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Sample records for underlying primary immune

  1. Primary Immune Deficiency Treatment Consortium (PIDTC) report

    NARCIS (Netherlands)

    L.M. Griffith (Linda); M. Cowan (Morton); L.D. Notarangelo (Luigi Daniele); R. Kohn (Robert); J. Puck (Jennifer); S.-Y. Pai (Sung-Yun); B. Ballard (Barbara); S.C. Bauer (Sarah); J. Bleesing (Jack); M. Boyle (Marcia); R.W. Brower (Ronald); R.H. Buckley (Rebecca); M. van der Burg (Mirjam); L.M. Burroughs (Lauri); F. Candotti (Fabio); A. Cant (Andrew); T. Chatila (Talal); C. Cunningham-Rundles (Charlotte); M.C. Dinauer (Mary); J. Dvorak (Jennie); A. Filipovich (Alexandra); L.A. Fleisher (Lee); H.B. Gaspar (Bobby); T. Gungor (Tayfun); E. Haddad (Elie); E. Hovermale (Emily); F. Huang (Faith); A. Hurley (Alan); M. Hurley (Mary); S.K. Iyengar (Sudha); E.M. Kang (Elizabeth); B.R. Logan (Brent); J.R. Long-Boyle (Janel); H. Malech (Harry); S.A. McGhee (Sean); S. Modell (Sieglinde); S. Modell (Sieglinde); H.D. Ochs (Hans); R.J. O'Reilly (Richard); R. Parkman (Robertson); D. Rawlings (D.); J.M. Routes (John); P. Shearer (P.); T.N. Small (Trudy); H. Smith (H.); K.E. Sullivan (Kathleen); P. Szabolcs (Paul); A.J. Thrasher (Adrian); D. Torgerson; P. Veys (Paul); K. Weinberg (Kenneth); J.C. Zuniga-Pflucker (Juan Carlos)

    2014-01-01

    textabstractThe Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency

  2. Mechanisms underlying UV-induced immune suppression

    Energy Technology Data Exchange (ETDEWEB)

    Ullrich, Stephen E. [Department of Immunology, University of Texas, MD Anderson Cancer Center, South Campus Research Building 1, 7455 Fannin St., P.O. Box 301402, Houston, TX 77030-1903 (United States)]. E-mail: sullrich@mdanderson.org

    2005-04-01

    Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression.

  3. Mechanisms underlying UV-induced immune suppression

    International Nuclear Information System (INIS)

    Ullrich, Stephen E.

    2005-01-01

    Skin cancer is the most prevalent form of human neoplasia. Estimates suggest that in excess of one million new cases of skin cancer will be diagnosed this year alone in the United States (www.cancer.org/statistics). Fortunately, because of their highly visible location, skin cancers are more rapidly diagnosed and more easily treated than other types of cancer. Be that as it may, approximately 10,000 Americans a year die from skin cancer. The cost of treating non-melanoma skin cancer is estimated to be in excess of US$ 650 million a year [J.G. Chen, A.B. Fleischer, E.D. Smith, C. Kancler, N.D. Goldman, P.M. Williford, S.R. Feldman, Cost of non-melanoma skin cancer treatment in the United States, Dermatol. Surg. 27 (2001) 1035-1038], and when melanoma is included, the estimated cost of treating skin cancer in the United States is estimated to rise to US$ 2.9 billion annually (www.cancer.org/statistics). Because the morbidity and mortality associated with skin cancer is a major public health problem, it is important to understand the mechanisms underlying skin cancer development. The primary cause of skin cancer is the ultraviolet (UV) radiation found in sunlight. In addition to its carcinogenic potential, UV radiation is also immune suppressive. In fact, data from studies with both experimental animals and biopsy proven skin cancer patients suggest that there is an association between the immune suppressive effects of UV radiation and its carcinogenic potential. The focus of this manuscript will be to review the mechanisms underlying the induction of immune suppression following UV exposure. Particular attention will be directed to the role of soluble mediators in activating immune suppression

  4. Primary immunodeficiencies of protective immunity to primary infections.

    Science.gov (United States)

    Bousfiha, Aziz; Picard, Capucine; Boisson-Dupuis, Stéphanie; Zhang, Shen-Ying; Bustamante, Jacinta; Puel, Anne; Jouanguy, Emmanuelle; Ailal, Fatima; El-Baghdadi, Jamila; Abel, Laurent; Casanova, Jean-Laurent

    2010-05-01

    The vast majority of primary immunodeficiencies (PIDs) predispose affected individuals to recurrent or chronic infectious diseases, because they affect protective immunity to both primary and secondary or latent infections. We discuss here three recently described groups of PIDs that seem to impair immunity to primary infections without compromising immunity to secondary and latent infections. Patients with mutations in IL12B or IL12RB1 typically present mycobacterial disease in childhood with a favorable progression thereafter. Cross-protection between mycobacterial infections has even been observed. Patients with mutations in IRAK4 or MYD88 suffer from pyogenic bacterial diseases, including invasive pneumococcal diseases in particular. These diseases often recur, although not always with the same serotype, but the frequency of these recurrences tails off, with no further infections observed from adolescence onwards. Finally, mutations in UNC93B1 and TLR3 are associated with childhood herpes simplex encephalitis, which strikes only once in most patients, with almost no recorded cases of more than two bouts of this disease. Unlike infections in patients with other PIDs, the clinical course of which typically deteriorates with age even if appropriate treatment is given, the prognosis of patients with these three newly described PIDs tends to improve spontaneously with age, provided, of course, that the initial infection is properly managed. In other words, although life-threatening in early childhood, these new PIDs are associated with a favorable outcome in adulthood. They provide proof-of-principle that infectious diseases of childhood striking only once may result from single-gene inborn errors of immunity. Copyright 2010. Published by Elsevier Inc.

  5. Primary Immune Deficiency Treatment Consortium (PIDTC) report.

    Science.gov (United States)

    Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D; Kohn, Donald B; Puck, Jennifer M; Pai, Sung-Yun; Ballard, Barbara; Bauer, Sarah C; Bleesing, Jack J H; Boyle, Marcia; Brower, Amy; Buckley, Rebecca H; van der Burg, Mirjam; Burroughs, Lauri M; Candotti, Fabio; Cant, Andrew J; Chatila, Talal; Cunningham-Rundles, Charlotte; Dinauer, Mary C; Dvorak, Christopher C; Filipovich, Alexandra H; Fleisher, Thomas A; Bobby Gaspar, Hubert; Gungor, Tayfun; Haddad, Elie; Hovermale, Emily; Huang, Faith; Hurley, Alan; Hurley, Mary; Iyengar, Sumathi; Kang, Elizabeth M; Logan, Brent R; Long-Boyle, Janel R; Malech, Harry L; McGhee, Sean A; Modell, Fred; Modell, Vicki; Ochs, Hans D; O'Reilly, Richard J; Parkman, Robertson; Rawlings, David J; Routes, John M; Shearer, William T; Small, Trudy N; Smith, Heather; Sullivan, Kathleen E; Szabolcs, Paul; Thrasher, Adrian; Torgerson, Troy R; Veys, Paul; Weinberg, Kenneth; Zuniga-Pflucker, Juan Carlos

    2014-02-01

    The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives. Published by Mosby, Inc.

  6. New genetic discoveries and primary immune deficiencies.

    Science.gov (United States)

    Hernandez-Trujillo, Vivian

    2014-04-01

    The field of immunology has undergone recent discoveries of genetic causes for many primary immunodeficiency diseases (PIDD). The ever-expanding knowledge has led to increased understanding behind the pathophysiology of these diseases. Since these diseases are rare, the patients are frequently misdiagnosed early in the presentation of their illnesses. The identification of new genes has increased our opportunities for recognizing and making the diagnosis in patients with PIDD before they succumb to infections that may result secondary to their PIDD. Some mutations lead to a variety of presentations of severe combined immunodeficiency (SCID). The myriad and ever-growing genetic mutations which lead to SCID phenotypes have been identified in recent years. Other mutations associated with some genetic syndromes have associated immunodeficiency and are important for making the diagnosis of primary immunodeficiency in patients with some syndromes, who may otherwise be missed within the larger context of their syndromes. A variety of mutations also lead to increased susceptibility to infections due to particular organisms. These patterns of infections due to specific organisms are important keys in properly identifying the part of the immune system which is affected in these patients. This review will discuss recent genetic discoveries that enhance our understanding of these complex diseases.

  7. Incidence of childhood primary immune thrombocytopenic purpura.

    Science.gov (United States)

    Higashigawa, Masamune; Maeyama, Takatoshi; Yoshino, Ayako; Matsuda, Kazuyuki; Ito, Mitsue; Maji, Tomoaki; Ichimi, Ryouji

    2015-10-01

    There is a discrepancy in the reported incidence of childhood immune thrombocytopenic purpura (ITP) between Europe (2.9-5.3 per 100 000 persons) and Japan (1.91). Ise district is a suitable area in which to conduct epidemiological study because there is little fluctuation in the sociodemographic factors. We performed a retrospective population-based study to clarify the incidence of primary childhood ITP. We calculated person-years for children aged <15 years based on the Ise district demographics between 2002 and 2012. The calculated person-years were 298 533. The number of hospitalized patients in Ise district was 25 (M/F, 14/11) during the study period. The calculated incidence was therefore 8.4 per 100 000 person-years. It is possible that the difference in incidence between the present calculation and that of the European studies is due to variation in accuracy and/or registration criteria between the studies. © 2015 Japan Pediatric Society.

  8. Gene therapy for primary adaptive immune deficiencies.

    Science.gov (United States)

    Fischer, Alain; Hacein-Bey-Abina, Salima; Cavazzana-Calvo, Marina

    2011-06-01

    Gene therapy has become an option for the treatment of 2 forms of severe combined immunodeficiency (SCID): X-linked SCID and adenosine deaminase deficiency. The results of clinical trials initiated more than 10 years ago testify to sustained and reproducible correction of the underlying T-cell immunodeficiency. Successful treatment is based on the selective advantage conferred on T-cell precursors through their expression of the therapeutic transgene. However, "first-generation" retroviral vectors also caused leukemia in some patients with X-linked SCID because of the constructs' tendency to insert into active genes (eg, proto-oncogenes) in progenitor cells and transactivate an oncogene through a viral element in the long terminal repeat. These elements have been deleted from the vectors now in use. Together with the use of lentiviral vectors (which are more potent for transducing stem cells), these advances should provide a basis for the safe and effective extension of gene therapy's indications in the field of primary immunodeficiencies. Nevertheless, this extension will have to be proved by examining the results of the ongoing clinical trials. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  9. Modulation of primary immune response by different vaccine adjuvants

    Directory of Open Access Journals (Sweden)

    Annalisa Ciabattini

    2016-10-01

    Full Text Available Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Since the primary immune response can influence the overall quality of the response generated, here we investigate early biomarkers of adjuvanticity after primary immunization with four different adjuvants combined with the chimeric tuberculosis vaccine antigen H56. C57BL/6 mice were immunized by the subcutaneous route with different vaccine formulations, and the modulation of primary CD4+ T cell and B cell responses was assessed within draining lymph nodes, blood and spleen, 7 and 12 days after priming. Vaccine formulations containing the liposome system CAF01 or a squalene-based oil-in-water emulsion (o/w Squalene, but not aluminum hydroxide (Alum or CpG ODN 1826, elicited a significant primary antigen-specific CD4+ T cell response compared to antigen alone, 7 days after immunization. The effector function of activated CD4+ T cells was skewed towards a Th1/Th17 response by CAF01, while a Th1/Th2 response was elicited by o/w Squalene. Differentiation of B cells in short-lived plasma cells, and subsequent early H56-specific IgG secretion, was observed in mice immunized with o/w Squalene or CpG adjuvants. Tested adjuvants promoted the germinal centre reaction with different magnitude. These results show that the immunological activity of different adjuvants can be characterized by profiling early immunization biomarkers after primary immunization. These data and this approach could give an important contribution to the rational development of heterologous prime-boost vaccine immunization protocols.

  10. Primary pulmonary immunity to a soluble antigen in the dog

    International Nuclear Information System (INIS)

    Weissman, D.N.; Bice, D.E.; Muggenburg, B.A.; Schuyler, M.R.

    1988-01-01

    In order to study primary lung immunity to soluble antigen, Beagle dogs underwent trans-bronchoscopic instillation of 10 mg keyhole limpet hemocyanin (KLH) into the right cardiac lobe and saline into the left cardiac lobe. Over the next 3 wk, specific immune responses were monitored in blood and bronchoalveolar lavage (BAL) fluids obtained from immunized and control lung lobes. Primary lung immunization of dogs with KLH resulted in easily measurable specific IgG, IgM, and IgA responses in blood and bronchoalveolar lavage fluids. Important class differences were noted to exist for these responses. Levels of specific IgG and IgA in BAL remained elevated at 21 days after immunization, while BAL-specific IgM levels fell to control values by 12 days after immunization. In unimmunized lung lobes, specific antibody levels in BAL and production of specific antibody by bronchoalveolar lavage cells was far greater for IgG than for IgM or IgA. Finally, despite easily detectable specific IgA in serum and BAL fluid, production of specific IgA by peripheral blood mononuclear cells or bronchoalveolar lavage cells after primary lung immunization with KLH could not be demonstrated, suggesting that specific IgA was produced by a compartment of cells poorly sampled in blood and BAL. (author)

  11. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS

    DEFF Research Database (Denmark)

    Bech Mortensen, Thomas; Frederiksen, Henrik; Marcher, Claus Werenberg

    2017-01-01

    A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological featu...

  12. Radioresistance and immunization effectiveness under internal irradiation

    International Nuclear Information System (INIS)

    Kal'nitskij, S.A.

    1978-01-01

    The effect of preliminary immunization on the radioresistance of mice to internal irradiation from incorporated 137 Cs or 90 Sr was studied, and it was found that a preliminary single immunization with bacterial vaccines had a favorable effect on the outcome of radiation injury. The present results suggested that vaccination had a very pronounced radioprotective effect and so may be used as a means of biologic protection from internal irradiation

  13. Routine primary immunization: status in two district of West Bengal.

    Science.gov (United States)

    Dasgupta, S; Karmakar, P Roy; Mandal, N K; Roy, R P; Mallik, S; Mandal, A K

    2005-01-01

    The study was conducted at Birbhum and Purba Medinipur districts of West Bengal to assess the routine primary immunization coverage following 40 cluster sampling technique was used to study 320 children in each of the districts. BCG coverage was found to be 79.69% at Birbhum and 84.38% at Purba Medinipur. Only 62.81% children at Birbhum and 67.81% children at Purba Medinipur received all the three primary doses of DPT. Regarding OPV, coverage with three primary doses were only 65% and 66.88% at Birbhum and Purba Medinipur respectively. Measles vaccine coverage was very poor at both the districts, 55.94% at Birbhum and 62.5% at Purba Medinipur. Full primary immunization was observed 53.13% and 61.56% in Birbhum and Purba Medinipur respectively. High drop-out rate was identified as a major deficiency in both the districts. Of the children who received at least one routine vaccine, more than 1/3rd at Birbhum and more than 1/4 th at Purba Medinipur did not turn up later for completion of their primary vaccine doses. It is evident that routine immunization coverage was poor in both the districts and it seems there has been no improvement in situation for last few years. It will influence not only the child morbidity and mortality situation but also will jeopardize the paralytic polio eradication programme. Urgent intervention should be undertaken to address the large number of non-immunized children as well as high proportion of drop-outs.

  14. Diagnostic Accuracy Comparison of Artificial Immune Algorithms for Primary Headaches

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    Ufuk Çelik

    2015-01-01

    Full Text Available The present study evaluated the diagnostic accuracy of immune system algorithms with the aim of classifying the primary types of headache that are not related to any organic etiology. They are divided into four types: migraine, tension, cluster, and other primary headaches. After we took this main objective into consideration, three different neurologists were required to fill in the medical records of 850 patients into our web-based expert system hosted on our project web site. In the evaluation process, Artificial Immune Systems (AIS were used as the classification algorithms. The AIS are classification algorithms that are inspired by the biological immune system mechanism that involves significant and distinct capabilities. These algorithms simulate the specialties of the immune system such as discrimination, learning, and the memorizing process in order to be used for classification, optimization, or pattern recognition. According to the results, the accuracy level of the classifier used in this study reached a success continuum ranging from 95% to 99%, except for the inconvenient one that yielded 71% accuracy.

  15. Effect of glucocorticoids on melatonin receptor expression under T-cell activated immune response

    International Nuclear Information System (INIS)

    Tauschanova, P.; Georgiev, G.; Manchev, S.; Konakchieva, R.

    2007-01-01

    The present study was aimed to explore the stress response in rats under conditions of T-cell antigen-activated immune function and to investigate the specific melatonin (MEL) receptor binding in primary and secondary immune tissue of rats employing 2-( 125 I)-iodo melatonin autoradiography and in vitro ligand binding assay. The study revealed that melatonin receptor binding was specifically expressed in discrete areas of the lymphoid sheath of the spleen and in a network of interdigitating cells of the experimental rats. Demonstration of the modulation of MEL receptor binding in the course of a primary immune response under hypercorticalemic conditions indicate that the pineal hormone might interfere in the processes of glucocorticoid-dependent immune competency. (authors)

  16. Expanded programme on immunization and primary health care.

    Science.gov (United States)

    Basu, R N

    1982-09-01

    The ultimate objective of the Expanded Program on Immunication, better known as EPI, is to reduce the morbidity of the diseases for which vaccine is available. The EPI is a key component of the country effort to provide Health for All by the year 2000. It is planned that by 1990 immunization services will be available for all infants against diphtheria, whooping cough, tetanus, tuberculosis, and poliomyelitis and for all school children for diptheria, tetanus, and typhoid, and for all pregnant women against tetanus. The immunization services will be a part of the comprehensive health care and will be integrated with all hospitals and dispensaries in urban areas and primary health centers/subcenters in the rural areas. Outreach operations are encouraged to bring these services as close to the mother and children as possible. Steps have already been taken to make the country self-sufficient in the production of different quality vaccines to meet the program requirements. New vaccines will be added where found to be epidemiologically necessary and administratively feasible. The vaccination program is effective only if given at the right age. A national immunization schedule has been prepared which emphasizes vaccination of all infants with 1 dose of BCG, 3 doses of DPT and polio at a minimum interval of 1 month, by the 1st birthday. School entrants are given a booster dose of DT and 2 doses of typhoid vaccine at an interval of 1 month. The children leaving primary school and leaving high school are given 1 booster dose of tetanus toxoid. In case of history of tetanus toxoid immunization in the earlier preganancy, 1 booster dose is adequate. Important components of management of EPI are cold chain maintenance, record keeping and evaluation, uniform vaccination coverage standards, and communication with the public through various media. A table gives the number of children/women proposed to be covered with full course of vaccine during each year of the 6th Plan. Disease

  17. Toll-like receptor signaling in primary immune deficiencies

    Science.gov (United States)

    Maglione, Paul J.; Simchoni, Noa; Cunningham-Rundles, Charlotte

    2015-01-01

    Toll-like receptors (TLRs) recognize common microbial or host-derived macromolecules and have important roles in early activation of the immune system. Patients with primary immune deficiencies (PIDs) affecting TLR signaling can elucidate the importance of these proteins to the human immune system. Defects in interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor 88 (MyD88) lead to susceptibility to infections with bacteria, while mutations in nuclear factor-κB essential modulator (NEMO) and other downstream mediators generally induce broader susceptibility to bacteria, viruses, and fungi. In contrast, TLR3 signaling defects are specific for susceptibility to herpes simplex virus type 1 (HSV-1) encephalitis. Other PIDs induce functional alterations of TLR signaling pathways, such as common variable immunodeficiency in which plasmacytoid dendritic cell (pDC) defects enhance defective responses of B cells to shared TLR agonists. Dampening of TLR responses is seen for TLRs 2 and 4 in chronic granulomatous disease (CGD) and X-linked agammaglobulinemia (XLA). Enhanced TLR responses, meanwhile, are seen for TLRs 5 and 9 in CGD, TLRs 4, 7/8, and 9 in XLA, TLRs 2 and 4 in hyper IgE syndrome, and for most TLRs in adenosine deaminase deficiency. PMID:25930993

  18. In Primary Health Care Childhood Immunization Services Costs, Practices

    Directory of Open Access Journals (Sweden)

    Zeynep Turk

    2014-03-01

    Full Text Available Human health has became a topic that is required exploration and development since the existence of humanity. Many of the diseases out of during the human life and with the miscellaneous invention; solution ways were sought. Development of antibiotics and vaccines are featured inventions in this warfare. Vaccine is known as the best alternative and may be primarily preferred method. Study was conducted to determine of costs and comparison of estimates of the families. In order to investigate the prediction of family about cost and vaccine applications a survey prepared that is reached with a link to the survey on the internet and 170 people participated. According to 2013 childhood immunization schedule; 21 doses of vaccine are administered for 13 varieties of disease. While in the market price of vaccines were identified as TL1094.54 Ministry of Health vaccine price is TL320.22 for a child. Families vaccinated or have been vaccinated their 98% of children to the family physicians or health care facilities. Primarialy reasons of families to prefer primary health care as a priority are vaccines stored in safer conditions and better monitoring of the vaccination time in family physician system. When the cost of immunization that is primary of protective health services analysed significant differences between the ministry prices with the market price is present, families are not aware enough about these costs have been identified.

  19. Immune Response And Anamnestic Immune Response In Children After A 3-Dose Primary Hepatitis B Vaccination.

    Science.gov (United States)

    Afzal, Muhammad Faheem; Sultan, Muhammad Ashraf; Saleemi, Ahmad Imran

    2016-01-01

    Diseases caused by Hepatitis B virus (HBV) have a worldwide distribution. Pakistan adopted the recommendations of World Health Organization (WHO) for routine universal infant vaccination against hepatitis B in 2002, currently being administered at 6, 10, and 14 weeks of age in a combination vaccine. This study was conducted to determine the immune response & anamnestic immune response in children, 9 months-10 years of age, after a 3dose primary Hepatitis B vaccination. This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/Mayo Hospital, Lahore, Pakistan, from January to June, 2014. A total of 200 children of either sex between the ages of 9 months to 10 years, documented to have received 3 doses of hepatitis B vaccines according to Expanded Program of Immunization (6,10,14 weeks) schedule in infancy, were recruited by consecutive sampling. The level of serum antiHBsAb by ELIZA was measured. Children with antiHBs titers ≥10 mIU/mL were considered to be immune. Those with anti HBsAb levels immune response was measured. Data was analysed using SPSS 17 to determine the relation between time interval since last vaccination and antibody titer. Chi square test was applied. Of the 200 children, protective antibody response was found in 58%. Median serological response was 18.60 (range 2.82 - 65.15). Antibody levels were found to have a statistically significant ( pvalue 0.019) negative correlation with the time since last administration of vaccine. A booster dose of Hepatitis B vacci ne was administered to all nonresponders, with each registering a statistically significant (pvalue 0.00) anamnestic response. The vaccination schedule with short dosage interval was unable to provide protection to 42% of the study population. Introduction of birth dose of Hepatitis B vaccine to the existing schedule is recommended.

  20. Primary immunodeficiency diseases: dissectors of the immune system.

    Science.gov (United States)

    Buckley, Rebecca H

    2002-07-01

    The past 50 years have seen enormous progress in this field. An unknown concept until 1952, there are now more than 100 different primary immunodeficiency syndromes in the world's literature. Each novel syndrome has shed new insight into the workings of the immune system, dissecting its multiple parts into unique functioning components. This has been especially true over the past decade, as the molecular bases of approximately 40 of these diseases have been identified in rapid succession. Advances in the treatment of these diseases have also been impressive. Antibody replacement has been improved greatly by the development of human immunoglobulin preparations that can be safely administered by the intravenous route, and cytokine and humanized anticytokine therapies are now possible through recombinant technologies. The ability to achieve life-saving immune reconstitution of patients with lethal severe combined immunodeficiency by administering rigorously T-cell-depleted allogeneic related haploidentical bone marrow stem cells has extended this option to virtually all such infants, if diagnosed before untreatable infections develop. Finally, the past 3 years have witnessed the first truly successful gene therapy. The impressive results in X-linked severe combined immunodeficiency offer hope that this approach can be extended to many more diseases in the future.

  1. Gene Therapy for the Treatment of Primary Immune Deficiencies.

    Science.gov (United States)

    Kuo, Caroline Y; Kohn, Donald B

    2016-05-01

    The use of gene therapy in the treatment of primary immune deficiencies (PID) has advanced significantly in the last decade. Clinical trials for X-linked severe combined immunodeficiency, adenosine deaminase deficiency (ADA), chronic granulomatous disease, and Wiskott-Aldrich syndrome have demonstrated that gene transfer into hematopoietic stem cells and autologous transplant can result in clinical improvement and is curative for many patients. Unfortunately, early clinical trials were complicated by vector-related insertional mutagenic events for several diseases with the exception of ADA-deficiency SCID. These results prompted the current wave of clinical trials for primary immunodeficiency using alternative retro- or lenti-viral vector constructs that are self-inactivating, and they have shown clinical efficacy without leukemic events thus far. The field of gene therapy continues to progress, with improvements in viral vector profiles, stem cell culturing techniques, and site-specific genome editing platforms. The future of gene therapy is promising, and we are quickly moving towards a time when it will be a standard cellular therapy for many forms of PID.

  2. Perception of Childhood Immunization among Mothers of Under ...

    African Journals Online (AJOL)

    This work is distributed under the terms of the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 59. Perception of. Childhood .... these successes, immunization is an unfinished agenda. An estimated 19.3 million ...

  3. Immune response and anamnestic immune response in children after a 3-dose primary hepatitis b vaccination

    International Nuclear Information System (INIS)

    Afzal, M.F.; Sultan, M.A.; Saleemi, A.I.

    2017-01-01

    Diseases caused by Hepatitis B virus (HBV) have a worldwide distribution. Pakistan adopted the recommendations of World Health Organization (WHO) for routine universal infant vaccination against hepatitis B in 2002, currently being administered at 6, 10, and 14 weeks of age in a combination vaccine. This study was conducted to determine the immune response and anamnestic immune response in children, 9 months-10 years of age, after a 3-dose primary Hepatitis B vaccination. Methods: This cross sectional study was conducted in the Department of Paediatrics, King Edward Medical University/Mayo Hospital, Lahore, Pakistan, from January to June, 2014. A total of 200 children of either sex between the ages of 9 months to 10 years, docu mented to have received 3 doses of hepatitis B vaccines according to Expanded Program of Immunization (6,10,14 weeks) schedule in infancy, were recruited by consecutive sampling. The level of serum anti-HBsAb by ELIZA was measured. Children with anti-HBs titers =10 mIU/mL were considered to be immune. Those with anti-HBsAb levels <10 mIU/mL were offered a booster dose of infant recombinant hepatitis B vaccine. The second serum sample was obtained 21-28 days following the administration of the booster dose and the anamnestic immune response was measured. Data was analysed using SPSS 17 to determine the relation between time interval since last vaccination and antibody titer. Chi square test was applied. Results: Of the 200 children, protective antibody response was found in 58 percent. Median serological response was 18.60 (range 2.82-65.15). Antibody levels were found to have a statistically significant (p-value 0.019) negative correlation with the time since last administration of vaccine. A booster dose of Hepatitis B vaccine was administered to all non-responders, with each registering a statistically significant (p-value 0.00) anamnestic response. Conclusion: The vaccination schedule with short dosage interval was unable to provide

  4. Adverse events following immunization in patients with primary immunodeficiencies.

    Science.gov (United States)

    Sarmiento, Juan David; Villada, Fabio; Orrego, Julio Cesar; Franco, Jose Luis; Trujillo-Vargas, Claudia M

    2016-03-18

    Adverse events following immunization (AEFI) requires special consideration in patients with primary immunodeficiency diseases (PID) because they may represent a "red flag" for the initial diagnosis and may cause disease complications. Therefore, the definition of appropriate vaccination schemes is a major issue in PID. The aim of this study is to describe the AEFI in a cohort of PID patients. Medical records from 379 PID patients were included. AEFI severity was classified according to the WHO 1999 guidelines. Causality was assessed using the Clinical Immunization Safety Assessment (CISA) 2009 criteria. Evidence of AEFI was found in 26 medical records and represented a total of 29 reactions. Most of the AEFI were observed in patients with idiopathic hypogammaglobulinemia (IHG), chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID), representing 10, 4 and 4 cases, respectively. A total of 21 reactions were associated with replicative vaccines, 7 of which were serious cases related to Bacille Calmette-Guérin (BCG). BCG was also the vaccine more often associated with definitive AEFI in PID. In addition to BCG-related complications, seizures were the most serious AEFI among PID patients. Our study included a large cohort of PID patients and confirmed an increased risk of serious AEFI in these populations. The design and implementation of neonatal screening strategies for the early detection of congenital lymphopenias and other PID are urgently needed to avoid serious complications of the BCG vaccine usually applied immediately after birth. Our findings also support the use of the acellular pertussis vaccine to minimize the appearance of seizures in PID patients vaccinated with diphtheria, pertussis and tetanus (DPT). Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Diagnostic Tools for Inborn Errors of Human Immunity (Primary Immunodeficiencies and Immune Dysregulatory Diseases).

    Science.gov (United States)

    Richardson, Annely M; Moyer, Ann M; Hasadsri, Linda; Abraham, Roshini S

    2018-02-22

    The purpose of this review is to provide an overview of diagnostic testing in primary immunodeficiency and immune dysregulatory disorders (PIDDs), particularly focusing on flow cytometry and genetic techniques, utilizing specific examples of PIDDs. Flow cytometry remains a vital tool in the diagnosis and monitoring of immunological diseases. Its utility ranges from cellular analysis and specific protein quantitation to functional assays and signaling pathway analysis. Mass cytometry combines flow cytometry and mass spectrometry to dramatically increase the throughput of multivariate single-cell analysis. Next-generation sequencing in combination with other molecular techniques and processing algorithms has become more widely available and identified the diverse and heterogeneous genetic underpinnings of these disorders. As the spectrum of disease is further clarified by increasing immunological, genetic, and epigenetic knowledge, the careful application of these diagnostic tools and bioinformatics will assist not only in our understanding of these complex disorders, but also enable the implementation of personalized therapeutic approaches for disease management.

  6. Primary immune deficiency disorders presenting as autoimmune diseases: IPEX and APECED.

    Science.gov (United States)

    Moraes-Vasconcelos, D; Costa-Carvalho, B T; Torgerson, T R; Ochs, H D

    2008-05-01

    Several primary immune deficiency disorders are associated with autoimmunity and malignancy, suggesting a state of immune dysregulation. The concept of immune dysregulation as a direct cause of autoimmunity in primary immune deficiency disorders (PIDDs) has been strengthened by the recent discovery of distinct clinical entities linked to single-gene defects resulting in multiple autoimmune phenomena including immune dysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome, and autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED) syndrome. Reviewing recent advances in our understanding of the small subgroup of PIDD patients with defined causes for autoimmunity may lead to the development of more effective treatment strategies for idiopathic human autoimmune diseases.

  7. Cell-mediated immunity in patients with carcinoma under immunotheraphy

    International Nuclear Information System (INIS)

    Almeida, C.E.

    1985-01-01

    'In vivo' and 'in vitro' cellular immunity is evaluated in 32 patients with carcinoma under immunotheraphy with subcutaneous or endovenous glucan, transfer factor and levamisole. The immunotheraphy is done relatively by intradermal tests with common antigens, by sensitization with dinitrochlorinebenzene and lymphocytes culture from whole blood. The levels of blood serum of human T lymphotocyte soluble receptor for sheep erythrocytes are detected. (M.A.C.) [pt

  8. Transcriptomic analyses of primary astrocytes under TNFα treatment

    Directory of Open Access Journals (Sweden)

    Cindy Birck

    2016-03-01

    Full Text Available Astrocytes, the most abundant glial cell population in the central nervous system, have important functional roles in the brain as blood brain barrier maintenance, synaptic transmission or intercellular communications [1,2]. Numerous studies suggested that astrocytes exhibit a functional and morphological high degree of plasticity. For example, following any brain injury, astrocytes become reactive and hypertrophic. This phenomenon, also called reactive gliosis, is characterized by a set of progressive gene expression and cellular changes [3]. Interestingly, in this context, astrocytes can re-acquire neurogenic properties. It has been shown that astrocytes can undergo dedifferentiation upon injury and inflammation, and may re-acquire the potentiality of neural progenitors [4,5,6,7].To assess the effect of inflammation on astrocytes, primary mouse astrocytes were treated with tumor necrosis factor α (TNFα, one of the main pro-inflammatory cytokines. The strength of this study is that pure primary astrocytes were used. As microglia are highly reactive immune cells, we used a magnetic cell sorting separation (MACS method to further obtain highly pure astrocyte cultures devoid of microglia.Here, we provide details of the microarray data, which have been deposited in the Gene Expression Omnibus (GEO under the series accession number GSE73022. The analysis and interpretation of these data are included in Gabel et al. (2015. Analysis of gene expression indicated that the NFκB pathway-associated genes were induced after a TNFα treatment. We have shown that primary astrocytes devoid of microglia can respond to a TNFα treatment with the re-expression of genes implicated in the glial cell development. Keywords: Primary astrocytes, Inflammation, Microarrays, Gene expression

  9. The quality of immunization data from routine primary health care reports

    DEFF Research Database (Denmark)

    Onta, S R; Sabroe, S; Hansen, E H

    1998-01-01

    different vaccines during one year was obtained from three sources: 1) the Immunization REgister of three Primary Health Care Service Outlets (PHCSOs) where each immunized child is recorded; 2) monthly PHC Reports, which are based on the Immunization Register; 3) monthly DHO Reports, which are based......Reported high immunization coverage achieved in Nepal over the last ten years is expected to reduce child mortality in the country. The present study, carried out in hill district in mid-west Nepal, aimed to assess the quality of immunization data in Nepal. The number of children who received...

  10. International consensus report on the investigation and management of primary immune thrombocytopenia

    NARCIS (Netherlands)

    Provan, Drew; Stasi, Roberto; Newland, Adrian C.; Blanchette, Victor S.; Bolton-Maggs, Paula; Bussel, James B.; Chong, Beng H.; Cines, Douglas B.; Gernsheimer, Terry B.; Godeau, Bertrand; Grainger, John; Greer, Ian; Hunt, Beverley J.; Imbach, Paul A.; Lyons, Gordon; McMillan, Robert; Rodeghiero, Francesco; Sanz, Miguel A.; Tarantino, Michael; Watson, Shirley; Young, Joan; Kuter, David J.

    2010-01-01

    Previously published guidelines for the diagnosis and management of primary immune thrombocytopenia (ITP) require updating largely due to the introduction of new classes of therapeutic agents, and a greater understanding of the disease pathophysiology. However, treatment-related decisions still

  11. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs.

    Science.gov (United States)

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A; Thörn, Karolina; Cairns, Tina M; Wegmann, Frank; Sattentau, Quentin J; Eisenberg, Roselyn J; Cohen, Gary H; Harandi, Ali M

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes.

  12. Nasal Immunization Confers High Avidity Neutralizing Antibody Response and Immunity to Primary and Recurrent Genital Herpes in Guinea Pigs

    Science.gov (United States)

    Persson, Josefine; Zhang, Yuan; Olafsdottir, Thorunn A.; Thörn, Karolina; Cairns, Tina M.; Wegmann, Frank; Sattentau, Quentin J.; Eisenberg, Roselyn J.; Cohen, Gary H.; Harandi, Ali M.

    2016-01-01

    Genital herpes is one of the most prevalent sexually transmitted infections in both the developing and developed world. Following infection, individuals experience life-long latency associated with sporadic ulcerative outbreaks. Despite many efforts, no vaccine has yet been licensed for human use. Herein, we demonstrated that nasal immunization with an adjuvanted HSV-2 gD envelope protein mounts significant protection to primary infection as well as the establishment of latency and recurrent genital herpes in guinea pigs. Nasal immunization was shown to elicit specific T cell proliferative and IFN-γ responses as well as systemic and vaginal gD-specific IgG antibody (Ab) responses. Furthermore, systemic IgG Abs displayed potent HSV-2 neutralizing properties and high avidity. By employing a competitive surface plasmon resonance (SPR) analysis combined with a battery of known gD-specific neutralizing monoclonal Abs (MAbs), we showed that nasal immunization generated IgG Abs directed to two major discontinuous neutralizing epitopes of gD. These results highlight the potential of nasal immunization with an adjuvanted HSV-2 envelope protein for induction of protective immunity to primary and recurrent genital herpes. PMID:28082979

  13. Tryptophan catabolism and immune activation in primary and chronic HIV infection

    DEFF Research Database (Denmark)

    Gelpi, Marco; Hartling, Hans J; Ueland, Per Magne

    2017-01-01

    BACKGROUND: Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. We hypothesized that early cART initiation results in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR prior to cART is a predictor of the magnitude...... of subsequent reduction in immune activation. METHODS: Prospective study including 57 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/μL, N = 24), late presenters (... follow-up was found after early initiation of cART. KTR in primary HIV infection and early presenters was positively associated with immune activation. Importantly, KTR in primary HIV infection predicted the magnitude of subsequent reduction in immune activation. Thus, a beneficial effect of early c...

  14. Primary Healthcare Spending : Striving for Equity under Fiscal ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Primary Healthcare Spending : Striving for Equity under Fiscal Federalism. Couverture du livre Primary Healthcare Spending: Striving for Equity under Fiscal Federalism. Auteur(s) : Okore Apia Okorafor. Maison(s) d'édition : UCT Press, CRDI. 1 avril 2010. ISBN : 9781919895215. 200 pages. e-ISBN : 9781552504895.

  15. Primary pump vibration under accident conditions

    International Nuclear Information System (INIS)

    Guthrie, B.M.; Currie, T.C.

    1984-06-01

    This report presents the results of an international survey on the subject of vibration in nuclear primary coolant pumps due to two-phase flow, accident conditions. The literature search also revealed few Canadian references other than those of Ontario Hydro. Ontario Hydro's work has been extensive. Confidence in the mechanical integrity of the pumpsets is good, given the extent of the testing. However, conclusions with respect to piping integrity and thermal-hydraulic performance are difficult to determine due to the inexact geometry of the piping and the difficulties in estimating fluid conditions at the pump. The tests help to understand the phenomena and provide background information for analysis, but should be applied with caution to plant analyses. Much of the discussion in the report relates to pump head instability. This is perceived to be the most important flow regime causing vibration, as attested by the emphasis of the reviewed literature. A method for quantitative assessment of the forcing functions acting on the pump-piping system due to void generation and collapse is recommended. A relatively fundamental analytical approach is proposed, supplemented by reduced scale testing in the latter stages. 151 refs

  16. Primary immune system responders to nucleus pulposus cells: evidence for immune response in disc herniation

    Directory of Open Access Journals (Sweden)

    K Murai

    2010-01-01

    Full Text Available Although intervertebral disc herniation and associated sciatica is a common disease, its molecular pathogenesis is not well understood. Immune responses are thought to be involved. This study provides direct evidence that even non-degenerated nucleus pulposus (NP cells elicit immune responses. An in vitro colony forming inhibition assay demonstrated the suppressive effects of autologous spleen cells on NP cells and an in vitro cytotoxicity assay showed the positive cytotoxic effects of natural killer (NK cells and macrophages on NP cells. Non-degenerated rat NP tissues transplanted into wild type rats and immune-deficient mice demonstrated a significantly higher NP cell survival rate in immune-deficient mice. Immunohistochemical staining showed the presence of macrophages and NK cells in the transplanted NP tissues. These results suggest that even non-degenerated autologous NP cells are recognized by macrophages and NK cells, which may have an immunological function in the early phase of disc herniation. These findings contribute to understanding resorption and the inflammatory reaction to disc herniation.

  17. Vaccination Timeliness in Children Under India's Universal Immunization Program.

    Science.gov (United States)

    Shrivastwa, Nijika; Gillespie, Brenda W; Lepkowski, James M; Boulton, Matthew L

    2016-09-01

    India has the highest number of deaths among children younger than 5 years of age globally; the majority are from vaccine preventable diseases. Untimely vaccination unnecessarily prolongs susceptibility to disease and contributes to the burden of childhood morbidity and mortality, yet there is scarce literature on vaccination delays. The aim of this study is to characterize the timeliness of childhood vaccinations administered under India's routine immunization program using a novel application of an existing statistical methodology. This study utilized the district level household and facility survey data, 2008 from India using vaccination data from children with and without immunization cards. Turnbull estimator of the cumulative distribution function was used to estimate the probability of vaccination at each age. Timeliness of Bacille Calmette-Guerin (BCG), all 3 doses of diphtheria, pertussis and tetanus vaccine (DPT) and measles-containing vaccine (MCV) were considered for this analysis. Vaccination data on 268,553 children who were 0-60 months of age were analyzed; timely administration of BCG, DPT3 and MCV occurred in 31%, 19% and 34% of children, respectively. The estimated vaccination probability plateaued for DPT and BCG around the age of 24 months, whereas MCV uptake increased another 5% after 24 months of age. The 5-year coverage of BCG, DPT3 and MCV in Indian children was 87%, 63% and 76%, respectively. Lack of timely administration of key childhood vaccines, especially DPT3 and MCV, remains a major challenge in India and likely contributes to the significant burden of vaccine preventable disease-related morbidity and mortality in children.

  18. Whole-Cell or Acellular Pertussis Primary Immunizations in Infancy Determines Adolescent Cellular Immune Profiles

    Directory of Open Access Journals (Sweden)

    Saskia van der Lee

    2018-01-01

    Full Text Available IntroductionPertussis is re-emerging worldwide, despite effective immunization programs for infants and children. Epidemiological studies show a more limited duration of protection against clinical pertussis in adolescents primed with acellular pertussis (aP vaccines during infancy than those who have been primed with whole-cell pertussis (wP vaccines. This study aimed to determine whether memory immune responses to aP, diphtheria, and tetanus vaccine antigens following booster vaccinations at 4 and 9 years of age differ between wP- versus aP-primed children.MethodsIn a cross-sectional study, blood was collected of DTwP- or diphtheria, tetanus, and aP (DTaP-primed children before, 1 month, and 2 years after the preschool DTaP booster administered at 4 years of age (n = 41–63 per time point. In a longitudinal study, blood was sampled of DTwP- or DTaP-primed children before, 1 month, and 1 year after a preadolescent Tdap booster at 9 years of age (n = 79–83 per time point. Pertussis, diphtheria, and tetanus vaccine antigen-specific IgG levels, B-cell and T-cell responses were determined.ResultsAfter the preschool booster vaccination, IgG levels were significantly higher in aP-primed as compared with wP-primed children until 6 years of age. Before the preadolescent Tdap booster vaccination, humoral and cellular immune responses were similar in aP- and wP-primed children. However, the Tdap booster vaccination induced lower vaccine antigen-specific humoral, B-cell, and T-helper 1 (Th1 cell responses resulting in significantly lower Th1/Th2 ratios in aP-primed compared with wP-primed children.ConclusionThe memory immune profiles at preadolescent age to all DTaP vaccine antigens are already determined by the wP or aP combination vaccines given in infancy, showing a beneficial Th1-dominated response after wP-priming. These immunological data corroborate epidemiological data showing that DTaP-primed adolescents are less

  19. [Screening of Serum Markers in Primary Immune Thrombocytopenia].

    Science.gov (United States)

    Zhang, Yang; Bai, Ju; Zhang, Wang-Gang; He, Ai-Li

    2016-06-01

    To analyze the serum protein fingerprints of immune thrombocytopenia (ITP) patients and healthy controls by using weak cation exchange nanometer magnetic beads and MALDI-TOF-MAS technology, to identify the proteins with different expression, to establish the diagnostic model for ITP and to explore the pathogenesis of ITP. A total of 40 patients with ITP and 40 healthy controls were selected, the serum protein components were captured by using weak cation exchange nanaometer magnetic beads, the protein spectra of all specimens were detected by Autoflex II matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI- TOF-MS) and then the data were analyzed by CliprotoolsTM2.2 software, by which the distinct protein molecules were screened to set up ITP diagnostic model. To identify the established model, the sera of 20 ITP patients and 20 healthy controls were selected to make category and cross validations. The detection of Clinprot system and the analysis of CliprotoolsTM2.2 software showed that about 55 protein peaks were detected with the range of 700 Da to 10 000 Da of molecular weight in the protein spectrum of serum speciments from 40 ITP patients and 40 healthy controls. Compared with healthy controls, 19 protein expression peaks with statistically significant difference were found in ITP patients (P Neural Network Algorithm (SNN) was established through 10 MS peaks with strongest capability in ITP group and control group automatically distinguished by software, and it is expected that the sensitivity of model group reached to 100%, and the specificity to 100%. The category validation showed that this diagnostic model correctly identificed all 20 ITP patients and 20 healthy controls, and in cross validation, the model sensitivity was 100% and the specificity was 100%. The ITP SNN model ertablished by using ChinProt System with high flax and good repetition is composed of 10 protein peaks with significant difference, this model can

  20. Dapsone for primary immune thrombocytopenia in adults and children: an evidence-based review.

    Science.gov (United States)

    Rodrigo, C; Gooneratne, L

    2013-11-01

    Primary immune thrombocytopenia is a potentially life-threatening condition. Approximately two-thirds of adult patients do not have a sustained response to steroids (first-line therapy). For these patients, a number of other treatment options exist, such as rituximab, splenectomy, immunosuppressants, and thrombopoietin receptor agonists, but they are costly and have side effects. Dapsone is an inexpensive drug with a well-established safety profile. Unfortunately, this treatment option has not been explored adequately. This review is aimed at analyzing the currently available evidence for the use of dapsone as second-line or third-line therapy in primary immune thrombocytopenia. © 2013 International Society on Thrombosis and Haemostasis.

  1. Primary cardiac lymphoma in a patient with acquired immune deficiency syndrome

    International Nuclear Information System (INIS)

    Constantino, A.; West, T.E.; Gupta, M.; Loghmanee, F.

    1987-01-01

    A 34-year-old male prisoner with a history of intravenous drug abuse presented with fever, lymphadenopathy, weight loss, and recent onset of congestive heart failure. Serologic testing was positive for antibodies to human immune deficiency virus. There was intense myocardial uptake of gallium. Autopsy showed a primary immunoblastic lymphoma involving only the myocardium. While primary cardiac lymphoma is an extremely rare condition, the incidence may be higher in patients with acquired immune deficiency syndrome (AIDS) and should be suspected in cases with atypical cardiomyopathy

  2. Comparison of immune microenvironments between primary tumors and brain metastases in patients with breast cancer.

    Science.gov (United States)

    Ogiya, Rin; Niikura, Naoki; Kumaki, Nobue; Yasojima, Hiroyuki; Iwasa, Tsutomu; Kanbayashi, Chizuko; Oshitanai, Risa; Tsuneizumi, Michiko; Watanabe, Ken-Ichi; Matsui, Akira; Fujisawa, Tomomi; Saji, Shigehira; Masuda, Norikazu; Tokuda, Yutaka; Iwata, Hiroji

    2017-11-28

    Immune checkpoint inhibitors are reported to be effective in patients with brain metastases. However, detailed characteristics of the brain metastasis immune microenvironment remain unexplored. The median tumor-infiltrating lymphocyte (TIL) category in brain metastases was 5% (1-70%). In 46 pair-matched samples, the percentages of TILs were significantly higher in primary breast tumors than in brain metastases (paired t-test, P L1, PD-L2, and HLA class I was also performed. There are significantly fewer TILs in brain metastases than in primary breast tumors.

  3. Viral immune evasion strategies and the underlying cell biology.

    Science.gov (United States)

    Lorenzo, M E; Ploegh, H L; Tirabassi, R S

    2001-02-01

    Evasion of the immune system by viruses is a well-studied field. It remains a challenge to understand how these viral tactics affect pathogenesis and the viral lifecycle. At the same time, the study of viral proteins involved in immune evasion has helped us to better understand a number of cellular processes at the molecular level. Here we review recent data on different viral tactics for immune evasion and highlight what these viral interventions might teach us about cell biology. Copyright 2001 Academic Press.

  4. [Factors associated with influenza immunization in primary care health workers].

    Science.gov (United States)

    Montserrat-Capdevila, Josep; Godoy, Pere; Marsal, Josep Ramon; Barbé-Illa, Ferran

    2015-01-01

    To identify the influenza vaccination coverage in healthcare workers in primary care and to determine the factors associated with vaccination (2013-2014 season). A cross-sectional study was carried out among 287 healthcare workers who completed a questionnaire that included questions about knowledge, beliefs and attitudes to influenza and vaccination. We estimated the vaccine coverage and identified the variables associated with vaccination of healthcare workers by using non-conditional logistic regression models. The participation rate was 47.2%. Vaccination coverage was 60.3% and was higher in workers older than 55 years, women and pediatricians. The factors associated with healthcare worker vaccination were the perception that vaccination confers protection (aOR: 11.1; 95%CI: 3.41-35.9) and the perception that it is effective (aOR: 7.5; 95%CI: 0.9-59.3). No association was found between receiving the vaccine and knowledge of influenza or vaccination. However, an association was found with prescribing vaccination to pregnant women, to persons older than 65 years, and to immunosuppressed individuals. Strategies should be designed to increase coverage, based on changing negative attitudes of healthcare workers to vaccination. Copyright © 2014 SESPAS. Published by Elsevier Espana. All rights reserved.

  5. Exercise Improves Immune Function, Antidepressive Response, and Sleep Quality in Patients with Chronic Primary Insomnia

    OpenAIRE

    Passos, Giselle Soares; Poyares, Dalva; Santana, Marcos Gonçalves; Teixeira, Alexandre Abílio de Souza; Lira, Fábio Santos; Youngstedt, Shawn D.; dos Santos, Ronaldo Vagner Thomatieli; Tufik, Sergio; de Mello, Marco Túlio

    2014-01-01

    The aim of this study was to evaluate the effects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 +/- 9 years) with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symp...

  6. Factors of Innate and Adaptive Local Immunity in Children with Primary Deficiencies of Antibody Formation

    Directory of Open Access Journals (Sweden)

    L.I. Chernyshova

    2013-10-01

    Full Text Available In 40 children with various types of primary immunodeficiencies (PID of antibody formation we examined factors of local immunity in saliva. It is found that in the saliva of children with PID of antibody formation in comparison with immunocompetent children the concentration of factors of adaptive immunity is significantly reduced. Lack of adaptive immunity in the PID of antibody formation to some extent is compensated by increased concentrations of innate immune factors on the mucous membranes — the free Sc, as well as lactoferrin in selective immunodeficiency of IgA. At PID of antibody formation we observed increased TNF-α level in the saliva, which may indicate the persistence of local inflammation on the membranes of the respiratory tract.

  7. Treatment of presumptive primary immune-mediated thrombocytopenia with mycophenolate mofetil versus cyclosporine in dogs.

    Science.gov (United States)

    Cummings, F O; Rizzo, S A

    2017-02-01

    The objective of this study was to compare hospitalisation duration, survival times, adverse events and cost of therapy in dogs with presumptive primary immune-mediated thrombocytopenia undergoing therapy with mycophenolate mofetil and corticosteroids versus cyclosporine and corticosteroids. A retrospective study of medical case records of dogs with presumed primary immune-mediated thrombocytopenia was conducted. Data collected included signalment, presenting complaints, haematologic and biochemical profiles, vector-borne disease testing, thoracic and abdominal radiographs, abdominal ultrasound, medications administered, duration of hospitalisation, 30- and 60-day survival, adverse events and cost of therapy. Variables were compared between dogs treated solely with mycophenolate mofetil and corticosteroids or cyclosporine and corticosteroids. A total of 55 dogs with primary immune-mediated thrombocytopenia were identified. Eighteen were excluded because multiple immunosuppressive medications were used during treatment. Hospitalisation times, 30-day survival and 60-day survival times were similar between both groups. Dogs in the mycophenolate mofetil/corticosteroid group experienced fewer adverse events than the cyclosporine/corticosteroid group. Therapy with mycophenolate mofetil was less expensive than that with cyclosporine. These results suggest that using the combination of mycophenolate mofetil and corticosteroids appears to be as effective as cyclosporine and corticosteroids in the treatment of presumed primary immune-mediated thrombocytopenia in dogs. Adverse events were less common and cost of therapy was lower in the mycophenolate mofetil group. Additional larger prospective, controlled, double-masked, outcome-based, multi-institutional studies are required to substantiate these preliminary findings. © 2017 British Small Animal Veterinary Association.

  8. Twenty-year mortality of adult patients with primary immune thrombocytopenia

    DEFF Research Database (Denmark)

    Frederiksen, Henrik; Maegbaek, Merete Lund; Nørgaard, Mette

    2014-01-01

    Studies have reported a 1·3- to 2·2-fold higher mortality rate among patients with primary immune thrombocytopenia (ITP) compared to the general population. However, long-term mortality estimates as well as cause-specific mortality data are sparse. In our population-based cohort of adult patients...

  9. To Give or Not to Give: Approaches to Early Childhood Immunization Delivery in Oregon Rural Primary Care Practices

    Science.gov (United States)

    Fagnan, Lyle J.; Shipman, Scott A.; Gaudino, James A.; Mahler, Jo; Sussman, Andrew L.; Holub, Jennifer

    2011-01-01

    Context: Little is known about rural clinicians' perspectives regarding early childhood immunization delivery, their adherence to recommended best immunization practices, or the specific barriers they confront. Purpose: To examine immunization practices, beliefs, and barriers among rural primary care clinicians for children in Oregon and compare…

  10. Tryptophan catabolism and immune activation in primary and chronic HIV infection.

    Science.gov (United States)

    Gelpi, Marco; Hartling, Hans J; Ueland, Per M; Ullum, Henrik; Trøseid, Marius; Nielsen, Susanne D

    2017-05-16

    Kynurenine/Tryptophan ratio (KTR) is increased in HIV infection, and linked to immune activation. We hypothesized that early cART initiation results in lower KTR compared to late initiation. Furthermore, we hypothesized that KTR prior to cART is a predictor of the magnitude of subsequent reduction in immune activation. Prospective study including 57 HIV-infected individuals (primary HIV infection (N = 14), early presenters (>350 CD4+ T cells/μL, N = 24), late presenters (tryptophan were analysed by liquid chromatography-tandem mass spectrometry. Total CD4+ and CD8+ T cells were determined and proportion of activated CD38 + HLA-DR+ Tcells was measured using flow cytometry at baseline and after 6 and 12 months of cART. At baseline, primary HIV infection had higher KTR than early presenters. However, similar KTR in primary HIV infection and early presenters was found after cART initiation, while late presenters had higher KTR at all time points. In primary HIV infection and early presenters, KTR was positively associated with proportion of activated cells at baseline. Furthermore, in early presenters the KTR at baseline was associated with proportion of activated cells after 6 and 12 months. Interestingly, in primary HIV infection the KTR at baseline was positively associated with reduction in proportion of CD8 + CD38 + HLA-DR T cells after 6 and 12 months. Lower kynurenine/tryptophan ratio during follow-up was found after early initiation of cART. KTR in primary HIV infection and early presenters was positively associated with immune activation. Importantly, KTR in primary HIV infection predicted the magnitude of subsequent reduction in immune activation. Thus, a beneficial effect of early cART on KTR was suggested.

  11. Kinetics of antibody responses after primary immunization with meningococcal serogroup C conjugate vaccine or secondary immunization with either conjugate or polysaccharide vaccine in adults

    NARCIS (Netherlands)

    de Voer, Richarda M.; van der Klis, Fiona R. M.; Engels, Carla W. A. M.; Schepp, Rutger M.; van de Kassteele, Jan; Sanders, Elisabeth A. M.; Rijkers, Ger T.; Berbers, Guy A. M.

    2009-01-01

    In the Netherlands the meningococcal serogroup C conjugate (MenCC) vaccine is administered as a single dose at 14 months. We evaluated the kinetics of isotype-specific antibodies in adults (n = 21) after primary immunization with MenCC or secondary immunization with MenCC or plain MenC

  12. Perception of Childhood Immunization among Mothers of Under ...

    African Journals Online (AJOL)

    Chain and Logistics systems are aging and often insufficient to accommodate the new vaccines. UNICEF, through ... of better cold chain and supply logistic systems and promoting national ownership for immunization6 ... clearance was obtained from the management of St. Charles Borromeo Hospital and informed consent.

  13. Permanence of suppression of the primary immune response in rainbow trout, Salmo gairdneri, sublethally exposed to tritiated water during embryognesis

    International Nuclear Information System (INIS)

    Strand, J.A.; Fujihara, M.P.; Poston, T.M.; Abernethy, C.S.

    1982-01-01

    Previous experiments demonstrated that antibody synthesis in response to a challenge from the bacterium, Flexibacter columnaris, was significantly suppressed in juvenile (5 month) rainbow trout following exposure to tritium at doses as low as 4.0 rads when administered during the first 20 days of embryogenesis. In continuing studies, a secondary challenge to columnaris cells delivered to yearling (17 month) trout was used to test the hypothesis that early embryonic exposure to tritium irradiation (0, 0.04, 0.4, 4.0, and 40.0 rads) resulted in permanent injury to the primary immune process. Results indicated that under the prescribed experimental conditions, suppression of the primary immune response was permanent; that is, the degree of injury in yearling fish (17 months) equaled or exceeded that found in juvenile fish (5 months). At levels in the range of the maximum permissible concentration (MPC), tritium produced measurable, dose dependent, and irreversible suppression of immune capacity in affected fish. The threshold-free and exponential nature of the dose-response curve suggests extrapolation of effects to even lower exposures. (author)

  14. Vaginal immunization to elicit primary T-cell activation and dissemination.

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    Elena Pettini

    Full Text Available Primary T-cell activation at mucosal sites is of utmost importance for the development of vaccination strategies. T-cell priming after vaginal immunization, with ovalbumin and CpG oligodeoxynucleotide adjuvant as model vaccine formulation, was studied in vivo in hormone-synchronized mice and compared to the one induced by the nasal route. Twenty-four hours after both vaginal or nasal immunization, antigen-loaded dendritic cells were detected within the respective draining lymph nodes. Vaginal immunization elicited a strong recruitment of antigen-specific CD4(+ T cells into draining lymph nodes that was more rapid than the one observed following nasal immunization. T-cell clonal expansion was first detected in iliac lymph nodes, draining the genital tract, and proliferated T cells disseminated towards distal lymph nodes and spleen similarly to what observed following nasal immunization. T cells were indeed activated by the antigen encounter and acquired homing molecules essential to disseminate towards distal lymphoid organs as confirmed by the modulation of CD45RB, CD69, CD44 and CD62L marker expression. A multi-type Galton Watson branching process, previously used for in vitro analysis of T-cell proliferation, was applied to model in vivo CFSE proliferation data in draining lymph nodes 57 hours following immunization, in order to calculate the probabilistic decision of a cell to enter in division, rest in quiescence or migrate/die. The modelling analysis indicated that the probability of a cell to proliferate was higher following vaginal than nasal immunization. All together these data show that vaginal immunization, despite the absence of an organized mucosal associated inductive site in the genital tract, is very efficient in priming antigen-specific CD4(+ T cells and inducing their dissemination from draining lymph nodes towards distal lymphoid organs.

  15. A microculture method for the generation of primary immune responses in vitro.

    Science.gov (United States)

    Pike, B L

    1975-11-01

    A microculture method for the generation and study of the primary immune response of murine spleen cells to defined antigens in vitro is described. Many of the variable parameters which occur in culture systems have been studied in an attempt to define the optimal culture conditions for this system. Cultures of 10(6) CBA spleen cells consistently produced an immune response of 300-600 hapten-specific plaque-forming cells after 3 days of incubation with the T cell-independent antigens DNP-POL and NIP-POL. Cultures were set up in Microtest II tissue culture plates in a volume of 0.2 ml of medium containing 10(-4) M 2-mercaptoethanol. The system described has the advantages of being highly efficient and reproducible and utilises small amounts of cells, medium and antigen. It provides a simple, economic and reliable approach for the systematic study of the immune response in vitro.

  16. related Factors of complete basic Immunization on children and Vaccine Management at Primary Health care and Health Post in X Subdistrict Depok city

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    Tri Afriani

    2015-01-01

    Full Text Available background:Immunization is an effective primary prevention against infectious diseases on children. The purpose of this study was to determine the related factors to the completeness of basic immunization on children and vaccine management at primary health care and posyandu in X Subdistric, Depok City. Methods:The study used a cross-sectional design with a sample of 140 mothers of children aged at least 11 months, and qualitatif study about vaccines management. Mother and child data collection using questionnaires and child health card (Kartu Menuju Sehat in December 2012–May 2013. Vaccine management data was collected at 2 primary health care and 2 posyandu with interview and observation. Data analysis was performed with Chi-square test. result:The largest percentage of mothers who have children under the age of at least 11 months of age <30 years, at least graduated from junior high school education, no work, have a low knowledge about immunization. Vaccine management in clinics and neighborhood health center for storage after use of vaccines in posyandu not be returned to the community health center, recording and reporting is not done on the book of the records so that the possibility of scattered or lost, and the person in charge of managing the vaccine instead of pharmacy personnel. Residual use of the vaccine in posyandu not directly returned to the health center. Recording the use of vaccines in posyandu not carried on the books, so it is probable scattered or lost. Manager vaccine at primary health care should a technical pharmacy in accordance with Government Regulation No. 51 of 2009 conclusion: Completeness of basic immunization of children under one years old (82,9%, incomplete biggest measles immunization (15,0%. Factors parental characteristics (age, education, occupation, knowledge and the availability of the vaccine were not significantly associated with children complete basic immunization. recommendation: Improving health

  17. Immunization

    Science.gov (United States)

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against things like measles, ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  18. To Give or Not to Give: Approaches to Early Childhood Immunization Delivery in Oregon Rural Primary Care Practices

    Science.gov (United States)

    Fagnan, Lyle J.

    2010-01-01

    Context Little is known about rural clinicians’ perspectives regarding early childhood immunization delivery, their adherence to recommended best immunization practices, or the specific barriers they confront. Purpose To examine immunization practices, beliefs, and barriers among rural primary care clinicians for children in Oregon and compare those who deliver all recommended immunizations in their practices with those who do not. Methods A mailed questionnaire sent to all physicians, nurse practitioners, and physician assistants practicing primary care in rural communities throughout Oregon. Findings While 39% of rural clinicians reported delivering all childhood immunizations in their clinic, 43% of clinicians reported that they refer patients elsewhere for some vaccinations and 18% provided no immunizations in the clinic whatsoever. Leading reasons for referral include inadequate reimbursement, parental request, and storage and stocking difficulties. Nearly a third of respondents reported that they had some level of concern about the safety of immunizations, and 14% reported that concerns about safety were a specific reason for referring. Clinicians who delivered only some of the recommended immunizations were less likely than non-referring clinicians to have adopted evidence-based best immunization practices. Conclusions This study of rural clinicians in Oregon demonstrates the prevalence of barriers to primary-care-based immunization delivery in rural regions. While some barriers may be difficult to overcome, others may be amenable to educational outreach and support. Thus, efforts to improve population immunization rates should focus on promoting immunization “best practices” and enhancing the capacity of practices to provide immunizations and assuring that any alternative means of delivering immunizations are effective. PMID:21967382

  19. Herd immunity effect of the HPV vaccination program in Australia under different assumptions regarding natural immunity against re-infection.

    Science.gov (United States)

    Korostil, Igor A; Peters, Gareth W; Law, Matthew G; Regan, David G

    2013-04-08

    Deterministic dynamic compartmental transmission models (DDCTMs) of human papillomavirus (HPV) transmission have been used in a number of studies to estimate the potential impact of HPV vaccination programs. In most cases, the models were built under the assumption that an individual who cleared HPV infection develops (life-long) natural immunity against re-infection with the same HPV type (this is known as SIR scenario). This assumption was also made by two Australian modelling studies evaluating the impact of the National HPV Vaccination Program to assist in the health-economic assessment of male vaccination. An alternative view denying natural immunity after clearance (SIS scenario) was only presented in one study, although neither scenario has been supported by strong evidence. Some recent findings, however, provide arguments in favour of SIS. We developed HPV transmission models implementing life-time (SIR), limited, and non-existent (SIS) natural immunity. For each model we estimated the herd immunity effect of the ongoing Australian HPV vaccination program and its extension to cover males. Given the Australian setting, we aimed to clarify the extent to which the choice of model structure would influence estimation of this effect. A statistically robust and efficient calibration methodology was applied to ensure credibility of our results. We observed that for non-SIR models the herd immunity effect measured in relative reductions in HPV prevalence in the unvaccinated population was much more pronounced than for the SIR model. For example, with vaccine efficacy of 95% for females and 90% for males, the reductions for HPV-16 were 3% in females and 28% in males for the SIR model, and at least 30% (females) and 60% (males) for non-SIR models. The magnitude of these differences implies that evaluations of the impact of vaccination programs using DDCTMs should incorporate several model structures until our understanding of natural immunity is improved. Copyright

  20. Humoral Immunity to Primary Smallpox Vaccination: Impact of Childhood versus Adult Immunization on Vaccinia Vector Vaccine Development in Military Populations.

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    Bonnie M Slike

    Full Text Available Modified Vaccinia virus has been shown to be a safe and immunogenic vector platform for delivery of HIV vaccines. Use of this vector is of particular importance to the military, with the implementation of a large scale smallpox vaccination campaign in 2002 in active duty and key civilian personnel in response to potential bioterrorist activities. Humoral immunity to smallpox vaccination was previously shown to be long lasting (up to 75 years and protective. However, using vaccinia-vectored vaccine delivery for other diseases on a background of anti-vector antibodies (i.e. pre-existing immunity may limit their use as a vaccine platform, especially in the military. In this pilot study, we examined the durability of vaccinia antibody responses in adult primary vaccinees in a healthy military population using a standard ELISA assay and a novel dendritic cell neutralization assay. We found binding and neutralizing antibody (NAb responses to vaccinia waned after 5-10 years in a group of 475 active duty military, born after 1972, who were vaccinated as adults with Dryvax®. These responses decreased from a geometric mean titer (GMT of 250 to baseline (30 years with a GMT of 210 (range 112-3234. This data suggests limited durability of antibody responses in adult vaccinees compared to those vaccinated in childhood and further that adult vaccinia recipients may benefit similarly from receipt of a vaccinia based vaccine as those who are vaccinia naïve. Our findings may have implications for the smallpox vaccination schedule and support the ongoing development of this promising viral vector in a military vaccination program.

  1. Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes

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    Christopher A. Aoki

    2006-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a chronic disease of the bile ducts characterized by an inflammatory infiltrate and obliterative fibrosis. The precise role of the immune system in the pathogenesis of PSC remains unknown. We used RNA microarray analysis to identify immune-related genes and pathways that are differentially expressed in PSC. Messenger RNA (mRNA from peripheral blood mononuclear cells (PBMC was isolated from both patients with PSC and age and sex matched healthy controls. Samples from 5 PSC patients and 5 controls were analyzed by microarray and based upon rigorous statistical analysis of the data, relevant genes were chosen for confirmation by RT-PCR in 10 PSC patients and 10 controls. Using unsupervised hierarchical clustering, gene expression in PSC was statistically different from our control population. Interestingly, genes within the IL-2 receptor beta, IL-6 and MAP Kinase pathways were found to be differently expressed in patients with PSC compared to controls. Further, individual genes, TNF-α induced protein 6 (TNFaip6 and membrane-spanning 4-domains, subfamily A (ms4a were found to be upregulated in PSC while similar to Mothers against decapentaplegic homolog 5 (SMAD 5 was downregulated. In conclusion, several immune-related pathways and genes were differentially expressed in PSC compared to control patients, giving further evidence that this disease is systemic and immune-mediated.

  2. Immune status during irradiation with combined chemotherapy in primary lung cancer

    International Nuclear Information System (INIS)

    Ogawa, Yasuhiro; Kimura, Shuji; Imajyo, Yosinari; Takashima, Hitoshi; Hiyoshi, Yukio

    1979-01-01

    This study was designed to determine the extent of changes in the general immune responses of patients with lung cancer receiving therapeutic irradiation with combined chemotherapy. 22 patients with primary lung cancer (stage III, UICC 1974) undergoing this therapy were employed. In vitro lymphocyte transformation test with PHA and quantitative assays of IgG, IgA and IgM were performed on blood obtained from each patient before and during therapy (at 2000 rad and 4000 rad). At these same testing intervals, skin tests with PHA and PPD were performed. During irradiation, lymphocyte transformation test was depressed to 47.1 percent (at 2000 rad) and 25.2 percent (at 4000 rad) of pretreatment baseline. A decrease in PHA skin test was noted. And the mean absolute lymphocyte count significantly falled out 60.1 percent (at 2000 rad), and 41.7 percent (at 4000 rad) of pretreatment baseline. Radiation effected no significant changes in the mean values of IgG, IgA and IgM. The responsiveness of the cell-mediated immunity in patients with lung cancer was more depressed by therapeutic irradiation with combined chemotherapy. An impaired cellular immunity may affect the clinical response and prognosis of cancer patients. It will be necessary to maintain the cellular immunity in host defense mechanisms. (author)

  3. Advances in the quantification of mitochondrial function in primary human immune cells through extracellular flux analysis.

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    Dequina Nicholas

    Full Text Available Numerous studies show that mitochondrial energy generation determines the effectiveness of immune responses. Furthermore, changes in mitochondrial function may regulate lymphocyte function in inflammatory diseases like type 2 diabetes. Analysis of lymphocyte mitochondrial function has been facilitated by introduction of 96-well format extracellular flux (XF96 analyzers, but the technology remains imperfect for analysis of human lymphocytes. Limitations in XF technology include the lack of practical protocols for analysis of archived human cells, and inadequate data analysis tools that require manual quality checks. Current analysis tools for XF outcomes are also unable to automatically assess data quality and delete untenable data from the relatively high number of biological replicates needed to power complex human cell studies. The objectives of work presented herein are to test the impact of common cellular manipulations on XF outcomes, and to develop and validate a new automated tool that objectively analyzes a virtually unlimited number of samples to quantitate mitochondrial function in immune cells. We present significant improvements on previous XF analyses of primary human cells that will be absolutely essential to test the prediction that changes in immune cell mitochondrial function and fuel sources support immune dysfunction in chronic inflammatory diseases like type 2 diabetes.

  4. Immunizations against respiratory infections in children in primary health care in poland: coverage and delays.

    Science.gov (United States)

    Miśkiewicz, K; Kuchar, E; Nitsch-Osuch, A; Preisner, K; Szenborn, L

    2015-01-01

    Pneumococcal infections, pertussis, and influenza are vaccine-preventable diseases. The aim of this study was to determine vaccine coverage and compliance with the dosage regimen among children in Poland. We performed a retrospective chart analysis of 1,356 children in a large primary healthcare establishment. The complete primary pertussis vaccination, 3 doses in the first year of life, was administered to 1,310/1,356 patients (96.6 %). The self-paid combined acellular vaccine was given in 55.2 % of children. The first dose of the pertussis vaccine was administered in a timely manner to 67.1 % of children. The self-paid pneumococcal vaccine was administered in 499/1,356 (36.8 %) children. In 46.1 % of them immunization started within the first 6 months of life; in 12.6 % aged 7-11 months, in 12.6 % aged 12-23 months, and in 28.7 % aged over 24 months. The dosage regimen was compliant in 49.2 % of patients. Only 3.5 % of patients were immunized against both pneumococci and influenza. Compliance with the Polish immunization program should be increased by reducing the number of injections and the cost of vaccines. Education is essential to facilitate simultaneous administration of vaccines during one visit and to prepare the parents for judicious decision-making when it comes to vaccinations.

  5. Local immune response to primary infection and re-infection by Clonorchis sinensis in FVB mice.

    Science.gov (United States)

    Kim, Eun-Min; Yu, Hak Sun; Jin, Yan; Choi, Min-Ho; Bae, Young Mee; Hong, Sung-Tae

    2017-08-01

    Although Clonorchis sinensis lives in the bile duct, few studies have investigated the local immune response in the liver and bile duct. To investigate the local immune response to C. sinensis, we investigated the activation and recruitment of various immune cells and cytokine levels in the liver and bile duct lymph nodes (BLN) in FVB mice after primary infection and re-infection. Male 4-week-old FVB mice were divided into 6 experimental groups: uninfected controls, primary infection lasting 1week (PI 1w), primary infection lasting 4weeks (PI 4w), praziquantel treatment after PI 4w (Tx), re-infection lasting 1week after Tx (RI 1w), and re-infection lasting 4weeks after Tx (RI 4w). Recovery rates were 80.0% and 73.0% in PI 1w and PI 4w mice, respectively, but significantly decreased during re-infection to 26.6% in RI 1w and 13.3% in RI 4w. This result suggested that the mice were resistant to re-infection. In the liver, Kupffer cells were augmented 70-fold in PI 1w mice (Psinensis-specific IgG1 and IgG2a strongly increased in RI 1w mice. Secretion of C. sinensis-specific IgE reached a plateau at 4weeks after primary infection, and remained elevated in all infected groups. In conclusion, during infection with C. sinensis, Kupffer cells likely act as antigen-presenting cells, stimulating the Th2 cytokine production system. Copyright © 2016. Published by Elsevier B.V.

  6. Under Pressure: Interactions between Commensal Microbiota and the Teleost Immune System

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    Cecelia Kelly

    2017-05-01

    Full Text Available Commensal microorganisms inhabit every mucosal surface of teleost fish. At these surfaces, microorganisms directly and indirectly shape the teleost immune system. This review provides a comprehensive overview of how the microbiota and microbiota-derived products influence both the mucosal and systemic immune system of fish. The cross talk between the microbiota and the teleost immune system shifts significantly under stress or disease scenarios rendering commensals into opportunists or pathogens. Lessons learnt from germ-free fish models as well as from oral administration of live probiotics to fish highlight the vast impact that microbiota have on immune development, antibody production, mucosal homeostasis, and resistance to stress. Future studies should dissect the specific mechanisms by which different members of the fish microbiota and the metabolites they produce interact with pathogens, with other commensals, and with the teleost immune system.

  7. Novel IFNγ homologue identified in Nile tilapia (Oreochromis niloticus) links with immune response in gills under different stimuli.

    Science.gov (United States)

    Velázquez, Janet; Acosta, Jannel; Herrera, Naylin; Morales, Antonio; González, Osmany; Herrera, Fidel; Estrada, Mario Pablo; Carpio, Yamila

    2017-12-01

    Interferon gamma (IFN-γ) has important roles in both innate and adaptive immune responses. This cytokine plays a very important role in defining Th1 immune response in all vertebrates. In the present study, we identified and isolated for the first time the gene coding for Nile tilapia (Oreochromis niloticus) IFNγ from spleen lymphocytes. The isolated tilapia IFNγ has between 24 and 62% of amino acid identity as compared to reported sequences for other teleost fishes. It has close phylogenetic relationships with IFNγ molecules belonging to the group of Perciforms and presents the typical structural characteristics of gamma interferon molecules. The tissue expression analysis showed that IFNγ is expressed constitutively in head kidney, skin, intestine, muscle and brain. Its expression was not detected in gills by conventional RT-PCR. However, under conditions of stimulation with Poly I:C and LPS, IFNγ expression was up-regulated in gills after 24 h post-stimulation. IFNγ expression was also induced in gills 24 h after Edwardsiella tarda infection suggesting its important role in immunity against intracellular bacteria. The recombinant protein produced in Escherichia coli induced Mx gene transcription in head kidney primary culture cells. These results are the first steps to characterize the role of tilapia IFNγ in the defense against pathogens in tilapia. Furthermore, the isolation of this molecule provides a new tool to characterize the cellular immune response to various stimuli in this organism. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Ensuring childhood vaccination among slums dwellers under the National Immunization Program in India - Challenges and opportunities.

    Science.gov (United States)

    Singh, Sanjeev; Sahu, Damodar; Agrawal, Ashish; Vashi, Meeta Dhaval

    2018-04-04

    Almost, one third of the world's urban population resides in slums and the number would double by 2030. Slums denotes collection of people from various communities having a meagre income and living in unhygienic conditions thus making themselves most vulnerable for outbreaks of communicable diseases. India contributes substantially to the global disease burden and under-five mortality rates i.e. 20% attributable to vaccine preventable diseases. Immunization plays a crucial role in combating high childhood mortality rates attributable to vaccine preventable diseases across the globe. This systematic review, provides insights on immunization status in slums, identifies various factors influencing it thus, exploring opportunities that may be available to improve vaccination coverage under the National Immunization Program. Taking into account the above aspects, a review of literature was undertaken in various databases that included studies published between 2006 and 2017. In India, ~33% of the urban population lives in slums with suboptimal vaccination coverage ranging from 14% to upto 90%. Few of the important causes for low coverage included socioeconomic factors such as poor community participation, lack of awareness, frequent migration, and loss of daily income. Hence, mere presence of vaccines in the National Immunization Program doesn't do the job, there is a definite unmet need to emphasize upon the importance of immunization among slums dwellers and take necessary steps. For instance, delivering immunization services at the doorstep (e.g. pulse polio program), community-based education, text messaging as reminders and incentivized immunization services are some of the opportunities that can be explored and implemented to improve immunization status in the slums. Thus, in addition to inclusion of more and more vaccines in the National Immunization Program, there is a definite need to focus on people living in high risk areas in order to improve coverage and

  9. Strain-specific protective effect of the immunity induced by live malarial sporozoites under chloroquine cover.

    Science.gov (United States)

    Wijayalath, Wathsala; Cheesman, Sandra; Tanabe, Kazuyuki; Handunnetti, Shiroma; Carter, Richard; Pathirana, Sisira

    2012-01-01

    The efficacy of a whole-sporozoite malaria vaccine would partly be determined by the strain-specificity of the protective responses against malarial sporozoites and liver-stage parasites. Evidence from previous reports were inconsistent, where some studies have shown that the protective immunity induced by irradiated or live sporozoites in rodents or humans were cross-protective and in others strain-specific. In the present work, we have studied the strain-specificity of live sporozoite-induced immunity using two genetically and immunologically different strains of Plasmodium cynomolgi, Pc746 and PcCeylon, in toque monkeys. Two groups of monkeys were immunized against live sporozoites of either the Pc746 (n = 5), or the PcCeylon (n = 4) strain, by the bites of 2-4 sporozoite-infected Anopheles tessellates mosquitoes per monkey under concurrent treatments with chloroquine and primaquine to abrogate detectable blood infections. Subsequently, a group of non-immunized monkeys (n = 4), and the two groups of immunized monkeys were challenged with a mixture of sporozoites of the two strains by the bites of 2-5 infective mosquitoes from each strain per monkey. In order to determine the strain-specificity of the protective immunity, the proportions of parasites of the two strains in the challenge infections were quantified using an allele quantification assay, Pyrosequencing™, based on a single nucleotide polymorphism (SNP) in the parasites' circumsporozoite protein gene. The Pyrosequencing™ data showed that a significant reduction of parasites of the immunizing strain in each group of strain-specifically immunized monkeys had occurred, indicating a stronger killing effect on parasites of the immunizing strain. Thus, the protective immunity developed following a single, live sporozoite/chloroquine immunization, acted specifically against the immunizing strain and was, therefore, strain-specific. As our experiment does not allow us to determine the parasite stage at

  10. The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

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    Priscila Menezes Ferri

    2016-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients.

  11. Mucosal and systemic immune responses in humans after primary and booster immunizations with orally administered invasive and noninvasive live attenuated bacteria.

    Science.gov (United States)

    Viret, J F; Favre, D; Wegmüller, B; Herzog, C; Que, J U; Cryz, S J; Lang, A B

    1999-07-01

    The mucosal and systemic immune responses after primary and booster immunizations with two attenuated live oral vaccine strains derived from a noninvasive (Vibrio cholerae) and an invasive (Salmonella typhi) enteric pathogen were comparatively evaluated. Vaccination with S. typhi Ty21a elicited antibody-secreting cell (ASC) responses specific for S. typhi O9, 12 lipopolysaccharide (LPS), as well as significant increases in levels of immunoglobulin G (IgG) and IgA antibodies to the same antigen in serum. A strong systemic CD4(+) T-helper type 1 cell-mediated immune (CMI) response was also induced. In contrast to results with Ty21a, no evidence of a CMI response was obtained after primary immunization with V. cholerae CVD 103-HgR in spite of the good immunogenicity of the vaccine. Volunteers who received a single dose of CVD 103-HgR primarily developed an IgM ASC response against whole vaccine cells and purified V. cholerae Inaba LPS, and seroconversion of serum vibriocidal antibodies occurred in four of five subjects. Serum IgG anti-cholera toxin antibody titers were of lower magnitude. For both live vaccines, the volunteers still presented significant local immunity 14 months after primary immunization, as revealed by the elevated baseline antibody titers at the time of the booster immunization and the lower ASC, serum IgG, and vibriocidal antibody responses after the booster immunization. These results suggest that local immunity may interfere with colonization of the gut by both vaccine strains at least up to 14 months after basis immunization. Interestingly, despite a low secondary ASC response, Ty21a was able to boost both humoral (anti-LPS systemic IgG and IgA) and CMI responses. Evidence of a CMI response was also observed for one of three volunteers given a cholera vaccine booster dose. The direct comparison of results with two attenuated live oral vaccine strains in human volunteers clearly showed that the capacity of the vaccine strain to colonize specific

  12. Autoradiographic study of gamma-irradiated mouse spleen during primary immune response

    International Nuclear Information System (INIS)

    Gitsov, L.G.; Kyncheva, L.S.; Burneva, V.G.; Martinova, J.Sh.; Viklichka, S.

    1978-01-01

    Study on the kinetics of the cells in the mouse spleen during the primary immune response against thymusdependent antigen after sublethal irradiation was carried out. For this purpose the animals were immunized with sheep erythrocytes one day after their irradiation with 700 r gamma rays. On the 5th day after the immunization, tritium labelled thymidine was injected three times at two hourly intervals. Mice were killed two hours after the third injection for preparation of routine histological samples and autoradiographs. Immunized, but not irradiated mice were utilized as controls. Extensive zones of lymphocyte destruction were observed in the spleen of the irradiated mice - accumulation of picnotic lymphocyte nuclei, surrounded by reticulo-histocyte elements. The number of the labelled cells and the intensity of labelled are lower than that of the germinal centres in control animal. There is no marked cell destruction in the periarteriolar zone nor labelled cells, whereas in the controls there is a considerable number of labelled blast cells. In the red pulp of the irradiated animals islands of erythroblasts were found, whereas in the controls - parallely to the erythroblast islands, there are islands of proliferating lymphocytes and plasmocytes. The decrease of lymphocyte number in irradiated mice is connected with their destruction and with the altered lymphocytopoiesis in the red pulp. It is assumed that the observed preservation of the periarteriolar lymphatic sheaths in an expression of a higher radioresistance of the T-cells as compared to the B-cells in the white pulp. This study contributes for elucidation of the irradiation immunosuppressive effect. It points out also that the post-irradiation lymphopaenia is due not only to the cell death but also to the exclusion of part of the T-lymphocytes from the circulation and their selective deposition in the thymus-dependent zones of the peripheral lymphoid organs. (A.B.)

  13. Immune Organs and Haemopoietic System Under Modelling of the Mission Factors

    Science.gov (United States)

    Sapin, M. R.; Grigoriev, A. I.; Erofeeva, L. M.; Grigorenko, D. E.; Fedorenko, B. S.

    1997-07-01

    Literary and experimental data on the character of changes in immune organs and lymphoid tissue of respiratory system and digestive system in laboratory animals during the mission factors model are given. Inhibition of reproductive function in bone marrow, thymus and spleen under irradiation of gamma-rays and accelerated carbon ions, tensity of immune response in the lymphoid structures of larynx, trachea and bronchi under the influence of acetaldehyde vapors and decrease of lymphoid tissue square on histological series in spleen and small intestine with an increase of concentration of microbial bodies in the drinking water were estimated.

  14. Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine

    Directory of Open Access Journals (Sweden)

    Danylo Sirskyj

    2016-07-01

    Full Text Available Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future.

  15. A quantitative quasispecies theory-based model of virus escape mutation under immune selection.

    Science.gov (United States)

    Woo, Hyung-June; Reifman, Jaques

    2012-08-07

    Viral infections involve a complex interplay of the immune response and escape mutation of the virus quasispecies inside a single host. Although fundamental aspects of such a balance of mutation and selection pressure have been established by the quasispecies theory decades ago, its implications have largely remained qualitative. Here, we present a quantitative approach to model the virus evolution under cytotoxic T-lymphocyte immune response. The virus quasispecies dynamics are explicitly represented by mutations in the combined sequence space of a set of epitopes within the viral genome. We stochastically simulated the growth of a viral population originating from a single wild-type founder virus and its recognition and clearance by the immune response, as well as the expansion of its genetic diversity. Applied to the immune escape of a simian immunodeficiency virus epitope, model predictions were quantitatively comparable to the experimental data. Within the model parameter space, we found two qualitatively different regimes of infectious disease pathogenesis, each representing alternative fates of the immune response: It can clear the infection in finite time or eventually be overwhelmed by viral growth and escape mutation. The latter regime exhibits the characteristic disease progression pattern of human immunodeficiency virus, while the former is bounded by maximum mutation rates that can be suppressed by the immune response. Our results demonstrate that, by explicitly representing epitope mutations and thus providing a genotype-phenotype map, the quasispecies theory can form the basis of a detailed sequence-specific model of real-world viral pathogens evolving under immune selection.

  16. Electronmicroscopic study of gamma irradiated mouse spleen during primary immune response

    International Nuclear Information System (INIS)

    Burneva, V.G.; Gitsov, L.G.; Boyadzhieva-Mikhajlova, A.; Kyncheva, L.S.; Viklichka, St.

    1978-01-01

    An electronmicroscopic study of the mouse spleen immunocompetent cells during the productive phase of the primary immune response after sublethal gamma ray irradiation is carried out. For this purpose the animals were immunized with sheep red blood cells 24 hours after irradiation and sacrified on the 5th day after immunization. The number of small lymphocytes is reduced in all zones of the spleen. Only in the periarteriolar area the lymphoid sheaths are well outlines and the ultrastructure of the cells preserved. Three types of reticulohistocytic elements, according to their radiosensitivity are observed. The most radioresistant cells are the fixed ''dark'' reticular cells which do not complete phagocytosis. The ultrastructure of their nucleus and cytoplasm is not damaged. The macrophages are also quite resistant. The ''light'' reticular cells are the most radiosensitive. The chromatine of their nuclei is dispersed. The mitochondria are imbibed, with a reduced number of cristae. The cytoplasm contains many electron light vesicles, different in size. The changes in the processes of the dendridic cells in the spleen lymph follicles are of particular interest. Compared with the control animals the processes of dendritic reticular cells are markedly reduced. The postirradiation ultrastructural changes of the spleen cells indicate that parallel with the basic factor (the death of a considerable part of the small lymphocytes, precursors of the antibody-synthetizing cells) the reduced antibody-formation is due also to the limited capacity for ''traping'' the antigen on the processes of the dendritic follicular cells and to the reduced capacity of the reticulo-histocytic cells for antigen phagocytosis. The later is determined both by the damage of a considerable part of the phagocytes (radiosensitive ''light'' reticulo-histocytic cells) and by the blocking of the functionally undamaged phagocytes from ingested debris. (K.M.)

  17. B-cell memory and primary immune deficiencies: interleukin-21 related defects.

    Science.gov (United States)

    Desjardins, Marylin; Mazer, Bruce D

    2013-12-01

    The purpose of this study is to describe recent advances in our understanding of the role of interleukin-21 (IL-21) in B-cell maturation, and how defects in IL-21 receptor (IL-21R) signalling pathways (IL-21R/γc/JAK3/STAT3) are related to primary immune deficiencies. Abnormal signalling through IL-21R/γc/JAK3/STAT3 pathway has been related to decreased specific antibody responses following vaccination, and to increased susceptibility to encapsulated bacterial infections. This is manifested in the hyper-IgE syndrome, X-linked and JAK3-related severe combined immunodeficiency (SCID) and loss-of-function mutations in the IL-21R gene. Common variable immunodeficiency is associated with impaired in-vitro development of peripheral blood mononuclear cells or purified B-cells into memory or CD38 B-cells following addition of IL-21. IL-21 is a key cytokine in development of B-cells into immunoglobulin-secreting cells. Abnormal signalling through the IL-21R/γc/JAK3/STAT3 pathway leads to defective humoral immune responses to both T-dependent and T-independent antigens and impairs the establishment of long-lasting B-cell memory. Studies involving patients with hyper-IgE syndrome demonstrated the nonredundant role of STAT3 in B-cell production of high-affinity specific antibodies, while total serum immunoglobulins could be maintained through STAT3-independent activation of AID (activation-induced cytidine-deaminase). IL-21 related defects may also be associated with reduced natural killer (NK)-cell cytotoxicity and TH17 cytokine production, indicating that abnormalities in the IL-21-IL-21R pathway have profound effects on crucial immune responses.

  18. Innate immunity drives the initiation of a murine model of primary biliary cirrhosis.

    Directory of Open Access Journals (Sweden)

    Chao-Hsuan Chang

    Full Text Available Invariant natural killer T (iNKT cells play complex roles in bridging innate and adaptive immunity by engaging with glycolipid antigens presented by CD1d. Our earlier work suggested that iNKT cells were involved in the initiation of the original loss of tolerance in primary biliary cirrhosis (PBC. To address this issue in more detail and, in particular, to focus on whether iNKT cells activated by a Th2-biasing agonist (2s,3s,4r-1-O-(α-D-galactopyranosyl-N-tetracosanoyl-2-amino-1,3,4-nonanetriol (OCH, can influence the development of PBC in a xenobiotic-induced PBC murine model. Groups of mice were treated with either OCH or, as a control, α-galactosylceramide (α-GalCer and thence serially followed for cytokine production, markers of T cell activation, liver histopathology and anti-mitochondrial antibody responses. Further, additional groups of CD1d deleted mice were similarly studied. Our data indicate that administration of OCH has a dramatic influence with exacerbation of portal inflammation and hepatic fibrosis similar to mice treated with α-GalCer. Further, iNKT cell deficient CD1d knockout mice have decreased inflammatory portal cell infiltrates and reduced anti-mitochondrial antibody responses. We submit that activation of iNKT cells can occur via overlapping and/or promiscuous pathways and highlight the critical role of innate immunity in the natural history of autoimmune cholangitis. These data have implications for humans with PBC and emphasize that therapeutic strategies must focus not only on suppressing adaptive responses, but also innate immunity.

  19. Characterisation of the primary local and systemic immune response in gnotobiotic lambs against rotavirus infection.

    Science.gov (United States)

    van Pinxteren, L A; Bruce, M G; Campbell, I; Clarke, C J; Snodgrass, D R

    1998-08-31

    This study characterised the primary immune response in gnotobiotic lambs after infection with a lamb rotavirus (RV). Lambs were infected and killed over a 7 week period together with controls. RV-ELISA and neutralising antibodies were determined in serum, nasal secretions, and intestinal scrapings. RV-antibody secreting cells (ASC) were enumerated in blood. Lymphocyte proliferations were determined in blood and gut-associated lymphoid tissues and cytokine expression was analysed in jejunal Peyer's patches (JPPs) and mesenteric lymph nodes (MLNs). Infected lambs cleared the virus by 8-9 days after infection without showing any clinical signs. The first indication of a specific immune response to RV was an increased expression of IL-4 mRNA in the JPPs in the infected group compared to the control group 3 days after infection. Rotavirus-specific IgA ASC in blood and IgA antibodies in serum and nasal secretions were detected from 7 days after infection followed at 10 days after infection by RV-specific IgG ASC and antibodies. Rotavirus-specific IgA antibodies were not detected in intestinal scrapings in the first 10 days after infection, but were detected by 52 days after infection. No RV-specific neutralising antibodies were seen in the intestine during the course of the experiment.

  20. CD8+ T cells Are Preferentially Activated during Primary Low Dose Leishmania major Infection but Are Completely Dispensable during Secondary Anti-Leishmania Immunity

    OpenAIRE

    Okwor, Ifeoma B.; Jia, Ping; Mou, Zhirong; Onyilagha, Chukwunonso; Uzonna, Jude E.

    2014-01-01

    We previously showed that CD8+ T cells are required for optimal primary immunity to low dose Leishmania major infection. However, it is not known whether immunity induced by low dose infection is durable and whether CD8+ T cells contribute to secondary immunity following recovery from low dose infection. Here, we compared primary and secondary immunity to low and high dose L. major infections and assessed the influence of infectious dose on the quality and magnitude of secondary anti-Leishman...

  1. Primary care monitoring of patients under oral anticoagulation.

    Science.gov (United States)

    Agnelo, Pedro; Alexandra, Denise; Matias, Sara

    2014-01-01

    With the advent of new oral anticoagulants that do not require regular laboratory control but are significantly more expensive, there has been renewed interest in the quality of the classic agents and the monitoring of patients taking them. We set out to analyze time in therapeutic range of patients under oral anticoagulation monitored in our health unit, to determine whether primary care monitoring is comparable to that in anticoagulation clinics. At the same time, we aimed to ascertain whether there was any association between the dosing method (unit protocol vs. computer-assisted) and the time in therapeutic range achieved.Methods We analyzed all INR values determined in our health unit during the first six months of 2012, using Excel 2007 and SPSS version 17.0, and applying the Student's t test for a level of significance of 0.05. All INR assessments during the first six months of 2012 were recorded, a total of 320 tests; mean patient age was 69.9±11.25 years, 63% male. Dose adjustments were made according to the unit protocol in 77% of cases. Atrial fibrillation was the most prevalent indication. Most values (65.3%) were within the target therapeutic range; 24.1% were subtherapeutic and 10.6% supratherapeutic. Computer-assisted dosing achieved better control than the protocol (72.5% vs. 62.9%), without statistical significance. Primary care monitoring of oral anticoagulation appears to be comparable to that in anticoagulation clinics, while affording better access and cost reductions. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  2. Effect of Recombination in the Evolutionary Dynamics of HIV under the Surveillance of Immune System

    Science.gov (United States)

    Peng, Weiqun; Yang, Wenjing; Wang, Guanyu

    2009-03-01

    Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS), which has become one of the most destructive pandemics in history. The fact that HIV virus evolves very fast plays a central role in AIDS immunopathogenesis and the difficulty we face in finding a cure or a vaccine for AIDS. A distinguishing feature of HIV is its high frequency of recombination. The effect of recombination in the HIV evolution is not clear. We establish a mathematical model of the evolutionary dynamics. This model incorporates both point mutation and recombination for genetic diversity, and employs a fitness function developed by Wang and Deem (PRL 97, 188106, 2006) that accounts for the effect of immune system. Using this model, we explore the role of recombination in the battle between the virus population and the immune system, with a special focus on the condition under which recombination helps the virus population to escape from the immune system.

  3. 75 FR 52860 - Final Airworthiness Design Standards for Acceptance Under the Primary Category Rule; Orlando...

    Science.gov (United States)

    2010-08-30

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration 14 CFR Part 21 Final Airworthiness Design Standards for Acceptance Under the Primary Category Rule; Orlando Helicopter Airways (OHA), Inc... Existence of Proposed Airworthiness Design Standards for Acceptance Under the Primary Category Rule; Orlando...

  4. Exercise Improves Immune Function, Antidepressive Response, and Sleep Quality in Patients with Chronic Primary Insomnia

    Directory of Open Access Journals (Sweden)

    Giselle Soares Passos

    2014-01-01

    Full Text Available The aim of this study was to evaluate the effects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 ± 9 years with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symptoms and plasma cortisol. Immunologic assays revealed a significant increase in plasma apolipoprotein A (140.9 ± 22 to 151.2 ± 22 mg/dL and decreases in CD4 (915.6 ± 361 to 789.6 ± 310 mm3 and CD8 (532.4 ± 259 to 435.7 ± 204 mm3. Decreases in cortisol were significantly correlated with increases in total sleep time (r=-0.51 and REM sleep (r=-0.52. In summary, long-term moderate aerobic exercise training improved sleep, reduced depression and cortisol, and promoted significant changes in immunologic variables.

  5. The Mucosal Innate Immune Response in Primary Human Papillomavirus Infection: A Pilot Study.

    Science.gov (United States)

    Gardella, Barbara; Iacobone, Anna Daniela; Musacchi, Valentina; Calvino, Isabel Giacoma; De Amici, Mara; Torre, Cristina; Bogliolo, Stefano; Spinillo, Arsenio

    2016-10-01

    The purpose of the study was to evaluate the mucosal immune response in women affected by primary human papillomavirus (HPV) infection, in comparison with HPV-negative women with no previous history of HPV. A case-control study comparing the activity of myeloperoxidase (MPO) and lactoferrin (LF) between 19 HPV-positive and 19 HPV-negative women matched for age. Plasmatic and cervicovaginal levels of polymorphonuclear neutrophils (PMN) exhibiting MPO and LF receptors were measured using cytofluorimetric analysis and expressed as mean of percentages. Cervicovaginal levels of MPO-/LF- PMN were lower among HPV-negative women, with a mean rate of 18.81% (SD, 21.38), as opposed to a mean rate of 35.56% (SD, 21.02) (P = 0.020) in HPV-positive women. A similar significant difference was not proven in plasma. The mean rates of plasmatic levels of MPO-/LF- PMN were 36.21% (SD, 16.87) and 36.93% (SD, 10.54) (P = 0.875) in cases and controls, respectively. All patients were evaluated 1 year later, and only 6 cases became negative. The presence of MPO-/LF- PMN has been considered as a marker of lower rate of apoptosis of HPV-infected cells. This could explain why HPV-positive women are less capable to deal with a primary infection.

  6. Exercise improves immune function, antidepressive response, and sleep quality in patients with chronic primary insomnia.

    Science.gov (United States)

    Passos, Giselle Soares; Poyares, Dalva; Santana, Marcos Gonçalves; Teixeira, Alexandre Abílio de Souza; Lira, Fábio Santos; Youngstedt, Shawn D; dos Santos, Ronaldo Vagner Thomatieli; Tufik, Sergio; de Mello, Marco Túlio

    2014-01-01

    The aim of this study was to evaluate the effects of moderate aerobic exercise training on sleep, depression, cortisol, and markers of immune function in patients with chronic primary insomnia. Twenty-one sedentary participants (16 women aged 44.7 ± 9 years) with chronic primary insomnia completed a 4-month intervention of moderate aerobic exercise. Compared with baseline, polysomnographic data showed improvements following exercise training. Also observed were reductions in depression symptoms and plasma cortisol. Immunologic assays revealed a significant increase in plasma apolipoprotein A (140.9 ± 22 to 151.2 ± 22 mg/dL) and decreases in CD4 (915.6 ± 361 to 789.6 ± 310 mm(3)) and CD8 (532.4 ± 259 to 435.7 ± 204 mm(3)). Decreases in cortisol were significantly correlated with increases in total sleep time (r = -0.51) and REM sleep (r = -0.52). In summary, long-term moderate aerobic exercise training improved sleep, reduced depression and cortisol, and promoted significant changes in immunologic variables.

  7. Cognitive consilience: Primate non-primary neuroanatomical circuits underlying cognition

    Directory of Open Access Journals (Sweden)

    Soren Van Hout Solari

    2011-12-01

    Full Text Available Interactions between the cerebral cortex, thalamus, and basal ganglia form the basis ofcognitive information processing in the mammalian brain. Understanding the principles ofneuroanatomical organization in these structures is critical to understanding the functions theyperform and ultimately how the human brain works. We have manually distilled and synthesizedhundreds of primate neuroanatomy facts into a single interactive visualization. The resultingpicture represents the fundamental neuroanatomical blueprint upon which cognitive functionsmust be implemented. Within this framework we hypothesize and detail 7 functional circuitscorresponding to psychological perspectives on the brain: consolidated long-term declarativememory, short-term declarative memory, working memory/information processing, behavioralmemory selection, behavioral memory output, cognitive control, and cortical information flow regulation. Each circuit is described in terms of distinguishable neuronal groups including thecerebral isocortex (9 pyramidal neuronal groups, parahippocampal gyrus and hippocampus,thalamus (4 neuronal groups, basal ganglia (7 neuronal groups, metencephalon, basal forebrainand other subcortical nuclei. We focus on neuroanatomy related to primate non-primary corticalsystems to elucidate the basis underlying the distinct homotypical cognitive architecture. To dis-play the breadth of this review, we introduce a novel method of integrating and presenting datain multiple independent visualizations: an interactive website (www.cognitiveconsilience.comand standalone iPhone and iPad applications. With these tools we present a unique, annotatedview of neuroanatomical consilience (integration of knowledge.

  8. Progranulin Protects Hippocampal Neurogenesis via Suppression of Neuroinflammatory Responses Under Acute Immune Stress.

    Science.gov (United States)

    Ma, Yanbo; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

    2017-07-01

    Immune stress is well known to suppress adult neurogenesis in the hippocampus. We have demonstrated that progranulin (PGRN) has a mitogenic effect on neurogenesis under several experimental conditions. We have also shown that PGRN suppresses excessive neuroinflammatory responses after traumatic brain injury. However, the role of PGRN in modulating neurogenesis under acute immune stress is yet to be elucidated. In the present study, we evaluated the involvement of PGRN in neurogenesis and inflammatory responses in the hippocampus using a lipopolysaccharide (LPS)-induced immune stress model. Treatment of mice with LPS significantly increased the expression of PGRN in activated microglia and decreased neurogenesis in the dentate gyrus of the hippocampus. PGRN deficiency increased CD68-immunoreactive area and exacerbated suppression of neurogenesis following LPS treatment. The expression levels of lysosomal genes including lysozyme M, macrophage expressed gene 1, and cathepsin Z were higher in PGRN-deficient than in wild-type mice, while PGRN deficiency decreased mammalian target of rapamycin (mTOR) mRNA levels, suggesting that PGRN suppresses excessive lysosomal biogenesis by promoting mTOR signaling. LPS treatment also increased the expression of proinflammatory genes such as interleukin (IL)-1β, tumor necrosis factor-α, and microsomal prostaglandin E synthase-1 (mPGES-1) in the hippocampus, and PGRN deficiency further enhanced gene expression of IL-6 and mPGES-1. These results suggest that PGRN plays a protecting role in hippocampal neurogenesis at least partially by attenuating neuroinflammatory responses during LPS-induced acute immune stress.

  9. Immune responsiveness of Japanese quail selected for egg yolk testosterone content under severe protein restriction.

    Science.gov (United States)

    Kankova, Zuzana; Okuliarova, Monika; Zeman, Michal

    2014-11-01

    Yolk testosterone concentrations vary in response to environmental conditions and different testosterone contents can subsequently modify the phenotypic traits of offspring. Apart from effects on growth, proactive behaviour and secondary sexual characteristics, the possible negative impacts of maternal testosterone on the immune system are often considered a limitation for its deposition. The effects of maternal testosterone can be modulated by postnatal environmental conditions, such as the availability of food resources. However, the majority of studies considering the effects of maternal testosterone on the immune system have been conducted under optimum conditions. We evaluated the influence of genetic selection for high (HET) and low (LET) egg testosterone content in Japanese quail on immune responsiveness of offspring to phytohaemagglutinin (PHA) and lipopolysaccharide (LPS) stimulation under severe protein restriction. Protein restriction negatively influenced body weight and performance in the PHA-test. We observed an increase in Cort (corticosterone) and He/Ly (heterophil/lymphocyte ratio) after LPS, while no changes occurred in total IgY levels in the protein-restricted group. HET quails showed higher body mass and total IgY levels and lower He/Ly ratio than LET quails, while the PHA index and Cort concentration did not differ between lines. No interactions were found between protein restriction and genetic line. In conclusion, the immune response was not compromised under conditions of severe protein restriction in the faster growing HET line compared with the LET line. We hypothesise that the immune responsiveness of birds with higher yolk testosterone may be linked with other maternally-derived substances in a context-dependent manner. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. MECHANISMS OF MELATONIN EFFECTS UPON IMMUNE STATE IN EXPERIMENTAL DESYNCHRONOSES PRODUCED UNDER THE LED ILLUMINATION CONDITIONS

    Directory of Open Access Journals (Sweden)

    M. V. Osikov

    2015-01-01

    Full Text Available Disorders of immune state in desynchronosis may be associated with reduced concentrations of melatonin in blood, thus being a prerequisite for pharmacological correction of appropriate homeostatic changes. The purpose of this work was to explore some mechanisms of exogenous melatonin actions upon parameters of innate and adaptive immunity in experimental model of desynchronosis under the conditions of LED illumination. The study was performed with 196 adult guinea pigs. Light desynchronosis was produced by day-and-night illumination of the animals having been continued for 30 days. Melatonin was administered applied per os daily at the total dose of 30 mg/kg. A solution of melatonin in isotonic NaCl solution was prepared from the Melaxen drug (INN: melatonin, “Unipharm Inc.,” USA ex tempore. To study innate immunity of blood cells, we determined leukocyte numbers, WBC differential counts, and functional activity of phagocytes, as spontaneous and induced NBT test, as well as engulfment of polystyrene latex particles. Th1-specific immune response was studied according to degree of delayed type hypersensitivity reaction; Th2-dependent response was assessed as the numbers of antibody-forming cells in the spleen of the animals after immunization with allogeneic erythrocytes. Serum concentrations of interleukin 4 (IL-4, interferon-gamma (IFNγ, melatonin, and cortisol were measured by enzyme immunoassay, using the “Immulayt 2000” (USA with guinea pigspecific test systems. It was found that experimental desynchronosis was associated with leukocytosis, lymphoand monocytopenia, activation of oxygen-dependent metabolism of blood phagocytes, suppression of Th1-and Th2-dependent immune response. Desynchronosis was also accompanied by decreased concentrations of serum melatonin, IFNγ and IL-4, along with increased cortisol concentrations. Reduced IFNγ and IL-4 amounts was associated with decreased melatonin concentrations

  11. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs

    Directory of Open Access Journals (Sweden)

    Wen-I Lee

    2011-12-01

    Full Text Available Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG or nontuberculous mycobacteria (NTM, and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM (CD40L mutation, CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations, chronic granulomatous disease (CGD and hyper IgE recurrent infection syndromes (HIES. The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8 for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one, presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ, which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively

  12. The quality of immunization data from routine primary health care reports

    DEFF Research Database (Denmark)

    Onta, S R; Sabroe, S; Hansen, E H

    1998-01-01

    , and measles; the number was lower for poliomyelitis. The overall number of immunizations was higher in the DHO Reports than in the Immunization Registers, by 31% for BCG, 44% for DPT, 155% for polio, and 71% for measles. We conclude that the official report overestimates the immunization coverage...

  13. Human primary adipocytes exhibit immune cell function: adipocytes prime inflammation independent of macrophages.

    Directory of Open Access Journals (Sweden)

    Kees Meijer

    Full Text Available BACKGROUND: Obesity promotes inflammation in adipose tissue (AT and this is implicated in pathophysiological complications such as insulin resistance, type 2 diabetes and cardiovascular disease. Although based on the classical hypothesis, necrotic AT adipocytes (ATA in obese state activate AT macrophages (ATM that then lead to a sustained chronic inflammation in AT, the link between human adipocytes and the source of inflammation in AT has not been in-depth and systematically studied. So we decided as a new hypothesis to investigate human primary adipocytes alone to see whether they are able to prime inflammation in AT. METHODS AND RESULTS: Using mRNA expression, human preadipocytes and adipocytes express the cytokines/chemokines and their receptors, MHC II molecule genes and 14 acute phase reactants including C-reactive protein. Using multiplex ELISA revealed the expression of 50 cytokine/chemokine proteins by human adipocytes. Upon lipopolysaccharide stimulation, most of these adipocyte-associated cytokines/chemokines and immune cell modulating receptors were up-regulated and a few down-regulated such as (ICAM-1, VCAM-1, MCP-1, IP-10, IL-6, IL-8, TNF-α and TNF-β highly up-regulated and IL-2, IL-7, IL-10, IL-13 and VEGF down-regulated. In migration assay, human adipocyte-derived chemokines attracted significantly more CD4+ T cells than controls and the number of migrated CD4+ cells was doubled after treating the adipocytes with LPS. Neutralizing MCP-1 effect produced by adipocytes reduced CD4+ migration by approximately 30%. CONCLUSION: Human adipocytes express many cytokines/chemokines that are biologically functional. They are able to induce inflammation and activate CD4+ cells independent of macrophages. This suggests that the primary event in the sequence leading to chronic inflammation in AT is metabolic dysfunction in adipocytes, followed by production of immunological mediators by these adipocytes, which is then exacerbated by

  14. Comparative transcriptome analyses reveal the genetic basis underlying the immune function of three amphibians' skin.

    Science.gov (United States)

    Fan, Wenqiao; Jiang, Yusong; Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Sun, Hanchang; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan

    2017-01-01

    Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians.

  15. Comparative transcriptome analyses reveal the genetic basis underlying the immune function of three amphibians’ skin

    Science.gov (United States)

    Zhang, Meixia; Yang, Donglin; Chen, Zhongzhu; Lan, Xuelian; Yan, Fan; Xu, Jingming; Yuan, Wanan

    2017-01-01

    Skin as the first barrier against external invasions plays an essential role for the survival of amphibians on land. Understanding the genetic basis of skin function is significant in revealing the mechanisms underlying immunity of amphibians. In this study, we de novo sequenced and comparatively analyzed skin transcriptomes from three different amphibian species, Andrias davidianus, Bufo gargarizans, and Rana nigromaculata Hallowell. Functional classification of unigenes in each amphibian showed high accordance, with the most represented GO terms and KEGG pathways related to basic biological processes, such as binding and metabolism and immune system. As for the unigenes, GO and KEGG distributions of conserved orthologs in each species were similar, with the predominantly enriched pathways including RNA polymerase, nucleotide metabolism, and defense. The positively selected orthologs in each amphibian were also similar, which were primarily involved in stimulus response, cell metabolic, membrane, and catalytic activity. Furthermore, a total of 50 antimicrobial peptides from 26 different categories were identified in the three amphibians, and one of these showed high efficiency in inhibiting the growth of different bacteria. Our understanding of innate immune function of amphibian skin has increased basis on the immune-related unigenes, pathways, and antimicrobial peptides in amphibians. PMID:29267366

  16. Suppression of the primary immune response in rainbow trout, Salmo gairdneri, sublethally irradiated during embryogenesis

    International Nuclear Information System (INIS)

    Strand, J.A.; Fujihara, M.P.; Burdett, R.D.

    1975-03-01

    Eggs of rainbow trout were spawned artificially in the laboratory, fertilized, and immediately immersed in 0, 0.01, 0.1, 1.0, and 10.0 μCi/ml tritium (biological grade) contaminated spring water (pathogen free). Rearing through 20 days of embryogenesis at 10.5 +- 0.2 0 C was facilitated within a recirculation drip incubation system of 150 liter capacity. Exposure of the embryos to 0, 0.01, 0.1, 1.0, and 10.0 μCi/ml tritium resulted in an estimated total dose of 0, 0.048, 0.470, 4.550, and 40.348 rads. At 5 months post hatch, control and irradiated test fish were administered intraperitoneally 0.1 cc of a heat killed antigen (1.8 X 10 8 cells per ml, Chondrococcus columnaris) in 25 percent Freund's incomplete adjuvant. A 0.1 cc sham vaccination containing saline and 25 percent Freund's incomplete adjuvant was similarly administered to another group of control fish. At 3 weeks post vaccination and at weekly intervals thereafter, a standard tube agglutination test for the specific antigen of vaccination was performed on serum from each fish. Results showed a marked suppression of the primary immune response in fish irradiated at the 4.550 and 40.348 rad levels. (U.S.)

  17. Significance of Periodontal Health in Primary Immune Thrombocytopenia- A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Rajinder K Sharma

    2013-01-01

    Full Text Available Primary immune thrombocytopenia is an acquired bleeding disorder with no clinically apparent cause of thrombocytopenia. Clinical indicators of ITP include easy bruising of the skin, prolonged bleeding on injury, mucocutaneous lesions such as petechiae and ecchymosis, epistaxis, gastrointestinal bleeding, hematuria and bleeding from the gums. It is important for a dentist to be aware of the clinical manifestations of ITP as it may not only lead to successful management of the patient, but in some cases it may even lead to formation of a provisional diagnosis of the condition in previously undetected cases. However, very few cases of ITP have been reported in dental practice making it difficult for a dentist to identify the disorder when a patient suffering from ITP reports for dental treatment. A case report of a female patient with ITP is thus described with emphasis on the importance of periodontal health in such patients to prevent consequent unwanted sequelae. It is followed by discussion of oral manifestations of the disorder and dental management of such patients.

  18. Herd Immunity Against Foot-and-Mouth Disease Under Different Vaccination Practices in India.

    Science.gov (United States)

    Sharma, G K; Mahajan, S; Matura, R; Biswal, J K; Ranjan, R; Subramaniam, S; Misri, J; Bambal, R G; Pattnaik, B

    2017-08-01

    A systematic vaccination programme is ongoing in India to control the three prevailing serotypes (A, O, Asia1) of foot-and-mouth disease (FMD) virus. Under the programme, more than 120 million bovine (term bovine applicable to both cattle and buffalo in this study) population of 221 of the 666 districts in the country are being bi-annually vaccinated with trivalent vaccine since 2010. Although clinical disease has reduced in these districts because of the systematic vaccinations, an abrupt increase in the number of FMD cases was recorded in 2013. Hence, a longitudinal field study was conducted in the year 2014 to estimate the serological herd immunity level in bovines, the impact of systematic vaccinations and field efficacy of the vaccines used. Serum samples (n = 115 963) collected from 295 districts of the 18 states of the country were analysed to estimate antibody titres against structural proteins of the three serotypes. The efficacy of the vaccine was demonstrated in the control group (group-D) where animals of the group were identified by ear tags for the purpose of repeated sampling after vaccination. Progressive building of the herd immunity in the field after systematic vaccination was demonstrated. The mean antibody titre against the serotypes O, A and Asia1 was estimated as log 10 1.93 (95% CI 1.92-1.93), 2.02 (2.02-2.02) and 2.02 (2.02-2.02), respectively, in the states covered under the control programme. However, in other states herd immunity was significantly low [mean titre log 10 1.68 (95% CI 1.67-1.69), 1.77 (1.76-1.78) and 1.85 (1.84-1.86) against the three serotypes]. Inverse relationship between the herd immunity and FMD incidences was observed the states following different vaccination practices. The study helped in demarcation of FMD risk zones in the country with low herd immunity. Estimation of herd immunity kinetics in the field helped in refining the vaccination schedule under the control programme. © 2016 Blackwell Verlag GmbH.

  19. Constant light suppresses production of Met-enkephalin-containing peptides in cultured splenic macrophages and impairs primary immune response in rats.

    Science.gov (United States)

    Valdés-Tovar, Marcela; Escobar, Carolina; Solís-Chagoyán, Héctor; Asai, Miguel; Benítez-King, Gloria

    2015-03-01

    The light-dark cycle is an environmental factor that influences immune physiology, and so, variations of the photoperiod length result in altered immune responsivity. Macrophage physiology comprises a spectrum of functions that goes from host defense to immune down-regulation, in addition to their homeostatic activities. Macrophages also play a key role in the transition from innate to adaptive immune responses. Met-enkephalin (MEnk) has been recognized as a modulator of macrophage physiology acting in an autocrine or paracrine fashion to influence macrophage activation, phenotype polarization and production of cytokines that would enhance lymphocyte activation at early stages of an immune response. Previously it was shown that splenic MEnk tissue content is reduced in rats exposed to constant light. In this work, we explored whether production of Met-enkephalin-containing peptides (MECPs) in cultured splenic macrophages is affected by exposure of rats to a constant light regime. In addition, we explored whether primary immune response was impaired under this condition. We found that in rats, 15 days in constant light was sufficient to disrupt their general activity rhythm. Splenic MEnk content oscillations and levels were also blunted throughout a 24-h period in animals subjected to constant light. In agreement, de novo synthesis of MECPs evaluated through incorporation of (35)S-methionine was reduced in splenic macrophages from rats exposed to constant light. Moreover, MECPs immunocytochemistry showed a decrease in the intracellular content and lack of granule-like deposits in this condition. Furthermore, we found that primary T-dependent antibody response was compromised in rats exposed to constant light. In those animals, pharmacologic treatment with MEnk increased IFN-γ-secreting cells. Also, IL-2 secretion from antigen-stimulated splenocytes was reduced after incubation with naloxone, suggesting that immune-derived opioid peptides and stimulation of opioid

  20. HIV-1 Cross-Reactive Primary Virus Neutralizing Antibody Response Elicited by Immunization in Nonhuman Primates.

    Science.gov (United States)

    Wang, Yimeng; O'Dell, Sijy; Turner, Hannah L; Chiang, Chi-I; Lei, Lin; Guenaga, Javier; Wilson, Richard; Martinez-Murillo, Paola; Doria-Rose, Nicole; Ward, Andrew B; Mascola, John R; Wyatt, Richard T; Karlsson Hedestam, Gunilla B; Li, Yuxing

    2017-11-01

    Elicitation of broadly neutralizing antibody (bNAb) responses is a major goal for the development of an HIV-1 vaccine. Current HIV-1 envelope glycoprotein (Env) vaccine candidates elicit predominantly tier 1 and/or autologous tier 2 virus neutralizing antibody (NAb) responses, as well as weak and/or sporadic cross-reactive tier 2 virus NAb responses with unknown specificity. To delineate the specificity of vaccine-elicited cross-reactive tier 2 virus NAb responses, we performed single memory B cell sorting from the peripheral blood of a rhesus macaque immunized with YU2gp140-F trimers in adjuvant, using JR-FL SOSIP.664, a native Env trimer mimetic, as a sorting probe to isolate monoclonal Abs (MAbs). We found striking genetic and functional convergence of the SOSIP-sorted Ig repertoire, with predominant VH4 or VH5 gene family usage and Env V3 specificity. Of these vaccine-elicited V3-specific MAbs, nearly 20% (6/33) displayed cross-reactive tier 2 virus neutralization, which recapitulated the serum neutralization capacity. Substantial similarities in binding specificity, neutralization breadth and potency, and sequence/structural homology were observed between selected macaque cross-reactive V3 NAbs elicited by vaccination and prototypic V3 NAbs derived from natural infections in humans, highlighting the convergence of this subset of primate V3-specific B cell repertories. Our study demonstrated that cross-reactive primary virus neutralizing B cell lineages could be elicited by vaccination as detected using a standardized panel of tier 2 viruses. Whether these lineages could be expanded to acquire increased breadth and potency of neutralization merits further investigation. IMPORTANCE Elicitation of antibody responses capable of neutralizing diverse HIV-1 primary virus isolates (designated broadly neutralizing antibodies [bNAbs]) remains a high priority for the vaccine field. bNAb responses were so far observed only in response to natural infection within a subset

  1. Molecular Mechanisms Underlying β-Adrenergic Receptor-Mediated Cross-Talk between Sympathetic Neurons and Immune Cells

    Directory of Open Access Journals (Sweden)

    Dianne Lorton

    2015-03-01

    Full Text Available Cross-talk between the sympathetic nervous system (SNS and immune system is vital for health and well-being. Infection, tissue injury and inflammation raise firing rates of sympathetic nerves, increasing their release of norepinephrine (NE in lymphoid organs and tissues. NE stimulation of β2-adrenergic receptors (ARs in immune cells activates the cAMP-protein kinase A (PKA intracellular signaling pathway, a pathway that interfaces with other signaling pathways that regulate proliferation, differentiation, maturation and effector functions in immune cells. Immune–SNS cross-talk is required to maintain homeostasis under normal conditions, to develop an immune response of appropriate magnitude after injury or immune challenge, and subsequently restore homeostasis. Typically, β2-AR-induced cAMP is immunosuppressive. However, many studies report actions of β2-AR stimulation in immune cells that are inconsistent with typical cAMP–PKA signal transduction. Research during the last decade in non-immune organs, has unveiled novel alternative signaling mechanisms induced by β2-AR activation, such as a signaling switch from cAMP–PKA to mitogen-activated protein kinase (MAPK pathways. If alternative signaling occurs in immune cells, it may explain inconsistent findings of sympathetic regulation of immune function. Here, we review β2-AR signaling, assess the available evidence for alternative signaling in immune cells, and provide insight into the circumstances necessary for “signal switching” in immune cells.

  2. Immune defects in active mycobacterial diseases in patients with primary immunodeficiency diseases (PIDs).

    Science.gov (United States)

    Lee, Wen-I; Huang, Jing-Long; Yeh, Kuo-Wei; Jaing, Tang-Her; Lin, Tzou-Yien; Huang, Yhu-Chering; Chiu, Cheng-Hsun

    2011-12-01

    Natural human immunity to the mycobacteria group, including Mycobacterium tuberculosis, Bacille Calmette-Guérin (BCG) or nontuberculous mycobacteria (NTM), and/or Salmonella species, relies on the functional IL-12/23-IFN-γ integrity of macrophages (monocyte/dendritic cell) connecting to T lymphocyte/NK cells. Patients with severe forms of primary immunodeficiency diseases (PIDs) have more profound immune defects involving this impaired circuit in patients with severe combined immunodeficiencies (SCID) including complete DiGeorge syndrome, X-linked hyper IgM syndrome (HIGM) (CD40L mutation), CD40 deficiency, immunodeficiency with or without anhidrotic ectodermal dysplasia (NEMO and IKBA mutations), chronic granulomatous disease (CGD) and hyper IgE recurrent infection syndromes (HIES). The patients with severe PIDs have broader diverse infections rather than mycobacterial infections. In contrast, patients with an isolated inborn error of the IL-12/23-IFN-γ pathway are exclusively prone to low-virulence mycobacterial infections and nontyphoid salmonella infections, known as Mendelian susceptibility to the mycobacterial disease (MSMD) phenotype. Restricted defective molecules in the circuit, including IFN-γR1, IFN-γR2, IL-12p40, IL-12R-β1, STAT-1, NEMO, IKBA and the recently discovered CYBB responsible for autophagocytic vacuole and proteolysis, and interferon regulatory factor 8 (IRF8) for dendritic cell immunodeficiency, have been identified in around 60% of patients with the MSMD phenotype. Among all of the patients with PIDs referred for investigation since 1985, we have identified four cases with the specific defect (IFNRG1 for three and IL12RB for one), presenting as both BCG-induced diseases and NTM infections, in addition to some patients with SCID, HIGM, CGD and HIES. Furthermore, manifestations in patients with autoantibodies to IFN-γ (autoAbs-IFN-γ), which is categorized as an anticytokine autoantibody syndrome, can resemble the relatively persistent

  3. Pediatric immunization-related safety incidents in primary care: A mixed methods analysis of a national database.

    Science.gov (United States)

    Rees, Philippa; Edwards, Adrian; Powell, Colin; Evans, Huw Prosser; Carter, Ben; Hibbert, Peter; Makeham, Meredith; Sheikh, Aziz; Donaldson, Liam; Carson-Stevens, Andrew

    2015-07-31

    Children are scheduled to receive 18-20 immunizations before their 18th birthday in England and Wales; this approximates to 13 million vaccines administered per annum. Each immunization represents a potential opportunity for immunization-related error and effective immunization is imperative to maintain the public health benefit from immunization. Using data from a national reporting system, this study aimed to characterize pediatric immunization-related safety incident reports from primary care in England and Wales between 2002 and 2013. A cross-sectional mixed methods study was undertaken. This comprised reading the free-text of incident reports and applying codes to describe incident type, potential contributory factors, harm severity, and incident outcomes. A subsequent thematic analysis was undertaken to interpret the most commonly occurring codes, such as those describing the incident, events leading up to it and reported contributory factors, within the contexts they were described. We identified 1745 reports and most (n=1077, 61.7%) described harm outcomes including three deaths, 67 reports of moderate harm and 1007 reports of low harm. Failure of timely vaccination was the potential cause of three child deaths from meningitis and pneumonia, and described in a further 113 reports. Vaccine administration incidents included the wrong number of doses (n=476, 27.3%), wrong timing (n=294, 16.8%), and wrong vaccine (n=249, 14.3%). Documentation failures were frequently implicated. Socially and medically vulnerable children were commonly described. This is the largest examination of reported contributory factors for immunization-related patient safety incidents in children. Our findings suggest investments in IT infrastructure to support data linkage and identification of risk predictors, development of consultation models that promote the role of parents in mitigating safety incidents, and improvement efforts to adapt and adopt best practices from elsewhere, are

  4. Primary Healthcare Spending: Striving for Equity under Fiscal ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    1 avr. 2010 ... This book highlights key factors that can help to achieve equity in the allocation of primary healthcare resources within fiscal federal systems and ... Les recherches sur le développement de la petite enfance a généralement porté sur des interventions uniques et sur des populations de non-réfugiés.

  5. Cytokine changes in response to TPO receptor agonist treatment in primary immune thrombocytopenia.

    Science.gov (United States)

    Qu, Ming-Ming; Liu, Xue-Na; Liu, Xin-Guang; Feng, Qi; Liu, Yang; Zhang, Xu; Liu, Shuang; Zhang, Lei; Li, Guo-Sheng; Zhu, Yuan-Yuan; Lv, Ming-Yun; Peng, Jun; Hou, Ming

    2017-04-01

    Thrombopoietin receptor agonists (TPO-RAs) have been clinically used in primary immune thrombocytopenia (ITP) with favorable outcomes, while their effect on cytokine regulation in ITP remains unknown. In the present study, plasma and mRNA expression levels of interleukin (IL)-2, interferon gamma (IFN-γ), IL-4, IL-17A, and transforming growth factor-β1 (TGF-β1) were determined by ELISA and real-time quantitative PCR in 26 corticosteroid-resistant/relapsed ITP patients receiving eltrombopag or rhTPO therapy and 15 healthy controls (HCs). Results showed that plasma and mRNA levels of IL-2, IFN-γ, IL-4, and IL-17A in ITP patients did not change significantly after TPO-RA treatment, whereas TGF-β1 levels increased remarkably. The pre- and post-treatment plasma and mRNA levels of IFN-γ and IL-2 were significantly higher, while the pre- and post-treatment IL-4 levels as well as the pre-treatment TGF-β1 levels were remarkably lower in ITP patients compared with HCs. There was no significant difference in TGF-β1 levels between TPO-RA-treated ITP patients and HCs. No statistical difference was found in plasma levels of IL-17A between ITP patients before or after treatment and HCs. However, the pre- and post-treatment mRNA expression of IL-17A and retinoic orphan receptor (ROR) γt in ITP patients were higher than that in HCs. Overall, these findings indicated that TPO-RA treatment could promote the secretion of TGF-β1, while it could not correct the Th1 and Th17 polarization in ITP patients. This study might improve our understanding of the mechanism of action of TPO-RAs and provide important information for optimizing therapeutic strategies for ITP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Dynamic immune cell recruitment after murine pulmonary Aspergillus fumigatus infection under different immunosuppressive regimens

    Directory of Open Access Journals (Sweden)

    Natarajaswamy Kalleda

    2016-07-01

    Full Text Available Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions.

  7. Dynamic Immune Cell Recruitment After Murine Pulmonary Aspergillus fumigatus Infection under Different Immunosuppressive Regimens

    Science.gov (United States)

    Kalleda, Natarajaswamy; Amich, Jorge; Arslan, Berkan; Poreddy, Spoorthi; Mattenheimer, Katharina; Mokhtari, Zeinab; Einsele, Hermann; Brock, Matthias; Heinze, Katrin Gertrud; Beilhack, Andreas

    2016-01-01

    Humans are continuously exposed to airborne spores of the saprophytic fungus Aspergillus fumigatus. However, in healthy individuals pulmonary host defense mechanisms efficiently eliminate the fungus. In contrast, A. fumigatus causes devastating infections in immunocompromised patients. Host immune responses against A. fumigatus lung infections in immunocompromised conditions have remained largely elusive. Given the dynamic changes in immune cell subsets within tissues upon immunosuppressive therapy, we dissected the spatiotemporal pulmonary immune response after A. fumigatus infection to reveal basic immunological events that fail to effectively control invasive fungal disease. In different immunocompromised murine models, myeloid, notably neutrophils, and macrophages, but not lymphoid cells were strongly recruited to the lungs upon infection. Other myeloid cells, particularly dendritic cells and monocytes, were only recruited to lungs of corticosteroid treated mice, which developed a strong pulmonary inflammation after infection. Lymphoid cells, particularly CD4+ or CD8+ T-cells and NK cells were highly reduced upon immunosuppression and not recruited after A. fumigatus infection. Moreover, adoptive CD11b+ myeloid cell transfer rescued cyclophosphamide immunosuppressed mice from lethal A. fumigatus infection but not cortisone and cyclophosphamide immunosuppressed mice. Our findings illustrate that CD11b+ myeloid cells are critical for anti-A. fumigatus defense under cyclophosphamide immunosuppressed conditions. PMID:27468286

  8. Influence of nanoparticle-mediated transfection on proliferation of primary immune cells in vitro and in vivo.

    Science.gov (United States)

    Przybylski, Susanne; Gasch, Michaela; Marschner, Anne; Ebert, Marcus; Ewe, Alexander; Helmig, Gisa; Hilger, Nadja; Fricke, Stephan; Rudzok, Susanne; Aigner, Achim; Burkhardt, Jana

    2017-01-01

    One of the main obstacles in the widespread application of gene therapeutic approaches is the necessity for efficient and safe transfection methods. For the introduction of small oligonucleotide gene therapeutics into a target cell, nanoparticle-based methods have been shown to be highly effective and safe. While immune cells are a most interesting target for gene therapy, transfection might influence basic immune functions such as cytokine expression and proliferation, and thus positively or negatively affect therapeutic intervention. Therefore, we investigated the effects of nanoparticle-mediated transfection such as polyethylenimine (PEI) or magnetic beads on immune cell proliferation. Human adherent and non-adherent PBMCs were transfected by various methods (e.g. PEI, Lipofectamine® 2000, magnetofection) and stimulated. Proliferation was measured by lymphocyte transformation test (LTT). Cell cycle stages as well as expression of proliferation relevant genes were analyzed. Additionally, the impact of nanoparticles was investigated in vivo in a murine model of the severe systemic immune disease GvHD (graft versus host disease). The proliferation of primary immune cells was influenced by nanoparticle-mediated transfection. In particular in the case of magnetic beads, proliferation inhibition coincided with short-term cell cycle arrest and reduced expression of genes relevant for immune cell proliferation. Notably, proliferation inhibition translated into beneficial effects in a murine GvHD model with animals treated with PEI-nanoparticles showing increased survival (pPEI = 0.002) most likely due to reduced inflammation. This study shows for the first time that nanoparticles utilized for gene therapeutic transfection are able to alter proliferation of immune cells and that this effect depends on the type of nanoparticle. For magnetic beads, this was accompanied by temporary cell cycle arrest. Notably, in GvHD this nonspecific anti-proliferative effect might

  9. PD-L1 expression and the immune microenvironment in primary invasive lobular carcinomas of the breast.

    Science.gov (United States)

    Thompson, Elizabeth D; Taube, Janis M; Asch-Kendrick, Rebecca J; Ogurtsova, Aleksandra; Xu, Haiying; Sharma, Rajni; Meeker, Alan; Argani, Pedram; Emens, Leisha A; Cimino-Mathews, Ashley

    2017-11-01

    Tumor-infiltrating lymphocytes and immune checkpoint proteins such as PD-L1 are potential prognostic factors and therapeutic targets in breast cancer. Most studies characterizing the breast tumor immune microenvironment have focused on ductal carcinomas. Here we investigate the tumor microenvironment of primary invasive lobular carcinomas. Previously constructed tissue microarrays of 47 lobular carcinomas were labeled by immunohistochemistry for PD-L1, CD8, CD20, and FoxP3. The stromal immune infiltrate density was qualitatively scored as a percentage of tumor area: 1+ (50%). The average immune cell subtype per high-power field was quantitatively scored. The percentage PD-L1 labeling on tumor-infiltrating lymphocytes was scored as none, focal (lobular carcinomas contained PD-L1 + tumor-infiltrating lymphocytes with the majority showing 1+ immune infiltrates with focal-moderate PD-L1 labeling. PD-L1 was expressed by tumor cells in 17% of lobular carcinomas. In contrast to ductal carcinomas, there was no correlation between the immune infiltrate density, the PD-L1 expression by lobular carcinoma cells, tumor grade, or the expression of estrogen receptor or human epidermal growth factor receptor-2. However, both the tumor-infiltrating lymphocyte density and the average CD8 + T-cell counts correlated with immune cell PD-L1 status (P=0.004 and 0.03, respectively). Similar to breast ductal carcinomas, PD-L1 + lobular breast carcinomas had higher numbers of PD-L1 + tumor-infiltrating lymphocytes (63%) than PD-L1 - lobular carcinomas (23%; P=0.04). These data show that a subset of primary breast lobular carcinomas both express PD-L1 on tumor cells and contain PD-L1 + tumor-infiltrating lymphocytes, suggesting the possibility of both constitutive and adaptive PD-L1 expression. Together, these results support immunotherapy as a potential treatment for a subset of patients with primary invasive lobular breast carcinomas.

  10. Full Immunization Status of Under-Five Children in an Urban ...

    African Journals Online (AJOL)

    Caregivers numbering 250 (96.5%) correctly stated at least one benefit of immunization. Overall, immunization coverage was low, despite accessible immunization services. Community members and household influencers should educate caregivers to ensure their children's full immunization and employers should grant ...

  11. The protective effect of γ-aminobutyric acid on the development of immune function in chickens under heat stress.

    Science.gov (United States)

    Tang, J; Chen, Z

    2016-08-01

    This study aimed to investigate the protective effect of γ-aminobutyric acid (GABA) on the development of immune function in chicks under heat stress (HS). One-day-old male Wenchang chicks were randomly divided into control (CK), HS and GABA+HS groups. The GABA+HS group was fed with 0.2 ml GABA solution (50 mg/kg) daily by oral gavage. The HS and GABA+HS groups were placed in 40 ± 0.5 °C environment for 2 h heat treatment from 13:00 each day. Blood samples were routinely taken at 14, 21, 28, 35 and 42 days respectively, and the contents of T and B lymphocyte subsets in the blood and tissue were analysed by flow cytometry after FITC/PE double staining; the plasma levels of interleukin (IL)-2, immunoglobulin (Ig)A, IgG and IgM were determined using ELISA. The thymus and the bursa of fabricius were also collected to analyse for organ index and observe for the changes in tissue microstructure. In addition, the chicks received primary and secondary immunizations with attenuated Newcastle disease (ND) vaccine (LaSota strain) at 7 and 28 days respectively; conventional hemagglutination inhibition (HI) assay was performed to monitor the titre changes in plasma antibody against ND virus in the birds. Our results indicated that the indices of both thymus and bursa of fabricius, the intactness of tissue structure and development, the plasma levels of IL-2, IgA, IgG and IgM, the titres of ND antibody, and the levels of B and T lymphocyte subsets in HS group were all significantly lower than those in CK group (p < 0.05). However, all above indices were significantly improved in GABA+HS group compared with those in HS group (p < 0.05). These results demonstrated that while HS seriously affected the development of immune function in Wenchang chicks, GABA effectively alleviated the damages of HS to the development of immune function in chicks. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  12. Comprehensive primary health care under neo-liberalism in Australia.

    Science.gov (United States)

    Baum, Fran; Freeman, Toby; Sanders, David; Labonté, Ronald; Lawless, Angela; Javanparast, Sara

    2016-11-01

    This paper applies a critical analysis of the impact of neo-liberal driven management reform to examine changes in Australian primary health care (PHC) services over five years. The implementation of comprehensive approaches to primary health care (PHC) in seven services: five state-managed and two non-government organisations (NGOs) was tracked from 2009 to 2014. Two questions are addressed: 1) How did the ability of Australian PHC services to implement comprehensive PHC change over the period 2009-2014? 2) To what extent is the ability of the PHC services to implement comprehensive PHC shaped by neo-liberal health sector reform processes? The study reports on detailed tracking and observations of the changes and in-depth interviews with 63 health service managers and practitioners, and regional and central health executives. The documented changes were: in the state-managed services (although not the NGOs) less comprehensive service coverage and more focus on clinical services and integration with hospitals and much less development activity including community development, advocacy, intersectoral collaboration and attention to the social determinants. These changes were found to be associated with practices typical of neo-liberal health sector reform: considerable uncertainty, more directive managerial control, budget reductions and competitive tendering and an emphasis on outputs rather than health outcomes. We conclude that a focus on clinical service provision, while highly compatible with neo-liberal reforms, will not on its own produce the shifts in population disease patterns that would be required to reduce demand for health services and promote health. Comprehensive PHC is much better suited to that task. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  13. Durability of immunity by hepatitis B vaccine in Japanese health care workers depends on primary response titers and durations.

    Directory of Open Access Journals (Sweden)

    Nori Yoshioka

    Full Text Available Health care workers (HCWs are frequently exposed to hepatitis B virus (HBV infection. The efficacy and safety of immunization with the hepatitis B (HB vaccine are well recognized, but the durability of immunity and need for booster doses in those with secondary vaccine response failure remains controversial.This was a retrospective cohort study performed at Osaka University Hospital, Japan. We examined antibodies against HB surface antigen (anti-HBs titers annually after immunization for previously non-immunized HCWs. Primary responders were categorized by their sero-positive durations as short responders (those whose anti-HBs titers declined to negative range within 3 years, and long responders (those who retained positive anti-HBs levels for 3 years and more. We re-immunized short responders with either single or 3-dose boosters, the long responders with a single booster when their titers dropped below protective levels, and examined their sero-protection rates over time thereafter.From 2001 to 2012, data of 264 HCWs with a median age of 25.3 were collected. The rate of anti-HBs positivity after primary vaccination were 93.0% after three doses (n = 229, 54.5% after two doses (n = 11, and 4.2% after a single dose (n = 24. Of 213 primary responders, the anti-HBs levels of 95 participants (44.6% fell below the protective levels, including 46 short responders and 49 long responders. HCWs with higher initial anti-HBs titers after primary vaccination had significantly longer durations of sero-positivity. For short responders, 3-dose booster vaccination induced a longer duration of anti-HBs positivity compared to a single-dose booster, whereas for long responders, a single-dose booster alone could induce prolonged anti-HBs positivity.Our preliminary data suggested that it may be useful to differentiate HB vaccine responders based on their primary response durations to maintain protective levels of anti-HBs efficiently. A randomized, prospective

  14. Mycoplasma hyorhinis-Contaminated Cell Lines Activate Primary Innate Immune Cells via a Protease-Sensitive Factor.

    Science.gov (United States)

    Heidegger, Simon; Jarosch, Alexander; Schmickl, Martina; Endres, Stefan; Bourquin, Carole; Hotz, Christian

    2015-01-01

    Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR) function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments.

  15. Mycoplasma hyorhinis-Contaminated Cell Lines Activate Primary Innate Immune Cells via a Protease-Sensitive Factor.

    Directory of Open Access Journals (Sweden)

    Simon Heidegger

    Full Text Available Mycoplasma are a frequent and occult contaminant of cell cultures, whereby these prokaryotic organisms can modify many aspects of cell physiology, rendering experiments that are conducted with such contaminated cells problematic. Chronic Mycoplasma contamination in human monocytic cells lines has been associated with suppressed Toll-like receptor (TLR function. In contrast, we show here that components derived from a Mycoplasma hyorhinis-infected cell line can activate innate immunity in non-infected primary immune cells. Release of pro-inflammatory cytokines such as IL-6 by dendritic cells in response to Mycoplasma hyorhinis-infected cell components was critically dependent on the adapter protein MyD88 but only partially on TLR2. Unlike canonical TLR2 signaling that is triggered in response to the detection of Mycoplasma infection, innate immune activation by components of Mycoplasma-infected cells was inhibited by chloroquine treatment and sensitive to protease treatment. We further show that in plasmacytoid dendritic cells, soluble factors from Mycoplasma hyorhinis-infected cells induce the production of large amounts of IFN-α. We conclude that Mycoplasma hyorhinis-infected cell lines release protein factors that can potently activate co-cultured innate immune cells via a previously unrecognized mechanism, thus limiting the validity of such co-culture experiments.

  16. Neither primary nor memory immunity to Mycobacterium tuberculosis infection is compromised in mice with chronic enteric helminth infection.

    Science.gov (United States)

    Rafi, Wasiulla; Bhatt, Kamlesh; Gause, William C; Salgame, Padmini

    2015-03-01

    Previously we had reported that Nippostrongylus brasiliensis, a helminth with a lung migratory phase, affected host resistance against Mycobacterium tuberculosis infection through the induction of alternatively activated (M2) macrophages. Several helminth species do not have an obligatory lung migratory phase but establish chronic infections in the host that include potent immune downregulatory effects, in part mediated through induction of a FoxP3(+) T regulatory cell (Treg) response. Treg cells exhibit duality in their functions in host defense against M. tuberculosis infection since their depletion leads to enhanced priming of T cells in the lymph nodes and attendant improved control of M. tuberculosis infection, while their presence in the lung granuloma protects against excessive inflammation. Heligmosomoides polygyrus is a strictly murine enteric nematode that induces a strong FoxP3 Treg response in the host. Therefore, in this study we investigated whether host immunity to M. tuberculosis infection would be modulated in mice with chronic H. polygyrus infection. We report that neither primary nor memory immunity conferred by Mycobacterium bovis BCG vaccination was affected in mice with chronic enteric helminth infection, despite a systemic increase in FoxP3(+) T regulatory cells. The findings indicate that anti-M. tuberculosis immunity is not similarly affected by all helminth species and highlight the need to consider this inequality in human coinfection studies. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  17. Suppression of the primary immune response in rainbow trout, Salmo gairdneri, sublethally exposed to tritiated water during embryogenesis

    International Nuclear Information System (INIS)

    Strand, J.A.

    1975-01-01

    Antibody synthesis in response to vaccination with a 0.1 cc (1.8 x 10 8 cells/cc) intraperitoneally injected heat-killed strain of Flexibacter columnaris was employed to investigate the effect of tritium irradiation (0, 0.04, 0.4, 4.0 and 40.0 rads total dose for 20 days during embryogenesis) on development of the primary immune response in 5-month rainbow trout, Salmo gairdneri. Total serum protein measurements and electrophoretic separation of blood serum proteins followed by densitometric analyses were performed to assess the potential for qualitative and quantitative changes in blood serum components which conceivably accounted for suppressed immune responsiveness in tritium-irradiated fish. Data on the biological effects of tritium on early life stages in terms of hatchability, abnormality, latent mortality, and growth were also collected. A review of all experiments directed at determining the effects of early radiation exposure on the parameters of hatchability, incidence of abnormality, latent mortality and depressed growth, revealed considerable variation among similar treatments and indicated that significant effects at dose levels of 50 rads and below were not consistently demonstrated. While present experimental results demonstrated that the primary immune response in juvenile rainbow trout was significantly suppressed following embryonic exposure to tritium at essentially the 1.0 μCi/ml level, and perhaps at the 0.1 μCi/ml level, these concentrations are no less than 5 to 6 orders of magnitude above present levels for tritium in the aquatic environment

  18. Local hepatic immune response in rats during primary infection with Fasciola hepatica

    Directory of Open Access Journals (Sweden)

    Tliba O.

    2000-03-01

    Full Text Available The distribution of lymphocyte subpopulations (TCD4+ , TCD8+, TCD43+ and Ig+ cells, macrophages and eosinophils were analysed in the inflammatory infiltrates associated with hepatic lesions and in hepatic lymph nodes (HLN from rats experimentally infected with F. hepatica and necropsied 1, 2, 3, 4, 6 and 8 week post infection (WPI. We also investigated the fixation of immunoglobulin isotypes on migrating flukes in the liver. As early as 1WPI, portal tract areas surrounding migratory tunnels were infiltrated with immune and inflammatory cells. The dominant cells were eosinophils and to lesser extent, macrophages and lymphocytes (TCD4+, TCD8+ and B. Most of the inflammatory and immune cells reached the posterior part of flukes, whereas in front of the parasites these cells were fewer in number. Except for eosinophils, no immune cells penetrated through granuloma consisting of hepatic necrotic cells. As early as 1WPI, IgM could be detected in the liver, and to a lesser extent IgA, IgG2a and IgG2b. At 2WPI, IgE and IgG1, began being detected. IgG2c was detectable at 3WPI. In HLN, we observed numerous microscopic follicles in the cortical zone with proliferation of germinal centres and medullary cords. The protective role of infiltrating cell populations and immunoglobulin isotypes and possible mechanisms of immune evasion by the parasite are discussed.

  19. The effect of infectious dose on humoral and cellular immune responses in Chlamydophila caviae primary ocular infection.

    Directory of Open Access Journals (Sweden)

    Ana Filipovic

    Full Text Available Following infection, the balance between protective immunity and immunopathology often depends on the initial infectious load. Several studies have investigated the effect of infectious dose; however, the mechanism by which infectious dose affects disease outcomes and the development of a protective immune response is not known. The aim of this study was to investigate how the infectious dose modulates the local and systemic humoral and the cellular immune responses during primary ocular chlamydial infection in the guinea pig animal model. Guinea pigs were infected by ocular instillation of a Chlamydophila caviae-containing eye solution in the conjunctival sac in three different doses: 1×102, 1×104, and 1×106 inclusion forming units (IFUs. Ocular pathology, chlamydial clearance, local and systemic C. caviae-specific humoral and cellular immune responses were assessed. All inocula of C. caviae significantly enhanced the local production of C. caviae-specific IgA in tears, but only guinea pigs infected with the higher doses showed significant changes in C. caviae-specific IgA levels in vaginal washes and serum. On complete resolution of infection, the low dose of C. caviae did not alter the ratio of CD4+ and CD8+ cells within guinea pigs' submandibular lymph node (SMLN lymphocytes while the higher doses increased the percentages of CD4+ and CD8+ cells within the SMLN lymphocytes. A significant negative correlation between pathology intensity and the percentage of CD4+ and CD8+ cells within SMLN lymphocyte pool at selected time points post-infection was recorded for both 1×104, and 1×106 IFU infected guinea pigs. The relevance of the observed dose-dependent differences on the immune response should be further investigated in repeated ocular chlamydial infections.

  20. Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines.

    Science.gov (United States)

    Blok, Bastiaan A; Arts, Rob J W; van Crevel, Reinout; Benn, Christine Stabell; Netea, Mihai G

    2015-09-01

    An increasing body of evidence shows that the innate immune system has adaptive characteristics that involve a heterologous memory of past insults. Both experimental models and proof-of-principle clinical trials show that innate immune cells, such as monocytes, macrophages, and NK cells, can provide protection against certain infections in vaccination models independently of lymphocytes. This process is regulated through epigenetic reprogramming of innate immune cells and has been termed "trained immunity." It has been hypothesized that induction of trained immunity is responsible for the protective, nonspecific effects induced by vaccines, such as BCG, measles vaccination, and other whole-microorganism vaccines. In this review, we will present the mechanisms of trained immunity responsible for the long-lasting effects of vaccines on the innate immune system. © Society for Leukocyte Biology.

  1. In Vitro experimental model of trained innate immunity in human primary monocytes

    DEFF Research Database (Denmark)

    Bekkering, S.; Blok, B. A.; Joosten, Leo A B

    2016-01-01

    three stimuli induced a switch to glycolysis (the Warburg effect). These effects were most pronounced when the training interval was 24 h and the resting time interval was 6 days. Training with BCG and oxLDL also led to the increased production of reactive oxygen species, whereas training with β...... training period with β-glucan, BCG, or oxLDL, followed by washing and resting of the cells and, thereafter, restimulation with secondary bacterial stimuli. The training and resting time intervals were varied to identify the optimal setting for the long-term induction of trained immunity. Trained immunity...... was assessed in terms of the secondary cytokine response, the production of reactive oxygen species, cell morphology, and induction of glycolysis. Monocytes primed with β-glucan, BCG, and oxLDL showed increased pro-and antiinflammatory cytokine responses upon restimulation with nonrelated stimuli. Also, all...

  2. Suspected primary immune deficiency in a Donge de Bordeaux dog : short communication

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti

    2002-07-01

    Full Text Available A young Donge de Bordeaux dog was presented with chronic intermittent antibiotic responsive gastrointestinal and respiratory disease. Further evaluation showed bacterial lymphadenitis, bacterial tracheitis, normal white cell and differential cell counts, hypogammaglobulinaemia, and the absence of B-lymphocytes but the presence of T-lymphocytes in the lymphoid tissue stained with lymphocyte markers. As the dog came from a narrow genetic base, with related dogs showing similar clinical signs, possible B-cell congenital immune deficiency was suspected.

  3. A novel immune evasion mechanism of LMP-1, an EBV-primary oncogene, in nasopharyngeal carcinoma.

    Science.gov (United States)

    Yoshizaki, Tomokazu

    2011-01-01

    Nasopharyngeal carcinoma is an Epstein-Barr virus (EBV)-associated tumor. Viruses that are associated with malignant transformation have evolved unique mechanisms to interfere with this interaction to evade antiviral T cell responses. EBV exploits many immune evasive strategies to successfully establish a latent infection in B cells. CD8+ T cell responses to LMP-1 are generally very low and rarely detected in healthy virus carriers. Activation of the NF-kB pathway by EBV-LMP-1 leads to an upregulation of the MHC class I antigen-processing pathway. Paradoxically, LMP-1itself induces a subdominant CD8+ T cell response and appears to have evolved to avoid immune recognition. An expression of LMP-1 in human cells enhanced the trans-presentation of CD8+ T cell epitopes; however, cis-presentation of LMP-1-derived epitopes was severely impaired. Deletion of the first transmembrane domain of LMP-1, which prevented self-aggregation, significantly enhanced the cis-presentation of T cell epitopes from this protein, whereas it lost its ability to upregulate trans-presentation. These results delineate a novel mechanism of immune evasion, which renders a virally encoded oncogene inaccessible to the conventional MHC class I pathway limiting its cis-presentation. Copyright © 2011 S. Karger AG, Basel.

  4. Therapeutic Touch Has Significant Effects on Mouse Breast Cancer Metastasis and Immune Responses but Not Primary Tumor Size.

    Science.gov (United States)

    Gronowicz, Gloria; Secor, Eric R; Flynn, John R; Jellison, Evan R; Kuhn, Liisa T

    2015-01-01

    Evidence-based integrative medicine therapies have been introduced to promote wellness and offset side-effects from cancer treatment. Energy medicine is an integrative medicine technique using the human biofield to promote well-being. The biofield therapy chosen for study was Therapeutic Touch (TT). Breast cancer tumors were initiated in mice by injection of metastatic 66cl4 mammary carcinoma cells. The control group received only vehicle. TT or mock treatments were performed twice a week for 10 minutes. Two experienced TT practitioners alternated treatments. At 26 days, metastasis to popliteal lymph nodes was determined by clonogenic assay. Changes in immune function were measured by analysis of serum cytokines and by fluorescent activated cells sorting (FACS) of immune cells from the spleen and lymph nodes. No significant differences were found in body weight gain or tumor size. Metastasis was significantly reduced in the TT-treated mice compared to mock-treated mice. Cancer significantly elevated eleven cytokines. TT significantly reduced IL-1-a, MIG, IL-1b, and MIP-2 to control/vehicle levels. FACS demonstrated that TT significantly reduced specific splenic lymphocyte subsets and macrophages were significantly elevated with cancer. Human biofield therapy had no significant effect on primary tumor but produced significant effects on metastasis and immune responses in a mouse breast cancer model.

  5. Therapeutic Touch Has Significant Effects on Mouse Breast Cancer Metastasis and Immune Responses but Not Primary Tumor Size

    Directory of Open Access Journals (Sweden)

    Gloria Gronowicz

    2015-01-01

    Full Text Available Evidence-based integrative medicine therapies have been introduced to promote wellness and offset side-effects from cancer treatment. Energy medicine is an integrative medicine technique using the human biofield to promote well-being. The biofield therapy chosen for study was Therapeutic Touch (TT. Breast cancer tumors were initiated in mice by injection of metastatic 66cl4 mammary carcinoma cells. The control group received only vehicle. TT or mock treatments were performed twice a week for 10 minutes. Two experienced TT practitioners alternated treatments. At 26 days, metastasis to popliteal lymph nodes was determined by clonogenic assay. Changes in immune function were measured by analysis of serum cytokines and by fluorescent activated cells sorting (FACS of immune cells from the spleen and lymph nodes. No significant differences were found in body weight gain or tumor size. Metastasis was significantly reduced in the TT-treated mice compared to mock-treated mice. Cancer significantly elevated eleven cytokines. TT significantly reduced IL-1-a, MIG, IL-1b, and MIP-2 to control/vehicle levels. FACS demonstrated that TT significantly reduced specific splenic lymphocyte subsets and macrophages were significantly elevated with cancer. Human biofield therapy had no significant effect on primary tumor but produced significant effects on metastasis and immune responses in a mouse breast cancer model.

  6. Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1

    Science.gov (United States)

    Borges, Andrew Rosa; Wieczorek, Lindsay; Johnson, Benitra; Benesi, Alan J.; Brown, Bruce K.; Kensinger, Richard D.; Krebs, Fred C.; Wigdahl, Brian; Blumenthal, Robert; Puri, Anu; McCutchan, Francine E.; Birx, Deborah L.; Polonis, Victoria R.; Schengrund, Cara-Lynne

    2010-01-01

    Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3’-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC50s ranging from 0.1 – 7.4 µg/ml. Inhibition of Env-mediated membrane fusion by MVC was also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions. PMID:20880566

  7. Recovery of humoral immunity parameters in mice under a long-term action of tritium oxide

    International Nuclear Information System (INIS)

    Kirillova, E.N.; Man'ko, V.M.; Muksinova, K.N.

    1986-01-01

    Using the mice-males of the CBA line at the age of 10-12 weeks and body mass of 20-23 g the recovery value of quantitative and qualitative factors of humoral immunity under a long-term action of tritium oxide which has been injected during 6 months in the quantity of 370 kBq per 1g of body mass (cumulative dose 8.73 Gy). The long-term internal mice irradiation with tritium oxide resulted in marked devastation of central and peripheral organs of immune system. An earlier and complete recovery of cells quantity in the bone marrow and spleen, recover up to 50% in lymphnodes and minimum repopulation (from 10 to 20%) in thymus as compared with tested animals of the same age is pointed out. In experimental mice CFU 5 pool decrease in bone marrow and spleen is found. CFUs content in the spleen recovered up to the norm, whereas in the bone marrow it constituted not more than 55% of the control. Deep function injury of V-lymphocyte and T - helper precursors the activity of which has not recovered during the whole observation period. The long-term tritium oxide intake lead to antibodies production suppression (by 30-50%), the tendency to the decrease of antibody formation of these animals has been conserved up to the end of life. The functional activity of T - suppressors in humoral response to thymus-dependent antigen during the remote periods upon long-term irradiation decreased more than twice

  8. Characterization of serum antibodies from women immunized with Gardasil: A study of HPV-18 infection of primary human keratinocytes.

    Science.gov (United States)

    Wang, Hsu-Kun; Wei, Qing; Moldoveanu, Zina; Huh, Warner K; Vu, Huong Lan; Broker, Thomas R; Mestecky, Jiri; Chow, Louise T

    2016-06-08

    The prevalent human papillomaviruses (HPVs) infect human epithelial tissues. Infections by the mucosotropic HPV genotypes cause hyperproliferative ano-genital lesions. Persistent infections by high-risk (HR) HPVs such as HPV-16, HPV-18 and related types can progress to high grade intraepithelial neoplasias and cancers. Prophylactic HPV vaccines are based on DNA-free virus-like particles (VLPs) composed of the major capsid protein L1 of HPV-16, -18, -6 and -11 (Gardasil) or HPV-16 and -18 (Cervarix). Sera from vaccinated animals effectively prevent HPV pseudovirions to infect cell lines and mouse cervical epithelia. Both vaccines have proven to be highly protective in people. HPV pseudovirions are assembled in HEK293TT cells from matched L1 and L2 capsid proteins to encapsidate a reporter gene. Pseudovirions and genuine virions have structural differences and they infect cell lines or primary human keratinocytes (PHKs) with different efficiencies. In this study, we show that sera and isolated IgG from women immunized with Gardasil prevent authentic HPV-18 virions from infecting PHKs, whereas non-immune sera and purified IgG thereof are uniformly ineffective. Using early passage PHKs, neutralization is achieved only if immune sera are added within 2-4h of infection. We attribute the timing effect to a conformational change in HPV virions, thought to occur upon initial binding to heparan sulfate proteoglycans (HSPG) on the cell surface. This interpretation is consistent with the inability of immune IgG bound to or taken up by PHKs to neutralize the virus. Interestingly, the window of neutralization increases to 12-16h in slow growing, late passage PHKs, suggestive of altered cell surface molecules. In vivo, this window might be further lengthened by the time required to activate the normally quiescent basal cells to become susceptible to infection. Our observations help explain the high efficacy of HPV vaccines. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. MiRNA-506 promotes primary biliary cholangitis-like features in cholangiocytes and immune activation

    NARCIS (Netherlands)

    Erice, Oihane; Munoz-Garrido, Patricia; Vaquero, Javier; Perugorria, Maria J.; Fernandez-Barrena, Maite G.; Saez, Elena; Santos-Laso, Alvaro; Arbelaiz, Ander; Jimenez-Agüero, Raul; Fernandez-Irigoyen, Joaquin; Santamaria, Enrique; Torrano, Verónica; Carracedo, Arkaitz; Ananthanarayanan, Meenakshisundaram; Marzioni, Marco; Prieto, Jesus; Beuers, Ulrich; Oude Elferink, Ronald P.; LaRusso, Nicholas F.; Bujanda, Luis; Marin, Jose J. G.; Banales, Jesus M.

    2017-01-01

    Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease associated with autoimmune phenomena targeting intrahepatic bile duct cells (cholangiocytes). Although PBC etiopathogenesis still remains obscure, development of anti-mitochondrial auto-antibodies against pyruvate dehydrogenase

  10. Contrasting the in situ behavior of a memory B cell clone during primary and secondary immune responses.

    Science.gov (United States)

    Vora, K A; Tumas-Brundage, K; Manser, T

    1999-10-15

    Whether memory B cells possess altered differentiative potentials and respond in a qualitatively distinct fashion to extrinsic signals as compared with their naive precursors is a current subject of debate. We have investigated this issue by examining the participation of a predominant anti-arsonate clonotype in the primary and secondary responses in the spleens of A/J mice. While this clonotype gives rise to few Ab-forming cells (AFC) in the primary response, shortly after secondary immunization its memory cell progeny produce a massive splenic IgG AFC response, largely in the red pulp. Extensive clonal expansion and migration take place during the secondary AFC response but Ab V region somatic hypermutation is not reinduced. The primary and secondary germinal center (GC) responses of this clonotype are both characterized by ongoing V gene hypermutation and phenotypic selection, little or no inter-GC migration, and derivation of multiple, spatially distinct GCs from a single progenitor. However, the kinetics of these responses differ, with V genes containing a high frequency of total as well as affinity-enhancing mutations appearing rapidly in secondary GCs, suggesting either recruitment of memory cells into this response, or accelerated rates of hypermutation and selection. In contrast, the frequency of mutation observed per V gene does not increase monotonically during the primary GC response of this clonotype, suggesting ongoing emigration of B cells that have sustained affinity- and specificity-enhancing mutations.

  11. CD8+ T cells are preferentially activated during primary low dose leishmania major infection but are completely dispensable during secondary anti-Leishmania immunity.

    Science.gov (United States)

    Okwor, Ifeoma B; Jia, Ping; Mou, Zhirong; Onyilagha, Chukwunonso; Uzonna, Jude E

    2014-01-01

    We previously showed that CD8+ T cells are required for optimal primary immunity to low dose Leishmania major infection. However, it is not known whether immunity induced by low dose infection is durable and whether CD8+ T cells contribute to secondary immunity following recovery from low dose infection. Here, we compared primary and secondary immunity to low and high dose L. major infections and assessed the influence of infectious dose on the quality and magnitude of secondary anti-Leishmania immunity. In addition, we investigated the contribution of CD8+ T cells in secondary anti-Leishmania immunity following recovery from low and high dose infections. We found that the early immune response to low and high dose infections were strikingly different: while low dose infection preferentially induced proliferation and effector cytokine production by CD8+ T cells, high dose infection predominantly induced proliferation and cytokine production by CD4+ T cells. This differential activation of CD4+ and CD8+ T cells by high and low dose infections respectively, was imprinted during in vitro and in vivo recall responses in healed mice. Both low and high dose-infected mice displayed strong infection-induced immunity and were protected against secondary L. major challenge. While depletion of CD4+ cells in mice that healed low and high dose infections abolished resistance to secondary challenge, depletion of CD8+ cells had no effect. Collectively, our results show that although CD8+ T cells are preferentially activated and may contribute to optimal primary anti-Leishmania immunity following low dose infection, they are completely dispensable during secondary immunity.

  12. Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines

    NARCIS (Netherlands)

    Blok, B.A.; Arts, R.J.W.; Crevel, R. van; Benn, C.S.; Netea, M.G.

    2015-01-01

    An increasing body of evidence shows that the innate immune system has adaptive characteristics that involve a heterologous memory of past insults. Both experimental models and proof-of-principle clinical trials show that innate immune cells, such as monocytes, macrophages, and NK cells, can provide

  13. Trained innate immunity as underlying mechanism for the long-term, nonspecific effects of vaccines

    DEFF Research Database (Denmark)

    Blok, Bastiaan A; Arts, Rob J W; van Crevel, Reinout

    2015-01-01

    An increasing body of evidence shows that the innate immune system has adaptive characteristics that involve a heterologous memory of past insults. Both experimental models and proof-of-principle clinical trials show that innate immune cells, such as monocytes, macrophages, and NK cells, can...

  14. Diagnostic value of DIAGNOdent in detecting caries under composite restorations of primary molars

    Directory of Open Access Journals (Sweden)

    Ava Vali Sichani

    2016-01-01

    Conclusion: DIAGNOdent showed a greater accuracy in detecting secondary caries under primary molar restorations, compared to radiographs. Although DIAGNOdent is an effective method for detecting caries under composite restorations, it is better to be used as an adjunctive method alongside other detecting procedures.

  15. Pediatric immunization-related safety incidents in primary care: A mixed methods analysis of a national database

    OpenAIRE

    Rees, Philippa; Edwards, Adrian; Powell, Colin; Evans, Huw Prosser; Carter, Ben; Hibbert, Peter; Makeham, Meredith; Sheikh, Aziz; Donaldson, Liam; Carson-Stevens, Andrew

    2015-01-01

    Background\\ud \\ud Children are scheduled to receive 18–20 immunizations before their 18th birthday in England and Wales; this approximates to 13 million vaccines administered per annum. Each immunization represents a potential opportunity for immunization-related error and effective immunization is imperative to maintain the public health benefit from immunization. Using data from a national reporting system, this study aimed to characterize pediatric immunization-related safety incident repo...

  16. Viral phenotype and immune response in primary human immunodeficiency virus type 1 infection

    NARCIS (Netherlands)

    Roos, M. T.; Lange, J. M.; de Goede, R. E.; Coutinho, R. A.; Schellekens, P. T.; Miedema, F.; Tersmette, M.

    1992-01-01

    Nineteen individuals were studied for virologic and immunologic events during primary human immunodeficiency virus type 1 (HIV-1) infection. In 16 individuals only non-syncytium-inducing (NSI) isolates were detected; syncytium-inducing (SI) isolates were obtained from 3. Studies of

  17. Noise-Immune Cavity-Enhanced Optical Heterodyne Molecular Spectrometry Modelling Under Saturated Absorption

    Science.gov (United States)

    Dupré, Patrick

    2015-06-01

    The Noise-Immune Cavity-Enhanced Optical Heterodyne Molecular Spectrometry (NICE-OHMS) is a modern technique renowned for its ultimate sensitivity, because it combines long equivalent absorption length provided by a high finesse cavity, and a detection theoretically limited by the sole photon-shot-noise. One fallout of the high finesse is the possibility to accumulating strong intracavity electromagnetic fields (EMF). Under this condition, molecular transitions can be easy saturated giving rise to the usual Lamb dips (or hole burning). However, the unusual shape of the basically trichromatic EMF (due to the RF lateral sidebands) induces nonlinear couplings, i.e., new crossover transitions. An analytical methodology will be presented to calculate spectra provided by NICE-OHMS experiments. It is based on the solutions of the equations of motion of an open two-blocked-level system performed in the frequency-domain (optically thin medium). Knowing the transition dipole moment, the NICE-OHMS signals (``absorption-like'' and ``dispersion-like'') can be simulated by integration over the Doppler shifts and by paying attention to the molecular Zeeman sublevels and to the EMF polarization The approach has been validated by discussion experimental data obtained on two transitions of {C2H2} in the near-infrared under moderated saturation. One of the applications of the saturated absorption is to be able to simultaneously determine the transition intensity and the density number while only one these 2 quantities can only be assessed in nonlinear absorption. J. Opt. Soc. Am. B 32, 838 (2015) Optics Express 16, 14689 (2008)

  18. Beryllium-specific immune response in primary cells from healthy individuals

    International Nuclear Information System (INIS)

    Chaudhary, Anu; Sauer, Nancy N.; Gupta, Goutam

    2004-01-01

    The effect of beryllium (Be) exposure has been extensively studied in patients with chronic beryllium disease (CBD). CBD patients carry mutated MHC class II alleles and show a hyperproliferation of T cells upon Be exposure. The exact mechanism of Be-induced T-cell proliferation in these patients is not clearly understood. It is also not known how the inflammatory and suppressive cytokines maintain a balance in healthy individuals and how this balance is lost in CBD patients. To address these issues, we have initiated cellular and biochemical studies to identify Be-responsive cytokines and other cellular markers that help maintain a balance in healthy individuals. We have established an immune cell model derived from a mixture of peripheral blood mononuclear cells (PBMCs) and dendritic cells (DCs). In this article, we demonstrate that pro-inflammatory cytokine IL6 shows decreased release whereas suppressive cytokine IL10 shows enhanced release after 5-10 h of Be treatment. Furthermore, the Be-specific pattern of IL6 and IL10 release is dependent upon induction of threonine phosphorylation of a 45 kDa cytosolic protein (p45), as early as 90 min after Be treatment. Pharmacological inhibition of phosphatidylinositol 3' kinase (PI3'K) by wortmannin and p38 mitogen-activated protein kinase (MAPK) by SB203580 reveal that PI3'K mediates Be-specific p45 phosphorylation and IL6 release, whereas p38 MAPK regulates the release of IL6 and IL10 and the phosphorylation of p45 independent of metal-salt treatment. While the IL10 and IL6 release pathways are uncoupled in these cells, they are linked to phosphorylation of p45. These findings suggest that the balance between IL10 and IL6 release and the correlated p45 phosphorylation are important components of the Be-mediated immune response in healthy individuals

  19. Multivalent dendrimeric compounds containing carbohydrates expressed on immune cells inhibit infection by primary isolates of HIV-1

    International Nuclear Information System (INIS)

    Rosa Borges, Andrew; Wieczorek, Lindsay; Johnson, Benitra; Benesi, Alan J.; Brown, Bruce K.; Kensinger, Richard D.; Krebs, Fred C.; Wigdahl, Brian; Blumenthal, Robert; Puri, Anu; McCutchan, Francine E.; Birx, Deborah L.; Polonis, Victoria R.; Schengrund, Cara-Lynne

    2010-01-01

    Specific glycosphingolipids (GSL), found on the surface of target immune cells, are recognized as alternate cell surface receptors by the human immunodeficiency virus type 1 (HIV-1) external envelope glycoprotein. In this study, the globotriose and 3'-sialyllactose carbohydrate head groups found on two GSL were covalently attached to a dendrimer core to produce two types of unique multivalent carbohydrates (MVC). These MVC inhibited HIV-1 infection of T cell lines and primary peripheral blood mononuclear cells (PBMC) by T cell line-adapted viruses or primary isolates, with IC 50 s ranging from 0.1 to 7.4 μg/ml. Inhibition of Env-mediated membrane fusion by MVC was also observed using a dye-transfer assay. These carbohydrate compounds warrant further investigation as a potential new class of HIV-1 entry inhibitors. The data presented also shed light on the role of carbohydrate moieties in HIV-1 virus-host cell interactions. -- Research Highlights: →Multivalent carbohydrates (MVCs) inhibited infection of PBMCs by HIV-1. →MVCs inhibited infection by T cell line-adapted viruses. →MVCs inhibited infection by primary isolates of HIV-1. →MVCs inhibited Env-mediated membrane fusion.

  20. A mathematical model of the immune and neuroendocrine systems mutual regulation under the technogenic chemical factors impact.

    Science.gov (United States)

    Zaitseva, N V; Kiryanov, D A; Lanin, D V; Chigvintsev, V M

    2014-01-01

    The concept of the triad regulatory metasystem, which includes the neuroendocrine and immune regulation systems, is currently generally accepted. Changes occurring in each of the regulatory systems in response to the impact of technogenic chemical factors are also well known. This paper presents mathematical models of the immune and neuroendocrine system functioning, using the interaction between these systems in response to bacterial invasion as an example, and changes in their performance under exposure to chemical factors, taking into account the stage of functional disorders in a producing organ, using the performance of the bone marrow as an example.

  1. The ratio of Treg/Th17 cells correlates with the disease activity of primary immune thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Lili Ji

    Full Text Available BACKGROUND: Primary immune thrombocytopenia (ITP is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. Regulatory T (Treg cells and T helper type 17 (Th17 cells are two subtypes of CD4(+ T helper (Th cells. They play opposite roles in immune tolerance and autoimmune diseases, while they share a common differentiation pathway. The imbalance of Treg/Th17 has been demonstrated in several autoimmune diseases. In this study, we aimed to investigate the ratio of the number of Treg cells to the number of Th17 cells in ITP patients and evaluate the clinical implications of the alterations in this ratio. METHODS: Thirty adult patients with newly diagnosed ITP enrolled in this study. Twelve patients had been clinically followed up for 12 months. The percentages of CD4(+CD25(hiFoxp3(+ Treg cells and CD3(+CD4(+IL-17-producing Th17 cells in these patients and healthy controls (n = 17 were longitudinally analyzed by flow cytometry. RESULTS: The percentage of Treg cells in ITP patients was significantly lower than that of healthy controls, and the percentage of Th17 cells increased significantly at disease onset. The ratio of Treg/Th17 correlated with the disease activity. CONCLUSION: The ratio of Treg/Th17 might be relevant to the clinical diversity of ITP patients, and this Treg/Th17 ratio might have prognostic role in ITP patients.

  2. Studies on herd-immunity and primary versus secondary infection of VHSV in challenge and vaccination trials with rainbow trout

    DEFF Research Database (Denmark)

    Lorenzen, Ellen; Kjær, Torben Egil; Lorenzen, Niels

    Abstract for Scofda meeting 4-5.11.09 Studies on herd-immunity effect and primary versus secondary infection of VHSV by Ellen Lorenzen, Torben Eigil Kjær & Niels Lorenzen, National Veterinary Laboratory, Århus The phenomenon of “herd-immunity” is one of the basal principles behind vaccination...... interpreted this as an effect of herd-immunity, where the vaccinated fish protected the naïve fish, probably by secreting less virus compared to the naïve fish. We tried to demonstrate this phenomenon in 3 later experiments, but without success, probably due to a too high challenge load in relation...... as well as selective breeding, i.e. the more non-susceptible individuals in a population, the lower the risk of disease among susceptible individuals. Thus as part of a recent field trial with a VHS-DNA-vaccine vaccinated as well as naïve fish from a Danish fish farm were brought to the laboratory...

  3. Early appearance of germinal center–derived memory B cells and plasma cells in blood after primary immunization

    Science.gov (United States)

    Blink, Elizabeth J.; Light, Amanda; Kallies, Axel; Nutt, Stephen L.; Hodgkin, Philip D.; Tarlinton, David M.

    2005-01-01

    Immunization with a T cell–dependent antigen elicits production of specific memory B cells and antibody-secreting cells (ASCs). The kinetic and developmental relationships between these populations and the phenotypic forms they and their precursors may take remain unclear. Therefore, we examined the early stages of a primary immune response, focusing on the appearance of antigen-specific B cells in blood. Within 1 wk, antigen-specific B cells appear in the blood with either a memory phenotype or as immunoglobulin (Ig)G1 ASCs expressing blimp-1. The memory cells have mutated VH genes; respond to the chemokine CXCL13 but not CXCL12, suggesting recirculation to secondary lymphoid organs; uniformly express B220; show limited differentiation potential unless stimulated by antigen; and develop independently of blimp-1 expression. The antigen-specific IgG1 ASCs in blood show affinity maturation paralleling that of bone marrow ASCs, raising the possibility that this compartment is established directly by blood-borne ASCs. We find no evidence for a blimp-1–expressing preplasma memory compartment, suggesting germinal center output is restricted to ASCs and B220+ memory B cells, and this is sufficient to account for the process of affinity maturation. PMID:15710653

  4. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    DEFF Research Database (Denmark)

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole...... blood (WB) clot formation in ITP. Blood from ITP patients (n = 12) was drawn into tubes containing 3·2% citrate and corn trypsin inhibitor 18·3 μg/ml. WB [mean platelet count 22 × 10(9) /l (range 0-42)] was spiked in vitro with buffer, donor platelets (+40 × 10(9) /l), rFVIIa (1 or 4 μg/ml), fibrinogen...... low platelet counts. These data suggest that rFVIIa combined with fibrinogen corrects the coagulopathy of ITP even at very low platelet counts, and may represent an alternative to platelet transfusion....

  5. Rate Adaptation for Cognitive Radio under Interference from Primary Spectrum User

    OpenAIRE

    Popovski, Petar; Yomo, Hiroyuki; Nishimori, Kentaro; Di Taranto, Rocco

    2007-01-01

    A cognitive radio can operate as a secondary system in a given spectrum. This operation should use limited power in order not to disturb the communication by primary spectrum user. Under such conditions, in this paper we investigate how to maximize the spectral efficiency in the secondary system. A secondary receiver observes a multiple access channel of two users, the secondary and the primary transmitter, respectively. We show that, for spectrally-efficient operation, the secondary system s...

  6. Immunosenescence Is Associated With Altered Gene Expression And Epigenetic Regulation In Primary And Secondary Immune Organs

    Directory of Open Access Journals (Sweden)

    Corinne eSidler

    2013-10-01

    Full Text Available Deterioration of the immune system (immunosenescence with age is associated with an increased susceptibility to infection, autoimmune disease and cancer, and reduced responsiveness to vaccination. Immunosenescence entails a reduced supply of naïve T cells from the thymus and increased specialization of peripheral T cell clones. Both thymic involution and peripheral T cell homeostasis are thought to involve cellular senescence. In order to analyze this at the molecular level, we studied gene expression profiles, epigenetic status and genome stability in the thymus and spleen of 1-month, 4-month and 18-month-old Long Evans rats. In the thymus, altered gene expression, DNA and histone hypomethylation, increased genome instability and apoptosis were observed in 18-month-old animals compared to 1- and 4-month-old animals. In the spleen, alterations in gene expression and epigenetic regulation occurred already by the age of 4 months compared to 1 month and persisted in 18-month-old compared to 1-month-old rats. In both organs, these changes were accompanied by the altered composition of resident T cell populations. Our study suggests that both senescence and apoptosis may be involved in altered organ function.

  7. Reduced PTEN involved in primary immune thrombocytopenia via contributing to B cell hyper-responsiveness.

    Science.gov (United States)

    Wang, Shixuan; Guan, Yue; Wang, Yunlong; Li, Huiyuan; Zhang, Donglei; Ju, Mankai; Hao, Yating; Song, Xuewen; Sun, Boyang; Dou, Xueqing; Yang, Renchi

    2018-01-01

    Phosphatase and tensin homolog (PTEN) is thought to mediate B cell activation by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. This pathway is important for activation, growth, and proliferation. Although enhanced B cell receptor (BCR) signaling contributes to increased B cell activity in immune thrombocytopenia (ITP), the role of PTEN is unclear. In this study, we analyzed B cells of ITP patients using flow cytometry and found that all B cell subsets, excluding memory B cells, showed lower PTEN expression than cells from healthy controls (HCs). PTEN expression was also positively-correlated with blood platelet count, although levels were lower in patients who were platelet autoantibody-positive compared with those who were negative. We next evaluated the effects of IL-21, anti-IgM, and CD40L on PTEN expression, demonstrating that they were potent inducers of PTEN expression in normal B cells. Induction of PTEN expression was lower in B cells of ITP patients. We also found that IL-21 increased the proportion of plasma cells in peripheral blood mononuclear cells (PBMCs) of ITP patients, independent of BCR signaling. This effect was reproducible using PTEN inhibitors with cells from HCs. In summary, defective PTEN expression, regulation, and function all contribute to the B cell hyper-responsiveness that associates with ITP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Mathematical modeling on T-cell mediated adaptive immunity in primary dengue infections.

    Science.gov (United States)

    Sasmal, Sourav Kumar; Dong, Yueping; Takeuchi, Yasuhiro

    2017-09-21

    At present, dengue is the most common mosquito-borne viral disease in the world, and the global dengue incidence is increasing day by day due to climate changing. Here, we present a mathematical model of dengue viruses (DENVs) dynamics in micro-environment (cellular level) consisting of healthy cells, infected cells, virus particles and T-cell mediated adaptive immunity. We have considered the explicit role of cytokines and antibody in our model. We find that the virus load goes down to zero within 6 days as it is common for DENV infection. From our analysis, we have identified the important model parameters and done the numerical simulation with respect to such important parameters. We have shown that the cytokine mediated virus clearance plays a very important role in dengue dynamics. It can change the dynamical behavior of the system and causes essential extinction of the virus. Finally, we have incorporated the antiviral treatment for dengue in our model and shown that the basic reproduction number is directly proportional to the antiviral treatment effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Effects of hepatitis B vaccine boosters on anti-HBs-negative children after primary immunization.

    Science.gov (United States)

    Lu, Shunshun; Ren, Jingjing; Li, Qian; Jiang, Zhenggang; Chen, Yongdi; Xu, Kaijin; Ruan, Bing; Yang, Shigui; Xie, Tiansheng; Yang, Linna; Li, Jing; Yao, Jun

    2017-04-03

    This study was aimed at evaluating the changes of hepatitis B surface antibody (anti-HBs) titer after booster vaccinations in 5-15-year-old children with negative antibodies (vaccination during infancy. The participants were divided into 3 groups according to their pre-booster anti-HBs level: Group I, vaccination (0-1-6 month, 20 µg), and changes in the levels of antibodies were examined at 4 time-points (one month after the first and the third dose, one year and 5 years after the third dose). The seroprotective rate (defined as anti-HBs ≥10.0 mIU/mL) among 225 subjects at the 4 time-points were 93.8%, 100%, 83.6% and 73.4%, respectively (χ 2 = 90.29, p anti-HBs geometric mean titer (GMT) in Group III were always higher than those in the other 2 groups (all p effect of a 3 -dose booster revaccination is good, and the booster-induced immune response was correlated with the pre-booster titer level, and ≥1.0 mIU/mL ensuring a robust positive response, whereas titers below this value may indicate the need for a course of booster vaccination.

  10. Mothers’ Characteristics and Immunization Status of Under-Five Children in Ojo Local Government Area, Lagos State, Nigeria

    Directory of Open Access Journals (Sweden)

    John Lekan Oyefara

    2014-08-01

    Full Text Available Immunization is a key element of public health, a pre-requisite to social and economic development, and a crucial element that enables every child to reach his or her full physical and intellectual potential. It is a prevention against various child killer diseases such as tuberculosis (Bacillus Calmette Gurine [BCG], tetanus, whooping cough, diphtheria, poliomyelitis, hepatitis B, yellow fever, and measles. The main objective of this study is to examine the relationships between household characteristics, social mobilization, and immunization status of under-5 children in Lagos metropolis, Nigeria. To achieve this objective, a non-experimental research design was adopted. The research method utilized in the design is cross-sectional survey. The sampled study location is Ojo local government area of Lagos State. A total of 265 respondents were randomly sampled for the survey using multistage random sampling technique. Generated data were analyzed using univariate, bivariate, and multivariate statistical techniques. The findings of the study reveal significant relationship between women’s level of education and full immunization of their children. Specifically, 38.9% of women without any formal education had fully immunized their children compared with 86.9% of women with secondary education. In addition, 90.9% of women who assessed themselves to be average on wealth assessment compared with 45.3% of the poor had fully immunized their children. On the basis of the study’s findings, there is a need for a holistic approach that will involve all social classes and communities on child immunization to have 100% immunization coverage and minimal child morbidity and mortality in all areas of the city.

  11. Signaling through the primary cilium affects glial cell survival under a stressed environment.

    Science.gov (United States)

    Yoshimura, Kentaro; Kawate, Toyoko; Takeda, Sen

    2011-02-01

    Sensing extracellular milieu is a fundamental requirement of cells. To facilitate and specify sensory reception, mammalian cells develop an antenna-like structure denoted as the primary cilia. Nearly all interphase and nondividing cells in vertebrates have a single, nonmotile seemingly unspecialized cilium (called a primary cilium). In the central nervous system, astrocytes express primary cilia, but their function in astrocytes has not been examined. Recent studies have shown that primary cilia unite receptors and the machinery of signal-transduction components, such as Wnt and Hedgehog (Hh) signaling cascades. Although, Hh signaling cascades are known to be activated in various cells during development, their physiological functions in the adult nervous system, especially in glial cells, are still unknown. In this study, we reveal that glial primary cilia receive the Hh signal and regulate the survival of astrocytes under stressed conditions such as starvation. Interestingly, increased astrocyte survival was reversed by knockdown of Ift20, which is one of the main components for building primary cilia. These results collectively indicate that the activation of Hh signaling in the primary cilia plays an important role in the survival of astrocytes under stressed conditions. © 2010 Wiley-Liss, Inc.

  12. Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D.

    Science.gov (United States)

    Wei, Ran; Christakos, Sylvia

    2015-09-24

    Non-classical actions of vitamin D were first suggested over 30 years ago when receptors for the active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), were detected in various tissues and cells that are not associated with the regulation of calcium homeostasis, including activated human inflammatory cells. The question that remained was the biological significance of the presence of vitamin D receptors in the different tissues and cells and, with regard to the immune system, whether or not vitamin D plays a role in the normal immune response and in modifying immune mediated diseases. In this article findings indicating that vitamin D is a key factor regulating both innate and adaptive immunity are reviewed with a focus on the molecular mechanisms involved. In addition, the physiological significance of vitamin D action, as suggested by in vivo studies in mouse models is discussed. Together, the findings indicate the importance of 1,25(OH)2D3 as a regulator of key components of the immune system. An understanding of the mechanisms involved will lead to potential therapeutic applications for the treatment of immune mediated diseases.

  13. MHC class II restricted innate-like double negative T cells contribute to optimal primary and secondary immunity to Leishmania major.

    Science.gov (United States)

    Mou, Zhirong; Liu, Dong; Okwor, Ifeoma; Jia, Ping; Orihara, Kanami; Uzonna, Jude Ezeh

    2014-09-01

    Although it is generally believed that CD4(+) T cells play important roles in anti-Leishmania immunity, some studies suggest that they may be dispensable, and that MHC II-restricted CD3(+)CD4(-)CD8(-) (double negative, DN) T cells may be more important in regulating primary anti-Leishmania immunity. In addition, while there are reports of increased numbers of DN T cells in Leishmania-infected patients, dogs and mice, concrete evidence implicating these cells in secondary anti-Leishmania immunity has not yet been documented. Here, we report that DN T cells extensively proliferate and produce effector cytokines (IFN-γ, TNF and IL-17) and granzyme B (GrzB) in the draining lymph nodes and spleens of mice following primary and secondary L. major infections. DN T cells from healed mice display functional characteristics of protective anti-Leishmania memory-like cells: rapid and extensive proliferation and effector cytokines production following L. major challenge in vitro and in vivo. DN T cells express predominantly (> 95%) alpha-beta T cell receptor (αβ TCR), are Leishmania-specific, restricted mostly by MHC class II molecules and display transcriptional profile of innate-like genes. Using in vivo depletion and adoptive transfer studies, we show that DN T cells contribute to optimal primary and secondary anti-Leishmania immunity in mice. These results directly identify DN T cells as important players in effective and protective primary and secondary anti-L. major immunity in experimental cutaneous leishmaniasis.

  14. Histological Architecture Underlying Brain-Immune Cell-Cell Interactions and the Cerebral Response to Systemic Inflammation.

    Science.gov (United States)

    Shimada, Atsuyoshi; Hasegawa-Ishii, Sanae

    2017-01-01

    Although the brain is now known to actively interact with the immune system under non-inflammatory conditions, the site of cell-cell interactions between brain parenchymal cells and immune cells has been an open question until recently. Studies by our and other groups have indicated that brain structures such as the leptomeninges, choroid plexus stroma and epithelium, attachments of choroid plexus, vascular endothelial cells, cells of the perivascular space, circumventricular organs, and astrocytic endfeet construct the histological architecture that provides a location for intercellular interactions between bone marrow-derived myeloid lineage cells and brain parenchymal cells under non-inflammatory conditions. This architecture also functions as the interface between the brain and the immune system, through which systemic inflammation-induced molecular events can be relayed to the brain parenchyma at early stages of systemic inflammation during which the blood-brain barrier is relatively preserved. Although brain microglia are well known to be activated by systemic inflammation, the mechanism by which systemic inflammatory challenge and microglial activation are connected has not been well documented. Perturbed brain-immune interaction underlies a wide variety of neurological and psychiatric disorders including ischemic brain injury, status epilepticus, repeated social defeat, and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. Proinflammatory status associated with cytokine imbalance is involved in autism spectrum disorders, schizophrenia, and depression. In this article, we propose a mechanism connecting systemic inflammation, brain-immune interface cells, and brain parenchymal cells and discuss the relevance of basic studies of the mechanism to neurological disorders with a special emphasis on sepsis-associated encephalopathy and preterm brain injury.

  15. Gender equality in primary immunisation

    Directory of Open Access Journals (Sweden)

    Deepak S Khismatrao

    2015-01-01

    Full Text Available Context: Immunization, a well-known and effective method of preventing childhood illnesses is basic service under primary health care. Most surveys in India measure primary immunization coverage and quality, but no "Gender Equality." Aims: Assess "Gender Equality" in primary immunization with reference to coverage, quality, and place of immunization. Settings and Design: Cross-sectional survey in a primary health center, Pune, Maharashtra using World Health Organization 30-cluster sampling method with 14 beneficiaries (7 girls and 7 boys to be selected from each cluster. Instead of 420 children, data collected for 345 children, as requisite numbers of children were not available in low population villages and also children whose mothers were not present during survey were excluded. Materials and Methods: Vaccination data collected from either records and/or history by mother. Children born on or between 13-09-2009 and 13-09-2010, were included. Statistical Analysis Used: SPSS 14.01 version with Chi-square as test of significance. Results: Of the study population, 171 (49.6% were females and 174 (50.4% males. A total of 64.1% children had immunization records with female proportion 69.0% and males 59.2%. Primary immunization coverage was 80.0%, with female proportion 82.5% and males 77.6%. One male child was completely unimmunized and remaining partially immunized, with unaware of schedule and illness of child being major reasons for partial immunization. There was no gender wise statistically significant difference observed in Primary Immunization with reference to coverage, quality, and place of immunization. Conclusions: Immunization coverage is nearing 85% benchmark with major contribution from Universal Immunization Program. Gender Equality observed in primary immunization. Preservation of immunization records by community and timely vaccinations are areas for improvement.

  16. The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

    Science.gov (United States)

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-04-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  17. Infections in non-splenectomized persistent or chronic primary immune thrombocytopenia adults: risk factors and vaccination effect.

    Science.gov (United States)

    Moulis, G; Lapeyre-Mestre, M; Palmaro, A; Sailler, L

    2017-04-01

    Essentials The risk factors for infection in immune thrombocytopenia are not well known. We conducted a national pharmacoepidemiological study. Pulmonary disease, corticosteroids and rituximab were the main risk factors for infections. Pneumococcal and influenza vaccines were protective against infections. Introduction Risk factors for infection and protective effect of vaccines in immune thrombocytopenia (ITP) patients in the era of rituximab therapy are unknown. Objectives To assess the risk factors for serious and non-serious infections (respectively, SIs and NSIs) in non-splenectomized adults treated for persistent or chronic primary ITP, including the effect of pneumococcal and influenza vaccines. Patients/Methods The population was the 2009-2012 FAITH cohort (n = 1805), which is the cohort of all incident (newly diagnosed) primary ITP adults treated > 3 months in France built into the national health insurance database (SNIIRAM). SIs were hospitalizations with any infection as the primary diagnosis code. NSIs were identified using out-of-hospital antibiotic dispensing. Cox models were performed. Results Incidence rates were 6.3/100 patient-years (95% confidence interval [CI], 5.4-7.4) for SIs (lower respiratory tract in 42.8% of the cases) and 100.5/100 patient-years (95% CI, 95.0-106.3) for NSIs. In multivariate analyses, increasing age and chronic pulmonary disease were associated with both SI and NSI occurrence. The hazard ratios (HRs) for corticosteroids and rituximab were, respectively, 3.83 (95% CI, 2.76-5.31) and 2.60 (95% CI, 1.67-4.03) for SIs and 2.46 (95% CI, 2.19-2.76) and 1.49 (95% CI, 1.28-1.74) for NSIs. Pneumococcal vaccine showed a protective effect for both SIs and NSIs (0.38 [95% CI, 0.20-0.73] and 0.52 [95% CI, 0.43-0.65], respectively), as did influenza vaccine (0.42 [95% CI, 0.27-0.64] and 0.49 [95% CI, 0.41-0.59], respectively). Conclusions Chronic pulmonary disease, corticosteroids and rituximab are the main risk factors for infections

  18. No evidence for selective follicle abortion underlying primary sex ratio adjustment in pigeons

    NARCIS (Netherlands)

    Goerlich, Vivian C.; Dijkstra, Cornelis; Groothuis, Antonius

    Primary sex ratio adjustment in birds has been extensively studied, yet the underlying physiological mechanisms are far from understood. Avian females are the heterogametic sex (ZW), and the future sex of the offspring is determined at chromosome segregation during meiosis I, shortly before the

  19. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis

    Science.gov (United States)

    Sawcer, Stephen; Hellenthal, Garrett; Pirinen, Matti; Spencer, Chris C.A.; Patsopoulos, Nikolaos A.; Moutsianas, Loukas; Dilthey, Alexander; Su, Zhan; Freeman, Colin; Hunt, Sarah E.; Edkins, Sarah; Gray, Emma; Booth, David R.; Potter, Simon C.; Goris, An; Band, Gavin; Oturai, Annette Bang; Strange, Amy; Saarela, Janna; Bellenguez, Céline; Fontaine, Bertrand; Gillman, Matthew; Hemmer, Bernhard; Gwilliam, Rhian; Zipp, Frauke; Jayakumar, Alagurevathi; Martin, Roland; Leslie, Stephen; Hawkins, Stanley; Giannoulatou, Eleni; D’alfonso, Sandra; Blackburn, Hannah; Boneschi, Filippo Martinelli; Liddle, Jennifer; Harbo, Hanne F.; Perez, Marc L.; Spurkland, Anne; Waller, Matthew J; Mycko, Marcin P.; Ricketts, Michelle; Comabella, Manuel; Hammond, Naomi; Kockum, Ingrid; McCann, Owen T.; Ban, Maria; Whittaker, Pamela; Kemppinen, Anu; Weston, Paul; Hawkins, Clive; Widaa, Sara; Zajicek, John; Dronov, Serge; Robertson, Neil; Bumpstead, Suzannah J.; Barcellos, Lisa F.; Ravindrarajah, Rathi; Abraham, Roby; Alfredsson, Lars; Ardlie, Kristin; Aubin, Cristin; Baker, Amie; Baker, Katharine; Baranzini, Sergio E.; Bergamaschi, Laura; Bergamaschi, Roberto; Bernstein, Allan; Berthele, Achim; Boggild, Mike; Bradfield, Jonathan P.; Brassat, David; Broadley, Simon A.; Buck, Dorothea; Butzkueven, Helmut; Capra, Ruggero; Carroll, William M.; Cavalla, Paola; Celius, Elisabeth G.; Cepok, Sabine; Chiavacci, Rosetta; Clerget-Darpoux, Françoise; Clysters, Katleen; Comi, Giancarlo; Cossburn, Mark; Cournu-Rebeix, Isabelle; Cox, Mathew B.; Cozen, Wendy; Cree, Bruce A.C.; Cross, Anne H.; Cusi, Daniele; Daly, Mark J.; Davis, Emma; de Bakker, Paul I.W.; Debouverie, Marc; D’hooghe, Marie Beatrice; Dixon, Katherine; Dobosi, Rita; Dubois, Bénédicte; Ellinghaus, David; Elovaara, Irina; Esposito, Federica; Fontenille, Claire; Foote, Simon; Franke, Andre; Galimberti, Daniela; Ghezzi, Angelo; Glessner, Joseph; Gomez, Refujia; Gout, Olivier; Graham, Colin; Grant, Struan F.A.; Guerini, Franca Rosa; Hakonarson, Hakon; Hall, Per; Hamsten, Anders; Hartung, Hans-Peter; Heard, Rob N.; Heath, Simon; Hobart, Jeremy; Hoshi, Muna; Infante-Duarte, Carmen; Ingram, Gillian; Ingram, Wendy; Islam, Talat; Jagodic, Maja; Kabesch, Michael; Kermode, Allan G.; Kilpatrick, Trevor J.; Kim, Cecilia; Klopp, Norman; Koivisto, Keijo; Larsson, Malin; Lathrop, Mark; Lechner-Scott, Jeannette S.; Leone, Maurizio A.; Leppä, Virpi; Liljedahl, Ulrika; Bomfim, Izaura Lima; Lincoln, Robin R.; Link, Jenny; Liu, Jianjun; Lorentzen, Åslaug R.; Lupoli, Sara; Macciardi, Fabio; Mack, Thomas; Marriott, Mark; Martinelli, Vittorio; Mason, Deborah; McCauley, Jacob L.; Mentch, Frank; Mero, Inger-Lise; Mihalova, Tania; Montalban, Xavier; Mottershead, John; Myhr, Kjell-Morten; Naldi, Paola; Ollier, William; Page, Alison; Palotie, Aarno; Pelletier, Jean; Piccio, Laura; Pickersgill, Trevor; Piehl, Fredrik; Pobywajlo, Susan; Quach, Hong L.; Ramsay, Patricia P.; Reunanen, Mauri; Reynolds, Richard; Rioux, John D.; Rodegher, Mariaemma; Roesner, Sabine; Rubio, Justin P.; Rückert, Ina-Maria; Salvetti, Marco; Salvi, Erika; Santaniello, Adam; Schaefer, Catherine A.; Schreiber, Stefan; Schulze, Christian; Scott, Rodney J.; Sellebjerg, Finn; Selmaj, Krzysztof W.; Sexton, David; Shen, Ling; Simms-Acuna, Brigid; Skidmore, Sheila; Sleiman, Patrick M.A.; Smestad, Cathrine; Sørensen, Per Soelberg; Søndergaard, Helle Bach; Stankovich, Jim; Strange, Richard C.; Sulonen, Anna-Maija; Sundqvist, Emilie; Syvänen, Ann-Christine; Taddeo, Francesca; Taylor, Bruce; Blackwell, Jenefer M.; Tienari, Pentti; Bramon, Elvira; Tourbah, Ayman; Brown, Matthew A.; Tronczynska, Ewa; Casas, Juan P.; Tubridy, Niall; Corvin, Aiden; Vickery, Jane; Jankowski, Janusz; Villoslada, Pablo; Markus, Hugh S.; Wang, Kai; Mathew, Christopher G.; Wason, James; Palmer, Colin N.A.; Wichmann, H-Erich; Plomin, Robert; Willoughby, Ernest; Rautanen, Anna; Winkelmann, Juliane; Wittig, Michael; Trembath, Richard C.; Yaouanq, Jacqueline; Viswanathan, Ananth C.; Zhang, Haitao; Wood, Nicholas W.; Zuvich, Rebecca; Deloukas, Panos; Langford, Cordelia; Duncanson, Audrey; Oksenberg, Jorge R.; Pericak-Vance, Margaret A.; Haines, Jonathan L.; Olsson, Tomas; Hillert, Jan; Ivinson, Adrian J.; De Jager, Philip L.; Peltonen, Leena; Stewart, Graeme J.; Hafler, David A.; Hauser, Stephen L.; McVean, Gil; Donnelly, Peter; Compston, Alastair

    2011-01-01

    Multiple sclerosis (OMIM 126200) is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability.1 Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals;2,3 and systematic attempts to identify linkage in multiplex families have confirmed that variation within the Major Histocompatibility Complex (MHC) exerts the greatest individual effect on risk.4 Modestly powered Genome-Wide Association Studies (GWAS)5-10 have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects play a key role in disease susceptibility.11 Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the Class I region. Immunologically relevant genes are significantly over-represented amongst those mapping close to the identified loci and particularly implicate T helper cell differentiation in the pathogenesis of multiple sclerosis. PMID:21833088

  20. The role of agri-business incentive on under-five child immunization ...

    African Journals Online (AJOL)

    A multinomial logistic regression model used to analyze the determinant of partial or noneimmunized. Maternal health practices and access to a motivating intervention are significant factors that ensure a parent/guardian's compliance to their child immunization. The study recommends sustainability and diversification of ...

  1. Impairment of antitoxic antitetanus immunity under the combined effect of radiation and heat

    International Nuclear Information System (INIS)

    Kurochkina, O.I.; Budagov, R.S.

    1990-01-01

    In experiments with mice a delay was noted in the development of secondary immune response to revaccination with a tetanic anatoxin after the combined effect of radiation and heat; the maximum antibody formation occured at later times. The low level of antitoxins within the first 10 days after the combined effect of radiation and heat correlated with the low tetanus resistance of animals

  2. Immune activation underlies a sustained clinical response to Yttrium-90 radioembolisation in hepatocellular carcinoma.

    Science.gov (United States)

    Chew, Valerie; Lee, Yun Hua; Pan, Lu; Nasir, Nurul J M; Lim, Chun Jye; Chua, Camillus; Lai, Liyun; Hazirah, Sharifah Nur; Lim, Tony Kiat Hon; Goh, Brian K P; Chung, Alexander; Lo, Richard H G; Ng, David; Filarca, Rene L F; Albani, Salvatore; Chow, Pierce K H

    2018-02-13

    Yttrium-90 (Y90)-radioembolisation (RE) significantly regresses locally advanced hepatocellular carcinoma and delays disease progression. The current study is designed to deeply interrogate the immunological impact of Y90-RE, which elicits a sustained therapeutic response. Time-of-flight mass cytometry and next-generation sequencing (NGS) were used to analyse the immune landscapes of tumour-infiltrating leucocytes (TILs), tumour tissues and peripheral blood mononuclear cells (PBMCs) at different time points before and after Y90-RE. TILs isolated after Y90-RE exhibited signs of local immune activation: higher expression of granzyme B (GB) and infiltration of CD8 + T cells, CD56 + NK cells and CD8 + CD56 + NKT cells. NGS confirmed the upregulation of genes involved in innate and adaptive immune activation in Y90-RE-treated tumours. Chemotactic pathways involving CCL5 and CXCL16 correlated with the recruitment of activated GB + CD8 + T cells to the Y90-RE-treated tumours. When comparing PBMCs before and after Y90-RE, we observed an increase in tumour necrosis factor-α on both the CD8 + and CD4 + T cells as well as an increase in percentage of antigen-presenting cells after Y90-RE, implying a systemic immune activation. Interestingly, a high percentage of PD-1 + /Tim-3 + CD8 + T cells coexpressing the homing receptors CCR5 and CXCR6 denoted Y90-RE responders. A prediction model was also built to identify sustained responders to Y90-RE based on the immune profiles from pretreatment PBMCs. High-dimensional analysis of tumour and systemic immune landscapes identified local and systemic immune activation that corresponded to the sustained response to Y90-RE. Potential biomarkers associated with a positive clinical response were identified and a prediction model was built to identify sustained responders prior to treatment. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is

  3. The Mycoplasma hyopneumoniae recombinant heat shock protein P42 induces an immune response in pigs under field conditions.

    Science.gov (United States)

    Jorge, Sérgio; de Oliveira, Natasha Rodrigues; Marchioro, Silvana Beutinger; Fisch, Andressa; Gomes, Charles Klazer; Hartleben, Cláudia Pinho; Conceição, Fabricio Rochedo; Dellagostin, Odir Antonio

    2014-09-01

    Enzootic pneumonia (EP), resulting from Mycoplasma hyopneumoniae infection is one of the most prevalent diseases in pigs and is a major cause of economic losses to the swine industry worldwide. EP is often controlled by vaccination with inactivated, adjuvanted whole-cell bacterin. However, these bacterins provide only partial protection and do not prevent M. hyopneumoniae colonization. Attempts to develop vaccines that are more efficient have made use of the recombinant DNA technology. The objective of this study was to assess the potential of recombinant M. hyopneumoniae heat shock protein P42 in vaccine preparations against EP, using piglets housed under field conditions in a M. hyopneumoniae-positive farm. The cellular and humoral immune responses were elicited after a single intramuscular inoculation of rP42 in an oil-based adjuvant, or in conjunction with whole-cell vaccine preparation. The production of INF-γ and IL-10 cytokines was quantified in the supernatant of the cultured mononuclear cells. The rP42 emulsified in oil-based adjuvant was able to trigger a strong humoral immune response. Further, it induced a cellular immune response, accompanied by the production of antibodies that reacted with the native M. hyopneumoniae protein. The rP42 mediated induction of cellular and humoral immune response in the host suggests that rP42 emulsified in an oil-based adjuvant holds promise as an effective recombinant subunit vaccine against EP. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Hypothyroidism in Cancer Patients on Immune Checkpoint Inhibitors with anti-PD1 Agents: Insights on Underlying Mechanisms.

    Science.gov (United States)

    Alhusseini, M; Samantray, J

    2017-04-01

    Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers have been reported to cause thyroid dysfunction. Little is known, however, about the underlying pathogenic mechanisms and the course of hypothyroidism that subsequently develops. In this report, we use the change in thyroglobulin and thyroid antibody levels in patients on immune therapy who develop hypothyroidism to better understand its pathogenesis as well as examine the status of hypothyroidism in the long term. Methods: We report a case series of 10 patients who developed hypothyroidism after initiation of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase (anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism was noted at 6 months. Summary: During the thyroiditis phase, 50% of the patients had elevated Tg titers, 40% had elevated anti-Tg, and 40% had elevated TSI. All of these titers decreased during the hypothyroid phase. Permanent hypothyroidism was noted in 80% of the cases. Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic mediated mechanisms and is likely to be persistent. © Georg Thieme Verlag KG Stuttgart · New York.

  5. Multiscale Modeling of Primary Cilium Deformations Under Local Forces and Shear Flows

    Science.gov (United States)

    Peng, Zhangli; Feng, Zhe; Resnick, Andrew; Young, Yuan-Nan

    2017-11-01

    We study the detailed deformations of a primary cilium under local forces and shear flows by developing a multiscale model based on the state-of-the-art understanding of its molecular structure. Most eukaryotic cells are ciliated with primary cilia. Primary cilia play important roles in chemosensation, thermosensation, and mechanosensation, but the detailed mechanism for mechanosensation is not well understood. We apply the dissipative particle dynamics (DPD) to model an entire well with a primary cilium and consider its different components, including the basal body, microtubule doublets, actin cortex, and lipid bilayer. We calibrate the mechanical properties of individual components and their interactions from experimental measurements and molecular dynamics simulations. We validate the simulations by comparing the deformation profile of the cilium and the rotation of the basal body with optical trapping experiments. After validations, we investigate the deformation of the primary cilium under shear flows. Furthermore, we calculate the membrane tensions and cytoskeleton stresses, and use them to predict the activation of mechanosensitive channels.

  6. Treatment of primary brain lymphoma without immune deficiency, The importance of chemotherapy before radiotherapy

    Directory of Open Access Journals (Sweden)

    Keihani M

    1999-09-01

    Full Text Available The purpose of this study was to find a more efficacious treatment for patients with primary central nervous system Lymphoma using chemotherapy. The objective was to determine the optimal time for radiotherapy treatment in relation to chemotherapy. Retrospective evaluation in patients with brain lymphoma was conducted from 1992 to 1998. Twenty-three patients were evaluated. Patients were divided into two groups based on the timing of radiotherapy in relation to the chemotherapy. The first group of patients (n=13 initially received radiotherapy followed by chemotherapy. Five of these patients receied classic CHOP (cyclophosphamide, Doxorubicine, Vincistine and Prednisone, six patients received Cis-platin (60 Megs/M2 and Etoposide (120 Megs/M2 and two patients received Cis-platin (60 Megs/M2, Etoposide (120 Megs/M2 and Cytarabine (600 Megs/M2 every 2 to 3 weeks. The second group of patients (Group II, n=10 received the followeing treatment regimen: a course of BCNU 120 Megs/M2 with Ifosfamide 1200 Megs/M2, Mesna and Etoposide 120 Megs/M2 on the first day of treatment (course A. Two weeks later, treatment was continued with a course of Cis-platin 35 Megs/M2 and Cytarabine 600 Megs/M2 (course B. The treatment was continued 14 days later with a course of Mitoxantron 12 Megs/M2, Ifosfamide 1200 Megs/M2 puls Mesna (course C. After the fourth week of chemotherapy, these patients received radiotherapy to the brain (5000 RADS in 4 weeks. During radiotherapy and at the beginning of course chemotherapy, intrathecal therapy with Methorexate 12 Megs/M2 and Cytarabine 60 Megs/M2 was given. Immediately after radiotherapy, the same chemothotrexate 12 Megs/M2 and Cytarabine 60 Megs/M2 was given. Immediately after radiotherapy, the same chemotherapy treatment was repeated to a total of 3 times. After complete clearance of the tumor determined by MRI and absence of tumor cells in the spinal fluid, the chemotherapeutic regimen was repeated one last time. The

  7. Effects of dietary selenium and vitamin E on immune response and biological blood parameters of broilers reared under thermoneutral or heat stress conditions

    Science.gov (United States)

    Habibian, Mahmood; Ghazi, Shahab; Moeini, Mohammad Mehdi; Abdolmohammadi, Alireza

    2014-07-01

    A study was conducted using 360 broiler chickens to evaluate the effects of dietary vitamin E (0, 125 and 250 mg/kg), selenium (Se, 0, 0.5 and 1 mg/kg), or their different combinations on immune response and blood biological parameters of broilers raised under either thermoneutral (TN, 23.9 °C constant) or heat stress (HS, 23.9 to 37 °C cycling) conditions. Humoral immunity was assessed by intravenous injection of 7 % sheep red blood cell (SRBC) followed by evaluation of serum for antibody titers in primary and secondary responses. Heterophil to lymphocyte (H/L) ratio also determined as an indicator of stress. Furthermore, at the end of the experiment, birds were bled for determination of some biological parameters. There was a significant reduction in body weight and feed intake, but the feed conversion ratio increased when the birds were exposed to HS ( P vitamin E and Se ( P > 0.05), whereas feed conversion was improved significantly by 125 mg/kg vitamin E ( P vitamin E resulted in improvement of primary and secondary antibody responses both in TN and HS broilers ( P Vitamin E and Se had interactive effects on anti-SRBC titers; however, no consistent differences were found between dietary levels during the study. The H/L ratio decreased by feeding vitamin E at both levels either under HS or TN conditions ( P < 0.05). The serum concentrations of glucose, triglycerides, total cholesterol, and LDL-cholesterol were increased but serum HDL-cholesterol decreased in HS broilers ( P < 0.05).

  8. Immunizing Children

    Directory of Open Access Journals (Sweden)

    Geraldine Jody Macdonald

    2014-11-01

    Full Text Available This article addresses the complex contexts within which Canadian health professionals engage in immunizing children and focuses on the Canadian practice guidelines and current scientific evidence that direct Canadian health professional competencies. The article begins by presenting two current global vaccine initiatives and links these to immunization in Canada. A selected literature review identifies current best immunization practices. With the purpose of promoting quality improvement, three key Canadian immunization competencies for health professional are highlighted: communication with parents, including those who are experiencing vaccine hesitancy; administration of immunizing agents; and documentation of immunizations. Health professionals are encouraged to reflect on immunization competencies and ensure evidence-based practices underpin vaccine delivery in their primary care settings.

  9. Immunization status and childhood morbidities as determinants of PEM among under-five children in slums of Kanpur

    Directory of Open Access Journals (Sweden)

    Neha Agarwal

    2014-12-01

    Full Text Available Introduction: Childhood morbidities like Acute Respiratory Infections (ARI, diarrhoea and malnutrition are very common.  As per NFHS-3, only 23% children aged 12-23 months were fully immunized in Uttar Pradesh. 9% under-five children had diarrhoea and 7.1% had ARI. Objective: To assess the impact of immunization status and childhood morbidities on nutritional status of under five children. Material & Methods: A cross sectional study was carried out among under five children in slums of Kanpur, using 30 cluster sampling technique. The sample size was calculated to be 375. From each slum, 13 subjects were studied thus giving a total sample size of 390. A pre-designed and pre-tested questionnaire was used to illicit the requisite information from the mothers of study subjects. Weight was recorded using standard technique for the same. Protein Energy Malnutrition (PEM was graded using IAP classification. Analysis of data was done using percentages and Chi square test. Results: The overall prevalence of PEM was found to be 54.87%. Malnutrition was found to be significantly higher (69.23% among unimmunized study subjects (p≤0.05. Among children who reported episodes of ARI and diarrhoea within last 1 month, 67.86% and 78.52% subjects respectively were malnourished. The association between PEM and these childhood morbidities was found to be statistically significant (p≤0.05. Conclusion: Prevention of diarrhoea and ARI and complete immunization of children under five years of age through National programmes and other health measures is the need of the hour for combating malnutrition in under five.

  10. Motions of Kepler circumbinary planets in restricted three-body problem under radiating primaries

    Energy Technology Data Exchange (ETDEWEB)

    Dermawan, B., E-mail: budider@as.itb.ac.id; Hidayat, T., E-mail: taufiq@as.itb.ac.id [Astronomy Research Division, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132 (Indonesia); Huda, I. N., E-mail: ibnu.nurul@students.itb.ac.id; Mandey, D., E-mail: mandey.de@gmail.com; Utama, J. A., E-mail: judhistira@yahoo.com; Tampubolon, I., E-mail: ihsan.tampubolon@gmail.com [Department of Astronomy, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132 (Indonesia); Wibowo, R. W., E-mail: ridlo.w.wibowo@gmail.com [Department of Computational Science, Faculty of Mathematics and Natural Sciences, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132 (Indonesia)

    2015-09-30

    By observing continuously a single field of view in the sky, Kepler mission reveals outstanding results on discoveries of exoplanets. One of its recent progress is the discoveries of circumbinary planets. A circumbinary planet is an exoplanet that moves around a binary system. In this study we investigate motions of Kepler circumbinary planets belong to six binary systems, namely Kepler-16, -34, -35, -38, -47, and -413. The motions are considered to follow the Restricted Three-Body Problem (RTBP). Because the primaries (central massive objects) are stars, they are both radiatives, while the planet is an infinitesimal object. The primaries move in nearly circular and elliptic orbits with respect to their center of masses. We describe, in general, motions of the circumbinary planets in RTBP under radiating primaries. With respect to the averaged zero velocity curves, we show that motions of the exoplanets are stable, in accordance with their Hill stabilities.

  11. Analysis of primary damage in silicon carbide under fusion and fission neutron spectra

    Science.gov (United States)

    Guo, Daxi; Zang, Hang; Zhang, Peng; Xi, Jianqi; Li, Tao; Ma, Li; He, Chaohui

    2014-12-01

    Irradiation parameters on primary damage states of SiC are evaluated and compared for the first wall of ITER under deuterium-deuterium (DD) and deuterium-tritium (DT) operation, the high temperature gas-cooled reactor (HTGR) and high flux isotope reactor (HFIR). With the same neutron fluence, the studied fusion spectra produce more damage and much higher gas production than the fission spectra. Due to comparable gas production and similar weighted primary recoil spectra, HFIR is considered suitable to simulate the neutron irradiation in an HTGR. In contrast to the significant differences between the weighted primary recoil spectra of the fission and the fusion spectra, the weighted secondary recoil spectra of HFIR and HTGR match those of DD and DT, indicating that displacement cascades by the fission and the fusion irradiation are similar when the damage distribution among damaged regions by secondary recoils is taken into account.

  12. Liver-primed memory T cells generated under noninflammatory conditions provide anti-infectious immunity.

    Science.gov (United States)

    Böttcher, Jan P; Schanz, Oliver; Wohlleber, Dirk; Abdullah, Zeinab; Debey-Pascher, Svenja; Staratschek-Jox, Andrea; Höchst, Bastian; Hegenbarth, Silke; Grell, Jessica; Limmer, Andreas; Atreya, Imke; Neurath, Markus F; Busch, Dirk H; Schmitt, Edgar; van Endert, Peter; Kolanus, Waldemar; Kurts, Christian; Schultze, Joachim L; Diehl, Linda; Knolle, Percy A

    2013-03-28

    Development of CD8(+) T cell (CTL) immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs) matured during inflammation generate effector/memory T cells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memory T cells that were spared from deletion by immature DCs. Similar to central memory T cells, liver-primed T cells differentiated into effector CTLs upon antigen re-encounter on matured DCs even after prolonged absence of antigen. Their reactivation required combinatorial signaling through the TCR, CD28, and IL-12R and controlled bacterial and viral infections. Gene expression profiling identified liver-primed T cells as a distinct Neuropilin-1(+) memory population. Generation of liver-primed memory T cells may prevent pathogens that avoid DC maturation by innate immune escape from also escaping adaptive immunity through attrition of the T cell repertoire. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Expression and putative function of innate immunity genes under in situ conditions in the symbiotic hydrothermal vent tubeworm Ridgeia piscesae.

    Directory of Open Access Journals (Sweden)

    Spencer V Nyholm

    Full Text Available The relationships between hydrothermal vent tubeworms and sulfide-oxidizing bacteria have served as model associations for understanding chemoautotrophy and endosymbiosis. Numerous studies have focused on the physiological and biochemical adaptations that enable these symbioses to sustain some of the highest recorded carbon fixation rates ever measured. However, far fewer studies have explored the molecular mechanisms underlying the regulation of host and symbiont interactions, specifically those mediated by the innate immune system of the host. To that end, we conducted a series of studies where we maintained the tubeworm, Ridgeia piscesae, in high-pressure aquaria and examined global and quantitative changes in gene expression via high-throughput transcriptomics and quantitative real-time PCR (qPCR. We analyzed over 32,000 full-length expressed sequence tags as well as 26 Mb of transcript sequences from the trophosome (the organ that houses the endosymbiotic bacteria and the plume (the gas exchange organ in contact with the free-living microbial community. R. piscesae maintained under conditions that promote chemoautotrophy expressed a number of putative cell signaling and innate immunity genes, including pattern recognition receptors (PRRs, often associated with recognizing microbe-associated molecular patterns (MAMPs. Eighteen genes involved with innate immunity, cell signaling, cell stress and metabolite exchange were further analyzed using qPCR. PRRs, including five peptidoglycan recognition proteins and a Toll-like receptor, were expressed significantly higher in the trophosome compared to the plume. Although PRRs are often associated with mediating host responses to infection by pathogens, the differences in expression between the plume and trophosome also implicate similar mechanisms of microbial recognition in interactions between the host and symbiont. We posit that regulation of this association involves a molecular "dialogue

  14. Differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses to single epicutaneous immunization.

    Science.gov (United States)

    Lee, Chih-Hung; Chen, Jau-Shiuh; Chiu, Hsien-Ching; Hong, Chien-Hui; Liu, Ching-Yi; Ta, Yng-Cun; Wang, Li-Fang

    2016-12-01

    Epicutaneous immunization with allergens is an important sensitization route for atopic dermatitis. We recently showed in addition to the Th2 response following single epicutaneous immunization, a remarkable Th1 response is induced in B6 mice, but not in BALB/c mice, mimicking the immune response to allergens in human non-atopics and atopics. We investigated the underlying mechanisms driving this differential Th1 response between BALB/c and B6 mice. We characterized dermal dendritic cells by flow cytometric analysis. We measured the induced Th1/Th2 responses by measuring the IFN-γ/IL-13 contents of supernatants of antigen reactivation cultures of lymph node cells. We demonstrate that more dermal dendritic cells with higher activation status migrate into draining lymph nodes of B6 mice compared to BALB/c mice. Dermal dendritic cells of B6 mice have a greater ability to capture protein antigen than those of BALB/c mice. Moreover, increasing the activation status or amount of captured antigen in dermal dendritic cells induced a Th1 response in BALB/c mice. Further, differential activation behavior, but not antigen-capturing ability of dermal dendritic cells between BALB/c and B6 mice is dendritic cell-intrinsic. These results show that the differential activation behavior of dermal dendritic cells underlies the strain-specific Th1 responses following single epicutaneous immunization. Furthermore, our findings highlight the potential differences between human atopics and non-atopics and provide useful information for the prediction and prevention of atopic diseases. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  15. Cobalt deposition studies in the primary circuit under BWR conditions (Phase 1 and 2)

    International Nuclear Information System (INIS)

    Bennett, Peter

    1996-04-01

    This report presents the results from the first 2 phases of an experiment performed to investigate the effects of water chemistry on cobalt transport and deposition in the primary circuit under BWR conditions. Two high pressure water loops have been used to compare the incorporation of cobalt into the oxide films on coupons of various LWR primary circuit constructional materials, with several pretreatments, under Hydrogen Water Chemistry (HWC) and Normal Water Chemistry (NWC) conditions. Cobalt-60 deposition rates onto samples that had been pre-oxidised in air were lower than on samples that had been exposed previously in a water loop or had untreated surfaces. In NWC, oxide layers were thicker, normalised Co-60 deposition rates were higher and Co-60 activities per unit volume of oxide were greater. Some evidence has been produced to support the conclusions of other workers that a chromium-rich outer oxide layer is responsible for enhanced cobalt incorporation. (author)

  16. Primary Babesia rodhaini infection followed by recovery confers protective immunity against B. rodhaini reinfection and Babesia microti challenge infection in mice.

    Science.gov (United States)

    Wang, Guanbo; Efstratiou, Artemis; Adjou Moumouni, Paul Franck; Liu, Mingming; Jirapattharasate, Charoonluk; Guo, Huanping; Gao, Yang; Cao, Shinuo; Zhou, Mo; Suzuki, Hiroshi; Igarashi, Ikuo; Xuan, Xuenan

    2016-10-01

    In the present study, we investigated the protective immunity against challenge infections with Babesia rodhaini and Babesia microti in the mice recovered from B. rodhaini infection. Six groups with 5 test mice in each group were used in this study, and were intraperitoneally immunized with alive and dead B. rodhaini. The challenge infections with B. rodhaini or B. microti were performed using different time courses. Our results showed that the mice recovered from primary B. rodhaini infection exhibited low parasitemia and no mortalities after the challenge infections, whereas mock mice which had received no primary infection showed a rapid increase of parasitemia and died within 7 days after the challenge with B. rodhaini. Mice immunized with dead B. rodhaini were not protected against either B. rodhaini or B. microti challenge infections, although high titers of antibody response were induced. These results indicate that only mice immunized with alive B. rodhaini could acquire protective immunity against B. rodhaini or B. microti challenge infection. Moreover, the test mice produced high levels of antibody response and low levels of cytokines (INF-γ, IL-4, IL-12, IL-10) against B. rodhaini or B. microti after challenge infection. Mock mice, however, showed rapid increases of these cytokines, which means disordered cytokines secretion occurred during the acute stage of challenge infection. The above results proved that mice immunized with alive B. rodhaini could acquire protective immunity against B. rodhaini and B. microti infections. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Small RNA profiles in soybean primary root tips under water deficit.

    Science.gov (United States)

    Zheng, Yun; Hivrale, Vandana; Zhang, Xiaotuo; Valliyodan, Babu; Lelandais-Brière, Christine; Farmer, Andrew D; May, Gregory D; Crespi, Martin; Nguyen, Henry T; Sunkar, Ramanjulu

    2016-12-05

    Soybean (Glycine max) production is significantly hampered by frequent droughts in many regions of the world including the United States. Identifying microRNA (miRNA)-controlled posttranscriptional gene regulation under drought will enhance our understanding of molecular basis of drought tolerance in this important cash crop. Indeed, miRNA profiles in soybean exposed to drought were studied but not from the primary root tips, which is not only a main zone of water uptake but also critical for water stress sensing and signaling. Here we report miRNA profiles specifically from well-watered and water-stressed primary root tips (0 to 8 mm from the root apex) of soybean. Small RNA sequencing confirmed the expression of vastly diverse miRNA (303 individual miRNAs) population, and, importantly several conserved miRNAs were abundantly expressed in primary root tips. Notably, 12 highly conserved miRNA families were differentially regulated in response to water-deficit; six were upregulated while six others were downregulated at least by one fold (log2) change. Differentially regulated soybean miRNAs are targeting genes include auxin response factors, Cu/Zn Superoxide dismutases, laccases and plantacyanin and several others. These results highlighted the importance of miRNAs in primary root tips both under control and water-deficit conditions; under control conditions, miRNAs could be important for cell division, cell elongation and maintenance of the root apical meristem activity including quiescent centre whereas under water stress differentially regulated miRNAs could decrease auxin signaling and oxidative stress as well as other metabolic processes that save energy and water.

  18. Primary vaccination with the LiESP/QA-21 vaccine (CaniLeish) produces a cell-mediated immune response which is still present 1 year later.

    Science.gov (United States)

    Moreno, Javier; Vouldoukis, Ioannis; Schreiber, Paul; Martin, Virginie; McGahie, David; Gueguen, Sylvie; Cuisinier, Anne-Marie

    2014-04-15

    Canine leishmaniasis, an important zoonotic disease of dogs, is the result of an ineffective and inappropriate immune response to infection with Leishmania infantum. It is widely accepted that the appropriate immune response is characterised by a T-helper (Th)1-dominated profile in an overall mixed Th1/Th2 response. The absence of a strong Th1 response is associated with progression to the clinical disease. Thus, there is a need for an effective vaccine that could modulate the immune response to a more appropriate profile against the parasite. In this study we measured the impact of the LiESP/QA-21 canine vaccine, recently launched commercially in Europe, on selected humoral and cellular immune markers for one year after a primary vaccination course. The humoral response to vaccination was characterised by a predominantly IgG2 profile. Vaccinated dogs developed long-lasting cell-mediated immune responses against L. infantum, specifically with a stronger ability of macrophages to reduce intracellular parasite burdens in co-culture with autologous lymphocytes compared to control dogs (p=0.0002), which was correlated with induction of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO) derivatives. These results confirm that vaccination with LiESP/QA-21 is capable of inducing an appropriate Th1-dominated immune profile which persists for a full year. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Primary Immune Deficiency Diseases

    Science.gov (United States)

    ... Publications Help Archive Site Map Información en español Employee Information Connect with NIAID Facebook Twitter Linkedin Google+ Youtube Flickr Instagram Pinterest Email Website Policies & Notices ...

  20. Liver-Primed Memory T Cells Generated under Noninflammatory Conditions Provide Anti-infectious Immunity

    OpenAIRE

    Böttcher, Jan P.; Schanz, Oliver; Wohlleber, Dirk; Abdullah, Zeinab; Debey-Pascher, Svenja; Staratschek-Jox, Andrea; Höchst, Bastian; Hegenbarth, Silke; Grell, Jessica; Limmer, Andreas; Atreya, Imke; Neurath, Markus F.; Busch, Dirk H.; Schmitt, Edgar; van Endert, Peter

    2013-01-01

    Development of CD8+ T cell (CTL) immunity or tolerance is linked to the conditions during T cell priming. Dendritic cells (DCs) matured during inflammation generate effector/memory T cells, whereas immature DCs cause T cell deletion/anergy. We identify a third outcome of T cell priming in absence of inflammation enabled by cross-presenting liver sinusoidal endothelial cells. Such priming generated memory T cells that were spared from deletion by immature DCs. Similar to central memory T cells...

  1. Recognition of Immune Reconstitution Syndrome Necessary for Better Management of Patients with Severe Drug Eruptions and Those under Immunosuppressive Therapy

    Directory of Open Access Journals (Sweden)

    Tetsuo Shiohara

    2010-01-01

    Full Text Available The immune reconstitution syndrome (IRS is an increasingly recognized disease concept and is observed with a broad-spectrum of immunosuppressive therapy-related opportunistic infectious diseases and severe drug eruptions complicated by viral reactivations. Clinical illness consistent with IRS includes tuberculosis, herpes zoster, herpes simples, cytomegalovirus infections and sarcoidosis: thus, the manifestations of this syndrome and diverse and depend on the tissue burden of the preexisting infectious agents during the immunosuppressive state, the nature of the immune system being restored, and underlying diseases of the hosts. Although IRS has originally been reported to occur in the setting of HIV infection, it has become clear that the development of IRS can also be in HIV-negative hosts receiving immunosuppressive agents, such as prednisolone and tumor necrosis factor α inhibitors, upon their reduction and withdrawal. Drug-induced hypersensitivity syndrome, a life-threatening multiorgan system reaction, is another manifestation of the newly observed IRS. Clinical recognition of the IRS is especially important in improving the outcome for diseases with an otherwise life-threatening progenosis. Clinicians should be aware of the implications of IRS and recognize that relieving the symptoms and signs of immune recovery by anti-inflammatory therapies needs to be balanced with anti-microbial therapies aiming at reducing the amplitude and duration of tissue burden of preexisting microbes.

  2. Effectiveness of community service models for increasing routine immunization coverage at primary healthcare facilities in a rural district of Pakistan: a quasi-experimental study

    International Nuclear Information System (INIS)

    Ali, Z.; Pongpanich, S.; Kumar, R.

    2015-01-01

    Background: In Pakistan Routine Immunization coverage has been reported to be significantly low due to multiple factors that results in high number of deaths in children under 5. This study was conducted to assess the effectiveness of integrating Community Services to improve Routine immunization coverage in rural district of Pakistan. Methods: A quasi-experimental study with control and intervention arms was conducted in government Basic Health units catchment population of Panjgur by interviewing household head/Fathers. Total 234 household head including fathers were interviewed during this baseline survey. Community service model was used for to increase routine immunization coverage at catchment area of Basic Health unit (BHU) in intervention group while routine services were given in control BHU. Results: 230 parents completed the questionnaire during the end line after three months of intervention. There were no significant differences found between two groups at baseline but after the intervention, there was statistically significance difference (<0.05) between both groups knowledge and practices regarding routine immunization. Moreover, there was no statistically significant difference in control group reported (>0.05) after the intervention period. Overall immunization status after intervention where fully immunization status in intervention group after intervention was 88.8% as compared to control group after intervention was 13.6% for partial immunization status in intervention group after intervention was 11.1% as compared to control group after intervention was 81.1 for the Non-Immunization status in intervention group after intervention was 0% as compared to control group after intervention was 5.1%. Conclusions: Community Service Model has significantly improved the Knowledge and Practices among households/parents of children under 5 in the intervention arm. (author)

  3. New insights into immune mechanisms underlying autoimmune diseases of the gastrointestinal tract.

    Science.gov (United States)

    Di Sabatino, Antonio; Lenti, Marco Vincenzo; Giuffrida, Paolo; Vanoli, Alessandro; Corazza, Gino Roberto

    2015-12-01

    Recent progresses in the immune mechanisms implicated in chronic inflammatory disorders have led to a more in-depth knowledge of the pathogenesis of autoimmune diseases of the gastrointestinal tract, including autoimmune atrophic gastritis, celiac disease, autoimmune enteropathy and ulcerative colitis. While the pathogenic role of specific circulating autoantibodies, i.e., respectively anti-parietal cell, anti-tissue transglutaminase, anti-enterocyte and anti-neutrophil cytoplasmic, is still controversial, some common T-cell mediated mechanisms for inflammation - increase in T helper cell type 1/type 17 pro-inflammatory cytokines- or losing self-tolerance-abnormal regulatory T cell function - are recognized as crucial mediators of the tissue damage causing atrophy of the stomach mucosa in autoimmune atrophic gastritis, villous flattening of the small bowel in celiac disease and autoimmune enteropathy, and mucosal ulceration of the colon in ulcerative colitis. This review deals with novel advances in the immunological bases of the aforementioned autoimmune gastrointestinal disorders, and it also highlights immune mechanisms of progression from chronic inflammation to cancer and implications for new therapeutic targets. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Timeliness of Childhood Primary Immunization and Risk Factors Related with Delays: Evidence from the 2014 Zhejiang Provincial Vaccination Coverage Survey.

    Science.gov (United States)

    Hu, Yu; Li, Qian; Chen, Yaping

    2017-09-20

    Background: this study aimed to assess both immunization coverage and timeliness, as well as reasons for non-vaccination, and identity the risk factors of delayed immunization, for the vaccines scheduled during the first year of life, in Zhejiang province, east China. Methods: A cluster survey among children aged 24-35 months was conducted. Demographic information and socio-economic characteristics of the selected child, the mother, and the household were collected. Immunization data were transcribed from immunization cards. Timeliness was assessed with Kaplan-Meier analysis for each vaccine given before 12 months of age, based on the time frame stipulated by the expanded program on immunization of China. Cox proportional hazard regression was applied to identify risk factors of delayed immunization. Results: A total of 2772 eligible children were surveyed. The age-appropriate coverage ranged from 25.4% (95% CI: 23.7-27.0%) for Bacillus Calmette-Guerin (BCG) to 91.3% (95% CI: 90.2-92.3%) for the first dose of oral poliomyelitis vaccine (OPV1). The most frequent reason for non-vaccination was parent's fear of adverse events of immunization. Delayed immunizations were associated with mother having a lower education level, mother having a job, delivery at home, increasing number of children per household, and having a lower household income. Conclusions: Although the timeliness of immunization has improved since 2011, necessary steps are still needed to achieve further improvement. Timeliness of immunization should be considered as another important indicator of expanded program on immunization (EPI) performance. Future interventions on vaccination coverage should take into consideration demographic and socio-economic risk factors identified in this study. The importance of adhering to the recommended schedule should be explained to parents.

  5. Predicting Outcome in dogs with Primary Immune-Mediated Hemolytic Anemia: Results of a Multicenter Case Registry.

    Science.gov (United States)

    Goggs, R; Dennis, S G; Di Bella, A; Humm, K R; McLauchlan, G; Mooney, C; Ridyard, A; Tappin, S; Walker, D; Warman, S; Whitley, N T; Brodbelt, D C; Chan, D L

    2015-01-01

    Outcome prediction in dogs with immune-mediated hemolytic anemia (IMHA) is challenging and few prognostic indicators have been consistently identified. An online case registry was initiated to: prospectively survey canine IMHA presentation and management in the British Isles; evaluate 2 previously reported illness severity scores, Canine Hemolytic Anemia Score (CHAOS) and Tokyo and to identify independent prognostic markers. Data from 276 dogs with primary IMHA across 10 referral centers were collected between 2008 and 2012. Outcome prediction by previously reported illness-severity scores was tested using univariate logistic regression. Independent predictors of death in hospital or by 30-days after admission were identified using multivariable logistic regression. Purebreds represented 89.1% dogs (n = 246). Immunosuppressive medications were administered to 88.4% dogs (n = 244), 76.1% (n = 210) received antithrombotics and 74.3% (n = 205) received packed red blood cells. Seventy-four per cent of dogs (n = 205) were discharged from hospital and 67.7% (n = 187) were alive 30-days after admission. Two dogs were lost to follow-up at 30-days. In univariate analyses CHAOS was associated with death in hospital and death within 30-days. Tokyo score was not associated with either outcome measure. A model containing SIRS-classification, ASA classification, ALT, bilirubin, urea and creatinine predicting outcome at discharge was accurate in 82% of cases. ASA classification, bilirubin, urea and creatinine were independently associated with death in hospital or by 30-days. Markers of kidney function, bilirubin concentration and ASA classification are independently associated with outcome in dogs with IMHA. Validation of this score in an unrelated population is now warranted. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  6. Children after Chernobyl: immune cells adaptive changes and stable alterations under low-dose irradiation

    International Nuclear Information System (INIS)

    Bazyka, D.A.; Chumak, A.A.; Bebeshko, V.G.; Beliaeva, N.V.

    1997-01-01

    Early changes of immune parameters in children evacuated from 30-km zone were characterized by E-rossette forming cells decrease and E-receptor non-stability in theophylline assay, surface Ig changes. Immunological follow-up of children inhabitants of territories contaminated with radionuclides after Chernobyl accident revealed TCR/CD3, CD4 and MHC CD3+, CD4+, CD57+ subsets, RIL-2, TrT expression and calcium channel activity. PMNC percentage with cortical thymocyte phenotype (CD1+, CD4+8+) was elevated during the first years after the accident and seemed to be of a compensatory origin. Combination of heterogenic activation and suppression subset reactions and changes in fine subset (Th1/Th2) organization were suggested. Adaptive and compensatory reactions were supposed and delayed hypersensitivity reactions increase as well. (author)

  7. Evaluation of the innate immune responses to influenza and live-attenuated influenza vaccine infection in primary differentiated human nasal epithelial cells.

    Science.gov (United States)

    Forero, Adriana; Fenstermacher, Katherine; Wohlgemuth, Nicholas; Nishida, Andrew; Carter, Victoria; Smith, Elise A; Peng, Xinxia; Hayes, Melissa; Francis, Doreen; Treanor, John; Morrison, Juliet; Klein, Sabra L; Lane, Andrew; Katze, Michael G; Pekosz, Andrew

    2017-10-27

    The host innate immune response to influenza virus is a key determinant of pathogenic outcomes and long-term protective immune responses against subsequent exposures. Here, we present a direct contrast of the host responses in primary differentiated human nasal epithelial cell (hNEC) cultures following infection with either a seasonal H3N2 influenza virus (WT) or the antigenically-matched live-attenuated vaccine (LAIV) strain. Comparison of the transcriptional profiles obtained 24 and 36h post-infection showed that the magnitude of gene expression was greater in LAIV infected relative to that observed in WT infected hNEC cultures. Functional enrichment analysis revealed that the antiviral and inflammatory responses were largely driven by type III IFN induction in both WT and LAIV infected cells. However, the enrichment of biological pathways involved in the recruitment of mononuclear leukocytes, antigen-presenting cells, and T lymphocytes was uniquely observed in LAIV infected cells. These observations were reflective of the host innate immune responses observed in individuals acutely infected with influenza viruses. These findings indicate that cell-intrinsic type III IFN-mediated innate immune responses in the nasal epithelium are not only crucial for viral clearance and attenuation, but may also play an important role in the induction of protective immune responses with live-attenuated vaccines. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. MAVS Is Essential for Primary CD4+T Cell Immunity but Not for Recall T Cell Responses following an Attenuated West Nile Virus Infection.

    Science.gov (United States)

    Luo, Huanle; Winkelmann, Evandro; Xie, Guorui; Fang, Rong; Peng, Bi-Hung; Li, Li; Lazear, Helen M; Paessler, Slobodan; Diamond, Michael S; Gale, Michael; Barrett, Alan D; Wang, Tian

    2017-03-15

    The use of pathogen recognition receptor (PRR) agonists and the molecular mechanisms involved have been the major focus of research in individual vaccine development. West Nile virus (WNV) nonstructural (NS) 4B-P38G mutant has several features for an ideal vaccine candidate, including significantly reduced neuroinvasiveness, induction of strong adaptive immunity, and protection of mice from wild-type (WT) WNV infection. Here, we determined the role of mitochondrial antiviral signaling protein (MAVS), the adaptor protein for RIG-I-like receptor in regulating host immunity against the NS4B-P38G vaccine. We found that Mavs -/- mice were more susceptible to NS4B-P38G priming than WT mice. Mavs -/- mice had a transiently reduced production of antiviral cytokines and an impaired CD4 + T cell response in peripheral organs. However, antibody and CD8 + T cell responses were minimally affected. NS4B-P38G induced lower type I interferon (IFN), IFN-stimulating gene, and proinflammatory cytokine responses in Mavs -/- dendritic cells and subsequently compromised the antigen-presenting capacity for CD4 + T cells. Interestingly, Mavs -/- mice surviving NS4B-P38G priming were all protected from a lethal WT WNV challenge. NS4B-P38G-primed Mavs -/- mice exhibited equivalent levels of protective CD4 + T cell recall response, a modestly reduced WNV-specific IgM production, but more robust CD8 + T cell recall response. Taken together, our results suggest that MAVS is essential for boosting optimal primary CD4 + T cell responses upon NS4B-P38G vaccination and yet is dispensable for host protection and recall T cell responses during secondary WT WNV infection. IMPORTANCE The production of innate cytokines induced by the recognition of pathogen recognition receptors (PRRs) via their cognate ligands are critical for enhancing antigen-presenting cell functions and influencing T cell responses during microbial infection. The use of PRR agonists and the underlying molecular mechanisms have

  9. Toward a Unified Integration Approach: Uniting Diverse Primary Care Strategies Under the Primary Care Behavioral Health (PCBH) Model.

    Science.gov (United States)

    Sandoval, Brian E; Bell, Jennifer; Khatri, Parinda; Robinson, Patricia J

    2017-12-12

    Primary care continues to be at the center of health care transformation. The Primary Care Behavioral Health (PCBH) model of service delivery includes patient-centered care delivery strategies that can improve clinical outcomes, cost, and patient and primary care provider satisfaction with services. This article reviews the link between the PCBH model of service delivery and health care services quality improvement, and provides guidance for initiating PCBH model clinical pathways for patients facing depression, chronic pain, alcohol misuse, obesity, insomnia, and social barriers to health.

  10. Suppression of Innate Immune Response by Primary Human Keratinocytes Expressing HPV-16 E6 and E7

    National Research Council Canada - National Science Library

    Guess, Jennifer L

    2005-01-01

    Human papillomavims (HPV) types infect the skin and mucosal epithelium. Lesions resulting from HPV infection can linger for months or years suggesting that HPV - presence goes unnoticed by the host immune system...

  11. Surface (glyco-)proteins: primary structure and crystallization under microgravity conditions

    Science.gov (United States)

    Claus, H.; Akca, E.; Schultz, N.; Karbach, G.; Schlott, B.; Debaerdemaeker, T.; De Clercq, J.-P.; König, H.

    2001-08-01

    The Archaea comprise microorganisms that live under environmental extremes, like high temperature, low pH value or high salt concentration. Their cells are often covered by a single layer of (glyco)protein subunits (S-layer) in hexagonal arrangement. In order to get further hints about the molecular mechanisms of protein stabilization we compared the primary and secondary structures of archaeal S-layer (glyco)proteins. We found an increase of charged amino acids in the S-layer proteins of the extreme thermophilic species compared to their mesophilic counterparts. Our data and those of other authors suggest that ionic interactions, e.g., salt bridges seem to be played a major role in protein stabilization at high temperatures. Despite the differences in the growth optima and the predominance of some amino acids the primary structures of S-layers revealed also a significant degree of identity between phylogenetically related archaea. These obervations indicate that protein sequences of S-layers have been conserved during the evolution from extremely thermophilic to mesophilic life. To support these findings the three-dimensional structure of the S-layer proteins has to be elucidated. Recently, we described the first successful crystallization of an extreme thermophilic surface(glyco)protein under microgravity conditions.

  12. Utilisation of podiatry services in Australia under the Medicare Enhanced Primary Care program, 2004-2008

    Directory of Open Access Journals (Sweden)

    Menz Hylton B

    2009-10-01

    Full Text Available Abstract Background In 2004, as an extension of the Enhanced Primary Care (EPC program, the Australian Government introduced a policy of providing Medicare rebates for allied health services provided to patients with chronic or complex health conditions. The objective of this study was to evaluate the utilisation of podiatry services provided under this scheme between 2004 and 2008. Methods Data pertaining to the Medicare item 10962 for the calendar years 2004-2008 were extracted from the Australian Medicare Benefits Schedule (MBS database and cross-tabulated by sex and age. Descriptive analyses were undertaken to assess sex and age differences in the number of consultations provided and to assess for temporal trends over the five-year assessment period. The total cost to Medicare over this period was also determined. Results During the 2004-2008 period, a total of 1,338,044 EPC consultations were provided by podiatrists in Australia. Females exhibited higher utilisation than males (63 versus 37%, and those aged over 65 years accounted for 75% of consultations. There was a marked increase in the number of consultations provided from 2004 to 2008, and the total cost of providing EPC podiatry services during this period was $62.9 M. Conclusion Podiatry services have been extensively utilised under the EPC program by primary care patients, particularly older women, and the number of services provided has increased dramatically between 2004 and 2008. Further research is required to determine whether the EPC program enhances clinical outcomes compared to standard practice.

  13. Utilisation of podiatry services in Australia under the Medicare Enhanced Primary Care program, 2004-2008.

    Science.gov (United States)

    Menz, Hylton B

    2009-10-30

    In 2004, as an extension of the Enhanced Primary Care (EPC) program, the Australian Government introduced a policy of providing Medicare rebates for allied health services provided to patients with chronic or complex health conditions. The objective of this study was to evaluate the utilisation of podiatry services provided under this scheme between 2004 and 2008. Data pertaining to the Medicare item 10962 for the calendar years 2004-2008 were extracted from the Australian Medicare Benefits Schedule (MBS) database and cross-tabulated by sex and age. Descriptive analyses were undertaken to assess sex and age differences in the number of consultations provided and to assess for temporal trends over the five-year assessment period. The total cost to Medicare over this period was also determined. During the 2004-2008 period, a total of 1,338,044 EPC consultations were provided by podiatrists in Australia. Females exhibited higher utilisation than males (63 versus 37%), and those aged over 65 years accounted for 75% of consultations. There was a marked increase in the number of consultations provided from 2004 to 2008, and the total cost of providing EPC podiatry services during this period was $62.9 M. Podiatry services have been extensively utilised under the EPC program by primary care patients, particularly older women, and the number of services provided has increased dramatically between 2004 and 2008. Further research is required to determine whether the EPC program enhances clinical outcomes compared to standard practice.

  14. Our Immune System

    Science.gov (United States)

    Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

  15. Evaluation of immune responses in dogs to oral rabies vaccine under field conditions.

    Science.gov (United States)

    Smith, Todd G; Millien, Max; Vos, Ad; Fracciterne, Franso A; Crowdis, Kelly; Chirodea, Cornelius; Medley, Alexandra; Chipman, Richard; Qin, Yunlong; Blanton, Jesse; Wallace, Ryan

    2017-10-17

    During the 20th century parenteral vaccination of dogs at central-point locations was the foundation of successful canine rabies elimination programs in numerous countries. However, countries that remain enzootic for canine rabies have lower infrastructural development compared to countries that have achieved elimination, which may make traditional vaccination methods less successful. Alternative vaccination methods for dogs must be considered, such as oral rabies vaccine (ORV). In 2016, a traditional mass dog vaccination campaign in Haiti was supplemented with ORV to improve vaccination coverage and to evaluate the use of ORV in dogs. Blisters containing live-attenuated, vaccine strain SPBNGAS-GAS were placed in intestine bait and distributed to dogs by hand. Serum was collected from 107 dogs, aged 3-12 months with no reported prior rabies vaccination, pre-vaccination and from 78/107 dogs (72.9%) 17 days post-vaccination. The rapid florescent focus inhibition test (RFFIT) was used to detect neutralizing antibodies and an ELISA to detect rabies binding antibodies. Post-vaccination, 38/41 (92.7%) dogs that received parenteral vaccine had detectable antibody (RFFIT >0.05 IU/mL), compared to 16/27 (59.3%, p dogs that received ORV or 21/27 (77.8%) as measured by ELISA (>40% blocking, p vaccines was recorded; 283 dogs (97.2%) consumed the bait; 272 dogs (93.4%) were observed to puncture the blister, and only 14 blisters (4.8%) could not be retrieved by vaccinators and were potentially left in the environment. Pre-vaccination antibodies (RFFIT >0.05 IU/mL) were detected in 10/107 reportedly vaccine-naïve dogs (9.3%). Parenteral vaccination remains the most reliable method for ensuring adequate immune response in dogs, however ORV represents a viable strategy to supplement existing parental vaccination campaigns in hard-to-reach dog populations. The hand-out model reduces the risk of unintended contact with ORV through minimizing vaccine blisters left in the

  16. A Quantitative Quasispecies Theory-Based Model of Virus Escape Mutation Under Immune Selection

    Science.gov (United States)

    2012-01-01

    extinction when its mu- tation rate exceeds a threshold. The existence of such a threshold is a central prediction of the quasispecies theory...and describe such experimental data, it is important to realisti- cally specify the nature of selection pressure. Viruses in animal hosts evolve under...Explicit fitness measure- ments of viral clones (35, 36) and biochemical assays of proteins (37) both indicate that single-nucleotide substitutions lead to

  17. [Persistence of hepatitis A virus antibodies after primary immunization and response to revaccination in children and adolescents with perinatal HIV exposure].

    Science.gov (United States)

    Gouvêa, Aída de Fátima Thomé Barbosa; Pinto, Maria Isabel de Moraes; Miyamoto, Maristela; Machado, Daisy Maria; Pessoa, Silvana Duarte; Carmo, Fabiana Bononi do; Beltrão, Suênia Cordeiro de Vasconcelos; Succi, Regina Célia de Menezes

    2015-01-01

    To assess possible factors associated with the loss of antibodies to hepatitis A 7 years after the primary immunization in children of HIV-infected mothers and the response to revaccination in patients seronegative for hepatitis A. Quantification of HAV antibodies by electrochemiluminescence was performed in 39 adolescents followed up at the Pediatric Aids Clinic of Federal University of São Paulo (Unifesp): 29 HIV-infected (HIVgroup) (median age: 12.8 years) and 10 HIV-exposed but non-infected (ENI group) (median age: 13.4 years). All of them received two doses of HAV vaccine (Havrix(®)) in 2002. The median age at primary immunization (PI) was 5.4 years for HIV group and 6.5 years for ENI group. All children, from both groups, had antibodies to HAV >20 mIU/mL after PI. Seven years later, the ENI group showed a median concentration of antibodies = 253.5 mIU/mL, while the HIV group = 113.0 mIU/mL (Mann-Whitney test, p=0.085). All ENI group and 23/29 (79.3%) from HIV group mantained HAV antibodies 7 years after PI. The levels of hepatitis A antibodies in the primary vaccination were the only factor independently associated with maintaining these antibodies for 7 years. The group that lost HAV seropositivity was revaccinated and 83.3% (5/6) responded with antibodies >20 mUI/mL. The antibodies levels acquired in the primary vaccination in the HIV group were the main factor associated with antibodies loss after HAV immunization. Copyright © 2015 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Persistence of hepatitis A virus antibodies after primary immunization and response to revaccination in children and adolescents with perinatal HIV exposure

    Directory of Open Access Journals (Sweden)

    Aída de Fátima Thomé Barbosa Gouvêa

    2015-06-01

    Full Text Available OBJECTIVE: To assess possible factors associated with the loss of antibodies to hepatitis A 7 years after the primary immunization in children of HIV-infected mothers and the response to revaccination in patients seronegative for hepatitis A. METHODS: Quantification of HAV antibodies by electrochemiluminescence was performed in 39 adolescents followed up at the Pediatric Aids Clinic of Federal University of São Paulo (Unifesp: 29 HIV-infected (HIV group (median age: 12.8 years and 10 HIV-exposed but non-infected (ENI group (median age: 13.4 years. All of them received two doses of HAV vaccine (Havrix(r in 2002. RESULTS: The median age at primary immunization (PI was 5.4 years for HIV group and 6.5 years for ENI group. All children, from both groups, had antibodies to HAV >20 mIU/mL after PI. Seven years later, the ENI group showed a median concentration of antibodies = 253.5 mIU/mL, while the HIV group = 113.0 mIU/mL (Mann-Whitney test, p=0.085. All ENI group and 23/29 (79.3% from HIV group mantained HAV antibodies 7 years after PI. The levels of hepatitis A antibodies in the primary vaccination were the only factor independently associated with maintaining these antibodies for 7 years. The group that lost HAV seropositivity was revaccinated and 83.3% (5/6 responded with antibodies >20 mUI/mL. CONCLUSIONS: The antibodies levels acquired in the primary vaccination in the HIV group were the main factor associated with antibodies loss after HAV immunization.

  19. Moment inertia pump analysis used in the Rsg-Gas primary coolant loop under lofa condition

    International Nuclear Information System (INIS)

    Sudarmono; Setiyanto; Dhandhang, P.; Dibyo, S.; Royadi

    1998-01-01

    The moment inertia of primary cooling system analysis under LOFA condition has been done. It is potentially one of limiting design constraints of the RSG-GAS safety because the coolant flow rate reduces very rapidly under LOFA condition due to the low inertia circulation pumps. If a loss of flow accident occurs, the mass flow will decrease rapidly and the heat transfer coefficient between cladding and coolant will also decreases. As a consequence the fuel and cladding temperature will increase. The whole core was represented by the 1/4 sector and divided into 19 subchannels and 40 axial nodes. In the present study, moment inertia of pump analysis for RSG-GAS reactor was performed with COBRA-IV-I subchannel code. As the DNB correlation, W-3 Correlation was selected for base case. The flow and power transients under pump trip accident were determined from experiments. The result above compared with the design data are 75 kg m 2 and 81 Kg m 2 respectively. The result shows that the RSG-GAS requires the inertia more than 75 kg m 2

  20. Energy spectra of primary knock-on atoms under neutron irradiation

    International Nuclear Information System (INIS)

    Gilbert, M.R.; Marian, J.; Sublet, J.-Ch.

    2015-01-01

    Materials subjected to neutron irradiation will suffer from a build-up of damage caused by the displacement cascades initiated by nuclear reactions. Previously, the main “measure” of this damage accumulation has been through the displacements per atom (dpa) index, which has known limitations. This paper describes a rigorous methodology to calculate the primary atomic recoil events (often called the primary knock-on atoms or PKAs) that lead to cascade damage events as a function of energy and recoiling species. A new processing code SPECTRA-PKA combines a neutron irradiation spectrum with nuclear recoil data obtained from the latest nuclear data libraries to produce PKA spectra for any material composition. Via examples of fusion relevant materials, it is shown that these PKA spectra can be complex, involving many different recoiling species, potentially differing in both proton and neutron number from the original target nuclei, including high energy recoils of light emitted particles such as α-particles and protons. The variations in PKA spectra as a function of time, neutron field, and material are explored. The application of PKA spectra to the quantification of radiation damage is exemplified using two approaches: the binary collision approximation and stochastic cluster dynamics, and the results from these different models are discussed and compared. - Highlights: • Recoil cross-section matrices under neutron irradiation are generated. • Primary knock-on atoms (PKA) spectra are calculated for fusion relevant materials. • Variation in PKA spectra due to changes in geometry are considered. • Inventory simulations to consider time-evolution in PKA spectra. • Damage quantification using damage functions from different approximations.

  1. Burnout of Physicians Working in Primary Health Care Centers under Ministry of Health Jeddah, Saudi Arabia.

    Science.gov (United States)

    Bawakid, Khalid; Abdulrashid, Ola; Mandoura, Najlaa; Shah, Hassan Bin Usman; Ibrahim, Adel; Akkad, Noura Mohammad; Mufti, Fauad

    2017-11-25

    Introduction The levels of physicians' job satisfaction and burnout directly affect their professionalism, punctuality, absenteeism, and ultimately, patients' care. Despite its crucial importance, little is known about professional burnout of the physicians in Saudi Arabia. The objectives of this research are two-fold: (1) To assess the prevalence of burnout in physicians working in primary health care centers under Ministry of Health; and (2) to find the modifiable factors which can decrease the burnout ratio. Methodology Through a cross-sectional study design, a representative sample of the physicians working in primary health care centers (PHCCs) Jeddah (n=246) was randomly selected. The overall burnout level was assessed using the validated abbreviated Maslach burnout inventory (aMBI) questionnaire. It measures the overall burnout prevalence based on three main domains i.e., emotional exhaustion, depersonalization, and personal accomplishment. Independent sample T-test, analysis of variance (ANOVA), and multivariate regression analysis were performed using Statistical Package for the Social Sciences (SPSS Version 22, IBM, Armonk, NY). Results Overall, moderate to high burnout was prevalent in 25.2% of the physicians. Emotional exhaustion was noted in 69.5%. Multivariate regression analysis showed that patient pressure/violence (p burnout. The patient's pressure/violence was the only significant independent predictor of overall burnout. Conclusion Emotional exhaustion is the most prominent feature of overall burnout in the physicians of primary health care centers. The main reasons include patient's pressure/violence, unorganized patient flow, less cooperative colleague doctors, fewer support services at the PHCCs, more paperwork, and less cooperative colleagues. Addressing these issues could lead to a decrease in physician's burnout.

  2. Avian malaria and bird humoral immune response.

    Science.gov (United States)

    Delhaye, Jessica; Jenkins, Tania; Glaizot, Olivier; Christe, Philippe

    2018-02-09

    Plasmodium parasites are known to impose fitness costs on their vertebrate hosts. Some of these costs are due to the activation of the immune response, which may divert resources away from self-maintenance. Plasmodium parasites may also immuno-deplete their hosts. Thus, infected individuals may be less able to mount an immune response to a new pathogen than uninfected ones. However, this has been poorly investigated. The effect of Plasmodium infection on bird humoral immune response when encountering a novel antigen was tested. A laboratory experiment was conducted on canaries (Serinus canaria) experimentally infected with Plasmodium relictum (lineage SGS1) under controlled conditions. Birds were immune challenged with an intra-pectoral injection of a novel non-pathogenic antigen (keyhole limpet haemocyanin, KLH). One week later they were challenged again. The immune responses to the primary and to the secondary contacts were quantified as anti-KLH antibody production via enzyme-linked immunosorbent assay (ELISA). There was no significant difference in antibody production between uninfected and Plasmodium infected birds at both primary and secondary contact. However, Plasmodium parasite intensity in the blood increased after the primary contact with the antigen. There was no effect of Plasmodium infection on the magnitude of the humoral immune response. However, there was a cost of mounting an immune response in infected individuals as parasitaemia increased after the immune challenge, suggesting a trade-off between current control of chronic Plasmodium infection and investment against a new immune challenge.

  3. Laboratory results gained from cold worked type 316Ti under simulated PWR primary environment

    International Nuclear Information System (INIS)

    Devrient, B.; Kilian, R.; Koenig, G.; Widera, M.; Wermelinger, T.

    2015-01-01

    Beginning in 2005, intergranular stress corrosion cracking (IGSCC) of barrel bolts made from cold worked type 316Ti (German Material No. 1.4571 K) was observed in several S/KWU type PWRs. This mechanism was so far less understood for PWR primary conditions. Therefore an extended joint research program was launched by AREVA GmbH and VGB e.V. to clarify the specific conditions which contributed to the observed findings on barrel bolts. In the frame of this research program beneath the evaluation of the operational experience also laboratory tests on the general cracking behavior of cold worked type 316Ti material, which followed the same production line as for barrel bolt manufacturing in the eighties, with different cold work levels covering up to 30 % were performed to determine whether there is a specific susceptibility of cold worked austenitic stainless steel specimens to suffer IGSCC under simulated PWR primary conditions. All these slow strain rate tests on tapered specimens and component specimens came to the results that first, much higher cold work levels than used for the existing barrel bolts are needed for IGSCC initiation. Secondly, additional high active plastic deformation is needed to generate and propagate intergranular cracking. And thirdly, all specimens finally showed ductile fracture at the applied strain rates. (authors)

  4. Can we predict the direction of marine primary production change under global warming?

    Science.gov (United States)

    Taucher, J.; Oschlies, A.

    2011-01-01

    A global Earth System model is employed to investigate the role of direct temperature effects in the response of marine ecosystems to climate change. While model configurations with and without consideration of explicit temperature effects can reproduce observed current biogeochemical tracer distributions and estimated carbon export about equally well, carbon flow through the model ecosystem reveals strong temperature sensitivities. Depending on whether biological processes are assumed temperature sensitive or not, simulated marine net primary production (NPP) increases or decreases under projected climate change driven by a business-as-usual CO2 emission scenario for the 21st century. This suggests that indirect temperature effects such as changes in the supply of nutrients and light are not the only relevant factors to be considered when modeling the response of marine ecosystems to climate change. A better understanding of direct temperature effects on marine ecosystems is required before even the direction of change in NPP can be reliably predicted.

  5. Changes in the fertility of a leached chernozem under different primary tillage technologies

    Science.gov (United States)

    Korolev, V. A.; Gromovik, A. I.; Borontov, O. K.

    2016-01-01

    Changes in the fertility of a leached chernozem under different tillage technologies (moldboard, non-inversive, and combined tillage) were studied in a multifactor stationary field experiment established in 1985 in Voronezh oblast on a low-humus medium-deep light clayey leached chernozem. The nine-field rotation of cereals and sugar beet was practiced. It was found that the major parameters of soil fertility—the content and qualitative composition of humus and the physicochemical and physical properties of the chernozem—remained relatively stable independently from the applied primary tillage technologies. However, taking into account economic characteristics (crop yields, production costs, energy expenses, etc.), the combined tillage system proved to be most efficient. It can be recommended for cereals-sugar beet rotation systems in the central chernozemic region, as it ensures the highest efficiency of crop growing and preserves the fertility of leached chernozems.

  6. ASSESSMENT OF KNOWLEDGE ABOUT IMMUNIZATION OF UNDER FIVE CHILDREN AMONG MOTHERS ATTENDING OUTPATIENT DEPARTMENT OF PEDIATRICS IN A TERTIARY CARE HOSPITAL IN KOLLAM, KERALA

    Directory of Open Access Journals (Sweden)

    Ahmad Nadeem

    2015-07-01

    Full Text Available BACKGROUND : Immunization is the most cost effective public health intervention to reduce childhood morbidity and mortality. Thousands of children can be saved from vaccine preventable diseases each year by immunization. The knowledge of mothers’ is an important factor for better immunization coverage. Less knowledge affects decision making regarding immunization. OBJECTIVES: To assess the knowledge about immunization of under five children among mothers a ttending outpatient department of paediatrics in a tertiary care hospital in Kollam, Kerala and to find out the association of the knowledge level of mothers with some selected variables. MATERIAL AND METHODS : A Cross sectional study was done among mothers of under five children attending the OPD of pediatrics in a tertiary care hospital in Kollam, Kerala from 1 st to 30 th May, 2014. The sample size was 210 and simple random sampling was used. Statistical analysis was done and chi - square test & percentages w ere calculated. RESULT: 93.8% of mothers knew that vaccines are beneficial for their child. 58% were aware about the side effects of few vaccines. 50% of mothers believed that as polio is eradicated from India, there is no need to give polio vaccine. 35% o f mothers acquired knowledge regarding immunization through health workers. All of them had knowledge about polio vaccine but only half of them knew about rotavirus vaccine. 60% mothers believed that multiple vaccines are beneficial although 26% hold their view that it has no benefit at all. 39.5% of mothers’ had adequate knowledge about immunization. It was positively associated with education, working class and high socio - economic status of mothers. CONCLUSION: There are several loopholes in the mother’s knowledge regarding immunization. Many of them had no knowledge about optional vaccines. There is a need to improve knowledge regarding immunization among general population. Adequate information about completin g the

  7. Immunogenicity of booster vaccination with a virosomal hepatitis A vaccine after primary immunization with an aluminum-adsorbed hepatitis A vaccine.

    Science.gov (United States)

    Beck, Bernard R; Hatz, Christoph F R; Loutan, Louis; Steffen, Robert

    2004-01-01

    Increasing numbers of individuals are traveling to areas of high hepatitis A endemicity and require immunization against the hepatitis A virus (HAV). The option of using a virosomal, aluminum-free, HAV vaccine (Epaxal) for booster immunization following primary vaccination with an aluminum-adsorbed vaccine has been assessed. In total, 142 healthy subjects, 79 men and 63 women, aged 12 to 72 years, were injected intramuscularly with a booster dose of Epaxal (0.5 mL containing aluminum hydroxide). Anti-HAV antibody titers were measured on days 0 and 28 by an enzyme immunoassay. Adverse events were recorded for 1 month postinjection. Overall, 98/118 subjects (83%) with no serologic evidence of past HAV infection were still seroprotected at enrolment (anti-HAV antibody titer aluminum-adsorbed vaccine, and is well tolerated.

  8. Offspring of xenogeneically-reconstituted scid scid mice are capable of a primary xenogeneic immune response to DNP-KLH

    NARCIS (Netherlands)

    Greenwood, JD; Bos, NA; Croy, BA

    Human peripheral blood leukocyte (PBL) reconstitution of severe combined immunodeficient (SCID) mice has provided a small animal model system (hu-PBL-SCID) useful for the study of the human immune system and disease pathogenesis. Transfer of xenogeneic PBL from donors other than humans has also been

  9. Effect of oral booster vaccination of rainbow trout against Yersinia ruckeri depends on type of primary immunization

    DEFF Research Database (Denmark)

    Jaafar, Rzgar M.; Al-Jubury, Azmi; Dalsgaard, Inger

    2017-01-01

    Vaccination of rainbow trout against Enteric Redmouth Disease (ERM) caused by Yersinia ruckeri can be successfully performed by administering vaccine (a bacterin consisting of formalin killed bacteria) by immersion, bath or injection. Booster immunization is known to increase the protection of fi...

  10. Regulation of the human cathelicidin antimicrobial peptide gene by 1α,25-dihydroxyvitamin D3 in primary immune cells

    DEFF Research Database (Denmark)

    Lowry, Malcolm B; Guo, Chunxiao; Borregaard, Niels

    2014-01-01

    Production of the human cathelicidin antimicrobial peptide gene (hCAP18/LL-37), is regulated by 1α,25-dihydroxyvitamin D3 (1,25D3) and is critical in the killing of pathogens by innate immune cells. In addition, secreted LL-37 binds extracellular receptors and modulates the recruitment and activity...

  11. CONCENTRATION OF CIRCULATING IMMUNE COMPLEXES IN EXPERIMENTAL GENERALIZED INFLAMMATORY PROCESS IN ANIMALS OF DIFFERENT AGE UNDER ACTION OF IMMUNOMODULATORS

    Directory of Open Access Journals (Sweden)

    Kovalenko T.I.

    2015-05-01

    Full Text Available Under physiological conditions a formation and a presence of the CEC in liquids is one of the manifestations of the immune response to receipt of antigens and an important factor, which provides immunity. Circulating immune complexes act as agents involved in the regulation of immune response and maintaining communication between the immune system and other regulatory systems of the body and direction to his defense. The intensity of the formation of the CEC may vary under the influence of infectious antigens and immune preparations. Material and methods. Material for the experiment were white male rats 3 months of age ("young" weighing 100 -140gr. (n = 40 and 22-month ("old" weighing 200 -240 g. (n = 40. And the first (n=10 and second (n=10 groups of rats served as controls. Third (n=15 and fourth (n=15 group of animals was injected intraperitoneal daily agar culture of Pseudomonas aeruginosa № 27835 ATCC (injected with 1.5 ml suspension of bacteria, which contained 109 CFU/ml. Fifth (n=15 and sixth (n=15 groups of animals were injected intraperitoneally daily agar culture of Escherichia coli number 25592, ATCC (injected with 1.5 ml of bacteria suspension which contain 109 CFU/ml. Control animals were taken from the experiment by decapitation 3rd day – n=20. Control and infected animals were taken from the experiment by decapitation at 3rd day - n=27, 5th day – n=27 and 7th day – n=26. In the second phase of the experiment Ia (n = 6 and IIa (n = 6 were the control group of rats following administration of the experimental composite preparation consisting amino acids, nucleotides, enzymes, vitamins (MF. In two age groups of animals with inflammation induced by E. coli suspension treated with MF 20 mсl 3- month rats (IIIa group n = 6 and 40 mсl 22-month rats (IVa group n = 6. Ib (n = 6 and IIb (n = 6 were the control group of rats after the injection of comparison, containing mannitol and natural antioxidant betakaroten (PO. In two age

  12. Impacts of climate extremes on gross primary production under global warming

    International Nuclear Information System (INIS)

    Williams, I N; Torn, M S; Riley, W J; Wehner, M F

    2014-01-01

    The impacts of historical droughts and heat-waves on ecosystems are often considered indicative of future global warming impacts, under the assumption that water stress sets in above a fixed high temperature threshold. Historical and future (RCP8.5) Earth system model (ESM) climate projections were analyzed in this study to illustrate changes in the temperatures for onset of water stress under global warming. The ESMs examined here predict sharp declines in gross primary production (GPP) at warm temperature extremes in historical climates, similar to the observed correlations between GPP and temperature during historical heat-waves and droughts. However, soil moisture increases at the warm end of the temperature range, and the temperature at which soil moisture declines with temperature shifts to a higher temperature. The temperature for onset of water stress thus increases under global warming and is associated with a shift in the temperature for maximum GPP to warmer temperatures. Despite the shift in this local temperature optimum, the impacts of warm extremes on GPP are approximately invariant when extremes are defined relative to the optimal temperature within each climate period. The GPP sensitivity to these relative temperature extremes therefore remains similar between future and present climates, suggesting that the heat- and drought-induced GPP reductions seen recently can be expected to be similar in the future, and may be underestimates of future impacts given model projections of increased frequency and persistence of heat-waves and droughts. The local temperature optimum can be understood as the temperature at which the combination of water stress and light limitations is minimized, and this concept gives insights into how GPP responds to climate extremes in both historical and future climate periods. Both cold (temperature and light-limited) and warm (water-limited) relative temperature extremes become more persistent in future climate projections

  13. Detailing profiles of Lawsonia intracellularis specific lymphocytes in the immune response to a challenge inoculation after oral vaccination or primary inoculation with virulent bacteria

    DEFF Research Database (Denmark)

    Riber, Ulla; Hvass, Henriette Cordes; Heegaard, Peter M. H.

    2012-01-01

    Vaccination against the intracellular porcine enteric pathogen Lawsonia intracellularis remains a challenge as the commercially available vaccine does not provide full protection. In an experimental challenge study, the Enterisol® Ileitis attenuated live vaccine against Lawsonia intracellularis did...... not induce measurable primary humoral or cell-mediated immune responses, nor was it able to reduce faecal shedding of bacteria from eight vaccinated pigs compared to seven age-matched naïve challenge-control pigs. Vaccinated pigs did, however, respond to vaccination with an acute phase protein response...

  14. Burnout of Physicians Working in Primary Health Care Centers under Ministry of Health Jeddah, Saudi Arabia

    Science.gov (United States)

    Bawakid, Khalid; Mandoura, Najlaa; Shah, Hassan Bin Usman; Ibrahim, Adel; Akkad, Noura Mohammad; Mufti, Fauad

    2017-01-01

    Introduction The levels of physicians' job satisfaction and burnout directly affect their professionalism, punctuality, absenteeism, and ultimately, patients' care. Despite its crucial importance, little is known about professional burnout of the physicians in Saudi Arabia. The objectives of this research are two-fold: (1) To assess the prevalence of burnout in physicians working in primary health care centers under Ministry of Health; and (2) to find the modifiable factors which can decrease the burnout ratio. Methodology Through a cross-sectional study design, a representative sample of the physicians working in primary health care centers (PHCCs) Jeddah (n=246) was randomly selected. The overall burnout level was assessed using the validated abbreviated Maslach burnout inventory (aMBI) questionnaire. It measures the overall burnout prevalence based on three main domains i.e., emotional exhaustion, depersonalization, and personal accomplishment. Independent sample T-test, analysis of variance (ANOVA), and multivariate regression analysis were performed using Statistical Package for the Social Sciences (SPSS Version 22, IBM, Armonk, NY). Results Overall, moderate to high burnout was prevalent in 25.2% of the physicians. Emotional exhaustion was noted in 69.5%. Multivariate regression analysis showed that patient pressure/violence (p <0.001), unorganized patients flow to clinics (p=0.021), more paperwork (p<0.001), and less co-operative colleague doctors (p=0.045) were the significant predictors for high emotional exhaustion. A positive correlation was noted between the number of patients per day and burnout. The patient’s pressure/violence was the only significant independent predictor of overall burnout. Conclusion Emotional exhaustion is the most prominent feature of overall burnout in the physicians of primary health care centers. The main reasons include patient’s pressure/violence, unorganized patient flow, less cooperative colleague doctors, fewer

  15. Adaptive immunity is the primary force driving selection of equine infectious anemia virus envelope SU variants during acute infection.

    Science.gov (United States)

    Mealey, Robert H; Leib, Steven R; Pownder, Sarah L; McGuire, Travis C

    2004-09-01

    Equine infectious anemia virus (EIAV) is a lentivirus that causes persistent infection in horses. The appearance of antigenically distinct viral variants during recurrent viremic episodes is thought to be due to adaptive immune selection pressure. To test this hypothesis, we evaluated envelope SU cloned sequences from five severe combined immunodeficient (SCID) foals infected with EIAV. Within the SU hypervariable V3 region, 8.5% of the clones had amino acid changes, and 6.4% had amino acid changes within the known cytotoxic T lymphocyte (CTL) epitope Env-RW12. Of all the SU clones, only 3.1% had amino acid changes affecting potential N-linked glycosylation sites. In contrast, a much higher degree of variation was evident in SU sequences obtained from four EIAV-infected immunocompetent foals. Within V3, 68.8% of the clones contained amino acid changes, and 50% of the clones had amino acid changes within the Env-RW12 CTL epitope. Notably, 31.9% of the clones had amino acid changes affecting one or more glycosylation sites. Marked amino acid variation occurred in cloned SU sequences from an immune-reconstituted EIAV-infected SCID foal. Of these clones, 100% had amino acid changes within V3, 100% had amino acid changes within Env-RW12, and 97.5% had amino acid changes affecting glycosylation sites. Analysis of synonymous and nonsynonymous nucleotide substitutions revealed statistically significant differences between SCID and immunocompetent foals and between SCID foals and the reconstituted SCID foal. Interestingly, amino acid selection at one site occurred independently of adaptive immune status. Not only do these data indicate that adaptive immunity primarily drives the selection of EIAV SU variants, but also they demonstrate that other selective forces exist during acute infection.

  16. Characterization of rat primary trigeminal satellite glial cells and associated extracellular vesicles under normal and inflammatory conditions

    DEFF Research Database (Denmark)

    Vinterhøj, Hye Sook Han; Stensballe, Allan; Duroux, Meg

    2018-01-01

    that are proposed as novel biomarkers of SGCs activation under inflammatory conditions. Findings from this study highlight the utility of using fresh primary SGC cultures as a model to further investigate EVs under normal and inflammatory conditions. SIGNIFICANCE: This study demonstrated that....

  17. Application of 125I-labelled soluble proteins in the histoautoradiographic detection of antigen and antibodies in the spleen of rabbits during primary immune response

    International Nuclear Information System (INIS)

    Rodak, L.

    1975-01-01

    An autoradiographic method for detecting soluble antigen (chicken serum albumin, CSA) and specific antibodies in the spleen of rabbits during a primary immune response is described. The method consists of incubating sections from the spleen with 125 I-labelled IgG 2 anti CSA (for demonstration of antigen) or with 125 I-labelled antigen (for demonstration of specific antibodies). This treatment of histological sections combines the advantages and principles of the immunofluorescence technique with the possibility of evaluating the exact localization of the proteins by light microscopy in preparations stained with haematoxylin or methyl green-pyronin. The sensitivity of detection is very high: both antigen and antibodies could be demonstrated in the spleen follicles for as long as 42 days after the primary intravenous injection

  18. Estimating forest net primary production under changing climate: adding pests into the equation.

    Science.gov (United States)

    Pinkard, E A; Battaglia, M; Roxburgh, S; O'Grady, A P

    2011-07-01

    The current approach to modelling pest impacts on forest net primary production (NPP) is to apply a constant modifier. This does not capture the large spatial and temporal variability in pest abundance and activity that can occur, meaning that overestimates or underestimates of pest impacts on forest NPP are likely. Taking a more mechanistic approach that incorporates an understanding of how physiology is influenced by pest attack, enables us to better capture system feedbacks and dynamics, thereby improving the capacity to predict into novel situations such as changing climate, and to account for both changes in pest activity and host responses to the growing environment now and into the future. We reviewed the effects of pests on forest NPP and found a range of responses and physiological mechanisms underlying those responses. Pest outbreaks can clearly be a major perturbation to forest NPP, and it seems likely that the frequency and intensity of pest outbreaks, and the ways in which host species respond to pest damage, will change in the future. We summarized these impacts in the form of a conceptual model at leaf, tree and stand scales, and compared the physiological processes embedded within that framework with the capacity of a representative range of NPP models to capture those processes. We found that some models can encapsulate some of the processes, but no model can comprehensively account for the range of physiological responses to pest attack experienced by trees. This is not surprising, given the paucity of empirical data for most of the world's forests, and that the models were developed primarily for other purposes. We conclude with a list of the key physiological processes and pathways that need to be included in forest growth models in order to adequately capture pest impacts on forest NPP under current and future climate scenarios, the equations that might enable this and the empirical data required to support them.

  19. Hypothalamus-Related Resting Brain Network Underlying Short-Term Acupuncture Treatment in Primary Hypertension

    Directory of Open Access Journals (Sweden)

    Hongyan Chen

    2013-01-01

    Full Text Available The present study attempted to explore modulated hypothalamus-seeded resting brain network underlying the cardiovascular system in primary hypertensive patients after short-term acupuncture treatment. Thirty right-handed patients (14 male were divided randomly into acupuncture and control groups. The acupuncture group received a continuous five-day acupuncture treatment and undertook three resting-state fMRI scans and 24-hour ambulatory blood pressure monitoring (ABPM as well as SF-36 questionnaires before, after, and one month after acupuncture treatment. The control group undertook fMRI scans and 24-hour ABPM. For verum acupuncture, average blood pressure (BP and heart rate (HR decreased after treatment but showed no statistical differences. There were no significant differences in BP and HR between the acupuncture and control groups. Notably, SF-36 indicated that bodily pain (P = 0.005 decreased and vitality (P = 0.036 increased after acupuncture compared to the baseline. The hypothalamus-related brain network showed increased functional connectivity with the medulla, brainstem, cerebellum, limbic system, thalamus, and frontal lobes. In conclusion, short-term acupuncture did not decrease BP significantly but appeared to improve body pain and vitality. Acupuncture may regulate the cardiovascular system through a complicated brain network from the cortical level, the hypothalamus, and the brainstem.

  20. Urinary incontinence in bitches under primary veterinary care in England: prevalence and risk factors.

    Science.gov (United States)

    O'Neill, D G; Riddell, A; Church, D B; Owen, L; Brodbelt, D C; Hall, J L

    2017-12-01

    To estimate prevalence and demographic risk factors for urinary incontinence in bitches under primary veterinary care in England. The study population included all bitches within the VetCompass database from September 1, 2009 to July 7, 2013. Electronic patient records were searched for urinary incontinence cases and additional demographic and clinical information was extracted. Of 100,397 bitches attending 119 clinics in England, an estimated 3108 were diagnosed with urinary incontinence. The prevalence of urinary incontinence was 3·14% (95% confidence intervals: 2·97 to 3·33). Medical therapy was prescribed to 45·6% cases. Predisposed breeds included the Irish setter (odds ratio: 8·09; 95% confidence intervals: 3·15 to 20·80; Prisk breeds including the Irish setter, Dobermann, bearded collie, rough collie and Dalmatian. These results provide an evidence base for clinicians to enhance clinical recommendations on neutering and weight control, especially in high-risk breeds. © 2017 British Small Animal Veterinary Association.

  1. Sporozoite immunization of human volunteers under mefloquine prophylaxis is safe, immunogenic and protective: a double-blind randomized controlled clinical trial.

    Science.gov (United States)

    Bijker, Else M; Schats, Remko; Obiero, Joshua M; Behet, Marije C; van Gemert, Geert-Jan; van de Vegte-Bolmer, Marga; Graumans, Wouter; van Lieshout, Lisette; Bastiaens, Guido J H; Teelen, Karina; Hermsen, Cornelus C; Scholzen, Anja; Visser, Leo G; Sauerwein, Robert W

    2014-01-01

    Immunization of healthy volunteers with chloroquine ChemoProphylaxis and Sporozoites (CPS-CQ) efficiently and reproducibly induces dose-dependent and long-lasting protection against homologous Plasmodium falciparum challenge. Here, we studied whether chloroquine can be replaced by mefloquine, which is the only other licensed anti-malarial chemoprophylactic drug that does not affect pre-erythrocytic stages, exposure to which is considered essential for induction of protection by CPS immunization. In a double blind randomized controlled clinical trial, volunteers under either chloroquine prophylaxis (CPS-CQ, n = 5) or mefloquine prophylaxis (CPS-MQ, n = 10) received three sub-optimal CPS immunizations by bites from eight P. falciparum infected mosquitoes each, at monthly intervals. Four control volunteers received mefloquine prophylaxis and bites from uninfected mosquitoes. CPS-MQ immunization is safe and equally potent compared to CPS-CQ inducing protection in 7/10 (70%) versus 3/5 (60%) volunteers, respectively. Furthermore, specific antibody levels and cellular immune memory responses were comparable between both groups. We therefore conclude that mefloquine and chloroquine are equally effective in CPS-induced immune responses and protection. Trial registration: ClinicalTrials.gov NCT01422954.

  2. Pathobiology of secondary immune thrombocytopenia

    Science.gov (United States)

    Cines, Douglas B.; Liebman, Howard; Stasi, Roberto

    2009-01-01

    Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes of secondary ITP differ from each other and from primary ITP, so accurate diagnosis is essential. Immune thrombocytopenia can be secondary to medications or to a concurrent disease, such as an autoimmune condition (eg, systemic lupus erythematosus [SLE], antiphospholipid antibody syndrome [APS], immune thyroid disease, or Evans syndrome), a lymphoproliferative disease (eg, chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia), or chronic infection, eg, with Helicobacter pylori, human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Response to infection may generate antibodies that cross-react with platelet antigens (HIV, H pylori) or immune complexes that bind to platelet Fcγ receptors (HCV) and platelet production may be impaired by infection of megakaryocyte bone marrow-dependent progenitor cells (HCV and HIV), decreased production of thrombopoietin (TPO), and splenic sequestration of platelets secondary to portal hypertension (HCV). Sudden and severe onset of thrombocytopenia has been observed in children after vaccination for measles, mumps, and rubella or natural viral infections, including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management. PMID:19245930

  3. Effect of thrombopoietin-receptor agonists on circulating cytokine and chemokine levels in patients with primary immune thrombocytopenia (ITP)

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Ghanima, Waleed; Nielsen, Claus H

    2017-01-01

    with TPO-RAs (median age 50 years (inter-quartile range; IQR 20-69), median platelet counts 24 × 10(9)/L (IQR 15-47 × 10(9)/L), 28 females) and 16 healthy controls (nine females, median age 37 years, IQR 22-51 years) were collected before and during treatment, and analyzed for a panel of cytokines...... increased platelet turnover. Levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-10 did not change during treatment. CONCLUSION: These findings suggest that treatment with TPO-RA creates a more balanced steady-state of immune activation....

  4. Hepatitis B Vaccine Coverage and the Immune Response in Children under ten years old in Sana'a, Yemen.

    Science.gov (United States)

    Al-Shamahy, Hassan A; Hanash, Samira H; Rabbad, Iqbal A; Al-Madhaji, Nameem M; Naser, Samarih M

    2011-02-01

    The study was undertaken, first, to determine the coverage rate of hepatitis B (HB) vaccine and second to evaluate the immune response to HB vaccine among children under 10 years old by measuring the level of circulating anti-HB surface antigen (anti-HBs) antibodies after immunisation with three doses. First, 840 children were randomly selected from 4 randomly selected sites in Sana'a city to study the coverage rate of the vaccine; of these, 504 children vaccinated against HBV prior to the study, were tested (56% males and 44% females). Sera were tested for anti-HBs antibodies by ELISA quantitative technique. Each individual's data was collected in a pre-designed questionnaire including: vaccination date, sex, and age at the time of the study. The coverage rate of HBV vaccine was only 69.9%, being slightly higher among male children (72.1%) than female children (66.8%). A total of 276 (54.8%) of the 504 children responded to the vaccine with anti-HBs antibody level ≥ 10 mIU/ml, while 228 (45.2%) of the 504 children had non-protective anti-HBs antibodies levels (Yemen.

  5. Local and systemic immune mechanisms underlying the anti-colitis effects of the dairy bacterium Lactobacillus delbrueckii.

    Directory of Open Access Journals (Sweden)

    Clarissa Santos Rocha

    Full Text Available Several probiotic bacteria have been proposed for treatment or prevention of inflammatory bowel diseases (IBD, showing a protective effect in animal models of experimental colitis and for some of them also in human clinical trials. While most of these probiotic bacteria are isolated from the digestive tract, we recently reported that a Lactobacillus strain isolated from cheese, L. delbrueckii subsp. lactis CNRZ327 (Lb CNRZ327, also possesses anti-inflammatory effects in vitro and in vivo, demonstrating that common dairy bacteria may be useful in the treatment or prevention of IBD. Here, we studied the mechanisms underlying the protective effects of Lb CNRZ327 in vivo, in a mouse dextran sodium sulfate (DSS colitis model. During colitis, Lb CNRZ327 modulated the production of TGF-β, IL-6, and IL-12 in colonic tissue and of TGF-β and IL-6 in the spleen, and caused an expansion of CD4+Foxp3+ regulatory T cells in the cecal lymph nodes. Moreover, a strong tendency to CD4+Foxp3+ expansion was also observed in the spleen. The results of this study for the first time show that orally administered dairy lactobacilli can not only modulate mucosal but also systemic immune responses and constitute an effective treatment of IBD.

  6. Primary Damage Characteristics in Metals Under Irradiation in the Cores of Thermal and Fast Reactors

    International Nuclear Information System (INIS)

    Pechenkin, V.A.

    2012-01-01

    For an analysis and forecasting of radiation-induced phenomena in structural materials of WWERs, PWRs and BN reactors the fast neutron fluence is usually used (for structural materials of the reactor cores and internals the fluence of neutrons with energy > 0.1 MeV, for WWER and PWRs vessel steels the fluence of neutrons with energy > 0.5 MeV in Russia and East Europe, and with energy > 1.0 MeV in USA and France). Displacements per atom (dpa) seem to be a more appropriate correlation parameter, because it allows comparing the results of materials irradiation in different neutron energy spectra or with different types of particles (neutrons, ions, fast electrons). Energy spectra of primary knocked atoms (PKA) and 'effective' dpa, which are introduced to take into account the point defect recombination during the relaxation stage of a displacement cascade, can be still better representation of the effect of irradiation on material properties. In this work the results of calculating dose rates (dpa/s, NRT-model), PKA energy spectra and PKA mean energies in metals under irradiation in the cores of Russian reactors WWER-440, WWER-1000 (both power thermal reactors) and BN-600 (power fast reactor) and BR-10 (test fast reactor) are presented. In all the reactors Fe and Zr are considered, with addition of Ti and W in BN-600. 'Effective' dose rates in these metals are calculated. Limitations and uncertainties in the standard dpa formulation (the NRT-dpa) are discussed. IPPE activities in the fields related to the TM subject are considered

  7. Arctigenin induces the apoptosis of primary effusion lymphoma cells under conditions of glucose deprivation.

    Science.gov (United States)

    Baba, Yusuke; Shigemi, Zenpei; Hara, Naoko; Moriguchi, Misato; Ikeda, Marina; Watanabe, Tadashi; Fujimuro, Masahiro

    2018-02-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of primary effusion lymphoma (PEL) and Kaposi's sarcoma. PEL is a type of non-Hodgkin's B-cell lymphoma, affecting immunosuppressed individuals, such as post-transplant or AIDS patients. However, since PEL is resistant to chemotherapeutic regimens, new effective treatment strategies are required. Arctigenin, a natural lignan compound found in the plant Arctium lappa, has been widely investigated as a potential anticancer agent in the clinical setting. In the present study, we examined the cytotoxic effects of arctigenin by cell viability assay and found that arctigenin markedly inhibited the proliferation of PEL cells compared with KSHV-uninfected B-lymphoma cells under conditions of glucose deprivation. Arctigenin decreased cellular ATP levels, disrupted mitochondrial membrane potential and triggered caspase-9-mediated apoptosis in the glucose-deprived PEL cells. In addition, western blot analysis using phospho-specific antibodies were used to evaluate activity changes in the signaling pathways of interest. As a result, arctigenin suppressed the activation of the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways by inhibiting ERK and p38 MAPK phosphorylation in the glucose-deprived PEL cells. We confirmed that an inhibitor of ERK (U0126) or p38 MAPK (SB202190 and SB203580) suppressed the proliferation of the BC3 PEL cells compared with the KSHV-negative DG75 cells. Moreover, RT-PCR and luciferase reporter assay revealed that arctigenin and p38 MAPK inhibition by SB202190 or SB203580 downregulated the transcriptional expression of unfolded protein response (UPR)‑related molecules, including GRP78 and ATF6α under conditions of glucose deprivation. Finally, we confirmed that arctigenin did not affect KSHV replication in PEL cells, suggesting that arctigenin treatment for PEL does not contribute to the risk of de novo KSHV

  8. Genome-wide transcriptome analysis of soybean primary root under varying water-deficit conditions.

    Science.gov (United States)

    Song, Li; Prince, Silvas; Valliyodan, Babu; Joshi, Trupti; Maldonado dos Santos, Joao V; Wang, Jiaojiao; Lin, Li; Wan, Jinrong; Wang, Yongqin; Xu, Dong; Nguyen, Henry T

    2016-01-15

    Soybean is a major crop that provides an important source of protein and oil to humans and animals, but its production can be dramatically decreased by the occurrence of drought stress. Soybeans can survive drought stress if there is a robust and deep root system at the early vegetative growth stage. However, little is known about the genome-wide molecular mechanisms contributing to soybean root system architecture. This study was performed to gain knowledge on transcriptome changes and related molecular mechanisms contributing to soybean root development under water limited conditions. The soybean Williams 82 genotype was subjected to very mild stress (VMS), mild stress (MS) and severe stress (SS) conditions, as well as recovery from the severe stress after re-watering (SR). In total, 6,609 genes in the roots showed differential expression patterns in response to different water-deficit stress levels. Genes involved in hormone (Auxin/Ethylene), carbohydrate, and cell wall-related metabolism (XTH/lipid/flavonoids/lignin) pathways were differentially regulated in the soybean root system. Several transcription factors (TFs) regulating root growth and responses under varying water-deficit conditions were identified and the expression patterns of six TFs were found to be common across the stress levels. Further analysis on the whole plant level led to the finding of tissue-specific or water-deficit levels specific regulation of transcription factors. Analysis of the over-represented motif of different gene groups revealed several new cis-elements associated with different levels of water deficit. The expression patterns of 18 genes were confirmed byquantitative reverse transcription polymerase chain reaction method and demonstrated the accuracy and effectiveness of RNA-Seq. The primary root specific transcriptome in soybean can enable a better understanding of the root response to water deficit conditions. The genes detected in root tissues that were associated with

  9. Model of Learning Organizational Development of Primary School Network under the Office of Basic Education Commission

    Science.gov (United States)

    Sai-rat, Wipa; Tesaputa, Kowat; Sriampai, Anan

    2015-01-01

    The objectives of this study were 1) to study the current state of and problems with the Learning Organization of the Primary School Network, 2) to develop a Learning Organization Model for the Primary School Network, and 3) to study the findings of analyses conducted using the developed Learning Organization Model to determine how to develop the…

  10. Yields of primary products from chloroethylenes in air under electron beam irradiation

    International Nuclear Information System (INIS)

    Hakoda, Teruyuki; Hashimoto, Shoji; Kojima, Takuji

    2003-01-01

    The quantitative analysis of toxic primary irradiation products was carried out for the development of the purification technology of chloroethylenes/air mixtures using an electron beam (EB). Degradation of chloroethylenes in humid air proceeded through the formation of primary products retaining a carbon-carbon (C-C) bond such as chloroacetyl chlorides and chloroacetyl aldehyde as well as that of primary products of COCl 2 and HCOCl through C-C bond cleavage. Chloroethylenes having one carbon bonded to two Cl atoms was decomposed into the primary products retaining a C-C bond prior to breaking a C-C bond. The number of Cl atoms of a chloroethylene molecule enhanced the formation ratio of primary products retaining a C-C bond. On the other hand, chloroethylene having two carbons bonded to one Cl atom was degraded thought the scission of a C-C bond predominantly C-C bond maintenance. (author)

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

    Science.gov (United States)

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

    2016-01-01

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

  12. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis

    NARCIS (Netherlands)

    Liu, Jimmy Z.; Hov, Johannes Roksund; Folseraas, Trine; Ellinghaus, Eva; Rushbrook, Simon M.; Doncheva, Nadezhda T.; Andreassen, Ole A.; Weersma, Rinse K.; Weismüller, Tobias J.; Eksteen, Bertus; Invernizzi, Pietro; Hirschfield, Gideon M.; Gotthardt, Daniel Nils; Pares, Albert; Ellinghaus, David; Shah, Tejas; Juran, Brian D.; Milkiewicz, Piotr; Rust, Christian; Schramm, Christoph; Müller, Tobias; Srivastava, Brijesh; Dalekos, Georgios; Nöthen, Markus M.; Herms, Stefan; Winkelmann, Juliane; Mitrovic, Mitja; Braun, Felix; Ponsioen, Cyriel Y.; Croucher, Peter J. P.; Sterneck, Martina; Teufel, Andreas; Mason, Andrew L.; Saarela, Janna; Leppa, Virpi; Dorfman, Ruslan; Alvaro, Domenico; Floreani, Annarosa; Onengut-Gumuscu, Suna; Rich, Stephen S.; Thompson, Wesley K.; Schork, Andrew J.; Næss, Sigrid; Thomsen, Ingo; Mayr, Gabriele; König, Inke R.; Hveem, Kristian; Cleynen, Isabelle; Gutierrez-Achury, Javier; Ricaño-Ponce, Isis; van Heel, David; Björnsson, Einar; Sandford, Richard N.; Durie, Peter R.; Melum, Espen; Vatn, Morten H.; Silverberg, Mark S.; Duerr, Richard H.; Padyukov, Leonid; Brand, Stephan; Sans, Miquel; Annese, Vito; Achkar, Jean-Paul; Boberg, Kirsten Muri; Marschall, Hanns-Ulrich; Chazouillères, Olivier; Bowlus, Christopher L.; Wijmenga, Cisca; Schrumpf, Erik; Vermeire, Severine; Albrecht, Mario; Rioux, John D.; Alexander, Graeme; Bergquist, Annika; Cho, Judy; Schreiber, Stefan; Manns, Michael P.; Färkkilä, Martti; Dale, Anders M.; Chapman, Roger W.; Lazaridis, Konstantinos N.; Franke, Andre; Anderson, Carl A.; Karlsen, Tom H.

    2013-01-01

    Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation. We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped

  13. Dense genotyping of immune-related disease regions identifies nine new risk loci for primary sclerosing cholangitis

    NARCIS (Netherlands)

    Liu, Jimmy Z.; Hov, Johannes Roksund; Folseraas, Trine; Ellinghaus, Eva; Rushbrook, Simon M.; Doncheva, Nadezhda T.; Andreassen, Ole A.; Weersma, Rinse K.; Weismueller, Tobias J.; Eksteen, Bertus; Invernizzi, Pietro; Hirschfield, Gideon M.; Gotthardt, Daniel Nils; Pares, Albert; Ellinghaus, David; Shah, Tejas; Juran, Brian D.; Milkiewicz, Piotr; Rust, Christian; Schramm, Christoph; Mueller, Tobias; Srivastava, Brijesh; Dalekos, Georgios; Noethen, Markus M.; Herms, Stefan; Winkelmann, Juliane; Mitrovic, Mitja; Braun, Felix; Ponsioen, Cyriel Y.; Croucher, Peter J. P.; Sterneck, Martina; Teufel, Andreas; Mason, Andrew L.; Saarela, Janna; Leppa, Virpi; Dorfman, Ruslan; Alvaro, Domenico; Floreani, Annarosa; Onengut-Gumuscu, Suna; Rich, Stephen S.; Thompson, Wesley K.; Schork, Andrew J.; Naess, Sigrid; Thomsen, Ingo; Mayr, Gabriele; Koenig, Inke R.; Hveem, Kristian; Cleynen, Isabelle; Gutierrez-Achury, Javier; Ricano-Ponce, Isis; van Heel, David; Bjoernsson, Einar; Sandford, Richard N.; Durie, Peter R.; Melum, Espen; Vatn, Morten H.; Silverberg, Mark S.; Duerr, Richard H.; Padyukov, Leonid; Brand, Stephan; Sans, Miquel; Annese, Vito; Achkar, Jean-Paul; Boberg, Kirsten Muri; Marschall, Hanns-Ulrich; Chazouilleres, Olivier; Bowlus, Christopher L.; Wijmenga, Cisca; Schrumpf, Erik; Vermeire, Severine; Albrecht, Mario; Rioux, John D.; Alexander, Graeme; Bergquist, Annika; Cho, Judy; Schreiber, Stefan; Manns, Michael P.; Farkkila, Martti; Dale, Anders M.; Chapman, Roger W.; Lazaridis, Konstantinos N.; Franke, Andre; Anderson, Carl A.; Karlsen, Tom H.

    Primary sclerosing cholangitis (PSC) is a severe liver disease of unknown etiology leading to fibrotic destruction of the bile ducts and ultimately to the need for liver transplantation(1-3). We compared 3,789 PSC cases of European ancestry to 25,079 population controls across 130,422 SNPs genotyped

  14. Proteomics plus genomics approaches in primary immunodeficiency: the case of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome.

    Science.gov (United States)

    Zennaro, D; Scala, E; Pomponi, D; Caprini, E; Arcelli, D; Gambineri, E; Russo, G; Mari, A

    2012-01-01

    Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a rare syndrome due to a mutation in the forkhead box protein 3 gene (FOXP3) leading to an impaired regulatory T cell (T(reg) ) activity associated both with skewed T helper type 2 (Th2) response and autoreactive phenomena. The purpose of this study was to describe a combined proteomics and genomics approach to comprehensively evaluate clinical and immunological phenotypes of patients affected by IPEX. T cell receptor (TCR)-Vβ repertoire and peripheral blood lymphocytes phenotype from three brothers affected by IPEX were studied by flow cytometry. Specific immunoglobulin (Ig)E were evaluated by means of an allergenic molecules microarray [immuno solid-phase allergen chip (ISAC)]. Total RNA was extracted and hybridized to Affymetrix oligonucleotide arrays to obtain quantitative gene-expression levels. No FOXP3 protein was detectable within CD127(-) CD25(high) CD4(+) T cells from peripheral blood. A T cell-naive phenotype (CD62L(+) CD45R0(-)) associated with a reduction of both CD26 and CD7 expression and a TCR-Vβ 8 and 22 family expansions were found. B lymphocytes were mainly CD5(+) (B1) cells expressing a naive phenotype (tcl1(+) CD27(-)). The three IPEX patients had severe food allergy and specific IgE reactivity to cow's milk allergens, a hen's egg allergen and a wheat allergen. Gene expression profile analysis revealed a dysregulation associated mainly with Th1/Th2 pathways. The multiplexing evaluation reported in this study represents a comprehensive approach in the assessment of genetic conditions affecting the immune system such as the IPEX syndrome, paving the way for the development of diagnostic tools to improve the standard clinical and immunological profiling of the disease. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  15. Activating transcription factor 4 underlies the pathogenesis of arsenic trioxide-mediated impairment of macrophage innate immune functions

    International Nuclear Information System (INIS)

    Srivastava, Ritesh K.; Li, Changzhao; Wang, Yong; Weng, Zhiping; Elmets, Craig A.; Harrod, Kevin S.; Deshane, Jessy S.; Athar, Mohammad

    2016-01-01

    Chronic arsenic exposure to humans is considered immunosuppressive with augmented susceptibility to several infectious diseases. The exact molecular mechanisms, however, remain unknown. Earlier, we showed the involvement of unfolded protein response (UPR) signaling in arsenic-mediated impairment of macrophage functions. Here, we show that activating transcription factor 4 (ATF4), a UPR transcription factor, regulates arsenic trioxide (ATO)-mediated dysregulation of macrophage functions. In ATO-treated ATF4 +/+ wild-type mice, a significant down-regulation of CD11b expression was associated with the reduced phagocytic functions of peritoneal and lung macrophages. This severe immuno-toxicity phenotype was not observed in ATO-treated ATF4 +/− heterozygous mice. To confirm these observations, we demonstrated in Raw 264.7 cells that ATF4 knock-down rescues ATO-mediated impairment of macrophage functions including cytokine production, bacterial engulfment and clearance of engulfed bacteria. Sustained activation of ATF4 by ATO in macrophages induces apoptosis, while diminution of ATF4 expression protects against ATO-induced apoptotic cell death. Raw 264.7 cells treated with ATO also manifest dysregulated Ca ++ homeostasis. ATO induces Ca ++ -dependent calpain-1 and caspase-12 expression which together regulated macrophage apoptosis. Additionally, apoptosis was also induced by mitochondria-regulated pathway. Restoring ATO-impaired Ca ++ homeostasis in ER/mitochondria by treatments with the inhibitors of inositol 1,4,5-trisphosphate receptor (IP3R) and voltage-dependent anion channel (VDAC) attenuate innate immune functions of macrophages. These studies identify a novel role for ATF4 in underlying pathogenesis of macrophage dysregulation and immuno-toxicity of arsenic. - Highlights: • ATF4 regulates arsenic-mediated impairment in macrophage functions. • Arsenic-mediated alterations in pulmonary macrophage are diminished in ATF4 +/− mice. • Changes in macrophage

  16. Phenotyping and comparing the immune cell populations of free-ranging Atlantic bottlenose dolphins (Tursiops truncatus) and dolphins under human care.

    Science.gov (United States)

    Nouri-Shirazi, Mahyar; Bible, Brittany F; Zeng, Menghua; Tamjidi, Saba; Bossart, Gregory D

    2017-03-27

    Studies suggest that free-ranging bottlenose dolphins exhibit a suppressed immune system because of exposure to contaminants or microorganisms. However, due to a lack of commercially available antibodies specific to marine mammal immune cell surface markers, the research has been indecisive. The purpose of this study was to identify cross-reactive terrestrial-specific antibodies in order to assess the changes in the immune cell populations of dolphins under human care and free-ranging dolphins. The blood and PBMC fraction of blood samples from human care and free-ranging dolphins were characterized by H&E staining of cytospin slides and flow cytometry using a panel of terrestrial-specific antibodies. In this study, we show that out of 65 terrestrial-specific antibodies tested, 11 were cross-reactive and identified dolphin immune cell populations within their peripheral blood. Using these antibodies, we found significant differences in the absolute number of cells expressing specific markers within their lymphocyte and monocyte fractions. Interestingly, the peripheral blood mononuclear cell profile of free-ranging dolphins retained an additional population of cells that divided them into two groups showing a low (56%) percentage of smaller cells resembling granulocytes. We found that the cross-reactive antibodies not only identified specific changes in the immune cells of free-ranging dolphins, but also opened the possibility to investigate the causal relationship between immunosuppression and mortality seen in free-ranging dolphins.

  17. 75 FR 36099 - Legislative Changes to Primary Care Loan Program Authorized Under Title VII of the Public Health...

    Science.gov (United States)

    2010-06-24

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Health Resources and Services Administration Legislative Changes to Primary Care Loan Program Authorized Under Title VII of the Public Health Service Act AGENCY... changes Section 723 of the Public Health Service Act (PHSA) regarding administration of the PCL program...

  18. Cortical Neural Synchronization Underlies Primary Visual Consciousness of Qualia: Evidence from Event-Related Potentials

    OpenAIRE

    Babiloni, Claudio; Marzano, Nicola; Soricelli, Andrea; Cordone, Susanna; Mill?n-Calenti, Jos? Carlos; Del Percio, Claudio; Buj?n, Ana

    2016-01-01

    This article reviews three experiments on event-related potentials (ERPs) testing the hypothesis that primary visual consciousness (stimulus self-report) is related to enhanced cortical neural synchronization as a function of stimulus features. ERP peak latency and sources were compared between “seen” trials and “not seen” trials, respectively related and unrelated to the primary visual consciousness. Three salient features of visual stimuli were considered (visuospatial, emotional face expre...

  19. RI-002, an intravenous immunoglobulin containing high titer neutralizing antibody to RSV and other respiratory viruses for use in primary immunodeficiency disease and other immune compromised populations.

    Science.gov (United States)

    Wasserman, Richard L; Greener, Benjamin N; Mond, James

    2017-12-01

    Novel immune globulin (IG) products (RI-002, RI-001) have been designed to provide protection against respiratory syncytial virus (RSV) mediated respiratory illness while at the same time meeting the manufacturing requirements established by FDA for antibody supplementation in immunocompromised subjects. Areas covered: This review covers the manufacture and development of both RI-001 and RI-002, including the selection of plasma donors for IG preparation with high-titers of anti-RSV antibody, in vitro, and preclinical data in the cotton rat model S. hispidus, and clinical trials including Phase II and compassionate use studies of RI-001 and a multi-center, pivotal Phase III study of RI-002 in PIDD patients. Expert commentary: The data demonstrate that RI-002 is efficacious in the prevention and treatment of RSV in preclinical normal and immune suppressed animal models and is safe and efficacious in the treatment of patients with various forms of primary immunodeficiency disease (PIDD). This product offers potential advantages over other available IG's for prophylaxis in immunocompromised patients requiring polyclonal immunoglobulin supplementation because of its unique antibody composition. In addition to its enhanced neutralizing anti-RSV activity and its polyclonal IG composition, there is preclinical data to support the use of RI-002 for humoral protection against other respiratory pathogens.

  20. The Immune System: Basis of so much Health and Disease: 4. Immunocytes.

    Science.gov (United States)

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-05-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covers cells of the immune system (immunocytes). Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  1. Clinical Outcome and Predictive Factors in the Response to Splenectomy in Elderly Patients with Primary Immune Thrombocytopenia: A Multicenter Retrospective Study.

    Science.gov (United States)

    Park, Young Hoon; Yi, Hyeon Gyu; Kim, Chul Soo; Hong, Junshik; Park, Jinny; Lee, Jae Hoon; Kim, Ho Young; Kim, Hyo Jung; Zang, Dae Young; Kim, Se Hyung; Park, Seong Kyu; Hong, Dae Sik; Lee, Guk Jin; Jin, Jong-Youl

    2016-01-01

    Because many physicians seem reluctant to recommend splenectomy for elderly patients with immune thrombocytopenia (ITP), we investigated the safety and efficacy of splenectomy and the predictive factors for response in these patients. 184 patients with primary ITP were retrospectively analyzed based on age at splenectomy: an elderly group (≥60 years, n = 52) and a younger group (splenectomy (HR 2.9, 95% CI: 1.24-6.80, p = 0.014) and platelet count on postoperative day 14 ≥200 × 109/l (HR 31.43, 95% CI: 4.15-238.28, p = 0.001) were independent factors for a favorable response. Age ≥60 years did not influence the response to splenectomy but was associated with increased relapse and postoperative complications. Splenectomy could provide a durable long-term response for elderly ITP patients. © 2016 S. Karger AG, Basel.

  2. Emergence of long-lived autoreactive plasma cells in the spleen of primary warm auto-immune hemolytic anemia patients treated with rituximab.

    Science.gov (United States)

    Mahévas, Matthieu; Michel, Marc; Vingert, Benoit; Moroch, Julien; Boutboul, David; Audia, Sylvain; Cagnard, Nicolas; Ripa, Julie; Menard, Cédric; Tarte, Karin; Mégret, Jérôme; Le Gallou, Simon; Patin, Pauline; Thai, Lan; Galicier, Lionel; Bonnotte, Bernard; Godeau, Bertrand; Noizat-Pirenne, France; Weill, Jean-Claude; Reynaud, Claude-Agnès

    2015-08-01

    Primary warm autoimmune hemolytic anemia (wAIHA) is a rare autoimmune disease in which red blood cells are eliminated by IgG autoantibodies. We analyzed the antibody-secreting cells in the spleen and the peripheral blood of wAIHA patients in various contexts of treatment. Plasmablasts were observed in peripheral blood of newly diagnosed wAIHA patients and, accordingly, active germinal center reactions were present in the spleen of patients receiving short-term corticosteroid therapy. Long-term corticosteroid regimens markedly reduced this response while splenic plasma cells were able to persist, a fraction of them secreting anti-red blood cell IgG in vitro. In wAIHA patients treated by rituximab and who underwent splenectomy because of treatment failure, plasma cells were still present in the spleen, some of them being autoreactive. By using a set of diagnostic genes that allowed us to assess the plasma cell maturation stage, we observed that these cells displayed a long-lived program, differing from the one of plasma cells from healthy donors or from wAIHA patients with various immunosuppressant treatments, and more similar to the one of normal long-lived bone-marrow plasma cells. Interestingly, an increased level of B-cell activating factor (BAFF) was observed in the supernatant of spleen cell cultures from such rituximab-treated wAIHA patients. These results suggest, in line with our previous report on primary immune thrombocytopenia, that the B-cell depletion induced by rituximab promoted a suitable environment for the maturation and survival of auto-immune long-lived plasma cells in the spleen. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Costs and benefits of experimentally induced changes in the allocation of growth versus immune function under differential exposure to ectoparasites.

    Directory of Open Access Journals (Sweden)

    Natalia Pitala

    2010-05-01

    Full Text Available Ecological immunology has focused on the costs of investment in immunocompetence. However, understanding optimal resource allocation to immune defence requires also identification of its benefits, which are likely to occur only when parasites are abundant.We manipulated the abundance of parasitic hen fleas in blue tit (Cyanistes caeruleus nests, and supplemented their hosts, the nestlings, with methionine (a sulphur amino acid enhancing cell-mediated immunity during day 3-6. We found a significant interaction between these two experimental factors on the development of immune defences and growth rates. Only in parasitized nests did methionine supplementation boost immune (PHA response, and did nestling with experimentally increased immunocompetence show a relatively faster growth rate than control nestlings between days 6-9. Hence, the allocation of resources into immune defence and its growth-benefits are apparent only in presence of parasites. The main cost of methionine-induced increased allocation to the immune system was an increase in mortality, independently of ectoparasites. Nestlings in all treatments compensated initial growth reduction and all reached equal body size at day 16 (just prior to fledging, indicating a lack of long-term benefits. In addition, methionine treatment tended (P = 0.09 to lower circulating plasma immunoglobulin levels, possibly indicating a trade-off between the cell-mediated and humoral components of the immune system.We found no strong benefits of an increased investment in immunocompetence in a parasite-rich environment. Any deviation from the growth trajectory (due to changes in allocation induced by methionine is largely detrimental for survival. Hence, while costs are apparent identifying the benefits of investment in immunocompetence during ontogeny is challenging.

  4. A quantitative assessment of primary and secondary immune responses in cattle using a B cell ELISPOT assay

    OpenAIRE

    Lefevre, Eric A.; Carr, B. Veronica; Prentice, Helen; Charleston, Bryan

    2008-01-01

    International audience; The aim of the study was to build a comprehensive picture of the appearance in the blood stream of Ag-specific plasma cells and memory B cells in the bovine model. For this purpose, we have developed a method allowing the detection and quantification of both cell types within individual calves immunised with ovalbumin. During the primary response, we detected a burst of ovalbumin-specific plasma cells at days 6 and 7 post-immunisation, which was followed by the product...

  5. Investigating Power System Primary and Secondary Reserve Interaction under High Wind Power Penetration

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yingchen [National Renewable Energy Lab. (NREL), Golden, CO (United States); Tan, Jin [National Renewable Energy Lab. (NREL), Golden, CO (United States); Krad, Ibrahim [National Renewable Energy Lab. (NREL), Golden, CO (United States); Yang, Rui [National Renewable Energy Lab. (NREL), Golden, CO (United States); Gevorgian, Vahan [National Renewable Energy Lab. (NREL), Golden, CO (United States); Ela, Erik [Electric Power Research Inst. (EPRI), Knoxville, TN (United States)

    2016-12-01

    Power system frequency needs to be maintained close to its nominal value at all times to successfully balance load and generation and maintain system reliability. Adequate primary frequency response and secondary frequency response are the primary forces to correct an energy imbalance at the second-to-minute level. As wind energy becomes a larger portion of the world's energy portfolio, there is an increased need for wind to provide frequency response. This paper addresses one of the major concerns about using wind for frequency regulation: the unknown factor of the interaction between primary and secondary reserves. The lack of a commercially available tool to model this has limited the energy industry's understanding of when the depletion of primary reserves will impact the performance of secondary response or vice versa. This paper investigates the issue by developing a multi-area frequency response integration tool with combined primary and secondary capabilities. The simulation is conducted in close coordination with economical energy scheduling scenarios to ensure credible simulation results.

  6. Primary Human Blood Dendritic Cells for Cancer Immunotherapy—Tailoring the Immune Response by Dendritic Cell Maturation

    Directory of Open Access Journals (Sweden)

    Simone P. Sittig

    2015-12-01

    Full Text Available Dendritic cell (DC-based cancer vaccines hold the great promise of tipping the balance from tolerance of the tumor to rejection. In the last two decades, we have gained tremendous knowledge about DC-based cancer vaccines. The maturation of DCs has proven indispensable to induce immunogenic T cell responses. We review the insights gained from the development of maturation cocktails in monocyte derived DC-based trials. More recently, we have also gained insights into the functional specialization of primary human blood DC subsets. In peripheral human blood, we can distinguish at least three primary DC subsets, namely CD1c+ and CD141+ myeloid DCs and plasmacytoid DCs. We reflect the current knowledge on maturation and T helper polarization by these blood DC subsets in the context of DC-based cancer vaccines. The maturation stimulus in combination with the DC subset will determine the type of T cell response that is induced. First trials with these natural DCs underline their excellent in vivo functioning and mark them as promising tools for future vaccination strategies.

  7. Newborn Screening for Primary T- and B-Cell Immune Deficiencies—A Prospective Study in Andalucía

    Directory of Open Access Journals (Sweden)

    Beatriz de Felipe

    2017-10-01

    Full Text Available Background: Quantification of T-cell-receptor-excision circles (TRECs and kappa-deleting-recombination-excision circles (KRECs from dried blood spots (DBS allows detection of neonates with severe T-cell and/or B-cell lymphopenia that are potentially affected by severe combined immunodeficiency (SCID, as well as X-linked agammaglobulinemia (XLA. Methods: Determination of TRECs and KRECs using a triplex RT-PCR (TRECS-KRECS-β-actin assay from prospectively collected DBS between February 2014 and December 2016 in three hospitals in Seville, Spain. Cut-off levels were TRECs < 6/punch, KRECs < 4/punch and b-actin > 700/punch. Internal (SCID, XLA, ataxia telangiectasia and external controls (CDC were included. Results: A total of 8943 DBS samples obtained from 8814 neonates were analysed. Re-punching was necessary in 124 samples (1.4% due to insufficient β-actin values (<700 copies/punch. Preterm neonates (GA < 37 weeks and neonates with a BW < 2500 g showed significantly lower TRECs and KRECs levels (p < 0.001. Due to repeated pathological results, ten neonates were re-sampled (0.11%, of which five neonates (0.055% confirmed the pathological results: one case was a fatal chromosomopathy (TRECs 1/KRECs 4; two were extreme premature newborns (TRECs 0/KRECs 0 and TRECs 1/KRECs 20 copies/punch; and 2 neonates were born to mothers receiving azathioprine during pregnancy (TRECs 92/KRECs 1 and TRECs 154/KRECs 3 copies/punch. All controls were correctly identified. Conclusions: Severe T- and B-cell lymphopenias were correctly identified by the TRECS-KRECS-β-actin assay. Prematurity and low BW are associated with lower TREC and KREC levels. Extreme prematurity and maternal immune suppressive therapy can cause false positive results of TRECs and KRECs values.

  8. Cortical Neural Synchronization Underlies Primary Visual Consciousness of Qualia: Evidence from Event-Related Potentials.

    Science.gov (United States)

    Babiloni, Claudio; Marzano, Nicola; Soricelli, Andrea; Cordone, Susanna; Millán-Calenti, José Carlos; Del Percio, Claudio; Buján, Ana

    2016-01-01

    This article reviews three experiments on event-related potentials (ERPs) testing the hypothesis that primary visual consciousness (stimulus self-report) is related to enhanced cortical neural synchronization as a function of stimulus features. ERP peak latency and sources were compared between "seen" trials and "not seen" trials, respectively related and unrelated to the primary visual consciousness. Three salient features of visual stimuli were considered (visuospatial, emotional face expression, and written words). Results showed the typical visual ERP components in both "seen" and "not seen" trials. There was no statistical difference in the ERP peak latencies between the "seen" and "not seen" trials, suggesting a similar timing of the cortical neural synchronization regardless the primary visual consciousness. In contrast, ERP sources showed differences between "seen" and "not seen" trials. For the visuospatial stimuli, the primary consciousness was related to higher activity in dorsal occipital and parietal sources at about 400 ms post-stimulus. For the emotional face expressions, there was greater activity in parietal and frontal sources at about 180 ms post-stimulus. For the written letters, there was higher activity in occipital, parietal and temporal sources at about 230 ms post-stimulus. These results hint that primary visual consciousness is associated with an enhanced cortical neural synchronization having entirely different spatiotemporal characteristics as a function of the features of the visual stimuli and possibly, the relative qualia (i.e., visuospatial, face expression, and words). In this framework, the dorsal visual stream may be synchronized in association with the primary consciousness of visuospatial and emotional face contents. Analogously, both dorsal and ventral visual streams may be synchronized in association with the primary consciousness of linguistic contents. In this line of reasoning, the ensemble of the cortical neural networks

  9. Analysis of corrosion product transport in PWR primary system under non-convective condition

    International Nuclear Information System (INIS)

    Han, Byoung Sub

    1992-02-01

    The increase of occupational radiation exposure (ORE) due to the increase of the operational period at existing nuclear power plant and also the publication of the new version of ICRP recommendation (ICRP publication No. 60) for radiological protection require much more strict reduction of radiation buildup in the nuclear power plant. The major sources of the radiation, i.e. the radioactive corrosion-products, are generated by the neutron activation of the corrosion products at the reactor core, and then the radioactive corrosion products are transported to the outside of the core, and accumulated near the steam generator side at PWR. Major radioactive corrosion-products of interest in PWR are Cr 51 ,: Mn 54 ,: Co 58 ,: Fe 59 and Co 60 . Among them Co 58 and Co 60 are known to contribute approximately more than 70% of the total ORE. Thus our main concerns are focused on predicting the transport and deposition of the Co radionuclides and suggesting the optimizing method which can minimize and control the ORE of the nuclear power plant. It is well known that Co-source is most effectively controlled by pH-solubility radiation control, and also some complex computer codes such as CORA and PACTOLE have been developed and revised to predict the corrosion product behavior. However these codes still imply some intrisic problems in simulating the real behavior of corrosion products in the reactor because of 1) the lack of important experimental data, coefficients and parameters of the transport and reactions under actual high temperature and pressure conditions, 2) no general theoretical modelling which can describe such many different mechanisms involved in the corrosion product movements, 3) the newly developed and measured behavior of the corrosion product transport mechanism. Since no sufficient and detailed information is available from the above-mentioned codes (also due to propriority problems), we concentrate on developing a new computer code, CP-TRAN (Corrosion

  10. Quantitative visual fields under binocular viewing conditions in primary and consecutive divergent strabismus

    NARCIS (Netherlands)

    Joosse, M. V.; Simonsz, H. J.; van Minderhout, E. M.; Mulder, P. G.; de Jong, P. T.

    1999-01-01

    Although there have been a number of studies on the size of the suppression scotoma in divergent strabismus, there have been no reports on the full extent (i.e. size as well as depth) of this scotoma. Binocular static perimetry was used to measure suppression scotomas in five patients with primary

  11. Optimal Cognitive Access and Packet Selection Under a Primary ARQ Process via Chain Decoding

    DEFF Research Database (Denmark)

    Michelusi, Nicolò; Popovski, Petar; Zorzi, Michele

    2016-01-01

    This paper introduces a novel technique that enables access by a cognitive secondary user (SU) to a spectrum occupied by an incumbent primary user (PU) that employs Type-I hybrid automatic retransmission request (ARQ). The technique allows the SU to perform selective retransmissions of SU data pa...

  12. Pedagogical actions under pressure? Primary school teachers’ perceptions of their pedagogical actions

    NARCIS (Netherlands)

    Gemmink, Michelle; Fokkens-Bruinsma, Marjon; Pauw, Ietje; van Veen, Klaas

    2017-01-01

    In Dutch primary schools, pedagogical actions seem to receive much less attention than content knowledge. This is the consequence of several developments and innovations that aimed at enhancing pupils’ learning outcomes and at improving teachers’ content knowledge and didactic actions. This results

  13. Small diversity effects on ocean primary production under environmental change in a diversity-resolving ocean ecosystem model

    DEFF Research Database (Denmark)

    Prowe, Friederike; Pahlow, M.; Dutkiewicz, S.

    2013-01-01

    Marine ecosystem models used to investigate how global change affects ocean ecosystems and their functioning typically omit pelagic diversity. Diversity, however, can affect functions such as primary production and their sensitivity to environmental changes. Using a global ocean ecosystem model...... that explicitly resolves phytoplankton diversity within four phytoplankton functional types (PFTs) we investigate the model's ability to capture diversity effects on primary production under environmental change. An idealized scenario with a sudden reduction in vertical mixing causes diversity and primary......-production changes that turn out to be largely independent of the number of coexisting phytoplankton types. The model provides a small number of niches with respect to nutrient use in accordance with the PFTs defined in the model, and increasing the number of phytoplankton types increases the resolution within...

  14. Rural-to-Urban Migrants' Experiences with Primary Care under Different Types of Medical Institutions in Guangzhou, China.

    Science.gov (United States)

    Zeng, Jiazhi; Shi, Leiyu; Zou, Xia; Chen, Wen; Ling, Li

    2015-01-01

    China is facing the unprecedented challenge of rapidly increasing rural-to-urban migration. Migrants are in a vulnerable state when they attempt to access to primary care services. This study was designed to explore rural-to-urban migrants' experiences in primary care, comparing their quality of primary care experiences under different types of medical institutions in Guangzhou, China. The study employed a cross-sectional survey of 736 rural-to-urban migrants in Guangzhou, China in 2014. A validated Chinese version of Primary Care Assessment Tool--Adult Short Version (PCAT-AS), representing 10 primary care domains was used to collect information on migrants' quality of primary care experiences. These domains include first contact (utilization), first contact (accessibility), ongoing care, coordination (referrals), coordination (information systems), comprehensiveness (services available), comprehensiveness (services provided), family-centeredness, community orientation and culturally competent. These measures were used to assess the quality of primary care performance as reported from patients' perspective. Analysis of covariance was conducted for comparison on PCAT scores among migrants accessing primary care in tertiary hospitals, municipal hospitals, community health centers/community health stations, and township health centers/rural health stations. Multiple linear regression models were used to explore factors associated with PCAT total scores. After adjustments were made, migrants accessing primary care in tertiary hospitals (25.49) reported the highest PCAT total scores, followed by municipal hospitals (25.02), community health centers/community health stations (24.24), and township health centers/rural health stations (24.18). Tertiary hospital users reported significantly better performance in first contact (utilization), first contact (accessibility), coordination (information system), comprehensiveness (service available), and cultural competence

  15. Physiological and proteomic evidences that domestication process differentially modulates the immune status of juvenile Eurasian perch (Perca fluviatilis) under chronic confinement stress.

    Science.gov (United States)

    Douxfils, J; Mathieu, C; Mandiki, S N M; Milla, S; Henrotte, E; Wang, N; Vandecan, M; Dieu, M; Dauchot, N; Pigneur, L-M; Li, X; Rougeot, C; Mélard, C; Silvestre, F; Van Doninck, K; Raes, M; Kestemont, P

    2011-12-01

    The current study aimed to evaluate the influence of domestication process on the stress response and subsequent immune modulation in Eurasian perch juveniles (Perca fluviatilis) submitted to chronic confinement. Briefly, F1 and F4 generations were confined into small-size tanks and sampled 7 and 55 days after stocking. Cortisol and glucose levels as well as lysozyme activity and immunoglobulin level were evaluated in the serum. Spleen Somatic Index and spleen ROS production were also measured. A proteomic analysis was performed on serum sampled on day 7. Finally, both generations were genetically characterized using a microsatellite approach. Globally, results revealed that chronic confinement did not elicit a typical stress response but resulted in a prolonged immune stimulation. Proteomic results suggested that domestication process influenced the immune status of perch submitted to chronic confinement as the F1 confined fish displayed lower abundance of C3 complement component, transferrin and Apolipoprotein E. Microsatellite data showed a strong genetic drift as well as reduced genetic diversity, allelic number and heterozygosity along with domestication process. The present work is the first to report that fish under domestication can develop an immune response, assessed by a combined approach, following recurrent challenges imposed by captive environment despite a reduced genetic variation. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. RNA-Seq of the Caribbean reef-building coral Orbicella faveolata (Scleractinia-Merulinidae under bleaching and disease stress expands models of coral innate immunity

    Directory of Open Access Journals (Sweden)

    David A. Anderson

    2016-02-01

    Full Text Available Climate change-driven coral disease outbreaks have led to widespread declines in coral populations. Early work on coral genomics established that corals have a complex innate immune system, and whole-transcriptome gene expression studies have revealed mechanisms by which the coral immune system responds to stress and disease. The present investigation expands bioinformatic data available to study coral molecular physiology through the assembly and annotation of a reference transcriptome of the Caribbean reef-building coral, Orbicella faveolata. Samples were collected during a warm water thermal anomaly, coral bleaching event and Caribbean yellow band disease outbreak in 2010 in Puerto Rico. Multiplex sequencing of RNA on the Illumina GAIIx platform and de novo transcriptome assembly by Trinity produced 70,745,177 raw short-sequence reads and 32,463 O. faveolata transcripts, respectively. The reference transcriptome was annotated with gene ontologies, mapped to KEGG pathways, and a predicted proteome of 20,488 sequences was generated. Protein families and signaling pathways that are essential in the regulation of innate immunity across Phyla were investigated in-depth. Results were used to develop models of evolutionarily conserved Wnt, Notch, Rig-like receptor, Nod-like receptor, and Dicer signaling. O. faveolata is a coral species that has been studied widely under climate-driven stress and disease, and the present investigation provides new data on the genes that putatively regulate its immune system.

  17. Immune Modulatory Cell Therapy for Hemophilia B Based on CD20-Targeted Lentiviral Gene Transfer to Primary B Cells

    Directory of Open Access Journals (Sweden)

    Xiaomei Wang

    2017-06-01

    Full Text Available Gene-modified B cells expressing immunoglobulin G (IgG fusion proteins have been shown to induce tolerance in several autoimmune and other disease models. However, lack of a vector suitable for gene transfer to human B cells has been an obstacle for translation of this approach. To overcome this hurdle, we developed an IgG-human factor IX (hFIX lentiviral fusion construct that was targeted to specifically transduce cells expressing human CD20 (hCD20. Receptor-specific retargeting by mutating envelope glycoproteins of measles virus (MV-lentiviral vector (LV and addition of a single-chain variable fragment specific for hCD20 resulted in gene delivery into primary human and transgenic hCD20 mouse B cells with high specificity. Notably, this protocol neither required nor induced activation of the B cells, as confirmed by minimal activation of inflammatory cytokines. Using this strategy, we were able to demonstrate induction of humoral tolerance, resulting in suppression of antibody formation against hFIX in a mouse model of hemophilia B (HB. In conclusion, transduction of receptor-specific retargeted LV into resting B cells is a promising method to develop B cell therapies for antigen-specific tolerance induction in human disease.

  18. Neural systems underlying aversive conditioning in humans with primary and secondary reinforcers

    Directory of Open Access Journals (Sweden)

    Mauricio R Delgado

    2011-05-01

    Full Text Available Money is a secondary reinforcer commonly used across a range of disciplines in experimental paradigms investigating reward learning and decision-making. The effectiveness of monetary reinforcers during aversive learning and its neural basis, however, remains a topic of debate. Specifically, it is unclear if the initial acquisition of aversive representations of monetary losses depends on similar neural systems as more traditional aversive conditioning that involves primary reinforcers. This study contrasts the efficacy of a biologically defined primary reinforcer (shock and a socially defined secondary reinforcer (money during aversive learning and its associated neural circuitry. During a two-part experiment, participants first played a gambling game where wins and losses were based on performance to gain an experimental bank. Participants were then exposed to two separate aversive conditioning sessions. In one session, a primary reinforcer (mild shock served as an unconditioned stimulus (US and was paired with one of two colored squares, the conditioned stimuli (CS+ and CS-, respectively. In another session, a secondary reinforcer (loss of money served as the US and was paired with one of two different CS. Skin conductance responses were greater for CS+ compared to CS- trials irrespective of type of reinforcer. Neuroimaging results revealed that the striatum, a region typically linked with reward-related processing, was found to be involved in the acquisition of aversive conditioned response irrespective of reinforcer type. In contrast, the amygdala was involved during aversive conditioning with primary reinforcers, as suggested by both an exploratory fMRI analysis and a follow-up case study with a patient with bilateral amygdala damage. Taken together, these results suggest that learning about potential monetary losses may depend on reinforcement learning related systems, rather than on typical structures involved in more biologically based

  19. Automated dose dispensing in Danish primary health care - a technology under construction

    OpenAIRE

    Herborg, Hanne; Haugbølle, Lotte S.; Lee, Anne

    2008-01-01

    Objectives: The purpose of this study was to conduct a health technology assessment (HTA) of automated dose dispensing in the Danish primary health care sector. The present article answers the sub question of how various groups of actors spoke about and understood the shaping of automated dose dispensing (positioning in discourses).Methods: The project utilized two methods: 11 qualitative research interviews with selected key actors and a net-based qualitative questionnaire of 97 selected pra...

  20. Primary and secondary metabolites production in signal grass around the year under nitrogen fertilizer

    OpenAIRE

    Syeda Maryam Hussain

    2016-01-01

    Plants produce a number of substances and products and primary and secondary metabolites (SM) are amongst them with many benefits but limitation as well. Usually, the fodder are not considered toxic to animals or as a source having higher SM. The Brachiaria decumbens has a considerable nutritional value, but it is considered as a toxic grass for causing photosensitization in animals, if the grass is not harvested for more than 30 days or solely. The absence of detailed information in the lite...

  1. Delayed antibiotic prescription for upper respiratory tract infections in children under primary care: Physicians' views.

    Science.gov (United States)

    Raft, Camilla Flintholm; Bjerrum, Lars; Arpi, Magnus; Jarløv, Jens Otto; Jensen, Jette Nygaard

    2017-12-01

    Overprescribing antibiotics for common or inaccurately diagnosed childhood infections is a frequent problem in primary healthcare in most countries. Delayed antibiotic prescriptions have been shown to reduce the use of antibiotics in primary healthcare. The aim was to examine primary care physicians' views on delayed antibiotic prescriptions to preschool children with symptoms of upper respiratory tract infections (URTIs). A questionnaire was sent to 1180 physicians working in general practice in the Capital Region of Denmark, between January and March 2015. The questions focused on physicians' attitude and use of delayed antibiotic prescriptions to children with URTIs. The response rate was 49% (n = 574). Seven per cent of the physicians often used delayed prescriptions to children with symptoms of URTI, but 46% believed that delayed prescription could reduce antibiotic use. The physicians' views on delayed antibiotic prescription were significantly associated with their number of years working in general practice. Parents' willingness to wait-and-see, need for reassurance, and knowledge about antibiotics influenced the physicians' views. Also, clinical symptoms and signs, parents' willingness to shoulder the responsibility, the capability of observation without antibiotic treatment, and structural factors like out-of-hour services were relevant factors in the decision. Most physicians, especially those with fewer years of practice, had a positive attitude towards delayed antibiotic prescription. Several factors influence the views of the physicians-from perceptions of parents to larger structural elements and years of experience.

  2. Proteomics analysis reveals the molecular mechanism underlying the transition from primary to secondary growth of poplar.

    Science.gov (United States)

    Li, Yuan; Jin, Feng; Chao, Qing; Wang, Bai-Chen

    2017-06-01

    Wood is the most important natural source of energy and also provides fuel and fiber. Considering the significant role of wood, it is critical to understand how wood is formed. Integration of knowledge about wood development at the cellular and molecular levels will allow more comprehensive understanding of this complex process. In the present study, we used a comparative proteomic approach to investigate the differences in protein profiles between primary and secondary growth in young poplar stems using tandem mass tag (TMT)-labeling. More than 10,816 proteins were identified, and, among these, 3106 proteins were differentially expressed during primary to secondary growth. Proteomic data were validated using a combination of histochemical staining, enzyme activity assays, and quantitative real-time PCR. Bioinformatics analysis revealed that these differentially expressed proteins are related to various metabolic pathways, mainly including signaling, phytohormones, cell cycle, cell wall, secondary metabolism, carbohydrate and energy metabolism, and protein metabolism as well as redox and stress pathways. This large proteomics dataset will be valuable for uncovering the molecular changes occurring during the transition from primary to secondary growth. Further, it provides new and accurate information for tree breeding to modify wood properties. Copyright © 2017 Elsevier GmbH. All rights reserved.

  3. Primary sclerosing cholangitis

    OpenAIRE

    Worthington, Joy; Chapman, Roger

    2006-01-01

    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphata...

  4. Season of birth and primary central nervous system tumors: a systematic review of the literature with critical appraisal of underlying mechanisms.

    Science.gov (United States)

    Georgakis, Marios K; Ntinopoulou, Erato; Chatzopoulou, Despoina; Petridou, Eleni Th

    2017-09-01

    Season of birth has been considered a proxy of seasonally varying exposures around perinatal period, potentially implicated in the etiology of several health outcomes, including malignancies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we have systematically reviewed published literature on the association of birth seasonality with risk of central nervous system tumors in children and adults. Seventeen eligible studies using various methodologies were identified, encompassing 20,523 cases. Eight of 10 studies in children versus four of eight in adults showed some statistically significant associations between birth seasonality and central nervous system tumor or tumor subtype occurrence, pointing to a clustering of births mostly in fall and winter months, albeit no consistent pattern was identified by histologic subtype. A plethora of perinatal factors might underlie or confound the associations, such as variations in birth weight, maternal diet during pregnancy, perinatal vitamin D levels, pesticides, infectious agents, immune system maturity, and epigenetic modifications. Inherent methodological weaknesses of to-date published individual investigations, including mainly underpowered size to explore the hypothesis by histological subtype, call for more elegant concerted actions using primary data of large datasets taking also into account the interplay between the potential underlying etiologic factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A therapeutic HIV-1 vaccine enhances anti-HIV-1 immune responses in patients under highly active antiretroviral therapy.

    Science.gov (United States)

    Tung, Frank Y; Tung, Jack K; Pallikkuth, Suresh; Pahwa, Savita; Fischl, Margaret A

    2016-04-27

    HIV-1 specific cellular immunity plays an important role in controlling viral replication. In this first-in-human therapeutic vaccination study, a replication-defective HIV-1 vaccine (HIVAX) was tested in HIV-1 infected participants undergoing highly active antiretroviral therapy (HAART) to enhance anti-HIV immunity (Clinicaltrials.gov, identifier NCT01428596). A010 was a randomized, placebo-controlled trial to evaluate the safety and the immunogenicity of a replication defective HIV-1 vaccine (HIVAX) given as a subcutaneous injection to HIV-1 infected participants who were receiving HAART with HIV-1 viral load 500 cells/mm(3). HIV-1 specific immune responses were monitored by INF-γ enzyme linked immunospot (Elispot) and intracellular cytokine staining (ICS) assay after vaccination. Following the randomized placebo-controlled vaccination phase, subjects who received HIVAX vaccine and who met eligibility underwent a 12-week analytical antiretroviral treatment interruption (ATI). Viral load was monitored throughout the study. HIVAX was well tolerated in trial participants. Transient grade 1 to 2 (mild to moderate) injection site reactions occurred in 8 of 10 vaccinated participants. HIVAX was immunogenic in all vaccinated participants. The functionality of T cells was significantly enhanced after vaccination. Median viral load (3.45 log10 copies/ml, range of 96-12,830 copies/ml) at the end of the 12-week treatment interruption in HIVAX vaccinated group was significantly lower than the pre-treatment levels. Three vaccinated participants extended ATI for up to 2 years with stable CD4 cells and low viral loads. HIVAX vaccine is generally safe, elicits strong anti-HIV-1 immune responses, and may play an important role in controlling viral load during treatment interruption in HIV-1 infected participants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Was exposure to directly antiviral cytokines during primary infection an important selective pressure in the evolution of unique immune evasion strategies by viruses?

    Science.gov (United States)

    Lidbury, B A

    1994-08-01

    Different virus families are characterized by various immune evasion strategies. These viruses have co-evolved with an increasingly sophisticated mammalian immune system which has continually placed pressure on their continued survival. This paper proposes that exposure to directly antiviral cytokines, namely TNF and members of the IFN family, during inflammatory and early immune responses, exerted particularly strong selective pressures on viruses, and has had a critical influence on the development of viral immune evasion strategies and pathogenesis. In the context of antiviral cytokine activity, this report concentrates on two DNA virus families with contrasting pathogenic and immune evasion strategies, namely poxviruses and HSV.

  7. Summary of problems associated with primary damage and secondary defect aggregation under CTR irradiation conditions

    International Nuclear Information System (INIS)

    Hayns, M.R.

    1982-01-01

    Some of the important new quantities which need experimental verification and characterization to further our understanding of the irradiation damage processes in materials in CTR environments were highlighted. We have particularly emphasized the need to thoroughly understand the available simulation experiment conditions so that a proper correlation with the, as yet unobtainable, CTR conditions can be made. We have only focused upon the primary stages of the damage process and the nucleation of secondary defects. This should in no way be taken as implying that our understanding of the more basic quantities, such as diffusion in complex alloys, surface energies, stacking fault-energies, dislocation bias values, trap nature and binding energies, and phase stability (not segregation) is anywhere near adequate and further work is needed here as well as in the rather more exotic fields discussed in the body of the paper

  8. Working under a clinic-level quality incentive: primary care clinicians' perceptions.

    Science.gov (United States)

    Greene, Jessica; Kurtzman, Ellen T; Hibbard, Judith H; Overton, Valerie

    2015-01-01

    A key consideration in designing pay-for-performance programs is determining what entity the incentive should be awarded to-individual clinicians or to groups of clinicians working in teams. Some argue that team-level incentives, in which clinicians who are part of a team receive the same incentive based on the team's performance, are most effective; others argue for the efficacy of clinician-level incentives. This study examines primary care clinicians' perceptions of a team-based quality incentive awarded at the clinic level. This research was conducted with Fairview Health Services, where 40% of the primary care compensation model was based on clinic-level quality performance. We conducted 48 in-depth interviews to explore clinicians' perceptions of the clinic-level incentive, as well as an online survey of 150 clinicians (response rate 56%) to investigate which entity the clinicians would consider optimal to target for quality incentives. Clinicians reported the strengths of the clinic-based quality incentive were quality improvement for the team and less patient "dumping," or shifting patients with poor outcomes to other clinicians. The weaknesses were clinicians' lack of control and colleagues riding the coattails of higher performers. There were mixed reports on the model's impact on team dynamics. Although clinicians reported greater interaction with colleagues, some described an increase in tension. Most clinicians surveyed (73%) believed that there should be a mix of clinic and individual-level incentives to maintain collaboration and recognize individual performance. The study highlights the important advantages and disadvantages of using incentives based upon clinic-level performance. Future research should test whether hybrid incentives that mix group and individual incentives can maintain some of the best elements of each design while mitigating the negative impacts. © 2015 Annals of Family Medicine, Inc.

  9. A primary study on the performance of piezoceramic based smart aggregate under various compressive stresses

    Science.gov (United States)

    Zou, Dujian; Liu, Tiejun; Yang, Antai; Zhao, Yanru; Du, Chengcheng

    2017-10-01

    The reliability of piezoceramic based smart aggregate (SA) used for damage detection of concrete structures has already been validated by laboratory tests. However, the in situ concrete members are generally under a big range of stress levels, and the performance of SA under various compressive stresses is still unclear. In this study, an electronic universal testing machine was employed to apply different stresses on the SAs. The received signals of SA sensor accompanying with different drive signals were recorded. The experimental results show that the amplitude of received signals increases firstly, and then tends to be stable with stress. This enhancement is mainly induced by the decrease in thickness of epoxy resin layer caused by compressive stress. It indicates that the change of load applied on monitored concrete members embedded with SAs may lead to a change in monitoring signal amplitude even in elastic range, but it does not stand for the change of health state of monitored concrete member.

  10. Reproductive coercion: an under-recognized challenge for primary care patients.

    Science.gov (United States)

    Phillips, Sharon J; Bennett, Ariana H; Hacker, Michele R; Gold, Marji

    2016-06-01

    Reproductive coercion impacts many women of reproductive age. We sought to explore how reproductive coercion, including pregnancy coercion and birth control sabotage, impacts women in a primary care population. We administered a survey to women accessing care at a family medicine clinic in the Bronx, NY. Reproductive coercion was defined as a positive response to at least one of five questions adapted from previous studies. We assessed the association of reproductive and demographic characteristics with a lifetime history of reproductive coercion. At least one form of reproductive coercion was reported by 24% of the 97 respondents. Current lack of personal safety and a history of transactional sex for money or a place to stay were significantly associated with having experienced reproductive coercion (all P ≤ 0.02). Reproductive coercion was common among women of reproductive age at this urban family medicine clinic in an underserved community, and was associated with other forms of control and violence. Clinicians are advised to discuss birth control sabotage and pregnancy coercion with their patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Morphology of the dentin on primary molars after the application of phosphoric acid under different conditions

    Directory of Open Access Journals (Sweden)

    Renata Antonini Pimenta

    2010-09-01

    Full Text Available The aim of this study was to evaluate changes in the superficial dentin pattern of primary teeth after applying different phosphoric acid concentrations and conditioning times. Twenty-four dentin surfaces were divided in 4 groups with 10 teeth each: GI -no treatment; GII to GIV -phosphoric acid at 37%, 32%, and 10% respectively. The samples were divided into two halves: one treated for 7 seconds (T1 and the other one for 15 seconds (T2. They were submitted to scanning electronic microscopy (SEM. A reticule was superimposed upon the images to randomly select dentinal tubules measured in µm². The conditioning times did not cause significant differences in the mean diameter values of the dentin tubules within each test group: GII (T1= 4.86; T2= 4.70; GIII (T1 = 3.83; T2= 3.08; GIV (T1= 5.04; T2= 5.23. Comparing different groups, there were no differences in T1. The same results were observed in T2, except for GIV which presented higher mean diameter values than GIII. The extent of acid conditioning did not influence tubule opening within groups. When different types of acids where compared, only the 10% phosphoric acid showed upper tubule opening than 32% phosphoric acid. The dentin pattern varied according to the type of acid used for conditioning.

  12. Automated dose dispensing in Danish primary health care - a technology under construction

    Directory of Open Access Journals (Sweden)

    Herborg H

    2008-06-01

    Full Text Available Objectives: The purpose of this study was to conduct a health technology assessment (HTA of automated dose dispensing in the Danish primary health care sector. The present article answers the sub question of how various groups of actors spoke about and understood the shaping of automated dose dispensing (positioning in discourses.Methods: The project utilized two methods: 11 qualitative research interviews with selected key actors and a net-based qualitative questionnaire of 97 selected practitioners.Results: Three main types of discourse were identified with respect to the development of automated dose dispensing, namely ‘optimistic’, ‘sceptical’ and ‘pragmatic’. A wide diversity of opinion about automated dose dispensing was identified among the three discourses and their attendant scenarios. A number of factors are found in all three types of discourse, and are therefore considered to express common recommendations for decision makers and practitioners. These factors are described in the article.Conclusions: The article argues in favour of HTA, which to a great extent clarifies and initiates the perspectives of various groups of actors about the same technology. Our analyses show that conscious strategies must be employed to make the technology work successfully with the actors involved. The preferences, ideas and proposals for future actions and initiatives identified in the project could be the basis for defining future development strategies.

  13. Automated dose dispensing in Danish primary health care - a technology under construction.

    Science.gov (United States)

    Herborg, Hanne; Haugbølle, Lotte S; Lee, Anne

    2008-04-01

    The purpose of this study was to conduct a health technology assessment (HTA) of automated dose dispensing in the Danish primary health care sector. The present article answers the sub question of how various groups of actors spoke about and understood the shaping of automated dose dispensing (positioning in discourses). THE PROJECT UTILIZED TWO METHODS: 11 qualitative research interviews with selected key actors and a net-based qualitative questionnaire of 97 selected practitioners. Three main types of discourse were identified with respect to the development of automated dose dispensing, namely 'optimistic', 'sceptical' and 'pragmatic'. A wide diversity of opinion about automated dose dispensing was identified among the three discourses and their attendant scenarios. A number of factors are found in all three types of discourse, and are therefore considered to express common recommendations for decision makers and practitioners. These factors are described in the article. The article argues in favour of HTA, which to a great extent clarifies and initiates the perspectives of various groups of actors about the same technology. Our analyses show that conscious strategies must be employed to make the technology work successfully with the actors involved. The preferences, ideas and proposals for future actions and initiatives identified in the project could be the basis for defining future development strategies.

  14. Oxide layers of Zr-1% Nb under PWR primary circuit conditions

    Energy Technology Data Exchange (ETDEWEB)

    Nagy, Gabor E-mail: nagyg@sunserv.kfki.hu; Kerner, Zsolt; Battistig, Gabor; Pinter-Csordas, Anna; Balogh, Janos; Pajkossy, Tamas

    2001-07-01

    Oxide layers were grown on Zr-1% Nb under conditions simulating those in VVER-type pressurised water reactors (PWRs), viz. in borate solutions in an autoclave at 290 deg. C. The layers were characterised by various methods: their respective thickness values were determined by weight gain measurements, Rutherford backscattering (RBS), nuclear reaction analysis (NRA) and scanning electron microscopy (SEM); the electrical properties were tested by electrochemical impedance spectroscopy. The results show that the oxide layer on Zr-1% Nb is homogeneous and somewhat thicker than that on Zircaloy-4.

  15. [Resting metabolic rate, stress, testosterone, and induced immune response in "spring" and "fall" males of Campbell dwarf hamsters. Rearing under the long day conditions].

    Science.gov (United States)

    Rogovin, K A; Bushuev, A V; Khrushchova, A M; Vasil'eva, N Iu

    2013-01-01

    We have studied morphological and physiological traits of even-young males of Campbell dwarf hamsters (Phodopus campbelli Thomas, 1905) born at the end of summer ("fall males") and at the end of winter ("spring males") in a vivarium with constant 14-hour day length (14D:10N). After removal from parental cages at the age of one month, males were kept in isolation under the same light conditions. The results obained signify the statistical difference between "fall" and "spring" males in resting metabolic rate, morphological traits associated with sexual activity, some endocrine and immunologic characteristics. Spring males had higher resting metabolic rate, higher body mass in the middle of experiment, bigger testes, seminal vesicles, higher concentration of testosterone in blood and more intensive T-cell immune response to the intracutaneous injection of phytohemagglutinin. They did not differ significantly in basal level of blood cortisole and antibodies production in response to sheep red blood cells (SRBC) antigen challenge, but possessed lower adrenocortical response to the social stressor and adrenocorticotropic hormone. GLM analysis showed that cortisol level in blood after 10 min encounter of males in the open arena, and resting metabolic rate were the only factors significantly influenced humoral immune response to SRBC. When intensity of T-cell immune response was considered as dependent variable, season turned out to be the only factor in the final model that caused a significant effect.

  16. Preliminary comparison of different immune and production components in local and imported Saanen goats reared under a sub-tropical environment.

    Science.gov (United States)

    Barbour, Elie K; Itani, Houssam H; Sleiman, Fawwak T; Saade, Maya F; Harakeh, Steve; Nour, Afif M Abdel; Shaib, Houssam A

    2012-01-01

    Three objectives were included in this research work. The first objective compared different immune components in healthy mature males, mature females, and female kids of local and imported Saanen goats, reared under a sub-tropical environment. The significantly differing immune components were the blood monocyte percent, blood CD8 count, and the total white blood cell count. The second objective compared the performance of Saanen versus local does. The means of the milk yield and prolificacy of the imported Saanen does were significantly higher than those of the local does (pchicken red blood cells (c-RBC). The HA titers showed a significant seroconversion only in imported Saanen (p<0.05) but not in local does; however, the CF titers increased significantly at 4 weeks following priming with c-RBC in local (p<0.05) but not in the imported Saanen does. The impact of the differences in blood immune components and responses to antigens in the compared goats on protection potential against prevalent diseases in the sub-tropical zone of the eastern Mediterranean countries is discussed.

  17. Immunity against fungi

    Science.gov (United States)

    Lionakis, Michail S.; Iliev, Iliyan D.; Hohl, Tobias M.

    2017-01-01

    Pathogenic fungi cause a wide range of syndromes in immune-competent and immune-compromised individuals, with life-threatening disease primarily seen in humans with HIV/AIDS and in patients receiving immunosuppressive therapies for cancer, autoimmunity, and end-organ failure. The discovery that specific primary immune deficiencies manifest with fungal infections and the development of animal models of mucosal and invasive mycoses have facilitated insight into fungus-specific recognition, signaling, effector pathways, and adaptive immune responses. Progress in deciphering the molecular and cellular basis of immunity against fungi is guiding preclinical studies into vaccine and immune reconstitution strategies for vulnerable patient groups. Furthermore, recent work has begun to address the role of endogenous fungal communities in human health and disease. In this review, we summarize a contemporary understanding of protective immunity against fungi. PMID:28570272

  18. Clinical Profile, Dosing, and Quality-of-Life Outcomes in Primary Immune Deficiency Patients Treated at Home with Immunoglobulin G: Data from the IDEaL Patient Registry.

    Science.gov (United States)

    Kearns, Sean; Kristofek, Loretta; Bolgar, William; Seidu, Luqman; Kile, Samantha

    2017-04-01

    Patients with primary immune deficiency (PID) often require immunoglobulin G (IgG, commonly referred to as Ig) replacement therapy to prevent infections and associated comorbidities. Ig therapy can be given either through intravenous or subcutaneous routes, and both can be done in the home setting. There is limited information available on the real-world diagnosis, management, and outcomes of this patient population, given the variable disease presentation and treatment options. The Immunoglobulin Diagnosis, Evaluation, and key Learnings (IDEaL) Patient Registry is designed to capture nursing, pharmacy, and patient-reported data for patients receiving Ig at home. To (a) present a real-world population of patients with PID who have received Ig at home and (b) examine how differences in administration, dosing, and insurance affect health and quality-of-life outcomes in these patients. As of July 2015, 383 patients receiving Ig therapy from Coram/CVS specialty infusion services, across multiple disease states, signed consent forms and enrolled in the IDEaL Patient Registry. Patients' referral paperwork, including lab values, and standard of care nursing and pharmacy follow-up forms were collected. Patients were mailed quality-of-life surveys at the time of enrollment and every 6 months after their enrollment. The most common diagnosis (78%) in these PID patients was common variable immunodeficiency (CVID). For Ig-naive adult patients, the average age at the start of treatment was 59 years. For pediatric patients, average age at start of treatment was 9 years. A majority of these PID patients (80%) received subcutaneous Ig (SCIg) at home, and 20% received intravenous Ig (IVIg). The average SCIg dose was 10 grams per week, or 130 mg per kg, and the average IVIg dose was 36 grams every 4 weeks, or 472 mg per kg. In the IVIg patient population, 34% had a dose or frequency change while on treatment, while 30% of the SCIg patients had a dose or frequency change. Patient

  19. Efficacy of Mycobacterium indicus pranii immunotherapy as an adjunct to chemotherapy for tuberculosis and underlying immune responses in the lung.

    Directory of Open Access Journals (Sweden)

    Ankan Gupta

    Full Text Available BACKGROUND: The 9-month-long chemotherapy of tuberculosis often results in poor compliance and emergence of drug-resistant strains. So, improved therapeutic strategy is urgently needed. Immunotherapy could be beneficial for the effective management of the disease. Previously we showed the protective efficacy of Mycobacterium indicus pranii (MIP when given as prophylactic vaccine in animal models of tuberculosis. METHODS: We sought to investigate whether MIP can be used as an adjunct to the chemotherapy in guinea pig models of tuberculosis. Efficacy of MIP was evaluated when given subcutaneously or by aerosol. RESULTS: MIP-therapy as an adjunct to the chemotherapy was found to be effective in accelerating bacterial killing and improving organ pathology. MIP-immunotherapy resulted in higher numbers of activated antigen-presenting cells and lymphocytes in the infected lungs and also modulated the granulomatous response. Early increase in protective Th1 immune response was observed in the immunotherapy group. Following subsequent doses of MIP, decrease in the inflammatory response and increase in the immunosuppressive response was observed, which resulted in the improvement of lung pathology. CONCLUSION: MIP immunotherapy is a valuable adjunct to chemotherapy for tuberculosis. Aerosol route of immunotherapy can play a crucial role for inducing immediate local immune response in the lung.

  20. Application of Lichtenstein Method in Primary Inguinal Hernia by Under Experienced Surgeons

    Directory of Open Access Journals (Sweden)

    Serkan Yilmaz

    2016-01-01

    Full Text Available Aim: Lichtenstein technique is a mostly used inguinal hernia repair that provides important advantages to patient. Complication and recurrence rates are low for surgeons and it is an easy way to learn and apply. We have explained our results of Lichtenstein method which was applied by our assistant surgeons in order to emphasize that it can be used as a start method in repair of primer inguinal hernia. Material and Method: 154 patients that were operated with Lichtenstein method by our assistant surgeons after being diagnosed with primer inguinal hernia in Ižzmir Training Research Hospital between February 2008 and February 2011 were included in the study. For all patients, spinal anaesthesia was used as anaesthesia technic. Preoperatif sefazolin Na 1 gr. iv. was injected. The patients were followed 21 months (8-43 months in average. Patients started oral feeding in the operation evening and were allowed mobilisation. Results: 149 of the patients were male and 5 were female and age average was 53,5 (18-83. In 85 patients right inguinal hernia, in 65 patients left inguinal hernia and in 4 patients bilateral inguinal hernia were diagnosed. In exploration, it was detected that there were direct hernia in 62 patients, indirect hernia in 85 patients, pantaloon hernia in 3 patients, bilateral direct hernia in 4 patients. Average stay in hospital was 1,8 days postoperative. Early complications were seen 4,5 % as infection (n=4 , seroma (n=1 , urinary retention (n=1 and scrotal edema (n=1. Late term complications were seen 6,4 % as neuralgia (n=10. Mesh reaction and recurrence weren%u2019t detected in any of the patients. Discussion: In our study, Lichtenstein method were applied especially by our underexperienced surgeons. The fact that complication rate was low and no recurrence occured support its easy learning and application. We suggest its usage as a starting method in surgery education and primary inguinal hernia repair.

  1. Transcriptome analysis and discovery of genes involved in immune pathways in large yellow croaker (Larimichthys crocea) under high stocking density stress.

    Science.gov (United States)

    Sun, Peng; Bao, Peibo; Tang, Baojun

    2017-09-01

    The large yellow croaker, Larimichthys crocea, is an economically important maricultured species in southeast China. Owing to the importance of stocking densities in commercial fish production, it is crucial to establish the physiological responses and molecular mechanisms that govern adaptation to crowding in order to optimize welfare and health. In the present study, an extensive immunity-related analysis was performed at the transcriptome level in L. crocea in response to crowding stress. Over 145 million high-quality reads were generated and de novo assembled into a final set of 40,123 unigenes. Gene Ontology and genome analyses revealed that molecular function, biological process, intracellular, ion binding, and cell process were the most highly enriched pathways among genes that were differentially expressed under stress. Among all of the pathways involved, 16 pathways were related to the immune system, among which the complement and coagulation cascades pathway was the most enriched for differentially expressed immunity-related genes, followed by the chemokine signaling pathway, toll-like receptor signaling pathway, and leukocyte transendothelial migration pathway. The consistently high expression of immune-related genes in the complement and coagulation cascades pathway (from 24 to 96 h after being subjected to stress) suggested its importance in both response to stress and resistance against bacterial invasion at an early stage. These results also demonstrated that crowding can significantly induce immunological responses in fish. However, long-term exposure to stress eventually impairs the defense capability in fish. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Research on cultivating martial art teachers of primary and secondary schools under the background of new national curriculum standard

    OpenAIRE

    HAN Xue

    2013-01-01

    Martial art instructors play an important role in martial art education,and the quality of martial art instructors determines the level of quality of martial art education. Therefore,under the background of new national curriculum standard,who is to teach martial art,or in other words,martial art teacher issues concern the development of martial art in primary and secondary schools.In this paper,by use of literature,interviews and other research methods,the history of martial art education in...

  3. Concerted changes in N and C primary metabolism in alfalfa (Medicago sativa) under water restriction.

    Science.gov (United States)

    Aranjuelo, Iker; Tcherkez, Guillaume; Molero, Gemma; Gilard, Françoise; Avice, Jean-Christophe; Nogués, Salvador

    2013-02-01

    Although the mechanisms of nodule N(2) fixation in legumes are now well documented, some uncertainty remains on the metabolic consequences of water deficit. In most cases, little consideration is given to other organs and, therefore, the coordinated changes in metabolism in leaves, roots, and nodules are not well known. Here, the effect of water restriction on exclusively N(2)-fixing alfalfa (Medicago sativa L.) plants was investigated, and proteomic, metabolomic, and physiological analyses were carried out. It is shown that the inhibition of nitrogenase activity caused by water restriction was accompanied by concerted alterations in metabolic pathways in nodules, leaves, and roots. The data suggest that nodule metabolism and metabolic exchange between plant organs nearly reached homeostasis in asparagine synthesis and partitioning, as well as the N demand from leaves. Typically, there was (i) a stimulation of the anaplerotic pathway to sustain the provision of C skeletons for amino acid (e.g. glutamate and proline) synthesis; (ii) re-allocation of glycolytic products to alanine and serine/glycine; and (iii) subtle changes in redox metabolites suggesting the implication of a slight oxidative stress. Furthermore, water restriction caused little change in both photosynthetic efficiency and respiratory cost of N(2) fixation by nodules. In other words, the results suggest that under water stress, nodule metabolism follows a compromise between physiological imperatives (N demand, oxidative stress) and the lower input to sustain catabolism.

  4. Research on cultivating martial art teachers of primary and secondary schools under the background of new national curriculum standard

    Directory of Open Access Journals (Sweden)

    HAN Xue

    2013-08-01

    Full Text Available Martial art instructors play an important role in martial art education,and the quality of martial art instructors determines the level of quality of martial art education. Therefore,under the background of new national curriculum standard,who is to teach martial art,or in other words,martial art teacher issues concern the development of martial art in primary and secondary schools.In this paper,by use of literature,interviews and other research methods,the history of martial art education in our country is reviewed at first,leading to a conclusion that there exist problems in primary and middle school martial art education in our country,i.e.professional martial art instructors in primary and middle schools are seriously deficient,martial art instructors are lacking in professional martial art knowledge and professional competence,the continuing education system is not perfect,and training and education are formalized.The author therefore puts forward countermeasures to improve the current situation.

  5. The plant pathogen Pseudomonas syringae pv. tomato is genetically monomorphic and under strong selection to evade tomato immunity.

    Directory of Open Access Journals (Sweden)

    Rongman Cai

    2011-08-01

    Full Text Available Recently, genome sequencing of many isolates of genetically monomorphic bacterial human pathogens has given new insights into pathogen microevolution and phylogeography. Here, we report a genome-based micro-evolutionary study of a bacterial plant pathogen, Pseudomonas syringae pv. tomato. Only 267 mutations were identified between five sequenced isolates in 3,543,009 nt of analyzed genome sequence, which suggests a recent evolutionary origin of this pathogen. Further analysis with genome-derived markers of 89 world-wide isolates showed that several genotypes exist in North America and in Europe indicating frequent pathogen movement between these world regions. Genome-derived markers and molecular analyses of key pathogen loci important for virulence and motility both suggest ongoing adaptation to the tomato host. A mutational hotspot was found in the type III-secreted effector gene hopM1. These mutations abolish the cell death triggering activity of the full-length protein indicating strong selection for loss of function of this effector, which was previously considered a virulence factor. Two non-synonymous mutations in the flagellin-encoding gene fliC allowed identifying a new microbe associated molecular pattern (MAMP in a region distinct from the known MAMP flg22. Interestingly, the ancestral allele of this MAMP induces a stronger tomato immune response than the derived alleles. The ancestral allele has largely disappeared from today's Pto populations suggesting that flagellin-triggered immunity limits pathogen fitness even in highly virulent pathogens. An additional non-synonymous mutation was identified in flg22 in South American isolates. Therefore, MAMPs are more variable than expected differing even between otherwise almost identical isolates of the same pathogen strain.

  6. Anaerobic co-digestion of food waste and chemically enhanced primary-treated sludge under mesophilic and thermophilic conditions.

    Science.gov (United States)

    Obulisamy, Parthiba Karthikeyan; Chakraborty, Debkumar; Selvam, Ammaiyappan; Wong, Jonathan W C

    2016-12-01

    Anaerobic co-digestion of food waste with primary sewage sludge is beneficial for urban centers, while the optimized conditions reported in the literature are not locally suitable for Hong Kong. Therefore, the present study was aimed to develop an optimized mixing ratio of food waste to chemically enhanced primary-treated sewer sludge (CEPT) for co-digestion using batch tests under mesophilic (37°C) and thermophilic (55°C) conditions. The mixing ratios of 1:1, 1:2, 1:3, 2:1 and 3:1 (v v(-1)) of food waste to CEPT sludge was tested under the following conditions: temperature - 35°C and 55°C; pH - not regulated; agitation - 150 rpm and time - 20 days. The thermophilic incubations led a good hydrolysis rate and 2-12-fold higher enzyme activities than in mesophilic incubations for different mixing ratios. While the acidogenesis were found retarded that leading to 'sour and stuck' digestion for all mixing ratio of food waste to CEPT sludge from thermophilic incubations. The measured zeta potential was most favourable (-5 to -16.8 mV) for methane production under thermophilic incubations; however the CH4 recovery was less than that in mesophilic incubations. The results suggested that the quick hydrolysis and subsequent acid accumulation under thermophilic incubation lead to inhibited methanogenesis at the early stage than in mesophilic systems. It is concluded that buffer addition is therefore required for any mixing ratio of food waste to CEPT sludge for improved CH4 recovery for both mesophilic and thermophilic operations.

  7. Characterization of rat primary trigeminal satellite glial cells and associated extracellular vesicles under normal and inflammatory conditions.

    Science.gov (United States)

    Vinterhøj, Hye Sook Han; Stensballe, Allan; Duroux, Meg; Gazerani, Parisa

    2018-03-23

    Satellite glial cells (SGCs) in sensory ganglia contribute to the pathogenesis of chronic pain, potentially through mediating extracellular or paracrine signaling. Recently, extracellular vesicles (EVs) in the form of exosomes have been found to play an important role in cell-cell communication. However, their release from SGCs and extent in modulating pain remain unknown. An in vitro cell platform using fresh primary SGCs was used to characterize the shed vesicles by size and proteomic profiling following activation of SGCs by lipopolysaccharide (LPS), simulating neurogenic inflammation in vivo. Results demonstrated that SGCs shed vesicles in the size range of exosomes (>150 nm) but with altered protein expression upon LPS-activation. Proteomic profiling of SGCs-shed EVs showed that a number of proteins were differentially regulated upon LPS stimulation such as junction plakoglobin and myosin 9 that are proposed as novel biomarkers of SGCs activation under inflammatory conditions. Findings from this study highlight the utility of using fresh primary SGC cultures as a model to further investigate EVs under normal and inflammatory conditions. This study demonstrated that. Copyright © 2018. Published by Elsevier B.V.

  8. Response characteristics of HPR1000 primary circuit under different working conditions of the atmospheric relief system after SBLOCA

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Danting, E-mail: suidanting@163.com [School of Nuclear Science and Engineering, North China Electric Power University, Beijing (China); Beijing Key Laboratory of Passive Safety Technology for Nuclear Energy, North China Electric Power University, Beijing (China); Lu, Daogang [School of Nuclear Science and Engineering, North China Electric Power University, Beijing (China); Beijing Key Laboratory of Passive Safety Technology for Nuclear Energy, North China Electric Power University, Beijing (China); Shang, Changzhong; Wei, Yuanyuan [China Nuclear Power Design Co., ltd (ShenZhen), Shenzhen (China); Zhang, Xianjie [School of Nuclear Science and Engineering, North China Electric Power University, Beijing (China); Beijing Key Laboratory of Passive Safety Technology for Nuclear Energy, North China Electric Power University, Beijing (China)

    2017-04-01

    Highlights: • Response of HPR1000 under different VDA conditions after SBLOCA was investigated. • Activation of VDA can trigger ACCU SI earlier with a critical point exists. • VDA capability design should compromise the critical point with reactivity feedback. - Abstract: To cope with SBLOCA in absence of High-Head Safety Injection (HHSI) from design of HPR1000, atmospheric relief system (originally named as VDA in French) is uniquely designed to help to trigger Middle Head Safety Injection (MHSI) or Low Head Safety Injection (LHSI) earlier through cooling primary system quickly after SBLOCA. To make the best use of VDA decay heat removal capability, primary and secondary system of HPR1000 was modeled with RELAP5/SCDAP computer code. After steady-state initialization, a cold leg 30 mm break SBLOCA was simulated with six simulation conditions and five additional cases including availability of ACCU, different VDA discharge locations and area. Response characteristics of primary loop under different VDA working conditions are investigated. Pressurizer pressure decreases rapidly to lower level to trigger the reactor scram, VDA activation and accumulator safety injection sequently. Peak cladding temperature is 899.45 K occurring at 222 s, which is far below the safety limit. Activation of VDA can trigger ACCU SI earlier with a critical point, while positive reactivity will be introduced due to negative moderator temperature effect and Doppler effect. Larger VDA discharge capability will introduce larger reactivity feedback, as well as induce lower core level and SG level. It's suggested that VDA discharge condition should be chosen before the critical point, with the compromise with reactivity feedback introduced due to the negative moderator temperature effect.

  9. Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age

    Science.gov (United States)

    Wallace, Ryan M.; Pees, Anna; Blanton, Jesse B.

    2017-01-01

    Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs’ failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57–1.72, ANOVA p vaccinated vaccinated 12–16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8–30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer. PMID:28759602

  10. Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age.

    Science.gov (United States)

    Wallace, Ryan M; Pees, Anna; Blanton, Jesse B; Moore, Susan M

    2017-07-01

    Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs' failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57-1.72, ANOVA p dogs vaccinated dogs vaccinated 12-16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8-30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer.

  11. Establishing diagnostic criteria for severe combined immunodeficiency disease (SCID), leaky SCID, and Omenn syndrome: the Primary Immune Deficiency Treatment Consortium experience.

    Science.gov (United States)

    Shearer, William T; Dunn, Elizabeth; Notarangelo, Luigi D; Dvorak, Christopher C; Puck, Jennifer M; Logan, Brent R; Griffith, Linda M; Kohn, Donald B; O'Reilly, Richard J; Fleisher, Thomas A; Pai, Sung-Yun; Martinez, Caridad A; Buckley, Rebecca H; Cowan, Morton J

    2014-04-01

    The approach to the diagnosis of severe combined immunodeficiency disease (SCID) and related disorders varies among institutions and countries. The Primary Immune Deficiency Treatment Consortium attempted to develop a uniform set of criteria for diagnosing SCID and related disorders and has evaluated the results as part of a retrospective study of SCID in North America. Clinical records from 2000 through 2009 at 27 centers in North America were collected on 332 children treated with hematopoietic stem cell transplantation (HCT), enzyme replacement therapy, or gene therapy for SCID and related disorders. Eligibility for inclusion in the study and classification into disease groups were established by using set criteria and applied by an expert review group. Two hundred eighty-five (86%) of the patients were determined to be eligible, and 47 (14%) were not eligible. Of the 285 eligible patients, 84% were classified as having typical SCID; 13% were classified as having leaky SCID, Omenn syndrome, or reticular dysgenesis; and 3% had a history of enzyme replacement or gene therapy. Detection of a genotype predicting an SCID phenotype was accepted for eligibility. Reasons for noneligibility were failure to demonstrate either impaired lymphocyte proliferation or maternal T-cell engraftment. Overall (n = 332) rates of testing were as follows: proliferation to PHA, 77%; maternal engraftment, 35%; and genotype, 79% (mutation identified in 62%). Lack of complete laboratory evaluation of patients before HCT presents a significant barrier to definitive diagnosis of SCID and related disorders and prevented inclusion of subjects in our observational HCT study. This lesson is critical for patient care, as well as the design of future prospective treatment studies for such children because a well-defined and consistent study population is important for precision in outcomes analysis. Published by Mosby, Inc.

  12. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  13. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun

    2008-04-01

    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull. 2008; 7(2: 159-166

  14. The protective immune response produced in dogs after primary vaccination with the LiESP/QA-21 vaccine (CaniLeish®) remains effective against an experimental challenge one year later.

    Science.gov (United States)

    Martin, Virginie; Vouldoukis, Ioannis; Moreno, Javier; McGahie, David; Gueguen, Sylvie; Cuisinier, Anne-Marie

    2014-06-25

    Control of canine leishmaniasis is an important objective for the benefit of dogs living in or visiting endemic areas and for public health because of the zoonotic nature of this disease. Resistance or susceptibility to developing canine leishmaniasis after exposure to Leishmania infantum is primarily determined by the ability of the immune system to develop an appropriate Th1-dominated specific response to the parasite. For this reason there is a need for effective canine vaccines that can decrease the number of dogs developing progressive infections. In this study, we followed the impact of the LiESP/QA-21 canine vaccine (composed of excreted-secreted proteins of L. infantum and the QA-21 saponin adjuvant), recently launched commercially in Europe, on selected humoral and cellular immune parameters following an infectious intravenous challenge with L. infantum promastigotes administered one year after the primary vaccine course. We also followed parasitological parameters to determine the parasitological status of the challenged dogs. In contrast to controls, vaccinated dogs retained significantly stronger cell-mediated immune responses against the parasite despite a virulent challenge and had significantly lower mean parasite burdens at the end of the study, associated with a lower probability of developing active infections. These results confirm that the immune responses generated by vaccination with LiESP/QA-21 are still effective against an intravenous challenge one year after the primary vaccine course.

  15. Primary Life Stage Boron Isotope and Trace Elements Incorporation in Aposymbiotic Acropora millepora Coral under Ocean Acidification and Warming

    Directory of Open Access Journals (Sweden)

    Henry C. Wu

    2017-05-01

    Full Text Available Early-life stages of reef-building corals are vital to coral existence and reef maintenance. It is therefore crucial to study juvenile coral response to future climate change pressures. Moreover, corals are known to be reliable recorders of environmental conditions in their skeletal materials. Aposymbiotic Acropora millepora larvae were cultured in different seawater temperature (27 and 29°C and pCO2 (390 and 750 μatm conditions to understand the impacts of “end of century” ocean acidification (OA and ocean warming (OW conditions on skeletal morphology and geochemistry. The experimental conditions impacted primary polyp juvenile coral skeletal morphology and growth resulting in asymmetric translucent appearances with brittle skeleton features. The impact of OA resulted in microstructure differences with decreased precipitation or lengthening of fasciculi and disorganized aragonite crystals that led to more concentrations of centers of calcifications. The coral skeletal δ11B composition measured by laser ablation MC-ICP-MS was significantly affected by pCO2 (p = 0.0024 and water temperature (p = 1.46 × 10−5. Reconstructed pH of the primary polyp skeleton using the δ11B proxy suggests a difference in coral calcification site and seawater pH consistent with previously observed coral pH up-regulation. Similarly, trace element results measured by laser ablation ICP-MS indicate the impact of pCO2. Primary polyp juvenile Sr/Ca ratio indicates a bias in reconstructed sea surface temperature (SST under higher pCO2 conditions. Coral microstructure content changes (center of calcification and fasciculi due to OA possibly contributed to the variability in B/Ca ratios. Our results imply that increasing OA and OW may lead to coral acclimation issues and species-specific inaccuracies of the commonly used Sr/Ca-SST proxy.

  16. J-Integral Estimate for Circumferential Cracked Pipes Under Primary and Secondary Stress in R, RBC-MR A

    Energy Technology Data Exchange (ETDEWEB)

    Nam, Hyun Suk; Oh, Chang Young; Kim, Yun Jae [Korea Univ., Seoul (Korea, Republic of)

    2013-05-15

    This paper provides a comparison of the J-integral estimation method under combined primary and secondary stress in the R, RBC-MR A code. The comparisons of each code are based on finite element analysis using Abacus with regard to the crack shape, crack depth, and magnitude of secondary load. The estimate of the R code is conservative near L{sub r} = 1, and that of the RBC-MR A code is conservative near L{sub r} = 0. As a result, this paper proposes a modified method of J-integral estimation in the R, RCC{sub M}R A code. The J-integral using the modified method corresponds to the finite element analysis result.

  17. Forecasting Epidemiological Consequences of Maternal Immunization.

    Science.gov (United States)

    Bento, Ana I; Rohani, Pejman

    2016-12-01

     The increase in the incidence of whooping cough (pertussis) in many countries with high vaccination coverage is alarming. Maternal pertussis immunization has been proposed as an effective means of protecting newborns during the interval between birth and the first routine dose. However, there are concerns regarding potential interference between maternal antibodies and the immune response elicited by the routine schedule, with possible long-term population-level effects.  We formulated a transmission model comprising both primary routine and maternal immunization. This model was examined to evaluate the long-term epidemiological effects of routine and maternal immunization, together with consequences of potential immune interference scenarios.  Overall, our model demonstrates that maternal immunization is an effective strategy in reducing the incidence of pertussis in neonates prior to the onset of the primary schedule. However, if maternal antibodies lead to blunting, incidence increases among older age groups. For instance, our model predicts that with 60% routine and maternal immunization coverage and 30% blunting, the incidence among neonates (0-2 months) is reduced by 43%. Under the same scenario, we observe a 20% increase in incidence among children aged 5-10 years. However, the downstream increase in the older age groups occurs with a delay of approximately a decade or more.  Maternal immunization has clear positive effects on infant burden of disease, lowering mean infant incidence. However, if maternally derived antibodies adversely affect the immunogenicity of the routine schedule, we predict eventual population-level repercussions that may lead to an overall increase in incidence in older age groups. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  18. A mathematical model of radiation effect on the immunity system

    International Nuclear Information System (INIS)

    Smirnova, O.A.

    1984-01-01

    A mathematical model, simulating the effect of ionizing radiation on the dynamics of humoral immune reaction is suggested. It represents the system of nonlinear differential equations and is realized in the form of program in Fortran computer language. The model describes the primary immune reaction of nonirradiated organism on T-independent antigen, reflects the postradiation lymphopoiesis dynamics in nonimmunized mammals, simulates the processes of injury and recovery of the humoral immunity system under the combined effect of ionizing radiation and antigenic stimulation. The model can be used for forecasting imminity state in irradiated mammals

  19. Empirical Modeling of Physiochemical Immune Response of Multilayer Zinc Oxide Nanomaterials under UV Exposure to Melanoma and Foreskin Fibroblasts

    Science.gov (United States)

    Fakhar-E-Alam, Muhammad; Akram, M. Waseem; Iqbal, Seemab; Alimgeer, K. S.; Atif, M.; Sultana, K.; Willander, M.; Wang, Zhiming M.

    2017-04-01

    Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX). Furthermore, PpIX-conjugated ZnO nanomaterials grown on the probe were inserted into human melanoma (FM55P) and foreskin fibroblasts cells (AG01518) under UV-A light exposure. Interestingly, significant cell necrosis was observed because of a loss in mitochondrial membrane potential just after insertion of the femtotip tool. Intense reactive oxygen species (ROS) fluorescence was observed after exposure to the ZnO NWs conjugated with PpIX femtotip model under UV exposure. Results were verified by applying several experimental techniques, e.g., ROS detection, MTT assay, and fluorescence spectroscopy. The present work reports experimental modelling of cell necrosis in normal human skin as well as a cancerous tissue. These obtained results pave the way for a more rational strategy for biomedical and clinical applications.

  20. Empirical Modeling of Physiochemical Immune Response of Multilayer Zinc Oxide Nanomaterials under UV Exposure to Melanoma and Foreskin Fibroblasts.

    Science.gov (United States)

    Fakhar-E-Alam, Muhammad; Akram, M Waseem; Iqbal, Seemab; Alimgeer, K S; Atif, M; Sultana, K; Willander, M; Wang, Zhiming M

    2017-04-24

    Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX). Furthermore, PpIX-conjugated ZnO nanomaterials grown on the probe were inserted into human melanoma (FM55P) and foreskin fibroblasts cells (AG01518) under UV-A light exposure. Interestingly, significant cell necrosis was observed because of a loss in mitochondrial membrane potential just after insertion of the femtotip tool. Intense reactive oxygen species (ROS) fluorescence was observed after exposure to the ZnO NWs conjugated with PpIX femtotip model under UV exposure. Results were verified by applying several experimental techniques, e.g., ROS detection, MTT assay, and fluorescence spectroscopy. The present work reports experimental modelling of cell necrosis in normal human skin as well as a cancerous tissue. These obtained results pave the way for a more rational strategy for biomedical and clinical applications.

  1. Human cytomegalovirus immunity and immune evasion.

    Science.gov (United States)

    Jackson, Sarah E; Mason, Gavin M; Wills, Mark R

    2011-05-01

    Human cytomegalovirus (HCMV) infection induces both innate immune responses including Natural Killer cells as well as adaptive humoral and cell mediated (CD4+ helper, CD8+ cytotoxic and γδ T cell) responses which lead to the resolution of acute primary infection. Despite such a robust primary immune response, HCMV is still able to establish latency. Long term memory T cell responses are maintained at high frequency and are thought to prevent clinical disease following periodic reactivation of the virus. As such, a balance is established between the immune response and viral reactivation. Loss of this balance in the immunocompromised host can lead to unchecked viral replication following reactivation of latent virus, with consequent disease and mortality. HCMV encodes multiple immune evasion mechanisms that target both the innate and acquired immune system. This article describes the current understanding of Natural killer cell, antibody and T cell mediated immune responses and the mechanisms that the virus utilizes to subvert these responses. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Molecular mechanism of catalase activity change under sodium dodecyl sulfate-induced oxidative stress in the mouse primary hepatocytes.

    Science.gov (United States)

    Wang, Jing; Wang, Jiaxi; Xu, Chi; Liu, Rutao; Chen, Yadong

    2016-04-15

    Sodium dodecyl sulfate (SDS) contributes to adverse effects of organisms probably because of its ability to induce oxidative stress via changing the activity of antioxidant enzyme catalase (CAT). But the underlying molecular mechanisms still remain unclear. This study characterized the harmful effects of SDS-induced oxidative stress on the mouse primary hepatocytes as well as the structure and function of CAT molecule and investigated the underlying molecular mechanism. After 12h SDS (0.1μM to 0.2mM) exposure, no significant change was observed in CAT activity of the hepatocytes. After 0.5 and 0.8mM SDS exposure, the state of oxidative stress stimulated CAT production in the hepatocytes. The inhibition of CAT activity induced by directly interacting with SDS was unable to catch the synthesis of CAT and therefore resulted in the increased activity and elevated ROS level. Further molecular experiments showed that SDS prefers to bind to the interface with no direct effect on the active site and the structure of heme groups of CAT molecule. When the sites in the interface is saturated, SDS interacts with VAL 73, HIS 74, ASN 147 and PHE 152, the key residues of the enzyme activity, and leads to the decrease of CAT activity. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Volatile release and structural stability of β-lactoglobulin primary and multilayer emulsions under simulated oral conditions.

    Science.gov (United States)

    Benjamin, O; Silcock, P; Beauchamp, J; Buettner, A; Everett, D W

    2013-09-01

    The relationship between emulsion structure and the release of volatile organic compounds (VOCs) was investigated using a model mouth system under oral conditions (tongue mastication, artificial saliva, pH and salt). The VOCs were monitored on-line by proton transfer reaction mass spectrometry (PTR-MS). Two types of emulsion system were compared: primary and multilayer oil-in-water (P-O/W, M-O/W) emulsions consisting of soy oil coated by β-lactoglobulin and pectin layers. The P-O/W emulsions showed intensive flocculation at pH 5 and above 200 mM NaCl where the electrostatic repulsive charge was at a minimum. Bridging and depletion flocculation were mostly observed for P-O/W emulsions containing artificial saliva with 1 wt% mucin. The VOC release was found to increase when the emulsion droplets flocculated, thus changing the oil volume phase distribution. The adsorbed pectin layer stabilised the emulsion structure under conditions of short-time oral processing, and hindered the release of hydrophobic VOCs. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Active Hexose Correlated Compound (AHCC) promotes an intestinal immune response in BALB/c mice and in primary intestinal epithelial cell culture involving toll-like receptors TLR-2 and TLR-4.

    Science.gov (United States)

    Mallet, Jean-François; Graham, Émilie; Ritz, Barry W; Homma, Kohei; Matar, Chantal

    2016-02-01

    Active Hexose Correlated Compound (AHCC(®)) is a cultured mushroom extract that is commercially available and promoted for immune support. Available data suggest that AHCC supplementation affects immune cell populations and immune outcomes, including natural killer cell response to infection. The mechanism by which AHCC exerts its effects is not well understood. The present work aimed to characterize the immunomodulatory activity of AHCC in the gut and to study the effects of AHCC on toll-like receptor (TLR) signaling in intestinal epithelial cells (IECs). BALB/c mice were fed AHCC by gavage. In vivo activities were assessed by immunohistochemistry and cytokine production. The effects of AHCC on ex vivo primary cell culture from IECs were examined after challenge with LPS or E. coli alone or in the presence of anti-TLR-2 and TLR-4 blocking antibodies. Feeding AHCC resulted in increased IgA+ cells in the intestine and increased sIgA, IL-10, and IFN-γ in the intestinal fluid. In IECs, contact with AHCC increased IL-6 production but not to the pro-inflammatory level of positive controls, LPS and E. coli. Blocking TLR-2 and TLR-4 reduced the induction of IL-6 by AHCC, suggesting that these innate receptors are involved in generating the immune response of IECs to AHCC. AHCC may play a role in the orchestration of immune response and the maintenance of immune homeostasis in part by priming the TLR-2 and TLR-4 gate at the intestinal epithelium. Such a response is likely due to the recognition of non-pathogenic food-associated molecular patterns (FAMPs) such as those found associated with other mushroom or yeast-derived compounds.

  5. Time-course of antibody and cell-mediated immune responses to Porcine Reproductive and Respiratory Syndrome virus under field conditions.

    Science.gov (United States)

    Dotti, S; Guadagnini, G; Salvini, F; Razzuoli, E; Ferrari, M; Alborali, G L; Amadori, M

    2013-06-01

    Major discrepancies are observed between experimental trials of PRRS-virus (PRRSV) infection in isolation facilities and observations made in the field on farm. Owing to the above, a cohort study was carried out in a farrow-to-finish, PRRSV-infected pig farm to characterize the time-course of the virus-specific immune response in two groups of replacement gilts. Despite the occurrence of three and two distinct waves of infection in groups 1 and 2, respectively, the large majority of animals showed little if any PRRSV-specific response in an interferon-gamma release assay on whole blood, whereas non-specific responses were consistently observed. To rule out any possible bias of our test procedure, this was used along with an ELISPOT assay for interferon-gamma-secreting cells with the same reagents on a group of PRRS-virus infected pigs in isolation facilities. A very good agreement was shown between the two sets of results. Also, as opposed to the PRRS model, plenty of Pseudorabies virus-vaccinated pigs under field conditions scored positive in another experiment in the interferon-gamma release assay, ad hoc modified for the Pseudorabies virus. Our results indicate that under field conditions poor or no development rather than delayed development of the PRRS virus-specific interferon-gamma response could be the rule for a long time in non-adult pigs after PRRS virus infection. Housing and hygiene conditions, as well as heavy exposure to environmental microbial payloads in intensive pig farms could adversely affect the host's immune response to PRRS virus and partly account for the discrepancies between experimental and field studies. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Differential Expression of MiR-106b-5p and MiR-200c-3p in Newly Diagnosed Versus Chronic Primary Immune Thrombocytopenia Patients Based on Systematic Analysis

    Directory of Open Access Journals (Sweden)

    Cheng Qian

    2018-01-01

    Full Text Available Background/Aims: MicroRNAs (miRNAs have been described to have important roles in primary immune thrombocytopenia (ITP. To gain additional understanding, we have now further evaluated the involvement of miRNAs in ITP. Methods: Microarray experiments were performed to examine the expression profiles of miRNAs and mRNAs in samples from subjects with newly diagnosed ITP (G1, chronic ITP (G2, and normal controls. The systematic Pipeline of Outlier MicroRNA Analysis framework was applied to identify key miRNAs expressed in the G1 and G2 samples. Quantitative PCR and receiver operator characteristic curves were used to confirm the performance of key miRNAs. Results: Compared with normal controls, 14 miRNAs (12 over-expressed and 2 under-expressed and 7 over-expressed miRNAs were identified as key in G1 and G2 samples, respectively. miR-106b-5p, miR-200c-3p, and miR-92a-3p exhibited significantly different expression profiles among the groups. In particular, miR-106b-5p and miR-200c-3p were expressed at higher levels in patients with ITP compared to the normal controls. Furthermore, these two miRNAs expressions were even higher in patients with chronic ITP. Conclusion: MiR-106b-5p and miR-200c-3p may represent valuable biomarkers of ITP, although further studies are needed to confirm and assess the value of these potential biomarkers at various stages of ITP.

  7. Non-specific immunization against babesiosis

    International Nuclear Information System (INIS)

    Cox, F.E.G.

    1980-01-01

    The rodent babesias, Babesia rodhaini and the less virulent B. microti, are useful models with which to study immunity to and immunization against babesiosis. In contrast with the difficulty in inducing specific immunity to these parasites it is comparatively easy to induce non-specific immunity by prior exposure to related and unrelated intra-erythrocytic protozoa, micro-organisms such as Mycobacterium bovis (BCG) and Corynebacterium parvum, microbial extracts and muramyl dipeptide. This non-specific immunity is long lasting and extremely effective. It is characterized by the facts that (a) it occurs early in the infection at the height of the first peak of parasitaemia, and (b) it involves the intra-erythrocytic death of the parasites. After the primary parasitaemia has resolved, some parasites continue to persist at a low level and when introduced into clean mice produce only low-level 'attenuated' infections in these. Non-specific immunity is not equally effective in all strains of mice. It is suggested that immunity to babesiosis, and infections caused by other intra-erythrocytic protozoa, involves two mechanisms, the first non-specific and the second specific. The actual balance between these two mechanisms varies from parasite to parasite and from host to host. An effective vaccine would have to be based on an understanding of the roles of non-specific immunity in the actual disease under consideration, and would ideally combine an adjuvant that would also stimulate non-specific immunity and an attenuated strain of parasite that would induce a specific response. (author)

  8. Assessment of Immunization to Hepatitis B Vaccine among Children under Five Years in Rural Areas of Taiz, Yemen

    Science.gov (United States)

    Al-Sonboli, Najla A.; Alkumaim, Fawzi A.; Alsayaad, Nader S.; Al-Ahdal, Mohammed S.; Higazi, Tarig B.; Elagib, Atif A.

    2017-01-01

    Background. Hepatitis B virus (HBV) infection poses a major health problem worldwide. approximately 1 million deaths annually due to cirrhosis and hepatocellular carcinoma. Objectives. This study was conducted to determine the coverage rate of HBV vaccine and assess the vaccine protective response among children under five years old in rural areas of Yemen. Methods. A cross-sectional study was conducted from January to December 2015 in four districts of countryside Yemen. The target population was children aged from 6 to 59 months. 227 children were enrolled in the study. Questionnaire was used to collect of data. Serum samples were tested for anti-HBs antibodies by enzyme linked immunosorbent assay (ELISA). Anti-HBs level ≥ 10 IU/L was considered a protective response to the vaccine. Results. The coverage rate of HBV vaccine among children was 87.3%. A total of 143 (72.2%) children responded to the vaccine with anti-HBs level ≥ 10 IU/L, while 55 (27.8%) of the children had nonprotective anti-HBs levels of <10 IU/L (P = 0.003). Conclusion. This study revealed a good coverage rate of HBV vaccine in rural areas but the protective rate against HBV infection was moderate. A considerable proportion of vaccinated children should be considered for either revaccination or booster doses. PMID:28367327

  9. Glucocorticoids Suppress the Protective Effect of Cyclooxygenase-2-Related Signaling on Hippocampal Neurogenesis Under Acute Immune Stress.

    Science.gov (United States)

    Ma, Yanbo; Matsuwaki, Takashi; Yamanouchi, Keitaro; Nishihara, Masugi

    2017-04-01

    Stress and glucocorticoids suppress adult neurogenesis in the hippocampus. However, the molecular mechanisms underlying stress-induced impairment of adult neurogenesis are poorly understood. We previously suggested that cyclooxygenase (COX)-2 is a common mediator of stresses in the brain. Here, using a lipopolysaccharide (LPS)-induced acute infectious stress model, we evaluated the roles of COX-2 and its major downstream product prostaglandin E2 (PGE2) in adult neurogenesis and the influence of glucocorticoids on COX-2-related signaling. Treatment of rats with LPS significantly decreased neurogenesis in the dentate gyrus (DG) of the hippocampus, and this inhibitory effect of LPS on neurogenesis was reversed by the glucocorticoid receptor antagonist RU486. Moreover, RU486 significantly enhanced the increase in messenger RNA (mRNA) levels of COX-2 and microsomal prostaglandin E synthase (mPGES)-1 in the hippocampus following LPS stimulation. Administration of AH6809, a selective antagonist of the PGE2 EP2 receptor, as well as NS398, a COX-2 selective inhibitor, exacerbated the suppression of proliferation of neural progenitor cells (NPCs) in the DG. Gene expression of EP1, EP2, and EP3, but not EP4, receptors was also increased following LPS stimulation. Immunohistochemical studies indicated that NPCs expressed EP2 receptor, whereas the majority of cells expressing COX-2 and mPGES-1 were mature neurons in the DG. These results suggest that acute infectious stress upregulates COX-2-related signaling in neurons in the DG, which plays a protective role in neurogenesis through EP2 receptor at least partially. In addition, LPS-induced glucocorticoids suppress this COX-2-related signaling, resulting in decreased neurogenesis.

  10. Bee venom phospholipase A2 induces a primary type 2 response that is dependent on the receptor ST2 and confers protective immunity.

    Science.gov (United States)

    Palm, Noah W; Rosenstein, Rachel K; Yu, Shuang; Schenten, Dominik D; Florsheim, Esther; Medzhitov, Ruslan

    2013-11-14

    Venoms consist of toxic components that are delivered to their victims via bites or stings. Venoms also represent a major class of allergens in humans. Phospholipase A2 (PLA2) is a conserved component of venoms from multiple species and is the major allergen in bee venom. Here we examined how bee venom PLA2 is sensed by the innate immune system and induces a type 2 immune response in mice. We found that bee venom PLA2 induced a T helper type 2 (Th2) cell-type response and group 2 innate lymphoid cell activation via the enzymatic cleavage of membrane phospholipids and release of interleukin-33. Furthermore, we showed that the IgE response to PLA2 could protect mice from future challenge with a near-lethal dose of PLA2. These data suggest that the innate immune system can detect the activity of a conserved component of venoms and induce a protective immune response against a venom toxin. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Primary lymphoma of the brain

    Science.gov (United States)

    Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

  12. Clinical immunity to malaria.

    Science.gov (United States)

    Schofield, Louis; Mueller, Ivo

    2006-03-01

    Under appropriate conditions of transmission intensity, functional immunity to malaria appears to be acquired in distinct stages. The first phase reduces the likelihood of severe or fatal disease; the second phase limits the clinical impact of 'mild' malaria; and the third provides partial but incomplete protection against pathogen burden. These findings suggest clinical immunity to mortality and morbidity is acquired earlier, with greater ease, and via distinct mechanisms as compared to anti-parasite immunity, which is more difficult to achieve, takes longer and is only ever partially efficacious. The implications of this view are significant in that current vaccination strategies aim predominantly to achieve anti-parasite immunity, although imparting clinical immunity is the public health objective. Despite enormous relevance for global public health, the mechanisms governing these processes remain obscure. Four candidate mechanisms might mediate clinical immunity, namely immunity to cytoadherence determinants, tolerance to toxins, acquired immunity to toxins, and immunoregulation. This review addresses the targets and determinants of clinical immunity, and considers the implications for vaccine development.

  13. Immunization Coverage

    Science.gov (United States)

    ... sheets Fact files Questions & answers Features Multimedia Contacts Immunization coverage Fact sheet Reviewed January 2018 Key facts ... at least 90% coverage of DTP3 vaccine. Global immunization coverage 2016 A summary of global vaccination coverage ...

  14. Immunizations - diabetes

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000331.htm Immunizations - diabetes To use the sharing features on this page, please enable JavaScript. Immunizations (vaccines or vaccinations) help protect you from some ...

  15. Immune response

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000821.htm Immune response To use the sharing features on this page, please enable JavaScript. The immune response is how your body recognizes and defends itself ...

  16. Routine Immunization of Adults in Canada: Review of the Epidemiology of Vaccine-Preventable Diseases and Current Recommendations for Primary Prevention

    Directory of Open Access Journals (Sweden)

    Michael D Parkins

    2009-01-01

    Full Text Available Vaccination is one of the greatest achievements in public health of the 20th century. However, the success of vaccine uptake and adherence to immunization guidelines seen in pediatric populations has not been observed among adult Canadians. As a result of the disparity in susceptibility to vaccine-preventable disease, there has been an increasing shift of vaccine-preventable childhood diseases into adult populations. Accordingly, morbidity and mortality due to vaccine-preventable illnesses now occur disproportionately in adults. All Canadians, irrespective of age, should have immunity to measles, mumps, rubella, tetanus, diphtheria, pertussis and varicella. All adult Canadians with significant medical comorbidities or those older than 65 years of age should receive the pneumococcal polysaccharide vaccine and yearly trivalent inactivate influenza vaccines. The present review summarizes the burden of illness of these vaccine-preventable diseases in the Canadian adult population and reviews the current immunization recommendations. Vaccination of all Canadians to these common agents remains a vital tool to decrease individual morbidity and mortality and reduce the overall burden of preventable disease in Canada.

  17. Who is on the primary care team? Professionals' perceptions of the conceptualization of teams and the underlying factors: a mixed-methods study.

    Science.gov (United States)

    Doekhie, Kirti D; Buljac-Samardzic, Martina; Strating, Mathilde M H; Paauwe, Jaap

    2017-12-28

    Due to the growing prevalence of elderly patients with multi-morbidity living at home, there is an increasing need for primary care professionals from different disciplinary backgrounds to collaborate as primary care teams. However, it is unclear how primary care professionals conceptualize teams and what underlying factors influence their perception of being part of a team. Our research question is: What are primary care professionals' perceptions of teams and team membership among primary care disciplines and what factors influence their perceptions? We conducted a mixed-methods study in the Dutch primary care setting. First, a survey study of 152 professionals representing 12 primary care disciplines was conducted, focusing on their perceptions of which disciplines are part of the team and the degree of relational coordination between professionals from different disciplinary backgrounds. Subsequently, we conducted semi-structured interviews with 32 professionals representing 5 primary care disciplines to gain a deeper understanding of the underlying factors influencing their perceptions and the (mis)alignment between these perceptions. Misalignments were found between perceptions regarding which disciplines are members of the team and the relational coordination between disciplines. For example, general practitioners were viewed as part of the team by helping assistants, (district) nurses, occupational therapists and geriatric specialized practice nurses, whereas the general practitioners themselves only considered geriatric specialized practice nurses to be part of their team. Professionals perceive multidisciplinary primary care teams as having multiple inner and outer layers. Three factors influence their perception of being part of a team and acting accordingly: a) knowing the people you work with, b) the necessity for knowledge exchange and c) sharing a holistic view of caregiving. Research and practice should take into account the misalignment between

  18. Oral all-trans retinoic acid plus danazol versus danazol as second-line treatment in adults with primary immune thrombocytopenia: a multicentre, randomised, open-label, phase 2 trial.

    Science.gov (United States)

    Feng, Fei-Er; Feng, Ru; Wang, Min; Zhang, Jia-Min; Jiang, Hao; Jiang, Qian; Lu, Jin; Liu, Hui; Peng, Jun; Hou, Ming; Shen, Jian-Liang; Wang, Jing-Wen; Xu, Lan-Ping; Liu, Kai-Yan; Huang, Xiao-Jun; Zhang, Xiao-Hui

    2017-10-01

    Primary immune thrombocytopenia is a severe bleeding disorder. About 50-85% of patients achieve initial remission from first-line therapies, but optimal second-line treatment remains a challenge. All-trans retinoic acid (ATRA) has an immunomodulatory effect on haemopoiesis, making it a possible treatment option. We aimed to evaluate the efficacy and safety of ATRA plus danazol versus danazol in non-splenectomised patients with corticosteroid-resistant or relapsed primary immune thrombocytopenia. We did a multicentre, randomised, open-label, phase 2 study of adult patients (≥18 years) with primary immune thrombocytopenia from five different tertiary medical centres in China. Those eligible were non-splenectomised, resistant to corticosteroid treatment or relapsed, and had a platelet count less than 30 × 10 9 per L. Masked statisticians used simple randomisation to assign patients (1:1) to receive oral ATRA (10 mg twice daily) plus oral danazol (200 mg twice daily) or oral danazol monotherapy (200 mg twice daily) for 16 weeks. Neither clinicians nor patients were masked to group assignments. All patients were assessed every week during the first 8 weeks of treatment, and at 2-week intervals thereafter. The primary endpoint was 12-month sustained response defined as platelet count of 30 × 10 9 per L or more and at least a doubling of baseline platelet count (partial response), or a platelet count of 100 × 10 9 per L or more (complete response) and the absence of bleeding without rescue medication at the 12-month follow-up. All randomly allocated patients, except for those who withdrew consent, were included in the modified intention-to-treat population and efficacy assessment, and all patients who received at least one dose of the study agents were included in the safety analysis. Study enrolment was stopped early because the trial results crossed the interim analysis efficacy boundary for sustained response. This trial is registered with Clinical

  19. Immunization Schedule

    Science.gov (United States)

    ... may be given as part of a combination vaccine so that a child gets fewer shots. Talk with your doctor about ... Kids Teens Frequently Asked Questions About Immunizations Your Child's Immunizations Is the Flu Vaccine a Good Idea for Your Family? Word! Immunizations ...

  20. Primary development and participation in a foreign antigen-driven immune response of a chromatin-reactive B cell clonotype are not influenced by TLR9 or other MyD88-dependent TLRs.

    Science.gov (United States)

    Coffey, Francis; Liu, Xiaohe; Manser, Tim

    2007-11-15

    Recent findings support a central role for TLRs in both foreign Ag-driven immune responses and systemic autoimmune diseases mediated by B lymphocytes. In vitro studies have shown that the Ag receptors (BCRs) on B cells specific for nuclear autoantigens can facilitate the delivery of these autoantigens to the endocytic compartment, resulting in activation of the nucleic acid-specific TLRs present in this subcellular locale. If this pathway is operative in vivo it might promote the development, survival, or activation of such autoreactive B cells. To test this idea, we evaluated the influence of a deficiency in the CpG DNA-specific TLR, TLR9, or all MyD88-dependent TLRs on the primary development and foreign Ag-driven immune response of B cells in a line of V(H) knockin mice that contains a high frequency of "dual reactive" B cells specific for DNA-based autoantigens such as chromatin, as well as the hapten arsonate. We found that although development and activation of these B cells in vitro are clearly influenced by DNA-based autoantigens, TLR9 or MyD88 deficiencies had no apparent effect on the primary development and participation in the anti-arsonate response of these B cells in vivo. We discuss these results in the context of previous models for the role of TLR9 and other TLRs in the regulation of antinuclear Ag B cell development and activity.

  1. CD4+ T cells play a critical role in the generation of primary and memory antitumor immune responses elicited by SA-4-1BBL and TAA-based vaccines in mouse tumor models.

    Science.gov (United States)

    Sharma, Rajesh K; Yolcu, Esma S; Srivastava, Abhishek K; Shirwan, Haval

    2013-01-01

    The role of CD4(+) T cells in the generation of therapeutic primary and memory immune responses in cancer diverse immunotherapy settings remains ambiguous. We herein investigated this issue using two vaccine formulations containing a novel costimulatory molecule, SA-4-1BBL, as adjuvant and HPV E7 or survivin (SVN) as tumor associated antigens (TAAs) in two mouse transplantable tumor models; the TC-1 cervical cancer expressing xenogeneic HPV E7 and 3LL lung carcinoma overexpressing autologous SVN. Single vaccination with optimized SA-4-1BBL/TAA formulations resulted in the eradication of 6-day established TC-1 and 3LL tumors in >70% of mice in both models. The in vivo depletion of CD4(+) T cells one day before tumor challenge resulted in compromised vaccine efficacy in both TC-1 (25%) and 3LL (12.5%) tumor models. In marked contrast, depletion of CD4(+) T cells 5 days post-tumor challenge and one day prior to vaccination did not significantly alter the therapeutic efficacy of these vaccines. However, long-term immunological memory was compromised in the 3LL, but not in TC-1 model as a significant number (85.7%) of tumor free-mice succumbed to tumor growth when rechallenged with 3LL cells 60 days after the initial tumor inoculation. Collectively, these results demonstrate the indispensable role CD4(+) T cells play in the generation of therapeutic primary immune responses elicited by SA-4-1BBL/TAA-based vaccines irrespective of the nature of TAAs and establish the importance of CD4(+) T cells for long-term immune memory against 3LL tumor expressing self-antigen SVN, but not TC-1 expressing xenogeneic viral antigen E7.

  2. Echinoderm immunity.

    Science.gov (United States)

    Smith, L Courtney; Ghosh, Julie; Buckley, Katherine M; Clow, Lori A; Dheilly, Nolwenn M; Haug, Tor; Henson, John H; Li, Chun; Lun, Cheng Man; Majeske, Audrey J; Matranga, Valeria; Nair, Sham V; Rast, Jonathan P; Raftos, David A; Roth, Mattias; Sacchi, Sandro; Schrankel, Catherine S; Stensvåg, Klara

    2010-01-01

    A survey for immune genes in the genome for the purple sea urchin has shown that the immune system is complex and sophisticated. By inference, immune responses of all echinoderms maybe similar. The immune system is mediated by several types of coelomocytes that are also useful as sensors of environmental stresses. There are a number of large gene families in the purple sea urchin genome that function in immunity and of which at least one appears to employ novel approaches for sequence diversification. Echinoderms have a simpler complement system, a large set of lectin genes and a number of antimicrobial peptides. Profiling the immune genes expressed by coelomocytes and the proteins in the coelomic fluid provide detailed information about immune functions in the sea urchin. The importance of echinoderms in maintaining marine ecosystem stability and the disastrous effects of their removal due to disease will require future collaborations between ecologists and immunologists working towards understanding and preserving marine habitats.

  3. Cytotoxic Capacity of SIV-Specific CD8+ T Cells against Primary Autologous Targets Correlates with Immune Control in SIV-Infected Rhesus Macaques

    Science.gov (United States)

    Mendoza, Daniel; Migueles, Stephen A.; Rood, Julia E.; Peterson, Bennett; Johnson, Sarah; Doria-Rose, Nicole; Schneider, Douglas; Rakasz, Eva; Trivett, Matthew T.; Trubey, Charles M.; Coalter, Vicky; Hallahan, Claire W.; Watkins, David; Franchini, Genoveffa; Lifson, Jeffrey D.; Connors, Mark

    2013-01-01

    Although the study of non-human primates has resulted in important advances for understanding HIV-specific immunity, a clear correlate of immune control over simian immunodeficiency virus (SIV) replication has not been found to date. In this study, CD8+ T-cell cytotoxic capacity was examined to determine whether this function is a correlate of immune control in the rhesus macaque (RM) SIV infection model as has been suggested in chronic HIV infection. SIVmac251-infected human reverse transcriptase (hTERT)-transduced CD4+ T-cell clone targets were co-incubated with autologous macaque effector cells to measure infected CD4+ T-cell elimination (ICE). Twenty-three SIV-infected rhesus macaques with widely varying plasma viral RNA levels were evaluated in a blinded fashion. Nineteen of 23 subjects (83%) were correctly classified as long-term nonprogressor/elite controller (LTNP/EC), slow progressor, progressor or SIV-negative rhesus macaques based on measurements of ICE (weighted Kappa 0.75). LTNP/EC had higher median ICE than progressors (67.3% [22.0–91.7%] vs. 23.7% [0.0–58.0%], p = 0.002). In addition, significant correlations between ICE and viral load (r = −0.57, p = 0.01), and between granzyme B delivery and ICE (r = 0.89, pspecific CD8+ T cells and efficient delivery of active granzyme B to SIV-infected targets are associated with superior control of SIV infection in rhesus macaques, consistent with observations of HIV infection in humans. Therefore, such measurements appear to represent a correlate of control of viral replication in chronic SIV infection and their role as predictors of immunologic control in the vaccine setting should be evaluated. PMID:23468632

  4. NW European shelf under climate warming: implications for open ocean – shelf exchange, primary production, and carbon absorption

    Directory of Open Access Journals (Sweden)

    M. Gröger

    2013-06-01

    Full Text Available Shelves have been estimated to account for more than one-fifth of the global marine primary production. It has been also conjectured that shelves strongly influence the oceanic absorption of anthropogenic CO2 (carbon shelf pump. Owing to their coarse resolution, currently applied global climate models are inappropriate to investigate the impact of climate change on shelves and regional models do not account for the complex interaction with the adjacent open ocean. In this study, a global ocean general circulation model and biogeochemistry model were set up with a distorted grid providing a maximal resolution for the NW European shelf and the adjacent northeast Atlantic. Using model climate projections we found that already a~moderate warming of about 2.0 K of the sea surface is linked with a reduction by ~ 30% of the biological production on the NW European shelf. If we consider the decline of anthropogenic riverine eutrophication since the 1990s, the reduction of biological production amounts is even larger. The relative decline of NW European shelf productivity is twice as strong as the decline in the open ocean (~ 15%. The underlying mechanism is a spatially well confined stratification feedback along the continental shelf break. This feedback reduces the nutrient supply from the deep Atlantic to about 50%. In turn, the reduced productivity draws down CO2 absorption in the North Sea by ~ 34% at the end of the 21st century compared to the end of the 20th century implying a strong weakening of shelf carbon pumping. Sensitivity experiments with diagnostic tracers indicate that not more than 20% of the carbon absorbed in the North Sea contributes to the long-term carbon uptake of the world ocean. The rest remains within the ocean's mixed layer where it is exposed to the atmosphere. The predicted decline in biological productivity, and decrease of phytoplankton concentration (in the North Sea by averaged 25% due to reduced nutrient imports from

  5. Immunity in urogenital protozoa.

    Science.gov (United States)

    Malla, N; Goyal, K; Dhanda, R S; Yadav, M

    2014-09-01

    Innate and adaptive immunity play a significant role in urogenital infections. Innate immunity is provided by the epithelial cells and mucus lining along with acidic pH, which forms a strong physical barrier against the pathogens in female reproductive tract. Cells of innate immune system, antimicrobial peptides, cytokines, chemokines and adaptive immunity in the reproductive tract are evolved during infection, and a pro-inflammatory response is generated to fight against the invading pathogen Trichomonas vaginalis, a primary urogenital protozoa, the etiological agent of human trichomoniasis, a curable sexually transmitted infection. The involvement of the urogenital tract by other protozoal infections such as P. falciparum, Trypanosoma, Leishmania, Toxoplasma, Entamoeba histolytica and Acanthamoeba infection is rarely reported. Trichomonas induce pro-inflammatory and immunosuppressive responses in infected subjects. Multifactorial pathogenic mechanisms including parasite adherence, cysteine proteases, lipophosphoglycan, free radical, cytokine generation and Toll-like receptors appear to interplay with the induction of local and systemic immune responses that ultimately determine the outcome of the infection. However, the involvement of urogenital pathogen-specific immune mechanisms and effect of normal local resident flora on the outcome (symptomatic vs. asymptomatic) of infection are poorly understood. Moreover, immune interactions in trichomoniasis subjects co-infected with bacterial and viral pathogens need to be elucidated. © 2014 John Wiley & Sons Ltd.

  6. The innate immune signaling in cancer and cardiometabolic diseases: Friends or foes?

    Science.gov (United States)

    Wang, Weijun; Zhang, Yaxing; Yang, Ling; Li, Hongliang

    2017-02-28

    The innate immune system is responsible for sensing pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) by several types of germline-encoded pattern-recognition receptors (PRRs). It has the capacity to help the human body maintain homeostasis under normal conditions. However, in pathological conditions, PAMPs or DAMPs trigger aberrant innate immune and inflammatory responses and thus negatively or positively influence the progression of cancer and cardiometabolic diseases. Interestingly, we found that some elements of innate immune signaling are involved in these diseases partially via immune-independent manners, indicating a deeper understanding of the function of innate immune signaling in these diseases is urgent. In this review, we summarize the primary innate immune signaling pathways and their association with cancer and cardiometabolic diseases, with the aim of providing effective therapies for these diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  7. Immunization in special populations.

    Science.gov (United States)

    Miller, Michael A; Rathore, Mobeen H

    2012-01-01

    In summary, immunizations in special populations require understanding the underlying disease and how it might affect the immune system's ability to mount an antibody response to vaccines or predispose certain patient populations to developing certain serious infections. There is still a great need for research on the optimal timing of vaccines after transplants, how to assess protection and development of a protective antibody response after immunization, and whether certain groups (eg, HIV) need to be revaccinated after a certain amount of time if their antibody levels decline. In addition, there are limited data on efficacy of the newer vaccines in these special patient populations, which also requires further investigation.

  8. Whole transcriptome data of primary human NK cells under hypoxia and interleukin 15 priming: A 2×2 factorial design experiment.

    Science.gov (United States)

    Figueiredo, Ana Sofia; Killian, Doreen; Schulte, Jutta; Sticht, Carsten; Lindner, Holger A

    2017-10-01

    Natural Killer (NK) cells mediate innate immunity against cancer and intracellular infection, at that, operating in often oxygen-deprived environments. We performed a microarray experiment with a 2×2 factorial design to profile gene expression in human NK cells (Velasquez et al., 2016) [1]. In this experiment, NK cells from 5 healthy volunteers were primed or not for 6 h with the survival factor and inflammatory cytokine interleukin 15 (IL-15) under hypoxic or normoxic culture conditions (20 samples in total). Here, we provide details on the culture setup that govern the actual O 2 partial pressure (pO 2 ) experienced by the cells, as well as on the RNA extraction procedure used, which we optimized from commercial spin column protocols to obtain highly concentrated total RNA. We present a quality control analysis of the normalized microarray data, as well as overviews for differentially regulated genes. These data provide insights into NK cell transcriptional responses to immune stimulation under physiologically relevant low oxygen conditions. This dataset is deposited in the Gene Expression Omnibus database (accession number GSE70214).

  9. Effects of dietary Spirulina on antioxidant status, lipid profile, immune response and performance characteristics of broiler chickens reared under high ambient temperature

    Science.gov (United States)

    Hosseini, Seyed Abdollah

    2018-01-01

    Objective Spirulina has been recognized formerly as a filamentous spiral-shaped blue-green algae but more recently as a genus of photosynthetic bacteria (Arthrospira). This microorganism is considered as a rich source of essential nutrients for human and animals. The present study was conducted to determine potential application of Spirulina for heat-exposed broilers. Methods Two hundred and fifty Cobb 500 chicks with male to female in equal ratio with average initial weight of 615.6 g at 17 days of age were divided into 5 treatments with 5 replicates of 10 chicks. Treatment groups were as follows: positive and negative controls with 0% Spirulina supplement and three Spirulina receiving groups with 5 g/kg (0.5%), 10 g/kg (1%), and 20 g/kg (2%) supplementation. Spirulina receiving groups as well as positive control were exposed to high ambient temperature at 36°C for 6 h/d from 38 to 44 days of age. Biochemical variables were measured in serum samples at 35, 38, 42, and 45 days of broiler chickens age. Results The results showed that supplementation of the diet with Spirulina decreased concentration of stress hormone and some serum lipid parameters while enhanced humoral immunity response and elevated antioxidant status whereas it didn’t meaningfully affect performance characteristics. Nevertheless, feed conversion ratio was improved numerically but not statistically in broilers fed with 1% Spirulina under high ambient temperature. Conclusion Overall, the present study suggests that alleviation of adverse impacts due to high ambient temperature at biochemical level including impaired enzymatic antioxidant system, elevated stress hormone and lipid profile can be approached in broiler chickens through supplementation of the diet with Spirulina platensis. PMID:28920419

  10. Dynamics of Carbohydrate and Lipid Metabolic Parameters under Complex Therapy in Patients with Type 2 Diabetes Mellitus Combined with Primary Hypothyroidism

    Directory of Open Access Journals (Sweden)

    T.Yu. Yuzvenko

    2015-05-01

    Full Text Available The aim of work was to study dynamics of carbohydrate and lipid metabolic parameters under complex therapy in patients with the type 2 diabetes mellitus (DM combined with primary hypothyroidism. 173 persons (26 men and 147 women were examined. The first (basic group consisted of 52 patients with  type 2 DM combined with primary hypothyroidism. The second group was formed with 55 patients with type 2 DM without thyroid pathology, the third group included 48 patients with primary hypothyroidism without DM (groups of comparison. In the group of type 2 DM patients with primary hypothyroidism in 4 and 12 weeks of complex therapy there were found the improvement of indexes of fasting glucose, postprandial glycemia and glycated haemoglobin, and there was compensation of hypothyroidism in 12 weeks. In patients with the combined pathology there were registered more severe violations of lipid metabolism as an increased values of triglycerides, total holesterol, declined high density lipoproteins, than in the groups of comparison. Under a complex therapy the positive dynamics of lipid spectrum is educed as a declined level of total holesterol, low density lipoproteins, atherogenic coefficient. Levels of total holesterol, triglycerides, atherogenic coefficient positively correlate with the level of thyreotrophin in primary hypothyroidism.

  11. Juzentaihoto Failed to Augment Antigen-Specific Immunity but Prevented Deterioration of Patients’ Conditions in Advanced Pancreatic Cancer under Personalized Peptide Vaccine

    Directory of Open Access Journals (Sweden)

    Shigeru Yutani

    2013-01-01

    Full Text Available Juzentaihoto (JTT is a well-known Japanese herbal medicine, which has been reported to modulate immune responses and enhance antitumor immunity in animal models. However, it is not clear whether JTT has similar effects on humans. In particular, there is little information on the effects of JTT in antigen-specific immunity in cancer patients. Here we conducted a randomized clinical study to investigate whether combined usage of JTT could affect antigen-specific immunity and clinical findings in advanced pancreatic cancer patients undergoing personalized peptide vaccination (PPV, in which HLA-matched vaccine antigens were selected based on the preexisting host immunity. Fifty-seven patients were randomly assigned to receive PPV with (n=28 or without (n=29 JTT. Unexpectedly, JTT did not significantly affect cellular or humoral immune responses specific to the vaccine antigens, which were determined by antigen-specific interferon-γ secretion in T cells and antigen-specific IgG titers in plasma, respectively. Nevertheless, JTT prevented deterioration of patients’ conditions, such as anemia, lymphopenia, hypoalbuminemia, plasma IL-6 elevation, and reduction of performance status, which are frequently observed in advanced cancers. To our knowledge, this is the first clinical study that examined the immunological and clinical effects of JTT in cancer patients undergoing immunotherapy in humans.

  12. Near-optimal Downlink precoding of a MISO system for a secondary network under the SINR constraints of a primary network

    KAUST Repository

    Park, Kihong

    2013-04-01

    In this paper, we study a multiple-input single-output cognitive radio (CR) system where only the primary base station (BS) has multiple antennas. We consider a rate maximization problem of the secondary network under signal-to-interference-plus-noise-ratio constraints on the primary network in order to guarantee the quality-of-service for the latter network. While the interference due to the secondary transmission in the conventional underlay CR approach may severely degrade the performance of the primary network, we propose a primary BS-aided approach in which the primary BS helps relay the secondary users\\' signals instead of allowing them to communicate with each other via a direct path between them. In addition, an algorithm to find a near-optimal beamforming solution at the primary BS is proposed. Finally, based on some selected numerical results, we show that the proposed scheme outperforms the conventional underlay CR configuration over a wide transmit power range. © 2013 IEEE.

  13. Evaluating a complex model designed to increase access to high quality primary mental health care for under-served groups: a multi-method study.

    Science.gov (United States)

    Dowrick, Christopher; Bower, Peter; Chew-Graham, Carolyn; Lovell, Karina; Edwards, Suzanne; Lamb, Jonathan; Bristow, Katie; Gabbay, Mark; Burroughs, Heather; Beatty, Susan; Waheed, Waquas; Hann, Mark; Gask, Linda

    2016-02-17

    Many people with mental distress are disadvantaged because care is not available or does not address their needs. In order to increase access to high quality primary mental health care for under-served groups, we created a model of care with three discrete elements: community engagement, primary care training and tailored wellbeing interventions. We have previously demonstrated the individual impact of each element of the model. Here we assess the effectiveness of the combined model in increasing access to and improving the quality of primary mental health care. We test the assumptions that access to the wellbeing interventions is increased by the presence of community engagement and primary care training; and that quality of primary mental health care is increased by the presence of community engagement and the wellbeing interventions. We implemented the model in four under-served localities in North-West England, focusing on older people and minority ethnic populations. Using a quasi-experimental design with no-intervention comparators, we gathered a combination of quantitative and qualitative information. Quantitative information, including referral and recruitment rates for the wellbeing interventions, and practice referrals to mental health services, was analysed descriptively. Qualitative information derived from interview and focus group responses to topic guides from more than 110 participants. Framework analysis was used to generate findings from the qualitative data. Access to the wellbeing interventions was associated with the presence of the community engagement and the primary care training elements. Referrals to the wellbeing interventions were associated with community engagement, while recruitment was associated with primary care training. Qualitative data suggested that the mechanisms underlying these associations were increased awareness and sense of agency. The quality of primary mental health care was enhanced by information gained from our

  14. Interferon-α is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers.

    Directory of Open Access Journals (Sweden)

    Gareth A D Hardy

    Full Text Available Type-I interferon (IFN-I has been increasingly implicated in HIV-1 pathogenesis. Various studies have shown elevated IFN-I and an IFN-I-induced gene and protein expression signature in HIV-1 infection, yet the elevated IFN-I species has not been conclusively identified, its source remains obscure and its role in driving HIV-1 pathogenesis is controversial. We assessed IFN-I species in plasma by ELISAs and bioassay, and we investigated potential sources of IFN-I in blood and lymph node tissue by qRT-PCR. Furthermore, we measured the effect of therapeutic administration of IFNα in HCV-infected subjects to model the effect of IFNα on chronic immune activation. IFN-I bioactivity was significantly increased in plasma of untreated HIV-1-infected subjects relative to uninfected subjects (p = 0.012, and IFNα was the predominant IFN-I subtype correlating with IFN-I bioactivity (r = 0.658, p<0.001. IFNα was not detectable in plasma of subjects receiving anti-retroviral therapy. Elevated expression of IFNα mRNA was limited to lymph node tissue cells, suggesting that peripheral blood leukocytes are not a major source of IFNα in untreated chronic HIV-1 infection. Plasma IFN-I levels correlated inversely with CD4 T cell count (p = 0.003 and positively with levels of plasma HIV-1 RNA and CD38 expression on CD8 T cells (p = 0.009. In hepatitis C virus-infected subjects, treatment with IFN-I and ribavirin increased expression of CD38 on CD8 T cells (p = 0.003. These studies identify IFNα derived from lymph nodes, rather than blood leukocytes, as a possible source of the IFN-I signature that contributes to immune activation in HIV-1 infection.

  15. Evaluation of a Lagrangian Soot Tracking Method for the prediction of primary soot particle size under engine-like conditions

    DEFF Research Database (Denmark)

    Cai Ong, Jiun; Pang, Kar Mun; Walther, Jens Honore

    2018-01-01

    particles when the mass of incipient soot exceeds a designated threshold value. Their trajectories are then computed using the particle momentum equation. The change of primary soot particle size is dependent on the modified Lagrangian surface growth and soot oxidation models. Performance of the LST model...

  16. Environmental effect on cracking of an 304L austenitic stainless steels in PWR primary environment under cyclic loading

    International Nuclear Information System (INIS)

    Huin, N.

    2013-01-01

    The present study was undertaken in order to get further insights on cracking mechanisms in a 304L stainless steel. More precisely, a first objective of this study was to evaluate the effect of various cold working conditions on the cyclic stress-strain behavior and the fatigue life in air and in PWR primary environment. In air a prior hardening was found to reduce the fatigue life in the LCF regime but not in primary environment. In both environments, the fatigue limit of the hardened materials was increased after cold working.The second objective addresses the effect of the air and the PWR primary environments on the cracking mechanisms (initiation and propagation) in the annealed material in the LCF regime. More precisely, the kinetics of crack initiation and micro crack propagation were evaluated with a multi scale microscopic approach in air and in primary environment. In PWR primary environment, during the first cycles, preferential oxidation occurs along emerging dissociated dislocation and each cycle generates a new C-rich/Fe-rich oxide layer. Then, during cycling, the microstructure evolves from stacking fault into micro twinning and preferential oxidation occurs by continuous shearing and dissolution of the passive film. Beyond a certain crack depth (≤3 μm), the crack starts to propagate with a direction close to a 90 degrees angle from the surface. The crack continues its propagation by successive generation of shear bands and fatigue striations at each cycle up to failure. The role of corrosion hydrogen on these processes is finally discussed. (author)

  17. Macrophages Subvert Adaptive Immunity to Urinary Tract Infection.

    Science.gov (United States)

    Mora-Bau, Gabriela; Platt, Andrew M; van Rooijen, Nico; Randolph, Gwendalyn J; Albert, Matthew L; Ingersoll, Molly A

    2015-07-01

    Urinary tract infection (UTI) is one of the most common bacterial infections with frequent recurrence being a major medical challenge. Development of effective therapies has been impeded by the lack of knowledge of events leading to adaptive immunity. Here, we establish conclusive evidence that an adaptive immune response is generated during UTI, yet this response does not establish sterilizing immunity. To investigate the underlying deficiency, we delineated the naïve bladder immune cell compartment, identifying resident macrophages as the most populous immune cell. To evaluate their impact on the establishment of adaptive immune responses following infection, we measured bacterial clearance in mice depleted of either circulating monocytes, which give rise to macrophages, or bladder resident macrophages. Surprisingly, mice depleted of resident macrophages, prior to primary infection, exhibited a nearly 2-log reduction in bacterial burden following secondary challenge compared to untreated animals. This increased bacterial clearance, in the context of a challenge infection, was dependent on lymphocytes. Macrophages were the predominant antigen presenting cell to acquire bacteria post-infection and in their absence, bacterial uptake by dendritic cells was increased almost 2-fold. These data suggest that bacterial uptake by tissue macrophages impedes development of adaptive immune responses during UTI, revealing a novel target for enhancing host responses to bacterial infection of the bladder.

  18. Development of a participatory Management approach of the Committee for Basic Education School under the Nongbualamphu Primary Educational Service Area Office 2

    Directory of Open Access Journals (Sweden)

    Jirayu Prommajak

    2016-10-01

    Full Text Available This study aimed: 1 study the present state and adverse conditions of administration with the participation of the basic education in schools. 2 Development of a participatory Management approach of the Committee for Basic Education school under the Nongbualamphu Primary Educational Service Area Office 2. Split data into 2 phases. Phase 1: The sample used for this research consisted of 128 members of the committee on basic education in school under the Nongbualamphu Primary Educational Service Area Office 2. Selected by using stratified random sampling. Instruments used included a set of rating scale questionnaires. Phase 2: Data from the interviews using a structured questionnaire and focus group discussion. The basic statistics used for analyzing the collected data were percentage, means and standard deviation. The results of this study were as follows: 1. On the present state administration with the participation of the basic education commission in schools underunder the Nongbualamphu Primary Educational Service Area Office 2 overall participation in management is moderate. Considering the individual aspects, found that the academic administration overall participation in management and budget management were moderate. The personnel management and general and administrative overall participation in management at a high level. 2. Adverse conditions of administration with the participation of the school board for basic education in schools underunder the Nongbualamphu Primary Educational Service Area Office 2 overall in a high level. Considering the individual aspects, found that the school board in basic education is desirable to participate in the management of all aspects. 3. Development of a participatory management approach of the committee for basic education school under the Nongbualamphu Primary Educational Service Area Office 2 is a developmental process management principles PDCA, 5 steps. Step 1: Creating a common understanding Step

  19. Carbon and water vapore balance in a primary subtropical evergreen forest in Southewest China under a changing climate

    Science.gov (United States)

    Song, Q. H.; Zhang, Y. P.

    2017-12-01

    The Ailaoshan Nature Reserve in Yunnan province, southwestern China hosts about 5000 ha of primary subtropical evergreen mountain cloud forest. A widespread and severe drought occurred in southwestern China in 2009 and 2010, providing a unique opportunity to directly evaluate how water use efficiency (WUE) changes with drought stress in the primary subtropical forest. We calculated WUE using measures of gross primary production (GPP) and evapotranspiration (ET) from five years of continuous eddy covariance measurements (2009-2013) obtained over a primary subtropical evergreen broadleaved forest in southwestern China. Annual mean WUE exhibited a decreasing trend from 2009 to 2013, varying from 2.28 to 2.68 g C kg H2O-1. The multiyear average WUE was 2.48 ± 0.17 (mean ± standard deviation) g C kg H2O-1. WUE increased greatly in the driest year (2009), due to a larger decline in ET than in GPP. Unfortunately, the same study site experienced a particularly extreme climate anomaly during January 2015, with a heavy snow of up to 50 cm in depth, which led to severe forest damage. The forest canopy was severely damaged by the heavy snow, and the leaf area index (LAI) decreased significantly from January to July 2015. GPP, net ecosystem exchange (NEE), and Ecosystem respiration (Reco) all sharply decreased in 2015 after the heavy snow. On average, a strong decrease of 544 g C m-2 year-1 in annual NEE in 2015 was associated with a decrease of 829 g C m-2 year-1 in annual GPP and a decrease of 285 g C m-2 year-1 in annual Reco. Overall, annual net C uptake in 2015 was reduced by 76% compared to the mean C uptake of the previous four years. A sharp increase in carbon uptake was also observed in 2016, indicating that long-term, continuous measurements should be carried out to evaluate the overall response to the disturbance.

  20. Immune System

    Science.gov (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  1. Innate immunity

    African Journals Online (AJOL)

    various types of pathogen recognition receptors on epithelial cells and resident cells of the innate immune system, especially macrophages, initiate a localised inflammatory response characterised by an early influx of blood neutrophils.1,2. A comparison of the major characteristics of innate and adaptive immune responses ...

  2. What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling.

    Science.gov (United States)

    Kelsoe, Garnett; Haynes, Barton F

    2017-06-19

    A key goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs) targeted to the vulnerable regions of the HIV envelope. BnAbs develop over time in ∼50% of HIV-1-infected individuals. However, to date, no vaccines have induced bnAbs and few or none of these vaccine-elicited HIV-1 antibodies carry the high frequencies of V(D)J mutations characteristic of bnAbs. Do the high frequencies of mutations characteristic of naturally induced bnAbs represent a fundamental barrier to the induction of bnAbs by vaccines? Recent studies suggest that high frequencies of V(D)J mutations can be achieved by serial vaccination strategies. Rather, it appears that, in the absence of HIV-1 infection, physiologic immune tolerance controls, including a germinal center process termed affinity reversion, may limit vaccine-driven bnAb development by clonal elimination or selecting for mutations incompatible with bnAb activity. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

  3. Standard-dose intravenous anti-D immunoglobulin versus intravenous immunoglobulin in the treatment of newly diagnosed childhood primary immune thrombocytopenia.

    Science.gov (United States)

    Papagianni, Andromachi; Economou, Marina; Tragiannidis, Athanasios; Karatza, Eliza; Tsatra, Ioanna; Gombakis, Nikolaos; Athanassiadou-Piperopoulou, Fani; Athanasiou-Metaxa, Miranda

    2011-05-01

    We conducted a study to evaluate the efficacy of intravenous (IV) anti-D against IV immunoglobulin (IVIG) in newly diagnosed immune thrombocytopenia (ITP) in children and to identify the clinical characteristics of the children most likely to benefit from one or the other treatment. Children (6 mo to 14 y) with newly diagnosed ITP and a platelet count D or with 0.8 to 1 g/kg IVIG in a randomized manner. Twenty-five patients, mean age of 6.8 years, were treated either with IV anti-D (n=10) or with IVIG (n=15). Both drugs were equally efficient in raising the platelet count above 20,000/μL at 24 hours posttreatment. Children who presented with bleeding stage 1 or 2 (no mucosal bleeding) responded better to IVIG treatment, in terms of an increase in platelet count at 24 hours posttreatment (P=0.04). Hemoglobin drop was greater in the anti-D group (P=0.002). A single bolus dose of 50 μg/kg of IV anti-D is a safe and effective first-line treatment in newly diagnosed ITP in childhood and mucosal bleeding is a poor prognostic factor for treatment with IVIG.

  4. Modulating plant primary amino acid metabolism as a necrotrophic virulence strategy: the immune-regulatory role of asparagine synthetase in Botrytis cinerea-tomato interaction.

    Science.gov (United States)

    Seifi, Hamed; De Vleesschauwer, David; Aziz, Aziz; Höfte, Monica

    2014-01-01

    The fungal plant pathogen Botrytis cinerea is the causal agent of the "gray mold" disease on a broad range of hosts. As an archetypal necrotroph, B. cinerea has evolved multiple virulence strategies for inducing cell death in its host. Moreover, progress of B. cinerea colonization is commonly associated with induction of senescence in the host tissue, even in non-invaded regions. In a recent study, we showed that abscisic acid deficiency in the sitiens tomato mutant culminates in an anti-senescence defense mechanism which effectively contributes to resistance against B. cinerea infection. Conversely, in susceptible wild-type tomato a strong induction of senescence could be observed following B. cinerea infection. Building upon this earlier work, we here discuss the immune-regulatory role of a key senescence-associated protein, asparagine synthetase. We found that infection of wild-type tomato leads to a strong transcriptional upregulation of asparagine synthetase, followed by a severe depletion of asparagine titers. In contrast, resistant sitiens plants displayed a strong induction of asparagine throughout the course of infection. We hypothesize that rapid activation of asparagine synthetase in susceptible tomato may play a dual role in promoting Botrytis cinerea pathogenesis by providing a rich source of N for the pathogen, on the one hand, and facilitating pathogen-induced host senescence, on the other.

  5. Effect of ultrasonic irradiation on the number of acetylsalicylic acid crystals produced under the supersaturated condition and the ability of controlling the final crystal size via primary nucleation

    Science.gov (United States)

    Miyasaka, Etsuko; Kato, Yumi; Hagisawa, Minoru; Hirasawa, Izumi

    2006-03-01

    The purposes of this study were to investigate the effects of ultrasound irradiation on the number of crystals formed in an acetylsalicyclic acid crystallization process and to assess the controllability of the final product size via the number of primary nuclei. The number of crystals present after primary nucleation was counted and the relationship between the final product size and the number of crystals was examined. Additionally, the growing ASA crystals were observed, since ultrasound energy not only may control primary nucleation but may also the perfection of the crystal shape. At a high level of ultrasonic energy, ultrasound irradiation increased the average number of crystals, an effect that has been reported often; however, at a low level of ultrasonic energy it decreased the average number of crystals, and moreover, these opposing ultrasonic effects on the number of crystals interchanged at a specific energy threshold. These results reveal two novel phenomena—that there is an energy region where ultrasonic irradiation inhibits primary nucleation, and that a specific amount of ultrasonic energy is needed to activate primary nucleation. On the other hand, the final product size almost depended upon the number of primary nuclei, indicating that the final product size could be controlled via the number of crystals influenced by ultrasound irradiation. According to the photographs of crystals, they were not destroyed by the process. Therefore, it was proposed that ultrasound energy does not destroy the perfection of the crystal shape but only controls primary nucleation under the condition: both short irradiation time and low supersaturated condition.

  6. Immunization to protect the US Armed Forces: heritage, current practice, and prospects.

    Science.gov (United States)

    Grabenstein, John D; Pittman, Phillip R; Greenwood, John T; Engler, Renata J M

    2006-01-01

    Americans serving with the US Armed Forces need protection from the dangerous infections that they can contract during training, based on occupation, during overseas deployment, or because of underlying health status. For over 230 years, the military health-care system has immunized troops to protect them personally and to help them accomplish their missions. Military researchers have invented, developed, and improved vaccines and immunization delivery methods against more than 20 diseases. This article consolidates content from several previous historical reviews, adds additional sources, and cites primary literature regarding military contributions and accomplishments. Discussion emphasizes smallpox, typhoid fever, tetanus, influenza, meningococcal disease, adenovirus, yellow fever, pneumococcal disease, and anthrax. Delivery issues include documentation, simultaneous immunization, seroscreening, safety surveillance, jet injection, and cold-chain management. Immunization policies for each major US conflict are described. Military immunization programs need to be individualized on the basis of personal contraindications and prior immunity. The proper conduct of military immunization programs respects the need for detailed education of military personnel, maximizes quality in immunization delivery, and supports quality clinical care to prevent and treat adverse events after immunization. Military immunization programs maintain the health of soldiers, marines, sailors, airmen, and coast guardsmen, the resources most critical to military success.

  7. Galectins and cutaneous immunity

    Directory of Open Access Journals (Sweden)

    Huan-Yuan Chen

    2012-12-01

    Full Text Available Galectins are highly expressed in epithelial cells and immune cells. In skin, they can be detected in keratinocytes, melanocytes, dendritic cells, macrophages, and T cells. Galectins are present outside and inside the cells and thus may exhibit different functions through extracellular and intracellular actions. Galectins can be involved in the pathogenesis of inflammatory skin diseases by affecting growth, apoptosis, maturation, activation, and motility of keratinocytes and immune cells. Expression of galectins may change depending on the cellular status, such as proliferation and activation. For example, galectin-3 expression is upregulated in T cells but downregulated in dendritic cells when these cells are activated. Furthermore, their expression may also change under pathological conditions. Understanding the function of each galectin in keratinocytes and different immune cell types may reveal how galectins contribute to the pathogenesis of immune-mediated skin diseases.

  8. Immunoglobulin G Avidities in Infants in Mexico after Primary Immunization with Three Doses of Polyribosylribitol Phosphate-Tetanus Toxoid Haemophilus influenzae Type b Vaccine▿ †

    Science.gov (United States)

    Gómez-de-León, Patricia; Díaz-García, F. Javier; Villaseñor-Sierra, Alberto; Segura, Jorge; Carranza, Martha I.; Arredondo-Garcia, José Luis; Santos, José Ignacio

    2008-01-01

    Serum immunoglobulin G concentrations and avidities specific to Haemophilus influenzae type b (Hib) were measured in 208 children living in Guadalajara and Mexico City. Protective concentrations were found in 98.9% and 100.0% of participants, respectively. Geometric mean concentrations differed between both populations and/or among age groups. Mean avidities differed only among the 7- to 12-month-old children. Diphtheria-tetanus-whole-cell pertussis-hepatitis B-Hib primary vaccination seems to induce protection in Mexican children. PMID:18417667

  9. Immunoglobulin G avidities in infants in Mexico after primary immunization with three doses of polyribosylribitol phosphate-tetanus toxoid Haemophilus influenzae type b vaccine.

    Science.gov (United States)

    Gómez-de-León, Patricia; Díaz-García, F Javier; Villaseñor-Sierra, Alberto; Segura, Jorge; Carranza, Martha I; Arredondo-Garcia, José Luis; Santos, José Ignacio

    2008-06-01

    Serum immunoglobulin G concentrations and avidities specific to Haemophilus influenzae type b (Hib) were measured in 208 children living in Guadalajara and Mexico City. Protective concentrations were found in 98.9% and 100.0% of participants, respectively. Geometric mean concentrations differed between both populations and/or among age groups. Mean avidities differed only among the 7- to 12-month-old children. Diphtheria-tetanus-whole-cell pertussis-hepatitis B-Hib primary vaccination seems to induce protection in Mexican children.

  10. Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xueyi, E-mail: xli12@partners.org [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B. [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); DiFiglia, Marian, E-mail: difiglia@helix.mgh.harvard.edu [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States)

    2012-05-18

    Highlights: Black-Right-Pointing-Pointer Primary Huntington's disease neurons are impaired in taking up glucose. Black-Right-Pointing-Pointer Rab11 modulates glucose uptake in neurons. Black-Right-Pointing-Pointer Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. Black-Right-Pointing-Pointer We provide a novel mechanism for glucose hypometabolism in Huntington's disease. -- Abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD{sup 140Q/140Q}). Primary HD{sup 140Q/140Q} cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD{sup 140Q/140Q} neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD{sup 140Q/140Q} neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

  11. Fission product chemistry and aerosol behaviour in the primary circuit of a pressurised water reactor under severe accident conditions

    International Nuclear Information System (INIS)

    Bowsher, B.R.

    1985-09-01

    Three key accident sequences are considered covering a representative range of different environments of pressure, flow, temperature history and degree of zircaloy oxidation, and their principle thermal hydraulic and physical characteristics affecting chemistry behaviour are identified. Inventories, chemical forms and timing of fission product release are summarized together with the major sources of structural materials and their release characteristics. Chemistry of each main fission product species is reviewed from available experimental and/or theoretical data. Studies modelling primary circuit fission product behaviour are reviewed. Requirements for further study are assessed. (UK)

  12. Mutational analysis of primary and metastatic colorectal cancer samples underlying the resistance to cetuximab-based therapy

    Directory of Open Access Journals (Sweden)

    Nemecek R

    2016-07-01

    Full Text Available Radim Nemecek,1 Jitka Berkovcova,2 Lenka Radova,3 Tomas Kazda,4 Jitka Mlcochova,3 Petra Vychytilova-Faltejskova,1,3 Ondrej Slaby,1,3 Marek Svoboda1 1Department of Comprehensive Cancer Care, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic; 2Department of Oncological and Experimental Pathology, Masaryk Memorial Cancer Institute, Brno, Czech Republic; 3Central European Institute of Technology, Masaryk University, Brno, Czech Republic; 4Department of Radiation Oncology, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech Republic Purpose: Although several molecular markers predicting resistance to cetuximab- or panitumumab-based therapy of metastatic colorectal cancer were described, mutations in RAS proto-oncogenes remain the only predictors being used in daily clinical practice. However, 35%–45% of wild-type RAS patients still do not respond to this anti-epidermal growth factor receptor (anti-EGFR monoclonal antibody-based therapy, and therefore the definition of other predictors forms an important clinical need. The aim of the present retrospective single-institutional study was to evaluate potential genes responsible for resistance to anti-EGFR therapy in relation to mutational analysis of primary versus metastatic lesions. Patients and methods: Twenty-four paired primary and corresponding metastatic tissue samples from eight nonresponding and four responding metastatic colorectal cancer patients treated with cetuximab-based therapy were sequenced using a next-generation sequencing panel of 26 genes involved in EGFR signaling pathway and colorectal carcinogenesis. Results: Mutational status of primary tumors and metastatic lesions was highly concordant in TP53, APC, CTNNB1, KRAS, PIK3CA, PTEN, and FBXW7 genes. Metastatic samples harbor significantly more mutations than primary tumors. Potentially negative predictive value of FBXW7 mutations in relationship to anti-EGFR treatment outcomes was confirmed

  13. Sporozoite Immunization of Human Volunteers under Mefloquine Prophylaxis Is Safe, Immunogenic and Protective: A Double-Blind Randomized Controlled Clinical Trial

    NARCIS (Netherlands)

    Bijker, E.M.; Schats, R.; Obiero, J.M.; Behet, M.C.; Gemert, G.J.A. van; Vegte-Bolmer, M. van de; Graumans, W.; Lieshout, L. van; Bastiaens, G.J.H.; Teelen, K.; Hermsen, C.C.; Scholzen, A.; Visser, L.G.; Sauerwein, R.W.

    2014-01-01

    Immunization of healthy volunteers with chloroquine ChemoProphylaxis and Sporozoites (CPS-CQ) efficiently and reproducibly induces dose-dependent and long-lasting protection against homologous Plasmodium falciparum challenge. Here, we studied whether chloroquine can be replaced by mefloquine, which

  14. Student Speech--The First Amendment and Qualified Immunity Under 42 U.S.C. Section 983: Conduct Implications for School Administrators

    Science.gov (United States)

    Araux, Jose Luis

    2013-01-01

    Purpose: The purpose of this study was to describe and analyze the conduct implications of qualified immunity in allegations of deprivation of civil rights by public school administrators regarding the First Amendment-student speech. Methodology: Data were collected using the LexisNexis and JuriSearch online legal research systems, which…

  15. Immunization of horses with a polyvalent live-attenuated African horse sickness vaccine: Serological response and disease occurrence under field conditions

    Directory of Open Access Journals (Sweden)

    Umberto Molini

    2015-01-01

    Our data confirm that vaccination with LAV is a useful tool to reduce the severity of the disease in endemic areas. However, clinical and sometimes fatal AHS can still affect young vaccinated horses, thus highlighting the necessity to better understand the immune response to AHSV and to dispose of more effective vaccines.

  16. Immunity booster

    International Nuclear Information System (INIS)

    Stefanescu, Ioan; Titescu, Gheorghe; Tamaian, Radu; Haulica, Ion; Bild, Walther

    2002-01-01

    The immunity booster is, according to its patent description, microbiologically pure water with an D/(D+H) isotopic concentration of 100 ppm, with physical-chemical characteristics similar to those of distilled water. It is obtained by sterilization of a mixture of deuterium depleted water, with a 25 ppm isotopic concentration, with distilled water in a volume ratio of 4:6. Unlike natural immunity boosters (bacterial agents as Bacillus Chalmette-Guerin, Corynebacterium parvum; lipopolysaccharides; human immunoglobulin) or synthetical products (levamysol; isoprinosyne with immunostimulating action), which cause hypersensitivity and shocks, thrill, fever, sickness and the immunity complex disease, the water of 100 ppm D/(D + H) isotopic concentration is a toxicity free product. The testing for immune reaction of the immunity booster led to the following results: - an increase of cell action capacity in the first immunity shielding stage (macrophages), as evidenced by stimulation of a number of essential characterizing parameters, as well as of the phagocytosis capacity, bactericide capacity, and opsonic capacity of serum; - an increase of the number of leucocyte particularly of the granulocyte in peripheral blood, produced especially when medullar toxic agents like caryolysine are used; - it hinders the effect of lowering the number of erythrocytes in peripheral blood produced by experimentally induced chronic inflammation; - an increase of nonspecific immunity defence capacity against specific bacterial aggression of both Gram-positive bacteria (Streptococcus pneumoniae 558 ) and of the Gram-negative ones (Klebsiella pneumoniae 507 ); - an increase of immunity - stimulating activity (proinflamatory), like that of levamisole as evidenced by the test of stimulation of experimentally induced inflammation by means of carrageenan. The following advantages of the immunity booster are stressed: - it is toxicity free and side effect free; - can be orally administrated as

  17. Metastatic carcinoma of the urinary bladder in a 67-year-old female with underlying triple primary cancers

    Directory of Open Access Journals (Sweden)

    Chia-Yen Hung

    2016-06-01

    A 67-year-old Taiwanese female presented to our institution in November 1997 with gastric signet ring cell carcinoma, pT2N0M0, status post subtotal gastrectomy. In February 2003 she was diagnosed with left breast invasive lobular carcinoma status post modified radical mastectomy, pT2N2M0. Further examination in January 2005 revealed proximal transverse colon cancer, Dukes' C2, with status post right hemicolectomy. She achieved disease-free status from all three malignancies after surgical resection and adjuvant chemotherapy for breast and colon cancers sequentially. In November 2011, she complained about sudden onset of gross hematuria for several days. Diagnostic cystoscopy showed a mass lesion over her urinary bladder. Cystoscope-assisted biopsy showed metastatic poorly differentiated adenocarcinoma with signet ring appearance. Herein we have discussed the pathologic role in the diagnosis of metastatic tumor involving a patient with multiple primary cancers. We also explored the epidemiologic risk and potential causal mechanism of patients with multiple primary cancers.

  18. Surgery under general anaesthesia in severe hidradenitis suppurativa : a study of 363 primary operations in 113 patients

    NARCIS (Netherlands)

    Blok, J. L.; Boersma, M.; Terra, J. B.; Spoo, J. R.; Leeman, F. W. J.; van den Heuvel, E. R.; Huizinga, J.; Jonkman, M. F.; Horvath, B.

    BackgroundTreatment of hidradenitis suppurativa (HS) is a difficult undertaking, especially as there is no consensus on what surgical technique is preferred. At our centre severe HS (Hurley II/III) is operated under general anaesthesia, mostly with the STEEP procedure. ObjectivesTo investigate

  19. Mechanisms of resistance to immune checkpoint inhibitors.

    Science.gov (United States)

    Jenkins, Russell W; Barbie, David A; Flaherty, Keith T

    2018-01-01

    Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer and are rapidly transforming the practice of medical oncology. Whereas cytotoxic chemotherapy and small molecule inhibitors ('targeted therapies') largely act on cancer cells directly, immune checkpoint inhibitors reinvigorate anti-tumour immune responses by disrupting co-inhibitory T-cell signalling. While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI. However, initial response appears to be a binary event, with most non-responders to single-agent ICI therapy progressing at a rate consistent with the natural history of disease. In addition, late relapses are now emerging with longer follow-up of clinical trial populations, suggesting the emergence of acquired resistance. As robust biomarkers to predict clinical response and/or resistance remain elusive, the mechanisms underlying innate (primary) and acquired (secondary) resistance are largely inferred from pre-clinical studies and correlative clinical data. Improved understanding of molecular and immunologic mechanisms of ICI response (and resistance) may not only identify novel predictive and/or prognostic biomarkers, but also ultimately guide optimal combination/sequencing of ICI therapy in the clinic. Here we review the emerging clinical and pre-clinical data identifying novel mechanisms of innate and acquired resistance to immune checkpoint inhibition.

  20. Power allocation and achievable data rate in spectrum-sharing channels under adaptive primary service outage constraints

    KAUST Repository

    Yang, Yuli

    2012-09-01

    In this paper, we focus on a cognitive radio network where adaptive modulation is adopted in primary links. The gap between the primary user (PU)\\'s received signal-to-noise ratio (SNR) and the lower SNR boundary of the modulation mode that is being used, provides an interference-tolerable zone. Based on this gap, a secondary user (SU) has an increased opportunity to access the licensed spectrum and to determine the transmit power it should use to keep the PU\\'s quality-of-service (QoS) unaffected. However, since the SU cannot obtain perfect information on the PU\\'s received SNR, it has to choose an SNR point between the lower and upper boundaries of the PU\\'s current modulation mode as if this point were the real SNR received by the PU. Considering this issue, in order to quantify the effect of the SU\\'s transmissions on the PU\\'s QoS, we define the PU\\'s service outage probability and obtain its closed-form expressions by taking into account whether the peak transmit power constraint is imposed on the secondary\\'s transmission or not. Subsequently, we derive the SU\\'s achievable data rate in closed form for counterpart scenarios. Numerical results provided here quantify the relation between the PU\\'s service outage probability and the SU\\'s achievable data rate, which further demonstrate that the higher the peak transmit power a secondary transmitter can support, the better performance the cognitive radio network can achieve. © 2012 IEEE.

  1. Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth

    Energy Technology Data Exchange (ETDEWEB)

    Kamburoglu, Kivanc; Sonmez, Gul; Kurt, Hakan; Berktas, Zeynep Serap [Dept. of Dentomaxillofacial Radiology, Faculty of Dentistry, Ankara University, Ankara (Turkmenistan); Ozen, Dogukan [Dept. of Biostatistics, Faculty of Veterinary Medicine, Ankara University, Ankara (Turkmenistan)

    2017-06-15

    The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The other 26 intact teeth that did not have caries served as controls. Teeth were imaged using a 100×90-mm field of view and a 0.2-mm voxel size with 9 different CBCT settings. Four observers assessed the images using a 5-point scale. Kappa values were calculated to assess observer agreement. CBCT settings were compared with the gold standard using a receiver operating characteristic analysis. The area under the curve (AUC) values for each setting were compared using the chi-square test, with a significance level of α=.05. Intraobserver kappa values ranged from 0.366 to 0.664 for observer 1, from 0.311 to 0.447 for observer 2, from 0.597 to 1.000 for observer 3, and from 0.869 to 1 for observer 4. Furthermore, interobserver kappa values among the observers ranged from 0.133 to 0.814 for the first reading and from 0.197 to 0.805 for the second reading. The highest AUC values were found for setting 5 (0.5916) and setting 3 (0.5886), and were not found to be statistically significant (P>.05). Variations in tube voltage and tube current did not affect the detection of recurrent caries under amalgam restorations in primary teeth.

  2. Effects of various cone-beam computed tomography settings on the detection of recurrent caries under restorations in extracted primary teeth

    International Nuclear Information System (INIS)

    Kamburoglu, Kivanc; Sonmez, Gul; Kurt, Hakan; Berktas, Zeynep Serap; Ozen, Dogukan

    2017-01-01

    The aim of this study was to assess the ex vivo diagnostic ability of 9 different cone-beam computed tomography (CBCT) settings in the detection of recurrent caries under amalgam restorations in primary teeth. Fifty-two primary teeth were used. Twenty-six teeth had dentine caries and 26 teeth did not have dentine caries. Black class II cavities were prepared and restored with amalgam. In the 26 carious teeth, recurrent caries were left under restorations. The other 26 intact teeth that did not have caries served as controls. Teeth were imaged using a 100×90-mm field of view and a 0.2-mm voxel size with 9 different CBCT settings. Four observers assessed the images using a 5-point scale. Kappa values were calculated to assess observer agreement. CBCT settings were compared with the gold standard using a receiver operating characteristic analysis. The area under the curve (AUC) values for each setting were compared using the chi-square test, with a significance level of α=.05. Intraobserver kappa values ranged from 0.366 to 0.664 for observer 1, from 0.311 to 0.447 for observer 2, from 0.597 to 1.000 for observer 3, and from 0.869 to 1 for observer 4. Furthermore, interobserver kappa values among the observers ranged from 0.133 to 0.814 for the first reading and from 0.197 to 0.805 for the second reading. The highest AUC values were found for setting 5 (0.5916) and setting 3 (0.5886), and were not found to be statistically significant (P>.05). Variations in tube voltage and tube current did not affect the detection of recurrent caries under amalgam restorations in primary teeth

  3. Effect of diesel exhaust generated by a city bus engine on stress responses and innate immunity in primary bronchial epithelial cell cultures.

    Science.gov (United States)

    Zarcone, M C; Duistermaat, E; Alblas, M J; van Schadewijk, A; Ninaber, D K; Clarijs, V; Moerman, M M; Vaessen, D; Hiemstra, P S; Kooter, I M

    2018-04-01

    Harmful effects of diesel emissions can be investigated via exposures of human epithelial cells, but most of previous studies have largely focused on the use of diesel particles or emission sources that are poorly representative of engines used in current traffic. We studied the cellular response of primary bronchial epithelial cells (PBECs) at the air-liquid interface (ALI) to the exposure to whole diesel exhaust (DE) generated by a Euro V bus engine, followed by treatment with UV-inactivated non-typeable Haemophilus influenzae (NTHi) bacteria to mimic microbial exposure. The effect of prolonged exposures was investigated, as well as the difference in the responses of cells from COPD and control donors and the effect of emissions generated during a cold start. HMOX1 and NQO1 expression was transiently induced after DE exposure. DE inhibited the NTHi-induced expression of human beta-defensin-2 (DEFB4A) and of the chaperone HSPA5/BiP. In contrast, expression of the stress-induced PPP1R15A/GADD34 and the chemokine CXCL8 was increased in cells exposed to DE and NTHi. HMOX1 induction was significant in both COPD and controls, while inhibition of DEFB4A expression by DE was significant only in COPD cells. No significant differences were observed when comparing cellular responses to cold engine start and prewarmed engine emissions. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Fracture risk in patients with type 2 diabetes under different antidiabetic treatment regimens: a retrospective database analysis in primary care

    Directory of Open Access Journals (Sweden)

    Pscherer S

    2016-02-01

    Full Text Available S Pscherer,1 K Kostev,2 FW Dippel,3 W Rathmann4 1Department of Diabetology, Klinikum Traunstein, Kliniken Südostbayern AG, Traunstein, 2Epidemiology Department, IMS Health, Frankfurt, 3Sanofi-Aventis Deutschland GmbH, Berlin, 4German Diabetes Center, Institute for Biometrics and Epidemiology, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany Aim: Type 2 diabetes is associated with an increased risk of fractures. There are a few studies on the effects of diabetes treatment on fracture risk. The aim was to investigate the fracture risk related to various types of insulin therapy in primary care practices. Methods: Data from 105,960 type 2 diabetes patients from 1,072 general and internal medicine practices in Germany were retrospectively analyzed (Disease Analyzer database; 01/2000–12/2013. Fracture risk of the following therapies was compared using multivariate logistic regression models adjusting for age, sex, diabetes care, comorbidity, and glycemic control (HbAlc: 1 incident insulin therapy versus oral antidiabetic drugs, 2 basal-supported oral therapy versus supplementary insulin therapy versus conventional insulin therapy, and 3 insulin glargine versus insulin detemir versus NPH insulin. Results: There was a lower odds of having incident fractures in the oral antidiabetic drug group compared to incident insulin users, although not significant (odds ratio [OR]; 95% confidence interval: 0.87; 0.72–1.06. There were increased odds for conventional insulin therapy (OR: 1.59; 95% CI [confidence interval] 0.89–2.84 and supplementary insulin therapy (OR: 1.20; 0.63–2.27 compared to basal-supported oral therapy, which was not significant as well. Overall, there was no significant difference in fracture risk for basal insulins (glargine, detemir, NPH insulin. After a treatment duration ≥2 years, insulin glargine showed a lower odds of having ≥1 fracture compared to NPH users (OR: 0.78; 0.65–0

  5. Physicians, Primary Caregivers and Topical Repellent: All Under-Utilised Resources in Stopping Dengue Virus Transmission in Affected Households.

    Directory of Open Access Journals (Sweden)

    Nguyet Minh Nguyen

    2016-05-01

    Full Text Available Primary health care facilities frequently manage dengue cases on an ambulatory basis for the duration of the patient's illness. There is a great opportunity for specific messaging, aimed to reduce dengue virus (DENV transmission in and around the home, to be directly targeted toward this high-risk ambulatory patient group, as part of an integrated approach to dengue management. The extent however, to which physicians understand, and can themselves effectively communicate strategies to stop focal DENV transmission around an ambulatory dengue case is unknown; the matter of patient comprehension and recollection then ensues. In addition, the effectiveness of N,N-diethyl-3-methylbenzamide (DEET-based insect repellent in protecting dengue patients from Aedes aegypti mosquitoes' bites has not been investigated.A knowledge, attitude and practice (KAP survey, focusing on the mechanisms of DENV transmission and prevention, was performed using semi-structured questionnaires. This survey was targeted towards the patients and family members providing supportive care, and physicians routinely involved in dengue patient management in Southern Vietnam. An additional clinical observational study was conducted to measure the efficacy of a widely-used 13% DEET-based insect repellent to repel Ae. aegypti mosquitoes from the forearms of dengue cases and matched healthy controls.Among both the physician (n = 50 and patient (n = 49 groups there were several respondents lacking a coherent understanding of DENV transmission, leading to some inappropriate attitudes and inadequate acute preventive practices in the household. The application of insect repellent to protect patients and their relatives from mosquito bites was frequently recommended by majority of physicians (78% participating in the survey. Nevertheless, our tested topical application of 13% DEET conferred only ~1hr median protection time from Ae. aegypti landing. This is notably shorter than that

  6. A basic mathematical model of the immune response

    Science.gov (United States)

    Mayer, H.; Zaenker, K. S.; an der Heiden, U.

    1995-03-01

    Interaction of the immune system with a target population of, e.g., bacteria, viruses, antigens, or tumor cells must be considered as a dynamic process. We describe this process by a system of two ordinary differential equations. Although the model is strongly idealized it demonstrates how the combination of a few proposed nonlinear interaction rules between the immune system and its targets are able to generate a considerable variety of different kinds of immune responses, many of which are observed both experimentally and clinically. In particular, solutions of the model equations correspond to states described by immunologists as ``virgin state,'' ``immune state'' and ``state of tolerance.'' The model successfully replicates the so-called primary and secondary response. Moreover, it predicts the existence of a threshold level for the amount of pathogen germs or of transplanted tumor cells below which the host is able to eliminate the infectious organism or to reject the tumor graft. We also find a long time coexistence of targets and immune competent cells including damped and undamped oscillations of both. Plausibly the model explains that if the number of transformed cells or pathogens exeeds definable values (poor antigenicity, high reproduction rate) the immune system fails to keep the disease under control. On the other hand, the model predicts apparently paradoxical situations including an increased chance of target survival despite enhanced immune activity or therapeutically achieved target reduction. A further obviously paradoxical behavior consists of a positive effect for the patient up to a complete cure by adding an additional target challenge where the benefit of the additional targets depends strongly on the time point and on their amount. Under periodically pulsed stimulation the model may show a chaotic time behavior of both target growth and immune response.

  7. 2. Cell-mediatedImmunity

    Indian Academy of Sciences (India)

    Admin

    Cell-mediated Immunity sma hmed', Banishree Saha', nand Patwardhan°,. Shwetha Shivaprasad and Dipankar Nandis. Our immune system, by and large, does a fine job in protect- ing us from opportunistic and infectious microbes, potential carcinogens and allergens. It is therefore crucial to under- stand the organization ...

  8. Primary EBV-positive Hodgkin's lymphoma of the CNS under azathioprine treatment. Case report and review of the literature

    International Nuclear Information System (INIS)

    Henkenberens, Christoph; Christiansen, Hans; Franzke, Anke; Raab, Peter; Oschlies, Ilske; Klapper, Wolfram

    2014-01-01

    Retrospective and prospective cohort studies suggest that central nervous system involvement occurs in approximately 0.5 % of patients with advanced Hodgkin's lymphoma. The isolated primary intracranial manifestation of Hodgkin's lymphoma is an extremely rare finding, with few cases reported in the literature. Little is known about the optimal treatment and prognosis of these tumors. Here, we present a case report with a review of the literature. A 47-year-old Caucasian man with persistent frontal headache and unspecific vertigo for half a month was diagnosed with nodular space-occupying lesions in the cerebellum. His medical history included multiple sclerosis, which was treated for 20 years with the immunosuppressive drug azathioprine. Further staging revealed no additional lesions suspected of being malignant. The patient underwent total tumor resection. Immunohistopathological examination showed Epstein-Barr virus-associated classic Hodgkin's lymphoma. Diagnostic bone marrow punction excluded lymphoma involvement of the bone marrow. The patient had no B symptoms. Consequently, the patient was classified as having stage I E A disease according to the Modified Ann Arbor Classification of Hodgkin Lymphoma and received systemic chemotherapy followed by radiation therapy for the former cerebellar tumor region. He was in complete clinical remission at the last follow-up 9 months after the initial diagnosis. This case report and literature review suggest that multimodal treatment leads to a remarkable clinical outcome in Hodgkin's lymphoma with intracranial involvement. (orig.) [de

  9. Primary percutaneous coronary intervention for coronary thrombosis during cisplatin, etoposide and bleomycin combination therapy under thromboprophylaxis with nadroparin

    Directory of Open Access Journals (Sweden)

    Mehmet Yaman

    2015-06-01

    Full Text Available Testicular cancer is the most common solid tumor among young men. Regimens containing cisplatin and bleomycin in combination with etoposide are used for treatment of non-seminomatous germ cell testicular tumors. Cancer patients are at increased risk of thrombosis. Epidemiological studies have identified chemotherapy as an additional risk factor for a hypercoagulability state and thrombosis. The risk is more pronounced with cisplatin-containing chemotherapy. Thromboprophylaxis with LMWH during chemotherapy has demonstrated to give substantial risk reduction of thromboembolic events. We present a case of acute myocardial infraction during combined chemotherapy with bleomycin, etoposide and cisplatin for testicular cancer under thromboprophylaxis with nadroparin. Emergency coronary angiography revealed total occlusion of the right coronary artery by a thrombus which was successfully removed by aspiration.

  10. Effect of mini-implant length and diameter on primary stability under loading with two force levels.

    Science.gov (United States)

    Chatzigianni, Athina; Keilig, Ludger; Reimann, Susanne; Eliades, Theodore; Bourauel, Christoph

    2011-08-01

    Mini-implants are widely utilized as anchorage units in orthodontic treatment. Nevertheless, there are factors that interfere with their clinical performance. The aim of this study was to examine the impact of length and diameter on the primary stability of two different types of orthodontic mini-implants loaded with two force levels. A total of 90 self-drilling mini-implants were inserted in bovine ribs in vitro, 62 of which were used in data analysis. The mini-implants were of two types, Aarhus (n=29) and Lomas (n=33), of two lengths (7 and 9 mm, n=26 and n=28, respectively), and of two diameters (1.5 and 2 mm, Lomas only, n=6 and n=8, respectively). A closed nickel-titanium (NiTi) coil spring was attached to each mini-implant. Half of the preparations were loaded with a low force of 0.5 N and the other half with a force of 2.5 N. Mini-implant deflections during force application were non-invasively registered using a three-dimensional (3D) laser-optical system. The results were analysed with analysis of variance for the effects of implant type, implant length, and force level, and with a t-test for the study of the effect of diameter in two different diameter variants of the same (Lomas) implant. In the low-force group, implant displacements were not statistically significant difference according to the investigated parameters. In the high-force group, the 9 mm long mini-implants displaced significantly less (10.5±7.5 μm) than the 7 mm long (22.3±11.3 μm, P<0.01) and the 2 mm wide significantly less (8.8±2.2 μm) than the 1.5 mm implants (21.9±1.5 μm, P<0.001). The force level at which significance occurred was 1 N. The rotation of the Lomas mini-implants in the form of tipping was significantly higher than that of the Aarhus mini-implants at all force levels. Implant length and diameter become statistically significant influencing parameters on implant stability only when a high force level is applied.

  11. Effects of flunixin and florfenicol combined with vitamins E and/or C on selected immune mechanisms in cattle under conditions of adaptive stress

    OpenAIRE

    Urban-Chmiel Renata; Stachura Rafał; Hola Piotr; Puchalski Andrzej; Dec Marta; Wernicki Andrzej

    2015-01-01

    The aim of the study was to evaluate the effect of flunixin and florfenicol administered in combination with vitamin E or C on selected leukocyte immune mechanisms and on the inflammatory process during the first few weeks in the feedlot. Fifty calves divided into 5 groups (n = 10) received florfenicol and flunixin with vitamin E or C. Blood was collected on the 1st, 3rd, 7th, 14th, 21st, and 28th d of the experiment. Intracellular metabolism (NBT), apoptosis, chemotaxis, susceptibility to M....

  12. Time evolution of secondary electron emission and trapped charge accumulation in polyimide film under various primary electron irradiation currents

    Energy Technology Data Exchange (ETDEWEB)

    Song, Bai-Peng; Zhou, Run-Dong; Su, Guo-Qiang [State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi ’ an Jiaotong University, Xi ’ an, Shaanxi 710049 (China); Mu, Hai-Bao, E-mail: haibaomu@xjtu.edu.cn [State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi ’ an Jiaotong University, Xi ’ an, Shaanxi 710049 (China); Zhang, Guan-Jun, E-mail: gjzhang@xjtu.edu.cn [State Key Laboratory of Electrical Insulation and Power Equipment, School of Electrical Engineering, Xi ’ an Jiaotong University, Xi ’ an, Shaanxi 710049 (China); Bu, Ren-An [School of Electronic and Information Engineering, Xi ’ an Jiaotong University, Xi ’ an, Shaanxi 710049 (China)

    2016-12-30

    Highlights: • Time resolved evolution of secondary electron emission and trapped charge accumulation in PI film is described. • The time constant is characterized as a function of incident current. • Evolution of SEY σ and trapped charge is dependent on incident dose but not the incident rate. • Trap density and capture cross section are discussed. - Abstract: Time-resolved evolution of secondary electron emission and trapped charge accumulation in polyimide film is investigated during two interval electrons bombardment, derived from the measurement of displacement current and secondary current via a hemispherical detector with the shielded grid. Under various irradiation current, secondary electron yield (SEY σ) at a certain injected energy decreases exponentially from initial amplitude σ{sub 0} to self-consistent steady value σ{sup ∞} close to 0.93. The time constant τ of charging process is characterized as a function of incident current I{sub p}, and the results indicate that the formula I{sub p} × τ is fitted by a hyperbolical law. The influence of I{sub p} on the amount of trapped charge is studied and no significant change in its saturation value is observed. The evolution of SEY σ and trapped charge is dependent on incident dose Q{sub p} but not the incident rate I{sub p}. Furthermore, the trap density and capture cross section are discussed.

  13. [Explore the influence factors on primary lung cancer in Fujian province Han population under the use of generalized linear model].

    Science.gov (United States)

    He, Fei; Xiao, Rendong; Yu, Tingting; Zhang, Xin; Liu, Zhiqiang; Cai, Lin

    2015-08-01

    The purpose of this study was to use the data on lung cancer in Han Chinese in Fujian province to explore the value of a generalized, linear model and to investigate the impact related to environment factors on lung cancer as well as the independent and interaction effects on the development of lung cancer. SAS 9.2 was used to build a generalized linear model to evaluate the influence factors and interaction of lung cancer on both smokers and non-smokers. Results showed that the relationship of the factors was multiplied. Under the logistic regression analysis, seven risk factors and nine risk factors were noticed in smokers or in non-smokers, respectively. Heavy smokers and lung diseases appeared a positive multiplying effect on smokers while passive smoking and fresh fruits showed positive multiplying effects on non-smokers. The generalized linear models could filter suitable models thus facilitating further research on the interaction between the two. It seemed easy to carry on the comprehensive and rational analysis on related epidemiological data.

  14. Primary wound closure after tooth extraction for prevention of medication-related osteonecrosis of the jaw in patients under denosumab.

    Science.gov (United States)

    Matsumoto, Akihiko; Sasaki, Masanori; Schmelzeisen, Rainer; Oyama, Yukiko; Mori, Yoshihide; Voss, Pit Jacob

    2017-01-01

    Some recent reports have indicated that local infection causes osteonecrosis of the jaw and described that tooth extraction may not be a direct cause of developing medication-related osteonecrosis of the jaw (MRONJ) in patients receiving antiresorptive medications. Tooth extraction and elimination of the source of infection are expected to reduce the risk of developing MRONJ. However, there is no data regarding prevention for developing osteonecrosis of the jaw in patients receiving denosumab. Therefore, the aim of this study was to investigate the outcome of tooth extractions with proper wound closure in patients receiving denosumab. Forty teeth in 19 patients treated with denosumab therapy were extracted under preoperative intravenous antibiotics. Patients who had already developed MRONJ in the extraction sites or who had a history of radiation therapy were excluded. During surgery, bone edges were smoothed and all wounds were closed using the double-layered technique. Thirty-seven extraction sites (92.5 %) in 17 out of 19 patients (89.5 %) were healed. However, three extraction sites in two patients had complications; one patient had exposed bone and developed MRONJ (stage 1) and the other developed a mucosa fistula. Additional surgical procedures were performed and all wounds were completely healed. Tooth extractions in patients receiving denosumab can be performed in an appropriate manner and result in good outcomes. This study indicated that tooth extraction with proper wound closure to avoid secondary infection may be effective for the prevention of MRONJ even in high-risk patients.

  15. Partitioning between primary and secondary metabolism of carbon allocated to roots in four maize genotypes under water deficit and its effects on productivity

    Directory of Open Access Journals (Sweden)

    Alyne Oliveira Lavinsky

    2015-10-01

    Full Text Available Plants may respond to drought by altering biomass allocation to shoots and roots or by changing the metabolic activities in these organs. To determine how drought changes the partitioning of carbon allocated to growth and secondary metabolism in maize roots and how it affects photosynthesis (A and productivity in maize, we evaluated leaf gas exchange, yield componentes, root morphology, and primary and secondary metabolites including total soluble sugars (TSS, starch (S, phenolics (PHE, and lignin (LIG. Data were collected from pot-grown plants of four maize genotypes: BRS 1010 and 2B710 (sensitive genotypes and DKB390 and BRS1055 (tolerant genotypes under two soil water tensions: field capacity (FC, − 18 kPa and water deficit (WD, − 138 kPa. WD was applied at the pre-flowering stage for 12 days and then the water supply was restored and maintained at optimum levels until the end of the cycle. For genotype BRS 1055 under FC, the greatest A did not result in greater grain biomass (DGB because the accumulated photoassimilates had already filled the cells, and thus the excessive TSS synthesized in leaves was allocated to roots in large amounts. However, the sharp decrease in A caused by WD imposition in this genotype did not affect the influx pressure of leaf TSS, which was due largely to conversion of primary metabolites to PHE compounds to increase the length of fine roots. In leaves of DKB390 under WD, both S and TSS were reduced, whereas PHE were increased to prevent excessive water loss and xylem cavitation. Under WD, both BRS1010 and 2B710 genotypes displayed reduced allocation of biomass to shoots and roots and LIG content in leaves, as well as lower A and DGB values. In BRS1010 this response was coupled to S decrease in leaves and TSS increase in roots, whereas in 2B710 there was a concomitant S increase in roots.

  16. Melatonin: Buffering the Immune System

    Directory of Open Access Journals (Sweden)

    Juan M. Guerrero

    2013-04-01

    Full Text Available Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed.

  17. Melatonin: Buffering the Immune System

    Science.gov (United States)

    Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

    2013-01-01

    Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

  18. Factors influencing secondary vibriocidal immune responses: relevance for understanding immunity to cholera.

    Science.gov (United States)

    Losonsky, G A; Yunyongying, J; Lim, V; Reymann, M; Lim, Y L; Wasserman, S S; Levine, M M

    1996-01-01

    Although serum vibriocidal activity is used extensively as a marker of immunity to O1 Vibrio cholerae, there are limitations in this assay to detect instances of reexposure. We define the conditions operative in producing secondary vibriocidal responses in North American volunteers primed with either wild-type V. cholerae 1, 4, or 6 months later. Secondary serum vibriocidal responses occurred under two distinct secondary challenge conditions. The first occurred when secondary challenge produced a breakthrough in clinical protection. Following secondary exposure, 14 of 22 (64%) and 1 of 29 (3%) subjects with and without vibrio stool excretion, respectively, had secondary responses (P CVD 103-HgR and given homologous wild-type challenge within 4 months mounted a secondary vibriocidal response (P = 0.0009). The majority of the serum vibriocidal activity was of the immunoglobulin M (IgM) isotype, seen in 96 and 73% of subjects following primary and secondary exposure, respectively. Vibriocidal activity in the IgG fraction following primary and secondary exposures occurred with LPS)-specific IgG1 and IgG3 subclass responses supported the vibriocidal isotype data. However, following primary exposure, IgG4 LPS responses predominated, occurring in 81% of responding volunteers. These data suggest that, under certain conditions of secondary exposure to V. cholerae O1 antigens, when there is sufficient active local immunity present, there is a block of vibrio antigen resampling at the M cell level. We discuss the implications of and possible explanations for these findings.

  19. Primary immunodeficiencies: a pictorial immunology primer for radiologists

    International Nuclear Information System (INIS)

    Manson, D.E.; Sikka, S.; Reid, B.; Roifman, C.

    2000-01-01

    The immune response constitutes a complex array of interconnecting pathways and mechanisms that result in a sophisticated series of communicative reactions designed to protect against foreign substances. Recent advances in immunologic investigations have begun to unlock many of the previous mysteries underlying the body's defense mechanisms. The complexities of organ transplantation, the isolation of organisms that selectively impair the immune system, and the widespread use of sophisticated anti-neoplastic therapies have necessitated a more comprehensive understanding of underlying immune mechanisms by all physicians. This review presents a simplified view of the development of the immune response. We present strategic examples of primary (i.e., congenital) disorders of immune function to create a framework to understand the major mechanisms that constitute the various ''arms'' of the immune system. It is sometimes easier to understand complex mechanisms when one sees how disease processes interfere with these mechanisms. We have excluded many of the more detailed and complicated mechanisms involved in the immune response in an effort to maintain simplicity

  20. Immune cells and non-immune cells with immune function in mammalian cochleae.

    Science.gov (United States)

    Hu, Bo Hua; Zhang, Celia; Frye, Mitchell D

    2017-12-20

    The cochlea has an immune environment dominated by macrophages under resting conditions. When stressed, circulating monocytes enter the cochlea. These immune mediators, along with cochlear resident cells, organize a complex defense response against pathological challenges. Since the cochlea has minimal exposure to pathogens, most inflammatory conditions in the cochlea are sterile. Although the immune response is initiated for the protection of the cochlea, off-target effects can cause collateral damage to cochlear cells. A better understanding of cochlear immune capacity and regulation would therefore lead to development of new therapeutic treatments. Over the past decade, there have been many advances in our understanding of cochlear immune capacity. In this review, we provide an update and overview of the cellular components of cochlear immune capacity with a focus on macrophages in mammalian cochleae. We describe the composition and distribution of immune cells in the cochlea and suggest that phenotypic and functional characteristics of macrophages have site-specific diversity. We also highlight the response of immune cells to acute and chronic stresses and comment on the potential function of immune cells in cochlear homeostasis and disease development. Finally, we briefly review potential roles for cochlear resident cells in immune activities of the cochlea. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Primary immunodeficiency

    Directory of Open Access Journals (Sweden)

    McCusker Christine

    2011-11-01

    Full Text Available Abstract Primary immunodeficiency disorder (PID refers to a heterogeneous group of over 130 disorders that result from defects in immune system development and/or function. PIDs are broadly classified as disorders of adaptive immunity (i.e., T-cell, B-cell or combined immunodeficiencies or of innate immunity (e.g., phagocyte and complement disorders. Although the clinical manifestations of PIDs are highly variable, most disorders involve at least an increased susceptibility to infection. Early diagnosis and treatment are imperative for preventing significant disease-associated morbidity and, therefore, consultation with a clinical immunologist is essential. PIDs should be suspected in patients with: recurrent sinus or ear infections or pneumonias within a 1 year period; failure to thrive; poor response to prolonged use of antibiotics; persistent thrush or skin abscesses; or a family history of PID. Patients with multiple autoimmune diseases should also be evaluated. Diagnostic testing often involves lymphocyte proliferation assays, flow cytometry, measurement of serum immunoglobulin (Ig levels, assessment of serum specific antibody titers in response to vaccine antigens, neutrophil function assays, stimulation assays for cytokine responses, and complement studies. The treatment of PIDs is complex and generally requires both supportive and definitive strategies. Ig replacement therapy is the mainstay of therapy for B-cell disorders, and is also an important supportive treatment for many patients with combined immunodeficiency disorders. The heterogeneous group of disorders involving the T-cell arm of the adaptive system, such as severe combined immunodeficiency (SCID, require immune reconstitution as soon as possible. The treatment of innate immunodeficiency disorders varies depending on the type of defect, but may involve antifungal and antibiotic prophylaxis, cytokine replacement, vaccinations and bone marrow transplantation. This article

  2. Analysis of Analytical Models Developed under the Uniaxial Strain Condition for Predicting Coal Permeability during Primary Depletion

    Directory of Open Access Journals (Sweden)

    Chuanming Li

    2017-11-01

    Full Text Available The stress-dependent permeability of coal during coalbed methane production has been extensively studied both experimentally and theoretically. However, how permeability changes as a function of stress variation is somewhat unclear to date, and currently used analytical models fail to accurately predict permeability evolution with gas depletion. Considering that the role played by changes in in situ stress in permeability evolution is critical, a comprehensive theoretical study was first conducted, through which it was found that coal permeability is determined by mean effective stress. Moreover, the influence of matrix shrinkage on cleat deformation and then coal permeability was overestimated by currently used models, leading to inaccuracy of the predicted permeability. By taking both mean effective stress and the influence of matrix shrinkage on cleat deformation into account, a new permeability model was developed under the uniaxial strain condition in order to precisely estimate permeability evolution during gas depletion. An in-depth investigation and comparison among four commonly-used permeability models, the Palmer and Mansoori (P&M model, Improved P&M model, Shi and Durucan (S&D model, and Cui and Bustin (C&B model, was then conducted. It was experimentally verified that a good match can be achieved between the lab data and the results predicted by the proposed model. Permeability variation of coalbed reservoirs associated with gas depletion is a consequence of two opposing effects: mechanical compaction and matrix shrinkage. In comparison, it was found that the coefficients of these two effects incorporated in those four models have a significant impact on permeability variation; and the accuracy of the values of initial cleat porosity and cleat compressibility, the bridges connecting permeability, and those two effects in analytical models, is extremely critical to permeability estimations. This study can shed light on improving the

  3. Developing a Novel Parameter Estimation Method for Agent-Based Model in Immune System Simulation under the Framework of History Matching: A Case Study on Influenza A Virus Infection

    Directory of Open Access Journals (Sweden)

    Tingting Li

    2017-12-01

    Full Text Available Since they can provide a natural and flexible description of nonlinear dynamic behavior of complex system, Agent-based models (ABM have been commonly used for immune system simulation. However, it is crucial for ABM to obtain an appropriate estimation for the key parameters of the model by incorporating experimental data. In this paper, a systematic procedure for immune system simulation by integrating the ABM and regression method under the framework of history matching is developed. A novel parameter estimation method by incorporating the experiment data for the simulator ABM during the procedure is proposed. First, we employ ABM as simulator to simulate the immune system. Then, the dimension-reduced type generalized additive model (GAM is employed to train a statistical regression model by using the input and output data of ABM and play a role as an emulator during history matching. Next, we reduce the input space of parameters by introducing an implausible measure to discard the implausible input values. At last, the estimation of model parameters is obtained using the particle swarm optimization algorithm (PSO by fitting the experiment data among the non-implausible input values. The real Influeza A Virus (IAV data set is employed to demonstrate the performance of our proposed method, and the results show that the proposed method not only has good fitting and predicting accuracy, but it also owns favorable computational efficiency.

  4. Diagnosis and treatment of hypothyroidism in TSH deficiency compared to primary thyroid disease: pituitary patients are at risk of under-replacement with levothyroxine.

    Science.gov (United States)

    Koulouri, Olympia; Auldin, Mohammed A; Agarwal, Ravi; Kieffer, Veronica; Robertson, Carole; Falconer Smith, James; Levy, Miles J; Howlett, Trevor A

    2011-06-01

    were generally under-replaced in pituitary patients compared to primary thyroid disease and the data imply that some untreated patients were actually TSH deficient. The distribution of fT4 in patients with primary thyroid disease on levothyroxine may guide optimum replacement levels in pituitary disease. © 2011 Blackwell Publishing Ltd.

  5. An outbreak of type π vaccine-derived poliovirus in Sichuan province, China: emergence and circulation in an under-immunized population.

    Science.gov (United States)

    Wang, Hai-Bo; Fang, Gang; Yu, Wen-Zhou; Du, Fei; Fan, Chun-Xiang; Liu, Qing-Lian; Hao, Li-Xin; Liu, Yu; Zheng, Jing-Shan; Qin, Zhi-Ying; Xia, Wei; Zhang, Shi-Yue; Yin, Zun-Dong; Jing, Qiong; Zhang, Yan-Xia; Huang, Rong-Na; Yang, Ru-Pei; Tong, Wen-Bin; Qi, Qi; Guan, Xu-Jing; Jing, Yu-Lin; Ma, Qian-Li; Wang, Jin; Ma, Xiao-Zhen; Chen, Na; Zheng, Hong-Ru; Li, Yin-Qiao; Ma, Chao; Su, Qi-Ru; Reilly, Kathleen H; Luo, Hui-Ming; Wu, Xian-Ping; Wen, Ning; Yang, Wei-Zhong

    2014-01-01

    During August 2011-February 2012, an outbreak of type Π circulating vaccine-derived poliovirus (cVDPVs) occurred in Sichuan Province, China. A field investigation of the outbreak was conducted to characterize outbreak isolates and to guide emergency response. Sequence analysis of poliovirus capsid protein VP1 was performed to determine the viral propagation, and a coverage survey was carried out for risk assessment. One clinical compatible polio case and three VDPV cases were determined in Ngawa County, Ngawa Tibetan and Qiang Autonomous Prefecture, Sichuan Province. Case patients were unimmunized children, 0.8-1 years old. Genetic sequencing showed that the isolates diverged from the VP1 region of the type Π Sabin strain by 5-12 nucleotides (nt) and shared the same 5 nt VP1 substitutions, which indicate single lineage of cVDPVs. Of the 7 acute flaccid paralysis cases (all>6 months) reported in Ngawa Prefecture in 2011, 4 (57.1%) cases (including 2 polio cases) did not receive oral attenuated poliovirus vaccine. Supplementary immunization activities (SIAs) were conducted in February-May, 2012, and the strain has not been isolated since. High coverage of routine immunization should be maintained among children until WPV transmission is globally eradicated. Risk assessments should be conducted regularly to pinpoint high risk areas or subpopulations, with SIAs developed if necessary.

  6. Immune Response After Measles Vaccination

    Directory of Open Access Journals (Sweden)

    Bhardwaj A.K

    1991-01-01

    Full Text Available Measles immunization of 192 under 5 years of age children was undertaken and the overall seroconversion was 76.0%. Seroconversion rate in the age group of 9-12 months was 70.9% and it was 100% after one year. Immune response in malnourished children was more as compared to normal children. There were negligible side reactions after measles vaccination, and this vaccine passed normal potency tests under field conditions.

  7. Nye behandlingsmuligheder ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved...

  8. Patofysiologien ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune-mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved...

  9. Nye behandlingsmuligheder ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathog...

  10. Immune persistence after pertussis vaccination.

    Science.gov (United States)

    Chen, Zhiyun; He, Qiushui

    2017-04-03

    Pertussis is one of the most prevalent vaccine-preventable diseases worldwide. The true infection rate is significantly higher than the reported incidence rate. An increased prevalence of pertussis in older populations has been found, mainly caused by waning immunity after vaccination. Vaccine-induced immunity differs due to variation in vaccine content, schedule and coverage. Protection following acellular pertussis vaccines has been suggested to wane faster than whole cell pertussis vaccines. However, long-term immune persistence of whole cell pertussis vaccines may be confounded by a progressive acquisition of natural immunity. The World Health Organization has recommended that a switch from whole cell to acellular pertussis vaccines for primary immunization in infants should only be considered if additional periodic boosters or maternal immunization can be ensured and sustained in the national immunization schedules. In this review, we present data on immune persistence after different pertussis vaccinations and compare the findings from countries with different vaccination strategies. Future aspects in serological studies are briefly discussed.

  11. Alcohol, aging, and innate immunity.

    Science.gov (United States)

    Boule, Lisbeth A; Kovacs, Elizabeth J

    2017-07-01

    The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

  12. Amyloid and immune homeostasis.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2018-03-01

    Extracellular amyloid deposition defines a range of amyloidosis and amyloid-related disease. Addition to primary and secondary amyloidosis, amyloid-related disease can be observed in different tissue/organ that sharing the common pathogenesis based on the formation of amyloid deposition. Currently, both Alzheimer's disease and type 2 diabetes can be diagnosed with certainly only based on the autopsy results, by which amyloidosis of the associative tissue/organ is observed. Intriguingly, since it demonstrated that amyloid deposits trigger inflammatory reaction through the activation of cascaded immune response, wherein several lines of evidence implies a protective role of amyloid in preventing autoimmunity. Furthermore, attempts for preventing amyloid formation and/or removing amyloid deposits from the brain have caused meningoencephalitis and consequent deaths among the subjects. Hence, it is important to note that amyloid positively participates in maintaining immune homeostasis and contributes to irreversible inflammatory response. In this review, we will focus on the interactive relationship between amyloid and the immune system, discussing the potential functional roles of amyloid in immune tolerance and homeostasis. Copyright © 2017 Elsevier GmbH. All rights reserved.

  13. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... component) of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by ...

  14. Nye behandlingsmuligheder ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathog......Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved...

  15. Patofysiologien ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune-mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathog......Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune-mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved...

  16. Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis.

    Science.gov (United States)

    Paiva, Bruno; Mateos, María Victoria; Sanchez-Abarca, Luis Ignacio; Puig, Noemi; Vidriales, María-Belén; López-Corral, Lucía; Corchete, Luis A; Hernandez, Miguel T; Bargay, Joan; de Arriba, Felipe; de la Rubia, Javier; Teruel, Ana-Isabel; Giraldo, Pilar; Rosiñol, Laura; Prosper, Felipe; Oriol, Albert; Hernández, José; Esteves, Graça; Lahuerta, Juan José; Bladé, Joan; Perez-Simon, Jose Antonio; San Miguel, Jesús F

    2016-03-03

    There is significant interest in immunotherapy for the treatment of high-risk smoldering multiple myeloma (SMM), but no available data on the immune status of this particular disease stage. Such information is important to understand the interplay between immunosurveillance and disease transformation, but also to define whether patients with high-risk SMM might benefit from immunotherapy. Here, we have characterized T lymphocytes (including CD4, CD8, T-cell receptor γδ, and regulatory T cells), natural killer (NK) cells, and dendritic cells from 31 high-risk SMM patients included in the treatment arm of the QUIREDEX trial, and with longitudinal peripheral blood samples at baseline and after 3 and 9 cycles of lenalidomide plus low-dose dexamethasone (LenDex). High-risk SMM patients showed at baseline decreased expression of activation-(CD25/CD28/CD54), type 1 T helper-(CD195/interferon-γ/tumor necrosis factor-α/interleukin-2), and proliferation-related markers (CD119/CD120b) as compared with age-matched healthy individuals. However, LenDex was able to restore the normal expression levels for those markers and induced a marked shift in T-lymphocyte and NK-cell phenotype. Accordingly, high-risk SMM patients treated with LenDex showed higher numbers of functionally active T lymphocytes. Together, our results indicate that high-risk SMM patients have an impaired immune system that could be reactivated by the immunomodulatory effects of lenalidomide, even when combined with low-dose dexamethasone, and support the value of therapeutic immunomodulation to delay the progression to multiple myeloma. The QUIREDEX trial was registered to www.clinicaltrials.gov as #NCT00480363. © 2016 by The American Society of Hematology.

  17. Origins of immunity: transcription factors and homologues of effector genes of the vertebrate immune system expressed in sea urchin coelomocytes.

    Science.gov (United States)

    Pancer, Z; Rast, J P; Davidson, E H

    1999-08-01

    Echinoderms share common ancestry with the chordates within the deuterostome clade. Molecular features that are shared between their immune systems and that of mammals thus illuminate the basal genetic framework on which these immune systems have been constructed during evolution. The immune effector cells of sea urchins are the coelomocytes, whose primary function is protection against invasive marine pathogens; here we identify six genes expressed in coelomocytes, homologues of which are also expressed in cells of the mammalian immune system. Three coelomocyte genes reported here encode transcription factors. These are an NFKB homologue (SpNFKB); a GATA-2/3 homologue (SpGATAc); and a runt domain factor (SpRunt-1). All three of these coelomocyte genes respond sharply to bacterial challenge: SpNFKB and SpRunt-1 genes are rapidly up-regulated, while transcripts of SpGATAc factor disappear within hours of injection of bacteria. Sham injection also activates SpNFKB and SpRunt, though with slower kinetics, but does not affect SpGATAc levels. Another gene, SpHS, encodes a protein related to the signal transduction intermediate HS1 of lymphoid cells. Two other newly discovered genes, SpSRCR1 and SpSRCR5, encode proteins featuring SRCR repeats. These genes are members of a complex family of SRCR genes all expressed specifically in coelomocytes. The SRCR repeats most closely resemble those of mammalian macrophage scavenger receptors. Remarkably, each individual sea urchin expresses a specific pattern of SRCR genes. Our results imply some shared immune functions and more generally, a shared regulatory architecture which underlies immune system gene expression in all deuterostomes. We conclude that the vertebrate immune system has evolved by inserting new genes into old gene regulatory networks dedicated to immunity.

  18. Development of Guidelines for Mentoring Internal Supervision for the Schools under Roi-Et Office of Primary Education Service Area 2

    Directory of Open Access Journals (Sweden)

    Natchana Sahunil

    2017-06-01

    Full Text Available The research aimed to 1 study the factors and indicators of mentoring internal supervision for schools, 2 study the current state and the desirable state of mentoring internal supervision for schools, and 3 study the guidelines on the operation of mentoring internal supervision for the schools under Roi-Et Office of Primary Education Service Area 2. The research was divided into 3 phases. In phase 1 the informants comprised 5 certified experts. In phase 2 the sample comprised 488 government teachers under Roi-Et Office of Primary Education Service Area 2, btained through multi-stage random sampling. In phase 3 the informants comprised school directors, school deputy directors and supervisor teachers under Roi-Et Office of Primary Education Service Area 2, totally 9 persons. The research instruments onsisted of 1 a questionnaire having the discrimination from 0.34 to 0.79 and the total reliability of 0.87, 2 a structured interview form, and 3 a suitability and feasibility assessment form for the guidelines on the operation of mentoring internal supervision. The analysis of data employed percentage, the mean and standard deviation. The results are as follows: 1. There are 4 factors of the guidelines on mentoring internal supervision for schools. They are: preparation of mentoring supervision, with 12 indicators ; management of mentoring supervision, with 12 indicators ; operation of mentoring supervision, with 14 indicators ; and evaluation of mentoring supervision, with 10 indicators, all of which had been evaluated by the experts as, on the whole, very suitable. 2. The current state of the mentoring internal supervision for schools, on the whole and factor by factor, was in the moderate level in every factor. Meanwhile, the desirable state of mentoring internal supervision for schools, on the whole, was in the high level. When considered factor by factor, the factor with the highest mean is management of mentoring supervision. The factor with

  19. Primary Immune Deficiency Disease Genetics & Inheritance

    Science.gov (United States)

    ... Publications Help Archive Site Map Información en español Employee Information Connect with NIAID Facebook Twitter Linkedin Google+ Youtube Flickr Instagram Pinterest Email Website Policies & Notices ...

  20. Primary Human Uterine Leiomyoma Cell Culture Quality Control: Some Properties of Myometrial Cells Cultured under Serum Deprivation Conditions in the Presence of Ovarian Steroids.

    Directory of Open Access Journals (Sweden)

    Camila Bonazza

    Full Text Available Cell culture is considered the standard media used in research to emulate the in vivo cell environment. Crucial in vivo experiments cannot be conducted in humans and depend on in vitro methodologies such as cell culture systems. However, some procedures involving the quality control of cells in culture have been gradually neglected by failing to acknowledge that primary cells and cell lines change over time in culture. Thus, we report methods based on our experience for monitoring primary cell culture of human myometrial cells derived from uterine leiomyoma. We standardized the best procedure of tissue dissociation required for the study of multiple genetic marker systems that include species-specific antigens, expression of myofibroblast or myoblast markers, growth curve, serum deprivation, starvation by cell cycle synchronization, culture on collagen coated plates, and 17 β-estradiol (E2 and progesterone (P4 effects. The results showed that primary myometrial cells from patients with uterine leiomyoma displayed myoblast phenotypes before and after in vitro cultivation, and leiomyoma cells differentiated into mature myocyte cells under the appropriate differentiation-inducing conditions (serum deprivation. These cells grew well on collagen coated plates and responded to E2 and P4, which may drive myometrial and leiomyoma cells to proliferate and adhere into a focal adhesion complex involvement in a paracrine manner. The establishment of these techniques as routine procedures will improve the understanding of the myometrial physiology and pathogenesis of myometrium-derived diseases such as leiomyoma. Mimicking the in vivo environment of fibrotic conditions can prevent false results and enhance results that are based on cell culture integrity.

  1. Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions.

    Science.gov (United States)

    Mwaba, P; Mwansa, J; Chintu, C; Pobee, J; Scarborough, M; Portsmouth, S; Zumla, A

    2001-12-01

    Inpatient medical wards, Department of Medicine, University Teaching Hospital, Lusaka, Zambia. To define the natural history, clinical presentation, and management outcome of microbiologically confirmed cryptococcal meningitis in adult AIDS patients treated under local conditions where antifungal and antiretroviral therapies are not routinely available. A descriptive, longitudinal, observational study. All adult patients admitted to the medical wards of the University Teaching Hospital, Lusaka, Zambia with cerebrospinal fluid culture proved, primary cryptococcal meningitis, during a 12 month period were enrolled into the study. The following details were acquired: clinical features, HIV status, laboratory data, treatment accorded, and survival. A total of 230 patients with primary cryptococcal meningitis were studied (median age 32 years; range 15-65 years; 112 males, 118 females). Cryptococcal meningitis was the first AIDS defining illness in 210 (91%) patients. One hundred and thirty of the 230 (56%) patients had received treatment with fluconazole monotherapy and 100 (43%) patients received palliative care only without any antifungal therapy. A 100% case fatality rate was observed in both groups at follow up: by seven weeks in the untreated group and at six months in the fluconazole treated group. The cumulative median survival from time of diagnosis was 19 days (range 1-164 days) for the fluconazole treated group and 10 days (range 0-42 days) for the untreated group. Cryptococcal meningitis, under current treatment accorded at the University Teaching Hospital, Lusaka, has a 100% mortality in young Zambian adults with AIDS. The current treatment accorded to Zambian adults with cryptococcal meningitis is inappropriate. An urgent need exists to improve strategies for the clinical management of AIDS patients in poor African countries. The wider ethical and operational issues of making available antifungals to African AIDS patients are discussed.

  2. No. 357-Immunization in Pregnancy.

    Science.gov (United States)

    Castillo, Eliana; Poliquin, Vanessa

    2018-03-02

    To review the evidence and provide recommendations on immunization in pregnancy. Outcomes evaluated include effectiveness of immunization and risks and benefits for mother and fetus. The Medline and Cochrane databases were searched for articles published up to January 2017 on the topic of immunization in pregnancy. The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the SOGC under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care (Table 1). Implementation of the recommendations in this guideline should result in more appropriate immunization of pregnant and breastfeeding women, decreased risk of contraindicated immunization, and better disease prevention. Copyright © 2017 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.

  3. Maternal Education and Immunization Status Among Children in Kenya.

    Science.gov (United States)

    Onsomu, Elijah O; Abuya, Benta A; Okech, Irene N; Moore, DaKysha; Collins-McNeil, Janice

    2015-08-01

    Child morbidity and mortality due to infectious diseases continues to be a major threat and public health concern worldwide. Although global vaccination coverage reached 90 % for diphtheria, tetanus and pertussis (DTP3) across 129 countries, Kenya and other sub-Saharan countries continue to experience under-vaccination. The purpose of this study was to examine the association between maternal education and child immunization (12-23 months) in Kenya. This study used retrospective cross-sectional data from the 2008-2009 Kenya Demographic and Health Survey for women aged 15-49, who had children aged 12-23 months, and who answered questions about vaccination in the survey (n = 1,707). The majority of the children had received vaccinations, with 77 % for poliomyelitis, 74 % for measles, 94 % for tuberculosis, and 91 % for diphtheria, whooping cough (pertussis), and tetanus. After adjusting for other covariates, women with primary, secondary, and college/university education were between 2.21 (p immunize their children than those who had less than a primary education. Maternal education is clearly crucial in ensuring good health outcomes among children, and integrating immunization knowledge with maternal and child health services is imperative. More research is needed to identify factors influencing immunization decisions among less-educated women in Kenya.

  4. Does capitation payment under national health insurance affect subscribers' trust in their primary care provider? a cross-sectional survey of insurance subscribers in Ghana.

    Science.gov (United States)

    Andoh-Adjei, Francis-Xavier; Cornelissen, Dennis; Asante, Felix Ankomah; Spaan, Ernst; van der Velden, Koos

    2016-08-24

    trust in their primary care provider giving them quality care under capitation payment despite their negative attitude towards capitation payment. They are guided by proximity and quality of care considerations in their choice of provider. The NHIA would, however, have to address itself to the negative perceptions about the capitation payment policy.

  5. Immune-Mediated Therapies for Liver Cancer

    Directory of Open Access Journals (Sweden)

    Rajagopal N. Aravalli

    2017-02-01

    Full Text Available In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer. Preclinical and clinical studies with immune-mediated therapies have shown potential benefits in patients with liver cancer. In this review, we summarize current knowledge and recent developments in tumor immunology by focusing on two main primary liver cancers: hepatocellular carcinoma and cholangiocarcinoma.

  6. The Site for Development of Cellular Immunity

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 23; Issue 2. Thymus: The site for Development of Cellular Immunity. Shamik Majumdar Sanomy ... The immune system protects our bodies against infectionsand cancers. This review introduce readers to the thymus. – a primary lymphoid organ – which is ...

  7. Initial experience with laparoscopic splenectomy for immune ...

    African Journals Online (AJOL)

    Immune thrombocytopenic purpura (ITP) is an immune- mediated disease characterised by thrombocytopenia, the degree of which determines the increased risk of bleeding.[1] It can be primary (idiopathic) or secondary. Secondary ITP can occur with systemic lupus erythematosus, chronic lymphocytic leukaemia,.

  8. Immune Evasion by Epstein-Barr Virus

    NARCIS (Netherlands)

    Ressing, Maaike E; van Gent, Michiel; Gram, Anna M; Hooykaas, Marjolein J G; Piersma, Sytse J; Wiertz, EJHJ

    2015-01-01

    Epstein-Bar virus (EBV) is widespread within the human population with over 90% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to

  9. Primary central nervous system lymphoma and atypical glioblastoma: differentiation using the initial area under the curve derived from dynamic contrast-enhanced MR and the apparent diffusion coefficient

    International Nuclear Information System (INIS)

    Choi, Yoon Seong; Lee, Ho-Joon; Ahn, Sung Soo; Lee, Seung-Koo; Chang, Jong Hee; Kang, Seok-Gu; Kim, Eui Hyun; Kim, Se Hoon

    2017-01-01

    To evaluate the ability of the initial area under the curve (IAUC) derived from dynamic contrast-enhanced MR imaging (DCE-MRI) and apparent diffusion coefficient (ADC) in differentiating between primary central nervous system lymphoma (PCNSL) and atypical glioblastoma (GBM). We retrospectively identified 19 patients with atypical GBM (less than 13 % necrosis of the enhancing tumour), and 23 patients with PCNSL. The histogram parameters of IAUC at 30, 60, 90 s (IAUC30, IAUC60, and IAUC90), and ADC were compared between PCNSL and GBM. The diagnostic performances and added values of the IAUC and ADC for differentiating between PCNSL and GBM were evaluated. Interobserver agreement was assessed via intraclass correlation coefficient (ICC). The IAUC and ADC parameters were higher in GBM than in PCNSL. The 90th percentile (p90) of IAUC30 and 10th percentile (p10) of ADC showed the best diagnostic performance. Adding p90 of IAUC30 to p10 of ADC improved the differentiation between PCNSL and GBM (area under the ROC curve [AUC] = 0.886), compared to IAUC30 or ADC alone (AUC = 0.789 and 0.744; P < 0.05 for all). The ICC was 0.96 for p90 of IAUC30. The IAUC may be a useful parameter together with ADC for differentiating between PCNSL and atypical GBM. (orig.)

  10. Enhancement of Leaf Gas Exchange and Primary Metabolites under Carbon Dioxide Enrichment Up-Regulates the Production of Secondary Metabolites in Labisia pumila Seedlings

    Directory of Open Access Journals (Sweden)

    Mohd Hafiz Ibrahim

    2011-05-01

    Full Text Available A split plot 3 by 3 experiment was designed to investigate and distinguish the relationships among production of primary metabolites (soluble sugar and starch, secondary metabolites (total phenolics, TP; total flavonoids, TF and leaf gas exchange of three varieties of the Malaysian medicinal herb Labisia pumila Blume, namely the varieties alata, pumila and lanceolata, under three levels of CO2 enrichment (400, 800 and 1,200 µmol mol−1 for 15 weeks. The treatment effects were solely contributed by CO2 enrichment levels; no varietal differences were observed. As CO2 levels increased from 400 to 1,200 µmol mol−1, the production of carbohydrates also increased steadily, especially for starch more than soluble sugar (sucrose. TF and TP content, simultaneously, reached their peaks under 1,200 µmol exposure, followed by 800 and 400 µmol mol−1. Net photosynthesis (A and quantum efficiency of photosystem II (fv/fm were also enhanced as CO2 increased from 400 to 1,200 µmol mol−1. Leaf gas exchange characteristics displayed a significant positive relationship with the production of secondary metabolites and carbohydrate contents. The increase in production of TP and TFs were manifested by high C/N ratio and low protein content in L. pumila seedlings, and accompanied by reduction in cholorophyll content that exhibited very significant negative relationships with total soluble sugar, starch and total non structural carbohydrate.

  11. Primary central nervous system lymphoma and atypical glioblastoma: differentiation using the initial area under the curve derived from dynamic contrast-enhanced MR and the apparent diffusion coefficient

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yoon Seong; Lee, Ho-Joon; Ahn, Sung Soo; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Seodaemun-gu, Seoul (Korea, Republic of); Chang, Jong Hee; Kang, Seok-Gu; Kim, Eui Hyun [Yonsei University College of Medicine, Department of Neurosurgery, Seoul (Korea, Republic of); Kim, Se Hoon [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of)

    2017-04-15

    To evaluate the ability of the initial area under the curve (IAUC) derived from dynamic contrast-enhanced MR imaging (DCE-MRI) and apparent diffusion coefficient (ADC) in differentiating between primary central nervous system lymphoma (PCNSL) and atypical glioblastoma (GBM). We retrospectively identified 19 patients with atypical GBM (less than 13 % necrosis of the enhancing tumour), and 23 patients with PCNSL. The histogram parameters of IAUC at 30, 60, 90 s (IAUC30, IAUC60, and IAUC90), and ADC were compared between PCNSL and GBM. The diagnostic performances and added values of the IAUC and ADC for differentiating between PCNSL and GBM were evaluated. Interobserver agreement was assessed via intraclass correlation coefficient (ICC). The IAUC and ADC parameters were higher in GBM than in PCNSL. The 90th percentile (p90) of IAUC30 and 10th percentile (p10) of ADC showed the best diagnostic performance. Adding p90 of IAUC30 to p10 of ADC improved the differentiation between PCNSL and GBM (area under the ROC curve [AUC] = 0.886), compared to IAUC30 or ADC alone (AUC = 0.789 and 0.744; P < 0.05 for all). The ICC was 0.96 for p90 of IAUC30. The IAUC may be a useful parameter together with ADC for differentiating between PCNSL and atypical GBM. (orig.)

  12. Co-ordinating innate and adaptive immunity to viral infection: mobility is the key

    DEFF Research Database (Denmark)

    Wern, Jeanette Erbo; Thomsen, Allan Randrup

    2009-01-01

    the very essence of immune system physiology, a key to a rapid, efficient and optimally regulated immune response is the ability of the involved cells to rapidly shift between a stationary and a mobile state, combined with stringent regulation of cell migration during the mobile state. Through the co-ordinated......The host counters a viral infection through a complex response made up of components belonging to both the innate and the adaptive immune system. In this report, we review the mechanisms underlying this response, how it is induced and how it is co-ordinated. As cell-cell communication represents...... in mounting an efficient host response and co-ordinating innate and adaptive immunity during a primary viral infection....

  13. Effects of flunixin and florfenicol combined with vitamins E and/or C on selected immune mechanisms in cattle under conditions of adaptive stress

    Directory of Open Access Journals (Sweden)

    Urban-Chmiel Renata

    2015-06-01

    Full Text Available The aim of the study was to evaluate the effect of flunixin and florfenicol administered in combination with vitamin E or C on selected leukocyte immune mechanisms and on the inflammatory process during the first few weeks in the feedlot. Fifty calves divided into 5 groups (n = 10 received florfenicol and flunixin with vitamin E or C. Blood was collected on the 1st, 3rd, 7th, 14th, 21st, and 28th d of the experiment. Intracellular metabolism (NBT, apoptosis, chemotaxis, susceptibility to M. haemolytica leukotoxin, and expression of β2-integrins were determined in leukocytes. The symptoms of respiratory tract infection were observed in 40% of calves in control group, while in the other groups the morbidity rate ranged from 10% to 20%. Leukocytes showed decreased NBT, and the mean values for apoptosis ranged from 14% to 24%. The lowest percentage of apoptotic cells was observed in the calves that received florfenicol with flunixin and vitamins E and C. The chemotactic activity confirmed the significant inhibitory effect of the preparations on migration of the cells. A significant decrease (P ≤ 0.05 in the susceptibility of leukocytes to leukotoxin was noted in the group that received florfenicol and flunixin with vitamin E. Expression of β2-integrin receptors was the lowest in calves receiving florfenicol with flunixin and vitamin E or C. The application of an antibiotic and a non-steroidal anti-inflammatory drug with antioxidants protected the leukocytes involved in defence against M. haemolytica virulence factors and effectively limited oxidative stress in the calves.

  14. Effect of the combination of ginseng, oriental bezoar and glycyrrhiza on autonomic nervous activity and immune system under mental arithmetic stress.

    Science.gov (United States)

    Zheng, Aisong; Moritani, Toshio

    2008-06-01

    Stress reduces physical and mental tolerances (immune potential) of humans and it induces progression of existing illness or causes latent disorders to become active. Thus, the control and suppression of stress plays an important role in the improvement of quality of life and prevention of diseases. Ginseng, oriental bezoar and glycyrrhiza have been used for Kampo (herbal treatment) for thousand years and a number of pharmacological and clinical studies have reported their effects. However, it has not been previously described how the combination of these most commonly used herbs affect mental stress. This is a randomized, double-blind, placebo-controlled experiment to examine the effectiveness of reducing stress response by taking Kampo. Ten healthy males (mean age 27+/-1) participated in the study. The effectiveness of stress reduction was assessed by measuring ECG, salivary chromogranin A (CgA), blood glucose, WBC, granulocytes, lymphocytes, NK cell activity, etc. Salivary and blood measurement values of pre- and post-mental arithmetic stress were compared. In addition, ECG measurement values of pre- and mid-mental arithmetic stress were compared. we observed a higher HF power and a lower SNS index, HR, CgA, WBC and granulocytes in the Kampo trial than those in the placebo trial. The HR, HF power and SNS index were changed significantly (p<0.05) and CgA, WBC and granulocytes tended to show some differences between the two trials (p<0.1). However, blood glucose, lymphocytes, and NK cell activity showed no significant differences between the Kampo and placebo trials. The result suggests that the Kampo should be useful in reducing mental stress.

  15. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill

    2012-11-01

    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  16. Fire Hydrants, Fire hydrants outside the City of Wichita. Primary attributes include hydrant number and ID. Layer is under development by Sedgwick County Fire Department. Primary attributes include GPS status, feature-mapped-to, hydrants ID, address, situs city, mai, Published in 2008, 1:1200 (1in=100ft) scale, Sedgwick County Government.

    Data.gov (United States)

    NSGIC Local Govt | GIS Inventory — Fire Hydrants dataset current as of 2008. Fire hydrants outside the City of Wichita. Primary attributes include hydrant number and ID. Layer is under development by...

  17. Childhood immunization perception and uptake among mothers of ...

    African Journals Online (AJOL)

    Childhood immunization perception and uptake among mothers of under-five children attending immunization clinics in Osogbo, South Western, Nigeria. ... nursing mothers are permitted to take their children for immunization during working hours would go a long way to improve rate of immunization uptake of children.

  18. Clinical presentation, natural history, and cumulative death rates of 230 adults with primary cryptococcal meningitis in Zambian AIDS patients treated under local conditions

    Science.gov (United States)

    Mwaba, P; Mwansa, J; Chintu, C; Pobee, J; Scarborough, M; Portsmouth, S; Zumla, A

    2001-01-01

    SETTING—Inpatient medical wards, Department of Medicine, University Teaching Hospital, Lusaka, Zambia.
OBJECTIVE—To define the natural history, clinical presentation, and management outcome of microbiologically confirmed cryptococcal meningitis in adult AIDS patients treated under local conditions where antifungal and antiretroviral therapies are not routinely available.
DESIGN—A descriptive, longitudinal, observational study.
METHODS—All adult patients admitted to the medical wards of the University Teaching Hospital, Lusaka, Zambia with cerebrospinal fluid culture proved, primary cryptococcal meningitis, during a 12 month period were enrolled into the study. The following details were acquired: clinical features, HIV status, laboratory data, treatment accorded, and survival.
RESULTS—A total of 230 patients with primary cryptococcal meningitis were studied (median age 32 years; range 15-65 years; 112 males, 118 females). Cryptococcal meningitis was the first AIDS defining illness in 210 (91%) patients. One hundred and thirty of the 230 (56%) patients had received treatment with fluconazole monotherapy and 100 (43%) patients received palliative care only without any antifungal therapy. A 100% case fatality rate was observed in both groups at follow up: by seven weeks in the untreated group and at six months in the fluconazole treated group. The cumulative median survival from time of diagnosis was 19 days (range 1-164 days) for the fluconazole treated group and 10 days (range 0-42 days) for the untreated group.
CONCLUSION—Cryptococcal meningitis, under current treatment accorded at the University Teaching Hospital, Lusaka, has a 100% mortality in young Zambian adults with AIDS. The current treatment accorded to Zambian adults with cryptococcal meningitis is inappropriate. An urgent need exists to improve strategies for the clinical management of AIDS patients in poor African countries. The wider ethical and operational issues of

  19. Who is on the primary care team? Professionals' perceptions of the conceptualization of teams and the underlying factors : A mixed-methods study

    NARCIS (Netherlands)

    Doekhie, K.; Buljac, M.; Strating, M.; Paauwe, J.

    2017-01-01

    Background: Due to the growing prevalence of elderly patients with multi-morbidity living at home, there is an increasing need for primary care professionals from different disciplinary backgrounds to collaborate as primary care teams. However, it is unclear how primary care professionals

  20. Who is on the primary care team? Professionals' perceptions of the conceptualization of teams and the underlying factors : A mixed-methods study

    NARCIS (Netherlands)

    K.D. Doekhie (Kirti); M. Buljac-Samardzic (Martina); M.M.H. Strating (Mathilde); J. Paauwe (Jaap)

    2017-01-01

    markdownabstract__Background:__ Due to the growing prevalence of elderly patients with multi-morbidity living at home, there is an increasing need for primary care professionals from different disciplinary backgrounds to collaborate as primary care teams. However, it is unclear how primary care

  1. Who is on the primary care team? Professionals' perceptions of the conceptualization of teams and the underlying factors: A mixed-methods study

    NARCIS (Netherlands)

    Doekhie, K.D. (Kirti D.); M. Buljac-Samardzic (Martina); M.M.H. Strating (Mathilde); J. Paauwe (Jaap)

    2017-01-01

    textabstractBackground: Due to the growing prevalence of elderly patients with multi-morbidity living at home, there is an increasing need for primary care professionals from different disciplinary backgrounds to collaborate as primary care teams. However, it is unclear how primary care

  2. Memorizing innate instructions requires a sufficiently specific adaptive immune system

    NARCIS (Netherlands)

    Borghans, J.A.M.; Boer, R.J. de

    2002-01-01

    During its primary encounter with a pathogen, the immune system has to decide which type of immune response is most appropriate. Based on signals from the innate immune system and the immunological context in which the pathogen is presented, responding lymphocytes will adopt a particular phenotype,

  3. A new single-dose bivalent vaccine of porcine circovirus type 2 and Mycoplasma hyopneumoniae elicits protective immunity and improves growth performance under field conditions.

    Science.gov (United States)

    Jeong, Jiwoon; Park, Changhoon; Choi, Kyuhyung; Chae, Chanhee

    2016-01-15

    The efficacy of the new single-dose bivalent vaccine of porcine circovirus type 2 (PCV2) and Mycoplasma hyopneumoniae was evaluated under field conditions for registration as recommended by the Republic of Korea's Animal, Plant & Fisheries Quarantine & Inspection Agency. Three farms were selected based on their history of co-infection with PCV2 and M. hyopneumoniae. On each farm, a total of 80 3-week-old pigs were randomly allocated to one of two treatment groups: (i) vaccinated (n=40) and (ii) unvaccinated (n=40) animals at 3 weeks of age. Protection by the bivalent vaccine helped increase the market weight by 6.2 kg/pig (106.2 kg in vaccinated group vs. 100 kg in unvaccinated group; Phyopneumoniae-specific IFN-γ-SC. Vaccinated animals displayed a reduced PCV2 load in the blood and M. hyopneumoniae load in nasal swabs compared to unvaccinated animals. Vaccination of pigs against PCV2 and M. hyopneumoniae effectively reduced the lung and lymphoid lesion scores compared to unvaccinated animals in all 3 farms. The new bivalent vaccine is very efficacious in controlling PCV2 and M. hyopneumoniae infection based on clinical, immunological, virological, and pathological evaluations under field conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Placental immune editing switch (PIES): learning about immunomodulatory pathways from a unique case report.

    Science.gov (United States)

    Bronchud, Miguel H; Tresserra, Francesc; Xu, Wenjie; Warren, Sarah; Cusido, Maite; Zantop, Bernat; Zenclussen, Ana Claudia; Cesano, Alessandra

    2016-12-13

    The hypothesis of this work is that, in order to escape the natural immune surveillance mechanisms, cancer cells and the surrounding microenvironment might express ectopically genes that are physiologically present in the placenta to mediate fetal immune-tolerance. These natural "placental immune-editing switch" mechanisms (PIES) may represent the result of millions of years of mammalian evolution developed to allow materno-fetal tolerance. Here, we introduce genes of the immune regulatory pathways that are either similarly over- or under-expressed in tumor vs normal tissue. Our analysis was carried out in primary breast cancer with metastatic homolateral axillary lymph nodes as well as placenta tissue (both uterine decidual tissue and term placenta tissue) from a pregnant woman. Gene expression profiling of paired non-self and self tissues (i.e. placenta/uterus; breast cancer/normal breast tissue; metastatic lymphnode/normal lymphnode tissue) was performed using the PanCancer Immune gene panel, a 770 Nanostring gene expression panel. Our findings reveal overlapping in specific immune gene expression in placenta and cancer tissue, suggesting that these genes might play an important role in maintaining immune tolerance both physiologically (in the placenta) and pathologically (in the cancer setting).

  5. EPIC Studies: Governments Finance, On Average, More Than 50 Percent Of Immunization Expenses, 2010-11.

    Science.gov (United States)

    Brenzel, Logan; Schütte, Carl; Goguadze, Keti; Valdez, Werner; Le Gargasson, Jean-Bernard; Guthrie, Teresa

    2016-02-01

    Governments in resource-poor settings have traditionally relied on external donor support for immunization. Under the Global Vaccine Action Plan, adopted in 2014, countries have committed to mobilizing additional domestic resources for immunization. Data gaps make it difficult to map how well countries have done in spending government resources on immunization to demonstrate greater ownership of programs. This article presents findings of an innovative approach for financial mapping of routine immunization applied in Benin, Ghana, Honduras, Moldova, Uganda, and Zambia. This approach uses modified System of Health Accounts coding to evaluate data collected from national and subnational levels and from donor agencies. We found that government sources accounted for 27-95 percent of routine immunization financing in 2011, with countries that have higher gross national product per capita better able to finance requirements. Most financing is channeled through government agencies and used at the primary care level. Sustainable immunization programs will depend upon whether governments have the fiscal space to allocate additional resources. Ongoing robust analysis of routine immunization should be instituted within the context of total health expenditure tracking. Project HOPE—The People-to-People Health Foundation, Inc.

  6. Placental immune editing switch (PIES): learning about immunomodulatory pathways from a unique case report

    Science.gov (United States)

    Bronchud, Miguel H.; Tresserra, Francesc; Xu, Wenjie; Warren, Sarah; Cusido, Maite; Zantop, Bernat; Zenclussen, Ana Claudia; Cesano, Alessandra

    2016-01-01

    The hypothesis of this work is that, in order to escape the natural immune surveillance mechanisms, cancer cells and the surrounding microenvironment might express ectopically genes that are physiologically present in the placenta to mediate fetal immune-tolerance. These natural “placental immune-editing switch” mechanisms (PIES) may represent the result of millions of years of mammalian evolution developed to allow materno-fetal tolerance. Here, we introduce genes of the immune regulatory pathways that are either similarly over- or under-expressed in tumor vs normal tissue. Our analysis was carried out in primary breast cancer with metastatic homolateral axillary lymph nodes as well as placenta tissue (both uterine decidual tissue and term placenta tissue) from a pregnant woman. Gene expression profiling of paired non-self and self tissues (i.e. placenta/uterus; breast cancer/normal breast tissue; metastatic lymphnode/normal lymphnode tissue) was performed using the PanCancer Immune gene panel, a 770 Nanostring gene expression panel. Our findings reveal overlapping in specific immune gene expression in placenta and cancer tissue, suggesting that these genes might play an important role in maintaining immune tolerance both physiologically (in the placenta) and pathologically (in the cancer setting). PMID:27852037

  7. Interactions between adipose tissue and the immune system in health and malnutrition.

    Science.gov (United States)

    Wensveen, Felix M; Valentić, Sonja; Šestan, Marko; Wensveen, Tamara Turk; Polić, Bojan

    2015-09-01

    Adipose tissue provides the body with a storage depot of nutrients that is drained during times of starvation and replenished when food sources are abundant. As such, it is the primary sensor for nutrient availability in the milieu of an organism, which it communicates to the body through the excretion of hormones. Adipose tissue regulates a multitude of body functions associated with metabolism, such as gluconeogenesis, feeding and nutrient uptake. The immune system forms a vital layer of protection against micro-organisms that try to gain access to the nutrients contained in the body. Because infections need to be resolved as quickly as possible, speed is favored over energy-efficiency in an immune response. Especially when immune cells are activated, they switch to fast, but energy-inefficient anaerobic respiration to fulfill their energetic needs. Despite the necessity for an effective immune system, it is not given free rein in its energy expenditure. Signals derived from adipose tissue limit immune cell numbers and activity under conditions of nutrient shortage, whereas they allow proper immune cell activity when food sources are sufficiently available. When excessive fat accumulation occurs, such as in diet-induced obesity, adipose tissue becomes the site of pathological immune cell activation, causing chronic low-grade systemic inflammation. Obesity is therefore associated with a number of disorders in which the immune system plays a central role, such as atherosclerosis and non-alcoholic steatohepatitis. In this review, we will discuss the way in which adipose tissue regulates activity of the immune system under healthy and pathological conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Dynamics of immune system vulnerabilities

    Science.gov (United States)

    Stromberg, Sean P.

    The adaptive immune system can be viewed as a complex system, which adapts, over time, to reflect the history of infections experienced by the organism. Understanding its operation requires viewing it in terms of tradeoffs under constraints and evolutionary history. It typically displays "robust, yet fragile" behavior, meaning common tasks are robust to small changes but novel threats or changes in environment can have dire consequences. In this dissertation we use mechanistic models to study several biological processes: the immune response, the homeostasis of cells in the lymphatic system, and the process that normally prevents autoreactive cells from entering the lymphatic system. Using these models we then study the effects of these processes interacting. We show that the mechanisms that regulate the numbers of cells in the immune system, in conjunction with the immune response, can act to suppress autoreactive cells from proliferating, thus showing quantitatively how pathogenic infections can suppress autoimmune disease. We also show that over long periods of time this same effect can thin the repertoire of cells that defend against novel threats, leading to an age correlated vulnerability. This vulnerability is shown to be a consequence of system dynamics, not due to degradation of immune system components with age. Finally, modeling a specific tolerance mechanism that normally prevents autoimmune disease, in conjunction with models of the immune response and homeostasis we look at the consequences of the immune system mistakenly incorporating pathogenic molecules into its tolerizing mechanisms. The signature of this dynamic matches closely that of the dengue virus system.

  9. Inflammatory Bowel Disease in Primary Immunodeficiencies.

    Science.gov (United States)

    Kelsen, Judith R; Sullivan, Kathleen E

    2017-08-01

    Inflammatory bowel disease is most often a polygenic disorder with contributions from the intestinal microbiome, defects in barrier function, and dysregulated host responses to microbial stimulation. There is, however, increasing recognition of single gene defects that underlie a subset of patients with inflammatory bowel disease, particularly those with early-onset disease, and this review focuses on the primary immunodeficiencies associated with early-onset inflammatory bowel disease. The advent of next-generation sequencing has led to an improved recognition of single gene defects underlying some cases of inflammatory bowel disease. Among single gene defects, immune response genes are the most frequent category identified. This is also true of common genetic variants associated with inflammatory bowel disease, supporting a pivotal role for host responses in the pathogenesis. This review focuses on practical aspects related to diagnosis and management of children with inflammatory bowel disease who have underlying primary immunodeficiencies.

  10. Increasing immunization coverage.

    Science.gov (United States)

    Hammer, Lawrence D; Curry, Edward S; Harlor, Allen D; Laughlin, James J; Leeds, Andrea J; Lessin, Herschel R; Rodgers, Chadwick T; Granado-Villar, Deise C; Brown, Jeffrey M; Cotton, William H; Gaines, Beverly Marie Madry; Gambon, Thresia B; Gitterman, Benjamin A; Gorski, Peter A; Kraft, Colleen A; Marino, Ronald Vincent; Paz-Soldan, Gonzalo J; Zind, Barbara

    2010-06-01

    In 1977, the American Academy of Pediatrics issued a statement calling for universal immunization of all children for whom vaccines are not contraindicated. In 1995, the policy statement "Implementation of the Immunization Policy" was published by the American Academy of Pediatrics, followed in 2003 with publication of the first version of this statement, "Increasing Immunization Coverage." Since 2003, there have continued to be improvements in immunization coverage, with progress toward meeting the goals set forth in Healthy People 2010. Data from the 2007 National Immunization Survey showed that 90% of children 19 to 35 months of age have received recommended doses of each of the following vaccines: inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella-zoster virus (VZB), hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib). For diphtheria and tetanus and acellular pertussis (DTaP) vaccine, 84.5% have received the recommended 4 doses by 35 months of age. Nevertheless, the Healthy People 2010 goal of at least 80% coverage for the full series (at least 4 doses of DTaP, 3 doses of IPV, 1 dose of MMR, 3 doses of Hib, 3 doses of HBV, and 1 dose of varicella-zoster virus vaccine) has not yet been met, and immunization coverage of adolescents continues to lag behind the goals set forth in Healthy People 2010. Despite these encouraging data, a vast number of new challenges that threaten continued success toward the goal of universal immunization coverage have emerged. These challenges include an increase in new vaccines and new vaccine combinations as well as a significant number of vaccines currently under development; a dramatic increase in the acquisition cost of vaccines, coupled with a lack of adequate payment to practitioners to buy and administer vaccines; unanticipated manufacturing and delivery problems that have caused significant shortages of various vaccine products; and the rise of a public antivaccination movement that uses the

  11. Effect of immunization against ox-LDL with two different antigens on formation and development of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Saberi Salb-Ali

    2007-11-01

    Full Text Available Abstract Background Several studies were pointed to oxidized LDL (ox-LDL as one of the main immunogenes which have important roles in primary lesions of atherosclerosis. In this study, by immunization against ox-LDL with two different antigens in an animal model (rabbit and consideration of its effect on two different dietary regimens; we tried to clear relation between immune system and atherosclerosis. Methods LDL was isolated from hypercholesterolemic rabbits plasma and oxidized with MDA or Cu++. Rabbits were divided to three groups and immunized with MDA-LDL or Cu-LDL or phosphate-buffer (PBS as a control group. Immunization was repeated after 2, 4, 6, and 8 weeks and concentration of antibodies against ox-LDL was measured in each stage. After immunization, rabbits in each group were divided to two subgroups based on the dietary regimen (fed normal or high cholesterol diet. At the beginning and the end of the study, biochemical factors were measured. Also, fatty streaks in aorta and left and right coronary arteries evaluated. Results Immunization with Cu2+-LDL and MDA-LDL induced statistically significant antibodies against ox-LDL. In hypercholesterolemic rabbits immunized with MDA-LDL the level of cholesterol, LDL-cholesterol, triglyceride, fasting blood sugar and fatty streak lesions in aorta and right coronary arteries were significantly decreased as compared with non-immunized high-cholesterol group. Immunization with Cu2+-LDL in hypercholesterolemic rabbits significantly decreased triglyceride, fasting blood sugar, cholesterol and CRP. No significant differences were detected in the fatty streak lesions in this group as compared with non-immunized high-cholesterol diet. In groups under normal diet immunized with MDA-LDL or Cu2+-LDL no significant effect on biochemical factors and atherosclerotic lesions were observed. Conclusion This study indicates that although the effect of produced antibodies in several methods and different dietary

  12. Mexico's immunization programme gets results.

    Science.gov (United States)

    1994-04-01

    With a decline of almost 60% over the past decade in the mortality of children under age 5 years old to the current rate of 33 child deaths/1000 live births, Mexico has joined the 20 countries listed by UNICEF as making the most progress in reducing child mortality since 1980. Much of this progress can be attributed to Mexico's immunization program, which has brought the proportion of fully immunized children under age 5 years to 94% over the past 5 years. Mexico's president has been instrumental in the program's success, having a personal interest in childhood vaccination and supervising the twice-yearly immunization coverage surveys. Even though presidential elections are being held this year, the immunization program should remain strong regardless of who wins because all of Mexico's political parties have pledged to remain committed to immunization. Awareness in the population about the need for vaccination is maintained with the help of the mass media, especially radio and television. The country's enthusiasm for vaccination seems to be paying off in terms of declining child mortality and the eradication of wild poliovirus. The immunization program reaches all but 2-3% of Mexico's children, despite some logistical difficulties and resistance to vaccines among certain religious groups such as the Mennonites and Jehovah's witnesses.

  13. Transcriptome Analysis of Gene Expression Provides New Insights into the Effect of Mild Therapeutic Hypothermia on Primary Human Cortical Astrocytes Cultured under Hypoxia.

    Science.gov (United States)

    Salman, Mootaz M; Kitchen, Philip; Woodroofe, M Nicola; Bill, Roslyn M; Conner, Alex C; Heath, Paul R; Conner, Matthew T

    2017-01-01

    Hypothermia is increasingly used as a therapeutic measure to treat brain injury. However, the cellular mechanisms underpinning its actions are complex and are not yet fully elucidated. Astrocytes are the most abundant cell type in the brain and are likely to play a critical role. In this study, transcriptional changes and the protein expression profile of human primary cortical astrocytes cultured under hypoxic conditions for 6 h were investigated. Cells were treated either with or without a mild hypothermic intervention 2 h post-insult to mimic the treatment of patients following traumatic brain injury (TBI) and/or stroke. Using human gene expression microarrays, 411 differentially expressed genes were identified following hypothermic treatment of astrocytes following a 2 h hypoxic insult. KEGG pathway analysis indicated that these genes were mainly enriched in the Wnt and p53 signaling pathways, which were inhibited following hypothermic intervention. The expression levels of 168 genes involved in Wnt signaling were validated by quantitative real-time-PCR (qPCR). Among these genes, 10 were up-regulated and 32 were down-regulated with the remainder unchanged. Two of the differentially expressed genes (DEGs), p38 and JNK, were selected for validation at the protein level using cell based ELISA. Hypothermic intervention significantly down-regulated total protein levels for the gene products of p38 and JNK. Moreover, hypothermia significantly up-regulated the phosphorylated (activated) forms of JNK protein, while downregulating phosphorylation of p38 protein. Within the p53 signaling pathway, 35 human apoptosis-related proteins closely associated with Wnt signaling were investigated using a Proteome Profiling Array. Hypothermic intervention significantly down-regulated 18 proteins, while upregulating one protein, survivin. Hypothermia is a complex intervention; this study provides the first detailed longitudinal investigation at the transcript and protein expression

  14. Transcriptome Analysis of Gene Expression Provides New Insights into the Effect of Mild Therapeutic Hypothermia on Primary Human Cortical Astrocytes Cultured under Hypoxia

    Directory of Open Access Journals (Sweden)

    Mootaz M. Salman

    2017-12-01

    Full Text Available Hypothermia is increasingly used as a therapeutic measure to treat brain injury. However, the cellular mechanisms underpinning its actions are complex and are not yet fully elucidated. Astrocytes are the most abundant cell type in the brain and are likely to play a critical role. In this study, transcriptional changes and the protein expression profile of human primary cortical astrocytes cultured under hypoxic conditions for 6 h were investigated. Cells were treated either with or without a mild hypothermic intervention 2 h post-insult to mimic the treatment of patients following traumatic brain injury (TBI and/or stroke. Using human gene expression microarrays, 411 differentially expressed genes were identified following hypothermic treatment of astrocytes following a 2 h hypoxic insult. KEGG pathway analysis indicated that these genes were mainly enriched in the Wnt and p53 signaling pathways, which were inhibited following hypothermic intervention. The expression levels of 168 genes involved in Wnt signaling were validated by quantitative real-time-PCR (qPCR. Among these genes, 10 were up-regulated and 32 were down-regulated with the remainder unchanged. Two of the differentially expressed genes (DEGs, p38 and JNK, were selected for validation at the protein level using cell based ELISA. Hypothermic intervention significantly down-regulated total protein levels for the gene products of p38 and JNK. Moreover, hypothermia significantly up-regulated the phosphorylated (activated forms of JNK protein, while downregulating phosphorylation of p38 protein. Within the p53 signaling pathway, 35 human apoptosis-related proteins closely associated with Wnt signaling were investigated using a Proteome Profiling Array. Hypothermic intervention significantly down-regulated 18 proteins, while upregulating one protein, survivin. Hypothermia is a complex intervention; this study provides the first detailed longitudinal investigation at the transcript and

  15. Perceptions of overweight by primary carers (mothers/grandmothers) of under five and elementary school-aged children in Bandung, Indonesia: a qualitative study.

    Science.gov (United States)

    Rachmi, Cut Novianti; Hunter, Cynthia Louise; Li, Mu; Baur, Louise Alison

    2017-07-27

    The prevalence of childhood overweight has increased in the past two decades in Indonesia. Even though prevalence is escalating, there is a lack of qualitative evidence to assist in the design and implementation of strategies to tackle this issue. This study aimed to explore the view of primary carers (mothers and grandmothers) from different socio-economic-status groups, on childhood overweight in the Greater Bandung Area, Indonesia. We conducted 12 focus groups discussions with a total of 94 carers of under-five and 7-12 years children, from June to October 2016. We used the grounded theory approach in our analysis. Three main categories emerged: the concept of overweight, factors contributing to overweight, and awareness and feelings towards overweight children. Most carers from all SES groups defined overweight subjectively, while a few from the low SES group defined it objectively. Most carers from low and high SES groups agreed with the concept "chubbier is healthier". All carers had some knowledge of the main factors that contribute to childhood overweight: dietary factors, activity levels and sedentary behavior, and hereditary factors. Carers from all SES groups described similar characteristics of overweight; carers from low and intermediate SES groups had mixed feelings while all high SES carers have negative feelings about overweight children, mostly related to stigma. However, carers who identified their own children as being overweight expressed sensitivity about this weight status, especially their physical abilities. Almost all carers knew their children's current weight while less than two thirds knew their children's height. There are several policy implications. Firstly, health-related knowledge of the primary carers is of great importance and needs augmenting. To increase that knowledge, there is a role for front-line health practitioners (doctors/midwives/nurses) to be more active in educating the community. Secondly, simpler and more effective

  16. Terapia hipolipemiante em situações especiais: síndrome de imunodeficiência adquirida Hypolipidemic therapy under special conditions: acquired immune deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Pai Ching Yu

    2005-10-01

    expectancy and reports of cardiovascular complications in these individuals. There is an insulin resistance state in patients with AIDS disease under treatment with HAART, who present with lypodistrophy, hypertriglyceridemia, low levels of HDL-C. Antiretroviral drugs are metabolized by CYP P450 3A4 and interactions with some statins, especially with simvastatin are expected to occur. Treatment with lipid-lowering agents should be based on lipid profile and coronary risk. For hypertriglyceridemias, fibrates (mainly fenofibrate or bezafibrate should be the drugs of choice, as well as statins (mainly pravastatin. Combined treatment using fibrates plus statins are recommended for severe mixed hyperlipidemias under very close monitoring for adverse effects.

  17. Immunization Schedules for Adults

    Science.gov (United States)

    ... ACIP Vaccination Recommendations Why Immunize? Vaccines: The Basics Immunization Schedule for Adults (19 Years of Age and ... diseases that can be prevented by vaccines . 2018 Immunization Schedule Recommended Vaccinations for Adults by Age and ...

  18. Instant Childhood Immunization Schedule

    Science.gov (United States)

    ... Recommendations Why Immunize? Vaccines: The Basics Instant Childhood Immunization Schedule Recommend on Facebook Tweet Share Compartir Get ... date. See Disclaimer for additional details. Based on Immunization Schedule for Children 0 through 6 Years of ...

  19. Immunizations and African Americans

    Science.gov (United States)

    ... Data > Minority Population Profiles > Black/African American > Immunizations Immunizations and African Americans African American adults are less ... 19 to 35 months had comparable rates of immunization. African American women are as likely to have ...

  20. Immune System Quiz

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! Partner Message ...

  1. Effect of different levels of vitamin C and L-carnitine on performance and some blood and immune parameters of broilers under heat stress.

    Directory of Open Access Journals (Sweden)

    Saeed Mirzapor Sarab

    2016-08-01

    Full Text Available Introduction: High Environmental temperature during summer months which leading to heat stress, is of great concern in all types of poultry production. Feed consumption, growth rate, hatchability, mortality, and other important traits governing the prosperity of the industry are adversely affected by severe heat stress. Literature suggests that the advantages of dietary L-carnitine and ascorbic acid have been particularly apparent under heat stress (8. L- carnitine is a zwitterionic compound synthesized in vivo from lysine and methonine, and is essential for the transport of long – chain fatty acid across the inner mitochondria membrane for β – oxidation and remove toxic accumulations of fatty acids from mitochondria (18. Vitamin C is an effective antioxidant, which is essential for collagen synthesis, helps to maintain various enzymes in their required reduced form, and participates in the biosynthesis of carnitine, norepinephrine and certain neuroendocrine peptides (11. Invertebrates, insects, most fishes, some birds, guinea-pigs, bats and primates are not able to synthesize ascorbic acid. Thus, these animals must depend upon a dietary supply of this vitamin C. In poultry, ascorbic acid has been demonstrated to be essential for growth (25. Materials and Methods: In this study, 396 of Ross 308 broiler chicks in a completely randomized design with 3 × 3 factorial arrangement with 4 replicates of 11 chicks in each replicate were used for 42 days. Treatments were 3 levels of vitamin C (0, 250 and 500 mg/ kg and 3 levels of L-carnitine (0, 50 and 100 mg kg. In the first 3 weeks of breeding, broilers were under normal temperature and heat stress was done from the beginning of forth week. Feed and water were provided ad-libitum. Performance parameters were recorded weekly. The 0.5 mL suspension of 5% SRBC was injected at 28 and 35 days of age in one bird of each pen. To determine the antibody titer, blood was collected 1 week after each

  2. Effective Nutrition Intervention to Treat Children Under 5 Years Old Suffering MAM in Public Primary Health Care Services in El Salvador

    International Nuclear Information System (INIS)

    Sanchez, Ana

    2014-01-01

    Full text: Background: In El Salvador Moderate Acute Malnutrition (MAM) affects less than 1% of children under 5 years old. The importance of MAM has been neglected as a public health issue. Although moderate wasting is not a condition of medical urgency, it can easily deteriorate. If some of these undernourished children with moderate wasting do not receive adequate support, they may progress towards severe acute malnutrition (SAM), defined by the presence of severe wasting and/or bilateral pitting oedema, which is a life-threatening condition. Since 2010, a complementary feeding program for children from 6 to 59 months old was implemented at the primary health clinics for the management of moderate malnutrition. Program was implemented in 100 municipalities identified with the greatest levels of poverty at national level and it consists of a corn-soy fortified flour to be prepared at home as a poudrige given to children during the routine health controls. During the first months of program implementation, an acceptability test was conducted and it was determined that more than 85% of children had good acceptance of the product. The treatment consists of 45 grams per day of complementary food. Mothers were instructed on how to prepare the product and every month they would have to bring their children to the clinic to receive complementary food and control weight gain. If mothers did not attend the control, a health promotion worker would go visit the mother at their home and bring the complementary food to the child. Objective: Assess the results on nutritional status of children under 5 years old with MAM treated with complementary food during health controls at primary health facilities in El Salvador during January to October 2013. Methods: Transversal study. Inclusion criteria was children 6 to 59 months old attending health controls coming from prioritize municipalities, diagnose with MAM by a health professional without other disease or infections that

  3. Defensins in innate immunity.

    Science.gov (United States)

    Zhao, Le; Lu, Wuyuan

    2014-01-01

    Defensins are a major family of antimicrobial peptides expressed predominantly in neutrophils and epithelial cells, and play important roles in innate immune defense against infectious pathogens. Their biological functions in and beyond innate immunity, structure and activity relationships, mechanisms of action, and therapeutic potential continue to be interesting research topics. This review examines recent progress in our understanding of alpha and theta-defensins - the two structural classes composed of members of myeloid origin. A novel mode of antibacterial action is described for human enteric alpha-defensin 6, which forms structured nanonets to entrap bacterial pathogens and protect against bacterial invasion of the intestinal epithelium. The functional multiplicity and mechanistic complexity of defensins under different experimental conditions contribute to a debate over the role of enteric alpha-defensins in mucosal immunity against HIV-1 infection. Contrary to common belief, hydrophobicity rather than cationicity plays a dominant functional role in the action of human alpha-defensins; hydrophobicity-mediated high-order assembly endows human alpha-defensins with an extraordinary ability to acquire structural diversity and functional versatility. Growing evidence suggests that theta-defensins offer the best opportunity for therapeutic development as a novel class of broadly active anti-infective and anti-inflammatory agents. Defensins are the 'Swiss army knife' in innate immunity against microbial pathogens. Their modes of action are often reminiscent of the story of 'The Blind Men and the Elephant'. The functional diversity and mechanistic complexity, as well as therapeutic potential of defensins, will continue to attract attention to this important family of antimicrobial peptides.

  4. Primary sclerosing cholangitis

    Directory of Open Access Journals (Sweden)

    Marina G Silveira

    2008-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a ‘beaded’ appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC.

  5. Immune system and melanoma biology: a balance between immunosurveillance and immune escape.

    Science.gov (United States)

    Passarelli, Anna; Mannavola, Francesco; Stucci, Luigia Stefania; Tucci, Marco; Silvestris, Francesco

    2017-12-01

    Melanoma is one of the most immunogenic tumors and its relationship with host immune system is currently under investigation. Many immunomodulatory mechanisms, favoring melanomagenesis and progression, have been described to interfere with the disablement of melanoma recognition and attack by immune cells resulting in immune resistance and immunosuppression. This knowledge produced therapeutic advantages, such as immunotherapy, aiming to overcome the immune evasion. Here, we review the current advances in cancer immunoediting and focus on melanoma immunology, which involves a dynamic interplay between melanoma and immune system, as well as on effects of "targeted therapies" on tumor microenvironment for combination strategies.

  6. Psoriasis, innate immunity, and gene pools

    NARCIS (Netherlands)

    Bos, Jan D.

    2007-01-01

    Recently, emphasis has shifted from T cells to innate (natural) immunity as the possible major culprit in psoriasis. All known elements of innate immune responses are up-regulated in psoriasis lesions, which must have a polygenetic origin. We hypothesize that urbanized populations have been under

  7. The Immune System and Bodily Defence

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 9. The Immune System and Bodily Defence How Does the Immune System Recognize Everything Under the Sun? Vineeta Bal Satyajit Rath. Series Article Volume 2 Issue 9 September 1997 pp 6-10 ...

  8. The Immune System and Bodily Defence

    Indian Academy of Sciences (India)

    The Immune System and Bodily Defence. 4.How Does the Immune System Recognize Everything Under the Sun? ... A major exception to this is, of course, the fairly recent innovation in biology called Homo sapiens that ... To do all this, first it is necessary to break the receptor down to its basic functional elements, so that the ...

  9. Immune System (For Parents)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Immune System KidsHealth / For Parents / Immune System What's in this ... can lead to illness and infection. About the Immune System The immune system is the body's defense against ...

  10. National Network for Immunization Information

    Science.gov (United States)

    ... everyone who needs to know the facts about immunization. NNii believes that immunization is one of the most important ways to ... published... What's New for 2002? The Recommended Childhood Immunization Schedule Download the 2002 Recommended Childhood Immunization... Immunization ...

  11. [Immune proteasomes in the development of rat immune system].

    Science.gov (United States)

    Karpova, Ia D; Lyupina, Iu V; Astakhova, T M; Stepanova, A A; Erokhov, P A; Abramova, E B; Sharova, N P

    2013-01-01

    their plunge by P5 may be related to the loss of liver function of a primary lymphoid organ of the immune system by this stage and disappearance of B-lymphocytes enriched by immune proteasomes in it. In the spleen and liver, MHC class I molecules were revealed at the periods of the raise of proteasome immune subunits level. On E21 , the liver was enriched by neuronal NO-synthase, its level decreased after birth and enhanced to P18. This fact indicates the possibility of the induction of the immune subunits LMP7 [character: see text] LMP2 expression in hepatocytes in signal way with neuronal NO-synthase participation. The results obtained prove that T-cell immune response with spleen participation as regards rat liver cells is possible starting with P19-P21 stage. First, at this period, white pulp T-area is formed in the spleen. Second, enhanced immune proteasomes and MHC class I molecules levels in hepatocytes can procure antigenic epitopes formation from foreign proteins and their delivery to cell surface for their subsequent presentation for cytotoxic T-lymphocytes.

  12. Reasons for non-immunization of children in an urban, low income group in North India.

    Science.gov (United States)

    Mathew, Joseph L; Babbar, Harsh; Yadav, Sangita

    2002-07-01

    A study was undertaken on 500 children under the age of 5 years belonging to a low income group. All were attending the paediatrics outpatient department of a large teaching hospital in New Delhi, India. Only 25% were found to have received complete primary immunization as per the National Immunization Schedule (bacille Calmette-Guérin at birth, three doses of diphtheria, pertussis and tetanus and oral poliovirus vaccine at 6,10 and 14 weeks and measles vaccine at 9 months). The major reasons for non-immunization of the children were: migration to a native village (26.4%); domestic problems (9.6%); the immunization centre was located too far from their home (9.6%); and the child was unwell when the vaccination was due (9%). Twelve per cent of mothers could not give any reason for non-immunization. In addition to the migration of children to rural areas, the other significant finding was an indirect effect of intensive OPV administration as part of polio eradication initiative. The lack of awareness and fear of side effects constituted a small minority of reasons for non-immunization.

  13. Immune Responses to Dengue and Zika Viruses—Guidance for T Cell Vaccine Development

    Directory of Open Access Journals (Sweden)

    Claude Roth

    2018-02-01

    Full Text Available Despite numerous efforts to identify the molecular and cellular effectors of the adaptive immunity that induce a long-lasting immunity against dengue or Zika virus infection, the specific mechanisms underlying such protective immunity remain largely unknown. One of the major challenges lies in the high level of dengue virus (DENV seroprevalence in areas where Zika virus (ZIKV is circulating. In the context of such a pre-existing DENV immunity that can exacerbate ZIKV infection and disease, and given the lack of appropriate treatment for ZIKV infection, there is an urgent need to develop an efficient vaccine against DENV and ZIKV. Notably, whereas several ZIKV vaccine candidates are currently in clinical trials, all these vaccine candidates have been designed to induce neutralizing antibodies as the primary mechanism of immune protection. Given the difficulty to elicit simultaneously high levels of neutralizing antibodies against the different DENV serotypes, and the potential impact of pre-existing subneutralizing antibodies induced upon DENV infection or vaccination on ZIKV infection and disease, additional or alternative strategies to enhance vaccine efficacy, through T cell immunity, are now being considered. In this review, we summarize recent discoveries about cross-reactive B and T cell responses against DENV and ZIKV and propose guidelines for the development of safe and efficient T cell vaccines targeting both viruses.

  14. Immune Regulation by Self-Recognition

    DEFF Research Database (Denmark)

    Andersen, Mads Hald

    2015-01-01

    Circulating T cells that specifically target normal self-proteins expressed by regulatory immune cells were first described in patients with cancer, but can also be detected in healthy individuals. The adaptive immune system is distinguished for its ability to differentiate between self...... reactions. This suggests that they may be involved in immune homeostasis. It is here proposed that these T cells should be termed antiregulatory T cells (anti-Tregs). The role of anti-Tregs in immune-regulatory networks may be diverse. For example, pro-inflammatory self-reactive T cells that react...... to regulatory immune cells may enhance local inflammation and inhibit local immune suppression. Further exploration is warranted to investigate their potential role under different malignant conditions and the therapeutic possibilities they possess. Utilizing anti-Tregs for anticancer immunotherapy implies...

  15. Distinct mechanisms of the newborn innate immunity.

    Science.gov (United States)

    Kumar, S Kingsley Manoj; Bhat, B Vishnu

    2016-05-01

    The ontogeny of immunity during early life is of high importance as it shapes the immune system for the entire course of life. The microbiome and the environment contribute to the development of immunity in newborns. As immune responses in newborns are predominantly less experienced they are increasingly susceptible to infections. Though the immune cells in newborns are in 'naïve' state, they have been shown to mount adult-like responses in several circumstances. The innate immunity plays a vital role in providing protection during the neonatal period. Various stimulants have been shown to enhance the potential and functioning of the innate immune cells in newborns. They are biased against the production of pro-inflammatory cytokines and this makes them susceptible to wide variety of intracellular pathogens. The adaptive immunity requires prior antigenic experience which is very limited in newborns. This review discusses in detail the characteristics of innate immunity in newborns and the underlying developmental and functional mechanisms involved in the immune response. A better understanding of the immunological milieu in newborns could help the medical fraternity to find novel methods for prevention and treatment of infection in newborns. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  16. The unresponsiveness of the immune system of the rat to hypergravity

    Science.gov (United States)

    Scibetta, S. M.; Caren, L. D.; Oyama, J.

    1984-01-01

    The immune response in rats exposed to simulated hypergravity (2.1 G and 3.1 G) by chronic centrifugation was assessed. Rats were immunized with sheep red blood cells (SRBC), either on the day of initial exposure to hypergravity (hyper-G), or after being centrifuged for 28 d and remaining on the centrifuge thereafter. Pair-fed and ad libitum fed noncentrifuged controls were used. Although there were some alterations in leukocyte counts, hyper-G did not systematically affect the primary or secondary anti-SRBC response, hematocrits, or the sizes of the liver, spleen, kidneys, thymus, or adrenal glands. The immune system is thus remarkably homeostatic under hypergravity conditions which do affect other physiologic parameters.

  17. Etiopathogenesis of primary sclerosing cholangitis

    OpenAIRE

    Chapman, Roger; Cullen, Sue

    2008-01-01

    Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease of unknown etiology but lymphocytic portal tract infiltration is suggestive of an immune-mediated basis for this disease. Associations with inflammatory bowel disease (IBD) especially ulcerative colitis (UC), and with particular autoimmune diseases, as well as the genetic associations further suggest PSC may be an immune-mediated disease. The immunogenetics of PSC have been the subject of active research and several H...

  18. Adiponectin: a versatile player of innate immunity.

    Science.gov (United States)

    Luo, Yan; Liu, Meilian

    2016-04-01

    Adiponectin acts as a key regulator of the innate immune system and plays a major role in the progression of inflammation and metabolic disorders. Macrophages and monocytes are representative components of the innate immune system, and their proliferation, plasticity, and polarization are a key component of metabolic adaption. Innate-like lymphocytes such as group 2 innate lymphoid cells (ILC2s), natural killer T (NKT) cells, and gamma delta T (γδ T) cells are also members of the innate immune system and play important roles in the development of obesity and its related diseases. Adiponectin senses metabolic stress and modulates metabolic adaption by targeting the innate immune system under physiological and pathological conditions. Defining the mechanisms underlying the role of adiponectin in regulating innate immunity is crucial to adiponectin-based therapeutic intervention. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  19. COMMUNITY HEALTH & PRIMARY HEALTH CARE

    African Journals Online (AJOL)

    the_monk

    Background and Objectives: Vaccine preventable diseases cause significant morbidity and mortality among children in developing countries despite the availability of vaccines. This study determined childhood immunization uptake and associated factors among mothers of under- fives in Kosofe, Lagos State. Methodology:.

  20. No compensatory relationship between the innate and adaptive immune system in wild-living European badgers

    NARCIS (Netherlands)

    Sin, Yung Wa; Newman, Chris; Dugdale, Hannah L.; Buesching, Christina; Mannarelli, Maria Elena; Annavi, Geetha; Burke, Terry; MacDonald, David W.

    2016-01-01

    The innate immune system provides the primary vertebrate defence system against pathogen invasion, but it is energetically costly and can have immune pathological effects. A previous study in sticklebacks found that intermediate major histocompatibility complex (MHC) diversity correlated with a

  1. Probiotics as an Immune Modulator.

    Science.gov (United States)

    Kang, Hye-Ji; Im, Sin-Hyeog

    2015-01-01

    Probiotics are nonpathogenic live microorganism that can provide a diverse health benefits on the host when consumed in adequate amounts. Probiotics are consumed in diverse ways including dairy product, food supplements and functional foods with specific health claims. Recently, many reports suggest that certain probiotic strains or multi strain mixture have potent immunomodulatory activity in diverse disorders including allergic asthma, atopic dermatitis and rheumatoid arthritis. However, underlying mechanism of action is still unclear and efficacy of probiotic administration is quite different depending on the type of strains and the amounts of doses. We and others have suggested that live probiotics or their metabolites could interact with diverse immune cells (antigen presenting cells and T cells) and confer them to have immunoregulatory functions. Through this interaction, probiotics could contribute to maintaining immune homeostasis by balancing pro-inflammatory and anti-inflammatory immune responses. However, the effect of probiotics in prevention or modulation of ongoing disease is quite diverse even within a same species. Therefore, identification of functional probiotics with specific immune regulatory property is a certainly important issue. Herein, we briefly review selection methods for immunomodulatory probiotic strains and the mechanism of action of probiotics in immune modulation.

  2. Targeting Immune Cell Checkpoints during Sepsis

    Directory of Open Access Journals (Sweden)

    Naeem K. Patil

    2017-11-01

    Full Text Available Immunosuppression is increasingly being recognized as one of the causes of increased morbidity and mortality during sepsis. Both innate and adaptive immune system dysfunction have been shown to cause an impaired ability to eradicate the primary infection and also lead to frequent occurrence of secondary opportunistic infections. Pre-clinical and clinical studies have shown that inhibitory immune checkpoint molecules, including programmed death-1 (PD-1, programmed death ligand-1 (PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4, T cell membrane protein-3 (TIM-3, Lymphocyte activation-gene-3 (LAG-3 and 2B4, are upregulated during the course of sepsis. Engagement of these inhibitory molecules on various immune cells has been consistently shown to inhibit innate immune cell functions (e.g., phagocytosis, cytokine production and pathogen clearance and also lead to impaired T cell competence. In numerous pre-clinical models of sepsis, therapeutic agents aimed at blocking engagement of inhibitory immune checkpoints on immune cells have been shown to improve innate and adaptive immune cell functions, increase host resistance to infection and significantly improve survival. Therefore, immunotherapy with immune cell checkpoint inhibitors holds significant potential for the future of sepsis therapy and merits further investigation.

  3. Assessing Effect of Manure and Chemical Fertilizer on Net Primary Production, Soil Respiration and Carbon Budget in Winter Wheat (Triticum aestivum L. Ecosystem under Mashhad Climatic Condition

    Directory of Open Access Journals (Sweden)

    Y alizade

    2018-02-01

    Full Text Available Introduction The imbalance between anthropogenic emissions of CO2 and the sequestration of CO2 from the atmosphere by ecosystems has led to an increase in the average concentration of this greenhouse gas (GHG in the atmosphere. Enhancing carbon sequestration in soil is an important issue to reduce net flux of carbon dioxide to the atmosphere. Soil organic carbon content is obtained from the difference between carbon input resulting from plant biomass and carbon losses the soil through different ways including soil respiration. CO2 emission varies largely during the year and is considerably affected by management type. The goal of this investigation was to study the effects of application of manure and chemical fertilizer on CO2 flux and carbon balance in agricultural system. Materials and Methods In order to evaluate the carbon dynamics and effect of fertilizer and manure management on soil respiration and carbon budget for winter wheat, an experiment was conducted as a randomized complete block design with three replications in research field of Faculty of Agriculture of Ferdowsi University of Mashhad for two years of 2010-2011 and 2011-2012 . The experimental treatments were 150 and 250 kg chemical nitrogen (N1 and N2, manure (M, manure plus chemical nitrogen (F-M and control (C. CO2 emission was measured six times during growth season and to minimize daily temperature variation error, the measurement was performed between 8 to 11 am. Chambers length and diameter were 50 cm and 30 cm respectively and their edges were held down 3 cm in soil in time of sampling so that no plant live mass was present in the chamber. Carbon budgets were estimated for two years using an ecological technique. Results and Discussion The net primary production (NPP was significantly higher in the F2 and F-M treatments with 6467 and 6294kg ha-1 in the first year and 6260 and 6410 kg ha-1 in the second year, respectively. The highest shoot to root ratio was obtained in

  4. Patients' acceptance of traditional and nontraditional immunization providers.

    Science.gov (United States)

    Ernst, M E; Bergus, G R; Sorofman, B A

    2001-01-01

    To examine patients' acceptance and reported use of traditional and nontraditional immunization providers and settings. Survey. Stratified sample of private family physician clinics, family medicine residency training programs, community pharmacies that provide immunizations under standing order protocols, and nonimmunizing community pharmacies, all located in Iowa. Individuals presenting for medical care or pharmacy services. Not applicable. Sources of past immunizations, 'access to immunizations, importance of immunization records, and future use of different health care providers and settings for immunizations. Univariate and multivariate analyses were performed to examine the relationships between patient demographics and recruitment site on the question responses. 420 surveys were returned (67% response rate). Respondents frequently received immunizations at sites other than physician offices. Younger patients and those living in smaller towns were more likely to report receiving an immunization from a nonphysician. Patients recruited in immunizing pharmacies more often reported previous immunization by a pharmacist (P < .001), most often for influenza. Respondents often reported that it was more convenient to receive an immunization outside a physician office. Greater support was noted for receiving adult immunizations from nonphysicians and in nontraditional settings, whereas traditional settings and providers (physician offices, community health departments) were preferred for childhood immunizations. Iowans report accessing different health care providers and settings for their routine immunizations. In general, they are more likely to support using traditional immunization providers and settings for childhood immunizations but are less exclusive about where they receive adult immunizations. Pharmacists should consider focusing initial efforts on administering adult immunizations, due to greater patient acceptance of nontraditional immunizers for adult

  5. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Immunity by equilibrium.

    Science.gov (United States)

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  7. Immune System and Disorders

    Science.gov (United States)

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  8. Pneumonia - weakened immune system

    Science.gov (United States)

    ... medlineplus.gov/ency/article/000093.htm Pneumonia - weakened immune system To use the sharing features on this page, ... fighting off infection because of problems with the immune system. This type of disease is called "pneumonia in ...

  9. [Immune system and tumors].

    Science.gov (United States)

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

  10. Immune Evasion by Epstein-Barr Virus.

    Science.gov (United States)

    Ressing, Maaike E; van Gent, Michiel; Gram, Anna M; Hooykaas, Marjolein J G; Piersma, Sytse J; Wiertz, Emmanuel J H J

    2015-01-01

    Epstein-Bar virus (EBV) is widespread within the human population with over 90% of adults being infected. In response to primary EBV infection, the host mounts an antiviral immune response comprising both innate and adaptive effector functions. Although the immune system can control EBV infection to a large extent, the virus is not cleared. Instead, EBV establishes a latent infection in B lymphocytes characterized by limited viral gene expression. For the production of new viral progeny, EBV reactivates from these latently infected cells. During the productive phase of infection, a repertoire of over 80 EBV gene products is expressed, presenting a vast number of viral antigens to the primed immune system. In particular the EBV-specific CD4+ and CD8+ memory T lymphocytes can respond within hours, potentially destroying the virus-producing cells before viral replication is completed and viral particles have been released. Preceding the adaptive immune response, potent innate immune mechanisms provide a first line of defense during primary and recurrent infections. In spite of this broad range of antiviral immune effector mechanisms, EBV persists for life and continues to replicate. Studies performed over the past decades have revealed a wide array of viral gene products interfering with both innate and adaptive immunity. These include EBV-encoded proteins as well as small noncoding RNAs with immune-evasive properties. The current review presents an overview of the evasion strategies that are employed by EBV to facilitate immune escape during latency and productive infection. These evasion mechanisms may also compromise the elimination of EBV-transformed cells, and thus contribute to malignancies associated with EBV infection.

  11. The mucosal immune system: From dentistry to vaccine development

    OpenAIRE

    KIYONO, Hiroshi; AZEGAMI, Tatsuhiko

    2015-01-01

    The oral cavity is the beginning of the aero-digestive tract, which is covered by mucosal epithelium continuously under the threat of invasion of pathogens, it is thus protected by the mucosal immune system. In the early phase of our scientific efforts for the demonstration of mucosal immune system, dental science was one of major driving forces due to their foreseeability to use oral immunity for the control of oral diseases. The mucosal immune system is divided functionally into, but interc...

  12. Innate immunity and adjuvants

    OpenAIRE

    Akira, Shizuo

    2011-01-01

    Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence aga...

  13. Immune Disorder HSCT Protocol

    Science.gov (United States)

    2017-11-17

    Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  14. The Immune System Game

    Science.gov (United States)

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  15. Immune system simulation online

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

    2011-01-01

    MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno...

  16. Plant innate immunity

    Indian Academy of Sciences (India)

    Plants are invaded by an array of pathogens of which only a few succeed in causing disease. The attack by others is countered by a sophisticated immune system possessed by the plants. The plant immune system is broadly divided into two, viz. microbial-associated molecular-patterns-triggered immunity (MTI) and ...

  17. Amenorrhea - primary

    Science.gov (United States)

    ... of periods - primary Images Primary amenorrhea Normal uterine anatomy (cut section) Absence of menstruation (amenorrhea) References Bulun SE. The physiology and pathology of the female reproductive axis. In: ...

  18. Immune mechanisms in Babesia-infected animals

    International Nuclear Information System (INIS)

    Phillips, R.S.

    1980-01-01

    The course of a Babesia infection depends on the species of host and parasite involved. Animals infected with virulent babesias may need chemotherapy before acquired immunity develops. Maintenance of immunity is not dependent on the presence of the parasite. Babesia infections are characteristically of long duration. The immune response to babesias includes both humoral and cellular components. Antibody levels detected in serodiagnostic tests do not relate to levels of resistance to the parasite. Some antibodies, however, appear to be protective. Antiparasitic antibodies may damage parasites in or outside the red cell and act as opsonins. T-cell-deficient and anti-lymphocyte-serum-treated rodents are more susceptible to rodent piroplasms indicating a role for T-cells as either helper cells and/or as mediators of cell-mediated immunity (CMI). There is indirect evidence of CMI, but the cell-mediated mechanisms involved in parasite killing are not known. In domestic animals immunity is largely species- and strain-specific. Antigenic variation by babesias occurs. In rodents, however, there is cross-immunity between different species of rodent piroplasms and between rodent piroplasms and some malaria parasites. Prior infection with agents such as BCG, and Corynebacterium parvum, gives mice non-specific resistance to rodent piroplasms possibly mediated through a soluble non-antibody factor. This factor may also be liberated during piroplasm infections and by being toxic to malaria parasites account for heterologous immunity. Active immunization against babesias has been achieved with avirulent strains, irradiated parasites and dead parasites in adjuvant. During Babesia infections the primary and, to a lesser degree, the secondary immune response to heterologous antigens can be depressed. Maximum depression coincides with peak parasitaemia when antigen priming may be abolished completely. Immunosuppression during Babesia infections can prolong or exacerbate concurrent

  19. Ex vivo cytosolic delivery of functional macromolecules to immune cells.

    Directory of Open Access Journals (Sweden)

    Armon Sharei

    Full Text Available Intracellular delivery of biomolecules, such as proteins and siRNAs, into primary immune cells, especially resting lymphocytes, is a challenge. Here we describe the design and testing of microfluidic intracellular delivery systems that cause temporary membrane disruption by rapid mechanical deformation of human and mouse immune cells. Dextran, antibody and siRNA delivery performance is measured in multiple immune cell types and the approach's potential to engineer cell function is demonstrated in HIV infection studies.

  20. Microbial-immune cross-talk and regulation of the immune system.

    Science.gov (United States)

    Cahenzli, Julia; Balmer, Maria L; McCoy, Kathy D

    2013-01-01

    We are all born germ-free. Following birth we enter into a lifelong relationship with microbes residing on our body's surfaces. The lower intestine is home to the highest microbial density in our body, which is also the highest microbial density known on Earth (up to 10(12) /g of luminal contents). With our indigenous microbial cells outnumbering our human cells by an order of magnitude our body is more microbial than human. Numerous immune adaptations confine these microbes within the mucosa, enabling most of us to live in peaceful homeostasis with our intestinal symbionts. Intestinal epithelial cells not only form a physical barrier between the bacteria-laden lumen and the rest of the body but also function as multi-tasking immune cells that sense the prevailing microbial (apical) and immune (basolateral) milieus, instruct the underlying immune cells, and adapt functionally. In the constant effort to ensure intestinal homeostasis, the immune system becomes educated to respond appropriately and in turn immune status can shape the microbial consortia. Here we review how the dynamic immune-microbial dialogue underlies maturation and regulation of the immune system and discuss recent findings on the impact of diet on both microbial ecology and immune function. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

  1. Kidney and innate immunity.

    Science.gov (United States)

    Wang, Ying-Hui; Zhang, Yu-Gen

    2017-03-01

    Innate immune system is an important modulator of the inflammatory response during infection and tissue injury/repair. The kidney as a vital organ with high energy demand plays a key role in regulating the disease related metabolic process. Increasing research interest has focused on the immune pathogenesis of many kidney diseases. However, innate immune cells such as dendritic cells, macrophages, NK cells and a few innate lymphocytes, as well as the complement system are essential for renal immune homeostasis and ensure a coordinated balance between tissue injury and regeneration. The innate immune response provides the first line of host defense initiated by several classes of pattern recognition receptors (PRRs), such as membrane-bound Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), together with inflammasomes responsible for early innate immune response. Although the innate immune system is well studied, the research on the detailed relationship between innate immunity and kidney is still very limited. In this review, we will focus on the innate immune sensing system in renal immune homeostasis, as well as the corresponding pathogenesis of many kidney diseases. The pivotal roles of innate immunity in renal injury and regeneration with special emphasis on kidney disease related immunoregulatory mechanism are also discussed. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  2. Cytokine regulation of immune tolerance

    OpenAIRE

    Wu, Jie; Xie, Aini; Chen, Wenhao

    2014-01-01

    The immune system provides defenses against invading pathogens while maintaining immune tolerance to self-antigens. This immune homeostasis is harmonized by the direct interactions between immune cells and the cytokine environment in which immune cells develop and function. Herein, we discuss three non-redundant paradigms by which cytokines maintain or break immune tolerance. We firstly describe how anti-inflammatory cytokines exert direct inhibitory effects on immune cells to enforce immune ...

  3. Immuno-epidemiology of a population structured by immune status: a mathematical study of waning immunity and immune system boosting.

    Science.gov (United States)

    Barbarossa, M V; Röst, G

    2015-12-01

    When the body gets infected by a