75 results on '"Barteneva N"'
Search Results
2. Differential stimulation of monocytic cells results in distinct populations of microparticles
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BERNIMOULIN, M., WATERS, E.K., FOY, M., STEELE, B.M., SULLIVAN, M., FALET, H., WALSH, M.T., BARTENEVA, N., GENG, J.G., HARTWIG, J.H., MAGUIRE, P.B., and WAGNER, D.D.
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- 2009
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3. Frühzeitige Identifizierung von Methicillin-Oxacillin-resistenten Staphylococcus aureus-Stämmen mittels Polymerase Chain Reaction (PCR). Ein diagnostisches Verfahren mit klinischer Bedeutung
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Dumon, K., Barteneva, N. S., Gorelov, V. N., Gross-Weege, W., Röher, H.-D., Goretzki, P. E., Beger, Hans G., editor, Hierholzer, G., editor, Seifert, J., editor, and Hartel, W., editor
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- 1995
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4. Fluorescent semiconductor nanocrystals in microscopy and flow cytometry
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Vorobjev, I. A., Rafalovskaya-Orlovskaya, E. P., Gladkih, A. A., Potashnikova, D. M., and Barteneva, N. S.
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- 2011
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5. Possible role of natural killer cells in pemphigus vulgaris − preliminary observations
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Stern, J. N. H., Keskin, D. B., Barteneva, N., Zuniga, J., Yunis, E. J., and Ahmed, A. R.
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- 2008
6. Use of molecular modeling to define the structural requirements for high affinity xenoantibody interaction with the Gal α-1,3 Gal carbohydrate
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Kearns-Jonker, M., Bolger, M., Mencel, R., Barteneva, N., Starnes, V., and Cramer, D.
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- 2001
7. Action of pertussis vaccine on mouse hematopoietic stem cells
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Khorobrykh, V. V., Barteneva, N. S., Sanin, A. V., and Snegireva, A. E.
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- 1982
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8. Stimulation of postradiation regeneration of erythropoiesis in mice byBordetella pertussis vaccine
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Khorobrykh, V. V., Sanin, A. V., Barteneva, N. S., and Snegireva, A. E.
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- 1983
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9. Proliferation of spleen cells in response to Bordetella pertussis
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Khorobrykh, V. V., Barteneva, N. S., Snegireva, A. E., Pronin, A. V., and Merimskaya, O. S.
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- 1983
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10. Role of neutrophils in controlling early stages of a Chlamydia trachomatis infection
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Barteneva, N, primary, Theodor, I, additional, Peterson, E M, additional, and de la Maza, L M, additional
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- 1996
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11. Identification and Sequencing of a Plasmid (pYV96)-Encoded Gene Product of Yersinia enterocolitica Recognized by Antibodies in Sera of Patients with Autoimmune Thyroid Disease
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BARTENEVA, N. S., primary, EVSTAFIEVA, A. G., additional, GORELOV, V. N., additional, and WENZEL, B. E., additional
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- 1994
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12. On the Possible Role of I-J+Suppressor Cells in Murine Hematopoiesis
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SANIN, A. V., primary, SOSNOVSKAYA, O. Yu., additional, BARTENEVA, N. S., additional, and PRONIN, A. V., additional
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- 1991
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13. On the Possible Role of I-J+ Suppressor Cells in Murine Hematopoiesis.
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SANIN, A. V., SOSNOVSKAYA, O. Yu., BARTENEVA, N. S., and PRONIN, A. V.
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- 1991
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14. Role of nitric oxide in the inhibition of cytochrome P450 in the liver of mice infected with Chlamydia trachomatis
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Khatsenko, O. G., Barteneva, N. S., Maza, L. M. De la, and Kikkawa, Y.
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- 1998
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15. Optimization of flow cytometric detection and cell sorting of transgenic Plasmodium parasites using interchangeable optical filters
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Vorobjev Ivan A, Buchholz Kathrin, Prabhat Prashant, Ketman Kenneth, Egan Elizabeth S, Marti Matthias, Duraisingh Manoj T, and Barteneva Natasha S
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Malaria ,Plasmodium ,Optical filter ,Fluorescent proteins ,Cell sorting ,Rare cells ,Arctic medicine. Tropical medicine ,RC955-962 ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Malaria remains a major cause of morbidity and mortality worldwide. Flow cytometry-based assays that take advantage of fluorescent protein (FP)-expressing malaria parasites have proven to be valuable tools for quantification and sorting of specific subpopulations of parasite-infected red blood cells. However, identification of rare subpopulations of parasites using green fluorescent protein (GFP) labelling is complicated by autofluorescence (AF) of red blood cells and low signal from transgenic parasites. It has been suggested that cell sorting yield could be improved by using filters that precisely match the emission spectrum of GFP. Methods Detection of transgenic Plasmodium falciparum parasites expressing either tdTomato or GFP was performed using a flow cytometer with interchangeable optical filters. Parasitaemia was evaluated using different optical filters and, after optimization of optics, the GFP-expressing parasites were sorted and analysed by microscopy after cytospin preparation and by imaging cytometry. Results A new approach to evaluate filter performance in flow cytometry using two-dimensional dot blot was developed. By selecting optical filters with narrow bandpass (BP) and maximum position of filter emission close to GFP maximum emission in the FL1 channel (510/20, 512/20 and 517/20; dichroics 502LP and 466LP), AF was markedly decreased and signal-background improve dramatically. Sorting of GFP-expressing parasite populations in infected red blood cells at 90 or 95% purity with these filters resulted in 50-150% increased yield when compared to the standard filter set-up. The purity of the sorted population was confirmed using imaging cytometry and microscopy of cytospin preparations of sorted red blood cells infected with transgenic malaria parasites. Discussion Filter optimization is particularly important for applications where the FP signal and percentage of positive events are relatively low, such as analysis of parasite-infected samples with in the intention of gene-expression profiling and analysis. The approach outlined here results in substantially improved yield of GFP-expressing parasites, and requires decreased sorting time in comparison to standard methods. It is anticipated that this protocol will be useful for a wide range of applications involving rare events.
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- 2012
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16. Visualization and quantitation of the expression of microRNAs and their target genes in neuroblastoma single cells using imaging cytometry
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Ponomarev Eugene D, Veremeyko Tatiana, and Barteneva Natasha S
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MicroRNA ,Target gene ,Imaging cytometry ,Neuroblastoma ,MiR-124 ,CDK6 ,Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Background MicroRNAs (miRNAs) are regulatory molecules that play an important role in many physiological processes, including cell growth, differentiation, and apoptosis. In addition to modulating normal cellular functions, it has also been reported that miRNAs are involved in the development of many pathologies, including cardiovascular diseases, cancer, inflammation, and neurodegeneration. Methods for the sensitive detection and measurement of specific miRNAs and their cellular targets are essential for both basic research endeavours, as well as diagnostic efforts aimed at understanding the role of miRNAs in disease processes. Findings In this study, we describe a novel, imaging cytometry-based protocol that allows for simultaneous visualisation and quantification of miRNAs and their putative targets. We validated this methodology in a neuronal cell line by examining the relationship of the miRNA miR-124 and its known target, cyclin dependent kinase 6 (CDK6). We found that ectopic overexpression of miR-124 resulted in the downregulation of CDK6, decreased cellular proliferation, and induced cellular morphological changes. Conclusions This method is suitable for analysing the expression and cellular localisation of miRNAs and target proteins in small cell subsets within a heterogeneous cell suspension. We believe that our cytometry-based methodology will be easily adaptable to miRNA studies in many areas of biomedical research including neuroscience, stem cell biology, immunology, and oncology.
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- 2011
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17. The use of HaloTag-based technology in flow and laser scanning cytometry analysis of live and fixed cells
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Goldfeld Anne E, Jasenosky Luke D, Ranjbar Shahin, Kovalenko Elena I, Vorobjev Ivan A, and Barteneva Natasha S
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Medicine ,Biology (General) ,QH301-705.5 ,Science (General) ,Q1-390 - Abstract
Abstract Background Combining the technologies of protein tag labeling and optical microscopy allows sensitive analysis of protein function in cells. Findings Here, we describe development of applications using protein tag technology (HaloTag (HT)-based) for flow and laser scanning cytometry (LSC). Cell lines, expressing recombinant surface β1-integrin-HT and HT-p65 fusion protein, and a CD4 T cell line (Jurkat) infected with human immunodeficiency virus type 1 (HIV-1) reporter virus expressing the unfused HT (HIV-1Lai-Halo), were stained with different HT ligands and successfully detected by flow cytometers equipped with 488 and 561 nm lasers as well as a laser scanning cytometer (equipped with 488 and 405 nm lasers) alone or combined with cell cycle and viability markers. Conclusions Use of HT technology for cytometric applications has advantages over its use in microscopy as it allows for the statistical measurement of protein expression levels in individual cells within a heterogeneous cell population in combination with cell cycle analysis. Another advantage is the ability of the HaloTag to withstand long fixation and high concentration of fixative, which can be useful in research of infectious agents like HIV and/or mycobacteria.
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- 2011
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18. Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens
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Yew Margaret, Xu Alan, Shulkin Irina, Hussain Namath, Mencel Robert, Barteneva Natasha, Kearns-Jonker Mary, and Cramer Donald V
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background Natural antibodies directed at carbohydrates reject porcine xenografts. They are initially expressed in germline configuration and are encoded by a small number of structurally-related germline progenitors. The transplantation of genetically-modified pig organs prevents hyperacute rejection, but delayed graft rejection still occurs, partly due to humoral responses. IgVH genes encoding induced xenoantibodies are predominantly, not exclusively, derived from germline progenitors in the VH3 family. We have previously identified the immunoglobulin heavy chain genes encoding VH3 xenoantibodies in patients and primates. In this manuscript, we complete the structural analysis of induced xenoantibodies by identifying the IgVH genes encoding the small proportion of VH4 xenoantibodies and the germline progenitors encoding xenoantibody light chains. This information has been used to define the xenoantibody/carbohydrate binding site using computer-simulated modeling. Results The VH4-59 gene encodes antibodies in the VH4 family that are induced in human patients mounting active xenoantibody responses. The light chain of xenoantibodies is encoded by DPK5 and HSIGKV134. The structural information obtained by sequencing analysis was used to create computer-simulated models. Key contact sites for xenoantibody/carbohydrate interaction for VH3 family xenoantibodies include amino acids in sites 31, 33, 50, 57, 58 and the CDR3 region of the IgVH gene. Site-directed mutagenesis indicates that mutations in predicted contact sites alter binding to carbohydrate xenoantigens. Computer-simulated modeling suggests that the CDR3 region directly influences binding. Conclusion Xenoantibodies induced during early and delayed xenograft responses are predominantly encoded by genes in the VH3 family, with a small proportion encoded by VH4 germline progenitors. This restricted group can be identified by the unique canonical structure of the light chain, heavy chain and CDR3. Computer-simulated models depict this structure with accuracy, as confirmed by site-directed mutagenesis. Computer-simulated drug design using computer-simulated models may now be applied to develop new drugs that may enhance the survival of xenografted organs.
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- 2007
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19. Diagnostic Potential of Imaging Flow Cytometry.
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Doan M, Vorobjev I, Rees P, Filby A, Wolkenhauer O, Goldfeld AE, Lieberman J, Barteneva N, Carpenter AE, and Hennig H
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- Data Analysis, Deep Learning, Flow Cytometry instrumentation, Humans, Image Processing, Computer-Assisted, Leukemia, Myeloid blood, Leukemia, Myeloid diagnostic imaging, Microscopy, Fluorescence instrumentation, Neoplastic Cells, Circulating classification, Precision Medicine instrumentation, Prognosis, Single Molecule Imaging instrumentation, Single-Cell Analysis instrumentation, Flow Cytometry methods, Microscopy, Fluorescence methods, Precision Medicine methods, Single Molecule Imaging methods, Single-Cell Analysis methods
- Abstract
Imaging flow cytometry (IFC) captures multichannel images of hundreds of thousands of single cells within minutes. IFC is seeing a paradigm shift from low- to high-information-content analysis, driven partly by deep learning algorithms. We predict a wealth of applications with potential translation into clinical practice., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2018
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20. Comparison of the mRNA expression profile of B-cell receptor components in normal CD5-high B-lymphocytes and chronic lymphocytic leukemia: a key role of ZAP70.
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Gladkikh AA, Potashnikova DM, Tatarskiy V Jr, Yastrebova M, Khamidullina A, Barteneva N, and Vorobjev I
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- Cell Separation methods, Flow Cytometry, Humans, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Signal Transduction, Transcriptome, ZAP-70 Protein-Tyrosine Kinase genetics, B-Lymphocytes immunology, B-Lymphocytes pathology, Biomarkers, Tumor genetics, CD5 Antigens genetics, Gene Expression Profiling methods, Leukemia, Lymphocytic, Chronic, B-Cell genetics, Palatine Tonsil immunology, RNA, Messenger genetics, RNA, Neoplasm genetics, Receptors, Antigen, B-Cell genetics
- Abstract
The B-cell receptor (BCR) signaling pathway is of great importance for B-cell survival and proliferation. The BCR expressed on malignant B-CLL cells contributes to the disease pathogenesis, and its signaling pathway is currently the target of several therapeutic strategies. Although various BCR alterations have been described in B-CLL at the protein level, the mRNA expression levels of tyrosine kinases in B-CLL compared to that in normal CD5-high and CD5-low B-lymphocytes remain unknown. In the current study, we measured the mRNA expression levels of CD79A, CD79B, LYN, SYK, SHP1, and ZAP70 in purified populations of CD5-high B-CLL cells, CD5-low B-cells from the peripheral blood of healthy donors, and CD5-high B-cells from human tonsils. Here, we report a clear separation in the B-CLL dataset between the ZAP70-high and ZAP70-low subgroups. Each subgroup has a unique expression profile of BCR signaling components that might reflect the functional status of the BCR signaling pathway. Moreover, the ZAP70-low subgroup does not resemble either CD5-high B-lymphocytes from the tonsils or CD5-low lymphocytes from PBMC (P < 0.05). We also show that ZAP70 is the only gene that is differentially expressed in CD5-high and CD5-low normal B-lymphocytes, confirming the key role of Zap-70 tyrosine kinase in BCR signaling alterations in B-CLL., (© 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2017
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21. Dynamic metabolic exchange governs a marine algal-bacterial interaction.
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Segev E, Wyche TP, Kim KH, Petersen J, Ellebrandt C, Vlamakis H, Barteneva N, Paulson JN, Chai L, Clardy J, and Kolter R
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- Aquatic Organisms growth & development, Aquatic Organisms metabolism, Bacterial Adhesion, Cell Survival drug effects, Haptophyta metabolism, Haptophyta microbiology, Haptophyta physiology, Indoleacetic Acids metabolism, Rhodobacteraceae growth & development, Rhodobacteraceae metabolism, Tryptophan metabolism
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Emiliania huxleyi is a model coccolithophore micro-alga that generates vast blooms in the ocean. Bacteria are not considered among the major factors influencing coccolithophore physiology. Here we show through a laboratory model system that the bacterium Phaeobacter inhibens , a well-studied member of the Roseobacter group, intimately interacts with E. huxleyi. While attached to the algal cell, bacteria initially promote algal growth but ultimately kill their algal host. Both algal growth enhancement and algal death are driven by the bacterially-produced phytohormone indole-3-acetic acid. Bacterial production of indole-3-acetic acid and attachment to algae are significantly increased by tryptophan, which is exuded from the algal cell. Algal death triggered by bacteria involves activation of pathways unique to oxidative stress response and programmed cell death. Our observations suggest that bacteria greatly influence the physiology and metabolism of E. huxleyi. Coccolithophore-bacteria interactions should be further studied in the environment to determine whether they impact micro-algal population dynamics on a global scale., Competing Interests: JC: Reviewing editor, eLife. The other authors declare that no competing interests exist.
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- 2016
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22. Combining miR-10b-Targeted Nanotherapy with Low-Dose Doxorubicin Elicits Durable Regressions of Metastatic Breast Cancer.
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Yoo B, Kavishwar A, Ross A, Wang P, Tabassum DP, Polyak K, Barteneva N, Petkova V, Pantazopoulos P, Tena A, Moore A, and Medarova Z
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- Animals, Apoptosis genetics, Breast Neoplasms pathology, Breast Neoplasms therapy, Cell Cycle genetics, Cell Line, Tumor, Cell Movement genetics, Cell Proliferation, Disease Models, Animal, Female, Gene Knockout Techniques, Humans, Mice, Neoplasm Metastasis, Phenotype, Tumor Burden drug effects, Tumor Burden genetics, Xenograft Model Antitumor Assays, Antibiotics, Antineoplastic administration & dosage, Breast Neoplasms genetics, Doxorubicin administration & dosage, MicroRNAs genetics, Nanoparticles
- Abstract
The therapeutic promise of microRNA (miRNA) in cancer has yet to be realized. In this study, we identified and therapeutically exploited a new role for miR-10b at the metastatic site, which links its overexpression to tumor cell viability and proliferation. In the protocol developed, we combined a miR-10b-inhibitory nanodrug with low-dose anthracycline to achieve complete durable regressions of metastatic disease in a murine model of metastatic breast cancer. Mechanistic investigations suggested a potent antiproliferative, proapoptotic effect of the nanodrug in the metastatic cells, potentiated by a cell-cycle arrest produced by administration of the low-dose anthracycline. miR-10b was overexpressed specifically in cells with high metastatic potential, suggesting a role for this miRNA as a metastasis-specific therapeutic target. Taken together, our results implied the existence of pathways that regulate the viability and proliferation of tumor cells only after they have acquired the ability to grow at distant metastatic sites. As illustrated by miR-10b targeting, such metastasis-dependent apoptotic pathways would offer attractive targets for further therapeutic exploration., (©2015 American Association for Cancer Research.)
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- 2015
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23. Dysfunctional HIV-specific CD8+ T cell proliferation is associated with increased caspase-8 activity and mediated by necroptosis.
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Gaiha GD, McKim KJ, Woods M, Pertel T, Rohrbach J, Barteneva N, Chin CR, Liu D, Soghoian DZ, Cesa K, Wilton S, Waring MT, Chicoine A, Doering T, Wherry EJ, Kaufmann DE, Lichterfeld M, Brass AL, and Walker BD
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- CD8-Positive T-Lymphocytes virology, Cell Proliferation genetics, Cells, Cultured, Disease Progression, Enzyme Activation, Gene Expression Regulation, HIV Core Protein p24 immunology, Humans, Necrosis, Peptide Fragments immunology, Programmed Cell Death 1 Receptor genetics, RNA, Small Interfering genetics, Receptor-Interacting Protein Serine-Threonine Kinases genetics, Receptor-Interacting Protein Serine-Threonine Kinases metabolism, Transcriptome, Viral Load, CD8-Positive T-Lymphocytes immunology, Caspase 8 metabolism, HIV physiology, HIV Infections immunology, Programmed Cell Death 1 Receptor metabolism
- Abstract
Decreased HIV-specific CD8(+) T cell proliferation is a hallmark of chronic infection, but the mechanisms of decline are unclear. We analyzed gene expression profiles from antigen-stimulated HIV-specific CD8(+) T cells from patients with controlled and uncontrolled infection and identified caspase-8 as a correlate of dysfunctional CD8(+) T cell proliferation. Caspase-8 activity was upregulated in HIV-specific CD8(+) T cells from progressors and correlated positively with disease progression and programmed cell death-1 (PD-1) expression, but negatively with proliferation. In addition, progressor cells displayed a decreased ability to upregulate membrane-associated caspase-8 activity and increased necrotic cell death following antigenic stimulation, implicating the programmed cell death pathway necroptosis. In vitro necroptosis blockade rescued HIV-specific CD8(+) T cell proliferation in progressors, as did silencing of necroptosis mediator RIPK3. Thus, chronic stimulation leading to upregulated caspase-8 activity contributes to dysfunctional HIV-specific CD8(+) T cell proliferation through activation of necroptosis and increased cell death., (Copyright © 2014 Elsevier Inc. All rights reserved.)
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- 2014
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24. Sequence-dependent combination therapy with doxorubicin and a survivin-specific small interfering RNA nanodrug demonstrates efficacy in models of adenocarcinoma.
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Ghosh SK, Yigit MV, Uchida M, Ross AW, Barteneva N, Moore A, and Medarova Z
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- Adenocarcinoma genetics, Animals, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Cell Line, Tumor, Combined Modality Therapy methods, Female, Humans, Mice, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms genetics, Survivin, Adenocarcinoma drug therapy, Doxorubicin pharmacology, Inhibitor of Apoptosis Proteins genetics, Nanoparticles administration & dosage, RNA, Small Interfering genetics
- Abstract
The clinical management of cancer reflects a balance between treatment efficacy and toxicity. While typically, combination therapy improves response rate and time to progression compared with sequential monotherapy, it causes increased toxicity. Consequently, in cases of advanced cancer, emerging guidelines recommend sequential monotherapy, as a means to enhance quality of life. An alternative approach that could overcome nonspecific toxicity while retaining therapeutic efficacy, involves the combination of chemotherapy with targeted therapy. In the current study, we tested the hypothesis that combination therapy targeting survivin (BIRC5) and low-dose doxorubicin (Dox) will show enhanced therapeutic potential in the treatment of cancer, as compared to monotherapy with Dox. We demonstrate in both in vitro and in vivo models of breast cancer that combination therapy with a low dose of Dox and an anti-survivin siRNA nanodrug (MN-siBIRC5) is superior to mono-therapy with either low- or high-dose Dox alone. Importantly, therapeutic efficacy showed prominent sequence dependence. Induction of apoptosis was observed only when the cells were treated with Dox followed by MN-siBIRC5, whereas the reverse sequence abrogated the benefit of the drug combination. In vivo, confirmation of successful sequence dependent combination therapy was demonstrated in a murine xenograft model of breast cancer. Finally, to determine if the observed effect is not limited to breast cancer, we extended our studies to a murine xenograft model of pancreatic adenocarcinoma and found similar outcomes as shown for breast cancer., (© 2013 UICC.)
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- 2014
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25. Detection of miRNA expression in intact cells using activatable sensor oligonucleotides.
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Yoo B, Kavishwar A, Ghosh SK, Barteneva N, Yigit MV, Moore A, and Medarova Z
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- Base Pairing, Cell Line, Tumor, Cell-Free System, Flow Cytometry, Fluorescent Dyes chemistry, Humans, MicroRNAs metabolism, Microscopy, Fluorescence, Oligonucleotides chemistry, Ribonucleases metabolism, Biosensing Techniques, MicroRNAs analysis, Oligonucleotides metabolism
- Abstract
We describe a technology for the profiling of miRNA expression in intact cells. The technology is based on sensor oligonucleotides that are cleavable, completely complementary to a target miRNA, and dual-labeled with a fluorescent dye and a quencher. Upon entering the cell, the sensor oligonucleotide binds its specific miRNA target through complementary base-pairing. This triggers assembly of the endogenous RNA Induced Silencing Complex (RISC) around the miRNA-sensor duplex and cleavage of the sensor oligonucleotide, resulting in separation between the dye and quencher, and a fluorescence turn-on. In the presented feasibility studies, we focus on a specific miRNA (miR-10b) implicated in breast cancer metastasis. Using a human breast adenocarcinoma cell line, we illustrate the application of this technology for miRNA detection with nanomolar sensitivity in both a cell-free system and intact cells., (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Published
- 2014
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26. Correction: Platelets Recognize Brain-Specific Glycolipid Structures, Respond to Neurovascular Damage and Promote Neuroinflammation.
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Sotnikov I, Veremeyko T, Starossom SC, Barteneva N, Weiner HL, and Ponomarev ED
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[This corrects the article DOI: 10.1371/journal.pone.0058979.].
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- 2014
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27. Malaria-infected erythrocyte-derived microvesicles mediate cellular communication within the parasite population and with the host immune system.
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Mantel PY, Hoang AN, Goldowitz I, Potashnikova D, Hamza B, Vorobjev I, Ghiran I, Toner M, Irimia D, Ivanov AR, Barteneva N, and Marti M
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- Host-Parasite Interactions, Humans, Macrophages immunology, Neutrophils immunology, Proteome analysis, Cell Communication, Cell-Derived Microparticles chemistry, Cell-Derived Microparticles metabolism, Erythrocytes parasitology, Plasmodium falciparum growth & development, Plasmodium falciparum immunology, Signal Transduction
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Humans and mice infected with different Plasmodium strains are known to produce microvesicles derived from the infected red blood cells (RBCs), denoted RMVs. Studies in mice have shown that RMVs are elevated during infection and have proinflammatory activity. Here we present a detailed characterization of RMV composition and function in the human malaria parasite Plasmodium falciparum. Proteomics profiling revealed the enrichment of multiple host and parasite proteins, in particular of parasite antigens associated with host cell membranes and proteins involved in parasite invasion into RBCs. RMVs are quantitatively released during the asexual parasite cycle prior to parasite egress. RMVs demonstrate potent immunomodulatory properties on human primary macrophages and neutrophils. Additionally, RMVs are internalized by infected red blood cells and stimulate production of transmission stage parasites in a dose-dependent manner. Thus, RMVs mediate cellular communication within the parasite population and with the host innate immune system., (Copyright © 2013 Elsevier Inc. All rights reserved.)
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- 2013
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28. Platelets recognize brain-specific glycolipid structures, respond to neurovascular damage and promote neuroinflammation.
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Sotnikov I, Veremeyko T, Starossom SC, Barteneva N, Weiner HL, and Ponomarev ED
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- Anaphylaxis immunology, Anaphylaxis metabolism, Animals, Astrocytes immunology, Astrocytes metabolism, Biological Transport, Blood Platelets immunology, Blood-Brain Barrier metabolism, Brain immunology, Cell Degranulation, Central Nervous System immunology, Central Nervous System metabolism, Cerebrovascular Disorders immunology, Cerebrovascular Disorders metabolism, Disease Models, Animal, Encephalomyelitis, Autoimmune, Experimental immunology, Encephalomyelitis, Autoimmune, Experimental metabolism, Gangliosides immunology, Glycolipids immunology, Inflammation immunology, Inflammation metabolism, Membrane Microdomains chemistry, Membrane Microdomains immunology, Mice, Neurons immunology, Neurons metabolism, Protein Binding, Receptors, Cell Surface metabolism, Blood Platelets metabolism, Brain metabolism, Glycolipids metabolism, Membrane Microdomains metabolism
- Abstract
Platelets respond to vascular damage and contribute to inflammation, but their role in the neurodegenerative diseases is unknown. We found that the systemic administration of brain lipid rafts induced a massive platelet activation and degranulation resulting in a life-threatening anaphylactic-like response in mice. Platelets were engaged by the sialated glycosphingolipids (gangliosides) integrated in the rigid structures of astroglial and neuronal lipid rafts. The brain-abundant gangliosides GT1b and GQ1b were specifically recognized by the platelets and this recognition involved multiple receptors with P-selectin (CD62P) playing the central role. During the neuroinflammation, platelets accumulated in the central nervous system parenchyma, acquired an activated phenotype and secreted proinflammatory factors, thereby triggering immune response cascades. This study determines a new role of platelets which directly recognize a neuronal damage and communicate with the cells of the immune system in the pathogenesis of neurodegenerative diseases.
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- 2013
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29. MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-α-PU.1 pathway.
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Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, and Weiner HL
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- Animals, Brain physiology, Encephalomyelitis, Autoimmune, Experimental genetics, Encephalomyelitis, Autoimmune, Experimental physiopathology, Homeostasis, Humans, Inflammation genetics, Inflammation physiopathology, Macrophages physiology, Mice, Monocytes physiology, Neurons physiology, Rats, CCAAT-Enhancer-Binding Proteins physiology, MicroRNAs genetics, MicroRNAs physiology, Microglia physiology
- Abstract
MicroRNAs are a family of regulatory molecules involved in many physiological processes, including differentiation and activation of cells of the immune system. We found that brain-specific miR-124 is expressed in microglia but not in peripheral monocytes or macrophages. When overexpressed in macrophages, miR-124 directly inhibited the transcription factor CCAAT/enhancer-binding protein-α (C/EBP-α) and its downstream target PU.1, resulting in transformation of these cells from an activated phenotype into a quiescent CD45(low), major histocompatibility complex (MHC) class II(low) phenotype resembling resting microglia. During experimental autoimmune encephalomyelitis (EAE), miR-124 was downregulated in activated microglia. Peripheral administration of miR-124 in EAE caused systemic deactivation of macrophages, reduced activation of myelin-specific T cells and marked suppression of disease. Conversely, knockdown of miR-124 in microglia and macrophages resulted in activation of these cells in vitro and in vivo. These findings identify miR-124 both as a key regulator of microglia quiescence in the central nervous system and as a previously unknown modulator of monocyte and macrophage activation.
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- 2011
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30. [Applications of fluorescent semiconductor nanocrystals in microscopy and cytometry].
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Vorob'ev IA, Rafalovskaia-Orlovskaia EP, Gladkikh AA, Potashnikova DM, and Barteneva NS
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- Animals, Cadmium Compounds chemistry, Flow Cytometry instrumentation, Fluorescent Dyes analysis, Fluorescent Dyes chemical synthesis, Humans, Immunoconjugates chemistry, Immunoconjugates immunology, Immunohistochemistry instrumentation, Immunohistochemistry methods, Microscopy, Fluorescence instrumentation, Nanostructures analysis, Nanostructures ultrastructure, Polyethylene Glycols chemistry, Selenium Compounds chemistry, Sulfides chemistry, Zinc Compounds chemistry, Flow Cytometry methods, Microscopy, Fluorescence methods, Quantum Dots
- Abstract
Quantum dots (QD) nanocrystals consisting of CdSe core with ZnS shell are a novel class of fluorophores with tremendous potential in microscopy and cytometry techniques. The unique optical features of Qdots, namely, high photostability and extinction coefficient, wide absorption and narrow emission spectra, and large Stokes shift make them desirable fluorescent tags for diverse biomedical applications. Applications of this novel technology in microscopy and cytometry produce reliable multicolor specimens due to increased photostability, ability for multiplexing and narrow emission spectra of nanocrystals. QD conjugates are available on the market and could be prepared in the laboratory. This paper describes the application of QD-conjugates for immunophenotyping and FISH assessment of cells and tissues, and the requirements for microscope and flow cytometer reengineering for successful use of QD in multiplex fluorescent format. Despite the considerable progress, important methodological issues still need to be solved in terms of QD nanocrystals' size, heterogeneity, functionalization and stability of their conjugates. We discuss practical approaches and challenges that need to be addressed to make QD immunostaining a standard method in biology.
- Published
- 2011
31. Cytokine signaling in the human brain capillary endothelial cell line hCMEC/D3.
- Author
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Fasler-Kan E, Suenderhauf C, Barteneva N, Poller B, Gygax D, and Huwyler J
- Subjects
- Blood-Brain Barrier immunology, Cell Line, Cell Proliferation, Cells, Cultured, Cytokines immunology, Endothelial Cells immunology, Endothelium, Vascular immunology, Flow Cytometry, Fluorescent Antibody Technique, Humans, Janus Kinases immunology, Janus Kinases metabolism, Microscopy, Confocal, Protein Transport immunology, STAT Transcription Factors immunology, STAT Transcription Factors metabolism, Blood-Brain Barrier metabolism, Cytokines metabolism, Endothelial Cells metabolism, Endothelium, Vascular metabolism, Signal Transduction immunology
- Abstract
Brain microvascular endothelial cells are part of the blood-brain barrier and participate actively in immunological processes including cytokine-mediated inflammatory reactions. Using the human brain capillary endothelial cell line hCMEC/D3, activation of JAK/STAT signaling pathways were studied in response to stimulation by cytokines. The phenotype of hCMEC/D3 cells was confirmed by flow cytometry analysis of cell adhesion factors (cluster of differentiation molecules CD31 and CD34) and the von Willebrand factor endothelial marker was detected by immunofluorescence. Strong STAT1, STAT6 and STAT3 activation was observed in response to interferon-gamma (IFN-gamma), interleukin 4 (IL-4) and interleukin 6 (IL-6), respectively. Nuclear translocation of phosphorylated STAT proteins was visualized by confocal microscopy. Treatment of hCMEC/D3 cells with IFN-gamma resulted in interferon-induced upregulation of major histocompatibility complex (MHC) class I within 48h. Interferon-alpha (IFN-alpha) did not activate STAT1 or STAT3 nor did it induce MHC class I upregulation. Therefore, hCMEC/D3 cells were judged to be non-responsive to IFN-alpha. We also observed that hCMEC/D3 cells exhibit functional expression of alternative cytokine signal transduction pathways (i.e. TNF-alpha mediated activation of NF-kappaB). Together these results indicate that human blood-brain barrier hCMEC/D3 cells are responsive towards stimulation with various cytokines. We conclude that this unique cell line can be used to explore in vitro human blood-brain barrier functionality under proinflammatory conditions., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)
- Published
- 2010
- Full Text
- View/download PDF
32. Unique biological properties of catalytic domain directed human anti-CAIX antibodies discovered through phage-display technology.
- Author
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Xu C, Lo A, Yammanuru A, Tallarico AS, Brady K, Murakami A, Barteneva N, Zhu Q, and Marasco WA
- Subjects
- Biomarkers, Tumor, Biotinylation, Carbonic Anhydrase IX, Carcinoma, Renal Cell metabolism, Catalytic Domain, Endosomes metabolism, Epitope Mapping methods, Humans, Immunotherapy methods, Kidney Neoplasms metabolism, Kinetics, Peptide Library, Signal Transduction, Surface Plasmon Resonance, Antibodies, Monoclonal chemistry, Antigens, Neoplasm immunology, Antigens, Neoplasm metabolism, Carbonic Anhydrases immunology, Carbonic Anhydrases metabolism
- Abstract
Carbonic anhydrase IX (CAIX, gene G250/MN-encoded transmembrane protein) is highly expressed in various human epithelial tumors such as renal clear cell carcinoma (RCC), but absent from the corresponding normal tissues. Besides the CA signal transduction activity, CAIX may serve as a biomarker in early stages of oncogenesis and also as a reliable marker of hypoxia, which is associated with tumor resistance to chemotherapy and radiotherapy. Although results from preclinical and clinical studies have shown CAIX as a promising target for detection and therapy for RCC, only a limited number of murine monoclonal antibodies (mAbs) and one humanized mAb are available for clinical testing and development. In this study, paramagnetic proteoliposomes of CAIX (CAIX-PMPLs) were constructed and used for anti-CAIX antibody selection from our 27 billion human single-chain antibody (scFv) phage display libraries. A panel of thirteen human scFvs that specifically recognize CAIX expressed on cell surface was identified, epitope mapped primarily to the CA domain, and affinity-binding constants (KD) determined. These human anti-CAIX mAbs are diverse in their functions including induction of surface CAIX internalization into endosomes and inhibition of the carbonic anhydrase activity, the latter being a unique feature that has not been previously reported for anti-CAIX antibodies. These human anti-CAIX antibodies are important reagents for development of new immunotherapies and diagnostic tools for RCC treatment as well as extending our knowledge on the basic structure-function relationships of the CAIX molecule.
- Published
- 2010
- Full Text
- View/download PDF
33. Numbers matter: quantitative and dynamic analysis of the formation of an immunological synapse using imaging flow cytometry.
- Author
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Ahmed F, Friend S, George TC, Barteneva N, and Lieberman J
- Subjects
- CD3 Complex metabolism, Cells, Cultured, Coculture Techniques, Humans, Image Processing, Computer-Assisted, Kinetics, Lymphocyte Specific Protein Tyrosine Kinase p56(lck) metabolism, Protein Transport, Antigen-Presenting Cells immunology, CD8-Positive T-Lymphocytes immunology, Flow Cytometry, Image Cytometry, Immunological Synapses, Lymphocyte Activation, Macrophages immunology, Signal Transduction
- Abstract
Activation of T lymphocytes by antigen-presenting cells (APC) results in the formation of an immunological synapse. Following contact with the target cell, key signaling and adhesion molecules polarize within minutes to hours to the T cell-APC interface. Multispectral imaging flow cytometry, a new technology which combines flow cytometry with imaging, was used to visualize and quantify the recruitment of the CD3epsilon and Lck signaling molecules during the evolution of an immune synapse. Using this technology, thousands of T cell/macrophage conjugates could be analyzed for each experimental time point. Following Ca++ triggered T cell activation, the dynamics of Lck and CD3epsilon recruitment to the synapse, analyzed by two independent methods, were comparable. However, CD3epsilon exhibited longer residence times (>8 min) at the synapse than Lck.
- Published
- 2009
- Full Text
- View/download PDF
34. Analysis of neuropeptide expression and localization in adult drosophila melanogaster central nervous system by affinity cell-capture mass spectrometry.
- Author
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Yew JY, Wang Y, Barteneva N, Dikler S, Kutz-Naber KK, Li L, and Kravitz EA
- Subjects
- Amino Acid Sequence, Animals, Brain ultrastructure, Central Nervous System metabolism, Central Nervous System ultrastructure, Molecular Sequence Data, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Brain metabolism, Drosophila melanogaster metabolism, Neuropeptides metabolism
- Abstract
A combined approach using mass spectrometry, a novel neuron affinity capture technique, and Drosophila melanogaster genetic manipulation has been developed to characterize the expression and localization of neuropeptides in the adult D. melanogaster brain. In extract from the whole adult brain, 42 neuropeptides from 18 peptide families were sequenced. Neuropeptide profiling also was performed on targeted populations of cells which were enriched with immunoaffinity purification using a genetically expressed marker.
- Published
- 2009
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- View/download PDF
35. Multifunctional magnetic nanocarriers for image-tagged SiRNA delivery to intact pancreatic islets.
- Author
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Medarova Z, Kumar M, Ng SW, Yang J, Barteneva N, Evgenov NV, Petkova V, and Moore A
- Subjects
- Animals, Diabetes Mellitus therapy, Ferric Compounds, Gene Expression Regulation, Genetic Therapy methods, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Islets of Langerhans Transplantation, Magnetic Resonance Imaging, Magnetics, Mice, Mice, Transgenic, Models, Animal, RNA Interference, Reproducibility of Results, Drug Delivery Systems methods, Islets of Langerhans metabolism, Islets of Langerhans pathology, Nanoparticles administration & dosage, RNA, Small Interfering administration & dosage
- Abstract
Background: With the ultimate hope of finding a cure for diabetes, researches are looking into altering the genetic profile of the beta cell as a way to manage metabolic dysregulation. One of the most powerful new approaches for the directed regulation of gene expression uses the phenomenon of RNA interference., Methods: Here, we establish the feasibility of a novel technology centered around multifunctional magnetic nanocarriers, which concurrently deliver siRNA to intact pancreatic islets and can be detected by magnetic resonance and optical imaging., Results: In the proof-of-principle studies described here, we demonstrate that, after in vitro incubation, magnetic nanoparticles carrying siRNA designed to target the model gene for enhanced green fluorescent protein are efficiently taken up by murine pancreatic islets, derived from egfp transgenic animals. This uptake can be visualized by magnetic resonance imaging and near-infrared fluorescence optical imaging and results in suppression of the target gene., Conclusions: These results illustrate the value of our approach in overcoming the challenges associated with genetic modification of intact pancreatic islets in a clinically acceptable manner. Furthermore, an added advantage of our technology derives from the combined capability of our magnetic nanoparticles for siRNA delivery and magnetic labeling of pancreatic islets.
- Published
- 2008
- Full Text
- View/download PDF
36. Chemogenomics and parasitology: small molecules and cell-based assays to study infectious processes.
- Author
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Muskavitch MA, Barteneva N, and Gubbels MJ
- Subjects
- Animals, Combinatorial Chemistry Techniques methods, Humans, Malaria drug therapy, Toxoplasmosis drug therapy, Trypanosomiasis drug therapy, Chemistry, Pharmaceutical, Genomics, Malaria parasitology, Toxoplasmosis parasitology, Trypanosomiasis parasitology
- Abstract
Infectious diseases caused by protozoan parasites--malaria, sleeping sickness, leishmaniasis, Chagas' disease, toxoplasmosis--remain chronic problems for humanity. We lack vaccines and have limited drug options effective against protozoa. Research into anti-protozoan drugs has accelerated with improved in vitro cultivation methods, enhanced genetic accessibility, completed genome sequences for key protozoa, and increased prominence of protozoan diseases on the agendas of well-resourced public figures and foundations. Concurrent advances in high-throughput screening (HTS) technologies and availability of diverse small molecule libraries offer the promise of accelerated discovery of new drug targets and new drugs that will reduce disease burdens imposed on humanity by parasitic protozoa. We provide a status report on HTS technologies in hand and cell-based assays under development for biological investigations and drug discovery directed toward the three best-characterized parasitic protozoa: Trypanosoma brucei, Plasmodium falciparum, and Toxoplasma gondii. We emphasize cell growth assays and new insights into parasite cell biology speeding development of better cell-based assays, useful in primary screens for anti-protozoan drug leads and secondary screens to decipher mechanisms of action of leads identified in growth assays. Small molecules that interfere with specific aspects of protozoan biology, identified in such screens, will be valuable tools for dissecting parasite cell biology and developing anti-protozoan drugs. We discuss potential impacts on drug development of new consortia among academic, corporate, and public partners committed to discovery of new, effective anti-protozoan drugs.
- Published
- 2008
- Full Text
- View/download PDF
37. IL-13 induces the expression of the alternative activation marker Ym1 in a subset of testicular macrophages.
- Author
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Maresz K, Ponomarev ED, Barteneva N, Tan Y, Mann MK, and Dittel BN
- Subjects
- Animals, Interleukin-4 immunology, Interleukin-4 metabolism, Lectins immunology, Liver cytology, Liver immunology, Liver metabolism, Lung cytology, Lung immunology, Lung metabolism, Macrophages metabolism, Male, Mice, Mice, Inbred Strains, Mice, Knockout, Receptors, Interleukin-13 immunology, Testis cytology, Testis metabolism, beta-N-Acetylhexosaminidases immunology, Interleukin-13 immunology, Lectins metabolism, Macrophage Activation, Macrophages immunology, Receptors, Interleukin-13 metabolism, Testis immunology, beta-N-Acetylhexosaminidases metabolism
- Abstract
Macrophages are thought to play an important role in the maintenance of immune privilege in the testis, which functions to prevent immune responses to developing sperm. Two populations of macrophages are known to exist in the testis, one of which exhibits immunosuppressive activity. Macrophages that are alternatively activated with either IL-4 or IL-13 have been shown to be anti-inflammatory and promote wound healing. Expression of the Ym1 protein is an established marker of alternatively activated macrophages. Testicular macrophages were examined for expression of Ym1 protein, and it was found to be highly expressed in a subpopulation of CD11b(+) cells. Furthermore, we have shown that Ym1 protein expression in the testis is dependent upon IL-13R signaling, and that IL-13 is produced in the testis. These data suggest that IL-13 plays a role in testicular immune privilege by the maintenance of an alternatively activated macrophage population.
- Published
- 2008
- Full Text
- View/download PDF
38. Possible role of natural killer cells in pemphigus vulgaris - preliminary observations.
- Author
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Stern JN, Keskin DB, Barteneva N, Zuniga J, Yunis EJ, and Ahmed AR
- Subjects
- Aged, Antigen Presentation immunology, Antigens, CD blood, B7 Antigens, CD4-Positive T-Lymphocytes immunology, Cell Proliferation, Coculture Techniques, Cytokines biosynthesis, Desmoglein 3 immunology, Female, Histocompatibility Antigens Class II blood, Humans, Lymphocyte Activation immunology, Male, Middle Aged, Receptors, Immunologic blood, Skin immunology, Killer Cells, Natural immunology, Pemphigus immunology
- Abstract
Pemphigus vulgaris (PV) is an autoimmune blistering disease that affects the skin and multiple mucous membranes, and is caused by antibodies to desmoglein (Dsg) 1 and 3. Natural killer (NK) cells have a role in autoimmunity, but their role in PV is not known. NK cells in the peripheral blood leucocytes (PBL) of 15 untreated Caucasian patients with active PV were studied and compared with healthy controls for the expression of major histocompatibility complex (MHC) class II and co-stimulatory molecules. CD56+ CD16- CD3- NK or CD56+ CD16+ CD3- NK cells from the PBL of PV patients co-express MHC class II and co-stimulatory molecule B7-H3 without exogenous stimulation. CD4+ T cells from the PBL and perilesional skin of PV patients were co-cultured with CD56+ CD3- NK cells from the PBL of the same patients; in the presence of Dsg3 peptides underwent statistically significant proliferation, indicating that NK cells functioned as antigen-presenting cells. Supernatants from these co-cultures and serum of the same patients with active PV had statistically significantly elevated levels of interleukin (IL)-6, IL-8 and interferon-gamma, compared with controls indicating that the NK cells stimulated CD4+ T cells to produce proinflammatory cytokines. In these experiments, we present preliminary evidence that NK cells may play a role in the pathobiology of PV.
- Published
- 2008
- Full Text
- View/download PDF
39. Yin Yang 1 is a critical regulator of B-cell development.
- Author
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Liu H, Schmidt-Supprian M, Shi Y, Hobeika E, Barteneva N, Jumaa H, Pelanda R, Reth M, Skok J, Rajewsky K, and Shi Y
- Subjects
- Animals, Cell Differentiation physiology, Chromatin genetics, Chromatin Immunoprecipitation, Flow Cytometry, Gene Rearrangement, B-Lymphocyte physiology, Immunoglobulin Heavy Chains physiology, In Situ Hybridization, Fluorescence, Mice, PAX5 Transcription Factor genetics, Reverse Transcriptase Polymerase Chain Reaction, YY1 Transcription Factor metabolism, B-Lymphocytes physiology, Gene Expression Regulation, Gene Rearrangement, B-Lymphocyte genetics, Immunoglobulin Heavy Chains genetics, YY1 Transcription Factor genetics
- Abstract
The role of the transcription factor Yin Yang 1 (YY1) in development is largely unknown. Here we show that specific ablation of YY1 in mouse B cells caused a defect in somatic rearrangement in the immunoglobulin heavy-chain (IgH) locus and a block in the progenitor-B-to-precursor-B-cell transition, which was partially rescued by a prerearranged IgH transgene. Three-dimensional DNA fluorescence in situ hybridization analysis revealed an important function for YY1 in IgH locus contraction, a process indispensable for distal V(H) to D(H)J(H) recombination. We provide evidence that YY1 binds the intronic Ei mu enhancer within the IgH locus, consistent with a direct role for YY1 in V(H)D(H)J(H) recombination. These findings identified YY1 as a critical regulator of early B-cell development.
- Published
- 2007
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- View/download PDF
40. Use of molecular modeling and site-directed mutagenesis to define the structural basis for the immune response to carbohydrate xenoantigens.
- Author
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Kearns-Jonker M, Barteneva N, Mencel R, Hussain N, Shulkin I, Xu A, Yew M, and Cramer DV
- Subjects
- Animals, Antibodies, Heterophile genetics, Antigens, Heterophile immunology, Carbohydrates immunology, Cells, Cultured, Epitopes chemistry, Epitopes immunology, Humans, Molecular Sequence Data, Swine, Antibodies, Heterophile chemistry, Antigens, Heterophile chemistry, Carbohydrates chemistry, Models, Molecular, Mutagenesis, Site-Directed
- Abstract
Background: Natural antibodies directed at carbohydrates reject porcine xenografts. They are initially expressed in germline configuration and are encoded by a small number of structurally-related germline progenitors. The transplantation of genetically-modified pig organs prevents hyperacute rejection, but delayed graft rejection still occurs, partly due to humoral responses. IgVH genes encoding induced xenoantibodies are predominantly, not exclusively, derived from germline progenitors in the VH3 family. We have previously identified the immunoglobulin heavy chain genes encoding VH3 xenoantibodies in patients and primates. In this manuscript, we complete the structural analysis of induced xenoantibodies by identifying the IgVH genes encoding the small proportion of VH4 xenoantibodies and the germline progenitors encoding xenoantibody light chains. This information has been used to define the xenoantibody/carbohydrate binding site using computer-simulated modeling., Results: The VH4-59 gene encodes antibodies in the VH4 family that are induced in human patients mounting active xenoantibody responses. The light chain of xenoantibodies is encoded by DPK5 and HSIGKV134. The structural information obtained by sequencing analysis was used to create computer-simulated models. Key contact sites for xenoantibody/carbohydrate interaction for VH3 family xenoantibodies include amino acids in sites 31, 33, 50, 57, 58 and the CDR3 region of the IgVH gene. Site-directed mutagenesis indicates that mutations in predicted contact sites alter binding to carbohydrate xenoantigens. Computer-simulated modeling suggests that the CDR3 region directly influences binding., Conclusion: Xenoantibodies induced during early and delayed xenograft responses are predominantly encoded by genes in the VH3 family, with a small proportion encoded by VH4 germline progenitors. This restricted group can be identified by the unique canonical structure of the light chain, heavy chain and CDR3. Computer-simulated models depict this structure with accuracy, as confirmed by site-directed mutagenesis. Computer-simulated drug design using computer-simulated models may now be applied to develop new drugs that may enhance the survival of xenografted organs.
- Published
- 2007
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41. Vascular endothelial cell apoptosis induced by anti-donor non-MHC antibodies: a possible injury pathway contributing to chronic allograft rejection.
- Author
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Wu GD, Jin YS, Salazar R, Dai WD, Barteneva N, Barr ML, Barsky LW, Starnes VA, and Cramer DV
- Subjects
- Animals, Cytotoxicity Tests, Immunologic, Endothelium, Vascular cytology, Flow Cytometry, Immunoglobulin G immunology, Immunohistochemistry, In Situ Nick-End Labeling, Male, Rats, Rats, Inbred F344, Rats, Inbred Lew, Transplantation, Homologous, Apoptosis immunology, Endothelium, Vascular immunology, Graft Rejection immunology, Heart Transplantation immunology, Isoantibodies blood
- Abstract
Background: Non-major histocompatibility complex (non-MHC) alloantibodies may play a pathogenic role in chronic rejection but remain poorly characterized., Methods: The kinetics of alloantibody production and the mechanism by which non-MHC alloantibodies cause graft injury were investigated in a Lewis-to-Fischer 344 (LEW-to-F344) rat model of cardiac transplantation., Results: Flow cytometry detected that all the F344 recipients of LEW allografts produced anti-donor immunoglobulin G (IgG) antibodies reactive with LEW lymphocytes and endothelial cells. A sub-group of recipients that rejected their grafts in 30 to 60 days exhibited markedly increased levels of anti-donor IgG antibodies (n = 6, mean fluorescence intensity [MFI]:23.85 +/- 2.7) than recipients with long-surviving allografts (n = 4, MFI:11.23 +/- 0.81; p = 0.00058). Passive transfer of anti-donor sera induced chronic rejection of LEW heart allografts in an immune non-responsiveness model of F344 rats induced by intrathymic inoculation of donor-specific lymphocytes. Immunoglobulin G antibodies purified from the anti-LEW sera exhibited complement-dependent cytotoxicity against LEW vascular endothelial cells in flow-cytometric cytotoxicity assay. The targeted endothelial cells displayed early (annexin V+) and late (TUNEL+) evidence for programmed cell death. Western blot analysis of poly (ADP-ribose) polymerase (PARP) demonstrated that the 25-kD PARP-cleavage fragment was present at the lysates of the vascular endothelial cells treated with anti-donor IgG antibodies, indicating apoptosis-associated caspase activity in these cells. In situ teminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining demonstrated that vascular endothelial cell apoptosis was consistently present in all LEW heart allografts with chronic rejection., Conclusions: Non-MHC alloantibodies are pathogenic and capable of causing chronic graft injury through an antibody-induced cell apoptosis mechanism. The results emphasize the importance of non-MHC antibodies as a common predisposing factor in the development of chronic rejection.
- Published
- 2002
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- View/download PDF
42. A modified PCR-based method for rapid non-radioactive detection of clinically important pathogens.
- Author
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Gorelov VN, Dumon K, Barteneva NS, Röher HD, and Goretzki PE
- Subjects
- Bacterial Infections urine, DNA, Bacterial genetics, DNA, Bacterial isolation & purification, Humans, Methicillin Resistance, Mucus microbiology, Pseudomonas aeruginosa isolation & purification, Reproducibility of Results, Sputum microbiology, Staphylococcus aureus isolation & purification, Streptococcus pneumoniae isolation & purification, Bacteria isolation & purification, Bacterial Infections microbiology, Polymerase Chain Reaction methods
- Abstract
We have devised a sensitive and rapid method for the detection of several bacterial pathogens in clinical specimens using PCR. This method has been named Direct Labeling and Detection Procedure (DLDP) and is based on the direct incorporation of a nonradioactive digoxigenin label (DIG-11-dUTP) into a microbial species-specific gene fragment during amplification. Following amplification, the resulting PCR products are cleansed of nonincorporated DIG-11-dUTP, spotted onto a nylon membrane, fixed by UV-crosslinking and the labeled DNA is visualized by digoxigenin detection reagents. Using cultivated reference bacteria (Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa) we were able to demonstrate a rapid and sensitive detection of < 20 CFU of bacteria in human secretions (sputum, urine, mucous). The present study suggests that DLDP can be used as a reliable method for indication of bacteria in clinical or environmental specimens with the proviso that the selected corresponding oligonucleotide primers provide amplification of strong species-specific genes.
- Published
- 1996
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- View/download PDF
43. Overexpression of Gs alpha subunit in thyroid tumors bearing a mutated Gs alpha gene.
- Author
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Gorelov VN, Dumon K, Barteneva NS, Palm D, Röher HD, and Goretzki PE
- Subjects
- Amino Acid Sequence, Animals, Antibody Specificity, Cell Membrane chemistry, Codon, GTP-Binding Proteins biosynthesis, GTP-Binding Proteins immunology, Gene Expression, Humans, Immunoblotting, Macromolecular Substances, Molecular Sequence Data, Peptide Fragments immunology, Rabbits, Subcellular Fractions, Thyroid Gland metabolism, Thyroid Gland physiology, Thyroid Neoplasms metabolism, Carcinoma, Papillary genetics, Carcinoma, Papillary, Follicular genetics, GTP-Binding Proteins genetics, Point Mutation, Thyroid Neoplasms genetics
- Abstract
Point mutations occurring at codon 201 of the gene coding for the alpha subunit of the stimulatory G protein impair intrinsic GTPase activity and lead to a constitutive activation of adenylate cyclase. We have examined thyroid follicular and papillary carcinomas and follicular adenomas and found samples that bear this mutation at codon 201 of the Gs alpha gene. Both mutation-positive and mutation-negative tissue samples were investigated for the level of Gs alpha expression relative to a pool of normal thyroid tissue, using immunoblotting against two (mid-region-specific and C-end-specific) antipeptide antibodies. Using 8000 g and 100,000 g membrane fractions of homogenized tissues we have demonstrated that the Gs alpha proteins in normal ad neoplastic thyroid tissues are represented by three isoforms: 43 kDa, 45 kDa and 52 kDa. We have quantified and compared the amount of Gs alpha protein and find it is overexpressed in mutation-bearing tissue samples.
- Published
- 1995
- Full Text
- View/download PDF
44. [The role of a plasmid with a molecular weight of 82 MD in the modulation of the action of Yersinia pseudotuberculosis on the proliferative activity of murine lymphoid cells].
- Author
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Volkov LV, Barteneva NS, Pronin AV, Markov AP, Fil'kova SL, Sanin AV, and Smirnov GB
- Subjects
- Animals, Gene Expression, Genes, Bacterial, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred CBA, Mitogens, Molecular Weight, Virulence genetics, Yersinia pseudotuberculosis pathogenicity, Cell Division, Lymphoid Tissue cytology, Plasmids, Yersinia pseudotuberculosis genetics
- Published
- 1991
45. On the possible role of I-J+ suppressor cells in murine hematopoiesis.
- Author
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Sanin AV, Sosnovskaya OYu, Barteneva NS, and Pronin AV
- Subjects
- Animals, Bone Marrow immunology, Bone Marrow Cells, Cells, Cultured, Colony-Forming Units Assay, Complement System Proteins pharmacology, Epitopes physiology, Haplotypes, Hematopoietic Stem Cells immunology, Immune Sera, Mice, Mice, Inbred Strains, Species Specificity, Spleen cytology, Spleen immunology, Thymus Gland cytology, Thymus Gland immunology, Hematopoiesis immunology, Hematopoietic Stem Cells cytology, Histocompatibility Antigens Class II physiology, T-Lymphocytes, Regulatory physiology
- Published
- 1991
- Full Text
- View/download PDF
46. Molecular biology of Yersinia pseudotuberculosis large plasmid pVM82.
- Author
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Smirnov GB, Shubin FN, Ginzburg AL, Shovadaeva G, Shaginyan IA, Ilyna TS, Markov AP, Pokrovskaya MS, Sever IS, and Barteneva NS
- Subjects
- Humans, Yersinia pseudotuberculosis Infections genetics, Yersinia pseudotuberculosis Infections microbiology, Plasmids genetics, Yersinia pseudotuberculosis genetics
- Published
- 1991
47. [A new inducer of immune interferon in human leukocytes--the organogermanium compound MOP-11].
- Author
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Khusainov RM, Ignatenko MA, Gritsenko LI, Frolova IS, Babaiants AA, Kuznetsov VP, Amchenkova AM, Narovlianskiĭ AN, Pokidysheva LN, and Barteneva NS
- Subjects
- Cells, Cultured drug effects, Cells, Cultured immunology, Cytopathogenic Effect, Viral drug effects, Dose-Response Relationship, Drug, Enterotoxins pharmacology, Humans, Interferon-gamma biosynthesis, Interferon-gamma blood, Leukocytes immunology, Staphylococcus aureus, Vesicular stomatitis Indiana virus, Germanium pharmacology, Interferon Inducers pharmacology, Interferon-gamma drug effects, Leukocytes drug effects, Organometallic Compounds pharmacology
- Published
- 1991
48. [Effect of the lymphocytosis-stimulating factor from Bordetella pertussis on murine lymphoid and hemopoietic cells].
- Author
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Gureeva AA, Sanin AV, Rybin VO, Barteneva NS, and Lapaeva IA
- Subjects
- Animals, Bone Marrow drug effects, Bone Marrow radiation effects, Bone Marrow Transplantation, Cell Count drug effects, Cell Count radiation effects, Colony-Forming Units Assay, Hematopoietic Stem Cells radiation effects, Interphase drug effects, Interphase radiation effects, Lymphocytes radiation effects, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Spleen drug effects, Spleen radiation effects, Spleen transplantation, Thymus Gland drug effects, Thymus Gland radiation effects, Time Factors, Virulence Factors, Bordetella isolation & purification, Hematopoietic Stem Cells drug effects, Lymphocytes drug effects, Pertussis Toxin, Virulence Factors, Bordetella pharmacology
- Abstract
Effect of B. pertussis lymphocytosis-promoting factor (LPF) on the lympho-hematopoietic system of mice was studied. The injection of LPF was shown to sharply enhance endogenous colony formation and to induce a severe depletion of thymus cells, reaching its maximum of day 4. Thymocytes obtained on day 2 or 3 after the injection of LPF produced a suppressive effect on endogenous colony formation. The proliferative activity of hematopoietic stem cells sharply increased under the influence of LPF, though it had no radioprotective action. On the following day after the injection of LPF a steep rise in the number of hematopoietic stem cells was observed in the blood of mice: their content increased 20-fold in comparison with the control level. These data may be important for the evaluation of the side effects of pertussis vaccine on the lympho-hematopoietic system.
- Published
- 1986
49. [Stimulation of postradiation regeneration of erythropoiesis in mice with Bordetells pertussis vaccine].
- Author
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Khorobrykh VV, Sanin AV, Barteneva NS, and Snegireva AE
- Subjects
- Animals, Erythropoiesis radiation effects, Leukemia, Experimental physiopathology, Male, Mice, Mice, Inbred BALB C, Mice, Inbred CBA, Rauscher Virus, Erythropoiesis drug effects, Pertussis Vaccine administration & dosage, Radiation Injuries, Experimental physiopathology
- Abstract
Inoculation into mice of killed B. pertussis vaccine (10(10) microbial cells) one day before their sublethal irradiation (6.0 Gy) was accompanied by accelerated regeneration of erythropoiesis in the bone marrow, particularly in the spleen as was judged by the 59Fe incorporation. B. pertussis also induced an increase in endocolonization when inoculated 4-5 days after irradiation. The latter suggests a possible effect of vaccine on the hematopoietic cells, less differentiated than erythropoietin-sensitive cells (ESC), inasmuch the sensitivity of the ESC to erythropoietin commonly appeared at the later stages. When B. pertussis was inoculated into BALB/c mice one day before their infection by Rauscher's leukemia virus noticeable activation of leukemogenicity was observed. It is believed that the reason for this is the stimulation of erythroid target cells for the virus after B. pertussis vaccination. The data obtained indicate that B. pertussis vaccine activates erythropoiesis in both normal and irradiated mice.
- Published
- 1983
50. [Action of Bordetella pertussis vaccine on mouse hematopoietic stem cells].
- Author
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Khorobrykh VV, Barteneva NS, Sanin AV, and Snegireva AE
- Subjects
- Animals, Colony-Forming Units Assay, Dose-Response Relationship, Immunologic, Hematopoietic Stem Cells immunology, Immunization, Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Time Factors, Hematopoietic Stem Cells drug effects, Pertussis Vaccine immunology
- Abstract
Intravenous inoculation of killed Bordetella pertussis vaccine into BALB/c, CBA, C57Bl/6 mice or (CBA x C57Bl/6) F2 hybrids 1 day or 3 days before sublethal irradiation (5.5 Gy) was shown to sharply increase the endogenous colony formation in the spleen 9 days after irradiation. Moreover, the CFUs content of the spleen and bone marrow was also enhanced 1 and 3 days after vaccination of the mice with 10(10) cells B. pertussis as revealed by the exocolonization technique (Till and McCulloch). Thus, a single injection of B. pertussis vaccine hastened the hematopoietic recovery after irradiation.
- Published
- 1982
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