26 results on '"Zohreh Naghashfar"'
Search Results
2. Data from Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells
- Author
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Herbert C. Morse, Siegfried Janz, Wendy F. Davidson, Derry C. Roopenian, Janet W. Hartley, Torgny N. Fredrickson, Alexander L. Kovalchuk, Shao Xiang, Zohreh Naghashfar, Chang Hoon Lee, Jeff X. Zhou, and Chen-Feng Qi
- Abstract
We have compared histologic features and gene expression profiles of newly identified plasmacytomas from NFS.V+ congenic mice with plasmacytomas of IL6 transgenic, Fasl mutant, and SJL-β2M−/− mice. NFS.V+ tumors comprised an overlapping morphologic spectrum of high-grade/anaplastic, intermediate-grade/plasmablastic, and low-grade/plasmacytic cases with similarities to subsets of human multiple myeloma and plasmacytoma. Microarray and immunohistochemical analyses of genes expressed by the most prevalent tumors, plasmablastic plasmacytomas, showed them to be most closely related to immunoblastic lymphomas, less so to plasmacytomas of Fasl mutant and SJL mice, and least to plasmacytic plasmacytomas of IL6 transgenic mice. Plasmablastic tumors seemed to develop in an inflammatory environment associated with gene signatures of T cells, natural killer cells, and macrophages not seen with plasmacytic plasmacytomas. Plasmablastic plasmacytomas from NFS.V+ and SJL-β2M−/− mice did not have structural alterations in Myc or T(12;15) translocations and did not express Myc at high levels, regular features of transgenic and pristane-induced plasmacytomas. These findings imply that, as for human multiple myeloma, Myc-independent routes of transformation contribute to the pathogenesis of these tumors. These findings suggest that plasma cell neoplasms of mice and humans exhibit similar degrees of complexity. Mouse plasmacytomas, previously considered to be homogeneous, may thus be as diverse as their human counterparts with respect to oncogenic mechanisms of plasma cell transformation. Selecting specific types of mouse plasmacytomas that relate most closely to subtypes of human multiple myeloma may provide new opportunities for preclinical testing of drugs for treatment of the human disease. [Cancer Res 2007;67(6):2439–47]
- Published
- 2023
3. Supplementary Figure 1 from Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells
- Author
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Herbert C. Morse, Siegfried Janz, Wendy F. Davidson, Derry C. Roopenian, Janet W. Hartley, Torgny N. Fredrickson, Alexander L. Kovalchuk, Shao Xiang, Zohreh Naghashfar, Chang Hoon Lee, Jeff X. Zhou, and Chen-Feng Qi
- Abstract
Supplementary Figure 1 from Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells
- Published
- 2023
4. Supplementary Figure 3 from Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells
- Author
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Herbert C. Morse, Siegfried Janz, Wendy F. Davidson, Derry C. Roopenian, Janet W. Hartley, Torgny N. Fredrickson, Alexander L. Kovalchuk, Shao Xiang, Zohreh Naghashfar, Chang Hoon Lee, Jeff X. Zhou, and Chen-Feng Qi
- Abstract
Supplementary Figure 3 from Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells
- Published
- 2023
5. Supplementary Figure 2 from Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells
- Author
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Herbert C. Morse, Siegfried Janz, Wendy F. Davidson, Derry C. Roopenian, Janet W. Hartley, Torgny N. Fredrickson, Alexander L. Kovalchuk, Shao Xiang, Zohreh Naghashfar, Chang Hoon Lee, Jeff X. Zhou, and Chen-Feng Qi
- Abstract
Supplementary Figure 2 from Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells
- Published
- 2023
6. ATP-degrading ENPP1 is required for survival (or persistence) of long-lived plasma cells
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Solomon Conteh, Javier Traba, Chen-Feng Qi, Dong-Mi Shin, Shweta Jain, Patrick E. Duffy, Jeongheon Yoon, Wendy Dubois, Ines Gonzalez-Garcia, Herbert C. Morse, Zohreh Naghashfar, Alexander L. Kovalchuk, Sadia Abbasi, Sungyun Kang, Hongsheng Wang, Michael N. Sack, Jiafang Sun, and Yuanyuan Gao
- Subjects
0301 basic medicine ,Cell Survival ,Plasma Cells ,lcsh:Medicine ,Bone Marrow Cells ,Carbohydrate metabolism ,Article ,Mice ,03 medical and health sciences ,Adenosine Triphosphate ,Antigen ,Downregulation and upregulation ,Bone Marrow ,medicine ,Animals ,Humans ,Glycolysis ,Pyrophosphatases ,lcsh:Science ,Cells, Cultured ,B cell ,B-Lymphocytes ,Multidisciplinary ,Phosphoric Diester Hydrolases ,Chemistry ,lcsh:R ,Phosphodiesterase ,Germinal center ,Germinal Center ,Molecular biology ,Up-Regulation ,Mice, Inbred C57BL ,Glucose ,030104 developmental biology ,medicine.anatomical_structure ,Antibody Formation ,lcsh:Q ,Bone marrow ,Spleen - Abstract
Survival of antibody-secreting plasma cells (PCs) is vital for sustained antibody production. However, it remains poorly understood how long-lived PCs (LLPCs) are generated and maintained. Here we report that ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) is preferentially upregulated in bone marrow LLPCs compared with their splenic short-lived counterparts (SLPCs). We studied ENPP1-deficient mice (Enpp1 −/− ) to determine how the enzyme affects PC biology. Although Enpp1 −/− mice generated normal levels of germinal center B cells and plasmablasts in periphery, they produced significantly reduced numbers of LLPCs following immunization with T-dependent antigens or infection with plasmodium C. chabaudi. Bone marrow chimeric mice showed B cell intrinsic effect of ENPP1 selectively on generation of bone marrow as well as splenic LLPCs. Moreover, Enpp1 −/− PCs took up less glucose and had lower levels of glycolysis than those of wild-type controls. Thus, ENPP1 deficiency confers an energetic disadvantage to PCs for long-term survival and antibody production.
- Published
- 2017
7. Associations of Autoimmunity, Immunodeficiency, Lymphomagenesis, and Gut Microbiota in Mice with Knockins for a Pathogenic Autoantibody
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Alexander L. Kovalchuk, Zohreh Naghashfar, Hongsheng Wang, Dong-Mi Shin, Shweta Jain, Jerrold M. Ward, and Herbert C. Morse
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Male ,0301 basic medicine ,Lymphoma, B-Cell ,Microarray ,Transgene ,Autoimmunity ,Mice, Transgenic ,Biology ,medicine.disease_cause ,Article ,Pathology and Forensic Medicine ,Mice ,03 medical and health sciences ,medicine ,Animals ,Receptor ,Immunodeficiency ,Autoantibodies ,B-Lymphocytes ,Immunologic Deficiency Syndromes ,Autoantibody ,Heterozygote advantage ,medicine.disease ,Gastrointestinal Microbiome ,Lymphoma ,030104 developmental biology ,Toll-Like Receptor 7 ,Immunology ,Female - Abstract
A number of mouse strains transgenic for B-cell receptors specific for nucleic acids or other autoantigens have been generated to understand how autoreactive B cells are regulated in normal and autoimmune mice. Previous studies of nonautoimmune C57BL/6 mice heterozygous for both the IgH and IgL knockins of the polyreactive autoantibody, 564, produced high levels of autoantibodies in a largely Toll-like receptor 7–dependent manner. Herein, we describe studies of mice homozygous for the knockins that also expressed high levels of autoantibodies but, unlike the heterozygotes, exhibited a high incidence of mature B-cell lymphomas and enhanced susceptibility to bacterial infections. Microarray analyses and serological studies suggested that lymphomagenesis might be related to chronic B-cell activation promoted by IL-21. Strikingly, mice treated continuously with antibiotic-supplemented water did not develop lymphomas or abscesses and exhibited less autoimmunity. This mouse model may help us understand the reasons for enhanced susceptibility to lymphoma development exhibited by humans with a variety of autoimmune diseases, such as Sjögren syndrome, systemic lupus erythematosus, and highly active rheumatoid arthritis.
- Published
- 2017
8. Transcription factors IRF8 and PU.1 are required for follicular B cell development and BCL6-driven germinal center responses
- Author
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Chen-Feng Qi, Yuanyuan Gao, Alexander L. Kovalchuk, Warren J. Leonard, Jian-Xin Lin, Peng Li, Hongsheng Wang, Shweta Jain, Jiafang Sun, Sadia Abbasi, Silvia Bolland, Tomomi Sakai, Herbert C. Morse, Jangsuk Oh, Zohreh Naghashfar, and Stephen L. Nutt
- Subjects
Mice, Knockout ,B-Lymphocytes ,Multidisciplinary ,Lymphocyte ,Germinal center ,Biology ,BCL6 ,Germinal Center ,Lymphocyte Activation ,Immunoglobulin Class Switching ,Cell biology ,Mice ,medicine.anatomical_structure ,Immunoglobulin class switching ,PNAS Plus ,Proto-Oncogene Proteins ,Interferon Regulatory Factors ,medicine ,Proto-Oncogene Proteins c-bcl-6 ,Trans-Activators ,Animals ,Follicular B cell ,IRF8 ,Transcription factor ,B cell - Abstract
The IRF and Ets families of transcription factors regulate the expression of a range of genes involved in immune cell development and function. However, the understanding of the molecular mechanisms of each family member has been limited due to their redundancy and broad effects on multiple lineages of cells. Here, we report that double deletion of floxed Irf8 and Spi1 (encoding PU.1) by Mb1-Cre (designated DKO mice) in the B cell lineage resulted in severe defects in the development of follicular and germinal center (GC) B cells. Class-switch recombination and antibody affinity maturation were also compromised in DKO mice. RNA-seq (sequencing) and ChIP-seq analyses revealed distinct IRF8 and PU.1 target genes in follicular and activated B cells. DKO B cells had diminished expression of target genes vital for maintaining follicular B cell identity and GC development. Moreover, our findings reveal that expression of B-cell lymphoma protein 6 (BCL6), which is critical for development of germinal center B cells, is dependent on IRF8 and PU.1 in vivo, providing a mechanism for the critical role for IRF8 and PU.1 in the development of GC B cells.
- Published
- 2019
9. Sequence Diversity, Intersubgroup Relationships, and Origins of the Mouse Leukemia Gammaretroviruses of Laboratory and Wild Mice
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Andrew J. Oler, Zohreh Naghashfar, Janet W. Hartley, Alicia Buckler-White, Christine A. Kozak, Joshua Kassner, Surendranath Baliji, Devinka Bamunusinghe, Ronald J. Plishka, and Qingping Liu
- Subjects
0301 basic medicine ,Sequence analysis ,viruses ,Immunology ,Mouse Leukemia Virus ,Molecular Sequence Data ,Endogenous retrovirus ,Animals, Wild ,Mice, Inbred Strains ,Genome, Viral ,Microbiology ,Genome ,House mouse ,03 medical and health sciences ,Mice ,Virology ,Animals, Laboratory ,Animals ,Gene ,Genetics ,biology ,Phylogenetic tree ,Base Sequence ,Sequence Analysis, RNA ,Laboratory mouse ,Genetic Variation ,biology.organism_classification ,Genes, pol ,Leukemia Virus, Murine ,030104 developmental biology ,Genetic Diversity and Evolution ,Insect Science ,RNA, Viral - Abstract
Mouse leukemia viruses (MLVs) are found in the common inbred strains of laboratory mice and in the house mouse subspecies of Mus musculus . Receptor usage and envelope ( env ) sequence variation define three MLV host range subgroups in laboratory mice: ecotropic, polytropic, and xenotropic MLVs (E-, P-, and X-MLVs, respectively). These exogenous MLVs derive from endogenous retroviruses (ERVs) that were acquired by the wild mouse progenitors of laboratory mice about 1 million years ago. We analyzed the genomes of seven MLVs isolated from Eurasian and American wild mice and three previously sequenced MLVs to describe their relationships and identify their possible ERV progenitors. The phylogenetic tree based on the receptor-determining regions of env produced expected host range clusters, but these clusters are not maintained in trees generated from other virus regions. Colinear alignments of the viral genomes identified segmental homologies to ERVs of different host range subgroups. Six MLVs show close relationships to a small xenotropic ERV subgroup largely confined to the inbred mouse Y chromosome. env variations define three E-MLV subtypes, one of which carries duplications of various sizes, sequences, and locations in the proline-rich region of env . Outside the env region, all E-MLVs are related to different nonecotropic MLVs. These results document the diversity in gammaretroviruses isolated from globally distributed Mus subspecies, provide insight into their origins and relationships, and indicate that recombination has had an important role in the evolution of these mutagenic and pathogenic agents. IMPORTANCE Laboratory mice carry mouse leukemia viruses (MLVs) of three host range groups which were acquired from their wild mouse progenitors. We sequenced the complete genomes of seven infectious MLVs isolated from geographically separated Eurasian and American wild mice and compared them with endogenous germ line retroviruses (ERVs) acquired early in house mouse evolution. We did this because the laboratory mouse viruses derive directly from specific ERVs or arise by recombination between different ERVs. The six distinctively different wild mouse viruses appear to be recombinants, often involving different host range subgroups, and most are related to a distinctive, largely Y-chromosome-linked MLV ERV subtype. MLVs with ecotropic host ranges show the greatest variability with extensive inter- and intrasubtype envelope differences and with homologies to other host range subgroups outside the envelope. The sequence diversity among these wild mouse isolates helps define their relationships and origins and emphasizes the importance of recombination in their evolution.
- Published
- 2015
10. Anaplastic, Plasmablastic, and Plasmacytic Plasmacytomas of Mice: Relationships to Human Plasma Cell Neoplasms and Late-Stage Differentiation of Normal B Cells
- Author
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Zohreh Naghashfar, Torgny N. Fredrickson, Jeff X. Zhou, Chang Hoon Lee, Janet W. Hartley, Alexander L. Kovalchuk, Chen-Feng Qi, Siegfried Janz, Herbert C. Morse, Wendy F. Davidson, Derry C. Roopenian, and Shao Xiang
- Subjects
Genetically modified mouse ,Cancer Research ,Pathology ,medicine.medical_specialty ,Cellular differentiation ,Genes, myc ,Mice, Transgenic ,Plasma cell ,Biology ,Mice ,immune system diseases ,hemic and lymphatic diseases ,medicine ,Animals ,Humans ,Cell Lineage ,neoplasms ,Multiple myeloma ,Neoplasm Staging ,Mice, Knockout ,B-Lymphocytes ,Mice, Inbred BALB C ,Interleukin-6 ,Gene Expression Profiling ,Cancer ,Cell Differentiation ,Plasma cell neoplasm ,medicine.disease ,Immunohistochemistry ,Gene expression profiling ,medicine.anatomical_structure ,Oncology ,Plasmacytoma - Abstract
We have compared histologic features and gene expression profiles of newly identified plasmacytomas from NFS.V+ congenic mice with plasmacytomas of IL6 transgenic, Fasl mutant, and SJL-β2M−/− mice. NFS.V+ tumors comprised an overlapping morphologic spectrum of high-grade/anaplastic, intermediate-grade/plasmablastic, and low-grade/plasmacytic cases with similarities to subsets of human multiple myeloma and plasmacytoma. Microarray and immunohistochemical analyses of genes expressed by the most prevalent tumors, plasmablastic plasmacytomas, showed them to be most closely related to immunoblastic lymphomas, less so to plasmacytomas of Fasl mutant and SJL mice, and least to plasmacytic plasmacytomas of IL6 transgenic mice. Plasmablastic tumors seemed to develop in an inflammatory environment associated with gene signatures of T cells, natural killer cells, and macrophages not seen with plasmacytic plasmacytomas. Plasmablastic plasmacytomas from NFS.V+ and SJL-β2M−/− mice did not have structural alterations in Myc or T(12;15) translocations and did not express Myc at high levels, regular features of transgenic and pristane-induced plasmacytomas. These findings imply that, as for human multiple myeloma, Myc-independent routes of transformation contribute to the pathogenesis of these tumors. These findings suggest that plasma cell neoplasms of mice and humans exhibit similar degrees of complexity. Mouse plasmacytomas, previously considered to be homogeneous, may thus be as diverse as their human counterparts with respect to oncogenic mechanisms of plasma cell transformation. Selecting specific types of mouse plasmacytomas that relate most closely to subtypes of human multiple myeloma may provide new opportunities for preclinical testing of drugs for treatment of the human disease. [Cancer Res 2007;67(6):2439–47]
- Published
- 2007
11. Histologic and molecular characterizations of megakaryocytic leukemia in mice
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Zohreh Naghashfar, Chang Hoon Lee, Min Sun Shin, Torgny N. Fredrickson, Chen Feng Qi, Xingpei Hao, Janet W. Hartley, Jerrold M. Ward, Herbert C. Morse, and Jeff X. Zhou
- Subjects
Cancer Research ,Microarray ,Spleen ,Biology ,Polymerase Chain Reaction ,Mice ,chemistry.chemical_compound ,Megakaryocyte ,Leukemia, Megakaryoblastic, Acute ,hemic and lymphatic diseases ,von Willebrand Factor ,medicine ,Animals ,Cell Lineage ,GATA1 Transcription Factor ,DNA Primers ,Oligonucleotide Array Sequence Analysis ,Base Sequence ,Integrin beta3 ,GATA1 ,Hematology ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Leukemia ,Ki-67 Antigen ,medicine.anatomical_structure ,Oncology ,RUNX1 ,chemistry ,Core Binding Factor Alpha 2 Subunit ,Cancer research ,Biomarker (medicine) - Abstract
Six cases of megakaryocytic leukemia (MKL) were identified and analyzed for morphology and molecular features. MKL were composed of megakaryocyte lineage cells ranging from immature to quite mature cells. VWF, GATA1 and RUNX1 were strongly expressed in megakaryocytes in both normal spleen and MKL as analyzed by immunohistochemistry (IHC). Altered expression of Meis1, Pbx1 and Psen2 and Lef1 in MKL detected with oligonucleotide microarrays was confirmed by qPCR and IHC. This is the first report of spontaneous MKL in mice, defining VWF as a biomarker for diagnosis and suggesting possible involvement of a series of genes in disease pathogenesis.
- Published
- 2006
12. SNP array profiling of mouse cell lines identifies their strains of origin and reveals cross-contamination and widespread aneuploidy
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John P. Didion, Fernando Pardo-Manuel de Villena, David W. Threadgill, Zohreh Naghashfar, Herbert C. Morse, and Ryan J. Buus
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DNA Copy Number Variations ,Genotype ,Copy number analysis ,Mice, Inbred Strains ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Cell Line ,Mice ,Genetics ,Animals ,SNP ,Crosses, Genetic ,Oligonucleotide Array Sequence Analysis ,Gene Expression Profiling ,Methodology Article ,Aneuploidy ,3. Good health ,Gene expression profiling ,Cell culture ,DNA microarray ,Microsatellite Repeats ,Biotechnology ,SNP array - Abstract
Background The crisis of Misidentified and contaminated cell lines have plagued the biological research community for decades. Some repositories and journals have heeded calls for mandatory authentication of human cell lines, yet misidentification of mouse cell lines has received little publicity despite their importance in sponsored research. Short tandem repeat (STR) profiling is the standard authentication method, but it may fail to distinguish cell lines derived from the same inbred strain of mice. Additionally, STR profiling does not reveal karyotypic changes that occur in some high-passage lines and may have functional consequences. Single nucleotide polymorphism (SNP) profiling has been suggested as a more accurate and versatile alternative to STR profiling; however, a high-throughput method for SNP-based authentication of mouse cell lines has not been described. Results We have developed computational methods (Cell Line Authentication by SNP Profiling, CLASP) for cell line authentication and copy number analysis based on a cost-efficient SNP array, and we provide a reference database of commonly used mouse strains and cell lines. We show that CLASP readily discriminates among cell lines of diverse taxonomic origins, including multiple cell lines derived from a single inbred strain, intercross or wild caught mouse. CLASP is also capable of detecting contaminants present at concentrations as low as 5%. Of the 99 cell lines we tested, 15 exhibited substantial divergence from the reported genetic background. In all cases, we were able to distinguish whether the authentication failure was due to misidentification (one cell line, Ba/F3), the presence of multiple strain backgrounds (five cell lines), contamination by other cells and/or the presence of aneuploid chromosomes (nine cell lines). Conclusions Misidentification and contamination of mouse cell lines is potentially as widespread as it is in human cell culture. This may have substantial implications for studies that are dependent on the expected background of their cell cultures. Laboratories can mitigate these risks by regular authentication of their cell cultures. Our results demonstrate that SNP array profiling is an effective method to combat cell line misidentification. Electronic supplementary material The online version of this article (doi:10.1186/1471-2164-15-847) contains supplementary material, which is available to authorized users.
- Published
- 2014
13. Evidence for Selective Transformation of Autoreactive Immature Plasma Cells in Mice Deficient in Fasl
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Thomas R. McCarty, Partha Mukhopadhyay, Zohreh Naghashfar, Jeff X. Zhou, Ted A. Torrey, Derry C. Roopenian, Mitsuo Hori, Chang Hoon Lee, Cheryl Y. M. Okumura, Herbert C. Morse, Min Sun Shin, Jian Qiao Zhang, and Wendy F. Davidson
- Subjects
Fas Ligand Protein ,Lymphoma, B-Cell ,T cell ,Plasma Cells ,Immunology ,Immunoglobulin Variable Region ,Plasma cell ,medicine.disease_cause ,Article ,Autoimmunity ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antibody Specificity ,medicine ,Animals ,Immunology and Allergy ,B cell ,030304 developmental biology ,B-Lymphocytes ,Mice, Inbred BALB C ,Mice, Inbred C3H ,0303 health sciences ,Membrane Glycoproteins ,biology ,Gene Expression Profiling ,autoimmunity ,Molecular biology ,Isotype ,B cell lymphoma ,Gene expression profiling ,Cell Transformation, Neoplastic ,medicine.anatomical_structure ,biology.protein ,Immunoglobulin heavy chain ,Antibody ,Immunoglobulin Heavy Chains ,030215 immunology - Abstract
Germline mutations in Fas and Fasl induce nonmalignant T cell hyperplasia and systemic autoimmunity and also greatly increase the risk of B cell neoplasms. B lymphomas occurring in Fasl mutant (gld) mice usually are immunoglobulin (Ig) isotype switched, secrete Ig, and are plasmacytoid in appearance but lack Myc translocations characteristic of other plasma cell (PC) neoplasms. Here, we explore the relationship between B cell autoreactivity and transformation and use gene expression profiling to further classify gld plasmacytoid lymphomas (PLs) and to identify genes of potential importance in transformation. We found that the majority of PLs derive from antigen-experienced autoreactive B cells producing antinuclear antibody or rheumatoid factor and exhibit the skewed Ig V gene repertoire and Ig gene rearrangement patterns associated with these specificities. Gene expression profiling revealed that both primary and transplanted PLs share a transcriptional profile that places them at an early stage in PC differentiation and distinguishes them from other B cell neoplasms. In addition, genes were identified whose altered expression might be relevant in lymphomagenesis. Our findings provide a strong case for targeted transformation of autoreactive B cells in gld mice and establish a valuable model for understanding the relationship between systemic autoimmunity and B cell neoplasia.
- Published
- 2004
14. Accelerated Appearance of Multiple B Cell Lymphoma Types in NFS/N Mice Congenic for Ecotropic Murine Leukemia Viruses
- Author
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Torgny N. Fredrickson, Janet W. Hartley, Lekidelu Taddesse-Heath, Marilyn R. Lander, Zohreh Naghashfar, Herbert C. Morse, and Sisir K. Chattopadhyay
- Subjects
Lymphoma, B-Cell ,Genome, Viral ,Biology ,Virus ,Pathology and Forensic Medicine ,Mice ,hemic and lymphatic diseases ,Murine leukemia virus ,medicine ,Animals ,Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ,B-cell lymphoma ,Molecular Biology ,B cell ,Ecotropism ,Cell Biology ,Gene rearrangement ,medicine.disease ,biology.organism_classification ,Immunohistochemistry ,Virology ,Lymphoma ,Leukemia Virus, Murine ,Blotting, Southern ,medicine.anatomical_structure ,Immunoglobulin heavy chain ,Immunoglobulin Heavy Chains - Abstract
Spontaneous lymphomas occur at high frequency in NFS x V+ mice, strains congenic for ecotropic murine leukemia virus (MuLV) proviral genes and expressing virus at high titer. In the present study, a total of 703 NFS x V+ lymphomas were studied by histopathology, immunophenotypic analysis, immunoglobulin heavy chain or T cell receptor beta chain rearrangements, and somatic ecotropic MuLV integrations; 90% of the lymphomas tested were of B cell lineage. Low-grade tumors included small lymphocytic, follicular, and splenic marginal zone lymphomas, while high-grade tumors comprised diffuse large-cell (centroblastic and immunoblastic types), splenic marginal zone, and lymphoblastic lymphomas. Comparison of mice of similar genetic background except for presence (NFS x V+) or absence (NFS x V-) of functional ecotropic MuLV genomes showed that NFS x V-clonal lymphomas developed at about one-half the rate of those occurring in NFS x V+ mice, and most were low-grade B cell lymphomas with extended latent periods. In NFS x V+ mice, clonal outgrowth, defined by Ig gene rearrangements, was associated with acquisition of somatic ecotropic proviral integrations, suggesting that, although generation of B cell clones can be virus independent, ecotropic virus may act to increase the rate of generation of clones and speed their evolution to lymphoma. The mechanism remains undefined, because only rare rearrangements were detected in several cellular loci previously associated with MuLV insertional mutagenesis.
- Published
- 2000
15. A Model System for Studying Mechanisms of B-cell Transformation in Systemic Autoimmunity
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Zohreh Naghashfar, Jeff X. Zhou, Wendy F. Davidson, Herbert C. Morse, Mark S. Williams, and Partha Mukhopadhyay
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Transformation (genetics) ,medicine.anatomical_structure ,Thyroid lymphoma ,business.industry ,Cancer research ,Medicine ,Model system ,MALT lymphoma ,Systemic autoimmunity ,business ,medicine.disease ,B cell - Published
- 2008
16. B lymphoid neoplasms of mice: characteristics of naturally occurring and engineered diseases and relationships to human disorders
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Herbert C, Morse, Tom, McCarty, Chen-Feng, Qi, Ted A, Torrey, Zohreh, Naghashfar, Sisir K, Chattopadhyay, Torgny N, Fredrickson, and Janet W, Hartley
- Subjects
Disease Models, Animal ,Mice ,Lymphoma, B-Cell ,Gene Expression Profiling ,Leukemia, B-Cell ,Animals ,Humans ,Genetic Engineering - Published
- 2004
17. B Lymphoid Neoplasms of Mice: Characteristics of Naturally Occurring and Engineered Diseases and Relationships to Human Disorders
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Zohreh Naghashfar, Sisir K. Chattopadhyay, Ted A. Torrey, Chen-Feng Qi, Thomas R. McCarty, Torgny N. Fredrickson, Janet W. Hartley, and Herbert C. Morse
- Subjects
Gene expression profiling ,Pathogenesis ,Immunology ,medicine ,Neoplasm ,Disease ,Biology ,DNA microarray ,medicine.disease ,Bioinformatics ,Gene ,Lymphoma ,Chromatin - Abstract
Publisher Summary Investigators have sought to understand the pathogenesis of hematopoietic neoplasms in mice as models for human disease. The spontaneous diseases of mice form an essential foundation of knowledge about efforts to molecularly model specific diseases, because it will be critically important to distinguish induced from background cases. Gene expression profiling of histologically defined spontaneous neoplasm provides additional richness to these analyses. One of the most striking findings to come from the latter studies is the intimate relationship between morphologic and genetic diagnoses. This clearly indicates that the pathologist—in screening hundreds of gene readouts that determine cell size, cytoplasmic volume, nuclear shape, chromatin pattern, and nucleolar number, size, and position—provides a valuable foil to play against the molecular fingerprints portrayed by the data from microarrays. The synergy provided by these approaches in understanding the disease holds tremendous promise for developing better treatments for human hematologic neoplasm.
- Published
- 2003
18. CD19 signaling pathways play a major role for murine AIDS induction and progression
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Zohreh Naghashfar, Sonja M. Knoetig, Herbert C. Morse, Ted A. Torrey, and Thomas R. McCarty
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Sialic Acid Binding Ig-like Lectin 2 ,Cell Cycle Proteins ,Lymphocyte Activation ,Virus Replication ,Severity of Illness Index ,Defective virus ,chemistry.chemical_compound ,Mice ,immune system diseases ,Murine Acquired Immunodeficiency Syndrome ,hemic and lymphatic diseases ,Lectins ,Immunology and Allergy ,Cell Line, Transformed ,Mice, Knockout ,B-Lymphocytes ,biology ,CD22 ,Leukemia Virus, Murine ,medicine.anatomical_structure ,Disease Progression ,Cell activation ,Protein Binding ,Signal Transduction ,Virus Integration ,Immunology ,B-cell receptor ,Antigens, CD19 ,chemical and pharmacologic phenomena ,Antiviral Agents ,CD19 ,Immunophenotyping ,Antigens, CD ,Proto-Oncogene Proteins ,medicine ,Animals ,Proto-Oncogene Proteins c-vav ,B cell ,Immune Sera ,Tyrosine phosphorylation ,Immunoglobulin E ,Immunoglobulin Class Switching ,Lymphoproliferative Disorders ,Antigens, Differentiation, B-Lymphocyte ,Mice, Inbred C57BL ,chemistry ,Viral replication ,biology.protein ,Cancer research ,Receptors, Complement 3d ,Cell Adhesion Molecules ,Spleen - Abstract
Infection of genetically susceptible mice with the LP-BM5 mixture of murine leukemia viruses including an etiologic defective virus (BM5def) causes an immunodeficiency syndrome called murine AIDS (MAIDS). The disease is characterized by interactions between B cells and CD4+ T cells resulting in polyclonal activation of both cell types. It is known that BM5def is expressed at highest levels in B cells and that B cells serve as viral APC. The CD19-CD21 complex and CD22 on the surface of B cells play critical roles as regulators of B cell responses to a variety of stimuli, influencing cell activation, differentiation, and survival. CD19 integrates positive signals induced by B cell receptor ligation by interacting with the protooncogene Vav, which leads to subsequent tyrosine phosphorylation of this molecule. In contrast, CD22 negatively regulates Vav phosphorylation. To analyze the role of CD19, CD21, Vav, and CD22 in MAIDS, we infected mice deficient in CD19, CD21 (CR2), Vav-1, or CD22 with LP-BM5 murine leukemia viruses. Infected CR2−/− mice developed MAIDS with a time course and severity indistinguishable from that of wild-type mice. In contrast, CD19 as well as Vav-1 deficiency restricted viral replication and suppressed the development of typical signs of MAIDS including splenomegaly, lymphadenopathy, and hypergammaglobulinemia. Finally, CD22 deficiency was found to accelerate MAIDS development. These results provide novel insights into the B cell signaling pathways required for normal induction and progression of MAIDS.
- Published
- 2002
19. Expression of infectious murine leukemia viruses by RAW264.7 cells, a potential complication for studies with a widely used mouse macrophage cell line
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Leonard H. Evans, Kim Y. Green, Janet W. Hartley, Patricia M. Zerfas, Alfonso R Macias, Zohreh Naghashfar, and Jerrold M. Ward
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lcsh:Immunologic diseases. Allergy ,Tumor Virus Infections ,Abelson murine leukemia virus ,viruses ,Short Report ,Virus Replication ,Virus ,Cell Line ,Mice ,Viral Proteins ,Virology ,hemic and lymphatic diseases ,Murine leukemia virus ,medicine ,Animals ,Mice, Inbred BALB C ,Leukemia, Experimental ,biology ,Macrophages ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,medicine.disease ,Leukemia Virus, Murine ,Leukemia ,Infectious Diseases ,Viral replication ,Animals, Newborn ,Cell culture ,Helper virus ,NIH 3T3 Cells ,Moloney murine leukemia virus ,lcsh:RC581-607 ,Retroviridae Infections - Abstract
The mouse macrophage-like cell line RAW264.7, the most commonly used mouse macrophage cell line in medical research, was originally reported to be free of replication-competent murine leukemia virus (MuLV) despite its origin in a tumor induced by Abelson MuLV containing Moloney MuLV as helper virus. As currently available, however, we find that it produces significant levels of ecotropic MuLV with the biologic features of the Moloney isolate and also MuLV of the polytropic or MCF class. Newborn mice developed lymphoma following inoculation with the MuLV mixture expressed by these cells. These findings should be considered in interpretation of increasingly widespread use of these cells for propagation of other viruses, studies of biological responses to virus infection and use in RNA interference and cell signalling studies.
- Published
- 2008
20. Identification of genital tract papillomaviruses HPV-6 and HPV-16 in warts of the oral cavity
- Author
-
J. Donald Woodruff, Richard W. Daniel, Jean Gupta, Haskins Kashima, Keerti Shah, Zohreh Naghashfar, Edward Sawada, James Swancar, and Mark J. Kutcher
- Subjects
Adult ,Male ,Pathology ,medicine.medical_specialty ,Adolescent ,In situ hybridization ,Papillomatosis ,Genitalia, Male ,Biology ,Virus ,Lesion ,Tongue ,Virology ,medicine ,Humans ,Child ,Antigens, Viral ,Papillomaviridae ,Base Sequence ,Nucleic Acid Hybridization ,virus diseases ,Histology ,Genitalia, Female ,female genital diseases and pregnancy complications ,Tumor Virus Infections ,Infectious Diseases ,medicine.anatomical_structure ,DNA, Viral ,Female ,Mouth Neoplasms ,Viral disease ,Warts ,medicine.symptom ,Mouth Diseases ,Tonsillar Pillar - Abstract
Warty lesions of the oral cavity were examined for etiologic association with genital tract papillomaviruses HPV-6, HPV-11, and HPV-16. DNAs extracted from ten oral biopsies were screened for HPV genomic sequences by Southern transfer hybridization with 32P-labeled viral DNA probes. Nonstringent hybridization with an HPV-6 probe revealed papillomavirus DNA sequences in four of seven tissues with histologic evidence of papillomatosis, in none of two tissues without histologic evidence of papillomatosis, and in one tissue that was not examined by histology. Stringent hybridization tests with HPV-6 and HPV-16 probes identified the genome in one tissue as being HPV-16, in a second tissue as being HPV-6 subtype a, and in a third tissue as HPV-6 (subtype unidentified); papillomavirus DNA sequences in two tissues are as yet not identified. An additional case of HPV-6 or HPV-11 related oral cavity lesion was diagnosed by in situ hybridization of paraffin sections with a 35S-labeled, mixed HPV-6 + HPV-11 probe. The hybridization in the positive section was extensive and confined to epithelial nuclei. The oral lesions associated with genital tract papillomaviruses were asymptomatic, multiple or single, and were located in different parts of the oral cavity, for example, on the gingivae, on the tongue, on the lip, on the tonsillar pillar, and on the floor of the mouth.
- Published
- 1985
21. Specific identification of human papillomavirus type in cervical smears and paraffin sections by in situ hybridization with radioactive probes: a preliminary communication
- Author
-
Zohreh Naghashfar, Prabodh K. Gupta, Woodruff Jd, Jayanta Gupta, Neil B. Rosenshein, Howard E. Gendelman, Keerti V. Shah, and E Sawada
- Subjects
Adult ,Genetic Markers ,Pathology ,medicine.medical_specialty ,In situ hybridization ,Cervix Uteri ,Biology ,Sulfur Radioisotopes ,Pathology and Forensic Medicine ,law.invention ,Uterine Cervical Diseases ,Nucleic acid thermodynamics ,law ,medicine ,Vaginal smear ,Humans ,Nick translation ,Papillomaviridae ,Vaginal Smears ,Immunoperoxidase ,Hybridization probe ,Obstetrics and Gynecology ,Nucleic Acid Hybridization ,Papanicolaou Test ,DNA ,Virology ,Paraffin ,Recombinant DNA ,Female - Abstract
Cervical Papanicolaou smears and paraffin sections of biopsy specimens obtained from women attending dysplasia clinics were examined for viral DNA sequences by in situ hybridization technique using 35S-labeled cloned recombinant DNA probes of human papillomavirus (HPV) types 6, 11, and 16. These and one unrelated DNA probe complementary to measles virus RNA were labeled by nick translation using either one or two 35S-labeled nucleotides. The radiolabeled probes were reduced in size with DNase to 60-160 nucleotides. Paraffin sections and cervical smears were collected on pretreated slides, hybridized with the probes under stringent or nonstringent conditions for 50 h, and autoradiographed. Additional cervical specimens from the same women were examined for the presence of genus-specific papillomavirus capsid antigen by the immunoperoxidase technique. Preliminary results may be summarized as follows. The infecting virus could be identified in smears as well as in sections. Viral DNA sequences were detected only when there were condylomatous cells in the specimen and in only a proportion of the condylomatous cells. Even under stringent conditions, some specimens reacted with both HPV-6 and HPV-11. None of the specimens hybridized with HPV-16 or with the unrelated probe. In some instances, the cells did not hybridize with any of the three probes even when duplicate specimens contained frankly condylomatous, capsid antigen-positive cells. In situ hybridization of Papanicolaou smears or of tissue sections is a practical method for diagnosis and follow-up of specific papillomavirus infection using routinely collected material.
- Published
- 1985
22. Characterization of human papillomavirus type 45, a new type 18-related virus of the genital tract
- Author
-
Neil B. Rosenshein, Attila T. Lorincz, Zohreh Naghashfar, Keerti V. Shah, and Joseph Buscema
- Subjects
Biology ,Virus ,Uterine Cervical Diseases ,Nucleic acid thermodynamics ,chemistry.chemical_compound ,Virology ,Sequence Homology, Nucleic Acid ,medicine ,Humans ,Papillomaviridae ,Moderate Dysplasia ,virus diseases ,Chromosome Mapping ,Nucleic Acid Hybridization ,DNA Restriction Enzymes ,Molecular biology ,female genital diseases and pregnancy complications ,Epithelium ,Koilocyte ,medicine.anatomical_structure ,chemistry ,Nucleic acid ,Restriction digest ,Female ,DNA - Abstract
DNA of human papillomavirus (HPV) type 45, a new HPV type 18-related papillomavirus of the genital tract, was cloned from a recurrent cervical lesion displaying mild to moderate dysplasia with koilocytosis. HPV-45 DNA was identified in paraffin sections of biopsies of both the initial and recurrent lesions of the patient, taken 7 months apart. HPV-45 DNA hybridized efficiently to that of many different HPV types under low and moderate stringency conditions (Tm - 37 degrees C to Tm - 25 degrees C) but with only HPV-18 DNA under high stringency conditions (Tm - 17 degrees C). HPV-45 DNA was distinguished from HPV-18 DNA by (i) differences in restriction enzyme digest patterns, (ii) lack of hybridization at Tm - 17 degrees C between HPV-18 and some fragments of HPV-45, (iii) a value of 25% in liquid reassociation kinetics between HPV-18 and HPV-45 and (iv) differences in intensities of hybridization with selected tissue DNAs. The prevalence of HPV-45 infection in the genital tract was low. In tests of over 600 tissue DNAs from female genital tract lesions, HPV-45 sequences were detected in three additional tissues, one each of invasive cervical carcinoma, condyloma, and normal cervical epithelium. HPV-45 is a newly recognized papillomavirus which rarely infects the genital tract and is associated with lesions across a wide histological spectrum.
- Published
- 1987
23. Genital tract papillomavirus type 6 in recurrent conjunctival papilloma
- Author
-
Jan M. McDonnell, William R. Green, Keerti V. Shah, Zohreh Naghashfar, and Peter J. McDonnell
- Subjects
Pathology ,medicine.medical_specialty ,Conjunctiva ,Conjunctival Neoplasms ,In situ hybridization ,Biology ,Genital warts ,Lesion ,Pregnancy ,Recurrence ,Biopsy ,otorhinolaryngologic diseases ,medicine ,Humans ,Maternal-Fetal Exchange ,Papillomaviridae ,Soft palate ,medicine.diagnostic_test ,Papilloma ,business.industry ,virus diseases ,Infant ,General Medicine ,Genitalia, Female ,medicine.disease ,Ophthalmology ,medicine.anatomical_structure ,Condylomata Acuminata ,Genital tract ,Surgery ,Female ,medicine.symptom ,business - Abstract
• An infant boy born of a mother who had condylomata (genital warts) during pregnancy and at delivery developed recurrent conjunctival papillomas and papillomas on the soft palate and the false vocal cords. A conjunctival lesion was first noticed by the mother when the infant was 4 months old and was excised and histologically diagnosed as a papilloma when he was 11 months old. The DNA sequences of genital tract human papillomavirus type 6 (HPV-6) were identified in conjunctival papilloma tissue by Southern transfer hybridization of tissue DNA extracted from a lesion excised at 29 months of age as well as by in situ hybridization of paraffin sections of the diagnostic biopsy specimen obtained at 11 months of age. It is probable that the infant acquired conjunctival infection from the mother, very likely during passage through the infected birth canal.
- Published
- 1986
24. Human papillomavirus type 16 in intraepithelial neoplasia (bowenoid papulosis) and coexistent invasive carcinoma of the vulva
- Author
-
Zohreh Naghashfar, Alex Ferenczy, Christine Bergeron, Yao Fu, Camille Canaan, and Keerti V. Shah
- Subjects
Adult ,Pathology ,medicine.medical_specialty ,Skin Neoplasms ,Genes, Viral ,Bowen's Disease ,Epithelium ,Pathology and Forensic Medicine ,Vulva ,medicine ,Humans ,Papillomaviridae ,Aged ,Vulvar neoplasm ,Aged, 80 and over ,Intraepithelial neoplasia ,Bowen's disease ,biology ,Vulvar Neoplasms ,urogenital system ,Carcinoma in situ ,Obstetrics and Gynecology ,DNA, Neoplasm ,biology.organism_classification ,Vulvar intraepithelial neoplasia ,medicine.disease ,Aneuploidy ,Bowenoid papulosis ,female genital diseases and pregnancy complications ,medicine.anatomical_structure ,DNA, Viral ,Carcinoma, Squamous Cell ,Hybridization, Genetic ,Female - Abstract
Tissues from two cases of bowenoid papulosis of the vulva with coexistent invasive squamous cell carcinoma were evaluated for the presence of human papillomaviruses (HPVs) and for nuclear DNA content. In both cases, HPV type 16 and nuclear aneuploidy were found in bowenoid papulosis as well as in invasive carcinoma. Patterns of hybridization suggested that the viral genome was integrated into the cellular genome in both bowenoid papulosis tissues as well as in invasive carcinoma tissues. These observations suggest that lesions designated as bowenoid papulosis may have invasive cancer potential. The term vulvar intraepithelial neoplasia seems to be more appropriate for HPV-16-containing aneuploid, intraepithelial lesions of the vulva.
- Published
- 1987
25. Human Papillomavirus Type 16 in Intraepithelial Neoplasia (Bowenoid Papulosis) and Coexistent Invasive Carcinoma of the Vulva
- Author
-
Alex Ferenczy, Yao Fu, Keerti V. Shah, Camille Canaan, Christine Bergeron, and Zohreh Naghashfar
- Subjects
Intraepithelial neoplasia ,Pathology ,medicine.medical_specialty ,Invasive carcinoma ,urogenital system ,business.industry ,Obstetrics and Gynecology ,Aneuploidy ,General Medicine ,medicine.disease ,Vulvar intraepithelial neoplasia ,Bowenoid papulosis ,female genital diseases and pregnancy complications ,Koilocyte ,Vulva ,medicine.anatomical_structure ,medicine ,Human papillomavirus ,business - Abstract
Tissues from two cases of bowenoid papulosis of the vulva with coexistent invasive squamous cell carcinoma were evaluated for the presence of human papillomaviruses (HPVs) and for nuclear DNA content. In both cases, HPV type 16 and nuclear aneuploidy were found in bowenoid papulosis as well as in invasive carcinoma. Patterns of hybridization suggested that the viral genome was integrated into the cellular genome in both bowenoid papulosis tissues as well as in invasive carcinoma tissues. These observations suggest that lesions designated as bowenoid papulosis may have invasive cancer potential. The term vulvar intraepithelial neoplasia seems to be more appropriate for HPV-16-containing aneuploid, intraepithelial lesions of the vulva.
- Published
- 1987
26. Genital Tract Papillomavirus Infection in Children
- Author
-
Keerti V. Shah, Joseph Buscema, Zohreh Naghashfar, J. Donald Woodruff, Barbara Rock, and Nancy Barnett
- Subjects
Male ,Genital Neoplasms, Female ,Poison control ,Dermatology ,Virus ,Humans ,Medicine ,Sex organ ,Human papillomavirus ,Child ,Papillomaviridae ,business.industry ,Transmission (medicine) ,virus diseases ,Child Abuse, Sexual ,General Medicine ,Virology ,female genital diseases and pregnancy complications ,Molecular hybridization ,Condylomata Acuminata ,Child, Preschool ,Genital tract ,Genital Neoplasms, Male ,Female ,Viral disease ,business - Abstract
• Genital tract papillomas in five children were examined for the presence of human papillomavirus (HPV) DNA by molecular hybridization. Papillomavirus DNA was detected in each sample and was identified as HPV-6 (three cases), HPV-6 or HPV-11 (one case), or HPV-16 (one case). These viruses are the same as are responsible for genital papillomas (condylomata) of adults. The transmission of adult genital tract viruses to children occurs primarily by a venereal route but may occur by a nonvenereal route. (Arch Dermatol1986;122:1129-1132)
- Published
- 1986
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