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Expression And Characterization Of Two Alternatively Spliced Isoforms Of Rat Type I Receptor For Inositol 1,4,5-Trisphosphate, Doris Da May Lin

Yale Medicine Thesis Digital Library

The transmembrane receptor for IP3 is a tetrameric calcium channel located in the endoplasmic reticulum. In many cell types the receptor mediates such complex signals as calcium waves and oscillations. There are multiple receptor isoforms, derived by alternative splicing as well as different genes. The functional significance of these many receptor isoforms has not been determined. To this end, I have generated cell lines that express homotetrameric receptors.Stable lines of the human embryonic kidney (HEK293) cells were established by transfection with cDNAs encoding for two splice variants of the rat type I receptor. The two variants differ in the presence …

The Spleen Focus-Forming Virus Envelope Glycoprotein, Gp55, And The Block In The Erythropoietin-Induced Differentiation Of Friend Murine Erythroleukemia Cells, Thomas Samuel Lin

Yale Medicine Thesis Digital Library

Unlike normal committed erythroid progenitor cells, which require erythropoietin (EPO) for both proliferation and terminal differentiation, Friend murine erythroleukemia (MEL) cells are EPO-independent and do not differentiate in response to the cytokine. Dimethylsulfoxide (DMSO) induces differentiation and restores responsiveness to EPO. DMSO-treated Friend cells responded to EPO with both increased proliferation and further hemoglobin synthesis. The effects of DMSO upon the expression of EPO receptor (EPOR) mRNA and cell surface receptor were examined. Clone DMSO/R1, an MEL subline resistant to the differentiation-inducing and EPO-sensitizing effects of DMSO, expressed a higher level of EPOR mRNA than parental Friend cells, and DMSO …

Syncope In A Population-Based Sample Of Elderly Persons: Prevalence, Predisposing Risk Factors, And Precipitating Events, Eric A. Gomes

Yale Medicine Thesis Digital Library

Syncope is a serious but potentially preventable occurrence commonly afflicting the elderly population. The objectives of this study were to estimate the incidence of syncope in the community-dwelling elderly population, to identify the clinical risk factors that predispose some elderly persons to syncope, and to describe situational factors and the morbidity associated with syncope. Study participants were members of the Project Safety cohort, representing a probability sample of non-institutionalized residents of New Haven, Connecticut aged 72 years or older. Age-restricted housing lists and utilities listings were used to generate an index of community dwellings from which 5,936 households were identified. …

The Identification And Characterization Of Protein Tyrosine Phosphatases Expressed In The Developing Rat Brain, Mustafa Sahin

Yale Medicine Thesis Digital Library

Previous studies of the developing nervous system have shown that cell-cell and cell-matrix interactions are involved in a variety of processes such as the proliferation, migration and differentiation of neurons. While many cell surface molecules have been identified, the signal transduction mechanisms through which they alter cellular responses are poorly understood. Recent studies have described a new and large family of enzymes, protein tyrosine phosphatases (PTPases), that may play a key role in transduction of cell surface events. Opposing the actions of protein tyrosine kinases (PTKs), PTPases may determine the state of tyrosine phosphorylation of a protein and regulate its …

Protein-Tyrosine Phosphatase In Normal And Malignant Melanocytes, James H. Ahn

Yale Medicine Thesis Digital Library

We embarked on a study to define the role of protein-tyrosine phosphatases (PTPases) in both normal melanocytes and melanoma cells, searching for specific differences that might provide clues to the malignant transformation process in these cells and to the role of PTPases as possible tumor suppressor genes. We used Northern blotting and RNase protection assays to measure mRNA expression levels, immunoprecipitation and immunoblotting to measure protein expression, and a bioassay to measure protein PTPase activity in normal melanocyte and melanoma cell lines.

Our experiments showed that all major PTPases are equally expressed at both mRNA and protein levels, except for …

Long-Term Outcomes Of Infants Identified As Being At High Risk Of Maltreatment, Jilda N. Vargus

Yale Medicine Thesis Digital Library

No abstract provided.

The Rotational Orientation Of The T Cell Receptor Bound To Peptide: Mhc, Sangwook Tim Yoon

Yale Medicine Thesis Digital Library

The T cell receptor (TCR) is the multi-chained cell surface molecule that mediates the specific recognition of antigen by the T cell. The alpha and beta chains of the TCR are members of the immunoglobulin gene superfamily and form the antigen binding components of the TCR. Although the function of alphabeta-TCRs has been well characterized, less is known about their molecular structure. Current three-dimensional structural models of TCR are based on the similarities in primary sequence between the TCR with immunoglobulin genes. Models of the ternary structure of the TCR and MHC complex have also been proposed. These models, however, …