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Full-Text Articles in Life Sciences

Atm-Dependent Erk Signaling In Response To Dna Double Strand Breaks, Ashraf Khalil Jan 2006

Atm-Dependent Erk Signaling In Response To Dna Double Strand Breaks, Ashraf Khalil

Theses and Dissertations

Ionizing radiation (IR) triggers many signaling pathways stemming from DNA damage, and, independently, from extra-nuclear events. To generate radio-mimetic DNA double-strand breaks (DSBs) without and minimizing the effects on extra-nuclear radiation targets, human (p53+) glioma and carcinoma cells containing bromodeoxyuridine (BrdU)- substituted DNA were treated with Hoechst 33258 followed by long wave-length UV (UV-A) (BrdU photolysis). BrdU photolysis resulted in well-controlled, dose-dependent generation of DSBs equivalent to 0.2 - 20 Gy of IR, as detected by pulse-field gel electrophoresis, accompanied by dose-dependent H2AX phosphorylation at ser-139 and ATM phosphorylation at ser-1981, indicating ATM activation. Furthermore, BrdU photolysis increased phosphorylation of …


Inhibition Of Margination And Diapedesis Of Neutrophils By Protein Synthesis Blockade, Phyllis V. Acquah Jan 2006

Inhibition Of Margination And Diapedesis Of Neutrophils By Protein Synthesis Blockade, Phyllis V. Acquah

Theses and Dissertations

Acute Respiratory Distress Syndrome (ARDS), an age-old clinical problem facing the Emergency Department and Intensive Care Units of all health systems, is a common debilitating lung condition consequent upon severe systemic inflammation. Although several studies have gone into understanding the epidemiology and pathogenesis of the disease thus making way for new advances in treatment strategies, there seems to be no known study tailored to its prevention. Neutrophil extravasation within the tissues during inflammation is the hallmark of this syndrome. Our study sought to block excessive neutrophil infiltration by inhibiting the biosynthesis of some essential proteins necessary for the process. In …


Characterization Of The Rank Ligand Positive Giant Cell Found In The Interfacial Membrane, Patrick Emerson Jones Jan 2006

Characterization Of The Rank Ligand Positive Giant Cell Found In The Interfacial Membrane, Patrick Emerson Jones

Theses and Dissertations

Aseptic osteolysis is a major complication to total joint arthroplasty requiring several thousand people a year to have to undergo revisions of their joint prosthesis. The formation of the interfacial membrane has been associated with aseptic osteolysis leading to the failure of all types of total joints. Recent evidence suggests that RANKL, a potent activator of bone reabsorption, is present in the interfacial membrane. Prior research in this laboratory to determine the source of RANKL in the interfacial membrane has revealed the presence of intense areas of RANKL concentration in the membrane. These areas of RANKL concentration correspond to multiple …


Phospholipase A2 Induced Monocyte Chemotaxis To Apoptotic Cells, Kwasi Karikari Jan 2006

Phospholipase A2 Induced Monocyte Chemotaxis To Apoptotic Cells, Kwasi Karikari

Theses and Dissertations

Apoptosis is a form of programmed cell death that is essential in such processes as organ and tissue remodeling and maturation of hematopoietic cells. The clearance of apoptotic cells is essential to prevent autoimmune responses to sequestered antigens. This process is mediated by phagocytes of the monocyte lineage. Before phagocytosis can occur, macrophages must be recruited to the apoptotic cells through chemotaxis. Products of the reaction catalyzed by the phospholipases A2 (PLA2) have been shown to induce monocyte chemotaxis either directly or indirectly. Some investigators have implicated a cytosolic calcium-independent PLA2 (iPLA2) in the production of these products during apoptosis. …


Characterization Of The Ftf/Hnf-4 Sites Within The 7alpha- And The 12alpha-Hydroxylase Promoters Involved In The Bile Acid-Mediated Transcription Of Their Regulation, Preeti Pramanik Jan 2006

Characterization Of The Ftf/Hnf-4 Sites Within The 7alpha- And The 12alpha-Hydroxylase Promoters Involved In The Bile Acid-Mediated Transcription Of Their Regulation, Preeti Pramanik

Theses and Dissertations

Bile acids regulate their own synthesis through a feedback regulatory mechanism of mainly two enzymes in the classic pathway, the 7α-hydroxylase and the 12α-hydroxylase. In the early 1990's it was shown that the regulatory responses of 7α-hydroxylase are mediated at the transcriptional level and since then many positive and negative transcription factors that mediate regulatory response have been identified. An important finding was that the transcription factors regulating the expression of 7α- and 12α-hydroxylase genes are nuclear receptors.One of the first nuclear receptors identified to play a role in the transcription of the 7α-hydroxylase gene was HNF-4 since then many …


Stretch-Dependant Tonic Force Maintenance In Rabbit Epigastric Artery, Krystina Michelle Berg Jan 2006

Stretch-Dependant Tonic Force Maintenance In Rabbit Epigastric Artery, Krystina Michelle Berg

Theses and Dissertations

The contractile state of vascular smooth muscle (VSM) plays a key role in blood pressure regulation. Abnormal VSM contractility characterizes hypertension and understanding the regulatory mechanisms of VSM may provide some insights to specific treatment of hypertension. Upon muscle stimulation, Ca2+, myosin light chain (MLC) phosphorylation, crossbridge cycling rates and force increase to high levels, but with time, force is maintained while all other parameters of muscle activation fall to low levels. Thus, contraction is divided temporally into early (phasic) and late (tonic) phases, as determined by the underlying regulatory mechanism. Muscles with more phasic characteristics have a higher peak …


Role Of Mdm2 In Cell Growth Regulation, Rebecca Anne Frum Jan 2006

Role Of Mdm2 In Cell Growth Regulation, Rebecca Anne Frum

Theses and Dissertations

MDM2 has been shown to induce G0-Gl/S phase arrest. To determine the cell cycle step targeted by MDM2, flow cytometry was employed to detect induction of events during the G1-S phase transition in MDM2-arrested cells. MDM2 overexpression does not prevent expression of cyclin D, cyclin D-CDK mediated phosphorylation of Rb or cyclin E in normal, immortal or tumor-derived cells. However, MDM2 down-regulates cyclin A expression specifically in normal cells, which is associated with G1 arrest. The domain of MDM2 capable of this function is located within its N-terminal 58-109 amino acids. To down-regulate cyclin A, MDM2 requires a functional pl6/Brg …


Monocyte Modulation Of Disease Pathogenesis And Progression In Localized Aggressive Periodontitis, Chu Ri Shin Jan 2006

Monocyte Modulation Of Disease Pathogenesis And Progression In Localized Aggressive Periodontitis, Chu Ri Shin

Theses and Dissertations

Localized Aggressive Periodontitis (LAgP) is an aggressive, early onset form of periodontitis characterized by a unique myeloid cell phenotype. In addition to its bacterial origin, the unique phenotype of the myeloid cell contributes to disease pathogenesis and progression through mechanisms mediating host inflammatory and immune responses. LAgP monocytes synthesize increased levels of the potent proinflammatory lipid mediator, Prostaglandin E2 (PGE2), preferentially differentiate into dendritic cells, and lead to increased IgG2 production. In addition, levels of Platelet Activating Factor (PAF) have shown to be elevated in the gingival tissue and gingival crevicular fluid of subjects with periodontitis. The aim of this …


Novel Cancer Therapeutics, The Generation Of Ros, And Cell Survival, Clint Mitchell Jan 2006

Novel Cancer Therapeutics, The Generation Of Ros, And Cell Survival, Clint Mitchell

Theses and Dissertations

The impact of Ad.mda-7 on the survival of renal cell carcinoma lines (RCC), primary renal epithelial cells, glioblastoma multiforme lines (GBM), and primary rodent astrocytes is unknown. The present studies examine whether the GST fusion protein, GST-MDA-7, and the adenovirus, Ad.mda-7, altered the growth and survival of the A498 and UOK121N RCC lines or radiosensitized GBM, respectively. Due to previous findings that the RCC lines, but not primary renal epithelial cells, were resistant to type 5 adenoviral infection, we used purified GST-MDA-7 protein to show that GST-MDA-7, but not GST, caused a dose-dependent reduction in A498 and UOK121N proliferation but …