Translating Rhetoric to Reality: The Future of Family and Children's Services

These remarks were first prepared by the author for the inauguration of the Marion Elizabeth Blue Endowed Professorship in Children and Families at the University of Michigan School of Social Work. They were delivered on October 5, 1999, and originally appeared as a monograph published by the University of Michigan School of Social Work in December 1999. They are reprinted here by permission.

The adolescent response to pregnancy: Accepting the reality

The research literature on adolescent pregnancy indicates a relationship between early prenatal care and positive pregnancy outcomes, yet fewer than half of pregnant teenagers seek prenatal care in the first trimester of pregnancy. Although social support theory speculates that there should be a relationship between support and health outcomes, available studies do not reflect the processes by which pregnant adolescents use their social resources in making decisions about their pregnancies. This study describes the processes by which the adolescent comes to accept the reality of her pregnancy.^ Drawing from the social-psychological theories of illness behavior and symbolic interactionism, this study examines the symptom diagnosis and help seeking behavior of the pregnant adolescent. This approach describes how the adolescent interprets events and draws conclusions based on her social reality.^ Interviews were conducted with ten young women, aged 15-17, who had recently delivered a first child. Onset of prenatal care ranged from the third month to the seventh month. None were married, and all but two lived with a parent. All but one were currently in school. Initial unstructured interviews were attempted to construe the modes of expression of the young women regarding the event of pregnancy. Subsequent interviews elicited the processes of recognition and explanation of symptoms of pregnancy.^ Analysis revealed a consistent natural history in the subjects' experiences as they come to accept the reality of pregnancy. Symptom appraisal and definition involves noticing changes in themselves, and evaluating and attempting to find suitable explanations for these symptoms. Lay consultation from friends and family aids in identifying the symptoms and to receive suggestions for treatment. It is at this point that prenatal care is usually initiated. Finally the young women describe the integration of pregnancy into their belief systems. ^

Generation of an hTERT-restricted, CMV-augmented oncolytic adenovirus capable of tumor-specific transgene expression: Development, characterization, and optimization

Current shortcomings in cancer therapy require the generation of new, broadly applicable, potent, targeted treatments. Here, an adenovirus is engineered to replicate specifically in cells with active human telomerase promotion using a modified hTERT promoter, fused to a CMV promoter element. The virus was also modified to contain a visible reporter transgene, GFP. The virus, Ad/hTC-GFP-E1 was characterized in vitro and demonstrated tumor specific activity both by dose and over time course experiments in a variety of cell lines. In vivo, Ad/hTC-GFP-E1 was affected at suppressing tumor growth and providing a survival benefit without causing any measurable toxicity. To increase the host range of the vector, the fiber region was modified to contain an RGD-motif. The vector, AdRGD/hTC-GFP-E1, was recharacterized in vitro, revealing heightened levels of infectivity and toxicity however maintaining a therapeutic window between cancer and normal cell toxicity. AdRGD/hTC-GFP-E1 was administered in vivo by limb perfusion and was observed to be tumor specific both in expression and replication. To further enhance the efficacy of viral vectors in lung delivery, asthma medications were investigated for their abilities to enhance transgene delivery and expression. A combination of bronchodilators, mast cell inhibitors, and mucolytic agents was devised which demonstrated fold increases in expression in immunocompetent mouse lungs as single agents and more homogenous, intense levels of expression when done in combination of all agents. To characterize the methods in which some cancers are resistant or may become resistant to oncolytic treatments, several small molecule inhibitors of metabolic pathways were applied in combination with oncolytic infection in vitro. SP600125 and PD 98059, respective JNK and ERK inhibitors, successfully suppressed oncolytic toxicity, however did not affect infectivity or transgene expression of Ad/hTC-GFP-E1. JNK and ERK inhibition did significantly suppress viral replication, however, as analyzed by lysate transfer and titration assays. In contrast, SB 203580, an inhibitor for p38, did not demonstrate any protective effects with infected cells. Flow cytometric analysis indicated a possible correlation with G1 arrest and suppressed viral production, however more compounds must be investigated to clarify this observation. ^