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  1. Characterising B cell numbers and memory B cells in HIV infected and uninfected Malawian adults

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    Gordon Stephen

    2010-09-01

    Full Text Available Abstract Background Untreated human immunodeficiency virus (HIV disease disrupts B cell populations causing reduced memory and reduced naïve resting B cells leading to increases in specific co-infections and impaired responses to vaccines. To what extent antiretroviral treatment reverses these changes in an African population is uncertain. Methods A cross-sectional study was performed. We recruited HIV-uninfected and HIV-infected Malawian adults both on and off antiretroviral therapy attending the Queen Elizabeth Central hospital in Malawi. Using flow cytometry, we enumerated B cells and characterized memory B cells and compared these measurements by the different recruitment groups. Results Overall 64 participants were recruited - 20 HIV uninfected (HIV-, 30 HIV infected ART naïve (HIV+N and 14 HIV-infected ART treated (HIV+T. ART treatment had been taken for a median of 33 months (Range 12-60 months. Compared to HIV- the HIV+N adults had low absolute number of naïve resting B cells (111 vs. 180 cells/μl p = 0.008; reduced memory B cells (27 vs. 51 cells/μl p = 0.0008. The HIV+T adults had B-cell numbers similar to HIV- except for memory B cells that remained significantly lower (30 vs. 51 cells/μl p = 0.02. In the HIV+N group we did not find an association between CD4 count and B cell numbers. Conclusions HIV infected Malawian adults have abnormal B-cell numbers. Individuals treated with ART show a return to normal in B-cell numbers but a persistent deficit in the memory subset is noted. This has important implications for long term susceptibility to co-infections and should be evaluated further in a larger cohort study.

  2. HIV-1/HSV-2 co-infected adults in early HIV-1 infection have elevated CD4+ T cell counts.

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    Jason D Barbour

    Full Text Available INTRODUCTION: HIV-1 is often acquired in the presence of pre-existing co-infections, such as Herpes Simplex Virus 2 (HSV-2. We examined the impact of HSV-2 status at the time of HIV-1 acquisition for its impact on subsequent clinical course, and total CD4+ T cell phenotypes. METHODS: We assessed the relationship of HSV-1/HSV-2 co-infection status on CD4+ T cell counts and HIV-1 RNA levels over time prior in a cohort of 186 treatment naïve adults identified during early HIV-1 infection. We assessed the activation and differentiation state of total CD4+ T cells at study entry by HSV-2 status. RESULTS: Of 186 recently HIV-1 infected persons, 101 (54% were sero-positive for HSV-2. There was no difference in initial CD8+ T cell count, or differences between the groups for age, gender, or race based on HSV-2 status. Persons with HIV-1/HSV-2 co-infection sustained higher CD4+ T cell counts over time (+69 cells/ul greater (SD = 33.7, p = 0.04 than those with HIV-1 infection alone (Figure 1, after adjustment for HIV-1 RNA levels (-57 cells per 1 log(10 higher HIV-1 RNA, p<0.0001. We did not observe a relationship between HSV-2 infection status with plasma HIV-1 RNA levels over time. HSV-2 acquisition after HIV-1 acquisition had no impact on CD4+ count or viral load. We did not detect differences in CD4+ T cell activation or differentiation state by HSV-2+ status. DISCUSSION: We observed no effect of HSV-2 status on viral load. However, we did observe that treatment naïve, recently HIV-1 infected adults co-infected with HSV-2+ at the time of HIV-1 acquisition had higher CD4+ T cell counts over time. If verified in other cohorts, this result poses a striking paradox, and its public health implications are not immediately clear.

  3. Evaluating risk factors for Clostridium difficile infection in adult and pediatric hematopoietic cell transplant recipients

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    Boyle, Nicole M.; Magaret, Amalia; Stednick, Zach; Morrison, Alex; Butler-Wu, Susan; Zerr, Danielle; Rogers, Karin; Podczervinski, Sara; Cheng, Anqi; Wald, Anna; Pergam, Steven A

    2015-01-01

    Background Although hematopoietic cell transplant (HCT) recipients are routinely exposed to classic risk factors for Clostridium difficile infection (CDI), few studies have assessed CDI risk in these high-risk patients, and data are especially lacking for pediatric HCT recipients. We aimed to determine incidence and risk factors for CDI in adult and pediatric allogeneic HCT recipients. Methods CDI was defined as having diarrhea that tested positive for C. difficile via PCR, cytotoxin assay, o...

  4. Impairment of pneumococcal antigen specific isotype-switched Igg memory B-cell immunity in HIV infected Malawian adults.

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    Oluwadamilola H Iwajomo

    Full Text Available Pneumococcal disease is associated with a particularly high morbidity and mortality amongst adults in HIV endemic countries. Our previous findings implicating a B-cell defect in HIV-infected children from the same population led us to comprehensively characterize B-cell subsets in minimally symptomatic HIV-infected Malawian adults and investigate the isotype-switched IgG memory B-cell immune response to the pneumococcus. We show that similar to vertically acquired HIV-infected Malawian children, horizontally acquired HIV infection in these adults is associated with IgM memory B-cell (CD19(+ CD27(+ IgM(+ IgD(+ depletion, B-cell activation and impairment of specific IgG B-cell memory to a range of pneumococcal proteins. Our data suggest that HIV infection affects both T-cell independent and T-cell dependent B-cell maturation, potentially leading to impairment of humoral responses to extracellular pathogens such as the pneumococcus, and thus leaving this population susceptible to invasive disease.

  5. [Sarcoidosis and leukemia/T-cell lymphoma associated with HTLV-1 virus infection in adults (apropos of a case)].

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    Panelatti, G; Plumelle, Y; Arfi, S; Pascaline, N; Caplanne, D; Jean-Baptiste, G

    1992-01-01

    The HTLV-1 virus causes a disturbance of the immune system, the evaluation of which is often difficult. We report a case of sarcoidosis in a 49 year old woman of Martinique as evidenced by bilateral hilar adenopathy, hypercalcaemia, uveitis and granulomatous lesions on histological examination. Serological was positive for HTLV-1 antibodies. Three years later she developed an adult T-cell leukemia/lymphoma. The relationships between the HTLV-1 retroviral infection and different pathologies observed are discussed. PMID:1287773

  6. HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma-A Tale of Two Proteins: Tax and HBZ.

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    Giam, Chou-Zen; Semmes, Oliver John

    2016-06-16

    HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10-20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%-5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling-the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)-to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided.

  7. HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ

    Science.gov (United States)

    Giam, Chou-Zen; Semmes, Oliver John

    2016-01-01

    HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling—the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)—to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided. PMID:27322308

  8. HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma-A Tale of Two Proteins: Tax and HBZ.

    Science.gov (United States)

    Giam, Chou-Zen; Semmes, Oliver John

    2016-01-01

    HTLV-1 (Human T-cell lymphotropic virus type 1) is a complex human delta retrovirus that currently infects 10-20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%-5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL) decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ), encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling-the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)-to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided. PMID:27322308

  9. HTLV-1 Infection and Adult T-Cell Leukemia/Lymphoma—A Tale of Two Proteins: Tax and HBZ

    Directory of Open Access Journals (Sweden)

    Chou-Zen Giam

    2016-06-01

    Full Text Available HTLV-1 (Human T-cell lymphotropic virus type 1 is a complex human delta retrovirus that currently infects 10–20 million people worldwide. While HTLV-1 infection is generally asymptomatic, 3%–5% of infected individuals develop a highly malignant and intractable T-cell neoplasm known as adult T-cell leukemia/lymphoma (ATL decades after infection. How HTLV-1 infection progresses to ATL is not well understood. Two viral regulatory proteins, Tax and HTLV-1 basic zipper protein (HBZ, encoded by the sense and antisense viral transcripts, respectively, are thought to play indispensable roles in the oncogenic process of ATL. This review focuses on the roles of Tax and HBZ in viral replication, persistence, and oncogenesis. Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling—the ubiquitin E3 ligase, ring finger protein 8 (RNF8 and the ubiquitin E2 conjugating enzyme (UBC13—to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB and other signaling pathways will be discussed. A perspective on how the Tax-RNF8 signaling axis might impact genomic instability and how Tax may collaborate with HBZ to drive oncogenesis is provided.

  10. Adult T-cell leukemia/lymphoma associated with HTLV-1 infection in a Brazilian adolescent

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    VALLE Antonio Carlos Francesconi do

    2001-01-01

    Full Text Available We present the case of a 15-year-old patient infected with HTLV-1 who developed a cutaneous T-cell lymphoma, confirmed by histopathological and immunohistochemical examination, as well as clinically and hematologically confirmed leukemia. The patient died 3 months after initial presentation of the disease. The rarity of the disease in this age group justifies the present report.

  11. The impact of B-cell perturbations on pneumococcal conjugate vaccine response in HIV-infected adults.

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    Thomas G Johannesson

    Full Text Available Untreated HIV infection results in severe perturbations of the B-cell population and hyporesponsiveness to vaccination. We studied associations between circulating B-cell subsets and antibody response to pneumococcal conjugate vaccine in treated and untreated HIV patients.Ninety-five HIV-infected adults were grouped according to antiretroviral therapy (ART and CD4+ cell count as follows: 20 ART-naïve (no prior ART, 62 ART-responders (received ART, and CD4 count >500 cells/µl, and 13 impaired responders (received ART for more than 3 years, and CD4 count <500 cells/µl. All subjects were immunized twice with double-dose 7-valent pneumococcal conjugate vaccine with or without 1 mg CPG 7909 (toll-like receptor 9 agonist at baseline and after three months. Pre-vaccination B-cell subpopulations were assessed by flow cytometry. Serum IgG concentrations for vaccine serotypes were quantified by ELISA at baseline and 3, 4, and 9 months post-vaccination. ART responders had more isotype-switched memory B cells and more marginal-zone (MZ-like B cells compared with impaired responders. Furthermore, ART-naïve patients had higher concentration of transitional B cells and plasmablasts compared with B cells of other patient groups. The concentration of MZ-like, isotype switched memory cells and plasmablasts correlated positively with post-vaccination IgG concentration at 3, 4, and 9 months. Low concentrations of isotype-switched memory B cells was the strongest independent predictor of poor pneumococcal conjugate vaccine responsiveness, emphasizing that B-cell subset disturbances are associated with poor vaccine response among HIV-infected patients.

  12. Strategies to control human cytomegalovirus infection in adult hematopoietic stem cell transplant recipients.

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    Lilleri, Daniele; Gerna, Giuseppe

    2016-09-01

    Human cytomegalovirus (HCMV) represents the major viral complication after hematopoietic stem cell transplantation. HCMV infection may be controlled by the reconstituting immune system and remain subclinical or can lead to severe systemic and/or organ disease (mainly pneumonia and gastroenteritis) when immune reconstitution is delayed or impaired. In order to prevent the occurrence of HCMV disease, a prompt diagnosis of HCMV infection is mandatory. The adoption of pre-emptive therapy strategies guided by virological monitoring dramatically reduced the occurrence of HCMV disease. However, late-onset end-organ disease may occur in some patients with apparent immune reconstitution. In the near future, introduction of immunological monitoring and immunotherapies could markedly improve management of HCMV infection. PMID:27485084

  13. Urinary tract infection - adults

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    ... infection spreads to your kidneys, symptoms may include: Chills and shaking or night sweats Fatigue and a ... kidney infection, such as: Back or side pain Chills Fever Vomiting Also call if UTI symptoms come ...

  14. Pediatric and Adult High-Grade Glioma Stem Cell Culture Models Are Permissive to Lytic Infection with Parvovirus H-1.

    Science.gov (United States)

    Josupeit, Rafael; Bender, Sebastian; Kern, Sonja; Leuchs, Barbara; Hielscher, Thomas; Herold-Mende, Christel; Schlehofer, Jörg R; Dinsart, Christiane; Witt, Olaf; Rommelaere, Jean; Lacroix, Jeannine

    2016-05-19

    Combining virus-induced cytotoxic and immunotherapeutic effects, oncolytic virotherapy represents a promising therapeutic approach for high-grade glioma (HGG). A clinical trial has recently provided evidence for the clinical safety of the oncolytic parvovirus H-1 (H-1PV) in adult glioblastoma relapse patients. The present study assesses the efficacy of H-1PV in eliminating HGG initiating cells. H-1PV was able to enter and to transduce all HGG neurosphere culture models (n = 6), including cultures derived from adult glioblastoma, pediatric glioblastoma, and diffuse intrinsic pontine glioma. Cytotoxic effects induced by the virus have been observed in all HGG neurospheres at half maximal inhibitory concentration (IC50) doses of input virus between 1 and 10 plaque forming units per cell. H-1PV infection at this dose range was able to prevent tumorigenicity of NCH421k glioblastoma multiforme (GBM) "stem-like" cells in NOD/SCID mice. Interestingly NCH421R, an isogenic subclone with equal capacity of xenograft formation, but resistant to H-1PV infection could be isolated from the parental NCH421k culture. To reveal changes in gene expression associated with H-1PV resistance we performed a comparative gene expression analysis in these subclones. Several dysregulated genes encoding receptor proteins, endocytosis factors or regulators innate antiviral responses were identified and represent intriguing candidates for to further study molecular mechanisms of H-1PV resistance.

  15. Maturation and Mip-1β Production of Cytomegalovirus-Specific T Cell Responses in Tanzanian Children, Adolescents and Adults: Impact by HIV and Mycobacterium tuberculosis Co-Infections.

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    Damien Portevin

    Full Text Available It is well accepted that aging and HIV infection are associated with quantitative and functional changes of CMV-specific T cell responses. We studied here the expression of Mip-1β and the T cell maturation marker CD27 within CMVpp65-specific CD4(+ and CD8(+ T cells in relation to age, HIV and active Tuberculosis (TB co-infection in a cohort of Tanzanian volunteers (≤ 16 years of age, n = 108 and ≥ 18 years, n = 79. Independent of HIV co-infection, IFNγ(+ CMVpp65-specific CD4(+ T cell frequencies increased with age. In adults, HIV co-infection further increased the frequencies of these cells. A high capacity for Mip-1β production together with a CD27(low phenotype was characteristic for these cells in children and adults. Interestingly, in addition to HIV co-infection active TB disease was linked to further down regulation of CD27 and increased capacity of Mip-1β production in CMVpp65-specific CD4+ T cells. These phenotypic and functional changes of CMVpp65-specific CD4 T cells observed during HIV infection and active TB could be associated with increased CMV reactivation rates.

  16. Binding of Excreted and/or Secreted Products of Adult Hookworms to Human NK Cells in Necator americanus-Infected Individuals from Brazil▿

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    Teixeira-Carvalho, Andréa; Fujiwara, Ricardo T.; Stemmy, Erik J.; Olive, Denise; Damsker, Jesse M.; Loukas, Alex; Corrêa-Oliveira, Rodrigo; Constant, Stephanie L.; Bethony, Jeffrey M.

    2008-01-01

    The impact of the interaction between excreted and/or secreted (ES) Necator americanus products and NK cells from Necator-infected individuals was analyzed. We investigated the binding of ES products to NK cells, the expression of NK cell receptors (CD56, CD159a/NKG2A, CD314/NKG2D, CD335/NKp46, and KLRF1/NKp80), the frequency of gamma interferon (IFN-γ)-producing NK cells after whole-blood in vitro stimulation, and the capacity of N. americanus ES products to induce NK cell chemotaxis. In contrast to those from noninfected individuals, NK cells from Necator-infected individuals demonstrated no binding with N. americanus ES products. This phenomenon was not due to alterations in NK cell receptor expression in infected subjects and could not be reproduced with NK cells from uninfected individuals by incubation with immunoregulatory cytokines (interleukin-10/transforming growth factor β). Further, we found that a significantly greater percentage of NK cells from infected subjects than NK cells from uninfected individuals spontaneously produced IFN-γ upon ex vivo culture. Our findings support a model whereby NK cells from Necator-infected individuals may interact with ES products, making these cells refractory to binding with exogenous ES products. During N. americanus infection, human NK cells are attracted to the site of infection by chemotactic ES products produced by adult Necator worms in the gut mucosa. Binding of ES products causes the NK cells to become activated and secrete IFN-γ locally, thereby contributing to the adult hookworm's ability to evade host immune responses. PMID:18838519

  17. Reconstitution of naive T cells during antiretroviral treatment of HIV-infected adults is dependent on age

    NARCIS (Netherlands)

    Cohen Stuart, James; Hamann, Dörte; Borleffs, Jan; Roos, Marijke; Miedema, Frank; Boucher, Charles; de Boer, Rob

    2002-01-01

    OBJECTIVE: To determine the influence of age on the regeneration rate of naive and memory T cells in the blood of 45 adults on highly active antiretroviral therapy (HAART). METHODS: The age of the patients ranged from 25 to 57 years. Naive cells were defined as CD45RA+CD27+. Cells negative for CD45R

  18. ADULT T CELL LEUKEMIA LYMPHOMA

    OpenAIRE

    Neely, S. M.

    2004-01-01

    Adult T cell leukemia lymphoma (ATLL) is a CD4+ lymphoproliferative malignancy resulting from human T-cell leukemia virus type 1 (HTLV1) infection. It includes differing clinical forms classified as smoldering, chronic, lymphomatous, and acute ATLL. The Tax protein of HTLV-1 has been implicated as a viral oncoprotein which enhances virus replication and alters cellular gene expression, including activation of nuclear factor kappa B (NF kB), to result in lymphoid transformation. Chemotherapy f...

  19. Vaccinations for Adults with Hepatitis C Infection

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    Vaccinations for Adults with Hepatitis C Infection This table shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  20. Vaccinations for Adults with HIV Infection

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    Vaccinations for Adults with HIV Infection The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  1. Intraabdominal Infections in Older Adults.

    Science.gov (United States)

    Berlin, Ana; Johanning, Jason Michael

    2016-08-01

    Intraabdominal infections represent a diagnostic and therapeutic challenge in the elderly population. Atypical presentations, diagnostic delays, additional comorbidities, and decreased physiologic reserve contribute to high morbidity and mortality, particularly among frail patients undergoing emergency abdominal surgery. While many infections are the result of age-related inflammatory, mechanical, or obstructive processes, infectious complications of feeding tubes are also common. The pillars of treatment are source control of the infection and judicious use of antibiotics. A patient-centered approach considering the invasiveness, risk, and efficacy of a procedure for achieving the desired outcomes is recommended. Structured communication and time-limited trials help ensure goal-concordant treatment. PMID:27394019

  2. Respiratory infections precede adult-onset asthma.

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    Aino Rantala

    Full Text Available BACKGROUND: Respiratory infections in early life are associated with an increased risk of developing asthma but there is little evidence on the role of infections for onset of asthma in adults. The objective of this study was to assess the relation of the occurrence of respiratory infections in the past 12 months to adult-onset asthma in a population-based incident case-control study of adults 21-63 years of age. METHODS/PRINCIPAL FINDINGS: We recruited all new clinically diagnosed cases of asthma (n = 521 during a 2.5-year study period and randomly selected controls (n = 932 in a geographically defined area in South Finland. Information on respiratory infections was collected by a self-administered questionnaire. The diagnosis of asthma was based on symptoms and reversible airflow obstruction in lung function measurements. The risk of asthma onset was strongly increased in subjects who had experienced in the preceding 12 months lower respiratory tract infections (including acute bronchitis and pneumonia with an adjusted odds ratio (OR 7.18 (95% confidence interval [CI] 5.16-9.99, or upper respiratory tract infections (including common cold, sinusitis, tonsillitis, and otitis media with an adjusted OR 2.26 (95% CI 1.72-2.97. Individuals with personal atopy and/or parental atopy were more susceptible to the effects of respiratory infections on asthma onset than non-atopic persons. CONCLUSIONS/SIGNIFICANCE: This study provides new evidence that recently experienced respiratory infections are a strong determinant for adult-onset asthma. Reducing such infections might prevent onset of asthma in adulthood, especially in individuals with atopy or hereditary propensity to it.

  3. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load

    DEFF Research Database (Denmark)

    Obel, Niels

    2012-01-01

    Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load.......Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load....

  4. Clinical Features of Infection in Older Adults.

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    Norman, Dean C

    2016-08-01

    The impact of infectious diseases on older adults is far greater than on younger adults because of significantly higher morbidity and mortality caused by infection. The reasons for this greater impact include factors such as lower physiologic reserve due to age and chronic disease, age-related changes in host defenses, loss of mobility, higher risk for polypharmacy and adverse drug reactions, and being on drugs that increase the risk for infection (e.g., anticholinergic and other sedating medications increase the risk for pneumonia). PMID:27394015

  5. B cell depletion in HIV-1 subtype A infected Ugandan adults: relationship to CD4 T cell count, viral load and humoral immune responses.

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    Peter Oballah

    Full Text Available To better understand the nature of B cell dysfunctions in subjects infected with HIV-1 subtype A, a rural cohort of 50 treatment-naïve Ugandan patients chronically infected with HIV-1 subtype A was studied, and the relationship between B cell depletion and HIV disease was assessed. B cell absolute counts were found to be significantly lower in HIV-1+ patients, when compared to community matched negative controls (p<0.0001. HIV-1-infected patients displayed variable functional and binding antibody titers that showed no correlation with viral load or CD4+ T cell count. However, B cell absolute counts were found to correlate inversely with neutralizing antibody (NAb titers against subtype A (p = 0.05 and subtype CRF02_AG (p = 0.02 viruses. A positive correlation was observed between subtype A gp120 binding antibody titers and NAb breadth (p = 0.02 and mean titer against the 10 viruses (p = 0.0002. In addition, HIV-1 subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D (p<0.001. These data demonstrate that in patients with chronic HIV-1 subtype A infection, significant B cell depletion can be observed, the degree of which does not appear to be associated with a decrease in functional antibodies. These findings also highlight the potential importance of subtype in the specificity of cross-clade neutralization in HIV-1 infection.

  6. Respiratory syncytial virus infection in elderly adults.

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    Falsey, Ann R; Walsh, Edward E

    2005-01-01

    Respiratory syncytial virus (RSV) infection is now recognised as a significant problem in elderly adults. Epidemiological evidence indicates the impact of RSV in older adults may be similar to non-pandemic influenza, both in the community and in long-term care facilities. Attack rates in nursing homes are approximately 5-10% per year with significant rates of pneumonia (10-20%) and death (2-5%). Estimates using US health care databases and viral surveillance results over a 9-year period indicate that RSV infection causes approximately 10,000 all-cause deaths annually among persons >64 years of age. In contrast, influenza A accounted for approximately 37,000 yearly deaths in the same age group. The clinical features of RSV infection may be difficult to distinguish from those of influenza but include nasal congestion, cough, wheezing and low-grade fever. Older persons with underlying heart and lung disease and immunocompromised patients are at highest risk for RSV infection-related pneumonia and death. Diagnosis of RSV infection in adults is difficult because viral culture and antigen detection are insensitive, presumably because of low viral titres. The combination of serology and reverse transcriptase polymerase chain reaction assay offers the best sensitivity and specificity for the diagnosis of RSV but unfortunately these techniques are not widely available; consequently, most adult RSV disease goes unrecognised. Although treatment of RSV infection in the elderly is largely supportive, early therapy with ribavirin and intravenous gamma-globulin improves survival in immunocompromised persons. An effective RSV vaccine has not yet been developed. Therefore, prevention of RSV is limited to standard infection control practices, such as hand washing and the use of gowns and gloves. PMID:16038573

  7. Infections Revealing Complement Deficiency in Adults

    Science.gov (United States)

    Audemard-Verger, A.; Descloux, E.; Ponard, D.; Deroux, A.; Fantin, B.; Fieschi, C.; John, M.; Bouldouyre, A.; Karkowsi, L.; Moulis, G.; Auvinet, H.; Valla, F.; Lechiche, C.; Davido, B.; Martinot, M.; Biron, C.; Lucht, F.; Asseray, N.; Froissart, A.; Buzelé, R.; Perlat, A.; Boutboul, D.; Fremeaux-Bacchi, V.; Isnard, S.; Bienvenu, B.

    2016-01-01

    Abstract Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies. A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis. Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35

  8. Factors associated with development of opportunistic infections in HIV-1 infected adults with high CD4 cell counts: a EuroSIDA study

    DEFF Research Database (Denmark)

    Podlekareva, Daria; Mocroft, A; Dragsted, Ulrik Bak;

    2006-01-01

    to the development of groups of OIs above their respective traditional upper CD4(+) cell count thresholds: group 1 (>or=100 cells/ microL), OIs caused by cytomegalovirus, Mycobacterium avium complex, and Toxoplasma gondii; group 2 (>or=200 cells/ microL), Pneumocystis pneumonia and esophageal candidiasis; and group...

  9. Adult Onset Langerhans’ Cell Histiocytosis

    OpenAIRE

    Rahime İnci; Hamide Sayar; Mehmet Fatih İnci; Perihan Öztürk

    2014-01-01

    Langerhans’ cell histiocytosis (LCH) is a group of diseases of unknown cause resulting from abnormal proliferation of bone marrow-originated dendritic cells called histiocytes. The incidence is between 0.5-5.4 per million. More common in childhood, it is extremely rare in adults. In adults, pulmonary involvement with Langerhans’ cell histiocytosis usually occurs as a single-system disease. In this article, the clinical, radiological and histopathological findings of a 51-year-old male patient...

  10. Defective Natural Killer cell antiviral capacity in paediatric HBV infection

    DEFF Research Database (Denmark)

    Heiberg, Ida Louise; Laura J., Pallett; Winther, Thilde Nordmann;

    2015-01-01

    Natural Killer (NK) cells exhibit dysregulated effector function in adult chronic HBV infection (CHB), which may contribute to virus persistence. The role of NK cells in children infected perinatally with HBV is less studied. Access to a unique cohort enabled the cross-sectional evaluation of NK...... cell frequency, phenotype and function in HBV-infected children relative to uninfected children. We observed a selective defect in NK cell IFN-γ production, with conserved cytolytic function, mirroring the functional dichotomy observed in adult infection. Reduced expression of NKp30 on NK cells...... suggests a role of impaired NK-Dendritic Cell (DC) cellular interactions as a potential mechanism leading to reduced IFN-γ production. The finding that NK cells are already defective in paediatric CHB, albeit less extensively than in adult CHB, has potential implications for the timing of antiviral therapy...

  11. Adult Onset Langerhans’ Cell Histiocytosis

    Directory of Open Access Journals (Sweden)

    Rahime İnci

    2014-12-01

    Full Text Available Langerhans’ cell histiocytosis (LCH is a group of diseases of unknown cause resulting from abnormal proliferation of bone marrow-originated dendritic cells called histiocytes. The incidence is between 0.5-5.4 per million. More common in childhood, it is extremely rare in adults. In adults, pulmonary involvement with Langerhans’ cell histiocytosis usually occurs as a single-system disease. In this article, the clinical, radiological and histopathological findings of a 51-year-old male patient with both skin, bone and pulmonary involvement were presented and discussed with recent literature.

  12. Mast cells in bacterial infections

    OpenAIRE

    Rönnberg, Elin

    2014-01-01

    Mast cells are implicated in immunity towards bacterial infection, but the molecular mechanisms by which mast cells contribute to the host response are only partially understood. Previous studies have examined how mast cells react to purified bacterial cell wall components, such as peptidoglycan and lipopolysaccharide. To investigate how mast cells react to live bacteria we co-cultured mast cells and the gram-positive bacteria Streptococcus equi (S. equi) and Staphylococcus aureus (S. aureus)...

  13. Group B Strep Infection in Adults

    Science.gov (United States)

    ... symptoms. Bacteremia and sepsis (blood infections) symptoms include: Fever Chills Low alertness Pneumonia (lung infection) symptoms include: Fever ... in the infected area and might also include: Fever Chills Swilling Stiffness or inability to use affected limb ...

  14. AIDS and Non-AIDS Morbidity and Mortality Across the Spectrum of CD4 Cell Counts in HIV-Infected Adults Before Starting Antiretroviral Therapy in Côte d’Ivoire

    Science.gov (United States)

    Minga, Albert; Gabillard, Delphine; Ouassa, Timothée; Messou, Eugene; Morris, Brandon; Traore, Moussa; Coulibaly, Ali; Freedberg, Kenneth A.; Lewden, Charlotte; Ménan, Hervé; Abo, Yao; Dakoury-Dogbo, Nicole; Toure, Siaka; Seyler, Catherine

    2012-01-01

    Background. In Western Europe, North America, and Australia, large cohort collaborations have been able to estimate the short-term CD4 cell count–specific risk of AIDS or death in untreated human immunodeficiency virus (HIV)–infected adults with high CD4 cell counts. In sub–Saharan Africa, these CD4 cell count–specific estimates are scarce. Methods. From 1996 through 2006, we followed up 2 research cohorts of HIV-infected adults in Côte d’Ivoire. This included follow-up off antiretroviral therapy (ART) across the entire spectrum of CD4 cell counts before the ART era, and only in patients with CD4 cell counts >200 cells/μL once ART became available. Data were censored at ART initiation. We modeled the CD4 cell count decrease using an adjusted linear mixed model. CD4 cell count–specific rates of events were obtained by dividing the number of first events occurring in a given CD4 cell count stratum by the time spent in that stratum. Results. Eight hundred sixty patients were followed off ART over 2789 person-years (PY). In the ≥650, 500–649, 350–499, 200–349, 100–199, 50–99, and 0–49 cells/μL CD4 cell count strata, the rates of AIDS or death were 0.9, 1.7, 3.7, 10.4, 30.9, 60.8, and 99.9 events per 100 PY, respectively. In patients with CD4 cell counts ≥200 CD4 cells/μL, the most frequent AIDS-defining disease was tuberculosis (decreasing from 4.0 to 0.6 events per 100 PY for 200–349 and ≥650 cells/μL, respectively), and the most frequent HIV non-AIDS severe diseases were visceral bacterial diseases (decreasing from 9.1 to 3.6 events per 100 PY). Conclusions. Rates of AIDS or death, tuberculosis, and invasive bacterial diseases are substantial in patients with CD4 cell counts ≥200 cells/μL. Tuberculosis and bacterial diseases should be the most important outcomes in future trials of early ART in sub–Saharan Africa. PMID:22173233

  15. Complicated Urinary Tract Infection in Adults

    Directory of Open Access Journals (Sweden)

    LE Nicolle

    2005-01-01

    Full Text Available BACKGROUND: Complicated urinary tract infection occurs in individuals with functional or structural abnormalities of the genitourinary tract.OBJECTIVE: To review current knowledge relevant to complicated urinary tract infection, and to provide evidence-based recommendations for management.METHODS: The literature was reviewed through a PubMed search, and additional articles were identified by journal reference review. A draft guideline was prepared and critically reviewed by members of the Association of Medical Microbiology and Infectious Disease Canada Guidelines Committee, with modifications incorporated following the review.RESULTS: Many urological abnormalities may be associated with complicated urinary infection. There is a wide spectrum of potential infecting organisms, and isolated bacteria tend to be more resistant to antimicrobial therapy. Morbidity and infection outcomes in subjects with complicated urinary infection are principally determined by the underlying abnormality rather than the infection. Principles of management include uniform collection of a urine specimen for culture before antimicrobial therapy, characterization of the underlying genitourinary abnormality, and nontreatment of asymptomatic bacteriuria except before an invasive genitourinary procedure. The antimicrobial regimen is determined by clinical presentation, patient tolerance, renal function and known or anticipated infecting organisms. If the underlying abnormality contributing to the urinary infection cannot be corrected, then early post-treatment recurrence of infection is anticipated.CONCLUSIONS: The management of complicated urinary infection is individualized depending on patient variables and the infecting organism. Further clinical investigations are necessary to assist in determining optimal antimicrobial regimens.

  16. O-Specific Polysaccharide-Specific Memory B Cell Responses in Young Children, Older Children, and Adults Infected with Vibrio cholerae O1 Ogawa in Bangladesh.

    Science.gov (United States)

    Aktar, Amena; Rahman, M Arifur; Afrin, Sadia; Faruk, M Omar; Uddin, Taher; Akter, Aklima; Sami, M Israk Nur; Yasmin, Tahirah; Chowdhury, Fahima; Khan, Ashraful I; Leung, Daniel T; LaRocque, Regina C; Charles, Richelle C; Bhuiyan, Taufiqur Rahman; Mandlik, Anjali; Kelly, Meagan; Kováč, Pavol; Xu, Peng; Calderwood, Stephen B; Harris, Jason B; Qadri, Firdausi; Ryan, Edward T

    2016-05-01

    Cholera caused by Vibrio cholerae O1 confers at least 3 to 10 years of protection against subsequent disease regardless of age, despite a relatively rapid fall in antibody levels in peripheral blood, suggesting that memory B cell responses may play an important role in protection. The V. cholerae O1-specific polysaccharide (OSP) component of lipopolysaccharide (LPS) is responsible for serogroup specificity, and it is unclear if young children are capable of developing memory B cell responses against OSP, a T cell-independent antigen, following cholera. To address this, we assessed OSP-specific memory B cell responses in young children (2 to 5 years, n = 11), older children (6 to 17 years, n = 21), and adults (18 to 55 years, n = 28) with cholera caused by V. cholerae O1 in Dhaka, Bangladesh. We also assessed memory B cell responses against LPS and vibriocidal responses, and plasma antibody responses against OSP, LPS, and cholera toxin B subunit (CtxB; a T cell-dependent antigen) on days 2 and 7, as well as days 30, 90, and 180 after convalescence. In all age cohorts, vibriocidal responses and plasma OSP, LPS, and CtxB-specific responses peaked on day 7 and fell toward baseline over the follow-up period. In comparison, we were able to detect OSP memory B cell responses in all age cohorts of patients with detectable responses over baseline for 90 to 180 days. Our results suggest that OSP-specific memory B cell responses can occur following cholera, even in the youngest children, and may explain in part the age-independent induction of long-term immunity following naturally acquired disease. PMID:27009211

  17. NK Cells and Poxvirus infection

    Directory of Open Access Journals (Sweden)

    Deborah N. Burshtyn

    2013-01-01

    Full Text Available In recent years our understanding of the role of NK cells in the response to viral infection has grown rapidly. Not only do we realize viruses have many immune evasion strategies to escape NK cell responses, but that stimulation of NK cell subsets during an antiviral response occurs through receptors seemingly geared directly at viral products and that NK cells can provide a memory response to viral pathogens. Tremendous knowledge has been gained in this area through the study of Herpes viruses, but appreciation for the significance of NK cells in the response to other types of viral infections is growing. The function of NK cells in defense against poxviruses has emerged over several decades beginning with the early seminal studies showing the role of NK cells and the NK gene complex in susceptibility of mouse strains to Ectromelia, a poxvirus pathogen of mice. More recently, greater understanding has emerged of the molecular details of the response. Given that human diseases caused by poxviruses can be as lethal as smallpox or as benign as Molluscum contagiosum, and that Vaccinia virus, the prototypic member of the pox family, persists as a mainstay of vaccine design and has potential as an oncolytic virus for tumor therapy, further research in this area remains important. This review focuses on recent advances in understanding the role of NK cells in the immune response to poxviruses, the receptors involved in activation of NK cells during poxvirus infection, and the viral evasion strategies poxviruses employ to avoid the NK response.

  18. An Infected Urachal Cyst in an Adult Woman

    Science.gov (United States)

    Kaya, Serdar; Bacanakgıl, Besim Haluk; Soyman, Zeynep; Kerımova, Roya; Battal Havare, Semiha; Kaya, Başak

    2015-01-01

    The urachus is an embryologic remnant which degenerates after the birth. Defective obliteration of the urachus leads to urachal abnormalities. An infected urachal cyst is one of the urachal abnormalities and this pathology is rare in adult women. We report a case of 33-year-old woman with pelvic pain and dysuria who was diagnosed with infected urachal cyst. Infected urachal cyst is a rare pathology in adult women and this pathology should be considered in the differential diagnosis of acute abdomen. PMID:26167317

  19. An Infected Urachal Cyst in an Adult Woman

    Directory of Open Access Journals (Sweden)

    Serdar Kaya

    2015-01-01

    Full Text Available The urachus is an embryologic remnant which degenerates after the birth. Defective obliteration of the urachus leads to urachal abnormalities. An infected urachal cyst is one of the urachal abnormalities and this pathology is rare in adult women. We report a case of 33-year-old woman with pelvic pain and dysuria who was diagnosed with infected urachal cyst. Infected urachal cyst is a rare pathology in adult women and this pathology should be considered in the differential diagnosis of acute abdomen.

  20. Mast cells in viral infections

    Directory of Open Access Journals (Sweden)

    Piotr Witczak

    2012-04-01

    Full Text Available  There are some premises suggesting that mast cells are involved in the mechanisms of anti-virus defense and in viral disease pathomechanisms. Mast cells are particularly numerous at the portals of infections and thus may have immediate and easy contact with the external environment and invading pathogens. These cells express receptors responsible for recognition of virus-derived PAMP molecules, mainly Toll-like receptors (TLR3, TLR7/8 and TLR9, but also RIG-I-like and NOD-like molecules. Furthermore, mast cells generate various mediators, cytokines and chemokines which modulate the intensity of inflammation and regulate the course of innate and adaptive anti-viral immunity. Indirect evidence for the role of mast cells in viral infections is also provided by clinical observations and results of animal studies. Currently, more and more data indicate that mast cells can be infected by some viruses (dengue virus, adenoviruses, hantaviruses, cytomegaloviruses, reoviruses, HIV-1 virus. It is also demonstrated that mast cells can release pre formed mediators as well as synthesize de novo eicosanoids in response to stimulation by viruses. Several data indicate that virus-stimulated mast cells secrete cytokines and chemokines, including interferons as well as chemokines with a key role in NK and Tc lymphocyte influx. Moreover, some information indicates that mast cell stimulation via TLR3, TLR7/8 and TLR9 can affect their adhesion to extracellular matrix proteins and chemotaxis, and influence expression of some membrane molecules. Critical analysis of current data leads to the conclusion that it is not yet possible to make definitive statements about the role of mast cells in innate and acquired defense mechanisms developing in the course of viral infection and/or pathomechanisms of viral diseases.

  1. Therapeutic potential of adult stem cells

    DEFF Research Database (Denmark)

    Serakinci, Nedime; Keith, W. Nicol

    2006-01-01

    lineages are an attractive alternative to human embryonic stem cells (hES) in regenerative medicine. In many countries, present legislation surrounding hES cells makes their use problematic, and indeed the origin of hES cells may represent a controversial issue for many communities. However, adult stem...... is the necessity to be able to identify, select, expand and manipulate cells outside the body. Recent advances in adult stem cell technologies and basic biology have accelerated therapeutic opportunities aimed at eventual clinical applications. Adult stem cells with the ability to differentiate down multiple...... cells are not subject to these issues. This review will therefore focus on adult stem cells. Based on their extensive differentiation potential and, in some cases, the relative ease of their isolation, adult stem cells are appropriate for clinical development. Recently, several observations suggest...

  2. Hematopoietic Stem and Immune Cells in Chronic HIV Infection

    Directory of Open Access Journals (Sweden)

    Jielin Zhang

    2015-01-01

    Full Text Available Hematopoietic stem cell (HSC belongs to multipotent adult somatic stem cells. A single HSC can reconstitute the entire blood system via self-renewal, differentiation into all lineages of blood cells, and replenishment of cells lost due to attrition or disease in a person’s lifetime. Although all blood and immune cells derive from HSC, immune cells, specifically immune memory cells, have the properties of HSC on self-renewal and differentiation into lineage effector cells responding to the invading pathogens. Moreover, the interplay between immune memory cell and viral pathogen determines the course of a viral infection. Here, we state our point of view on the role of blood stem and progenitor cell in chronic HIV infection, with a focus on memory CD4 T-cell in the context of HIV/AIDS eradication and cure.

  3. Hematopoietic Stem and Immune Cells in Chronic HIV Infection.

    Science.gov (United States)

    Zhang, Jielin; Crumpacker, Clyde

    2015-01-01

    Hematopoietic stem cell (HSC) belongs to multipotent adult somatic stem cells. A single HSC can reconstitute the entire blood system via self-renewal, differentiation into all lineages of blood cells, and replenishment of cells lost due to attrition or disease in a person's lifetime. Although all blood and immune cells derive from HSC, immune cells, specifically immune memory cells, have the properties of HSC on self-renewal and differentiation into lineage effector cells responding to the invading pathogens. Moreover, the interplay between immune memory cell and viral pathogen determines the course of a viral infection. Here, we state our point of view on the role of blood stem and progenitor cell in chronic HIV infection, with a focus on memory CD4 T-cell in the context of HIV/AIDS eradication and cure. PMID:26300920

  4. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE.

    Directory of Open Access Journals (Sweden)

    Jim Young

    Full Text Available BACKGROUND: Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART. It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. METHODS AND FINDINGS: Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger, we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements 500 copies/µl, the first of two consecutive measurements between 50-500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI of: 0.35 (0.30-0.40 for counts <200 cells/µl, 0.81 (0.71-0.92 for counts 200 to <350 cells/µl, 0.74 (0.66-0.83 for counts 350 to <500 cells/µl, and 0.96 (0.92-0.99 for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. CONCLUSIONS: Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

  5. Mesenchymal Stromal Cells and Viral Infection

    Directory of Open Access Journals (Sweden)

    Maytawan Thanunchai

    2015-01-01

    Full Text Available Mesenchymal Stromal Cells (MSCs are a subset of nonhematopoietic adult stem cells, readily isolated from various tissues and easily culture-expanded ex vivo. Intensive studies of the immune modulation and tissue regeneration over the past few years have demonstrated the great potential of MSCs for the prevention and treatment of steroid-resistant acute graft-versus-host disease (GvHD, immune-related disorders, and viral diseases. In immunocompromised individuals, the immunomodulatory activities of MSCs have raised safety concerns regarding the greater risk of primary viral infection and viral reactivation, which is a major cause of mortality after allogeneic transplantation. Moreover, high susceptibilities of MSCs to viral infections in vitro could reflect the destructive outcomes that might impair the clinical efficacy of MSCs infusion. However, the interplay between MSCs and virus is like a double-edge sword, and it also provides beneficial effects such as allowing the proliferation and function of antiviral specific effector cells instead of suppressing them, serving as an ideal tool for study of viral pathogenesis, and protecting hosts against viral challenge by using the antimicrobial activity. Here, we therefore review favorable and unfavorable consequences of MSCs and virus interaction with the highlight of safety and efficacy for applying MSCs as cell therapy.

  6. Adult stem cells and tissue repair.

    Science.gov (United States)

    Körbling, M; Estrov, Z; Champlin, R

    2003-08-01

    Recently, adult stem cells originating from bone marrow or peripheral blood have been suggested to contribute to repair and genesis of cells specific for liver, cardiac and skeletal muscle, gut, and brain tissue. The mechanism involved has been termed transdifferentiation, although other explanations including cell fusion have been postulated. Using adult stem cells to generate or repair solid organ tissue obviates the immunologic, ethical, and teratogenic issues that accompany embryonic stem cells. PMID:12931235

  7. An adult case of oral infection with Kingella kingae.

    NARCIS (Netherlands)

    Damme, P.A. van; Herpen, C.M.L. van; Meis, J.F.G.M.

    2004-01-01

    An exceptional case of microbiologically confirmed oral infection with Kingella kingae in an immunocompetent adult (30-year-old woman) is presented and the pathogenesis is discussed and related to known literature data.K. kingae is a rather common but yet relatively unknown commensal corroding bacte

  8. Management of gonococcal infection among adults and youth

    Science.gov (United States)

    Pogany, Lisa; Romanowski, Barbara; Robinson, Joan; Gale-Rowe, Margaret; Latham-Carmanico, Cathy; Weir, Christine; Wong, Tom

    2015-01-01

    Abstract Objective To provide recommendations on the management of gonococcal infection among adults and youth. Quality of evidence Treatment recommendations in the Canadian guidelines on sexually transmitted infections are based on review of the literature, as well as the grades of recommendations and the levels of evidence quality determined by a minimum of 2 reviewers. The recommendations are peer-reviewed and require approval by the expert working group. Main message The new key recommendations for managing gonococcal infection among adults and youth include using culture as a diagnostic tool when practical, providing treatment with combination antibiotic therapy (ceftriaxone combined with azithromycin), and promptly reporting all cases with treatment failure to public health. Conclusion Following these new key recommendations might reduce treatment failure, contribute to better surveillance of antibiotic-resistance trends in Neisseria gonorrhoeae, and contribute to the prevention of transmission of multidrug-resistant gonorrhea. PMID:26472793

  9. Perivascular ancestors of adult multipotent stem cells

    NARCIS (Netherlands)

    M. Corselli (Mirko); C.W. Chen; M. Crisan (Mihaela); L. Lazzari (Lorenza); B. Péault (Bruno)

    2010-01-01

    textabstractIndependent studies by numerous investigators have shown that it is possible to harvest multipotent progenitor cells from diverse dissociated and cultured fetal, perinatal, and principally adult developed tissues. Despite the increasingly recognized medical value of these progenitor cell

  10. Immunological control of adult neural stem cells

    OpenAIRE

    Gonzalez-Perez, Oscar; Quiñones-Hinojosa, Alfredo; Garcia-Verdugo, Jose Manuel

    2010-01-01

    Adult neurogenesis occurs only in discrete regions of adult central nervous system: the subventricular zone and the subgranular zone. These areas are populated by adult neural stem cells (aNSC) that are regulated by a number of molecules and signaling pathways, which control their cell fate choices, survival and proliferation rates. For a long time, it was believed that the immune system did not exert any control on neural proliferative niches. However, it has been observed that many patholog...

  11. Nosema ceranae Can Infect Honey Bee Larvae and Reduces Subsequent Adult Longevity.

    Directory of Open Access Journals (Sweden)

    Daren M Eiri

    Full Text Available Nosema ceranae causes a widespread disease that reduces honey bee health but is only thought to infect adult honey bees, not larvae, a critical life stage. We reared honey bee (Apis mellifera larvae in vitro and provide the first demonstration that N. ceranae can infect larvae and decrease subsequent adult longevity. We exposed three-day-old larvae to a single dose of 40,000 (40K, 10,000 (10K, zero (control, or 40K autoclaved (control N. ceranae spores in larval food. Spores developed intracellularly in midgut cells at the pre-pupal stage (8 days after egg hatching of 41% of bees exposed as larvae. We counted the number of N. ceranae spores in dissected bee midguts of pre-pupae and, in a separate group, upon adult death. Pre-pupae exposed to the 10K or 40K spore treatments as larvae had significantly elevated spore counts as compared to controls. Adults exposed as larvae had significantly elevated spore counts as compared to controls. Larval spore exposure decreased longevity: a 40K treatment decreased the age by which 75% of adult bees died by 28%. Unexpectedly, the low dose (10K led to significantly greater infection (1.3 fold more spores and 1.5 fold more infected bees than the high dose (40K upon adult death. Differential immune activation may be involved if the higher dose triggered a stronger larval immune response that resulted in fewer adult spores but imposed a cost, reducing lifespan. The impact of N. ceranae on honey bee larval development and the larvae of naturally infected colonies therefore deserve further study.

  12. Pericardial Tamponade in an Adult Suffering from Acute Mumps Infection

    Science.gov (United States)

    Flieger, Robert Rainer; Mankertz, Annette; Yilmaz, Kadir; Roepke, Torsten Kai

    2016-01-01

    Here, we report a case of a 51-year-old man with acute pericardial tamponade requiring emergency pericardiocentesis after he suffered from sore throat, headache, malaise, and sweats for two weeks. Serological analyses revealed increased mumps IgM and IgG indicating an acute mumps infection whereas other bacterial and viral infections were excluded. In addition, MRI revealed atypical swelling of the left submandibular gland. Whereas mumps has become a rare entity in children due to comprehensive vaccination regimens in western civilizations, our case highlights mumps as an important differential diagnosis also in adults, where the virus can induce life-threatening complications such as pericardial tamponade.

  13. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    Energy Technology Data Exchange (ETDEWEB)

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  14. Clinical grade adult stem cell banking

    OpenAIRE

    Thirumala, Sreedhar; Goebel, W. Scott; Woods, Erik J

    2009-01-01

    There has been a great deal of scientific interest recently generated by the potential therapeutic applications of adult stem cells in human care but there are several challenges regarding quality and safety in clinical applications and a number of these challenges relate to the processing and banking of these cells ex-vivo. As the number of clinical trials and the variety of adult cells used in regenerative therapy increases, safety remains a primary concern. This has inspired many nations t...

  15. Epidemiology of invasive Streptococcus pneumoniae infections in adults in Finland.

    Science.gov (United States)

    Sankilampi, U.; Herva, E.; Haikala, R.; Liimatainen, O.; Renkonen, O. V.; Leinonen, M.

    1997-01-01

    Laboratory-based surveillance of invasive pneumococcal infections in adults in Finland from 1983 to 1992 identified 862 episodes of pneumococcal bacteraemia and 97 episodes of meningitis. The overall incidence of invasive pneumococcal infections was 9.1 per 100,000 for all adults per year, but 27.1, 35.8, and 44.5 per 100,000 in those aged 65 years or over, 75 years or over, and 85 years or over, respectively. Most (99.7%) of the pneumococcal strains were sensitive to penicillin. Ninety-five percent of the strains belonged to serogroups/types present in the 23-valent pneumococcal polysaccharide vaccine. Group/type distribution was different in patients aged 16-64 years compared to those 65 years or over (P < 0.001), in bacteraemia compared to meningitis (P < 0.001), and in the years 1983-7 compared to 1988-92 (P < 0.05). PMID:9042030

  16. Coronavirus infection of polarized epithelial cells

    NARCIS (Netherlands)

    Rossen, J W; Horzinek, M C; Rottier, P J

    1995-01-01

    Epithelial cells are the first host cells to be infected by incoming c oronaviruses. Recent observations in vitro show that coronaviruses are released from a specific side of these polarized cells, and this polarized release might be important for the spread of the infection in vivo. Mechanisms for

  17. Infected Urachal Cyst in an Adult: A Laparoscopic Approach

    Science.gov (United States)

    Kwok, Ching-Ming

    2016-01-01

    Urachal cysts occur infrequently in adults and are rarely reported in the literature. Laparoscopic excision or robot-assisted laparoscopic excision of urachal cysts has widely been applied in recent years. We present a case of urachal cyst infection treated with antibiotics and two-staged operation. The laparoscopic procedure was performed without any complications. Strong suspicion is the key for early diagnosis. PMID:27462196

  18. Inapparent Streptococcus agalactiae infection in adult/commercial tilapia.

    Science.gov (United States)

    Sun, Jiufeng; Fang, Wei; Ke, Bixia; He, Dongmei; Liang, Yuheng; Ning, Dan; Tan, Hailing; Peng, Hualin; Wang, Yunxin; Ma, Yazhou; Ke, Changwen; Deng, Xiaoling

    2016-01-01

    We report on inapparent infections in adult/commercial tilapia in major tilapia fish farms in Guangdong. A total of 146 suspected isolates were confirmed to be S. agalactiae using an API 20 Strep system and specific PCR amplification. All isolates were identified as serotype Ia using multiplex serotyping PCR. An MLST assay showed single alleles of adhP (10), atr (2), glcK (2), glnA (1), pheS (1), sdhA (3) and tkt (2), and this profile was designated 'unique ST 7'. The analysis of virulence genes resulted in 10 clusters, of which dltr-bca-sodA-spb1-cfb-bac (62, 42.47%) was the predominant virulence gene profile. The PFGE analysis of S. agalactiae yielded 6 distinct PFGE types (A, B, C, D, F and G), of which Pattern C (103) was the predominant type, accounting for approximately 70.55% (103/146) of the total S. agalactiae strains. Therefore, unlike what has been found in juvenile tilapia, in which PFGE pattern D/F is the major prevalent pattern, we found that pattern C was the major prevalent pattern in inapparent infected adult/commercial tilapia in Guangdong, China. In conclusion, we close a gap in the current understanding of S. agalactiae epidemiology and propose that researchers should be alert for inapparent S. agalactiae infections in adult/commercial tilapia to prevent a potential threat to food safety. PMID:27215811

  19. Plague Bacteria Target Immune Cells During Infection

    OpenAIRE

    Marketon, Melanie M.; DePaolo, R. William; DeBord, Kristin L.; Jabri, Bana; Schneewind, Olaf

    2005-01-01

    The plague is caused by the bacterium Yersinia pestis. Plague bacteria are thought to inject effector Yop proteins into host cells via the type III pathway. The identity of the host cells targeted for injection during plague infection is unknown. We found, using Yop β-lactamase hybrids and fluorescent staining of live cells from plague-infected animals, that Y. pestis selected immune cells for injection. In vivo, dendritic cells, macrophages, and neutrophils were injected most frequently, whe...

  20. HCV Infection and B-Cell Lymphomagenesis

    Directory of Open Access Journals (Sweden)

    Masahiko Ito

    2011-01-01

    Full Text Available Hepatitis C virus (HCV has been recognized as a major cause of chronic liver diseases worldwide. It has been suggested that HCV infects not only hepatocytes but also mononuclear lymphocytes including B cells that express the CD81 molecule, a putative HCV receptor. HCV infection of B cells is the likely cause of B-cell dysregulation disorders such as mixed cryoglobulinemia, rheumatoid factor production, and B-cell lymphoproliferative disorders that may evolve into non-Hodgkin's lymphoma (NHL. Epidemiological data indicate an association between HCV chronic infection and the occurrence of B-cell NHL, suggesting that chronic HCV infection is associated at least in part with B-cell lymphomagenesis. In this paper, we aim to provide an overview of recent literature, including our own, to elucidate a possible role of HCV chronic infection in B-cell lymphomagenesis.

  1. Helicobacter pylori Infection and Anemia in Taiwanese Adults

    Directory of Open Access Journals (Sweden)

    Hsiang-Yao Shih

    2013-01-01

    Full Text Available Background. Chronic Helicobacter pylori infection and iron-deficiency anemia (IDA are common in adults. Although the most common causes of IDA usually arise from the gastrointestinal tract, the association between chronic Helicobacter pylori infection and anemia remains unclear. Aim. To evaluate the association of chronic Helicobacter pylori infection and IDA. Materials and Methods. We enrolled 882 patients from January 2010 to April 2013. The status of Helicobacter pylori (H.p infection was confirmed and blood samples from the same participants were taken on the same day to check the level of hemoglobin, serum iron, ferritin, and total iron-binding capacity (TIBC. Results. No significant difference was noted from the demographic data. The average level of hemoglobin (Hb was not different between negative and positive groups, pos 13.57 g/dL versus neg 13.65 g/dL (P=0.699. Although the levels of serum IDA related parameters were expected in positive group (lower serum iron and ferritin and higher TIBC these differences did not reach statistical significance (P=0.824 for iron, P=0.360 for ferritin, and P=0.252 for TIBC. Conclusion. Chronic Helicobacter pylori infection is not attributed to IDA. The levels of hemoglobin, serum iron and ferritin, and TIBC remain unaffected after chronic H.p infection. Large-scale clinical studies are needed to prove the association.

  2. Sexually Transmitted Infections (STIs among young adult in Italy

    Directory of Open Access Journals (Sweden)

    Maria Cristina Salfa

    2010-12-01

    Full Text Available Sexually transmitted infections (STIs include a large group of widespread infectious diseases, which may cause acute symptoms, chronic infections and severe long term complications.The control and prevention of these infections are public health priorities for several reasons: • the large number of people that acquire an STI per year; • the major proportion of asymptomatic infected individuals; • the high circulation in patients with sexual risk behavior (young adults, pluripartner, men who have sex with men, foreigners, commercial sex workers; • increased biological susceptibility of some subjects, such as young adults (immature genital tissues and more receptive to pathogens, women (genital apparatus more complex and extended in which pathogens are more likely to settle, or individuals carrying states of severe immunodeficiency; • the serious complications in the event of failure or incorrect diagnosis and treatment (chronic disease, infertility, oncogenic transformation, synergy with HIV infection; • the possibility of preventing and treating many of these infections. Therefore, recent guidelines from international agencies have recommended countries from the European Union to improve epidemiological STI surveillance systems in order to standardize data collection to facilitate their comparability between different geographical areas and to improve the information flow for faster tracking of the impact; furthermore, to extend surveillance to widespread, but often asymptomatic, disease (e.g. Chlamydia trachomatis, to conduct behavioural surveillance in patients with STIs, to increase public awareness of the role of STIs in the transmission/acquisition of HIV, and to increase the commitment of institutions in the prevention and control of STIs.

  3. Bladder cancer in HIV-infected adults: an emerging concern?

    Directory of Open Access Journals (Sweden)

    Sylvain Chawki

    2014-11-01

    Full Text Available Introduction: As HIV-infected patients get older more non-AIDS-related malignancies are to be seen. Cancer now represents almost one third of all causes of deaths among HIV-infected patients (1. Albeit bladder cancer is one of the most common malignancy worldwide (2, only 13 cases of bladder cancer in HIV-infected patients have been reported in the literature so far (3. Materials and Methods: We conducted a monocentric study in our hospital. We selected all patients who were previously admitted (from 1998 to 2013 in our hospital with diagnoses of HIV and bladder cancer. The objective was to assess the prevalence and characteristics of bladder cancers in HIV-infected patients in our hospital. Results: Based on our administrative HIV database (6353 patients, we found 15 patients (0.2% with a bladder cancer. Patients’ characteristics are presented in Table 1. Patients were mostly men and heavy smokers. Their median nadir CD4 cell count was below 200 and most had a diagnosis of AIDS. A median time of 14 years was observed in those patients, between the diagnosis of HIV-infection and the occurrence of bladder cancer, although in patients much younger (median age 56 than those developing bladder cancer without HIV infection (71.1 years (4. Haematuria was the most frequent diagnosis circumstance in HIV-infected patients who had relatively preserved immune function on highly active antiretroviral therapy (HAART. Histopathology showed relatively advanced cancers at diagnosis with a high percentage of non transitional cell carcinoma (TCC tumor and of TCC with squamous differentiation, suggesting a potential role for human papilloma virus (HPV co-infection. Death rate was high in this population. Conclusions: Bladder cancers in HIV-infected patients remain rare but occur in relatively young HIV-infected patients with a low CD4 nadir, presenting with haematuria, most of them being smokers, and have aggressive pathological features that are associated with

  4. [Hypercalcemia of T-cell leukemia in adults].

    Science.gov (United States)

    Jean-Baptiste, G; Arfi, S; Plumelle, Y; Panelatti, G; Mangin, J L; Pascaline, N

    1993-04-01

    A retrospective study of 26 adults with acute T-cell leukemia showed that 14 patients (54%) had hypercalcemia at some point of the disease. Hypercalcemia was found at presentation in nine patients and revealed the disease in one. Eight patients had hypercalcemia at the time of death. Serum phosphorus and parathyroid hormone levels were normal. All patients with hypercalcemia tested positive for the HTLV-1 by Elisa and Western blot. Six patients had focalized or diffuse lytic roentgenographic bone lesions. Hypercalcemia in acute T-cell leukemia may involve production of interleukin-1-alpha and parathyroid hormone-related protein by HTLV-1-infected cells. PMID:8167627

  5. Multisystem langerhans cell histiocytosis in adult

    OpenAIRE

    Anubhav Garg; Pramod Kumar

    2012-01-01

    Langerhans cell histiocytosis (LCH), is a rare disorder, clinically presents with heterogeneous manifestations, and has an unpredictable outcome. Commonly seen in infancy or early childhood, the disorder is characterized by proliferation of abnormal and clonal Langerhans cell in skin, bone, lymph nodes, lungs, liver, spleen, and bone marrow. Occurrence of LCH in adults is rare. Here, we report the case of an adult with acute onset of polymorphic eruptions all over the body, which on biopsy sh...

  6. The Effect of Arthrospira platensis Capsules on CD4 T-Cells and Antioxidative Capacity in a Randomized Pilot Study of Adult Women Infected with Human Immunodeficiency Virus Not under HAART in Yaoundé, Cameroon

    Directory of Open Access Journals (Sweden)

    Frank Stéphane Winter

    2014-07-01

    Full Text Available Dietary supplements are often used to improve the nutritional status of people living with HIV/AIDS (PLHIV. Arthrospira platensis (Asp, also known as Spirulina, is a cyanobacterium rich in proteins and micronutrients. Cell and animal trials described immune-modulating, antiretroviral and antioxidant activities. This pilot study describes the effects of the supplementation of 5 g/day of Asp on a pre-highly-active antiretroviral therapy (pre-HAART, HIV-infected, adult female population. It was conducted as a three-month randomized controlled trial (RCT that compared a cup supplementation of five grams/day of Asp with a placebo of equal protein content and energy. The study included 73 HIV-infected women. The immediate outcome variables were CD4 T-cells, viral load and immune activation by CD8 T-cells expressing CD38. The antioxidant status was assessed by way of the total antioxidant capacity of the serum (TAOS. The renal function was documented by way of creatinine, urea and the calculated glomerular filtration rate. Statistical analyses were carried out with non-parametric tests, and the effect size of each interaction was calculated. No differences in the immunological and virological markers between the Asp and the placebo group could be observed. In the placebo group, 21 of 30 patients (70% developed concomitant events, while in the Asp group, only 12 of 28 patients (43% did. Both groups registered a significant weight increase; 0.5 kg (p < 0.05 in the Asp group and 0.65 kg (p < 0.05 in the placebo group. The antioxidant capacity increase of 56 (1–98 µM for Asp was significantly different from the decrease observed in the placebo group (p < 0.001. A slight increase in the creatinine level of 0.1 g/dL (p < 0.001 was observed in the Asp group, and no effect was observed in the urea levels. The improvement of the antioxidant capacity under Asp, shown for the first time on PLHIV, could become a focus for future research on the nutritional and

  7. The association between Helicobacter pylori infection and adult height

    International Nuclear Information System (INIS)

    Objectives: A cross-sectional survey was performed to evaluate the association between H. pylori and adult height. Methods: H. pylori infection was assessed using a 13C-urea breath test and height measured by a research nurse using a stadiometer in participants between the ages of 40-49 years. Results: Height was measured in 2932/3682 participants that attended and were evaluable. H. pylori infected women were 1.4 cm shorter than uninfected women (95% confidence interval, CI=0.7-2.1 cm) and this statistically significant difference persisted after adjusting for age, ethnicity, childhood and present socio-economic status (H. pylori positives 0.79 cm shorter; 95%CI: 0.05-1.52 cm). H. pylori positive men were 0.7 cm shorter than uninfected men but this did not reach statistical significance (95% CI: -0.1-1.5 cm). Conclusion: Although H. pylori infection is associated with reduced adult height in women, this maybe due to residual confounding

  8. Ex vivo infection of human embryonic spinal cord neurons prior to transplantation into adult mouse cord

    Directory of Open Access Journals (Sweden)

    Dénes Ádám

    2010-05-01

    Full Text Available Abstract Background Genetically modified pseudorabies virus (Prv proved suitable for the delivery of foreign genes to rodent embryonic neurons ex vivo and maintaining foreign gene expression after transplantation into spinal cord in our earlier study. The question arose of whether human embryonic neurons, which are known to be more resistant to Prv, could also be infected with a mutant Prv. Specifically, we investigated whether a mutant Prv with deleted ribonucleotide reductase and early protein 0 genes has the potential to deliver marker genes (gfp and β-gal into human embryonic spinal cord neurons and whether the infected neurons maintain expression after transplantation into adult mouse cord. Results The results revealed that the mutant Prv effectively infected human embryonic spinal cord neurons ex vivo and the grafted cells exhibited reporter gene expression for several weeks. Grafting of infected human embryonic cells into the spinal cord of immunodeficient (rnu-/rnu- mice resulted in the infection of some of the host neurons. Discussion These results suggest that Prv is suitable for the delivery of foreign genes into transplantable human cells. This delivery method may offer a new approach to use genetically modified cells for grafting in animal models where spinal cord neuronal loss or axon degeneration occurs.

  9. The impact of juvenile coxsackievirus infection on cardiac progenitor cells and postnatal heart development.

    Science.gov (United States)

    Sin, Jon; Puccini, Jenna M; Huang, Chengqun; Konstandin, Mathias H; Gilbert, Paul E; Sussman, Mark A; Gottlieb, Roberta A; Feuer, Ralph

    2014-07-01

    Coxsackievirus B (CVB) is an enterovirus that most commonly causes a self-limited febrile illness in infants, but cases of severe infection can manifest in acute myocarditis. Chronic consequences of mild CVB infection are unknown, though there is an epidemiologic association between early subclinical infections and late heart failure, raising the possibility of subtle damage leading to late-onset dysfunction, or chronic ongoing injury due to inflammatory reactions during latent infection. Here we describe a mouse model of juvenile infection with a subclinical dose of coxsackievirus B3 (CVB3) which showed no evident symptoms, either immediately following infection or in adult mice. However following physiological or pharmacologically-induced cardiac stress, juvenile-infected adult mice underwent cardiac hypertrophy and dilation indicative of progression to heart failure. Evaluation of the vasculature in the hearts of adult mice subjected to cardiac stress showed a compensatory increase in CD31+ blood vessel formation, although this effect was suppressed in juvenile-infected mice. Moreover, CVB3 efficiently infected juvenile c-kit+ cells, and cardiac progenitor cell numbers were reduced in the hearts of juvenile-infected adult mice. These results suggest that the exhausted cardiac progenitor cell pool following juvenile CVB3 infection may impair the heart's ability to increase capillary density to adapt to increased load.

  10. Adult Stem Cells and Diabetes Therapy

    OpenAIRE

    Ilgun, Handenur; Kim, Joseph William; Luo, LuGuang

    2015-01-01

    The World Health Organization estimates that diabetes will be the fourth most prevalent disease by 2050. Developing a new therapy for diabetes is a challenge for researchers and clinicians in field. Many medications are being used for treatment of diabetes however with no conclusive and effective results therefore alternative therapies are required. Stem cell therapy is a promising tool for diabetes therapy, and it has involved embryonic stem cells, adult stem cells, and pluripotent stem cell...

  11. Mortality, AIDS-morbidity and loss to follow-up by current CD4 cell count among HIV-1 infected adults receiving antiretroviral therapy in Africa and Asia: data from the ANRS 12222 collaboration

    Science.gov (United States)

    Gabillard, Delphine; Lewden, Charlotte; Ndoye, Ibra; Moh, Raoul; Ségéral, Olivier; Tonwe-Gold, Besigin; Etard, Jean-François; Pagnaroat, Men; Fournier-Nicolle, Isabelle; Eholié, Serge; Konate, Issouf; Minga, Albert; Mpoudi-Ngolé, Eitel; Koulla-Shiro, Sinata; Zannou, Djimon Marcel; Anglaret, Xavier; Laurent, Christian

    2013-01-01

    Background In resource-limited countries, estimating CD4-specific incidence rates of mortality and morbidity among patients receiving antiretroviral therapy (ART) may help assess the effectiveness of care and treatment programmes, identify program weaknesses and inform decisions. Methods We pooled data from 13 research cohorts in five sub-Saharan African (Benin, Burkina Faso, Cameroon, Cote d'Ivoire and Senegal) and two Asian (Cambodia and Laos) countries. HIV-infected adults (≥18 years) who received ART in 1998-2008 and had at least one CD4 count available were eligible. Changes in CD4 counts over time were estimated by a linear mixed regression. CD4-specific incidence rates were estimated as the number of first events occurring in a given CD4 stratum divided by the time spent within the stratum. Results Overall 3,917 adults (62% women) on ART were followed-up during 10,154 person-years. In the ≤50, 51-100, 101-200, 201-350, 351-500, 501-650 and >650/mm3 CD4 cells strata, death rates were: 20.6, 11.8, 6.7, 3.3, 1.8, 0.9 and 0.3 per 100 person-years; AIDS rates were: 50.5, 32.9, 11.5, 4.8, 2.8, 2.2 and 2.2 per 100 person-years; and loss to follow-up rates were: 4.9, 6.1, 3.5, 3.1, 2.9, 1.7 and 1.2 per 100 person-years, respectively. Mortality and morbidity were higher during the first year following ART initiation. Conclusion In these resource-limited settings, death and AIDS rates remained substantial after ART initiation, even in individuals with high CD4 cell counts. Ensuring earlier ART initiation and optimizing case finding and treatment for AIDS-defining diseases should be seen as priorities. PMID:23274931

  12. Vaccine Therapy in Preventing Cytomegalovirus Infection in Patients With Hematological Malignancies Undergoing Donor Stem Cell Transplant

    Science.gov (United States)

    2016-05-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Adult Acute Promyelocytic Leukemia (M3); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma; Anaplastic Large Cell Lymphoma; B-cell Adult Acute Lymphoblastic Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cytomegalovirus Infection; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Isolated Plasmacytoma of Bone; Monoclonal Gammopathy of Undetermined Significance; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously

  13. Inapparent Streptococcus agalactiae infection in adult/commercial tilapia

    OpenAIRE

    Jiufeng Sun; Wei Fang; Bixia Ke; Dongmei He; Yuheng Liang; Dan Ning; Hailing Tan; Hualin Peng; Yunxin Wang; Yazhou Ma; Changwen Ke; Xiaoling Deng

    2016-01-01

    We report on inapparent infections in adult/commercial tilapia in major tilapia fish farms in Guangdong. A total of 146 suspected isolates were confirmed to be S. agalactiae using an API 20 Strep system and specific PCR amplification. All isolates were identified as serotype Ia using multiplex serotyping PCR. An MLST assay showed single alleles of adhP (10), atr (2), glcK (2), glnA (1), pheS (1), sdhA (3) and tkt (2), and this profile was designated ‘unique ST 7’. The analysis of virulence ge...

  14. Brain abscess caused by Citrobacter koseri infection in an adult.

    Science.gov (United States)

    Liu, Heng-Wei; Chang, Chih-Ju; Hsieh, Cheng-Ta

    2015-04-01

    Citrobacter koseri is a gram-negative bacillus that causes mostly meningitis and brain abscesses in neonates and infants. However, brain abscess caused by Citrobacter koseri infection in an adult is extremely rare, and only 2 cases have been described. Here, we reported a 73-year-old male presenting with a 3-week headache. A history of diabetes mellitus was noted. The images revealed a brain abscess in the left frontal lobe and pus culture confirmed the growth of Citrobacter koseri. The clinical symptoms improved completely postoperatively.

  15. Thymic involvement in immune recovery during antiretroviral treatment of HIV infection in adults; comparison of CT and sonographic findings

    DEFF Research Database (Denmark)

    Kolte, Lilian; Strandberg, Charlotte; Dreves, Anne-Mette;

    2002-01-01

    In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size and predict......In adult HIV-infected patients, thymic size evaluated from CT scans seems to be important to the degree of immune reconstitution obtainable during treatment with highly active antiretroviral therapy (HAART). To examine whether ultrasound is as reliable as CT for estimating thymic size...... and predicting immune recovery, CT and ultrasound scans were performed in 25 adult HIV-infected patients and 10 controls. CD4 counts and naive CD4 counts were measured in order to determine immune reconstitution. Furthermore, the CD4+ T-cell receptor excision circle (TREC) frequency and T-cell receptor (TCR...

  16. Genetic polymorphisms and HPV infection in oral squamous cell carcinomas.

    Science.gov (United States)

    Sun, Yan; Zhang, Yang; Liu, Limei; Song, Xicheng; Li, Guojun

    2015-10-01

    Despite declining smoking rates in the United States, the incidence of oral squamous cell carcinomas (OSCC, including oral cavity and oropharynx) is rising in young adults. The reasons have been attributed to changes in sexual behaviors and the increasingly prevalent infection of oncogenic subtypes of human papillomavirus (HPV), principally type16 and occasionally type18. However, only small proportion of individuals who have contracted HPV infection will develop OSCC, suggesting that there is an inter-individual variation in susceptibility to HPV infection and related OSCC. Identification of susceptible biomarkers for HPV status would be useful to identify those individuals who are susceptible to HPV infection, to refine the prognostication of HPV associated OSCC, and ultimately to improve prevention efforts for OSCC and potentially other HPV-associated diseases. Our public health OSCC prevention paradigm will need to expand beyond tobacco and alcohol control.

  17. Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells.

    Directory of Open Access Journals (Sweden)

    Leonardo D'Aiuto

    Full Text Available Human cytomegalovirus (HCMV infection is one of the leading prenatal causes of congenital mental retardation and deformities world-wide. Access to cultured human neuronal lineages, necessary to understand the species specific pathogenic effects of HCMV, has been limited by difficulties in sustaining primary human neuronal cultures. Human induced pluripotent stem (iPS cells now provide an opportunity for such research. We derived iPS cells from human adult fibroblasts and induced neural lineages to investigate their susceptibility to infection with HCMV strain Ad169. Analysis of iPS cells, iPS-derived neural stem cells (NSCs, neural progenitor cells (NPCs and neurons suggests that (i iPS cells are not permissive to HCMV infection, i.e., they do not permit a full viral replication cycle; (ii Neural stem cells have impaired differentiation when infected by HCMV; (iii NPCs are fully permissive for HCMV infection; altered expression of genes related to neural metabolism or neuronal differentiation is also observed; (iv most iPS-derived neurons are not permissive to HCMV infection; and (v infected neurons have impaired calcium influx in response to glutamate.

  18. Delayed expulsion of adult Trichinella spiralis by mast cell-deficient W/Wv mice.

    OpenAIRE

    Ha, T. Y.; Reed, N D; Crowle, P K

    1983-01-01

    Mast cell-deficient W/Wv mice and their mast cell-sufficient littermates were given infections of Trichinella spiralis. W/Wv mice were slower than their littermates to expel adult T. spiralis. Repair of the mast cell deficiency of W/Wv mice by bone marrow grafting was accompanied by accelerated expulsion of T. spiralis.

  19. Adult Stem Cells and Diseases of Aging

    Directory of Open Access Journals (Sweden)

    Lisa B. Boyette

    2014-01-01

    Full Text Available Preservation of adult stem cells pools is critical for maintaining tissue homeostasis into old age. Exhaustion of adult stem cell pools as a result of deranged metabolic signaling, premature senescence as a response to oncogenic insults to the somatic genome, and other causes contribute to tissue degeneration with age. Both progeria, an extreme example of early-onset aging, and heritable longevity have provided avenues to study regulation of the aging program and its impact on adult stem cell compartments. In this review, we discuss recent findings concerning the effects of aging on stem cells, contributions of stem cells to age-related pathologies, examples of signaling pathways at work in these processes, and lessons about cellular aging gleaned from the development and refinement of cellular reprogramming technologies. We highlight emerging therapeutic approaches to manipulation of key signaling pathways corrupting or exhausting adult stem cells, as well as other approaches targeted at maintaining robust stem cell pools to extend not only lifespan but healthspan.

  20. 28. Embryonic and adult stem cell therapy.

    Science.gov (United States)

    Henningson, Carl T; Stanislaus, Marisha A; Gewirtz, Alan M

    2003-02-01

    Stem cells are characterized by the ability to remain undifferentiated and to self-renew. Embryonic stem cells derived from blastocysts are pluripotent (able to differentiate into many cell types). Adult stem cells, which were traditionally thought to be monopotent multipotent, or tissue restricted, have recently also been shown to have pluripotent properties. Adult bone marrow stem cells have been shown to be capable of differentiating into skeletal muscle, brain microglia and astroglia, and hepatocytes. Stem cell lines derived from both embryonic stem and embryonic germ cells (from the embryonic gonadal ridge) are pluripotent and capable of self-renewal for long periods. Therefore embryonic stem and germ cells have been widely investigated for their potential to cure diseases by repairing or replacing damaged cells and tissues. Studies in animal models have shown that transplantation of fetal, embryonic stem, or embryonic germ cells may be able to treat some chronic diseases. In this review, we highlight recent developments in the use of stem cells as therapeutic agents for three such diseases: Diabetes, Parkinson disease, and congestive heart failure. We also discuss the potential use of stem cells as gene therapy delivery cells and the scientific and ethical issues that arise with the use of human stem cells. PMID:12592319

  1. A morphometric study of antral G-cell density in a sample of adult general population: comparison of three different methods and correlation with patient demography, helicobacter pylori infection, histomorphology and circulating gastrin levels

    DEFF Research Database (Denmark)

    Petersson, Fredrik; Borch, Kurt; Rehfeld, Jens F;

    2008-01-01

    Helicobacter pylori infection has been linked to hypergastrinemia and either decreased or normal G-cell content in the antral mucosa. To clarify this controversial issue, we quantitatively determined antral G-cell content on the same biopsy specimens with three different methods and examined whet...... colonization seem to be determinants of the G-cell density. That common morphometric techniques correlate poorly is of utmost importance to bear in mind when quantitative morphological studies are planned, compared or interpreted....

  2. Ibrutinib in Treating Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma in Patients With HIV Infection

    Science.gov (United States)

    2015-08-18

    Adult B Acute Lymphoblastic Leukemia; Chronic Lymphocytic Leukemia; Cutaneous B-Cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; HIV Infection; Intraocular Lymphoma; Multicentric Angiofollicular Lymphoid Hyperplasia; Nodal Marginal Zone Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Plasma Cell Myeloma; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

  3. Infection Prophylaxis and Management in Treating Cytomegalovirus (CMV) Infection in Patients With Hematologic Malignancies Previously Treated With Donor Stem Cell Transplant

    Science.gov (United States)

    2015-06-03

    Hematopoietic/Lymphoid Cancer; Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); 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); Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Aplastic Anemia; Atypical Chronic Myeloid Leukemia, BCR-ABL Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Cytomegalovirus Infection; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma

  4. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults

    Science.gov (United States)

    Günthard, Huldrych F.; Saag, Michael S.; Benson, Constance A.; del Rio, Carlos; Eron, Joseph J.; Gallant, Joel E.; Hoy, Jennifer F.; Mugavero, Michael J.; Sax, Paul E.; Thompson, Melanie A.; Gandhi, Rajesh T.; Landovitz, Raphael J.; Smith, Davey M.; Jacobsen, Donna M.; Volberding, Paul A.

    2016-01-01

    IMPORTANCE New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. OBJECTIVE To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. EVIDENCE REVIEW A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. FINDINGS Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory

  5. Fungal cell gigantism during mammalian infection.

    Science.gov (United States)

    Zaragoza, Oscar; García-Rodas, Rocío; Nosanchuk, Joshua D; Cuenca-Estrella, Manuel; Rodríguez-Tudela, Juan Luis; Casadevall, Arturo

    2010-01-01

    The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

  6. Fungal cell gigantism during mammalian infection.

    Directory of Open Access Journals (Sweden)

    Oscar Zaragoza

    Full Text Available The interaction between fungal pathogens with the host frequently results in morphological changes, such as hyphae formation. The encapsulated pathogenic fungus Cryptococcus neoformans is not considered a dimorphic fungus, and is predominantly found in host tissues as round yeast cells. However, there is a specific morphological change associated with cryptococcal infection that involves an increase in capsule volume. We now report another morphological change whereby gigantic cells are formed in tissue. The paper reports the phenotypic characterization of giant cells isolated from infected mice and the cellular changes associated with giant cell formation. C. neoformans infection in mice resulted in the appearance of giant cells with cell bodies up to 30 microm in diameter and capsules resistant to stripping with gamma-radiation and organic solvents. The proportion of giant cells ranged from 10 to 80% of the total lung fungal burden, depending on infection time, individual mice, and correlated with the type of immune response. When placed on agar, giant cells budded to produce small daughter cells that traversed the capsule of the mother cell at the speed of 20-50 m/h. Giant cells with dimensions that approximated those in vivo were observed in vitro after prolonged culture in minimal media, and were the oldest in the culture, suggesting that giant cell formation is an aging-dependent phenomenon. Giant cells recovered from mice displayed polyploidy, suggesting a mechanism by which gigantism results from cell cycle progression without cell fission. Giant cell formation was dependent on cAMP, but not on Ras1. Real-time imaging showed that giant cells were engaged, but not engulfed by phagocytic cells. We describe a remarkable new strategy for C. neoformans to evade the immune response by enlarging cell size, and suggest that gigantism results from replication without fission, a phenomenon that may also occur with other fungal pathogens.

  7. Can thymic epithelial cells be infected by human T-lymphotropic virus type 1?

    Directory of Open Access Journals (Sweden)

    Klaysa Moreira-Ramos

    2011-09-01

    Full Text Available The human T-lymphotropic virus type-1 (HTLV-1 is the cause of adult T cell leukaemias/lymphoma. Because thymic epithelial cells (TEC express recently defined receptors for the virus, it seemed conceivable that these cells might be a target for HTLV-1 infection. We developed an in vitro co-culture system comprising HTLV-1+-infected T cells and human TECs. Infected T cells did adhere to TECs and, after 24 h, the viral proteins gp46 and p19 were observed in TECs. After incubating TECs with culture supernatants from HTLV-1+-infected T cells, we detected gp46 on TEC membranes and the HTLV-1 tax gene integrated in the TEC genome. In conclusion, the human thymic epithelium can be infected in vitro by HTLV-1, not only via cell-cell contact, but also via exposure to virus-containing medium.

  8. Can thymic epithelial cells be infected by human T-lymphotropic virus type 1?

    Science.gov (United States)

    Moreira-Ramos, Klaysa; Castro, Flávia Madeira Monteiro de; Linhares-Lacerda, Leandra; Savino, Wilson

    2011-09-01

    The human T-lymphotropic virus type-1 (HTLV-1) is the cause of adult T cell leukaemias/lymphoma. Because thymic epithelial cells (TEC) express recently defined receptors for the virus, it seemed conceivable that these cells might be a target for HTLV-1 infection. We developed an in vitro co-culture system comprising HTLV-1+-infected T cells and human TECs. Infected T cells did adhere to TECs and, after 24 h, the viral proteins gp46 and p19 were observed in TECs. After incubating TECs with culture supernatants from HTLV-1+-infected T cells, we detected gp46 on TEC membranes and the HTLV-1 tax gene integrated in the TEC genome. In conclusion, the human thymic epithelium can be infected in vitro by HTLV-1, not only via cell-cell contact, but also via exposure to virus-containing medium. PMID:22012233

  9. Predictive diagnostic value of the tourniquet test for the diagnosis of dengue infection in adults

    OpenAIRE

    Mayxay, Mayfong; Phetsouvanh, Rattanaphone; Catrin E Moore; Chansamouth, Vilada; Vongsouvath, Manivanh; Sisouphone, Syho; Vongphachanh, Pankham; Thaojaikong, Thaksinaporn; Thongpaseuth, Soulignasack; Phongmany, Simmaly; Keolouangkhot, Valy; Strobel, Michel; Newton, Paul N.

    2011-01-01

    Objective To examine the accuracy of the admission tourniquet test in the diagnosis of dengue infection among Lao adults. Methods Prospective assessment of the predictive diagnostic value of the tourniquet test for the diagnosis of dengue infection, as defined by IgM, IgG and NS1 ELISAs (Panbio Ltd, Australia), among Lao adult inpatients with clinically suspected dengue infection. Results Of 234 patients with clinically suspected dengue infection on admission, 73% were serologically confirmed...

  10. Translational research of adult stem cell therapy

    Institute of Scientific and Technical Information of China (English)

    Gen; Suzuki

    2015-01-01

    Congestive heart failure(CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  11. Translational research of adult stem cell therapy.

    Science.gov (United States)

    Suzuki, Gen

    2015-11-26

    Congestive heart failure (CHF) secondary to chronic coronary artery disease is a major cause of morbidity and mortality world-wide. Its prevalence is increasing despite advances in medical and device therapies. Cell based therapies generating new cardiomyocytes and vessels have emerged as a promising treatment to reverse functional deterioration and prevent the progression to CHF. Functional efficacy of progenitor cells isolated from the bone marrow and the heart have been evaluated in preclinical large animal models. Furthermore, several clinical trials using autologous and allogeneic stem cells and progenitor cells have demonstrated their safety in humans yet their clinical relevance is inconclusive. This review will discuss the clinical therapeutic applications of three specific adult stem cells that have shown particularly promising regenerative effects in preclinical studies, bone marrow derived mesenchymal stem cell, heart derived cardiosphere-derived cell and cardiac stem cell. We will also discuss future therapeutic approaches.

  12. Research progress of adult cardiac stem cells

    OpenAIRE

    Zheng, Nan; Ning-kun ZHANG; Lian-ru GAO

    2013-01-01

    The traditional view is that the heart is a terminal organ. This dogma, however, has been widely questioned with the discovery of adult cardiac stem cells (CSCs). Since CSCs have a highly self-renewal capacity and specific myocardial differentiation potential, nowadays they have been regarded as the most promising type of stem cells used in ischemic heart disease and other replacement therapy of end-stage heart disease. The present paper will focus on current results of scientific research on...

  13. Adult Stem Cell Therapy for Periodontal Disease

    OpenAIRE

    Kim, Su-Hwan; Seo, Byoung-Moo; Choung, Pill-Hoon; Lee, Yong-Moo

    2010-01-01

    Periodontal disease is a major cause of tooth loss and characterized by inflammation of tooth-supporting structures. Recently, the association between periodontal disease and other health problems has been reported, the importance of treating periodontal disease for general health is more emphasized. The ultimate goal of periodontal therapy is regeneration of damaged periodontal tissues. The development of adult stem cell research enables to improve the cell-based tissue engineering for perio...

  14. Modulation of innate antigen-presenting cell function by pre-patent schistosome infection.

    Directory of Open Access Journals (Sweden)

    Christine E Ferragine

    Full Text Available Schistosomes are intravascular helminths that infect over 200 million people worldwide. Deposition of eggs by adult schistosomes stimulates Th2 responses to egg antigens and induces granulomatous pathology that is a hallmark of schistosome infection. Paradoxically, schistosomes require host immune function for their development and reproduction and for egress of parasite eggs from the host. To identify potential mechanisms by which immune cells might influence parasite development prior to the onset of egg production, we assessed immune function in mice infected with developing schistosomes. We found that pre-patent schistosome infection is associated with a loss of T cell responsiveness to other antigens and is due to a diminution in the ability of innate antigen-presenting cells to stimulate T cells. Diminution of stimulatory capacity by schistosome worms specifically affected CD11b(+ cells and did not require concomitant adaptive responses. We could not find evidence for production of a diffusible inhibitor of T cells by innate cells from infected mice. Rather, inhibition of T cell responsiveness by accessory cells required cell contact and only occurred when cells from infected mice outnumbered competent APCs by more than 3∶1. Finally, we show that loss of T cell stimulatory capacity may in part be due to suppression of IL-12 expression during pre-patent schistosome infection. Modulation of CD4(+ T cell and APC function may be an aspect of host immune exploitation by schistosomes, as both cell types influence parasite development during pre-patent schistosome infection.

  15. Research progress of adult cardiac stem cells

    Directory of Open Access Journals (Sweden)

    Nan ZHENG

    2013-04-01

    Full Text Available The traditional view is that the heart is a terminal organ. This dogma, however, has been widely questioned with the discovery of adult cardiac stem cells (CSCs. Since CSCs have a highly self-renewal capacity and specific myocardial differentiation potential, nowadays they have been regarded as the most promising type of stem cells used in ischemic heart disease and other replacement therapy of end-stage heart disease. The present paper will focus on current results of scientific research on human adult CSCs and epicardium-derived cell (EPDC, as well as the treatment strategies in the field of cardiac regeneration, and the problems and prospect disclosed in the research.

  16. Concise Review: Quiescence in Adult Stem Cells

    DEFF Research Database (Denmark)

    Rumman, M; Dhawan, J; Kassem, Moustapha

    2015-01-01

    Adult stem cells (ASCs) are tissue resident stem cells responsible for tissue homeostasis and regeneration following injury. In uninjured tissues, ASCs exist in a nonproliferating, reversibly cell cycle-arrested state known as quiescence or G0. A key function of the quiescent state is to preserve...... stemness in ASCs by preventing precocious differentiation, and thus maintaining a pool of undifferentiated ASCs. Recent evidences suggest that quiescence is an actively maintained state and that excessive or defective quiescence may lead to compromised tissue regeneration or tumorigenesis. The aim...

  17. Adult stem-like cells in kidney

    Institute of Scientific and Technical Information of China (English)

    Keiichi Hishikawa; Osamu Takase; Masahiro Yoshikawa; Taro Tsujimura; Masaomi Nangaku; Tsuyoshi Takato

    2015-01-01

    Human pluripotent cells are promising for treatmentfor kidney diseases, but the protocols for derivationof kidney cell types are still controversial. Kidneytissue regeneration is well confirmed in several lowervertebrates such as fish, and the repair of nephronsafter tubular damages is commonly observed after renalinjury. Even in adult mammal kidney, renal progenitorcell or system is reportedly presents suggesting thatadult stem-like cells in kidney can be practical clinicaltargets for kidney diseases. However, it is still unclearif kidney stem cells or stem-like cells exist or not. Ingeneral, stemness is defined by several factors suchas self-renewal capacity, multi-lineage potency andcharacteristic gene expression profiles. The definiteuse of stemness may be obstacle to understand kidneyregeneration, and here we describe the recent broadfindings of kidney regeneration and the cells thatcontribute regeneration.

  18. Cell pattern in adult human corneal endothelium.

    Directory of Open Access Journals (Sweden)

    Carlos H Wörner

    Full Text Available A review of the current data on the cell density of normal adult human endothelial cells was carried out in order to establish some common parameters appearing in the different considered populations. From the analysis of cell growth patterns, it is inferred that the cell aging rate is similar for each of the different considered populations. Also, the morphology, the cell distribution and the tendency to hexagonallity are studied. The results are consistent with the hypothesis that this phenomenon is analogous with cell behavior in other structures such as dry foams and grains in polycrystalline materials. Therefore, its driving force may be controlled by the surface tension and the mobility of the boundaries.

  19. Magnitude of opportunistic infections and associated factors in HIV-infected adults on antiretroviral therapy in eastern Ethiopia

    Directory of Open Access Journals (Sweden)

    Mitiku H

    2015-05-01

    Full Text Available Habtamu Mitiku, Fitsum Weldegebreal, Zelalem Teklemariam Haramaya University, College of Health and Medical Sciences, Department of Medical Laboratory Sciences, Harar, Ethiopia Purpose: The aim of this study was to assess the prevalence of opportunistic infections (OIs and associated factors among HIV-infected adults on anti-retroviral therapy (ART in Hiwot Fana Specialized University Hospital, Eastern Ethiopia. Patients and methods: A hospital-based retrospective study was conducted in 358 HIV-infected adult patients on ART from April to June 2014. Data were collected through review of clinical records. The data was entered and analyzed by using SPSS version 16.0. Univariate and multivariate analyses were performed to determine the association of each independent variable with occurrence of OIs. A 95% confidence interval (CI and P-value less than 0.05 were considered as significant association. Results: A total of 358 patients were included in the study, in which majority (68.4% were females. The mean age of patients was 34 (standard deviation [SD] ±9.8 years. The overall of prevalence of OIs among HIV/AIDS patients on ART was 48%. The highest prevalent rates of OIs observed were tuberculosis (TB (21.23%, followed by Herpes zoster (11.2% and oral candidiasis (9.5%. Baseline CD4 cell count <200 cells/mm3 (adjusted odds ratio [AOR] =1.645, 95% CI =2.187, 3.983, baseline World Health Organization (WHO clinical stage III (AOR =2.801, 95% CI =1.958, 7.165 and IV (AOR =3.856; 95% CI =2.691, 10.390, and not using prophylaxis (AOR =1.912, 95% CI =1.444, 3.824 were found to have strong association with acquisition of OIs. Conclusion: There was a high prevalence of OIs observed in this study. Baselines CD4 count of <200 cells/mm3, advanced WHO clinical stages, and not using prophylaxis were found to be predictors of OIs. Interventions were aimed at promoting early HIV testing and enrollment of HIV-infected individuals into ART services needed before CD4

  20. Neural Crest As the Source of Adult Stem Cells

    Science.gov (United States)

    Pierret, Chris; Spears, Kathleen; Maruniak, Joel A.; Kirk, Mark D.

    2012-01-01

    Recent studies suggest that adult stem cells can cross germ layer boundaries. For example, bone marrow-derived stem cells appear to differentiate into neurons and glial cells, as well as other types of cells. How can stem cells from bone marrow, pancreas, skin, or fat become neurons and glia; in other words, what molecular and cellular events direct mesodermal cells to a neural fate? Transdifferentiation, dediffereniation, and fusion of donor adult stem cells with fully differentiated host cells have been proposed to explain the plasticity of adult stem cells. Here we review the origin of select adult stem cell populations and propose a unifying hypothesis to explain adult stem cell plasticity. In addition, we outline specific experiments to test our hypothesis. We propose that peripheral, tissue-derived, or adult stem cells are all progeny of the neural crest. PMID:16646675

  1. Activation of Divergent Neuronal Cell Death Pathways in Different Target Cell Populations during Neuroadapted Sindbis Virus Infection of Mice

    OpenAIRE

    Havert, Michael B.; Schofield, Brian; Griffin, Diane E.; Irani, David N.

    2000-01-01

    Infection of adult mice with neuroadapted Sindbis virus (NSV) results in a severe encephalomyelitis accompanied by prominent hindlimb paralysis. We find that the onset of paralysis parallels morphologic changes in motor neuron cell bodies in the lumbar spinal cord and in motor neuron axons in ventral nerve roots, many of which are eventually lost over time. However, unlike NSV-induced neuronal cell death found in the brain of infected animals, the loss of motor neurons does not appear to be a...

  2. NKT cells in HIV-1 infection

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Natural killer T (NKT) cells are a unique T cell population that have important immunoregulatory functions and have been shown to be involved in host immunity against a range of microorganisms. It also emerges that they might play a role in HIV-1 infection, and therefore be selectively depleted during the early stages of infection. Recent studies are reviewed regarding the dynamics of NKT depletion during HIV-I infection and their recovery under highly active antiretrovirai treatment (HAART). Possible mechanisms for these changes are proposed based on the recent developments in HIV pathogenesis. Further discussions are focused on HIV's disruption of NKT activation by downregulating CDId expression on antigen presentation cells (APC). HIV-1 protein Nefis found to play the major role by interrupting the intraceilular trafficking of nascent and recycling CDId molecules.

  3. Adult stem cell coatings for regenerative medicine

    Directory of Open Access Journals (Sweden)

    David W. Green

    2012-01-01

    Full Text Available Stem cells can become potent tools for the treatment of degenerative disorders such as heart failure, eye disease and osteoarthritis. Housing stem cells inside a hydrogel coating, directly deposited around them individually and in groups, may be an important solution to the problem of increasing stem cell viability and protection in cultivation. Such coatings can target regulatory proteins and genes for maintenance, differentiation and development into tissues. Already polymer coatings are being applied directly to protect insulin producing pancreatic islet cells in the hope of treating type I diabetes. Here, we review current emerging developments in adult mesenchymal stem cell nanocoating and microcoating techniques and assess their unique practical engineering, biological and potential clinical advantages.

  4. CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections.

    Science.gov (United States)

    Cronan, Mark R; Rosenberg, Allison F; Oehlers, Stefan H; Saelens, Joseph W; Sisk, Dana M; Jurcic Smith, Kristen L; Lee, Sunhee; Tobin, David M

    2015-12-01

    Visualization of infection and the associated host response has been challenging in adult vertebrates. Owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functional adaptive immune system. Cells involved in adaptive immunity mature later and have therefore been difficult to access optically in intact animals. Thus, the study of many aspects of vertebrate infection requires dissection of adult organs or ex vivo isolation of immune cells. Recently, CLARITY and PACT (passive clarity technique) methodologies have enabled clearing and direct visualization of dissected organs. Here, we show that these techniques can be applied to image host-pathogen interactions directly in whole animals. CLARITY and PACT-based clearing of whole adult zebrafish and Mycobacterium tuberculosis-infected mouse lungs enables imaging of mycobacterial granulomas deep within tissue to a depth of more than 1 mm. Using established transgenic lines, we were able to image normal and pathogenic structures and their surrounding host context at high resolution. We identified the three-dimensional organization of granuloma-associated angiogenesis, an important feature of mycobacterial infection, and characterized the induction of the cytokine tumor necrosis factor (TNF) within the granuloma using an established fluorescent reporter line. We observed heterogeneity in TNF induction within granuloma macrophages, consistent with an evolving view of the tuberculous granuloma as a non-uniform, heterogeneous structure. Broad application of this technique will enable new understanding of host-pathogen interactions in situ. PMID:26449262

  5. CLARITY and PACT-based imaging of adult zebrafish and mouse for whole-animal analysis of infections

    Directory of Open Access Journals (Sweden)

    Mark R. Cronan

    2015-12-01

    Full Text Available Visualization of infection and the associated host response has been challenging in adult vertebrates. Owing to their transparency, zebrafish larvae have been used to directly observe infection in vivo; however, such larvae have not yet developed a functional adaptive immune system. Cells involved in adaptive immunity mature later and have therefore been difficult to access optically in intact animals. Thus, the study of many aspects of vertebrate infection requires dissection of adult organs or ex vivo isolation of immune cells. Recently, CLARITY and PACT (passive clarity technique methodologies have enabled clearing and direct visualization of dissected organs. Here, we show that these techniques can be applied to image host-pathogen interactions directly in whole animals. CLARITY and PACT-based clearing of whole adult zebrafish and Mycobacterium tuberculosis-infected mouse lungs enables imaging of mycobacterial granulomas deep within tissue to a depth of more than 1 mm. Using established transgenic lines, we were able to image normal and pathogenic structures and their surrounding host context at high resolution. We identified the three-dimensional organization of granuloma-associated angiogenesis, an important feature of mycobacterial infection, and characterized the induction of the cytokine tumor necrosis factor (TNF within the granuloma using an established fluorescent reporter line. We observed heterogeneity in TNF induction within granuloma macrophages, consistent with an evolving view of the tuberculous granuloma as a non-uniform, heterogeneous structure. Broad application of this technique will enable new understanding of host-pathogen interactions in situ.

  6. Updates on the Diagnosis of Helicobacter pylori Infection in Children: What Are the Differences between Adults and Children?

    Science.gov (United States)

    Yang, Hye Ran

    2016-06-01

    Helicobacter pylori infection is acquired mainly during childhood and causes various diseases such as gastritis, peptic ulcer disease, mucosa-associated lymphoid tissue (MALT) lymphoma, and iron deficiency anemia. Although H. pylori infection in children differs from adults in many ways, this is often overlooked in clinical practice. Unlike adults, nodular gastritis may be a pathognomonic endoscopic finding of childhood H. pylori infection. Histopathological findings of gastric tissues are also different in children due to predominance of lymphocytes and plasma cells and the formation of gastric MALT. Although endoscopy is recommended for the initial diagnosis of H. pylori infection, several non-invasive diagnostic tests such as the urea breath test (UBT) and the H. pylori stool antigen test (HpSA) are available and well validated even in children. According to recent data, both the (13)C-UBT and HpSA using enzyme-linked immunosorbent assay are reliable non-invasive tests to determine H. pylori status after eradication therapy, although children younger than 6 years are known to have high false positives. When invasive or noninvasive tests are applied to children to detect H. pylori infection, it should be noted that there are differences between children and adults in diagnosing H. pylori infection. PMID:27437185

  7. Prevalence of parasitemia and associated immunodeficiency among HIV-malaria co-infected adult patients with highly active antiretroviral therapy

    Institute of Scientific and Technical Information of China (English)

    Caroline E Omoti; Chiedozie K Ojide; Patrick V Lofor; Emeka Eze; Joy C Eze

    2013-01-01

    Objective:To investigate the malaria parasitemia,CD4+ cell counts and some haematological indices amongHIV-malaria co-infected adult patients with highly active antiretroviral therapy (HAART).Methods:A total of342 adultHIV positive subjects were recruited at the consultant outpatientHIV/AIDS clinic,University ofBeninTeachingHospital,BeninCity,Nigeria between June2011 toNovember2011.Blood samples were taken for malaria parasite count,CD4+ cell count and other haematological counts.Results:Out of the342 adultHIV positive subjects a total of254 patients (74.3%) were found to have malaria parasitemia.The incidence of malaria parasitemia increased with advancing clinical stage ofHIV infection and this was statistically significant (P=0.002).There was no statistical significance when gender was compared with the HIV-malaria status (P>0.05).Of the254 co-infected patients,134 (52.8%) had high parasitemia (>1.25×109/L).Sixty patients were found to be hyperparasitemic (>2.5 parasites/L).There was a significant association betweenCD4+ cell count and having significant parasitemia (P 0.05).Conclusions:The prevalence of parasitemia is high among theHIV/AIDS infected patients.

  8. Human Cytomegalovirus Manipulation of Latently Infected Cells

    Directory of Open Access Journals (Sweden)

    John H. Sinclair

    2013-11-01

    Full Text Available Primary infection with human cytomegalovirus (HCMV results in the establishment of a lifelong infection of the host which is aided by the ability of HCMV to undergo a latent infection. One site of HCMV latency in vivo is in haematopoietic progenitor cells, resident in the bone marrow, with genome carriage and reactivation being restricted to the cells of the myeloid lineage. Until recently, HCMV latency has been considered to be relatively quiescent with the virus being maintained essentially as a “silent partner” until conditions are met that trigger reactivation. However, advances in techniques to study global changes in gene expression have begun to show that HCMV latency is a highly active process which involves expression of specific latency-associated viral gene products which orchestrate major changes in the latently infected cell. These changes are argued to help maintain latent infection and to modulate the cellular environment to the benefit of latent virus. In this review, we will discuss these new findings and how they impact not only on our understanding of the biology of HCMV latency but also how they could provide tantalising glimpses into mechanisms that could become targets for the clearance of latent HCMV.

  9. Murine cellular cytotoxicity to syngeneic and xenogeneic herpes simplex virus-infected cells.

    Science.gov (United States)

    Kohl, S; Drath, D B; Loo, L S

    1982-12-01

    Cellular cytotoxicity of C57BL/6 adult mice peritoneal cells to xenogeneic (Chang liver) and syngeneic (BL/6-WT3) herpes simplex virus (HSV)-infected cells was analyzed in a 6-h 51Cr release assay. There was no difference in antibody-dependent cellular cytotoxicity to either target. There was no natural killer cytotoxicity to targets with cells from uninfected mice except at very high effector cell ratios. HSV-infected (2 X 10(4) PFU intraperitoneally 1 day previously) mice mediated significantly higher antibody-dependent cellular cytotoxicity and required less antibody (10(-5) versus 10(-2) dilution), fewer cells, and less time to kill than cells from uninfected mice. HSV-infected mice mediated natural killer cytotoxicity but preferentially killed syngeneic HSV-infected cells. Stimulation of cytotoxicity was not virus specific since influenza-infected mice mediated similar levels of cytotoxicity to HSV-infected targets. There was no difference in morphology (95% macrophage) or in the percentage of FcR-positive cells, but infected mice had more peritoneal cells and generated higher levels of superoxide in response to opsonized zymosan or phorbolmyristate acetate. These data demonstrate nonspecific virus-stimulated metabolic and effector cell function which may enhance clearance of virus in an infected host. PMID:6295943

  10. Alteration of cell cycle progression by Sindbis virus infection

    Energy Technology Data Exchange (ETDEWEB)

    Yi, Ruirong; Saito, Kengo [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Isegawa, Naohisa [Laboratory Animal Center, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Shirasawa, Hiroshi, E-mail: sirasawa@faculty.chiba-u.jp [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan)

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  11. Acceleration of age-associated methylation patterns in HIV-1-infected adults.

    Science.gov (United States)

    Rickabaugh, Tammy M; Baxter, Ruth M; Sehl, Mary; Sinsheimer, Janet S; Hultin, Patricia M; Hultin, Lance E; Quach, Austin; Martínez-Maza, Otoniel; Horvath, Steve; Vilain, Eric; Jamieson, Beth D

    2015-01-01

    Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC) of young (20-35) and older (36-56) adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, pnetwork analysis (WGCNA) identified 17 co-methylation modules; module 3 (ME3) was significantly correlated with age (cor=0.70) and HIV-1 status (cor=0.31). Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015). In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage=0.007088, p=2.08 x 10(-9); βHIV=0.099574, p=0.0011; Data set 2: βage=0.008762, p=1.27 x 10(-5); βHIV=0.128649, p=0.0001). Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10(-6), odds ratio=1.91). These data demonstrate that HIV-1 infection is associated with methylation patterns that are similar to age-associated patterns and suggest that general aging

  12. Congenitally acquired persistent lymphocytic choriomeningitis viral infection reduces neuronal progenitor pools in the adult hippocampus and subventricular zone.

    Directory of Open Access Journals (Sweden)

    Tony Sun

    Full Text Available Lymphocytic choriomeningitis virus (LCMV can be transmitted through congenital infection, leading to persistent infection of numerous organ systems including the central nervous system (CNS. Adult mice persistently infected with LCMV (LCMV-cgPi mice exhibit learning deficits, such as poor performance in spatial discrimination tests. Given that deficits in spatial learning have been linked to defects in adult neurogenesis, we investigated the impact of congenital LCMV infection on generation of neuroblasts from neural progenitor cells within neurogenic zones of adult mice. In LCMV-cgPi mice, QPCR and immunohistochemistry detected presence of LCMV glycoprotein-coding RNA and nucleoprotein in the hippocampal dentate gyrus and subventricular zone (SVZ, sites of neurogenesis that harbor populations of neuroblasts. Numbers of neuroblasts were reduced in LCMV-cgPi mice, as determined by IHC quantification, and analysis of BrdU incorporation by flow cytometry revealed lower numbers of BrdU-labeled neuroblasts. Additionally, TUNEL assays performed in situ showed increased numbers of apoptotic cells in the two neurogenic regions. Next, neurosphere cultures were infected in vitro with LCMV and differentiated to create a population of cells that consisted of both transit amplifying cells and neuroblasts. Immunocytochemical and TUNEL assays revealed increased numbers of TUNEL-positive cells that express nestin, suggesting that the drop in numbers of neuroblasts was due to a combination of impaired proliferation and apoptosis of progenitor cells. LCMV-cgPi mice exhibited transcriptional up-regulation several cytokines and chemokines, including gamma-interferon inducible chemokines CXCL9 and CXCL10. Chronic up-regulation of these chemokines can facilitate a pro-inflammatory niche that may contribute to defects in neurogenesis.

  13. Safety and immunogenicity of H1/IC31®, an adjuvanted TB subunit vaccine, in HIV-infected adults with CD4+ lymphocyte counts greater than 350 cells/mm3: a phase II, multi-centre, double-blind, randomized, placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Klaus Reither

    Full Text Available Novel tuberculosis vaccines should be safe, immunogenic, and effective in various population groups, including HIV-infected individuals. In this phase II multi-centre, double-blind, placebo-controlled trial, the safety and immunogenicity of the novel H1/IC31 vaccine, a fusion protein of Ag85B-ESAT-6 (H1 formulated with the adjuvant IC31, was evaluated in HIV-infected adults.HIV-infected adults with CD4+ T cell counts >350/mm3 and without evidence of active tuberculosis were enrolled and followed until day 182. H1/IC31 vaccine or placebo was randomly allocated in a 5:1 ratio. The vaccine was administered intramuscularly at day 0 and 56. Safety assessment was based on medical history, clinical examinations, and blood and urine testing. Immunogenicity was determined by a short-term whole blood intracellular cytokine staining assay.47 of the 48 randomised participants completed both vaccinations. In total, 459 mild or moderate and 2 severe adverse events were reported. There were three serious adverse events in two vaccinees classified as not related to the investigational product. Local injection site reactions were more common in H1/IC31 versus placebo recipients (65.0% vs. 12.5%, p = 0.015. Solicited systemic and unsolicited adverse events were similar by study arm. The baseline CD4+ T cell count and HIV viral load were similar by study arm and remained constant over time. The H1/IC31 vaccine induced a persistent Th1-immune response with predominately TNF-α and IL-2 co-expressing CD4+ T cells, as well as polyfunctional IFN-γ, TNF-α and IL-2 expressing CD4+ T cells.H1/IC31 was well tolerated and safe in HIV-infected adults with a CD4+ Lymphocyte count greater than 350 cells/mm3. The vaccine did not have an effect on CD4+ T cell count or HIV-1 viral load. H1/IC31 induced a specific and durable Th1 immune response.Pan African Clinical Trials Registry (PACTR PACTR201105000289276.

  14. Cells in Dengue Virus Infection In Vivo

    Directory of Open Access Journals (Sweden)

    Sansanee Noisakran

    2010-01-01

    Full Text Available Dengue has been recognized as one of the most important vector-borne emerging infectious diseases globally. Though dengue normally causes a self-limiting infection, some patients may develop a life-threatening illness, dengue hemorrhagic fever (DHF/dengue shock syndrome (DSS. The reason why DHF/DSS occurs in certain individuals is unclear. Studies in the endemic regions suggest that the preexisting antibodies are a risk factor for DHF/DSS. Viremia and thrombocytopenia are the key clinical features of dengue virus infection in patients. The amounts of virus circulating in patients are highly correlated with severe dengue disease, DHF/DSS. Also, the disturbance, mainly a transient depression, of hematological cells is a critical clinical finding in acute dengue patients. However, the cells responsible for the dengue viremia are unresolved in spite of the intensive efforts been made. Dengue virus appears to replicate and proliferate in many adapted cell lines, but these in vitro properties are extremely difficult to be reproduced in primary cells or in vivo. This paper summarizes reports on the permissive cells in vitro and in vivo and suggests a hematological cell lineage for dengue virus infection in vivo, with the hope that a new focus will shed light on further understanding of the complexities of dengue disease.

  15. Association of CMV, HBV, or HCV co-infection with vaccine response in adults with well-controlled HIV infection.

    Science.gov (United States)

    Troy, S B; Rossheim, A E B; Siik, J; Cunningham, T D; Kerry, J A

    2016-05-01

    Even after CD4 count recovery on antiretroviral therapy, HIV infection is associated with decreased response to most vaccines compared to the general population. Chronic infections with viruses such as cytomegalovirus (CMV), hepatitis B virus (HBV), and hepatitis C virus (HCV), which are more prevalent in HIV-infected populations, have been linked to immune dysfunction and decreased vaccine response in the general population. However, whether co-infection with these other viruses contributes to the decreased vaccine response seen in adults with well-controlled HIV infection is unknown. We conducted a secondary analysis of data and serum from adults with well-controlled HIV infection from an inactivated polio vaccine trial (224 subjects) and a pneumococcal conjugate vaccine study (128 subjects). We evaluated the association of CMV, HBV, or HCV co-infection with post-vaccination antibody levels using both univariate and multivariate analyses, controlling for factors such as age, race, CD4 count, comorbidities, smoking status, and baseline antibody levels. Ninety-three percent, 7%, and 14% of subjects were co-infected with CMV, HBV, and HCV respectively. On both univariate and multivariate analysis, neither CMV nor HCV co-infection were significantly associated with post-vaccination antibody levels to either vaccine. HBV co-infection was significantly associated with post-vaccination antibody concentrations for pneumococcal serotype 7F on univariate analysis and 6A on multivariate analysis, but the association was with higher antibody concentrations. In conclusion, co-infection with CMV, HBV, or HCV does not appear to contribute to the decreased vaccine response seen in adults with well-controlled HIV infection. PMID:26751638

  16. Nutritional Status and Lipid Profile in HIV-Infected Adults.

    Science.gov (United States)

    Stambullian, M; Feliu, M S; Cassetti, L I; Slobodianik, N H

    2015-01-01

    In the last decades, there have been many reports of HIV infection and abnormalities in lipid metabolism and cardiovascular disease (CVD). This study aims at describing the nutritional status of HIV-infected adults and its relation to lipid profile through traditional [total cholesterol (TC), HDL cholesterol (HDL), triglycerides (TG), non-HDL cholesterol and LDL cholesterol (LDL)] and other parameters [Apolipoprotein B (ApoB), fibrinogen, and high sensitive-C-reactive protein (hs-CRP)]. A cross-sectional descriptive study was performed. Body mass index (BMI) was calculated and references were taken from WHO. TC, HDL, TG and glucose were determined and non-HDL cholesterol and LDL were calculated. ApoB and fibrinogen were determined by quantitative radial immunodiffusion on agar plates (Diffuplate,Biocientífica SA,Argentina) and hs-CRP by immunoturbidimetric test. Qualitative variables were compared with the Chi-square test or Fisher's exact test. Quantitative variables were compared applying parametrics or nonparametric tests. Pearson test for correlations. Software SPSS 17.0. 97 patients were analyzed: 69.1% were men. 80% were on antiretroviral treatment. Average (SD) BMI was 24.3 (4.1) kg/m(2). 29.4% were overweight and 5.9% obese. Patients with a BMI ≥25.0 kg/m(2) presented significantly higher levels of TG, ApoB and glycemia than well-nourished people [246.1(169.0) vs. 142.9(78.4) mg/dL;p=0.029, 198.6(69.3) vs. 126.4(50.6) mg/dL;p=0.01 and 100 (3.2) vs. 90.2 (6.9) mg/dL;p=0.008 resp.] and a significantly decreased HDL [37.2(1.5) vs. 49.8(10.4) mg/dL;pNutritional education is needed to promote a healthy weight to warn against the risk of cardiovascular disease.

  17. Adult mouse cortical cell taxonomy revealed by single cell transcriptomics.

    Science.gov (United States)

    Tasic, Bosiljka; Menon, Vilas; Nguyen, Thuc Nghi; Kim, Tae Kyung; Jarsky, Tim; Yao, Zizhen; Levi, Boaz; Gray, Lucas T; Sorensen, Staci A; Dolbeare, Tim; Bertagnolli, Darren; Goldy, Jeff; Shapovalova, Nadiya; Parry, Sheana; Lee, Changkyu; Smith, Kimberly; Bernard, Amy; Madisen, Linda; Sunkin, Susan M; Hawrylycz, Michael; Koch, Christof; Zeng, Hongkui

    2016-02-01

    Nervous systems are composed of various cell types, but the extent of cell type diversity is poorly understood. We constructed a cellular taxonomy of one cortical region, primary visual cortex, in adult mice on the basis of single-cell RNA sequencing. We identified 49 transcriptomic cell types, including 23 GABAergic, 19 glutamatergic and 7 non-neuronal types. We also analyzed cell type-specific mRNA processing and characterized genetic access to these transcriptomic types by many transgenic Cre lines. Finally, we found that some of our transcriptomic cell types displayed specific and differential electrophysiological and axon projection properties, thereby confirming that the single-cell transcriptomic signatures can be associated with specific cellular properties.

  18. A Mathematical Model of Baculovirus Infection on Insect Cells at Low Multiplicity of Infection

    Institute of Scientific and Technical Information of China (English)

    You-Hong ZHANG; Josée C. MERCHUK

    2004-01-01

    The expression efficiency of the insect cells-baculovirus system used for insecticidal virus production and the expression of medically useful foreign genes is closely related with the dynamics of infection. The present studies develop a model of the dynamic process of insect cell infection with baculovirus at low multiplicity of infection (MOI), which is based on the multi-infection cycles of insect cell infection at low MOI. A mathematical model for the amount of viruses released from primary infected cells and the amount of free viruses before secondary infected cells release viruses has been developed. Comparison of the simulation results with the experimental data confirms qualitatively that this model is highly reasonable before secondary infected cells release viruses. This model is considered as a base for further modeling the entire complicated infection process.

  19. Adult Mesenchymal Stem Cells and Radiation Injury.

    Science.gov (United States)

    Kiang, Juliann G

    2016-08-01

    Recent understanding of the cellular and molecular signaling activations in adult mesenchymal stem cells (MSCs) has provided new insights into their potential clinical applications, particularly for tissue repair and regeneration. This review focuses on these advances, specifically in the context of self-renewal for tissue repair and recovery after radiation injury. Thus far, MSCs have been characterized extensively and shown to be useful in mitigation and therapy for acute radiation syndrome and cognitive dysfunction. Use of MSCs for treating radiation injury alone or in combination with additional trauma is foreseeable. PMID:27356065

  20. Aplastic crisis caused by parvovirus B19 in an adult patient with sickle-cell disease

    OpenAIRE

    Setúbal Sérgio; Gabriel Adelmo H.D.; Nascimento Jussara P.; Oliveira Solange A.

    2000-01-01

    We describe a case of aplastic crisis caused by parvovirus B19 in an adult sickle-cell patient presenting with paleness, tiredness, fainting and dyspnea. The absence of reticulocytes lead to the diagnosis. Anti-B19 IgM and IgG were detected. Reticulocytopenia in patients with hereditary hemolytic anemia suggests B19 infection.

  1. A Review of Influenza Vaccine Immunogenicity and Efficacy in HIV-Infected Adults

    Directory of Open Access Journals (Sweden)

    Curtis Cooper

    2008-01-01

    Full Text Available BACKGROUND: HIV-seropositive adults are at an increased risk for influenza infection. They also develop more severe influenza disease and are hyporesponsive to current influenza vaccinations.

  2. Infection of SARS-CoV on juvenile and adult Brandt's vole Microtus brandtii

    Institute of Scientific and Technical Information of China (English)

    GAO Hong; PENG Jingpian; DENG Wei; SHI Dazhao; BAO Linlin; WANG Dehua; ZHANG Binglin; QIN Chuan; ZHANG Zhibin

    2005-01-01

    We studied the infectious effect of SARS-CoV virus on juvenile and adult Brandt's Vole (Microtus brandtii) by nasal cavity spraying method (CCID50 is 105.7). SARS virus caused serious deaths in adults. The death adults demonstrated hemorrhage from mouth, nasal cavity and intestine, hemorrhageious interstitial pneumonia and gore in liver, spleen and kidney. The survival adults demonstrated local hemorrhagic spot in lung and emphysema, but the other organs showed no pathological abnormality. SARS virus caused no deaths in juveniles, but locomotion of infected juveniles became slower. In the early stage, there was local pneumonia in lung and SARS viruses were isolated from the pathological tissue. Only one control juvenile lived and the infected juvenile showed local pneumonia in lung. The results demonstrated that SARS-CoV infected Brandt's vole seriously and adults were more susceptive to SARS-CoV than juveniles. The Brandt's vole may be a potential animal model for SARS research.

  3. Murid herpesvirus-4 exploits dendritic cells to infect B cells

    OpenAIRE

    Miguel Gaspar; May, Janet S.; Soumi Sukla; Bruno Frederico; Michael B Gill; Smith, Christopher M.; Belz, Gabrielle T.; Stevenson, Philip G.

    2011-01-01

    Author Summary We detect invading viruses with dendritic cells and eliminate them with lymphocytes. A key interaction is lymphocyte activation by dendritic cells presenting viral antigens. Not all viruses can be eliminated, and some that persist deliberately colonize lymphocytes and dendritic cells, such that parasitism and host defence co-exist within the same sites. Once established, these infections are very hard to eliminate. Therefore to vaccinate against them we must determine how infec...

  4. A Multicenter Study of Pertussis Infection in Adults with Coughing in Korea: PCR-Based Study

    OpenAIRE

    Park, Sunghoon; Lee, Myung-Gu; Lee, Kwan Ho; Park, Yong Bum; Yoo, Kwang Ha; Park, Jeong-Woong; Kim, Changhwan; Lee, Yong Chul; Park, Jae Seuk; Kwon, Yong Soo; Seo, Ki-Hyun; Kim, Hui Jung; Kwak, Seung Min; Kim, Ju-Ock; Lim, Seong Yong

    2012-01-01

    Background Limited data on the incidence and clinical characteristics of adult pertussis infections are available in Korea. Methods Thirty-one hospitals and the Korean Centers for Disease Control and Prevention collaborated to investigate the incidence and clinical characteristics of pertussis infections among adults with a bothersome cough in non-outbreak, ordinary outpatient settings. Nasopharyngeal aspirates or nasopharyngeal swabs were collected for polymerase chain reaction (PCR) and cul...

  5. Children Living with HIV-Infected Adults: Estimates for 23 Countries in sub-Saharan Africa.

    Directory of Open Access Journals (Sweden)

    Susan E Short

    Full Text Available In sub-Saharan Africa many children live in extreme poverty and experience a burden of illness and disease that is disproportionately high. The emergence of HIV and AIDS has only exacerbated long-standing challenges to improving children's health in the region, with recent cohorts experiencing pediatric AIDS and high levels of orphan status, situations which are monitored globally and receive much policy and research attention. Children's health, however, can be affected also by living with HIV-infected adults, through associated exposure to infectious diseases and the diversion of household resources away from them. While long recognized, far less research has focused on characterizing this distinct and vulnerable population of HIV-affected children.Using Demographic and Health Survey data from 23 countries collected between 2003 and 2011, we estimate the percentage of children living in a household with at least one HIV-infected adult. We assess overlaps with orphan status and investigate the relationship between children and the adults who are infected in their households.The population of children living in a household with at least one HIV-infected adult is substantial where HIV prevalence is high; in Southern Africa, the percentage exceeded 10% in all countries and reached as high as 36%. This population is largely distinct from the orphan population. Among children living in households with tested, HIV-infected adults, most live with parents, often mothers, who are infected; nonetheless, in most countries over 20% live in households with at least one infected adult who is not a parent.Until new infections contract significantly, improvements in HIV/AIDS treatment suggest that the population of children living with HIV-infected adults will remain substantial. It is vital to on-going efforts to reduce childhood morbidity and mortality to consider whether current care and outreach sufficiently address the distinct vulnerabilities of these

  6. Murine cellular cytotoxicity to syngeneic and xenogeneic herpes simplex virus-infected cells.

    OpenAIRE

    Kohl, S; Drath, D B; Loo, L S

    1982-01-01

    Cellular cytotoxicity of C57BL/6 adult mice peritoneal cells to xenogeneic (Chang liver) and syngeneic (BL/6-WT3) herpes simplex virus (HSV)-infected cells was analyzed in a 6-h 51Cr release assay. There was no difference in antibody-dependent cellular cytotoxicity to either target. There was no natural killer cytotoxicity to targets with cells from uninfected mice except at very high effector cell ratios. HSV-infected (2 X 10(4) PFU intraperitoneally 1 day previously) mice mediated significa...

  7. Hematopoietic Stem Cell Transplantation in Adult Sickle Cell Disease: Problems and Solutions

    Directory of Open Access Journals (Sweden)

    Hakan Özdoğu

    2015-09-01

    Full Text Available Sickle cell disease-related organ injuries cannot be prevented despite hydroxyurea use, infection prophylaxis, and supportive therapies. As a consequence, disease-related mortality reaches 14% in adolescents and young adults. Hematopoietic stem cell transplantation is a unique curative therapeutic approach for sickle cell disease. Myeloablative allogeneic hematopoietic stem cell transplantation is curative for children with sickle cell disease. Current data indicate that long-term disease-free survival is about 90% and overall survival about 95% after transplantation. However, it is toxic in adults due to organ injuries. In addition, this curative treatment approach has several limitations, such as difficulties to find donors, transplant-related mortality, graft loss, graft-versus-host disease (GVHD, and infertility. Engraftment effectivity and toxicity for transplantations performed with nonmyeloablative reduced-intensity regimens in adults are being investigated in phase 1/2 trials at many centers. Preliminary data indicate that GVHD could be prevented with transplantations performed using reduced-intensity regimens. It is necessary to develop novel regimens to prevent graft loss and reduce the risk of GVHD.

  8. [Pulmonary Langerhans cell histiocytosis in adults].

    Science.gov (United States)

    Feuillet, Séverine; Giroux-Leprieur, Bénédicte; Tazi, Abdellatif

    2010-01-01

    Pulmonary Langerhans-cell histiocytosis in adults is a rare condition of unknown etiology characterized by the accumulation of Langerhans cells organized in granulomas involving the distal bronchioles and destroying their walls. It occurs in young subjects who smoke, with frequency peaking between 20 and 40 years. High-resolution thoracic CT is essential for diagnosis; in typical forms it shows a combination of nodules, cavitary nodules, thick-walled cysts, and thin-walled cysts. Diagnostic certainty requires a surgical lung biopsy, by videothoracoscopy, but only if a specialist considers it indicated. It is difficult to predict the disease course for any given patient. A prospective multicenter cohort study currently underway should provide more information about the natural history of this disease. Management is empirical, for efficacy has not been proved for any treatment. Stopping smoking is especially important to prevent the added development of chronic obstructive pulmonary disease (COPD), cardiovascular complications, or the onset of bronchopulmonary cancer, the frequency of which appears elevated in these patients. Oral corticosteroids are used to treat disease progression, especially in the symptomatic mainly nodular forms, but their efficacy for respiratory function has not been shown. Vinblastine, the reference treatment for multisystem forms of Langerhans-cell histiocytosis, is not indicated for pulmonary involvement in adults. Better knowledge of the pathogenic mechanisms involved in this condition should eventually make it possible to develop innovative treatment strategies. The creation of the national reference center for Langerhans-cell histiocytosis has given new momentum to clinical and pathophysiologic research on this orphan disease. PMID:19959324

  9. Sertoli cells maintain Leydig cell number and peritubular myoid cell activity in the adult mouse testis.

    Directory of Open Access Journals (Sweden)

    Diane Rebourcet

    Full Text Available The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health.

  10. Antiretroviral treatment of adult HIV infection: 2014 recommendations of the International Antiviral Society-USA Panel

    NARCIS (Netherlands)

    Gunthard, H.F.; Aberg, J.A.; Eron, J.J.; Hoy, J.F.; Telenti, A.; Benson, C.A.; Burger, D.M.; Cahn, P.; Gallant, J.E.; Glesby, M.J.; Reiss, P.; Saag, M.S.; Thomas, D.L.; Jacobsen, D.M.; Volberding, P.A.

    2014-01-01

    IMPORTANCE: New data and antiretroviral regimens expand treatment choices in resource-rich settings and warrant an update of recommendations to treat adults infected with human immunodeficiency virus (HIV). OBJECTIVE: To provide updated treatment recommendations for adults with HIV, emphasizing when

  11. Safety and immunogenicity of influenza vaccine among HIV-infected adults: Conventional vaccine vs. intradermal vaccine

    Science.gov (United States)

    Seo, Yu Bin; Lee, Jacob; Song, Joon Young; Choi, Hee Jung; Cheong, Hee Jin; Kim, Woo Joo

    2016-01-01

    Several studies have reported poor immune responses to conventional influenza vaccines in HIV-infected individuals. This study sought to elicit more potent immunogenicity in HIV-infected adults using an intradermal vaccine compared with a conventional intramuscular vaccine. This multicenter, randomized, controlled, open-label study was conducted at 3 university hospitals during the 2011/2012 pre-influenza season. Three vaccines were used in HIV-infected adults aged 18 – 60 years: an inactivated intramuscular vaccine (Agrippal), a reduced-content intradermal vaccine (IDflu9μg) and a standard-content intradermal vaccine (IDflu15μg). Serum hemagglutination-inhibiting (HI) antibodies and INF-γ ELISpot assay were measured at the time of vaccination and 1 month after vaccination. Adverse events were recorded for 7 d. A total of 28 Agrippal, 30 IDflu9μg, and 28 IDflu15μg volunteers were included in this analysis. One month after vaccination, the GMTs and differences in INF-γ ELISpot assay results were similar among the 3 groups. Seroprotection rates, seroconversion rates and mean fold increases (MFI) among the 3 groups were also similar, at approximately 80%, 50–60% and 2.5 – 10.0, respectively. All three vaccines satisfied the CHMP criteria for the A/H1N1 and A/H3N2 strains, but not those for the B strain. In univariate analysis, no demographic or clinical factors, including age, CD4+ T-cell counts, HIV viral load, ART status and vaccine type, were related to failure to achieve seroprotection. The three vaccines were all well-tolerated and all reported reactions were mild to moderate. However, there was a tendency toward a higher incidence of local and systemic reactions in the intradermal vaccine groups. The intradermal vaccine did not result in higher immunogenicity compared to the conventional intramuscular vaccine, even with increased antigen dose. PMID:26431466

  12. PARASITIC INFECTIONS IN HEMATOPOIETIC STEM CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Isidro Jarque

    2016-07-01

    Full Text Available Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However, they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients.

  13. Parasitic Infections in Hematopoietic Stem Cell Transplantation.

    Science.gov (United States)

    Jarque, Isidro; Salavert, Miguel; Pemán, Javier

    2016-01-01

    Parasitic infections are rarely documented in hematopoietic stem cell transplant recipients. However they may be responsible for fatal complications that are only diagnosed at autopsy. Increased awareness of the possibility of parasitic diseases both in autologous and allogeneic stem cell transplant patients is relevant not only for implementing preventive measures but also for performing an early diagnosis and starting appropriate therapy for these unrecognized but fatal infectious complications in hematopoietic transplant recipients. In this review, we will focus on parasitic diseases occurring in this population especially those with major clinical relevance including toxoplasmosis, American trypanosomiasis, leishmaniasis, malaria, and strongyloidiasis, among others, highlighting the diagnosis and management in hematopoietic transplant recipients. PMID:27413527

  14. Immunotherapy of invasive fungal infection in hematopoietic stem cell transplant recipients

    OpenAIRE

    Lehrnbecher, Thomas; Schmidt, Stanislaw; Tramsen, Lars; Klingebiel, Thomas

    2013-01-01

    Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT recipients suffer from a long lasting defect of different arms of the immune system, which increases the risk for and deteriorates the prognosis of invasive fungal infections. In turn, advances in understanding these immune deficits have resulted in pro...

  15. The role of imaging in adult acute urinary tract infection

    Energy Technology Data Exchange (ETDEWEB)

    Webb, J.A.W. [Diagnostic Radiology Department, St. Bartholomew`s Hospital, West Smithfield, London EC1A 7BE (United Kingdom)

    1997-08-01

    Imaging is required in only a minority of patients with urinary tract infection. Some patients who present with severe loin pain are imaged because ureteric colic is suspected. If urinary tract infection does not respond normally to antibiotics, imaging is undertaken to check for evidence of renal obstuction or sepsis. Finally, after the acute infection has been treated, imaging is required in some patients to check for factors pre-disposing to renal damage or to relapsing or recurrent infection. This review discusses the appropriate choice of imaging technique to use in each clinical situation and summarises the expected findings. (orig.). With 15 figs., 1 tab.

  16. [Severe Haemophilus influenzae b infection in healthy male adult

    DEFF Research Database (Denmark)

    Vilmar, A.C.; Gjorup, I.; David, Kim Peter

    2008-01-01

    Haemophilus influenzae b (Hib) can be the cause of serious infections, and is mainly observed affecting children and immuno-compromised patients. We report a case of a healthy 49-year old male with a severe Hib infection complicated by septicaemia, meningitis and anuria. The risk of invasive Hib...

  17. Anaplasma phagocytophilum Manipulates Host Cell Apoptosis by Different Mechanisms to Establish Infection

    Directory of Open Access Journals (Sweden)

    Pilar Alberdi

    2016-07-01

    Full Text Available Anaplasma phagocytophilum is an emerging zoonotic pathogen that causes human and animal granulocytic anaplasmosis and tick-borne fever of ruminants. This obligate intracellular bacterium evolved to use common strategies to establish infection in both vertebrate hosts and tick vectors. Herein, we discuss the different strategies used by the pathogen to modulate cell apoptosis and establish infection in host cells. In vertebrate neutrophils and human promyelocytic cells HL-60, both pro-apoptotic and anti-apoptotic factors have been reported. Tissue-specific differences in tick response to infection and differential regulation of apoptosis pathways have been observed in adult female midguts and salivary glands in response to infection with A. phagocytophilum. In tick midguts, pathogen inhibits apoptosis through the Janus kinase/signal transducers and activators of transcription (JAK/STAT pathway, while in salivary glands, the intrinsic apoptosis pathways is inhibited but tick cells respond with the activation of the extrinsic apoptosis pathway. In Ixodes scapularis ISE6 cells, bacterial infection down-regulates mitochondrial porin and manipulates protein processing in the endoplasmic reticulum and cell glucose metabolism to inhibit apoptosis and facilitate infection, whereas in IRE/CTVM20 tick cells, inhibition of apoptosis appears to be regulated by lower caspase levels. These results suggest that A. phagocytophilum uses different mechanisms to inhibit apoptosis for infection of both vertebrate and invertebrate hosts.

  18. Neonatal infection with neurotropic influenza A virus affects working memory and expression of type III Nrg1 in adult mice.

    Science.gov (United States)

    Asp, Linnéa; Beraki, Simret; Kristensson, Krister; Ogren, Sven Ove; Karlsson, Håkan

    2009-08-01

    Epidemiological studies suggest that early life infections may contribute to the development of psychiatric disorders characterized by cognitive deficits. Here, we studied the effects of a neonatal influenza A/WSN/33 virus infection on locomotor activity, working memory and emotional behavior in adult mice. In addition to wild type mice, immunodeficient (Tap1(-/-)) mice lacking functional CD8(+) T cells, were included in the study to model the potential influence of a genetic deficit relating to virus clearance. Three to four months after the infection, infected Tap1(-/-) mice, but not wild type mice, exhibited deficits in working memory as well as increased rearing activity and anxiety. In the medial prefrontal cortices of these infected Tap1(-/-) mice reduced levels of type III Nrg1 transcripts were observed supporting a role for neuregulin 1 signaling in neuronal circuits involved in working memory. Virus replication, distribution or clearance did not differ between the two genotypes. The lack of CD8(+) T cells, however, appeared to contribute to a more pronounced glia response in Tap1(-/-) than in wild type mice. Thus, the present study suggest that the risk of developing deficits in cognitive and emotional behavior following a CNS infection during brain development is influenced by genetic variation in genes involved in the immune response.

  19. Whooping cough in adults: an update on a reemerging infection.

    Science.gov (United States)

    Paisley, Robert D; Blaylock, Jason; Hartzell, Joshua D

    2012-02-01

    Pertussis, or whooping cough, which is commonly thought of as a pediatric illness, is an underappreciated adult pathogen. Recent outbreaks highlight the significance of pertussis in adults and the risk of transmission to at-risk infants who are most susceptible to complications, including death. This article describes the recent epidemiologic shifts and reviews the clinical presentation, diagnosis, and treatment of pertussis. New vaccination recommendations by the Advisory Committee on Immunization Practices in response to recent outbreaks and infant deaths are highlighted.

  20. Differential anti-glycan antibody responses in Schistosoma mansoni-infected children and adults studied by shotgun glycan microarray.

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    Angela van Diepen

    Full Text Available BACKGROUND: Schistosomiasis (bilharzia is a chronic and potentially deadly parasitic disease that affects millions of people in (subtropical areas. An important partial immunity to Schistosoma infections does develop in disease endemic areas, but this takes many years of exposure and maturation of the immune system. Therefore, children are far more susceptible to re-infection after treatment than older children and adults. This age-dependent immunity or susceptibility to re-infection has been shown to be associated with specific antibody and T cell responses. Many antibodies generated during Schistosoma infection are directed against the numerous glycans expressed by Schistosoma. The nature of glycan epitopes recognized by antibodies in natural schistosomiasis infection serum is largely unknown. METHODOLOGY/PRINCIPAL FINDINGS: The binding of serum antibodies to glycans can be analyzed efficiently and quantitatively using glycan microarray approaches. Very small amounts of a large number of glycans are presented on a solid surface allowing binding properties of various glycan binding proteins to be tested. We have generated a so-called shotgun glycan microarray containing natural N-glycan and lipid-glycan fractions derived from 4 different life stages of S. mansoni and applied this array to the analysis of IgG and IgM antibodies in sera from children and adults living in an endemic area. This resulted in the identification of differential glycan recognition profiles characteristic for the two different age groups, possibly reflecting differences in age or differences in length of exposure or infection. CONCLUSIONS/SIGNIFICANCE: Using the shotgun glycan microarray approach to study antibody response profiles against schistosome-derived glycan elements, we have defined groups of infected individuals as well as glycan element clusters to which antibody responses are directed in S. mansoni infections. These findings are significant for further

  1. Adult neural stem cells-Functional potential and therapeutic applications

    Institute of Scientific and Technical Information of China (English)

    YANG Lin; ZHU Jianhong

    2004-01-01

    The adult brain has been thought traditionally as a structure with a very limited regenerative capacity. It is now evident that neurogenesis in adult mammalian brain is a prevailing phenomenon. Neural stem cells with the ability to self-renew, differentiate into neurons, astrocytes and oligodendrocytes reside in some regions of the adult brain. Adult neurogenesis can be stimulated by many physiological factors including pregnancy. More strikingly, newborn neurons in hippocampus integrally function with local neurons, thus neural stem cells might play important roles in memory and learning function. It seems that neural stem cells could transdifferentiate into other tissues, such as blood cells and muscles. Although there are some impediments in this field, some attempts have been made to employ adult neural stem cells in the cell replacement therapy for traumatic and ischemic brain injuries.

  2. Interferon Response in Hepatitis C Virus (HCV) Infection: Lessons from Cell Culture Systems of HCV Infection.

    Science.gov (United States)

    Sung, Pil Soo; Shin, Eui-Cheol; Yoon, Seung Kew

    2015-01-01

    Hepatitis C virus (HCV) is a positive-stranded RNA virus that infects approximately 130-170 million people worldwide. In 2005, the first HCV infection system in cell culture was established using clone JFH-1, which was isolated from a Japanese patient with fulminant HCV infection. JFH-1 replicates efficiently in hepatoma cells and infectious virion particles are released into the culture supernatant. The development of cell culture-derived HCV (HCVcc) systems has allowed us to understand how hosts respond to HCV infection and how HCV evades host responses. Although the mechanisms underlying the different outcomes of HCV infection are not fully understood, innate immune responses seem to have a critical impact on the outcome of HCV infection, as demonstrated by the prognostic value of IFN-λ gene polymorphisms among patients with chronic HCV infection. Herein, we review recent research on interferon response in HCV infection, particularly studies using HCVcc infection systems.

  3. CD8+ T cells in Leishmania infections: friends or foes?

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    Simona eStager

    2012-01-01

    Full Text Available Host protection against several intracellular pathogens requires the induction of CD8+ T cell responses. CD8+ T cells are potent effector cells that can produce high amounts of pro-inflammatory cytokines and kill infected target cells efficiently. However, a protective role for CD8+ T cells during Leishmania infections is still controversial and largely depends on the infection model. In this review, we discuss the role of CD8+ T cells during various types Leishmania infections, following vaccination, and as potential immunotherapeutic targets.

  4. Urinary Tract Infections in Adolescents and Adults (Beyond the Basics)

    Science.gov (United States)

    ... for prevention of UTI)]. Stephen B Calderwood, MD Patent Holder: Vaccine Technologies Inc [Vaccines (Cholera vaccines)]. Equity ... frequently or having a new sex partner ● Having diabetes ● Having a bladder or kidney infection in the ...

  5. Clinical characteristics analysis of adult human adenovirus type 7 infection

    Institute of Scientific and Technical Information of China (English)

    张乃春

    2014-01-01

    Objective To investigate the clinical characteristics of patients infected with human adenovirus type 7 and to provide guidance for early diagnosis and timely control of the outbreak.Methods A total of 301 patients infected with the human adenoviruses who were quarantined in hospital from December 2012 to February 2013 were observed.Epidemiological questionnaires were used to collect data of clinical features of the disease including

  6. The impact of inflammation and immune activation on B cell differentiation during HIV-1 infection

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    Nicolas eRuffin

    2012-01-01

    Full Text Available HIV-1 infection is characterized by continuous antigenic stimulation, chronic immune activation and impaired survival of T and B cells. A decline of resting memory B cells has previously been reported to occur in both children and adults infected with HIV-1; these cells are responsible for mounting and maintaining an adequate serological response to antigens previously encountered in life through natural infection or vaccination. Further understanding of the mechanisms leading to impaired B cell differentiation and germinal center reaction might be essential to design new HIV vaccines and therapies that could improve humoral immune responses in HIV-1 infected individuals. In the present article we summarize the literature and present our view on critical mechanisms of B cell development which are impaired during HIV-1 infection. We also discuss the impact of microbial translocation, a driving force for persistent inflammation during HIV-1 infection, on survival of terminally differentiated B cells and how the altered expression of cytokines/chemokines pivotal for communication between T and B cells in lymphoid tissues may impair formation of memory B cells.

  7. Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections

    Science.gov (United States)

    McFarland, Lynne Vernice; Ozen, Metehan; Dinleyici, Ener Cagri; Goh, Shan

    2016-01-01

    Antibiotic-associated diarrhea (AAD) and Clostridum difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics. PMID:27003987

  8. Comparison of pediatric and adult antibiotic-associated diarrhea and Clostridium difficile infections.

    Science.gov (United States)

    McFarland, Lynne Vernice; Ozen, Metehan; Dinleyici, Ener Cagri; Goh, Shan

    2016-03-21

    Antibiotic-associated diarrhea (AAD) and Clostridum difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics. PMID:27003987

  9. Acceleration of age-associated methylation patterns in HIV-1-infected adults.

    Directory of Open Access Journals (Sweden)

    Tammy M Rickabaugh

    Full Text Available Patients with treated HIV-1-infection experience earlier occurrence of aging-associated diseases, raising speculation that HIV-1-infection, or antiretroviral treatment, may accelerate aging. We recently described an age-related co-methylation module comprised of hundreds of CpGs; however, it is unknown whether aging and HIV-1-infection exert negative health effects through similar, or disparate, mechanisms. We investigated whether HIV-1-infection would induce age-associated methylation changes. We evaluated DNA methylation levels at >450,000 CpG sites in peripheral blood mononuclear cells (PBMC of young (20-35 and older (36-56 adults in two separate groups of participants. Each age group for each data set consisted of 12 HIV-1-infected and 12 age-matched HIV-1-uninfected samples for a total of 96 samples. The effects of age and HIV-1 infection on methylation at each CpG revealed a strong correlation of 0.49, p<1 x 10(-200 and 0.47, p<1 x 10(-200. Weighted gene correlation network analysis (WGCNA identified 17 co-methylation modules; module 3 (ME3 was significantly correlated with age (cor=0.70 and HIV-1 status (cor=0.31. Older HIV-1+ individuals had a greater number of hypermethylated CpGs across ME3 (p=0.015. In a multivariate model, ME3 was significantly associated with age and HIV status (Data set 1: βage=0.007088, p=2.08 x 10(-9; βHIV=0.099574, p=0.0011; Data set 2: βage=0.008762, p=1.27 x 10(-5; βHIV=0.128649, p=0.0001. Using this model, we estimate that HIV-1 infection accelerates age-related methylation by approximately 13.7 years in data set 1 and 14.7 years in data set 2. The genes related to CpGs in ME3 are enriched for polycomb group target genes known to be involved in cell renewal and aging. The overlap between ME3 and an aging methylation module found in solid tissues is also highly significant (Fisher-exact p=5.6 x 10(-6, odds ratio=1.91. These data demonstrate that HIV-1 infection is associated with methylation patterns that

  10. Single-Dose Pharmacokinetics and Safety of Abacavir (1592U89), Zidovudine, and Lamivudine Administered Alone and in Combination in Adults with Human Immunodeficiency Virus Infection

    OpenAIRE

    Wang, Laurene H.; Chittick, Gregory E.; McDowell, James A.

    1999-01-01

    Abacavir (1592U89), a nucleoside reverse transcriptase inhibitor with in vitro activity against human immunodeficiency virus type-1 (HIV-1), has been evaluated for efficacy and safety in combination regimens with other nucleoside analogs, including zidovudine (ZDV) and lamivudine (3TC). To evaluate the potential pharmacokinetic interactions between these agents, 15 HIV-1-infected adults with a median CD4+ cell count of 347 cells/mm3 (range, 238 to 570 cells/mm3) were enrolled in a randomized,...

  11. Lopinavir/ritonavir significantly influences pharmacokinetic exposure of artemether/lumefantrine in HIV-infected Ugandan adults

    OpenAIRE

    Byakika-Kibwika, Pauline; Lamorde, Mohammed; Okaba-Kayom, Violet; Mayanja-Kizza, Harriet; Katabira, Elly; Hanpithakpong, Warunee; Pakker, Nadine; Dorlo, Thomas P. C.; Tarning, Joel; Lindegardh, Niklas; de Vries, Peter J; Back, David; Khoo, Saye; Merry, Concepta

    2012-01-01

    Background Treatment of HIV/malaria-coinfected patients with antiretroviral therapy (ART) and artemisinin-based combination therapy has potential for drug interactions. We investigated the pharmacokinetics of artemether, dihydroartemisinin and lumefantrine after administration of a single dose of 80/480 mg of artemether/lumefantrine to HIV-infected adults, taken with and without lopinavir/ritonavir. Methods A two-arm parallel study of 13 HIV-infected ART-naive adults and 16 HIV-infected adult...

  12. Adult neural stem cells in the mammalian central nervous system

    Institute of Scientific and Technical Information of China (English)

    Dengke K Ma; Michael A Bonaguidi; Guo-li Ming; Hongjun Song

    2009-01-01

    Neural stem cells (NSCs) are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, in-cluding topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.

  13. Risk factors for perceived unmet medical needs in human immunodeficiency virus-infected adults in Seoul, Korea.

    Science.gov (United States)

    Kang, Cho Ryok; Bang, Ji Hwan; Cho, Sung-Il; Kim, Kui Nam; Lee, Hee-Jin; Lee, Young Hwa; Ryu, Bo Yeong; Cho, Soo Kyung; Oh, Myoung-Don; Lee, Jong-Koo

    2016-09-01

    To identify the factors associated with perceived unmet medical needs in human immunodeficiency virus (HIV)-infected adults, we analyzed the results from a series of city-wide cross-sectional surveys of HIV-infected adults living in Seoul, Korea. Multivariate logistic regression analysis was used to identify factors related to unmet medical needs. Among the 775 subjects included in the study, 15.4% had perceived unmet medical needs. Significant factors included age group (35-49 years; adjusted odds ratio [aOR], 1.80; 95% confidence interval [CI], 1.06-3.06), lower monthly income (aOR, 3.75 for the <$900/mo group and 2.44 for the $900-$1800/mo group; 95% CI, 1.68-8.35 and 1.18-5.04, respectively), beneficiaries of the National Medical Aid Program (aOR, 1.78; 95% CI, 1.01-3.17), recent CD4 cell counts <500/µL (aOR, 1.53; 95% CI, 1.01-2.33). Taken together, these data reveal strong associations of middle age and low socioeconomic status with perceived unmet medical needs among HIV-infected adults. PMID:27009447

  14. Respiratory infections in adults with atopic disease and IgE antibodies to common aeroallergens.

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    Aino Rantala

    Full Text Available BACKGROUND: Atopic diseases, including allergic rhinitis, allergic dermatitis and asthma, are common diseases with a prevalence of 30-40% worldwide and are thus of great global public health importance. Allergic inflammation may influence the immunity against infections, so atopic individuals could be susceptible to respiratory infections. No previous population-based study has addressed the relation between atopy and respiratory infections in adulthood. We assessed the relation between atopic disease, specific IgE antibodies and the occurrence of upper and lower respiratory infections in the past 12 months among working-aged adults. METHODS AND FINDINGS: A population-based cross-sectional study of 1008 atopic and non-atopic adults 21-63 years old was conducted. Information on atopic diseases, allergy tests and respiratory infections was collected by a questionnaire. Specific IgE antibodies to common aeroallergens were measured in serum. Adults with atopic disease had a significantly increased risk of lower respiratory tract infections (LRTI; including acute bronchitis and pneumonia with an adjusted risk ratio (RR 2.24 (95% confidence interval [CI] 1.43, 3.52 and upper respiratory tract infections (URTI; including common cold, sinusitis, tonsillitis, and otitis media with an adjusted RR 1.55 (1.14, 2.10. The risk of LRTIs increased with increasing level of specific IgE (linear trend P = 0.059. CONCLUSIONS: This study provides new evidence that working-aged adults with atopic disease experience significantly more LRTIs and URTIs than non-atopics. The occurrence of respiratory infections increased with increasing levels of specific IgE antibodies to common aeroallergens, showing a dose-response pattern with LRTIs. From the clinical point of view it is important to recognize that those with atopies are a risk group for respiratory infections, including more severe LRTIs.

  15. Cytokine production by endothelial cells infected with human T cell lymphotropic virus type I.

    OpenAIRE

    H. Takashima; Eguchi, K.; Kawakami, A; Kawabe, Y; Migita, K; Sakai, M; Origuchi, T; Nagataki, S.

    1996-01-01

    OBJECTIVE: To investigate the ability of human T cell lymphotropic virus type I (HTLV-I) to infect endothelial cells and induce cytokine production by these cells. METHODS: Human umbilical vein endothelial cells (HUVEC) were cocultured with HTLV-I infected T cell line (MT-2 cells) or uninfected T cell line (CEM cells). RESULTS: Following coculture with MT-2 cells, endothelial cells expressed HTLV-I specific core antigens. Endothelial cells cocultured with MT-2 cells produced significant amoun...

  16. Susceptibility of different leukocyte cell types to Vaccinia virus infection

    Directory of Open Access Journals (Sweden)

    Sánchez-Puig Juana M

    2004-11-01

    Full Text Available Abstract Background Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Results We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP, and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. Conclusions When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.

  17. Risk Factors for Acquisition and Clearance of Oral Human Papillomavirus Infection Among HIV-Infected and HIV-Uninfected Adults

    Science.gov (United States)

    Beachler, Daniel C.; Sugar, Elizabeth A.; Margolick, Joseph B.; Weber, Kathleen M.; Strickler, Howard D.; Wiley, Dorothy J.; Cranston, Ross D.; Burk, Robert D.; Minkoff, Howard; Reddy, Susheel; Xiao, Weihong; Guo, Yingshi; Gillison, Maura L.; D'Souza, Gypsyamber

    2015-01-01

    Human papillomavirus (HPV) causes the majority of oropharyngeal cancers in the United States, yet the risk factors for and natural history of oral HPV infection are largely unknown. In 2010–2011, a US-based longitudinal cohort study of 761 human immunodeficiency virus (HIV)-infected and 469 at-risk HIV-uninfected participants from the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study was initiated. Semiannually collected oral rinses were evaluated for 37 HPV genotypes using the Roche LINEAR ARRAY HPV Genotyping Test (Roche Molecular Systems, Pleasanton, California), and factors associated with oral HPV incidence and clearance were explored using adjusted Wei-Lin-Weissfeld modeling. Through 2013, the 2-year cumulative incidence of any type of oral HPV infection was 34% in HIV-infected persons and 19% in HIV-uninfected persons. However, many of these infections cleared. Seven percent of incident infections and 35% of prevalent infections persisted for at least 2 years. After adjustment for other risk factors, HIV infection (adjusted hazard ratio = 2.3, 95% confidence interval: 1.7, 3.2), reduced current CD4 cell count, and increased numbers of oral sex and “rimming” partners increased the risk of incident oral HPV infection, whereas male sex, older age, and current smoking increased the risk of oral HPV persistence (each P < 0.05). This helps explain the consistent associations observed between these factors and prevalent oral HPV infection in previous cross-sectional studies. PMID:25480823

  18. SECONDARY BACTERIAL INFECTION IN ADULT PATIENTS WITH PROLONGED AND SEVERE DENGUE FEVER

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    Anil Kumar

    2016-05-01

    Full Text Available INTRODUCTION Generally, in dengue shock syndrome antibiotics are not advised. But unrecognised bacterial infection is likely to contribute to morbidity and mortality, probably because of increased vascular permeability. OBJECTIVES To assess the incidence of secondary bacterial infection in adult patients with prolonged and severe dengue fever. METHODS A prospective study was conducted recruiting patients with confirmed acute dengue infection who had prolonged fever (>5 days. Prior to institution of antibiotic therapy, two sets of blood cultures were taken from patients. Demographic, clinical, haematological and biochemical parameters were recorded. Severity of fever & associated symptoms assessed. Ultrasonography done to find out development of ascites and pleural effusions. RESULTS Sixty patients (60.0% males with a mean age of 33.5 years (SD 12.1 were studied. The average duration of fever was 6.9 days (SD 1.6. Fifteen patients (25% had bacterial isolates in their blood cultures; Staphylococcus aureus (n=3, coliforms (n=7, pseudomonas (n=2 and 3 had mixed growths. The culture positive group had severe body aches and joints paint at admission and high grade fever, third space fluid accumulation and significant drop in platelets compared to culture-negative group. CONCLUSIONS A quarter of dengue patients with prolonged fever had a bacterial isolate. Culture-positive patients appeared more ill with body aches and had higher degrees of fever during the course of the illness. Increased vascular permeability may predispose to bacterial seepage into blood. Although white cell count is not helpful in detecting bacteraemia in dengue fever, low platelet count and severe symptoms at presentation may be helpful.

  19. Transmitted drug-resistance in human immunodeficiency virus-infected adult population in El Salvador, Central America.

    Science.gov (United States)

    Holguín, Á; Yebra, G; Martín, L; de Pineda, A T; Ruiz, L E; Quezada, A Y; Nieto, A I; Escobar, G

    2013-12-01

    El Salvador harbours one of the largest Central American human immunodeficiency virus (HIV) epidemics, but few studies have analysed it in depth. Here, we describe the presence of transmitted drug resistance (TDR) and HIV variants in the HIV-infected adult population in El Salvador. Dried blood spots from 119 HIV-infected antiretroviral-naive adults attended in El Salvador were collected in 2011. The TDR was assessed according to the list recommended by the WHO. HIV-1 variants were described using phylogeny. Pol sequences could be amplified in 88 patients (50.6% men), with a mean age of 35 years. Almost all (96.7%) were infected with HIV through sexual practice and 58.7% were recently diagnosed. The mean CD4(+) count was 474 cells/mm(3) and 43.1% and 15.5% of patients showed moderate (100 000 copies/mL in 24.7% of patients and Salvador, lower than in other Central American studies. Periodical studies are essential to monitor and prevent TDR emergence in low-income and middle-income regions. Also, more efforts are needed to promote early diagnosis and prevention of infection in El Salvador.

  20. Cell Phone Use by Adults with Intellectual Disabilities

    Science.gov (United States)

    Bryen, Diane Nelson; Carey, Allison; Friedman, Mark

    2007-01-01

    Although cell phone use has grown dramatically, there is a gap in cell phone access between people with disabilities and the general public. The importance of cell phone use among people with intellectual disabilities and studies about use of cell phones by adults with intellectual disabilities was described. Our goal was to determine the extent…

  1. A Case of Respiratory Syncytial Virus Infection in an HIV-Positive Adult

    Directory of Open Access Journals (Sweden)

    Aakriti Gupta

    2012-01-01

    Full Text Available Respiratory syncytial virus (RSV is commonly known to cause an influenza-like illness. However, it can also cause more severe disease in young children and older adults comprising of organ transplant patients with immunocompromised status. Till date, only four cases of RSV infections have been reported in HIV-positive adults. We describe here a case of HIV-positive female with relatively preserved immune function who presented with RSV infection requiring ventilation and showed improvement after prompt treatment with intravenous immunoglobulin.

  2. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Delaisse, Jean-Marie; Hinge, Maja;

    2016-01-01

    . Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone...... demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic....

  3. Establishment of human papillomavirus infection requires cell cycle progression.

    Directory of Open Access Journals (Sweden)

    Dohun Pyeon

    2009-02-01

    Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

  4. Prevalence of sapovirus infection among infant and adult patients with acute gastroenteritis in Tehran, Iran

    OpenAIRE

    Romani, Sara; Azimzadeh, Pedram; Mohebbi, Seyed Reza; Bozorgi, Sajad Majidizadeh; Zali, Narges; JADALI, Farzaneh

    2012-01-01

    Aim This study investigated the prevalence of sapovirus infections in patient with acute gastroenteritis in Tehran, Iran. Background Sapovirus, a member of the family Caliciviridae is one of the major causative agents of viral gastroenteritis affecting both children and adult individuals. There isn't enough data about prevalence and genotypes of sapovirus infection in Tehran, the capital city of Iran. Patients and methods A total of 42 fecal samples were collected from patients with acute gas...

  5. Active Epstein-Barr virus infection after allogeneic stem cell transplantation : re-infection or reactivation?

    NARCIS (Netherlands)

    Meijer, E; Spijkers, S; Moschatsis, S; Boland, GJ; Thijsen, SFT; van Loon, AM; Verdonck, LF

    2005-01-01

    Recipients of allogeneic stem cell transplants (SCT) often show active Epstein-Barr virus (EBV) infection, which may progress to EBV-associated lymphoproliferative disorders. It is not known whether these EBV infections are true reactivations of the endogenous EBV strain or re-infections with an exo

  6. B-Cell Response during Protozoan Parasite Infections

    OpenAIRE

    Amezcua Vesely, María C; Bermejo, Daniela A.; Montes, Carolina L.; Acosta-Rodríguez, Eva V.; Adriana Gruppi

    2012-01-01

    In this review, we discuss how protozoan parasites alter immature and mature B cell compartment. B1 and marginal zone (MZ) B cells, considered innate like B cells, are activated during protozoan parasite infections, and they generate short lived plasma cells providing a prompt antibody source. In addition, protozoan infections induce massive B cell response with polyclonal activation that leads to hypergammaglobulnemia with serum antibodies specific for the parasites and self and/or non relat...

  7. An adult case of urinary tract infection with Kingella kingae: a case report

    Directory of Open Access Journals (Sweden)

    Ramana KV

    2009-05-01

    Full Text Available Abstract Introduction Kingella kingae, though part of the normal upper respiratory tract and genitourinary tract, is increasingly being recognized as an important human pathogen. During the past decade, it has emerged as a significant pathogen in the pediatric age group primarily causing bacteremia and osteoarticular infections. Adult infection usually occurs in individuals who are severely immunocompromised and most infections have taken the form of septicemia or septic arthritis. Bacteremia due to K. kingae has been reported as the immediate cause of death in patients with acquired immunodeficiency syndrome. Case presentation We present a microbiologically confirmed urinary tract infection with K. kingae in an immunocompetent 45-year-old adult woman with post-menopausal bleeding and with a history of clots. Her urine was subjected to culture and sensitivity tests. The isolated colonies were identified as K. kingae because of their typical culture characteristics such as long incubation period required for growth, beta-hemolysis, positive oxidase and negative catalase, urease indole, nitrate and citrate tests. Penicillin G disc test was positive. They were sensitive to all conventional antibiotics. Conclusion K. kingae infection is a rare occurrence in immunocompetent adults. Very few cases of microbiologically confirmed infections have been reported so far. The isolation of K. kingae from urine sample has rarely been reported. K. kingae isolates are either missed or misinterpreted by clinical microbiologists. Therefore, K. kingae deserves recognition as a pathogen.

  8. Canadian Helicobacter pylori Consensus Conference Update: Infections in Adults

    OpenAIRE

    Hunt, RH; Fallone, CA; Thomson, ABR

    1999-01-01

    The first Canadian Helicobacter pylori Consensus Conference took place in April 1997. The initial recommendations of the conference were published in early 1998. An update meeting was held in June 1998, and the present paper updates and complements the earlier recommendations. Key changes included the following: the recommendation for testing and treating H pylori infection in patients with known peptic ulcer disease was extended to testing and treating patients with ulcer-like dyspepsia; it ...

  9. Hematopoietic Stem and Immune Cells in Chronic HIV Infection

    OpenAIRE

    Jielin Zhang; Clyde Crumpacker

    2015-01-01

    Hematopoietic stem cell (HSC) belongs to multipotent adult somatic stem cells. A single HSC can reconstitute the entire blood system via self-renewal, differentiation into all lineages of blood cells, and replenishment of cells lost due to attrition or disease in a person's lifetime. Although all blood and immune cells derive from HSC, immune cells, specifically immune memory cells, have the properties of HSC on self-renewal and differentiation into lineage effector cells responding to the in...

  10. Specific infections, infection-related behavior, and risk of non-Hodgkin lymphoma in adults.

    Science.gov (United States)

    Vajdic, Claire M; Grulich, Andrew E; Kaldor, John M; Fritschi, Lin; Benke, Geza; Hughes, Ann Maree; Kricker, Anne; Turner, Jennifer J; Milliken, Sam; Armstrong, Bruce K

    2006-06-01

    Infections were examined as possible risk factors for non-Hodgkin lymphoma in a population-based case-control study in New South Wales and the Australian Capital Territory, Australia. Incident cases (n = 694) had no history of HIV infection or transplantation. Controls (n = 694) were randomly selected from electoral rolls and frequency matched to cases by age, sex, and area of residence. A postal questionnaire and telephone interview measured history of specific infections, occupational exposures, and behavioral and other risk factors for infection. Blood samples were tested for antibodies to human T-lymphotrophic virus type I and hepatitis C virus. Logistic regression models included the three matching variables and ethnicity. There was no association between risk of non-Hodgkin lymphoma and any of the variables analyzed, including sexually transmitted infections, sexual behavior, blood transfusions, influenza, acne, and either occupational or domestic exposure to zoonotic infections. Non-Hodgkin lymphoma risk was nonsignificantly elevated (odds ratio, 2.99; 95% confidence interval, 0.78-11.51) for those with a history of injecting drug use. Three cases and two controls (odds ratio, 1.32; 95% confidence interval, 0.22-7.98) tested positive to hepatitis C virus infection and none tested positive to human T-lymphotrophic virus type I/II infection. This study provides consistent evidence that sexually transmitted infections and zoonoses are not risk factors for non-Hodgkin lymphoma.

  11. Potential of embryonic and adult stem cells in vitro.

    Science.gov (United States)

    Czyz, Jaroslaw; Wiese, Cornelia; Rolletschek, Alexandra; Blyszczuk, Przemyslaw; Cross, Michael; Wobus, Anna M

    2003-01-01

    Recent developments in the field of stem cell research indicate their enormous potential as a source of tissue for regenerative therapies. The success of such applications will depend on the precise properties and potentials of stem cells isolated either from embryonic, fetal or adult tissues. Embryonic stem cells established from the inner cell mass of early mouse embryos are characterized by nearly unlimited proliferation, and the capacity to differentiate into derivatives of essentially all lineages. The recent isolation and culture of human embryonic stem cell lines presents new opportunities for reconstructive medicine. However, important problems remain; first, the derivation of human embryonic stem cells from in vitro fertilized blastocysts creates ethical problems, and second, the current techniques for the directed differentiation into somatic cell populations yield impure products with tumorigenic potential. Recent studies have also suggested an unexpectedly wide developmental potential of adult tissue-specific stem cells. Here too, many questions remain concerning the nature and status of adult stem cells both in vivo and in vitro and their proliferation and differentiation/transdifferentiation capacity. This review focuses on those issues of embryonic and adult stem cell biology most relevant to their in vitro propagation and differentiation. Questions and problems related to the use of human embryonic and adult stem cells in tissue regeneration and transplantation are discussed.

  12. Molecular Pathology of Adult T-Cell Leukemia/Lymphoma.

    Science.gov (United States)

    Ohshima, Koichi

    2015-01-01

    Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm of highly pleomorphic lymphoid cells. ATLL is usually widely disseminated, and it is caused by human T-cell leukemia virus type 1 (HTLV-1). It is a disease with a long latency, and affected individuals are usually exposed to the virus very early in life. The cumulative incidence of ATLL is estimated to be 2.5% among HTLV-1 carriers. ATLL cells express CD2, CD3, CD5, CD4, and CD25, as well as CCR4 and FoxP3 of the regulatory T-cell marker. HTLV-1 is causally linked to ATLL, but infection alone is not sufficient to result in neoplastic transformation. A significant finding in this connection is that the Tax viral protein leads to transcriptional activation of many genes, while the HTLV-1 basic leucine zipper factor is thought to be important for T-cell proliferation and oncogenesis. Half of ATLL cases retain the ability to express HTLV-1 Tax, which is a target of HTLV-1-specific cytotoxic T lymphocytes (CTL). An increase in HTLV-1-specific CTL responses is observed in some asymptomatic HTLV-1 carriers. Although HTLV-1-specific CTL are also present in the peripheral blood of ATLL patients, they do not expand sufficiently. We investigated the clinicopathological features and analyzed the staining of Tax-specific CTL and FoxP3. Tax-specific CTL correlated inversely with FoxP3, an increase in the ratio of CD163+ tumor-associated macrophages was associated with worse clinical prognosis, and ATLL cell lines proliferated significantly following direct co-culture with M2 macrophages. Several clinical variants of ATLL have been identified: acute, lymphomatous, chronic, and smoldering. Oligo-array comparative genomic hybridization revealed that genomic loss of 9p21.3 was a significant characteristic of acute-type, but not of chronic-type ATLL. Furthermore, we found that genomic alteration of CD58, which is implicated in immune escape, is more frequently observed in acute than in chronic ATLL. Interestingly

  13. Nosocomial infection in adult admissions with hematological malignancies originating from different lineages: a prospective observational study.

    Directory of Open Access Journals (Sweden)

    Hui Liu

    Full Text Available Nosocomial infection (NI causes prolonged hospital stays, increased healthcare costs, and higher mortality among patients with hematological malignancies (HM. However, few studies have compared the incidence of NI according to the HM lineage.To compare the incidence of NI according to the type of HM lineage, and identify the risk factors for NI.This prospective observational study monitored adult patients with HM admitted for >48 hours to the General Hospital of the People's Liberation Army during 2010-2013. Attack rates and incidences of NI were compared, and multivariable logistic regression was used to control for confounding effects.This study included 6,613 admissions from 1,922 patients. During these admissions, 1,023 acquired 1,136 NI episodes, with an attack rate of 15.47% and incidence of 9.6‰ (95% CI: 9.1-10.2. Higher rates and densities of NIs were observed among myeloid neoplasm (MN admissions, compared to lymphoid neoplasm (LN admissions (28.42% vs. 11.00%, P<0.001 and 11.4% vs. 8.4‰, P<0.001. NI attack rates in acute myeloid leukemia (AML and myelodysplastic/myeloproliferative neoplasm (MDS/MPN were higher than those in MDS (30.69% vs. 20.19%, P<0.001; 38.89% vs. 20.19%, P = 0.003. Attack rates in T/NK-cell neoplasm and B-cell neoplasm were higher than those in Hodgkin lymphoma (15.04% vs. 3.65%; 10.94% vs. 3.65%, P<0.001. Multivariable regression analysis indicated prolonged hospitalization, presence of central venous catheterization, neutropenia, current stem cell transplant, infection on admission, and old age were independently associated with higher NI incidence. After adjusting for these factors, MN admissions still had a higher risk of infection (odds ratio 1.34, 95% CI: 1.13-1.59, P<0.001.Different NI attack rates were observed for HM from different lineages, with MN lineages having a higher attack rate and incidence than LN lineages. Special attention should be paid to MN admissions, especially AML and MDS

  14. Bioinformatic analysis reveals the expression of unique transcriptomic signatures in Zika virus infected human neural stem cells

    OpenAIRE

    Rolfe, Alyssa J.; Bosco, Dale B.; Wang, Jingying; Nowakowski, Richard S.; Fan, Jianqing; Ren, Yi

    2016-01-01

    Background The single-stranded RNA Flavivirus, Zika virus (ZIKV), has recently re-emerged and spread rapidly across the western hemisphere’s equatorial countries, primarily through Aedes mosquito transmission. While symptoms in adult infections appear to be self-limiting and mild, severe birth defects, such as microcephaly, have been linked to infection during early pregnancy. Recently, Tang et al. (Cell Stem Cell 2016, doi: 10.1016/j.stem.2016.02.016) demonstrated that ZIKV efficiently infec...

  15. Distal Airway Stem Cells Render Alveoli in Vitro and During Lung Regeneration Following H1N1 Influenza Infection

    OpenAIRE

    Kumar, Pooja A.; Hu, Yuanyu; Yamamoto, Yusuke; Hoe, Neo Boon; Wei, Tay Seok; Mu, Dakai; Sun, Yan; Joo, Lim Siew; Dagher, Rania; Zielonka, Elisabeth; Wang, Yun; Chow, Vincent T.; Crum, Christopher P.; Xian, Wa; McKeon, Frank

    2011-01-01

    The extent of lung regeneration following catastrophic damage and the potential role of adult stem cells in such a process remains obscure. Sublethal infection of mice with an H1N1 influenza virus related to that of the 1918 pandemic triggers massive airway damage followed by apparent regeneration. We show here that p63-expressing stem cells in the bronchiolar epithelium undergo rapid proliferation after infection and radiate to interbronchiolar regions of alveolar ablation. Once there, these...

  16. Kinetics of Oestrus ovis infection and activity of adult flies

    Directory of Open Access Journals (Sweden)

    Gracia M.J.

    2006-12-01

    Full Text Available Oestrus Ovis is a common sheep parasite in the Mediterranean region. This study was carried out in the Ebro River Valley near Zaragoza (northeast Spain using tracer animals to describe the seasons when infestation is more likely. Based on that information and an analysis of the evolution of the parasite within the host, we suggest the most appropriate time for treatment. Adult instars appeared in May until November and there was a diapause beginning in October-November and as least until February, so it is suggested than sheep be treated with larvicide in December.

  17. Intestinal stem cells in the adult Drosophila midgut

    International Nuclear Information System (INIS)

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: ► The homeostasis and regeneration of adult fly midguts are mediated by ISCs. ► Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). ► EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. ► Notch signaling regulates ISC self-renewal and differentiation.

  18. Brucella abortus-infected B cells induce osteoclastogenesis.

    Science.gov (United States)

    Pesce Viglietti, Ayelén Ivana; Arriola Benitez, Paula Constanza; Giambartolomei, Guillermo Hernán; Delpino, María Victoria

    2016-09-01

    Brucella abortus is an intracellular bacterium that establishes lifelong infections in livestock and humans although the mechanisms of its chronicity are poorly understood. Activated B cells have long lifespan and B. abortus infection activates B cells. Our results indicate that the direct infection of B cells with B. abortus induced matrix metalloproteinase-9 (MMP-9), receptor activator for NF κB ligand (RANKL), tumor necrosis factor (TNF)-α and interleukin (IL)-6 secretion. In addition, supernatants from B. abortus-infected B cells induced bone marrow-derived monocytes to undergo osteoclastogenesis. Using osteoprotegerin, RANKL's decoy receptor, we determined that RANKL is involved in osteoclastogenesis induced by supernatants from B. abortus-infected B cells. The results presented here shed light on how the interactions of B. abortus with B cells may have a role in the pathogenesis of brucellar osteoarticular disease.

  19. A case-control study of risk factors for rotavirus infections in adults, Denmark, 2005-2009

    DEFF Research Database (Denmark)

    Dorleans, F; Falkenhorst, G; Böttiger, B;

    2016-01-01

    Rotavirus (RV) infections affect young children, but can also occur in adults. We sought to identify risk factors for RV infections in adults aged ⩾18 years in Denmark, and to describe illness and genotyping characteristics. From March 2005 to February 2009, we recruited consecutive cases...

  20. Adult Reye-like syndrome associated with serologic evidence of acute parvovirus B19 infection

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    Paulo Sérgio Gonçalves da Costa

    2011-10-01

    Full Text Available Reye's syndrome is an infrequently diagnosed medical condition affecting mainly children. The etiology, epidemiology and natural history of Reye's syndrome have been cloudily written in footnotes of medical books and exotic papers since the initial description in early 1950s. We report here a case of adult Reye's syndrome associated with serologic evidence of parvovirus B19 infection.

  1. Risk factors for mortality among malnourished HIV-infected adults eligible for antiretroviral therapy

    DEFF Research Database (Denmark)

    Woodd, Susannah L; Kelly, Paul; Koethe, John R;

    2016-01-01

    BACKGROUND: A substantial proportion of HIV-infected adults starting antiretroviral therapy (ART) in sub-Saharan Africa are malnourished. We aimed to increase understanding of the factors affecting their high mortality, particularly in the high-risk period before ART initiation. METHODS: We analy...

  2. Increased Coronary Vessel Wall Thickness in HIV-Infected Young Adults

    OpenAIRE

    Abd-Elmoniem, Khaled Z.; Unsal, Aylin B.; Eshera, Sarah; Matta, Jatin R.; Muldoon, Nancy; McAreavey, Dorothea; Purdy, Julia B.; HAZRA, Rohan; Hadigan, Colleen; Gharib, Ahmed M.

    2014-01-01

    Young adults infected with HIV early in life have significantly thicker right coronary artery walls than controls as measured by black-blood coronary magnetic resonance imaging. Vessel wall thickening in patients correlated with length of antiretroviral exposure, smoking pack-years, and hyperlipidemia.

  3. Overwhelming postsplenectomy infection syndrome in adults - A clinically preventable disease

    Institute of Scientific and Technical Information of China (English)

    Takehiro Okabayashi; Kazuhiro Hanazaki

    2008-01-01

    Overwhelming postsplenectomy infection (OPSI)syndrome is a rare condition, but is associated with high mortality. However, recognition and clinical management of OPSI is not well established. The prevalence of splenectomy increased recently because it was a clinically effective treatment for hepatitis C virus-associated thrombocytopenia before the introduction of the interferon/ribavirin combination therapy. We reviewed the literature characterizing the clinicopathological features of OPSI and assessed the most effective and feasible administration of the condition. A Medline search was performed using the keywords 'overwhelming','postsplenectomy infection', 'postsplenectomy sepsis','chronic liver disease', and/or 'splenectomy'. Additional articles were obtained from references within the papers identified by the Medilne search. Durations between splenectomy and onset of OPSI ranged from less than 1 wk to more than 20 years. Autopsy showed that many patients with OPSI also had Waterhouse-Friderichsen syndrome. Although the mortality rate from OPSI has been reduced by appropriate vaccination and education,the precise pathogenesis and a suitable therapeutic strategy remain to be elucidated. Protein energy malnutrition (PEM) is commonly observed in cirrhotic patients. Since the immune response in patients with PEM is compromised, a more careful management for OPSI should therefore be applied for cirrhotic patients after splenectomy. In addition, strict long-term follow up of OPST patients including informed consent will lead to a better prognosis.

  4. Financial burden of morbidity in HIV infected adults in Manipur, India: comparison between patients with different co-infection

    Directory of Open Access Journals (Sweden)

    Ngaihte EN

    2013-01-01

    Full Text Available Background: The negative impact of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS is seen to have lessened with the introduction of the highly active anti-retroviral therapy (HAART. However, there is a few consensus on whether the introduction of HAART has significantly relieved the economic burden of HIV/AIDS, particularly with regards to out-of-pocket expenditure (OOPE for people living with HIV/AIDS (PLHAs and the possible differential impact of HIV/AIDS care and treatment on PLHAs with different co-infection. The health related expenditure of HIV-infected adults with different co-infections who are at different stage of treatment is reported and analysed in this paper.Methods: Cross-sectional data were collected from 496 PLHA respondents through interview schedule. Respondents were also asked to report all costs due to the PLHA's infection in the reference period. Differences in the components of costs were analysed using Statistical Package for Social Sciences (SPSS software version 20.0.Results: There was no statistically significant relationship between presence or absence of opportunistic infections (OI and the amount of expenditure incurred on all other component of costs except the expenditure on medicine. The difference in mean expenditure for medicines, test and others were statistically significant between those on Anti-Retroviral Therapy (ART and the pre-ART group at 95% level of confidence. The mean costs incurred on all components of costs were significantly different across different types of OI/co-infection.Conclusions: The cost of healthcare for those infected with HIV is significant even when there is free provision of HIV/AIDS related care and treatment. The costs of healthcare are significant especially with the presence of certain specific co-infection.

  5. Evolutionary insights into postembryonic development of adult intestinal stem cells

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    Ishizuya-Oka Atsuko

    2011-11-01

    Full Text Available Abstract In the adult vertebrate intestine, multi-potent stem cells continuously generate all of the epithelial cells throughout the adulthood. While it has long been known that the frog intestine is formed via the development of adult intestinal stem cells during thyroid hormone (TH-dependent metamorphosis, the basic structure of the adult intestine is formed by birth in mammals and it is unclear if the subsequent maturation of the intestine involves any changes in the intestinal stem cells. Two recent papers showing that B lymphocyte-induced maturation protein 1 (Blimp1 regulates postnatal epithelial stem cell reprogramming during mouse intestinal maturation support the model that adult intestinal stem cells are developed during postembryonic development in mammals, in a TH-dependent process similar to intestinal remodeling during amphibian metamorphosis. Since the formation of the adult intestine in both mammals and amphibians is closely associated with the adaptation from aquatic to terrestrial life during the peak of endogenous TH levels, the molecular mechanisms by which the adult stem cells are developed are likely evolutionally conserved.

  6. Adult Stromal (Skeletal, Mesenchymal) Stem Cells: Advances Towards Clinical Applications

    DEFF Research Database (Denmark)

    Kermani, Abbas Jafari; Harkness, Linda; Zaher, Walid;

    2014-01-01

    Mesenchymal Stem Cells (MSC) are non-hematopoietic adult stromal cells that reside in a perivascular niche in close association with pericytes and endothelial cells and possess self-renewal and multi-lineage differentiation capacity. The origin, unique properties, and therapeutic benefits of MSC ...

  7. Coexistence of Quiescent and Active Adult Stem Cells in Mammals

    NARCIS (Netherlands)

    Li, Linheng; Clevers, Hans

    2010-01-01

    Adult stem cells are crucial for physiological tissue renewal and regeneration after injury. Prevailing models assume the existence of a single quiescent population of stem cells residing in a specialized niche of a given tissue. Emerging evidence indicates that both quiescent (out of cell cycle and

  8. [Molecular features of beta-hemolytic streptococci isolated from blood in adult invasive infection and the clinical background factors].

    Science.gov (United States)

    Asami, Ryoko; Okada, Keisuke; Chiba, Naoko; Ubukata, Kimiko; Takahashi, Takashi

    2010-05-01

    We studied the relationship between features of beta-hemolytic streptococci (n = 45) isolated from blood in adult invasive infection and the clinical background factors observed from January 2001 through August at a hospital for the elderly. The meanage of subjects having invasive streptococcal infection with 22 invasive Streptococcus dysgalactiae subspecies equisimilis (SDSE) strains, 2 S. pyogenes isolates, and 21 S. agalactiae (GBS) was 80 years, and 85.7% and 86.4% had underly diseases in the GBS and SDSE infections. SDSE-infected were mainly emergency woman outpatients and GBS infected were mainly man inpatients. The clinical syndrome involved pneumonia, urosepsis, and cellulitis. GBS mortality was 14.3% and SDSE mortality 27.3%. Compared to survivors, nonsurvivors had more thrombocytopenia and marked serum C-reactive protein elevation when blood culture were performed. No difference was seen in white blood cell count between bath groups. Our observations suggest that blood culture should be obtained before antimicrobials administration in elderly individuals with underlying illness who are seen at the emergency department and have laboratory blood data suggestive of infectious disease. PMID:20560419

  9. Identifying research priorities on infections in older adults: proceedings of an interdisciplinary workshop

    Directory of Open Access Journals (Sweden)

    Lohfeld Lynne

    2001-08-01

    Full Text Available Abstract Background Infections pose a substantial burden to the health of older adults. In this report, we describe the proceedings of a workshop to formulate and prioritize research questions about infections in older adults using an interdisciplinary approach. Methods Researchers from four sectors (basic science, clinical sciences, health services and epidemiology/determinants of health and representatives from various Canadian local, provincial, and federal stakeholder groups were invited to a two-day workshop. Five multi-disciplinary groups and stakeholders from each of three healthcare settings (long term, acute care and community discussed research priorities for each of the settings. Five to ten research questions were identified for each setting. Results The research questions proposed ranged from risk factors and outcomes for different infections to the effect of nutrition on infection and the role of alternative and complementary medicine in treating infections. Health service issues included barriers to immunization, prolongation of hospital length of stay by infection, use of care paths for managing infections, and decision-making in determining the site of care for individuals with infections. Clinical questions included risk factor assessment for infection, the effectiveness of preventative strategies, and technology evaluation. Epidemiologic issues included the challenge of achieving a better understanding of respiratory infections in the community and determining the prevalence of colonization with multi-resistant bacteria. Conclusions The questions are of direct relevance to researchers in a wide variety of fields. Bringing together a multi-disciplinary group of researchers to frame and prioritize research questions about aging is feasible, participants valued the opinions of people working in other areas.

  10. Wnt signaling in adult intestinal stem cells and cancer

    OpenAIRE

    Krausová, M. (Michaela); Kořínek, V. (Vladimír)

    2014-01-01

    Signaling initiated by secreted glycoproteins of the Wnt family regulates many aspects of embryonic development and it is involved in homeostasis of adult tissues. In the gastrointestinal (GI) tract the Wnt pathway maintains the self-renewal capacity of epithelial stem cells. The stem cell attributes are conferred by mutual interactions of the stem cell with its local microenvironment, the stem cell niche. The niche ensures that the threshold of Wnt signaling in the stem cell is kept in physi...

  11. Modulation of host-cell MAPkinase signaling during fungal infection

    OpenAIRE

    Nir Osherov

    2015-01-01

    Fungal infections contribute substantially to human suffering and mortality. The interaction between fungal pathogens and their host involves the invasion and penetration of the surface epithelium, activation of cells of the innate immune system and the generation of an effective response to block infection. Numerous host-cell signaling pathways are activated during fungal infection. This review will focus on the main fungal pathogens Aspergillus fumigatus, Candida albicans and Cryptococcus n...

  12. Walking Stability during Cell Phone Use in Healthy Adults

    OpenAIRE

    Kao, Pei-Chun; Higginson, Christopher I.; Seymour, Kelly; Kamerdze, Morgan; Jill S. Higginson

    2015-01-01

    The number of falls and/or accidental injuries associated with cellular phone use during walking is growing rapidly. Understanding the effects of concurrent cell phone use on human gait may help develop safety guidelines for pedestrians. It was shown previously that older adults had more pronounced dual-task interferences than younger adults when concurrent cognitive task required visual information processing. Thus, cell phone use might have greater impact on walking stability in older than ...

  13. Development of neural stem cell in the adult brain

    OpenAIRE

    Duan, Xin; Kang, Eunchai; Liu, Cindy Y.; Ming, Guo-li; Song, Hongjun

    2008-01-01

    New neurons are continuously generated in the dentate gyrus of the mammalian hippocampus and in the subventricular zone of the lateral ventricles throughout life. The origin of these new neurons is believed to be from multipotent adult neural stem cells. Aided by new methodologies, significant progress has been made in the characterization of neural stem cells and their development in the adult brain. Recent studies have also begun to reveal essential extrinsic and intrinsic molecular mechani...

  14. French 2013 guidelines for antiretroviral therapy of HIV-1 infection in adults

    Directory of Open Access Journals (Sweden)

    Bruno Hoen

    2014-06-01

    Full Text Available Introduction: These guidelines are part of the French Experts’ recommendations for the management of people living with HIV/AIDS, which were made public and submitted to the French health authorities in September 2013. The objective was to provide updated recommendations for antiretroviral treatment (ART of HIV-positive adults. Guidelines included the following topics: when to start, what to start, specific situations for the choice of the first session of antiretroviral therapy, optimization of antiretroviral therapy after virologic suppression, and management of virologic failure. Methods: Ten members of the French HIV 2013 expert group were responsible for guidelines on ART. They systematically reviewed the most recent literature. The chairman of the subgroup was responsible for drafting the guidelines, which were subsequently discussed within, and finalized by the whole expert group to obtain a consensus. Recommendations were graded for strength and level of evidence using predefined criteria. Economic considerations were part of the decision-making process for selecting preferred first-line options. Potential conflicts of interest were actively managed throughout the whole process. Results: ART should be initiated in any HIV-positive person, whatever his/her CD4 T-cell count, even when >500/mm3. The level of evidence of the individual benefit of ART in terms of mortality or progression to AIDS increases with decreasing CD4 cell count. Preferred initial regimens include two nucleoside reverse transcriptase inhibitors (tenofovir/emtricitabine or abacavir/lamivudine plus a non-nucleoside reverse transcriptase inhibitor (efavirenz or rilpivirine, or a ritonavir-boosted protease inhibitor (atazanavir or darunavir. Raltegravir, lopinavir/r, and nevirapine are recommended as alternative third agents, with specific indications and restrictions. Specific situations such as HIV infection in women, primary HIV infection, severe immune suppression

  15. Extracellular vesicles from infected cells: potential for direct pathogenesis

    Directory of Open Access Journals (Sweden)

    Angela M Schwab

    2015-10-01

    Full Text Available Infections that result in natural or manmade spread of lethal biological agents are a concern and require national and focused preparedness. In this manuscript, as part of an early diagnostics and pathogen treatment strategy, we have focused on extracellular vesicles (EVs that arise following infections. Although the field of biodefense does not currently have a rich resource in EVs literature, none the less, similar pathogens belonging to the more classical emerging and non-emerging diseases have been studied in their EV/exosomal contents and function. These exosomes are formed in late endosomes and released from the cell membrane in almost every cell type in vivo. These vesicles contain proteins, RNA, and lipids from the cells they originate from and function in development, signal transduction, cell survival, and transfer of infectious material. The current review focuses on how different forms of infection exploit the exosomal pathway and how exosomes can be exploited artificially to treat infection and disease and potentially also be used as a source of vaccine. Virally-infected cells can secrete viral as well as cellular proteins and RNA in exosomes, allowing viruses to cause latent infection and spread of miRNA to nearby cells prior to a subsequent infection. In addition to virally-infected host cells, bacteria, protozoa, and fungi can all release small vesicles that contain Pathogen-Associated Molecular Patterns (PAMPs, regulating the neighboring uninfected cells. Examples of exosomes from both virally and bacterially infected cells point toward a re-programming network of pathways in the recipient cells. Finally, many of these exosomes contain cytokines and miRNAs that in turn can effect gene expression in the recipient cells through the classical TLR and NFkB pathway. Therefore, although exosomes do not replicate as an independent entity, they however facilitate movement of infectious material through tissues and may be the cause of

  16. Nematode-induced interference with vaccination efficacy targets follicular T helper cell induction and is preserved after termination of infection.

    Directory of Open Access Journals (Sweden)

    Irma Haben

    2014-09-01

    Full Text Available One-third of the human population is infected with parasitic worms. To avoid being eliminated, these parasites actively dampen the immune response of their hosts. This immune modulation also suppresses immune responses to third-party antigens such as vaccines. Here, we used Litomosoides sigmodontis-infected BALB/c mice to analyse nematode-induced interference with vaccination. Chronic nematode infection led to complete suppression of the humoral response to thymus-dependent vaccination. Thereby the numbers of antigen-specific B cells as well as the serum immunoglobulin (Ig G titres were reduced. TH2-associated IgG1 and TH1-associated IgG2 responses were both suppressed. Thus, nematode infection did not bias responses towards a TH2 response, but interfered with Ig responses in general. We provide evidence that this suppression indirectly targeted B cells via accessory T cells as number and frequency of vaccine-induced follicular B helper T cells were reduced. Moreover, vaccination using model antigens that stimulate Ig response independently of T helper cells was functional in nematode-infected mice. Using depletion experiments, we show that CD4+Foxp3+ regulatory T cells did not mediate the suppression of Ig response during chronic nematode infection. Suppression was induced by fourth stage larvae, immature adults and mature adults, and increased with the duration of the infection. By contrast, isolated microfilariae increased IgG2a responses to vaccination. This pro-inflammatory effect of microfilariae was overruled by the simultaneous presence of adults. Strikingly, a reduced humoral response was still observed if vaccination was performed more than 16 weeks after termination of L. sigmodontis infection. In summary, our results suggest that vaccination may not only fail in helminth-infected individuals, but also in individuals with a history of previous helminth infections.

  17. Nematode-Induced Interference with Vaccination Efficacy Targets Follicular T Helper Cell Induction and Is Preserved after Termination of Infection

    Science.gov (United States)

    Haben, Irma; Hartmann, Wiebke; Breloer, Minka

    2014-01-01

    One-third of the human population is infected with parasitic worms. To avoid being eliminated, these parasites actively dampen the immune response of their hosts. This immune modulation also suppresses immune responses to third-party antigens such as vaccines. Here, we used Litomosoides sigmodontis-infected BALB/c mice to analyse nematode-induced interference with vaccination. Chronic nematode infection led to complete suppression of the humoral response to thymus-dependent vaccination. Thereby the numbers of antigen-specific B cells as well as the serum immunoglobulin (Ig) G titres were reduced. TH2-associated IgG1 and TH1-associated IgG2 responses were both suppressed. Thus, nematode infection did not bias responses towards a TH2 response, but interfered with Ig responses in general. We provide evidence that this suppression indirectly targeted B cells via accessory T cells as number and frequency of vaccine-induced follicular B helper T cells were reduced. Moreover, vaccination using model antigens that stimulate Ig response independently of T helper cells was functional in nematode-infected mice. Using depletion experiments, we show that CD4+Foxp3+ regulatory T cells did not mediate the suppression of Ig response during chronic nematode infection. Suppression was induced by fourth stage larvae, immature adults and mature adults, and increased with the duration of the infection. By contrast, isolated microfilariae increased IgG2a responses to vaccination. This pro-inflammatory effect of microfilariae was overruled by the simultaneous presence of adults. Strikingly, a reduced humoral response was still observed if vaccination was performed more than 16 weeks after termination of L. sigmodontis infection. In summary, our results suggest that vaccination may not only fail in helminth-infected individuals, but also in individuals with a history of previous helminth infections. PMID:25255463

  18. Suppression of HIV-1 Infectivity by Human Glioma Cells.

    Science.gov (United States)

    Hoque, Sheikh Ariful; Tanaka, Atsushi; Islam, Salequl; Ahsan, Gias Uddin; Jinno-Oue, Atsushi; Hoshino, Hiroo

    2016-05-01

    HIV-1 infection to the central nervous system (CNS) is very common in AIDS patients. The predominant cell types infected in the brain are monocytes and macrophages, which are surrounded by several HIV-1-resistant cell types, such as astrocytes, oligodendrocytes, neurons, and microvascular cells. The effect of these HIV-1-resistant cells on HIV-1 infection is largely unknown. In this study, we examined the stability of HIV-1 cultured with several human glioblastoma cell lines, for example, NP-2, U87MG, T98G, and A172, to determine whether these HIV-1-resistant brain cells could enhance or suppress HIV-1 infection and thus modulate HIV-1 infection in the CNS. The HIV-1 titer was determined using the MAGIC-5A indicator cell line as well as naturally occurring CD4(+) T cells. We found that the stability of HIV-1 incubated with NP-2 or U87MG cells at 37°C was significantly shorter (half-life, 2.5-4 h) compared to that of HIV-1 incubated with T98G or A172 cells or in culture medium without cells (half-life, 8-18 h). The spent culture media (SCM) of NP-2 and U87MG cells had the ability to suppress both R5- and X4-HIV-1 infection by inhibiting HIV-1 attachment to target cells. This inhibitory effect was eliminated by the treatment of the SCM with chondroitinase ABC but not heparinase, suggesting that the inhibitory factor(s) secreted by NP-2 and U87MG cells was chiefly mediated by chondroitin sulfate (CS) or CS-like moiety. Thus, this study reveals that some but not all glioma cells secrete inhibitory molecules to HIV-1 infection that may contribute in lowering HIV-1 infection in the CNS in vivo.

  19. Adult stem cell-based apexogenesis

    OpenAIRE

    Li, Yao; Shu, Li-Hong; Yan, Ming; Dai, Wen-Yong; Li, Jun-Jun; Zhang, Guang-Dong; Yu, Jin-Hua

    2014-01-01

    Generally, the dental pulp needs to be removed when it is infected, and root canal therapy (RCT) is usually required in which infected dental pulp is replaced with inorganic materials (paste and gutta percha). This treatment approach ultimately brings about a dead tooth. However, pulp vitality is extremely important to the tooth itself, since it provides nutrition and acts as a biosensor to detect the potential pathogenic stimuli. Despite the reported clinical success rate, RCT-treated teeth ...

  20. Human cytomegalovirus gene expression in long-term infected glioma stem cells.

    Directory of Open Access Journals (Sweden)

    Estefania Fiallos

    Full Text Available The most common adult primary brain tumor, glioblastoma (GBM, is characterized by fifteen months median patient survival and has no clear etiology. We and others have identified the presence of human cytomegalovirus (HCMV gene products endogenously expressed in GBM tissue and primary cells, with a subset of viral genes being consistently expressed in most samples. Among these viral genes, several have important oncomodulatory properties, regulating tumor stemness, proliferation, immune evasion, invasion and angiogenesis. These findings lead us to hypothesize that a specific HCMV gene signature may be associated with GBM pathogenesis. To investigate this hypothesis, we used glioma cell lines and primary glioma stem-like cells (GSC infected with clinical and laboratory HCMV strains and measured relative viral gene expression levels along several time points up to 15 weeks post-infection. While HCMV gene expression was detected in several infected glioma lines through week 5 post-infection, only HCMV-infected GSC expressed viral gene products 15 weeks post-infection. Efficiency of infection across time was higher in GSC compared to cell lines. Importantly, HCMV-infected GSC outlived their uninfected counterparts, and this extended survival was paralleled by increased tumorsphere frequency and upregulation of stemness regulators, such as SOX2, p-STAT3, and BMX (a novel HCMV target identified in this study. Interleukin 6 (IL-6 treatment significantly upregulated HCMV gene expression in long-term infected glioma cultures, suggesting that pro-inflammatory signaling in the tumor milieu may further augment HCMV gene expression and subsequent tumor progression driven by viral-induced cellular signaling. Together, our data support a critical role for long-term, low-level HCMV infection in promoting survival, stemness, and proliferation of GSC that could significantly contribute to GBM pathogenesis.

  1. Histomorphometric study on blood cells in male adult ostrich

    Directory of Open Access Journals (Sweden)

    Mina Tadjalli

    2013-09-01

    Full Text Available In order to perform a histomorphometric study of blood cells in male adult ostrich, blood samples were obtained from jugular vein of 10 clinically healthy male adult ostriches (2 - 3 years old. The slides were stained with the Giemsa methods and the smears were evaluated for cellular morphology, with cellular size being determined by micrometry. The findings of this study revealed that the shape of the cell, cytoplasm and nucleus of erythrocytes in male adult ostriches were similar to those in other birds such as quails, chickens, Iranian green-head ducks.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Predictors of mortality in a cohort of HIV-1-infected adults in rural Africa

    DEFF Research Database (Denmark)

    Erikstrup, Christian; Kallestrup, Per; Zinyama, Rutendo;

    2007-01-01

    CD4 cell count and plasma HIV RNA level are used to monitor HIV-infected patients in high-income countries, but the applicability in an African context with frequent concomitant infections has only been studied sparsely. Moreover, alternative inexpensive markers are needed in the attempts to roll...

  4. Facial Emotion Processing in Aviremic HIV-infected Adults.

    Science.gov (United States)

    González-Baeza, A; Carvajal, F; Bayón, C; Pérez-Valero, I; Montes-Ramírez, M; Arribas, J R

    2016-08-01

    The emotional processing in human immunodeficiency virus-seropositive individuals (HIV+) has been scarcely studied. We included HIV+ individuals (n = 107) on antiretroviral therapy (≥2 years) who completed 6 facial processing tasks and neurocognitive testing. We compared HIV+ and healthy adult (HA) participants (n = 40) in overall performance of each facial processing task. Multiple logistic regressions were conducted to explore predictors of poorer accuracy in those measures in which HIV+ individuals performed poorer than HA participants. We separately explored the impact of neurocognitive status, antiretroviral regimen, and hepatitis C virus (HCV) coinfection on the tasks performance. We found similar performance in overall facial emotion discrimination, recognition, and recall between HIV+ and HA participants. The HIV+ group had poorer recognition of particular negative emotions. Lower WAIS-III Vocabulary scores and active HCV predicted poorer accuracy in recognition of particular emotions. Our results suggest that permanent damage of emotion-related brain systems might persist despite long-term effective antiretroviral therapy. PMID:27193364

  5. The association of recent incarceration and health outcomes among HIV-infected adults receiving care in the United States.

    Science.gov (United States)

    Nasrullah, Muazzam; Frazier, Emma; Fagan, Jennifer; Hardnett, Felicia; Skarbinski, Jacek

    2016-09-12

    Purpose The purpose of this paper is to describe factors associated with incarceration as well as the association between recent incarceration and HIV-related sexual risk behaviors, access to insurance, healthcare utilization (emergency department (ED) and hospital use), antiretroviral therapy (ART) prescription, and viral suppression. Design/methodology/approach Using 2009-2010 data from a cross-sectional, nationally representative three-stage sample of HIV-infected adults receiving care in the USA, the authors assessed the demographic characteristics, healthcare utilization, and clinical outcomes of HIV-infected persons who had been recently incarcerated (detention for>24 hours in the past year) using bivariate analyses. The authors used multivariable logistic regression to examine associations of recent incarceration with insurance status as well as clinical and behavioral outcomes. Findings An estimated 22,949 (95 percent confidence interval (CI) 19,062-26,836) or 5.4 percent (CI: 4.7-6.1) of all HIV-infected persons receiving care were recently incarcerated. Factors associated with recent incarceration were age homeless, income at or below the poverty guidelines, having a geometric mean of CD4 count <500 cells/ μL, and using drugs in the past 12 months. Results from multivariable modeling indicated that incarcerated persons were more likely to use ED services, and to have been hospitalized, and less likely to have achieved viral suppression. Originality/value Recent incarceration independently predicted worse health outcomes and greater use of emergency services among HIV-infected adults currently in HIV care. Options to improve the HIV continuum of care, including pre-enrollment for healthcare coverage and discharge planning, may lead to better health outcomes for HIV-infected inmates post-release. PMID:27548016

  6. Tax unleashed: fulminant Tax-positive Adult T-cell Leukemia/Lymphoma after failed allogeneic stem cell transplantation.

    Science.gov (United States)

    Ghez, David; Renand, Amédée; Lepelletier, Yves; Sibon, David; Suarez, Felipe; Rubio, Marie-Thérèse; Delarue, Richard; Buzyn, Agnès; Beljord, Kheira; Tanaka, Yuetsu; Varet, Bruno; Hermine, Olivier

    2009-12-01

    The human retrovirus HTLV-1 causes Adult T-cell Leukemia/Lymphoma (ATLL), a malignant lymphoproliferative disease of CD4+ T cells of dismal prognosis, in 3-5% of the 20 million infected individuals (Proietti et al.(1) and Bazarbachi et al.(2)). Infection with HTLV-1 represents a prototypical model of virus-mediated oncogenesis by virtue of the viral transactivator Tax, a potent oncogenic protein that exerts pleiotropic effects through its ability to deregulate the transcription of various cellular genes and signal transduction pathways and inhibit DNA repair enzymes, which are critical for T-cell homeostasis and genetic stability (Matsuoka and Jeang(3)) (et Boxus Retrovirology 2009). However, the oncogenic potential of Tax remains a conundrum. Tax protein expression is undetectable using conventional methods in freshly harvested ATLL cells and in non-malignant infected CD4+ T cells (Furukawa et al.(4)) but is up regulated after only a few hours of culture in vitro (Hanon et al.(5)). These observations strongly suggest that a host-derived mechanism is able to either actively repress the transcription of viral proteins in vivo or refrain the emergence of Tax-expressing cells, which would have a growth advantage. We report herein a unique case of CD4+ T-cell leukemia highly expressing Tax following rejection of an allogenic peripheral blood stem cell graft for an HTLV-1 associated lymphoma. PMID:19836302

  7. Hyperglycemia increases the complicated infection and mortality rates during induction therapy in adult acute leukemia patients

    Directory of Open Access Journals (Sweden)

    Carolina do Nascimento Matias

    2013-01-01

    Full Text Available OBJECTIVE: To determine the prevalence of hyperglycemia during induction therapy in adult patients with acute leukemia and its effect on complicated infections and mortality during the first 30 days of treatment. METHODS: An analysis was performed in a retrospective cohort of 280 adult patients aged 18 to 60 years with previously untreated acute leukemia who received induction chemotherapy from January 2000 to December 2009 at the Hemocentro de Pernambuco (HEMOPE, Brazil. Hyperglycemia was defined as the finding of at least one fasting glucose measurement > 100 mg/dL observed one week prior to induction therapy until 30 days after. The association between hyperglycemia and complicated infections, mortality and complete remission was evaluated using the Chi-square or Fisher's exact tests by the Statistical Package for Social Sciences (SPSS in the R software package version 2.9.0. RESULTS: One hundred and eighty-eight patients (67.1% presented hyperglycemia at some moment during induction therapy. Eighty-two patients (29.3% developed complicated infections. Infection-related mortality during the neutropenia period was 20.7% (58 patients. Mortality from other causes during the first 30 days after induction was 2.8%. Hyperglycemia increased the risk of complicated infections (OR 3.97; 95% confidence interval: 2.08 - 7.57; p-value < 0.001 and death (OR 3.55; 95% confidence interval: 1.77-7.12; p-value < 0.001 but did not increase the risk of fungal infections or decrease the probability of achieving complete remission. CONCLUSION: This study demonstrates an association between the presence of hyperglycemia and the development of complicated infections and death in adult patients during induction therapy for acute leukemia.

  8. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration.

    Science.gov (United States)

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-06-21

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  9. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    Directory of Open Access Journals (Sweden)

    Shan Liu

    2016-06-01

    Full Text Available Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous. The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells, early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium, using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration, timing for cell therapy (immediate vs. a few days after injury, single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications.

  10. Strategies to Optimize Adult Stem Cell Therapy for Tissue Regeneration

    Science.gov (United States)

    Liu, Shan; Zhou, Jingli; Zhang, Xuan; Liu, Yang; Chen, Jin; Hu, Bo; Song, Jinlin; Zhang, Yuanyuan

    2016-01-01

    Stem cell therapy aims to replace damaged or aged cells with healthy functioning cells in congenital defects, tissue injuries, autoimmune disorders, and neurogenic degenerative diseases. Among various types of stem cells, adult stem cells (i.e., tissue-specific stem cells) commit to becoming the functional cells from their tissue of origin. These cells are the most commonly used in cell-based therapy since they do not confer risk of teratomas, do not require fetal stem cell maneuvers and thus are free of ethical concerns, and they confer low immunogenicity (even if allogenous). The goal of this review is to summarize the current state of the art and advances in using stem cell therapy for tissue repair in solid organs. Here we address key factors in cell preparation, such as the source of adult stem cells, optimal cell types for implantation (universal mesenchymal stem cells vs. tissue-specific stem cells, or induced vs. non-induced stem cells), early or late passages of stem cells, stem cells with endogenous or exogenous growth factors, preconditioning of stem cells (hypoxia, growth factors, or conditioned medium), using various controlled release systems to deliver growth factors with hydrogels or microspheres to provide apposite interactions of stem cells and their niche. We also review several approaches of cell delivery that affect the outcomes of cell therapy, including the appropriate routes of cell administration (systemic, intravenous, or intraperitoneal vs. local administration), timing for cell therapy (immediate vs. a few days after injury), single injection of a large number of cells vs. multiple smaller injections, a single site for injection vs. multiple sites and use of rodents vs. larger animal models. Future directions of stem cell-based therapies are also discussed to guide potential clinical applications. PMID:27338364

  11. Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

    Directory of Open Access Journals (Sweden)

    Felix R Stahl

    Full Text Available Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+ T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control.

  12. HAIR CELL-LIKE CELL GENERATION INDUCED BY NATURE CULTURE OF ADULT RAT AUDITORY EPITHELIUM

    Institute of Scientific and Technical Information of China (English)

    Liu Hui; Zhu Hongliang; Li Shengli; Yao Xiaobao; Wang Xiaoxia

    2006-01-01

    Objective To establish adult rat auditory epithelial cell culture and try to find precursor cells of auditory hair cells in vitro. Methods With refinement of culture media and techniques, cochlear sensory epithelial cells of adult rat were cultured. Immunocytochemistry and Bromodeoxyuridine (BrdU)labeling were used to detect properties and mitotic status of cultured cells. Results The cultured auditory epithelial cells showed a large, flat epithelial morphotype and expressed F-actin and cytokeratin, a subset of cells generated from auditory epithelium were labeled by calretinin, a specific marker of early hair cell. Conclusion Adult rat auditory epithelium can be induced to generate hair cell-like cells by nature culture, this phenomenon suggests that progenitor cells may exist in rat cochlea and they may give birth to new hair cells. Whether these progenitor cells are tissue specific stem cells is still need more study.

  13. Growth in Agarose of Human Cells Infected with Cytomegalovirus

    Science.gov (United States)

    Lang, David J.; Montagnier, Luc; Latarjet, Raymond

    1974-01-01

    After infection by human cytomegalovirus (CMV), human diploid fibroblasts could grow in agarose medium for several generations. Clones of infected cells grew for weeks, although in every case they ultimately underwent lysis owing to the cytopathic effect of the virus. Virus was inoculated at high dilution and after UV irradiation in an effort to derive cells infected with noninfectious defective particles still capable of inducing cell stimulation. Dilute or irradiated virus occasionally yielded large colonies of replicating cells, although permanent transformation was not observed. One clone derived from UV-CMV-infected cells was passaged four times before undergoing lysis. During these passages the cells exhibited alterations in morphology and orientation. Images PMID:4367907

  14. Engineering of the Embryonic and Adult Stem Cell Niches

    OpenAIRE

    Hosseinkhani, Mohsen; Shirazi, Reza; Rajaei, Farzad; Mahmoudi, Masoud; Mohammadi, Navid; Abbasi, Mahnaz

    2013-01-01

    Context Stem cells have the potential to generate a renewable source of cells for regenerative medicine due to their ability to self-renew and differentiate to various functional cell types of the adult organism. The extracellular microenvironment plays a pivotal role in controlling stem cell fate responses. Therefore, identification of appropriate environmental stimuli that supports cellular proliferation and lineage-specific differentiation is critical for the clinical application of the st...

  15. HIV-Infected Adolescent, Young Adult and Pregnant Smokers: Important Targets for Effective Tobacco Control Programs

    Directory of Open Access Journals (Sweden)

    Gerome Escota

    2013-06-01

    Full Text Available Tobacco use is inextricably linked to a number of health risks both in the general and HIV-infected populations. There is, however, a dearth of research on effective tobacco control programs among people living with HIV, and especially among adolescents, young adults and pregnant women, groups with heightened or increased vulnerability secondary to tobacco use. Adolescents and young adults constitute a growing population of persons living with HIV infection. Early and continued tobacco use in this population living with a disease characterized by premature onset multimorbidity and chronic inflammation is of concern. Additionally, there is an increased acuity for tobacco control among HIV-infected pregnant women to reduce pregnancy morbidity and improve fetal outcome. This review will provide an important summary of current knowledge of tobacco use among HIV-infected adolescents, young adults and pregnant women. The effects of tobacco use in these specific populations will be presented and the current state of tobacco control within these populations, assessed.

  16. HCMV Infection Depress NGF Expression in Human Glioma Cells

    Institute of Scientific and Technical Information of China (English)

    Hai-tao WANG; Bin WANG; Zhi-jun LIU; Zhi-qiang BAI; Ling LI; Dong-meng QIAN; Zhi-yong YAN; Xu-xia SONG

    2009-01-01

    Human cytomegalovirus (HCMV) is the most common cause of congenital infection, resulting in birth defects such as microcephaly. In this study, RT-PCR and Western Blotting were performed to quantify the regulation of endogenic nerve growth factor expression in neuroglia cells by HCMV infection. The results showed that basal, endogenous NGF expression in U251 was unchanged during early HCMV infection. NGF expression is strongly down-regulated during the latent phase of infection. These results suggest that HCMV can depress the NGF expression in U251 cells.

  17. The homeostasis of Plasmodium falciparum-infected red blood cells.

    Directory of Open Access Journals (Sweden)

    Jakob M A Mauritz

    2009-04-01

    Full Text Available The asexual reproduction cycle of Plasmodium falciparum, the parasite responsible for severe malaria, occurs within red blood cells. A merozoite invades a red cell in the circulation, develops and multiplies, and after about 48 hours ruptures the host cell, releasing 15-32 merozoites ready to invade new red blood cells. During this cycle, the parasite increases the host cell permeability so much that when similar permeabilization was simulated on uninfected red cells, lysis occurred before approximately 48 h. So how could infected cells, with a growing parasite inside, prevent lysis before the parasite has completed its developmental cycle? A mathematical model of the homeostasis of infected red cells suggested that it is the wasteful consumption of host cell hemoglobin that prevents early lysis by the progressive reduction in the colloid-osmotic pressure within the host (the colloid-osmotic hypothesis. However, two critical model predictions, that infected cells would swell to near prelytic sphericity and that the hemoglobin concentration would become progressively reduced, remained controversial. In this paper, we are able for the first time to correlate model predictions with recent experimental data in the literature and explore the fine details of the homeostasis of infected red blood cells during five model-defined periods of parasite development. The conclusions suggest that infected red cells do reach proximity to lytic rupture regardless of their actual volume, thus requiring a progressive reduction in their hemoglobin concentration to prevent premature lysis.

  18. Prolonged activation of virus-specific CD8+T cells after acute B19 infection.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available BACKGROUND: Human parvovirus B19 (B19 is a ubiquitous and clinically significant pathogen, causing erythema infectiosum, arthropathy, transient aplastic crisis, and intrauterine fetal death. The phenotype of CD8+ T cells in acute B19 infection has not been studied previously. METHODS AND FINDINGS: The number and phenotype of B19-specific CD8+ T cell responses during and after acute adult infection was studied using HLA-peptide multimeric complexes. Surprisingly, these responses increased in magnitude over the first year post-infection despite resolution of clinical symptoms and control of viraemia, with T cell populations specific for individual epitopes comprising up to 4% of CD8+ T cells. B19-specific T cells developed and maintained an activated CD38+ phenotype, with strong expression of perforin and CD57 and downregulation of CD28 and CD27. These cells possessed strong effector function and intact proliferative capacity. Individuals tested many years after infection exhibited lower frequencies of B19-specific cytotoxic T lymphocytes, typically 0.05%-0.5% of CD8+ T cells, which were perforin, CD38, and CCR7 low. CONCLUSION: This is the first example to our knowledge of an "acute" human viral infection inducing a persistent activated CD8+ T cell response. The likely explanation--analogous to that for cytomegalovirus infection--is that this persistent response is due to low-level antigen exposure. CD8+ T cells may contribute to the long-term control of this significant pathogen and should be considered during vaccine development.

  19. Therapeutics from Adult Stem Cells and the Hype Curve.

    Science.gov (United States)

    Maguire, Greg

    2016-05-12

    The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment. PMID:27190588

  20. Therapeutics from Adult Stem Cells and the Hype Curve.

    Science.gov (United States)

    Maguire, Greg

    2016-05-12

    The Gartner curve for regenerative and stem cell therapeutics is currently climbing out of the "trough of disillusionment" and into the "slope of enlightenment". Understanding that the early years of stem cell therapy relied on the model of embryonic stem cells (ESCs), and then moved into a period of the overhype of induced pluripotent stem cells (iPSCs), instead of using the model of 40 years of success, i.e. adult stem cells used in bone marrow transplants, the field of stem cell therapy has languished for years, trying to move beyond the early and poorly understood success of bone marrow transplants. Recent studies in the lab and clinic show that adult stem cells of various types, and the molecules that they release, avoid the issues associated with ESCs and iPSCs and lead to better therapeutic outcomes and into the slope of enlightenment.

  1. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking

    OpenAIRE

    Ratajczak, M Z

    2015-01-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of t...

  2. Cell proliferation and neurogenesis in adult mouse brain.

    Directory of Open Access Journals (Sweden)

    Olivia L Bordiuk

    Full Text Available Neurogenesis, the formation of new neurons, can be observed in the adult brain of many mammalian species, including humans. Despite significant progress in our understanding of adult neurogenesis, we are still missing data about the extent and location of production of neural precursors in the adult mammalian brain. We used 5-ethynyl-2'-deoxyuridine (EdU to map the location of proliferating cells throughout the entire adult mouse brain and found that neurogenesis occurs at two locations in the mouse brain. The larger one we define as the main proliferative zone (MPZ, and the smaller one corresponds to the subgranular zone of the hippocampus. The MPZ can be divided into three parts. The caudate migratory stream (CMS occupies the middle part of the MPZ. The cable of proliferating cells emanating from the most anterior part of the CMS toward the olfactory bulbs forms the rostral migratory stream. The thin layer of proliferating cells extending posteriorly from the CMS forms the midlayer. We have not found any additional aggregations of proliferating cells in the adult mouse brain that could suggest the existence of other major neurogenic zones in the adult mouse brain.

  3. Distinct immune responses of juvenile and adult oysters (Crassostrea gigas) to viral and bacterial infections.

    Science.gov (United States)

    Green, Timothy J; Vergnes, Agnes; Montagnani, Caroline; de Lorgeril, Julien

    2016-01-01

    Since 2008, massive mortality events of Pacific oysters (Crassostrea gigas) have been reported worldwide and these disease events are often associated with Ostreid herpesvirus type 1 (OsHV-1). Epidemiological field studies have also reported oyster age and other pathogens of the Vibrio genus are contributing factors to this syndrome. We undertook a controlled laboratory experiment to simultaneously investigate survival and immunological response of juvenile and adult C. gigas at different time-points post-infection with OsHV-1, Vibrio tasmaniensis LGP32 and V. aestuarianus. Our data corroborates epidemiological studies that juveniles are more susceptible to OsHV-1, whereas adults are more susceptible to Vibrio. We measured the expression of 102 immune-genes by high-throughput RT-qPCR, which revealed oysters have different transcriptional responses to OsHV-1 and Vibrio. The transcriptional response in the early stages of OsHV-1 infection involved genes related to apoptosis and the interferon-pathway. Transcriptional response to Vibrio infection involved antimicrobial peptides, heat shock proteins and galectins. Interestingly, oysters in the later stages of OsHV-1 infection had a transcriptional response that resembled an antibacterial response, which is suggestive of the oyster's microbiome causing secondary infections (dysbiosis-driven pathology). This study provides molecular evidence that oysters can mount distinct immune response to viral and bacterial pathogens and these responses differ depending on the age of the host.

  4. Distinct immune responses of juvenile and adult oysters (Crassostrea gigas) to viral and bacterial infections.

    Science.gov (United States)

    Green, Timothy J; Vergnes, Agnes; Montagnani, Caroline; de Lorgeril, Julien

    2016-01-01

    Since 2008, massive mortality events of Pacific oysters (Crassostrea gigas) have been reported worldwide and these disease events are often associated with Ostreid herpesvirus type 1 (OsHV-1). Epidemiological field studies have also reported oyster age and other pathogens of the Vibrio genus are contributing factors to this syndrome. We undertook a controlled laboratory experiment to simultaneously investigate survival and immunological response of juvenile and adult C. gigas at different time-points post-infection with OsHV-1, Vibrio tasmaniensis LGP32 and V. aestuarianus. Our data corroborates epidemiological studies that juveniles are more susceptible to OsHV-1, whereas adults are more susceptible to Vibrio. We measured the expression of 102 immune-genes by high-throughput RT-qPCR, which revealed oysters have different transcriptional responses to OsHV-1 and Vibrio. The transcriptional response in the early stages of OsHV-1 infection involved genes related to apoptosis and the interferon-pathway. Transcriptional response to Vibrio infection involved antimicrobial peptides, heat shock proteins and galectins. Interestingly, oysters in the later stages of OsHV-1 infection had a transcriptional response that resembled an antibacterial response, which is suggestive of the oyster's microbiome causing secondary infections (dysbiosis-driven pathology). This study provides molecular evidence that oysters can mount distinct immune response to viral and bacterial pathogens and these responses differ depending on the age of the host. PMID:27439510

  5. Tax fingerprint in adult T-cell leukemia.

    Science.gov (United States)

    Bazarbachi, Ali

    2016-04-01

    In this issue of Blood, Fujikawa et al demonstrate that the human T-cell leukemia virus type 1 (HTLV-1) oncoprotein Tax induces an epigenetic-dependent global modification of host gene expression in adult T-cell leukemia-lymphoma (ATL). Hence, the fingerprint of Tax is all over ATL and this may be used for finally capturing ATL. PMID:27056993

  6. Multiple skin tumors of indeterminate cells in an adult.

    Science.gov (United States)

    Kolde, G; Bröcker, E B

    1986-10-01

    An adult patient with multiple unusual histiocytic tumors of the skin is described. As shown by immunohistologic study, electron microscopy, and immunoelectron microscopy, the tumors represent circumscribed proliferations of the Langerhans cell-related indeterminate dendritic cells of the skin. This distinct cutaneous histiocytosis may represent a paraneoplastic syndrome.

  7. National prevalence of oral HPV infection and related risk factors in the U.S. adult population.

    Science.gov (United States)

    Sanders, A E; Slade, G D; Patton, L L

    2012-07-01

    This article reviews the rapidly growing evidence that oral human papilloma viruses (HPV) infection contributes to the risk of oral squamous cell carcinoma. It also reports the first nationally representative estimates of oral HPV prevalence in the United States adult population. An estimated 7.3% (95% CI: 6.0, 8.9) of the U.S. population had one or more oral HPV types detected in oral rinse; 3.1% (95%CI: 2.4, 3.9) of the U.S. population had one or more oncogenic HPV types. A substantial excess risk of HPV infection in men is not explained by education, smoking, age of sexual debut, or number of lifetime sex partners. Based on the published finding from a case-control study, where there was an odds ratio of 2.6 (95% CI: 1.5, 4.2) for the association of head and neck cancer oncogenic oral HPV infection, the estimated population attributable risk for head and neck cancer in the U.S. population was 4.7%. In other words, there would be a 4.7% reduction in incidence rate of head and neck cancer in the United States if oncogenic HPV infection could be prevented. The results also provide population data that help evaluate the likely public health benefits of prophylactic vaccination against oral HPV acquisition.

  8. Cytomegalovirus-Infected Cells Resist T Cell Mediated Killing in an HLA-Recognition Independent Manner.

    Science.gov (United States)

    Proff, Julia; Walterskirchen, Christian; Brey, Charlotte; Geyeregger, Rene; Full, Florian; Ensser, Armin; Lehner, Manfred; Holter, Wolfgang

    2016-01-01

    In order to explore the potential of HLA-independent T cell therapy for human cytomegalovirus (HCMV) infections, we developed a chimeric antigen receptor (CAR) directed against the HCMV encoded glycoprotein B (gB), which is expressed at high levels on the surface of infected cells. T cells engineered with this anti-gB CAR recognized HCMV-infected cells and released cytokines and cytotoxic granules. Unexpectedly, and in contrast to analogous approaches for HIV, Hepatitis B or Hepatitis C virus, we found that HCMV-infected cells were resistant to killing by the CAR-modified T cells. In order to elucidate whether this phenomenon was restricted to the use of CARs, we extended our experiments to T cell receptor (TCR)-mediated recognition of infected cells. To this end we infected fibroblasts with HCMV-strains deficient in viral inhibitors of antigenic peptide presentation and targeted these HLA-class I expressing peptide-loaded infected cells with peptide-specific cytotoxic T cells (CTLs). Despite strong degranulation and cytokine production by the T cells, we again found significant inhibition of lysis of HCMV-infected cells. Impairment of cell lysis became detectable 1 day after HCMV infection and gradually increased during the following 3 days. We thus postulate that viral anti-apoptotic factors, known to inhibit suicide of infected host cells, have evolved additional functions to directly abrogate T cell cytotoxicity. In line with this hypothesis, CAR-T cell cytotoxicity was strongly inhibited in non-infected fibroblasts by expression of the HCMV-protein UL37x1, and even more so by additional expression of UL36. Our data extend the current knowledge on Betaherpesviral evasion from T cell immunity and show for the first time that, beyond impaired antigen presentation, infected cells are efficiently protected by direct blockade of cytotoxic effector functions through viral proteins.

  9. Bartonella henselae infection presenting with a picture of adult-onset Still's disease.

    Science.gov (United States)

    Durey, Areum; Kwon, Hea Yoon; Im, Jae-Hyoung; Lee, Sun Myoung; Baek, JiHyeon; Han, Seung Baik; Kang, Jae-Seung; Lee, Jin-Soo

    2016-05-01

    We report a patient with a clinical picture of suggestive for adult-onset Still's Disease (ASOD) due to Bartonella infection. A 42-year-old immunocompetent man was admitted with fever, rash, arthralgia and sore throat. As his clinical picture suggested ASOD except unusual skin manifestation, we treated him on steroid and ibuprofen. His fever and constitutional symptoms responded immediately within 24hrs of commencing therapy, yet rash and leukocytosis remained. Meanwhile, Bartonella infection was proved by culture of bone marrow. Minocyclin treatment started combined with hydroxychloroquine sulfate and the patient discharged with overall improvement. PMID:27000538

  10. Nipah virus infection and glycoprotein targeting in endothelial cells

    Directory of Open Access Journals (Sweden)

    Maisner Andrea

    2010-11-01

    Full Text Available Abstract Background The highly pathogenic Nipah virus (NiV causes fatal respiratory and brain infections in animals and humans. The major hallmark of the infection is a systemic endothelial infection, predominantly in the CNS. Infection of brain endothelial cells allows the virus to overcome the blood-brain-barrier (BBB and to subsequently infect the brain parenchyma. However, the mechanisms of NiV replication in endothelial cells are poorly elucidated. We have shown recently that the bipolar or basolateral expression of the NiV surface glycoproteins F and G in polarized epithelial cell layers is involved in lateral virus spread via cell-to-cell fusion and that correct sorting depends on tyrosine-dependent targeting signals in the cytoplasmic tails of the glycoproteins. Since endothelial cells share many characteristics with epithelial cells in terms of polarization and protein sorting, we wanted to elucidate the role of the NiV glycoprotein targeting signals in endothelial cells. Results As observed in vivo, NiV infection of endothelial cells induced syncytia formation. The further finding that infection increased the transendothelial permeability supports the idea of spread of infection via cell-to-cell fusion and endothelial cell damage as a mechanism to overcome the BBB. We then revealed that both glycoproteins are expressed at lateral cell junctions (bipolar, not only in NiV-infected primary endothelial cells but also upon stable expression in immortalized endothelial cells. Interestingly, mutation of tyrosines 525 and 542/543 in the cytoplasmic tail of the F protein led to an apical redistribution of the protein in endothelial cells whereas tyrosine mutations in the G protein had no effect at all. This fully contrasts the previous results in epithelial cells where tyrosine 525 in the F, and tyrosines 28/29 in the G protein were required for correct targeting. Conclusion We conclude that the NiV glycoprotein distribution is responsible for

  11. Splenectomy associated changes in IgM memory B cells in an adult spleen registry cohort.

    Directory of Open Access Journals (Sweden)

    Paul U Cameron

    Full Text Available Asplenic patients have a lifelong risk of overwhelming post-splenectomy infection and have been reported to have low numbers of peripheral blood IgM memory B cells. The clinical value of quantitation of memory B cells as an indicator of splenic abnormality or risk of infection has been unclear. To assess changes in B cell sub-populations after splenectomy we studied patients recruited to a spleen registry (n = 591. A subset of 209 adult asplenic or hyposplenic subjects, and normal controls (n = 140 were tested for IgM memory B cells. We also determined a changes in IgM memory B cells with time after splenectomy using the cross-sectional data from patients on the registry and b the kinetics of changes in haematological markers associated with splenectomy(n = 45. Total B cells in splenectomy patients did not differ from controls, but memory B cells, IgM memory B cells and switched B cells were significantly (p<0.001 reduced. The reduction was similar for different indications for splenectomy. Changes of asplenia in routine blood films including presence of Howell-Jolly bodies (HJB, occurred early (median 25 days and splenectomy associated thrombocytosis and lymphocytosis peaked by 50 days. There was a more gradual decrease in IgM memory B cells reaching a stable level within 6 months after splenectomy. IgM memory B cells as proportion of B cells was the best discriminator between splenectomized patients and normal controls and at the optimal cut-off of 4.53, showed a true positive rate of 95% and false positive rate of 20%. In a survey of 152 registry patients stratified by IgM memory B cells around this cut-off there was no association with minor infections and no registry patients experienced OPSI during the study. Despite significant changes after splenectomy, conventional measures of IgM memory cells have limited clinical utility in this population.

  12. Gram-Negative Infections in Adult Intensive Care Units of Latin America and the Caribbean

    Directory of Open Access Journals (Sweden)

    Carlos M. Luna

    2014-01-01

    Full Text Available This review summarizes recent epidemiology of Gram-negative infections in selected countries from Latin American and Caribbean adult intensive care units (ICUs. A systematic search of the biomedical literature (PubMed was performed to identify articles published over the last decade. Where appropriate, data also were collected from the reference list of published articles, health departments of specific countries, and registries. Independent cohort data from all countries (Argentina, Brazil, Chile, Colombia, Cuba, Mexico, Trinidad and Tobago, and Venezuela signified a high rate of ICU infections (prevalence: Argentina, 24%; Brazil, 57%. Gram-negative pathogens, predominantly Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli, accounted for >50% of ICU infections, which were often complicated by the presence of multidrug-resistant strains and clonal outbreaks. Empirical use of antimicrobial agents was identified as a strong risk factor for resistance development and excessive mortality. Infection control strategies utilizing hygiene measures and antimicrobial stewardship programs reduced the rate of device-associated infections. To mitigate the poor health outcomes associated with infections by multidrug-resistant Gram-negative bacteria, urgent focus must be placed on infection control strategies and local surveillance programs.

  13. Networked T cell death following macrophage infection by Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Stephen H-F Macdonald

    Full Text Available BACKGROUND: Depletion of T cells following infection by Mycobacterium tuberculosis (Mtb impairs disease resolution, and interferes with clinical test performance that relies on cell-mediated immunity. A number of mechanisms contribute to this T cell suppression, such as activation-induced death and trafficking of T cells out of the peripheral circulation and into the diseased lungs. The extent to which Mtb infection of human macrophages affects T cell viability however, is not well characterised. METHODOLOGY/PRINCIPAL FINDINGS: We found that lymphopenia (<1.5 × 10(9 cells/l was prevalent among culture-positive tuberculosis patients, and lymphocyte counts significantly improved post-therapy. We previously reported that Mtb-infected human macrophages resulted in death of infected and uninfected bystander macrophages. In the current study, we sought to examine the influence of infected human alveolar macrophages on T cells. We infected primary human alveolar macrophages (the primary host cell for Mtb or PMA-differentiated THP-1 cells with Mtb H37Ra, then prepared cell-free supernatants. The supernatants of Mtb-infected macrophages caused dose-dependent, caspase-dependent, T cell apoptosis. This toxic effect of infected macrophage secreted factors did not require TNF-α or Fas. The supernatant cytotoxic signal(s were heat-labile and greater than 50 kDa in molecular size. Although ESAT-6 was toxic to T cells, other Mtb-secreted factors tested did not influence T cell viability; nor did macrophage-free Mtb bacilli or broth from Mtb cultures. Furthermore, supernatants from Mycobacterium bovis Bacille de Calmette et Guerin (BCG- infected macrophages also elicited T cell death suggesting that ESAT-6 itself, although cytotoxic, was not the principal mediator of T cell death in our system. CONCLUSIONS: Mtb-Infected macrophages secrete heat-labile factors that are toxic to T cells, and may contribute to the immunosuppression seen in tuberculosis as well as

  14. Hepatitis B and hepatitis C virus infections among antiretroviral-naive and -experienced HIV co-infected adults.

    Science.gov (United States)

    Manyazewal, Tsegahun; Sisay, Zufan; Biadgilign, Sibhatu; Abegaz, Woldaregay Erku

    2014-05-01

    Most HIV positive people have not been tested for viral hepatitis and their treatments have not been optimized for possible co-infections. The aim of this study was to investigate the serological pattern of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections among antiretroviral (ARV)-naive and -experienced HIV co-infected adults in Addis Ababa, Ethiopia. A total of 500 frozen HIV positive serum and plasma samples collected from ARV-naive (n = 250) and -experienced (n = 250) adults were randomly selected and screened for HBsAg, anti-HBs, HBeAg and anti-HCV using rapid two-site sandwich immunochromatographic assay. The test was performed at Aklilu Lemma Institute of Pathobiology, Addis Ababa University. Positive specimens for HBsAg and anti-HCV markers were further confirmed using third generation ELISA. Of the 500 specimens tested, 15 (3 %), 58 (11.6 %), 3 (0.6 %), 18 (3.6 %), 3 (0.6 %) and 1 (0.2 %) were positive for HBsAg, anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. No specimen tested positive for both HBeAg and anti-HBs, and 442 (88.4 %) individuals were non-immune to HBV. Of the 250 ARV-naive individuals, 8 (3.2 %), 33 (13.2 %), 2 (0.8 %), 10 (4 %), 2 (0.8 %), and 1 (0.4 %) were positive for HBsAg, anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. Of the 250 ARV-experienced individuals, 7 (2.8 %), 25 (10 %), 1 (0.4 %), 8 (3.2 %), 1 (0.4 %), and 0 (0 %) were positive for HBsAg, Anti-HBs, HBeAg, anti-HCV, HBsAg and HBeAg, and HBsAg and anti-HBs markers, respectively. In summary, seroprevalence of HIV/HBV and HIV/HCV co-infections was lower in Addis Ababa, Ethiopia, than in Sub-Saharan Africa and globally. HBV and HCV infections were not significantly different between HIV positive subjects who were or who were not on ARV. This suggests that the two groups have equal chance of being infected with these two viruses; despite

  15. Frequent detection of respiratory viruses in adult recipients of stem cell transplants with the use of real-time polymerase chain reaction, compared with viral culture.

    NARCIS (Netherlands)

    Kraaij, M.G.J. van; Elden, L.J. van; Loon, A.M. van; Hendriksen, K.A.; Laterveer, L.; Dekker, A.W.; Nijhuis, M.

    2005-01-01

    BACKGROUND: Respiratory virus infections have been recognized as important causes of severe pneumonia in patients who have undergone stem cell transplantation (SCT). Reported incidences of respiratory virus infection in adult SCT recipients vary in the literature from 3.5% to 36% when determined by

  16. HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection

    Science.gov (United States)

    2016-09-06

    HIV Infection; Stage I Adult Hodgkin Lymphoma; Stage I Adult Non-Hodgkin Lymphoma; Stage II Adult Hodgkin Lymphoma; Stage II Adult Non-Hodgkin Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Non-Hodgkin Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Non-Hodgkin Lymphoma

  17. Cell mechanics and immune system link up to fight infections

    Science.gov (United States)

    Ekpenyong, Andrew; Man, Si Ming; Tourlomousis, Panagiotis; Achouri, Sarra; Cammarota, Eugenia; Hughes, Katherine; Rizzo, Alessandro; Ng, Gilbert; Guck, Jochen; Bryant, Clare

    2015-03-01

    Infectious diseases, in which pathogens invade and colonize host cells, are responsible for one third of all mortality worldwide. Host cells use special proteins (immunoproteins) and other molecules to fight viral and bacterial invaders. The mechanisms by which immunoproteins enable cells to reduce bacterial loads and survive infections remain unclear. Moreover, during infections, some immunoproteins are known to alter the cytoskeleton, the structure that largely determines cellular mechanical properties. We therefore used an optical stretcher to measure the mechanical properties of primary immune cells (bone marrow derived macrophages) during bacterial infection. We found that macrophages become stiffer upon infection. Remarkably, macrophages lacking the immunoprotein, NLR-C4, lost the stiffening response to infection. This in vitro result correlates with our in vivo data whereby mice lacking NLR-C4 have more lesions and hence increased bacterial distribution and spread. Thus, the immune-protein-dependent increase in cell stiffness in response to bacterial infection (in vitro result) seems to have a functional role in the system level fight against pathogens (in vivo result). We will discuss how this functional link between cell mechanical properties and innate immunity, effected by actin polymerization, reduces the spread of infection.

  18. Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein.

    Science.gov (United States)

    Jaworski, Elizabeth; Narayanan, Aarthi; Van Duyne, Rachel; Shabbeer-Meyering, Shabana; Iordanskiy, Sergey; Saifuddin, Mohammed; Das, Ravi; Afonso, Philippe V; Sampey, Gavin C; Chung, Myung; Popratiloff, Anastas; Shrestha, Bindesh; Sehgal, Mohit; Jain, Pooja; Vertes, Akos; Mahieux, Renaud; Kashanchi, Fatah

    2014-08-01

    Human T-lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. The HTLV-1 transactivator protein Tax controls many critical cellular pathways, including host cell DNA damage response mechanisms, cell cycle progression, and apoptosis. Extracellular vesicles called exosomes play critical roles during pathogenic viral infections as delivery vehicles for host and viral components, including proteins, mRNA, and microRNA. We hypothesized that exosomes derived from HTLV-1-infected cells contain unique host and viral proteins that may contribute to HTLV-1-induced pathogenesis. We found exosomes derived from infected cells to contain Tax protein and proinflammatory mediators as well as viral mRNA transcripts, including Tax, HBZ, and Env. Furthermore, we observed that exosomes released from HTLV-1-infected Tax-expressing cells contributed to enhanced survival of exosome-recipient cells when treated with Fas antibody. This survival was cFLIP-dependent, with Tax showing induction of NF-κB in exosome-recipient cells. Finally, IL-2-dependent CTLL-2 cells that received Tax-containing exosomes were protected from apoptosis through activation of AKT. Similar experiments with primary cultures showed protection and survival of peripheral blood mononuclear cells even in the absence of phytohemagglutinin/IL-2. Surviving cells contained more phosphorylated Rb, consistent with the role of Tax in regulation of the cell cycle. Collectively, these results suggest that exosomes may play an important role in extracellular delivery of functional HTLV-1 proteins and mRNA to recipient cells.

  19. DNA damage response in adult stem cells.

    Science.gov (United States)

    Insinga, Alessandra; Cicalese, Angelo; Pelicci, Pier Giuseppe

    2014-04-01

    This review discusses the processes of DNA-damage-response and DNA-damage repair in stem and progenitor cells of several tissues. The long life-span of stem cells suggests that they may respond differently to DNA damage than their downstream progeny and, indeed, studies have begun to elucidate the unique stem cell response mechanisms to DNA damage. Because the DNA damage responses in stem cells and progenitor cells are distinctly different, stem and progenitor cells should be considered as two different entities from this point of view. Hematopoietic and mammary stem cells display a unique DNA-damage response, which involves active inhibition of apoptosis, entry into the cell-cycle, symmetric division, partial DNA repair and maintenance of self-renewal. Each of these biological events depends on the up-regulation of the cell-cycle inhibitor p21. Moreover, inhibition of apoptosis and symmetric stem cell division are the consequence of the down-regulation of the tumor suppressor p53, as a direct result of p21 up-regulation. A deeper understanding of these processes is required before these findings can be translated into human anti-aging and anti-cancer therapies. One needs to clarify and dissect the pathways that control p21 regulation in normal and cancer stem cells and define (a) how p21 blocks p53 functions in stem cells and (b) how p21 promotes DNA repair in stem cells. Is this effect dependent on p21s ability to inhibit p53? Such molecular knowledge may pave the way to methods for maintaining short-term tissue reconstitution while retaining long-term cellular and genomic integrity.

  20. Dynamics Analysis of an HIV Infection Model including Infected Cells in an Eclipse Stage

    Directory of Open Access Journals (Sweden)

    Shengyu Zhou

    2013-01-01

    Full Text Available In this paper, an HIV infection model including an eclipse stage of infected cells is considered. Some quicker cells in this stage become productively infected cells, a portion of these cells are reverted to the uninfected class, and others will be latent down in the body. We consider CTL-response delay in this model and analyze the effect of time delay on stability of equilibrium. It is shown that the uninfected equilibrium and CTL-absent infection equilibrium are globally asymptotically stable for both ODE and DDE model. And we get the global stability of the CTL-present equilibrium for ODE model. For DDE model, we have proved that the CTL-present equilibrium is locally asymptotically stable in a range of delays and also have studied the existence of Hopf bifurcations at the CTL-present equilibrium. Numerical simulations are carried out to support our main results.

  1. In vitro Study on Human Trophoblast Cells Infected with HCMV

    Institute of Scientific and Technical Information of China (English)

    肖娟; 张丹丹; 陈娟娟; 尹宗智; 刘涛; 艾继辉; 陈素华

    2010-01-01

    Human trophoblast cells were isolated and cultured in vitro in order to investigate possible pathogenesis of intrauterine infection caused by HCMV.Trophoblast cells were obtained by compound enzymes digestion and discontinuous percoll gradient.Cells and purity were identified by using immunocytochemistry assay with anti-CK7,Vim and β-hCG antibodies.HCMV AD169 strain replication in isolated trophoblast cells and cell apoptosis were detected at different time points post infection(p.i.).The results showed tha...

  2. Infection Mobilizes Hematopoietic Stem Cells through Cooperative NOD-like Receptor and Toll-like Receptor Signaling

    OpenAIRE

    Burberry, Aaron; Zeng, Melody Y.; Ding, Lei; Wicks, Ian; Inohara, Naohiro; Morrison, Sean J; Núñez, Gabriel

    2014-01-01

    Adult hematopoietic stem cells (HSCs) are maintained in specialized niches within the bone marrow under steady-state conditions and mobilized for extramedullary hematopoiesis during periods of stress such as bacterial infections. However, the underlying mechanisms are unclear. We show that systemic infection of mice with Escherichia coli, commonly associated with bacteremia in humans, mobilizes functional HSCs to the spleen. Accumulation of splenic HSCs (CD150+CD48-Lin−/lowScal1+cKit+) was di...

  3. Early infection with respiratory syncytial virus impairs regulatory T cell function and increases susceptibility to allergic asthma

    OpenAIRE

    Krishnamoorthy, Nandini; Khare, Anupriya; Oriss, Timothy B.; Raundhal, Mahesh; Morse, Christina; Yarlagadda, Manohar; Wenzel, Sally E.; Moore, Martin L.; Peebles, R. Stokes; Ray, Anuradha; Ray, Prabir

    2012-01-01

    Immune tolerance is instituted early in life, during which time regulatory T (Treg) cells have an important role. Recurrent infections with respiratory syncytial virus (RSV) in early life increase the risk for asthma in adult life. Repeated infection of infant mice tolerized to ovalbumin (OVA) through their mother’s milk with RSV induced allergic airway disease in response to OVA sensitization and challenge, including airway inflammation, hyper-reactivity and higher OVA-specific IgE, as compa...

  4. Incidence of surgical site infection following adult spinal deformity surgery: an analysis of patient risk

    OpenAIRE

    Pull ter Gunne, Albert F.; Laarhoven, C.J.H.M. van; Cohen, David B.

    2010-01-01

    Surgical site infection (SSI) following spinal surgery is a frequent complication and results in higher morbidity, mortality and healthcare costs. Patients undergoing surgery for spinal deformity (scoliosis/kyphosis) have longer surgeries, involving more spinal levels and larger blood losses than typical spinal procedures. Previous research has identified risk factors for SSI in spinal surgery, but few studies have looked at adult deformity surgeries. We retrospectively performed a large case...

  5. Comprehensively Assessing Cognitive and Behavioral Risks for HIV Infection among Middle-Aged and Older Adults

    Science.gov (United States)

    Paniagua, Freddy A.; O'Boyle, Michael

    2008-01-01

    A comprehensive survey of HIV/AIDS with middle-aged and older adults should include six domains (e.g., factual knowledge regarding the acquisition and transmission of HIV, traditionally-accepted behavioral risks for HIV infection). A sample of 23 women (54.8%) and 19 men (45.2%), ranging in age from 51 to 85 were surveyed across such domains.…

  6. Antibody screening tests variably overestimate the prevalence of hepatitis C virus infection among HIV-infected adults in Ghana.

    Science.gov (United States)

    King, S; Adjei-Asante, K; Appiah, L; Adinku, D; Beloukas, A; Atkins, M; Sarfo, S F; Chadwick, D; Phillips, R O; Geretti, A M

    2015-05-01

    HIV coinfection with HCV has been poorly studied in sub-Saharan Africa, and the reliability of available seroprevalence estimates remains uncertain. The study aim was to determine HCV RNA prevalence in HIV-infected subjects receiving care in Kumasi, Ghana, and relate the findings to HCV antibody detection. From a population of 1520 HIV-infected adults, all HBsAg-positive subjects (n = 236) and a random subset of HBsAg-negative subject (n = 172) were screened for HCV RNA using pooled plasma; positive samples were genotyped by core and NS5B sequencing. HCV antibodies were detected by three commercial screening assays and confirmed by the line immunoassay. HCV RNA was detected in 4/408 subjects (1.0%, 95% confidence interval 0.0-1.9%), comprising 3/236 (1.3%; 0.0-2.8%) HBsAg-positive and 1/172 (0.6%; 0.0-1.8%) HBsAg-negative subjects. HCV RNA-positive subjects showed reactivity in all three antibody screening assays. Among HCV RNA-negative subjects, 5/67 (7.5%), 5/67 (7.5%) and 19/67 (28.4%) showed antibody reactivity by each screening assay, respectively, including two (3.0%) with reactivity by all three assays. Only one sample (1.5%) had confirmed antibody reactivity by line immunoassay indicating past HCV infection. HCV-positive subjects (three males, two females) were aged 30-46 years, by questionnaire-based interview reported surgical procedures and blood transfusion as risk factors for infection. HCV genotypes were 2 (subtypes 2j, 2l, 2k/unassigned) and 1 (subtype unassigned). Without further testing, HCV antibody screening assays variably overestimated HCV prevalence among HIV-infected subjects in Ghana. These findings inform the interpretation of previous seroprevalence estimates based upon screening assays alone.

  7. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells.

    Science.gov (United States)

    Cobellis, Gilda; Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Fasano, Silvia; Pierantoni, Riccardo

    2016-01-01

    Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID:27375550

  8. Switching roles: the functional plasticity of adult tissue stem cells

    OpenAIRE

    Wabik, A.; Jones, P H

    2015-01-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept...

  9. Effects of Neuroendocrine CB1 Activity on Adult Leydig Cells

    Science.gov (United States)

    Cobellis, Gilda; Meccariello, Rosaria; Chianese, Rosanna; Chioccarelli, Teresa; Fasano, Silvia; Pierantoni, Riccardo

    2016-01-01

    Endocannabinoids control male reproduction acting at central and local level via cannabinoid receptors. The cannabinoid receptor CB1 has been characterized in the testis, in somatic and germ cells of mammalian and non-mammalian animal models, and its activity related to Leydig cell differentiation, steroidogenesis, spermiogenesis, sperm quality, and maturation. In this short review, we provide a summary of the insights concerning neuroendocrine CB1 activity in male reproduction focusing on adult Leydig cell ontogenesis and steroid biosynthesis. PMID:27375550

  10. A Method to Isolate Viable Schwann Cells from Adult Rat

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 Introduction Schwann cells (SCs) are the glial cells of the peripheral nervous system, which play an important role for repairing nerve injuries and demyelination diseases. The ability to generate large numbers of viable SCs in a short period of time from adult peripheral nerves makes them potential candidates for the clinical application of cell transplantation to enhance remyelination in human demyelinating disease and repair nerve damage. Previously most methods to isolate SCs are not clinically accept...

  11. High Prevalence of Hepatitis B Virus Infection in Young Adults in Ternate, Eastern Indonesia.

    Science.gov (United States)

    Ie, Susan Irawati; Turyadi; Sidarta, Erick; Sadhewa, Arkasha; Purnomo, Gludhug Ariyo; Soedarmono, Yuyun S M; Pattiiha, Mochtar Zein; Thedja, Meta Dewi; Harahap, Alida R; Muljono, David H

    2015-12-01

    The incidence of hepatitis B virus (HBV) infection has been declining thanks to the universal hepatitis B infant immunization program. Nevertheless, young adults born before the program implementation might have acquired HBV in early childhood or remain susceptible to infection. This study aimed to evaluate hepatitis B epidemiology in asymptomatic young adult population in Ternate, eastern Indonesia. Serum samples of 376 subjects (aged 17-25, mean 19.82 ± 1.69 years; male/female 138/238) were screened for HBV parameters serologically (HBV surface antigen [HBsAg]; its antibody [anti-HBs]; anti-core antigen [anti-HBc]), and molecularly (HBV DNA). HBsAg, anti-HBc, anti-HBs, and HBV DNA prevalence were 15.7%, 36.2%, 24.2%, and 27.9%, respectively, with male predominance. Of all subjects, 13.0% were HBsAg negative with detectable HBV DNA (occult hepatitis B [OHB]), and 56.4% showed negativity for all seromarkers. This population showed high hepatitis B prevalence with substantial occurrence of OHB. However, a high percentage of the population were still susceptible and at risk of HBV infection. This study emphasizes the necessity to improve prevention strategies to screen and manage HBV carriers, including the adoption of catch-up or booster vaccination targeted to young adult populations. Investigations on the roles of host-virus interactions associated with OHB and its implications are warranted.

  12. Regulatory T cells subsets in filarial infection and their function

    Directory of Open Access Journals (Sweden)

    Simon eMetenou

    2013-09-01

    Full Text Available Filarial infections in humans are chronic infections that cause significant morbidity. The chronic nature of these infections with continuous antigen release is associated with a parasite-specific T cell hypo-responsiveness that may over time also affect the immune responses to bystander antigens. Previous studies have shown the filarial parasite antigen-specific T cells hypo-responsiveness is mediated by regulatory cytokines -- IL-10 and TGF-β in particular. Recent studies have suggested that the modulated/regulated T cell responses associated with patent filarial infection may reflect an expansion of regulatory T cells (Tregs that include both Tregs induced in peripheral circulation or pTregs and the thymus-derived Tregs or tTregs. Although much is known about the phenotype of these regulatory populations, the mechanisms underlying their expansion and their mode of action in filarial and other infections remain unclear. Nevertheless there are data to suggest that while many of these regulatory cells are activated in an antigen-specific manner the ensuing effectors of this activation are relatively non-specific and may affect a broad range of immune cells. This review will focus on the subsets and function of regulatory T cells in filarial infection.

  13. Ectopic Human Fasciola hepatica Infection by an Adult Worm in the Mesocolon.

    Science.gov (United States)

    Kim, Ah Jin; Choi, Chang Hwan; Choi, Sun Keun; Shin, Yong Woon; Park, Yun-Kyu; Kim, Lucia; Choi, Suk Jin; Han, Jee Young; Kim, Joon Mee; Chu, Young Chae; Park, In Suh

    2015-12-01

    We report here an ectopic case of Fasciola hepatica infection confirmed by recovery of an adult worm in the mesocolon. A 56-year-old female was admitted to our hospital with discomfort and pain in the left lower quadrant of the abdomen. Abdominal CT showed 3 abscesses in the left upper quadrant, mesentery, and pelvic cavity. On surgical exploration, abscess pockets were found in the mesocolon of the sigmoid colon and transverse colon. A leaf-like worm found in the abscess pocket of the mesocolon of the left colon was diagnosed as an adult fluke of F. hepatica. Histologically, numerous eggs of F. hepatica were noted with acute and chronic granulomatous inflammations in the subserosa and pericolic adipose tissues. Conclusively, a rare case of ectopic fascioliasis has been confirmed in this study by the adult worm recovery of F. hepatica in the mesocolon.

  14. Induction of apoptosis in frog virus 3-infected cells.

    Science.gov (United States)

    Chinchar, V G; Bryan, Locke; Wang, J; Long, Scott; Chinchar, G D

    2003-02-15

    The ability of frog virus 3 (FV3), the type species of the family Iridoviridae, to induce apoptosis was examined by monitoring DNA cleavage, chromatin condensation, and cell-surface expression of phosphotidylserine (PS) in fathead minnow (FHM) and baby hamster kidney (BHK) cells. In productively infected FHM cells, DNA fragmentation was first noted at 6-7 h postinfection and was clearly seen by 17 h postinfection, while chromatin condensation was detected at 8.5 h postinfection. As with some other viruses, FV3-induced apoptosis did not require de novo viral gene expression as both heat-inactivated and UV-inactivated virus readily triggered DNA fragmentation in FHM cells. Moreover, FV3-induced apoptosis was blocked in FHM cells by the pan-caspase inhibitor Z-VAD-FMK, suggesting that virus infection triggers programmed cell death through activation of the caspase cascade. FV3 infection also triggered apoptosis in BHK cells as monitored by TUNEL and annexin V binding assays. To determine whether FV3, similar to other large DNA viruses, encoded proteins that block or delay apoptosis, mock- and FV3-infected FHM cells were osmotically shocked and assayed for DNA fragmentation 3 hours later. DNA fragmentation was clearly seen whether or not shocked cells were previously infected with FV3, indicating that infection with FV3 did not block apoptosis induced by osmotic shock in FHM cells. The above results demonstrate that iridoviruses triggered apoptosis and that the induction of programmed cell death did not require viral gene expression. However, it remains to be determined if virion attachment to target cells is sufficient to induce cell death, or if apoptosis is triggered directly or indirectly by one or more virion-associated proteins. PMID:12642103

  15. Multipotent adult progenitor cell and stem cell plasticity

    OpenAIRE

    Jahagirdar, Balkrishna N; Verfaillie, Catherine

    2005-01-01

    Stem cells are defined by their biological function. A stem cell is an undifferentiated cell that self-renews to maintain the stem cell pool and at the single-cell level differentiates into more than one mature, functional cell. In addition, when transplanted, a stem cell should be capable of replacing a damaged organ or tissue for the lifetime of the recipient. Some would argue that stem cells should also be capable of functionally integrating into nondamaged tissues. Stem cells are critical...

  16. Seroepidemiology of dengue virus infection in the adult population in tropical Singapore.

    Science.gov (United States)

    Ang, L W; Cutter, J; James, L; Goh, K T

    2015-06-01

    To assess the impact of past dengue epidemics in Singapore, we undertook a national seroepidemiological study to determine the prevalence of past dengue virus (DENV) infection in the adult population in 2010 and make comparisons with the seroprevalence in 2004. The study involved residual sera from 3293 adults aged 18-79 years who participated in a national health survey in 2010. The overall prevalence of anti-DENV IgG antibodies was 56·8% (95% confidence interval 55·1-58·5) in 2010. The seroprevalence increased significantly with age. Males had significantly higher seroprevalence than females (61·5% vs. 53·2%). Among the three major ethnic groups, Malays had the lowest seroprevalence (50·2%) compared to Chinese (57·0%) and Indians (62·0%). The age-standardized seroprevalence in adults was significantly lower in 2010 (54·4%) compared to 2004 (63·1%). Older age, male gender, Indian ethnicity, permanent residency and being home-bound were independent risk factors significantly associated with seropositivity. About 43% of the Singapore adult resident population remain susceptible to DENV infection as a result of the successful implementation of a comprehensive nationwide Aedes surveillance and control programme since the 1970s. Vector suppression and concerted efforts of all stakeholders in the community remain the key strategy in the prevention and control of dengue.

  17. Adult granulosa cell tumor of the testis masquerading as hydrocele

    Directory of Open Access Journals (Sweden)

    Archana George Vallonthaiel

    2015-12-01

    Full Text Available Adult testicular granulosa cell tumor is a rare, potentially malignant sex cord-stromal tumor, of which 30 cases have been described to date. We report the case of a 43-year-old male who complained of a left testicular swelling. Scrotal ultrasound showed a cystic lesion, suggestive of hydrocele. However, due to a clinical suspicion of a solid-cystic neoplasm, a high inguinal orchidectomy was performed, which, on pathological examination, was diagnosed as adult granulosa cell tumor. Adult testicular granulosa cell tumors have aggressive behaviour as compared to their ovarian counterparts. They may rarely be predominantly cystic and present as hydrocele. Lymph node and distant metastases have been reported in few cases. Role of MIB-1 labelling index in prognostication is not well defined. Therefore, their recognition and documentation of their behaviour is important from a diagnostic, prognostic and therapeutic point of view.

  18. Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy

    DEFF Research Database (Denmark)

    Ibitokou, Samad; Oesterholt, Mayke; Brutus, Laurent;

    2012-01-01

    Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM) is scarce. We conducted a longitudinal, prospective ...

  19. Detection of multiple mycoplasma infection in cell cultures by PCR

    Directory of Open Access Journals (Sweden)

    J. Timenetsky

    2006-07-01

    Full Text Available A total of 301 cell cultures from 15 laboratories were monitored for mycoplasma (Mollicutes using PCR and culture methodology. The infection was detected in the cell culture collection of 12 laboratories. PCR for Mollicutes detected these bacteria in 93 (30.9% samples. Although the infection was confirmed by culture for 69 (22.9% samples, PCR with generic primers did not detect the infection in five (5.4%. Mycoplasma species were identified with specific primers in 91 (30.2% of the 98 samples (32.6% considered to be infected. Mycoplasma hyorhinis was detected in 63.3% of the infected samples, M. arginini in 59.2%, Acholeplasma laidlawii in 20.4%, M. fermentans in 14.3%, M. orale in 11.2%, and M. salivarium in 8.2%. Sixty (61.2% samples were co-infected with more than one mycoplasma species. M. hyorhinis and M. arginini were the microorganisms most frequently found in combination, having been detected in 30 (30.6% samples and other associations including up to four species were detected in 30 other samples. Failure of the treatments used to eliminate mycoplasmas from cell cultures might be explained by the occurrence of these multiple infections. The present results indicate that the sharing of non-certified cells among laboratories may disseminate mycoplasma in cell cultures.

  20. Cell competition modifies adult stem cell and tissue population dynamics in a JAKSTAT dependent manner

    OpenAIRE

    Kolahgar, Golnar; Suijkerbuijk, Saskia J. E.; Kucinski, Iwo; Poirier, Enzo Z.; Mansour, Sarah; Simons, Benjamin D.; Piddini, Eugenia

    2015-01-01

    Summary Throughout their lifetime, cells may suffer insults that reduce their fitness and disrupt their function, and it is unclear how these potentially harmful cells are managed in adult tissues. We address this question using the adult Drosophila posterior midgut as a model of homeostatic tissue and ribosomal Minute mutations to reduce fitness in groups of cells. We take a quantitative approach combining lineage tracing and biophysical modeling and address how cell competition affects stem...

  1. Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection.

    Science.gov (United States)

    Kamaladasa, A; Wickramasinghe, N; Adikari, T N; Gomes, L; Shyamali, N L A; Salio, M; Cerundolo, V; Ogg, G S; Malavige, G Neelika

    2016-08-01

    Invariant natural killer T (iNKT) cells are capable of rapid activation and production of cytokines upon recognition of antigenic lipids presented by CD1d molecules. They have been shown to play a significant role in many viral infections and were observed to be highly activated in patients with acute dengue infection. In order to characterize further their role in dengue infection, we investigated the proportion of iNKT cells and their phenotype in adult patients with acute dengue infection. The functionality of iNKT cells in patients was investigated by both interferon (IFN)-γ and interleukin (IL)-4 ex-vivo enzyme-linked immunospot (ELISPOT) assays following stimulation with alpha-galactosyl-ceramide (αGalCer). We found that circulating iNKT cell proportions were significantly higher (P = 0·03) in patients with acute dengue when compared to healthy individuals and were predominantly of the CD4(+) subset. iNKT cells of patients with acute dengue had reduced proportions expressing CD8α and CD161 when compared to healthy individuals. The iNKT cells of patients were highly activated and iNKT activation correlated significantly with dengue virus-specific immunoglobulin (Ig)G antibody levels. iNKT cells expressing Bcl-6 (P = 0·0003) and both Bcl-6 and inducible T cell co-stimulator (ICOS) (P = 0·006) were increased significantly in patients when compared to healthy individuals. Therefore, our data suggest that in acute dengue infection there is an expansion of highly activated CD4(+) iNKT cells, with reduced expression of CD161 markers. PMID:26874822

  2. In vitro proliferation of adult human beta-cells.

    Directory of Open Access Journals (Sweden)

    Sabine Rutti

    Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

  3. Intensified microbiological investigations in adult patients admitted to hospital with lower respiratory tract infections

    DEFF Research Database (Denmark)

    Korsgaard, Jens; Rasmussen, TR; Sommer, T;

    2002-01-01

    The objective of this study was to investigate the diagnostic yield of a programme with intensified microbiological investigations in immunocompetent adult patients with lower respiratory tract infections (LRTI). Patients in the study group were included prospectively and consecutively from...... lavage (BAL). Only 7% in the historic control group were discharged with an aetiological diagnosis of their infections; while the diagnostic yield in the study group increased to 51% of patients. In the study group the presence of new infiltrates on chest X-ray increased the detection...... of a microbiological aetiology from 37% with no infiltrates to 62% with infiltrates and recent antibiotic therapy reduced the detection of a microbiological cause of infection from 61% in 36 patients who had not received antibiotic therapy to 39% in 31 patients who had received recent antibiotic therapy prior...

  4. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients

    International Nuclear Information System (INIS)

    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) is broad and comprises predominantly opportunistic infections and neoplasms. It is estimated that approximately one-third of all patients with AIDS develop neurological complications. The organisms responsible for AIDS are human retroviruses: primarily the human immunodeficiency virus type 1 (HIV). In this review we shall focus on the neurological complications of HIV and AIDS which are applicable to the more frequently occurring intracranial infective organisms. Attention will be paid specifically to those CNS manifestations occurring in the adult HIV and AIDS population as infection in the paediatric HIV and AIDS group, although bearing some similarities, demonstrates some important differences

  5. Adenoviruses Expressing PDX-1, BETA2/NeuroD and MafA Induces the Transdifferentiation of Porcine Neonatal Pancreas Cell Clusters and Adult Pig Pancreatic Cells into Beta-Cells

    Directory of Open Access Journals (Sweden)

    Young-Hye You

    2011-04-01

    Full Text Available BackgroundA limitation in the number of insulin-producing pancreatic beta-cells is a special feature of diabetes. The identification of alternative sources for the induction of insulin-producing surrogate beta-cells is a matter of profound importance. PDX-1/VP16, BETA2/NeuroD, and MafA overexpression have been shown to influence the differentiation and proliferation of pancreatic stem cells. However, few studies have been conducted using adult animal pancreatic stem cells.MethodsAdult pig pancreatic cells were prepared from the non-endocrine fraction of adult pig pancreata. Porcine neonatal pancreas cell clusters (NPCCs were prepared from neonatal pigs aged 1-2 days. The dispersed pancreatic cells were infected with PDX-1/VP16, BETA2/NeuroD, and MafA adenoviruses. After infection, these cells were transplanted under the kidney capsules of normoglycemic nude mice.ResultsThe adenovirus-mediated overexpression of PDX-1, BETA2/NeuroD and MafA induced insulin gene expression in NPCCs, but not in adult pig pancreatic cells. Immunocytochemistry revealed that the number of insulin-positive cells in NPCCs and adult pig pancreatic cells was approximately 2.6- and 1.1-fold greater than those in the green fluorescent protein control group, respectively. At four weeks after transplantation, the relative volume of insulin-positive cells in the grafts increased in the NPCCs, but not in the adult porcine pancreatic cells.ConclusionThese data indicate that PDX-1, BETA2/NeuroD, and MafA facilitate the beta-cell differentiation of NPCCs, but not adult pig pancreatic cells. Therefore PDX-1, BETA2/NeuroD, and MafA-induced NPCCs can be considered good sources for the induction of pancreatic beta-cells, and may also have some utility in the treatment of diabetes.

  6. Properties of Adult Lung Stem and Progenitor Cells.

    Science.gov (United States)

    Bertoncello, Ivan

    2016-12-01

    The last decade has seen significant progress in understanding the organisation of regenerative cells in the adult lung. Cell-lineage tracing and in vitro clonogenic assays have enabled the identification and characterisation of endogenous lung epithelial stem and progenitor cells. Selective lung injury models, and genetically engineered mice have revealed highly conserved gene networks, factors, signalling pathways, and cellular interactions important in maintaining lung homeostasis and regulating lung regeneration and repair following injury. This review describes the current models of lung epithelial stem and progenitor cell organisation in adult mice, and the impediments encountered in translational studies aiming to identify and characterise their human homologs. J. Cell. Physiol. 231: 2582-2589, 2016. © 2016 Wiley Periodicals, Inc. PMID:27062064

  7. Adult stem cells and their ability to differentiate.

    Science.gov (United States)

    Tarnowski, Maciej; Sieron, Aleksander L

    2006-08-01

    This is a review of the current status of knowledge on adult stem cells as well as the criteria and evidence for their potential to transform into different cell types and cell lineages. Reports on stem cell sources, focusing on tissues from adult subjects, were also investigated. Numerous reports have been published on the search for early markers of both stem cells and the precursors of various cell lineages. The question is still open about the characteristics of the primary stem cell. The existing proofs and hypotheses have not yielded final solutions to this problem. From a practical point of view it is also crucial to find a minimal set of markers determining the phenotypes of the precursor cells of a particular cell lineage. Several lines of evidence seem to bring closer the day when we will be able to detect the right stem cell niche and successfully isolate precursor cells that are needed for the treatment of a particular disorder. Recent reports on cases of cancer in patients subjected to stem cell therapy are yet another controversial issue looked into in this review, although the pros and cons emerging from the results of published studies still do not provide satisfying evidence to fully understand this issue. PMID:16865077

  8. Adult stem cells and their ability to differentiate.

    Science.gov (United States)

    Tarnowski, Maciej; Sieron, Aleksander L

    2006-08-01

    This is a review of the current status of knowledge on adult stem cells as well as the criteria and evidence for their potential to transform into different cell types and cell lineages. Reports on stem cell sources, focusing on tissues from adult subjects, were also investigated. Numerous reports have been published on the search for early markers of both stem cells and the precursors of various cell lineages. The question is still open about the characteristics of the primary stem cell. The existing proofs and hypotheses have not yielded final solutions to this problem. From a practical point of view it is also crucial to find a minimal set of markers determining the phenotypes of the precursor cells of a particular cell lineage. Several lines of evidence seem to bring closer the day when we will be able to detect the right stem cell niche and successfully isolate precursor cells that are needed for the treatment of a particular disorder. Recent reports on cases of cancer in patients subjected to stem cell therapy are yet another controversial issue looked into in this review, although the pros and cons emerging from the results of published studies still do not provide satisfying evidence to fully understand this issue.

  9. Mycobacterium marinum causes a latent infection that can be reactivated by gamma irradiation in adult zebrafish.

    Directory of Open Access Journals (Sweden)

    Mataleena Parikka

    2012-09-01

    Full Text Available The mechanisms leading to latency and reactivation of human tuberculosis are still unclear, mainly due to the lack of standardized animal models for latent mycobacterial infection. In this longitudinal study of the progression of a mycobacterial disease in adult zebrafish, we show that an experimental intraperitoneal infection with a low dose (≈ 35 bacteria of Mycobacterium marinum, results in the development of a latent disease in most individuals. The infection is characterized by limited mortality (25%, stable bacterial loads 4 weeks following infection and constant numbers of highly organized granulomas in few target organs. The majority of bacteria are dormant during a latent mycobacterial infection in zebrafish, and can be activated by resuscitation promoting factor ex vivo. In 5-10% of tuberculosis cases in humans, the disease is reactivated usually as a consequence of immune suppression. In our model, we are able to show that reactivation can be efficiently induced in infected zebrafish by γ-irradiation that transiently depletes granulo/monocyte and lymphocyte pools, as determined by flow cytometry. This immunosuppression causes reactivation of the dormant mycobacterial population and a rapid outgrowth of bacteria, leading to 88% mortality in four weeks. In this study, the adult zebrafish presents itself as a unique non-mammalian vertebrate model for studying the development of latency, regulation of mycobacterial dormancy, as well as reactivation of latent or subclinical tuberculosis. The possibilities for screening for host and pathogen factors affecting the disease progression, and identifying novel therapeutic agents and vaccine targets make this established model especially attractive.

  10. Embryonic and adult stem cell therapy.

    Science.gov (United States)

    Brignier, Anne C; Gewirtz, Alan M

    2010-02-01

    There are many types of stem cells. All share the characteristics of being able to self-renew and to give rise to differentiated progeny. Over the last decades, great excitement has been generated by the prospect of being able to exploit these properties for the repair, improvement, and/or replacement of damaged organs. However, many hurdles, both scientific and ethical, remain in the path of using human embryonic stem cells for tissue-engineering purposes. In this report we review current strategies for isolating, enriching, and, most recently, inducing the development of human pluripotent stem cells. In so doing, we discuss the scientific and ethical issues associated with this endeavor. Finally, progress in the use of stem cells as therapies for type 1 diabetes mellitus, congestive heart failure, and various neurologic and immunohematologic disorders, and as vehicles for the delivery of gene therapy, is briefly discussed. PMID:20061008

  11. Treatment Outcomes for HIV and MDR-TB Co-infected Adults and Children: Systematic Review and Meta-analysis.

    OpenAIRE

    Isaakidis, P.; Casas, E C; Das, M.; Tseretopoulou, X; Ntzani, E E; Ford, N

    2015-01-01

    The incidence of multidrug-resistant tuberculosis (MDR-TB) is increasing in high human immunodeficiency virus (HIV) prevalence settings, with high associated mortality. Treatment outcomes in HIV-co-infected adults and children are poorly documented.

  12. CD4+ T cell responses in hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Nasser Semmo; Paul Klenerman

    2007-01-01

    Hepatitis C virus (HCV) infection is a major cause of liver damage, with virus-induced end-stage disease such as liver cirrhosis and hepatocellular carcinoma resulting in a high rate of morbidity and mortality worldwide. Evidence that CD4+ T cell responses to HCV play an important role in the outcome of acute infection has been shown in several studies. However, the mechanisms behind viral persistence and the failure of CD4+ T cell responses to contain virus are poorly understood. During chronic HCV infection, HCV-specific CD4+ T cell responses are relatively weak or absent whereas in resolved infection these responses are vigorous and multispecific. Persons with a T-helper type Ⅰ profile, which promotes cellular effector mechanisms are thought to be more likely to experience viral clearance, but the overall role of these cells in the immunopathogenesis of chronic liver disease is not known. To define this, much more data is required on the function and specificity of virus-specific CD4+ T cells,especially in the early phases of acute disease and in the liver during chronic infection. The role and possible mechanisms of action of CD4+ T cell responses in determining the outcome of acute and chronic HCV infection will be discussed in this review.

  13. Septic arthritis of the hips in adults with sickle cell anemia

    Directory of Open Access Journals (Sweden)

    Alexandre Poignard

    2011-01-01

    Full Text Available Although the presence of osteonecrotic bone is known to make joints more prone to infection, acute septic joint in hip osteonecrosis has not frequently been reported in adults with sickle cell disease. The clinical features at the time of admission, imaging findings suggesting the diagnosis, modes of treatment and sequelae of septic arthritis of twenty-four hip joints with osteonecrosis in patients with sickle cell disease were studied retrospectively over a 25-years period. This study evaluated also the complications, the efficiency and the risk of total hip arthroplasty in these patients. Most patients were in the third decade of life. Staphylococcus and Gram negative infection predominated. Treatment was first conservative but most of the patients needed surgery to treat infection and sequelae related to infection. A total hip arthroplasty was performed later in twenty joints. No deaths were observed, but complications occurred. Twenty of the patients in our study underwent delayed total hip arthroplasties following repeated aspirations of the joint and intravenous antibiotics. With an experienced surgical and medical team and multidisciplinary management of these patients undergoing total hip arthroplasty after hip infection, our rate of complications was acceptable.

  14. Angiogenic factors stimulate growth of adult neural stem cells.

    Directory of Open Access Journals (Sweden)

    Andreas Androutsellis-Theotokis

    Full Text Available BACKGROUND: The ability to grow a uniform cell type from the adult central nervous system (CNS is valuable for developing cell therapies and new strategies for drug discovery. The adult mammalian brain is a source of neural stem cells (NSC found in both neurogenic and non-neurogenic zones but difficulties in culturing these hinders their use as research tools. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that NSCs can be efficiently grown in adherent cell cultures when angiogenic signals are included in the medium. These signals include both anti-angiogenic factors (the soluble form of the Notch receptor ligand, Dll4 and pro-angiogenic factors (the Tie-2 receptor ligand, Angiopoietin 2. These treatments support the self renewal state of cultured NSCs and expression of the transcription factor Hes3, which also identifies the cancer stem cell population in human tumors. In an organotypic slice model, angiogenic factors maintain vascular structure and increase the density of dopamine neuron processes. CONCLUSIONS/SIGNIFICANCE: We demonstrate new properties of adult NSCs and a method to generate efficient adult NSC cultures from various central nervous system areas. These findings will help establish cellular models relevant to cancer and regeneration.

  15. B-Cell Response during Protozoan Parasite Infections

    Directory of Open Access Journals (Sweden)

    María C. Amezcua Vesely

    2012-01-01

    Full Text Available In this review, we discuss how protozoan parasites alter immature and mature B cell compartment. B1 and marginal zone (MZ B cells, considered innate like B cells, are activated during protozoan parasite infections, and they generate short lived plasma cells providing a prompt antibody source. In addition, protozoan infections induce massive B cell response with polyclonal activation that leads to hypergammaglobulnemia with serum antibodies specific for the parasites and self and/or non related antigens. To protect themselves, the parasites have evolved unique ways to evade B cell immune responses inducing apoptosis of MZ and conventional mature B cells. As a consequence of the parasite induced-apoptosis, the early IgM response and an already establish humoral immunity are affected during the protozoan parasite infection. Moreover, some trypanosomatides trigger bone marrow immature B cell apoptosis, influencing the generation of new mature B cells. Simultaneously with their ability to release antibodies, B cells produce cytokines/quemokines that influence the characteristic of cellular immune response and consequently the progression of parasite infections.

  16. Hypoxia modulates infection of epithelial cells by Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Bettina Schaible

    Full Text Available Pseudomonas aeruginosa (P. aeruginosa is an opportunistic pathogen commonly associated with lung and wound infections. Hypoxia is a frequent feature of the microenvironment of infected tissues which induces the expression of genes associated with innate immunity and inflammation in host cells primarily through the activation of the hypoxia-inducible factor (HIF and Nuclear factor kappaB (NF-κB pathways which are regulated by oxygen-dependent prolyl-hydroxylases. Hypoxia also affects virulence and antibiotic resistance in bacterial pathogens. However, less is known about the impact of hypoxia on host-pathogen interactions such as bacterial adhesion and infection. In the current study, we demonstrate that hypoxia decreases the internalization of P. aeruginosa into cultured epithelial cells resulting in decreased host cell death. This response can also be elicited by the hydroxylase inhibitor Dimethyloxallyl Glycine (DMOG. Reducing HIF-2α expression or Rho kinase activity diminished the effects of hypoxia on P. aeruginosa infection. Furthermore, in an in vivo pneumonia infection model, application of DMOG 48 h before infection with P. aeruginosa significantly reduced mortality. Thus, hypoxia reduces P. aeruginosa internalization into epithelial cells and pharmacologic manipulation of the host pathways involved may represent new therapeutic targets in the treatment of P. aeruginosa infection.

  17. Effect of herpesvirus infection on pancreatic duct cell secretion

    Institute of Scientific and Technical Information of China (English)

    Péter Hegyi; András Varró; Mária K Kovács; Mike A Gray; Barry E Argent; Zsolt Boldogk(o)i; Balázs (O)rd(o)g; Zoltán Rakonczai Jr; Tamás Takács; János Lonovics; Annamária Szabolcs; Réka Sári; András Tóth; Julius G Papp

    2005-01-01

    AIM: To examine the effect of acute infection caused by herpesvirus (pseudorabies virus, PRV) on pancreatic ductal secretion.METHODS: The virulent Ba-DupGreen (BDG) and nonvirulent Ka-RREpOlacgfp (KEG) genetically modified strains of PRV were used in this study and both of them contain the gene for green fluorescent protein (GFP). Small intra/interlobular ducts were infected with BDG virus (107 PFU/mL for 6 h) or with KEG virus (1010 PFU/mL for 6 h), while non-infected ducts were incubated only with the culture media. The ducts were then cultured for a further 18 h.The rate of HCO3- secretion [base efflux -J(B-)] was determined from the buffering capacity of the cells and the initial rate of intracellular acidification (1) after sudden blockage of basolateral base loaders with dihydro-4,4,-diisothiocyanatostilbene-2,2,-disulfonic acid (500 μmol/L)and amiloride (200 μmol/L), and (2) after alkali loading the ducts by exposure to NH4Cl. All the experiments were performed in HCO3--buffered Ringer solution at 37 ℃ (n = 5ducts for each experimental condition). Viral structural proteins were visualized by immunohistochemistry. Virallyencoded GFP and immunofluorescence signals were recorded by a confocal laser scanning microscope.RESULTS: The BDG virus infected the majority of accessible cells of the duct as judged by the appearance of GFP and viral antigens in the ductal cells. KEG virus caused a similarly high efficiency of infection. After blockage of basolateral base loaders, BDG infection significantly elevated -J(B-) 24 h after the infection, compared to the non-infected group. However, KEG infection did not modify -J(B-). After alkali loading the ducts, -J(B-) was significantly elevated in the BDG group compared to the control group 24 h after the infection. As we found with the inhibitor stop method, no change was observed in the group KEG compared to the non-infected group.CONCLUSION: Incubation with the BDG or KEG strains of PRV results in an effective

  18. Neural stem cells and the regulation of adult neurogenesis

    Directory of Open Access Journals (Sweden)

    Conover Joanne C

    2003-11-01

    Full Text Available Abstract Presumably, the 'hard-wired' neuronal circuitry of the adult brain dissuades addition of new neurons, which could potentially disrupt existing circuits. This is borne out by the fact that, in general, new neurons are not produced in the mature brain. However, recent studies have established that the adult brain does maintain discrete regions of neurogenesis from which new neurons migrate and become incorporated into the functional circuitry of the brain. These neurogenic zones appear to be vestiges of the original developmental program that initiates brain formation. The largest of these germinal regions in the adult brain is the subventricular zone (SVZ, which lines the lateral walls of the lateral ventricles. Neural stem cells produce neuroblasts that migrate from the SVZ along a discrete pathway, the rostral migratory stream, into the olfactory bulb where they form mature neurons involved in the sense of smell. The subgranular layer (SGL of the hippocampal dentate gyrus is another neurogenic region; new SGL neurons migrate only a short distance and differentiate into hippocampal granule cells. Here, we discuss the surprising finding of neural stem cells in the adult brain and the molecular mechanisms that regulate adult neurogenesis.

  19. Mycobacterium tuberculosis infection induces non-apoptotic cell death of human dendritic cells

    LENUS (Irish Health Repository)

    Ryan, Ruth CM

    2011-10-24

    Abstract Background Dendritic cells (DCs) connect innate and adaptive immunity, and are necessary for an efficient CD4+ and CD8+ T cell response after infection with Mycobacterium tuberculosis (Mtb). We previously described the macrophage cell death response to Mtb infection. To investigate the effect of Mtb infection on human DC viability, we infected these phagocytes with different strains of Mtb and assessed viability, as well as DNA fragmentation and caspase activity. In parallel studies, we assessed the impact of infection on DC maturation, cytokine production and bacillary survival. Results Infection of DCs with live Mtb (H37Ra or H37Rv) led to cell death. This cell death proceeded in a caspase-independent manner, and without nuclear fragmentation. In fact, substrate assays demonstrated that Mtb H37Ra-induced cell death progressed without the activation of the executioner caspases, 3\\/7. Although the death pathway was triggered after infection, the DCs successfully underwent maturation and produced a host-protective cytokine profile. Finally, dying infected DCs were permissive for Mtb H37Ra growth. Conclusions Human DCs undergo cell death after infection with live Mtb, in a manner that does not involve executioner caspases, and results in no mycobactericidal effect. Nonetheless, the DC maturation and cytokine profile observed suggests that the infected cells can still contribute to TB immunity.

  20. In vivo dedifferentiation of adult adipose cells.

    Directory of Open Access Journals (Sweden)

    Yunjun Liao

    Full Text Available Adipocytes can dedifferentiate into fibroblast-like cells in vitro and thereby acquire proliferation and multipotent capacities to participate in the repair of various organs and tissues. Whether dedifferentiation occurs under physiological or pathological conditions in vivo is unknown.A tissue expander was placed under the inguinal fat pads of rats and gradually expanded by injection of water. Samples were collected at various time points, and morphological, histological, cytological, ultrastructural, and gene expression analyses were conducted. In a separate experiment, purified green fluorescent protein+ adipocytes were transplanted into C57 mice and collected at various time points. The transplanted adipocytes were assessed by bioluminescence imaging and whole-mount staining.The expanded fat pad was obviously thinner than the untreated fat pad on the opposite side. It was also tougher in texture and with more blood vessels attached. Hematoxylin and eosin staining and transmission electron microscopy indicated there were fewer monolocular adipocytes in the expanded fat pad and the morphology of these cells was altered, most notably their lipid content was discarded. Immunohistochemistry showed that the expanded fat pad contained an increased number of proliferative cells, which may have been derived from adipocytes. Following removal of the tissue expander, many small adipocytes were observed. Bioluminescence imaging suggested that some adipocytes survived when transplanted into an ischemic-hypoxic environment. Whole-mount staining revealed that surviving adipocytes underwent a process similar to adipocyte dedifferentiation in vitro. Monolocular adipocytes became multilocular adipocytes and then fibroblast-like cells.Mature adipocytes may be able to dedifferentiate in vivo, and this may be an adipose tissue self-repair mechanism. The capacity of adipocytes to dedifferentiate into stem cell-like cells may also have a more general role in the

  1. Intestinal stem cells in the adult Drosophila midgut

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Huaqi, E-mail: Huaqi.Jiang@UTSouthwestern.edu [Department of Developmental Biology, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX, 75235 (United States); Edgar, Bruce A., E-mail: b.edgar@dkfz.de [ZMBH-DKFZ Alliance, Im Neuenheimer Feld 282, D-69120 Heidelberg (Germany); Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98109 (United States)

    2011-11-15

    Drosophila has long been an excellent model organism for studying stem cell biology. Notably, studies of Drosophila's germline stem cells have been instrumental in developing the stem cell niche concept. The recent discovery of somatic stem cells in adult Drosophila, particularly the intestinal stem cells (ISCs) of the midgut, has established Drosophila as an exciting model to study stem cell-mediated adult tissue homeostasis and regeneration. Here, we review the major signaling pathways that regulate the self-renewal, proliferation and differentiation of Drosophila ISCs, discussing how this regulation maintains midgut homeostasis and mediates regeneration of the intestinal epithelium after injury. -- Highlights: Black-Right-Pointing-Pointer The homeostasis and regeneration of adult fly midguts are mediated by ISCs. Black-Right-Pointing-Pointer Damaged enterocytes induce the proliferation of intestinal stem cells (ISC). Black-Right-Pointing-Pointer EGFR and Jak/Stat signalings mediate compensatory ISC proliferation. Black-Right-Pointing-Pointer Notch signaling regulates ISC self-renewal and differentiation.

  2. The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models.

    Science.gov (United States)

    Ford, Deborah; Robins, James M; Petersen, Maya L; Gibb, Diana M; Gilks, Charles F; Mugyenyi, Peter; Grosskurth, Heiner; Hakim, James; Katabira, Elly; Babiker, Abdel G; Walker, A Sarah

    2015-10-01

    In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003-2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for management in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal structural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group on mortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm(3) or non-Candida World Health Organization stage 4 event (with CD4 count findings support a benefit from identifying patients immunologically failing first-line ART at 48 weeks. PMID:26316598

  3. Stirred bioreactors for the expansion of adult pancreatic stem cells.

    Science.gov (United States)

    Serra, Margarida; Brito, Catarina; Leite, Sofia B; Gorjup, Erwin; von Briesen, Hagen; Carrondo, Manuel J T; Alves, Paula M

    2009-01-01

    Adult pluripotent stem cells are a cellular resource representing unprecedented potential for cell therapy and tissue engineering. Complementary to this promise, there is a need for efficient bioprocesses for their large scale expansion and/or differentiation. With this goal in mind, our work focused on the development of three-dimensional (3-D) culture systems for controlled expansion of adult pancreatic stem cells (PSCs). For this purpose, two different culturing strategies were evaluated, using spinner vessels: cell aggregated cultures versus microcarrier technology. The use of microcarrier supports (Cytodex 1 and Cytodex 3) rendered expanded cell populations which retained their self-renewal ability, cell marker, and the potential to differentiate into adipocytes. This strategy surmounted the drawbacks of aggregates in culture which were demonstrably unfeasible as cells clumped together did not proliferate and lost PSC marker expression. Furthermore, the results obtained showed that although both microcarriers tested here were suitable for sustaining cell expansion, Cytodex 3 provided a better substrate for the promotion of cell adherence and growth. For the latter approach, the potential of bioreactor technology was combined with the efficient Cytodex 3 strategy under controlled environmental conditions (pH-7.2, pO2-30% and temperature-37 degrees C); cell growth was more efficient, as shown by faster doubling time, higher growth rate and higher fold increase in cell concentration, when compared to spinner cultures. This study describes a robust bioprocess for the controlled expansion of adult PSC, representing an efficient starting point for the development of novel technologies for cell therapy.

  4. Peripheral blood cell signatures of Plasmodium falciparum infection during pregnancy.

    Directory of Open Access Journals (Sweden)

    Samad Ibitokou

    Full Text Available Sequestration of Plasmodium falciparum-infected erythrocytes in placental intervillous spaces causes inflammation and pathology. Knowledge of the profiles of immune cells associated with the physiopathology of pregnancy-associated malaria (PAM is scarce. We conducted a longitudinal, prospective study, both in Benin and Tanzania, including ∼1000 pregnant women in each site with systematic follow-up at scheduled antenatal visits until delivery. We used ex vivo flow cytometry to identify peripheral blood mononuclear cell (PBMC profiles that are associated with PAM and anaemia, determining the phenotypic composition and activation status of PBMC in selected sub-groups with and without PAM both at inclusion and at delivery in a total of 302 women. Both at inclusion and at delivery PAM was associated with significantly increased frequencies both of B cells overall and of activated B cells. Infection-related profiles were otherwise quite distinct at the two different time-points. At inclusion, PAM was associated with anaemia, with an increased frequency of immature monocytes and with a decreased frequency of regulatory T cells (Treg. At delivery, infected women presented with significantly fewer plasmacytoid dendritic cells (DC, more myeloid DC expressing low levels of HLA-DR, and more effector T cells (Teff compared to uninfected women. Independent associations with an increased risk of anaemia were found for altered antigen-presenting cell frequencies at inclusion, but for an increased frequency of Teff at delivery. Our findings emphasize the prominent role played by B cells during PAM whenever it arises during pregnancy, whilst also revealing signature changes in other circulating cell types that, we conclude, primarily reflect the relative duration of the infections. Thus, the acute, recently-acquired infections present at delivery were marked by changes in DC and Teff frequencies, contrasting with infections at inclusion, considered chronic in

  5. Langerhans' cell histiocytosis in an adult.

    Science.gov (United States)

    Lindelöf, B; Forslind, B; Hilliges, M; Johansson, O; Aström, L

    1991-01-01

    A woman with typical skin lesions of histiocytosis X is reported. Electron microscopic and immunohistochemical investigations revealed a large number of markedly long Birbeck Langerhans' cell granulae. During treatment with Interferon alpha -2b, the patient developed infarctus cerebri and died. PMID:1675535

  6. Adult stem cells for chronic lung diseases.

    Science.gov (United States)

    Mora, Ana L; Rojas, Mauricio

    2013-10-01

    Idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are chronic, progressive and lethal lung diseases. The incidence of IPF and COPD increases with age, independent of exposure to common environmental risk factors. At present, there is limited understanding of the relationship between ageing and the development of chronic lung diseases. One hypothesis is that chronic injury drives to exhaustion the local and systemic repair responses in the lung. These changes are accentuated during ageing where there is a progressive accumulation of senescent cells. Recently, stem cells have emerged as a critical reparative mechanism for lung injury. In this review, we discuss the repair response of bone marrow-derived mesenchymal stem cells (B-MSC) after lung injury and how their function is affected by ageing. Our own work has demonstrated a protective role of B-MSC in several animal models of acute and chronic lung injury. We recently demonstrated the association, using animal models, between age and an increase in the susceptibility to develop severe injury and fibrosis. At the same time, we have identified functional differences between B-MSC isolated from young and old animals. Further studies are required to understand the functional impairment of ageing B-MSC, ultimately leading to a rapid stem cell depletion or fatigue, interfering with their ability to play a protective role in lung injury. The elucidation of these events will help in the development of rational and new therapeutic strategies for COPD and IPF. PMID:23648014

  7. Primary culture of adult rat liver cells. I. Preparation of isolated cells from trypsin-perfused liver of adult rat

    Directory of Open Access Journals (Sweden)

    Miyazaki,Masahiro

    1977-12-01

    Full Text Available Isolated hepatic cells from adult rats were prepared by perfusing the livers with trypsin. The highest yield of viable cells was obtained by perfusing the liver with 0.1% trypsin, pH 7.0, at 37 degrees C for 30 min. Following this treatment about 70% of cells excluded trypan blue. The isolated cells contained many binucleate cells. Between 60 and 70% of DNA present originally in the liver was recovered from the isolated hepatic cells, which had higher glucose 6-phosphatase activity than the liver. Thus the resulting cell population seems to be rich in hepatocytes. The isolated hepatic cells, however, lost some of their cellular proteins such as alanine and tyrosine amino-transferases. It was suggested that the membranes of isolated hepatic cells might be damaged by both enzymatic digestion and mechanical destruction.

  8. Metabolic stress in infected cells may represent a therapeutic target for human immunodeficiency virus infection.

    Science.gov (United States)

    Alonso-Villaverde, Carlos; Menéndez, Javier A; Joven, Jorge

    2013-07-01

    Worldwide, there are thousands of new cases of human immunodeficiency virus-1 (HIV-1) infection per day. The effectiveness of current combination antiretroviral therapy (ART) is relative; to prioritize finding vaccines and/or cure-oriented initiatives should be reinforced because there is little room, if any, for procrastination. Basic and clinical findings on HIV-1 reservoirs suggest that disruption of virus latency is feasible. Because the goal is curing HIV-1 infection, we should be aware that the challenge is to eradicate the viruses of every single infected cell and consequently acting upon virus latency is necessary but not sufficient. The large majority of the virus reservoir, CD4(+) T lymphocytes, is readily accessible but other minor reservoirs, where ART does not diffuse, require innovative strategies. The situation closely resembles that currently faced in the treatment of cancer. Exploiting the fact that histone deacetylase inhibitors, mainly vorinostat, may disrupt the latency of HIV-1, we propose to supplement this effect with a programmed interference in the metabolic stress of infected cells. Metformin and chloroquine are cheap and accessible modulators of pro-survival mechanisms to which viruses are constantly confronted to generate alternative energy sources and maximize virus production. Metformin restrains the use of the usurped cellular biosynthetic machinery by viral genes and chloroquine contributes to death of infected cells. We suggest that the combination of vorinostat, chloroquine and metformin should be combined with ART to pursue viral eradication in infected cells. PMID:23639282

  9. Application of adult stem cells in neural tissue engineering

    Institute of Scientific and Technical Information of China (English)

    Lihong Piao; Wei Wang

    2006-01-01

    OBJECTTIVE:To investigate the progress in finding,isolation and culture.proliferation and differentiation,and application in neural tissue engineering of adult stem cells(ASCs).DATA SOURCES:Using the terms"adult stem cells,nerve,tissue engineering".we searched the PubMed for adult stem ceils-related studies published in English from January 2001 to August 2006.Meanwhile,we also performed a China National Knowledge Infrastructure(CNKI)search for homochronous correlative literatures on the computer by inputting the terms"adult stem cells,nerve,tissue engineering"in Chinese.texts were searched for.Inclusive criteria:①Literatures about the sources,distribution,culture.proliferation and differentiation.and application in the repair of neural ASCs by tissue engineering.②Articles recommended either by randomized.blind or by other methods were not excluded.Exclusive criteria:①Embryonic stem cells.②Review,repetitive study,case report,Meta analysis. DATA EXTRACTION:Totally 1 278 articles related to ASCs were collected,32 were involved and the other 1 246 were excluded. DATA SYNTHESIS:Adult stem cell has the ability of self-renewal.unceasing proliferation and transdifferentiation.It has wide source,which does not involved in ethical problems.It has advantages over embryonic stem cell.Studies on the isolation and culture,induction and differentiation and application in neural ASCs by tissue engineering contribute to obtaining considerable ASCs,so as to provide experimental and theoretical bases for CONCLUSION:ASCs play a very important role in neural tissue engineering.

  10. Comparative analysis of different oral approaches to treat Vibrio cholerae infection in adult mice.

    Science.gov (United States)

    Jaiswal, Abhishek; Koley, Hemanta; Mitra, Soma; Saha, Dhira Rani; Sarkar, Banwarilal

    2014-05-01

    In this study, we have established an oral phage cocktail therapy in adult mice model and also performed a comparative analysis between phage cocktail, antibiotic and oral rehydration treatment for orally developed Vibrio cholerae infection. Four groups of mice were orally infected with Vibrio cholerae MAK 757 strain. Phage cocktail and antibiotic treated groups received 1×10(8) plaque forming unit/ml (once a daily) and 40mg/kg (once a daily) as an oral dose respectively for consecutive three days after bacterial infection. In case of oral rehydration group, the solution was supplied after bacterial infection mixed with the drinking water. To evaluate the better and safer approach of treatment, tissue and serum samples were collected. Here, phage cocktail treated mice reduced the log10 numbers of colony per gram by 3log10 (p0.05). Besides, it was evident that antibiotic and phage cocktail treated group had a gradual decrease in both IL-6 and TNF-α level for 3 days (pVibrio cholerae infection.

  11. Stimulation of adult oligodendrogenesis by myelin-specific T cells

    DEFF Research Database (Denmark)

    Hvilsted Nielsen, Helle; Toft-Hansen, Henrik; Lambertsen, Kate Lykke;

    2011-01-01

    In multiple sclerosis (MS), myelin-specific T cells are normally associated with destruction of myelin and axonal damage. However, in acute MS plaque, remyelination occurs concurrent with T-cell infiltration, which raises the question of whether T cells might stimulate myelin repair. We investiga...... of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system....

  12. Gr1(intCD11b+ myeloid-derived suppressor cells in Mycobacterium tuberculosis infection.

    Directory of Open Access Journals (Sweden)

    Andrés Obregón-Henao

    Full Text Available BACKGROUND: Tuberculosis is one of the world's leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1(intCD11b(+ cells are called myeloid-derived suppressor cells (MDSC and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design. METHODOLOGY/PRINCIPAL FINDINGS: We compared the bacterial burden, lung pathology and Gr1(intCD11b(+ myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1(+ cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1(+CD11b(+ cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1(hi and Gr1(int populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1(int populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1(hi and Gr1(int cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4(+ T to Gr1(+ cells increased. Our results

  13. Gr1intCD11b+ Myeloid-Derived Suppressor Cells in Mycobacterium tuberculosis Infection

    Science.gov (United States)

    Obregón-Henao, Andrés; Henao-Tamayo, Marcela; Orme, Ian M.; Ordway, Diane J.

    2013-01-01

    Background Tuberculosis is one of the world’s leading killers, stealing 1.4 million lives and causing 8.7 million new and relapsed infections in 2011. The only vaccine against tuberculosis is BCG which demonstrates variable efficacy in adults worldwide. Human infection with Mycobacterium tuberculosis results in the influx of inflammatory cells to the lung in an attempt to wall off bacilli by forming a granuloma. Gr1intCD11b+ cells are called myeloid-derived suppressor cells (MDSC) and play a major role in regulation of inflammation in many pathological conditions. Although MDSC have been described primarily in cancer their function in tuberculosis remains unknown. During M. tuberculosis infection it is crucial to understand the function of cells involved in the regulation of inflammation during granuloma formation. Understanding their relative impact on the bacilli and other cellular phenotypes is necessary for future vaccine and drug design. Methodology/Principal Findings We compared the bacterial burden, lung pathology and Gr1intCD11b+ myeloid-derived suppressor cell immune responses in M. tuberculosis infected NOS2-/-, RAG-/-, C3HeB/FeJ and C57/BL6 mice. Gr-1+ cells could be found on the edges of necrotic lung lesions in NOS2-/-, RAG-/-, and C3HeB/FeJ, but were absent in wild-type mice. Both populations of Gr1+CD11b+ cells expressed high levels of arginase-1, and IL-17, additional markers of myeloid derived suppressor cells. We then sorted the Gr1hi and Gr1int populations from M. tuberculosis infected NOS-/- mice and placed the sorted both Gr1int populations at different ratios with naïve or M. tuberculosis infected splenocytes and evaluated their ability to induce activation and proliferation of CD4+T cells. Our results showed that both Gr1hi and Gr1int cells were able to induce activation and proliferation of CD4+ T cells. However this response was reduced as the ratio of CD4+ T to Gr1+ cells increased. Our results illustrate a yet unrecognized interplay

  14. Dendritic Cells Enhance HIV Infection of Memory CD4(+) T Cells in Human Lymphoid Tissues.

    Science.gov (United States)

    Reyes-Rodriguez, Angel L; Reuter, Morgan A; McDonald, David

    2016-02-01

    Dendritic cells (DCs) play a key role in controlling infections by coordinating innate and adaptive immune responses to invading pathogens. Paradoxically, DCs can increase HIV-1 dissemination in vitro by binding and transferring infectious virions to CD4(+) T cells, a process called transinfection. Transinfection has been well characterized in cultured cell lines and circulating primary T cells, but it is unknown whether DCs enhance infection of CD4(+) T cells in vivo. In untreated HIV infection, massive CD4(+) T-cell infection and depletion occur in secondary lymphoid tissues long before decline is evident in the peripheral circulation. To study the role of DCs in HIV infection of lymphoid tissues, we utilized human tonsil tissues, cultured either as tissue blocks or as aggregate suspension cultures, in single-round infection experiments. In these experiments, addition of monocyte-derived DCs (MDDCs) to the cultures increased T-cell infection, particularly in CD4(+) T cells expressing lower levels of HLA-DR. Subset analysis demonstrated that MDDCs increased HIV-1 infection of central and effector memory T-cell populations. Depletion of endogenous myeloid DCs (myDCs) from the cultures decreased memory T-cell infection, and readdition of MDDCs restored infection to predepletion levels. Using an HIV-1 fusion assay, we found that MDDCs equally increased HIV delivery into naïve, central, and effector memory T cells in the cultures, whereas predepletion of myDCs reduced fusion into memory T cells. Together, these data suggest that resident myDCs facilitate memory T-cell infection in lymphoid tissues, implicating DC-mediated transinfection in driving HIV dissemination within these tissues in untreated HIV/AIDS.

  15. Dynamics of Epstein-Barr Virus (EBV) in human immunodeficiency virus (HIV)-1 infected adults and children

    OpenAIRE

    Petrara, Maria Raffaella

    2013-01-01

    Epstein-Barr Virus (EBV) is involved in a wide range of malignancies, particularly in immunocompromised subjects. Besides immunodepression, chronic immune activation may induce B-cell stimulation leading to an expansion of EBV-infected cells, thus increasing the risk of EBV-related malignancies. The factors that may contribute to HIV-1-induced B cell activation and expansion of EBV-infected cells are largely unknown. In Africa EBV primary infection occurs during infancy and early childhood a...

  16. Infantile and adult testicular germ cell tumors : a different pathogenesis?

    NARCIS (Netherlands)

    van Echten, J; Timmer, A; van der Veen, AY; Molenaar, WM; de Jong, B

    2002-01-01

    Most adult testicular germ cell tumors have a characteristic chromosomal abnormality that is an isochromosome 12p [i(12p)]. Furthermore. these tumors are characterized by a chromosome number in the triploid range and gains and losses of (parts of) specific chromosomes. Cytogenetic investigation of t

  17. Translocation Renal Cell Carcinomas in Adults: A Single Institution Experience

    OpenAIRE

    Zhong, Minghao; De Angelo, Patricia; Osborne, Lisa; Mondolfi, Paniz; Geller, Matthew; Yang, Youfeng; Linehan, W. Marston; Merino, Maria J.; Cordon-Cardo, Carlos; Cai, Dongming

    2012-01-01

    Translocation renal cell carcinoma is a newly recognized subtype of renal cell carcinoma (RCC) with chromosomal translocations involving TFE3 (Xp11.2) or, less frequently, TFEB (6p21). Xp11 translocation RCC was originally described as a pediatric neoplasm representing 20–40% of pediatric RCCs with a much lower frequency in the adult population. TFEB translocation RCC is very rare, with approximately 10 cases reported in the literature. Here, we describe the clinicopathological features of ad...

  18. Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement

    OpenAIRE

    Bruno Araujo; Francisco Costa; Joanne Lopes; Ricardo Castro

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocyt...

  19. Morphometric study of Schistosoma mansoni adult worms recovered from undernourished infected mice

    Directory of Open Access Journals (Sweden)

    Oliveira Sheilla A

    2003-01-01

    Full Text Available Some unfavourable effects of malnutrition of the host on Schistosoma mansoni worm biology and structure have been reported based upon brigthfield microscopy. This paper aims to study by morphometric techniques, some morphological parameters in male and female adult worms recovered from undernourished albino mice in comparison with parasites recovered from well-fed infected mice. Undernourished animals were fed a multideficient and essentially low protein diet (RBD diet and compared to well-fed control mice fed with the commercial diet NUVILAB. Seventy-five days post-infection with 80 cercarie (BL strain animals were sacrificed. All adult worms were fixed in 10% formalin and stained with carmine chloride. One hundred male and 60 female specimens from each group (undernourished and control were examined using an image system analysis Leica Quantimet 500C and the Sigma Scan Measurement System. The following morphometrical parameters were studied: body length and width, oral and ventral suckers, number and area of testicular lobes, length and width of ovary and uterine egg. For statistical analysis, the Student's t test for unpaired samples was applied. Significant differences (p < 0.05 were detected in body length and width, in parameters of suckers, uterine egg width, ovary length and area of testicular lobes, with lower values for specimens from undernourished mice. The nutritional status of the host has negative influence on S. mansoni adult worms, probably through unavailability of essential nutrients to the parasites.

  20. Potent inhibition of Junín virus infection by interferon in murine cells.

    Science.gov (United States)

    Huang, Cheng; Walker, Aida G; Grant, Ashley M; Kolokoltsova, Olga A; Yun, Nadezhda E; Seregin, Alexey V; Paessler, Slobodan

    2014-06-01

    The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice.

  1. Early events associated with infection of Epstein-Barr virus infection of primary B-cells.

    Directory of Open Access Journals (Sweden)

    Sabyasachi Halder

    Full Text Available Epstein Barr virus (EBV is closely associated with the development of a vast number of human cancers. To develop a system for monitoring early cellular and viral events associated with EBV infection a self-recombining BAC containing 172-kb of the Epstein Barr virus genome BAC-EBV designated as MD1 BAC (Chen et al., 2005, J.Virology was used to introduce an expression cassette of green fluorescent protein (GFP by homologous recombination, and the resultant BAC clone, BAC-GFP-EBV was transfected into the HEK 293T epithelial cell line. The resulting recombinant GFP EBV was induced to produce progeny virus by chemical inducer from the stable HEK 293T BAC GFP EBV cell line and the virus was used to immortalize human primary B-cell as monitored by green fluorescence and outgrowth of the primary B cells. The infection, B-cell activation and cell proliferation due to GFP EBV was monitored by the expression of the B-cell surface antigens CD5, CD10, CD19, CD23, CD39, CD40 , CD44 and the intercellular proliferation marker Ki-67 using Flow cytometry. The results show a dramatic increase in Ki-67 which continues to increase by 6-7 days post-infection. Likewise, CD40 signals showed a gradual increase, whereas CD23 signals were increased by 6-12 hours, maximally by 3 days and then decreased. Monitoring the viral gene expression pattern showed an early burst of lytic gene expression. This up-regulation of lytic gene expression prior to latent genes during early infection strongly suggests that EBV infects primary B-cell with an initial burst of lytic gene expression and the resulting progeny virus is competent for infecting new primary B-cells. This process may be critical for establishment of latency prior to cellular transformation. The newly infected primary B-cells can be further analyzed for investigating B cell activation due to EBV infection.

  2. In Vivo Dedifferentiation of Adult Adipose Cells

    OpenAIRE

    Yunjun Liao; Zhaowei Zeng; Feng Lu; Ziqing Dong; Qiang Chang; Jianhua Gao

    2015-01-01

    Introduction Adipocytes can dedifferentiate into fibroblast-like cells in vitro and thereby acquire proliferation and multipotent capacities to participate in the repair of various organs and tissues. Whether dedifferentiation occurs under physiological or pathological conditions in vivo is unknown. Methods A tissue expander was placed under the inguinal fat pads of rats and gradually expanded by injection of water. Samples were collected at various time points, and morphological, histologica...

  3. Calcium exchange, structure, and function in cultured adult myocardial cells

    International Nuclear Information System (INIS)

    Cells digested from adult rat heart and cultured for 14 days demonstrate all the structural elements, in mature form, associated with the process of excitation-contraction (EC) coupling. The transverse tubular (TT) system is well developed with an extensive junctional sarcoplasmic reticulum (JSR). In nonphosphate-containing buffer contraction of the cells is lost as rapidly as zero extracellular Ca concentration ([Ca]0) solution is applied and a negative contraction staircase is produced on increase of stimulation frequency. Structurally and functionally the cells have the characteristics of adult cells in situ. 45Ca exchange and total 45Ca measurement in N-2-hydroxyethylpiperazine N'-2-ethanesulfonic acid (HEPES)-buffered perfusate define three components of cellular Ca: 1) a rapidly exchangeable component accounting for 36% of total Ca, 2) a slowly exchangeable component (t/sub 1/2/ 53 min) accounting for 7% total Ca, and 3) the remaining 57% cellular Ca is inexchangeable (demonstrates no significant exchange within 60 min). The slowly exchangeable component can be increased 10-fold within 60 min by addition of phosphate to the perfusate. The Ca distribution and exchange characteristics are little different from those of 3-day cultures of neonatal rat heart previously studied. The results suggest that the cells are representative of adult cells in situ and that both sarcolemmal-bound and sarcoplasmic reticular Ca contribute to the component of Ca that is rapidly exchangeable

  4. Vaccination against feline immunodeficiency virus using fixed infected cells

    NARCIS (Netherlands)

    Horzinek, M.C.; Verschoor, E.J.; Vliet, A.L.W. van; Egberink, H.F.; Hesselink, W.; Alphen, W.E. van; Joosten, I.; Boog, C.J.P.; Ronde, A. de

    1995-01-01

    Crandell feline kidney cells and feline thymocytes, either feline immunodeficiency virus (FIV) infected or uninfected, were fixed with paraformaldehyde and used to vaccinate cats. The cells were mixed with a 30:70 water/mineral oil emulsion containing 250 mu g ml−1 N-acetyl-d-glucosaminyl-beta-(1 4)

  5. Hepatitis C virus infection of cholangiocarcinoma cell lines

    NARCIS (Netherlands)

    Fletcher, Nicola F.; Humphreys, Elizabeth; Jennings, Elliott; Osburn, William; Lissauer, Samantha; Wilson, Garrick K.; van Ijzendoorn, Sven C. D.; Baumert, Thomas F.; Balfe, Peter; Afford, Simon; McKeating, Jane A.

    2015-01-01

    Hepatitis C virus (HCV) infects the liver and hepatocytes are the major cell type supporting viral replication. Hepatocytes and cholangiocytes derive from a common hepatic progenitor cell that proliferates during inflammatory conditions, raising the possibility that cholangiocytes may support HCV re

  6. Multiploid CD61+ cells are the pre-dominant cell lineage infected during acute dengue virus infection in bone marrow.

    Directory of Open Access Journals (Sweden)

    Kristina B Clark

    Full Text Available Depression of the peripheral blood platelet count during acute infection is a hallmark of dengue. This thrombocytopenia has been attributed, in part, to an insufficient level of platelet production by megakaryocytes that reside in the bone marrow (BM. Interestingly, it was observed that dengue patients experience BM suppression at the onset of fever. However, few studies focus on the interaction between dengue virus (DENV and megakaryocytes and how this interaction can lead to a reduction in platelets. In the studies reported herein, BM cells from normal healthy rhesus monkeys (RM and humans were utilized to identify the cell lineage(s that were capable of supporting virus infection and replication. A number of techniques were employed in efforts to address this issue. These included the use of viral RNA quantification, nonstructural protein and infectivity assays, phenotypic studies utilizing immunohistochemical staining, anti-differentiation DEAB treatment, and electron microscopy. Cumulative results from these studies revealed that cells in the BM were indeed highly permissive for DENV infection, with human BM having higher levels of viral production compared to RM. DENV-like particles were predominantly observed in multi-nucleated cells that expressed CD61+. These data suggest that megakaryocytes are likely the predominant cell type infected by DENV in BM, which provides one explanation for the thrombocytopenia and the dysfunctional platelets characteristic of dengue virus infection.

  7. Outbreak of respiratory syncytial virus (RSV) infection in immunocompromised adults on a hematology ward.

    Science.gov (United States)

    Jensen, Tomas Ostergaard; Stelzer-Braid, Sacha; Willenborg, Christiana; Cheung, Carol; Andresen, David; Rawlinson, William; Clezy, Kate

    2016-10-01

    We describe an outbreak of respiratory syncytial virus (RSV) infection on a hematology ward without allogeneic stem cell transplant patients. Twelve patients and one staff member infected with RSV were identified from the laboratory database. Five patients had lower respiratory tract infection, seven had upper respiratory tract infection, one was asymptomatic, and there were two (15.4%) deaths. Most patients had overlapping periods of potential infectiousness on the ward. Sequencing was possible on eight specimens and five of these had identical sequences. Results were consistent with transmission occurring both on the ward and by introduction of RSV from the community. J. Med. Virol. 88:1827-1831, 2016. © 2016 Wiley Periodicals, Inc. PMID:26990584

  8. Immunosuppressive CD71+ erythroid cells compromise neonatal host defence against infection

    Science.gov (United States)

    Elahi, Shokrollah; Ertelt, James M.; Kinder, Jeremy M.; Jiang, Tony T.; Zhang, Xuzhe; Xin, Lijun; Chaturvedi, Vandana; Strong, Beverly S.; Qualls, Joseph E.; Steinbrecher, Kris A.; Kalfa, Theodosia A.; Shaaban, Aimen F.; Way, Sing Sing

    2013-12-01

    Newborn infants are highly susceptible to infection. This defect in host defence has generally been ascribed to the immaturity of neonatal immune cells; however, the degree of hyporesponsiveness is highly variable and depends on the stimulation conditions. These discordant responses illustrate the need for a more unified explanation for why immunity is compromised in neonates. Here we show that physiologically enriched CD71+ erythroid cells in neonatal mice and human cord blood have distinctive immunosuppressive properties. The production of innate immune protective cytokines by adult cells is diminished after transfer to neonatal mice or after co-culture with neonatal splenocytes. Neonatal CD71+ cells express the enzyme arginase-2, and arginase activity is essential for the immunosuppressive properties of these cells because molecular inhibition of this enzyme or supplementation with L-arginine overrides immunosuppression. In addition, the ablation of CD71+ cells in neonatal mice, or the decline in number of these cells as postnatal development progresses parallels the loss of suppression, and restored resistance to the perinatal pathogens Listeria monocytogenes and Escherichia coli. However, CD71+ cell-mediated susceptibility to infection is counterbalanced by CD71+ cell-mediated protection against aberrant immune cell activation in the intestine, where colonization with commensal microorganisms occurs swiftly after parturition. Conversely, circumventing such colonization by using antimicrobials or gnotobiotic germ-free mice overrides these protective benefits. Thus, CD71+ cells quench the excessive inflammation induced by abrupt colonization with commensal microorganisms after parturition. This finding challenges the idea that the susceptibility of neonates to infection reflects immune-cell-intrinsic defects and instead highlights processes that are developmentally more essential and inadvertently mitigate innate immune protection. We anticipate that these

  9. Hyperparathyroidism and Complications Associated with Vitamin D Deficiency in HIV-Infected Adults in New York City, New York

    OpenAIRE

    Kwan, Candice K.; Eckhardt, Benjamin; Baghdadi, Jonathan; Judith A. Aberg

    2012-01-01

    Although recent studies report a high prevalence of vitamin D deficiency in HIV-infected adults similar to that in the general population, metabolic complications of vitamin D deficiency may be worsened with HIV infection and remain insufficiently characterized. We conducted a retrospective cross-sectional cohort study to determine prevalence and correlates of vitamin D deficiency and hyperparathyroidism among HIV-infected patients attending an urban clinic. Vitamin D deficiency was defined a...

  10. Langerhans cell histiocytosis in the adult.

    Science.gov (United States)

    Malpas, J S; Norton, A J

    1996-12-01

    A study of 47 well-documented patients with Langerhans cell histiocytosis (LCH) showed a slight female preponderance, with onset as late as the ninth decade. The skin was the commonest site of presentation, but pulmonary and bone involvement was frequent. Patients with single-site disease did best. The worst prognosis was seen in the elderly or those with organ dysfunction. A high incidence of associated malignant disease was seen, which could precede, be coincidental with, or occur after a diagnosis of LCH. PMID:8888814

  11. Plasma cytokine levels in Tanzanian HIV-1-infected adults and the effect of antiretroviral treatment

    DEFF Research Database (Denmark)

    Haissman, J.M.; Vestergaard, L.S.; Sembuche, S.;

    2009-01-01

    counts below 200 cells per microliter than individuals with CD4 cell counts above 200 cells per microliter. HIV RNA was the strongest predictor of all cytokine expression in multivariate analysis. ART leads to a decrease in all cytokines to levels close to those of HIV-uninfected individuals. CONCLUSIONS......OBJECTIVE: To evaluate the role immune activation leading to the production and circulation of cytokines has in the pathogenesis of HIV infection in sub-Saharan Africa and the effect of antiretroviral treatment (ART) on these parameters. METHODS: Plasma concentrations of tumor necrosis factor (TNF......)-alpha, interleukin (IL)-6, IL-8, monocyte chemotactic protein (MCP)-1, IL-10, and IL-1 receptor antagonist; plasma HIV RNA; hemoglobin concentration; and white blood cells were measured in 229 HIV-infected, 54 HIV-uninfected, and after 2 and 4 months, respectively, of ART in 35 eligible individuals in northeastern...

  12. Anti-adult T-cell leukemia/lymphoma effects of indole-3-carbinol

    Directory of Open Access Journals (Sweden)

    Okudaira Taeko

    2009-01-01

    Full Text Available Abstract Background Adult T-cell leukemia/lymphoma (ATLL is a malignancy derived from T cells infected with human T-cell leukemia virus type 1 (HTLV-1, and it is known to be resistant to standard anticancer therapies. Indole-3-carbinol (I3C, a naturally occurring component of Brassica vegetables such as cabbage, broccoli and Brussels sprout, is a promising chemopreventive agent as it is reported to possess antimutagenic, antitumorigenic and antiestrogenic properties in experimental studies. The aim of this study was to determine the potential anti-ATLL effects of I3C both in vitro and in vivo. Results In the in vitro study, I3C inhibited cell viability of HTLV-1-infected T-cell lines and ATLL cells in a dose-dependent manner. Importantly, I3C did not exert any inhibitory effect on uninfected T-cell lines and normal peripheral blood mononuclear cells. I3C prevented the G1/S transition by reducing the expression of cyclin D1, cyclin D2, Cdk4 and Cdk6, and induced apoptosis by reducing the expression of XIAP, survivin and Bcl-2, and by upregulating the expression of Bak. The induced apoptosis was associated with activation of caspase-3, -8 and -9, and poly(ADP-ribose polymerase cleavage. I3C also suppressed IκBα phosphorylation and JunD expression, resulting in inactivation of NF-κB and AP-1. Inoculation of HTLV-1-infected T cells in mice with severe combined immunodeficiency resulted in tumor growth. The latter was inhibited by treatment with I3C (50 mg/kg/day orally, but not the vehicle control. Conclusion Our preclinical data suggest that I3C could be potentially a useful chemotherapeutic agent for patients with ATLL.

  13. Exosomes Secreted by Toxoplasma gondii-Infected L6 Cells: Their Effects on Host Cell Proliferation and Cell Cycle Changes

    OpenAIRE

    Kim, Min Jae; Jung, Bong-Kwang; Cho, Jaeeun; Song, Hyemi; Pyo, Kyung-Ho; Lee, Ji Min; Kim, Min-Kyung; Chai, Jong-Yil

    2016-01-01

    Toxoplasma gondii infection induces alteration of the host cell cycle and cell proliferation. These changes are not only seen in directly invaded host cells but also in neighboring cells. We tried to identify whether this alteration can be mediated by exosomes secreted by T. gondii-infected host cells. L6 cells, a rat myoblast cell line, and RH strain of T. gondii were selected for this study. L6 cells were infected with or without T. gondii to isolate exosomes. The cellular growth patterns w...

  14. Satellite cell proliferation in adult skeletal muscle

    Science.gov (United States)

    Booth, Frank W. (Inventor); Thomason, Donald B. (Inventor); Morrison, Paul R. (Inventor); Stancel, George M. (Inventor)

    1995-01-01

    Novel methods of retroviral-mediated gene transfer for the in vivo corporation and stable expression of eukaryotic or prokaryotic foreign genes in tissues of living animals is described. More specifically, methods of incorporating foreign genes into mitotically active cells are disclosed. The constitutive and stable expression of E. coli .beta.-galactosidase gene under the promoter control of the Moloney murine leukemia virus long terminal repeat is employed as a particularly preferred embodiment, by way of example, establishes the model upon which the incorporation of a foreign gene into a mitotically-active living eukaryotic tissue is based. Use of the described methods in therapeutic treatments for genetic diseases, such as those muscular degenerative diseases, is also presented. In muscle tissue, the described processes result in genetically-altered satellite cells which proliferate daughter myoblasts which preferentially fuse to form a single undamaged muscle fiber replacing damaged muscle tissue in a treated animal. The retroviral vector, by way of example, includes a dystrophin gene construct for use in treating muscular dystrophy. The present invention also comprises an experimental model utilizable in the study of the physiological regulation of skeletal muscle gene expression in intact animals.

  15. Characterization of TLX Expression in Neural Stem Cells and Progenitor Cells in Adult Brains

    OpenAIRE

    Shengxiu Li; Guoqiang Sun; Kiyohito Murai; Peng Ye; Yanhong Shi

    2012-01-01

    TLX has been shown to play an important role in regulating the self-renewal and proliferation of neural stem cells in adult brains. However, the cellular distribution of endogenous TLX protein in adult brains remains to be elucidated. In this study, we used immunostaining with a TLX-specific antibody to show that TLX is expressed in both neural stem cells and transit-amplifying neural progenitor cells in the subventricular zone (SVZ) of adult mouse brains. Then, using a double thymidine analo...

  16. [Serological evaluation of Bordetella pertussis infection in adults with prolonged cough].

    Science.gov (United States)

    Sönmez, Cemile; Çöplü, Nilay; Gözalan, Ayşegül; Yılmaz, Ülkü; Bilekli, Selen; Demirci, Nilgün Yılmaz; Biber, Çiğdem; Erdoğan, Yurdanur; Esen, Berrin; Çöplü, Lütfi

    2016-07-01

    Pertussis is a vaccine-preventable disease that is transmitted from infected to susceptible individuals by respiratory route. Bordetella pertussis infection may occur at any age as neither vaccine nor natural infection induced immunity lasts life-long. This study was planned to demonstrate the serological evidence of infection among adults, to raise awareness among clinicians and to provide data for the development of strategies to protect vulnerable infants. A total of 538 patients (345 female, 193 male) ages between 18-87 years who had a complain of prolonged cough for more than two weeks were included in the study. Anti-pertussis toxin (PT) IgG and anti-filamentous hemagglutinin (FH) IgG levels from single serum samples were measured by an in-house ELISA test which was standardized and shown to be efficient previously. Anti-PT IgG antibody levels of ≥ 100 EU/ml were considered as acute/recent infection with B.pertussis. In our study, 9.7% (52/538) of the patients had high levels of anti-PT IgG (≥ 100 EU/ml) and among those patients 43 (43/52; 82.7%) also had high (≥ 100 EU/ml) anti-FHA IgG levels. There were no statistically significant differences in terms of age, gender, education level, DPT (diphtheria-pertussis-tetanus) vaccination history, smoking history or average daily cigarette consumption (p> 0.05) between the cases with high antibody levels (n= 52). When the symptoms and the presence of cases with high antibody levels were evaluated, it was detected that no one parameter was significantly different from others, except that 24.1% of the cases with inspiratory whooping had high anti-PT levels. There was also no statistically significant difference between high anti-PT levels ≥ 100 EU/ml and the patients with risk factors [smoking (21/200; 10.5%), presence of disease that cause chronic cough and/or drug usage (19/171; %11.1), and whole factors which cause chronic cough (32/306; %10.5)] and without risk factors (p= 0.581; p= 0.357; p= 0

  17. [Serological evaluation of Bordetella pertussis infection in adults with prolonged cough].

    Science.gov (United States)

    Sönmez, Cemile; Çöplü, Nilay; Gözalan, Ayşegül; Yılmaz, Ülkü; Bilekli, Selen; Demirci, Nilgün Yılmaz; Biber, Çiğdem; Erdoğan, Yurdanur; Esen, Berrin; Çöplü, Lütfi

    2016-07-01

    Pertussis is a vaccine-preventable disease that is transmitted from infected to susceptible individuals by respiratory route. Bordetella pertussis infection may occur at any age as neither vaccine nor natural infection induced immunity lasts life-long. This study was planned to demonstrate the serological evidence of infection among adults, to raise awareness among clinicians and to provide data for the development of strategies to protect vulnerable infants. A total of 538 patients (345 female, 193 male) ages between 18-87 years who had a complain of prolonged cough for more than two weeks were included in the study. Anti-pertussis toxin (PT) IgG and anti-filamentous hemagglutinin (FH) IgG levels from single serum samples were measured by an in-house ELISA test which was standardized and shown to be efficient previously. Anti-PT IgG antibody levels of ≥ 100 EU/ml were considered as acute/recent infection with B.pertussis. In our study, 9.7% (52/538) of the patients had high levels of anti-PT IgG (≥ 100 EU/ml) and among those patients 43 (43/52; 82.7%) also had high (≥ 100 EU/ml) anti-FHA IgG levels. There were no statistically significant differences in terms of age, gender, education level, DPT (diphtheria-pertussis-tetanus) vaccination history, smoking history or average daily cigarette consumption (p> 0.05) between the cases with high antibody levels (n= 52). When the symptoms and the presence of cases with high antibody levels were evaluated, it was detected that no one parameter was significantly different from others, except that 24.1% of the cases with inspiratory whooping had high anti-PT levels. There was also no statistically significant difference between high anti-PT levels ≥ 100 EU/ml and the patients with risk factors [smoking (21/200; 10.5%), presence of disease that cause chronic cough and/or drug usage (19/171; %11.1), and whole factors which cause chronic cough (32/306; %10.5)] and without risk factors (p= 0.581; p= 0.357; p= 0

  18. Preventing Infections in Sickle Cell Disease: The Unfinished Business.

    Science.gov (United States)

    Obaro, Stephen K; Tam, P Y Iroh

    2016-05-01

    While encapsulated bacterial agents, particularly Streptococcus pneumoniae, are recognized as important microbes that are associated with serious illness in hosts with sickle cell disease (SCD), multiple pathogens are implicated in infectious manifestations of SCD. Variations in clinical practice have been an obstacle to the universal implementation of infection preventive management through active, targeted vaccination of these individuals and routine usage of antibiotic prophylaxis. Paradoxically, in low-income settings, there is evidence that SCD also increases the risk for several other infections that warrant additional infection preventive measures. The infection preventive care among patients with SCD in developed countries does not easily translate to the adoption of these recommendations globally, which must take into account the local epidemiology of infections, available vaccines and population-specific vaccine efficacy, environment, health care behaviors, and cultural beliefs, as these are all factors that play a complex role in the manifestation of SCD and the prevention of infectious disease morbidity. PMID:26840500

  19. Preventing Infections in Sickle Cell Disease: The Unfinished Business.

    Science.gov (United States)

    Obaro, Stephen K; Tam, P Y Iroh

    2016-05-01

    While encapsulated bacterial agents, particularly Streptococcus pneumoniae, are recognized as important microbes that are associated with serious illness in hosts with sickle cell disease (SCD), multiple pathogens are implicated in infectious manifestations of SCD. Variations in clinical practice have been an obstacle to the universal implementation of infection preventive management through active, targeted vaccination of these individuals and routine usage of antibiotic prophylaxis. Paradoxically, in low-income settings, there is evidence that SCD also increases the risk for several other infections that warrant additional infection preventive measures. The infection preventive care among patients with SCD in developed countries does not easily translate to the adoption of these recommendations globally, which must take into account the local epidemiology of infections, available vaccines and population-specific vaccine efficacy, environment, health care behaviors, and cultural beliefs, as these are all factors that play a complex role in the manifestation of SCD and the prevention of infectious disease morbidity.

  20. Helicobacter pylori infection generates genetic instability in gastric cells

    DEFF Research Database (Denmark)

    Machado, Ana Manuel Dantas; Figueiredo, Céu; Seruca, Raquel;

    2010-01-01

    The discovery that Helicobacter pylori is associated with gastric cancer has led to numerous studies that investigate the mechanisms by which H. pylori induces carcinogenesis. Gastric cancer shows genetic instability both in nuclear and mitochondrial DNA, besides impairment of important DNA repair...... pathways. As such, this review highlights the consequences of H. pylori infection on the integrity of DNA in the host cells. By down-regulating major DNA repair pathways, H. pylori infection has the potential to generate mutations. In addition, H. pylori infection can induce direct changes on the DNA...... of the host, such as oxidative damage, methylation, chromosomal instability, microsatellite instability, and mutations. Interestingly, H. pylori infection generates genetic instability in nuclear and mitochondrial DNA. Based on the reviewed literature we conclude that H. pylori infection promotes gastric...

  1. Adult stem cells applied to tissue engineering and regenerative medicine.

    Science.gov (United States)

    Cuenca-López, M D; Zamora-Navas, P; García-Herrera, J M; Godino, M; López-Puertas, J M; Guerado, E; Becerra, J; Andrades, J A

    2008-01-01

    Regeneration takes place in the body at a moment or another throughout life. Bone, cartilage, and tendons (the key components of the structure and articulation in the body) have a limited capacity for self-repair and, after traumatic injury or disease, the regenerative power of adult tissue is often insufficient. When organs or tissues are irreparably damaged, they may be replaced by an artificial device or by a donor organ. However, the number of available donor organs is considerably limited. Generation of tissue-engineered replacement organs by extracting stem cells from the patient, growing them and modifying them in clinical conditions after re-introduction in the body represents an ideal source for corrective treatment. Mesenchymal stem cells (MSCs) are the multipotential progenitors that give rise to skeletal cells, vascular smooth muscle cells, muscle (skeletal and cardiac muscle), adipocytes (fat tissue) and hematopoietic (blood)-supportive stromal cells. MSCs are found in multiple connective tissues, in adult bone marrow, skeletal muscles and fat pads. The wide representation in adult tissues may be related to the existence of a circulating blood pool or that MSCs are associated to the vascular system.

  2. Germ Cell Tumors in Adolescents and Young Adults.

    Science.gov (United States)

    Calaminus, Gabriele; Joffe, Jonathan

    2016-01-01

    Germ cell tumors (GCTs) represent a group of biologically complex malignancies that affect patients at different sites within the body and at different ages. The varying nature of these tumors reflects their cell of origin which is the primordial germ cell, which normally gives rise to ovarian and testicular egg and sperm producing cells. These cells retain an ability to give rise to all types of human tissues, and this is illustrated by the different kinds of GCTs that occur. In adolescent and young adult (AYA) patients, GCTs predominantly present as testicular, ovarian or mediastinal primary GCTs, and represent some of the most complex therapeutic challenges within any AYA practice. The varying types of GCTs, defined by primary site and/or age at presentation, can look very similar microscopically. However, there is growing evidence that they may have different molecular characteristics, different biology and different requirements for curative treatments. Whilst in adult testicular GCTs there is evidence for an environmental cause during fetal development and a genetic component, these causative factors are much less well understood in other GCTs. GCTs are some of the most curable cancers in adults, but some patients exhibit resistance to standard treatments. Because of this, today's clinical research is directed at understanding how to best utilize toxic therapies and promote healthy survivorship. This chapter explores the biology, behavior and treatment of GCTs and discusses how the AYA group of GCTs may hold some of the keys to understanding fundamental unanswered questions of biological variance and curability in GCTs. PMID:27595361

  3. Activation of Natural Killer cells during microbial infections

    Directory of Open Access Journals (Sweden)

    Amir eHorowitz

    2012-01-01

    Full Text Available Natural killer (NK cells are large granular lymphocytes that express a diverse array of germline encoded inhibitory and activating receptors for MHC Class I and Class I-like molecules, classical co-stimulatory ligands and cytokines. The ability of NK cells to be very rapidly activated by inflammatory cytokines, to secrete effector cytokines and to kill infected or stressed host cells, suggests that they may be among the very early responders during infection. Recent studies have also identified a small number of pathogen-derived ligands that can bind to NK cell surface receptors and directly induce their activation. Here we review recent studies that have begun to elucidate the various pathways by which viral, bacterial and parasite pathogens activate NK cells. We also consider two emerging themes of NK cell-pathogen interactions, namely their contribution to adaptive immune responses and their potential to take on regulatory and immunomodulatory functions.

  4. Modeling dynamics of HIV infected cells using stochastic cellular automaton

    Science.gov (United States)

    Precharattana, Monamorn; Triampo, Wannapong

    2014-08-01

    Ever since HIV was first diagnosed in human, a great number of scientific works have been undertaken to explore the biological mechanisms involved in the infection and progression of the disease. Several cellular automata (CA) models have been introduced to gain insights into the dynamics of the disease progression but none of them has taken into account effects of certain immune cells such as the dendritic cells (DCs) and the CD8+ T lymphocytes (CD8+ T cells). In this work, we present a CA model, which incorporates effects of the HIV specific immune response focusing on the cell-mediated immunities, and investigate the interaction between the host immune response and the HIV infected cells in the lymph nodes. The aim of our work is to propose a model more realistic than the one in Precharattana et al. (2010) [10], by incorporating roles of the DCs, the CD4+ T cells, and the CD8+ T cells into the model so that it would reproduce the HIV infection dynamics during the primary phase of HIV infection.

  5. In vivo cell tracking and quantification method in adult zebrafish

    Science.gov (United States)

    Zhang, Li; Alt, Clemens; Li, Pulin; White, Richard M.; Zon, Leonard I.; Wei, Xunbin; Lin, Charles P.

    2012-03-01

    Zebrafish have become a powerful vertebrate model organism for drug discovery, cancer and stem cell research. A recently developed transparent adult zebrafish using double pigmentation mutant, called casper, provide unparalleled imaging power in in vivo longitudinal analysis of biological processes at an anatomic resolution not readily achievable in murine or other systems. In this paper we introduce an optical method for simultaneous visualization and cell quantification, which combines the laser scanning confocal microscopy (LSCM) and the in vivo flow cytometry (IVFC). The system is designed specifically for non-invasive tracking of both stationary and circulating cells in adult zebrafish casper, under physiological conditions in the same fish over time. The confocal imaging part in this system serves the dual purposes of imaging fish tissue microstructure and a 3D navigation tool to locate a suitable vessel for circulating cell counting. The multi-color, multi-channel instrument allows the detection of multiple cell populations or different tissues or organs simultaneously. We demonstrate initial testing of this novel instrument by imaging vasculature and tracking circulating cells in CD41: GFP/Gata1: DsRed transgenic casper fish whose thrombocytes/erythrocytes express the green and red fluorescent proteins. Circulating fluorescent cell incidents were recorded and counted repeatedly over time and in different types of vessels. Great application opportunities in cancer and stem cell researches are discussed.

  6. Recent advances in bone regeneration using adult stem cells.

    Science.gov (United States)

    Zigdon-Giladi, Hadar; Rudich, Utai; Michaeli Geller, Gal; Evron, Ayelet

    2015-04-26

    Bone is a highly vascularized tissue reliant on the close spatial and temporal association between blood vessels and bone cells. Therefore, cells that participate in vasculogenesis and osteogenesis play a pivotal role in bone formation during prenatal and postnatal periods. Nevertheless, spontaneous healing of bone fracture is occasionally impaired due to insufficient blood and cellular supply to the site of injury. In these cases, bone regeneration process is interrupted, which might result in delayed union or even nonunion of the fracture. Nonunion fracture is difficult to treat and have a high financial impact. In the last decade, numerous technological advancements in bone tissue engineering and cell-therapy opened new horizon in the field of bone regeneration. This review starts with presentation of the biological processes involved in bone development, bone remodeling, fracture healing process and the microenvironment at bone healing sites. Then, we discuss the rationale for using adult stem cells and listed the characteristics of the available cells for bone regeneration. The mechanism of action and epigenetic regulations for osteogenic differentiation are also described. Finally, we review the literature for translational and clinical trials that investigated the use of adult stem cells (mesenchymal stem cells, endothelial progenitor cells and CD34(+) blood progenitors) for bone regeneration.

  7. 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.

  8. TRIM32-dependent transcription in adult neural progenitor cells regulates neuronal differentiation

    OpenAIRE

    Hillje, Anna-Lena; Pavlou, Maria Angeliki; Beckmann, Elisabeth; Worlitzer, Maik; Bahnassawy, Lamiaa; Lewejohann, Lars; Palm, Thomas; Schwamborn, Jens Christian

    2013-01-01

    In the adult mammalian brain, neural stem cells in the subventricular zone continuously generate new neurons for the olfactory bulb. Cell fate commitment in these adult neural stem cells is regulated by cell fate-determining proteins. Here, we show that the cell fate-determinant TRIM32 is upregulated during differentiation of adult neural stem cells into olfactory bulb neurons. We further demonstrate that TRIM32 is necessary for the correct induction of neuronal differentiation in these cells...

  9. Seroprevalence and Risk Factors for Hepatitis B Infection in an Adult Population in Northeast China

    Directory of Open Access Journals (Sweden)

    Hong Zhang, Qingmei Li, Jie Sun, Chunyan Wang, Qing Gu, Xiangwei Feng, Bing Du, Wei Wang, Xiaodong Shi, Siqi Zhang, Wanyu Li, Yanfang Jiang, Junyan Feng, Shumei He, Junqi Niu

    2011-01-01

    Full Text Available Background and aim: The prevalence of the hepatitis B virus (HBV is higher in adults than in children. We determined the seroepidemiology of HBV infection in an adult population in JiLin, China, to guide effective preventive measures.Methods: A cross-sectional serosurvey was conducted throughout JiLin, China. A total of 3833 people was selected and demographic and behavioral information gathered. Serum samples were tested for HBV markers and liver enzymes.Results: The prevalence of the hepatitis B surface antigen (HBsAg, the antibody to the hepatitis B surface antigen (anti-HBs, the hepatitis B e antigen (HBeAg, the antibody to HBeAg (anti-HBe, and the antibody to the hepatitis B core antigen (anti-HBc were 4.38%, 35.66%, 1.38%, 6.65%, and 40.88%, respectively. Alanine aminotransferase (ALT and aspartate aminotransferase (AST levels were significantly higher among HBsAg (+ than HBsAg (- subjects. By multivariate logistic regression analysis, independent predictors for chronic HBV infection were smoking, poor sleep quality; occupation as private small-businessmen, laborers, or peasants; male gender; family history of HBV; personal history of vaccination; and older age. Independent predictors for exposure to HBV were large family size, occupation as a private small-businessman, male gender, family history of HBV, personal history of vaccination, and older age. Independent predictors for immunity by vaccination were occupation as a private small-businessman, high income, personal history of vaccination, and young age. Independent predictors for immunity by exposure were drinking, male gender, personal history of vaccination, and older age.Conclusions: The prevalence rate of HBV infection (4.38% was lower than the previous rate of general HBV vaccination. However, 44.59% of the population remained susceptible to HBV. The prevalence of HBV infection was high in young adults, private small-businessmen, peasants, those with a family history of HBV, and

  10. The Immunodominant Brugia malayi Paramyosin as a Marker of Current Infection with Wuchereria bancrofti Adult Worms

    OpenAIRE

    Langy, Sandra; Plichart, Catherine; Luquiaud, Patrick; Williams, Steven A.; Nicolas, Luc

    1998-01-01

    The full-length cDNA sequence encoding Brugia malayi L3 paramyosin has been isolated by immunoscreening a cDNA library with a mouse antiserum raised against Wuchereria bancrofti L3 infective larvae. A recombinant truncated form of paramyosin was expressed as a glutathione S-transferase fusion protein and used to evaluate humoral responses of adults from a W. bancrofti-endemic area in French Polynesia according to their parasitological status. Immunoglobulin G4 (IgG4) preferentially bound to p...

  11. Smoking behaviors in a community-based cohort of HIV-infected indigent adults

    OpenAIRE

    Vijayaraghavan, M.; Penko, J; Vittinghoff, E.; Bangsberg, DR; Miaskowski, C; Kushel, MB

    2014-01-01

    We conducted a longitudinal study of a community-based cohort of HIV-infected indigent adults to examine smoking behaviors and factors associated with quitting. We assessed "hardcore" smoking behaviors associated with a low probability of quitting. Of the 296 participants, 218 were current smokers (73.6 %). The prevalence of "hardcore" smoking was high: 59.6 % smoked ≥15 cigarettes per day, and 67.3 % were daily smokers. During the study interval, 20.6 % made at least one quit attempt. Of the...

  12. Molecular analysis of early host cell infection by Trypanosoma cruzi

    OpenAIRE

    Villalta, Fernando; Madison, M. Nia; Kleshchenko, Yuliya Y.; Nde, Pius N.; Lima, Maria F.

    2008-01-01

    Trypanosoma cruzi, the causative agent of Chagas heart disease, infects heart and other cells leading to cardiac arrest frequently followed by death (1). The disease affects millions of individuals in the Americas and is posing health problems because of blood transmission in the US due to large Latin American immigration (2–3). Since the current drugs present serious side effects and do not cure the chronic infection (4), it is critically important to understand the early process of cellular...

  13. Receptor-Dependent Coronavirus Infection of Dendritic Cells

    Science.gov (United States)

    Turner, Brian C.; Hemmila, Erin M.; Beauchemin, Nicole; Holmes, Kathryn V.

    2004-01-01

    In several mammalian species, including humans, coronavirus infection can modulate the host immune response. We show a potential role of dendritic cells (DC) in murine coronavirus-induced immune modulation and pathogenesis by demonstrating that the JAW SII DC line and primary DC from BALB/c mice and p/p mice with reduced expression of the murine coronavirus receptor, murine CEACAM1a, are susceptible to murine coronavirus infection by a receptor-dependent pathway. PMID:15113927

  14. Embryonic and adult neural stem cell research in China

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Neural stem cells(NSCs) are one specific type of multipotential stem cells that have the ability to proliferate for a long time and to differentiate into neural cells,including neurons,astrocytes and oligodendrocytes.These NSCs exist in both the embryonic and adult central nervous system(CNS) of all mammalian species.Progress has been made in the understanding of the developmental regulation of NSCs and their function in neurogenesis.This review discusses recent progress in this area,with emphasis on work done by investigators in China.

  15. Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

    Directory of Open Access Journals (Sweden)

    Kevon Parmesar

    2016-01-01

    Full Text Available Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients.

  16. Evidence for unapparent Brucella canis infections among adults with occupational exposure to dogs.

    Science.gov (United States)

    Krueger, W S; Lucero, N E; Brower, A; Heil, G L; Gray, G C

    2014-11-01

    Human serological assays designed to detect brucellosis will miss infections caused by Brucella canis, and low levels of periodic bacteremia limit diagnosis by blood culture. Recent B. canis outbreaks in dogs and concomitant illnesses in caretakers suggest that unapparent human infections may be occurring. With more than a quarter of a million persons in occupations involving dogs, and nearly 80 million dog owners in the United States, this pathogen is an under-recognized human health threat. To investigate occupational exposure to B. canis, we adapted a commercial canine serological assay and present the first controlled seroepidemiological study of human B. canis infections in recent years. 306 adults with occupational exposure to dogs and 101 non-matched, non-canine-exposed subjects were enrolled. Antibodies were detected using the canine D-Tec(®) CB rapid slide agglutination test (RSAT) kit with a secondary 2-mercaptoethanol (ME)-RSAT. Results were validated on a blinded subset of sera with an additional RSAT and indirect enzyme-linked immunoassay at the National Administration of Laboratories and Health Institutes (ANLIS) in Argentina. Seroprevalence ranged from 10.8% (RSAT) to 3.6% (ME-RSAT) among canine-exposed subjects. Kennel employees were more likely to test RSAT seropositive compared with other canine exposures (OR = 2.7; 95% CI, 1.3-5.8); however, low seroprevalence limited meaningful occupational risk factor analyses. Two seropositive participants reported experiencing symptoms consistent with brucellosis and having exposure to B. canis-infected dogs; however, temporality of symptom onset with reported exposure could not be determined. D-Tec(®) CB results had substantial agreement with ANLIS assays (Cohen's kappa = 0.60-0.68). These data add to a growing body of literature suggesting that people occupationally exposed to dogs may be at risk of unapparent B. canis infection. It seems prudent to consider B. canis as an occupational public health

  17. Dendritic Cell-Based Vaccine Against Fungal Infection.

    Science.gov (United States)

    Ueno, Keigo; Urai, Makoto; Ohkouchi, Kayo; Miyazaki, Yoshitsugu; Kinjo, Yuki

    2016-01-01

    Several pathogenic fungi, including Cryptococcus gattii, Histoplasma capsulatum, Coccidioides immitis, and Penicillium marneffei, cause serious infectious diseases in immunocompetent humans. However, currently, prophylactic and therapeutic vaccines are not clinically used. In particular, C. gattii is an emerging pathogen and thus far protective immunity against this pathogen has not been well characterized. Experimental vaccines such as component and attenuated live vaccines have been used as tools to study protective immunity against fungal infection. Recently, we developed a dendritic cell (DC)-based vaccine to study protective immunity against pulmonary infection by highly virulent C. gattii strain R265 that was clinically isolated from bronchial washings of infected patients during the Vancouver Island outbreak. In this approach, bone marrow-derived DCs (BMDCs) are pulsed with heat-killed C. gattii and then transferred into mice prior to intratracheal infection. This DC vaccine significantly increases interleukin 17A (IL-17A)-, interferon gamma (IFN-γ)-, and tumor necrosis factor alpha (TNF-α)-producing T cells in the lungs and spleen and ameliorates the pathology, fungal burden, and mortality following C. gattii infection. This approach may result in the development of a new means of controlling lethal fungal infections. In this chapter, we describe the procedures of DC vaccine preparation and murine pulmonary infection model for analysis of immune response against C. gattii.

  18. Simple clinical and laboratory predictors of Chikungunya versus dengue infections in adults.

    Directory of Open Access Journals (Sweden)

    Vernon J Lee

    Full Text Available BACKGROUND: Dengue and chikungunya are co-circulating vector-borne diseases with substantial overlap in clinical presentations. It is important to differentiate between them during first presentation as their management, especially for dengue hemorrhagic fever (DHF, is different. This study compares their clinical presentation in Singapore adults to derive predictors to assist doctors in diagnostic decision-making. METHODS: We compared 117 patients with chikungunya infection diagnosed with reverse transcription-polymerase chain reaction (RT-PCR with 917 dengue RT-PCR-positive adult patients (including 55 with DHF. We compared dengue fever (DF, DHF, and chikungunya infections by evaluating clinical characteristics of dengue and chikungunya; developing classification tools via multivariate logistic regression models and classification trees of disease etiology using clinical and laboratory factors; and assessing the time course of several clinical variables. FINDINGS: At first presentation to hospital, significantly more chikungunya patients had myalgia or arthralgia, and fewer had a sore throat, cough (for DF, nausea, vomiting, diarrhea, abdominal pain, anorexia or tachycardia than DF or DHF patients. From the decision trees, platelets <118 × 10(9/L was the only distinguishing feature for DF versus chikungunya with an overall correct classification of 89%. For DHF versus chikungunya using platelets <100 × 10(9/L and the presence of bleeding, the overall correct classification was 98%. The time course analysis supported platelet count as the key distinguishing variable. INTERPRETATION: There is substantial overlap in clinical presentation between dengue and chikungunya infections, but simple clinical and laboratory variables can predict these infections at presentation for appropriate management.

  19. Adherence with isoniazid for prevention of tuberculosis among HIV-infected adults in South Africa

    Directory of Open Access Journals (Sweden)

    Muller F James

    2006-06-01

    Full Text Available Abstract Background Tuberculosis (TB is the most common opportunistic infection in HIV-infected adults in developing countries. Isoniazid (INH is recommended for treatment of latent TB infection, however non-adherence is common. The purpose of this study was to apply in-house prepared isoniazid (INH urine test strips in a clinical setting, and identify predictors of positive test results in an adherence questionnaire in HIV-infected adults taking INH for prevention of TB. Methods Cross-sectional study of adherence using a questionnaire and urine test strips for detection of INH metabolites at two hospitals in Pietermaritzburg, South Africa. Participants were aged at least 18 years, HIV positive, and receiving INH for prevention of tuberculosis disease. Univariate and multivariate analyses are used to identify factors relevant to adherence. Results 301 consecutive patients were recruited. 28% of participants had negative urine tests. 32 (37.2%, 95% CI25.4, 45.0 of the 86 patients who received INH from peripheral pharmacies said the pharmacy had run out of INH at some time, compared with central hospital pharmacies (p = 0.0001. In univariate analysis, a negative test was associated with self-reported missed INH doses (p = 0.043. Each 12-hour increment since last reported dose increased the likelihood of a negative test by 34% (p = 0.0007. Belief in INH safety was associated with a positive test (p = 0.021. In multivariate analysis, patients who believed INH is important for prevention of TB disease were more likely to be negative (p = 0.0086. Conclusion Adequate drug availability at peripheral pharmacies remains an important intervention for TB prevention. Key questions may identify potentially non-adherent patients. In-house prepared urine tests strips are an effective and cheap method of objectively assessing INH adherence, and could be used an important tool in TB control programs.

  20. Infection Rates among Acute Leukemia Patients Receiving Alternative Donor Hematopoietic Cell Transplantation.

    Science.gov (United States)

    Ballen, Karen; Woo Ahn, Kwang; Chen, Min; Abdel-Azim, Hisham; Ahmed, Ibrahim; Aljurf, Mahmoud; Antin, Joseph; Bhatt, Ami S; Boeckh, Michael; Chen, George; Dandoy, Christopher; George, Biju; Laughlin, Mary J; Lazarus, Hillard M; MacMillan, Margaret L; Margolis, David A; Marks, David I; Norkin, Maxim; Rosenthal, Joseph; Saad, Ayman; Savani, Bipin; Schouten, Harry C; Storek, Jan; Szabolcs, Paul; Ustun, Celalettin; Verneris, Michael R; Waller, Edmund K; Weisdorf, Daniel J; Williams, Kirsten M; Wingard, John R; Wirk, Baldeep; Wolfs, Tom; Young, Jo-Anne H; Auletta, Jeffrey; Komanduri, Krishna V; Lindemans, Caroline; Riches, Marcie L

    2016-09-01

    Alternative graft sources (umbilical cord blood [UCB], matched unrelated donors [MUD], or mismatched unrelated donors [MMUD]) enable patients without a matched sibling donor to receive potentially curative hematopoietic cell transplantation (HCT). Retrospective studies demonstrate comparable outcomes among different graft sources. However, the risk and types of infections have not been compared among graft sources. Such information may influence the choice of a particular graft source. We compared the incidence of bacterial, viral, and fungal infections in 1781 adults with acute leukemia who received alternative donor HCT (UCB, n= 568; MUD, n = 930; MMUD, n = 283) between 2008 and 2011. The incidences of bacterial infection at 1 year were 72%, 59%, and 65% (P < .0001) for UCB, MUD, and MMUD, respectively. Incidences of viral infection at 1 year were 68%, 45%, and 53% (P < .0001) for UCB, MUD, and MMUD, respectively. In multivariable analysis, bacterial, fungal, and viral infections were more common after either UCB or MMUD than after MUD (P < .0001). Bacterial and viral but not fungal infections were more common after UCB than MMUD (P = .0009 and <.0001, respectively). The presence of viral infection was not associated with an increased mortality. Overall survival (OS) was comparable among UCB and MMUD patients with Karnofsky performance status (KPS) ≥ 90% but was inferior for UCB for patients with KPS < 90%. Bacterial and fungal infections were associated with poorer OS. Future strategies focusing on infection prevention and treatment are indicated to improve HCT outcomes.

  1. Further proof of the plasticity of adult stem cells and their role in tissue repair

    OpenAIRE

    Prockop, Darwin J.

    2003-01-01

    In this issue, De Bari et al. (2003) present elegant data to counter the recent claims that adult stem cells have a limited plasticity. Further, they provide evidence that adult stem cells can seek out damaged tissues and repair them.

  2. Fatal splenic sequestration crisis in adult sickle cell-beta thalassaemia.

    OpenAIRE

    van Rhee, F; Balsitis, M.; French, E. A.

    1991-01-01

    Fatal acute splenic sequestration crisis in an adult patient with sickle cell-beta+ thalassaemia is described. To our knowledge fatal splenic sequestration in adult sickle cell-beta thalassaemia has not been previously reported.

  3. Changes in cell adhesion molecule expression on T cells associated with systemic virus infection

    DEFF Research Database (Denmark)

    Andersson, E C; Christensen, Jan Pravsgaard; Marker, O;

    1994-01-01

    -4, LFA-1, and ICAM-1, are up-regulated on CD8+ cells, whereas the lymph node homing receptor MEL-14 is down-regulated during the infection; only marginal changes were observed for CD4+ cells. Basically similar but less marked results were obtained in mice infected with Pichinde virus. Further...

  4. DNA synthesis and cell division in the adult primate brain

    International Nuclear Information System (INIS)

    It is generally accepted that the adult human brain is incapable of producing new neuron. Even cursory examination of neurologic, neuropathologic, or neurobiological textbooks published during the past 50 years will testify that this belief is deeply entrenched. In his classification of cell populations on the basis of their proliferative behavior, Leblond regarded neurons of the central nervous system as belonging to a category of static, nonrenewing epithelial tissue incapable of expanding or replenishing itself. This belief, however needs to re reexamined for two major reasons: First, as reviewed below, a number of reports have provided evidence of neurogenesis in adult brain of several vertebrate species. Second, the capacity for neurogenesis in the adult primate central nervous system has never been examined by modern methods. In this article the author described recent results from an extensive autoradiographic analysis performed on twelve rhesus monkeys injected with the specific DNA precursor [3H] thymidine at ages ranging from 6 postnatal months to 17 years

  5. Promotion of Cortical Neurogenesis from the Neural Stem Cells in the Adult Mouse Subcallosal Zone.

    Science.gov (United States)

    Kim, Joo Yeon; Choi, Kyuhyun; Shaker, Mohammed R; Lee, Ju-Hyun; Lee, Boram; Lee, Eunsoo; Park, Jae-Yong; Lim, Mi-Sun; Park, Chang-Hwan; Shin, Ki Soon; Kim, Hyun; Geum, Dongho; Sun, Woong

    2016-04-01

    Neurogenesis occurs spontaneously in the subventricular zone (SVZ) of the lateral ventricle in adult rodent brain, but it has long been debated whether there is sufficient adult neurogenesis in human SVZ. Subcallosal zone (SCZ), a posterior continuum of SVZ closely associated with posterior regions of cortical white matter, has also been reported to contain adult neural stem cells (aNSCs) in both rodents and humans. However, little is known whether SCZ-derived aNSC (SCZ-aNSCs) can produce cortical neurons following brain injury. We found that SCZ-aNSCs exhibited limited neuronal differentiation potential in culture and after transplantation in mice. Neuroblasts derived from SCZ initially migrated toward injured cortex regions following brain injury, but later exhibited apoptosis. Overexpression of anti-apoptotic bcl-xL in the SCZ by retroviral infection rescued neuroblasts from cell death in the injured cortex, but neuronal maturation was still limited, resulting in atrophy. In combination with Bcl-xL, infusion of brain-derived neurotropic factor rescued atrophy, and importantly, a subset of such SCZ-aNSCs differentiated and attained morphological and physiological characteristics of mature, excitatory neurons. These results suggest that the combination of anti-apoptotic and neurotrophic factors might enable the use of aNSCs derived from the SCZ in cortical neurogenesis for neural replacement therapy. Stem Cells 2016;34:888-901. PMID:26701067

  6. Role And Relevance Of Mast Cells In Fungal Infections

    Directory of Open Access Journals (Sweden)

    Rohit eSaluja

    2012-06-01

    Full Text Available In addition to their detrimental role in allergic diseases, mast cells (MCs are well known to be important cells of the innate immune system. In the last decade, they have been shown to contribute significantly to optimal host defense against numerous pathogens including parasites, bacteria, and viruses. The contribution of MCs to the immune responses in fungal infections, however, is largely unknown. In this review, we first discuss key features of mast cell responses to pathogens in general and then summarize the current knowledge on the function of MCs in the defense against fungal pathogens. We especially focus on the potential and proven mechanisms by which MC can detect fungal infections and on possible MC effector mechanisms in protecting from fungal infections.

  7. Hepatitis B virus infection in human immunodeficiency virus infected southern African adults: occult or overt--that is the question.

    Directory of Open Access Journals (Sweden)

    Trevor G Bell

    Full Text Available Hepatitis B virus (HBV and human immunodeficiency virus (HIV share transmission routes and are endemic in sub-Saharan Africa. The objective of the present study was to use the Taormina definition of occult HBV infection, together with stringent amplification conditions, to determine the prevalence and characteristics of HBV infection in antiretroviral treatment (ART-naïve HIV(+ve adults in a rural cohort in South Africa. The presence of HBV serological markers was determined by enzyme linked immunoassay (ELISA tests. HBV DNA-positivity was determined by polymerase chain reaction (PCR of at least two of three different regions of the HBV genome. HBV viral loads were determined by real-time PCR. Liver fibrosis was determined using the aspartate aminotransferase-to-platelet ratio index. Of the 298 participants, 231 (77.5% showed at least one HBV marker, with 53.7% HBV DNA(-ve (resolved and 23.8% HBV DNA(+ve (current [8.7% HBsAg(+ve: 15.1% HBsAg(-ve]. Only the total number of sexual partners distinguished HBV DNA(+ve and HBV DNA(-ve participants, implicating sexual transmission of HBV and/or HIV. It is plausible that sexual transmission of HBV and/or HIV may result in a new HBV infection, superinfection and re-activation as a consequence of immunesuppression. Three HBsAg(-ve HBV DNA(+ve participants had HBV viral loads <200 IU/ml and were therefore true occult HBV infections. The majority of HBsAg(-ve HBV DNA(+ve participants did not differ from HBsAg(+ve HBV DNA(+ve (overt participants in terms of HBV viral loads, ALT levels or frequency of liver fibrosis. Close to a quarter of HIV(+ve participants were HBV DNA(+ve, of which the majority were HBsAg(-ve and were only detected using nucleic acid testing. Detection of HBsAg(-ve HBV DNA(+ve subjects is advisable considering they were clinically indistinguishable from HBsAg(+ve HBV DNA(+ve individuals and should not be overlooked, especially if lamivudine is included in the ART.

  8. Regulation of cell survival and death during Flavivirus infections

    Institute of Scientific and Technical Information of China (English)

    Sounak; Ghosh; Roy; Beata; Sadigh; Emmanuel; Datan; Richard; A; Lockshin; Zahra; Zakeri

    2014-01-01

    Flaviviruses, ss(+) RNA viruses, include many of mankind’s most important pathogens. Their pathogenicity derives from their ability to infect many types of cells including neurons, to replicate, and eventually to kill the cells. Flaviviruses can activate tumor necrosis factor α and both intrinsic(Bax-mediated) and extrinsic pathways to apoptosis. Thus they can use many approaches for activating these pathways. Infection can lead to necrosis if viral load is extremely high or to other types of cell death if routes to apoptosis are blocked. Dengue and Japanese Encephalitis Virus can also activate autophagy. In this case the autophagy temporarily spares the infected cell, allowing a longer period of reproduction for the virus, and the autophagy further protects the cell against other stresses such as those caused by reactive oxygen species. Several of the viral proteins have been shown to induce apoptosis or autophagy on their own, independent of the presence of other viral proteins. Given the versatility of these viruses to adapt to and manipulate the metabolism, and thus to control the survival of, the infected cells, we need to understand much better how the specific viral proteins affect the pathways to apoptosis and autophagy. Only in this manner will we be able to minimize the pathology that they cause.

  9. Stem Cell Transplant Patients and Fungal Infections

    Science.gov (United States)

    ... Zoonotic Infectious Disease Division of Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch Stem Cell Transplant Patients and ... Zoonotic Infectious Disease Division of Foodborne, Waterborne, and Environmental Diseases Mycotic Diseases Branch File Formats Help: How do ...

  10. [Therapeutic use of stem cells. II. Adult stem cells].

    Science.gov (United States)

    Uzan, Georges

    2004-09-30

    Many degenerative diseases are not curable by means of classical medicine. The long term objective of cell therapy is to treat the patients with their own stem cells that could be either purified from the diseased organ or from "reservoirs" of stem cells such as that constituted by the bone marrow. The existence of stem cells in the organs or reservoirs is now established in vitro and in some cases, in animal models. Numbers of technical problems linked to the scarcity of these cells still delay the clinical use of purified stem cells. However, clinical protocols using heterogeneous cell populations have already started to treat a growing number of diseases. In some case, autologous cells can be used, as it is the case for bone marrow transplantation in blood diseases. Mesenchymal cells, also purified from the bone marrow are currently used in orthopaedic diseases. Because these cells reveal a broad differentiation potential, active research programs explore their possible use for treatment of other diseases. Bone marrow also contains vascular stem cells that could be active in reappearing defective vessels responsible for ischaemic diseases. Indeed, clinical trials in which bone marrow cells are injected in the cardiac muscle of patients with myocardial infarction or in the leg muscle (gastrocnemius) of patients with hind limb ischaemia have already started. Artificial skin prepared from skin biopsies is used for the reconstitution of the derma of severely burned patients. Clinical trials have also started, using allogenic cells. The patients must be treated by immunosuppressive drugs. Neurodegenerative diseases such as Parkinson have been successfully treated by intra-cerebral injection of foetal neurones. Pancreatic islets implanted in the liver have shown to re-establish a normal glycaemia in diabetic patients. However, all these clinical trials use differentiated cells or at least progenitors which display differentiation potential and lifetime much more

  11. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    International Nuclear Information System (INIS)

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development

  12. A developmentally plastic adult mouse kidney cell line spontaneously generates multiple adult kidney structures

    Energy Technology Data Exchange (ETDEWEB)

    Webb, Carol F., E-mail: carol-webb@omrf.org [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Ratliff, Michelle L., E-mail: michelle-ratliff@omrf.org [Immunobiology and Cancer Research, Oklahoma Medical Research Foundation, Oklahoma City, OK (United States); Powell, Rebecca, E-mail: rebeccapowell@gmail.com [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Wirsig-Wiechmann, Celeste R., E-mail: celeste-wirsig@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Lakiza, Olga, E-mail: olga-lakiza@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States); Obara, Tomoko, E-mail: tomoko-obara@ouhsc.edu [Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK (United States)

    2015-08-07

    Despite exciting new possibilities for regenerative therapy posed by the ability to induce pluripotent stem cells, recapitulation of three-dimensional kidneys for repair or replacement has not been possible. ARID3a-deficient mouse tissues generated multipotent, developmentally plastic cells. Therefore, we assessed the adult mouse ARID3a−/− kidney cell line, KKPS5, which expresses renal progenitor surface markers as an alternative cell source for modeling kidney development. Remarkably, these cells spontaneously developed into multicellular nephron-like structures in vitro, and engrafted into immunocompromised medaka mesonephros, where they formed mouse nephron structures. These data implicate KKPS5 cells as a new model system for studying kidney development. - Highlights: • An ARID3a-deficient mouse kidney cell line expresses multiple progenitor markers. • This cell line spontaneously forms multiple nephron-like structures in vitro. • This cell line formed mouse kidney structures in immunocompromised medaka fish kidneys. • Our data identify a novel model system for studying kidney development.

  13. Theory of hantavirus infection spread incorporating localized adult and itinerant juvenile mice

    Science.gov (United States)

    Kenkre, V. M.; Giuggioli, L.; Abramson, G.; Camelo-Neto, G.

    2007-02-01

    A generalized model of the spread of the Hantavirus in mice populations is presented on the basis of recent observational findings concerning the movement characteristics of the mice that carry the infection. The factual information behind the generalization is based on mark-recapture observations reported in Giuggioli et al. [Bull. Math. Biol. 67, 1135 (2005)] that have necessitated the introduction of home ranges in the simple model of Hantavirus spread presented by Abramson and Kenkre [Phys. Rev. E 66, 11912 (2002)]. The essential feature of the model presented here is the existence of adult mice that remain largely confined to locations near their home ranges, and itinerant juvenile mice that are not so confined, and, during their search for their own homes, move and infect both other juveniles and adults that they meet during their movement. The model is presented at three levels of description: mean field, kinetic and configuration. Results of calculations are shown explicitly from the mean field equations and the simulation rules, and are found to agree in some respects and to differ in others. The origin of the differences is shown to lie in spatial correlations. It is indicated how mark-recapture observations in the field may be employed to verify the applicability of the theory.

  14. Oral Human Papillomavirus Detection in Older Adults Who Have Human Immunodeficiency Virus Infection

    Science.gov (United States)

    Fatahzadeh, Mahnaz; Schlecht, Nicolas F.; Chen, Zigui; Bottalico, Danielle; McKinney, Sharod; Ostoloza, Janae; Dunne, Anne; Burk, Robert D.

    2014-01-01

    Objective To evaluate reproducibility of oral rinse self-collection for HPV detection and investigate associations between oral HPV, oral lesions, immune and sociodemographic factors, we performed a cross-sectional study of older adults with HIV infection. Study Design We collected oral rinse samples from 52 subjects at two different times of day followed by an oral examination and interview. We identified HPV using PCR platforms optimized for detection of mucosal and cutaneous types. Results Eighty seven percent of individuals had oral HPV, of which 23% had oncogenic alpha, 40% had non-oncogenic alpha, and 46% had beta or gamma HPV. Paired oral specimens were concordant in all parameters tested. Significant associations observed for oral HPV with increased HIV viral load, hepatitis-C seropositivity, history of sexually transmitted diseases and lifetime number of sexual partners. Conclusions Oral cavity may be a reservoir of subclinical HPV in older adults who have HIV infection. Understanding natural history, transmission and potential implications of oral HPV warrants further investigations. PMID:23375488

  15. A modified enrichment protocol for adult caprine skeletal muscle stem cell

    OpenAIRE

    Tripathi, Ajai K.; Ramani, Umed V.; Ahir, Viral B.; Rank, Dharamshi N.; Joshi, Chaitanya G.

    2010-01-01

    To establish an adequate model to study the proliferation and differentiation of adult caprine skeletal muscle in response to bioactive compounds, a pool of satellite cells (SC) was derived from the rectus abdominis muscle of adult goat. Skeletal muscle contains a population of adult stem cells, named as satellite cells that reside beneath the basal lamina of skeletal muscle fiber and other populations of cells. These SC are multipotent stem cells, since cells cultured in the presence of spec...

  16. Bioactive molecules released from cells infected with the Human Cytomegalovirus

    Directory of Open Access Journals (Sweden)

    Anna eLuganini

    2016-05-01

    Full Text Available Following primary infection in humans, the Human Cytomegalovirus (HCMV persists in a latent state throughout the host’s lifetime despite a strong and efficient immune response. If the host experiences some form of immune dysregulation, such as immunosuppression or immunodeficiency, HCMV reactivates, thereby emerging from latency. Thus, in the absence of effective functional immune responses, as occurs in immunocompromised or immunoimmature individuals, both HCMV primary infections and reactivations from latency can cause significant morbidity and mortality. However, even in immunocompetent hosts, HCMV represents a relevant risk factor for the development of several chronic inflammatory diseases and certain forms of neoplasia. HCMV infection may shift between the lytic and latent state, regulated by a delicate and intricate balance between virus-mediated immunomodulation and host immune defenses. Indeed, HCMV is a master in manipulating innate and adaptive host defense pathways, and a large portion of its genome is devoted to encoding immunomodulatory proteins; such proteins may thus represent important virulence determinants. However, the pathogenesis of HCMV-related diseases is strengthened by the activities of bioactive molecules, of both viral and cellular origin, that are secreted from infected cells and collectively named as the secretome. Here, we review the state of knowledge on the composition and functions of HCMV-derived secretomes. In lytic infections of fibroblasts and different types of endothelial cells, the majority of HCMV-induced secreted proteins act in a paracrine fashion to stimulate the generation of an inflammatory microenvironment around infected cells; this may lead to vascular inflammation and angiogenesis that, in turn, foster HCMV replication and its dissemination through host tissues. Conversely, the HCMV secretome derived from latently infected hematopoietic progenitor cells induces an immunosuppressive

  17. Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement

    Science.gov (United States)

    Araujo, Bruno; Costa, Francisco; Lopes, Joanne; Castro, Ricardo

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment. PMID:25977828

  18. Adult Langerhans Cell Histiocytosis with Hepatic and Pulmonary Involvement

    Directory of Open Access Journals (Sweden)

    Bruno Araujo

    2015-01-01

    Full Text Available Langerhans cell histiocytosis (LCH is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment.

  19. Adult langerhans cell histiocytosis with hepatic and pulmonary involvement.

    Science.gov (United States)

    Araujo, Bruno; Costa, Francisco; Lopes, Joanne; Castro, Ricardo

    2015-01-01

    Langerhans cell histiocytosis (LCH) is a rare proliferative disorder of Langerhans cells of unknown etiology. It can involve multiple organ systems with different clinical presentation, which complicates the diagnosis. It can range from isolated to multisystem disease with different prognosis. Although common among children, liver involvement is relatively rare in adults and frequently overlooked. Natural history of liver LCH fits into two stages: an early stage with infiltration by histiocytes and a late stage with sclerosis of the biliary tree. Pulmonary findings are more common and include multiple nodules in different stages of cavitation, predominantly in the upper lobes. We present a case of adult LCH with pulmonary and biopsy proven liver involvement with resolution of the hepatic findings after treatment. PMID:25977828

  20. Mortality by causes in HIV-infected adults: comparison with the general population

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    Floristan Yugo

    2011-05-01

    Full Text Available Abstract Background We compared mortality by cause of death in HIV-infected adults in the era of combined antiretroviral therapy with mortality in the general population in the same age and sex groups. Methods Mortality by cause of death was analyzed for the period 1999-2006 in the cohort of persons aged 20-59 years diagnosed with HIV infection and residing in Navarre (Spain. This was compared with mortality from the same causes in the general population of the same age and sex using standardized mortality ratios (SMR. Results There were 210 deaths among 1145 persons diagnosed with HIV (29.5 per 1000 person-years. About 50% of these deaths were from AIDS. Persons diagnosed with HIV infection had exceeded all-cause mortality (SMR 14.0, 95% CI 12.2 to 16.1 and non-AIDS mortality (SMR 6.9, 5.7 to 8.5. The analysis showed excess mortality from hepatic disease (SMR 69.0, 48.1 to 78.6, drug overdose or addiction (SMR 46.0, 29.2 to 69.0, suicide (SMR 9.6, 3.8 to 19.7, cancer (SMR 3.2, 1.8 to 5.1 and cardiovascular disease (SMR 3.1, 1.3 to 6.1. Mortality in HIV-infected intravenous drug users did not change significantly between the periods 1999-2002 and 2003-2006, but it declined by 56% in non-injecting drug users (P = 0.007. Conclusions Persons with HIV infection continue to have considerable excess mortality despite the availability of effective antiretroviral treatments. However, excess mortality in the HIV patients has declined since these treatments were introduced, especially in persons without a history of intravenous drug use.

  1. Larval Temperature-Food Effects on Adult Mosquito Infection and Vertical Transmission of Dengue-1 Virus.

    Science.gov (United States)

    Buckner, Eva A; Alto, Barry W; Lounibos, L Philip

    2016-01-01

    Temperature-food interactions in the larval environment can affect life history and population growth of container mosquitoes Aedes aegypti (L.) and Aedes albopictus Skuse, the primary vectors of chikungunya and dengue viruses. We used Ae. aegypti, Ae. albopictus, and dengue-1 virus (DENV-1) from Florida to investigate whether larval rearing temperature can alter the effects of larval food levels on Ae. aegypti and Ae. albopictus life history and DENV-1 infection and vertical transmission. Although we found no effect of larval treatments on survivorship to adulthood, DENV-1 titer, or DENV-1 vertical transmission, rates of vertical transmission up to 16-24% were observed in Ae. albopictus and Ae. aegypti, which may contribute to maintenance of this virus in nature. Larval treatments had no effect on number of progeny and DENV-1 infection in Ae. aegypti, but the interaction between temperature and food affected number of progeny and DENV-1 infection of the female Ae. albopictus parent. The cooler temperature (24°C) yielded the most progeny and this effect was accentuated by high food relative to the other conditions. Low and high food led to the highest (∼90%) and lowest (∼65%) parental infection at the cooler temperature, respectively, whereas intermediate infection rates (∼75-80%) were observed for all food conditions at the elevated temperature. These results suggest that temperature and food availability have minimal influence on rate of vertical transmission and a stronger influence on adults of Ae. albopictus than of Ae. aegypti, which could have consequences for dengue virus epidemiology. PMID:26489999

  2. Regulatory T cells and the immune pathogenesis of prenatal infection.

    Science.gov (United States)

    Rowe, Jared H; Ertelt, James M; Xin, Lijun; Way, Sing Sing

    2013-12-01

    Pregnancy in placental mammals offers exceptional comprehensive benefits of in utero protection, nutrition, and metabolic waste elimination for the developing fetus. However, these benefits also require durable strategies to mitigate maternal rejection of fetal tissues expressing foreign paternal antigens. Since the initial postulate of expanded maternal immune tolerance by Sir Peter Medawar 60 years ago, an amazingly elaborate assortment of molecular and cellular modifications acting both locally at the maternal-placental interface and systemically have been shown to silence potentially detrimental maternal immune responses. In turn, simultaneously maintaining host defense against the infinite array of potential pathogens during pregnancy is equally important. Fortunately, resistance against most infections is preserved seamlessly throughout gestation. On the other hand, recent studies on pathogens with unique predisposition for prenatal infections have uncovered distinctive holes in host defense associated with the reproductive process. Using these infections to probe the response during pregnancy, the immune suppressive regulatory subset of maternal CD4 T cells has been increasingly shown to dictate the inter-workings between prenatal infection susceptibility and pathogenesis of ensuing pregnancy complications. Herein, the recent literature suggesting a necessity for maternal regulatory T cells (Tregs) in pregnancy-induced immunological shifts that sustain fetal tolerance is reviewed. Additional discussion is focused on how expansion of maternal Treg suppression may become exploited by pathogens that cause prenatal infections and the perilous potential of infection-induced immune activation that may mitigate fetal tolerance and inadvertently inject hostility into the protective in utero environment.

  3. Creation and characterization of a cell-death reporter cell line for hepatitis C virus infection

    Science.gov (United States)

    Chen, Zhilei; Simeon, Rudo; Chockalingam, Karuppiah; Rice, Charles M.

    2010-01-01

    The present study describes the creation and characterization of a hepatoma cell line, n4mBid, that supports all stages of the hepatitis C virus (HCV) life cycle and strongly reports HCV infection by a cell-death phenotype. The n4mBid cell line is derived from the highly HCV-permissive Huh-7.5 hepatoma cell line and contains a modified Bid protein (mBid) that is cleaved and activated by the HCV serine protease NS3-4A. N4mBid exhibited a 10–20 fold difference in cell viability between the HCV-infected and mock-infected states, while the parental Huh-7.5 cells showed <2 fold difference under the same conditions. The pronounced difference in n4mBid cell viability between the HCV- and mock-infected states in a 96-well plate format points to its usefulness in cell survival-based high-throughput screens for anti-HCV molecules. The degree of cell death was found to be proportional to the intracellular load of HCV. HCV-low n4mBid cells, expressing an anti-HCV short hairpin RNA, showed a significant growth advantage over naïve cells and could be rapidly enriched after HCV infection, suggesting the possibility of using n4mBid cells for the cell survival-based selection of genetic anti-HCV factors. PMID:20188762

  4. Epigenetic deregulation of Ellis Van Creveld confers robust Hedgehog signaling in adult T-cell leukemia.

    Science.gov (United States)

    Takahashi, Ryutaro; Yamagishi, Makoto; Nakano, Kazumi; Yamochi, Toshiko; Yamochi, Tadanori; Fujikawa, Dai; Nakashima, Makoto; Tanaka, Yuetsu; Uchimaru, Kaoru; Utsunomiya, Atae; Watanabe, Toshiki

    2014-09-01

    One of the hallmarks of cancer, global gene expression alteration, is closely associated with the development and malignant characteristics associated with adult T-cell leukemia (ATL) as well as other cancers. Here, we show that aberrant overexpression of the Ellis Van Creveld (EVC) family is responsible for cellular Hedgehog (HH) activation, which provides the pro-survival ability of ATL cells. Using microarray, quantitative RT-PCR and immunohistochemistry we have demonstrated that EVC is significantly upregulated in ATL and human T-cell leukemia virus type I (HTLV-1)-infected cells. Epigenetic marks, including histone H3 acetylation and Lys4 trimethylation, are specifically accumulated at the EVC locus in ATL samples. The HTLV-1 Tax participates in the coordination of EVC expression in an epigenetic fashion. The treatment of shRNA targeting EVC, as well as the transcription factors for HH signaling, diminishes the HH activation and leads to apoptotic death in ATL cell lines. We also showed that a HH signaling inhibitor, GANT61, induces strong apoptosis in the established ATL cell lines and patient-derived primary ATL cells. Therefore, our data indicate that HH activation is involved in the regulation of leukemic cell survival. The epigenetically deregulated EVC appears to play an important role for HH activation. The possible use of EVC as a specific cell marker and a novel drug target for HTLV-1-infected T-cells is implicated by these findings. The HH inhibitors are suggested as drug candidates for ATL therapy. Our findings also suggest chromatin rearrangement associated with active histone markers in ATL.

  5. Adult Stem Cells for Acute Lung Injury: Remaining Questions & Concerns

    OpenAIRE

    Zhu, Ying-Gang; Hao, Qi; Monsel, Antoine; Feng, Xiao-mei; Lee, Jae W.

    2013-01-01

    Acute lung injury (ALI) or acute respiratory distress syndrome remains a major cause of morbidity and mortality in hospitalized patients. The pathophysiology of ALI involves complex interactions between the inciting event, such as pneumonia, sepsis or aspiration, and the host immune response resulting in lung protein permeability, impaired resolution of pulmonary edema, an intense inflammatory response in the injured alveolus and hypoxemia. In multiple pre-clinical studies, adult stem cells h...

  6. Fluoxetine targets early progenitor cells in the adult brain

    OpenAIRE

    Encinas, Juan M.; Vaahtokari, Anne; Enikolopov, Grigori

    2006-01-01

    Chronic treatment with antidepressants increases neurogenesis in the adult hippocampus. This increase in the production of new neurons may be required for the behavioral effects of antidepressants. However, it is not known which class of cells within the neuronal differentiation cascade is targeted by the drugs. We have generated a reporter mouse line, which allows identification and classification of early neuronal progenitors. It also allows accurate quantitation of changes induced by neuro...

  7. Protective role of Th17 cells in pulmonary infection.

    Science.gov (United States)

    Rathore, Jitendra Singh; Wang, Yan

    2016-03-18

    Th17 cells are characterized as preferential producer of interleukins including IL-17A, IL-17F, IL-21 and IL-22. Corresponding receptors of these cytokines are expressed on number of cell types found in the mucosa, including epithelial cells and fibroblasts which constitute the prime targets of the Th17-associated cytokines. Binding of IL-17 family members to their corresponding receptors lead to modulation of antimicrobial functions of target cells including alveolar epithelial cells. Stimulated alveolar epithelial cells produce antimicrobial peptides and are involved in granulepoesis, neutrophil recruitment and tissue repair. Mucosal immunity mediated by Th17 cells is protective against numerous pulmonary pathogens including extracellular bacterial and fungal pathogens. This review focuses on the protective role of Th17 cells during pulmonary infection, highlighting subset differentiation, effector cytokines production, followed by study of the binding of these cytokines to their corresponding receptors, the subsequent signaling pathway they engender and their effector role in host defense.

  8. Multiple helminth infection of the skin causes lymphocyte hypo-responsiveness mediated by Th2 conditioning of dermal myeloid cells.

    Directory of Open Access Journals (Sweden)

    Peter C Cook

    2011-03-01

    Full Text Available Infection of the mammalian host by schistosome larvae occurs via the skin, although nothing is known about the development of immune responses to multiple exposures of schistosome larvae, and/or their excretory/secretory (E/S products. Here, we show that multiple (4x exposures, prior to the onset of egg laying by adult worms, modulate the skin immune response and induce CD4(+ cell hypo-responsiveness in the draining lymph node, and even modulate the formation of hepatic egg-induced granulomas. Compared to mice exposed to a single infection (1x, dermal cells from multiply infected mice (4x, were less able to support lymph node cell proliferation. Analysis of dermal cells showed that the most abundant in 4x mice were eosinophils (F4/80(+MHC-II(-, but they did not impact the ability of antigen presenting cells (APC to support lymphocyte proliferation to parasite antigen in vitro. However, two other cell populations from the dermal site of infection appear to have a critical role. The first comprises arginase-1(+, Ym-1(+ alternatively activated macrophage-like cells, and the second are functionally compromised MHC-II(hi cells. Through the administration of exogenous IL-12 to multiply infected mice, we show that these suppressive myeloid cell phenotypes form as a consequence of events in the skin, most notably an enrichment of IL-4 and IL-13, likely resulting from an influx of RELMα-expressing eosinophils. We further illustrate that the development of these suppressive dermal cells is dependent upon IL-4Rα signalling. The development of immune hypo-responsiveness to schistosome larvae and their effect on the subsequent response to the immunopathogenic egg is important in appreciating how immune responses to helminth infections are modulated by repeated exposure to the infective early stages of development.

  9. Epidemiology, outcomes, and predictors of mortality in hospitalized adults with Clostridium difficile infection.

    Science.gov (United States)

    Khanna, Sahil; Gupta, Arjun; Baddour, Larry M; Pardi, Darrell S

    2016-08-01

    Studies have demonstrated an increasing Clostridium difficile infection (CDI) incidence in hospitals and the community, with increasing morbidity and mortality. In this study, we analyzed data from the National Hospital Discharge Survey (NHDS) to evaluate CDI epidemiology, outcomes, and predictors of mortality in hospitalized adults. We identified cases of CDI (and associated comorbid conditions) from NHDS data from 2005 through 2009 using ICD-9 codes. Weighted univariate and multivariate analyses were performed to ascertain CDI incidence, associations between CDI and outcomes [length of stay (LOS), colectomy, all-cause in-hospital mortality, and discharge to a care facility], and predictors of all-cause in-hospital mortality. Of an estimated 162 million adult inpatients, 1.26 million (0.8 %) had CDI. The overall CDI incidence is 77.8/10,000 hospitalizations, with no statistically significant change over the study period. On multivariate analysis, after adjusting for age, gender, and comorbid conditions, CDI is an independent predictor of longer LOS (mean difference, 2.35 days), all-cause mortality [odds ratio (OR) 1.45], colectomy (OR 1.41), and discharge to a care facility (OR 2.12) (all P coagulation abnormalities. Despite stable CDI incidence and advances in management, CDI is associated with increased LOS, colectomy, all-cause in-hospital mortality, and discharge to a care facility in hospitalized, especially elderly, adults. Age older than 65 years should be added to the severity criteria for CDI. PMID:26694494

  10. Thyroid Hormone Regulation of Adult Intestinal Stem Cell Development: Mechanisms and Evolutionary Conservations

    OpenAIRE

    Sun, Guihong; Shi, Yun-Bo

    2012-01-01

    The adult mammalian intestine has long been used as a model to study adult stem cell function and tissue renewal as the intestinal epithelium is constantly undergoing self-renewal throughout adult life. This is accomplished through the proliferation and subsequent differentiation of the adult stem cells located in the crypt. The development of this self-renewal system is, however, poorly understood. A number of studies suggest that the formation/maturation of the adult intestine is conserved ...

  11. Intestinal CD103+ dendritic cells are key players in the innate immune control of Cryptosporidium parvum infection in neonatal mice.

    Directory of Open Access Journals (Sweden)

    Louis Lantier

    Full Text Available Cryptosporidium parvum is a zoonotic protozoan parasite found worldwide, that develops only in the gastrointestinal epithelium and causes profuse diarrhea. Using a mouse model of C. parvum infection, we demonstrated by conditional depletion of CD11c+ cells that these cells are essential for the control of the infection both in neonates and adults. Neonates are highly susceptible to C. parvum but the infection is self-limited, whereas adults are resistant unless immunocompromised. We investigated the contribution of DC to the age-dependent susceptibility to infection. We found that neonates presented a marked deficit in intestinal CD103+ DC during the first weeks of life, before weaning, due to weak production of chemokines by neonatal intestinal epithelial cells (IEC. Increasing the number of intestinal CD103+ DC in neonates by administering FLT3-L significantly reduced susceptibility to the infection. During infections in neonates, the clearance of the parasite was preceded by a rapid recruitment of CD103+ DC mediated by CXCR3-binding chemokines produced by IEC in response to IFNγ. In addition to this key role in CD103+ DC recruitment, IFNγ is known to inhibit intracellular parasite development. We demonstrated that during neonatal infection CD103+ DC produce IL-12 and IFNγ in the lamina propria and the draining lymph nodes. Thus, CD103+DC are key players in the innate immune control of C. parvum infection in the intestinal epithelium. The relative paucity of CD103+ DC in the neonatal intestine contributes to the high susceptibility to intestinal infection.

  12. Immunological efficacy of pneumococcal vaccine strategies in HIV-infected adults: a randomized clinical trial

    Science.gov (United States)

    Sadlier, C.; O’Dea, S.; Bennett, K.; Dunne, J.; Conlon, N.; Bergin, C.

    2016-01-01

    The aim of this study was to compare the immunologic response to a prime-boost immunization strategy combining the 13-valent conjugate pneumococcal vaccine (PCV13) with the 23-valent polysaccharide pneumococcal vaccine (PPSV23) versus the PPSV23 alone in HIV-infected adults. HIV-infected adults were randomized to receive PCV13 at week 0 followed by PPSV23 at week 4 (n = 31, prime-boost group) or PPSV23 alone at week 4 (n = 33, PPSV23-alone group). Serotype specific IgG geometric mean concentration (GMC) and functional oposonophagocytic (OPA) geometric mean titer (GMT) were compared for 12 pneumococcal serotypes shared by both vaccines at week 8 and week 28. The prime-boost vaccine group were more likely to achieve a ≥2-fold increase in IgG GMC and a GMC >1 ug/ml at week 8 (odds ratio (OR) 2.00, 95% confidence interval (CI) 1.46–2.74, p < 0.01) and week 28 (OR 1.95, 95% CI 1.40–2.70, p < 0.01). Similarly, the prime-boost vaccine group were more likely to achieve a ≥4-fold increase in GMT at week 8 (OR 1.71, 95% CI 1.22–2.39, p < 0.01) and week 28 (OR 1.6, 95% CI 1.15–2.3, p < 0.01). This study adds to evidence supporting current pneumococcal vaccination recommendations combining the conjugate and polysaccharide pneumococcal vaccines in the United States and Europe for HIV-infected individuals. PMID:27580688

  13. Prise en charge de l’infection gonococcique chez les adultes et les jeunes

    Science.gov (United States)

    Pogany, Lisa; Romanowski, Barbara; Robinson, Joan; Gale-Rowe, Margaret; Latham-Carmanico, Cathy; Weir, Christine; Wong, Tom

    2015-01-01

    Résumé Objectif Présenter des recommandations sur la prise en charge de l’infection gonococcique chez les adultes et les jeunes. Qualité des données Les recommandations thérapeutiques des lignes directrices canadiennes sur les infections transmissibles sexuellement reposent sur une recherche documentaire de même que sur des catégories de recommandations et des niveaux de qualité de données déterminés par au moins 2 évaluateurs. Les recommandations ont été revues par des pairs et sont en instance d’approbation par le groupe de travail d’experts. Message principal Les nouvelles recommandations portant sur la prise en charge de l’infection gonococcique chez les adultes et les jeunes préconisent les cultures à titre d’outil diagnostique lorsqu’elles sont pratiques, le traitement par antibiothérapie combinée (ceftriaxone associée à l’azithromycine) et le signalement sans délai de tous les cas dont le traitement a échoué aux autorités de santé publique. Conclusion Si elles sont suivies, ces nouvelles recommandations pourraient réduire l’échec thérapeutique, contribuer à une surveillance plus étroite des tendances à la résistance de Neisseria gonorrhoeae aux antibiotiques et contribuer à prévenir la transmission de gonorrhée résistante à plusieurs médicaments.

  14. Innate immune control of EBV-infected B cells by invariant natural killer T cells.

    Science.gov (United States)

    Chung, Brian K; Tsai, Kevin; Allan, Lenka L; Zheng, Dong Jun; Nie, Johnny C; Biggs, Catherine M; Hasan, Mohammad R; Kozak, Frederick K; van den Elzen, Peter; Priatel, John J; Tan, Rusung

    2013-10-10

    Individuals with X-linked lymphoproliferative disease lack invariant natural killer T (iNKT) cells and are exquisitely susceptible to Epstein-Barr virus (EBV) infection. To determine whether iNKT cells recognize or regulate EBV, resting B cells were infected with EBV in the presence or absence of iNKT cells. The depletion of iNKT cells increased both viral titers and the frequency of EBV-infected B cells. However, EBV-infected B cells rapidly lost expression of the iNKT cell receptor ligand CD1d, abrogating iNKT cell recognition. To determine whether induced CD1d expression could restore iNKT recognition in EBV-infected cells, lymphoblastoid cell lines (LCL) were treated with AM580, a synthetic retinoic acid receptor-α agonist that upregulates CD1d expression via the nuclear protein, lymphoid enhancer-binding factor 1 (LEF-1). AM580 significantly reduced LEF-1 association at the CD1d promoter region, induced CD1d expression on LCL, and restored iNKT recognition of LCL. CD1d-expressing LCL elicited interferon γ secretion and cytotoxicity by iNKT cells even in the absence of exogenous antigen, suggesting an endogenous iNKT antigen is expressed during EBV infection. These data indicate that iNKT cells may be important for early, innate control of B cell infection by EBV and that downregulation of CD1d may allow EBV to circumvent iNKT cell-mediated immune recognition.

  15. Noninvasive and label-free determination of virus infected cells by Raman spectroscopy

    Science.gov (United States)

    Moor, Kamila; Ohtani, Kiyoshi; Myrzakozha, Diyas; Zhanserkenova, Orik; Andriana, Bibin. B.; Sato, Hidetoshi

    2014-06-01

    The present study demonstrates that Raman spectroscopy is a powerful tool for the detection of virus-infected cells. Adenovirus infection of human embryonic kidney 293 cells was successfully detected at 12, 24, and 48 h after initiating the infection. The score plot of principal component analysis discriminated the spectra of the infected cells from those of the control cells. The viral infection was confirmed by the conventional immunostaining method performed 24 h after the infection. The newly developed method provides a fast and label-free means for the detection of virus-infected cells.

  16. Inhibition of proliferation by agricultural plant extracts in seven human adult T-cell leukaemia (ATL)-related cell lines.

    Science.gov (United States)

    Kai, Hisahiro; Akamatsu, Ena; Torii, Eri; Kodama, Hiroko; Yukizaki, Chizuko; Sakakibara, Yoichi; Suiko, Masahito; Morishita, Kazuhiro; Kataoka, Hiroaki; Matsuno, Koji

    2011-07-01

    Adult T-cell leukaemia (ATL) is caused by human T-cell leukaemia virus type I (HTLV-I) infection and is resistant to conventional chemotherapy. We evaluated the inhibitory effects of agricultural plants on the proliferation of seven ATL-related human leukaemia cells, using three ATL cell lines (ED, Su9T01 and S1T), two human T-cell lines transformed by HTLV-I infection (HUT-102 and MT-2) and two HTLV-I-negative human T-cell acute lymphoblastic leukaemia cell lines (Jurkat and MOLT-4). A total of 52 samples of 80% ethanol extracts obtained from 30 types of agricultural plants were examined. On the basis of IC(50) values, we selected samples with greater activity than genistein, which was used as a positive control. The highest inhibitory effect was observed with extracts from leaves of Vaccinium virgatum Aiton (blueberry) on four cell lines (ED, Su9T01, HUT-102 and Jurkat); seeds of Momordica charantia L. (bitter gourd) exhibited the second highest activity. The bitter gourd seeds suppressed the proliferation of three cell lines (Su9T01, HUT-102 and Jurkat). The extracts from edible parts of Ipomea batatas LAM. (sweet potato), edible parts of Colocasia esculenta (L.) Schott (taro), skin of taro and seeds of Prunus mume Sieb. et Zucc. (mume) showed markedly greater inhibitory effects on Su9T01 than genistein. These findings suggest that ATL-preventative bioactive compounds may exist in these agricultural plants, which are considered to be functional foods. PMID:21293936

  17. Innate immune cell response upon Candida albicans infection.

    Science.gov (United States)

    Qin, Yulin; Zhang, Lulu; Xu, Zheng; Zhang, Jinyu; Jiang, Yuan-Ying; Cao, Yongbing; Yan, Tianhua

    2016-07-01

    Candida albicans is a polymorphic fungus which is the predominant cause of superficial and deep tissue fungal infections. This microorganism has developed efficient strategies to invade the host and evade host defense systems. However, the host immune system will be prepared for defense against the microbe by recognition of receptors, activation of signal transduction pathways and cooperation of immune cells. As a consequence, C. albicans could either be eliminated by immune cells rapidly or disseminate hematogenously, leading to life-threatening systemic infections. The interplay between Candida albicans and the host is complex, requiring recognition of the invaded pathogens, activation of intricate pathways and collaboration of various immune cells. In this review, we will focus on the effects of innate immunity that emphasize the first line protection of host defense against invaded C. albicans including the basis of receptor-mediated recognition and the mechanisms of cell-mediated immunity. PMID:27078171

  18. Oral Human Papillomavirus (HPV Infection among Unvaccinated High-Risk Young Adults

    Directory of Open Access Journals (Sweden)

    Gypsyamber D'Souza

    2014-08-01

    Full Text Available Oral HPV infection, the cause of most oropharyngeal cancer in the U.S., is not well studied among high-risk young adults. Men (n = 340 and women (n = 270 aged 18–25 years attending Baltimore County STD clinics were recruited if they declined HPV vaccination. Each participant had a 30-second oral rinse and gargle sample tested for 37 types of HPV DNA, and a risk-factor survey. Factors associated with prevalent infection were explored using log binomial regression. Men had higher prevalence of any oral HPV (15.3% vs. 7.8%, p = 0.004 and vaccine-type oral HPV (i.e., HPV16/18/6/11: 5.0% vs. 1.1%, p = 0.007 infection than women. In multivariate analysis, male gender (aPR = 1.93, 95% CI = 1.10–3.39, number of recent oral sex partners (p-trend = 0.013 and having ever performed oral sex on a woman (aPR = 1.73, 95% CI = 1.06–2.82 were associated with increased oral HPV prevalence. Performing oral sex on a woman may confer higher risk of oral HPV acquisition than performing oral sex on a man.

  19. Oral Human Papillomavirus (HPV) Infection among Unvaccinated High-Risk Young Adults.

    Science.gov (United States)

    D'Souza, Gypsyamber; Kluz, Nicole; Wentz, Alicia; Youngfellow, Renee M; Griffioen, Anne; Stammer, Emily; Guo, Yingshi; Xiao, Weihong; Gillison, Maura L

    2014-01-01

    Oral HPV infection, the cause of most oropharyngeal cancer in the U.S., is not well studied among high-risk young adults. Men (n = 340) and women (n = 270) aged 18-25 years attending Baltimore County STD clinics were recruited if they declined HPV vaccination. Each participant had a 30-second oral rinse and gargle sample tested for 37 types of HPV DNA, and a risk-factor survey. Factors associated with prevalent infection were explored using log binomial regression. Men had higher prevalence of any oral HPV (15.3% vs. 7.8%, p = 0.004) and vaccine-type oral HPV (i.e., HPV16/18/6/11: 5.0% vs. 1.1%, p = 0.007) infection than women. In multivariate analysis, male gender (aPR = 1.93, 95% CI = 1.10-3.39), number of recent oral sex partners (p-trend = 0.013) and having ever performed oral sex on a woman (aPR = 1.73, 95% CI = 1.06-2.82) were associated with increased oral HPV prevalence. Performing oral sex on a woman may confer higher risk of oral HPV acquisition than performing oral sex on a man.

  20. Exosomes released from Mycoplasma infected tumor cells activate inhibitory B cells.

    Directory of Open Access Journals (Sweden)

    Chenjie Yang

    Full Text Available Mycoplasmas cause numerous human diseases and are common opportunistic pathogens in cancer patients and immunocompromised individuals. Mycoplasma infection elicits various host immune responses. Here we demonstrate that mycoplasma-infected tumor cells release exosomes (myco+ exosomes that specifically activate splenic B cells and induce splenocytes cytokine production. Induction of cytokines, including the proinflammatory IFN-γ and the anti-inflammatory IL-10, was largely dependent on the presence of B cells. B cells were the major IL-10 producers. In splenocytes from B cell deficient μMT mice, induction of IFN-γ+ T cells by myco+ exosomes was greatly increased compared with wild type splenocytes. In addition, anti-CD3-stimulated T cell proliferation was greatly inhibited in the presence of myco+ exosome-treated B cells. Also, anti-CD3-stimulated T cell signaling was impaired by myco+ exosome treatment. Proteomic analysis identified mycoplasma proteins in exosomes that potentially contribute to the effects. Our results demonstrate that mycoplasma-infected tumor cells release exosomes carrying mycoplasma components that preferentially activate B cells, which in turn, are able to inhibit T cell activity. These results suggest that mycoplasmas infecting tumor cells can exploit the exosome pathway to disseminate their own components and modulate the activity of immune cells, in particular, activate B cells with inhibitory activity.

  1. Cotrimoxazole Prophylaxis Discontinuation among Antiretroviral-Treated HIV-1-Infected Adults in Kenya: A Randomized Non-inferiority Trial

    OpenAIRE

    Polyak, Christina S.; Krista Yuhas; Benson Singa; Monica Khaemba; Judd Walson; Richardson, Barbra A.; Grace John-Stewart

    2016-01-01

    Editors' Summary Background AIDS has killed 39 million people over the past three decades, and 35 million people (mostly living in resource-limited countries) are currently infected with HIV, the virus that causes AIDS. HIV, which is usually transmitted through unprotected sex with an infected individual, gradually destroys CD4 lymphocytes and other immune system cells. Because destruction of the immune system leaves HIV-infected individuals susceptible to “opportunistic” infections, early in...

  2. Switching roles: the functional plasticity of adult tissue stem cells.

    Science.gov (United States)

    Wabik, Agnieszka; Jones, Philip H

    2015-05-01

    Adult organisms have to adapt to survive, and the same is true for their tissues. Rates and types of cell production must be rapidly and reversibly adjusted to meet tissue demands in response to both local and systemic challenges. Recent work reveals how stem cell (SC) populations meet these requirements by switching between functional states tuned to homoeostasis or regeneration. This plasticity extends to differentiating cells, which are capable of reverting to SCs after injury. The concept of the niche, the micro-environment that sustains and regulates stem cells, is broadening, with a new appreciation of the role of physical factors and hormonal signals. Here, we review different functions of SCs, the cellular mechanisms that underlie them and the signals that bias the fate of SCs as they switch between roles. PMID:25812989

  3. Regulatory T Cells in Chronic Hepatitis B Virus Infection

    NARCIS (Netherlands)

    J.N. Stoop (Jeroen Nicolaas)

    2007-01-01

    textabstractWorldwide 400 million people suffer from chronic hepatitis B virus (HBV) infection and approximately 1 million people die annually from HBV-related disease. To clear HBV, an effective immune response, in which several cell types and cytokines play a role, is important. It is known that p

  4. Phospholipid Synthesis in Sindbis Virus-Infected Cells

    Science.gov (United States)

    Waite, Marilynn R. F.; Pfefferkorn, E. R.

    1970-01-01

    We investigated the metabolic requirements for the decrease in phospholipid synthesis previously observed by Pfefferkorn and Hunter in primary cultures of chick embryo fibroblasts infected with Sindbis virus. The incorporation of 32PO4 into all classes of phospholipids was found to decline at the same rate and to the same extent; thus, incorporation of 14C-choline into acid-precipitable form provided a convenient measure of phospholipid synthesis that was used in subsequent experiments. Experiments with temperature-sensitive mutants suggested that some viral ribonucleic acid (RNA) synthesis was essential for the inhibition of choline incorporation, but that functional viral structural proteins were not required. The reduction in phospholipid synthesis was probably a secondary effect of infection resulting from viral inhibition of the cellular RNA and protein synthesis. All three inhibitory effects required about the same amount of viral RNA synthesis; the inhibition of host RNA and protein synthesis began sooner than the decline in phospholipid synthesis; and both actinomycin D and cycloheximide inhibited 14C-choline incorporation in uninfected cells. In contrast, incorporation of 14C-choline into BHK-21 cells was not decreased by 10 hr of exposure to actinomycin D and declined only slowly after cycloheximide treatment. Growth of Sindbis virus in BHK cells did not cause the marked stimulation of phospholipid synthesis seen in picornavirus infections of other mammalian cells; however, inhibition was seen only late in infection. PMID:5530011

  5. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba

    2009-07-01

    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  6. Adult Stem Cells as a Renewable Source of Insulin-Producing Cells

    OpenAIRE

    Jun, Hee-Sook; Park, Eun-Young

    2009-01-01

    Diabetes mellitus is a metabolic disorder resulting from an inadequate mass of insulin-producing pancreatic beta cells. The replacement or restoration of damaged beta cells would be considered the optimal therapeutic options. Islet transplantation seems to be a promising approach for replacement therapy; however, the main obstacle is the shortage of organ donors. As mature beta cells have been shown to be difficult to expand in vitro, regeneration of beta cells from embryonic or adult stem ce...

  7. HIV-1 Trans Infection of CD4+ T Cells by Professional Antigen Presenting Cells

    Directory of Open Access Journals (Sweden)

    Charles R. Rinaldo

    2013-01-01

    Full Text Available Since the 1990s we have known of the fascinating ability of a complex set of professional antigen presenting cells (APCs; dendritic cells, monocytes/macrophages, and B lymphocytes to mediate HIV-1 trans infection of CD4+ T cells. This results in a burst of virus replication in the T cells that is much greater than that resulting from direct, cis infection of either APC or T cells, or trans infection between T cells. Such APC-to-T cell trans infection first involves a complex set of virus subtype, attachment, entry, and replication patterns that have many similarities among APC, as well as distinct differences related to virus receptors, intracellular trafficking, and productive and nonproductive replication pathways. The end result is that HIV-1 can sequester within the APC for several days and be transmitted via membrane extensions intracellularly and extracellularly to T cells across the virologic synapse. Virus replication requires activated T cells that can develop concurrently with the events of virus transmission. Further research is essential to fill the many gaps in our understanding of these trans infection processes and their role in natural HIV-1 infection.

  8. Impact of Gastrointestinal Bacillus anthracis Infection on Hepatic B Cells

    Directory of Open Access Journals (Sweden)

    Natacha Colliou

    2015-09-01

    Full Text Available Ingestion of Bacillus anthracis results in rapid gastrointestinal (GI infection, known as GI anthrax. We previously showed that during GI anthrax, there is swift deterioration of intestinal barrier function leading to translocation of gut-associated bacteria into systemic circulation. Additionally, we described dysfunction in colonic B cells. In concordance with our previous studies, here, we report early migration of the Sterne strain of B. anthracis along with other gut-resident bacteria into the infected murine liver. Additionally, despite a global decrease in the B cell population, we observed an increase in both B-1a and marginal zone (MZ-like B cells. Both of these cell types are capable of producing immunoglobulins against common pathogens and commensals, which act as a general antibody barrier before an antigen-specific antibody response. Accumulation of these cells in the liver was associated with an increase in chemokine expression. These data suggest that the presence of Sterne and other commensals in the liver trigger migration of MZ-like B cells from the spleen to the liver to neutralize systemic spread. Further research is required to evaluate the possible cause of their failure to clear the infection within the liver, including the potential role of dysfunctional mitogen-activated protein kinase (MAPK signaling.

  9. Cuban experience with the therapeutic use of adult stem cells

    International Nuclear Information System (INIS)

    The basic and clinical researches carried out during past years on the stem cells and its therapeutic possibilities are at present times, one of the most interesting subjects of the contemporaneous medicine. There are advances in the study and application of adult stem cells showing remarkable advantages on the embryonic ones, since its handling is more simple, economic and they are obtained from the own subject to be treated. For the introduction in Cuba of the regenerative cellular therapy in the Institute of Hematology and Immunology the cellular sources selected were the adult stem cells derived from bone marrow and the mobilized ones to the peripheral blood. To make easy the expansion of treatment to other hospital centers, authors standardized a technique for the mobilization of the hematopoietic stem cells to peripheral blood using a granulocyte colony-stimulating factor (Filgrastim, of national production) developing a simple, economic and more tolerable method for patients. In this way, the cellular therapy has been expanded to 6 Cuban provinces and until April, 2009 562 cases with autologous adult stem cells transplant have been treated, from which the 81.7% to correspond to patients presenting with Angiology diseases with a significant reduction of major amputations. Also, the results have been very promising in the bone lesions and periodontal processes among other diseases treated. The results obtained until now may be considered as a new achievement of revolutionary science and of our national health systems and of science and technique. The method used is an economic and feasible procedure for the institutions with scarce resources

  10. POTENTIAL CONTRIBUTION OF ADULT POPULATIONS TO THE MAINTENANCE OF SCHISTOSOMIASIS AND SOIL-TRANSMITTED HELMINTH INFECTIONS IN THE SIAVONGA AND MAZABUKA DISTRICTS OF ZAMBIA

    DEFF Research Database (Denmark)

    Halwindi, Hikabasa; Magnussen, Pascal; Olsen, Annette;

    2016-01-01

    . lumbricoides and hookworm. Additionally, no Trichuris trichiura infections were observed in the two districts. Despite most of these infections being categorized as light intensity, heavy infection intensities were also found for all four parasite species. If this infected adult population is left untreated...

  11. Brefeldin A inhibits pestivirus release from infected cells, without affecting its assembly and infectivity

    International Nuclear Information System (INIS)

    The enveloped bovine viral diarrhea virus (BVDV) is a member of the Pestivirus genus within the Flaviviridae family. While considerable information has been gathered on virus entry into the host cell, genome structure and protein function, little is known about pestivirus morphogenesis and release from cells. Here, we analyzed the intracellular localization, N-glycan processing and secretion of BVDV using brefeldin A (BFA), which blocks protein export from the endoplasmic reticulum (ER) and causes disruption of the Golgi complex with subsequent fusion of its cis and medial cisternae with the ER. BFA treatment of infected cells resulted in complete inhibition of BVDV secretion and increased co-localization of the envelope glycoproteins with the cis-Golgi marker GM 130. Processing of the N-linked glycans was affected by BFA, however, virus assembly was not perturbed and intracellular virions were fully infectious, suggesting that trafficking beyond the cis-Golgi is not a prerequisite for pestivirus infectivity

  12. Angiotensin II type 1 receptor blocker telmisartan induces apoptosis and autophagy in adult T-cell leukemia cells.

    Science.gov (United States)

    Kozako, Tomohiro; Soeda, Shuhei; Yoshimitsu, Makoto; Arima, Naomichi; Kuroki, Ayako; Hirata, Shinya; Tanaka, Hiroaki; Imakyure, Osamu; Tone, Nanako; Honda, Shin-Ichiro; Soeda, Shinji

    2016-05-01

    Adult T-cell leukemia/lymphoma (ATL), an aggressive T-cell malignancy that develops after long-term infection with human T-cell leukemia virus (HTLV-1), requires new treatments. Drug repositioning, reuse of a drug previously approved for the treatment of another condition to treat ATL, offers the possibility of reduced time and risk. Among clinically available angiotensin II receptor blockers, telmisartan is well known for its unique ability to activate peroxisome proliferator-activated receptor-γ, which plays various roles in lipid metabolism, cellular differentiation, and apoptosis. Here, telmisartan reduced cell viability and enhanced apoptotic cells via caspase activation in ex vivo peripheral blood monocytes from asymptomatic HTLV-1 carriers (ACs) or via caspase-independent cell death in acute-type ATL, which has a poor prognosis. Telmisartan also induced significant growth inhibition and apoptosis in leukemia cell lines via caspase activation, whereas other angiotensin II receptor blockers did not induce cell death. Interestingly, telmisartan increased the LC3-II-enriched protein fraction, indicating autophagosome accumulation and autophagy. Thus, telmisartan simultaneously caused caspase activation and autophagy. A hypertension medication with antiproliferation effects on primary and leukemia cells is intriguing. Patients with an early diagnosis of ATL are generally monitored until the disease progresses; thus, suppression of progression from AC and indolent ATL to acute ATL is important. Our results suggest that telmisartan is highly effective against primary cells and leukemia cell lines in caspase-dependent and -independent manners, and its clinical use may suppress acute transformation and improve prognosis of patients with this mortal disease. This is the first report demonstrating a cell growth-inhibitory effect of telmisartan in fresh peripheral blood mononuclear cells from leukemia patients. PMID:27419050

  13. Point-of-care lateral flow assays for tuberculosis and cryptococcal antigenuria predict death in HIV infected adults in Uganda.

    Directory of Open Access Journals (Sweden)

    Yukari C Manabe

    Full Text Available Mortality in hospitalized, febrile patients in Sub-Saharan Africa is high due to HIV-infected, severely immunosuppressed patients with opportunistic co-infection, particularly disseminated tuberculosis (TB and cryptococcal disease. We sought to determine if a positive lateral flow assay (LFA result for urine lipoarabinomannan (LAM and cryptococcal antigenuria was associated with mortality.351 hospitalized, HIV-positive adults with symptoms consistent with TB and who were able to provide both urine and sputum specimens were prospectively enrolled at Mulago National Referral Hospital in Uganda as part of a prospective accuracy evaluation of the lateral flow Determine TB LAM test. Stored frozen urine was retrospectively tested for cryptococcal antigen (CRAG using the LFA. We fitted a multinomial logistic regression model to analyze factors associated with death within 2 months after initial presentation.The median CD4 of the participants was 57 (IQR: 14-179 cells/µl and 41% (145 were microbiologically confirmed TB cases. LAM LFA was positive in 38% (134, 7% (25 were CRAG positive, and 43% (151 were positive for either test in urine. Overall, 21% (75 died within the first 2 months, and a total of 32% (114 were confirmed dead by 6 months. At 2 months, 30% of LAM or CRAG positive patients were confirmed dead compared to 15.0% of those who were negative. In an adjusted model, LAM or CRAG positive results were associated with an increased risk of death (RRR 2.29, 95% CI: 1.29, 4.05; P = 0.005.In hospitalized HIV-infected patients, LAM or CRAG LFA positivity was associated with subsequent death within 2 months. Further studies are warranted to examine the impact of POC diagnostic 'test and treat' approach on patient-centered outcomes.

  14. Dental Stem Cell in Tooth Development and Advances of Adult Dental Stem Cell in Regenerative Therapies.

    Science.gov (United States)

    Tan, Jiali; Xu, Xin; Lin, Jiong; Fan, Li; Zheng, Yuting; Kuang, Wei

    2015-01-01

    Stem cell-based therapies are considered as a promising treatment for many clinical usage such as tooth regeneration, bone repairation, spinal cord injury, and so on. However, the ideal stem cell for stem cell-based therapy still remains to be elucidated. In the past decades, several types of stem cells have been isolated from teeth, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), periodontal ligament stem cells (PDLSCs), dental follicle progenitor stem cells (DFPCs) and stem cells from apical papilla (SCAP), which may be a good source for stem cell-based therapy in certain disease, especially when they origin from neural crest is considered. In this review, the specific characteristics and advantages of the adult dental stem cell population will be summarized and the molecular mechanisms of the differentiation of dental stem cell during tooth development will be also discussed.

  15. Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units.

    Directory of Open Access Journals (Sweden)

    Vu Dinh Phu

    Full Text Available Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs. We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs across Vietnam.Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08:00 a.m. on the survey day were included.Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing. Pneumonia accounted for 79.4% (804/1012 of HAIs Most HAIs (84.5% [855/1012] were acquired in the survey hospital with 42.5% (363/855 acquired prior to ICU admission and 57.5% (492/855 developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76, urinary catheter (OR 2.12, no involvement of a family member in patient care (OR 1.94, and surgery after admission (OR 1.66. 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%], Pseudomonas aeruginosa (100/726 [13.8%], and Klebsiella pneumoniae (84/726 [11.6%], with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/3287 patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively.A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts.

  16. Burden of Hospital Acquired Infections and Antimicrobial Use in Vietnamese Adult Intensive Care Units

    Science.gov (United States)

    Larsson, Mattias; Nadjm, Behzad; Dinh, Quynh-Dao; Nilsson, Lennart E.; Rydell, Ulf; Le, Tuyet Thi Diem; Trinh, Son Hong; Pham, Hung Minh; Tran, Cang Thanh; Doan, Hanh Thi Hong; Tran, Nguyen Thua; Le, Nhan Duc; Huynh, Nhuan Van; Tran, Thao Phuong; Tran, Bao Duc; Nguyen, Son Truong; Pham, Thao Thi Ngoc; Dang, Tam Quang; Nguyen, Chau Van Vinh; Lam, Yen Minh; Thwaites, Guy; Van Nguyen, Kinh; Hanberger, Hakan

    2016-01-01

    Background Vietnam is a lower middle-income country with no national surveillance system for hospital-acquired infections (HAIs). We assessed the prevalence of hospital-acquired infections and antimicrobial use in adult intensive care units (ICUs) across Vietnam. Methods Monthly repeated point prevalence surveys were systematically conducted to assess HAI prevalence and antimicrobial use in 15 adult ICUs across Vietnam. Adults admitted to participating ICUs before 08:00 a.m. on the survey day were included. Results Among 3287 patients enrolled, the HAI prevalence was 29.5% (965/3266 patients, 21 missing). Pneumonia accounted for 79.4% (804/1012) of HAIs Most HAIs (84.5% [855/1012]) were acquired in the survey hospital with 42.5% (363/855) acquired prior to ICU admission and 57.5% (492/855) developed during ICU admission. In multivariate analysis, the strongest risk factors for HAI acquired in ICU were: intubation (OR 2.76), urinary catheter (OR 2.12), no involvement of a family member in patient care (OR 1.94), and surgery after admission (OR 1.66). 726 bacterial isolates were cultured from 622/1012 HAIs, most frequently Acinetobacter baumannii (177/726 [24.4%]), Pseudomonas aeruginosa (100/726 [13.8%]), and Klebsiella pneumoniae (84/726 [11.6%]), with carbapenem resistance rates of 89.2%, 55.7%, and 14.9% respectively. Antimicrobials were prescribed for 84.8% (2787/3287) patients, with 73.7% of patients receiving two or more. The most common antimicrobial groups were third generation cephalosporins, fluoroquinolones, and carbapenems (20.1%, 19.4%, and 14.1% of total antimicrobials, respectively). Conclusion A high prevalence of HAIs was observed, mainly caused by Gram-negative bacteria with high carbapenem resistance rates. This in combination with a high rate of antimicrobial use illustrates the urgent need to improve rational antimicrobial use and infection control efforts. PMID:26824228

  17. Serum metabolome and lipidome changes in adult patients with primary dengue infection.

    Directory of Open Access Journals (Sweden)

    Liang Cui

    Full Text Available BACKGROUND: Dengue virus (DENV is the most widespread arbovirus with an estimated 100 million infections occurring every year. Endemic in the tropical and subtropical areas of the world, dengue fever/dengue hemorrhagic fever (DF/DHF is emerging as a major public health concern. The complex array of concurrent host physiologic changes has hampered a complete understanding of underlying molecular mechanisms of dengue pathogenesis. METHODOLOGY/PRINCIPLE FINDINGS: Systems level characterization of serum metabolome and lipidome of adult DF patients at early febrile, defervescence, and convalescent stages of DENV infection was performed using liquid chromatography- and gas chromatography-mass spectrometry. The tractability of following metabolite and lipid changes in a relatively large sample size (n = 44 across three prominent infection stages allowed the identification of critical physiologic changes that coincided with the different stages. Sixty differential metabolites were identified in our metabolomics analysis and the main metabolite classes were free fatty acids, acylcarnitines, phospholipids, and amino acids. Major perturbed metabolic pathways included fatty acid biosynthesis and β-oxidation, phospholipid catabolism, steroid hormone pathway, etc., suggesting the multifactorial nature of human host responses. Analysis of phospholipids and sphingolipids verified the temporal trends and revealed association with lymphocytes and platelets numbers. These metabolites were significantly perturbed during the early stages, and normalized to control levels at convalescent stage, suggesting their potential utility as prognostic markers. CONCLUSIONS/SIGNIFICANCE: DENV infection causes temporally distinct serum metabolome and lipidome changes, and many of the differential metabolites are involved in acute inflammatory responses. Our global analyses revealed early anti-inflammatory responses working in concert to modulate early pro-inflammatory processes

  18. Pneumococcal disease in HIV-infected Malawian adults: acute mortality and long-term survival

    Science.gov (United States)

    Gordon, Stephen B.; Chaponda, Mas; Walsh, Amanda L.; Whitty, Christopher J.M.; Gordon, Melita A.; Machili, C. Edward; Gilks, Charles F.; Boeree, Martin J.; Kampondeni, Sam; Read, Robert C.; Molyneux, Malcolm E.

    2016-01-01

    Objective HIV-infected patients in Africa are vulnerable to severe recurrent infection with Streptococcus pneumoniae, but no effective preventive strategy has been developed. We set out to determine which factors influence in-hospital mortality and long-term survival of Malawians with invasive pneumococcal disease. Design, setting and patients Acute clinical features, inpatient mortality and long-term survival were described among consecutively admitted hospital patients with S. pneumoniae in the blood or cerebrospinal fluid. Factors associated with inpatient mortality were determined, and patients surviving to discharge were followed to determine their long-term outcome. Results A total of 217 patients with pneumococcal disease were studied over an 18-month period. Among these, 158 out of 167 consenting to testing (95%) were HIV positive. Inpatient mortality was 65% for pneumococcal meningitis (n = 64), 20% for pneumococcaemic pneumonia (n = 92), 26% for patients with pneumococcaemia without localizing signs (n = 43), and 76% in patients with probable meningitis (n = 17). Lowered consciousness level, hypotension, and age exceeding 55 years at presentation were associated with inpatient death, but not long-term outcome in survivors. Hospital survivors were followed for a median of 414 days; 39% died in the community during the study period. Outpatient death was associated with multilobar chest signs, oral candidiasis, and severe anaemia as an inpatient. Conclusion Most patients with pneumococcal disease in Malawi have HIV co-infection. They have severe disease with a high mortality rate. At discharge, all HIV-infected adults have a poor prognosis but patients with multilobar chest signs or anaemia are at particular risk. PMID:12131218

  19. Primary care providers' judgments of opioid analgesic misuse in a community-based cohort of HIV-infected indigent adults

    OpenAIRE

    Vijayaraghavan, M.; Penko, J; D. Guzman; Miaskowski, C; Kushel, MB

    2011-01-01

    BACKGROUND: Primary care providers (PCPs) must balance treatment of chronic non-cancer pain with opioid analgesics with concerns about opioid misuse. OBJECTIVE: We co-enrolled community-based indigent adults and their PCPs to determine PCPs' accuracy of estimating opioid analgesic misuse and illicit substance use. DESIGN: Patient-provider dyad study. PARTICIPANTS: HIV-infected, community-based indigent adults ('patients') and their PCPs. MAIN MEASURES: Using structured interviews, we queried ...

  20. Procalcitonin versus C-reactive protein for predicting pneumonia in adults with lower respiratory tract infection in primary care

    DEFF Research Database (Denmark)

    Holm, Anette; Pedersen, Svend S; Nexoe, Joergen;

    2007-01-01

    BACKGROUND: The role of procalcitonin in diagnosing bacterial infection has mainly been studied in patients with severe infections. There is no study on the value of procalcitonin measurements in adults with lower respiratory tract infection (LRTI) treated in primary care. AIM: To evaluate the...... accuracy of plasma procalcitonin in predicting radiographic pneumonia, bacterial infection, and adverse outcome in a population of adults with LRTI treated in primary care. DESIGN OF STUDY: Prospective, observational study. SETTING: Forty-two general practices and an outpatient clinic at the Department of...... Infectious Diseases, Odense University Hospital, Denmark. METHOD: A total of 364 patients with LRTI were prospectively enrolled from 42 general practices. Patients were examined with chest radiography, microbiological analyses, and measurements of C-reactive protein (CRP) and procalcitonin. The outcome...

  1. Adult human neural stem cell therapeutics: Currentdevelopmental status and prospect

    Institute of Scientific and Technical Information of China (English)

    Hyun Nam; Kee-Hang Lee; Do-Hyun Nam; Kyeung Min Joo

    2015-01-01

    Over the past two decades, regenerative therapies usingstem cell technologies have been developed for variousneurological diseases. Although stem cell therapy is anattractive option to reverse neural tissue damage and torecover neurological deficits, it is still under developmentso as not to show significant treatment effects in clinicalsettings. In this review, we discuss the scientific andclinical basics of adult neural stem cells (aNSCs), andtheir current developmental status as cell therapeuticsfor neurological disease. Compared with other typesof stem cells, aNSCs have clinical advantages, suchas limited proliferation, inborn differentiation potentialinto functional neural cells, and no ethical issues. Inspite of the merits of aNSCs, difficulties in the isolationfrom the normal brain, and in the in vitro expansion,have blocked preclinical and clinical study using aNSCs.However, several groups have recently developed noveltechniques to isolate and expand aNSCs from normaladult brains, and showed successful applications ofaNSCs to neurological diseases. With new technologiesfor aNSCs and their clinical strengths, previous hurdlesin stem cell therapies for neurological diseases could beovercome, to realize clinically efficacious regenerativestem cell therapeutics.

  2. Cloned goats (Capra hircus) from adult ear cells

    Institute of Scientific and Technical Information of China (English)

    GUO; Jitong(郭继彤); AN; Zhixing(安志兴); LI; Yu(李煜); LI; Xuefeng(李雪峰); LI; Yuqiang(李裕强); GUO; Zekun(郭泽坤); ZHANG; Yong(张涌)

    2002-01-01

    The average number of available oocytes recovered per ovary collected during the breeding season in dairy goats was 5.5 (1815/330). 66.17% (1201/1815) of oocytes extruded the first polar body after maturation in vitro for 20 h. 75.44% (906/1201) of matured oocytes with membrane evagination around the MⅡchromosomes were enucleated. Ear skin fibroblast cells were derived from an adult female Jining Grey goat (C. hircus). The cells were cryopreserved in liquid nitrogen after passage 2. Thawed cells were further cultured for 3-6 passages and were subjected to serum starvation by 0.5% FBS for 2-10 d, then used as donor cells for nuclear transfer. 98.12% (889/906) of the enucleated oocytes were reconstructed by intracytoplasmic injection of karyoplast. The reconstructed embryos were activated by 5 μmol/L ionomycin for 4.5 min and further activated by culturing with 6-dimethylaminopurine (6-DMAP) for 3 h. After 36 h of culture in mCR1aaBF, 76.69% (645/841) of the cloned embryos cleaved. There were no significant differences in development in vitro between the cloned embryos derived from donor cells precooled at 4℃ for 24 h and nonprecooled donor cells. The cleavage rates, 4-cell development, and blastocyst development of reconstructed embryos were 72.48% (79/109), 53.16% (42/79), and 19.05% (8/42) in precooled group; 68.5% (211/308), 59.72% (126/211), and 17.46% (22/126) in nonprecooled group, respectively. Eighteen cloned 4-cell embryos derived from precooled donor cells were transferred and one cloned kid was born. Eighty-four cloned 4-cell embryos derived from nonprecooled donor cells were transferred and no offspring were produced. Of 18 cloned morale from nonprecooled donor cells transferred, one kid was born. The results of microsatellite DNA analyses indicated that the two cloned kids were from the same donor fibroblast cell line derived from an adult goat ear skin.

  3. A novel view of the adult bone marrow stem cell hierarchy and stem cell trafficking.

    Science.gov (United States)

    Ratajczak, M Z

    2015-04-01

    This review presents a novel view and working hypothesis about the hierarchy within the adult bone marrow stem cell compartment and the still-intriguing question of whether adult bone marrow contains primitive stem cells from early embryonic development, such as cells derived from the epiblast, migrating primordial germ cells or yolk sac-derived hemangioblasts. It also presents a novel view of the mechanisms that govern stem cell mobilization and homing, with special emphasis on the role of the complement cascade as a trigger for egress of hematopoietic stem cells from bone marrow into blood as well as the emerging role of novel homing factors and priming mechanisms that support stromal-derived factor 1-mediated homing of hematopoietic stem/progenitor cells after transplantation. PMID:25486871

  4. Inverse Relationship Between Helicobacter Pylori Infection and Asthma Among Adults Younger than 40 Years: A Cross-Sectional Study.

    Science.gov (United States)

    Lim, Joo Hyun; Kim, Nayoung; Lim, Seon Hee; Kwon, Jin-Won; Shin, Cheol Min; Chang, Yoon-Seok; Kim, Joo Sung; Jung, Hyun Chae; Cho, Sang-Heon

    2016-02-01

    Recent studies have suggested that Helicobacter pylori could prevent allergic disease, particularly in children. However, whether this is true in adults is controversial. The aim of this study was to investigate whether there is negative association between H. pylori infection and asthma among adults in an area with a high prevalence of H. pylori.This was a cross-sectional study using 2011 health surveillance data. Blood samples were taken from all participants to measure serum H. pylori IgG status. Information on demographics, socioeconomic status, and medical history, including asthma and other allergic conditions were collected by a questionnaire.Of the 15,032 patients, 9492 (63.1%) had a history of H. pylori infection, 359 (2.4%) had asthma, and 3277 (21.8%) had other allergic conditions. H. pylori infection was positively correlated with age (OR, 1.050; 95% CI, 1.047-1.053, P Asthma history was positively correlated with age (OR, 1.022; 95% CI, 1.013-1.032, P asthma in the total participants (OR, 1.041; 95% CI, 1.021-1.062, P asthma (OR, 0.503; 95% CI, 0.280-0.904, P = 0.021). Other allergic conditions were not related with H. pylori infection among the total and those asthma among young adults suggests that the underlying immune mechanism induced by H. pylori infection may affect allergic reactions associated with asthma in young adults.

  5. Reduced mucosal associated invariant T-cells are associated with increased disease severity and Pseudomonas aeruginosa infection in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Daniel J Smith

    Full Text Available BACKGROUND: Primary defects in host immune responses have been hypothesised to contribute towards an inability of subjects with cystic fibrosis (CF to effectively clear pulmonary infections. Innate T-lymphocytes provide rapid pathogen-specific responses prior to the development of classical MHC class I and II restricted T-cell responses and are essential to the initial control of pulmonary infection. We aimed to examine the relationship between peripheral blood lymphocyte phenotype and clinical outcomes in adults with CF. METHODS: We studied 41 subjects with CF and 22, age matched, non-smoking healthy control subjects. Lymphocytes were extracted from peripheral blood samples and phenotyped by flow-cytometry. Lymphocyte phenotype was correlated with sputum microbiology and clinical parameters. RESULTS: In comparison to healthy control subjects, mucosal associated invariant T (MAIT-lymphocytes were significantly reduced in the peripheral blood of subjects with CF (1.1% versus 2.0% of T-lymphocytes, P = 0.002. MAIT cell concentration was lowest in CF subjects infected with P. aeruginosa and in subjects receiving treatment for a pulmonary exacerbation. Furthermore a reduced MAIT cell concentration correlated with severity of lung disease. CONCLUSION: Reduced numbers of MAIT cells in subjects with CF were associated with P. aeruginosa pulmonary infection, pulmonary exacerbations and more severe lung disease. These findings provide the impetus for future studies examining the utility of MAIT cells in immunotherapies and vaccine development. Longitudinal studies of MAIT cells as biomarkers of CF pulmonary infection are awaited.

  6. Dynamic Imaging of CD8(+) T cells and dendritic cells during infection with Toxoplasma gondii.

    Science.gov (United States)

    John, Beena; Harris, Tajie H; Tait, Elia D; Wilson, Emma H; Gregg, Beth; Ng, Lai Guan; Mrass, Paulus; Roos, David S; Dzierszinski, Florence; Weninger, Wolfgang; Hunter, Christopher A

    2009-07-01

    To better understand the initiation of CD8(+) T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs) and parasite specific CD8(+) T cells. Infection with T. gondii induced localization of both these populations to the sub-capsular/interfollicular region of the draining lymph node and DCs were required for the expansion of the T cells. Consistent with current models, in the presence of cognate antigen, the average velocity of CD8(+) T cells decreased. Unexpectedly, infection also resulted in modulation of the behavior of non-parasite specific T cells. This TCR-independent process correlated with the re-modeling of the lymph node micro-architecture and changes in expression of CCL21 and CCL3. Infection also resulted in sustained interactions between the DCs and CD8(+) T cells that were visualized only in the presence of cognate antigen and were limited to an early phase in the response. Infected DCs were rare within the lymph node during this time frame; however, DCs presenting the cognate antigen were detected. Together, these data provide novel insights into the earliest interaction between DCs and CD8(+) T cells and suggest that cross presentation by bystander DCs rather than infected DCs is an important route of antigen presentation during toxoplasmosis.

  7. Dynamic Imaging of CD8(+ T cells and dendritic cells during infection with Toxoplasma gondii.

    Directory of Open Access Journals (Sweden)

    Beena John

    2009-07-01

    Full Text Available To better understand the initiation of CD8(+ T cell responses during infection, the primary response to the intracellular parasite Toxoplasma gondii was characterized using 2-photon microscopy combined with an experimental system that allowed visualization of dendritic cells (DCs and parasite specific CD8(+ T cells. Infection with T. gondii induced localization of both these populations to the sub-capsular/interfollicular region of the draining lymph node and DCs were required for the expansion of the T cells. Consistent with current models, in the presence of cognate antigen, the average velocity of CD8(+ T cells decreased. Unexpectedly, infection also resulted in modulation of the behavior of non-parasite specific T cells. This TCR-independent process correlated with the re-modeling of the lymph node micro-architecture and changes in expression of CCL21 and CCL3. Infection also resulted in sustained interactions between the DCs and CD8(+ T cells that were visualized only in the presence of cognate antigen and were limited to an early phase in the response. Infected DCs were rare within the lymph node during this time frame; however, DCs presenting the cognate antigen were detected. Together, these data provide novel insights into the earliest interaction between DCs and CD8(+ T cells and suggest that cross presentation by bystander DCs rather than infected DCs is an important route of antigen presentation during toxoplasmosis.

  8. The proteome of neural stem cells from adult rat hippocampus

    Directory of Open Access Journals (Sweden)

    Fütterer Carsten D

    2003-06-01

    Full Text Available Abstract Background Hippocampal neural stem cells (HNSC play an important role in cerebral plasticity in the adult brain and may contribute to tissue repair in neurological disease. To describe their biological potential with regard to plasticity, proliferation, or differentiation, it is important to know the cellular composition of their proteins, subsumed by the term proteome. Results Here, we present for the first time a proteomic database for HNSC isolated from the brains of adult rats and cultured for 10 weeks. Cytosolic proteins were extracted and subjected to two-dimensional gel electrophoresis followed by protein identification through mass spectrometry, database search, and gel matching. We could map about 1141 ± 209 (N = 5 protein spots for each gel, of which 266 could be identified. We could group the identified proteins into several functional categories including metabolism, protein folding, energy metabolism and cellular respiration, as well as cytoskeleton, Ca2+ signaling pathways, cell cycle regulation, proteasome and protein degradation. We also found proteins belonging to detoxification, neurotransmitter metabolism, intracellular signaling pathways, and regulation of DNA transcription and RNA processing. Conclusions The HNSC proteome database is a useful inventory which will allow to specify changes in the cellular protein expression pattern due to specific activated or suppressed pathways during differentiation or proliferation of neural stem cells. Several proteins could be identified in the HNSC proteome which are related to differentiation and plasticity, indicating activated functional pathways. Moreover, we found a protein for which no expression has been described in brain cells before.

  9. Autonomous interconversion between adult pancreatic α-cells and β-cells after differential metabolic challenges

    Directory of Open Access Journals (Sweden)

    Risheng Ye

    2016-07-01

    Conclusions: We identify the origins and fates of adult β-cells upon post-challenge upon autonomous regeneration of islet mass and establish the quantitative contributions of the different cell types using a lineage tracing system with high temporal resolution.

  10. Relative concentrations of serum neutralizing antibody to VP3 and VP7 proteins in adults infected with a human rotavirus.

    OpenAIRE

    Ward, R. L.; Knowlton, D R; Schiff, G M; Hoshino, Y.; Greenberg, H B

    1988-01-01

    Two outer capsid rotavirus proteins, VP3 and VP7, have been found to elicit neutralizing-antibody production, but the immunogenicity of these proteins during human rotavirus infection has not been determined. The relative amounts of serum neutralizing antibody against the VP3 and VP7 proteins of the CJN strain of human rotavirus were, therefore, determined in adult subjects before and after infection with this virus. Reassortant strains of rotavirus that contained the CJN gene segment for onl...

  11. Aetiologies of Central Nervous System infections in adults in Kathmandu, Nepal: A prospective hospital-based study

    OpenAIRE

    Giri, Abhishek; Arjyal, Amit; Koirala, Samir; Karkey, Abhilasha; Dongol, Sabina; Thapa, Sudeep Dhoj; Shilpakar, Olita; Shrestha, Rishav; Van Tan, Le; Thi Thuy Chinh, Bkrong Nguyen; Krishna K. C., Radheshyam; Pathak, Kamal Raj; Shakya, Mila; Farrar, Jeremy; Van Doorn, H. Rogier

    2013-01-01

    We conducted a prospective hospital based study from February 2009-April 2011 to identify the possible pathogens of central nervous system (CNS) infections in adults admitted to a tertiary referral hospital (Patan Hospital) in Kathmandu, Nepal. The pathogens of CNS infections were confirmed in cerebrospinal fluid (CSF) using molecular diagnostics, culture (bacteria) and serology. 87 patients were recruited for the study and the etiological diagnosis was established in 38% (n = 33). The bacter...

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

    OpenAIRE

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

    2012-01-01

    Honeybees, Apis mellifera, show age-related division of labor in which young adults perform maintenance ("housekeeping") tasks inside the colony before switching to outside foraging at approximately 23 days old. Disease resistance is an important feature of honeybee biology, but little is known about the interaction of pathogens and age-related division of labor. We tested a hypothesis that older forager bees and younger "house" bees differ in susceptibility to infection. We coupled an infect...

  13. The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java

    OpenAIRE

    Herman Kosasih; Bachti Alisjahbana; Nurhayati,; Quirijn de Mast; Irani F Rudiman; Susana Widjaja; Ungke Antonjaya; Harli Novriani; Susanto, Nugroho H.; Hadi Jusuf; Andre van der Ven; Beckett, Charmagne G.; Blair, Patrick J; Burgess, Timothy H.; Maya Williams

    2016-01-01

    Background Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology o...

  14. Differential proteome analysis of chikungunya virus infection on host cells.

    Directory of Open Access Journals (Sweden)

    Christina Li-Ping Thio

    Full Text Available BACKGROUND: Chikungunya virus (CHIKV is an emerging mosquito-borne alphavirus that has caused multiple unprecedented and re-emerging outbreaks in both tropical and temperate countries. Despite ongoing research efforts, the underlying factors involved in facilitating CHIKV replication during early infection remains ill-characterized. The present study serves to identify host proteins modulated in response to early CHIKV infection using a proteomics approach. METHODOLOGY AND PRINCIPAL FINDINGS: The whole cell proteome profiles of CHIKV-infected and mock control WRL-68 cells were compared and analyzed using two-dimensional gel electrophoresis (2-DGE. Fifty-three spots were found to be differentially modulated and 50 were successfully identified by MALDI-TOF/TOF. Eight were significantly up-regulated and 42 were down-regulated. The mRNA expressions of 15 genes were also found to correlate with the corresponding protein expression. STRING network analysis identified several biological processes to be affected, including mRNA processing, translation, energy production and cellular metabolism, ubiquitin-proteasome pathway (UPP and cell cycle regulation. CONCLUSION/SIGNIFICANCE: This study constitutes a first attempt to investigate alteration of the host cellular proteome during early CHIKV infection. Our proteomics data showed that during early infection, CHIKV affected the expression of proteins that are involved in mRNA processing, host metabolic machinery, UPP, and cyclin-dependent kinase 1 (CDK1 regulation (in favour of virus survival, replication and transmission. While results from this study complement the proteomics results obtained from previous late host response studies, functional characterization of these proteins is warranted to reinforce our understanding of their roles during early CHIKV infection in humans.

  15. Phagocytosis by glomerular endothelial cells in infection-related glomerulopathy.

    Science.gov (United States)

    van Velthuysen, M L; Mayen, A E; Prins, F A; de Heer, E; Bruijn, J A; Fleuren, G J

    1994-01-01

    Glomerulonephritis in BALB/c mice following infection with Trypanosoma brucei is characterized by albuminuria and glomerular deposition of immunoglobulins. Electron-dense deposits are present in the mesangium, as well as subendothelially and subepithelially along the glomerular capillary wall. In this study the nature of intracytoplasmic, electron-dense, round structures observed in glomerular endothelial cells was investigated by immunoelectron-microscopy and enzyme histochemistry. The presence of these structures was related in time with the development of proteinuria. Mice from the C57BL10 strain, which upon infection develop glomerular immune complexes without proteinuria, were examined as well. The results demonstrated that the first endothelial changes, occurring 3-4 weeks after infection, were swelling of endothelial cells containing intracytoplasmic, electron-dense, round structures. These changes were seen prior to the onset of proteinuria, and were not present in glomeruli of mice that did not develop proteinuria. The endothelial granules were shown to contain immunoglobulins and typical lysosomal enzymes, providing evidence for phagocytosis by the glomerular endothelial cells. Liver endothelial cells did not show comparable changes. Thus, local phagocytosis by glomerular endothelial cells is shown to be a specific event in the development of glomerular disease. PMID:7800204

  16. A cross-sectional survey of dental caries, oral hygiene, and Helicobacter pylori infection in adults.

    Science.gov (United States)

    Liu, Peng; Yue, Ji; Han, Shufang; Deng, Tianzheng; Fu, Chongjian; Zhu, Guoxiong; Chen, Dong

    2013-07-01

    We explored the epidemiological risk factors for dental caries to help explain differences in the prevalence of adult dental caries. We examined 841 people for the presence of Helicobacter pylori in their dental plaque and for dental caries. Of the 841 subjects, 574 (68.25%) were infected with H pylori, and 516 (61.36%) were diagnosed with dental caries. Among the 574 subjects with H pylori, the prevalence of dental caries was 73.52% (422/574), while the prevalence among the 267 cases without H pylori was 35.21% (94/267). A correlation existed between the presence of H pylori and the occurrence of dental caries (χ(2) = 112.8, P caries and poor dental hygiene.

  17. Serious systemic infection caused by non-encapsulated Haemophilus influenzae biotype III in an adult

    DEFF Research Database (Denmark)

    Lester, Anne; Pedersen, P B

    1991-01-01

    Haemophilus influenzae is the aetiological agent in less than 1% of septic arthritis cases in adults and most often serotype b is involved. We report here a case of severe systemic infection due to non-encapsulated H. influenzae biotype III in a 40-year-old man, previously healthy although alcohol...... abuser. Cholangitis and acute alcoholic hepatitis were diagnosed simultaneously. The organism was grown from blood and from synovial fluid of the left knee, but several other joints were also affected. The close relationship between H. influenzae biotype III and H. aegyptius is mentioned in view...... of recent reports of fatal childhood illness caused by a special clone of H. aegyptius and the importance of reporting both serotype and biotype in severe H. influenzae induced disease is emphasized....

  18. Giardia infection: Protein-losing enteropathy in an adult with immunodeficiency

    Institute of Scientific and Technical Information of China (English)

    Alexandre Khodr Furtado; Virginia Lucia Ribeiro Cabral; Thiago Nunes Santos; Eli Mansour; Cristiane Kibune Nagasako; Sonia Leticia Lorena; Rogerio Antunes Pereira-Filho

    2012-01-01

    The case of a 52-year-old woman with a past history of thymoma resection who presented with chronic diarrhea and generalized edema is the focal point of this article.A diagnosis of Giardia lamblia infection was established,which was complicated by protein-losing enteropathy and severely low serum protein level in a patient with no urinary protein loss and normal liver function.After anti-helmintic treatment,there was recovery from hypoalbuminemia,though immunoglobulins persisted at low serum levels leading to the hypothesis of an immune system disorder.Good's syndrome is a rare cause of immunodeficiency characterized by the association of hypogammaglobulinemia and thymoma.This primary immune disorder may be complicated by severe infectious diarrhea secondary to disabled humoral and cellular immune response.This is the first description in the literature of an adult patient with an immunodeficiency syndrome who presented with protein-losing enteropathy secondary to giardiasis.

  19. Differential outcome of neurological HCMV infection in two hematopoietic stem cell transplant recipients

    Directory of Open Access Journals (Sweden)

    Colombo Anna

    2012-10-01

    Full Text Available Abstract Background Human cytomegalovirus (HCMV infection of the central nervous system (CNS is a rare but life threatening condition which may follow hematopoietic stem cell transplantation. Diagnosis, monitoring and treatment approaches rely on anecdotal reports. Case presentations The different outcomes of HCMV CNS disease in an adult and a pediatric T-cell depleted hematopoietic stem cell transplant (HSCT recipient are reported. In the first case, HCMV encephalitis emerged in the context of simultaneous impairment of the T- and B-cell immunity. Antiviral treatment only reduced viral load in peripheral blood and the patient died. In the second case, an HCMV radiculopathy was observed and antiviral treatment was adjusted on the basis of intrathecal drug level. In addition, donor HCMV-specific cytotoxic T lymphocytes (CTLs were infused. Viral load in the CNS decreased and the patient recovered from the acute event. In neither case were drug-resistant HCMV variants observed in blood or CNS samples. Conclusions T-cell depleted HSCT appears a predisposing condition for CNS HCMV infection since never observed in other HSCT recipients at our center in the last 15 years. Intensive diagnostic approaches and timely aggressive combination treatments might improve clinical outcome in these patients.

  20. Impairment of T cell function in parasitic infections.

    Directory of Open Access Journals (Sweden)

    Vasco Rodrigues

    2014-02-01

    Full Text Available In mammals subverted as hosts by protozoan parasites, the latter and/or the agonists they release are detected and processed by sensors displayed by many distinct immune cell lineages, in a tissue(s-dependent context. Focusing on the T lymphocyte lineage, we review our present understanding on its transient or durable functional impairment over the course of the developmental program of the intracellular parasites Leishmania spp., Plasmodium spp., Toxoplasma gondii, and Trypanosoma cruzi in their mammalian hosts. Strategies employed by protozoa to down-regulate T lymphocyte function may act at the initial moment of naïve T cell priming, rendering T cells anergic or unresponsive throughout infection, or later, exhausting T cells due to antigen persistence. Furthermore, by exploiting host feedback mechanisms aimed at maintaining immune homeostasis, parasites can enhance T cell apoptosis. We will discuss how infections with prominent intracellular protozoan parasites lead to a general down-regulation of T cell function through T cell anergy and exhaustion, accompanied by apoptosis, and ultimately allowing pathogen persistence.

  1. Discovery and Validation of Prognostic Biomarker Models to Guide Triage among Adult Dengue Patients at Early Infection

    Science.gov (United States)

    Tolfvenstam, Thomas; Thein, Tun-Linn; Naim, Ahmad Nazri Mohamed; Ling, Ling; Chow, Angelia; Chen, Mark I-Cheng; Ooi, Eng Eong; Leo, Yee Sin; Hibberd, Martin L.

    2016-01-01

    Background Dengue results in a significant public health burden in endemic regions. The World Health Organization (WHO) recommended the use of warning signs (WS) to stratify patients at risk of severe dengue disease in 2009. However, WS is limited in stratifying adult dengue patients at early infection (Day 1–3 post fever), who require close monitoring in hospitals to prevent severe dengue. The aim of this study is to identify and validate prognostic models, built with differentially expressed biomarkers, that enable the early identification of those with early dengue infection that require close clinical monitoring. Methods RNA microarray and protein assays were performed to identify differentially expressed biomarkers of severity among 92 adult dengue patients recruited at early infection from years 2005–2008. This comprised 47 cases who developed WS after first presentation and required hospitalization (WS+Hosp), as well as 45 controls who did not develop WS after first presentation and did not require hospitalization (Non-WS+Non-Hosp). Independent validation was conducted with 80 adult dengue patients recruited from years 2009–2012. Prognostic models were developed based on forward stepwise and backward elimination estimation, using multiple logistic regressions. Prognostic power was estimated by the area under the receiver operating characteristic curve (AUC). Results The WS+Hosp group had significantly higher viral load (Pdengue patients at early infection, with sensitivity and specificity up to 83% and 84%, respectively. These results were tested in the independent validation group, showing sensitivity and specificity up to 96% and 54.6%, respectively. Conclusions At early infection, adult dengue patients who later presented WS and require hospitalization have significantly different pathophysiology compared with patients who consistently presented no WS and / or require no hospitalization. The molecular prognostic models developed and validated here

  2. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    OpenAIRE

    Sabine Wislet-Gendebien; Emerence Laudet; Virginie Neirinckx; Bernard Rogister

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In th...

  3. Isolation of alveolar epithelial type II progenitor cells from adult human lungs

    OpenAIRE

    Fujino, Naoya; Kubo, Hiroshi; Suzuki, Takaya; Ota, Chiharu; Hegab, Ahmed E.; He, Mei; Suzuki, Satoshi; Suzuki, Takashi; Yamada, Mitsuhiro; Kondo, Takashi; Kato, Hidemasa; Yamaya, Mutsuo

    2010-01-01

    Resident stem/progenitor cells in the lung are important for tissue homeostasis and repair. However, a progenitor population for alveolar type II (ATII) cells in adult human lungs has not been identified. The aim of this study is to isolate progenitor cells from adult human lungs with the ability to differentiate into ATII cells. We isolated colony-forming cells that had the capability for self-renewal and the potential to generate ATII cells in vitro. These undifferentiated progenitor cells ...

  4. Is Urinary Lipoarabinomannan the Result of Renal Tuberculosis? Assessment of the Renal Histology in an Autopsy Cohort of Ugandan HIV-Infected Adults.

    Directory of Open Access Journals (Sweden)

    Janneke A Cox

    Full Text Available The detection of urinary lipoarabinomannan (LAM, a mycobacterial cell wall component, is used to diagnose tuberculosis (TB. How LAM enters the urine is not known. To investigate if urinary LAM-positivity is the result of renal TB infection we correlated the outcomes of urinary LAM-antigen testing to renal histology in an autopsy cohort of hospitalized, Ugandan, HIV-infected adults.We performed a complete autopsy, including renal sampling, in HIV-infected adults that died during hospitalization after written informed consent was obtained from the next of kin. Urine was collected postmortem through post-mortem catheterisation or by bladder puncture and tested for LAM with both a lateral flow assay (LFA and an ELISA assay. Two pathologists assessed the kidney histology. We correlated the LAM-assay results and the histology findings.Of the 13/36 (36% patients with a positive urinary LAM ELISA and/or LFA, 8/13 (62% had renal TB. The remaining 5 LAM-positive patients had disseminated TB without renal involvement. Of the 23 LAM-negative patients, 3 had disseminated TB without renal involvement. The remaining LAM-negative patients had no TB infection and died mostly of fungal and bacterial infections. LAM LFA had a sensitivity of 81% and specificity of 100% to diagnose TB at any location, and the LAM ELISA a sensitivity of 63% and a specificity of 100%. 54% (7/13 LAM LFA-positive patients were not on anti-TB treatment at the time of death.Renal TB infection explained LAM-positivity in the majority of patients. Patients with disseminated TB without renal involvement can also be diagnosed with LAM. This suggests that other mechanisms that lead to urinary LAM-positivity exist in a minority of patients.

  5. High-resolution CT of nontuberculous mycobacterium infection in adult CF patients: diagnostic accuracy

    Energy Technology Data Exchange (ETDEWEB)

    McEvoy, Sinead; Lavelle, Lisa; Kilcoyne, Aoife; McCarthy, Colin; Dodd, Jonathan D. [St. Vincent' s University Hospital, Department of Radiology, Dublin (Ireland); DeJong, Pim A. [University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Loeve, Martine; Tiddens, Harm A.W.M. [Erasmus MC-Sophia Children' s Hospital, Department of Radiology, Department of Pediatric Pulmonology and Allergology, Rotterdam (Netherlands); McKone, Edward; Gallagher, Charles G. [St. Vincent' s University Hospital, Department of Respiratory Medicine and National Referral Centre for Adult Cystic Fibrosis, Dublin (Ireland)

    2012-12-15

    To determine the diagnostic accuracy of high-resolution computed tomography (HRCT) for the detection of nontuberculous mycobacterium infection (NTM) in adult cystic fibrosis (CF) patients. Twenty-seven CF patients with sputum-culture-proven NTM (NTM+) underwent HRCT. An age, gender and spirometrically matched group of 27 CF patients without NTM (NTM-) was included as controls. Images were randomly and blindly analysed by two readers in consensus and scored using a modified Bhalla scoring system. Significant differences were seen between NTM (+) and NTM (-) patients in the severity of the bronchiectasis subscore [45 % (1.8/4) vs. 35 % (1.4/4), P = 0.029], collapse/consolidation subscore [33 % (1.3/3) vs. 15 % (0.6/3)], tree-in-bud/centrilobular nodules subscore [43 % (1.7/3) vs. 25 % (1.0/3), P = 0.002] and the total CT score [56 % (18.4/33) vs. 46 % (15.2/33), P = 0.002]. Binary logistic regression revealed BMI, peribronchial thickening, collapse/consolidation and tree-in-bud/centrilobular nodules to be predictors of NTM status (R{sup 2} = 0.43). Receiver-operator curve analysis of the regression model showed an area under the curve of 0.89, P < 0.0001. In adults with CF, seven or more bronchopulmonary segments showing tree-in-bud/centrilobular nodules on HRCT is highly suggestive of NTM colonisation. (orig.)

  6. High-resolution CT of nontuberculous mycobacterium infection in adult CF patients: diagnostic accuracy

    International Nuclear Information System (INIS)

    To determine the diagnostic accuracy of high-resolution computed tomography (HRCT) for the detection of nontuberculous mycobacterium infection (NTM) in adult cystic fibrosis (CF) patients. Twenty-seven CF patients with sputum-culture-proven NTM (NTM+) underwent HRCT. An age, gender and spirometrically matched group of 27 CF patients without NTM (NTM-) was included as controls. Images were randomly and blindly analysed by two readers in consensus and scored using a modified Bhalla scoring system. Significant differences were seen between NTM (+) and NTM (-) patients in the severity of the bronchiectasis subscore [45 % (1.8/4) vs. 35 % (1.4/4), P = 0.029], collapse/consolidation subscore [33 % (1.3/3) vs. 15 % (0.6/3)], tree-in-bud/centrilobular nodules subscore [43 % (1.7/3) vs. 25 % (1.0/3), P = 0.002] and the total CT score [56 % (18.4/33) vs. 46 % (15.2/33), P = 0.002]. Binary logistic regression revealed BMI, peribronchial thickening, collapse/consolidation and tree-in-bud/centrilobular nodules to be predictors of NTM status (R2 = 0.43). Receiver-operator curve analysis of the regression model showed an area under the curve of 0.89, P < 0.0001. In adults with CF, seven or more bronchopulmonary segments showing tree-in-bud/centrilobular nodules on HRCT is highly suggestive of NTM colonisation. (orig.)

  7. Sustained Arc expression in adult-generated granule cells.

    Science.gov (United States)

    Meconi, Alicia; Lui, Erika; Marrone, Diano F

    2015-08-31

    The dentate gyrus (DG) plays a critical role in memory formation and maintenance. Fitting this specialized role, the DG has many unique characteristics. In addition to being one of the few places in which new neurons are continually added in adulthood, the region also shows a unique long-term sustained transcriptional response of the immediate-early gene Arc to sensory input. Although we know that adult-generated granule cells are reliably recruited into behaviorally-driven neuronal network, it remains unknown whether they display robust late-phase sustained transcription in response to activity like their developmentally-generated counterparts. Since this late-phase of transcription is required for enduring plasticity, knowing if sustained transcription appears as soon as these cells are incorporated provides information on their potential for plasticity. To address this question, adult F344 rats were injected with BrdU (50mg/kg/day for 5 days) and 4 weeks later explored a novel environment. Arc expression in both BrdU- and BrdU+ neurons was determined 0.5h, 1h, 2h, 6h, 8h, 12h, or 24h following this behavior. Recently-generated granule cells showed a robust sustained Arc expression following a discrete behavioral experience. These data provide information on a potential mechanism to sculpt the representations of events occurring within hours of each other to create uncorrelated representations of episodes despite a highly excitable population of neurons. PMID:26219984

  8. Effect of Human Cytomegalovirus Infection on Nerve Growth Factor Expression in Human Glioma U251 Cells

    Institute of Scientific and Technical Information of China (English)

    HAI-TAO WANG; BIN WANG; ZHI-JUN LIU; ZHI-QIANG BAI; LING LI; HAI-YAN LIU; DONG-MENG QIAN; ZHI-YONG YAN; XU-XIA SONG

    2009-01-01

    Objectives To explore the change of endogenic nerve growth factor (NGF) expression in human glioma cells infected with human cytomegalovirus (HCMV). Methods U251 cells were cultured in RPMI 1640 culture medium and infected with HCMV AD169 strain in vitro to establish a cell model of viral infection. Morphologic changes of U251 cells were observed under inverted microscope before and after infection with HCMV. Expression of NGF gene and protein of cells was detected by RT-PCR and Western blotting before and after infection with HCMV. Results The cytopathic effects of HCMV-infected cells appeared on day 5 after infection. However, differential NGF expression was evident on day 7. NGF expression was decreased significantly in U251 cells on day 7 after infection in comparison with control group (P<0.05). Conclusion HCMV can down-regulate endogenous NGF levels in human glioma cell line U251.

  9. A Three-Dimensional Cell Culture Model To Study Enterovirus Infection of Polarized Intestinal Epithelial Cells.

    Science.gov (United States)

    Drummond, Coyne G; Nickerson, Cheryl A; Coyne, Carolyn B

    2016-01-01

    Despite serving as the primary entry portal for coxsackievirus B (CVB), little is known about CVB infection of the intestinal epithelium, owing at least in part to the lack of suitable in vivo models and the inability of cultured cells to recapitulate the complexity and structure associated with the gastrointestinal (GI) tract. Here, we report on the development of a three-dimensional (3-D) organotypic cell culture model of Caco-2 cells to model CVB infection of the gastrointestinal epithelium. We show that Caco-2 cells grown in 3-D using the rotating wall vessel (RWV) bioreactor recapitulate many of the properties of the intestinal epithelium, including the formation of well-developed tight junctions, apical-basolateral polarity, brush borders, and multicellular complexity. In addition, transcriptome analyses using transcriptome sequencing (RNA-Seq) revealed the induction of a number of genes associated with intestinal epithelial differentiation and/or intestinal processes in vivo when Caco-2 cells were cultured in 3-D. Applying this model to CVB infection, we found that although the levels of intracellular virus production were similar in two-dimensional (2-D) and 3-D Caco-2 cell cultures, the release of infectious CVB was enhanced in 3-D cultures at early stages of infection. Unlike CVB, the replication of poliovirus (PV) was significantly reduced in 3-D Caco-2 cell cultures. Collectively, our studies show that Caco-2 cells grown in 3-D using the RWV bioreactor provide a cell culture model that structurally and transcriptionally represents key aspects of cells in the human GI tract and can thus be used to expand our understanding of enterovirus-host interactions in intestinal epithelial cells. IMPORTANCE Coxsackievirus B (CVB), a member of the enterovirus family of RNA viruses, is associated with meningitis, pericarditis, diabetes, dilated cardiomyopathy, and myocarditis, among other pathologies. CVB is transmitted via the fecal-oral route and encounters the

  10. Occurrence and genetic characterization of Echinococcus granulosus in naturally infected adult sheep and cattle in Romania.

    Science.gov (United States)

    Mitrea, Ioan Liviu; Ionita, Mariana; Costin, Irina Ioana; Predoi, Gabriel; Avram, Eugeniu; Rinaldi, Laura; Maurelli, Maria Paola; Cringoli, Giuseppe; Genchi, Claudio

    2014-12-15

    An epidemiological and molecular study was conducted to investigate the occurrence and genetic diversity of Echinococcus granulosus isolates from adult sheep and cattle in Romania. Overall, 642 sheep (aged over 3 years) and 1878 cattle (aged over 5 years) from 16 counties were examined for hydatid cysts. Of them, 421 (65.6%) sheep and 754 (40.1%) cattle were found infected by cystic echinococcosis (CE). Germinal layers were collected from 98 individual cysts (one cyst per animal; 31 from sheep and 67 from cattle), DNA was extracted and two different mitochondrial DNA genes, namely cytochrome c oxidase subunits 1 (CO1) and 12S ribosomal DNA (12S rDNA) were used as genetic markers. The assessment of the genetic diversity of the Echinococcus strains showed the presence of the E. granulosus sensu stricto complex and disclosed an apparent dominance of the G1 genotype within the G1–G3 complex. Furthermore, several mitochondrial variants were identified for the G1 and G2 genotypes of E. granulosus s.s. complex. Overall, the findings were of epidemiological relevance and highlighted a high potential risk of zoonotic infection.

  11. Schmallenberg virus infection of adult type I interferon receptor knock-out mice.

    Directory of Open Access Journals (Sweden)

    Kerstin Wernike

    Full Text Available Schmallenberg virus (SBV, a novel orthobunyavirus, was discovered in Europe in late 2011. It causes mild and transient disease in adult ruminants, but fetal infection can lead to abortion or severe malformations. There is considerable demand for SBV research, but in vivo studies in large animals are complicated by their long gestation periods and the cost of high containment housing. The goal of this study was to investigate whether type I interferon receptor knock-out (IFNAR(-/- mice are a suitable small animal model for SBV. Twenty IFNAR(-/- mice were inoculated with SBV, four were kept as controls. After inoculation, all were observed and weighed daily; two mice per day were sacrificed and blood, brain, lungs, liver, spleen, and intestine were harvested. All but one inoculated mouse lost weight, and two mice died spontaneously at the end of the first week, while another two had to be euthanized. Real-time RT-PCR detected large amounts of SBV RNA in all dead or sick mice; the controls were healthy and PCR-negative. IFNAR(-/- mice are susceptible to SBV infection and can develop fatal disease, making them a handy and versatile tool for SBV vaccine research.

  12. Female Adult Aedes albopictus Suppression by Wolbachia-Infected Male Mosquitoes

    Science.gov (United States)

    Mains, James W.; Brelsfoard, Corey L.; Rose, Robert I.; Dobson, Stephen L.

    2016-01-01

    Dengue, chikungunya and zika viruses are pathogens with an increasing global impact. In the absence of an approved vaccine or therapy, their management relies on controlling the mosquito vectors. But traditional controls are inadequate, and the range of invasive species such as Aedes albopictus (Asian Tiger Mosquito) is expanding. Genetically modified mosquitoes are being tested, but their use has encountered regulatory barriers and public opposition in some countries. Wolbachia bacteria can cause a form of conditional sterility, which can provide an alternative to genetic modification or irradiation. It is unknown however, whether openly released, artificially infected male Ae. albopictus can competitively mate and sterilize females at a level adequate to suppress a field population. Also, the unintended establishment of Wolbachia at the introduction site could result from horizontal transmission or inadvertent female release. In 2014, an Experimental Use Permit from the United States Environmental Protection Agency approved a pilot field trial in Lexington, Kentucky, USA. Here, we present data showing localized reduction of both egg hatch and adult female numbers. The artificial Wolbachia type was not observed to establish in the field. The results are discussed in relation to the applied use of Wolbachia-infected males as a biopesticide to suppress field populations of Ae. albopictus. PMID:27659038

  13. Hepatitis B and A vaccination in HIV-infected adults: A review.

    Science.gov (United States)

    Mena, G; García-Basteiro, A L; Bayas, J M

    2015-01-01

    Hepatitis B and A account for considerable morbidity and mortality worldwide. Immunization is the most effective means of preventing hepatitis B and A. However, the immune response to both hepatitis vaccines seems to be reduced in HIV-infected subjects. The aim of this review was to analyze the immunogenicity, safety, long-term protection and current recommendations of hepatitis B and A vaccination among HIV-infected adults. The factors most frequently associated with a deficient level of anti-HBs or IgG anti-HAV after vaccination are those related to immunosuppression (CD4 level and HIV RNA viral load) and to the frequency of administration and/or the amount of antigenic load per dose. The duration of the response to both HBV and HAV vaccines is associated with suppression of the viral load at vaccination and, in the case of HBV vaccination, with a higher level of antibodies after vaccination. In terms of safety, there is no evidence of more, or different, adverse effects compared with HIV-free individuals. Despite literature-based advice on the administration of alternative schedules, revaccination after the failure of primary vaccination, and the need for periodic re-evaluation of antibody levels, few firm recommendations are found in the leading guidelines.

  14. Dendritic cells are less susceptible to human immunodeficiency virus type 2 (HIV-2) infection than to HIV-1 infection

    NARCIS (Netherlands)

    M.G. Duvall (Melody); K. Loré (Karin); H. Blaak (Hetty); D.A. Ambrozak (David); W.C. Adams (William); K. Santos (Kathlyn); C. Geldmacher (Christof); J.R. Mascola (John); A.J. McMichael (Andrew); A. Jaye (Assan); H. Whittle; S.L. Rowland-Jones (Sarah); R.A. Koup (Richard)

    2007-01-01

    textabstractHuman immunodeficiency virus type 1 (HIV-1) infection of dendritic cells (DCs) has been documented in vivo and may be an important contributor to HIV-1 transmission and pathogenesis. HIV-1-specific CD4+T cells respond to HIV antigens presented by HIV-1-infected DCs and in this process be

  15. The Drosophila hindgut lacks constitutively active adult stem cells but proliferates in response to tissue damage

    OpenAIRE

    D.T., Fox; Spradling, A.C.

    2009-01-01

    The adult Drosophila hindgut was recently reported to contain active, tissue-replenishing stem cells, like those of the midgut, but located within an anterior ring so as to comprise a single giant crypt. In contrast to this view, we observed no active stem cells and little cell turnover in adult hindgut tissue based on clonal marking and BrdU incorporation studies. Again contradicting the previous proposal, we showed that the adult hindgut is not generated by anterior stem cells during larval...

  16. Prevalence and risk factors of sleep disturbances in a large HIV-infected adult population

    Directory of Open Access Journals (Sweden)

    Clotilde Allavena

    2014-11-01

    Full Text Available Introduction: Sleep disturbances are frequently reported in HIV-infected patients but there is a lack of large studies on prevalence and risk factors, particularly in the context of current improved immuno-clinical status and use of the newest antiretrovirals (ARV. Method: Cross-sectional study to evaluate the prevalence and factors associated with sleep disturbance in adult HIV-infected patients in six French centres of the region “Pays de la Loire”. Patients filled a self-administered questionnaire on their health behaviour, sleep attitudes (Pittsburgh Sleep Quality Index PSQI, quality of life (WHO QOL HIV BREF questionnaire and depression (Beck depression Inventory (BDI-II questionnaire. Socio-demographic and immunovirologic data, medical history, ARVs were collected. Results: From November 2012 to May 2013, 1354 consecutive non-selected patients were enrolled. Patients’ characteristics were: 73.5% male, median age 47 years, active employment 56.7%, France-native 83% and Africa-native 14.7%, CDC stage C 21%, hepatitis co-infection 13%, lipodystrophy 11.8%, dyslipidemia 20%, high BP 15.1%, diabetes 3%, tobacco smokers 39%, marijuana and cocaine users, 11.7% and 1.7% respectively, and excessive alcohol drinkers 9%. Median (med duration of HIV infection was 12.4 years, med CD4 count was 604/mm3; 94% of Patients were on ARVs, 87% had undetectable viral load. Median sleeping time was 7 hours. Sleep disturbances (defined as PSQI score >5 were observed in 47% of the patients, more frequently in female (56.4% than in male (43.9% (p19 in 19.7% of the patients. In multivariate analysis, factors associated with sleep disturbances (p10 vs. <10 y. (OR 1.5; CI 1.1–2.0, ARV regimen containing nevirapine (OR 0.7; CI 0.5–0.9 or efavirenz (OR 0.5; CI 0.3–0.7. Conclusions: Prevalence of sleep disturbances is high in this HIV population and roughly similar to the French population. Associated factors are rather related to social and psychological

  17. Human herpesvirus 6 infects cervical epithelial cells and transactivates human papillomavirus gene expression.

    OpenAIRE

    Chen, M.; Popescu, N; Woodworth, C; Berneman, Z; M. Corbellino; Lusso, P.; Ablashi, D V; Dipaolo, J. A.

    1994-01-01

    To examine whether human herpesvirus 6 (HHV-6) is capable of infecting human cervical epithelial cells and altering expression of human papillomavirus (HPV) genes, HPV-immortalized or -transformed carcinoma cell lines were infected with HHV-6 variant A. No cytopathic effect was observed in infected cervical cells. However, immunofluorescence indicated that infected cells expressed early-late proteins of HHV-6 by day 3 postinfection. HHV-6 DNA was also detected by Southern blot hybridization a...

  18. Reduction of prion infectivity in packed red blood cells

    International Nuclear Information System (INIS)

    The link between a new variant form of Creutzfeldt-Jakob disease (vCJD) and the consumption of prion contaminated cattle meat as well as recent findings showing that vCJD can be transmitted by blood transfusion have raised public health concerns. Currently, a reliable test to identify prions in blood samples is not available. The purpose of this study was to evaluate the possibility to remove scrapie prion protein (PrPSc) and infectivity from red blood cell (RBC) suspensions by a simple washing procedure using a cell separation and washing device. The extent of prion removal was assessed by Western blot, PMCA and infectivity bioassays. Our results revealed a substantial removal of infectious prions (≥3 logs of infectivity) by all techniques used. These data suggest that a significant amount of infectivity present in RBC preparations can be removed by a simple washing procedure. This technology may lead to increased safety of blood products and reduce the risk of further propagation of prion diseases.

  19. Turnover rates of B cells, T cells, and NK cells in simian immunodeficiency virus-infected and uninfected rhesus macaques

    NARCIS (Netherlands)

    Boer, R.J. de; Mohri, H.; Ho, D.D.; Perelson, A.S.

    2003-01-01

    We determined average cellular turnover rates by fitting mathematical models to 5-bromo-2'-deoxyuridine measurements in SIV-infected and uninfected rhesus macaques. The daily turnover rates of CD4(+) T cells, CD4(-) T cells, CD20(+) B cells, and CD16(+) NK cells in normal uninfected rhesus macaques

  20. Optimal Use of Raltegravir (Isentress® in the Treatment of HIV-Infected Adults – Canadian Consensus Guidelines

    Directory of Open Access Journals (Sweden)

    Anita Rachlis

    2009-01-01

    Full Text Available BACKGROUND AND OBJECTIVES: A meeting of a Canadian group with significant experience and knowledge in HIV management, consisting of five physicians, a pharmacist and an AIDS researcher, was convened. Their goal was to develop guidance for Canadian HIV-treating physicians on the appropriate use of raltegravir (MK-0518, Isentress®, Merck Frosst Canada Inc in HIV-infected adults.

  1. Identifying Factors Associated with Changes in CD4+ Count in HIV-Infected Adults in Saskatoon, Saskatchewan

    Directory of Open Access Journals (Sweden)

    Kelsey Hunt

    2015-01-01

    Full Text Available OBJECTIVE: To assess the impact of clinical and social factors unique to HIV-infected adults in Saskatoon, Saskatchewan, regarding the rate of CD4+ count change, and to identify factors associated with a risk of CD4+ count decline.

  2. Screening of early antigen genes of adult-stage Trichinella spiralis using pig serum from different stages of early infection

    Science.gov (United States)

    The goal of this work was to identify novel, early antigens present in Trichinella spiralis. To this end, a cDNA library generated from 3-day old adult worms (Ad3) was immunologically screened using serum from a pig infected with 20,000 muscle larvae. The serum was obtained from multiple, time cours...

  3. Study Development of Adult Mycoplasma Pneumoniae Infection%成人肺炎支原体感染研究进展

    Institute of Scientific and Technical Information of China (English)

    易海峰

    2011-01-01

    Mycoplasma pneumoniae is a common pathogen of respiratory tract, which is frequently complicated with respiratory infections and extrapulmonary disorders.Adult Mycoplasma pneumoniae infection has been increasingly recognized.Adult form is significantly different from pediatric form.Due to the small number of studies, more concepts of adult Mycoplasma pneumoniae infection require to be supplemented and standardized.This article reviews epidemiology, pathogenesis, clinical features, laboratory diagnosis, and pharmacotherapy of adult Mycoplasma pneumoniae infection.%肺炎支原体是呼吸道常见致病原,常引起呼吸道感染及各种肺外并发症.近年来成人肺炎支原体感染受到重视,成人肺炎支原体感染在许多方面有其不同于儿童的特点,由于研究相对较少,许多认识有待完善和统一,现就成人肺炎支原体感染的流行病学、致病机制、临床表现、实验诊断、药物治疗等方面的研究进展予以简要综述.

  4. TLR3 signaling in macrophages is indispensable for the protective immunity of invariant natural killer T cells against enterovirus 71 infection.

    Directory of Open Access Journals (Sweden)

    Kai Zhu

    2015-01-01

    Full Text Available Enterovirus 71 (EV71 is the most virulent pathogen among enteroviruses that cause hand, foot and mouth disease in children but rarely in adults. The mechanisms that determine the age-dependent susceptibility remain largely unclear. Here, we found that the paucity of invariant natural killer T (iNKT cells together with immaturity of the immune system was related to the susceptibility of neonatal mice to EV71 infection. iNKT cells were crucial antiviral effector cells to protect young mice from EV71 infection before their adaptive immune systems were fully mature. EV71 infection led to activation of iNKT cells depending on signaling through TLR3 but not other TLRs. Surprisingly, iNKT cell activation during EV71 infection required TLR3 signaling in macrophages, but not in dendritic cells (DCs. Mechanistically, interleukin (IL-12 and endogenous CD1d-restricted antigens were both required for full activation of iNKT cells. Furthermore, CD1d-deficiency led to dramatically increased viral loads in central nervous system and more severe disease in EV71-infected mice. Altogether, our results suggest that iNKT cells may be involved in controlling EV71 infection in children when their adaptive immune systems are not fully developed, and also imply that iNKT cells might be an intervention target for treating EV71-infected patients.

  5. PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing

    Science.gov (United States)

    Neff, C. Preston; Gibbert, Kathrin; Dietze, Kirsten K.; Werner, Tanja; Liu, Jia; Chen, Lieping; Lang, Karl S.; Palmer, Brent E.; Dittmer, Ulf; Zelinskyy, Gennadiy

    2015-01-01

    Cytotoxic CD8+ T Lymphocytes (CTL) efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs. We observed increased levels of PD-L1 expression after infection of cells with the murine Friend retrovirus (FV) or with HIV. In FV infected mice, virus-specific CTLs efficiently eliminated infected target cells that expressed low levels of PD-L1 or that were deficient for PD-L1 but the population of PD-L1high cells escaped elimination and formed a reservoir for chronic FV replication. Infected cells with high PD-L1 expression mediated a negative feedback on CD8+ T cells and inhibited their expansion and cytotoxic functions. These findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on PD-L1 expression levels on virus infected target cells. PMID:26484769

  6. PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8+ T Cell Killing.

    Directory of Open Access Journals (Sweden)

    Ilseyar Akhmetzyanova

    2015-10-01

    Full Text Available Cytotoxic CD8+ T Lymphocytes (CTL efficiently control acute virus infections but can become exhausted when a chronic infection develops. Signaling of the inhibitory receptor PD-1 is an important mechanism for the development of virus-specific CD8+ T cell dysfunction. However, it has recently been shown that during the initial phase of infection virus-specific CD8+ T cells express high levels of PD-1, but are fully competent in producing cytokines and killing virus-infected target cells. To better understand the role of the PD-1 signaling pathway in CD8+ T cell cytotoxicity during acute viral infections we analyzed the expression of the ligand on retrovirus-infected cells targeted by CTLs. We observed increased levels of PD-L1 expression after infection of cells with the murine Friend retrovirus (FV or with HIV. In FV infected mice, virus-specific CTLs efficiently eliminated infected target cells that expressed low levels of PD-L1 or that were deficient for PD-L1 but the population of PD-L1high cells escaped elimination and formed a reservoir for chronic FV replication. Infected cells with high PD-L1 expression mediated a negative feedback on CD8+ T cells and inhibited their expansion and cytotoxic functions. These findings provide evidence for a novel immune escape mechanism during acute retroviral infection based on PD-L1 expression levels on virus infected target cells.

  7. Infection strategies of intestinal parasite pathogens and host cell responses

    Directory of Open Access Journals (Sweden)

    Bruno Martorell Di Genova

    2016-03-01

    Full Text Available Giardia lamblia, Cryptosporidium spp. and Entamoeba histolytica are important pathogenic intestinal parasites and are amongst the leading cause worldwide of diarrheal illness in humans. Diseases caused by these organisms, Giardiasis, Cryptosporidiosis and Amoebiasis, respectively, are characterized by self-limited diarrhea but can evolve to long-term complications. The cellular and molecular mechanisms underlying the pathogenesis of diarrhea associated with these tree pathogens are being unraveled, with knowledge of both the strategies explored by the parasites to establish infection and the methods evolved by hosts to avoid it. Special attention is being given to molecules participating in parasite-host interaction and in the mechanisms implicated in the diseases pathophysiologic processes. This review focuses on cell mechanisms that are modulated during infection, including gene transcription, cytoskeleton rearrangements, signal transduction pathways and cell death.

  8. Infection Strategies of Intestinal Parasite Pathogens and Host Cell Responses.

    Science.gov (United States)

    Di Genova, Bruno M; Tonelli, Renata R

    2016-01-01

    Giardia lamblia, Cryptosporidium sp., and Entamoeba histolytica are important pathogenic intestinal parasites and are amongst the leading causes worldwide of diarrheal illness in humans. Diseases caused by these organisms, giardiasis, cryptosporidiosis, and amoebiasis, respectively, are characterized by self-limited diarrhea but can evolve to long-term complications. The cellular and molecular mechanisms underlying the pathogenesis of diarrhea associated with these three pathogens are being unraveled, with knowledge of both the strategies explored by the parasites to establish infection and the methods evolved by hosts to avoid it. Special attention is being given to molecules participating in parasite-host interaction and in the mechanisms implicated in the diseases' pathophysiologic processes. This review focuses on cell mechanisms that are modulated during infection, including gene transcription, cytoskeleton rearrangements, signal transduction pathways, and cell death. PMID:26973630

  9. Changed iron regulation in scrapie-infected neuroblastoma cells.

    Science.gov (United States)

    Fernaeus, Sandra; Hälldin, Jonas; Bedecs, Katarina; Land, Tiit

    2005-02-18

    Prion diseases are characterized by the conversion of the normal cellular prion protein PrP(C) into a pathogenic isoform, PrP(Sc). The mechanisms involved in neuronal cell death in prion diseases are largely unknown, but accumulating evidence has demonstrated oxidative impairment along with metal imbalances in scrapie-infected brains. In this study, we report changes in cellular iron metabolism in scrapie-infected mouse neuroblastoma N2a cells (ScN2a). We detected twofold lower total cellular iron and calcein-chelatable cytosolic labile iron pool (LIP) in ScN2a cells as compared to the N2a cells. We also measured in ScN2a cells significantly lower activities of iron regulatory proteins 1 and 2 (IRP1 and IRP2, respectively), regulators of cellular iron by sensing cytosolic free iron levels and controlling posttranscriptionally the expression of the major iron transport protein transferrin receptor 1 (TfR1) and the iron sequestration protein ferritin. IRP1 and IRP2 protein levels were decreased by 40% and 50%, respectively, in ScN2a cells. TfR1 protein levels were fourfold reduced and ferritin levels were threefold reduced in ScN2a cells. TfR1 and ferritin mRNA levels were significantly reduced in ScN2a cells. ScN2a cells responded normally to iron and iron chelator treatment with respect to the activities of IRP1 and IRP2, and biosynthesis of TfR1 and ferritin. However, the activities of IRP1 and IRP2, and protein levels of TfR1 and ferritin, were still significantly lower in iron-depleted ScN2a cells as compared to the N2a cells, suggesting lower need for iron in ScN2a cells. Our results demonstrate that scrapie infection leads to changes in cellular iron metabolism, affecting both total cellular and cytosolic free iron, and the activities and expression of major regulators of cellular iron homeostasis. PMID:15710243

  10. Isolation and Culture of Adult Epithelial Stem Cells from Human Skin

    OpenAIRE

    Guo, Zhiru; Draheim, Kyle; Lyle, Stephen

    2011-01-01

    The homeostasis of all self-renewing tissues is dependent on adult stem cells. As undifferentiated stem cells undergo asymmetric divisions, they generate daughter cells that retain the stem cell phenotype and transit-amplifying cells (TA cells) that migrate from the stem cell niche, undergo rapid proliferation and terminally differentiate to repopulate the tissue.

  11. Incidence of Dengue Virus Infection in Adults and Children in a Prospective Longitudinal Cohort in the Philippines.

    Directory of Open Access Journals (Sweden)

    Maria Theresa Alera

    2016-02-01

    Full Text Available The mean age of dengue has been increasing in some but not all countries. We sought to determine the incidence of dengue virus (DENV infection in adults and children in a prospective cohort study in the Philippines where dengue is hyperendemic.A prospective cohort of subjects ≥6 months old in Cebu City, Philippines, underwent active community-based surveillance for acute febrile illnesses by weekly contact. Fever history within the prior seven days was evaluated with an acute illness visit followed by 2, 5, and 8-day, and 3-week convalescent visits. Blood was collected at the acute and 3-week visits. Scheduled visits took place at enrolment and 12 months that included blood collections. Acute samples were tested by DENV PCR and acute/convalescent samples by DENV IgM/IgG ELISA to identify symptomatic infections. Enrolment and 12-month samples were tested by DENV hemagglutination inhibition (HAI assay to identify subclinical infections. Of 1,008 enrolled subjects, 854 completed all study activities at 12 months per-protocol undergoing 868 person-years of surveillance. The incidence of symptomatic and subclinical infections was 1.62 and 7.03 per 100 person-years, respectively. However, in subjects >15 years old, only one symptomatic infection occurred whereas 27 subclinical infections were identified. DENV HAI seroprevalence increased sharply with age with baseline multitypic HAIs associated with fewer symptomatic infections. Using a catalytic model, the historical infection rate among dengue naïve individuals was estimated to be high at 11-22%/year.In this hyperendemic area with high seroprevalence of multitypic DENV HAIs in adults, symptomatic dengue rarely occurred in individuals older than 15 years. Our findings demonstrate that dengue is primarily a pediatric disease in areas with high force of infection. However, the average age of dengue could increase if force of infection decreases over time, as is occurring in some hyperendemic

  12. Optimal therapy for adults with Langerhans cell histiocytosis bone lesions.

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    Maria A Cantu

    Full Text Available BACKGROUND: There is little data on treatment of Langerhans cell histiocytosis (LCH in adults. Available data is on small numbers of patients with short follow-up times and no comparison of results from different treatment regimens. We analyzed the responses of adult LCH patients with bone lesions to three primary chemotherapy treatments to define the optimal one. METHODS AND FINDINGS: Fifty-eight adult patients with bone lesions, either as a solitary site or as a component of multisystem disease, were analyzed for disease location and response to surgery, curettage, steroids, radiation, vinblastine/prednisone, 2-Chlorodeoxyadenosine (2-CdA, or cytosine arabinoside (ARA-C. The mean age of patients was 32 years, with equal gender distribution. Twenty-nine patients had 1 lesion; 16, 2 lesions; 5, 3 lesions; and 8 had 4 or more. Most bone lesions were in the skull, spine, or jaw. Chemotherapy, surgery, curettage, or radiation, but not steroids alone, achieved improvement or resolution of lesions in a majority of patients. Comparison of the three chemotherapy regimens revealed 84% of patients treated with vinblastine/prednisone either did not respond or relapsed within a year, whereas 59% of patients treated with 2-CdA and 21% treated with ARA-C failed. Toxicity was worse with the vinblastine/prednisone group as 75% had grade 3-4 neuropathy. Grade 3-4 cytopenias occurred in 37% of the 2-CdA -treated patients and 20% of the ARA-C-treated patients. The major limitation of this study is it is retrospective and not a clinical trial. CONCLUSIONS: ARA-C is an effective and minimally toxic treatment for LCH bone lesions in adults. In contrast, vinblastine/prednisone results in poor overall responses and excessive toxicity.

  13. Epithelial cells with hepatobiliary phenotype: Is it another stem cell candidate for healthy adult human liver?

    Institute of Scientific and Technical Information of China (English)

    Dung Ngoc Khuu; Mustapha Najimi; Etienne M Sokal

    2007-01-01

    AIM: To investigate the presence and role of liver epithelial cells in the healthy human adult liver.METHODS: Fifteen days after human hepatocyte primary culture, epithelial like cells emerged and started proliferating. Cell colonies were isolated and sub-cultured for more than 160 d under specific culture conditions. Cells were analyzed for each passage using immunofluorescence, flow cytometry and reverse transcriptionpolymerase chain reaction (RT-PCR).RESULTS: Flow cytometry analysis demonstrated that liver epithelial cells expressed common markers for hepatic and stem cells such as CD90, CD44 and CD29 but were negative for CD34 and CD117. Using immunofluorescence we demonstrated that liver epithelial cells expressed not only immature (a-fetoprotein) but also differentiated hepatocyte (albumin and CK-18) and biliary markers (CK-7 and 19), whereas they were negative for OV-6. RT-PCR analysis confirmed immunofluorescence data and revealed that liver epithelial cells did not express mature hepatocyte markers such as CYP2B6, CYP3A4 and tyrosine amino-transferase. Purified liver epithelial cells were transplanted into SCID mice. One month after transplantation, albumin positive cell foci were detected in the recipient mouse parenchyma.CONCLUSION: According to their immature and bipotential phenotype, liver epithelial cells might represent a pool of precursors in the healthy human adult liver other than oval cells.

  14. SAMHD1 controls cell cycle status, apoptosis and HIV-1 infection in monocytic THP-1 cells.

    Science.gov (United States)

    Bonifati, Serena; Daly, Michele B; St Gelais, Corine; Kim, Sun Hee; Hollenbaugh, Joseph A; Shepard, Caitlin; Kennedy, Edward M; Kim, Dong-Hyun; Schinazi, Raymond F; Kim, Baek; Wu, Li

    2016-08-01

    SAMHD1 limits HIV-1 infection in non-dividing myeloid cells by decreasing intracellular dNTP pools. HIV-1 restriction by SAMHD1 in these cells likely prevents activation of antiviral immune responses and modulates viral pathogenesis, thus highlighting a critical role of SAMHD1 in HIV-1 physiopathology. Here, we explored the function of SAMHD1 in regulating cell proliferation, cell cycle progression and apoptosis in monocytic THP-1 cells. Using the CRISPR/Cas9 technology, we generated THP-1 cells with stable SAMHD1 knockout. We found that silencing of SAMHD1 in cycling cells stimulates cell proliferation, redistributes cell cycle population in the G1/G0 phase and reduces apoptosis. These alterations correlated with increased dNTP levels and more efficient HIV-1 infection in dividing SAMHD1 knockout cells relative to control. Our results suggest that SAMHD1, through its dNTPase activity, affects cell proliferation, cell cycle distribution and apoptosis, and emphasize a key role of SAMHD1 in the interplay between cell cycle regulation and HIV-1 infection. PMID:27183329

  15. Human herpesvirus 6 infection after allogeneic stem cell transplantation

    OpenAIRE

    Wang, Fu-Zhang

    1999-01-01

    Human herpesvirus 6 (HHV-6) is a lymphotropic virus mainly infecting T lymphocytes but also other types of cells. Seroepidemiological studies have shown that more than 90% of individuals older than 2 years are seropositive for HHV-6. There are two variants (A and B) of HHV-6, and variant B has been much more often coupled to diseases than variant A. The prevalence of the two variants is still not known since the serological responses can not be differentiated by currently av...

  16. PROPHYLACTIC ADMINISTRATION OF DOXYCYCLINE REDUCES CENTRAL VENOUS CATHETER INFECTIONS IN PATIENTS UNDERGOING HEMATOPOIETIC CELL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    Mohamed Kharfan-Dabaja

    2013-02-01

    Full Text Available Hematopoietic stem cells are usually transfused through a central venous catheter (CVC, which also facilitates administration of medications and intravenous fluids. We had observed high rate of catheter-related blood-stream infection (CR-BSI at our Bone Marrow Transplantation (BMT unit despite prescribing fluoroquinolones for anti-bacterial prophylaxis. Accordingly, we implemented prophylactic use of a relatively inexpensive broad spectrum antibiotic, namely doxycycline to address this problem. We wanted to investigate whether doxycycline prophylaxis reduces CR-BSI rate. Data was collected retrospectively on 54 consecutive patients, 26 of whom received doxycycline (doxycycline group, and we compared their outcomes to a previous cohort of 28 patients who did not receive doxycycline (comparison group. The groups were comparable in regards to age, gender, hematopoietic cell transplant type, and primary diagnosis. No CVC infection (0% was observed in the doxycycline group, while 5 infection episodes (18.5% occurred in 4 patients in the comparison group (p<0.001. Episodes of CR-BSI were due to: Escherichia-coli (EC=1, coagulase-negative Staphylococcus-spp (CNSS=2, both EC & CNSS=1. Our results demonstrate that CR-BSI was reduced significantly after introducing doxycycline. This finding suggests a beneficial role for systemic use of doxycycline prophylaxis to prevent CR-BSI in adult BMT patients. Nevertheless, a randomized controlled study is warranted to confirm these findings.

  17. Hypoglycaemia induced by Trichinella infection is due to the increase of glucose uptake in infected muscle cells.

    Science.gov (United States)

    Wu, Z; Nagano, I; Kajita, K; Nishina, M; Takahashi, Y

    2009-03-01

    The present study investigates how Trichinella infection induces host hypoglycaemia and explores a potential relationship between infection and the insulin signalling pathway. The results showed that mice infected with Trichinella spiralis or Trichinella pseudospiralis exhibited a temporary decrease in blood glucose level between 8 and 28 days p.i. and the kinetics of the glucose levels corresponded to the process of muscle larval growth and development. Histochemical results showed that glycogen accumulation increased in infected muscle cells during the period of hypoglycaemia. Analysis of gene expression profiles with quantitative PCR demonstrated that insulin signalling pathway-related genes, such as insulin receptor (IR), insulin receptor substance 1 (IRS-1), IRS-2, phosphatidylinositol 3-kinase (PI3-K) and V-akt murine thymoma viral oncogene homologue 2 (Akt2) were up-regulated in infected muscle cells during infection and these expression changes correlated with the kinetics of blood glucose level, glycogen accumulation and the process of larval growth and development in infected muscle cells. Western blot analysis clarified that the expression of IR and Akt2 proteins increased in muscle tissues infected with both species of Trichinella. This study suggests that hypoglycaemia induced by Trichinella infection is the result of an increase in glucose uptake by infected muscle cells via up-regulation of insulin signalling pathway factors. PMID:18838075

  18. Cerebellar giant cell glioblastoma multiforme in an adult

    Directory of Open Access Journals (Sweden)

    Sudhansu Sekhar Mishra

    2014-01-01

    Full Text Available Cerebellar glioblastoma multiforme (GBM is a rare tumor that accounts for only 1% of all cases of GBM and its giant cell variant is even much rarely encountered in adults. A case of cerebellar giant cell GBM managed at our institution reporting its clinical presentation, radiological and histological findings, and treatment instituted is described. In conjunction, a literature review, including particular issues, clinical data, advances in imaging studies, pathological characteristics, treatment options, and the behavior of such malignant tumor is presented. It is very important for the neurosurgeon to make the differential diagnosis between the cerebellar GBM, and other diseases such as metastasis, anaplastic astrocytomas, and cerebellar infarct because their treatment modalities, prognosis, and outcome are different.

  19. Quantitative phosphoproteomic analysis of prion-infected neuronal cells

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    Löwer Johannes

    2010-09-01

    Full Text Available Abstract Prion diseases or transmissible spongiform encephalopathies (TSEs are fatal diseases associated with the conversion of the cellular prion protein (PrPC to the abnormal prion protein (PrPSc. Since the molecular mechanisms in pathogenesis are widely unclear, we analyzed the global phospho-proteome and detected a differential pattern of tyrosine- and threonine phosphorylated proteins in PrPSc-replicating and pentosan polysulfate (PPS-rescued N2a cells in two-dimensional gel electrophoresis. To quantify phosphorylated proteins, we performed a SILAC (stable isotope labeling by amino acids in cell culture analysis and identified 105 proteins, which showed a regulated phosphorylation upon PrPSc infection. Among those proteins, we validated the dephosphorylation of stathmin and Cdc2 and the induced phosphorylation of cofilin in PrPSc-infected N2a cells in Western blot analyses. Our analysis showed for the first time a differentially regulated phospho-proteome in PrPSc infection, which could contribute to the establishment of novel protein markers and to the development of novel therapeutic intervention strategies in targeting prion-associated disease.

  20. Neuro-muscular differentiation of adult porcine skin derived stem cell-like cells.

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    Dominik Lermen

    Full Text Available BACKGROUND: Due to the genetic relationship to humans, porcine stem cells are a very important model system to investigate cell differentiation, associated cell signaling pathways, and cell fate. Porcine skin derived stem cells have been isolated from mid-gestation porcine fetus recently. To our knowledge, stem cells from the skin of the adult porcine organism have not been isolated until now. Hence, to our knowledge, we here describe the isolation, expansion, characterization and differentiation of multipotent porcine skin derived stem cell-like cells (pSSCs from the adult porcine organism for the first time. METHODOLOGY/PRINCIPAL FINDINGS: pSSCs had a spindle shaped morphology similar to mesenchymal stem cells (MSCs. They could be maintained proliferatively active in vitro for more than 120 days and were able to form colonies from single cells. pSSCs expressed Sox2 and Oct3/4, both transcription factors essential to the pluripotent and self-renewing phenotypes of embryonic stem cells, which recently gained attention due to their function in inducing pluripotent stem cells. Furthermore, the expression of the progenitor marker nestin, the somatic stem cell markers Bcrp1/ABCG2, Bmi1, and Stat3 was detected by reverse transcriptase-polymerase chain reaction (RT-PCR in undifferentiated pSSCs. Flow cytometry revealed the expression of the MSC related proteins CD9, CD29, CD44 and CD105, but not CD90. After neuronal differentiation cells with a characteristic morphology of neuronal and smooth muscle-like cells were present in the cultures. Subsequent immunochemistry and flow cytometry revealed the down-regulation of nestin and the up-regulation of the neuron specific protein beta-III-tubulin and the astrocyte marker GFAP. Also, alpha-SMA expressing cells increased during differentiation suggesting the neuro-muscular differentiation of these skin derived cells. pSSCs could also be induced to differentiate into adipocyte-like cells when cultured under

  1. GREAT PROMISE OF TISSUE-RESIDENT ADULT STEM/PROGENITOR CELLS IN TRANSPLANTATION AND CANCER THERAPIES

    OpenAIRE

    Mimeault, Murielle; Batra, Surinder K.

    2012-01-01

    Recent progress in tissue-resident adult stem/progenitor cell research has inspired great interest because these immature cells from your own body can act as potential, easily accessible cell sources for cell transplantation in regenerative medicine and cancer therapies. The use of adult stem/progenitor cells endowed with a high self-renewal ability and multilineage differentiation potential, which are able to regenerate all the mature cells in the tissues from their origin, offers great prom...

  2. Steroid hormone signaling is essential to regulate innate immune cells and fight bacterial infection in Drosophila.

    Directory of Open Access Journals (Sweden)

    Jennifer C Regan

    2013-10-01

    Full Text Available Coupling immunity and development is essential to ensure survival despite changing internal conditions in the organism. Drosophila metamorphosis represents a striking example of drastic and systemic physiological changes that need to be integrated with the innate immune system. However, nothing is known about the mechanisms that coordinate development and immune cell activity in the transition from larva to adult. Here, we reveal that regulation of macrophage-like cells (hemocytes by the steroid hormone ecdysone is essential for an effective innate immune response over metamorphosis. Although it is generally accepted that steroid hormones impact immunity in mammals, their action on monocytes (e.g. macrophages and neutrophils is still not well understood. Here in a simpler model system, we used an approach that allows in vivo, cell autonomous analysis of hormonal regulation of innate immune cells, by combining genetic manipulation with flow cytometry, high-resolution time-lapse imaging and tissue-specific transcriptomic analysis. We show that in response to ecdysone, hemocytes rapidly upregulate actin dynamics, motility and phagocytosis of apoptotic corpses, and acquire the ability to chemotax to damaged epithelia. Most importantly, individuals lacking ecdysone-activated hemocytes are defective in bacterial phagocytosis and are fatally susceptible to infection by bacteria ingested at larval stages, despite the normal systemic and local production of antimicrobial peptides. This decrease in survival is comparable to the one observed in pupae lacking immune cells altogether, indicating that ecdysone-regulation is essential for hemocyte immune functions and survival after infection. Microarray analysis of hemocytes revealed a large set of genes regulated at metamorphosis by EcR signaling, among which many are known to function in cell motility, cell shape or phagocytosis. This study demonstrates an important role for steroid hormone regulation of

  3. First report of Toxoplasma gondii infection in market-sold adult chickens, ducks and pigeons in northwest China

    Directory of Open Access Journals (Sweden)

    Cong Wei

    2012-06-01

    Full Text Available Abstract Background Toxoplasma gondii infection is a global concern, affecting a wide range of warm-blooded animals and humans worldwide, including poultry. Domestic and companion birds are considered to play an important role in the transmission of T. gondii to humans and other animals. However, little information on T. gondii infection in domestic birds in Lanzhou, northwest China was available. Therefore, this study was performed to determine the seroprevalence of T. gondii infection in domestic birds in Lanzhou, northwest China. Methods In the present study, the seroprevalence of T. gondii antibodies in 413 (305 caged and 108 free-range adult chickens, 334 (111 caged and 223 free-range adult ducks and 312 adult pigeons in Lanzhou, northwest China, were examined using the modified agglutination test (MAT. Results 30 (7.26% chickens, 38 (11.38% ducks and 37 (11.86% pigeons were found to be positive for T. gondii antibodies at the cut-off of 1:5. The prevalences in caged and free-range chickens were 6.23% and 10.19% respectively, however, statistical analysis showed that the difference was not significant (P > 0.05. The seroprevalences in caged and free-range ducks were 6.31% and 13.90% respectively, but the difference was not statistically significant (P > 0.05. Conclusions The results of the present survey indicated the presence of T. gondii infection in adult chickens, ducks and pigeons sold for meat in poultry markets in Lanzhou, northwest China, which poses a potential risk for T. gondii infection in humans and other animals in this region. This is the first seroprevalence study of T. gondii infection in domestic birds in this region.

  4. Identification of enteropathogenic Escherichia coli in simian immunodeficiency virus-infected infant and adult rhesus macaques.

    Science.gov (United States)

    Mansfield, K G; Lin, K C; Newman, J; Schauer, D; MacKey, J; Lackner, A A; Carville, A

    2001-03-01

    Enteropathogenic Escherichia coli (EPEC) was recognized as a common opportunistic pathogen of simian immunodeficiency virus-infected rhesus macaques (Macaca mulatta) with AIDS. Retrospective analysis revealed that 27 of 96 (28.1%) animals with AIDS had features of EPEC infection, and EPEC was the most frequent pathogen of the gastrointestinal tract identified morphologically. In 7.3% of animals dying with AIDS, EPEC represented the sole opportunistic agent of the gastrointestinal tract at death. In 20.8% of cases, it was seen in combination with one or more gastrointestinal pathogens, including Cryptosporidium parvum, Enterocytozoon bieneusi, Mycobacterium avium, Entamoeba histolytica, Balantidium coli, Strongyloides stercoralis, cytomegalovirus, and adenovirus. Clinically, infection was associated with persistent diarrhea and wasting and was more frequent in animals that died at under 1 year of age (P < 0.001, Fisher exact test). The organism was associated with the characteristic attaching and effacing lesion in colonic tissue sections and produced a focal adherence pattern on a HEp-2 assay but was negative for Shiga toxin production as assessed by PCR and a HeLa cell cytotoxicity assay. A 2.6-kb fragment encompassing the intimin gene was amplified and sequenced and revealed 99.2% identity to sequences obtained from human isolates (GenBank AF116899) corresponding to the epsilon intimin subtype. Further investigations with rhesus macaques may offer opportunities to study the impact of EPEC on AIDS pathogenesis and gastrointestinal dysfunction. PMID:11230413

  5. The Multiplicity of Cellular Infection Changes Depending on the Route of Cell Infection in a Plant Virus

    Science.gov (United States)

    Gutiérrez, Serafín; Pirolles, Elodie; Yvon, Michel; Baecker, Volker; Michalakis, Yannis

    2015-01-01

    ABSTRACT The multiplicity of cellular infection (MOI) is the number of virus genomes of a given virus species that infect individual cells. This parameter chiefly impacts the severity of within-host population bottlenecks as well as the intensity of genetic exchange, competition, and complementation among viral genotypes. Only a few formal estimations of the MOI currently are available, and most theoretical reports have considered this parameter as constant within the infected host. Nevertheless, the colonization of a multicellular host is a complex process during which the MOI may dramatically change in different organs and at different stages of the infection. We have used both qualitative and quantitative approaches to analyze the MOI during the colonization of turnip plants by Turnip mosaic virus. Remarkably, different MOIs were observed at two phases of the systemic infection of a leaf. The MOI was very low in primary infections from virus circulating within the vasculature, generally leading to primary foci founded by a single genome. Each lineage then moved from cell to cell at a very high MOI. Despite this elevated MOI during cell-to-cell progression, coinfection of cells by lineages originating in different primary foci is severely limited by the rapid onset of a mechanism inhibiting secondary infection. Thus, our results unveil an intriguing colonization pattern where individual viral genomes initiate distinct lineages within a leaf. Kin genomes then massively coinfect cells, but coinfection by two distinct lineages is strictly limited. IMPORTANCE The MOI is the size of the viral population colonizing cells and defines major phenomena in virus evolution, like the intensity of genetic exchange and the size of within-host population bottlenecks. However, few studies have quantified the MOI, and most consider this parameter as constant during infection. Our results reveal that the MOI can depend largely on the route of cell infection in a systemically

  6. {sup 18}F-FDG PET/CT evaluation of children and young adults with suspected spinal fusion hardware infection

    Energy Technology Data Exchange (ETDEWEB)

    Bagrosky, Brian M. [University of Colorado School of Medicine, Department of Pediatric Radiology, Children' s Hospital Colorado, 12123 E. 16th Ave., Box 125, Aurora, CO (United States); University of Colorado School of Medicine, Department of Radiology, Division of Nuclear Medicine, Aurora, CO (United States); Hayes, Kari L.; Fenton, Laura Z. [University of Colorado School of Medicine, Department of Pediatric Radiology, Children' s Hospital Colorado, 12123 E. 16th Ave., Box 125, Aurora, CO (United States); Koo, Phillip J. [University of Colorado School of Medicine, Department of Radiology, Division of Nuclear Medicine, Aurora, CO (United States)

    2013-08-15

    Evaluation of the child with spinal fusion hardware and concern for infection is challenging because of hardware artifact with standard imaging (CT and MRI) and difficult physical examination. Studies using {sup 18}F-FDG PET/CT combine the benefit of functional imaging with anatomical localization. To discuss a case series of children and young adults with spinal fusion hardware and clinical concern for hardware infection. These people underwent FDG PET/CT imaging to determine the site of infection. We performed a retrospective review of whole-body FDG PET/CT scans at a tertiary children's hospital from December 2009 to January 2012 in children and young adults with spinal hardware and suspected hardware infection. The PET/CT scan findings were correlated with pertinent clinical information including laboratory values of inflammatory markers, postoperative notes and pathology results to evaluate the diagnostic accuracy of FDG PET/CT. An exempt status for this retrospective review was approved by the Institution Review Board. Twenty-five FDG PET/CT scans were performed in 20 patients. Spinal fusion hardware infection was confirmed surgically and pathologically in six patients. The most common FDG PET/CT finding in patients with hardware infection was increased FDG uptake in the soft tissue and bone immediately adjacent to the posterior spinal fusion rods at multiple contiguous vertebral levels. Noninfectious hardware complications were diagnosed in ten patients and proved surgically in four. Alternative sources of infection were diagnosed by FDG PET/CT in seven patients (five with pneumonia, one with pyonephrosis and one with superficial wound infections). FDG PET/CT is helpful in evaluation of children and young adults with concern for spinal hardware infection. Noninfectious hardware complications and alternative sources of infection, including pneumonia and pyonephrosis, can be diagnosed. FDG PET/CT should be the first-line cross-sectional imaging study in

  7. 18F-FDG PET/CT evaluation of children and young adults with suspected spinal fusion hardware infection

    International Nuclear Information System (INIS)

    Evaluation of the child with spinal fusion hardware and concern for infection is challenging because of hardware artifact with standard imaging (CT and MRI) and difficult physical examination. Studies using 18F-FDG PET/CT combine the benefit of functional imaging with anatomical localization. To discuss a case series of children and young adults with spinal fusion hardware and clinical concern for hardware infection. These people underwent FDG PET/CT imaging to determine the site of infection. We performed a retrospective review of whole-body FDG PET/CT scans at a tertiary children's hospital from December 2009 to January 2012 in children and young adults with spinal hardware and suspected hardware infection. The PET/CT scan findings were correlated with pertinent clinical information including laboratory values of inflammatory markers, postoperative notes and pathology results to evaluate the diagnostic accuracy of FDG PET/CT. An exempt status for this retrospective review was approved by the Institution Review Board. Twenty-five FDG PET/CT scans were performed in 20 patients. Spinal fusion hardware infection was confirmed surgically and pathologically in six patients. The most common FDG PET/CT finding in patients with hardware infection was increased FDG uptake in the soft tissue and bone immediately adjacent to the posterior spinal fusion rods at multiple contiguous vertebral levels. Noninfectious hardware complications were diagnosed in ten patients and proved surgically in four. Alternative sources of infection were diagnosed by FDG PET/CT in seven patients (five with pneumonia, one with pyonephrosis and one with superficial wound infections). FDG PET/CT is helpful in evaluation of children and young adults with concern for spinal hardware infection. Noninfectious hardware complications and alternative sources of infection, including pneumonia and pyonephrosis, can be diagnosed. FDG PET/CT should be the first-line cross-sectional imaging study in patients

  8. Transition of adult T-cell leukemia/lymphoma clones during clinical progression.

    Science.gov (United States)

    Aoki, Sakura; Firouzi, Sanaz; López, Yosvany; Yamochi, Tadanori; Nakano, Kazumi; Uchimaru, Kaoru; Utusnomiya, Atae; Iwanaga, Masako; Watanabe, Toshiki

    2016-09-01

    Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell neoplasm caused by the transformation of HTLV-1-infected T cells. ATLL, especially its aggressive form, is known for its poor prognosis, even with intensive chemotherapy. ATLL cells are considered to be monoclonal; however, multiclonal proliferation or emergence of a new clone over time has been reported based on Southern blot analysis, although direct molecular evidence remains elusive. Furthermore, it is thought that clonal change may be a cause of early drug resistance in ATLL. To directly analyze potential clonal changes in ATLL during its clinical course, we used inverse PCR to detect integration sites in combination with a newly developed method using next-generation sequencing, and compared ATLL cell clonality at different time points. The results of inverse PCR indicated that the major clone was altered in three of 19 patients. Together with results from five patients, using this new method, we found direct evidence of clonal change occurring during the clinical course or in response to chemotherapy in ATLL. These results also highlight the importance of clonality analysis for understanding the mechanisms of ATLL development and drug resistance. PMID:27383637

  9. Development and application of human adult stem or progenitor cell organoids

    NARCIS (Netherlands)

    Rookmaaker, Maarten B; Schutgens, Frans; Verhaar, Marianne C; Clevers, Hans

    2015-01-01

    Adult stem or progenitor cell organoids are 3D adult-organ-derived epithelial structures that contain self-renewing and organ-specific stem or progenitor cells as well as differentiated cells. This organoid culture system was first established in murine intestine and subsequently developed for sever

  10. Differentiation of adult human bone marrow mesenchymal stem cells into Schwann-like cells in vitro

    Institute of Scientific and Technical Information of China (English)

    YANG Li-ye; ZHENG Jia-kun; WANG Chao-yang; LI Wen-yu

    2005-01-01

    Objective: To investigate the differentiative capability of adult human bone marrow mesenchymal stem cells (BMSCs) into Schwann-like cells. Methods: Bone marrows were aspirated from healthy donors and mononuclear cells were separated by Percoll lymphocytes separation liquid (1.073 g/ml) with centrifugation, cells were cultured in DMEM/F12 (1:1) medium containing 10% fetal bovine serum (FBS), 20 ng/ml epidermal growth factor (EGF) and 20 ng/ml basic fibroblast growth factor (bFGF). Cells of passage 1 were identified with immunocytochemistry. Conclusions: Bone marrow contains the stem cells with the ability of differentiating into Schwann-like cells, which may represent an alternative stem cell sources for neural transplantation.

  11. Association of low level viremia with inflammation and mortality in HIV-infected adults.

    Directory of Open Access Journals (Sweden)

    Abigail Eastburn

    Full Text Available Whether HIV viremia, particularly at low levels is associated with inflammation, increased coagulation, and all-cause mortality is unclear.The associations of HIV RNA level with C-reactive protein (CRP, fibrinogen, interleukin (IL-6 and mortality were evaluated in 1116 HIV-infected participants from the Study of Fat Redistribution and Metabolic Change in HIV infection. HIV RNA level was categorized as undetectable (i.e., "target not detected", 1-19, 20-399, 400-9999, and ≥ 10,000 copies/ml. Covariates included demographics, lifestyle, adipose tissue, and HIV-related factors.HIV RNA level had little association with CRP. Categories of HIV RNA below 10,000 copies/ml had similar levels of IL-6 compared with an undetectable HIV RNA level, while HIV RNA ≥ 10,000 copies/ml was associated with 89% higher IL-6 (p<0.001. This association was attenuated by ~50% after adjustment for CD4+ cell count. Higher HIV RNA was associated with higher fibrinogen. Compared to an undetectable HIV RNA level, fibrinogen was 0.6%, 1.9%, 4.5%, 4.6%, and 9.4% higher across HIV RNA categories, respectively, and statistically significant at the highest level (p = 0.0002 for HIV RNA ≥ 10,000 copies/ml. Higher HIV RNA was associated with mortality during follow-up in unadjusted analysis, but showed little association after adjustment for CD4+ cell count and inflammation.HIV RNA ≥ 10,000 copies/ml was associated with higher IL-6 and fibrinogen, but lower levels of viremia appeared similar, and there was little association with CRP. The relationship of HIV RNA with IL-6 was strongly affected by CD4 cell depletion. After adjustment for CD4+ cell count and inflammation, viremia did not appear to be substantially associated with mortality risk over 5 years.

  12. The epidemiology, evaluation and treatment of stroke in adults with sickle cell disease

    OpenAIRE

    Strouse, John J.; Lanzkron, Sophie; Urrutia, Victor

    2011-01-01

    Stroke is a frequent and severe complication in adults with sickle cell disease. Ischemic stroke often causes physical and cognitive disability, while hemorrhagic stroke has a high mortality rate. As more children survive, the number of strokes in adults is increasing, yet stroke remains poorly understood. We review the epidemiology of ischemic and hemorrhagic stroke in adults with sickle cell disease and outline a practical approach to the evaluation of stroke including both sickle cell dise...

  13. Two specific drugs, BMS-345541 and purvalanol A induce apoptosis of HTLV-1 infected cells through inhibition of the NF-kappaB and cell cycle pathways

    Directory of Open Access Journals (Sweden)

    Wu Weilin

    2008-06-01

    Full Text Available Abstract Human T-cell leukemia virus type-1 (HTLV-1 induces adult T-cell leukemia/lymphoma (ATL/L, a fatal lymphoproliferative disorder, and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, a chronic progressive disease of the central nervous system after a long period of latent infection. Although the mechanism of transformation and leukemogenesis is not fully elucidated, there is evidence to suggest that the viral oncoprotein Tax plays a crucial role in these processes through the regulation of several pathways including NF-κB and the cell cycle pathways. The observation that NF-κB, which is strongly induced by Tax, is indispensable for the maintenance of the malignant phenotype of HTLV-1 by regulating the expression of various genes involved in cell cycle regulation and inhibition of apoptosis provides a possible molecular target for these infected cells. To develop potential new therapeutic strategies for HTLV-1 infected cells, in this present study, we initially screened a battery of NF-κB and CDK inhibitors (total of 35 compounds to examine their effects on the growth and survival of infected T-cell lines. Two drugs namely BMS-345541 and Purvalanol A exhibited higher levels of growth inhibition and apoptosis in infected cell as compared to uninfected cells. BMS-345541 inhibited IKKβ kinase activity from HTLV-1 infected cells with an IC50 (the 50% of inhibitory concentration value of 50 nM compared to 500 nM from control cells as measured by in vitro kinase assays. The effects of Purvalanol A were associated with suppression of CDK2/cyclin E complex activity as previously shown by us. Combination of both BMS-345541 and Purvalanol A showed a reduced level of HTLV-1 p19 Gag production in cell culture. The apparent apoptosis in these infected cells were associated with increased caspase-3 activity and PARP cleavage. The potent and selective apoptotic effects of these drugs suggest that both BMS-345541 and Purvalanol A

  14. Memory CD8+ T cell differentiation in viral infection: A cell for all seasons

    Institute of Scientific and Technical Information of China (English)

    Henry Radziewicz; Luke Uebelhoer; Bertram Bengsch; Arash Grakoui

    2007-01-01

    Chronic viral infections such as hepatitis B virus (HBV),hepatitis C virus (HCV) and human immunodeficiency virus (HIV) are major global health problems affecting more than 500 million people worldwide. Virus-specific CD8+ T cells play an important role in the course and outcome of these viral infections and it is hypothesized that altered or impaired differentiation of virusspecific CD8+ T cells contributes to the development of persistence and/or disease progression. A deeper understanding of the mechanisms responsible for functional differentiation of CD8+ T cells is essential for the generation of successful therapies aiming to strengthen the adaptive component of the immune system.

  15. Cell cycle restriction by histone H2AX limits proliferation of adult neural stem cells

    OpenAIRE

    Fernando, R. N.; Eleuteri, B.; Abdelhady, S.; Nussenzweig, A; Andang, M; Ernfors, P.

    2011-01-01

    Adult neural stem cell proliferation is dynamic and has the potential for massive self-renewal yet undergoes limited cell division in vivo. Here, we report an epigenetic mechanism regulating proliferation and self-renewal. The recruitment of the PI3K-related kinase signaling pathway and histone H2AX phosphorylation following GABAA receptor activation limits subventricular zone proliferation. As a result, NSC self-renewal and niche size is dynamic and can be directly modulated in both directio...

  16. Cytomegalovirus-infected cells express Leu-M1 antigen. A potential source of diagnostic error.

    OpenAIRE

    Rushin, J. M.; Riordan, G. P.; Heaton, R. B.; Sharpe, R. W.; Cotelingam, J. D.; Jaffe, E S

    1990-01-01

    The authors examined cytomegalovirus (CMV)-infected tissues and Hodgkin's Disease (HD) cases with immunohistochemical assays for Leu-M1 and CMV. The cytologic characteristics were correlated with immunostaining patterns. Cytomegalovirus-infected cells in lymph node, lung, and esophagus sections showed Cowdry type A inclusions, and many had granular cytoplasmic inclusions. All infected cells showed nuclear staining with an anti-CMV antibody. Leu-M1 reacted with CMV-infected cells in cytoplasmi...

  17. Pluripotency of adult stem cells derived from human and rat pancreas

    Science.gov (United States)

    Kruse, C.; Birth, M.; Rohwedel, J.; Assmuth, K.; Goepel, A.; Wedel, T.

    Adult stem cells are undifferentiated cells found within fully developed tissues or organs of an adult individuum. Until recently, these cells have been considered to bear less self-renewal ability and differentiation potency compared to embryonic stem cells. In recent studies an undifferentiated cell type was found in primary cultures of isolated acini from exocrine pancreas termed pancreatic stellate cells. Here we show that pancreatic stellate-like cells have the capacity of extended self-renewal and are able to differentiate spontaneously into cell types of all three germ layers expressing markers for smooth muscle cells, neurons, glial cells, epithelial cells, chondrocytes and secretory cells (insulin, amylase). Differentiation and subsequent formation of three-dimensional cellular aggregates (organoid bodies) were induced by merely culturing pancreatic stellate-like cells in hanging drops. These cells were developed into stable, long-term, in vitro cultures of both primary undifferentiated cell lines as well as organoid cultures. Thus, evidence is given that cell lineages of endodermal, mesodermal, and ectodermal origin arise spontaneously from a single adult undifferentiated cell type. Based on the present findings it is assumed that pancreatic stellate-like cells are a new class of lineage uncommitted pluripotent adult stem cells with a remarkable self-renewal ability and differentiation potency. The data emphasize the versatility of adult stem cells and may lead to a reappraisal of their use for the treatment of inherited disorders or acquired degenerative diseases.

  18. Adult Bone Marrow: Which Stem Cells for Cellular Therapy Protocols in Neurodegenerative Disorders?

    Directory of Open Access Journals (Sweden)

    Sabine Wislet-Gendebien

    2012-01-01

    Full Text Available The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs. In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy.

  19. Adult bone marrow: which stem cells for cellular therapy protocols in neurodegenerative disorders?

    Science.gov (United States)

    Wislet-Gendebien, Sabine; Laudet, Emerence; Neirinckx, Virginie; Rogister, Bernard

    2012-01-01

    The generation of neuronal cells from stem cells obtained from adult bone marrow is of significant clinical interest in order to design new cell therapy protocols for several neurological disorders. The recent identification in adult bone marrow of stem cells derived from the neural crests (NCSCs) might explain the neuronal phenotypic plasticity shown by bone marrow cells. However, little information is available about the nature of these cells compared to mesenchymal stem cells (MSCs). In this paper, we will review all information available concerning NCSC from adult tissues and their possible use in regenerative medicine. Moreover, as multiple recent studies showed the beneficial effect of bone marrow stromal cells in neurodegenerative diseases, we will discuss which stem cells isolated from adult bone marrow should be more suitable for cell replacement therapy. PMID:22319243

  20. Cells from the adult corneal stroma can be reprogrammed to a neuron-like cell using exogenous growth factors

    Energy Technology Data Exchange (ETDEWEB)

    Greene, Carol Ann, E-mail: carol.greene@auckland.ac.nz; Chang, Chuan-Yuan; Fraser, Cameron J.; Nelidova, Dasha E.; Chen, Jing A.; Lim, Angela; Brebner, Alex; McGhee, Jennifer; Sherwin, Trevor; Green, Colin R.

    2014-03-10

    Cells thought to be stem cells isolated from the cornea of the eye have been shown to exhibit neurogenic potential. We set out to uncover the identity and location of these cells within the cornea and to elucidate their neuronal protein and gene expression profile during the process of switching to a neuron-like cell. Here we report that every cell of the adult human and rat corneal stroma is capable of differentiating into a neuron-like cell when treated with neurogenic differentiation specifying growth factors. Furthermore, the expression of genes regulating neurogenesis and mature neuronal structure and function was increased. The switch from a corneal stromal cell to a neuron-like cell was also shown to occur in vivo in intact corneas of living rats. Our results clearly indicate that lineage specifying growth factors can affect changes in the protein and gene expression profiles of adult cells, suggesting that possibly many adult cell populations can be made to switch into another type of mature cell by simply modifying the growth factor environment. - Highlights: • Adult corneal stromal cells can differentiated into neuron-like cells. • Neuronal specification of the adult stromal cell population is stochastic. • Neuronal specification in an adult cell population can be brought about by growth factors.

  1. Recent Progress on Tissue-Resident Adult Stem Cell Biology and Their Therapeutic Implications

    OpenAIRE

    Mimeault, Murielle; Batra, Surinder K.

    2008-01-01

    Recent progress in the field of the stem cell research has given new hopes to treat and even cure diverse degenerative disorders and incurable diseases in human. Particularly, the identification of a rare population of adult stem cells in the most tissues/organs in human has emerged as an attractive source of multipotent stem/progenitor cells for cell replacement-based therapies and tissue engineering in regenerative medicine. The tissue-resident adult stem/progenitor cells offer the possibil...

  2. Gene expression in epithelial cells in response to pneumovirus infection

    Directory of Open Access Journals (Sweden)

    Rosenberg Helene F

    2001-05-01

    Full Text Available Abstract Respiratory syncytial virus (RSV and pneumonia virus of mice (PVM are viruses of the family Paramyxoviridae, subfamily pneumovirus, which cause clinically important respiratory infections in humans and rodents, respectively. The respiratory epithelial target cells respond to viral infection with specific alterations in gene expression, including production of chemoattractant cytokines, adhesion molecules, elements that are related to the apoptosis response, and others that remain incompletely understood. Here we review our current understanding of these mucosal responses and discuss several genomic approaches, including differential display reverse transcription-polymerase chain reaction (PCR and gene array strategies, that will permit us to unravel the nature of these responses in a more complete and systematic manner.

  3. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection

    Science.gov (United States)

    Doitsh, Gilad; Galloway, Nicole L. K.; Geng, Xin; Yang, Zhiyuan; Monroe, Kathryn M.; Zepeda, Orlando; Hunt, Peter W.; Hatano, Hiroyu; Sowinski, Stefanie; Muñoz-Arias, Isa; Greene, Warner C.

    2014-01-01

    The pathway causing CD4 T-cell death in HIV-infected hosts remains poorly understood although apoptosis has been proposed as a key mechanism. We now show that caspase-3-mediated apoptosis accounts for the death of only a small fraction of CD4 T cells corresponding to those that are both activated and productively infected. The remaining over 95% of quiescent lymphoid CD4 T cells die by caspase-1-mediated pyroptosis triggered by abortive viral infection. Pyroptosis corresponds to an intensely inflammatory form of programmed cell death in which cytoplasmic contents and pro-inflammatory cytokines, including IL-1β, are released. This death pathway thus links the two signature events in HIV infection--CD4 T-cell depletion and chronic inflammation--and creates a pathogenic vicious cycle in which dying CD4 T cells release inflammatory signals that attract more cells to die. This cycle can be broken by caspase 1 inhibitors shown to be safe in humans, raising the possibility of a new class of `anti-AIDS' therapeutics targeting the host rather than the virus.

  4. Multipotent stem cells isolated from the adult mouse retina are capable of producing functional photoreceptor cells

    Institute of Scientific and Technical Information of China (English)

    Tianqing Li; Michelle Lewallen; Shuyi Chen; Wei Yu; Nian Zhang; Ting Xie

    2013-01-01

    Various stem cell types have been tested for their potential application in treating photoreceptor degenerative diseases,such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD).Only embryonic stem cells (ESCs) have so far been shown to generate functional photoreceptor cells restoring light response of photoreceptordeficient mice,but there is still some concern of tumor formation.In this study,we have successfully cultured Nestin+Sox2+Pax6+ multipotent retinal stem cells (RSCs) from the adult mouse retina,which are capable of producing functional photoreceptor cells that restore the light response of photoreceptor-deficient rd1 mutant mice following transplantation.After they have been expanded for over 35 passages in the presence of FGF and EGF,the cultured RSCs still maintain stable proliferation and differentiation potential.Under proper differentiation conditions,they can differentiate into all the major retinal cell types found in the adult retina.More importantly,they can efficiently differentiate into photoreceptor cells under optimized differentiation conditions.Following transplantation into the subretinal space of slowly degenerating rd7 mutant eyes,RSC-derived photoreceptor cells integrate into the retina,morphologically resembling endogenous photoreceptors and forming synapases with resident retinal neurons.When transplanted into eyes of photoreceptor-deficient rd1 mutant mice,a RP model,RSC-derived photoreceptors can partially restore light response,indicating that those RSC-derived photoreceptors are functional.Finally,there is no evidence for tumor formation in the photoreceptor-transplanted eyes.Therefore,this study has demonstrated that RSCs isolated from the adult retina have the potential of producing functional photoreceptor cells that can potentially restore lost vision caused by loss of photoreceptor cells in RP and AMD.

  5. Influence of supplementary immunization activities for adults dynamics of chronic disease HBV-infection and its outcomes

    Directory of Open Access Journals (Sweden)

    S. V. Baramzina

    2014-01-01

    Full Text Available Purpose: to evaluate the effect of additional vaccination of adult HBV- infection years 2007–2010 on the incidence of chronic hepatitis B and its outcomes on the example of the Kirov region.Materials and Methods: the evaluation of epidemiological features process in patients with chronic HBV infection in adults, depending on the vaccination carried out on the basis of official data Rospotrebnadzora in Russia and Kirov region on incidence of infectious disease for the period 1999–2012. Diagnosis of chronic hepatitis B was based on clinical and biochemical, instrumental, virological data. Structure outcomes of chronic hepatitis B was studied in 295 patients aged 18–75 years who were hospitalized in the department of viral hepatitis Kirov infectious diseases hospital in 2006–2010.Results: In the Kirov region tended to decrease the incidence of chronic hepatitis B in adults. Additional adult vaccination against hepatitis B has not led to the expected significant decrease of the number of patients with chronic forms. One reason for this is the low (20,3–64% of the adult population immunization coverage. Chronic HBV- monoinfected was observed in 17.1% , cirrhosis in the outcome of chronic hepatitis B in 5,4% of cases, in hospital mortality from complications of HBV- cirrhosis was 0,7%. Association virus C and D have increased the total cohort, compared to a mono- infection by 3,8% and 0,5% lethality.Conclusion: Additional adult vaccination against hepatitis B in the area has led to a slight decrease in the overall incidence of chronic hepatitis B, but has not reduced the incidence of adverse events – cirrhosis and liver- mediated lethality.

  6. Topography of Purkinje cells and other calbindin-immunoreactive cells within adult and hatchling turtle cerebellum.

    Science.gov (United States)

    Ariel, Michael; Ward, Kyle C; Tolbert, Daniel L

    2009-12-01

    The turtle's cerebellum (Cb) is an unfoliated sheet, so the topography of its entire cortex can be easily studied physiologically by optical recordings. However, unlike the mammalian Cb, little is known about the topography of turtle Purkinje cells (PCs). Here, topography was examined using calbindin-D(28K) immunohistochemistry of adult and hatchling turtles (Trachemys scripta elegans, 2.5-15 cm carapace length). Each Cb was flattened between two Sylgard sheets and fixed in paraformaldehyde. Sections (52 microm thick) were cut parallel to the flattened cortex (tangential), resulting in calbindin-immunolabeled PCs being localized to three to six sections for each turtle. PC position and size were quantified using Neurolucida Image Analysis system. Although hatchling Cb were medial-laterally narrower (3.0 vs. 6.5 mm) and rostral-caudally shorter (2.5 vs. 5.5 mm) than adult Cb, both averaged near 15,000 PCs distributed uniformly. Hatchling PCs were smaller than adult PCs (178 vs. 551 microm(2)) and more densely packed (2,180 vs. 625 cells/mm(2)). Calbindin immunoreactivity also labeled non-PCs along the Cb's marginal rim and its caudal pole. Many of these were very small (22.9 microm(2)) ovoid-shaped cells clustered together, possibly proliferating external granule layer cells. Other labeled cells were larger and fusiform-shaped (12.6 x 33.4 microm) adjacent to inner granule cells along the marginal rim, suggestive of migrating cells. It is not known whether these are new neurons being generated within the adult and hatchling Cb and if they connect to efferent and afferent paths. Based on these anatomical findings, we suggest that unique physiological features may exist along the rim of the turtle Cb.

  7. Kinetics of liver macrophages (Kupffer cells) in SIV-infected macaques

    International Nuclear Information System (INIS)

    Since the liver drains antigens from the intestinal tract, and since the intestinal tract is a major site of viral replication, we examined the dynamics of liver macrophages (Kupffer cells) throughout SIV infection. Absolute numbers of Kupffer cells increased in the livers in acute infection, and in animals with AIDS. Significantly higher percentages of proliferating (BrdU+) Kupffer cells were detected in acute infection and in AIDS with similar trends in blood monocytes. Significantly higher percentages of apoptotic (AC3+) Kupffer cells were also found in acute and AIDS stages. However, productively infected cells were not detected in liver of 41/42 animals examined, despite abundant infected cells in gut and lymph nodes of all animals. Increased rates of Kupffer cell proliferation resulting in an increase in Kupffer cells without productive infection indicate SIV infection affects Kupffer cells, but the liver does not appear to be a major site of productive viral replication. - Highlights: • Kupffer cells increase in the liver of SIV-infected macaques. • Increased proliferation and apoptosis of Kupffer cells occurs in SIV infection. • Productively infected cells are rarely detected in the liver. • The liver is not a major site for SIV replication

  8. Embryonic and adult stem cells as a source for cell therapy in Parkinson's disease.

    Science.gov (United States)

    Levy, Yossef S; Stroomza, Merav; Melamed, Eldad; Offen, Daniel

    2004-01-01

    The rationale behind the use of cells as therapeutic modalities for neurodegenerative diseases in general, and in Parkinson's disease (PD) in particular, is that they will improve patient's functioning by replacing the damaged cell population. It is reasoned that these cells will survive, grow neurites, establish functional synapses, integrate best and durably with the host tissue mainly in the striatum, renew the impaired wiring, and lead to meaningful clinical improvement. To increase the generation of dopamine, researchers have already transplanted non-neuronal cells, without any genetic manipulation or after introduction of genes such as tyrosine hydroxylase, in animal models of PD. Because these cells were not of neuronal origin, they developed without control, did not integrate well into the brain parenchyma, and their survival rates were low. Clinical experiments using cell transplantation as a therapy for PD have been conducted since the 1980s. Most of these experiments used fetal dopaminergic cells originating in the ventral mesencephalic tissue obtained from fetuses. Although it was shown that the transplanted cells survived and some patients benefited from this treatment, others suffered from severe dyskinesia, probably caused by the graft's excessive and uncontrolled production and release of dopamine. It is now recognized that cell-replacement strategy will be effective in PD only if the transplanted cells have the same abilities, such as dopamine synthesis and control release, reuptake, and metabolizing dopamine, as the original dopaminergic neurons. Recent studies on embryonic and adult stem cells have demonstrated that cells are able to both self-renew and produce differentiated tissues, including dopaminergic neurons. These new methods offer real hope for tissue replacement in a wide range of diseases, especially PD. In this review we summarize the evidence of dopaminergic neuron generation from embryonic and adult stem cells, and discuss their

  9. Langerhans cell histiocytosis of the atlas in an adult.

    Science.gov (United States)

    Zhong, Wo Quan; Jiang, Liang; Ma, Qing Jun; Liu, Zhong Jun; Liu, Xiao Guang; Wei, Feng; Yuan, Hui Shu; Dang, Geng Ting

    2010-01-01

    Langerhans cell histiocytosis (LCH), formerly known as histiocytosis X, is a rare disorder (approximately 1:1,500,000 inhabitants) characterized by clonal proliferation and excess accumulation of pathologic Langerhans cells causing local or systemic effects. The exact etiology of LCH is still unknown. LCH could affect patients of any age, although most present when they are children. The most frequent sites of the bony lesions are the skull, femur, mandible, pelvis and spine. A variety of treatment modalities has been reported, but there was no evidence suggesting that any one treatment was more advantageous than another. We present an adult with LCH of the atlas. A 26-year-old young man presented with a 2-month history of neck pain and stiffness. CT revealed osteolytic lesion in the left lateral mass of atlas with compression fracture. Histopathological diagnosis was Langerhans cell histiocytosis by percutaneous needle biopsy under CT guidance. The patient underwent conservative treatment, including Halo-vest immobilization and radiotherapy. At 7-year follow-up, the patient was asymptomatic except for mild motion restriction of the neck. CT revealed a significant reconstruction of the C1 lateral mass. PMID:19844749

  10. Pseudomonas aeruginosa forms Biofilms in Acute InfectionIndependent of Cell-to-Cell Signaling

    Energy Technology Data Exchange (ETDEWEB)

    Schaber, J. Andy; Triffo, W.J.; Suh, Sang J.; Oliver, Jeffrey W.; Hastert, Mary C.; Griswold, John A.; Auer, Manfred; Hamood, Abdul N.; Rumbaugh, Kendra P.

    2006-09-20

    Biofilms are bacterial communities residing within a polysaccharide matrix that are associated with persistence and antibiotic resistance in chronic infections. We show that the opportunistic pathogen Pseudomonas aeruginosa forms biofilms within 8 hours of infection in thermally-injured mice, demonstrating that biofilms contribute to bacterial colonization in acute infections. P. aeruginosa biofilms were visualized within burned tissue surrounding blood vessels and adipose cells. Although quorum sensing (QS), a bacterial signaling mechanism, coordinates differentiation of biofilms in vitro, wild type and QS-deficient P. aeruginosa formed similar biofilms in vivo. Our findings demonstrate that P. aeruginosa forms biofilms on specific host tissues independent of QS.

  11. The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java.

    Directory of Open Access Journals (Sweden)

    Herman Kosasih

    2016-02-01

    Full Text Available Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies.Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000-2004 and 2006-2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%. The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections.Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with most infections resulting in asymptomatic disease. The

  12. Regulation of T cell migration during viral infection: role of adhesion molecules and chemokines

    DEFF Research Database (Denmark)

    Thomsen, Allan Randrup; Nansen, Anneline; Madsen, Andreas Nygaard;

    2003-01-01

    T cell mediated immunity and in particular CD8+ T cells are pivotal for the control of most viral infections. T cells exclusively exert their antiviral effect through close cellular interaction with relevant virus-infected target cells in vivo. It is therefore imperative that efficient mechanisms...

  13. Murine granulated metrial gland cells are susceptible to Chlamydia psittaci infection in vivo.

    OpenAIRE

    Sánchez, J.; Buendía, A.J.; Salinas, J.; Bernabé, A.; Rodolakis, A; Stewart, I J

    1996-01-01

    Granulated metrial gland (GMG) cells are the most numerous lymphoid cells in the uteroplacental unit in rodent pregnancy. In an experimental murine model of abortion-causing infection, we have studied the responses of GMG cells to Chlamydia psittaci. Chlamydial inclusions have been found within GMG cells, both in apparently healthy cells and in cells with degenerative changes. Establishing the existence of GMG cells infected by C. psittaci opens a new and interesting chapter in the study of t...

  14. CD3+CD8+CD161high Tc17 cells are depleted in HIV-infection.

    Science.gov (United States)

    Gaardbo, Julie Christine; Hartling, Hans Jakob; Thorsteinsson, Kristina; Ullum, Henrik; Nielsen, Susanne Dam

    2013-02-20

    CD8 Tc17 cells with pro-inflammatory properties have only recently been acknowledged, and Tc17 cells in HIV-infection are not described. CD3CD8CD161 Tc17 cells and the production of interleukin (IL)-17 were examined in untreated and treated HIV-infected patients, HIV-hepatitis C virus co-infected patients, and healthy controls. Depletion of CD3CD8CD161 Tc17 cells and diminished production of IL-17 in HIV-infected patients were found. The level of Tc17 cells was associated with the CD4 cell count in treated patients. PMID:23135168

  15. Detection of bacteriophage-infected cells of Lactococcus lactis using flow cytometry

    DEFF Research Database (Denmark)

    Michelsen, Ole; Cuesta-Dominguez, Álvaro; Albrektsen, Bjarne;

    2007-01-01

    Bacteriophage infection in dairy fermentation constitutes a serious problem worldwide. We have studied bacteriophage infection in Lactococcus lactis by using the flow cytometer. The first effect of the infection of the bacterium is a change from cells in chains toward single cells. We interpret...

  16. A new in vitro model using small intestinal epithelial cells to enhance infection of Cryptosporidium parvum

    Science.gov (United States)

    To better understand and study the infection of the protozoan parasite Cryptosporidium parvum, a more sensitive in vitro assay is required. In vivo, this parasite infects the epithelial cells of the microvilli layer in the small intestine. While cell infection models using colon,...

  17. Human Intestinal Tissue with Adult Stem Cell Properties Derived from Pluripotent Stem Cells

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    Ryan Forster

    2014-06-01

    Full Text Available Genetically engineered human pluripotent stem cells (hPSCs have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the isolation of defined functional tissues. Here, using an endogenous LGR5-GFP reporter, we derived adult stem cells from hPSCs that gave rise to functional human intestinal tissue comprising all major cell types of the intestine. Histological and functional analyses revealed that such human organoid cultures could be derived with high purity and with a composition and morphology similar to those of cultures obtained from human biopsies. Importantly, hPSC-derived organoids responded to the canonical signaling pathways that control self-renewal and differentiation in the adult human intestinal stem cell compartment. This adult stem cell system provides a platform for studying human intestinal disease in vitro using genetically engineered hPSCs.