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Autoantibodies To Centrosomes Are Diagnostic For Human Scleroderma And Can Be Induced By Experimental Mycoplasma Infection In Mice: A Dissertation, Irina Catrinel Gavanescu Dec 2002

Autoantibodies To Centrosomes Are Diagnostic For Human Scleroderma And Can Be Induced By Experimental Mycoplasma Infection In Mice: A Dissertation, Irina Catrinel Gavanescu

GSBS Dissertations and Theses

The overall objective of this thesis work was to develop new insights into the etiology of scleroderma, a human systemic autoimmune disease, by analyzing the autoantibodies to centrosome antigens that develop during the disease. Centrosomes are perinuclear organelles that form microtubule arrays, including mitotic spindles that ensure the faithful segregation of chromosomes during mitosis.

These studies used a novel methodology to determine the prevalence of anti-centrosome autoantibodies in patients with scleroderma. Recombinant centrosome antigens were used to determine the antigenic specificity of anti-centrosome antibody subsets by immunoblotting. Centrosome marker antibodies were used in indirect immunofluorescence assays to distinguish centrosomes within ...


Activation And Role Of Memory Cd8 T Cells In Heterologous Antiviral Immunity And Immunopathology In The Lung: A Dissertation, Hong Chen Dec 2002

Activation And Role Of Memory Cd8 T Cells In Heterologous Antiviral Immunity And Immunopathology In The Lung: A Dissertation, Hong Chen

GSBS Dissertations and Theses

Each individual experiences many sequential infections throughout the lifetime. An increasing body of work indicates that prior exposure to unrelated pathogens can greatly alter the disease course during a later infection. This can be a consequence of a phenomenon known as heterologous immunity. Most viruses invade the host through the mucosa of a variety of organs and tissues. Using the intranasal mucosal route of infection, the thesis focused on studying modulation of lymphocytic choriomeningitis virus (LCMV)-specific memory CD8 T cells upon respiratory vaccinia virus (VV) infection and the role of these memory CD8 T cells in heterologous immunity against ...


Mechanisms Contributing To Transcriptional Regulation And Chromatin Remodeling Of The Bone Specific Osteocalcin Gene, Soraya Elisa Gutierrez Gallegos Nov 2002

Mechanisms Contributing To Transcriptional Regulation And Chromatin Remodeling Of The Bone Specific Osteocalcin Gene, Soraya Elisa Gutierrez Gallegos

GSBS Dissertations and Theses

Activation of tissue-specific genes is a tightly controlled process that normally involves the combined action of several transcription factors and transcriptional co-regulators. The bone-specific osteoca1cin gene (OC) has been used as a prototype to study both tissue-specific and hormonal responsiveness. In this study we have examined the role of Runx2, VDR and C/EBP factors in the regulation of OC gene transcription. Contributions of the Runx and VDRE motifs to OC promoter activity were addressed by introducing point mutations within the context of the rat (-1.1 kb) osteocalcin promoter fused to a CAT-reporter gene. The functional significance of these ...


The Role Of Human Cytomegalovirus Immediate Early Proteins In Cell Growth Control: A Dissertation, Jonathan Patrick Castillo Oct 2002

The Role Of Human Cytomegalovirus Immediate Early Proteins In Cell Growth Control: A Dissertation, Jonathan Patrick Castillo

GSBS Dissertations and Theses

The proper maintenance of the pathways governing cell growth is critical to ensure cell survival and DNA fidelity. Much of our understanding of how the cell cycle is regulated comes from studies examining the relationship between DNA viruses and the mechanisms of cell proliferation control. There are numerous examples demonstrating that viruses can alter the host cell environment to their advantage. In particular, the small DNA tumor viruses, which include adenovirus, simian-virus 40 (SV-40), and human papillomavirus (HPV), can modulate the host cell cycle to facilitate viral DNA replication. Due to the fact that these viruses infect quiescent, non-cycling cells ...


Roles Of Lissencephaly Gene, Lis1, In Regulating Cytoplasmic Dynein Functions: A Dissertation, Chin-Yin Tai Sep 2002

Roles Of Lissencephaly Gene, Lis1, In Regulating Cytoplasmic Dynein Functions: A Dissertation, Chin-Yin Tai

GSBS Dissertations and Theses

Spontaneous mutations in the human LIS1 gene are responsible for Type I lissencephaly ("smooth brain"). The distribution of neurons within the cerebral cortex of lissencephalic children appears randomized, probably owing to a defect in neuronal migration during early development.

LIS1 has been implicated in the dynein pathway by genetic analyses in fungi. We previously reported that the vertebrate LIS1 co-localized with dynein at prometaphase kinetochores, and interference with LIS1 function at kinetochore caused misalignment of chromosomes onto the metaphase plate. This leads to a hypothesis that LIS1 might regulate kinetochore protein targeting. In order to test this hypothesis, I created ...


The Human Rad52 Protein: A Correlation Of Protein Function With Oligomeric State: A Dissertation, Janice A. Lloyd Sep 2002

The Human Rad52 Protein: A Correlation Of Protein Function With Oligomeric State: A Dissertation, Janice A. Lloyd

GSBS Dissertations and Theses

The regulation of protein function through oligomerization is a common theme in biological systems. In this work, I have focused on the effects of the oligomeric states of the human Rad52 protein on activities related to DNA binding. HsRad52, a member of the RAD52 epistasis group, is thought to play an important and as yet undefined role in homologous recombination. HsRad52 preferentially binds to ssDNA over dsDNA and stimulates HsRad51-mediated strand exchange (Benson et al., 1998). In either the presence or absence of DNA, HsRad52 has been observed to form both 10 nm ring-like structures as well as higher ...


Viral Abrogation Of Stem Cell Transplantation Tolerance Causes Graft Rejection And Host Death By Different Mechanisms: A Dissertation, Daron Forman May 2002

Viral Abrogation Of Stem Cell Transplantation Tolerance Causes Graft Rejection And Host Death By Different Mechanisms: A Dissertation, Daron Forman

GSBS Dissertations and Theses

Tolerance-based stem cell transplantation using sub-lethal conditioning is being considered for the treatment of human disease, but safety and efficacy remain to be established. In order to study these two issues, we first established that mouse bone marrow recipients treated with sub-lethal irradiation plus transient blockade of the CD40-CD154 costimulatory pathway develop permanent hematopoietic chimerism across allogeneic barriers. Our conditioning regimen of 6 Gy irradiation, a short course of anti-CD154 mAb and 25 million fully allogeneic BALB/c bone marrow cells consistently produced long-term, stable, and multilineage chimerism in C57BL/6 recipients. Furthermore, chimeric mice displayed donor-specific transplantation tolerance, as ...


A Characterization Of Substrates And Factors Involved In Yeast Nonsense-Mediated Mrna Decay: A Dissertation, Jonathan Philip Belk Jan 2002

A Characterization Of Substrates And Factors Involved In Yeast Nonsense-Mediated Mrna Decay: A Dissertation, Jonathan Philip Belk

GSBS Dissertations and Theses

Many intricate and highly conserved mechanisms have evolved to safeguard organisms against errors in gene expression. The nonsense-mediated mRNA decay pathway (NMD) exemplifies one such mechanism, specifically by eliminating mRNAs containing premature translation termination codons within their protein coding regions, thereby limiting the synthesis of potentially deleterious truncated polypeptides. Studies in Saccharomyces Cerevisiae have found that the activity of at least three trans-acting factors, known as UPF1, UPF2/NMD2, and UPF3is necessary for the proper function of the NMD pathway. Further research conducted in yeast indicates that the degradation of substrates of the NMD pathway is dependent on ...