    2013-03-15

    3-Methylsulfonyl-DDE (MeSO₂-DDE) is a potent adrenal toxicant formed from the persistent insecticide DDT. MeSO₂-DDE is widely present in human plasma, milk and fat, and in tissues of marine mammals. In the present study, we investigated endocrine-disrupting properties of MeSO₂-DDE in primary neonatal porcine Leydig cells. Unstimulated and LH-stimulated cells were exposed to MeSO₂-DDE at concentrations ranging from 0.6 to 20 μM for 48 h. Cell viability, hormone secretion and expression of steroidogenesis related genes were recorded. Secretion of testosterone and estradiol was increased in a concentration-dependent fashion in unstimulated Leydig cells, while in LH-stimulated cells, secretion of testosterone, estradiol and progesterone was decreased. The expression of important steroidogenic genes was down-regulated both in unstimulated and LH-stimulated cells. Notably, no significant impairment of cell viability occurred at any exposure except the highest concentration (20 μM) in LH-stimulated cells. This indicated that the effects on hormone secretion and gene expression were not caused by cytotoxicity. We conclude that the adrenal toxicant MeSO₂-DDE disrupts hormone secretion in a complex fashion in neonatal porcine Leydig cells. The different endocrine responses in unstimulated and LH-stimulated cells imply that the endocrine disruptive activity of MeSO₂-DDE is determined by the physiological status of the Leydig cells.

  11. Persistence of collagen type II-specific T-cell clones in the synovial membrane of a patient with rheumatoid arthritis

    International Nuclear Information System (INIS)

    Rheumatoid arthritis is an autoimmune disease characterized by T-cell infiltration of the synovium of joints. Analysis of the phenotype and antigen specificity of the infiltrating cells may thus provide insight into the pathogenesis of rheumatoid arthritis. T cells were cloned with interleukin 2, a procedure that selects for in vivo-activated cells. All clones had the CD4 CDW29 phenotype. Their antigen specificity was tested by using a panel of candidate joint autoantigens. Four of 17 reacted against autologous blood mononuclear cells. Two clones proliferated in response to collagen type II. After 21 months, another set of clones was derived from synovial tissue of the same joint. One of eight clones tested showed a strong proliferative response against collagen type II. The uncloned synovial T cells of a third operation from another joint also responded to collagen type II. The persistence of collagen type II-specific T cells in active rheumatoid joints over a period of 3 years suggests that collagen type II could be one of the autoantigens involved in perpetuating the inflammatory process in rheumatoid arthritis

  12. Persistent pain is common 1 year after ankle and wrist fracture surgery: a register-based questionnaire study

    DEFF Research Database (Denmark)

    Friesgaard, Kristian Dahl; Gromov, Kirill; Knudsen, Lone;

    2016-01-01

    and pain characteristics are required. METHODS: All patients undergoing primary surgery because of ankle or wrist fracture at Hvidovre and Odense University Hospitals, Denmark, between April 15, 2013 and April 15, 2014, were identified from the Danish Fracture Database. A questionnaire regarding pain...... neuropathic pain, and 4.0% fulfilled the diagnostic patient-reported research criteria for CRPS. CONCLUSIONS: Persistent postsurgical pain 1 yr after wrist and ankle fracture surgery is frequent, and a large proportion of patients experience symptoms suggestive of neuropathic pain and CRPS. Patients should be...

  13. Endometrial stem/progenitor cells: the first 10 years

    OpenAIRE

    Gargett, Caroline E; Schwab, Kjiana E.; Deane, James A

    2015-01-01

    BACKGROUND The existence of stem/progenitor cells in the endometrium was postulated many years ago, but the first functional evidence was only published in 2004. The identification of rare epithelial and stromal populations of clonogenic cells in human endometrium has opened an active area of research on endometrial stem/progenitor cells in the subsequent 10 years. METHODS The published literature was searched using the PubMed database with the search terms ‘endometrial stem cells and menstru...

  14. Persistence of antiretroviral treatment in emtricitabine/tenofovir (FTC/TDF users vs other NRTI in ART-naïve patients>50 years: TRIP study

    Directory of Open Access Journals (Sweden)

    E Pedrol

    2012-11-01

    Full Text Available The major antiretroviral guidelines recommend starting ART in patients>50 y of age, regardless of CD4 cell count. However, no references to the preferred cART for these patients have been described. The combination FTC/TDF is one of the cornerstones of combined antiretroviral therapy (cART in naïve patients. We studied the persistence of coformulated FTC/TDF in this scenario. National, retrospective cohort analysis of HIV-infected patients>50 y at the time they began the first cART regimen (January 1, 2006 – December 31, 2009. Patients were selected in a proportion 2:1 to FTC/TDF vs. other NRTI regimens (no-TDF. We compared the persistence of treatment in FTC/TDF users vs. no-TDF (main groups. Among TDF users, we compared the persistence in PI vs. NNRTI users and in lopinavir/r vs. efavirenz users. Persistence was defined as the duration of the initial treatment; we analyzed time to any change or discontinuation according to initial regimen. We included 161 patients: median age: 54.6 y, 83% males, median CD4 count 191 cells/μl, median viral load 4.7 log, follow up: median 19 months, max 48 months. Of them, 112 started with FTC/TDF (53 with PIs, 57 with NNRTIs; and 49 with other NRTIs (no-TDF (22 with PI, 23 NNRTI. During the follow-up period 79 patients (49% modified their treatment, with statistically significant differences among groups, as shown in Table 1.*Adjusted by age, sex, transmission category and baseline CD4 count and viral load. In our study (antiretroviral-naïve patients>50 y, the persistence of FTC/TDF regimens was significantly higher than other NRTI regimens. According to the third agent, there was a trend to a higher persistence with NNRTI vs. PI. This reaches statistical significance when we compare EFV vs. LPV/r. In the absence of randomized clinical trials, our data may contribute to a better understanding on how cART works in this ageing population, which is progressively increasing.

  15. 13-year-old girl with recurrent, episodic, persistent vomiting: out of the pot and into the fire.

    Science.gov (United States)

    Felton, Diana; Zitomersky, Naamah; Manzi, Shannon; Lightdale, Jenifer R

    2015-04-01

    Cyclic vomiting syndrome (CVS) is a well-established cause of recurrent vomiting in the pediatric population. Severe vomiting with chronic cannabis use, known as cannabinoid hyperemesis syndrome, has recently been more widely recognized as an etiology of persistent episodic vomiting. In turn, patients presenting with frequent episodes of CVS are now increasingly being screened for cannabinoid use. Because patients with persistent vomiting are also frequently prescribed a proton pump inhibitor (PPI) for their gastrointestinal symptoms, it is important to be aware of the potential for a PPI to cause an interaction that can lead to false-positive urine cannabinoid screening. We describe a case of a false-positive urine cannabinoid screen in a patient with CVS who received a dose of intravenous pantoprazole. The primary reference regarding drug screen interference from PPIs can be found in the pantoprazole package insert that refers to pre-Food and Drug Administration approval data. Although multiple sources on the Internet report the possibility of positive cannabinoid screens from pantoprazole, there are no known published reports of the phenomenon in the medical literature. PMID:25733759

  16. Survival and persistence of fecal host-specific Bacteroidales cells and their DNA assessed by PMA-qPCR

    Science.gov (United States)

    Bae, S.; Bombardelli, F.; Wuertz, S.

    2008-12-01

    Understanding and managing microbial pollutions in water is one of the foremost challenges of establishing effective managements and remediation strategies to impaired water bodies polluted by uncharacterized fecal sources. Quantitative microbial source tracking (MST) approaches using fecal Bacteroidales and quantitative PCR (qPCR) assays to measure gene copies of host-specific 16S rRNA genetic markers are promising because they can allow for identifying and quantifying fecal loadings from a particular animal host and understanding the fate and transport of host-specific Bacteroidales over a range of conditions in water bodies. Similar to the case of traditional fecal indicator bacteria, a relatively long persistence of target DNA may hamper applied MST studies, if genetic markers cannot be linked to recent fecal pollution in water. We report a successful approach to removing the qPCR signal derived from free DNA and dead host-specific Bacteroidales cells by selectively binding the DNA and consequently inhibiting PCR amplification using light- activated propidium monoazide (PMA). Optimal PMA-qPCR conditions were determined as 100 µM of PMA concentration and a 10-min light exposure time at different solids concentrations in order to mimic a range of water samples. Under these conditions, PMA-qPCR resulted in the selective exclusion of DNA from heat- treated cells of non-culturable Bacteroidales in human feces and wastewater influent and effluent samples. Also, the persistence of feces-derived host-specific Bacteroidales DNA and their cells (determined by universal, human-, cow- and dog-specific Bacteroidales qPCR assays) in seawater was investigated in microcosms at environmental conditions. The average T99 (two log reduction) value for host-specific viable Bacteroidales cells was 28 h, whereas that for total host-specific Bacteroidales DNA was 177 h. Natural sunlight did not have a strong influence on the fate of fecal Bacteroidales cells and their DNA, presumably

  17. Sundials in the shade: A study of women's persistence in the first year of a computer science program in a selective university

    Science.gov (United States)

    Powell, Rita Manco

    Currently women are underrepresented in departments of computer science, making up approximately 18% of the undergraduate enrollment in selective universities. Most attrition in computer science occurs early in this major, in the freshman and sophomore years, and women drop out in disproportionately greater numbers than their male counterparts. Taking an ethnographic approach to investigating women's experiences and progress in the first year courses in the computer science major at the University of Pennsylvania, this study examined the pre-college influences that led these women to the major and the nature of their experiences in and outside of class with faculty, peers, and academic support services. This study sought an understanding of the challenges these women faced in the first year of the major with the goal of informing institutional practice about how to best support their persistence. The research reviewed for this study included patterns of leaving majors in science, math and engineering (Seymour & Hewitt 1997), the high school preparation needed to pursue math and engineering majors in college (Strenta, Elliott, Adair, Matier, & Scott, 1994), and intervention programs that have positively impacted persistence of women in computer science (Margolis & Fisher, 2002). The research method of this study employed a series of personal interviews over the course of one calendar year with fourteen first year women who had either declared on intended to declare the computer science major in the School of Engineering and Applied Science at the University of Pennsylvania. Other data sources were focus groups and personal interviews with faculty, administrators, admissions and student life professionals, teaching assistants, female graduate students, and male first year students at the University of Pennsylvania. This study found that the women in this study group came to the University of Pennsylvania with a thorough grounding in mathematics, but many either had

  18. Defective interfering particles of Sindbis virus do not interfere with the homologous virus obtained from persistently infected BHK cells but do interfere with Semliki Forest virus.

    OpenAIRE

    Weiss, B; Schlesinger, S

    1981-01-01

    Defective interfering particles derived from wild-type Sindbis virus no longer interfere with the infectious virus cloned from BHK cells persistently infected with Sindbis virus for 16 months. These particles do interfere with the replication of Semliki Forest virus.

  19. [INTERCONNECTION BETWEEN CELL MICROVESICULAR TRANSPORT AND PATHOGENS PERSISTENCE IN VITRO AND IN VIVO].

    Science.gov (United States)

    Miller, G G; Mukhachev, A Ya; Bykovsky, A F

    2015-01-01

    This review presents an information and proof evidence toward to the role of microvesicles, originating from the different sources pro- and eucaryotes in the initiation and development of persistence of several human and animal pathogens. Also an information about another properties of microvesicles, as well as the reference of role in the different somatic pathology, intercellular interaction and in the intracellular transport of biologically active macromolecules as well as life origin and evolutionary events.

  20. DAMPAK DEFISIENSI IODIUM MATERNAL PADA PERSISTENSI DISFUNGSI NEUROPSIKOLOGIS ANAK USIA 12 TAHUN (EFFECT OF MATERNAL IODINE DEFICIENCY ON THE PERSISTENCE OF NEUROLOGICAL DYSFUNCTIONS IN CHILDREN AGED 12 YEARS

    Directory of Open Access Journals (Sweden)

    Basuki Budiman

    2012-06-01

    Full Text Available ABSTRACT Study on the last effect of neuropsychologic dysfunction due to iodine deficiency during gestation is still scarce. This study is to confirm the persistence of neuropsychological dysfunctions at 12-year-old of children born from pregnant mothers with iodine deficiency in endemic iodine deficient area. The study is 13-year-cohort design. Iodine status (Total T4, TSH and UIE of pregnant mothers at initial study, neonatal (TSH and 12 year-old iodine status (fT4, TSH are performed. Neurological dysfunction of infants is examined every 6 weeks until the child age is 24 months. Neuropsychological dysfunction of children 12 years of age such as minimal brain dysfunction and psychological battery of Wechsler Intelligence Scale for Children (WISC are also administered. A screening to determine case and reference using is done using mini mental status examination (MMSE. Score MMSE of 28 or less are implemented as cases while others as reference. The relationship of neurological and cognitive dysfunction with both maternal iodine status and neurological dysfunction at 2 months of neonates age are elaborated. The persistency risk of neurological dysfunction at 12 years of age is 8% (95%ci: 1-15%. Maternal and neonatal iodine status (as indicated by TSH, T4 are the risk factors for the persistency at 12-years. However, delays of neurological development in two-month old infants are found as directly risk factors. Median Total IQ score for all participants are far lower than the lowest limit of normal range. A very significant difference (p=0.000 are found in Total IQ score between cases and references. Discrepancy analysis of IQV-IQP indicates brain lesions in subtle form, such as diadokhokinesis, praxis, memory, distractibility and lowered IQ score. Neuropsychological dysfunctions due maternal iodine deficiency are still persistence at 12 years. Maternal T4 during gestation is not only influences on the persistency but also impaires directly on the

  1. Leukemic stem cell persistence in chronic myeloid leukemia patients in deep molecular response induced by tyrosine kinase inhibitors and the impact of therapy discontinuation

    Science.gov (United States)

    Chomel, Jean Claude; Bonnet, Marie Laure; Sorel, Nathalie; Sloma, Ivan; Bennaceur-Griscelli, Annelise; Rea, Delphine; Legros, Laurence; Marfaing-Koka, Anne; Bourhis, Jean-Henri; Ame, Shanti; Guerci-Bresler, Agnès; Rousselot, Philippe; Turhan, Ali G.

    2016-01-01

    During the last decade, the use of tyrosine kinase inhibitor (TKI) therapy has modified the natural history of chronic myeloid leukemia (CML) allowing an increase of the overall and disease-free survival, especially in patients in whom molecular residual disease becomes undetectable. However, it has been demonstrated that BCR-ABL1- expressing leukemic stem cells (LSCs) persist in patients in deep molecular response. It has also been shown that the discontinuation of Imatinib leads to a molecular relapse in the majority of cases. To determine a possible relationship between these two phenomena, we have evaluated by clonogenic and long-term culture initiating cell (LTC-IC) assays, the presence of BCR-ABL1-expressing LSCs in marrow samples from 21 patients in deep molecular response for three years after TKI therapy (mean duration seven years). LSCs were detected in 4/21 patients. Discontinuation of TKI therapy in 13/21 patients led to a rapid molecular relapse in five patients (4 without detectable LSCs and one with detectable LSCs). No relapse occurred in the eight patients still on TKI therapy, whether LSCs were detectable or not. Thus, this study demonstrates for the first time the in vivo efficiency of TKIs, both in the progenitor and the LSC compartments. It also confirms the persistence of leukemic stem cells in patients in deep molecular response, certainly at the origin of relapses. Finally, it emphasizes the difficulty of detecting residual LSCs due to their rarity and their low BCR-ABL1 mRNA expression. PMID:27167108

  2. Leukemic stem cell persistence in chronic myeloid leukemia patients in deep molecular response induced by tyrosine kinase inhibitors and the impact of therapy discontinuation.

    Science.gov (United States)

    Chomel, Jean Claude; Bonnet, Marie-Laure; Sorel, Nathalie; Sloma, Ivan; Bennaceur-Griscelli, Annelise; Rea, Delphine; Legros, Laurence; Marfaing-Koka, Anne; Bourhis, Jean-Henri; Ame, Shanti; Guerci-Bresler, Agnès; Rousselot, Philippe; Turhan, Ali G

    2016-06-01

    During the last decade, the use of tyrosine kinase inhibitor (TKI) therapy has modified the natural history of chronic myeloid leukemia (CML) allowing an increase of the overall and disease-free survival, especially in patients in whom molecular residual disease becomes undetectable. However, it has been demonstrated that BCR-ABL1- expressing leukemic stem cells (LSCs) persist in patients in deep molecular response. It has also been shown that the discontinuation of Imatinib leads to a molecular relapse in the majority of cases. To determine a possible relationship between these two phenomena, we have evaluated by clonogenic and long-term culture initiating cell (LTC-IC) assays, the presence of BCR-ABL1-expressing LSCs in marrow samples from 21 patients in deep molecular response for three years after TKI therapy (mean duration seven years). LSCs were detected in 4/21 patients. Discontinuation of TKI therapy in 13/21 patients led to a rapid molecular relapse in five patients (4 without detectable LSCs and one with detectable LSCs). No relapse occurred in the eight patients still on TKI therapy, whether LSCs were detectable or not. Thus, this study demonstrates for the first time the in vivo efficiency of TKIs, both in the progenitor and the LSC compartments. It also confirms the persistence of leukemic stem cells in patients in deep molecular response, certainly at the origin of relapses. Finally, it emphasizes the difficulty of detecting residual LSCs due to their rarity and their low BCR-ABL1 mRNA expression. PMID:27167108

  3. Altered growth, differentiation, and responsiveness to epidermal growth factor of human embryonic mesenchymal cells of palate by persistent rubella virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Yoneda, T.; Urade, M.; Sakuda, M.; Miyazaki, T.

    1986-05-01

    We previously demonstrated that human embryonic mesenchymal cells derived from the palate (HEMP cells) retain alkaline phosphatase (ALP) content and capacity for collagen synthesis after long-term culture, and their growth is markedly stimulated by epidermal growth factor (EGF). There was a dramatic decrease in ALP content and capacity to synthesize collagen in HEMP cells (HEMP-RV cells) persistently infected with rubella virus (RV). EGF increased ALP activity and decreased collagen synthesis in HEMP cells, whereas EGF showed no effect on these activities in HEMP-RV cells. Growth of HEMP-RV cells was slightly reduced compared with that of HEMP cells. EGF stimulated growth of HEMP cells and to a lesser extent of HEMP-RV cells. Binding of /sup 125/I-EGF to cell-surface receptors in HEMP-RV cells was, to our surprise, twice as much as that in HEMP cells. However, internalization of bound /sup 125/I-EGF in HEMP-RV cells was profoundly diminished. Thus, persistent RV infection causes not only changes in HEMP cell growth and differentiation but a decrease in or loss of HEMP cell responsiveness to EGF. The effects of persistent RV infection on palatal cell differentiation as well as growth may be responsible for the pathogenesis of congenital rubella. Furthermore, since HEMP cells appear to be closely related to osteoblasts, these results suggest a mechanism for RV-induced osseous abnormalities manifested in congenital rubella patients.

  4. Modulation of Cell Sialoglycophenotype: A Stylish Mechanism Adopted by Trypanosoma cruzi to Ensure Its Persistence in the Infected Host

    Science.gov (United States)

    Freire-de-Lima, Leonardo; da Fonseca, Leonardo M.; da Silva, Vanessa A.; da Costa, Kelli M.; Morrot, Alexandre; Freire-de-Lima, Célio G.; Previato, Jose O.; Mendonça-Previato, Lucia

    2016-01-01

    Trypanosoma cruzi, the etiological agent of Chagas disease exhibits multiple mechanisms to guarantee its establishment and persistence in the infected host. It has been well demonstrated that T. cruzi is not able to synthesize sialic acids (Sia). To acquire the monosaccharide, the parasite makes use of a multifunctional enzyme called trans-sialidase (Tc-TS). Since this enzyme has no analogous in the vertebrate host, it has been used as a target in drug therapy development. Tc-TS preferentially catalyzes the transfer of Sia from the host glycoconjugates to the terminal β-galactopyranosyl residues of mucin-like molecules present on the parasite’s cell surface. Alternatively, the enzyme can sialylate/re-sialylate glycoconjugates expressed on the surface of host cells. Since its discovery, several studies have shown that T. cruzi employs the Tc-TS activity to modulate the host cell sialoglycophenotype, thus favoring its perpetuation in the infected vertebrate. In this review, we summarize the dynamic of host/parasite sialoglycophenotype modulation, highlighting its role in the subversion of host immune response in order to promote the establishment of persistent chronic infection. PMID:27242722

  5. Persistence at one year of age of antigen-induced cellular immune responses in preterm infants vaccinated against whooping cough: comparison of three different vaccines and effect of a booster dose.

    Science.gov (United States)

    Vermeulen, Françoise; Dirix, Violette; Verscheure, Virginie; Damis, Eliane; Vermeylen, Danièle; Locht, Camille; Mascart, Françoise

    2013-04-01

    Due to their high risk of developing severe Bordetella pertussis (Bp) infections, it is recommended to immunize preterm infants at their chronological age. However, little is known about the persistence of their specific immune responses, especially of the cellular responses recognized to play a role in protection. We compared here the cellular immune responses to two major antigens of Bp between three groups of one year-old children born prematurely, who received for their primary vaccination respectively the whole cell vaccine Tetracoq(®) (TC), the acellular vaccine Tetravac(®) (TV), or the acellular vaccine Infanrix-hexa(®) (IR). Whereas most children had still detectable IFN-γ responses at one year of age, they were lower in the IR-vaccinated children compared to the two other groups. In contrast, both the TV- and the IR-vaccinated children displayed higher Th2-type immune responses, resulting in higher antigen-specific IFN-γ/IL-5 ratios in TC- than in TV- or IR-vaccinated children. The IFN-γ/IL-5 ratio of mitogen-induced cytokines was also lower in IR- compared to TC- or TV-vaccinated children. No major differences in the immune responses were noted after the booster compared to the pre-booster responses for each vaccine. The IR-vaccinated children had a persistently low specific Th1-type immune response associated with high specific Th2-type immune responses, resulting in lower antigen-specific IFN-γ/IL-5 ratios compared to the two other groups. We conclude that antigen-specific cellular immune responses persisted in one year-old children born prematurely and vaccinated during infancy at their chronological age, that a booster dose did not significantly boost the cellular immune responses, and that the Th1/Th2 balance of the immune responses is modulated by the different vaccines.

  6. Exploitation of the complement system by oncogenic Kaposi's sarcoma-associated herpesvirus for cell survival and persistent infection.

    Directory of Open Access Journals (Sweden)

    Myung-Shin Lee

    2014-09-01

    Full Text Available During evolution, herpesviruses have developed numerous, and often very ingenious, strategies to counteract efficient host immunity. Specifically, Kaposi's sarcoma-associated herpesvirus (KSHV eludes host immunity by undergoing a dormant stage, called latency wherein it expresses a minimal number of viral proteins to evade host immune activation. Here, we show that during latency, KSHV hijacks the complement pathway to promote cell survival. We detected strong deposition of complement membrane attack complex C5b-9 and the complement component C3 activated product C3b on Kaposi's sarcoma spindle tumor cells, and on human endothelial cells latently infected by KSHV, TIME-KSHV and TIVE-LTC, but not on their respective uninfected control cells, TIME and TIVE. We further showed that complement activation in latently KSHV-infected cells was mediated by the alternative complement pathway through down-regulation of cell surface complement regulatory proteins CD55 and CD59. Interestingly, complement activation caused minimal cell death but promoted the survival of latently KSHV-infected cells grown in medium depleted of growth factors. We found that complement activation increased STAT3 tyrosine phosphorylation (Y705 of KSHV-infected cells, which was required for the enhanced cell survival. Furthermore, overexpression of either CD55 or CD59 in latently KSHV-infected cells was sufficient to inhibit complement activation, prevent STAT3 Y705 phosphorylation and abolish the enhanced survival of cells cultured in growth factor-depleted condition. Together, these results demonstrate a novel mechanism by which an oncogenic virus subverts and exploits the host innate immune system to promote viral persistent infection.

  7. The MqsRA Toxin-Antitoxin System from Xylella fastidiosa Plays a Key Role in Bacterial Fitness, Pathogenicity, and Persister Cell Formation.

    Science.gov (United States)

    Merfa, Marcus V; Niza, Bárbara; Takita, Marco A; De Souza, Alessandra A

    2016-01-01

    Through the formation of persister cells, bacteria exhibit tolerance to multidrug and other environmental stresses without undergoing genetic changes. The toxin-antitoxin (TA) systems are involved in the formation of persister cells because they are able to induce cell dormancy. Among the TA systems, the MqsRA system has been observed to be highly induced in persister cells of Xylella fastidiosa (causal agent of citrus variegated chlorosis-CVC) activated by copper stress, and has been described in Escherichia coli as related to the formation of persister cells and biofilms. Thus, we evaluated the role of this TA system in X. fastidiosa by overexpressing the MqsR toxin, and verified that the toxin positively regulated biofilm formation and negatively cell movement, resulting in reduced pathogenicity in citrus plants. The overexpression of MqsR also increased the formation of persister cells under copper stress. Analysis of the gene and protein expression showed that this system likely has an autoregulation mechanism to express the toxin and antitoxin in the most beneficial ratio for the cell to oppose stress. Our results suggest that this TA system plays a key role in the adaptation and survival of X. fastidiosa and reveal new insights into the physiology of phytopathogen-host interactions. PMID:27375608

  8. Mutant human FUS Is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells.

    Directory of Open Access Journals (Sweden)

    Jamie Rae Acosta

    Full Text Available FUS mutations can occur in familial amyotrophic lateral sclerosis (fALS, a neurodegenerative disease with cytoplasmic FUS inclusion bodies in motor neurons. To investigate FUS pathology, we generated transgenic zebrafish expressing GFP-tagged wild-type or fALS (R521C human FUS. Cell cultures were made from these zebrafish and the subcellular localization of human FUS and the generation of stress granule (SG inclusions examined in different cell types, including differentiated motor neurons. We demonstrate that mutant FUS is mislocalized from the nucleus to the cytosol to a similar extent in motor neurons and all other cell types. Both wild-type and R521C FUS localized to SGs in zebrafish cells, demonstrating an intrinsic ability of human FUS to accumulate in SGs irrespective of the presence of disease-associated mutations or specific cell type. However, elevation in relative cytosolic to nuclear FUS by the R521C mutation led to a significant increase in SG assembly and persistence within a sub population of vulnerable cells, although these cells were not selectively motor neurons.

  9. Mutant human FUS Is ubiquitously mislocalized and generates persistent stress granules in primary cultured transgenic zebrafish cells.

    Science.gov (United States)

    Acosta, Jamie Rae; Goldsbury, Claire; Winnick, Claire; Badrock, Andrew P; Fraser, Stuart T; Laird, Angela S; Hall, Thomas E; Don, Emily K; Fifita, Jennifer A; Blair, Ian P; Nicholson, Garth A; Cole, Nicholas J

    2014-01-01

    FUS mutations can occur in familial amyotrophic lateral sclerosis (fALS), a neurodegenerative disease with cytoplasmic FUS inclusion bodies in motor neurons. To investigate FUS pathology, we generated transgenic zebrafish expressing GFP-tagged wild-type or fALS (R521C) human FUS. Cell cultures were made from these zebrafish and the subcellular localization of human FUS and the generation of stress granule (SG) inclusions examined in different cell types, including differentiated motor neurons. We demonstrate that mutant FUS is mislocalized from the nucleus to the cytosol to a similar extent in motor neurons and all other cell types. Both wild-type and R521C FUS localized to SGs in zebrafish cells, demonstrating an intrinsic ability of human FUS to accumulate in SGs irrespective of the presence of disease-associated mutations or specific cell type. However, elevation in relative cytosolic to nuclear FUS by the R521C mutation led to a significant increase in SG assembly and persistence within a sub population of vulnerable cells, although these cells were not selectively motor neurons.

  10. Impairment of social behaviour persists two years after embryonic alcohol exposure in zebrafish: A model of fetal alcohol spectrum disorders.

    Science.gov (United States)

    Fernandes, Yohaan; Rampersad, Mindy; Gerlai, Robert

    2015-10-01

    Zebrafish naturally form social groups called shoals. Previously, we have shown that submerging zebrafish eggs into low concentrations of alcohol (0.00, 0.25, 0.50, 0.75 and 1.00 vol/vol% external bath concentration) during development (24h post-fertilization) for two hours resulted in impaired shoaling response in seven month old young adult zebrafish. Here we investigate whether this embryonic alcohol exposure induced behavioural deficit persists to older age. Zebrafish embryos were exposed either to fresh system water (control) or to 1% alcohol for two hours, 24h after fertilization, and were raised in a high-density tank system. Social behaviour was tested by presenting the experimental fish with a computer animated group of zebrafish images, while automated tracking software measured their behaviour. Control fish were found to respond strongly to animated conspecific images by reducing their distanceand remaining close to the images during image presentation, embryonic alcohol treated fish did not. Our results suggest that the impaired shoaling response of the alcohol exposed fish was not due to altered motor function or visual perception, but likely to a central nervous system alteration affecting social behaviour itself. We found the effects of embryonic alcohol exposure on social behaviour not to diminish with age, a result that demonstrates the deleterious and potentially life-long consequences of exposure to even small amount of alcohol during embryonic development in vertebrates.

  11. The relation of plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) with HPV persistence in HIV-infected and HIV-uninfected women.

    Science.gov (United States)

    Strickler, Howard D; Martinson, Jeffrey; Desai, Seema; Xie, Xianhong; Burk, Robert D; Anastos, Kathryn; Massad, L Stewart; Minkoff, Howard; Xue, Xiaonan; D'Souza, Gypsyamber; Levine, Alexandra M; Colie, Christine; Watts, D Heather; Palefsky, Joel M; Landay, Alan

    2014-02-01

    Other than CD4+ count, the immunologic factors that underlie the relationship of HIV/AIDS with persistent oncogenic HPV (oncHPV) and cervical cancer are not well understood. Plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) are of particular interest. pDCs have both effector and antigen presenting activity and, in HIV-positive patients, low pDC levels are associated with opportunistic infections. Tregs downregulate immune responses, and are present at high levels in HIV-positives. The current pilot study shows for the first time that low pDC and high Treg levels may be significantly associated with oncHPV persistence in both HIV-positive and HIV-negative women. Larger studies are now warranted.

  12. Antibody persistence and immune memory in adults, 15 years after a three-dose schedule of a combined hepatitis A and B vaccine.

    Science.gov (United States)

    Van Damme, P; Leroux-Roels, G; Crasta, P; Messier, M; Jacquet, J-M; Van Herck, K

    2012-01-01

    A combined hepatitis A and B vaccine is available since 1996. Two separate open-label primary studies evaluated the immunogenicity and safety of this hepatitis A and B vaccine (720 EI.U of HAV and 20 µg of HBsAg) in 306 healthy subjects aged 17-43 years who received three doses of the vaccine following a 0, 1, and 6 months schedule. These subjects were followed up annually for the next 15 years to evaluate long-term persistence of anti-HAV and anti-HBs antibodies. The subjects whose antibody concentrations fell below the cut-offs between Year 11 and Year 15 (anti-HAV: hepatitis A and/or B vaccine. In subjects who received the additional vaccine dose, a blood sample was collected 1 month after vaccination. At the Year 15 time point, all subjects in Study A and Study B were seropositive for anti-HAV antibodies and 89.3% and 92.9% of subjects in the respective studies had anti-HBs antibody concentrations ≥10 mIU/ml. Four subjects (two in each study) received an additional dose of monovalent hepatitis B vaccine and mounted anamnestic responses to vaccination. No vaccine-related serious adverse events were reported. This study confirms the long-term immunogenicity of the three-dose regimen of the combined hepatitis A and B vaccine, as eliciting long-term persistence of antibodies and immune memory against hepatitis A and B for up to at least 15 years after a primary vaccination.

  13. Stochastic induction of persister cells by HipA through (p)ppGpp-mediated activation of mRNA endonucleases

    DEFF Research Database (Denmark)

    Germain-Maisonneuve, Elsa; Roghanian, Mohammad; Gerdes, Kenn;

    2015-01-01

    The model organism Escherichia coli codes for at least 11 type II toxin-antitoxin (TA) modules, all implicated in bacterial persistence (multidrug tolerance). Ten of these encode messenger RNA endonucleases (mRNases) inhibiting translation by catalytic degradation of mRNA, and the 11th module, hip......BA, encodes HipA (high persister protein A) kinase, which inhibits glutamyl tRNA synthetase (GltX). In turn, inhibition of GltX inhibits translation and induces the stringent response and persistence. Previously, we presented strong support for a model proposing (p)ppGpp (guanosine tetra and penta......-phosphate) as the master regulator of persistence. Stochastic variation of [(p)ppGpp] in single cells induced TA-encoded mRNases via a pathway involving polyphosphate and Lon protease. Polyphosphate activated Lon to degrade all known type II antitoxins of E. coli. In turn, the activated mRNases induced persistence...

  14. Persistent downregulation of the pancarcinoma-associated epithelial cell adhesion molecule via active intranuclear methylation

    NARCIS (Netherlands)

    van der Gun, Bernardina T. F.; Wasserkort, Reinhold; Monami, Amelie; Jeltsch, Albert; Rasko, Tamits; Slaska-Kiss, Krystyna; Cortese, Rene; Rots, Marianne G.; de Leij, Lou F. M. H.; Ruiters, Marcel H. J.; Kiss, Antal; Weinhold, Elmar; McLaughlin, Pamela M. J.

    2008-01-01

    The epithelial cell adhesion molecule (EpCAM) is expressed at high levels on the surface of most carcinoma cells. SiRNA silencing of EpCAM expression leads to reduced metastatic potential of tumor cells demonstrating its importance in oncogenesis and tumor progression. However, siRNA therapy require

  15. Systemic BCG immunization induces persistent lung mucosal multifunctional CD4 T(EM cells which expand following virulent mycobacterial challenge.

    Directory of Open Access Journals (Sweden)

    Daryan A Kaveh

    Full Text Available To more closely understand the mechanisms of how BCG vaccination confers immunity would help to rationally design improved tuberculosis vaccines that are urgently required. Given the established central role of CD4 T cells in BCG induced immunity, we sought to characterise the generation of memory CD4 T cell responses to BCG vaccination and M. bovis infection in a murine challenge model. We demonstrate that a single systemic BCG vaccination induces distinct systemic and mucosal populations of T effector memory (T(EM cells in vaccinated mice. These CD4+CD44(hiCD62L(loCD27⁻ T cells concomitantly produce IFN-γ and TNF-α, or IFN-γ, IL-2 and TNF-α and have a higher cytokine median fluorescence intensity MFI or 'quality of response' than single cytokine producing cells. These cells are maintained for long periods (>16 months in BCG protected mice, maintaining a vaccine-specific functionality. Following virulent mycobacterial challenge, these cells underwent significant expansion in the lungs and are, therefore, strongly associated with protection against M. bovis challenge. Our data demonstrate that a persistent mucosal population of T(EM cells can be induced by parenteral immunization, a feature only previously associated with mucosal immunization routes; and that these multifunctional T(EM cells are strongly associated with protection. We propose that these cells mediate protective immunity, and that vaccines designed to increase the number of relevant antigen-specific T(EM in the lung may represent a new generation of TB vaccines.

  16. Persistent tumor cells in bone marrow of non-metastatic breast cancer patients after primary surgery are associated with inferior outcome

    Directory of Open Access Journals (Sweden)

    Tjensvoll Kjersti

    2012-05-01

    Full Text Available Abstract Background To investigate the prognostic significance of disseminated tumor cells (DTCs in bone marrow (BM from non-metastatic breast cancer patients before and after surgery. Methods Patients with non-metastatic breast cancer were consecutively recruited to this project during the years 1998–2000. Real-time RT-PCR quantification of a DTC multimarker panel consisting of cytokeratin 19, mammaglobin A and TWIST1 mRNA was performed in BM samples obtained from 154 patients three weeks (BM2 and/or six months after surgery (BM3. The results were compared to previously published data from pre-operative BM analyses for the same patients. Results DTCs were identified in post-operative BM samples (BM2 and/or BM3 from 23 (15% of the 154 patients investigated. During a median follow-up of 98 months, 10 (44% of these patients experienced systemic relapse as compared to 16 (12% of 131 DTC-negative patients. Kaplan-Meier estimates of systemic recurrence-free- and breast-cancer specific survival demonstrated significantly shorter survival for patients with persistent DTCs in BM after surgery (p≤0.001. By multivariate Cox regression analyses, persistent DTCs after surgery was an independent predictor of both systemic recurrence-free- (HR = 5.4, p p p p  Conclusions Detection of persistent DTCs in BM samples obtained after surgery identified non-metastatic breast cancer patients at high risk for systemic relapse, and with reduced breast-cancer specific survival. Furthermore, patients with positive DTC status both before and after surgery had a particularly poor prognosis.

  17. Stochastic induction of persister cells by HipA through (p)ppGpp-mediated activation of mRNA endonucleases.

    Science.gov (United States)

    Germain, Elsa; Roghanian, Mohammad; Gerdes, Kenn; Maisonneuve, Etienne

    2015-04-21

    The model organism Escherichia coli codes for at least 11 type II toxin-antitoxin (TA) modules, all implicated in bacterial persistence (multidrug tolerance). Ten of these encode messenger RNA endonucleases (mRNases) inhibiting translation by catalytic degradation of mRNA, and the 11th module, hipBA, encodes HipA (high persister protein A) kinase, which inhibits glutamyl tRNA synthetase (GltX). In turn, inhibition of GltX inhibits translation and induces the stringent response and persistence. Previously, we presented strong support for a model proposing (p)ppGpp (guanosine tetra and penta-phosphate) as the master regulator of persistence. Stochastic variation of [(p)ppGpp] in single cells induced TA-encoded mRNases via a pathway involving polyphosphate and Lon protease. Polyphosphate activated Lon to degrade all known type II antitoxins of E. coli. In turn, the activated mRNases induced persistence and multidrug tolerance. However, even though it was known that activation of HipA stimulated (p)ppGpp synthesis, our model did not explain how hipBA induced persistence. Here we show that, in support of and consistent with our initial model, HipA-induced persistence depends not only on (p)ppGpp but also on the 10 mRNase-encoding TA modules, Lon protease, and polyphosphate. Importantly, observations with single cells convincingly show that the high level of (p)ppGpp caused by activation of HipA does not induce persistence in the absence of TA-encoded mRNases. Thus, slow growth per se does not induce persistence in the absence of TA-encoded toxins, placing these genes as central effectors of bacterial persistence.

  18. Employment persistence

    OpenAIRE

    Fleischman, Charles A.; Joshua H. Gallin

    2001-01-01

    The recent U.S. expansion has provided employment experience to individuals at tail of the skill distribution. Will these opportunities bestow persistent benefits in the form of greater future employability? Using synthetic cohorts constructed from the CPS, this paper estimates the degree of persistence in cohort-level employment rates in excess of persistence in aggregate macroeconomic conditions. This approach is in some ways superior to testing for hysteresis in the aggregate unemployment ...

  19. On URL and content persistence

    OpenAIRE

    Gomes, Daniel; Silva, Mário J

    2005-01-01

    This report presents a study of URL and content persistence among 51 million pages from a national web harvested 8 times over almost 3 years. This study differs from previous ones because it describes the evolution of a large set of web pages for several years, studying in depth the characteristics of persistent data. We found that the persistence of URLs and contents follows a logarithmic distribution. We characterized persistent URLs and contents, and identified reasons for URL death. We fo...

  20. Flare, persistently active disease, and serologically active clinically quiescent disease in systemic lupus erythematosus: a 2-year follow-up study.

    Directory of Open Access Journals (Sweden)

    Fabrizio Conti

    Full Text Available OBJECTIVE: Several indices have been proposed to assess disease activity in patients with Systemic Lupus Erythematosus (SLE. Recent studies have showed a prevalence of flare between 28-35.3%, persistently active disease (PAD between 46%-52% and serologically active clinically quiescent (SACQ disease ranging from 6 to 15%. Our goal was to evaluate the flare, PAD and SACQ rate incidence in a cohort of SLE patients over a 2-year follow-up. METHODS: We evaluated 394 SLE patients. Flare was defined as an increase in SLEDAI-2K score of ≥4 from the previous visit; PAD was defined as a SLEDAI-2K score of ≥4, on >2 consecutive visits; SACQ was defined as at least a 2-year period without clinical activity and with persistent serologic activity. RESULTS: Among the 95 patients eligible for the analysis in 2009, 7 (7.3% had ≥1 flare episode, whereas 9 (9.4% had PAD. Similarly, among the 118 patients selected for the analysis in 2010, 6 (5% had ≥1 flare episode, whereas 16 (13.5% had PAD. Only 1/45 patient (2.2% showed SACQ during the follow-up. CONCLUSION: We showed a low incidence of flare, PAD and SACQ in Italian SLE patients compared with previous studies which could be partly explained by ethnic differences.

  1. Persistence of virus reservoirs in ART-treated SHIV-infected rhesus macaques after autologous hematopoietic stem cell transplant.

    Directory of Open Access Journals (Sweden)

    Maud Mavigner

    2014-09-01

    Full Text Available Despite many advances in AIDS research, a cure for HIV infection remains elusive. Here, we performed autologous hematopoietic stem cell transplantation (HSCT in three Simian/Human Immunodeficiency Virus (SHIV-infected, antiretroviral therapy (ART-treated rhesus macaques (RMs using HSCs collected prior to infection and compared them to three SHIV-infected, ART-treated, untransplanted control animals to assess the effect of conditioning and autologous HSCT on viral persistence. As expected, ART drastically reduced virus replication, below 100 SHIV-RNA copies per ml of plasma in all animals. After several weeks on ART, experimental RMs received myeloablative total body irradiation (1080 cGy, which resulted in the depletion of 94-99% of circulating CD4+ T-cells, and low to undetectable SHIV-DNA levels in peripheral blood mononuclear cells. Following HSC infusion and successful engraftment, ART was interrupted (40-75 days post-transplant. Despite the observed dramatic reduction of the peripheral blood viral reservoir, rapid rebound of plasma viremia was observed in two out of three transplanted RMs. In the third transplanted animal, plasma SHIV-RNA and SHIV DNA in bulk PBMCs remained undetectable at week two post-ART interruption. No further time-points could be assessed as this animal was euthanized for clinical reasons; however, SHIV-DNA could be detected in this animal at necropsy in sorted circulating CD4+ T-cells, spleen and lymph nodes but not in the gastro-intestinal tract or tonsils. Furthermore, SIV DNA levels post-ART interruption were equivalent in several tissues in transplanted and control animals. While persistence of virus reservoir was observed despite myeloablation and HSCT in the setting of short term ART, this experiment demonstrates that autologous HSCT can be successfully performed in SIV-infected ART-treated RMs offering a new experimental in vivo platform to test innovative interventions aimed at curing HIV infection in humans.

  2. Persistent Simian Immunodeficiency Virus Infection Causes Ultimate Depletion of Follicular Th Cells in AIDS.

    Science.gov (United States)

    Xu, Huanbin; Wang, Xiaolei; Malam, Naomi; Lackner, Andrew A; Veazey, Ronald S

    2015-11-01

    CD4(+) T follicular helper (Tfh) cells are critical for the generation of humoral immune responses to pathogenic infections, providing help for B cell development, survival, and affinity maturation of Abs. Although CD4(+) Tfh cells are reported to accumulate in HIV or SIV infection, we found that germinal center Tfh cells, defined in this study as CXCR5(+)PD-1(HIGH)CD4(+) T cells, did not consistently accumulate in chronically SIV-infected rhesus macaques compared with those infected with less pathogenic simian HIV, vaccinated and SIVmac-challenged, or SIVmac-infected Mamu-A*01(+) macaques, all of which are associated with some control of virus replication and slower disease progression. Interestingly, CXCR5(+)PD-1(HIGH) Tfh cells in lymphoid tissues were eventually depleted in macaques with AIDS compared with the other cohorts. Chronic activation and proliferation of CXCR5(+)PD-1(HIGH) Tfh were increased, but PD-L2 expression was downregulated on B cells, possibly resulting in germinal center Tfh cell apoptosis. Together, these findings suggest that changes in CXCR5(+)PD-1(HIGH) Tfh cells in lymph nodes correlate with immune control during infection, and their loss or dysregulation contribute to impairment of B cell responses and progression to AIDS.

  3. Oxidative stress induces persistent telomeric DNA damage responsible for nuclear morphology change in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Elisa Coluzzi

    Full Text Available One main function of telomeres is to maintain chromosome and genome stability. The rate of telomere shortening can be accelerated significantly by chemical and physical environmental agents. Reactive oxygen species are a source of oxidative stress and can produce modified bases (mainly 8-oxoG and single strand breaks anywhere in the genome. The high incidence of guanine residues in telomeric DNA sequences makes the telomere a preferred target for oxidative damage. Our aim in this work is to evaluate whether chromosome instability induced by oxidative stress is related specifically to telomeric damage. We treated human primary fibroblasts (MRC-5 in vitro with hydrogen peroxide (100 and 200 µM for 1 hr and collected data at several time points. To evaluate the persistence of oxidative stress-induced DNA damage up to 24 hrs after treatment, we analysed telomeric and genomic oxidative damage by qPCR and a modified comet assay, respectively. The results demonstrate that the genomic damage is completely repaired, while the telomeric oxidative damage persists. The analysis of telomere length reveals a significant telomere shortening 48 hrs after treatment, leading us to hypothesise that residual telomere damage could be responsible for the telomere shortening observed. Considering the influence of telomere length modulation on genomic stability, we quantified abnormal nuclear morphologies (Nucleoplasmic Bridges, Nuclear Buds and Micronuclei and observed an increase of chromosome instability in the same time frame as telomere shortening. At subsequent times (72 and 96 hrs, we observed a restoration of telomere length and a reduction of chromosome instability, leaving us to conjecture a correlation between telomere shortening/dysfunction and chromosome instability. We can conclude that oxidative base damage leads to abnormal nuclear morphologies and that telomere dysfunction is an important contributor to this effect.

  4. A respiratory syncytial virus persistent-infected cell line system reveals the involvement of SOCS1 in the innate antiviral response

    Institute of Scientific and Technical Information of China (English)

    Junwen; Zheng; Pu; Yang; Yan; Tang; Dongchi; Zhao

    2015-01-01

    HEp-2 cells persistently infected with respiratory syncytial virus(RSV) are a heterogeneous mixture of viral antigen-positive and-negative variants; however, the mechanism through which viral replication becomes latent remains unclear. In this study, we investigated the potential mechanism by which RSV escapes from innate immune surveillance. Persistent-infected RSV HEp-2 cells were isolated and cell clones were passaged. The RSV-persistent cells produced viruses at a lower titer, resisted wild-type RSV re-infection, and secreted high levels of interferon-β(IFN-β), macrophage inflammatory protein-1α(Mip-1α), interleukin-8(IL-8), and Rantes. Toll-like receptor 3(TLR3), retinoic acid inducible gene-I(RIG-I), and suppressor of cytokine signaling 1(SOCS1) levels were upregulated in these cells. The silencing of TLR3 m RNA decreased the expression of SOCS1 protein and the secretion of cytokines. RSV-persistent cells are in an inflammatory state; upregulation of SOCS1 is related to the TLR3 signaling pathway, which could be associated with the mechanism of viral persistence.

  5. Embryonic Development following Somatic Cell Nuclear Transfer Impeded by Persisting Histone Methylation

    OpenAIRE

    Matoba, Shogo; Liu, Yuting; Lu, Falong; Iwabuchi, Kumiko A.; Inoue, Azusa; Zhang, Yi

    2014-01-01

    Mammalian oocytes can reprogram somatic cells into a totipotent state enabling animal cloning through somatic cell nuclear transfer (SCNT). However, the majority of SCNT embryos fail to develop to term due to undefined reprogramming defects. Here we identify histone H3 lysine 9 trimethylation (H3K9me3) of donor cell genome as a major epigenetic barrier for efficient reprogramming by SCNT. Comparative transcriptome analysis identified reprogramming resistant regions (RRRs) that are expressed n...

  6. Privileged Communication Embryonic Development Following Somatic Cell Nuclear Transfer Impeded by Persisting Histone Methylation

    OpenAIRE

    Matoba, Shogo; Liu, Yuting; Lu, Falong; Iwabuchi, Kumiko A.; Shen, Li; Inoue, Azusa; Zhang, Yi

    2014-01-01

    Mammalian oocytes can reprogram somatic cells into a totipotent state enabling animal cloning through somatic cell nuclear transfer (SCNT). However, the majority of SCNT embryos fail to develop to term due to undefined reprogramming defects. Here we identify histone H3 lysine 9 trimethylation (H3K9me3) of donor cell genome as a major epigenetic barrier for efficient reprogramming by SCNT. Comparative transcriptome analysis identified reprogramming resistant regions (RRRs) that are expressed n...

  7. Mild leptospirosis with three-year persistence of IgG- and IgM-antibodies, initially manifesting as carpal tunnel syndrome.

    Science.gov (United States)

    Finsterer, Josef; Stöllberger, Claudia; Sehnal, Ernst; Stanek, Gerold

    2005-08-01

    Long-term persistence of IgG- and IgM-antibodies against leptospira after mild leptospirosis has not been reported. In a 45-year-old female pet-shop worker with carpal tunnel syndrome, accompanied by arthralgias, coughing, repeatedly elevated temperature, followed by easy fatigability, personality change, memory and speech disturbance, blurred vision, myalgia and swollen lymph nodes, leptospirosis was diagnosed, based upon history, clinical findings, and serological investigations. After the described symptoms had disappeared following doxycyclin for 2 weeks, IgG- and IgM-antibodies against leptospira remained positive during the next three years. This case illustrates that leptospirosis may start as carpal tunnel syndrome and that the severity of leptospirosis does not seem to be related to the intensity of the humoral immune response against the causative agent. PMID:16038755

  8. Distinct Trajectories of Separation Anxiety in the Preschool Years: Persistence at School Entry and Early-Life Associated Factors

    Science.gov (United States)

    Battaglia, Marco; Touchette, Évelyne; Garon-Carrier, Gabrielle; Dionne, Ginette; Côté, Sylvana M.; Vitaro, Frank; Tremblay, Richard E.; Boivin, Michel

    2016-01-01

    Background: Little is known about how children differ in the onset and evolution of separation anxiety (SA) symptoms during the preschool years, and how SA develops into separation anxiety disorder. In a large, representative population-based sample, we investigated the developmental trajectories of SA symptoms from infancy to school entry, their…

  9. Persistence of disseminated tumor cells after neoadjuvant treatment for locally advanced breast cancer predicts poor survival

    OpenAIRE

    Mathiesen, Randi R.; Borgen, Elin; Renolen, Anne; Løkkevik, Erik; Nesland, Jahn M; Anker, Gun; Østenstad, Bjørn; Lundgren, Steinar; Risberg, Terje; Mjaaland, Ingvil; Kvalheim, Gunnar; Lønning, Per E.; Naume, Bjørn

    2012-01-01

    Introduction Presence of disseminated tumor cells (DTCs) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood (PB) predicts reduced survival in early breast cancer. The aim of this study was to determine the presence of and alterations in DTC- and CTC-status in locally advanced breast cancer patients undergoing neoadjuvant chemotherapy (NACT) and to evaluate their prognostic impact. Methods ...

  10. Inflammatory memories: is epigenetics the missing link to persistent stromal cell activation in rheumatoid arthritis?

    NARCIS (Netherlands)

    C. Ospelt; K.A. Reedquist; S. Gay; P.P. Tak

    2011-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease leading to joint destruction. Synovial fibroblasts are recognized as key cells in the pathogenesis of RA since they attract and activate immune cells and produce matrix degrading enzymes. Most notably synovial fibroblasts from patients with

  11. Decreased QOL and muscle strength are persistentyear after intramedullary nailing of a tibial shaft fracture

    DEFF Research Database (Denmark)

    Larsen, Peter; Elsoe, Rasmus; Laessoe, Uffe;

    2016-01-01

    INTRODUCTION: To evaluate the development in patient-reported quality of life (QOL) and muscle strength in the period from surgery to 12 months postoperatively after intramedullary nailing of a tibial shaft fracture. MATERIALS AND METHODS: The design was a prospective, follow-up cohort study. QOL...... was measured with the questionnaire Eq5D-5L and compared to norm data from a reference population. Recordings of pain and contralateral muscle strength (isometric maximal voluntary contraction (MVC) for knee flexion and extension were collected at 6 weeks, 3, 6, and 12 months postoperatively....... Ipsilateral MVCs were recorded at 6 and 12 months. RESULTS: Forty-nine patients were included. The mean age at the time of fracture was 43.1 years (18-79 years). Twelve months postoperatively, the mean Eq5D-5L index was 0.792 (95 % CI 0.747-0.837). Throughout the 12 months postoperatively, patients reported...

  12. Latent and persistent lethal injury in mouse salivary gland cells following gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, T.

    1976-07-01

    Newly synthesized DNA in previously irradiated and isoproterenol-stimulated mouse salivary gland cells was found to be quickly degraded when the stimulation for DNA synthesis was given 10 days after a dose of 1000 rad ..gamma.. radiation. The degradation of the DNA was due to degeneration of acinar cells prior to mitosis. When the stimulation with isoproterenol was given 1 or 3 months after irradiation, DNA degradation in parotids was not detectable. An autoradiographic analysis revealed, however, that about half of the acinar cells labeled with tritiated thymidine were eliminated from irradiated parotids in a few days, even when the stimulation with isoproterenol was given 3 months after irradiation. This indicates that irradiation of mouse salivary gland cells produced latent lethal damage and that this damage is unmasked by the stimulation for DNA synthesis and cell division.

  13. Long-Term Monitoring of Field Trial Sites with Genetically Modified Oilseed Rape (Brassica napus L.) in Saxony-Anhalt, Germany. Fifteen Years Persistence to Date but No Spatial Dispersion

    OpenAIRE

    Anke Belter

    2016-01-01

    Oilseed rape is known to persist in arable fields because of its ability to develop secondary seed dormancy in certain agronomic and environmental conditions. If conditions change, rapeseeds are able to germinate up to 10 years later to build volunteers in ensuing crops. Extrapolations of experimental data acted on the assumption of persistence periods for more than 20 years after last harvest of rapeseed. Genetically-modified oilseed rape—cultivated widely in Northern America since 1996—is a...

  14. 2008: year of the rat for stem cell research

    Institute of Scientific and Technical Information of China (English)

    Duanqing Pei

    2009-01-01

    @@ 2008 breakthrough of the year went to reprogramming as announced by magazine Science recently [1], highlighting a stem cell revolution in the scientific world underway commencing at 2006. For the field of stem cell and developmental biology, 2008 ended with a truly exciting achievement for the Rat, i.e., the generation of germline competent embryonic stem cells from rat blastocysts (Figure 1) [2, 3].

  15. Health risk or resource? Gradual and independent association between self-rated health and mortality persists over 30 years.

    Directory of Open Access Journals (Sweden)

    Matthias Bopp

    Full Text Available BACKGROUND: Poor self-rated health (SRH is associated with increased mortality. However, most studies only adjust for few health risk factors and/or do not analyse whether this association is consistent also for intermediate categories of SRH and for follow-up periods exceeding 5-10 years. This study examined whether the SRH-mortality association remained significant 30 years after assessment when adjusting for a wide range of known clinical, behavioural and socio-demographic risk factors. METHODS: We followed-up 8,251 men and women aged ≥ 16 years who participated 1977-79 in a community based health study and were anonymously linked with the Swiss National Cohort (SNC until the end of 2008. Covariates were measured at baseline and included education, marital status, smoking, medical history, medication, blood glucose and pressure. RESULTS: 92.8% of the original study participants could be linked to a census, mortality or emigration record of the SNC. Loss to follow-up 1980-2000 was 5.8%. Even after 30 years of follow-up and after adjustment for all covariates, the association between SRH and all-cause mortality remained strong and estimates almost linearly increased from "excellent" (reference: hazard ratio, HR 1 to "good" (men: HR 1.07 95% confidence interval 0.92-1.24, women: 1.22, 1.01-1.46 to "fair" (1.41, 1.18-1.68; 1.39, 1.14-1.70 to "poor"(1.61, 1.15-2.25; 1.49, 1.07-2.06 to "very poor" (2.85, 1.25-6.51; 1.30, 0.18-9.35. Persons answering the SRH question with "don't know" (1.87, 1.21-2.88; 1.26, 0.87-1.83 had also an increased mortality risk; this was pronounced in men and in the first years of follow-up. CONCLUSIONS: SRH is a strong and "dose-dependent" predictor of mortality. The association was largely independent from covariates and remained significant after decades. This suggests that SRH provides relevant and sustained health information beyond classical risk factors or medical history and reflects salutogenetic rather than

  16. Dislocation dynamics. II. Applications to the formation of persistent slip bands, planar arrays, and dislocation cells

    International Nuclear Information System (INIS)

    The dynamic organization of dislocations into spatially heterogeneous substructures is demonstrated by applying the principles of dislocation dynamics that were outlined in the preceding paper. Here it is shown that the formation of persistent slip bands is a consequence of the competition between dipole formation and annihilation of dislocations of opposite Burgers vectors in the absence of temperature-enhanced climb recovery under cyclic stress conditions. Planar arrays, which are also uniaxial structures, are shown to arise from enhanced dislocation multiplication and the formation of stable dipole configurations along a slip plane at lower temperatures where climb is unimportant. Biaxial dislocation systems experience additional degrees of freedom compared with uniaxial systems because of available motion along additional slip systems. It is demonstrated that for a system of orthogonal slip directions at high temperatures in which climb and glide motion are competitive, dislocation cellular structures form as a result of immobile dipole and junction formation and by the internal elastic strain energy minimization caused by long-range self-shielding. It is shown that the internal elastic strain energy is reduced by the self-organization process. However, the short-range nonlinear processes (i.e., dipole and junction formation) are shown not to allow absolute elastic energy minimization

  17. Prenatal exposure to persistent organic pollutants and offspring allergic sensitization and lung function at 20 years of age

    DEFF Research Database (Denmark)

    Hansen, Susanne; Strøm, Marin; Olsen, Sjurdur F;

    2016-01-01

    in archived maternal serum drawn in gestational week 30 (n=872). At age 20 years, 416 offspring (45% of those invited) attended a clinical examination including measurements of allergic sensitization (serum specific IgE > 0.35 kUA /L) and lung function (forced expiratory volume in one second (FEV1...... ) and forced vital capacity (FVC)). RESULTS: There were no associations between maternal concentrations of POPs and offspring allergic sensitization at 20 years of age. Maternal concentrations of POPs were, however, positively associated with offspring airway obstruction (FEV1 /FVC... in the first tertile of exposure, offspring in the third tertile of dioxin-like PCB exposure had an OR of 2.96 (95% CI: 1.14-7.70). Similar associations for non-dioxin-like PCBs, HCB, and p,p'-DDE were 2.68 (1.06-6.81), 2.63 (1.07, 6.46), and 2.87 (1.09, 7.57), respectively. No associations were observed...

  18. Persistence of lipoatrophy after a four-year long interruption of antiretroviral therapy for HIV1 infection: case report

    Directory of Open Access Journals (Sweden)

    Toro Giuseppe

    2005-10-01

    Full Text Available Abstract Background HIV-infected patients on long-term highly active antiretroviral therapy often present peculiar patterns of fat redistribution, referred to as lipodystrophy. In spite of recent investigations, it is not known whether and to what extent the main features of lipodystrophy – that is lipoatrophy of peripheral fat at face, limbs and buttocks, as well as fat accumulation at breasts, abdomen and the dorso-cervical region – can be reversible once clinically manifest. Case presentation A 35 year old Caucasian HIV infected female developed severe diffuse lipodystrophy while on highly active antiretroviral therapy. A remarkable increase of breast size, fat accumulation at waist, and a fat pad on her lumbar spine were paralleled by progressive and disfiguring lipoatrophy of face, limbs and buttocks. The patient decided to interrupt her therapy after 20 months, with a stably suppressed viremia and a CD4 lymphocyte count >500/μL. She could carry on a safe treatment interruption for longer than 4 years. Most sites of fat accumulation switched to nearly normal appearance, whereas lipoatrophy was substantially unchanged at all affected sites. Conclusion our observation provides pictorial evidence that lipoatrophy may not be reversible even under ideal circumstances. Therefore, strategies to prevent lipoatrophy should be considered when defining therapeutic regimens for HIV infected patients, especially those at high risk.

  19. Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection

    OpenAIRE

    Lang, P A; Meryk, A; Pandyra, A A; Brenner, D; A. Brüstle; Xu, H. C.; Merches, K; Lang, F; Khairnar, V; Sharma, P; Funkner, P; Recher, M.; Shaabani, N.; Duncan, G S; Duhan, V

    2014-01-01

    During virus infection and autoimmune disease, inflammatory dendritic cells (iDCs) differentiate from blood monocytes and infiltrate infected tissue. Following acute infection with hepatotropic viruses, iDCs are essential for re-stimulating virus-specific CD8+ T cells and therefore contribute to virus control. Here we used the lymphocytic choriomeningitis virus (LCMV) model system to identify novel signals, which influence the recruitment and activation of iDCs in the liver. We observed that ...

  20. Ipilimumab After Allogeneic Stem Cell Transplant in Treating Patients With Persistent or Progressive Cancer

    Science.gov (United States)

    2013-03-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Childhood Myelodysplastic Syndromes; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Disseminated Neuroblastoma; Malignant Neoplasm; Ovarian Choriocarcinoma; Ovarian Embryonal Carcinoma; Ovarian Immature Teratoma; Ovarian Mature Teratoma; Ovarian Mixed Germ Cell Tumor; Ovarian Monodermal and Highly Specialized Teratoma; Ovarian Polyembryoma; Ovarian Yolk Sac Tumor; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Malignant Testicular Germ Cell Tumor; Recurrent Mantle Cell Lymphoma; Recurrent Neuroblastoma; Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage II Ovarian Epithelial Cancer; Stage III Malignant Testicular Germ Cell Tumor; Stage III Multiple Myeloma; Stage III Ovarian Epithelial Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Testicular Choriocarcinoma; Testicular Choriocarcinoma and Embryonal Carcinoma; Testicular Choriocarcinoma and Seminoma; Testicular Choriocarcinoma and Teratoma; Testicular Choriocarcinoma and Yolk Sac Tumor; Testicular Embryonal Carcinoma; Testicular

  1. Hydrocephalus in mice following X-irradiation at early gestational stage. Possibly due to persistent deceleration of cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Aolad, H.M.; Inouye, Minoru; Darmanto, W.; Hayasaka, Shizu; Murata, Yoshiharu [Nagoya Univ. (Japan). Research Inst. of Environmental Medicine

    2000-09-01

    The pathogenesis of X-ray-induced congenital hydrocephalus was studied. Pregnant mice were irradiated at 1.4 Gy on gestational day 7 (G7). Four hours after irradiation, extensive cell death was evident in the neuroepithelium and underlying mesoderm of the head region, and proliferating cell nuclear antigen (PCNA)-immunoreactive cells almost disappeared. Embryos with thinner lamina terminalis of the telecephalon, when compared with that of the control, were found in the irradiated group on G9. As early as G11 in some irradiated embryos the telencephalic wall was thinner and lateral ventricles were larger than those of the control. The choroid invagination from the lamina terminalis began on G11 in the control brain, but not in the affected brain. During the following development, fetuses with readily apparent hydrocephalus were consistently found among irradiated fetuses. In these brains the brain mantle was thinner, the corpus striatum and thalamic regions were smaller, and lateral ventricles were larger than those of the control. Even on G11 and G13 the frequencies of PCNA-positive cells in the brain mantle and other brain regions were lower in the hydrocephalic brain than those of the control, suggesting a decelerated proliferation of successive cell generations following exposure to X-rays. The cerebral aqueduct was open in the hydrocephalic brain during the fetal period when the lateral ventricles were dilated. The head was vaulted after birth but the cerebral aqueduct was not completely occluded even in these animals. These findings suggested that cell death in the neuroepithelium followed by a persistent deceleration of neural cell proliferation, resulting in the hypoplasia of brain parenchyma with compensatory ventricular dilatation, is important for the establishment of hydrocephalus. (author)

  2. Generation of a persistently infected MDBK cell line with natural bovine spongiform encephalopathy (BSE).

    Science.gov (United States)

    Tark, Dongseob; Kim, Hyojin; Neale, Michael H; Kim, Minjeong; Sohn, Hyunjoo; Lee, Yoonhee; Cho, Insoo; Joo, Yiseok; Windl, Otto

    2015-01-01

    Bovine spongiform encephalopathy (BSE) is a zoonotic transmissible spongiform encephalopathy (TSE) thought to be caused by the same prion strain as variant Creutzfeldt-Jakob disease (vCJD). Unlike scrapie and chronic wasting disease there is no cell culture model allowing the replication of proteinase K resistant BSE (PrPBSE) and the further in vitro study of this disease. We have generated a cell line based on the Madin-Darby Bovine Kidney (MDBK) cell line over-expressing the bovine prion protein. After exposure to naturally BSE-infected bovine brain homogenate this cell line has shown to replicate and accumulate PrPBSE and maintain infection up to passage 83 after initial challenge. Collectively, we demonstrate, for the first time, that the BSE agent can infect cell lines over-expressing the bovine prion protein similar to other prion diseases. These BSE infected cells will provide a useful tool to facilitate the study of potential therapeutic agents and the diagnosis of BSE.

  3. Persistent exposure to Mycoplasma induces malignant transformation of human prostate cells.

    Directory of Open Access Journals (Sweden)

    Kazunori Namiki

    Full Text Available Recent epidemiologic, genetic, and molecular studies suggest infection and inflammation initiate certain cancers, including those of the prostate. The American Cancer Society, estimates that approximately 20% of all worldwide cancers are caused by infection. Mycoplasma, a genus of bacteria that lack a cell wall, are among the few prokaryotes that can grow in close relationship with mammalian cells, often without any apparent pathology, for extended periods of time. In this study, the capacity of Mycoplasma genitalium, a prevalent sexually transmitted infection, and Mycoplasma hyorhinis, a mycoplasma found at unusually high frequency among patients with AIDS, to induce a malignant phenotype in benign human prostate cells (BPH-1 was evaluated using a series of in vitro and in vivo assays. After 19 weeks of culture, infected BPH-1 cells achieved anchorage-independent growth and increased migration and invasion. Malignant transformation of infected BPH-1 cells was confirmed by the formation of xenograft tumors in athymic mice. Associated with these changes was an increase in karyotypic entropy, evident by the accumulation of chromosomal aberrations and polysomy. This is the first report describing the capacity of M. genitalium or M. hyorhinis infection to lead to the malignant transformation of benign human epithelial cells and may serve as a model to further study the relationship between prostatitis and prostatic carcinogenesis.

  4. Generation of a persistently infected MDBK cell line with natural bovine spongiform encephalopathy (BSE.

    Directory of Open Access Journals (Sweden)

    Dongseob Tark

    Full Text Available Bovine spongiform encephalopathy (BSE is a zoonotic transmissible spongiform encephalopathy (TSE thought to be caused by the same prion strain as variant Creutzfeldt-Jakob disease (vCJD. Unlike scrapie and chronic wasting disease there is no cell culture model allowing the replication of proteinase K resistant BSE (PrPBSE and the further in vitro study of this disease. We have generated a cell line based on the Madin-Darby Bovine Kidney (MDBK cell line over-expressing the bovine prion protein. After exposure to naturally BSE-infected bovine brain homogenate this cell line has shown to replicate and accumulate PrPBSE and maintain infection up to passage 83 after initial challenge. Collectively, we demonstrate, for the first time, that the BSE agent can infect cell lines over-expressing the bovine prion protein similar to other prion diseases. These BSE infected cells will provide a useful tool to facilitate the study of potential therapeutic agents and the diagnosis of BSE.

  5. Recursion-based depletion of human immunodeficiency virus-specific naive CD4(+) T cells may facilitate persistent viral replication and chronic viraemia leading to acquired immunodeficiency syndrome.

    Science.gov (United States)

    Tsukamoto, Tetsuo; Yamamoto, Hiroyuki; Okada, Seiji; Matano, Tetsuro

    2016-09-01

    Although antiretroviral therapy has made human immunodeficiency virus (HIV) infection a controllable disease, it is still unclear how viral replication persists in untreated patients and causes CD4(+) T-cell depletion leading to acquired immunodeficiency syndrome (AIDS) in several years. Theorists tried to explain it with the diversity threshold theory in which accumulated mutations in the HIV genome make the virus so diverse that the immune system will no longer be able to recognize all the variants and fail to control the viraemia. Although the theory could apply to a number of cases, macaque AIDS models using simian immunodeficiency virus (SIV) have shown that failed viral control at the set point is not always associated with T-cell escape mutations. Moreover, even monkeys without a protective major histocompatibility complex (MHC) allele can contain replication of a super infected SIV following immunization with a live-attenuated SIV vaccine, while those animals are not capable of fighting primary SIV infection. Here we propose a recursion-based virus-specific naive CD4(+) T-cell depletion hypothesis through thinking on what may happen in individuals experiencing primary immunodeficiency virus infection. This could explain the mechanism for impairment of virus-specific immune response in the course of HIV infection. PMID:27515208

  6. The fate of persistent organic pollutants in the North Sea. Multiple year model simulations of {gamma}-HCH, {alpha}-HCH and PCB 153

    Energy Technology Data Exchange (ETDEWEB)

    Ilyina, T.P. [Hawaii Univ., Manoa, Honolulu, HI (United States). Dept. of Oceanography

    2007-07-01

    Persistent organic pollutants (POPs) are harmful to human health and to the environment. Their fate in the marine environment is not yet fully understood. An ocean model (FANTOM) has been developed to investigate the fate of selected POPs in the North Sea. The main focus of the model is on quantifying the distribution of POPs and their aquatic pathways. This is the first time that a spatially-resolved, measurement-based ocean transport model has been used to study POP-like substances, at least on the regional scale. The model was applied for the southern North Sea and tested by studying the behaviour of g-HCH, a-HCH and PCB 153 in sea water. This model study proves that transport models, such as FANTOM, are capable of reproducing realistic multi-year temporal and spatial trends of selected POPs and can be used to address further scientific questions. (orig.)

  7. Isolation and Short-Term Persistence of Ehrlichia ewingii in Cell Culture.

    Science.gov (United States)

    Killmaster, Lindsay F; Levin, Michael L

    2016-07-01

    Ehrlichia ewingii is the causative agent of human and canine granulocytic ehrlichiosis. Since its discovery in 1970, little work has been done to characterize the pathogen or study the transmission dynamics due to the inability to grow the agent in vitro. The aim of this study was to assess the suitability of multiple cell lines and media formulations for propagation of E. ewingii in cell culture. In this study, we present an overview of attempts to isolate E. ewingii from the buffy coat of goats naturally infected by Amblyomma americanum ticks, as well as a methodology for maintaining the pathogen for up to 16 weeks in culture. The most promising results were seen with HL-60 cells differentiated by the addition of 1.5% DMSO to the media and supplemented with 8 mM l-glutamine. Cultures were passaged multiple times, and fluorescence and morulae were observed by indirect fluorescent antibody test and Diff-Quik staining. It is our hope that this information will provide a foundation for future attempts to propagate and maintain E. ewingii in cell culture. PMID:27228133

  8. Persistent circulating human insulin in sheep transplanted in utero with human mesenchymal stem cells

    Science.gov (United States)

    Ersek, Adel; Pixley, John S.; Goodrich, A. Daisy; Porada, Christopher D.; Almeida-Porada, Graca; Thain, David S.; Zanjani, Esmail D.

    2010-01-01

    Objective To determine if mesenchymal stem cells (MSC) derived from human fetal pancreatic tissue (pMSC) would engraft and differentiate in sheep pancreas following transplantation in utero. Methods A three-step culture system was established for generating human fetal pMSC. Sheep fetuses were transplanted during the fetal transplant receptivity period with human pMSC and evaluated for in situ and functional engraftment in their pancreas, liver and bone marrow. Results Isolation and expansion of adherent cells from the human fetal pancreas yielded a cell population with morphologic and phenotypic characteristics similar to MSC derived from bone marrow. This putative stem cell population could undergo multilineage differentiation in vitro. Three to 27 months after fetal transplantation, the pancreatic engraftment frequency (chimeric index) was 79% while functional engraftment was noted in 50% of transplanted sheep. Hepatic and marrow engraftment and expression was noted as well. Conclusion We have established a procedure for isolation of human fetal pMSC that display characteristics similar to bone marrow derived MSC. In vivo results suggest the pMSC engraft, differentiate and secrete human insulin from the sheep pancreas. PMID:20170708

  9. Occurrence and persistence of organic emerging contaminants and priority pollutants in five sewage treatment plants of Spain: Two years pilot survey monitoring

    International Nuclear Information System (INIS)

    This work summarized all results obtained during almost two-years of a monitoring programme carried out in five municipal sewage treatment plants (STPs) located in the north, centre and south-east of Spain. The study evaluated the occurrence and persistence of a group of 100 organic compounds belonging to several chemical groups (pharmaceuticals, personal care products, pesticides and metabolites). The average removal efficiencies of the STPs studied varied from 20% (erythromycin) to 99% (acetaminophen). In analysed samples, we identified a large number of compounds at mean range concentrations between 7–59,495 ng/L and 5–32,720 ng/L for influent and effluent samples, respectively. This study also identified 20 of the mostly detected and persistent compounds in wastewater effluent, of which hydrochlorothiazide, atenolol, gemfibrozil, galaxolide and three metabolites (fenofibric acid, 4-AAA and 4-FAA), presented the highest average contribution percentages, in relation to the total load of contaminants for the different STPs effluent studied. Highlights: ► The results summarize two-years of a monitoring programme. ► 100 organic compounds (priority substances and emerging contaminants) were analysed. ► The removal efficiency of 5 STPs of Spain was evaluated. ► The presence of target compounds in treated wastewater was also checked. ► The most frequently drugs detected were: antibiotics< anti-inflammatories<β-blockers. - Antibiotics and analgesics/anti-inflammatories were the most frequently drugs detected, following by some β-blockers, synthetic fragrances, lipid regulators and diuretics.

  10. Long-term (5-year) antibody persistence following two- and three-dose regimens of a combined hepatitis A and B vaccine in children aged 1-11 years.

    Science.gov (United States)

    Marshall, Helen; Nolan, Terry; Díez Domingo, Javier; Rombo, Lars; Sokal, Etienne M; Marès, Josep; Casanovas, Josep M; Kuriyakose, Sherine; Leyssen, Maarten; Jacquet, Jeanne-Marie

    2010-06-17

    This study compared the long-term persistence of anti-hepatitis A (anti-HAV) and B (anti-HBs) antibodies, 5 years after vaccination of subjects aged 1-11 years with a combined hepatitis A and B vaccine either in a two-dose (0, 6 months, Adult formulation) or a three-dose (0, 1, 6 months, Paediatric formulation) schedule. At the end of the 5 years, all subjects (100%) in both groups continued to have anti-HAV antibodies > or =15mIU/mL, while 94-97% of subjects in both groups had anti-HBs antibody concentrations > or =10mIU/mL. Subjects with anti-HBs antibody concentration hepatitis B vaccine. All subjects mounted a vigorous immune response to the challenge indicating the presence of immunological memory to HBV.

  11. Excitation energy transfer from long-persistent phosphors for enhancing power conversion of dye-sensitized solar cells

    Science.gov (United States)

    Puntambekar, Ajinkya; Chakrapani, Vidhya

    2016-06-01

    Incorporation of inorganic phosphors to improve the spectral absorption range of a dye-sensitized solar cell (DSSC) is a promising strategy to enhance efficiency beyond 15%. However, only marginal improvements have been achieved so far, which is mainly due to the use of nonoptimized device architecture and the lack of understanding of the energy transfer mechanism. Here we report results of DSSCs employing long-persistence phosphor coupled to the sensitizing dye. Detailed time-resolved photoluminescence measurements suggest that excitation energy is transferred radiatively as opposed to Förster resonance energy transfer. As a result of efficient energy transfer, large-area solar cells show a 63% increase in the photocurrent density along with a 54% increase in power conversion efficiency. In addition, the device works as a "nighttime solar cell" with generation of 52 μ W c m-2 power density in the dark. Under short-circuit conditions, the device can output 300 mV for 30 h in the dark.

  12. The Effect of Exposure to Persistent Organic Pollutants on Metabolic Health among KOREAN Children during a 1-Year Follow-Up

    Directory of Open Access Journals (Sweden)

    Hye Ah Lee

    2016-02-01

    Full Text Available Previous evidence suggests the potential for adverse effects of persistent organic pollutants (POPs on metabolic health even at low-dose exposure levels common among the general population, but there is less evidence of these associations among children. Therefore, as part of a prospective cohort study, 214 children were measured for POPs exposure. After the 1-year follow-up, we assessed the effect of circulating POPs exposure among 158 children aged 7–9 years (at baseline on the change of metabolic components of metabolic syndrome using multiple regression analysis. In addition, we calculated the continuous metabolic syndrome (cMetS score and assessed the variation among individuals by POPs exposure. The concentrations of marker polychlorinated biphenyls (PCBs were significantly associated with increased change in diastolic blood pressure (BP and triglyceride levels during a 1-year follow-up, after controlling for sex, age, household income, and change in body mass index. Total PCBs also showed a marginal association with increasing cMetS score from the baseline. Of the metabolic components, change in diastolic BP over time showed a notable association with specific PCBs, but no association with organochlorine pesticides. Here, we found that low-dose exposures to PCBs among children in the general population could negatively influence metabolic health, particularly diastolic BP. Increased disease sensitivity during childhood can continue to adulthood, thus, these results support the need for continuous assessment of the health impact of POPs.

  13. The Effect of Exposure to Persistent Organic Pollutants on Metabolic Health among KOREAN Children during a 1-Year Follow-Up.

    Science.gov (United States)

    Lee, Hye Ah; Park, Su Hyun; Hong, Young Sun; Ha, Eun Hee; Park, Hyesook

    2016-03-01

    Previous evidence suggests the potential for adverse effects of persistent organic pollutants (POPs) on metabolic health even at low-dose exposure levels common among the general population, but there is less evidence of these associations among children. Therefore, as part of a prospective cohort study, 214 children were measured for POPs exposure. After the 1-year follow-up, we assessed the effect of circulating POPs exposure among 158 children aged 7-9 years (at baseline) on the change of metabolic components of metabolic syndrome using multiple regression analysis. In addition, we calculated the continuous metabolic syndrome (cMetS) score and assessed the variation among individuals by POPs exposure. The concentrations of marker polychlorinated biphenyls (PCBs) were significantly associated with increased change in diastolic blood pressure (BP) and triglyceride levels during a 1-year follow-up, after controlling for sex, age, household income, and change in body mass index. Total PCBs also showed a marginal association with increasing cMetS score from the baseline. Of the metabolic components, change in diastolic BP over time showed a notable association with specific PCBs, but no association with organochlorine pesticides. Here, we found that low-dose exposures to PCBs among children in the general population could negatively influence metabolic health, particularly diastolic BP. Increased disease sensitivity during childhood can continue to adulthood, thus, these results support the need for continuous assessment of the health impact of POPs. PMID:26938545

  14. Human glioblastoma cells persistently infected with simian virus 40 carry nondefective episomal viral DNA and acquire the transformed phenotype and numerous chromosomal abnormalities.

    Science.gov (United States)

    Norkin, L C; Steinberg, V I; Kosz-Vnenchak, M

    1985-02-01

    A stable, persistent infection of A172 human glioblastoma cells with simian virus 40 (SV40) was readily established after infection at an input of 450 PFU per cell. Only 11% of the cells were initially susceptible to SV40, as shown by indirect immunofluorescent staining for the SV40 T antigen at 48 h. However, all cells produced T antigen by week 11. In contrast, viral capsid proteins were made in only about 1% of the cells in the established carrier system. Weekly viral yields ranged between 10(4) and 10(6) PFU/ml. Most of the capsid protein-producing cells contained enormous aberrant (lobulated or multiple) nuclei. Persistent viral DNA appeared in an episomal or "free" state exclusively in Southern blots and was indistinguishable from standard SV40 DNA by restriction analysis. Viral autointerference activity was not detected, and yield reduction assays did not indicate defective interfering particle activity, further implying that variant viruses were not a factor in this carrier system. Interferon was also not a factor in the system, as shown by direct challenge with vesicular stomatitis virus. Persistent infection resulted in cellular growth changes (enhanced saturation density and plating efficiency) characteristic of SV40 transformation. Persistent infection also led to an increased frequency of cytogenetic effects. These included sister chromatid exchanges, a variety of chromosomal abnormalities (ring chromosomes, acentric fragments, breaks, and gaps), and an increase in the chromosome number. Nevertheless, the persistently infected cells continued to display a bipolar glial cell-like morphology with extensive process extension and intercellular contacts.

  15. Pediatric Germ Cell Tumors; A 10-year Experience

    OpenAIRE

    Khaleghnejad-tabari, Ahmad; Mirshemirani, Alireza; Rouzrokh, Mohsen; Mohajerzadeh, Leily; Khaleghnejad-Tabari, Nasibeh; Hasas-Yeganeh, Shaghayegh

    2014-01-01

    Objective: The aim of this study was to evaluate the outcome of germ cell tumors in patients admitted to our center during a ten year period. Methods: In a retrospective descriptive study, patients with the pathological diagnosis of germ cell tumor (GCT) were included. All records were evaluated and patients followed by personal visit in clinic or phone call. Data regarding age, sex, tumor site, bio-chemical assay, pathology, treatment and outcomes were gathered. For qualitative variables we ...

  16. Twenty Years of Experience on Stem Cell Transplantation in Iran

    OpenAIRE

    Ghavamzadeh, Ardeshir; Alimoghaddam, Kamran; Ghaffari, Fatemeh; Derakhshandeh, Roshanak; Jalali, Arash; Jahani, Mohammad

    2013-01-01

    Background Hematopoietic stem cell transplantation (HSCT) is a new window to therapy of many diseases. From March 1991 through April 2011, a total of 3237 HSCT were performed in the Hematology-Oncology and Stem Cell Transplantation Research Center, affiliated to Tehran University of Medical Sciences. Here we report 20 years experience of HSCT. Objectives Our strategy and aim include the protraction of cytogenetic and molecular biological diagnostic tests, the expansion of the first Iranian Co...

  17. Persistence of cisplatin-induced mutagenicity in hematopoietic stem cells: implications for secondary cancer risk following chemotherapy.

    Science.gov (United States)

    Dertinger, Stephen D; Avlasevich, Svetlana L; Torous, Dorothea K; Bemis, Jeffrey C; Phonethepswath, Souk; Labash, Carson; Carlson, Kristine; Mereness, Jared; Cottom, John; Palis, James; MacGregor, James T

    2014-08-01

    Cisplatin is a cytostatic agent used in the treatment of many types of cancer, but its use is associated with increased incidences of secondary leukemia. We evaluated cisplatin's in vivo genotoxic potential by analyzing peripheral blood for Pig-a mutant phenotype erythrocytes and for chromosomal damage in the form of micronuclei. Mutant phenotype reticuloyte and erythrocyte frequencies, based on anti-CD59 antibody labeling and flow cytometric analysis, were determined in male Sprague Dawley rats treated for 28 consecutive days (days 1-28) with up to 0.4 mg cisplatin/kg/day, and sampled on days -4, 15, 29, and 56. Vehicle and highest dose groups were evaluated at additional time points post-treatment up to 6 months. Day 4 and 29 blood samples were also analyzed for micronucleated reticulocyte frequency using flow cytometry and anti-CD71-based labeling. Mutant phenotype reticulocytes were significantly elevated at doses ≥0.1 mg/kg/day, and mutant phenotype erythrocytes were elevated at doses ≥0.05 mg/kg/day. In the 0.4 mg/kg/day group, these effects persisted for the 6 month observation period. Cisplatin also induced a modest but statistically significant increase in micronucleus frequency at the highest dose tested. The prolonged persistence in the production of mutant erythrocytes following cisplatin exposure suggests that this drug mutates hematopoietic stem cells and that this damage may ultimately contribute to the increased incidence of secondary leukemias seen in patients cured of primary malignancies with platinum-based regimens.

  18. Association between 5-HTTLPR genotypes and persisting patterns of anxiety and alcohol use: results from a 10-year longitudinal study of adolescent mental health.

    Science.gov (United States)

    Olsson, C A; Byrnes, G B; Lotfi-Miri, M; Collins, V; Williamson, R; Patton, C; Anney, R J L

    2005-09-01

    The serotonin transporter gene (5-HTT) encodes a transmembrane protein that plays an important role in regulating serotonergic neurotransmission and related aspects of mood and behaviour. The short allele of a 44 bp insertion/deletion polymorphism (S-allele) within the promoter region of the 5-HTT gene (5-HTTLPR) confers lower transcriptional activity relative to the long allele (L-allele) and may act to modify the risk of serotonin-mediated outcomes such as anxiety and substance use behaviours. The purpose of this study was to determine whether (or not) 5-HTTLPR genotypes moderate known associations between attachment style and adolescent anxiety and alcohol use outcomes. Participants were drawn from an eight-wave study of the mental and behavioural health of a cohort of young Australians followed from 14 to 24 years of age (Victorian Adolescent Health Cohort Study, 1992 - present). No association was observed within low-risk attachment settings. However, within risk settings for heightened anxiety (ie, insecurely attached young people), the odds of persisting ruminative anxiety (worry) decreased with each additional copy of the S-allele (approximately 30% per allele: OR 0.77, 95% CI 0.62-0.97, P=0.029). Within risk settings for binge drinking (ie, securely attached young people), the odds of reporting persisting high-dose alcohol consumption (bingeing) decreased with each additional copy of the S-allele (approximately 35% per allele: OR 0.74, 95% CI 0.64-0.86, P<0.001). Our data suggest that the S-allele is likely to be important in psychosocial development, particularly in those settings that increase risk of anxiety and alcohol use problems.

  19. Blood Patch Pleurodesis in the Treatment of Persistant Air Leakage in Langerhans Cell Histiocytosis; A Case Report

    OpenAIRE

    Ayse Baccioglu

    2013-01-01

    Pulmonary langerhans cell histiocytosis is a rare reactive disorder with unclear pathogenesis. 16-year-old male patient complained about shortness of breath induced with exercise, non-productive cough, and intermittent chest pain for one year. Pulmonary function tests were in restrictive nature. There were multiple air cysts in lung parenchyma smaller than one cm and minimal pneumothorax on the left hemithorax in high resolution computed tomography of thorax. There was no hypoxemia in arteria...

  20. A Resource for the Transcriptional Signature of Bona Fide Trophoblast Stem Cells and Analysis of Their Embryonic Persistence

    Directory of Open Access Journals (Sweden)

    Georg Kuales

    2015-01-01

    Full Text Available Trophoblast stem cells (TSCs represent the multipotent progenitors that give rise to the different cells of the embryonic portion of the placenta. Here, we analysed the expression of key TSC transcription factors Cdx2, Eomes, and Elf5 in the early developing placenta of mouse embryos and in cultured TSCs and reveal surprising heterogeneity in protein levels. We analysed persistence of TSCs in the early placenta and find that TSCs remain in the chorionic hinge until E9.5 and are lost shortly afterwards. To define the transcriptional signature of bona fide TSCs, we used inducible gain- and loss-of-function alleles of Eomes or Cdx2, and EomesGFP, to manipulate and monitor the core maintenance factors of TSCs, followed by genome-wide expression profiling. Combinatorial analysis of resulting expression profiles allowed for defining novel TSC marker genes that might functionally contribute to the maintenance of the TSC state. Analyses by qRT-PCR and in situ hybridisation validated novel TSC- and chorion-specific marker genes, such as Bok/Mtd, Cldn26, Duox2, Duoxa2, Nr0b1, and Sox21. Thus, these expression data provide a valuable resource for the transcriptional signature of bona fide and early differentiating TSCs and may contribute to an increased understanding of the transcriptional circuitries that maintain and/or establish stemness of TSCs.

  1. Cell Surface Display Fungal Laccase as a Renewable Biocatalyst for Degradation of Persistent Micropollutants Bisphenol A and Sulfamethoxazole.

    Science.gov (United States)

    Chen, Yingying; Stemple, Brooke; Kumar, Manish; Wei, Na

    2016-08-16

    Fungal laccases have high activity in degrading various persistent organic pollutants. However, using enzymes in solution for water treatment has limitations of nonreusability, short enzyme lifetimes, and high cost of single use. In this study, we developed a new type of biocatalyst by immobilizing fungal laccase on the surface of yeast cells using synthetic biology techniques. The biocatalyst, referred to as surface display laccase (SDL), had an enzyme activity of 104 ± 3 mU/g dry cell (with 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonate (ABTS)). The SDL retained over 90% of the initial enzyme activity after 25 days storage at room temperature, while, in contrast, activity of free laccase declined to 60% of its initial activity. The SDL could be reused with high stability as it retained 74% of initial activity after eight repeated batch reactions. Proof-of-concept evaluations of the effectiveness of SDL in treating contaminants of emerging concern were performed with bisphenol A and sulfamethoxazole. Results from contaminant degradation kinetics and the effects of redox mediator amendment provided insights into the factors affecting the efficacy of the SDL system. This study reports, for the first time, the development of a surface display enzyme biocatalyst as an effective and renewable alternative for treating recalcitrant organic micropollutants. PMID:27414990

  2. 1070 myeloablative megatherapy procedures followed by stem cell rescue for neuroblastoma: 17 years of European experience and conclusions

    International Nuclear Information System (INIS)

    1070 myeloablative procedures followed by stem cell rescue for neuroblastoma are reviewed. These 1070 procedures are part of the European Group for Blood and Marrow Transplant (EBMTG) registry from the last 17 years (in 4536 patients). In 1070 neuroblastoma patients, survival at 2 years was 49%, at 5 years, 33% and relapses were observed as late as 7 years post-BMT (bone marrow transplant). However, 5-year survivors after megatherapy with BMT for stage 4 disease do have an 80% chance of becoming a long-term survivor. When BMT had been used in first complete response (CR1) no salvage was possible, whereas 15% survivors may be seen if BMT is used for the first time at relapse. Infants with stage 4 neuroblastoma had a 17% toxic death rate and indication in this group is exceptional and not recommended. In a matched cohort (17 allogeneic and 34 autologous), autologous stem cell rescue (SCR) was shown to be at least equal to allogeneic SCR. Multivariate analysis of clinical prognostic factors in children with stage 4 disease over 1 year showed that event-free survival was mainly influenced by two adverse factors before the megatherapy procedure: persisting skeleton lesions (99Tc and/or mIBG scan positive) as well as persisting bone marrow (BM) involvement. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  3. 1070 myeloablative megatherapy procedures followed by stem cell rescue for neuroblastoma: 17 years of European experience and conclusions

    Energy Technology Data Exchange (ETDEWEB)

    Chauvin, F. [Centre Leon Berard, Unit of Biostatistics, 28, rue Laennec, 69373 Lyon (France); Rosti, G. [Ospedale Civile, Oncologia Medica, Via Le Randi 5, 48100 Ravenna (Italy); Bernard, J.L. [Hopital d' Enfants de la Timone, Department of Paediatrics, Boulevard Jean Moulin, 13385 Marseille (France); Kremens, B. [Universitats Klinikum Essen, Department of Paediatrics, Hufelandstrasse, 55, 45122 Essen (Germany); Garaventa, A. [Istituto Giannina Gaslini, Department of Haematology/Oncology, Via Maggio 5, 16148 Genova Quarto (Italy); Klingebiel, T. [University Hospital, Abteilung Hamatologie Oncologie, Ruemelinstrasse 18-23, 7400 Tuebingen (Germany); Pearson, A.D.J. [Royal Victoria Infirmary, Sir J. Spence Institute of Child Health, Children' s Cancer Unit, Queen Victoria Road, Newcastle Upon Tyne (United Kingdom); Pinkerton, R. [The Royal Marsden Hospital, Children' s Department, Downs Road, Sutton (United Kingdom); Zucker, J.M. [Institut Curie, Department of Paediatrics, 3 rue Thuillier, 75231 Paris (France); Hartmann, O. [Institut Gustave Roussy, Department of Paediatrics, rue Camille Desmoulins, 94805 Villejuif (France); Lasset, C. [Centre Leon Berard, Unit of Biostatistics, 28, rue Laennec, 69373 Lyon (France); Ladenstein, R. [St. Anna Kinderhospital, Department of Haematology, Wiener Rotes Kreuz, Kinderspitalgasse 6, 1086 Vienna (Austria); Philip, T. [Centre Leon Berard, Department of Paediatrics, 28, rue Laennec, 69373 Lyon (France)

    1997-10-01

    1070 myeloablative procedures followed by stem cell rescue for neuroblastoma are reviewed. These 1070 procedures are part of the European Group for Blood and Marrow Transplant (EBMTG) registry from the last 17 years (in 4536 patients). In 1070 neuroblastoma patients, survival at 2 years was 49%, at 5 years, 33% and relapses were observed as late as 7 years post-BMT (bone marrow transplant). However, 5-year survivors after megatherapy with BMT for stage 4 disease do have an 80% chance of becoming a long-term survivor. When BMT had been used in first complete response (CR1) no salvage was possible, whereas 15% survivors may be seen if BMT is used for the first time at relapse. Infants with stage 4 neuroblastoma had a 17% toxic death rate and indication in this group is exceptional and not recommended. In a matched cohort (17 allogeneic and 34 autologous), autologous stem cell rescue (SCR) was shown to be at least equal to allogeneic SCR. Multivariate analysis of clinical prognostic factors in children with stage 4 disease over 1 year showed that event-free survival was mainly influenced by two adverse factors before the megatherapy procedure: persisting skeleton lesions ({sup 99}Tc and/or mIBG scan positive) as well as persisting bone marrow (BM) involvement. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

  4. Lives of a Cell: 40 Years Later, A Third Interpretation

    Centers for Disease Control (CDC) Podcasts

    2015-06-16

    Reginald Tucker reads an abridged version of the article Lives of a Cell: 40 Years Later, A Third Interpretation.  Created: 6/16/2015 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 6/18/2015.

  5. Spatial distribution of the persistent organic pollutants across the Tibetan Plateau and its linkage with the climate systems: a 5-year air monitoring study

    Science.gov (United States)

    Wang, Xiaoping; Ren, Jiao; Gong, Ping; Wang, Chuanfei; Xue, Yonggang; Yao, Tandong; Lohmann, Rainer

    2016-06-01

    The Tibetan Plateau (TP) has been contaminated by persistent organic pollutants (POPs), including legacy organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) through atmospheric transport. The exact source regions, transport pathways and time trends of POPs to the TP are not well understood. Here polystyrene-divinylbenzene copolymer resin (XAD)-based passive air samplers (PASs) were deployed at 16 Tibetan background sites from 2007 to 2012 to gain further insight into spatial patterns and temporal trends of OCPs and PCBs. The southeastern TP was characterized by dichlorodiphenyltrichloroethane (DDT)-related chemicals delivered by Indian monsoon air masses. The northern and northwestern TP displayed the greatest absolute concentration and relative abundance of hexachlorobenzene (HCB) in the atmosphere, caused by the westerly-driven European air masses. The interactions between the DDT polluted Indian monsoon air and the clean westerly winds formed a transition zone in central Tibet, where both DDT and HCB were the dominant chemicals. Based on 5 years of continuous sampling, our data indicated declining concentrations of HCB and hexachlorocyclohexanes (HCHs) across the Tibetan region. Inter-annual trends of DDT class chemicals, however, showed less variation during this 5-year sampling period, which may be due to the ongoing usage of DDT in India. This paper demonstrates the possibility of using POP fingerprints to investigate the climate interactions and the validity of using PAS to derive inter-annual atmospheric POP time trends.

  6. Persistent Modelling

    DEFF Research Database (Denmark)

    2012-01-01

    The relationship between representation and the represented is examined here through the notion of persistent modelling. This notion is not novel to the activity of architectural design if it is considered as describing a continued active and iterative engagement with design concerns – an evident...... characteristic of architectural practice. But the persistence in persistent modelling can also be understood to apply in other ways, reflecting and anticipating extended roles for representation. This book identifies three principle areas in which these extensions are becoming apparent within contemporary....... It also provides critical insight into the use of contemporary modelling tools and methods, together with an examination of the implications their use has within the territories of architectural design, realisation and experience....

  7. Evaluation of the persistence of functional and biological respiratory health effects in clean-up workers 6 years after the prestige oil spill.

    Science.gov (United States)

    Zock, Jan-Paul; Rodríguez-Trigo, Gema; Rodríguez-Rodríguez, Emma; Souto-Alonso, Ana; Espinosa, Ana; Pozo-Rodríguez, Francisco; Gómez, Federico P; Fuster, Carme; Castaño-Vinyals, Gemma; Antó, Josep Maria; Barberà, Joan Albert

    2014-01-01

    Fishermen who had participated in clean-up activities of the Prestige oil spill showed increased bronchial responsiveness and higher levels of respiratory biomarkers 2 years later. We aimed to evaluate the persistence of these functional and biological respiratory health effects 6 years after clean-up work. In 2008/2009 a follow-up study was done in 230 never-smoking fishermen who had been exposed to clean-up work in 2002/2003 and 87 non-exposed fishermen. Lung function and bronchial responsiveness testing and the determination of respiratory biomarkers in exhaled breath condensate were done identically as in the baseline survey in 2004/2005. Associations between participation in clean-up work and respiratory health parameters were assessed using linear and logistic regression analyses adjusting for sex and age. Information from 158 exposed (69%) and 57 non-exposed (66%) fishermen was obtained. Loss to follow-up in the non-exposed was characterised by less respiratory symptoms at baseline. During the 4-year follow-up period lung function, bronchial hyperresponsiveness and the levels of respiratory biomarkers of oxidative stress and growth factors had deteriorated notably more among non-exposed than among exposed. At follow-up, respiratory health indices were similar or better in clean-up workers than in non-exposed. No clear differences between highly exposed and moderately exposed clean-up workers were found. In conclusion, we could not detect long-term respiratory health effects in clean-up workers 6 years after the Prestige oil spill. Methodological issues that need to be considered in this type of studies include the choice of a non-exposed control group and limitation of follow-up to subgroups such as never smokers.

  8. Comparison of flow cytometry and virus isolation in cell culture for identification of cattle persistently infected with bovine viral diarrhea virus.

    OpenAIRE

    Qvist, P.; Houe, H.; Aasted, B.; Meyling, A

    1991-01-01

    Detection of bovine viral diarrhea virus in 143 blood samples by virus isolation in cell culture and flow cytometry was performed. The material included 37 samples later shown to originate from persistently infected cattle. Thirty-three samples were positive by virus isolation, and all 37 samples were positive by the flow cytometric assay.

  9. Linking Cellular Mechanisms to Behavior: Entorhinal Persistent Spiking and Membrane Potential Oscillations May Underlie Path Integration, Grid Cell Firing, and Episodic Memory

    Directory of Open Access Journals (Sweden)

    Michael E. Hasselmo

    2008-01-01

    Full Text Available The entorhinal cortex plays an important role in spatial memory and episodic memory functions. These functions may result from cellular mechanisms for integration of the afferent input to entorhinal cortex. This article reviews physiological data on persistent spiking and membrane potential oscillations in entorhinal cortex then presents models showing how both these cellular mechanisms could contribute to properties observed during unit recording, including grid cell firing, and how they could underlie behavioural functions including path integration. The interaction of oscillations and persistent firing could contribute to encoding and retrieval of trajectories through space and time as a mechanism relevant to episodic memory.

  10. Persistence of immunity from 1 year of age after one or two doses of hepatitis A vaccine given to children in Argentina

    Directory of Open Access Journals (Sweden)

    Espul C

    2012-08-01

    booster dose. Anti-hepatitis A concentrations increased in 135 children (34.9% in the second year and 50 (13.7% in the third year; none lived in a family with a case of hepatitis A. Three confirmed cases of hepatitis A occurred in family members. Participants belonged to a middle-income, urban/suburban population with good sanitation facilities and water supplies.Conclusion: A single dose of hepatitis A vaccine at 12–23 months of age resulted in hepatitis A seropositivity in all but one vaccinee after 3 years. Increased anti-hepatitis A serum concentrations suggested exposure to wild-type hepatitis A virus in this middle-class socioeconomic environment. Continuing surveillance is required to confirm the effectiveness of a single-dose hepatitis A vaccination; however, the results of the first three years are encouraging.Keywords: hepatitis A vaccine, single dose, antibody persistence, immunization programs

  11. Three year performance of the NTS-2 solar cell experiment

    Science.gov (United States)

    Statler, R. L.; Walker, D. H.

    1980-01-01

    Twelve different solar cell modules from the NTS 2 experiment are functioning after more than three years in a severe trapped radiation orbit of 20,367 km (10,990 nm) circular, 63 deg inclination. The rate of maximum power degradation may be fit to a predicted rate which is based on twice the value of 1 MeV electron equivalent damage fluence calculated from the space electron model AEI 7. The photovoltaic parameters of the cells are compared to their original values to demonstrate rank order of performance.

  12. WIP regulates persistence of cell migration and ruffle formation in both mesenchymal and amoeboid modes of motility.

    Directory of Open Access Journals (Sweden)

    Inmaculada Banon-Rodriguez

    Full Text Available The spatial distribution of signals downstream from receptor tyrosine kinases (RTKs or G-protein coupled receptors (GPCR regulates fundamental cellular processes that control cell migration and growth. Both pathways rely significantly on actin cytoskeleton reorganization mediated by nucleation-promoting factors such as the WASP-(Wiskott-Aldrich Syndrome Protein family. WIP (WASP Interacting Protein is essential for the formation of a class of polarised actin microdomain, namely dorsal ruffles, downstream of the RTK for PDGF (platelet-derived growth factor but the underlying mechanism is poorly understood. Using lentivirally-reconstituted WIP-deficient murine fibroblasts we define the requirement for WIP interaction with N-WASP (neural WASP and Nck for efficient dorsal ruffle formation and of WIP-Nck binding for fibroblast chemotaxis towards PDGF-AA. The formation of both circular dorsal ruffles in PDGF-AA-stimulated primary fibroblasts and lamellipodia in CXCL13-treated B lymphocytes are also compromised by WIP-deficiency. We provide data to show that a WIP-Nck signalling complex interacts with RTK to promote polarised actin remodelling in fibroblasts and provide the first evidence for WIP involvement in the control of migratory persistence in both mesenchymal (fibroblast and amoeboid (B lymphocytes motility.

  13. Neural stem cell apoptosis after low-methylmercury exposures in postnatal hippocampus produce persistent cell loss and adolescent memory deficits.

    Science.gov (United States)

    Sokolowski, Katie; Obiorah, Maryann; Robinson, Kelsey; McCandlish, Elizabeth; Buckley, Brian; DiCicco-Bloom, Emanuel

    2013-12-01

    The developing brain is particularly sensitive to exposures to environmental contaminants. In contrast to the adult, the developing brain contains large numbers of dividing neuronal precursors, suggesting that they may be vulnerable targets. The postnatal day 7 (P7) rat hippocampus has populations of both mature neurons in the CA1-3 region as well as neural stem cells (NSC) in the dentate gyrus (DG) hilus, which actively produce new neurons that migrate to the granule cell layer (GCL). Using this well-characterized NSC population, we examined the impact of low levels of methylmercury (MeHg) on proliferation, neurogenesis, and subsequent adolescent learning and memory behavior. Assessing a range of exposures, we found that a single subcutaneous injection of 0.6 µg/g MeHg in P7 rats induced caspase activation in proliferating NSC of the hilus and GCL. This acute NSC death had lasting impact on the DG at P21, reducing cell numbers in the hilus by 22% and the GCL by 27%, as well as reductions in neural precursor proliferation by 25%. In contrast, non-proliferative CA1-3 pyramidal neuron cell number was unchanged. Furthermore, animals exposed to P7 MeHg exhibited an adolescent spatial memory deficit as assessed by Morris water maze. These results suggest that environmentally relevant levels of MeHg exposure may decrease NSC populations and, despite ongoing neurogenesis, the brain may not restore the hippocampal cell deficits, which may contribute to hippocampal-dependent memory deficits during adolescence.

  14. FIFTY YEARS OF MELPHALAN USE IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    OpenAIRE

    Bayraktar, Ulas D.; Bashir, Qaiser; Qazilbash, Muzaffar; Champlin, Richard E.; Ciurea, Stefan O.

    2012-01-01

    Melphalan remains the most widely used agent in preparative regimens for hematopoietic stem-cell transplantation. From its initial discovery more than 50 years ago, it has been gradually incorporated in the conditioning regimens for both autologous and allogeneic transplantation due to its myeloablative properties and broad antitumor effects as a DNA alkylating agent. Melphalan remains the mainstay conditioning for multiple myeloma and lymphomas; and has been used successfully in preparative ...

  15. Optimization of psychopharmacotherapy for schizophrenia in a male, locked, non-acute unit serving for persistently ill patients over one year.

    Science.gov (United States)

    Suzuki, Takefumi; Uchida, Hiroyuki; Takeuchi, Hiroyoshi; Tsunoda, Kenichi; Ishizuki, Tomomi; Mimura, Masaru

    2015-07-30

    We describe real-world psychopharmacological treatment in a Japanese, male, closed psychiatric unit where clozapie was still unavailable. Fifty-five persistently-ill patients with schizophrenia (ICD-10), mean ± S.D. age: 57.5 ± 13.0 y.o., duration of illness and admissions: 30.9 ± 15.2 years and 20.7 ± 14.5 years, respectively) treated longitudinally were evaluated. The rule was to treat with a simplest possible psychotropic regimen without polypharmacy. Compared to the baseline, the number and dose of antipsychotics were reduced from 1.9 to 1.1 and 1012 mg/day to 607 mg/day, respectively. The number of total psychotropics was minimized from 4.7 to 2.1, with a simplified once or twice daily dosing. Overall, the CGI-Severity and FACT-Sz (global functioning) improved slightly from 5.8 to 5.5 and 28.7 to 32.6, respectively. Of note, no patients got worse in comparison with the baseline clinical presentation. Forty-four patients were successfully treated with a single antipsychotic; only seven needed two antipsychotics simultaneously while 36 had been treated with antipsychotic polypharmacy at baseline. Benzodiazepines (mostly lorazepam) and antiparkinsonian drugs were prescribed in 28 and only two, respectively. Nineteen needed adjunctive valproate (average blood levels: 99.3 ± 21.8 μg/mL) and nine used lithium (0.61 ± 0.26 mEq/L). Optimization of psychopharmacotherapy is still possible for difficult-to-treat patients and, while augmentation of an antipsychotic with mood stabilizers is frequently needed, antipsychotic polypharmacy should be exceptional. PMID:25935376

  16. Genetic characterization of bovine viral diarrhea virus strains in Beijing, China and innate immune responses of peripheral blood mononuclear cells in persistently infected dairy cattle.

    Science.gov (United States)

    Weng, Xiao Gang; Song, Quan Jiang; Wu, Qiong; Liu, Ming Chao; Wang, Meng Ling; Wang, Jiu Feng

    2015-01-01

    To acquire epidemiological data on the bovine viral diarrhea virus (BVDV) and identify cattle persistently infected (PI) with this virus, 4,327 samples from Holstein dairy cows were screened over a four-year period in Beijing, China. Eighteen BVD viruses were isolated, 12 from PI cattle. Based on genetic analysis of their 5'-untranslated region (5'-UTR), the 18 isolates were assigned to subgenotype BVDV-1m, 1a, 1d, 1q, and 1b. To investigate the innate immune responses in the peripheral-blood mononuclear cells of PI cattle, the expression of Toll-like receptors (TLRs), RIG-I-like receptors, interferon-α (IFN-α), IFN-β, myxovirus (influenza virus) resistance 1 (MX1), and interferon stimulatory gene 15 (ISG15) was assessed by qPCR. When compared with healthy cattle, the expression of TLR-7, IFN-α, and IFN-β mRNA was downregulated, but the expression of MX1 and ISG-15 mRNA was upregulated in PI cattle. Immunoblotting analysis revealed that the expression of interferon regulatory factor 3 (IRF-3) and IRF-7 was lower in PI cattle than in healthy cattle. Thus, BVDV-1m and 1a are the predominant subgenotypes in the Beijing region, and the strains are highly divergent. Our findings also suggest that the TLR-7/IRF-7 signaling pathway plays a role in evasion of host restriction by BVDV.

  17. Characterization of virus obtained from MDBK cells persistently infected with a variant of herpes simplex virus type 1 strain MP [HSV-1(MP)].

    Science.gov (United States)

    Bartoletti, A M; Tognon, M; Manservigi, R; Mannini-Palenzona, A

    1985-03-01

    Virus clones which express glycoprotein gC (gC+) were obtained from two persistently infected (p.i.) MDBK cell lines which had been independently established by infection with HSV-1(MP)10311, a gC- syncytial (syn) variant of herpes simplex virus type 1 strain MP [HSV-1(MP)]. The gC+ revertants were syn in MDBK, HEp-2, and Vero cell lines and in primary human fibroblasts; this offers further evidence that glycoprotein gC does not inhibit cell fusion. The gC+ revertants represented from 70 to 100 percent of the virions present in the virus populations examined, thus suggesting a possible selective advantage of the gC+ revertants in this system of persistent infection.

  18. Specific Recognition of Breast Cancer Cells In Vitro Using Near Infrared-Emitting Long-Persistence Luminescent Zn3Ga2Ge2O10:Cr3+Nanoprobes

    Institute of Scientific and Technical Information of China (English)

    Jinlei Li; Junpeng Shi; Jiangshan Shen; Huizi Man; Mingxi Wang; Hongwu Zhang

    2015-01-01

    In this paper, near-infrared emitting long-persistence luminescent Zn3Ga2Ge2O10:Cr3? (ZGG) nanoparticles with diameters of 30–100 nm and bright luminescence were prepared by a sol–gel synthesis method. After the surface amination, the nanoparticles were further bioconjugated with breast cancer-specific monoclonal antibody (anti-EpCAM) to form ZGG-EpCAM nanoprobes which can specifically target breast cancer cell lines (MCF7) in vitro. The results of in vitro images show that the luminescence signals from the cells treated with ZGG-EpCAM nanoprobes are stronger than those from cells treated with ZGG-unconjugated antibody, indicating that the prepared ZGG-EpCAM nanoprobes pos-sessed excellent specific recognition capability. Furthermore, due to their long afterglow properties, the imaging could persist more than 1 h. Therefore, these nanoprobes could not only provide a high specificity detection method for cancer cells but also realize the long-time monitoring. Developed near-infrared emitting long-persistence luminescent nanoprobes will be expected to find new perspectives for cell therapy research and diagnosis applications.

  19. Persistence of viral genes in a variant of MDBK cell after productive replication of a mutant of influenza virus A/WSN.

    Science.gov (United States)

    Urabe, M; Tanaka, T; Odagiri, T; Tashiro, M; Tobita, K

    1993-01-01

    The MDBK-R cell line is a variant of the MDBK cell line, which was derived by three consecutive high multiplicity superinfections of MDBK cells with AWBY-140 virus, a mutant of influenza virus A/WSN (H 1N 1). MDBK-R cells are permissive for productive replication of AWBY-140, but resist lysis by the virus and grew normally without producing infectious virus after replication of the mutant occurred there. By polymerase chain reaction (PCR), we demonstrated nucleotide sequences specific to all the 8 genes of AWBY-140 in MDBK-R cells which had been infected with the mutant at a high multiplicity and subsequently received 25 passages. This suggests that the genes of influenza virus mutant persisted in the dividing host cells for a long time after productive infection, when none of the cells was producing virus. We were also able to amplify the M gene related sequence of the mutant from both poly(A)+ and poly(A)- fractions of the RNA extracted from the cells at 27th passage level by PCR, which suggests that the persisting genes were replicated and transcribed, but we failed to demonstrate any viral protein in the cells by Western blotting.

  20. High-dose cyclophosphamide followed by autologous peripheral blood progenitor cell transplantation improves the salvage treatment for persistent or sensitive relapsed malignant lymphoma

    Directory of Open Access Journals (Sweden)

    Baldissera R.C.

    2002-01-01

    Full Text Available Trials have demonstrated that high-dose escalation followed by autologous transplantation can promote better long-term survival as salvage treatment in malignant lymphomas. The aim of the present nonrandomized clinical trial was to demonstrate the role of high-dose cyclophosphamide (HDCY in reducing tumor burden and also to determine the effectiveness of HDCY followed by etoposide (VP-16 and methotrexate (MTX in Hodgkin's disease plus high-dose therapy with peripheral blood progenitor cell (PBPC transplantation as salvage treatment. From 1998 to 2000, 33 patients with a median age of 33 years (13-65 affected by aggressive non-Hodgkin's lymphoma (NHL (60.6% or persistent or relapsed Hodgkin's disease (39.4% were enrolled and treated using high dose escalation (HDCY + HDVP-16 plus HDMTX in Hodgkin's disease followed by autologous PBPC transplantation. On an "intention to treat" basis, 33 patients with malignant lymphomas were evaluated. The overall median follow-up was 400 days (40-1233. Thirty-one patients underwent autografting and received a median of 6.19 x 10(6/kg (1.07-29.3 CD34+ cells. Patients who were chemosensitive to HDCY (N = 22 and patients who were chemoresistant (N = 11 presented an overall survival of 96 and 15%, respectively (P<0.0001. Overall survival was 92% for chemosensitive patients and 0% for patients who were still chemoresistant before transplantation (P<0.0001. Toxicity-related mortality was 12% (four patients, related to HDCY in two cases and to transplant in the other two. HDCY + HDVP-16 plus HDMTX in only Hodgkin's disease followed by autologous PBPC proved to be effective and safe as salvage treatment for chemosensitive patients affected by aggressive NHL and Hodgkin's disease, with acceptable mortality rates related to sequential treatment.

  1. The Decision to Stay: A Multiple-Case Study Exploring College Choice and Persistence Factors of Second-Year Students at Religiously-Affiliated Institutions Associated with the Churches of Christ

    Science.gov (United States)

    White, Patti Jo

    2009-01-01

    Factors that influenced the college choice and persistence of twenty-eight undergraduate, second-year students at religiously-affiliated institutions associated with the churches of Christ were examined using a cross-case comparative qualitative analysis. Student pre-college characteristics and campus environment factors were also investigated…

  2. Habit persistence

    DEFF Research Database (Denmark)

    Vinther Møller, Stig

    2009-01-01

    This paper uses an iterated GMM approach to estimate and test the consumption based habit persistence model of Campbell and Cochrane (1999) on the US stock market. The empirical evidence shows that the model is able to explain the size premium, but fails to explain the value premium. Further, the......, the state variable of the model - the surplus consumption ratio - explains counter-cyclical time-varying expected returns on stocks. The model also produces plausible low real risk-free rates despite high relative risk aversion....

  3. Bacterial persistence: some new insights into an old phenomenon

    Indian Academy of Sciences (India)

    R Jayaraman

    2008-12-01

    Bigger discovered more than 60 years ago, at the very beginning of the antibiotic era, that populations of antibiotic-sensitive bacteria contained a very small fraction (approximately 10–6) of antibiotic-tolerant cells (persisters). Persisters are different from antibiotic-resistant mutants in that their antibiotic tolerance is non-heritable and reversible. In spite of its importance as an interesting biological phenomenon and in the treatment of infectious diseases, persistence did not attract the attention of the scientific community for more than four decades since its discovery. The main reason for this lack of interest was the difficulty in isolating sufficient numbers of persister cells for experimentation, since the proportion of persisters in a population of wild-type cells is extremely small. However, with the discovery of high-persister (hip) mutants of Escherichia coli by Moyed and his group in the early 1980s, the phenomenon attracted the attention of many groups and significant progress has occurred since then. It is now believed that persistence is the end result of a stochastic switch in the expression of some toxin–antitoxin (TA) modules (of which the hipA and hipB genes could be examples), creating an imbalance in their intracellular levels. There are also models invoking the involvement of the alarmone (p) ppGpp in the generation of persisters. However, the precise mechanisms are still unknown. Bacterial persistence is part of a wider gamut of phenomena variously called as bistability, multistability, phenotypic heterogeneity, stochastic switching processes, etc. It has attracted the attention of not only microbiologists but also a diverse band of researchers such as biofilm researchers, evolutionary biologists, sociobiologists, etc. In this article, I attempt to present a broad overview of bacterial persistence to illustrate its significance and the need for further exploration.

  4. IL-17A and serum amyloid A are elevated in a cigarette smoke cessation model associated with the persistence of pigmented macrophages, neutrophils and activated NK cells.

    Directory of Open Access Journals (Sweden)

    Michelle J Hansen

    Full Text Available While global success in cessation advocacy has seen smoking rates fall in many developed countries, persistent lung inflammation in ex-smokers is an increasingly important clinical problem whose mechanistic basis remains poorly understood. In this study, candidate effector mechanisms were assessed in mice exposed to cigarette smoke (CS for 4 months following cessation from long term CS exposure. BALF neutrophils, CD4+ and CD8+ T cells and lung innate NK cells remained significantly elevated following smoking cessation. Analysis of neutrophil mobilization markers showed a transition from acute mediators (MIP-2α, KC and G-CSF to sustained drivers of neutrophil and macrophage recruitment and activation (IL-17A and Serum Amyoid A (SAA. Follicle-like lymphoid aggregates formed with CS exposure and persisted with cessation, where they were in close anatomical proximity to pigmented macrophages, whose number actually increased 3-fold following CS cessation. This was associated with the elastolytic protease, MMP-12 (macrophage metallo-elastase which remained significantly elevated post-cessation. Both GM-CSF and CSF-1 were significantly increased in the CS cessation group relative to the control group. In conclusion, we show that smoking cessation mediates a transition to accumulation of pigmented macrophages, which may contribute to the expanded macrophage population observed in COPD. These macrophages together with IL-17A, SAA and innate NK cells are identified here as candidate persistence determinants and, we suggest, may represent specific targets for therapies directed towards the amelioration of chronic airway inflammation.

  5. Long-Term Monitoring of Field Trial Sites with Genetically Modified Oilseed Rape (Brassica napus L.) in Saxony-Anhalt, Germany. Fifteen Years Persistence to Date but No Spatial Dispersion.

    Science.gov (United States)

    Belter, Anke

    2016-01-01

    Oilseed rape is known to persist in arable fields because of its ability to develop secondary seed dormancy in certain agronomic and environmental conditions. If conditions change, rapeseeds are able to germinate up to 10 years later to build volunteers in ensuing crops. Extrapolations of experimental data acted on the assumption of persistence periods for more than 20 years after last harvest of rapeseed. Genetically-modified oilseed rape-cultivated widely in Northern America since 1996-is assumed not to differ from its conventional form in this property. Here, experimental data are reported from official monitoring activities that verify these assumptions. At two former field trial sites in Saxony-Anhalt genetically-modified herbicide-resistant oilseed rape volunteers are found up to fifteen years after harvest. Nevertheless, spatial dispersion or establishment of GM plants outside of the field sites was not observed within this period. PMID:26784233

  6. Population Dynamics of Bacterial Persistence

    OpenAIRE

    Patra, Pintu; Klumpp, Stefan

    2013-01-01

    Persistence is a prime example of phenotypic heterogeneity, where a microbial population splits into two distinct subpopulations with different growth and survival properties as a result of reversible phenotype switching. Specifically, persister cells grow more slowly than normal cells under unstressed growth conditions, but survive longer under stress conditions such as the treatment with bactericidal antibiotics. We analyze the population dynamics of such a population for several typical ex...

  7. Genome sequencing identifies two nearly unchanged strains of persistent Listeria monocytogenes isolated in two different fish processing plants sampled six years apart

    Science.gov (United States)

    Listeria monocytogenes is a food-borne human pathogenic bacterium that can cause infections with a high mortality rate. It has a remarkable ability to persist in food processing facilities and here we report the complete genome sequences for two L. monocytogenes strains (N53-1 and La111) that were i...

  8. Genome Sequencing Identifies Two Nearly Unchanged Strains of Persistent Listeria monocytogenes Isolated at Two Different Fish Processing Plants Sampled 6 Years Apart

    DEFF Research Database (Denmark)

    Holch, Anne; Webb, Kristen; Lukjancenko, Oksana;

    2013-01-01

    distinguished by two genome deletions: one, of 2,472 bp, typically contains the gene for inlF, and the other, of 3,017 bp, includes three genes potentially related to bacteriocin production and transport (lmo2774, lmo2775, and the 3′-terminal part of lmo2776). Further studies of highly persistent strains...

  9. Possible role of minor h antigens in the persistence of donor chimerism after stem cell transplantation; relevance for sustained leukemia remission.

    Directory of Open Access Journals (Sweden)

    Cornelis R van der Torren

    Full Text Available Persistent complete donor chimerism is an important clinical indicator for remissions of hematological malignancies after HLA-matched allogeneic stem cell transplantation (SCT. However, the mechanisms mediating the persistence of complete donor chimerism are poorly understood. The frequent coincidence of complete donor chimerism with graft-versus-leukemia effects and graft-versus-host disease suggests that immune responses against minor histocompatibility antigens (mHags are playing an important role in suppressing the host hematopoiesis after allogeneic SCT. Here, we investigated a possible relationship between donor immune responses against the hematopoiesis-restricted mHag HA-1 and the long-term kinetics of host hematopoietic chimerism in a cohort of 10 patients after allogeneic HLA-matched, HA-1 mismatched SCT. Functional HA-1 specific CTLs (HA-1 CTLs were detectable in 6/10 patients lysing host-type hematopoietic cells in vitro. Presence of HA-1 CTLs in the peripheral blood coincided with low host hematopoiesis levels quantified by highly sensitive mHag specific PCR. Additionally, co-incubation of host type CD34+ cells with HA-1 CTLs isolated after allogeneic SCT prevented progenitor and cobblestone area forming cell growth in vitro and human hematopoietic engraftment in immunodeficient mice. Conversely, absence or loss of HA-1 CTLs mostly coincided with high host hematopoiesis levels and/or relapse. In summary, in this first study, presence of HA-1 CTLs paralleled low host hematopoiesis levels. This coincidence might be supported by the capacity of HA-1 CTLs isolated after allogeneic SCT to specifically eliminate host type hematopoietic stem/progenitor cells. Additional studies involving multiple mismatched mHags in more patients are required to confirm this novel characteristic of mHag CTLs as factor for the persistence of complete donor chimerism and leukemia remission after allogeneic SCT.

  10. Persistence and drug tolerance in pathogenic yeast

    DEFF Research Database (Denmark)

    Bojsen, Rasmus Kenneth; Regenberg, Birgitte; Folkesson, Sven Anders

    2016-01-01

    are quiescent in G0 of the cell cycle. This knowledge leads us to suggest that the identified shared drug-tolerance mechanisms of persister and quiescent cells may serve as a foundation for developing novel treatment strategies that are independent of growth mode against systemic fungal infections....... leading to drug recalcitrance is the formation of antifungal persister cells. These cells have wild-type genotype with the ability to survive exposure to antifungal agents due to changed membrane composition, upregulated stress response, and enhanced cell wall integrity. Knowledge of the mechanisms...... regulating entry and exit of the persister phenotype is limited, but it has recently been shown that the inhibition of the growth regulating TORC1 pathway induces fungal persistence. The phenotypic properties of persister cells and the involvement of the TORC1 pathway indicate that persister cells...

  11. Metabolic aspects of bacterial persisters

    Directory of Open Access Journals (Sweden)

    Marcel ePrax

    2014-10-01

    Full Text Available Persister cells form a multi-drug tolerant subpopulation within an isogenic culture of bacteria that are genetically susceptible to antibiotics. Studies with different Gram negative and Gram positive bacteria have identified a large number of genes associated with the persister state. In contrast, the revelation of persister metabolism has only been addressed recently. We here summarize metabolic aspects of persisters, which includes an overview about the bifunctional role of selected carbohydrates as both triggers for the exit from the drug tolerant state and metabolites which persisters feed on. Also alarmones as indicators for starvation have been shown to influence persister levels via different signaling cascades involving the activation of toxin-antitoxin systems and other regulatory factors. Finally, recent data obtained by 13C-isotopologue profiling demonstrated an active amino acid anabolism in Staphylococcus aureus cultures challenged with high drug concentrations. Understanding the metabolism of persister cells poses challenges but also paves the way for the development of anti-persister compounds.

  12. On Level persistence (Relevant level persistence numbers)

    OpenAIRE

    Du, Dong

    2014-01-01

    The purpose of this note is to describe of a new set of numerical invariants, the relevant level persistence numbers, and make explicit their relationship with the four types of bar codes, a more familiar set of complete invariants for level persistence. The paper provides the opportunity to compare level persistence with the persistence introduced by Edelsbrunner- Letscher-Zomorodian called in this paper, as sub-level persistence.

  13. Impact of clonal competition for peptide-MHC complexes on the CD8[superscript +] T-cell repertoire selection in a persistent viral infection

    Energy Technology Data Exchange (ETDEWEB)

    Wynn, Katherine K.; Fulton, Zara; Cooper, Leanne; Silins, Sharon L.; Gras, Stephanie; Archbold, Julia K.; Tynan, Fleur E.; Miles, John J.; McCluskey, James; Burrows, Scott R.; Rossjohn, Jamie; Khanna, Rajiv (Monash); (Queensland Inst. of Med. Rsrch.); (Melbourne)

    2008-04-29

    CD8{sup +} T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)-specific CD8{sup +} T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)-peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more 'featureless' landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype.

  14. Combined Double Sleeve Lobectomy and Superior Vena Cava Resection for Non-small Cell Lung Cancer with Persistent Left Superior Vena Cava

    Directory of Open Access Journals (Sweden)

    Daxing ZHU

    2015-11-01

    Full Text Available A 65-year-old man with right central type of lung squamous carcinoma was admitted to our department. Bronchoscopy displayed complete obstruction of right upper lobe bronchus and infiltration of the bronchus intermedius with tumor. Chest contrast computed tomography revealed the tumor invaded right pulmonary artery, superior vena cava, and the persistant left superior vena cava flowed into the coronary sinus. The tumor was successfully removed by means of bronchial and pulmonary artery sleeve resection of the right upper and middle lobes combined with resection and reconstruction of superior vena cava (SVC utilizing ringed polytetrafluoroethylene graft. To the best of our knowledge, this was the first report of complete resection of locally advanced lung cancer involving superior vena cava, right pulmonary artery trunk and main bronchus with persistant left superior vena cava.

  15. Combined Double Sleeve Lobectomy and Superior Vena Cava Resection for Non-small Cell Lung Cancer with Persistent Left Superior Vena Cava

    Institute of Scientific and Technical Information of China (English)

    Daxing ZHU; Xiaoming QIU; Qinghua ZHOU

    2015-01-01

    A 65-year-old man with right central type of lung squamous carcinoma was admitted to our department. Bronchoscopy displayed complete obstruction of right upper lobe bronchus and inifltration of the bronchus intermedius with tumor. Chest contrast computed tomography revealed the tumor invaded right pulmonary artery, superior vena cava, and the persistant letf superior vena cava lfowed into the coronary sinus. hTe tumor was successfully removed by means of bronchial and pulmonary artery sleeve resection of the right upper and middle lobes combined with resection and reconstruction of superior vena cava (SVC) utilizing ringed polytetralfuoroethylene gratf. To the best of our knowledge, this was the ifrst report of complete resection of locally advanced lung cancer involving superior vena cava, right pulmonary artery trunk and main bronchus with persistant letf superior vena cava.

  16. Poor Invasion of Trophoblastic Cells but Normal Plaque Formation in Fibroblastic Cells despite actA Deletion in a Group of Listeria monocytogenes Strains Persisting in Some Food Processing Environments

    DEFF Research Database (Denmark)

    Holch, Anne; Gottlieb, Caroline Trebbien; Larsen, Marianne Halberg;

    2010-01-01

    We determined mammalian cell invasion and virulence gene (inlA, inlB, and actA) sequences of Listeria monocytogenes strains belonging to a molecular subtype (RAPD 9) that often persists in Danish fish-processing plants. These strains invaded human placental trophoblasts less efficiently than other...

  17. Transcriptomic Analysis of Persistent Infection with Foot-and-Mouth Disease Virus in Cattle Suggests Impairment of Apoptosis and Cell-Mediated Immunity in the Nasopharynx.

    Science.gov (United States)

    Eschbaumer, Michael; Stenfeldt, Carolina; Smoliga, George R; Pacheco, Juan M; Rodriguez, Luis L; Li, Robert W; Zhu, James; Arzt, Jonathan

    2016-01-01

    In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vaccine, 10 non-vaccinated) were challenged with FMDV A24 Cruzeiro, and the gene expression profiles of nasopharyngeal tissues collected between 21 and 35 days after challenge were compared between 11 persistently infected carriers and 7 non-carriers. Carriers and non-carriers were further compared to 2 naïve animals that had been neither vaccinated nor challenged. At a controlled false-discovery rate of 10% and a minimum difference in expression of 50%, 648 genes were differentially expressed between FMDV carriers and non-carriers, and most (467) had higher expression in carriers. Among these, genes associated with cellular proliferation and the immune response-such as chemokines, cytokines and genes regulating T and B cells-were significantly overrepresented. Differential gene expression was significantly correlated between non-vaccinated and vaccinated animals (biological correlation +0.97), indicating a similar transcriptome profile across these groups. Genes related to prostaglandin E2 production and the induction of regulatory T cells were overexpressed in carriers. In contrast, tissues from non-carrier animals expressed higher levels of complement regulators and pro-apoptotic genes that could promote virus clearance. Based on these findings, we propose a working hypothesis for FMDV persistence in nasopharyngeal tissues of cattle, in which the virus may be maintained by an impairment of apoptosis and the local suppression of cell-mediated antiviral immunity by inducible regulatory T cells. PMID:27643611

  18. An annoying persistent cough

    OpenAIRE

    Francesco Cipollini

    2007-01-01

    Chronic cough is a stressful condition and can lead to extensive investigations. We report a case of a 48-year-old woman who had suffered from persistent chronic cough for more than 3 months. She had been treated with cough suppressant. However, her cough was not alleviated by these treatments, and the patient was referred to our hospital. She did not exhibit typical gastroesophageal reflux disease (GERD) symptoms heartburn and regurgitation. Esophagoscopy did not disclose reflux esophagitis....

  19. The role of metabolism in bacterial persistence

    Directory of Open Access Journals (Sweden)

    Stephanie M. Amato

    2014-03-01

    Full Text Available Bacterial persisters are phenotypic variants with extraordinary tolerances toward antibiotics. Persister survival has been attributed to inhibition of essential cell functions during antibiotic stress, followed by reversal of the process and resumption of growth upon removal of the antibiotic. Metabolism plays a critical role in this process, since it participates in the entry, maintenance, and exit from the persister phenotype. Here, we review the experimental evidence that demonstrates the importance of metabolism to persistence, highlight the successes and potential for targeting metabolism in the search for anti-persister therapies, and discuss the current methods and challenges to understand persister physiology.

  20. Impact of the Maturation of Human Primary Bone-Forming Cells on Their Behavior in Acute or Persistent Staphylococcus aureus Infection Models.

    Science.gov (United States)

    Josse, Jérôme; Guillaume, Christine; Bour, Camille; Lemaire, Flora; Mongaret, Céline; Draux, Florence; Velard, Frédéric; Gangloff, Sophie C

    2016-01-01

    Staphylococcus aureus is one of the most frequently involved pathogens in bacterial infections such as skin abscess, pneumonia, endocarditis, osteomyelitis, and implant-associated infection. As for bone homeostasis, it is partly altered during infections by S. aureus by the induction of various responses from osteoblasts, which are the bone-forming cells responsible for extracellular matrix synthesis and its mineralization. Nevertheless, bone-forming cells are a heterogeneous population with different stages of maturation and the impact of the latter on their responses toward bacteria remains unclear. We describe the impact of S. aureus on two populations of human primary bone-forming cells (HPBCs) which have distinct maturation characteristics in both acute and persistent models of interaction. Cell maturation did not influence the internalization and survival of S. aureus inside bone-forming cells or the cell death related to the infection. By studying the expression of chemokines, cytokines, and osteoclastogenic regulators by HPBCs, we observed different profiles of chemokine expression according to the degree of cell maturation. However, there was no statistical difference in the amounts of proteins released by both populations in the presence of S. aureus compared to the non-infected counterparts. Our findings show that cell maturation does not impact the behavior of HPBCs infected with S. aureus and suggest that the role of bone-forming cells may not be pivotal for the inflammatory response in osteomyelitis. PMID:27446812

  1. Persistence of decidual NK cells and KIR genotypes in healthy pregnant and preeclamptic women: a case-control study in the third trimester of gestation

    Directory of Open Access Journals (Sweden)

    Cerbón Marco

    2011-01-01

    Full Text Available Abstract Background Natural Killer (NK cells are the most abundant lymphocytes in the decidua during early gestation. The interactions of NK cells with the extravillous cytotrophoblast have been associated with a normal spiral artery remodeling process, an essential event for a successful pregnancy. Recent data indicate that alterations in the amount of decidual NK (dNK cells contribute to the development of preeclampsia (PE. Moreover, genetic studies suggest that Killer Immunoglobulin-like Receptors (KIR expressed in dNK cells influence the susceptibility to PE. Although dNK cells have been well characterized during early pregnancy, they have been scarcely studied in the third trimester of gestation. The aim of this work was to characterize dNK cells at the last trimester of gestation and to analyze the KIR genotype of healthy and PE women. Methods Decidual samples were obtained during Caesarean section from control (n = 10 and PE (n = 9 women. Flow cytometric analysis of CD3, CD56, CD16 and CD9 was used to characterize and quantify dNK cells in both groups. Cell surface markers from decidual leukocytes were compared with PBMC from healthy donors. KIR genotyping was performed in genomic DNA (control, n = 86; PE, n = 90 using PCR-SSP. Results The results indicate that dNK cells persist throughout pregnancy. They represented 20% of total leukocytes in control and PE groups, and they expressed the same cell surface markers (CD3-, CD56+, CD16- and CD9+ as dNK in the first trimester of gestation. There were no significant differences in the percentage of dNK cells between control and PE groups. The analysis of KIR gene frequencies and genotypes was not statistically different between control and PE groups. The ratio of activating to inhibitory genes indicated that the overall inhibitory balance (0.2-0.5 was more frequent in the PE group (control, 31.3% vs PE, 45.5%, and the activating balance (0.6-1.1 was more frequent in the control group (control

  2. CD4+ T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques

    Science.gov (United States)

    Saito, Naoki; Chono, Hideto; Shibata, Hiroaki; Ageyama, Naohide; Yasutomi, Yasuhiro; Mineno, Junichi

    2014-01-01

    MazF, an endoribonuclease encoded by Escherichia coli, specifically cleaves the ACA (adenine–cytosine–adenine) sequence of single-stranded RNAs. Conditional expression of MazF under the control of the HIV-1 LTR promoter rendered CD4+ T cells resistant to HIV-1 replication without affecting cell growth. To investigate the safety, persistence and efficacy of MazF-modified CD4+ T cells in a nonhuman primate model in vivo, rhesus macaques were infected with a pathogenic simian/human immunodeficiency virus (SHIV) and transplanted with autologous MazF-modified CD4+ T cells. MazF-modified CD4+ T cells were clearly detected throughout the experimental period of more than 6 months. The CD4+ T cell count values increased in all four rhesus macaques. Moreover, the transplantation of the MazF-modified CD4+ T cells was not immunogenic, and did not elicit cellular or humoral immune responses. These data suggest that the autologous transplantation of MazF-modified CD4+ T cells in the presence of SHIV is effective, safe and not immunogenic, indicating that this is an attractive strategy for HIV-1 gene therapy. PMID:24914931

  3. CD4(+) T Cells Modified by the Endoribonuclease MazF Are Safe and Can Persist in SHIV-infected Rhesus Macaques.

    Science.gov (United States)

    Saito, Naoki; Chono, Hideto; Shibata, Hiroaki; Ageyama, Naohide; Yasutomi, Yasuhiro; Mineno, Junichi

    2014-06-10

    MazF, an endoribonuclease encoded by Escherichia coli, specifically cleaves the ACA (adenine-cytosine-adenine) sequence of single-stranded RNAs. Conditional expression of MazF under the control of the HIV-1 LTR promoter rendered CD4(+) T cells resistant to HIV-1 replication without affecting cell growth. To investigate the safety, persistence and efficacy of MazF-modified CD4(+) T cells in a nonhuman primate model in vivo, rhesus macaques were infected with a pathogenic simian/human immunodeficiency virus (SHIV) and transplanted with autologous MazF-modified CD4(+) T cells. MazF-modified CD4(+) T cells were clearly detected throughout the experimental period of more than 6 months. The CD4(+) T cell count values increased in all four rhesus macaques. Moreover, the transplantation of the MazF-modified CD4(+) T cells was not immunogenic, and did not elicit cellular or humoral immune responses. These data suggest that the autologous transplantation of MazF-modified CD4(+) T cells in the presence of SHIV is effective, safe and not immunogenic, indicating that this is an attractive strategy for HIV-1 gene therapy.

  4. [MOLECULAR ASPECTS OF BRUCELLA PERSISTENCE].

    Science.gov (United States)

    Kulakov Yu K

    2016-01-01

    Brucellosis is a dangerous zoonotic disease of animals and humans caused by bacteria of the genus Brucella, which are able to survive, multiply, and persist in host cells. The review is devoted to the Brucella species persistence connected to the molecular mechanisms of escape from innate and adaptive immunity of the host and active interaction of effector proteins of the type IV secretion system with the host's signaling pathways. Understanding of the molecular mechanisms used by Brucella for the intracellular persistence in the host organism can allow us to develop new and effective means for the prevention and treatment of chronic brucellosis infection.

  5. Persistence of HBV Vaccine’s Protection and Response to Hepatitis B Booster Immunization in 5- to 7-Year-Old Children in the Kohgiloyeh and Boyerahmad Province, Iran

    OpenAIRE

    Shahrzad Yazdanpanah; Mitra Safari; Behrouz Yazdanpanah

    2010-01-01

    Background and Aims: The duration of the protection of hepatitis B vaccination for infants and the necessity of a booster dose administration is unknown. The aim of the present study was to evaluate the persistence of seroprotection after hepatitis B virus (HBV) vaccination in order to determine the necessity of a single booster dose in 5- to 7-year-old children.Methods: This clinical trial study was conducted from 2004 to 2005. The study population included all children aged 5 to 7 years old...

  6. Rhesus monkeys kidney cells persistently infected with Simian Virus 40: production of defective interfering virus and acquisition of the transformed phenotype.

    Science.gov (United States)

    Norkin, L C

    1976-09-01

    Monolayer cultures of LLC-MK2 rhesus monkey kidney cells became persistently infected with simian virus 40 (SV40) when infected at a multiplicity of infection of 100 plaque-forming units/cell. A stable carrier state developed characterized by extensive viral proliferation without obvious cytopathic effect other than the slow growth of these cultures. By 11 weeks all cells produced the SV40 T antigen. In contrast, less than 5% of the cells produced V antigen. Virus-free clonal isolates were obtained by cloning in SV40 antiserum. Continuous cultivation in antiserum resulted in a temporary cure of unclone cultures. When virus did eventually reappear in the "cured" cultures the titers remained low. The virus produced by the carrier culture was defective at both 31 and 37% c, and it interfered with the growth of standard s40 during mixed infection of CV-1 green monkey kidney cells. All of the interfering activity in carrier culture homogenates could be sedimented by centrifugation at 109,000 x g for 3 h. These cultures were completely susceptible to vesicular stomatitis virus. Extensive viral deoxyribonucleic acid synthesis occurred in CV-1 cells infected with carrier culture virus. Carrier culture homogenates are only slightly less cytopathic to CV-1 cells than standard SV40. The carrier culture express several properties of SV40 transformation.

  7. Persistent Hiccups Following Stapedectomy

    Directory of Open Access Journals (Sweden)

    Aidonis I

    2010-10-01

    Full Text Available Objective: We report a case of a 37 year-old man who developed persistent hiccups after elective stapedectomy. Method and Results: The diagnostic approach is discussed as well as the non-pharmacologic and pharmacologic treatments and overall management. The aim is to stress that there is a variety of potential factors that can induce hiccups perioperatively and in cases like this a step by step approach must be taken. Conclusion: Persistent hiccups are very rare following stapedectomy, control of them is crucial for the successful outcome. The trigger may be more than one factors and the good response to treatment may be due to dealing successfully with more than one thing.

  8. Merkel Cell Carcinoma Analysis of Outcomes: A 30-Year Experience.

    Directory of Open Access Journals (Sweden)

    Evan Liang

    Full Text Available Merkel cell carcinoma (MCC is an aggressive cutaneous malignancy with poor prognosis. Limited data exists to guide treatment decisions. Here we report on our institutional experience and outcomes treating patients with MCC.A database search (1984-2014 of patients treated at the University of Wisconsin Hospital and Clinics was used to identify patients with histologically confirmed MCC. Patient, tumor, and treatment characteristics were examined via review of medical records. Statistical analyses were performed to assess outcomes and associated prognostic factors.A total of 87 patients with MCC were identified with a median follow-up of 17 months (mean: 38, range: 0-210 months. Two and five-year overall survival rates were 53.9% and 32.8%, respectively. Recurrence was documented in 31.0% of patients (85.2% locoregional, 48.1% distant and 33.3% both. Patients with a history of immunosuppression exhibited significantly worse survival (hazard ratio, 2.01; 95% CI, 1.1-3.7 when compared to immune-competent individuals. The head and neck region was the most common location of primary lesion (N=49 followed by the extremities (N=31. Upper extremity primaries predicted significantly better overall survival (hazard ratio, 0.48; 95% CI, 0.23-0.99 while lower extremity primaries did not have significantly better results (hazard ratio, 0.5; 95% CI, 0.21-1.2 in comparison to head and neck site of primary. Nodal involvement (hazard ratio, 2.95; 95% CI, 1.5-5.79 was also a negative prognostic factor associated with poor overall survival when compared with clinically node negative patients. Primary tumor size > 2 cm (hazard ratio, 1.76; 95% CI, 0.91-3.4 was not associated with survival.This study highlights the role of various factors in determining prognosis of Merkel cell carcinoma; history of immunosuppression, nodal involvement, and head/neck primary predicted worse overall survival. These findings suggest that improvements in both distant and locoregionally

  9. Twenty years of embryonic stem cell research in farm animals

    Science.gov (United States)

    Notable distinctions between an embryonic stem cell (ESC) and somatic cell are that the ESC can maintain an undifferentiated state indefinitely, self renew, and is pluripotent, meaning that the ESC can potentially generate cells representing all the three primordial germ layers and contribute to the...

  10. : Socioeconomic position and depression persistence.

    OpenAIRE

    Melchior, Maria; Chastang, Jean-François; Leclerc, Annette; Ribet, Céline; Rouillon, Frédéric

    2010-01-01

    International audience Research examining the association between socioeconomic position and depression course has yielded inconsistent results. We tested the association between low socioeconomic position and 7-year depression persistence among 298 community-based individuals with depression (subset of the GAZEL cohort study based in France). Data were analyzed using Generalized Estimating Equation (GEE models). Low socioeconomic position predicted depression persistence (men: low vs. int...

  11. Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury.

    Science.gov (United States)

    Li, Ge; Che, Ming-Tian; Zhang, Ke; Qin, Li-Na; Zhang, Yu-Ting; Chen, Rui-Qiang; Rong, Li-Min; Liu, Shu; Ding, Ying; Shen, Hui-Yong; Long, Si-Mei; Wu, Jin-Lang; Ling, Eng-Ang; Zeng, Yuan-Shan

    2016-03-01

    Persistent neurotrophic factor delivery is crucial to create a microenvironment for cell survival and nerve regeneration in spinal cord injury (SCI). This study aimed to develop a NT-3/fibroin coated gelatin sponge scaffold (NF-GS) as a novel controlled artificial release therapy for SCI. In vitro, bone marrow-derived mesenchymal stem cells (MSCs) were planted into the NF-GS and release test showed that NF-GS was capable to generate a sustainable NT-3 release up to 28 days. MSCs in NF-GS had high cell activity with excellent cell distribution and phenotype. Then, the NF-GS was transplanted into the injury site of spinal cord of rat and canine in vivo, which exhibited strong biocompatibility during post-transplantation period. Four weeks following transplantation, the concentration of NT-3 was much higher than that in control groups. Cavity areas in the injury/graft site were significantly reduced due to tissue regeneration and axonal extensions associated with myelin sheath through the glial scar into the NF-GS. Additionally, the NF-GS decreased the inflammation by reducing the CD68 positive cells and TNF-α. A striking feature was the occurrence of some cells and myelin-like structure that appeared to traverse the NF-GS. The present results demonstrate that the NF-GS has the property to control the release of NT-3 from the NT-3/fibroin complex thus facilitating regeneration of injured spinal cord. PMID:26774562

  12. Culture of skeletal myoblasts from human donors aged over 40 years: dynamics of cell growth and expression of differentiation markers

    Directory of Open Access Journals (Sweden)

    Cherubino Paolo

    2005-05-01

    Full Text Available Abstract Background Local myogenesis, neoangiogenesis and homing of progenitor cells from the bone marrow appear to contribute to repair of the infarcted myocardium. Implantation into heart tissues of autologous skeletal myoblasts has been associated with improved contractile function in animal models and in humans with acute myocardial ischemia. Since heart infarction is most prevalent in individuals of over 40 years of age, we tested whether culture methods available in our laboratory were adequate to obtain sufficient numbers of differentiated skeletal myoblasts from muscle biopsy specimens obtained from patients aged 41 to 91. Methods and results No matter of donor age, differentiated skeletal muscle cells could be produced in vitro in amounts adequate for cellular therapy (≥300 millions. Using desmin as a cytoplasmic marker, about 50% cultured cells were differentiated along myogenic lineages and expressed proteins proper of skeletal muscle (myosin type I and II, actin, actinin, spectrin and dystrophin. Cytogenetic alterations were not detected in cultured muscle cells that had undergone at least 10 population doublings. Molecular methods employed for the screening of persistent viral infections evidenced that HCV failed to replicate in muscle cells cultured from one patient with chronic HCV infection. Conclusion The proposed culture methods appear to hold promise for aged patients not only in the field of cardiovascular medicine, but also in the urologic and orthopedic fields.

  13. The Attenuated Brucella abortus Strain 19 Invades, Persists in, and Activates Human Dendritic Cells, and Induces the Secretion of IL-12p70 but Not IL-23.

    Directory of Open Access Journals (Sweden)

    Mario Weinhold

    Full Text Available Bacterial vectors have been proposed as novel vaccine strategies to induce strong cellular immunity. Attenuated strains of Brucella abortus comprise promising vector candidates since they have the potential to induce strong CD4(+ and CD8(+ T-cell mediated immune responses in the absence of excessive inflammation as observed with other Gram-negative bacteria. However, some Brucella strains interfere with the maturation of dendritic cells (DCs, which is essential for antigen-specific T-cell priming. In the present study, we investigated the interaction of human monocyte-derived DCs with the smooth attenuated B. abortus strain (S 19, which has previously been employed successfully to vaccinate cattle.We first looked into the potential of S19 to hamper the cytokine-induced maturation of DCs; however, infected cells expressed CD25, CD40, CD80, and CD86 to a comparable extent as uninfected, cytokine-matured DCs. Furthermore, S19 activated DCs in the absence of exogeneous stimuli, enhanced the expression of HLA-ABC and HLA-DR, and was able to persist intracellularly without causing cytotoxicity. Thus, DCs provide a cellular niche for persisting brucellae in vivo as a permanent source of antigen. S19-infected DCs produced IL-12/23p40, IL-12p70, and IL-10, but not IL-23. While heat-killed bacteria also activated DCs, soluble mediators were not involved in S19-induced activation of human DCs. HEK 293 transfectants revealed cellular activation by S19 primarily through engagement of Toll-like receptor (TLR2.Thus, as an immunological prerequisite for vaccine efficacy, B. abortus S19 potently infects and potently activates (most likely via TLR2 human DCs to produce Th1-promoting cytokines.

  14. The Attenuated Brucella abortus Strain 19 Invades, Persists in, and Activates Human Dendritic Cells, and Induces the Secretion of IL-12p70 but Not IL-23

    Science.gov (United States)

    Weinhold, Mario; Eisenblätter, Martin; Jasny, Edith; Fehlings, Michael; Finke, Antje; Gayum, Hermine; Rüschendorf, Ursula; Renner Viveros, Pablo; Moos, Verena; Allers, Kristina; Schneider, Thomas; Schaible, Ulrich E.; Schumann, Ralf R.; Mielke, Martin E.; Ignatius, Ralf

    2013-01-01

    Background Bacterial vectors have been proposed as novel vaccine strategies to induce strong cellular immunity. Attenuated strains of Brucella abortus comprise promising vector candidates since they have the potential to induce strong CD4+ and CD8+ T-cell mediated immune responses in the absence of excessive inflammation as observed with other Gram-negative bacteria. However, some Brucella strains interfere with the maturation of dendritic cells (DCs), which is essential for antigen-specific T-cell priming. In the present study, we investigated the interaction of human monocyte-derived DCs with the smooth attenuated B. abortus strain (S) 19, which has previously been employed successfully to vaccinate cattle. Methodology/Principal findings We first looked into the potential of S19 to hamper the cytokine-induced maturation of DCs; however, infected cells expressed CD25, CD40, CD80, and CD86 to a comparable extent as uninfected, cytokine-matured DCs. Furthermore, S19 activated DCs in the absence of exogeneous stimuli, enhanced the expression of HLA-ABC and HLA-DR, and was able to persist intracellularly without causing cytotoxicity. Thus, DCs provide a cellular niche for persisting brucellae in vivo as a permanent source of antigen. S19-infected DCs produced IL-12/23p40, IL-12p70, and IL-10, but not IL-23. While heat-killed bacteria also activated DCs, soluble mediators were not involved in S19-induced activation of human DCs. HEK 293 transfectants revealed cellular activation by S19 primarily through engagement of Toll-like receptor (TLR)2. Conclusions/Significance Thus, as an immunological prerequisite for vaccine efficacy, B. abortus S19 potently infects and potently activates (most likely via TLR2) human DCs to produce Th1-promoting cytokines. PMID:23805193

  15. Preleukemic TEL-AML1-positive clones at cell level of 10(-3) to 10(-4) do not persist into adulthood.

    Science.gov (United States)

    Olsen, Marianne; Madsen, Hans O; Hjalgrim, Henrik; Gregers, Jannie; Rostgaard, Klaus; Schmiegelow, Kjeld

    2006-11-01

    The TEL-AML1 translocation, t(12;21)(p13;q22), is one of the most frequent genetic aberrations in childhood B-cell precursor acute lymphoblastic leukemia (ALL), where it occurs in 25% of all cases. In contrast, the translocation is seen in only 3% of adult ALL cases. Evidence suggests that the TEL-AML1 translocation occurs in utero in 1% of all newborn children at cell levels of 10 to 10. In this study, we explore the prevalence of TEL-AML1-positive cells in 2 cohorts of healthy blood donors by real-time and nested reverse transcription-polymerase chain reaction. Overall, TEL-AML1-positive cells were demonstrated in 10 of 2005 healthy donors, that is, a prevalence of 0.5% (95% confidence interval, 0.2-0.3%). The level of TEL-AML1-positive cells was estimated to 10 to 10. The observed prevalence of TEL-AML1-positive cells in healthy adults is of the same order of magnitude as the prevalence reported in healthy newborns, but the observed cell level of 10 to 10 is much lower. These data indicates that prenatal TEL-AML1 subclones does not persist throughout adult life at cell levels of 10 to 10. The findings are compatible with the risk of t(12;21)(p13;q22) ALL correlating with the total number of TEL-AML1-positive cells in peripheral blood in both childhood and adulthood. PMID:17114960

  16. HIV Integration at Certain Sites in Host DNA Is Linked to the Expansion and Persistence of Infected Cells | Poster

    Science.gov (United States)

    Editor’s note: This article was originally published on the Center for Cancer Research website. When the Human Immunodeficiency Virus (HIV) infects a cell, the virus inserts a copy of its genetic material into the host cell’s DNA. The inserted genetic material, which is also called a provirus, is used to produce new viruses. Because the viral DNA can be inserted at many sites in the host cell DNA, the site of integration marks each infected cell. Patients infected with HIV are currently treated with combined antiretroviral therapy (cART), which prevents viral replication in the majority of treated patients. When cART is initiated, most HIV-infected cells die in one or two days, and more of the infected cells die over a period of weeks to months. However there are some long-lived infected cells that do not die, which prevents patients from being cured.

  17. Persistent changes in circulating and intestinal γδ T cell subsets, invariant natural killer T cells and mucosal-associated invariant T cells in children and adults with coeliac disease.

    Directory of Open Access Journals (Sweden)

    Margaret R Dunne

    Full Text Available Coeliac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The only current therapy is a lifelong gluten free diet. While much work has focused on the gliadin-specific adaptive immune response in coeliac disease, little is understood about the involvement of the innate immune system. Here we used multi-colour flow cytometry to determine the number and frequency of γδ T cells (Vδ1, Vδ2 and Vδ3 subsets, natural killer cells, CD56(+ T cells, invariant NKT cells, and mucosal associated invariant T cells, in blood and duodenum from adults and children with coeliac disease and healthy matched controls. All circulating innate lymphocyte populations were significantly decreased in adult, but not paediatric coeliac donors, when compared with healthy controls. Within the normal small intestine, we noted that Vδ3 cells were the most abundant γδ T cell type in the adult epithelium and lamina propria, and in the paediatric lamina propria. In contrast, patients with coeliac disease showed skewing toward a predominant Vδ1 profile, observed for both adult and paediatric coeliac disease cohorts, particularly within the gut epithelium. This was concurrent with decreases in all other gut lymphocyte subsets, suggesting a specific involvement of Vδ1 cells in coeliac disease pathogenesis. Further analysis showed that γδ T cells isolated from the coeliac gut display an activated, effector memory phenotype, and retain the ability to rapidly respond to in vitro stimulation. A profound loss of CD56 expression in all lymphocyte populations was noted in the coeliac gut. These findings demonstrate a sustained aberrant innate lymphocyte profile in coeliac disease patients of all ages, persisting even after elimination of gluten from the diet. This may lead to impaired immunity, and could potentially account for the increased incidence of autoimmune co-morbidity.

  18. Prenatal cadmium exposure produces persistent changes to thymus and spleen cell phenotypic repertoire as well as the acquired immune response

    International Nuclear Information System (INIS)

    Cadmium (Cd) is a common environmental contaminant. Adult exposure to Cd alters the immune system, however, there are limited studies on the effects of prenatal exposure to Cd. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl2 (10 ppm) and the effects on the immune system of the offspring were assessed at 20 weeks of age. Prenatal Cd exposure caused an increase in the percent of CD4−CD8−CD44+CD25− (DN1) thymocytes in both sexes and a decrease in the percent of CD4−CD8−CD44−CD25+ (DN3) thymocytes in females. Females had an increase in the percent of splenic CD4+ T cells, CD8+ T cells, and CD45R/B220+ B cells and a decrease in the percent of NK cells and granulocytes (Gr-1+). Males had an increase in the percent of splenic CD4+ T cells and CD45R/B220+ B cells and a decrease in the percent of CD8+ T cells, NK cells, and granulocytes. The percentage of neutrophils and myeloid-derived suppressor cells were reduced in both sexes. The percent of splenic nTreg cells was decreased in all Cd-exposed offspring. Cd-exposed offspring were immunized with a streptococcal vaccine and the antibody response was determined. PC-specific serum antibody titers were decreased in Cd exposed female offspring but increased in the males. PspA-specific serum IgG titers were increased in both females and males compared to control animals. Females had a decrease in PspA-specific serum IgM antibody titers. Females and males had a decrease in the number of splenic anti-PspA antibody-secreting cells when standardized to the number of B cells. These findings demonstrate that very low levels of Cd exposure during gestation can result in long term sex-specific alterations on the immune system of the offspring. -- Highlights: ► Prenatal exposure to cadmium alters the immune system of 20 week old offspring. ► The percentage of DN1 and DN3 thymocytes was changed. ► Males and females had changed percentages of numerous splenic cell populations. ► The

  19. Prenatal cadmium exposure produces persistent changes to thymus and spleen cell phenotypic repertoire as well as the acquired immune response

    Energy Technology Data Exchange (ETDEWEB)

    Holásková, Ida; Elliott, Meenal; Hanson, Miranda L.; Schafer, Rosana [Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: jbarnett@hsc.wvu.edu [Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506 (United States); Mary Babb Randolph Cancer Center, West Virginia University School of Medicine, Morgantown, WV 26506 (United States)

    2012-12-01

    Cadmium (Cd) is a common environmental contaminant. Adult exposure to Cd alters the immune system, however, there are limited studies on the effects of prenatal exposure to Cd. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at 20 weeks of age. Prenatal Cd exposure caused an increase in the percent of CD4{sup −}CD8{sup −}CD44{sup +}CD25{sup −} (DN1) thymocytes in both sexes and a decrease in the percent of CD4{sup −}CD8{sup −}CD44{sup −}CD25{sup +} (DN3) thymocytes in females. Females had an increase in the percent of splenic CD4{sup +} T cells, CD8{sup +} T cells, and CD45R/B220{sup +} B cells and a decrease in the percent of NK cells and granulocytes (Gr-1{sup +}). Males had an increase in the percent of splenic CD4{sup +} T cells and CD45R/B220{sup +} B cells and a decrease in the percent of CD8{sup +} T cells, NK cells, and granulocytes. The percentage of neutrophils and myeloid-derived suppressor cells were reduced in both sexes. The percent of splenic nTreg cells was decreased in all Cd-exposed offspring. Cd-exposed offspring were immunized with a streptococcal vaccine and the antibody response was determined. PC-specific serum antibody titers were decreased in Cd exposed female offspring but increased in the males. PspA-specific serum IgG titers were increased in both females and males compared to control animals. Females had a decrease in PspA-specific serum IgM antibody titers. Females and males had a decrease in the number of splenic anti-PspA antibody-secreting cells when standardized to the number of B cells. These findings demonstrate that very low levels of Cd exposure during gestation can result in long term sex-specific alterations on the immune system of the offspring. -- Highlights: ► Prenatal exposure to cadmium alters the immune system of 20 week old offspring. ► The percentage of DN1 and DN3 thymocytes was changed

  20. Persistent primitive trigeminal arteries (PTA) and its variant (PTAV): analysis of 103 cases detected in 16,415 cases of MRA over 3 years

    Energy Technology Data Exchange (ETDEWEB)

    O' uchi, Eri; O' uchi, Toshihiro [Kameda Medical Center, Department of Radiology, Kamogawa, Chiba (Japan)

    2010-12-15

    The primitive persistent trigeminal artery (PTA) is the most common carotid-basilar anastomosis, but because of its extremely low incidence, it is poorly understood. The purpose of this study is to clarify the features of PTA and its variants (PTAV) based on a large magnetic resonance angiography (MRA) series. MRA was performed on continuous 16,415 patients (8,610 males and 7,805 females) between October 2005 and September 2008 using two 1.5-T systems and one 1.0-T system. These all MRAs were evaluated by neuroradiologists. The incidence of both PTA and PTAV was 0.68% (48 cases of PTA, 50 cases of PTAV, and five unclassified). Among them, 65 cases originated from the left internal carotid artery and 38 from the right. There were 44 cases of lateral type PTA and four cases of medial type. Hypoplasia of the basilar artery proximal to the union of PTA was recognized as follows: no hypoplasia in 12 cases, moderate hypoplasia in 22 cases, and severe hypoplasia in 13 cases. Distance from SCA and the union was an average of 6.7 mm. Four cases of pre- and postoperative cerebral aneurysms were recognized in 103 cases (3.9%). We have identified details of both PTA/PTAV. The incidence of PTA was similar to previous studies, and the co-existence of cerebral aneurysm was also similar when compared to patients in the general population without PTA or PTAV. (orig.)

  1. Fast intracellular dissolution and persistent cellular uptake of silver nanoparticles in CHO-K1 cells: implication for cytotoxicity

    DEFF Research Database (Denmark)

    Jiang, Xiumei; Miclaus, Teodora; Wang, Liming;

    2015-01-01

    Toxicity of silver nanoparticles (Ag NPs) has been reported both in vitro and in vivo. However, the intracellular stability and chemical state of Ag NPs are still not very well studied. In this work, we systematically investigated the cellular uptake pathways, intracellular dissolution and chemical...... species, and cytotoxicity of Ag NPs (15.9 ± 7.6 nm) in Chinese hamster ovary cell subclone K1 cells, a cell line recommended by the OECD for genotoxicity studies. Quantification of intracellular nanoparticle uptake and ion release was performed through inductively coupled plasma mass spectrometry. X...

  2. Donor Lymphocyte Infusion in Treating Patients With Persistent, Relapsed, or Progressing Cancer After Donor Hematopoietic Cell Transplant

    Science.gov (United States)

    2016-07-25

    Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Hodgkin Lymphoma; Recurrent Non-Hodgkin Lymphoma; Recurrent Plasma Cell Myeloma

  3. Genetically Attenuated Plasmodium berghei Liver Stages Persist and Elicit Sterile Protection Primarily via CD8 T Cells

    OpenAIRE

    Mueller, Ann-Kristin; Deckert, Martina; Heiss, Kirsten; Goetz, Kristin; Matuschewski, Kai; Schlüter, Dirk

    2007-01-01

    Live-attenuated Plasmodium liver stages remain the only experimental model that confers complete sterile protection against malaria. Irradiation-attenuated Plasmodium parasites mediate protection primarily by CD8 T cells. In contrast, it is unknown how genetically attenuated liver stage parasites provide protection. Here, we show that immunization with uis3(−) sporozoites does not cause breakthrough infection in T and B-cell-deficient rag1−/− and IFN-γ−/− mice. However, protection was abolish...

  4. Remodeling of the Host Cell Plasma Membrane by HIV-1 Nef and Vpu: A Strategy to Ensure Viral Fitness and Persistence

    Directory of Open Access Journals (Sweden)

    Scott M. Sugden

    2016-03-01

    Full Text Available The plasma membrane protects the cell from its surroundings and regulates cellular communication, homing, and metabolism. Not surprisingly, the composition of this membrane is highly controlled through the vesicular trafficking of proteins to and from the cell surface. As intracellular pathogens, most viruses exploit the host plasma membrane to promote viral replication while avoiding immune detection. This is particularly true for the enveloped human immunodeficiency virus (HIV, which assembles and obtains its lipid shell directly at the plasma membrane. HIV-1 encodes two proteins, negative factor (Nef and viral protein U (Vpu, which function primarily by altering the quantity and localization of cell surface molecules to increase virus fitness despite host antiviral immune responses. These proteins are expressed at different stages in the HIV-1 life cycle and employ a variety of mechanisms to target both unique and redundant surface proteins, including the viral receptor CD4, host restriction factors, immunoreceptors, homing molecules, tetraspanins and membrane transporters. In this review, we discuss recent progress in the study of the Nef and Vpu targeting of host membrane proteins with an emphasis on how remodeling of the cell membrane allows HIV-1 to avoid host antiviral immune responses leading to the establishment of systemic and persistent infection.

  5. RECURRENT/PERSISTENT PNEUMONIA AMONG CHILDREN IN UPPER EGYPT

    Directory of Open Access Journals (Sweden)

    Khaled Saad

    2013-04-01

    Full Text Available Abstract Objectives: Recurrent/persistent pneumonia in children continues to be a major challenge for the paediatricians. We aimed to determine the prevalence and underlying causes of recurrent/persistent pneumonia in children in Upper Egypt. Settings: Assiut University Children Hospital, Assiut, Egypt.   Methods: Patients with pneumonia admitted to the hospital during 2 years were investigated (microbiological, biochemical, immunological and radiological tests for recurrent/persistent pneumonia to determine its prevalence and to find out the underlying causes.   Results: 113 out of 1228 patients (9.2% met the diagnosis of recurrent/persistent pneumonia. Identified causes were;  aspiration syndromes (17.7%, pulmonary TB (14%, congenital heart disease (11.5%, bronchial asthma (9.7%, immune deficiency disorders (8.8% and vitamin D deficiency rickets (7%. Other causes included; congenital anomalies of the respiratory tract, interstitial lung diseases, bronchiectasis, and sickle cell anemia. No predisposing factors could be identified in 15% of cases. Conclusion: Approximately 1 in 10 children with pneumonia in our locality had recurrent/persistent pneumonia. The most frequent underlying cause for recurrent/persistent pneumonia in children in Upper Egypt is aspiration syndromes, followed by pulmonary TB.

  6. Persistence of Th17/Tc17 Cell Expression upon Smoking Cessation in Mice with Cigarette Smoke-Induced Emphysema

    Directory of Open Access Journals (Sweden)

    Min-Chao Duan

    2013-01-01

    Full Text Available Th17 and Tc17 cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD, a disease caused predominantly by cigarette smoking. Smoking cessation is the only intervention in the management of COPD. However, even after cessation, the airway inflammation may be present. In the current study, mice were exposed to room air or cigarette smoke for 24 weeks or 24 weeks followed by 12 weeks of cessation. Morphological changes were evaluated by mean linear intercepts (Lm and destructive index (DI. The frequencies of CD8+IL-17+(Tc17 and CD4+IL-17+(Th17 cells, the mRNA levels of ROR gamma and IL-17, and the levels of IL-8, TNF-alpha, and IFN-gamma in lungs or bronchoalveolar lavage fluid of mice were assayed. Here we demonstrated that alveolar enlargement and destruction induced by cigarette smoke exposure were irreversible and that cigarette smokeenhanced these T-cell subsets, and related cytokines were not significantly reduced after smoking cessation. In addition, the frequencies of Th17 and Tc17 cells in lungs of smoke-exposed mice and cessation mice were positively correlated with emphysematous lesions. More important, the frequencies of Tc17 cells were much higher than Th17 cells, and there was a significantly positive correlation between Th17 and Tc17. These results suggested that Th17/Tc17 infiltration in lungs may play a critical role in sustaining lung inflammation in emphysema. Blocking the abnormally increased numbers of Tc17 and Th17 cells may be a reasonable therapeutic strategy for emphysema.

  7. Persistence of Th17/Tc17 cell expression upon smoking cessation in mice with cigarette smoke-induced emphysema.

    Science.gov (United States)

    Duan, Min-Chao; Tang, Hai-Juan; Zhong, Xiao-Ning; Huang, Ying

    2013-01-01

    Th17 and Tc17 cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), a disease caused predominantly by cigarette smoking. Smoking cessation is the only intervention in the management of COPD. However, even after cessation, the airway inflammation may be present. In the current study, mice were exposed to room air or cigarette smoke for 24 weeks or 24 weeks followed by 12 weeks of cessation. Morphological changes were evaluated by mean linear intercepts (Lm) and destructive index (DI). The frequencies of CD8(+)IL-17(+)(Tc17) and CD4(+)IL-17(+)(Th17) cells, the mRNA levels of ROR gamma and IL-17, and the levels of IL-8, TNF-alpha, and IFN-gamma in lungs or bronchoalveolar lavage fluid of mice were assayed. Here we demonstrated that alveolar enlargement and destruction induced by cigarette smoke exposure were irreversible and that cigarette smokeenhanced these T-cell subsets, and related cytokines were not significantly reduced after smoking cessation. In addition, the frequencies of Th17 and Tc17 cells in lungs of smoke-exposed mice and cessation mice were positively correlated with emphysematous lesions. More important, the frequencies of Tc17 cells were much higher than Th17 cells, and there was a significantly positive correlation between Th17 and Tc17. These results suggested that Th17/Tc17 infiltration in lungs may play a critical role in sustaining lung inflammation in emphysema. Blocking the abnormally increased numbers of Tc17 and Th17 cells may be a reasonable therapeutic strategy for emphysema. PMID:24489575

  8. Persistent recurring wheezing in the fifth year of life after laboratory-confirmed, medically attended respiratory syncytial virus infection in infancy

    OpenAIRE

    Escobar, Gabriel J; Masaquel, Anthony S; Li, Sherian X; Walsh, Eileen M.; Kipnis, Patricia

    2013-01-01

    Background Respiratory syncytial virus (RSV) infection in infancy is associated with subsequent recurrent wheezing. Methods A retrospective cohort study examined children born at ≥32 weeks gestation between 1996–2004. All children were enrolled in an integrated health care delivery system in Northern California and were followed through the fifth year of life. The primary endpoint was recurrent wheezing in the fifth year of life and its association with laboratory-confirmed, medically-attende...

  9. Loss of quiescence and impaired function of CD34+/CD38low cells one year following autologous stem cell transplantation

    OpenAIRE

    Woolthuis, Carolien M.; Brouwers-Vos, Annet Z.; Huls, Gerwin; de Wolf, Joost Th. M.; Schuringa, Jan Jacob; Vellenga, Edo

    2013-01-01

    Patients who have undergone autologous stem cell transplantation are subsequently more susceptible to chemotherapy-induced bone marrow toxicity. In the present study, bone marrow primitive progenitor cells were examined one year after autologous stem cell transplantation and compared with normal bone marrow and mobilized peripheral blood stem cells. Post-transplantation bone marrow contained a significantly lower percentage of quiescent cells in the CD34+/CD38low fraction compared to normal b...

  10. Cerebellar clear cell ependymoma in a 10 year old girl

    Energy Technology Data Exchange (ETDEWEB)

    Thinzar Aye Nyein; Moon, Ah Rim; Hwang, Sun Chul; Hong, Hyun Sook; Lee, A Leum; Chang, Kee Hyun; Kim, Hee Kyung; Chin, Su Sie [Soonchunhyang University Bucheon Hospital, Bucheon (Korea, Republic of); Park, Ji Sang [Soonchunhyang University Gumi Hospital, Gumi (Korea, Republic of)

    2016-01-15

    Clear cell ependymoma (CCE) is a histological rare variant (1–5%) of ependymoma, which is distinguished from other histological subtypes by the presence of fusiform cells arrayed radially around small blood vessels. These alleged perivascular pseudorosettes are significant characteristic features of ependymomas. About 95% of infratentorial ependymomas are found in the fourth ventricle and the remainder occurs as cerebellopontine angle lesions. In previous reports, the cerebellum is found to be a rare location for ependymoma. In this study we report one case of CCE originating from the cerebellar hemisphere, showing unusual morphology on 3T MRI.

  11. Malformations of the epididymis, incomplete regression of the mesonephric tubules and hyperplasia of Leydig cells in canine persistence of Müllerian duct syndrome.

    Science.gov (United States)

    Whyte, Ana; Monteagudo, Luis V; Díaz-Otero, Angel; Lebrero, M Eugenia; Tejedor, M Teresa; Falceto, M Victoria; Whyte, Jaime; Gallego, Margarita

    2009-10-01

    Persistence of the Müllerian duct syndrome (PMDS) is a rare form of pseudohermaphroditism characterized by the presence of uterus and oviducts in otherwise normally differentiated SRY-positive 78 XY canine males. Undescended testicles are also common. We report a case of a male PMDS dog with a uterus and bilateral cryptorchidism. The dog had an incomplete regression of the mesonephric tubules. As a consequence of this an abnormally enlarged head of the epididymis was observed. In addition, an extreme reduction in size of both the body and the tail was found. Microscopic examination of both testicles revealed bilateral hyperplasia of Leydig cells. The progesterone blood level was measured by ELISA and was found to be abnormally high (3.18 ng/ml) compared to that of normal male dogs (lower than 1 ng/ml). Three months after surgical removal of the internal genitalia, the serum progesterone, testosterone and oestradiol levels were normal for a castrated male dog.

  12. Persistent Müllerian duct syndrome of mixed anatomical variant (combined male and female type with mixed germ cell tumor of left intra-abdominal testis

    Directory of Open Access Journals (Sweden)

    Manisha Mohapatra

    2016-01-01

    Full Text Available Persistent Müllerian duct syndrome (PMDS is a rare form of internal male pseudohermaphroditism characterized by retention of Müllerian duct derivatives in a phenotypically and karyotypically male patient. Deficiency of anti-Müllerian hormone (AMH secretion or resistance to AMH action due to defective AMH-II receptor is presumed to cause such syndrome in the majority of cases. About 158 PMDS cases have been reported so far, out of which 31 cases are associated with testicular neoplasms. Herein, we describe an interesting case of young male initially diagnosed and treated for inguinal hernia, but finally diagnosed as “PMDS of mixed anatomical variant (combined male and female type with mixed germ cell tumor of left intra-abdominal testis” comprising components of seminoma and yolk sac tumor and treated successfully.

  13. Persistent HIV-1 replication during antiretroviral therapy

    Science.gov (United States)

    Martinez-Picado, Javier; Deeks, Steven G.

    2016-01-01

    Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on efficiently targeting these three aspects. The degree to which HIV replicates during ART remains controversial. Most studies have failed to find any evidence of HIV evolution in blood, even with samples collected over many years, although a recent very intensive study of three individuals suggested that the virus population does shift, at least during the first few months of therapy. Stronger but still not definitive evidence for replication comes from a series of studies in which standard regimens were intensified with an integration inhibitor, resulting in changes in episomal DNA (blood) and cell-associated RNA (tissue). Limited drug penetration within tissues and the presence of immune sanctuaries have been argued as potential mechanisms allowing HIV to spread during ART. Mathematical models suggest that HIV replication and evolution is possible even without the selection of fully drug-resistant variants. As persistent HIV replication could have clinical consequences and might limit the efficacy of curative interventions, determining if HIV replicates during ART and why, should remain a key focus of the HIV research community. Summary Residual viral replication likely persists in lymphoid tissues, at least in a subset of individuals. Abnormal levels of immune activation might contribute to sustain virus replication. PMID:27078619

  14. Occult persistence and lymphotropism of hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Tram NQ Pham; Tomasz I Michalak

    2008-01-01

    Recent discovery of occult hepatitis C virus (HCV)infection persisting after spontaneous or antiviral therapy-induced resolution of hepatitis C was made possible by the introduction of nucleic acid amplification assays capable of detecting HCV RNA at sensitivities superseding those offered by clinical tests. Although individuals with this seemingly silent HCV infection are usually anti-HCV antibody reactive and have normal liver function tests, occult HCV infection has also been reported in anti-HCV-negative individuals with persistently elevated liver enzymes of unknown etiology. Studies have shown that HCV RNA can persist for years in serum, iymphomononuciear cells and liver in the absence of clinical symptoms, although histological evidence of a mild inflammatory liver injury can be occasionally encountered. Furthermore, while HCV RNA can be detected in circulating lymphoid cells in approximately 30% of cases, a short-term culture under stimulatory conditions augments HCV replication in these cells allowing detection of virus in otherwise HCV-negative cases. HCV infects different immune cell subsets, including CD4+ and CD8+ T lymphocytes, B cells and monocytes. Studies employing cional sequencing and single-stranded conformational polymorphism analyses have revealed unique HCV variants residing in immune cells, further strengthening the notion of HCV lymphotropism. Overall, the data accumulated suggest that occult HCV infection is a common consequence of resolution of symptomatic hepatitis C and that examination of the cells of the immune system is an effective approach to diagnosis of HCV infection and its long-term persistence. Further work is required to fully realize pathogenic and epidemiological consequences of occult HCV persistence.

  15. Sexual function 1-year after allogeneic hematopoietic stem cell transplantation

    DEFF Research Database (Denmark)

    Noerskov, K H; Schjødt, I; Syrjala, K L;

    2016-01-01

    Treatment with allogeneic hematopoietic stem cell transplantation (HSCT) is associated with short and long-term toxicities that can result in alterations in sexual functioning. The aims of this prospective evaluation were to determine: (1) associations between HSCT and increased sexual dysfunction...

  16. HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

    Science.gov (United States)

    Jongwe, Tsungai Ivai; Chapman, Ros; Douglass, Nicola; Chetty, Shivan; Chege, Gerald; Williamson, Anna-Lise

    2016-01-01

    Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C) viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA) vaccines expressing HIV-1C mosaic Gag (GagM) were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu) can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C). PMID:27427967

  17. HIV-1 Subtype C Mosaic Gag Expressed by BCG and MVA Elicits Persistent Effector T Cell Responses in a Prime-Boost Regimen in Mice.

    Directory of Open Access Journals (Sweden)

    Tsungai Ivai Jongwe

    Full Text Available Over 90% of HIV/AIDS positive individuals in sub-Saharan Africa are infected with highly heterogeneous HIV-1 subtype C (HIV-1C viruses. One of the best ways to reduce the burden of this disease is the development of an affordable and effective prophylactic vaccine. Mosaic immunogens are computationally designed to overcome the hurdle of HIV diversity by maximizing the expression of potential T cell epitopes. Mycobacterium bovis BCG ΔpanCD auxotroph and modified vaccinia Ankara (MVA vaccines expressing HIV-1C mosaic Gag (GagM were tested in a prime-boost regimen to demonstrate immunogenicity in a mouse study. The BCG-GagM vaccine was stable and persisted 11.5 weeks post vaccination in BALB/c mice. Priming with BCG-GagM and boosting with MVA-GagM elicited higher Gag-specific IFN-γ ELISPOT responses than the BCG-GagM only and MVA-GagM only homologous vaccination regimens. The heterologous vaccination also generated a more balanced and persistent CD4+ and CD8+ T cell Gag-specific IFN-γ ELISPOT response with a predominant effector memory phenotype. A Th1 bias was induced by the vaccines as determined by the predominant secretion of IFN-γ, TNF-α, and IL-2. This study shows that a low dose of MVA (104 pfu can effectively boost a BCG prime expressing the same mosaic immunogen, generating strong, cellular immune responses against Gag in mice. Our data warrants further evaluation in non-human primates. A low dose vaccine would be an advantage in the resource limited countries of sub-Saharan Africa and India (where the predominating virus is HIV-1 subtype C.

  18. Persistent growth of a human plasma-derived hepatitis C virus genotype 1b isolate in cell culture.

    OpenAIRE

    Erica Silberstein; Kathleen Mihalik; Laura Ulitzky; Ewan P Plant; Montserrat Puig; Sara Gagneten; Yu, Mei-ying W.; Neerja Kaushik-Basu; Feinstone, Stephen M.; Taylor, Deborah R.

    2010-01-01

    HCV (hepatitis C virus) research, including therapeutics and vaccine development, has been hampered by the lack of suitable tissue culture models. Development of cell culture systems for the growth of the most drug-resistant HCV genotype (1b) as well as natural isolates has remained a challenge. Transfection of cultured cells with adenovirus-associated RNA(I) (VA RNA(I)), a known interferon (IFN) antagonist and inhibitor of dsRNA-mediated antiviral pathways, enhanced the growth of plasma-deri...

  19. The Adherent/Invasive Escherichia coli Strain LF82 Invades and Persists in Human Prostate Cell Line RWPE-1, Activating a Strong Inflammatory Response

    Science.gov (United States)

    Aleandri, Marta; Marazzato, Massimiliano; Conte, Antonietta L.; Ambrosi, Cecilia; Nicoletti, Mauro; Zagaglia, Carlo; Gambara, Guido; Palombi, Fioretta; De Cesaris, Paola; Ziparo, Elio; Palamara, Anna T.; Riccioli, Anna

    2016-01-01

    Adherent/invasive Escherichia coli (AIEC) strains have recently been receiving increased attention because they are more prevalent and persistent in the intestine of Crohn's disease (CD) patients than in healthy subjects. Since AIEC strains show a high percentage of similarity to extraintestinal pathogenic E. coli (ExPEC), neonatal meningitis-associated E. coli (NMEC), and uropathogenic E. coli (UPEC) strains, here we compared AIEC strain LF82 with a UPEC isolate (strain EC73) to assess whether LF82 would be able to infect prostate cells as an extraintestinal target. The virulence phenotypes of both strains were determined by using the RWPE-1 prostate cell line. The results obtained indicated that LF82 and EC73 are able to adhere to, invade, and survive within prostate epithelial cells. Invasion was confirmed by immunofluorescence and electron microscopy. Moreover, cytochalasin D and colchicine strongly inhibited bacterial uptake of both strains, indicating the involvement of actin microfilaments and microtubules in host cell invasion. Moreover, both strains belong to phylogenetic group B2 and are strong biofilm producers. In silico analysis reveals that LF82 shares with UPEC strains several virulence factors: namely, type 1 pili, the group II capsule, the vacuolating autotransporter toxin, four iron uptake systems, and the pathogenic island (PAI). Furthermore, compared to EC73, LF82 induces in RWPE-1 cells a marked increase of phosphorylation of mitogen-activated protein kinases (MAPKs) and of NF-κB already by 5 min postinfection, thus inducing a strong inflammatory response. Our in vitro data support the hypothesis that AIEC strains might play a role in prostatitis, and, by exploiting host-cell signaling pathways controlling the innate immune response, likely facilitate bacterial multiplication and dissemination within the male genitourinary tract. PMID:27600504

  20. The proteolysis of mitotic cyclins in mammalian cells persists from the end of mitosis until the onset of S phase.

    Science.gov (United States)

    Brandeis, M; Hunt, T

    1996-10-01

    We have studied how the cell cycle-specific oscillations of mitotic B-type cyclins are generated in mouse fibroblasts. A reporter enzyme comprising the N-terminus of a B-type cyclin fused to bacterial chloramphenicol acetyl transferase (CAT) was degraded at the end of mitosis like endogenous cyclins. Point mutations in the destruction box of this construct completely abolished its mitotic instability. When the destructible reporter was driven by the cyclin B2 promoter, CAT activity mimicked the oscillations in the level of the endogenous cyclin B2. These oscillations were largely conserved when the reporter was transcribed constitutively from the SV40 promoter. Pulse-chase experiments or addition of the proteasome inhibitors lactacystin and ALLN showed that cyclin synthesis continued after the end of mitosis. The destruction box-specific degradation of cyclins normally ceases at the onset of S phase, and is active in fibroblasts arrested in G0 and in differentiated C2 myoblasts. We were able to reproduce this proteolysis in vitro in extracts of synchronized cells. Extracts of G1 cells degraded cyclin B1 whereas p27Kip1 was stable, in contrast, cyclin B1 remained stable and p27Kip1 was degraded in extracts of S phase cells. PMID:8895573

  1. Dendritic cell science: more than 40 years of history

    NARCIS (Netherlands)

    Spriel, A.B. van; Jong, E.C. de

    2013-01-01

    Over 40 years of research into the field of DCs has revolutionized our understanding into the activation and regulation of the immune system. This minireview discusses the major breakthroughs in DC science that have paved the way to the 2011 Nobel Prize in Physiology-Medicine awarded to Bruce A. Beu

  2. Diagnostic performance of whole-body MRI for the detection of persistent or relapsing disease in multiple myeloma after stem cell transplantation

    International Nuclear Information System (INIS)

    To compare the diagnostic performance of whole-body MRI (WBMRI) with haematological parameters for detecting persistent or relapsing disease in patients with multiple myeloma after stem cell transplantation. Sixty-six WBMRI acquisitions were performed in 33 patients with multiple myeloma at two time points after stem cell transplantation. Extent of disease and inter-test dynamics of intra- and extramedullary myeloma manifestations were compared (kappa statistics) with Uniform Response Criteria, comprising haematological parameters. Using data from 66 sequential WBMRI acquisitions in 33 patients, 10 patients (30.3 %) were classified as having progressive disease and 23 (69.7 %) as being in remission. Eight (80 %) of the ten patients with progressive disease revealed intramedullary lesions, and two patients (20 %) had intra- and extramedullary lesions. WBMRI and laboratory tests were concordant in 26/33 (78.8 %) patients. We found an agreement of 51.2 %, 95 % confidence interval 19.8 %-82.6 %, between results from WBMRI and haematological parameters. WBMRI had a sensitivity of 63.6 %, specificity of 86.4 %, PPV of 70.0 %, NPV of 82.6 % and accuracy of 78.8 % for detection of remission. WBMRI allows the detection and exact localisation of intra- and extramedullary myeloma manifestations after stem cell transplantation, but shows only moderate agreement with routinely performed laboratory tests for determination of remission. (orig.)

  3. Diagnostic performance of whole-body MRI for the detection of persistent or relapsing disease in multiple myeloma after stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Bannas, Peter; Hentschel, Hannah B.; Bley, Thorsten A.; Derlin, Thorsten; Yamamura, Jin; Adam, Gerhard; Weber, Christoph [University Medical Center Hamburg-Eppendorf, Department of Diagnostic and Interventional Radiology, Hamburg (Germany); Treszl, Andras; Eulenburg, Christine [University Medical Center Hamburg-Eppendorf, Department of Medical Biometry and Epidemiology, Hamburg (Germany); Stuebig, Thomas; Kroeger, Nicolaus [University Medical Center Hamburg-Eppendorf, Department of Stem Cell Transplantation, Hamburg (Germany)

    2012-09-15

    To compare the diagnostic performance of whole-body MRI (WBMRI) with haematological parameters for detecting persistent or relapsing disease in patients with multiple myeloma after stem cell transplantation. Sixty-six WBMRI acquisitions were performed in 33 patients with multiple myeloma at two time points after stem cell transplantation. Extent of disease and inter-test dynamics of intra- and extramedullary myeloma manifestations were compared (kappa statistics) with Uniform Response Criteria, comprising haematological parameters. Using data from 66 sequential WBMRI acquisitions in 33 patients, 10 patients (30.3 %) were classified as having progressive disease and 23 (69.7 %) as being in remission. Eight (80 %) of the ten patients with progressive disease revealed intramedullary lesions, and two patients (20 %) had intra- and extramedullary lesions. WBMRI and laboratory tests were concordant in 26/33 (78.8 %) patients. We found an agreement of 51.2 %, 95 % confidence interval 19.8 %-82.6 %, between results from WBMRI and haematological parameters. WBMRI had a sensitivity of 63.6 %, specificity of 86.4 %, PPV of 70.0 %, NPV of 82.6 % and accuracy of 78.8 % for detection of remission. WBMRI allows the detection and exact localisation of intra- and extramedullary myeloma manifestations after stem cell transplantation, but shows only moderate agreement with routinely performed laboratory tests for determination of remission. (orig.)

  4. Persistent detection of Babesia EU1 and Babesia microti in Ixodes ricinus in The Netherlands during a 5-year surveillance: 2003-2007

    NARCIS (Netherlands)

    Wielinga, P.R.; Fonville, M.; Sprong, H.; Gaasenbeek, C.P.H.; Borgsteede, F.H.M.

    2009-01-01

    We report the finding of Babesia EU1 and Babesia microti in Ixodes ricinus ticks in the Netherlands. During 5 years of surveillance between 2003 and 2007, 1488 ticks were collected in a dune forest area near the North Sea and were screened for Babesia infections. In 17 ticks, DNA of the protozoan pa

  5. Induction and Persistence of Large γH2AX Foci by High Linear Energy Transfer Radiation in DNA-Dependent protein kinase–Deficient Cells

    Energy Technology Data Exchange (ETDEWEB)

    Bracalente, Candelaria; Ibañez, Irene L. [Departamento de Micro y Nanotecnología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires (Argentina); Molinari, Beatriz [Departamento de Radiobiología, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires (Argentina); Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires (Argentina); Palmieri, Mónica [Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires (Argentina); Kreiner, Andrés [Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires (Argentina); Gerencia de Investigación y Aplicaciones, Comisión Nacional de Energía Atómica, San Martín, Buenos Aires (Argentina); Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, San Martín, Buenos Aires (Argentina); Valda, Alejandro [Escuela de Ciencia y Tecnología, Universidad Nacional de San Martín, San Martín, Buenos Aires (Argentina); and others

    2013-11-15

    Purpose: To evaluate the cell response to DNA double-strand breaks induced by low and high linear energy transfer (LET) radiations when the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs), an essential protein of the nonhomologous end-joining repair pathway, lacks kinase activity. Methods and Materials: CHO10B2, a Chinese hamster ovary cell line, and its derived radiosensitive mutant cell line, irs-20, lacking DNA-PKcs activity, were evaluated after 0 to 3 Gy of γ-rays, plateau and Bragg peak protons, and lithium beams by clonogenic assay, and as a measurement of double-strand breaks, phosphorylated H2AX (γH2AX) foci number and size were quantified by immunocytofluorescence. Results: Irs-20 exhibited greater radiosensitivity and a higher amount of γH2AX foci than CHO10B2 at 6 hours after irradiation for all types of radiations. Remarkably, CHO10B2 and irs-20 maintained their difference in radiosensitivity after high-LET radiation. Six hours after low-LET radiations, irs-20 did not reach basal levels of γH2AX at high doses, whereas CHO10B2 recovered basal levels for all doses. After high-LET radiation, only CHO10B2 exhibited a reduction in γH2AX foci, but it never reached basal levels. Persistent foci in irs-20 confirmed a repair deficiency. Interestingly, after 30 minutes of high-LET radiation both cell lines exhibited large foci (size >0.9 μm{sup 2}) related to the damage nature, whereas at 6 hours irs-20 showed a higher amount of large foci than CHO10B2, with a 7-fold increase at 3 Gy, that could also be associated to radiosensitivity. Conclusions: We demonstrated, for the first time, an association between deficient DNA-PKcs activity and not only high levels of H2AX phosphorylation but also persistence and size increase of γH2AX foci after high-LET irradiation.

  6. The proteolysis of mitotic cyclins in mammalian cells persists from the end of mitosis until the onset of S phase.

    OpenAIRE

    Brandeis, M.; Hunt, T

    1996-01-01

    We have studied how the cell cycle-specific oscillations of mitotic B-type cyclins are generated in mouse fibroblasts. A reporter enzyme comprising the N-terminus of a B-type cyclin fused to bacterial chloramphenicol acetyl transferase (CAT) was degraded at the end of mitosis like endogenous cyclins. Point mutations in the destruction box of this construct completely abolished its mitotic instability. When the destructible reporter was driven by the cyclin B2 promoter, CAT activity mimicked t...

  7. Persistence of Th17/Tc17 Cell Expression upon Smoking Cessation in Mice with Cigarette Smoke-Induced Emphysema

    OpenAIRE

    Min-Chao Duan; Hai-Juan Tang; Xiao-Ning Zhong; Ying Huang

    2013-01-01

    Th17 and Tc17 cells may be involved in the pathogenesis of chronic obstructive pulmonary disease (COPD), a disease caused predominantly by cigarette smoking. Smoking cessation is the only intervention in the management of COPD. However, even after cessation, the airway inflammation may be present. In the current study, mice were exposed to room air or cigarette smoke for 24 weeks or 24 weeks followed by 12 weeks of cessation. Morphological changes were evaluated by mean linear intercepts (Lm)...

  8. Effects of defined mixtures of persistent organic pollutants (POPs) on multiple cellular responses in the human hepatocarcinoma cell line, HepG2, using high content analysis screening.

    Science.gov (United States)

    Wilson, Jodie; Berntsen, Hanne Friis; Zimmer, Karin Elisabeth; Frizzell, Caroline; Verhaegen, Steven; Ropstad, Erik; Connolly, Lisa

    2016-03-01

    Persistent organic pollutants (POPs) are toxic substances, highly resistant to environmental degradation, which can bio-accumulate and have long-range atmospheric transport potential. Most studies focus on single compound effects, however as humans are exposed to several POPs simultaneously, investigating exposure effects of real life POP mixtures on human health is necessary. A defined mixture of POPs was used, where the compound concentration reflected its contribution to the levels seen in Scandinavian human serum (total mix). Several sub mixtures representing different classes of POPs were also constructed. The perfluorinated (PFC) mixture contained six perfluorinated compounds, brominated (Br) mixture contained seven brominated compounds, chlorinated (Cl) mixture contained polychlorinated biphenyls and also p,p'-dichlorodiphenyldichloroethylene, hexachlorobenzene, three chlordanes, three hexachlorocyclohexanes and dieldrin. Human hepatocarcinoma (HepG2) cells were used for 2h and 48h exposures to the seven mixtures and analysis on a CellInsight™ NXT High Content Screening platform. Multiple cytotoxic endpoints were investigated: cell number, nuclear intensity and area, mitochondrial mass and membrane potential (MMP) and reactive oxygen species (ROS). Both the Br and Cl mixtures induced ROS production but did not lead to apoptosis. The PFC mixture induced ROS production and likely induced cell apoptosis accompanied by the dissipation of MMP. Synergistic effects were evident for ROS induction when cells were exposed to the PFC+Br mixture in comparison to the effects of the individual mixtures. No significant effects were detected in the Br+Cl, PFC+Cl or total mixtures, which contain the same concentrations of chlorinated compounds as the Cl mixture plus additional compounds; highlighting the need for further exploration of POP mixtures in risk assessment. PMID:26772051

  9. Dualities in Persistent (Co)Homology

    Energy Technology Data Exchange (ETDEWEB)

    de Silva, Vin; Morozov, Dmitriy; Vejdemo-Johansson, Mikael

    2011-09-16

    We consider sequences of absolute and relative homology and cohomology groups that arise naturally for a filtered cell complex. We establishalgebraic relationships between their persistence modules, and show that they contain equivalent information. We explain how one can use the existingalgorithm for persistent homology to process any of the four modules, and relate it to a recently introduced persistent cohomology algorithm. Wepresent experimental evidence for the practical efficiency of the latter algorithm.

  10. Reduced persistence of the macrolide antibiotics erythromycin, clarithromycin and azithromycin in agricultural soil following several years of exposure in the field.

    Science.gov (United States)

    Topp, Edward; Renaud, Justin; Sumarah, Mark; Sabourin, Lyne

    2016-08-15

    The macrolide antibiotics erythromycin, clarithromycin and azithromycin are very important in human and animal medicine, and can be entrained onto agricultural ground through application of sewage sludge or manures. In the present study, a series of replicated field plots were left untreated or received up to five annual spring applications of a mixture of three drugs to achieve a nominal concentration for each of 10 or 0.1mgkg(-1) soil; the latter an environmentally relevant concentration. Soil samples were incubated in the laboratory, and supplemented with antibiotics to establish the dissipation kinetics of erythromycin and clarithromycin using radioisotope methods, and azithromycin using HPLC-MS/MS. All three drugs were dissipated significantly more rapidly in soils with a history of field exposure to 10mgkg(-1) macrolides, and erythromycin and clarithromycin were also degraded more rapidly in field soil exposed to 0.1mgkg(-1) macrolides. Rapid mineralization of (14)C-labelled erythromycin and clarithromycin are consistent with biodegradation. Analysis of field soils revealed no carryover of parent compound from year to year. Azithromycin transformation products were detected consistent with removal of the desosamine and cladinose moieties. Overall, these results have revealed that following several years of exposure to macrolide antibiotics these are amenable to accelerated degradation. The potential accelerated degradation of these drugs in soils amended with manure and sewage sludge should be investigated as this phenomenon would attenuate environmental exposure and selection pressure for clinically relevant resistance. PMID:27096634

  11. Application of a Persistent Heparin Treatment Inhibits the Malignant Potential of Oral Squamous Carcinoma Cells Induced by Tumor Cell-Derived Exosomes.

    Science.gov (United States)

    Sento, Shinya; Sasabe, Eri; Yamamoto, Tetsuya

    2016-01-01

    Exosomes are 30-100 nm-sized membranous vesicles, secreted from a variety of cell types into their surrounding extracellular space. Various exosome components including lipids, proteins, and nucleic acids are transferred to recipient cells and affect their function and activity. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression. However, the effect of exosomes released from oral squamous cell carcinoma (OSCC) into the tumor microenvironment remains unclear. In the present study, we isolated exosomes from OSCC cells and investigated the influence of OSCC cell-derived exosomes on the tumor cell behavior associated with tumor development. We demonstrated that OSCC cell-derived exosomes were taken up by OSCC cells themselves and significantly promoted proliferation, migration, and invasion through the activation of the PI3K/Akt, MAPK/ERK, and JNK-1/2 pathways in vitro. These effects of OSCC cell-derived exosomes were obviously attenuated by treatment with PI3K, ERK-1/2, and JNK-1/2 pharmacological inhibitors. Furthermore, the growth rate of tumor xenografts implanted into nude mice was promoted by treatment with OSCC cell-derived exosomes. The uptake of exosomes by OSCC cells and subsequent tumor progression was abrogated in the presence of heparin. Taken together, these data suggest that OSCC cell-derived exosomes might be a novel therapeutic target and the use of heparin to inhibit the uptake of OSCC-derived exosomes by OSCC cells may be useful for treatment.

  12. Cell Persistence of Allogeneic Keratinocytes and Fibroblasts Applied in a Fibrin Matrix to Acute, Full Thickness Wounds

    OpenAIRE

    Dickerson, Jaime E; Planz, John V.; Reece, Barry T.; Weedon, Kathy A.; Kirkpatrick, Sandy D.; Slade, Herbert B

    2012-01-01

    HP802-247 is a living cell suspension of cultured allogeneic growth-arrested human male keratinocytes and fibroblasts (1:9 ratio), intended for spray application to chronic wounds. In this study, a small wound was created on the arms of 28 healthy female volunteers (3-mm punch), followed by a single application of HP802-247. At each subsequent week for 8 weeks, a punch excision of the wounds was performed on a cohort of three subjects. Excised specimens were analyzed for allogeneic fibroblast...

  13. Clofarabine Targets the Large Subunit (α) of Human Ribonucleotide Reductase in Live Cells by Assembly into Persistent Hexamers

    OpenAIRE

    Aye, Yimon; Brignole, Edward J; Long, Marcus J. C.; Chittuluru, Johnathan; Drennan, Catherine L.; Asturias, Francisco J; Stubbe, JoAnne

    2012-01-01

    Clofarabine (ClF) is a drug used in the treatment of leukemia. One of its primary targets is human ribonucleotide reductase (hRNR), a dual-subunit, (α2)m(β2)n, regulatory enzyme indispensable in de novo dNTP synthesis. We report that in live mammalian cells, ClF targets hRNR by converting its α-subunit into kinetically-stable hexamers. We established mammalian expression platforms that enabled isolation of functional α and characterization of its altered oligomeric associations in response to...

  14. Repeat Catheter Ablation of Long-standing Persistent Atrial Fibrillation in Patients with a Total Atrial Fibrillation Duration of More Than 2 Years: Effects of the CHA2DS2-VASc Score and Estimated Glomerular Filtration Rate on the Outcomes.

    Science.gov (United States)

    Wang, Qian; Jiang, Shi-Li; Liu, Xu; Yang, Yi-Qing

    2016-01-01

    Objective Little is known about the outcome of repeat catheter ablation of long-standing persistent atrial fibrillation (AF) in patients with a total AF duration of more than 2 years. The main objective of this study was to explore the results and factors affecting the clinical success rate of these repeat procedures. Methods We enrolled 99 patients with a total AF duration of more than 2 years and recurrent atrial arrhythmias after the initial catheter ablation of long-standing persistent AF. The enrolled patients were divided into two groups named the AF-recurrence group (50 patients) and the atrial tachycardia (AT)-recurrence group (49 patients) and all underwent a strict follow-up. The quality of life (QOL) and AF-related symptom classification were assessed at baseline and at 24 months post re-ablation. Results After a mean follow-up of 31 months, 30 (30.3%) patients were free from arrhythmia recurrence, and the success rate in the AT-recurrence group was higher than that in the AF-recurrence group (32.7% vs. 28.0%, p=0.614). A Cox regression analysis revealed a CHA2DS2-VASc score ≥3 to be a predictor of recurrence. AF recurrent patients with an abnormal renal function were more prone to undergo a failed procedure. However, an abnormal renal function had no effect on the outcome of the repeat procedure for patients with AT recurrence. At the 24-month follow-up, patients maintaining sinus rhythm (SR) had a significantly improved QOL and AF-related symptoms. Conclusion The success rate of repeat procedures for long-standing persistent AF and a total AF duration of more than 2 years is poor for patients with a CHA2DS2-VASc score ≥3. An impaired renal function has an unfavorable effect on the outcome for patients with AF recurrence. For patients maintaining SR, both the QOL and AF symptomatology improve significantly. PMID:27629945

  15. Application of a Persistent Heparin Treatment Inhibits the Malignant Potential of Oral Squamous Carcinoma Cells Induced by Tumor Cell-Derived Exosomes

    OpenAIRE

    Sento, Shinya; Sasabe, Eri; Yamamoto, Tetsuya

    2016-01-01

    Exosomes are 30–100 nm-sized membranous vesicles, secreted from a variety of cell types into their surrounding extracellular space. Various exosome components including lipids, proteins, and nucleic acids are transferred to recipient cells and affect their function and activity. Numerous studies have showed that tumor cell-derived exosomes play important roles in tumor growth and progression. However, the effect of exosomes released from oral squamous cell carcinoma (OSCC) into the tumor micr...

  16. Persistent Hyperprolactinemia and Bilateral Galactocele in a Male Infant

    OpenAIRE

    Tomasi, Paolo A.; Giuseppe Fanciulli; Tiziana Casti; Giuseppe Delitala

    2009-01-01

    Galactocele is a benign breast lesion, usually occurring in nursing women. This lesion is a rare cause of breast enlargement in children. In this paper we describe the case of an infant with hyperprolactinemia (which persisted throughout 15 years of clinical observation) and bilateral galactocele. We speculate that a congenital midline defect in our patient might have impaired the normal dopaminergic inhibitory tone on pituitary lactotroph cells, thus leading to an increased prolactin secr...

  17. Synergistic and persistent effect of T-cell immunotherapy with anti-CD19 or anti-CD38 chimeric receptor in conjunction with rituximab on B-cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Mihara, Keichiro; Yanagihara, Kazuyoshi; Takigahira, Misato; Kitanaka, Akira; Imai, Chihaya; Bhattacharyya, Joyeeta; Kubo, Takanori; Takei, Yoshifumi; Yasunaga, Shin'ichiro; Takihara, Yoshihiro; Kimura, Akiro

    2010-10-01

    Using artificial receptors, it is possible to redirect the specificity of immune cells to tumour-associated antigens, which is expected to provide a useful strategy for cancer immunotherapy. Given that B-cell non-Hodgkin lymphoma (B-NHL) cells invariably express CD19 and CD38, these antigens may be suitable molecular candidates for such immunotherapy. We transduced human peripheral T cells or a T-cell line with either anti-CD19-chimeric receptor (CAR) or anti-CD38-CAR, which contained an anti-CD19 or anti-CD38 antibody-derived single-chain variable domain respectively. Retroviral transduction led to anti-CD19-CAR or anti-CD38-CAR expression in T cells with high efficiency (>60%). The T cell line, Hut78, when transduced with anti-CD19-CAR or anti-CD38-CAR, exerted strong cytotoxicity against the B-NHL cell lines, HT and RL, and lymphoma cells isolated from patients. Interestingly, use of both CARs had an additive cytotoxic effect on HT cells in vitro. In conjunction with rituximab, human peripheral T cells expressing either anti-CD19-CAR or anti-CD38-CAR enhanced cytotoxicity against HT-luciferase cells in xenografted mice. Moreover, the synergistic tumour-suppressing activity was persistent in vivo for over 2 months. These results provide a powerful rationale for clinical testing of the combination of rituximab with autologous T cells carrying either CAR on aggressive or relapsed B-NHLs. PMID:20678160

  18. Caliber-Persistent Artery

    Directory of Open Access Journals (Sweden)

    Sabrina Araújo Pinho Costa

    2015-01-01

    Full Text Available Caliber-persistent artery (CPLA of the lip is a common vascular anomaly in which a main arterial branch extends to the surface of the mucous tissue with no reduction in its diameter. It usually manifests as pulsatile papule, is easily misdiagnosed, and is observed more frequently among older people, suggesting that its development may involve a degenerative process associated with aging; CPLA is also characterized by the loss of tone of the adjacent supporting connective tissue. Although the diagnosis is clinical, high-resolution Doppler ultrasound is a useful noninvasive tool for evaluating the lesion. This report describes the case of a 58-year-old male patient who complained of a lesion of the lower lip with bleeding and recurrent ulceration. The patient was successfully treated in our hospital after a diagnosis of CPLA and is currently undergoing a clinical outpatient follow-up with no complaints.

  19. An annoying persistent cough

    Directory of Open Access Journals (Sweden)

    Francesco Cipollini

    2007-03-01

    Full Text Available Chronic cough is a stressful condition and can lead to extensive investigations. We report a case of a 48-year-old woman who had suffered from persistent chronic cough for more than 3 months. She had been treated with cough suppressant. However, her cough was not alleviated by these treatments, and the patient was referred to our hospital. She did not exhibit typical gastroesophageal reflux disease (GERD symptoms heartburn and regurgitation. Esophagoscopy did not disclose reflux esophagitis. The patient was treated with a proton-pump inhibitor, which markedly alleviated her cough. Chronic cough due to GERD was diagnosed. Although the diagnosis of chronic cough due to GERD is not easy when traditionally symptoms are not present, our case report underscores the importance of this association to the differential diagnosis of chronic cough. In these cases a relatively simple test as high dose proton pump-inhibitors trial may be useful to confirm GERD related cough.

  20. A rare case of plasma cell leukemia in a 35 year old

    OpenAIRE

    Dosi, Rupal V; Annirudh Ambaliya; Patell, Rushad D.; Harshal J Joshi

    2010-01-01

    Plasma cell leukemia is a rare, aggressive form of multiple myeloma. A 35-year-old male presented with backache, generalized weakness, and facial puffiness. His complete blood count showed anemia and a high WBC count with atypical cells on peripheral smear. Bone marrow examination showed more than 90% of atypical plasma cells, confirming a diagnosis of plasma cell leukemia. Patient also had azotemia, hypercalcemia, and hyperuricemia. The patient was started on chemotherapy along with supporti...

  1. Young of the year bluefish (Pomatomus saltatrix) as a bioindicator of estuarine health: Establishing a new baseline for persistent organic pollutants after Hurricane Sandy for selected estuaries in New Jersey and New York

    Science.gov (United States)

    Smalling, Kelly; Deshpande, Ashok D.; Blazer, Vicki; Bruce W Dockum,; DeMond Timmons,; Beth L. Sharack,; Baker, Ronald J.; Jennifer Samson,; Reilly, Timothy J.

    2016-01-01

    Atlantic coastal bays of the US are essential habitat for young of year bluefish (Pomatomus saltatrix). Their residence in these estuaries during critical life stages, high lipid content, and piscivory make bluefish an ideal bioindicator species for evaluating estuarine health. Individual whole fish from four estuaries impacted by Hurricane Sandy were collected in August 2013, analyzed for a suite of persistent organic pollutants (POPs) including polychlorinated biphenyls, polybrominated diphenyl ethers and organochlorine pesticides and evaluated using health metrics. Concentrations in whole bluefish differed by estuary; however, concentrations for many POPs decreased or were similar to those observed prior to the hurricane. Prevalence of the ectoparasitic gill isopod (Lironeca ovalis) varied by estuary and no relationships between contaminants and lesions were observed. Bluefish should be considered for monitoring programs and, if sampled frequently, could be an effective bioindicator of incremental and episodic changes in contaminants within aquatic food webs.

  2. CPV Cell Characterization Following One-Year Exposure in Golden, Colorado: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Bosco, N.; Kurtz, S.

    2014-08-01

    A CPV module containing 30 III-V multijunction cells was operated on?sun for one year in Golden, Colorado. Each cell was characterized prior to and following exposure. A module power degradation of 10% was observed and found to be a result as an overall decrease in cell short circuit current and the presence of at least one shunted cell. A positive correlation between initial shunt current and an increase in shunt current following exposure was also found. Cell exfoliation was also observed and found to be coincident with the presence of water and/or charring of the cell package due to an off-sun event.

  3. Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells.

    Science.gov (United States)

    Osipov, Andreyan N; Pustovalova, Margarita; Grekhova, Anna; Eremin, Petr; Vorobyova, Natalia; Pulin, Andrey; Zhavoronkov, Alex; Roumiantsev, Sergey; Klokov, Dmitry Y; Eremin, Ilya

    2015-09-29

    Diagnostic imaging delivering low doses of radiation often accompany human mesenchymal stem cells (MSCs)-based therapies. However, effects of low dose radiation on MSCs are poorly characterized. Here we examine patterns of phosphorylated histone H2AX (γH2AX) and phospho-S1981 ATM (pATM) foci formation in human gingiva-derived MSCs exposed to X-rays in time-course and dose-response experiments. Both γH2AX and pATM foci accumulated linearly with dose early after irradiation (5-60 min), with a maximum induction observed at 30-60 min (37 ± 3 and 32 ± 3 foci/cell/Gy for γH2AX and pATM, respectively). The number of γH2AX foci produced by intermediate doses (160 and 250 mGy) significantly decreased (40-60%) between 60 and 240 min post-irradiation, indicating rejoining of DNA double-strand breaks. In contrast, γH2AX foci produced by low doses (20-80 mGy) did not change after 60 min. The number of pATM foci between 60 and 240 min decreased down to control values in a dose-independent manner. Similar kinetics was observed for pATM foci co-localized with γH2AX foci. Collectively, our results suggest differential DNA double-strand break signaling and processing in response to low vs. intermediate doses of X-rays in human MSCs. Furthermore, mechanisms governing the prolonged persistence of γH2AX foci in these cells appear to be ATM-independent.

  4. An case report of persistent giardiasis

    Directory of Open Access Journals (Sweden)

    Daniele Crotti

    2009-06-01

    Full Text Available The authors describe a persistent case of autoctonous giardiasis in an Italian adult man. Patient’s habits, clinical findings and diagnostic criteria are reported.The persistent elimination of Giardia spp. cysts with faeces along several month and years could be related to a repeated environmental ingestion or due to the onset of resistance towards the antiprotozoal drug.

  5. An case report of persistent giardiasis

    OpenAIRE

    Daniele Crotti; Elisabetta Antonelli; Maria Letizia D’Annibale

    2009-01-01

    The authors describe a persistent case of autoctonous giardiasis in an Italian adult man. Patient’s habits, clinical findings and diagnostic criteria are reported.The persistent elimination of Giardia spp. cysts with faeces along several month and years could be related to a repeated environmental ingestion or due to the onset of resistance towards the antiprotozoal drug.

  6. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines

    Science.gov (United States)

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela

    2016-01-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  7. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines.

    Science.gov (United States)

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela; Van Der Wielen, Marie

    2016-07-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  8. Antibody Persistence in Young Children 5 Years after Vaccination with a Combined Haemophilus influenzae Type b-Neisseria meningitidis Serogroup C Conjugate Vaccine Coadministered with Diphtheria-Tetanus-Acellular Pertussis-Based and Pneumococcal Conjugate Vaccines.

    Science.gov (United States)

    Tejedor, Juan Carlos; Brzostek, Jerzy; Konior, Ryszard; Grunert, Detlef; Kolhe, Devayani; Baine, Yaela; Van Der Wielen, Marie

    2016-07-01

    We evaluated antibody persistence in children up to 5 years after administration of a combined Haemophilus influenzae type b (Hib)-Neisseria meningitidis serogroup C (MenC)-tetanus toxoid (TT) conjugate vaccine coadministered with a pneumococcal conjugate vaccine. This is the follow-up study of a randomized trial (ClinicalTrials.gov registration no. NCT00334334/00463437) in which healthy children were vaccinated (primary vaccinations at 2, 4, and 6 months of age and booster vaccination at 11 to 18 months of age) with Hib-MenC-TT or a control MenC conjugate vaccine, coadministered with diphtheria-tetanus-acellular pertussis (DTPa)-based combination vaccines (DTPa/Hib for control groups) and a pneumococcal conjugate vaccine (10-valent pneumococcal nontypeable H. influenzae protein D conjugate vaccine [PHiD-CV] or 7-valent cross-reacting material 197 [CRM197] conjugate vaccine [7vCRM]). MenC antibody titers were measured with a serum bactericidal antibody (SBA) assay using rabbit complement (i.e., rabbit SBA [rSBA]), and antibodies against Hib polyribosylribitol phosphate (PRP) were measured with an enzyme-linked immunosorbent assay. Antibody persistence up to 5 years after booster vaccination is reported for 530 children ∼6 years of age. The percentages of children with seroprotective rSBA-MenC titers were between 24.2% and 40.1% in all groups approximately 5 years after booster vaccination. More than 98.5% of children in each group retained seroprotective anti-PRP concentrations. No vaccine-related serious adverse events and no events related to a lack of vaccine efficacy were reported. Approximately 5 years after booster vaccination, the majority of children retained seroprotective anti-PRP antibody concentrations. The percentage of children retaining seroprotective rSBA-MenC titers was low (≤40%), suggesting that a significant proportion of children may be unprotected against MenC disease. (This study has been registered at ClinicalTrials.gov under

  9. Chimeric antigen receptor T cell therapy: 25years in the making.

    Science.gov (United States)

    Gill, Saar; Maus, Marcela V; Porter, David L

    2016-05-01

    Chimeric antigen receptor (CAR) T cell therapy of cancer is generating enormous enthusiasm. Twenty-five years after the concept was first proposed, major advances in molecular biology, virology, and good manufacturing practices (GMP)-grade cell production have transformed antibody-T cell chimeras from a scientific curiosity to a fact of life for academic cellular immunotherapy researchers and, increasingly, for patients. In this review, we explain the preclinical concept, outline how it has been translated to the clinic, and draw lessons from the first years of CAR T cell therapy for the practicing clinician. PMID:26574053

  10. Human immunodeficiency virus type I-specific CD8+ T cell subset abnormalities in chronic infection persist through effective antiretroviral therapy

    Directory of Open Access Journals (Sweden)

    Gallant Maureen E

    2010-05-01

    Full Text Available Abstract Background Effective highly active antiretroviral therapy (HAART reduces human immunodeficiency virus (HIV replication, restores CD4+ T lymphocyte counts and greatly reduces the incidence of opportunistic infections. While this demonstrates improved generalized immune function, rapid rebound to pre-treatment viral replication levels following treatment interruption indicates little improvement in immune control of HIV replication. The extent to which HAART can normalize HIV-specific CD8+ T cell function over time in individuals with chronic infection remains an important unresolved issue. In this study, we evaluated the magnitude, general specificity and character of HIV specific CD8+ T cell responses at four time points across 2-9 years in 2 groups of chronically infected individuals separated on the basis of either effective antiretroviral suppression or ongoing replication of HIV. Methods Peripheral blood mononuclear cells (PBMC were stimulated with overlapping 15mer peptides spanning HIV Gag, Pol, Env and Nef proteins. Cells producing interferon-γ (IFN-γ or interleukin-2 (IL-2 were enumerated by ELISPOT and phenotyped by flow cytometry. Results and Conclusions The magnitude of the HIV-specific CD8+ T cell response ranged from +CD45RA- effector memory cells producing IFN-γ, but not IL-2. Magnitude, general specificity and character of the HIV-specific CD8+ T cell response changed little over the study period. While antiretroviral suppression of HIV in chronic infection reduces HIV-specific CD8+ T cell response magnitude in the short term, it had no significant effect on response character over periods up to 9 years.

  11. Persistent coordination patterns in a complex task after 10 years delay: subtitle: how validate the old saying "once you have learned how to ride a bicycle, you never forget!".

    Science.gov (United States)

    Nourrit-Lucas, Déborah; Zelic, Grégory; Deschamps, Thibault; Hilpron, Michael; Delignières, Didier

    2013-12-01

    Motor learning studies have for a long time focused on performance variables (in terms of speed or accuracy) in assessing learning, transfer and retention of motor skills. We argue, however, that learning essentially resides in changes in coordination variables (in terms of qualitative organization of behavior) and that relevant tests for assessing the effectiveness of learning and retention should consider these variables. The aim of this experiment was to test the retention of a complex motor skill, after a long-term delay. Ten years ago, five participants were involved in an experiment during which they practiced for 39 sessions of ten 1-min trials on a ski-simulator. All participants volunteered for a retention test, ten years after, for one session of ten 1-min trials. Analyses focused on the oscillations of the platform of the simulator. Performance was assessed in terms of amplitude and frequency. Coordination was accounted for by an analysis of dynamical properties of the motion of the platform, and especially the nature of the damping function that was exploited for sustaining the limit cycle dynamics. Results showed a significant decrement in performance variables. In contrast, all participants adopted from the first trial onwards the coordination mode they learned 10years ago. These results confirm the strong persistence of coordination modes, once acquired and stabilized in the behavioral repertoire. They also support the importance of coordination variables for a valid assessment of learning and retention.

  12. Human T-cell leukemia virus type 2 post-transcriptional control protein p28 is required for viral infectivity and persistence in vivo

    Directory of Open Access Journals (Sweden)

    Kesic Matthew

    2008-05-01

    Full Text Available Abstract Background Human T-cell leukemia virus (HTLV type 1 and type 2 are related but distinct pathogenic complex retroviruses. HTLV-1 is associated with adult T-cell leukemia and a variety of immune-mediated disorders including the chronic neurological disease termed HTLV-1-associated myelopathy/tropical spastic paraparesis. In contrast, HTLV-2 displays distinct biological differences and is much less pathogenic, with only a few reported cases of leukemia and neurological disease associated with infection. In addition to the structural and enzymatic proteins, HTLV encodes regulatory (Tax and Rex and accessory proteins. Tax and Rex positively regulate virus production and are critical for efficient viral replication and pathogenesis. Using an over-expression system approach, we recently reported that the accessory gene product of the HTLV-1 and HTLV-2 open reading frame (ORF II (p30 and p28, respectively acts as a negative regulator of both Tax and Rex by binding to and retaining their mRNA in the nucleus, leading to reduced protein expression and virion production. Further characterization revealed that p28 was distinct from p30 in that it was devoid of major transcriptional modulating activity, suggesting potentially divergent functions that may be responsible for the distinct pathobiologies of HTLV-1 and HTLV-2. Results In this study, we investigated the functional significance of p28 in HTLV-2 infection, proliferation, and immortaliztion of primary T-cells in culture, and viral survival in an infectious rabbit animal model. An HTLV-2 p28 knockout virus (HTLV-2Δp28 was generated and evaluated. Infectivity and immortalization capacity of HTLV-2Δp28 in vitro was indistinguishable from wild type HTLV-2. In contrast, we showed that viral replication was severely attenuated in rabbits inoculated with HTLV-2Δp28 and the mutant virus failed to establish persistent infection. Conclusion We provide direct evidence that p28 is dispensable for

  13. Long-term persistence of zoster vaccine efficacy

    OpenAIRE

    Johnson, GR; Zhang, Jh; Betts, R.; Gelb, L; Guatelli, JC; Harbecke, R; Pachucki, C.; Keay, S; Marques, A; Toney, J.; Boardman, K; Su, SC; Li, X.; Chan, ISF; Parrino, J

    2015-01-01

    Background. The Shingles Prevention Study (SPS) demonstrated zoster vaccine efficacy through 4 years postvaccination. A Short-Term Persistence Substudy (STPS) demonstrated persistence of vaccine efficacy for at least 5 years. A Long-Term Persistence Substudy (LTPS) was undertaken to further assess vaccine efficacy in SPS vaccine recipients followed for up to 11 years postvaccination. Study outcomes were assessed for the entire LTPS period and for each year from 7 to 11 years postvaccination. ...

  14. Recurrent acute pancreatitis and persistent hyperamylasemia as a presentation of pancreatic osteoclastic giant cell tumor: an unusual presentation of a rare tumor.

    Science.gov (United States)

    Rustagi, Tarun; Rampurwala, Murtuza; Rai, Mridula; Golioto, Michael

    2011-01-01

    Giant cell tumors of the pancreas are rare neoplasms divided into three forms: osteoclastic, pleomorphic, and mixed. We report an unusual case of a 62-year-old male presenting with recurrent acute pancreatitis and found to have a mass in the head of the pancreas on routine imaging. Endoscopic retrograde cholangiopancreatography showed a main pancreatic duct stricture, with brush cytology revealing the diagnosis of osteoclastic giant cell tumor of the pancreas. Whipple's procedure was successfully performed for resection of this tumor. and IAP.

  15. I131 therapy induces persistent radiation-dose dependent increases in glycophorin a locus somatic mutations in bone marrow stem cells

    International Nuclear Information System (INIS)

    Patients with thyroid diseases treated with I131 receive known sub-acute marrow exposures to ionizing radiation of ∼2 to >200 cGy. Time-series sampling of peripheral blood from these patients, assayed for the frequency of erythrocytes expressing glycophorin A (GPA) allele-loss variant phenotypes, demonstrates the induction, accumulation, and long-term persistence of radiation-induced in vivo somatic mutations at this locus in erythroid marrow progenitor cells. Initial dosimetry and assay data from 5 patients yielded a linear GPA dose response of ∼6.5 induced variants/106 cells/Gy which is 1/3 to 1/4 of that previously observed for Hiroshima A-bomb survivors and individuals exposed at the Chernobyl nuclear reactor and Goiania Cs137 source accidents who predominantly received external exposures to ionizing radiation. The lower slope of the dose response observed in the I131 treated patients may reflect a reduced biological effectiveness of this exposure due to differences in the energy spectra of the γ radiation, internal versus external exposure, and/or protracted versus acute dose rate effects. Ongoing studies of I131 treated patients are designed to define the shape of the low dose response and limit of sensitivity of the GPA assay; parameters that are required for the application of the assay as a quantitative cumulative radiation biodosimeter in medical, occupational, and accidental exposure settings. This biodosimetric analysis of patients receiving very similar marrow exposures will also permit an assessment of the inter-individual variability in biological response to ionizing radiation

  16. Survival and persistence of host-associated Bacteroidales cells and DNA in comparison with Escherichia coli and Enterococcus in freshwater sediments as quantified by PMA-qPCR and qPCR.

    Science.gov (United States)

    Kim, Minji; Wuertz, Stefan

    2015-12-15

    Decay of the fecal source identifier Bacteroidales in sediments has not been studied until now. Two types of microcosms inoculated with human, cow and dog feces were constructed to investigate the survival and persistence of host-associated Bacteroidales cells and their DNA, respectively, in freshwater sediments: (i) a completely anaerobic microcosm where feces were entirely mixed with sediments for estimating decay of Bacteroidales in oxygen-free sediments at two temperatures (6 °C and 20 °C) and (ii) a core microcosm where feces in the overlying water column settled on top of undisturbed core sediments. Quantitative PCR (qPCR) along with propidium monoazide (PMA) was used to differentiate between genetic markers present in intact cells and total intracellular as well as extracellular marker DNA. Regulated fecal indicator bacteria were measured by cultivation (Escherichia coli and Enterococcus) and qPCR (Enterococcus) in relation to Bacteroidales-associated host markers. In anaerobic microcosms, the survival and persistence of Bacteroidales cells and DNA in sediments were considerably extended, especially at the lower temperature of 6 °C, with two-log reduction times (T99) >56 d (cells) and >169 d (DNA). Bacteroidales DNA persisted up to five times longer than cells in anaerobic microcosms at 6 °C, whereas decay rates of cells and DNA were not significantly different at 20 °C in anaerobic microcosms. In core microcosms, the levels of Bacteroidales cells and DNA decreased approximately six times more slowly in sediments than in overlying water; T99 values of Bacteroidales cells and DNA were 6-9 d (water) and 29-82 d (sediment). The survival of universal, human-, ruminant- and dog-associated Bacteroidales cells in sediments was similar in both microcosms under each given condition, as was the persistence of DNA. Decay rate constants of Bacteroidales cells and DNA were comparable with those of cultivable Enterococcus and E. coli cells in core sediments while

  17. Extreme and Persistent Feature of Drought and Flood of Southwest China in Past 60 Years%近60年来西南地区旱涝变化及极端和持续性特征认识

    Institute of Scientific and Technical Information of China (English)

    杨金虎; 张强; 王劲松; 姚玉璧; 尚军林

    2015-01-01

    利用1953~2012年中国西南地区44个气象台站的逐日降水、温度资料,通过降水和潜在蒸发均一化旱涝指数,从旱涝的年代际、年际、季节内变化以及极端和持续性特征等方面进行了分析,结果表明:从旱涝的空间趋势变化来看,西南近60 a来秋季和年变化呈显著的一致变旱趋势,而春、夏、冬3季旱涝变化趋势表现出一定的区域性特征;从旱涝的时间演变来看,在温度与降水双重因子驱动下春、夏、秋、冬均表现为干旱化趋势,相比较秋季的干旱化程度最强,而春季的最弱,夏、冬两季相当,而全年的干旱程度比四季的程度更强;从极端旱涝的多时间尺度来看,在年代际和年际尺度上,极端洪涝发生频次逐渐减少,而极端干旱发生频次逐渐增多,从季节尺度看,春、冬两季极端干旱发生频次较多,而夏季最少,极端洪涝发生频次夏季最多,春季次之,秋季最少。从旱涝的持续性特征来看,持续性干旱事件的持续时间有增长趋势,发生频率有增多趋势,发生强度有增强趋势,并且主要发生在冬春两季,而持续性洪涝事件的持续时间、发生强度没明显变化趋势,发生频率有减少趋势,发生的季节也没明显差异。%Using 44 stations temperature and precipitation data of day by day in Southwest China in 1953-2012, latency evaporation is calculated by Thornthwaite method, from inter-decadal, inter-annual, inter-seasonal vari-ability, extreme and persistent characteristic of drought and flood analyzed over southwest China in past 60 years by homogenized drought-flood index of precipitation and latency evaporation. The results showed that:From the point of view of space trends to see, it displayed consistent drought trend in autumn and whole year over southwest China in past 60 years, but it displayed regional drought-flood trend feature in spring, summer and

  18. Population dynamics of bacterial persistence.

    Directory of Open Access Journals (Sweden)

    Pintu Patra

    Full Text Available Persistence is a prime example of phenotypic heterogeneity, where a microbial population splits into two distinct subpopulations with different growth and survival properties as a result of reversible phenotype switching. Specifically, persister cells grow more slowly than normal cells under unstressed growth conditions, but survive longer under stress conditions such as the treatment with bactericidal antibiotics. We analyze the population dynamics of such a population for several typical experimental scenarios, namely a constant environment, shifts between growth and stress conditions, and periodically switching environments. We use an approximation scheme that allows us to map the dynamics to a logistic equation for the subpopulation ratio and derive explicit analytical expressions for observable quantities that can be used to extract underlying dynamic parameters from experimental data. Our results provide a theoretical underpinning for the study of phenotypic switching, in particular for organisms where detailed mechanistic knowledge is scarce.

  19. Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Wiegel, Thomas, E-mail: thomas.wiegel@uniklinik-ulm.de [Department of Radiation Oncology, University Hospital Ulm (Germany); Bartkowiak, Detlef; Bottke, Dirk; Thamm, Reinhard [Department of Radiation Oncology, University Hospital Ulm (Germany); Hinke, Axel [WiSP, Research Institute Pharma GmbH, Langenfeld (Germany); Stöckle, Michael [Department of Urology, University Hospital Homburg/Saar (Germany); Rübe, Christian [Department of Radiation Oncology, University Hospital Homburg/Saar (Germany); Semjonow, Axel [Department of Urology, University Hospital Münster (Germany); Wirth, Manfred [Department of Urology, University Hospital Dresden (Germany); Störkel, Stephan; Golz, Reinhard [Department of Pathology, HELIOS Hospital Wuppertal (Germany); Engenhart-Cabillic, Rita [Department of Radiation Oncology, University Hospital Giessen-Marburg (Germany); Hofmann, Rainer [Department of Urology, University Hospital Giessen-Marburg (Germany); Feldmann, Horst-Jürgen [Department of Radiation Oncology, General Hospital Fulda (Germany); Kälble, Tilman [Department of Urology, General Hospital Fulda (Germany); Siegmann, Alessandra; Hinkelbein, Wolfgang [Department of Radiation Oncology, University Hospital Berlin (Germany); Steiner, Ursula; Miller, Kurt [Department of Urology, University Hospital Berlin (Germany)

    2015-02-01

    Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups

  20. Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

    International Nuclear Information System (INIS)

    Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups

  1. Langerhans Cell Histiocytosis of the Clavicle in a 13-Year-Old Boy

    OpenAIRE

    Parikh, Shital N.; Desai, Vishal R.; Anita Gupta; Anton, Christopher G.

    2014-01-01

    Langerhans Cell Histiocytosis (LCH) is a rare neoplasm characterized by abnormal proliferation of histiocytic cells. In this case report, we describe a unique case of a 13-year-old boy who presented to the clinic with an insidious onset of mid-clavicular pain. The provisional radiologic diagnosis of Langerhans Cell Histiocytosis of the clavicle was confirmed by an incisional biopsy of the left mid-clavicle lesion. The patient’s lesion was treated by curettage, bone grafting, and internal fixa...

  2. Cardiac anaplastic large cell lymphoma in an 8-year old boy

    Directory of Open Access Journals (Sweden)

    Melchior Lauten

    2014-01-01

    Full Text Available We report on an 8 year old boy with primary cardiac anaplastic large cell lymphoma (ALCL, in whom the diagnosis was challenging and who was treated with modified chemotherapy without radiation therapy according to the ALCL 99 study protocol [1]. Two years and 4 months after completion of therapy the boy is in complete remission with normal cardiac function.

  3. Cardiac anaplastic large cell lymphoma in an 8-year old boy

    OpenAIRE

    Melchior Lauten; Simon Vieth; Christopher Hart; Wilhelm Wössmann; Birte Tröger; Christoph Härtel; Martin Bethge; André Schrauder; Gunnar Cario

    2014-01-01

    We report on an 8 year old boy with primary cardiac anaplastic large cell lymphoma (ALCL), in whom the diagnosis was challenging and who was treated with modified chemotherapy without radiation therapy according to the ALCL 99 study protocol [1]. Two years and 4 months after completion of therapy the boy is in complete remission with normal cardiac function.

  4. Persistence of pathological distribution of NK cells in HIV-infected patients with prolonged use of HAART and a sustained immune response.

    Directory of Open Access Journals (Sweden)

    Mario Frias

    Full Text Available A prospective analysis of the distribution of NK subsets and natural cytotoxicity receptors (NKp30/NKp46 in HIV patients with long-term HAART use and sustained virological and immunological response.The main inclusion criteria were: at least 3 years' receipt of HAART; current CD4+ count ≥ 500 cells/mm3; undetectable viral load for at least 24 months; no hepatotropic virus co-infection. Percentages of CD56dim, CD56bright NK cells and CD56neg CD16+ cells were obtained. Expression of the NCRs, NKp30 and NKp46 was analysed in CD56+ cells. Thirty-nine infected patients and sixteen healthy donors were included in the study.The percentages of total CD56+ and CD56dim NK cells were significantly lower in HIV-infected patients than in healthy donors (70.4 vs. 50.3 and 80.9 vs. 66.1 respectively. The percentage of total CD56+ NK cells expressing NCR receptors was lower in HIV patients than in healthy donors (NKp30: 25.20 vs. 58.63; NKp46: 24.8 vs. 50.59. This was also observed for CD56dim and CD56bright NK cells. Length of time with undetectable HIV viral load was identified as an independent factor associated with higher expression of NKp30 and NKp46.Despite the prolonged and effective use of HAART, HIV-infected patients do not fully reconstitute the distribution of NK cells. Length of time with an undetectable viral load was related to greater recovery of NKp30/NKp46 receptors.

  5. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2)

    DEFF Research Database (Denmark)

    Eskelund, Christian W.; Kolstad, Arne; Jerkeman, Mats;

    2016-01-01

    , developed by the Nordic Lymphoma Group. We here present the 15-year updated results of the Nordic MCL2 study after a median follow-up of 11·4 years: For all patients on an intent-to-treat basis, the median overall and progression-free survival was 12·7 and 8·5 years, respectively. The MCL International......In recent decades, the prognosis of Mantle Cell Lymphoma (MCL) has been significantly improved by intensified first-line regimens containing cytarabine, rituximab and consolidation with high-dose-therapy and autologous stem cell transplantation. One such strategy is the Nordic MCL2 regimen...

  6. Persistence of Biomarker ATP and ATP-Generating Capability in Bacterial Cells and Spores Contaminating Spacecraft Materials under Earth Conditions and in a Simulated Martian Environment▿

    OpenAIRE

    Fajardo-Cavazos, Patricia; Schuerger, Andrew C.; Nicholson, Wayne L.

    2008-01-01

    Most planetary protection research has concentrated on characterizing viable bioloads on spacecraft surfaces, developing techniques for bioload reduction prior to launch, and studying the effects of simulated martian environments on microbial survival. Little research has examined the persistence of biogenic signature molecules on spacecraft materials under simulated martian surface conditions. This study examined how endogenous adenosine-5′-triphosphate (ATP) would persist on aluminum coupon...

  7. A rare case of plasma cell leukemia in a 35 year old

    Directory of Open Access Journals (Sweden)

    Rupal V Dosi

    2010-01-01

    Full Text Available Plasma cell leukemia is a rare, aggressive form of multiple myeloma. A 35-year-old male presented with backache, generalized weakness, and facial puffiness. His complete blood count showed anemia and a high WBC count with atypical cells on peripheral smear. Bone marrow examination showed more than 90% of atypical plasma cells, confirming a diagnosis of plasma cell leukemia. Patient also had azotemia, hypercalcemia, and hyperuricemia. The patient was started on chemotherapy along with supportive care. Patient improved dramatically and he was discharged on regular follow-up.

  8. Persistence of antimuscarinic drug use

    DEFF Research Database (Denmark)

    Brostrøm, Søren; Hallas, Jesper

    2009-01-01

    PURPOSE: Evidence suggests antimuscarinic drugs for the overactive-bladder syndrome only confer modest improvements in quality of life. We wanted to describe the persistence of therapy, including an extended analysis beyond the 1-year follow-up employed in other studies. METHODS: All prescriptions...... for drugs in ATC category G04BD were retrieved for the period 1999-2006 from a regional database with complete capture of all reimbursed prescriptions. Kaplan-Meyer curves were generated for duration of treatment for each substance and analyzed for determinants of termination. RESULTS: With the exception...... of trospium chloride, all drugs had continuation rates of less than 50% at 6 months, less than 25% at 1 year, and less than 10% at 2 years and longer. Trospium chloride, however, exhibited continuation rates of 46% at 6 months, 36% at 1 year, 22% at 2 years, and 16% at 3 years. CONCLUSIONS: In a setting...

  9. GIANT CELL-RICH LESIONS OF BONE AND JOINTS: A ONE YEAR PROSPECTIVE STUDY

    Directory of Open Access Journals (Sweden)

    Sri Nithisa H

    2016-07-01

    Full Text Available BACKGROUND Giant cell-rich lesions constitute a group of biologically and morphologically diverse bone and joint tumours. The common feature is presence of numerous multinucleated osteoclast-like giant cells. However, they differ from each other by in terms of clinical and radiographic features and in many cases by their distinct morphological features. METHODS All the bone and joint specimens with giant cell-rich lesions received in the period of one year were studied along with clinical and radiological data available. Gross and microscopic findings were noted. RESULTS In a period of one year, 10 cases of giant cell-rich lesions of bone and joints have been studied, which were and correlated with clinical and radiological findings. Five were lesions from bone and two were from joints, which are chondroblastoma, chondromyxoid fibroma, osteoclastoma, aneurysmal bone cyst, pigmented villonodular synovitis, giant cell lesion of tendon sheath, and tendinous xanthoma. CONCLUSION In the present study, variety of giant cell lesions of bone and joints are studied. Of which, the mean age in young patients being 20 years and in elderly patients being 50 years. The common site being lower end of femur.

  10. Qubit persistence probability

    International Nuclear Information System (INIS)

    In this work, I formulate the persistence probability for a qubit device as the probability of measuring its computational degrees of freedom in the unperturbed state without the decoherence arising from environmental interactions. A decoherence time can be obtained from the persistence probability. Drawing on recent work of Garg, and also Palma, Suomine, and Ekert, I apply the persistence probability formalism to a generic single-qubit device coupled to a thermal environment, and also apply it to a trapped-ion quantum register coupled to the ion vibrational modes. (author)

  11. Langerhans Cell Histiocytosis of the Clavicle in a 13-Year-Old Boy

    Directory of Open Access Journals (Sweden)

    Shital N. Parikh

    2014-01-01

    Full Text Available Langerhans Cell Histiocytosis (LCH is a rare neoplasm characterized by abnormal proliferation of histiocytic cells. In this case report, we describe a unique case of a 13-year-old boy who presented to the clinic with an insidious onset of mid-clavicular pain. The provisional radiologic diagnosis of Langerhans Cell Histiocytosis of the clavicle was confirmed by an incisional biopsy of the left mid-clavicle lesion. The patient’s lesion was treated by curettage, bone grafting, and internal fixation, due to the presence of pathologic fracture. At the 2-year followup, the patient was asymptomatic, and the lesion showed complete resolution without recurrence. The case report highlights the characteristic features of Langerhans Cell Histiocytosis in an unusual location, the knowledge of which would help avoid delayed or missed diagnosis in the future.

  12. Virilizing ovarian steroid cell tumor in a 40 year old South Indian female: a case report

    OpenAIRE

    Salim, Shihas; Shantha, Ghanshyam Palamaner Subash; Patel, Amish Dilip; Kumar, Anita A; Ganeshram, Prasanthi; Mehra, Nikita; Rajan, Anish George; Joseph, Tarun; Sudhakar, Lavangi

    2009-01-01

    Virilism is the masculinization and enhancement of male secondary sexual characteristics in females. The etiology is usually of adrenal or ovarian origin. Here we report a case of virilizing Leydig cell type, steroid cell tumor of the left ovary, in a 40 year old female who presented with clinical signs and symptoms of virilization: deepening of voice, hirsutism (Ferriman-Gallwey score 26), clitoromegaly, and androgenic alopecia. On further evaluation, laboratory investigations revealed hyper...

  13. Giant Basal Cell Carcinoma: A 12-Year Follow-up Case Report.

    Science.gov (United States)

    Jiménez-Hernández, Fabiola; Caballero-Centeno, Ana M; Barrera-Pérez, María; Ramos-Garibay, José A

    2016-01-01

    Giant basal cell carcinomas (GBCCs) are a strange and aggressive variety of basal cell carcinomas (BCCs); they are characterized by deep tissue invasion, rapid growth, high risk of metastasis, and a poor prognosis. GBCCs represent 0.4%-1% of all BCCs. The pathogenesis of GBCC is sometimes linked to a spontaneous mutation in the PTCH gene, mapped to the q22.33 locus of chromosome 9. The key factor in the development of GBCC, in at least 30% of the cases, is the delay in seeking medical attention (7.5 ± 3.1 years). This is associated to a poor socioeconomic level, deficient hygiene, mental illness, advanced age, and the fact that BCCs are painless lesions. The authors present a Mexican female with a 2-year ulcer diagnosed as a GBCC in the year 2000, its initial therapeutic approach, and her follow-up during the next 12 years. PMID:26332533

  14. Odontogenic tumors and giant cell lesions of jaws - a nine year study

    Directory of Open Access Journals (Sweden)

    Boindala Sesikeran

    2011-07-01

    Full Text Available Abstract Objectives A definite geographic variation has been observed in the frequency of odontogenic tumors and giant cell lesions of the jaws reported from different parts of the world. However, there are a few studies on these lesions, especially giant cell lesions, reported from India. Hence, this study was designed to provide a demographic data on the odontogenic tumors and giant cell lesions reported from our institute located in the city of Hyderabad. Hyderabad is the capital city of the southern state of Andhra Pradesh in India. A retrospective analysis of odontogenic tumors and giant cell lesions of jaws reported in our institute between the years 2000 and 2009 was done and this data was compared with previous reports from different parts of the world and India. Methods Biopsies of the lesions received between the years 2000 and 2009 were reviewed and patient's history, clinical, radiological and histopathological characteristics were analyzed. Results A total of 77 biopsies were received during the nine year study period. These lesions were more frequently seen in the males, in a younger age group and showed a predilection for the mandible. Most of them presented as radiolucent, slow growing and painless lesions. Ameloblastomas (71.4% constituted the majority of odontogenic tumors while central giant cell granulomas (7.8% constituted the majority of giant cell lesions. Conclusion These lesions showed a definite geographic variation with ameloblastomas being the most common odontogenic tumors and odontomas being relatively rarer lesions in our region.

  15. Persistent Monitoring Platforms Final Report

    Energy Technology Data Exchange (ETDEWEB)

    Bennett, C L

    2007-02-22

    This project was inspired and motivated by the need to provide better platforms for persistent surveillance. In the years since the inception of this work, the need for persistence of surveillance platforms has become even more widely appreciated, both within the defense community and the intelligence community. One of the most demanding technical requirements for such a platform involves the power plant and energy storage system, and this project concentrated almost exclusively on the technology associated with this system for a solar powered, high altitude, unmanned aircraft. An important realization for the feasibility of such solar powered aircraft, made at the outset of this project, was that thermal energy may be stored with higher specific energy density than for any other known practical form of rechargeable energy storage. This approach has proved to be extraordinarily fruitful, and a large number of spin-off applications of this technology were developed in the course of this project.

  16. Persistent HIV-1 replication during antiretroviral therapy

    OpenAIRE

    Martinez-Picado, Javier; Deeks, Steven G

    2016-01-01

    Purpose of review The present review will highlight some of the recent findings regarding the capacity of HIV-1 to replicate during antiretroviral therapy (ART). Recent findings Although ART is highly effective at inhibiting HIV replication, it is not curative. Several mechanisms contribute to HIV persistence during ART, including HIV latency, immune dysfunction, and perhaps persistent low-level spread of the virus to uninfected cells (replication). The success in curing HIV will depend on ef...

  17. The 40-year history of modeling active dendrites in cerebellar Purkinje cells: Emergence of the first single cell 'Community Model'

    Directory of Open Access Journals (Sweden)

    James M Bower

    2015-10-01

    Full Text Available The subject of the effects of the active properties of the Purkinje cell dendrite on neuronal function has been an active subject of study for more than 40 years. Somewhat unusually, some of these investigations, from the outset have involved an interacting combination of experimental and model-based techniques. This paper recounts that 40-year history, and the view of the functional significance of the active properties of the Purkinje cell dendrite that has emerged. It specifically considers the emergence from these efforts of what is arguably the first single cell ‘community’ model in neuroscience. The paper also considers the implications of the development of this model for future studies of the complex properties of neuronal dendrites.

  18. Persistent depressive disorder

    Science.gov (United States)

    PDD; Chronic depression; Depression - chronic ... The exact cause of persistent depressive disorder (PDD) is unknown. It tends to run in families. PDD occurs more often in women. Most people with PDD will also ...

  19. Is Inflation Persistence Over?

    Directory of Open Access Journals (Sweden)

    Fernando N. de Oliveira

    2014-09-01

    Full Text Available We analyze inflation persistence in several industrial and emerging countries in the recent past by implementing unit root tests in the presence of unknown structural breaks and by estimating reduced-form models of inflation dynamics. We select a very representative group of 23 industrial and 17 emerging economies. Our sample period is comprised of quarterly data and differs for each country. Our results indicate that inflation persistence is decreasing over time for the great majority of industrial economies. Many emerging economies, however, show increasing persistence and even a few have highly persistent inflationary processes. We also observe structural breaks in all inflation processes we study with the exception of the inflation processes of Germany and Austria. Our results are robust to different reduced forms of the inflation processes and different econometric techniques.

  20. Orthogonal Persistence Revisited

    CERN Document Server

    Dearle, Alan; Morrison, Ron

    2010-01-01

    The social and economic importance of large bodies of programs and data that are potentially long-lived has attracted much attention in the commercial and research communities. Here we concentrate on a set of methodologies and technologies called persistent programming. In particular we review programming language support for the concept of orthogonal persistence, a technique for the uniform treatment of objects irrespective of their types or longevity. While research in persistent programming has become unfashionable, we show how the concept is beginning to appear as a major component of modern systems. We relate these attempts to the original principles of orthogonal persistence and give a few hints about how the concept may be utilised in the future.

  1. 8-year survival in a patient with several recurrences of renal cell carcinoma after radical nephrectomy

    OpenAIRE

    Joshi, Shivam; Eldefrawy, Ahmed; Ciancio, Gaetano

    2012-01-01

    We describe the case of a patient with a large renal cell carcinoma (RCC) who underwent cytoreductive nephrectomy utilizing liver mobilization techniques similar to those used in transplantation. Despite recurrent metastases, our patient continues to survive eight years later with several metastasectomies and adjuvant chemotherapy. We report the case of a 48-year-old Hispanic American man who presented with a 4-month history of an enlarging right upper quadrant abdominal mass and hematuria. C...

  2. Elites and institutional persistence

    OpenAIRE

    Robinson, James A.

    2010-01-01

    Particular sets of institutions, once they become established in a society, have a strong tendency to persist. In this paper I argue that understanding how elites form and reproduce is key to understanding the persistence of institutions over time. I illustrate this idea with a simple political economy theory of institutions and through examples from Liberia, the US, South Africa and Germany I show how elites influence institutions. To change institutions requires having an understanding of h...

  3. A seventeen-year-old female with hepatosplenic T-cell lymphoma associated with parvoviral infection

    Directory of Open Access Journals (Sweden)

    Saadiya Haque

    2010-05-01

    Full Text Available Normal 0 false false false MicrosoftInternetExplorer4 Hepatosplenic T-cell lymphoma (HSTL is rare, being derived from cytotoxic T-cells, and manifests as an extranodal systemic lymphoma. We present an unusual case of a seventeen-year-old female, with no significant prior medical history, presenting with a hepato­splenic T-cell lymphoma. The diagnosis was confirmed by histological examination, immunohistochemisty, and flow cytometry. A staging work-up demonstrated bone marrow involvement by HSTL with concomitant intranuclear parvoviral inclusions.

  4. Stem cell Transplantation for Eradication of Minimal PAncreatic Cancer persisting after surgical Excision (STEM PACE Trial, ISRCTN47877138): study protocol for a phase II study

    International Nuclear Information System (INIS)

    Pancreatic cancer is the third most common cancer related cause of death. Even in the 15% of patients who are eligible for surgical resection the outlook is dismal with less than 10% of patients surviving after 5 years. Allogeneic hematopoietic (allo-HSCT) stem cell transplantation is an established treatment capable of to providing cure in a variety of hematopoietic malignancies. Best results are achieved when the underlying neoplasm has been turned into a stage of minimal disease by chemotherapy. Allo-HSCT in advanced solid tumors including pancreatic cancer have been of limited success, however studies of allo-HSCT in solid tumors in minimal disease situations have never been performed. The aim of this trial is to provide evidence for the clinical value of allo-HSCT in pancreatic cancer put into a minimal disease status by effective surgical resection and standard adjuvant chemotherapy. The STEM PACE trial is a single center, phase II study to evaluate adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection. The study will evaluate as primary endpoint 2 year progression free survival and will generate first time state-of-the-art scientific clinical evidence if allo-HSCT is feasible and if it can provide long term disease control in patients with effectively resected pancreatic cancer. Screened eligible patients after surgical resection and standard adjuvant chemotherapy with HLA matched related stem cell donor can participate. Patients without a matched donor will be used as a historical control. Study patients will undergo standard conditioning for allo-HSCT followed by transplantation of allogeneic unmanipulated peripheral blood stem cells. The follow up of the patients will continue for 2 years. Secondary endpoints will be evaluated on 7 postintervention visits. The principal question addressed in this trial is whether allo-HSCT can change the unfavourable natural course of this disease. The underlying

  5. Performance Persistence of Equity Funds in Hungary

    Directory of Open Access Journals (Sweden)

    Dariusz Filip

    2011-03-01

    Full Text Available This study examines the phenomenon of performance persistence of equity funds in Hungary in two time perspectives: 1-year and 6-month perspectives. The empirical results confirm the occurrence of performance dependence in consecutive periods. There is also a strong evidence of short-term persistence in the total horizon of the study (from the beginning of 2000 to the end of 2009, and in several sub-periods. The 1-year persistence was also found in the tested sample and, in general, depended on the measure applied. Furthermore, I observed performance reversal, which can be partly explained by trend changes in the financial markets. The persistence of equity funds performance in Hungary is shaped by market factors rather than the diversity of managerial characteristics.

  6. The Sertoli cell: one hundred fifty years of beauty and plasticity.

    Science.gov (United States)

    França, L R; Hess, R A; Dufour, J M; Hofmann, M C; Griswold, M D

    2016-03-01

    It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular 'nurse cell', not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell's role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways.

  7. The Sertoli cell: one hundred fifty years of beauty and plasticity.

    Science.gov (United States)

    França, L R; Hess, R A; Dufour, J M; Hofmann, M C; Griswold, M D

    2016-03-01

    It has been one and a half centuries since Enrico Sertoli published the seminal discovery of the testicular 'nurse cell', not only a key cell in the testis, but indeed one of the most amazing cells in the vertebrate body. In this review, we begin by examining the three phases of morphological research that have occurred in the study of Sertoli cells, because microscopic anatomy was essentially the only scientific discipline available for about the first 75 years after the discovery. Biochemistry and molecular biology then changed all of biological sciences, including our understanding of the functions of Sertoli cells. Immunology and stem cell biology were not even topics of science in 1865, but they have now become major issues in our appreciation of Sertoli cell's role in spermatogenesis. We end with the universal importance and plasticity of function by comparing Sertoli cells in fish, amphibians, and mammals. In these various classes of vertebrates, Sertoli cells have quite different modes of proliferation and epithelial maintenance, cystic vs. tubular formation, yet accomplish essentially the same function but in strikingly different ways. PMID:26846984

  8. High School Economic Composition and College Persistence

    OpenAIRE

    Niu, Sunny X.; Tienda, Marta

    2013-01-01

    Using a longitudinal sample of Texas high school seniors of 2002 who enrolled in college within the calendar year of high school graduation, we examine variation in college persistence according to the economic composition of their high schools, which serves as a proxy for unmeasured high school attributes that are conductive to postsecondary success. Students who graduated from affluent high schools have the highest persistence rates and those who attended poor high schools have the lowest r...

  9. Persistence of HBV Vaccine’s Protection and Response to Hepatitis B Booster Immunization in 5- to 7-Year-Old Children in the Kohgiloyeh and Boyerahmad Province, Iran

    Directory of Open Access Journals (Sweden)

    Shahrzad Yazdanpanah

    2010-01-01

    Full Text Available Background and Aims: The duration of the protection of hepatitis B vaccination for infants and the necessity of a booster dose administration is unknown. The aim of the present study was to evaluate the persistence of seroprotection after hepatitis B virus (HBV vaccination in order to determine the necessity of a single booster dose in 5- to 7-year-old children.Methods: This clinical trial study was conducted from 2004 to 2005. The study population included all children aged 5 to 7 years old in the Kohgiloyeh and Boyerahmad province who had been vaccinated starting at birth with hepatitis B vaccine. Among these children, 729 were selected via a multiple-stage sampling method. Parents gave their informed consent, and blood specimens (3 ml were obtained from children. Hepatitis B surface antibody (HBsAb and hepatitis B surface antigen (HBsAg were determined by enzyme-linked immunosorbent assay (ELISA. Subjects with nonprotective titer levels (< 10 mIU/ml received a booster does of the DNA recombinant vaccine. Four weeks after the administration of a booster dose, the antibody to HBsAg (anti-HBs titer was measured. Data were analyzed using SPSS software, and analyses included chi-square, ANOVA, and independent-samples and paired-samples t-tests.Results: 615 children (84.4% had a protective antibody titer. The mean antibody titer was 230.5 ± 308.9 IU/ml, with a range of 10.6 to 1175 IU/ml. 15.6% of subjects had a nonprotective antibody titer, and the mean antibody titer was 4.97 ± 3.5 IU/ml. All subjects were HBsAg negative. No statistically significant differences were found by sex or by urban versus rural area of residence. The seroprotection rates significantly decreased by as the age of the children increased. Following the booster dose, 78.1 % of the children had a protective titer, and the mean titer significantly increased from 4.97 ± 3.5 at birth to 332.1 ± 402 IU/ml after the booster (P < 0.001. Conclusions: According to our results

  10. Transcriptomic analysis of persistent infection with foot-and-mouth disease virus in cattle suggests impairment of cell-mediated immunity in the nasopharynx

    Science.gov (United States)

    In order to investigate the mechanisms of persistent foot-and-mouth disease virus (FMDV) infection in cattle, transcriptome alterations associated with the FMDV carrier state were characterized using a bovine whole-transcriptome microarray. Eighteen cattle (8 vaccinated with a recombinant FMDV A vac...

  11. A rare case of peripheral T-cell lymphoma in 1-year-old child

    Directory of Open Access Journals (Sweden)

    Vignesh Kandakumar

    2011-01-01

    Full Text Available Peripheral T-cell lymphoma (PTCL represents approximately 12% of lymphoid neoplasms. They are even rarer in children and represent only 1% of Non-Hodgkin′s lymphoma in this age group. We report a case of PTCL in a 1-year-old female child for its rarity.

  12. A rare case of peripheral T-cell lymphoma in 1-year-old child

    OpenAIRE

    Vignesh Kandakumar; Prasanth Ganesan; Peush Bajpai; Rejiv Rajendranath; Sagar Tenali; Urmila Majhi; Ponni Sivaprakasam

    2011-01-01

    Peripheral T-cell lymphoma (PTCL) represents approximately 12% of lymphoid neoplasms. They are even rarer in children and represent only 1% of Non-Hodgkin′s lymphoma in this age group. We report a case of PTCL in a 1-year-old female child for its rarity.

  13. Premature Thelarche and Precocious Puberty in a Three-Year-Old Girl with Granulosa Cell Tumor

    Directory of Open Access Journals (Sweden)

    Zahra Ghanbari

    2013-07-01

    Full Text Available Granulosa cell tumors (GCTs are tumors that arise from granulosa cells, occurring in women 50 to 55 years of age but may occur at any age whereas Juvenile granulosa cell tumors usually occur in children and adolescents. A three years old girl with breast development but without any significant past medical history was referred to the Pediatric Clinic in Children hospital(University of Medical Sciences, Tabriz, Iran in July 2011.We have reported this patient with premature thelarche and isosexual precocity in this paper. Pelvic ultrasonography showed a hypoechoic solid mass and abdominopelvic MRI showed left adnexal mass with cystic components. Microscopic features of the resected mass were characteristic of juvenile GCT. Although in most of girls with precocious puberty the etiology is idiopathic, some important causes, such as ovarian tumors must be considered because most common presenting manifestation of GCT in children is precocious puberty.

  14. Persistence Mechanisms of Conjugative Plasmids

    DEFF Research Database (Denmark)

    Bahl, Martin Iain; Hansen, Lars H.; Sørensen, Søren Johannes

    2009-01-01

    maintenance in the host cell. These importantly include the ability to self-mobilize in a process termed conjugative transfer, which may occur across species barriers. Other plasmid stabilizing mechanisms include the multimer resolution system, active partitioning, and post-segregational-killing of plasmid......Are plasmids selfish parasitic DNA molecules or an integrated part of the bacterial genome? This chapter reviews the current understanding of the persistence mechanisms of conjugative plasmids harbored by bacterial cells and populations. The diversity and intricacy of mechanisms affecting the...... successful propagation and long-term continued existence of these extra-chromosomal elements is extensive. Apart from the accessory genetic elements that may provide plasmid-harboring cells a selective advantage, special focus is placed on the mechanisms conjugative plasmids employ to ensure their stable...

  15. The Histochemistry and Cell Biology omnium-gatherum: the year 2015 in review.

    Science.gov (United States)

    Taatjes, Douglas J; Roth, Jürgen

    2016-03-01

    We provide here our annual review/synopsis of all of the articles published in Histochemistry and Cell Biology (HCB) for the preceding year. In 2015, HCB published 102 articles, representing a wide variety of topics and methodologies. For ease of access to these differing topics, we have created categories, as determined by the types of articles presented to provide a quick index representing the general areas covered. This year, these categories include: (1) advances in methodologies; (2) molecules in health and disease; (3) organelles, subcellular structures, and compartments; (4) the nucleus; (5) stem cells and tissue engineering; (6) cell cultures: properties and capabilities; (7) connective tissues and extracellular matrix; (8) developmental biology; (9) nervous system; (10) musculoskeletal system; (11) respiratory and cardiovascular system; (12) liver and gastrointestinal tract; and (13) male and female reproductive systems. Of note, the categories proceed from methods development, to molecules, intracellular compartments, stem cells and cell culture, extracellular matrix, developmental biology, and finishing with various organ systems, hopefully presenting a logical journey from methods to organismal molecules, cells, and whole tissue systems.

  16. Renal Cell Carcinoma of Contralateral Kidney with Secondaries in Gallbladder Eight Years After Nephrectomy

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    Kechrid Mohamed

    2000-01-01

    Full Text Available A 55-year-old female underwent right nephrectomy for renal cell carcinoma (RCC. The histopathology showed clear cell carcinoma. There was no evidence of metastasis. After remaining asymptomatic for eight years, she developed pain in the right loin. Abdominal ultrasound, computerized tomography (CT Scan and magnetic resonance imaging (MRI were suggestive of a tumor mass in the right renal area, multiple tumor masses in the left kidney and a mass in the gallbladder. Cholecystectomy, left radical nephrectomy and right adrenal mass with excision of adjacent lymph nodes were performed. The histopathology from all sites was suggestive of RCC. She was maintained on hemodialysis. Two and half years later she died after surgical exploration for spinal cord decompression due to metastasis to the dorsal spine.

  17. Study on Persistence of Physical Exercise Training of First-Year Students%大学一年级学生体育锻炼坚持性培养研究

    Institute of Scientific and Technical Information of China (English)

    李继军

    2012-01-01

    开展"阳光体育运动"的基本要求是学生每天能够坚持锻炼,在此前提要求下,对刚进入大学校园的一年级学生来说,正是从初期培养其参与阳光体育运动,并养成自我锻炼的内部约束机制的最佳时机,为其顺利完成大学体育教育,终身受益体育锻炼带来的益处,具有重要意义。通过对200名大学一年级男生与女生体育锻炼价值认识、坚持性意志品质的自我认识、运动技能掌握情况的调查结果分析,提出培养大学一年级学生体育锻炼坚持性需从终身体育锻炼思想培养、课内体育锻炼技能培养、课外体育活动兴趣激发、加强女生锻炼的组织引导几个主要方面进行。%The essential requirements of sunlight sports are the student insisting on exercise every day.Under such premise request,for the first-year students,it is the best time to training self-exercise constraint mechanism from the initial period of sunlight sports participation.It has significant meaning for students finishing their college physical education successfully,and enjoying the benefit of physical exercise.Through analysis on male and female students' sports exercise value cognition,persistence and willpower,skill master condition,this paper put forwards that the cultivation of first-year students insisting on physical exercise should strength the physical exercise skills training in the class,stimulate interest of extracurricular sports activities,and guide the female students exercise.

  18. Visual persistence and cinema?

    Science.gov (United States)

    Galifret, Yves

    2006-01-01

    In Faraday and Plateau's days, both apparent motion and the fusion of intermittent lights, two phenomena that are hardly connected, were explained by retinal persistence. The works of Exner and of the 'Gestalt' psychologists, as well as the modern works on 'sampled' motion and smooth motion, disregarded retinal persistence. One tried, originally, to measure this persistence using intermittent stimulation, but under the pressure of practical concern, what was established in 1902 was the logarithmic relation between fusion frequency and the intensity of the stimulation. One had to wait until the 1950s for the use of harmonic analysis to finally allow a renewal in which many problems that, for decades, had only given rise to discussions that led nowhere and to groundless assertions, were correctly stated and easily solved.

  19. Secondary osteosarcoma developing 10 years after chemoradiotherapy for non-small-cell lung cancer.

    Science.gov (United States)

    Yagishita, Shigehiro; Horinouchi, Hidehito; Yorozu, Takashi; Kitazono, Satoru; Mizugaki, Hidenori; Kanda, Shintaro; Fujiwara, Yutaka; Nokihara, Hiroshi; Yamamoto, Noboru; Mori, Taisuke; Tsuta, Koji; Sumi, Minako; Tamura, Tomohide

    2014-02-01

    A 53-year-old female patient was admitted with pain and a progressively enlarging mass in the right upper chest. Chest computed tomography revealed a mass lesion in the region of the right upper ribs. Ten years prior to this admission, the patient had undergone right lobectomy for lung adenocarcinoma. One year after the surgery, follow-up computed tomography had revealed tumor recurrence in the mediastinal and supraclavicular lymph nodes, and the patient had been treated by chemoradiotherapy. Thereafter, regular follow-up had revealed no evidence of recurrence of the non-small-cell lung cancer. Histopathological findings revealed proliferation of spindle-shaped malignant tumor cells in a background of osteoid, consistent with the diagnosis of osteosarcoma. The location of the tumor was consistent with the radiation field. Based on the clinicopathological findings, the patient was diagnosed as having secondary osteosarcoma occurring as a result of the chemoradiotherapy administered previously for the recurrent non-small-cell lung cancer. Unfortunately, the patient died of rapid progression of the osteosarcoma within a week of admission to the hospital. The autopsy revealed contiguous invasion by the tumor of the heart, with massive thrombus formation. The peripheral pulmonary arteries were diffusely occluded by metastatic tumors. Our case serves to highlight the risk of development of secondary sarcoma as a life-threatening late complication after chemoradiotherapy for locally advanced non-small-cell lung cancer, even after complete cure of the primary tumor. PMID:24338556

  20. How persistent is civilization growth?

    CERN Document Server

    Garrett, Timothy J

    2011-01-01

    In a recent study (Garrett, 2011), I described theoretical arguments and empirical evidence showing how civilization evolution might be considered from a purely physical basis. One implication is that civilization exhibits the property of persistence in its growth. Here, this argument is elaborated further, and specific near-term forecasts are provided for key economic variables and anthropogenic CO2 emission rates at global scales. Absent some external shock, civilization wealth, energy consumption and carbon dioxide emissions will continue to grow exponentially at an average rate of about 2.3% per year.

  1. Role of T-helper type 2 cytokines in down-modulation of fas mRNA and receptor on the surface of activated CD4(+) T cells: molecular basis for the persistence of the allergic immune response.

    Science.gov (United States)

    Spinozzi, F; Agea, E; Fizzotti, M; Bassotti, G; Russano, A; Droetto, S; Bistoni, O; Grignani, F; Bertotto, A

    1998-12-01

    The mechanisms responsible for persistence of T lymphocytes at the sites of allergic inflammation are not completely understood. Activated T cells, usually expressing Fas on their surface, undergo activation-induced apoptotic death, thus limiting the dangerous consequences of a persistent immune reaction. We have previously shown that pulmonary T lymphocytes from untreated asthmatic subjects do not express surface Fas receptors nor do they contain Fas mRNA, yet they display normal levels of Fas ligand. This is not an inherited defect and is confined to mucosal T cells. To gain insights into the mechanism responsible for these findings, we performed a set of experiments with both purified Dermatophagoides pteronyssinus allergen and recombinant human cytokines: interleukin 2 (IL-2), IL-4, IL-5, transforming growth factor beta1, interferon gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF). In vitro exposure of purified CD4(+) lymphocytes to allergen yielded only transient up-regulation of surface Fas but did not influence susceptibility to Fas-mediated cell death. T-helper type 2 cytokines (IL-4, IL-5, and GM-CSF) had a dose-dependent and specific inhibitory effect on Fas mRNA, suggesting a new fundamental biological role in the survival of inflammatory cells during allergen exposure. PMID:9837865

  2. A case of multiple basal cell carcinomas developed about 50 years after irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Chu; Minamimoto, Toshiyuki; Hamada, Yoshimi; Sasaki, Harue; Furuya, Kazuhiko [Hakodate Central General Hospital, Hokkaido (Japan); Funayama, Emi

    1998-10-01

    Malignant skin tumors are known to develop in areas of chronic radiodermatitis. We experienced a patient with multiple basal cell carcinomas that developed about 50 years after irradiation. The patient was a 77-year-old man who underwent radiotherapy in his twenties for caries in the left shoulder joint. The dose given was unknown. Black skin tumor appeared initially about 10 years before the first consultation. The skin around the tumor began to erode about six months before presentation. Biopsy of the tumor was done at another institution and revealed basal cell carcinoma (BCC), so the patients was referred to our department. In addition to the BCC measuring 35 x 20 mm in the left shoulder, BCC measuring 17 x 20 mm and 15 x 15 mm were found on the chest and the left axilla, respectively. The lesions were excised with a margin of 5 mm from the radiodermatitis, and the resultant skin defects were covered with latissimus dorsi flaps. All three tumors were basal cell carcinomas. The patients died of an unrelated disease six years after surgery and there was no recurrence of his tumors. (author)

  3. Persistent Hyperprolactinemia and Bilateral Galactocele in a Male Infant

    Directory of Open Access Journals (Sweden)

    Casti Tiziana

    2009-02-01

    Full Text Available Galactocele is a benign breast lesion, usually occurring in nursing women. This lesion is a rare cause of breast enlargement in children. In this paper we describe the case of an infant with hyperprolactinemia (which persisted throughout 15 years of clinical observation and bilateral galactocele. We speculate that a congenital midline defect in our patient might have impaired the normal dopaminergic inhibitory tone on pituitary lactotroph cells, thus leading to an increased prolactin secretion by the pituitary gland; this, in turn, might have favored the development of the galactocele.

  4. Financial Markets and Persistence

    CERN Document Server

    Jain, S

    2005-01-01

    Persistence is studied in a financial context by mapping the time evolution of the values of the shares quoted on the London Financial Times Stock Exchange 100 index (FTSE 100) onto Ising spins. By following the time dependence of the spins, we find evidence for power law decay of the proportion of shares that remain either above or below their ` starting\\rq values. As a result, we estimate a persistence exponent for the underlying financial market to be $\\theta_f\\sim 0.5$.

  5. PERSISTENT LEFT SUPERIOR VENACAVA

    Directory of Open Access Journals (Sweden)

    Devinder Singh

    2014-05-01

    Full Text Available A Persistent Left Superior Venacava (PLSVC is the most common variation of the thoracic venous system and rare congenital vascular anomaly and is prevalent in 0.3% of the population. It may be associated with other cardiovascular abnormalities including atrial septal defect, bicuspid aortic valve, coarctation of aorta, coronary sinus ostial atresia, and cor triatriatum. Incidental rotation of a dilated coronary sinus on echocardiography should raise the suspicion of PLSVC. The diagnosis should be confirmed by saline contrast echocardiography. Condition is usually asymptomatic. Here we present a rare case of persistent left superior vena cava presented in OPD with dyspnoea & palpitations.

  6. Patients' perceptions of their cosmetic appearance more than ten years after radiotherapy for basal cell carcinoma

    International Nuclear Information System (INIS)

    Of 47 elderly patients treated by simple radiotherapeutic techniques for basal cell carcinomas, 12 are alive and free of disease more than 10 years after treatment. They were asked to rate their perception of the current cosmetic appearance of their lesions on a scale consisting of: excellent, very good, good, mediocre, and poor. Six of the 12 rated their cosmetic appearance as excellent, three considered it very good, and three called it good. Despite undeniable objective deterioration of the cosmetic appearance of irradiated basal cell carcinomas, patients appear to be pleased with the results. (author)

  7. 自体骨髓干细胞动员移植联合神经营养因子和综合康复治疗持续植物状态%Autologous bone marrow stem cells mobilization combined with neurotrophic factors and comprehensive rehabilitation for patients with persistent vegetative state

    Institute of Scientific and Technical Information of China (English)

    翟亚萍; 步星耀; 王新军; 程培训; 郭晓鹤; 周长江; 王智敏; 钱宝延

    2012-01-01

    目的 观察自体骨髓干细胞(bone marrow stem cells,BMSCs)动员联合神经营养因子及综合康复治疗持续植物状态(persistent vegetative state,PVS)患者的疗效及安全性.方法 60例PVS患者根据治疗方案分为对照组与观察组各30例,对照组给予神经营养因子及综合康复治疗,观察组在对照组治疗基础上行BMSCs动员治疗,比较2组治疗前、后PVS评分.结果 治疗前观察组与对照组PVS评分分别为(0.92±0.67)和(0.91±0.75)分,差异无统计学意义(P<0.05);治疗后3,6个月、1 a观察组PVS评分分别为(12.92±3.55),(13,58±3.53),(14.42±3.68)分,对照组分别为(10.45±4.58),(11.82±5.06),(12.27±5.06)分,2组比较差异均有统计学意义(P均<0.05);治疗后1 a,观察组与对照组治愈率分别为80.0%,56.7%,差异有统计学意义(P<0.05);治疗过程中2组均未出现明显不良反应.结论 BMSCs动员联合神经营养因子及综合康复治疗PVS安全、疗效满意.%Objective To observe the therapeutic effect and safety of autologous bone marrow stem cells (BMSCs) mobilization combined with neurotrophic factors and comprehensive rehabilitation on persistent vegetative state. Methods Sixty cases of persistent vegetative state were divided into the observation group and control group, with 30 cases in each group. Control group received neurotrophic factors and comprehensive rehabilitation, and the observation group received autologous BMSCs mobilization in addition to the therapy in control group. The persistent vegetative state scores were evaluated before and after treatment in two groups. Results There was no significant difference in persistent vegetative state scores between the observation group (0. 92±0. 67) and control group (0. 91 ±0. 75) before treatment (P>0. 05). The persistent vegetative state scores were (12. 92±3. 55), (13. 58±3. 53), and (14. 42±3. 68) in the observation group, and were (10. 45±4. 58), (11. 82±5. 06), and (12. 27

  8. PERSISTENT MULLERIAN DUCT SYNDROME: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Siddalingeshwar V

    2014-11-01

    Full Text Available : A 3-year-old boy presenting with right inguinal hernia was found to have uterus, fallopian tube and testes in a position analogous to ovaries in hernial sac, warranting a diagnosis of persistent Mullerian duct syndrome (PMDS. PMDS is an extremely rare form of internal male pseudo-hermaphroditism in which female internal sex organs, including the uterus, cervix and proximal vagina, persist in a 46XY male with normal external genitalia. The condition results from a congenital insensitivity to anti-Mullerian hormone, or lack of anti-Mullerian hormone, leading to persistence of the female internal sex organs in a male. Clinically, this condition is associated with cryptochoridism. Controversy persists regarding the appropriate treatment of PMDS, since resection of the remnant structures is associated with potential morbidity, but retention risks development of occasional malignancies. We review the literature and discuss various aspects of pathophysiology, diagnosis, and management of PMDS.

  9. De Novo Renal Cell Carcinoma in a Kidney Allograft 20 Years after Transplant

    Directory of Open Access Journals (Sweden)

    Masataka Banshodani

    2015-01-01

    Full Text Available Renal cell carcinoma (RCC in a kidney allograft is rare. We report the successful diagnosis and treatment of a de novo RCC in a nonfunctioning kidney transplant 20 years after engraftment. A 54-year-old man received a kidney transplant from his mother when he was 34 years old. After 10 years, chronic rejection resulted in graft failure, and the patient became hemodialysis-dependent. Intravenous contrast-enhanced computed tomography (CT for the evaluation of gastrointestinal symptoms revealed a solid 13 mm tumor in the kidney graft. The tumor was confirmed on ultrasound examination. This tumor had not been detected on a surveillance noncontrast CT scan. Needle biopsy showed that the tumor was an RCC. Allograft nephrectomy was performed. Pathological examination showed that the tumor was a Fuhrman Grade 2 RCC. XY-fluorescence hybridization analysis of the RCC showed that the tumor cells were of donor origin. One year after the surgery, the patient is alive and has no evidence of tumor recurrence. Regardless of whether a kidney transplant is functioning, it should periodically be imaged for RCC throughout the recipient’s lifetime. In our experience, ultrasonography or CT with intravenous contrast is better than CT without contrast for the detection of tumor in a nonfunctioning kidney transplant.

  10. A Retrospective Analysis of Oral Langerhans Cell Histiocytosis in an Iranian Population: a 20-year Evaluation

    Science.gov (United States)

    Atarbashi Moghadam, Saede; Lotfi, Ali; Piroozhashemi, Batool; Mokhtari, Sepideh

    2015-01-01

    Statement of the Problem Langerhans cell histiocytosis is a rare disease with unknown pathogenesis and is characterized by local or disseminated proliferation of Langerhans cells. There is no previous investigation on prevalence of oral Langerhans cell histiocytosis in Iranian population. Purpose The purpose of this study was to assess the relative frequency of oral Langerhans cell histiocytosis in an Iranian population and to compare the data with previous reports. Materials and Method Pathology files of Oral and Maxillofacial Pathology Department of Dental School of Shahid Beheshti University of Medical Sciences from 1992 to 2012 were searched for cases recorded as oral Langerhans cell histiocytosis. A total number of 20 cases were found and the clinical information of patients was recorded. Results The relative frequency of oral Langerhans cell histiocytosis was 0.34% and the most common location was the posterior mandible. In addition, the mean age of patients was 27 years and there was a definite male predominance. Most lesions were localized and tooth mobility was the most common oral presentation. Conclusion In Iranian population as in many other countries, the relative frequency of oral Langerhans cell histiocytosis is low. Moreover, tooth mobility and periodontal lesions are the frequent early signs of disease. Therefore, in patients with periodontal problems, good oral health, and no response to the treatment; Langerhans cell histiocytosis must be considered. Additionally, although most cases of oral Langerhans cell histiocytosis are localized, systemic involvement must also be considered and dental professionals have an important role in early detection of the disease. PMID:26535408

  11. Characterization of Bacillus anthracis persistence in vivo.

    Directory of Open Access Journals (Sweden)

    Sarah A Jenkins

    Full Text Available Pulmonary exposure to Bacillus anthracis spores initiates inhalational anthrax, a life-threatening infection. It is known that dormant spores can be recovered from the lungs of infected animals months after the initial spore exposure. Consequently, a 60-day course antibiotic treatment is recommended for exposed individuals. However, there has been little information regarding details or mechanisms of spore persistence in vivo. In this study, we investigated spore persistence in a mouse model. The results indicated that weeks after intranasal inoculation with B. anthracis spores, substantial amounts of spores could be recovered from the mouse lung. Moreover, spores of B. anthracis were significantly better at persisting in the lung than spores of a non-pathogenic Bacillus subtilis strain. The majority of B. anthracis spores in the lung were tightly associated with the lung tissue, as they could not be readily removed by lavage. Immunofluorescence staining of lung sections showed that spores associated with the alveolar and airway epithelium. Confocal analysis indicated that some of the spores were inside epithelial cells. This was further confirmed by differential immunofluorescence staining of lung cells harvested from the infected lungs, suggesting that association with lung epithelial cells may provide an advantage to spore persistence in the lung. There was no or very mild inflammation in the infected lungs. Furthermore, spores were present in the lung tissue as single spores rather than in clusters. We also showed that the anthrax toxins did not play a role in persistence. Together, the results suggest that B. anthracis spores have special properties that promote their persistence in the lung, and that there may be multiple mechanisms contributing to spore persistence.

  12. The first five years of single-cell cancer genomics and beyond.

    Science.gov (United States)

    Navin, Nicholas E

    2015-10-01

    Single-cell sequencing (SCS) is a powerful new tool for investigating evolution and diversity in cancer and understanding the role of rare cells in tumor progression. These methods have begun to unravel key questions in cancer biology that have been difficult to address with bulk tumor measurements. Over the past five years, there has been extraordinary progress in technological developments and research applications, but these efforts represent only the tip of the iceberg. In the coming years, SCS will greatly improve our understanding of invasion, metastasis, and therapy resistance during cancer progression. These tools will also have direct translational applications in the clinic, in areas such as early detection, noninvasive monitoring, and guiding targeted therapy. In this perspective, I discuss the progress that has been made and the myriad of unexplored applications that still lie ahead in cancer research and medicine. PMID:26430160

  13. Contributions to Persistence Theory

    Directory of Open Access Journals (Sweden)

    Du Dong

    2014-12-01

    Full Text Available Persistence theory discussed in this paper is an application of algebraic topology (Morse Theory [29] to Data Analysis, precisely to qualitative understanding of point cloud data, or PCD for short. PCD can be geometrized as a filtration of simplicial complexes (Vietoris-Rips complex [25] [36] and the homology changes of these complexes provide qualitative information about the data. Bar codes describe the changes in homology with coefficients in a fixed field. When the coefficient field is ℤ2, the calculation of bar codes is done by ELZ algorithm (named after H. Edelsbrunner, D. Letscher, and A. Zomorodian [20]. When the coefficient field is ℝ, we propose an algorithm based on the Hodge decomposition [17]. With Dan Burghelea and Tamal K. Dey we developed a persistence theory which involves level sets discussed in Section 4. We introduce and discuss new computable invariants, the “relevant level persistence numbers” and the “positive and negative bar codes”, and explain how they are related to the bar codes for level persistence. We provide enhancements and modifications of ELZ algorithm to calculate such invariants and illustrate them by examples.

  14. Persistent organic pollutants

    NARCIS (Netherlands)

    Dungen, van den M.W.

    2016-01-01

    Fish wild caught in polluted areas, may contain high levels of persistent organic pollutants (POPs). In the Netherlands, especially eel from the main rivers have high POP levels. Health concerns led to a ban on eel fishing in 2011 due to health concerns. We showed that men consuming eel from the hig

  15. Introduction: Persistent Modelling

    DEFF Research Database (Denmark)

    Ayres, Phil

    2012-01-01

    , familiar contemporary and, perhaps, not so familiar emerging manifestations of this relation. What persists from this probing, fully intact, is that representation and the represented remain inextricably related in our contemporary and emerging practices. What comes into focus is that the nature...

  16. Persistent Trigeminal Artery

    Directory of Open Access Journals (Sweden)

    Dijo T George

    2015-04-01

    Full Text Available Trigeminal artery is the commonest of the four primitive anastomoses between the carotid and vertebrobasilar system that may rarely persist in adults, with an angiographic incidence of 0.1 - 0.6%. We present the CT and MR angiograms of a patient who presented with a minor stroke and was detected to have this anomaly and briefly discuss the significance

  17. Chilly Ties Persist

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Sino-Japanese relations seem unlikely to improve under the leadership of Shinzo Abe The deteriorating state of relations between China and Japan may persist under the government of Shinzo Abe, who won the presidential election of the ruling Liberal Democratic Party (LDP) on September 20 and was

  18. Surgically Treated Central Giant Cell Granuloma in Six-Year-Old Child: A Case Report

    OpenAIRE

    Patloth, Tarasingh; Reddy, J. Sharada

    2013-01-01

    ABSTRACT Central giant cell granuloma (CGCG) is a benign intraosseous lesion of the jaws that is found predominantly in children and young adults. Although benign, it may be locally aggressive, causing extensive bone destruction, tooth displacement and root resorption. The common therapy is aggressive curettage, peripheral ostectomy or resection, which may be associated with loss of teeth and in younger patient's loss of dental germs. In this article, a 6-year-old girl with CGCG is successful...

  19. Langerhans cell histiocytosis: A case report of a three year old boy with primary oral manifestations

    Directory of Open Access Journals (Sweden)

    Seraj B

    2006-06-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare disease with formation of granulomatous infiltrations consisting of Langerhans cells, histiocytes, lymphocytes and eosinophilic granulocytes. The ethiopathogenesis of the disease has not been fully clarified yet. It can occur as focal or disseminated form - acute or chronic. Oral manifestations may be the first signs. This article reports a case of a 3 year old boy with LCH suffering from severe dental mobility and foul breathe. Radiographically, the lesions appeared as well-defined radiolucent defects in maxilla and mandible. The microscopic findings consisted of sheet like arrangements of histiocytes with a mixture of eosinophils and other inflammatory cells. Biochemical tests were within normal limits.

  20. Persistent strabismus after cataract extraction

    Directory of Open Access Journals (Sweden)

    Dujić Mirjana P.

    2005-01-01

    Full Text Available Background. Transient ocular misalignment as a complication of parabulbar and peribulbar anesthesia has already been reported in the literature. The aim of our study was to present a case of irreversible iatrogenic vertical strabismus after cataract surgery, which had to be operated on. Methods. Clinical and orthoptic evaluation of a female patient with vertical diplopia after phacoemulsification cataract surgery. Results. One week after the uneventful surgery, a 68-year-old patient complained of a sudden vertical deviation in the operated eye. The patient had not had a history of previous motility disorders. On examination, the patient showed hypertropia in the left eye of 15−20 degrees in primary position. Three and 6 months postoperatively, there was no a spontaneous improvement, while the persistent vertical deviation was 40 prism dioptres. Strabismus surgery was required 1 year after the cataract surgery. Conclusion. Diplopia is a complication of peribulbar anesthesia which could be persistent. The superior and inferior rectus muscle are especially vulnerable. Its occurrence may be technique - related and the incidence increases when hyaluronidase is not available.

  1. Herbicide Persistence in Seawater Simulation Experiments.

    Directory of Open Access Journals (Sweden)

    Philip Mercurio

    Full Text Available Herbicides are detected year-round in marine waters, including those of the World Heritage listed Great Barrier Reef (GBR. The few previous studies that have investigated herbicide persistence in seawater generally reported half-lives in the order of months, and several studies were too short to detect significant degradation. Here we investigated the persistence of eight herbicides commonly detected in the GBR or its catchments in standard OECD simulation flask experiments, but with the aim to mimic natural conditions similar to those found on the GBR (i.e., relatively low herbicide concentrations, typical temperatures, light and microbial communities. Very little degradation was recorded over the standard 60 d period (Experiment 1 so a second experiment was extended to 365 d. Half-lives of PSII herbicides ametryn, atrazine, diuron, hexazinone and tebuthiuron were consistently greater than a year, indicating high persistence. The detection of atrazine and diuron metabolites and longer persistence in mercuric chloride-treated seawater confirmed that biodegradation contributed to the breakdown of herbicides. The shortest half-life recorded was 88 d for growth-regulating herbicide 2,4-D at 31°C in the dark, while the fatty acid-inhibitor metolachlor exhibited a minimum half-life of 281 d. The presence of moderate light and elevated temperatures affected the persistence of most of the herbicides; however, the scale and direction of the differences were not predictable and were likely due to changes in microbial community composition. The persistence estimates here represent some of the first appropriate data for application in risk assessments for herbicide exposure in tropical marine systems. The long persistence of herbicides identified in the present study helps explain detection of herbicides in nearshore waters of the GBR year round. Little degradation of these herbicides would be expected during the wet season with runoff and associated

  2. Photo-induced charge transfer and relaxation of persistent charge carriers in polymer/nanocrystal composites for applications in hybrid solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Heinemann, Marc Daniel; Zutz, Folker; Kolny-Olesiak, Joanna; Borchert, Holgert; Riedel, Ingo; Parisi, Juergen [University of Oldenburg, Department of Physics, Energy and Semiconductor Research Laboratory, Oldenburg (Germany); Maydell, Karsten von [EWE Research Center for Energy Technology, Oldenburg (Germany)

    2009-12-09

    The photo-induced charge transfer and the dynamics of persistent charge carriers in blends of semiconducting polymers and nanocrystals are investigated. Regioregular poly(3-hexylthiophene) (P3HT) is used as the electron donor material, while the acceptor moiety is established by CdSe nanocrystals (nc-CdSe) prepared via colloidal synthesis. As a reference system, organic blends of P3HT and [6,6]-phenyl C{sub 61}-butyric acid methyl ester (PCBM) are studied as well. The light-induced charge transfer between P3HT and the acceptor materials is studied by photoluminescence (PL), photo-induced absorption (PIA) and light-induced electron spin resonance spectroscopy (LESR). Compared to neat P3HT samples, both systems show an intensified formation of polarons in the polymer upon photo-excitation, pointing out successful separation of photogenerated charge carriers. Additionally, relaxation of the persistent charge carriers is investigated, and significant differences are found between the hybrid composite and the purely organic system. While relaxation, reflected in the transient signal decay of the polaron signal, is fast in the organic system, the hybrid blends exhibit long-term persistence. The appearance of a second, slow recombination channel indicates the existence of deep trap states in the hybrid system, which leads to the capture of a large fraction of charge carriers. A change of polymer conformation due to the presence of nc-CdSe is revealed by low temperature LESR measurements and microwave saturation techniques. The impact of the different recombination behavior on the photovoltaic efficiency of both systems is discussed. (Abstract Copyright [2009], Wiley Periodicals, Inc.)

  3. Five year survival of non-small cell lung cancer patients in Brunei Darussalam

    Directory of Open Access Journals (Sweden)

    Muhd Syafiq ABDULLAH

    2013-02-01

    Full Text Available Introduction: Lung cancer has been the leading cause of cancer deaths in Brunei Darussalam for the past five years. This study is the first to supply data for the 5-year survival of patients diagnosed with non-small cell lung cancer (NSCLC in Brunei Darussalam. Materials and Methods: From 2002 to 2009, 302 patients diagnosed with NSCLC were identified from the National Cancer Registry of Brunei Darussalam. Demographic and clinical data were retrospectively retrieved from the clinical notes. All deaths and dates of death were obtained and crosschecked with the National Birth and Death Registry at the Immigration Department. Data were analysed using SPSS statistical software and 5-year Kaplan-Meier survival curves were derived and analysed. Predictors of 5-year survival were analysed using Cox regression analysis. Results: Mean age of the 302 patients was 64.9 ± 12.8 (27.4–90.6 years with male to female ratio of 194:108. Racial distribution consisted of 84.4% (n=255 Malay, 12.5% (n=38 Chinese and 3.1% of other racial origin (indigenous and foreign nationals. Histological types of NSCLC consisted of 67.9% (n=205 adenocarcinoma, 16.2% (n=49 squamous cell carcinoma, 6.3% (n=19 large cell carcinoma, 5.3% (n=16 bronchioalveolar carcinoma and 4.3% of other origin. Only 13.9% of patients underwent surgical resection. At completion of follow-up, only 47 (15.5% patients were still alive. There were 255 deaths. Overall 5-year survival for the whole group was 3.6% with a median survival time of 6.5 ± 0.9 months (95% CI: 4.7-8.4 months but according to stage of disease was 60.9% for Stage IA, 29.9% for Stage IB, 10.0% for Stage IIB, 7% for Stage IIIB and 3% for Stage IV. Significant prognostic factors were younger age at diagnosis, surgical resection, tumour types and tumour stages. Conclusion: Overall 5-year survival of patients diagnosed with NSCLC in Brunei Darussalam is still generally poor but comparable to previously reported data. Significant

  4. Intergenerational Top Income Persistence

    DEFF Research Database (Denmark)

    Munk, Martin D.; Bonke, Jens; Hussain, M. Azhar

    2016-01-01

    In this paper, we investigate intergenerational top earnings and top income mobility in Denmark. Access to administrative registers allowed us to look at very small fractions of the population. We find that intergenerational mobility is lower in the top when including capital income in the income...... measure— for the rich top 0.1% fathers and sons the elasticity is 0.466. Compared with Sweden, however, the intergenerational top income persistence is about half the size in Denmark....

  5. Persistence in corporate networks

    OpenAIRE

    Milaković, Mishael; Raddant, Matthias; Birg, Laura

    2014-01-01

    We examine the bipartite graphs of German corporate boards in 1993, 1999 and 2005, and identify cores of directors who are highly central in the entire network while being densely connected among themselves. The novel feature of this paper is the focus on the dynamics of these networks. Germany's corporate governance has experienced significant changes during this time, and there is substantial turnover in the identity of core members, yet we observe the persistent presence of a network core,...

  6. Neoadjuvant Chemoradiation in Squamous Cell Carcinoma of the Maxillary Sinus: A 26-Year Experience

    Directory of Open Access Journals (Sweden)

    Matthias Kreppel

    2012-01-01

    Full Text Available Background. The aim of our study was to evaluate the effects of neoadjuvant platinum-based radiochemotherapy (RCT in patients with maxillary sinus squamous cell carcinoma and to compare the results with other multimodality treatment concepts for advanced-stage maxillary sinus carcinoma in the literature. Methods. In total, 53 patients with squamous cell carcinoma of the maxillary sinus were reviewed retrospectively. All patients received a neoadjuvant RCT containing either cisplatin or carboplatin followed by radical surgery. Overall survival and locoregional control were plotted by Kaplan-Meier analysis. Prognostic factors were identified through univariate and multivariate analysis. Results. Five-year overall survival for all patients was 35%. Eleven patients achieved a complete response after radiochemotherapy. The complete response rate was significantly higher for patients treated with cisplatin (P=0.028; however the 5-year overall survival rates did not differ significantly (P=0.673 for patients treated with cisplatin (37% and carboplatin (32%. Orbital invasion (P=0.005 and complete response to radiochemotherapy (P=0.021 had a significant impact on overall survival in univariate analysis. Conclusions. Neoadjuvant radiochemotherapy followed by radical surgery is an effective treatment for patients with advanced maxillary sinus squamous cell carcinoma. In terms of treatment response cisplatin seems to be more effective than carboplatin.

  7. Natural killer cells contribute to hepatic injury and help in viral persistence during progression of hepatitis B e-antigen-negative chronic hepatitis B virus infection.

    Science.gov (United States)

    Ghosh, S; Nandi, M; Pal, S; Mukhopadhyay, D; Chakraborty, B C; Khatun, M; Bhowmick, D; Mondal, R K; Das, S; Das, K; Ghosh, R; Banerjee, S; Santra, A; Chatterjee, M; Chowdhury, A; Datta, S

    2016-08-01

    Hepatitis B e-antigen negative (e(-)) chronic HBV infection (CHI) encompasses a heterogeneous clinical spectrum ranging from inactive carrier (IC) state to e(-) chronic hepatitis B (CHB), cirrhosis and hepatic decompensation. In the backdrop of dysfunctional virus-specific T cells, natural killer (NK) cells are emerging as innate effectors in CHI. We characterized CD3(-) CD56(+) NK cells in clinically well-defined, treatment-naive e(-) patients in IC, e(-)CHB or decompensated liver cirrhosis (LC) phase to appraise their role in disease progression. The NK cell frequencies increased progressively with disease severity (IC 8.2%, e(-)CHB 13.2% and LC 14.4%). Higher proportion of NK cells from LC/e(-)CHB expressed CD69, NKp46, NKp44, TRAIL and perforin, the last two being prominent features of CD56(bright) and CD56(dim) NK subsets, respectively. The frequencies of CD3(-) CD56(+) NK cells together with TRAIL(+) CD56(bright) and Perforin(+) CD56(dim) NK cells correlated positively with serum alanine transaminase levels in e(-)CHB/LC. K562 cell-stimulated NK cells from e(-)CHB/LC exhibited significantly greater degranulation but diminished interferon-γ production than IC. Further, Perforin(+) NK cell frequency inversely correlated with autologous CD4(+) T-cell count in e(-) patients and ligands of NK receptors were over-expressed in CD4(+) T cells from e(-)CHB/LC relative to IC. Co-culture of sorted CD56(dim) NK cells and CD4(+) T cells from e(-)CHB showed enhanced CD4(+) T-cell apoptosis, which was reduced by perforin inhibitor, concanamycin A, suggesting a possible perforin-dependent NK cell-mediated CD4(+) T-cell depletion. Moreover, greater incidence of perforin-expressing NK cells and decline in CD4(+) T cells were noticed intrahepatically in e(-)CHB than IC. Collectively, NK cells contribute to the progression of e(-)CHI by enhanced TRAIL- and perforin-dependent cytolytic activity and by restraining anti-viral immunity through reduced interferon-γ secretion and

  8. Candida albicans Amphotericin B-Tolerant Persister Formation is Closely Related to Surface Adhesion.

    Science.gov (United States)

    Sun, Jing; Li, Zhigang; Chu, Haoyue; Guo, Jing; Jiang, Guangshui; Qi, Qingguo

    2016-02-01

    Candida albicans persisters have so far been observed only in biofilm environment; the biofilm element(s) that trigger(s) persister formation are still unknown. In this study, we tried to further elucidate the possible relationship between C. albicans persisters and the early phases of biofilm formation, especially the surface adhesion phase. Three C. albicans strains were surveyed for the formation of persisters. We tested C. albicans persister formation dynamically at different time points during the process of adhesion and biofilm formation. The number of persister cells was determined based on an assessment of cell viability after amphotericin B treatment and colony-forming unit assay. None of the planktonic cultures contained persisters. Immediately following adhesion of C. albicans cells to the surface, persister cells emerged and the proportion of persisters reached a peak of 0.2-0.69 % in approximately 2-h biofilm. As the biofilm matured, the proportion of persisters decreased and was only 0.01-0.02 % by 24 h, while the number of persisters remained stable with no significant change. Persisters were not detected in the absence of an attachment surface which was pre-coated. Persisters were also absent in biofilms that were scraped to disrupt surface adhesion prior to amphotericin B treatment. These results indicate that C. albicans antifungal-tolerant persisters are produced mainly in surface adhesion phase and surface adhesion is required for the emergence and maintenance of C. albicans persisters.

  9. Persistent autoantibody-production by intermediates between short-and long-lived plasma cells in inflamed lymph nodes of experimental epidermolysis bullosa acquisita.

    Directory of Open Access Journals (Sweden)

    Benjamin Tiburzy

    Full Text Available Autoantibodies are believed to be maintained by either the continuous generation of short-lived plasma cells in secondary lymphoid tissues or by long-lived plasma cells localized in bone marrow and spleen. Here, we show in a mouse model for the autoimmune blistering skin disease epidermolysis bullosa acquisita (EBA that chronic autoantibody production can also be maintained in inflamed lymph nodes, by plasma cells exhibiting intermediate lifetimes. After EBA induction by immunization with a mCOL7c-GST-fusion protein, antigen-specific plasma cells and CD4 T cells were analyzed. Plasma cells were maintained for months in stable numbers in the draining lymph nodes, but not in spleen and bone marrow. In contrast, localization of mCOL7c-GST -specific CD4 T cells was not restricted to lymph nodes, indicating that availability of T cell help does not limit plasma cell localization to this site. BrdU-incorporation studies indicated that pathogenic mCOL7c- and non-pathogenic GST-specific plasma cells resemble intermediates between short-and long-lived plasma cells with half-lives of about 7 weeks. Immunization with mCOL7c-GST also yielded considerable numbers of plasma cells neither specific for mCOL7c- nor GST. These bystander-activated plasma cells exhibited much shorter half-lives and higher population turnover, suggesting that plasma cell lifetimes were only partly determined by the lymph node environment but also by the mode of activation. These results indicate that inflamed lymph nodes can harbor pathogenic plasma cells exhibiting distinct properties and hence may resemble a so far neglected site for chronic autoantibody production.

  10. Persistent γδ T large granular lymphocytosis in a patient with refractory pure red cell aplasia, celiac disease, and chronic hepatitis B infection

    Science.gov (United States)

    Sreedharanunni, S; Sachdeva, MUS; Prakash, G; Das, R

    2016-01-01

    The disorders of large granular lymphocytes include reactive proliferation as well as indolent or aggressive neoplasms of cytotoxic T cells, γδ T cells, and natural killer (NK) cells. They are associated with autoimmune and infectious disorders and have varied immunophenotypic features. We report a case, which highlights this complex association of autoimmune and infectious diseases with large granular lymphocytosis, the overlapping spectrum of large granular lymphocyte leukemias, and γδ T cell lymphomas as well as the difficulties in the diagnosis and management of these indolent T cell lymphomas in the usual clinical settings. PMID:26515990

  11. Langerhans cell histiocytosis of the mandible in a six-year-old child

    Directory of Open Access Journals (Sweden)

    Ramani Pratibha

    2007-01-01

    Full Text Available Histiocytosis is a term applied to a group of rare disorders of the reticuloendothelial system. Eosinophilic granuloma, the most benign and localized of the three Langerhans cell histiocytosis entities, may be solitary or multiple. Eosinophilic granuloma can affect almost any bone, but commonly involves the mandible when the jaws are affected. Conventional treatment of LCH is with surgery, radiotherapy, chemotherapy and steroid injections, alone or in combination. Spontaneous regression of localized disease has also been reported. We report a six and a half-year-old patient with Langerhans cell histiocytosis - solitary eosinophilic granuloma of the mandible that initially regressed but rapidly recurred even after radical treatment and had a fatal outcome.

  12. A Review and Report of Peripheral Giant Cell Granuloma in a 4-Year-Old Child

    Directory of Open Access Journals (Sweden)

    Afsaneh Nekouei

    2016-01-01

    Full Text Available Peripheral giant cell granuloma is a common benign and reactive gingival epulis in oral cavity. It is often difficult to make a clinical diagnosis; thereby definitive diagnosis depends on histopathologic features. We report a case of a 4-year-old Caucasian boy presenting with a five-month history a 20 × 15 × 12 mm pedunculated, lobular soft tissue mass of the left anterior maxilla gingiva which was misdiagnosed and maltreated before his referral. An excisional biopsy of the lesion followed by histopathologic examination of the biopsy specimen revealed distinctive features of peripheral giant cell granuloma. Early detection and excision of this hyperplastic nodule especially in children are important to minimize potential dentoalveolar complications.

  13. Ocular Surface Reconstruction with Cultivated Limbal Epithelial Cells in Limbal Stem Cell Deficiency: One-year Follow-up Results

    Directory of Open Access Journals (Sweden)

    İsmet Durak

    2012-05-01

    Full Text Available Pur po se: To evaluate the 1-year follow-up results of cultivated limbal epithelial cell (CLEC transplantation in unilateral limbal stem cell deficiency (LSCD. Ma te ri al and Met hod: One-year follow-up results of five unilateral LSCD patients who had undergone CLEC transplantation were evaluated. Parameters for this evaluation were: fluorescein staining of ocular surface, corneal vascularization and status of epithelium with slit lamp, and visual acuity. 1.5-mm limbal biopsy was performed from the superior limbus of the healthy eyes, broke into two equal pieces, expanded on human amniotic membrane (hAM and inserts for 14 days until getting 20 mm in size. CLECs on hAMs were used directly, and cells on inserts were usedafter detachment procedure. The symblepharon and pannus tissues were removed, superficial keratectomy was performed. CLEC on hAMs were transplanted with the epithelial side up onto the bare corneal stroma, sutured to the conjunctiva with 10-0 nylon sutures. Free CLEC layer from insert was placed on hAM as a second layer, additional hAM was used as a protective layer all over other tissues. Re sults: Median age was 44.4 years (14-71. The etiology was chemical burn in all patients. Median duration of symptoms was 10 years (2-18, median follow-up period was 12.6 (12-12.5 months. Preoperative best corrected visual acuities (BCVA were light perception in three patients, counting fingers at 50 cm in one patient and 3/10 in one patient. Visions were improved in all patients. Postoperative BCVA 12 months after the surgery were between counting fingers at 3 meters to 6/10. There was a temporary hemorrhage between the two layers of hAMs in one patient at the early postoperative period. Peripheral corneal vascularization has occurred in three patients, in patient corneal vascularization has reached to the paracentral area. Dis cus si on: CLEC transplantation is an efficient treatment option for unilateral LSCD in mid-long term. (Turk J

  14. One-Year Safety Analysis of the COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133+ Bone Marrow Stem Cells to Placebo in Patients after Acute Myocardial Infarction and Left Ventricular Dysfunction

    Directory of Open Access Journals (Sweden)

    Samer Mansour

    2011-01-01

    Full Text Available Bone marrow stem cell therapy has emerged as a promising approach to improve healing of the infarcted myocardium. Despite initial excitement, recent clinical trials using non-homogenous stem cells preparations showed variable and mixed results. Selected CD133+ hematopoietic stem cells are candidate cells with high potential. Herein, we report the one-year safety analysis on the initial 20 patients enrolled in the COMPARE-AMI trial, the first double-blind randomized controlled trial comparing the safety, efficacy, and functional effect of intracoronary injection of selected CD133+ cells to placebo following acute myocardial infarction with persistent left ventricular dysfunction. At one year, there is no protocol-related complication to report such as death, myocardial infarction, stroke, or sustained ventricular arrhythmia. In addition, the left ventricular ejection fraction significantly improved at four months as compared to baseline and remained significantly higher at one year. These data indicate that in the setting of the COMPARE-AMI trial, the intracoronary injection of selected CD133+ stem cells is secure and feasible in patients with left ventricle dysfunction following acute myocardial infarction.

  15. Giant Cell Arteritis in a 12-Year-Old Girl Presenting with Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Zeinab A. El-Sayed

    2014-01-01

    Full Text Available Giant cell arteritis (GCA is rare in children. The kidneys are generally spared. We present a case of GCA in a 12-year-old girl with severe headache and tender scalp especially over the right temporal area. The right superficial temporal artery was cord like and nodular and the pulsations were barely felt. Several small tender nodular swellings were felt in the occipital area. She had been previously diagnosed as a case of nephrotic syndrome due to underlying membranoproliferative glomerulonephritis. This report is aimed at drawing attention to this rare form of vasculitis in children aiming at decreasing its morbidities.

  16. Warty Condylomatous Squamous Cell Carcinoma of the Penis in a 19-Year-Old

    Directory of Open Access Journals (Sweden)

    Yauhen Tarbunou

    2014-05-01

    Full Text Available Warty carcinoma of the penis is an unusual neoplasm and a variant of penile squamous cell carcinoma. As with other types of penile cancer, risk factors include human papillomavirus infection, poor personal hygiene, and being uncircumcised. The typical case is an exophytic mass arising from the glans penis, frequently large (4-5 cm, and with invasion into corpus spongiosum. The diagnosis is typically made by tumor biopsy. Treatment depends on the stage of disease and includes partial vs total penectomy, with or without prophylactic or therapeutic bilateral lymphadenectomy. We present an unusual case of penile cancer in a 19-year-old patient.

  17. Clear cell adenocarcinoma of the ulterine cervix in a 15 year old girl: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seung Joon; Kim, Jee Eun; KIm, Hyung Sik; Choi, Hye Young [Dept. of Radiology, Gachon University Gil Hospital, Incheon (Korea, Republic of)

    2013-10-15

    Cervical cancer is rare in the pediatric population. In cases of cervical cancer, adenocarcinoma is predominantly reported. Clear cell adenocarcinoma (CCAC) of the uterine cervix is a very rare tumor and accounts for only 4% of all adenocarcinomas of the uterine cervix. Risk factors and pathogenesis of this disease are not exactly revealed. The intrauterine exposure to diethylstilbestrol (DES) and associated non-steroidal estrogen during pregnancy before 18 weeks is the only known risk factor. This study reports the imaging finding of primary uterine cervical tumor in a 15-year-old girl, who was finally diagnosed with CCAC, with no maternal history of DES exposure in utero.

  18. Rebuilding the heart in Darwin's year: stem cell therapies in a Darwinian context.

    Science.gov (United States)

    Sánchez-Ron, José M

    2010-02-01

    The present paper tries to honour Charles Darwin's memory in the year in which the world celebrates the 200 anniversary of his birth and the 150 of the publication of The Origin of Species. After pointing out that the basis of his theory of evolution, "improvement of species", is a time-dependent concept, commenting on the role that atrophied organs played in Darwin's work and relating this with Darwinian medicine, it is suggested that stem cell and cardiovascular therapies could be perhaps connected with some of the ideas and possibilities already envisaged by Darwin and mentioned in one of his books, The Variation of Animals and Plants under Domestication (1868).

  19. Persistently increased intestinal fraction of alkaline phosphatase

    DEFF Research Database (Denmark)

    Nathan, E; Baatrup, G; Berg, H;

    1984-01-01

    Persistent elevation of the intestinal fraction of the alkaline phosphatase (API) as an isolated finding has to our knowledge not been reported previously. It was found in a boy followed during a period of 5.5 years. The only symptom was transient periodic fatigue observed at home, but not apparent...... phosphatase activity could be demonstrated....

  20. Anger Expression and Persistence in Young Children

    Science.gov (United States)

    He, Jie; Xu, Qinmei; Degnan, Kathryn Amey

    2012-01-01

    This study investigated anger expression during toy removal (TR) in 92 young Chinese children, two to five years of age, and its relations to their persistence in responding to obstacles during two challenging tasks with highly desirable goals [TR and locked box (LB)] and one challenging task with a less desirable goal [impossible perfect circles…

  1. The Academic Library Impact on Student Persistence

    Science.gov (United States)

    Emmons, Mark; Wilkinson, Frances C.

    2011-01-01

    What impact does the academic library have on student persistence? This study explores the relationship between traditional library input and output measures of staff, collections, use, and services with fall-to-fall retention and six-year graduation rates at Association of Research Libraries member libraries. When controlling for race/ethnicity…

  2. Poverty persistence and poverty dynamics

    OpenAIRE

    Biewen, Martin

    2014-01-01

    A considerable part of the poverty that is measured in a single period is transitory rather than persistent. In most countries, only a portion of people who are currently poor are persistently poor. People who are persistently poor or who cycle into and out of poverty should be the main focus of anti-poverty policies. Understanding the characteristics of the persistently poor, and the circumstances and mechanisms associated with entry into and exit from poverty, can help to inform governments...

  3. 'Inflation Targeting and Inflation Persistence'

    OpenAIRE

    George J. Bratsiotis; Jakob Madsen; Christopher Martin

    2015-01-01

    This paper argues that the adoption of an inflation target reduces the persistence of inflation. We develop the theoretical literature on inflation persistence by introducing a Taylor rule for monetary policy into a model of persistence and showing that inflation targets reduce inflation persistence. We investigate changes in the time series properties of inflation in seven countries that introduced inflation targets in the late 1980s or early 1990s. We find that the persistenc...

  4. Persistence of autoreactive T cell drive is required to elicit anti-chromatin antibodies in a murine model of drug-induced lupus.

    Science.gov (United States)

    Kretz-Rommel, A; Rubin, R L

    1999-01-15

    Long-term treatment with procainamide and numerous other medications is occasionally associated with the development of drug-induced lupus. We recently established a murine model for this syndrome by disrupting central T cell tolerance. Two intrathymic injections of procainamide-hydroxylamine (PAHA), a reactive metabolite of procainamide, into (C57BL/6 x DBA/2)F1 mice resulted in the appearance of chromatin-reactive T cells and anti-chromatin autoantibodies. The current study explores in this model the role of autoreactive T cells in autoantibody production and examines why autoantibodies after a single intrathymic drug injection were much more limited in isotype and specificity. Injection of as few as 5000 chromatin-reactive T cells into naive, syngeneic mice induced a rapid IgM anti-denatured DNA response, while injection of at least 100-fold greater number of activated T cells was required for induction of IgG anti-chromatin Abs, suggesting that small numbers of autoreactive T cells can be homeostatically controlled. Mice subjected to a single intrathymic PAHA injection after receiving splenic B cells from an intrathymic PAHA-injected syngeneic donor also developed anti-chromatin Abs, but adoptive transfer of similarly primed T cells or of B cells without intrathymic PAHA injection of the recipient failed to produce an anti-chromatin response. However, anti-chromatin Abs developed after a single intrathymic PAHA injection in Fas-deficient C57BL/6-lpr/lpr mice, suggesting that activation-induced cell death limited autoimmunity in normal mice. Taken together, these results imply that chromatin-reactive T cells produced by intrathymic PAHA created a B cell population primed to somatically mutate and Ig class switch when subjected to a heavy load or second wave of autoreactive T cells.

  5. Intraoperative EBRT and resection for renal cell carcinoma. Twenty-year outcomes

    Energy Technology Data Exchange (ETDEWEB)

    Calvo, F.A. [Hospital Gneral Universitario Gregorio Maranon, Madrid (Spain). Dept. of Oncology; Complutense Univ., Madrid (Spain). School of Medicine; Sole, C.V. [Hospital Gneral Universitario Gregorio Maranon, Madrid (Spain). Dept. of Oncology; Complutense Univ., Madrid (Spain). School of Medicine; Instituto de Radiomedicina, Santiago (Spain). Service of Radiation Oncology; Martinez-Monge, R.; Aristu, J. [Clinica Universitaria de Navarra, Pamplona (Spain). Dept. of Radiation Oncology; Azinovic, I. [Hospital de San Jaime, Torrevieja (Spain). Dept. of Radiation Oncology; Zudaire, J.; Berian, J.M. [Clinica Universitaria de Navarra, Pamplona (Spain). Dept. of Urology; Garcia-Sabrido, J.L. [Hospital General Universitario Gregorio Maranon, Madrid (Spain). Dept. of General Surgery

    2013-02-15

    Purpose: We report the outcomes of a multimodality treatment approach combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) with or without external beam radiation therapy (EBRT) in patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC. Patients and methods: From 1983 to 2008, 25 patients with LR recurrent (n = 10) or LR advanced primary (n = 15) RCC were treated with this approach. Median patient age was 60 years (range, 16-79 years). Fifteen patients (60%) received perioperative EBRT (median dose, 44 Gy). Surgical resection was R0 (negative margins) in 6 patients (24%) and R1 (residual microscopic disease) in 19 patients (76%). The median dose of IOERT was 14 Gy (range, 9-15). Overall survival (OS) and relapse patterns were calculated using the Kaplan-Meier method. Results: Median follow-up for surviving patients was 22.2 years (range, 3.6-26 years). OS and DFS at 5 and 10 years were 38% and 18% and 19% and 14%, respectively. LR control (tumor bed or regional lymph nodes) and distant metastases-free survival rates at 5 years were 80% and 22%, respectively. The death rate within 30 days of surgery and IOERT was 4% (n = 1). Six patients (24%) experienced acute or late toxicities of grade 3 or higher according to the National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) v4. Conclusion: In patients with LR recurrent or LR advanced primary RCC, a multimodality approach consisting of maximal surgical resection and IOERT with or without adjuvant EBRT yielded encouraging local control results, justifying further evaluation. (orig.)

  6. Persistence of gamma-H2AX and 53BP1 foci in proliferating and nonproliferating human mammary epithelial cells after exposure to gamma-rays or iron ions

    Energy Technology Data Exchange (ETDEWEB)

    Groesser, Torsten; Chang, Hang; Fontenay, Gerald; Chen, James; Costes, Sylvain V.; Barcellos-Hoff, Mary Helen; Parvin, Bahram; Rydberg, Bjorn

    2010-12-22

    To investigate {gamma}-H2AX (phosphorylated histone H2AX) and 53BP1 (tumour protein 53 binding protein No. 1) foci formation and removal in proliferating and non-proliferating human mammary epithelial cells (HMEC) after exposure to sparsely and densely ionizing radiation under different cell culture conditions. HMEC cells were grown either as monolayers (2D) or in extracellular matrix to allow the formation of acinar structures in vitro (3D). Foci numbers were quantified by image analysis at various time points after exposure. Our results reveal that in non-proliferating cells under 2D and 3D cell culture conditions, iron-ion induced {gamma}-H2AX foci were still present at 72 h after exposure, although 53BP1 foci returned to control levels at 48 h. In contrast in proliferating HMEC, both {gamma}-H2AX and 53BP1 foci decreased to control levels during the 24-48 h time interval after irradiation under 2D conditions. Foci numbers decreased faster after {gamma}-ray irradiation and returned to control levels by 12 h regardless of marker, cell proliferation status, and cell culture condition. Conclusions: The disappearance of radiation induced {gamma}-H2AX and 53BP1 foci in HMEC have different dynamics that depend on radiation quality and proliferation status. Notably, the general patterns do not depend on the cell culture condition (2D versus 3D). We speculate that the persistent {gamma}-H2AX foci in iron-ion irradiated non-proliferating cells could be due to limited availability of double strand break (DSB) repair pathways in G0/G1-phase, or that repair of complex DSB requires replication or chromatin remodeling.

  7. Persistent Leukocytosis—Is this a Persistent Problem for Patients with Acute Ischemic Stroke?

    Science.gov (United States)

    Boehme, Amelia K.; Kumar, Andre D.; Lyerly, Michael J.; Gillette, Michael A.; Siegler, James E.; Albright, Karen C.; Beasley, T. Mark; Martin-Schild, Sheryl

    2016-01-01

    Background In the setting of acute ischemic stroke (AIS), leukocytosis has been shown to be an indicator of inflammatory response. Although leukocytosis on admission has been shown to correlate with initial stroke severity in AIS patients, no work has been done to assess if there are differences in transient or persistent leukocytosis in patients without infection. The objective of this study is to determine the clinical significance of persistent versus transient leukocytosis during the early phase of AIS. Methods Patients who presented with AIS to our center within 48 hours of symptom onset between July 2008 and June 2010 were retrospectively identified by chart review. Patients were included if they had leukocytosis on admission (defined as white blood cell count >11,000/μL based on laboratory reference range values). A logistic regression model was used to evaluate persistent leukocytosis (leukocytosis 48 hours after admission) as a predictor of several outcome measures, including good functional outcome (discharge modified Rankin Scale score of 0-2). Marginal effects were used to estimate the probability of poor functional outcome. Results Of the 438 patients screened, 49 had leukocytosis on admission and of those 24 (49%) had persistent leukocytosis. NIHSS score correlated significantly with persistence of leukocytosis (r = .306; P =.0044). More people with transient leukocytosis (leukocytosis lasting <48 hours) had a good functional outcome (44% versus 16%; P = .006). After adjusting for baseline NIHSS score, persistent leukocytosis was not a significant independent predictor of good functional outcome, but showed an association (OR, 2.5; 95% CI, .562-10.7; P = .2322). Persistent leukocytosis after adjusting for age and NIHSS score at admission is associated with a poor functional outcome, but it is not statistically significant (OR, 2.43; 95% CI, .59-9.87; P = .2151). After controlling for age and NIHSS score on admission, for patients with persistent

  8. Caliber-persistent labial artery.

    Science.gov (United States)

    Lewis, David M

    2003-01-01

    Caliber-persistent labial artery presents as a soft tissue elevation of labial mucosa that can be bluish or normal in color, disappears when stretched, and pulsates on gentle palpation. Often the artery can be visualized through the stretched mucosa. Such lesions occur in an elderly population (average age = 58 years), are equally distributed between males and females, and are twice as common in the upper lip than in the lower (Figs. 4 & 5). The occurrence of multiple lesions has been reported, along with increased incidence of other vascular lesions. The [figure: see text] lesions are usually asymptomatic with a few being associated with surface ulceration. When the lesion is clinically mistaken for a mucocele, fibroma [figure: see text] or other vascular lesion and biopsied, brisk bleeding is encountered. PMID:12674712

  9. TCR's genetically linked to CD28 and CD3e do not mispair with endogous TCR chains and mediate enhanced T cell persistance and anti-melanoma activity

    NARCIS (Netherlands)

    Govers, C.C.F.M.; Sebestyen, Z.; Roszik, J.; Brakel, van M.; Berrevoets, C.; Szoor, A.; Panoutsopoulou, K.; Broertjes, M.; Van, T.; Vereb, G.; Szollosi, J.; Debets, R.

    2014-01-01

    Adoptive transfer of T cells that are gene engineered to express a defined TCR represents a feasible and promising therapy for patients with tumors. However, TCR gene therapy is hindered by the transient presence and effectiveness of transferred T cells, which are anticipated to be improved by adequ

  10. Inflation Targeting and Inflation Persistence

    Institute of Scientific and Technical Information of China (English)

    GEORGE; J.BRATSIOTIS; JAKOB; MADSEN; CHRISTOPHER; MARTIN

    2015-01-01

    This paper argues that the adoption of an inflation target reduces the persistence of inflation.We develop the theoretical literature on inflation persistence by introducing a Taylor Rule for monetary policy into a model of persistence and showing that inflation targets reduce inflation persistence.We investigate changes in the time series properties of inflation in seven countries that introduced inflation targets in the late 1980s or early 1990s.We find that the persistence of inflation is greatly reduced or eliminated following the introduction of inflation targets.

  11. 浙江省近50年持续性暴雨事件的天气气候分析%The Weather and Climate Analysis of the Persistent Heavy Rainfall in Zhejiang Province in the Last 50 Years

    Institute of Scientific and Technical Information of China (English)

    姜盈

    2012-01-01

    The persistent heavy rain cases in Zhejiang province from 1961 to 2008 were analyzed and discussed by utilizing the daily precipitation data at stations in Zhejiang and NCEP/NCAR reanalysis data from 1961 to 2008. Based on the statistics and the different of 500hPa upper air synoptic situation,circulation background of the regional persistent heavy rain can be divided into two different types: (1) tropical depression, (2) westerly trough. The analyzed results indicate that: (1) the persistent heavy rainfall in Zhejiang province concentrates during meiyu and autumn flood period, and it happens more frequent in the western part of Zhejiang than any other parts; (2)the west wind trough,tropical depression , subtropical high and jet are the main motion systems that lead to the persistent heavy rainfall in Zhejiang whose location is closely correlated with the impact system. The distribution of the strength of the precipitation changes with different motion systems.%用1961-2008年的浙江省各台站的逐日降水量资料和NCEP/NCAR的逐日再分析资料对浙江省1961-2008年发生的持续性暴雨过程进行统计分析,探讨近50年来浙江省持续性暴雨的主要特征.在统计的基础上,进一步对造成浙江省大范围持续性暴雨过程的主要影响系统进行归类和研究,本文将浙江省持续性暴雨过程的影响系统分为:(1)热带低压类;(2)西风带类两大类.结果表明:(1)浙江省持续性暴雨主要集中在梅汛期和秋汛期,浙西的持续性暴雨过程多于其他地区;(2)热带低压和西风带低槽、高低空急流、副热带高压是导致浙江省持续性暴雨发生的重要天气系统.其雨带位置的分布与系统所在的位置密切相关,降水强度的分布随着影响系统的不同而变化.

  12. Employment Status as an Indicator of Recovery and Function One Year after Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Morrison, Eleshia J; Ehlers, Shawna L; Bronars, Carrie A; Patten, Christi A; Brockman, Tabetha A; Cerhan, James R; Hogan, William J; Hashmi, Shahrukh K; Gastineau, Dennis A

    2016-09-01

    Employment after hematopoietic stem cell transplantation (HSCT) is an indicator of post-transplantation recovery and function, with economic and social implications. As survival rates for HSCT continue to improve, greater emphasis can be placed on factors affecting the quality of post-transplantation survival, including the ability to resume employment. A sample of recipients of autologous or allogeneic HSCT was accrued (n = 1000) to complete a longitudinal lifestyle survey before transplantation and at 1 year after transplantation. The present study examines associations between employment and patient characteristics, disease variables, illness status, and quality of life among 1-year survivors (n = 702). Participants had a mean age of 55 years (range, 18 to 78) and were predominately male (59.7%), married/partnered (77.1%), and non-Hispanic Caucasian (89.5%); most (79.4%) had received autologous transplantation. Of the 690 participants reporting some form of employment before illness diagnosis, 62.4% had returned to work by 1 year after HSCT. Full-time employment at 1 year after HSCT was significantly associated with remission of illness, improved illness, fewer post-transplantation hospitalizations, less fatigue and pain, higher quality of life, and higher rating of perceived health. Those unemployed because of their health reported the highest rates of fatigue and pain and lowest quality of life, and they were most likely to report poor perceived health. These findings highlight work reintegration as an important outcome and marker of survivors' overall adjustment after transplantation. Identifying factors affecting post-transplantation employment offers opportunities for behavioral interventions to target modifiable risk factors to optimize post-transplantation survivorship, inclusive of increased rates of return to work and decreased rates of associated disability. PMID:27220264

  13. Employment Status as an Indicator of Recovery and Function One Year after Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Morrison, Eleshia J; Ehlers, Shawna L; Bronars, Carrie A; Patten, Christi A; Brockman, Tabetha A; Cerhan, James R; Hogan, William J; Hashmi, Shahrukh K; Gastineau, Dennis A

    2016-09-01

    Employment after hematopoietic stem cell transplantation (HSCT) is an indicator of post-transplantation recovery and function, with economic and social implications. As survival rates for HSCT continue to improve, greater emphasis can be placed on factors affecting the quality of post-transplantation survival, including the ability to resume employment. A sample of recipients of autologous or allogeneic HSCT was accrued (n = 1000) to complete a longitudinal lifestyle survey before transplantation and at 1 year after transplantation. The present study examines associations between employment and patient characteristics, disease variables, illness status, and quality of life among 1-year survivors (n = 702). Participants had a mean age of 55 years (range, 18 to 78) and were predominately male (59.7%), married/partnered (77.1%), and non-Hispanic Caucasian (89.5%); most (79.4%) had received autologous transplantation. Of the 690 participants reporting some form of employment before illness diagnosis, 62.4% had returned to work by 1 year after HSCT. Full-time employment at 1 year after HSCT was significantly associated with remission of illness, improved illness, fewer post-transplantation hospitalizations, less fatigue and pain, higher quality of life, and higher rating of perceived health. Those unemployed because of their health reported the highest rates of fatigue and pain and lowest quality of life, and they were most likely to report poor perceived health. These findings highlight work reintegration as an important outcome and marker of survivors' overall adjustment after transplantation. Identifying factors affecting post-transplantation employment offers opportunities for behavioral interventions to target modifiable risk factors to optimize post-transplantation survivorship, inclusive of increased rates of return to work and decreased rates of associated disability.

  14. Diffuse large B-cell non Hodgkin's lymphoma in a 65-year-old woman presenting with hypopituitarism and recovering after chemotherapy: a case report

    Directory of Open Access Journals (Sweden)

    Hyer Steve L

    2011-10-01

    Full Text Available Abstract Introduction Diffuse large B-cell non Hodgkin's lymphoma may involve the pituitary either as a primary central nervous system lymphoma or, more frequently, as metastasis from systemic lymphoma leading to hypopituitarism. A partial recovery of pituitary function after treatment with chemotherapy has previously been described but complete recovery with cessation of all hormone supplements is excessively rare. We report a patient presenting with anterior hypopituitarism with subsequent complete and sustained recovery of pituitary function after successful treatment of the lymphoma. Case presentation A 65-year-old Caucasian woman with lethargy, loss of appetite and peripheral edema was found to have anterior hypopituitarism. Magnetic resonance imaging showed no mass lesions in the pituitary although a positron emission tomography scan showed abnormal pituitary activity. An abdominal computed tomography scan revealed multiple intra-abdominal lymph nodes, which on histology proved diagnostic of diffuse large B-cell non Hodgkin's lymphoma. She received six cycles of R-CHOP chemotherapy, after which she achieved a complete metabolic response at all known previous sites of the disease, confirmed by positron emission tomography scanning. Concomitant with the tumor response, there was full recovery of adrenal, thyroid and gonadal axes which has persisted at 10 months follow-up. Conclusion Although rare, it is important to recognize lymphomatous infiltration of the pituitary as a potentially reversible cause of hypopituitarism.

  15. [Vascular prostheses: 50 years of advancement from synthetic towards tissue engineering and cell therapy].

    Science.gov (United States)

    Chlupác, J; Filová, E; Bacáková, L

    2010-01-01

    Since more than 50 years, the gold standard in synthetic vascular prostheses has been represented by polyethylene terephtalate (PET, Dacron) and expanded polytetrafluoroethylene (ePTFE). These polymers perform well as sustitutes of large-caliber vessels, however, their long-term patencies are disappointing in small-caliber applications (< 6 mm). Thus, patient's own artery or vein remains the material of choice in coronary, crural or microvessel bypass surgery. Synthetic materials fail due to thrombosis and insufficient healing process that consists in highly incomplete endothelial cells coverage and intimal hyperplasia caused by compliance mismatch and hemodynamic imbalance. To find better small-caliber vascular graft, surgical techniques have been modified, novel biomaterials have been investigated and cell and tissue culture technologies have been adopted. Partly or fully tissue-engineered vascular grafts have been produced and experimentally and clinically evaluated with some promising result. The aim of this review is to briefly list currently used and examined vascular graft materials with special attention to cell/biomaterial ineractions, tissue engineering and authors' own experience. PMID:21351411

  16. Persistence of airline accidents.

    Science.gov (United States)

    Barros, Carlos Pestana; Faria, Joao Ricardo; Gil-Alana, Luis Alberiko

    2010-10-01

    This paper expands on air travel accident research by examining the relationship between air travel accidents and airline traffic or volume in the period from 1927-2006. The theoretical model is based on a representative airline company that aims to maximise its profits, and it utilises a fractional integration approach in order to determine whether there is a persistent pattern over time with respect to air accidents and air traffic. Furthermore, the paper analyses how airline accidents are related to traffic using a fractional cointegration approach. It finds that airline accidents are persistent and that a (non-stationary) fractional cointegration relationship exists between total airline accidents and airline passengers, airline miles and airline revenues, with shocks that affect the long-run equilibrium disappearing in the very long term. Moreover, this relation is negative, which might be due to the fact that air travel is becoming safer and there is greater competition in the airline industry. Policy implications are derived for countering accident events, based on competition and regulation.

  17. Bacterial persistence: a winning strategy?

    CERN Document Server

    Schinazi, Rinaldo B

    2011-01-01

    It has long been known that antibiotic treatment will not completely kill off a bacteria population. For many species a small fraction of bacteria is not sensitive to antibiotics. These bacteria are said to persist. Recently it has been shown that persistence is not a permanent state and that in fact a bacterium can switch back and forth between persistent and non persistent states. We introduce two stochastic models for bacteria persistence. In both models there are mass killings of non persistent bacteria at certain times. The first model has deterministic killing times and the second one has random killing times. Both models suggest that persistence may be a successful strategy for a wide range of parameter values.

  18. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans

    Science.gov (United States)

    Borgogni, Erica; Zedda, Luisanna; Cantisani, Rocco; Chiappini, Nico; Schiavetti, Francesca; Rosa, Domenico; Castellino, Flora; Montomoli, Emanuele; Bodinham, Caroline L.; Lewis, David J.; Medini, Duccio; Bertholet, Sylvie; Del Giudice, Giuseppe

    2016-01-01

    CD4+ T follicular helper cells (TFH) have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4+IL-21+ICOS1+ T helper (TH) cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV), MF59®-adjuvanted TIIV (ATIIV), or saline placebo. Frequencies of circulating CD4+ TFH1 ICOS+ TFH cells and H1N1-specific CD4+IL-21+ICOS+ CXCR5+ TFH and CXCR5- TH cell subsets were determined at various time points after vaccination and were then correlated with hemagglutination inhibition (HI) titers. All three CD4+ T cell subsets expanded in response to TIIV and ATIIV, and peaked 7 days after vaccination. To demonstrate that these TFH cell subsets correlated with functional antibody titers, we defined an alternative endpoint metric, decorrelated HI (DHI), which removed any correlation between day 28/day 168 and day 0 HI titers, to control for the effect of preexisting immunity to influenza vaccine strains. The numbers of total circulating CD4+ TFH1 ICOS+ cells and of H1N1-specific CD4+IL-21+ICOS+ CXCR5+, measured at day 7, were significantly associated with day 28, and day 28 and 168 DHI titers, respectively. Altogether, our results show that CD4+ TFH subsets may represent valuable biomarkers of vaccine-induced long-term functional immunity. Trial Registration ClinicalTrials.gov NCT01771367 PMID:27336786

  19. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans.

    Science.gov (United States)

    Spensieri, Fabiana; Siena, Emilio; Borgogni, Erica; Zedda, Luisanna; Cantisani, Rocco; Chiappini, Nico; Schiavetti, Francesca; Rosa, Domenico; Castellino, Flora; Montomoli, Emanuele; Bodinham, Caroline L; Lewis, David J; Medini, Duccio; Bertholet, Sylvie; Del Giudice, Giuseppe

    2016-01-01

    CD4+ T follicular helper cells (T(FH)) have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4(+)IL-21(+)ICOS1(+) T helper (T(H)) cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV), MF59(®)-adjuvanted TIIV (ATIIV), or saline placebo. Frequencies of circulating CD4(+) T(FH)1 ICOS(+) T(FH) cells and H1N1-specific CD4(+-)IL-21(+)ICOS(+) CXCR5(+) T(FH) and CXCR5(-) T(H) cell subsets were determined at various time points after vaccination and were then correlated with hemagglutination inhibition (HI) titers. All three CD4(+) T cell subsets expanded in response to TIIV and ATIIV, and peaked 7 days after vaccination. To demonstrate that these T(FH) cell subsets correlated with functional antibody titers, we defined an alternative endpoint metric, decorrelated HI (DHI), which removed any correlation between day 28/day 168 and day 0 HI titers, to control for the effect of preexisting immunity to influenza vaccine strains. The numbers of total circulating CD4(+)T(FH)1 ICOS(+) cells and of H1N1-specific CD4(+)IL-21(+)ICOS(+) CXCR5(+), measured at day 7, were significantly associated with day 28, and day 28 and 168 DHI titers, respectively. Altogether, our results show that CD4(+) T(FH) subsets may represent valuable biomarkers of vaccine-induced long-term functional immunity. PMID:27336786

  20. Calibre persistent labial artery: clinical features and noninvasive radiological diagnosis.

    Science.gov (United States)

    Kocyigit, P; Kocyigit, D; Akay, B N; Ustuner, E; Kisnisci, R

    2006-07-01

    Calibre persistent labial artery (CPLA) is defined as a primary arterial branch that penetrates into the submucosal tissue without division or decrease in diameter. It usually presents as an asymptomatic papule on the lower lip and can be easily misdiagnosed as a varix, haemangioma, venous lake, mucocele or fibroma. When it is ulcerated, squamous cell carcinoma is the most usual differential diagnosis. The most frequently used method to confirm the diagnosis of CPLA has been excisional biopsy, which carries the risk of profuse bleeding. Angiography, another invasive method, has also been used. Here, we report a case of a 20-year-old woman with a 5-year history of multiple CPLA lesions involving both upper and lower lips. In this case, the diagnosis was made clinically and confirmed by Doppler ultrasonography, which is a noninvasive and simple diagnostic tool. PMID:16716155

  1. A Longitudinal Behavioral Genetic Analysis of Task Persistence

    Science.gov (United States)

    Deater-Deckard, Kirby; Petrill, Stephen A.; Thompson, Lee A.; DeThorne, Laura S.

    2006-01-01

    Change in task persistence was assessed in two annual assessments using teachers', testers', and observers' ratings. Participants included 79 monozygotic and 116 same-sex dizygotic twin pairs who were in Kindergarten or 1st grade (4.3 to 7.9 years old) at the initial assessment. Task persistence was widely distributed and higher among older…

  2. Effect of montelukast as monotherapy in mild persistent asthma

    Directory of Open Access Journals (Sweden)

    Bharathi Senthilvelan

    2015-12-01

    Conclusions: Montelukast provides significant symptom control and improvement in PEFR in mild persistent asthma compared to placebo. It is effective as monotherapy in mild persistent asthma in children aged 2-12 years. Symptom control is good during therapy and until three months after discontinuation of drug. [Int J Res Med Sci 2015; 3(12.000: 3786-3789

  3. Vehicle Technologies and Fuel Cell Technologies Program: Prospective Benefits Assessment Report for Fiscal Year 2016

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, T. S. [Argonne National Lab. (ANL), Argonne, IL (United States); Taylor, C. H. [TA Engineering, Inc., Catonsville, MD (United States); Moore, J. S. [TA Engineering, Inc., Catonsville, MD (United States); Ward, J. [United States Department of Energy, Washington, DC (United States). Office of Energy Efficiency and Renewable Energy

    2016-02-23

    % higher than in the No Program case. On-road medium- and heavy-duty vehicle stock could be as much as 39% higher. The resulting petroleum savings in 2035 were estimated to be as high as 3.1 million barrels per day, and reductions in GHG emissions were estimated to be as high as 500 million metric tons of CO2 equivalent per year. The benefits of continuing to invest government resources in advanced vehicle and fuel cell technologies would have significant economic value in the U.S. transportation sector and reduce its dependency on oil and its vulnerability to oil price shocks.

  4. Systematic Epstein-Barr virus-positive T-cell lymphoproliferative disease presenting as a persistent fever and cough: a case report

    OpenAIRE

    Ameli, Fereshteh; Ghafourian, Firouzeh; Masir, Noraidah

    2014-01-01

    Introduction Systemic Epstein-Barr virus-positive T-cell lymphoproliferative childhood disease is an extremely rare disorder and classically arises following primary acute or chronic active Epstein-Barr virus infection. It is characterized by clonal proliferation of Epstein-Barr virus-infected T-cells with an activated cytotoxic phenotype. This disease has a rapid clinical course and is more frequent in Asia and South America, with relatively few cases being reported in Western countries. The...

  5. The Attenuated Brucella abortus Strain 19 Invades, Persists in, and Activates Human Dendritic Cells, and Induces the Secretion of IL-12p70 but Not IL-23

    OpenAIRE

    Mario Weinhold; Martin Eisenblätter; Edith Jasny; Michael Fehlings; Antje Finke; Hermine Gayum; Ursula Rüschendorf; Pablo Renner Viveros; Verena Moos; Kristina Allers; Thomas Schneider; Schaible, Ulrich E; Schumann, Ralf R.; Martin E Mielke; Ralf Ignatius

    2013-01-01

    Background: Bacterial vectors have been proposed as novel vaccine strategies to induce strong cellular immunity. Attenuated strains of Brucella abortus comprise promising vector candidates since they have the potential to induce strong CD4+ and CD8+ T-cell mediated immune responses in the absence of excessive inflammation as observed with other Gram-negative bacteria. However, some Brucella strains interfere with the maturation of dendritic cells (DCs), which is essential for antigen-speci...

  6. Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs.

    Science.gov (United States)

    Muñoz-González, Sara; Perez-Simó, Marta; Muñoz, Marta; Bohorquez, José Alejandro; Rosell, Rosa; Summerfield, Artur; Domingo, Mariano; Ruggli, Nicolas; Ganges, Llilianne

    2015-07-09

    Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs.

  7. Efficacy of a live attenuated vaccine in classical swine fever virus postnatally persistently infected pigs.

    Science.gov (United States)

    Muñoz-González, Sara; Perez-Simó, Marta; Muñoz, Marta; Bohorquez, José Alejandro; Rosell, Rosa; Summerfield, Artur; Domingo, Mariano; Ruggli, Nicolas; Ganges, Llilianne

    2015-01-01

    Classical swine fever (CSF) causes major losses in pig farming, with various degrees of disease severity. Efficient live attenuated vaccines against classical swine fever virus (CSFV) are used routinely in endemic countries. However, despite intensive vaccination programs in these areas for more than 20 years, CSF has not been eradicated. Molecular epidemiology studies in these regions suggests that the virus circulating in the field has evolved under the positive selection pressure exerted by the immune response to the vaccine, leading to new attenuated viral variants. Recent work by our group demonstrated that a high proportion of persistently infected piglets can be generated by early postnatal infection with low and moderately virulent CSFV strains. Here, we studied the immune response to a hog cholera lapinised virus vaccine (HCLV), C-strain, in six-week-old persistently infected pigs following post-natal infection. CSFV-negative pigs were vaccinated as controls. The humoral and interferon gamma responses as well as the CSFV RNA loads were monitored for 21 days post-vaccination. No vaccine viral RNA was detected in the serum samples and tonsils from CSFV postnatally persistently infected pigs for 21 days post-vaccination. Furthermore, no E2-specific antibody response or neutralising antibody titres were shown in CSFV persistently infected vaccinated animals. Likewise, no of IFN-gamma producing cell response against CSFV or PHA was observed. To our knowledge, this is the first report demonstrating the absence of a response to vaccination in CSFV persistently infected pigs. PMID:26159607

  8. Persistent Aerial Tracking

    KAUST Repository

    Mueller, Matthias

    2016-04-13

    In this thesis, we propose a new aerial video dataset and benchmark for low altitude UAV target tracking, as well as, a photo-realistic UAV simulator that can be coupled with tracking methods. Our benchmark provides the rst evaluation of many state of-the-art and popular trackers on 123 new and fully annotated HD video sequences captured from a low-altitude aerial perspective. Among the compared trackers, we determine which ones are the most suitable for UAV tracking both in terms of tracking accuracy and run-time. We also present a simulator that can be used to evaluate tracking algorithms in real-time scenarios before they are deployed on a UAV "in the field", as well as, generate synthetic but photo-realistic tracking datasets with free ground truth annotations to easily extend existing real-world datasets. Both the benchmark and simulator will be made publicly available to the vision community to further research in the area of object tracking from UAVs. Additionally, we propose a persistent, robust and autonomous object tracking system for unmanned aerial vehicles (UAVs) called Persistent Aerial Tracking (PAT). A computer vision and control strategy is applied to a diverse set of moving objects (e.g. humans, animals, cars, boats, etc.) integrating multiple UAVs with a stabilized RGB camera. A novel strategy is employed to successfully track objects over a long period, by \\'handing over the camera\\' from one UAV to another. We integrate the complete system into an off-the-shelf UAV, and obtain promising results showing the robustness of our solution in real-world aerial scenarios.

  9. Squamous cell carcinoma of the oral cavity; An unselected material from a 5-year period

    Energy Technology Data Exchange (ETDEWEB)

    Lindeloev, B.; Kirkegaard, J.; Hansen, H.S. (Copenhagen Univ. Hospital (Denmark). Dept. of Head and Neck Oncology Copenhagen Univ. Hospital (Denmark). Dept. of Otolaryngology)

    1990-01-01

    Three hundred and four patients with squamous cell carcinomas of the oral cavity were treated at the Finsen Institute in cooperation with the ENT-surgical departments between 1978 and 1982. The primary treatment consisted of radiotherapy alone in 74%, surgery alone in 4%, and a combination of radiotherapy and surgery in 15% of the patients. 2% received other treatment (cryotherapy), 5% did not complete the planned radiotherapy, and 1% were not treated at all. Of 203 patients with tumour remnant or first recurrence, 45% were operated, 2% received radiotherapy, and 2% combined treatment. This treatment strategy made 38% of the patients free of disease in the follow-up period (3 1/2 to 8 years) or until the patients died from other causes. Fifty-nine percent of the patients died from their oral carcinomas. Tumour size (T), lymph node status (N), and tumour stage were as expected important prognostic factors. (orig.).

  10. Patients' experience of sexuality 1-year after allogeneic Haematopoietic Stem Cell Transplantation

    DEFF Research Database (Denmark)

    Nørskov, Kristina H; Schmidt, Mette; Jarden, Mary

    2015-01-01

    body image, which directly or indirectly resulted in sexual dysfunction or problems with intimacy. Symptoms related to chronic GVHD, could explain experiences of sexual dysfunction. Sexual needs were deprioritized as survival became paramount. The experience of changed social roles, both in family life...... and social network, affected self-image and identity. Finally, communication about sexuality and sexual needs was of significant importance to the current state of their relationship. CONCLUSION: Physical body alterations, challenges in mastering their new life situation and identity changes affected......PURPOSE: This study explores how patients' experience of sexuality is influenced by physical, psychological and social changes one year after undergoing haematopoietic stem cell transplantation (HSCT). METHODS: A qualitative study using semi-structured in-depth interviews. The respondents (n = 9...

  11. Chronic hepatitis caused by persistent parvovirus B19 infection

    Directory of Open Access Journals (Sweden)

    Mogensen Trine H

    2010-08-01

    Full Text Available Abstract Background Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions. Case Presentation Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection. Conclusions In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual

  12. Clinicopathological and immunohistochemical features of primary central nervous system germ cell tumors: a 24-years experience.

    Science.gov (United States)

    Gao, Yuping; Jiang, Jiyao; Liu, Qiang

    2014-01-01

    Primary central nervous system (CNS) germ cell tumors (GCTs) are a rare heterogeneous group of lesions, which the clinicopathological features have a marked degree of heterogeneity comparing with that of gonadal GCTs. Accurately diagnosing CNS GCTs might be extremely difficult and requires immunohistochemical verification. This study was to investigate the biological feature of CNS GCTs and diagnostic value of immunohistochemical markers OCT3/4, C-kit, PLAP, and CD30 in CNS GCTs. A retrospective study was performed on 34 patients with CNS germ cell tumors between 1990 and 2014. 34 CNS GCTs account for 9.2% of all primary CNS neoplasms. The sellar region (35.3%) and pineal gland (17.6%) were the most common sites of intracranial GCTs. Hydrocephalus (82.4%) and diplopia (46.9%) were the two most common clinical presentations. The most common histological subtypes were germinoma (67.6%). PLAP, c-kit, OCT3/4 were highly expressed in gernimomas. CD30 and CK AE1/3 stainings were positive in embryonal carcinoma. Yolk sac tumor component showed positive staining for AFP and CK AE1/3. β-HCG staining was positive in choriocarcinoma and STGC. Patients with mature teratomas and germinomas had a better prognosis (a 5-year survival rate) than those with embryonal carcinoma and choriocarcinoma (a 5-year survival rates were 0). Our finding suggest that the incidences of primary CNS GCTs are higher in South China than in the West, but mixed GCTs are uncommon in our study. The judicious use of a panel of selected markers is helpful in diagnosing and predicting the prognosis for CNS GCTs.

  13. Perivascular epithelioid cell tumour of the vagina in an 8 year old girl.

    Science.gov (United States)

    Ong, Lin Yin; Hwang, Wei Sek; Wong, Adelina; Chan, Mei Yoke; Chui, Chan Hon

    2007-03-01

    Perivascular epithelioid cell tumor (PEComa) is a rare mesenchymal tumor with an unpredictable natural history. We present the first reported case of PEComa of the vagina diagnosed in an 8-year-old girl. This was initially diagnosed on biopsy as an embryonal rhabdomyosarcoma, and the patient underwent 3 cycles of chemotherapy according to the Mesenchymal Malignant Tumour 1989 protocol. A repeat scan, however, revealed an increase in tumor size. Total resection was achieved via a transvaginal (vertical sleeve) partial vaginectomy. The resected tumor had the typical appearance of a PEComa. Immunostains showed positive staining of tumor cells for HMB45, neuron-specific enolase, and calponin but were negative for S100 protein, melaninA, chromogranin, smooth muscle actin, desmin, caldesmon, epithelial membrane antigen, AE1/3, and synaptophysin. Six months after surgery, she remains free of tumor and is on follow-up with regular local examinations under anesthesia and computed tomography scans. Our case highlights the importance of an accurate initial diagnosis, and we stress the importance of regular surveillance over a significant period. PMID:17336201

  14. 25 Years of Tension over Actin Binding to the Cadherin Cell Adhesion Complex: The Devil is in the Details.

    Science.gov (United States)

    Nelson, W James; Weis, William I

    2016-07-01

    Over the past 25 years, there has been a conceptual (re)evolution in understanding how the cadherin cell adhesion complex, which contains F-actin-binding proteins, binds to the actin cytoskeleton. There is now good synergy between structural, biochemical, and cell biological results that the cadherin-catenin complex binds to F-actin under force. PMID:27166091

  15. A Gluteal Mass Of Langerhans Cell Histiocytosis Mimicking Malignancy In A Two-Year-Old Boy: A Case Report

    OpenAIRE

    Ibrahim, Zainal Abidin; Lung, Wong Siong; Long, Pan Kok

    2009-01-01

    Langerhans cell histiocytosis is a disease primarily affects the bone. More than 50 percent of the disease occurs between the age of 1 and 15. We reported a case of a 2 year old boy who presented with a gluteal mass. Radiographic imaging showed an osteolytic lesion suspicious of malignancy. However, the histological diagnosis was Langerhans cell histiocytosis.

  16. A 150-year record of coastline dynamics within a sediment cell: Eastern England

    Science.gov (United States)

    Montreuil, Anne-Lise; Bullard, Joanna E.

    2012-12-01

    Coastal sediment cells reflect processes operating at a range of scales, but it is the medium spatial and temporal scales (decades to centuries) that are of greatest interest for coastal management. This paper focuses on coastline position change within a single sediment cell over 150 years where the geomorphology includes cliffs, beaches and saltmarshes. The focus is the east coast of England from Flamborough Head to Gibraltar Point. Although the updrift sector of this sediment cell has been studied for well over a century, the downdrift sector has attracted significantly less attention. Using topographic profiles, bathymetric profiles, aerial photographs and historical maps we mapped coastline erosion and accretion using the Digital Shoreline Analysis System (DSAS) and calculated volumetric changes for different morphometric units. Rapid erosion of the updrift Holderness cliffs has been counterbalanced with accretion on beaches along the downdrift Lincolnshire coast. The amount of accretion in Lincolnshire corresponds to around 29% of the volume of sediment eroded from Holderness. Much of the eroded cliff material is likely to be deposited temporarily into nearshore and offshore sand banks before being redistributed by cross-shore currents. An exploration of storm surge impact on long-term erosion and accretion rates showed no clear relationship between storm surge frequency and change in coastline position, however this may be in part due to the relative timing of storm occurrence and data acquisition. The Jenkinson daily weather type classification was found to be a reasonable proxy for the occurrence of strong onshore winds which may offer scope for further investigation of the role of forcing factors over time periods beyond the length of the meteorological and tidal station records. Winter North Atlantic Oscillation phase was not a good indicator of storminess on the east coast of England but may be a useful proxy for quiescence.

  17. Oral squamous cell carcinoma in patients twenty years of age or younger - Review and analysis of 186 reported cases

    NARCIS (Netherlands)

    L. Bodner; E. Manor; M.D. Friger; I. van der Waal

    2014-01-01

    To review the literature on reported cases of squamous cell carcinoma (SCC) of the oral cavity in patients twenty-years-of-age or younger. All well-documented cases of oral SCC in patients twenty-years-of-age or less, published between 1936 and 2012, were collected and the clinicopathologic features

  18. Persistence of social signatures in human communication

    OpenAIRE

    Saramäki, Jari; Leicht, E. A.; López, Eduardo; Roberts, Sam G. B.; Reed-Tsochas, Felix; Robin I M Dunbar

    2014-01-01

    We combine cell phone data with survey responses to show that a person’s social signature, as we call the pattern of their interactions with different friends and family members, is remarkably robust. People focus a high proportion of their communication efforts on a small number of individuals, and this behavior persists even when there are changes in the identity of the individuals involved. Although social signatures vary between individuals, a given individual appears to retain a specific...

  19. The pattern of immune cell infiltration in chromoblastomycosis: involvement of macrophage inflammatory protein-1 alpha/CCL3 and fungi persistence Padrão de infiltração de células do sistema imune na cromomicose: envolvimento de MIP-1 alfa da persistência fúngica

    Directory of Open Access Journals (Sweden)

    Vanuza Cristina Sá

    2007-02-01

    Full Text Available Chromoblastomycosis (CR is a subcutaneous chronic mycosis characterized by a granulomatous inflammatory response. However, little is known regarding the pattern of leukocyte subsets in CR and the pathways involved in their recruitment. The objective of this study was to assess the cellular subsets, chemokine, chemokine receptors and enzymes in CR. The inflammatory infiltrate was characterized by immunohistochemistry using antibodies against macrophages (CD68, Langerhans'cells (S100, lymphocytes (CD3, CD4, CD8, CD45RO, CD20 and CD56 and neutrophils (CD15. The expression of MIP-1alpha (Macrophage inflammatory protein-1alpha, chemokine receptors (CXCR3 and CCR1 and enzymes (superoxide dismutase-SOD and nitric oxide synthase-iNOS was also evaluated by the same method. We observed an increase in all populations evaluated when compared with the controls. Numbers of CD15+ and CD56+ were significantly lower than CD3+, CD4+, CD20+ and CD68+ cells. Statistical analysis revealed an association of fungi numbers with CD3, CD45RO and iNOS-positive cells. Furthermore, MIP-1alpha expression was associated with CD45RO, CD68, iNOS and CXCR3. Our results suggest a possible role of MIP-1alpha and fungi persistence in the cell infiltration in CR sites.A cromomicose é micose subcutânea crônica sistêmica caracterizada por resposta inflamatória crônica granulomatosa. No entanto, existem poucos dados a respeito do padrão de subtipos de leucócitos na cromomicose e sobre as vias envolvidas no recrutamento destas células. O objetivo deste trabalho foi avaliar os tipos celulares, bem como a expressão de quimiocinas, receptores de quimiocinas e enzimas em lesões de cromomicose. O infiltrado inflamatório foi caracterizado por meio de técnica imuno-histoquímica utilizando os seguintes marcadores CD68 (macrófagos, S100 (células de Langerhans, CD3, CD4, CD8, CD45RO, CD20 e CD56 (linfócitos e CD15 (neutrófilos. A expressão de MIP-1alfa (Proteína Inflamat

  20. Pathways of Student Persistence at RSC (Includes Persistence of Matriculants).

    Science.gov (United States)

    Fredericksen, Marlene

    In 1991, a study was conducted of semester-to-semester persistence patterns at Rancho Santiago College (RSC). The study involved tracking the attendance patterns of all RSC students entering as new students in fall 1983 and each subsequent fall until 1990; and comparing the persistence rates of matriculated and non-matriculated students in the…

  1. Nucleated red blood cells and early EEG: predicting Sarnat stage and two year outcome.

    LENUS (Irish Health Repository)

    Walsh, B H

    2012-01-31

    AIMS: Hypoxic Ischaemic Encephalopathy (HIE) causes characteristic changes of the electroencephalogram (EEG), and a raised Nucleated Red Blood Cell (NRBC) count compared to controls. We wished to examine whether combining these markers could improve their ability to predict HIE severity in the first 24h. METHODS: Term infants with HIE were recruited. NRBC count and continuous multi-channel EEG were recorded within the first 24h. Neurological assessment was carried out at 24 months. A control population with NRBC counts in the first 24h was recruited. RESULTS: 44 infants with HIE and 43 control infants were recruited. Of the HIE population 39 completed a 2 year follow-up. The median NRBC count differed significantly between the controls and those with HIE (3\\/100 WBC [range of 0-11] vs 12.3\\/100 WBC [0-240]) (p<0.001). Within the HIE population the median NRBC count was significantly greater in infants with moderate\\/severe HIE than mild (16\\/100 WBC [range of 0-240] vs 8\\/100 WBC [1-23]) (p=0.016), and among infants with abnormal outcome compared to normal (21.3\\/100 WBC [1-239.8] vs 8.3\\/100 WBC [0-50])(p=0.03). The predictive ability of EEG changed with time post-delivery, therefore results are given at both 12 and 24h of age. At both time points the combined marker had a stronger correlation than EEG alone; with HIE severity (12h: r=0.661 vs r=0.622), (24h: r=0.645 vs r=0.598), and with outcome at 2 years (12h: r=0.756 vs r=0.652), (24h: r=0.802 vs r=0.746). CONCLUSION: Combining early EEG and NRBC count to predict HIE severity and neurological outcome, improved the predictive ability of either in isolation.

  2. The simple persistent unique digital store (SPUDS)

    OpenAIRE

    Gibson, Hilton

    2010-01-01

    This paper introduces the concept of the simple persistent unique digital store which is an attempt to provide a means of digital object storage that will survive one hundred years into the future using open standards , technologies and formats. In addition it will attempt to make the digital object store independent of the software used to ingest, store, manage and disseminate the objects. Doing this greatly eliminates the risk of the present interdependence of the digital object store with ...

  3. Complicated Composting: Persistent Pyridine Carboxylic Acid Herbicides

    OpenAIRE

    Reimer, Julie

    2013-01-01

    This paper reviews pyridine carboxylic acid herbicide impacts on compost. Pyridine carboxylic acid herbicides are not completely broken down during grass growth, harvest and drying of hay, in the digestive tract of livestock, or during composting. These herbicides are a popular choice for broadleaf weed control because of this persistence: they remain effective for months or years. Pyridine carboxylic acids are also more effective than the common herbicide 2, 4-dichlorophenoxyacetic acid and ...

  4. The persistence of depression score

    NARCIS (Netherlands)

    Spijker, J.; de Graaf, R.; Ormel, J.; Nolen, W. A.; Grobbee, D. E.; Burger, H.

    2006-01-01

    Objective: To construct a score that allows prediction of major depressive episode (MDE) persistence in individuals with MDE using determinants of persistence identified in previous research. Method: Data were derived from 250 subjects from the general population with new MDE according to DSM-III-R.

  5. Placental abruption: a persisting killer

    Directory of Open Access Journals (Sweden)

    Shakuntala Amirchand Chhabra

    2014-06-01

    Full Text Available Background: Placental abruption, common disorder in obstetric practice, enigma too, is uniquely fraught with dangers to mother baby. Objectives of study were to study trends of placental abruption, risk factors, management strategies to learn more for reduction in morbidity-mortality of mother-baby, even with low resources, also get insight for future research. Methods: Records of cases of placental abruption managed over 27 years (between 1985 to 2011 were divided into three yearly blocks, A to I and analysed. Details including operative procedures like dilatation-curettage, Caesarean Section (CS or Ante-Partum Haemorrhage (APH in past, disorders like chronic hypertension, threatened abortion, pregnancy specific hypertension, diabetes, anaemia in index pregnancy, management done maternal-neonatal outcome were analysed using stata 6 software. Results: There were 66,459 births during analysis period with 667 cases of placental abruption, 1% births, increasing trends from, 0.73% between 1985-1987 to, 1.11% in 2009-2011. In these 667 cases of placental abruption, 211 (32.5% perinatal deaths occurred. Ratio of perinatal deaths due to placental abruption to overall perinatal deaths increased from 2.12% (8 cases between 1985-1987 (Block A to 5.12% (37 cases between 2009-2011 (Block I. Case fatality in cases of placental abruption has been fluctuating between 3 to 5% till 2004, contributing to around 12-15%, maternal mortality, with no fatality in last 7 years. Conclusions: Cases of placental abruption have been increasing with no obvious reason. In recent past maternal deaths could be prevented but perinatal deaths, have been persisting actually more in last decade. [Int J Reprod Contracept Obstet Gynecol 2014; 3(3.000: 604-609

  6. THE PERSISTENCE OF INSURERS PROFITABILITY

    Directory of Open Access Journals (Sweden)

    Maja Pervan

    2013-02-01

    Full Text Available Most of the academic researches have analyzed the persistence of profit for the manufacturing and (non-financial services sector. These studies were mainly conducted in advance market economies. In order to shed some light on the issue of persistence in corporate rates of return, this research aims to examine the persistence of profitability of financial entities i.e. non-life insurance companies operating in an emerging market economy, Croatia. In order to determine persistence of insurers’ profitability, a Markov Chains stochastic process is applied on the profitability classes that were formulated based on the changes of insurers’ ROA (return on assets indicator during the period from 2002 to 2011. The empirical results showed that profit persistence was more likely to occur within moderate profit classes/states.

  7. SOS response induces persistence to fluoroquinolones in Escherichia coli.

    Directory of Open Access Journals (Sweden)

    Tobias Dörr

    2009-12-01

    Full Text Available Bacteria can survive antibiotic treatment without acquiring heritable antibiotic resistance. We investigated persistence to the fluoroquinolone ciprofloxacin in Escherichia coli. Our data show that a majority of persisters to ciprofloxacin were formed upon exposure to the antibiotic, in a manner dependent on the SOS gene network. These findings reveal an active and inducible mechanism of persister formation mediated by the SOS response, challenging the prevailing view that persisters are pre-existing and formed purely by stochastic means. SOS-induced persistence is a novel mechanism by which cells can counteract DNA damage and promote survival to fluoroquinolones. This unique survival mechanism may be an important factor influencing the outcome of antibiotic therapy in vivo.

  8. Study of T Cell subsets and IL-7 protein expression in HIV-1-infected patients after 7 years HAART

    Directory of Open Access Journals (Sweden)

    Shou C

    2011-11-01

    Full Text Available Abstract Objective To study the changes in T cell subsets and IL-7 in HIV-1-infected patients after seven years of highly active antiretroviral therapy (HAART. Methods Seventy-five individuals were included in this study (25 with effective HAART, 18 with ineffective HAART, 17 untreated HIV+ patients, and 15 volunteers in the HIV negative control group. The counts of CD4+, CD8+, CD8/CD38+, and CD8/HLADR+ T cells as well as the IL-7 protein expression was measured at 5 time points during a period of seven years in patients starting HAART (baseline and in the HIV negative control group. The expression of CD127 on CD3+ T cells was measured by flow cytometry at a single time point (after 7 years in patients with HAART and was compared with untreated HIV+ patients and the HIV negative control group. Results At baseline CD4+ T cell counts of HIV-1-infected patients were lower than that in the control group (p +, CD8/HLADR+ and CD8/CD38+ T cell counts were higher than those in the control group (p 0.01. After seven years of effective HAART, the CD4+ T cell counts had increased and the CD8+ T cell count had decreased, although not to the normal levels (p + and CD8/CD38+ T cell counts had gradually approached those of the control group (p > 0.05. In the ineffective HAART group, the CD8/CD38+ T cell count had not decreased significantly, and CD8/HLADR+ T cell count gradually decreased. Before treatment, IL-7 serum levels of patients were significantly higher than that in the control group (p p + CD8+ T cells in effective HAART patients was higher than in untreated HIV+ patients (p p + CD4+ T cells was not significantly different among the control group, untreated HIV+ patients and effective HAART group. Conclusion After seven years of effective HAART, the quantity and capacity of T cell subsets and IL-7 in HIV-1-infected patients had been partially restored, and the abnormal immune activation has significantly diminished.

  9. Calibre Persistent Labial Artery: Clinical Features and Immunohistochemistry Diagnosis.

    Science.gov (United States)

    Santagata, M; Maglione, M; Colella, G; D'Amato, S

    2015-09-01

    Calibre persistent labial artery (CPLA) usually presents as an asymptomatic papule on the lower lip and can be easily misdiagnosed as a mucocele, haemangioma, venous lake, varix or fibroma. When it is ulcerated, squamous cell carcinoma is the most usual differential diagnosis. Here, we report a case of a 25-year-old woman with no previous relevant medical history who presented with a complaint of an asymptomatic, non-ulcerated, progressively growing nodule (over the last 5 months) on the upper lip. In this case, the diagnosis was made clinically and confirmed by immunohistochemical analysis. We conclude that clinicians should be aware of CPLA and it should be included in the differential diagnosis of labial mucosal papules. Sometimes, the immunohistochemical analysis is necessary to make a correct diagnosis. PMID:26225087

  10. Translating Romans: some persistent headaches

    Directory of Open Access Journals (Sweden)

    A.B. du Toit

    2010-07-01

    Full Text Available Translating Romans: some persistent headaches Gone are the days when it was axiomatic that expertise in biblical languages automatically qualified one as a Bible translator. In 1949, Ronald Knox, who for nine years conscientiously struggled with translating the Bible for his generation, published a booklet under the title The trials of a translator. At that stage Bible translation as the subject of scientific study was still in its infancy. Since then, research into the intricacies of communicating the biblical message in an authentic but understandable manner, has made significant progress (cf. Roberts, 2009. However, the frustrations of Bible translators, first of all to really understand what the biblical authors wanted to convey to their original addressees, and then to commu-nicate that message to their own targeted readers in a meaningful way, have not disappeared. In fact, the challenge to meet the vary-ing requirements of the multiple kinds of translation that are present-ly in vogue, has only increased.

  11. Resonant activation: a strategy against bacterial persistence

    International Nuclear Information System (INIS)

    A bacterial colony may develop a small number of cells genetically identical to, but phenotypically different from, other normally growing bacteria. These so-called persister cells keep themselves in a dormant state and thus are insensitive to antibiotic treatment, resulting in serious problems of drug resistance. In this paper, we proposed a novel strategy to 'kill' persister cells by triggering them to switch, in a fast and synchronized way, into normally growing cells that are susceptible to antibiotics. The strategy is based on resonant activation (RA), a well-studied phenomenon in physics where the internal noise of a system can constructively facilitate fast and synchronized barrier crossings. Through stochastic Gilliespie simulation with a generic toggle switch model, we demonstrated that RA exists in the phenotypic switching of a single bacterium. Further, by coupling single cell level and population level simulations, we showed that with RA, one can greatly reduce the time and total amount of antibiotics needed to sterilize a bacterial population. We suggest that resonant activation is a general phenomenon in phenotypic transition, and can find other applications such as cancer therapy

  12. Persistence, resistance, resonance

    Science.gov (United States)

    Tsadka, Maayan

    form of musical consumption and experience. The three pieces draw lines connecting different aspects of persistence, resistance, and resonance.

  13. In-cell clean-up pressurized liquid extraction and gas chromatography-tandem mass spectrometry determination of hydrophobic persistent and emerging organic pollutants in coastal sediments.

    Science.gov (United States)

    Pintado-Herrera, Marina G; González-Mazo, Eduardo; Lara-Martín, Pablo A

    2016-01-15

    The main goal of this work was to develop, optimize and validate a multi-residue method for the simultaneous determination of 97 contaminants, including fragrances, UV filters, repellents, endocrine disruptors, biocides, polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), organophosphorus flame retardants, and several types of pesticides in marine sediment samples. Extraction and cleanup were integrated into the same step using pressurized liquid extraction (PLE) with in-cell clean-up (1g of alumina). The extraction was performed using dichloromethane at 100 °C, 1500 psi and 3 extraction cycles (5 min per cycle). Extracts were derivatized with N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide (MTBSTFA) to improve the signal and sensitivity of some target compounds (i.e., triclosan, 2-hydroxybenzophenone). Separation, identification and quantification of analytes were carried out by gas chromatography (GC) coupled to tandem mass spectrometry. Under optimal conditions, the optimized protocol showed good recovery percentages (70-100%), linearity (>0.99) and limits of detection below 1 ng g(-1) for all compounds. Finally, the method was applied to the analysis of sediment samples from different coastal areas from Andalusia (Spain), where occurrence and distribution of emerging contaminants in sediments is very scarce. Twenty five compounds out of 98 were detected in all samples, with the endocrine disruptor nonylphenol and the fragrance galaxolide showing the highest concentrations, up to 377.6 ng g(-1) and 237.4 ng g(-1), respectively.

  14. Comparative 2D-DIGE Proteomic Analysis of Bovine Mammary Epithelial Cells during Lactation Reveals Protein Signatures for Lactation Persistency and Milk Yield

    Science.gov (United States)

    Janjanam, Jagadeesh; Singh, Surender; Jena, Manoj K.; Varshney, Nishant; Kola, Srujana; Kumar, Sudarshan; Kaushik, Jai K.; Grover, Sunita; Dang, Ajay K.; Mukesh, Manishi; Prakash, B. S.; Mohanty, Ashok K.

    2014-01-01

    Mammary gland is made up of a branching network of ducts that end with alveoli which surrounds the lumen. These alveolar mammary epithelial cells (MEC) reflect the milk producing ability of farm animals. In this study, we have used 2D-DIGE and mass spectrometry to identify the protein changes in MEC during immediate early, peak and late stages of lactation and also compared differentially expressed proteins in MEC isolated from milk of high and low milk producing cows. We have identified 41 differentially expressed proteins during lactation stages and 22 proteins in high and low milk yielding cows. Bioinformatics analysis showed that a majority of the differentially expressed proteins are associated in metabolic process, catalytic and binding activity. The differentially expressed proteins were mapped to the available biological pathways and networks involved in lactation. The proteins up-regulated during late stage of lactation are associated with NF-κB stress induced signaling pathways and whereas Akt, PI3K and p38/MAPK signaling pathways are associated with high milk production mediated through insulin hormone signaling. PMID:25111801

  15. Intrahepatic and peripheral T-cell responses in genotype 1b hepatitis C virus-infected patients with persistently normal and elevated aminotransferase levels

    Institute of Scientific and Technical Information of China (English)

    Filiz Akyüz; Nuray Polat; Sabahattin Kaymakoglu; Nevzat Aksoy; Kadir Demir; Fatih Be(s)i(s)ik; Selim Badur; Yilmaz (C)akaloglu; Atilla (O)kten

    2005-01-01

    AIM: To evaluate whether the cytokine responses in liver and serum differ in chronic hepatitis C patients with normal and high alanine aminotransferase (ALT) levels.METHODS: Thirty-three (16 with normal ALT level as group 1 and 17 with elevated ALT level as group 2) patients infected with genotype 1b hepatitis C virus (HCV) were examined. Liver infiltrating lymphomononuclear cells (LILMCs) were isolated from liver biopsy by collagenase type 1 and stimulated with phytohemagglutinin and interleukin 2 (IL-2). IL-10, IL-12,interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) were determined in serum and LILMCs by ELISA.RESULTS: Serum cytokine levels were similar in both groups (P>0.05). Stimulated IFN-γ and TNF-α levels in LILMCs were increased in both groups. IL-12 and IL-10levels stimulated with IL-2 were higher in group 1 than in group 2 (P = 0.023). Histological activity index (HAI)and stage had a negative correlation with TNF-α and IFN-γ levels in group 2.CONCLUSION: Increased T-helper type 2 (Th2)cytokine response may regress inflammatory and biochemical activity. Progression of histological abnormalities in persons with elevated ALT probably depends on insufficient Th2 cytokine response, which does not balance Th1 cytokine response.

  16. Energy landscapes and persistent minima

    International Nuclear Information System (INIS)

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests

  17. Energy landscapes and persistent minima

    Energy Technology Data Exchange (ETDEWEB)

    Carr, Joanne M.; Wales, David J., E-mail: dw34@cam.ac.uk [University Chemical Laboratories, University of Cambridge, Lensfield Road, Cambridge CB2 1EW (United Kingdom); Mazauric, Dorian; Cazals, Frédéric, E-mail: frederic.cazals@inria.fr [Inria Sophia Antipolis Méditerranée, 2004 route des Lucioles, F-06902 Sophia Antipolis (France)

    2016-02-07

    We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests.

  18. A Retrospective Analysis of Oral Langerhans Cell Histiocytosis in an Iranian Population: a 20-year Evaluation

    OpenAIRE

    Saede Atarbashi Moghadam; Ali Lotfi; Batool Piroozhashemi; Sepideh Mokhtari

    2015-01-01

    Statement of the Problem: Langerhans cell histiocytosis is a rare disease with unknown pathogenesis and is characterized by local or disseminated proliferation of Langerhans cells. There is no previous investigation on prevalence of oral Langerhans cell histiocytosis in Iranian population. Purpose: The purpose of this study was to assess the relative frequency of oral Langerhans cell histiocytosis in an Iranian population and to compare the data with previous reports. Materials and Meth...

  19. Persisting Plastic Addiction

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The policy on curbing plastic shopping bag use implemented three years ago has produced mixed results In a bustling farmers’market tucked in a narrow street in Xisanqi residential community in north Beijing,stalls selling vegetables,fruits and other foods line the sidewalk.

  20. Persistence Length of DNA Macromolecule with Kinks

    CERN Document Server

    Simonov, Kyrylo

    2014-01-01

    The study of configurational parameters of deformed DNA is a relevant problem in research of such important biological process as double helix compactization in cell. The deformations accompanied with local disruptions of the regular macromolecule structure cause significant bending of the double helix, or kinks. In this paper an approach for Kratky-Porod model to calculate persistence length of DNA macromolecule with kinks is developed. The presented approach considers kinks of arbitrary configuration, including two basic types of kinks, type 1 - sharp kink caused by unstacking a single base pair step, and type 2 - intrinsic-induced kink that involves several base pairs. Within developed approach analytical expressions for persistence length, coil size and gyration radius of kinky double helix were obtained.