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Role Of Chromodomain Helicase Dna-Binding Protein 2 In Dna Damage Response Signaling And Tumorigenesis., Thandi M. Onami, P. Nagarajan, S. Rajagopalan, S. Kania, R. Donnell, S. Venkatachalam Jan 2009

Role Of Chromodomain Helicase Dna-Binding Protein 2 In Dna Damage Response Signaling And Tumorigenesis., Thandi M. Onami, P. Nagarajan, S. Rajagopalan, S. Kania, R. Donnell, S. Venkatachalam

Thandi M. Onami

The chromodomain helicase DNA-binding proteins (CHDs) are known to affect transcription through their ability to remodel chromatin and modulate histone deacetylation. In an effort to understand the functional role of the CHD2 in mammals, we have generated a Chd2 mutant mouse model. Remarkably, the Chd2 protein appears to play a critical role in the development, hematopoiesis and tumor suppression. The Chd2 heterozygous mutant mice exhibit increased extramedullary hematopoiesis and susceptibility to lymphomas. At the cellular level, Chd2 mutants are defective in hematopoietic stem cell differentiation, accumulate higher levels of the chromatin-associated DNA damage response mediator, cH2AX, and exhibit an aberrant …


Systemic And Mucosal Infection Program Protective Memory Cd8 T Cells In The Vaginal Mucosa., Thandi M. Onami, P. K. Suvas, H. M. Dech, J. Zeng Dec 2007

Systemic And Mucosal Infection Program Protective Memory Cd8 T Cells In The Vaginal Mucosa., Thandi M. Onami, P. K. Suvas, H. M. Dech, J. Zeng

Thandi M. Onami

Whether mucosal immunization is required for optimal protective CD8 T cell memory at mucosal surfaces is controversial. In this study, using an adoptive transfer system, we compare the efficacy of two routes of acute lymphocytic choriomeningitis viral infection on the generation, maintenance, and localization of Ag-specific CD8 T cells in tissues, including the vaginal mucosa. Surprisingly, at day 8, i.p. infection results in higher numbers of Ag-specific CD8 T cells in the vaginal mucosa and iliac lymph node, as well as 2-3x more Ag-specific CD8 T cells that coexpress both IFN-gamma and TNF-alpha in comparison to the intranasal route of …


Evidence Of Plasmotomy In Blastocystis Hominis, Tan Tian Chye Jan 2007

Evidence Of Plasmotomy In Blastocystis Hominis, Tan Tian Chye

Tan Tian Chye

Blastocystis hominis has been regarded as an enigmatic parasite as many aspects of its basic biology remain uncertain. Many reproductive processes have been suggested for the organism; however, to date, only the binary fission has been proven. Plasmotomy is one of the modes of reproduction previously suggested to be seen in in vitro cultures. The present study provides trichrome and acridine orange staining evidence for the existence of nucleic acid suggestive of division of nucleus into multinucleate forms with the respective cytoplasm dividing giving rise to two or three progeny B. hominis. Transmission electron micrographs further confirmed that these daughter …


Frog Virus 3 Prevalence In Tadpole Populations Inhabiting Cattle-Access And Non-Access Wetlands In Tennessee., Matthew J. Gray, Debra L. Miller, Anne C. Schmutzer, Charles A. Baldwin Jan 2007

Frog Virus 3 Prevalence In Tadpole Populations Inhabiting Cattle-Access And Non-Access Wetlands In Tennessee., Matthew J. Gray, Debra L. Miller, Anne C. Schmutzer, Charles A. Baldwin

Debra L Miller

Ranaviruses have been associated with most of the reported larval anuran die-offs in the United States. It is hypothesized that anthropogenically induced stress may increase pathogen prevalence in amphibian populations by compromising immunity. Cattle use of wetlands may stress resident tadpole populations by reducing water quality. We isolated a Ranavirus from green frog Rana clamitans (n = 80) and American bullfrog R. catesbeiana (n = 104) tadpoles collected at 5 cattle-access and 3 non-access wetlands on the Cumberland Plateau, Tennessee, USA. Sequencing confirmed Frog virus 3 (FV3); therefore, we compared its prevalence between tadpole populations inhabiting cattle-access and non-access wetlands, …


Probability Of Real -Time Detection Vs Probability Of Infection For Aerosolized Biowarfare Agents: A Model Study., Alexander G. Sabelnikov, Vladimir Zhukov, C Ruth Kempf May 2006

Probability Of Real -Time Detection Vs Probability Of Infection For Aerosolized Biowarfare Agents: A Model Study., Alexander G. Sabelnikov, Vladimir Zhukov, C Ruth Kempf

Alexander G Sabelnikov

No abstract provided.


Amoeboid Form Of Blastocystis Hominis - A Detailed Ultrastructural Insight, Tan Tian Chye Jan 2006

Amoeboid Form Of Blastocystis Hominis - A Detailed Ultrastructural Insight, Tan Tian Chye

Tan Tian Chye

The amoeboid form of Blastocystis hominis has been reported infrequently, and its morphological descriptions have yielded conflicting and confusing reports. In the present study, we used the amoeboid forms seen predominantly in symptomatic patients infected with Blastocystis to provide detailed descriptions on the fine surface structure and intracellular morphology. Scanning electron microscopy revealed the irregular shape of the amoeboid form, with an intercalated fibrillar structure and a highly convoluted surface with deep indentations and projected pseudopodia. Transmission electron microscopy showed the existence of two types of amoeboid forms of B. hominis in in vitro culture, one with a large central …


Predominance Of Amoeboid Forms Of Blastocystis Hominis In Isolates From Symptomatic Patients, Tan Tian Chye Jan 2006

Predominance Of Amoeboid Forms Of Blastocystis Hominis In Isolates From Symptomatic Patients, Tan Tian Chye

Tan Tian Chye

Blastocystis hominis is one of the most common human parasites that inhabit the intestinal tract. Conflicting reports continue to exist regarding the existence and the functional role of the amoeboid forms in the life cycle of the parasite. The present study investigates the presence of these forms in 20 isolates obtained from ten symptomatic and asymptomatic patients respectively. A total of 10,000 parasite cells per ml from each isolate were inoculated into three culture tubes each containing 3 ml of Jones' medium supplemented with 10% horse serum, incubated at 37 degrees C. The contents were examined daily for 10 days. …


Pcr Fingerprinting Of Blastocystis Isolated From Symptomatic And Asymptomatic Human Hosts, Tan Tian Chye Jan 2006

Pcr Fingerprinting Of Blastocystis Isolated From Symptomatic And Asymptomatic Human Hosts, Tan Tian Chye

Tan Tian Chye

Genomic DNA from 16 Blastocystis hominis isolates comprising of eight asymptomatic isolates (A1-A8) and eight symptomatic isolates (S1-S8) was amplified by arbitrarily primed polymerase chain reaction (AP-PCR) using 38 arbitrary 10-mer primers. Six primers (A10, B5, C20, D1, F6, and F10) generated reproducible DNA fingerprints. AP-PCR amplification revealed similar DNA fingerprints among all symptomatic isolates (S1-S8) with common bands at 850 bp using primer A10, 920 bp using primer B5, and 1.3 kbp using primer D1. Isolates A1, A3, A4, A5, A6, and A7 showed similar DNA banding patterns and all asymptomatic isolates (A1-A8) shared a major band at I …


Viable Blastocystis Cysts In Scottish And Malaysian Sewage Samples, Tan Tian Chye Jan 2005

Viable Blastocystis Cysts In Scottish And Malaysian Sewage Samples, Tan Tian Chye

Tan Tian Chye

Blastocystis cysts were detected in 38% (47/123) (37 Scottish, 17 Malaysian) of sewage treatment works. Fifty percent of influents (29% Scottish, 76% Malaysian) and 28% of effluents (9% Scottish, 60% Malaysian) contained viable cysts. Viable cysts, discharged in effluent, provide further evidence for the potential for waterborne transmission of Blastocystis.


Lack Of Antigen-Specific Tissue Remodeling In Mice Deficient In The Macrophage Galactose-Type Calcium-Type Lectin 1/Cd301a., Thandi M. Onami, K. Sato, Y. Imai, N. Higashi, Y. Kumamoto, S. M. Hedrick, T. Irimura Jan 2005

Lack Of Antigen-Specific Tissue Remodeling In Mice Deficient In The Macrophage Galactose-Type Calcium-Type Lectin 1/Cd301a., Thandi M. Onami, K. Sato, Y. Imai, N. Higashi, Y. Kumamoto, S. M. Hedrick, T. Irimura

Thandi M. Onami

Macrophage galactose-type C-type lectins (MGLs), which were recently named CD301, have 2 homologues in mice: MGL1 and MGL2. MGLs are expressed on macrophages and immature dendritic cells. The persistent presence of granulation tissue induced by a protein antigen was observed in wild-type mice but not in mice lacking an endogenous, macrophage-specific, galactose-type calcium-type lectin 1 (MGL1) in an air pouch model. The anti-MGL1 antibody suppressed the granulation tissue formation in wild-type mice. A large number of cells, present only in the pouch of MGL1-deficient mice, were not myeloid or lymphoid lineage cells and the number significantly declined after administration of …


Cd43 Modulates Severity And Onset Of Experimental Autoimmune Encephalomyelitis., Thandi M. Onami, M. L. Ford, A. Sperling, R. Ahmed, B. D. Evavold Dec 2003

Cd43 Modulates Severity And Onset Of Experimental Autoimmune Encephalomyelitis., Thandi M. Onami, M. L. Ford, A. Sperling, R. Ahmed, B. D. Evavold

Thandi M. Onami

Experimental autoimmune encephalomyelitis (EAE) is a mouse model of multiple sclerosis characterized by infiltration of activated CD4(+) T lymphocytes into tissues of the CNS. This study investigated the role of CD43 in the induction and progression of EAE. Results demonstrate that CD43-deficient mice have reduced and delayed clinical and histological disease severity relative to CD43(+/+) mice. This reduction was characterized by decreased CD4(+) T cell infiltration of the CNS of CD43(-/-) mice but similar numbers of Ag-specific T cells in the periphery, suggesting a defect in T cell trafficking to the CNS. The absence of CD43 also affected cytokine production, …


Primary And Secondary Immunocompetence In Mixed Allogeneic Chimeras, Thandi M. Onami, M. A. Williams, A. B. Adams, M. B. Walsh, N. Shirasugi, T. C. Pearson, R. Ahmed, C. P. Larsen Mar 2003

Primary And Secondary Immunocompetence In Mixed Allogeneic Chimeras, Thandi M. Onami, M. A. Williams, A. B. Adams, M. B. Walsh, N. Shirasugi, T. C. Pearson, R. Ahmed, C. P. Larsen

Thandi M. Onami

Targeted disruption of T cell costimulatory pathways, particularly CD28 and CD40, has allowed for the development of minimally myeloablative strategies for the induction of mixed allogeneic chimerism and donor-specific tolerance across full MHC barriers. In this study we analyze in depth the ability of mixed allogeneic chimeras in two strain combinations to mount effective host-restricted and donor-restricted antiviral CD4 and CD8 responses, as well as the impact of development of mixed chimerism on the maintenance of pre-existing memory populations. While antiviral CD8 responses in mixed chimeras following acute viral infection with lymphocytic choriomeningitis virus Armstrong or vaccinia virus are largely …


Tcr Signal Transduction In Antigen-Specific Memory Cd8 T Cells, Thandi M. Onami, Ellen N. Kersh, Susan M. Kaech, Miriana Moran, E. John Wherry, M. Carrie Miceli, Rafi Ahmed Jan 2003

Tcr Signal Transduction In Antigen-Specific Memory Cd8 T Cells, Thandi M. Onami, Ellen N. Kersh, Susan M. Kaech, Miriana Moran, E. John Wherry, M. Carrie Miceli, Rafi Ahmed

Thandi M. Onami

Memory T cells are more responsive to Ag than naive cells. To determine whether memory T cells also have more efficient TCR signaling, we compared naive, effector, and memory CD8 T cells of the same antigenic specificity. Surprisingly, initial CD3 signaling events are indistinguishable. However, memory T cells have more extensive lipid rafts with higher phosphoprotein content before TCR engagement. Upon activation in vivo, they more efficiently induce phosphorylation of-LAT (linker for activation of T cells), ERK (extracellular signal-regulated kinase), JNK (c-Jun N-terminal kinase), and p38. Thus, memory CD8 T cells do not increase their TCR sensitivity, but are better …


Cutting Edge: Persistent Viral Infection Prevents Tolerance Induction And Escapes Immune Control Following Cd28/Cd40 Blockade-Based Regimen, Thandi M. Onami, M. A. Williams, A. B. Adams, M. M. Durham, T. C. Pearson, R. Ahmed, C. P. Larsen Nov 2002

Cutting Edge: Persistent Viral Infection Prevents Tolerance Induction And Escapes Immune Control Following Cd28/Cd40 Blockade-Based Regimen, Thandi M. Onami, M. A. Williams, A. B. Adams, M. M. Durham, T. C. Pearson, R. Ahmed, C. P. Larsen

Thandi M. Onami

A continuing concern with CD28 and/or CD40 blockade-based strategies to induce tolerance and mixed chimerism is their potential to disrupt protective immunity to preexisting infections. In this report, we find that preexisting persistent infection with lymphocytic choriomeningitis virus (LCMV) clone 13 prevents the induction of tolerance, mixed chimerism, and donor-reactive T cell deletion. Mice continue to be refractory to tolerance induction even after viremia has been resolved and virus is present only at very low levels in peripheral tissues. Conversely, we find that the full tolerance regimen, or costimulation blockade alone, specifically inhibits already ongoing antiviral immune responses, leading to …


Molecular Cloning And Characterization Of A Novel Mouse Macrophage C-Type Lectin, Mmgl2, Which Has A Distinct Carbohydrate Specificity From Mmgl1, Thandi M. Onami, M. Tsuiji, M. Fujimori, Y. Ohashi, N. Higashi, S. M. Hendrick, T. Irimura Aug 2002

Molecular Cloning And Characterization Of A Novel Mouse Macrophage C-Type Lectin, Mmgl2, Which Has A Distinct Carbohydrate Specificity From Mmgl1, Thandi M. Onami, M. Tsuiji, M. Fujimori, Y. Ohashi, N. Higashi, S. M. Hendrick, T. Irimura

Thandi M. Onami

A novel mouse macrophage galactose-type C-type lectin 2 (mMGL2) was identified by BLAST analysis of expressed sequence tags. The sequence of mMGL2 is highly homologous to the mMGL, which should now be called mMGL1. The open reading frame of mMGL2 contains a sequence corresponding to a type II transmembrane protein with 332 amino acids having a single extracellular C-type lectin domain. The 3'-untranslated region included long terminal repeats of mouse early transposon. The Mgl2 gene was cloned from a 129/SvJ mouse genomic library and sequenced. The gene spans 7,136 base pairs and consists of 10 exons, which is similar to …


Generation Of Mice Deficient For Macrophage Galactose- And N-Acetylgalactosamine-Specific Lectin: Limited Role In Lymphoid And Erythroid Homeostasis And Evidence For Multiple Lectins, Thandi M. Onami, M. Y. Lin, D. M. Page, S. A. Reynolds, C. D. Katayama, J. D. Marth, T. Irimura, A. Varki, N. Varki, S. M. Hedrick Jul 2002

Generation Of Mice Deficient For Macrophage Galactose- And N-Acetylgalactosamine-Specific Lectin: Limited Role In Lymphoid And Erythroid Homeostasis And Evidence For Multiple Lectins, Thandi M. Onami, M. Y. Lin, D. M. Page, S. A. Reynolds, C. D. Katayama, J. D. Marth, T. Irimura, A. Varki, N. Varki, S. M. Hedrick

Thandi M. Onami

Macrophage receptors function in pattern recognition for the induction of innate immunity, in cellular communication to mediate the regulation of adaptive immune responses, and in the clearance of some glycosylated cells or glycoproteins from the circulation. They also function in homeostasis by initiating the engulfment of apoptotic cells. Evidence has suggested that macrophage receptors function to recognize cells that are destined for programmed cell death but not yet overtly apoptotic. We have examined the function of a macrophage receptor specific for unsialylated glycoproteins, known as the mouse macrophage galactose- and N-acetylgalactosamine-specific lectin (mMGL) (Ii et al., J. Biol. Chem. 265:11295-11298, …


Dynamic Regulation Of T Cell Immunity By Cd43, Thandi M. Onami, L. E. Harrington, M. A. Williams, M. Galvan, C. P. Larsen, T. C. Pearson, N. Manjunath, L. G. Baum, B. D. Pearce, R. Ahmed Jun 2002

Dynamic Regulation Of T Cell Immunity By Cd43, Thandi M. Onami, L. E. Harrington, M. A. Williams, M. Galvan, C. P. Larsen, T. C. Pearson, N. Manjunath, L. G. Baum, B. D. Pearce, R. Ahmed

Thandi M. Onami

During a viral response, Ag-specific effector T cells show dramatically increased binding by the mAb 1B11 and the lectin peanut agglutinin (PNA). We investigated the contribution of CD43 expression to 1B11 and PNA binding as well as its role in generation and maintenance of a CD8 T cell response. Analysis of CD43(-/-) mice revealed no increased 1B11 binding and reduced PNA binding on virus-specific CD8 T cells from -/- mice compared with +/+ mice. Furthermore, we examined the role of CD43 in the kinetics of an immune response. We show that CD43 expression modestly effects generation of a primary virus-specific …