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[PMID]: 27148736
[Au] Autor:Rai V; Rao VH; Shao Z; Agrawal DK
[Ad] Address:Department of Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska 68178, United States of America....
[Ti] Title:Dendritic Cells Expressing Triggering Receptor Expressed on Myeloid Cells-1 Correlate with Plaque Stability in Symptomatic and Asymptomatic Patients with Carotid Stenosis.
[So] Source:PLoS One;11(5):e0154802, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Atherosclerosis is a chronic inflammatory disease with atherosclerotic plaques containing inflammatory cells, including T-lymphocytes, dendritic cells (DCs) and macrophages that are responsible for progression and destabilization of atherosclerotic plaques. Stressed cells undergoing necrosis release molecules that act as endogenous danger signals to alert and activate innate immune cells. In atherosclerotic tissue the number of DCs increases with the progression of the lesion and produce several inflammatory cytokines and growth factors. Triggering receptor expressed on myeloid cells (TREM)-1 plays a crucial role in inflammation. However, relationship of DCs and the role of TREM-1 with the stability of atherosclerotic plaques have not been examined. In this study, we investigated the heterogeneity of the plaque DCs, myeloid (mDC1 and mDC2) and plasmacytoid (pDCs), and examined the expression of TREM-1 and their co-localization with DCs in the plaques from symptomatic (S) and asymptomatic (AS) patients with carotid stenosis. We found increased expression of HLA-DR, fascin, and TREM-1 and decreased expression of TREM-2 and α-smooth muscle actin in S compared to AS atherosclerotic carotid plaques. Both TREM-1 and fascin were co-localized suggesting increased expression of TREM-1 in plaque DCs of S compared to AS patients. These data were supported by increased mRNA transcripts of TREM-1 and decreased mRNA transcripts of TREM-2 in carotid plaques of S compared to AS patients. There was higher density of both CD1c+ mDC1 and CD141+ mDC2 in the carotid plaques from AS compared to S patients, where as the density of CD303+ pDCs were higher in the carotid plaques of S compared to AS patients. These findings suggest a potential role of pDCs and TREM-1 in atherosclerotic plaque vulnerability. Thus, newer therapies could be developed to selectively block TREM-1 for stabilizing atherosclerotic plaques.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0154802

  2 / 466304 MEDLINE  
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[PMID]: 27136093
[Au] Autor:Assadian F; Sandström K; Bondeson K; Laurell G; Lidian A; Svensson C; Akusjärvi G; Bergqvist A; Punga T
[Ad] Address:Department of Medical Biochemistry and Microbiology, Uppsala Biomedical Center, Uppsala University, Uppsala, Sweden....
[Ti] Title:Distribution and Molecular Characterization of Human Adenovirus and Epstein-Barr Virus Infections in Tonsillar Lymphocytes Isolated from Patients Diagnosed with Tonsillar Diseases.
[So] Source:PLoS One;11(5):e0154814, 2016.
[Is] ISSN:1932-6203
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Surgically removed palatine tonsils provide a conveniently accessible source of T and B lymphocytes to study the interplay between foreign pathogens and the host immune system. In this study we have characterised the distribution of human adenovirus (HAdV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in purified tonsillar T and B cell-enriched fractions isolated from three patient age groups diagnosed with tonsillar hypertrophy and chronic/recurrent tonsillitis. HAdV DNA was detected in 93 out of 111 patients (84%), while EBV DNA was detected in 58 patients (52%). The most abundant adenovirus type was HAdV-5 (68%). None of the patients were positive for HCMV. Furthermore, 43 patients (39%) showed a co-infection of HAdV and EBV. The majority of young patients diagnosed with tonsillar hypertrophy were positive for HAdV, whereas all adult patients diagnosed with chronic/recurrent tonsillitis were positive for either HAdV or EBV. Most of the tonsils from patients diagnosed with either tonsillar hypertrophy or chronic/recurrent tonsillitis showed a higher HAdV DNA copy number in T compared to B cell-enriched fraction. Interestingly, in the majority of the tonsils from patients with chronic/recurrent tonsillitis HAdV DNA was detected in T cells only, whereas hypertrophic tonsils demonstrated HAdV DNA in both T and B cell-enriched fractions. In contrast, the majority of EBV positive tonsils revealed a preference for EBV DNA accumulation in the B cell-enriched fraction compared to T cell fraction irrespective of the patients' age.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1605
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1371/journal.pone.0154814

  3 / 466304 MEDLINE  
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[PMID]: 26330121
[Au] Autor:Wold WS; Toth K
[Ad] Address:a 1 Saint Louis University School of Medicine, Department of Molecular Microbiology and Immunology , 1100 S. Grand Boulevard, St. Louis, MO, USA +1 314 977 8857 ; +1 314 977 8717 ; woldws@slu.edu.
[Ti] Title:New drug on the horizon for treating adenovirus.
[So] Source:Expert Opin Pharmacother;16(14):2095-9, 2015.
[Is] ISSN:1744-7666
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Human adenoviruses can cause serious disseminated infections including death in immunosuppressed patients, especially pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) patients. There are no drugs approved to treat such infections. Cidofovir is used intravenously in many transplant clinics, probably with some effect, but controlled trials have not been completed. Cidofovir is an acyclic nucleoside phosphonate analog of cytidine monophosphate. Following conversion to its diphosphate form within cells, cidofovir is a preferred substrate for the adenovirus DNA polymerase, leading to viral DNA chain termination. Problems with cidofovir include poor cellular uptake and nephrotoxicity. Brincidofovir, a lipid-linked derivative of cidofovir which is active against five families of double-stranded DNA viruses, represents a major advance in anti-adenovirus therapy. It is administered orally, taken up readily by cells followed by release of cidofovir within cells, and is not nephrotoxic. Brincidofovir, under development by Chimerix, Inc., is being evaluated against adenovirus infections in transplant patients including allo-HSCT patients in a phase III clinical trial (AdVise Study). Preliminary results indicate that brincidofovir is safe and very effective at decreasing adenovirus viremia and adenovirus-induced pathogenicity and mortality. Anti-adenovirus adoptive T cell therapy is another very promising approach to treating allo-HSCT patients as demonstrated in clinical studies.
[Mh] MeSH terms primary: Adenoviridae Infections/drug therapy
Antiviral Agents/therapeutic use
Cytosine/analogs & derivatives
Organophosphonates/therapeutic use
[Mh] MeSH terms secundary: Adenoviridae Infections/therapy
Adenoviruses, Human
Adoptive Transfer
Animals
Cytosine/therapeutic use
DNA, Viral
Humans
Immunocompromised Host
T-Lymphocytes/transplantation
[Pt] Publication type:EDITORIAL
[Nm] Name of substance:0 (Antiviral Agents); 0 (DNA, Viral); 0 (Organophosphonates); 0 (cidofovir hexadecyloxypropyl ester); 8J337D1HZY (Cytosine); JIL713Q00N (cidofovir)
[Em] Entry month:1512
[Cu] Class update date: 160514
[Lr] Last revision date:160514
[Js] Journal subset:IM
[Da] Date of entry for processing:150914
[St] Status:MEDLINE
[do] DOI:10.1517/14656566.2015.1083975

  4 / 466304 MEDLINE  
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[PMID]: 26048402
[Au] Autor:Wang Q; Klinke DJ; Wang Z
[Ad] Address:Department of Computer Sciences, Mathematics, and Engineering, Shepherd University, Shepherdstown, 25443, WV, USA. qwang@shepherd.edu....
[Ti] Title:CD8(+) T cell response to adenovirus vaccination and subsequent suppression of tumor growth: modeling, simulation and analysis.
[So] Source:BMC Syst Biol;9:27, 2015.
[Is] ISSN:1752-0509
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: Using immune checkpoint modulators in the clinic to increase the number and activity of cytotoxic T lymphocytes that recognize tumor antigens can prolong survival for metastatic melanoma. Yet, only a fraction of the patient population receives clinical benefit. In short, these clinical trials demonstrate proof-of-principle but optimizing the specific therapeutic strategies remains a challenge. In many fields, CAD (computer-aided design) is a tool used to optimize integrated system behavior using a mechanistic model that is based upon knowledge of constitutive elements. The objective of this study was to develop a predictive simulation platform for optimizing anti-tumor immunity using different treatment strategies. METHODS: To better understand the therapeutic role that cytotoxic CD8(+) T cells can play in controlling tumor growth, we developed a multi-scale mechanistic model of the biology using impulsive differential equations and calibrated it to a self-consistent data set. RESULTS: The multi-scale model captures the activation and differentiation of naïve CD8(+) T cells into effector cytotoxic T cells in the lymph node following adenovirus-mediated vaccination against a tumor antigen, the trafficking of the resulting cytotoxic T cells into blood and tumor microenvironment, the production of cytokines within the tumor microenvironment, and the interactions between tumor cells, T cells and cytokines that control tumor growth. The calibrated model captures the modest suppression of tumor cell growth observed in the B16F10 model, a transplantable mouse model for metastatic melanoma, and was used to explore the impact of multiple vaccinations on controlling tumor growth. CONCLUSIONS: Using the calibrated mechanistic model, we found that the cytotoxic CD8(+) T cell response was prolonged by multiple adenovirus vaccinations. However, the strength of the immune response cannot be improved enough by multiple adenovirus vaccinations to reduce tumor burden if the cytotoxic activity or local proliferation of cytotoxic T cells in response to tumor antigens is not greatly enhanced. Overall, this study illustrates how mechanistic models can be used for in silico screening of the optimal therapeutic dosage and timing in cancer treatment.
[Mh] MeSH terms primary: Adenoviridae/physiology
CD8-Positive T-Lymphocytes/immunology
Cancer Vaccines/immunology
Melanoma, Experimental/immunology
Melanoma, Experimental/pathology
Models, Biological
Vaccination
[Mh] MeSH terms secundary: Adenoviridae/genetics
Algorithms
Animals
Antigens, Neoplasm/immunology
CD8-Positive T-Lymphocytes/metabolism
Cell Proliferation
Humans
Interferon-gamma/metabolism
Melanoma, Experimental/prevention & control
Melanoma, Experimental/virology
Mice
Tumor Microenvironment/immunology
Tumor Necrosis Factor-alpha/metabolism
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Name of substance:0 (Antigens, Neoplasm); 0 (Cancer Vaccines); 0 (Tumor Necrosis Factor-alpha); 82115-62-6 (Interferon-gamma)
[Em] Entry month:1605
[Cu] Class update date: 150819
[Lr] Last revision date:150819
[Js] Journal subset:IM
[Da] Date of entry for processing:150606
[St] Status:MEDLINE
[do] DOI:10.1186/s12918-015-0168-9

  5 / 466304 MEDLINE  
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[PMID]: 25786570
[Au] Autor:Hönger G; Krähenbühl N; Dimeloe S; Stern M; Schaub S; Hess C
[Ad] Address:Immunobiology Laboratory, Department of Biomedicine, University of Basel, Basel, Switzerland; Transplantation Immunology and Nephrology, University Hospital Basel, Basel, Switzerland.
[Ti] Title:Inter-individual differences in HLA expression can impact the CDC crossmatch.
[So] Source:Tissue Antigens;85(4):260-6, 2015 Apr.
[Is] ISSN:1399-0039
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:How human leucocyte antigen (HLA) expression levels on human lymphocytes relate to clinically relevant in vitro cytotoxicity testing has not been defined. Here, cross-sectional (n = 14) and longitudinal (n = 6) semi-quantitative assessment of HLA expression on lymphocytes was performed. Complement-dependent cytotoxicity (CDC) and cellular allo-reactivity were assessed vis-à-vis target cells with defined levels of HLA expression. On CD4(+) and CD8(+) T-cells, and on B-cells, intra-individual HLA levels varied ≤1.5-fold, whereas inter-individual HLA expression varied 2.34-fold and 2.07-fold on CD4(+) and CD8(+) T-cells, respectively, and 2.90-fold on B-cells. Importantly, CDC crossmatch reactions induced by anti-HLA-A2 monoclonal antibody as well as patient sera solely containing HLA-A2 antibodies were significantly impacted by HLA-A2 expression levels on donor cells. Likewise, cytotoxicity of HLA-A2 reactive effector cells was induced proportionate to availability of HLA-A2. These data demonstrate that human HLA expression on lymphocytes from healthy blood donors is fairly stable intra-individually, yet varies significantly from person to person. Variability in HLA expression levels can impact functional cytotoxic reactions in vitro, including the widely used CDC crossmatch assay. Prospective studies are required to test the clinical relevance of this finding.
[Mh] MeSH terms primary: Genetic Variation
HLA-A2 Antigen/genetics
HLA-B Antigens/genetics
HLA-C Antigens/genetics
HLA-DQ Antigens/genetics
HLA-DR Antigens/genetics
HLA-DRB1 Chains/genetics
[Mh] MeSH terms secundary: Adult
B-Lymphocytes/cytology
B-Lymphocytes/immunology
CD4-Positive T-Lymphocytes/cytology
CD4-Positive T-Lymphocytes/immunology
CD8-Positive T-Lymphocytes/cytology
CD8-Positive T-Lymphocytes/immunology
Complement System Proteins/genetics
Complement System Proteins/immunology
Cytotoxicity Tests, Immunologic
Cytotoxicity, Immunologic
Female
Gene Expression Regulation
HLA-A2 Antigen/immunology
HLA-B Antigens/immunology
HLA-C Antigens/immunology
HLA-DQ Antigens/immunology
HLA-DR Antigens/immunology
HLA-DRB1 Chains/immunology
Histocompatibility Testing
Humans
Immunoglobulin Allotypes/biosynthesis
Immunoglobulin Allotypes/genetics
Male
Middle Aged
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (HLA-A2 Antigen); 0 (HLA-B Antigens); 0 (HLA-C Antigens); 0 (HLA-DQ Antigens); 0 (HLA-DR Antigens); 0 (HLA-DRB1 Chains); 0 (Immunoglobulin Allotypes); 9007-36-7 (Complement System Proteins)
[Em] Entry month:1605
[Js] Journal subset:IM
[Da] Date of entry for processing:150319
[St] Status:MEDLINE
[do] DOI:10.1111/tan.12537

  6 / 466304 MEDLINE  
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[PMID]: 24596313
[Au] Autor:Egger C; Cannet C; Gérard C; Debon C; Stohler N; Dunbar A; Tigani B; Li J; Beckmann N
[Ad] Address:Novartis Institutes for BioMedical Research, Analytical Sciences and Imaging, Basel, Switzerland; University of Basel, Biocenter, Basel, Switzerland.
[Ti] Title:Adriamycin-induced nephropathy in rats: functional and cellular effects characterized by MRI.
[So] Source:J Magn Reson Imaging;41(3):829-40, 2015 Mar.
[Is] ISSN:1522-2586
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: To assess with magnetic resonance imaging (MRI) adriamycin-induced nephropathy in living rats, an established model for proteinuric renal disease was used. MATERIALS AND METHODS: Functional information of contrast agent clearance was obtained with dynamic contrast-enhanced (DCE) imaging following intravenous Gd-DOTA administration. Perfusion data were obtained with a bolus tracking technique comprising intravenous injection of superparamagnetic iron oxide (SPIO) nanoparticles. Cellular information was derived from anatomical images acquired 24 hours after SPIO. Treatment with the transforming growth factor-ß123 (TGF-ß1,2,3 ) antibody, 1D11, started 1 week after adriamycin. Histology was performed at week 6 post-adriamycin. RESULTS: Tracer washout rates derived by DCE-MRI decreased by 65.5% with respect to baseline at week 6 post-adriamycin. The impaired kidney function agreed with glomerulopathy, nephropathy and fibrosis revealed histologically (picrosirius collagen staining in adriamycin-treated rats increased by 125.8% [P = 0.005] with respect to controls). Perfusion was reduced by 16.1%. Images acquired 24 hours after SPIO presented contrast changes that correlated inversely with the histologically determined iron content (R = -0.74, P = 2.6 × 10(-4) ). In adriamycin-challenged animals, iron was found in macrophages and in sclerotic tubuli, only in areas where macrophages were present. Treatment with 1D11 did not improve the adriamycin-induced renal injury. CONCLUSION: MRI provides longitudinal functional and cellular (macrophage infiltration) information that correlates with nephropathy development in adriamycin-challenged rats.
[Mh] MeSH terms primary: Kidney Diseases/physiopathology
Magnetic Resonance Imaging
[Mh] MeSH terms secundary: Animals
Contrast Media/metabolism
Disease Models, Animal
Doxorubicin
Ferric Compounds/metabolism
Heterocyclic Compounds/metabolism
Image Enhancement
Kidney/metabolism
Kidney/physiopathology
Male
Organometallic Compounds/metabolism
Rats
Rats, Wistar
T-Lymphocytes, Regulatory/metabolism
[Pt] Publication type:JOURNAL ARTICLE
[Nm] Name of substance:0 (Contrast Media); 0 (Ferric Compounds); 0 (Heterocyclic Compounds); 0 (Organometallic Compounds); 1K09F3G675 (ferric oxide); 80168379AG (Doxorubicin); 92923-44-9 (gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate)
[Em] Entry month:1605
[Js] Journal subset:IM
[Da] Date of entry for processing:150219
[St] Status:MEDLINE
[do] DOI:10.1002/jmri.24603

  7 / 466304 MEDLINE  
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[PMID]: 25483667
[Au] Autor:Nougarede N; Bisceglia H; Rozières A; Goujon C; Boudet F; Laurent P; Vanbervliet B; Rodet K; Hennino A; Nicolas JF
[Ad] Address:a Sanofi Pasteur ; Marcy l'Etoile , France.
[Ti] Title:Nine µg intradermal influenza vaccine and 15 µg intramuscular influenza vaccine induce similar cellular and humoral immune responses in adults.
[So] Source:Hum Vaccin Immunother;10(9):2713-20, 2014.
[Is] ISSN:2164-554X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Intanza® 9 µg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 µg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 µg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 µg (n=38) or IM 15 µg (n=42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination. Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 µg vaccine are similar to those to the standard IM 15 µg vaccine.
[Mh] MeSH terms primary: Immunity, Cellular
Immunity, Humoral
Influenza Vaccines/administration & dosage
Influenza Vaccines/immunology
[Mh] MeSH terms secundary: Adolescent
Adult
Antibodies, Viral/analysis
Antibodies, Viral/blood
B-Lymphocytes/immunology
Europe
Female
Hemagglutination Inhibition Tests
Humans
Injections, Intradermal
Injections, Intramuscular
Leukocytes, Mononuclear/immunology
Male
Saliva/immunology
Serum/immunology
Young Adult
[Pt] Publication type:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Antibodies, Viral); 0 (Influenza Vaccines)
[Em] Entry month:1605
[Js] Journal subset:IM
[Da] Date of entry for processing:141222
[St] Status:MEDLINE
[do] DOI:10.4161/hv.29695

  8 / 466304 MEDLINE  
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[PMID]: 25483494
[Au] Autor:Hamidi A; Kreeftenberg H
[Ad] Address:a Institute for Translational Vaccinology (Intravacc) ; Bilthoven , The Netherlands.
[Ti] Title:Use of immuno assays during the development of a Hemophilus influenzae type b vaccine for technology transfer to emerging vaccine manufacturers.
[So] Source:Hum Vaccin Immunother;10(9):2697-703, 2014.
[Is] ISSN:2164-554X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Quality control of Hemophilus Influenzae type b (Hib) conjugate vaccines is mainly dependent on physicochemical methods. Overcoming sample matrix interference when using physicochemical tests is very challenging, these tests are therefore only used to test purified samples of polysaccharide, protein, bulk conjugate, and final product. For successful development of a Hib conjugate vaccine, several ELISA (enzyme-linked immunosorbent assay) methods were needed as an additional tool to enable testing of in process (IP) samples. In this paper, three of the ELISA's that have been very valuable during the process development, implementation and scaling up are highlighted. The PRP-ELISA, was a very efficient tool in testing in process (IP) samples generated during the development of the cultivation and purification process of the Hib-polysaccharide. The antigenicity ELISA, was used to confirm the covalent linkage of PRP and TTd in the conjugate. The anti-PRP IgG ELISA was developed as part of the immunogenicity test, used to demonstrate the ability of the Hib conjugate vaccine to elicit a T-cell dependent immune response in mice. ELISA methods are relatively cheap and easy to implement and therefore very useful during the development of polysaccharide conjugate vaccines.
[Mh] MeSH terms primary: Haemophilus Vaccines/immunology
Quality Control
Technology Transfer
Technology, Pharmaceutical/methods
[Mh] MeSH terms secundary: Animals
Enzyme-Linked Immunosorbent Assay/methods
Haemophilus Infections/microbiology
Haemophilus Infections/prevention & control
Haemophilus Vaccines/administration & dosage
Haemophilus Vaccines/isolation & purification
Haemophilus influenzae type b/immunology
Mice
T-Lymphocytes/immunology
Vaccines, Conjugate/administration & dosage
Vaccines, Conjugate/immunology
Vaccines, Conjugate/isolation & purification
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Name of substance:0 (Haemophilus Vaccines); 0 (Vaccines, Conjugate)
[Em] Entry month:1605
[Js] Journal subset:IM
[Da] Date of entry for processing:141222
[St] Status:MEDLINE
[do] DOI:10.4161/hv.29300

  9 / 466304 MEDLINE  
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[PMID]: 25483491
[Au] Autor:Kovjazin R; Carmon L
[Ad] Address:a Vaxil BioTherapeutics Ltd. ; Nes-Ziona , Israel.
[Ti] Title:The use of signal peptide domains as vaccine candidates.
[So] Source:Hum Vaccin Immunother;10(9):2733-40, 2014.
[Is] ISSN:2164-554X
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Signal peptide (SP) domains have a common motif but also sequence specific features. This knowledge was mainly ignored by immunologists who considered SP as generic, short-lived, targeting sequences. Consequently, while SP-derived MHC class I, class II and HLA-E epitopes have been isolated, their use as antigen-specific vaccine candidates (VCs) was mostly neglected. Recently we demonstrated the rational of selecting entire SP domains as multi-epitope long peptide VCs based on their high T and B-cell epitope densities. This review summarizes preclinical and clinical results demonstrating the various advantages of human SP domain VCs derived from both bacterial and tumor antigens. Such vaccine design provides for a straightforward, yet unique immunotherapeutic means of generating robust, non-toxic, diversified, combined antigen-specific CD4+/CD8+ T/B-cell immunity, irrespective of patient HLA repertoire also in disease associated transporter-associated with antigen processing (TAP) deficiencies. Subsequent clinical trials will further assess the full potential of this approach.
[Mh] MeSH terms primary: Bacterial Vaccines/immunology
Cancer Vaccines/immunology
Protein Sorting Signals
Vaccination/methods
[Mh] MeSH terms secundary: B-Lymphocytes/immunology
CD4-Positive T-Lymphocytes/immunology
CD8-Positive T-Lymphocytes/immunology
Clinical Trials as Topic
Drug Evaluation, Preclinical
Epitopes/immunology
Humans
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Nm] Name of substance:0 (Bacterial Vaccines); 0 (Cancer Vaccines); 0 (Epitopes); 0 (Protein Sorting Signals)
[Em] Entry month:1605
[Js] Journal subset:IM
[Da] Date of entry for processing:141222
[St] Status:MEDLINE
[do] DOI:10.4161/21645515.2014.970916

  10 / 466304 MEDLINE  
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[PMID]: 24877655
[Au] Autor:Yuan S; Ruan J; Huang S; Chen S; Xu A
[Ad] Address:State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou 510275, People's Republic of China....
[Ti] Title:Amphioxus as a model for investigating evolution of the vertebrate immune system.
[So] Source:Dev Comp Immunol;48(2):297-305, 2015 Feb.
[Is] ISSN:1879-0089
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:As the most basal chordate, the cephalochordate amphioxus has unique features that make it a valuable model for understanding the phylogeny of immunity. Vertebrate adaptive immunity (VAI) mediated by lymphocytes bearing variable receptors has been well-studied in mammals but not observed in invertebrates. However, the identification of lymphocyte-like cells in the gill along with genes related with lymphoid proliferation and differentiation indicates the presence of some basic components of VAI in amphioxus. Without VAI, amphioxus utilizes about 10% of its gene repertoires, and an ongoing domain reshuffling mechanism among these genes, for innate immunity, suggesting extraordinary innate complexity and diversity not observed in other species. Innate diversity may not be comparable to the somatic diversity of the VAI, but there is no doubt of the success of this immune system, since amphioxus has existed for over 500 million years. Studies of amphioxus immunity may provide information on the reduction of innate immune complexity and the conflict between microbiota and host shaped the evolution of adaptive immune systems (AIS) during chordate evolution.
[Mh] MeSH terms primary: Biological Evolution
Lancelets/immunology
Vertebrates/immunology
[Mh] MeSH terms secundary: Animals
Complement Activation
Immunity, Innate
Lancelets/genetics
Lancelets/metabolism
Signal Transduction
[Pt] Publication type:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Entry month:1605
[Js] Journal subset:IM
[Da] Date of entry for processing:141206
[St] Status:MEDLINE


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