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J Tilly

Publications and source records attributed to J Tilly.

5 recordsLinked to original sources
PubMed2006

Molecular requirements for doxorubicin-mediated death in murine oocytes.

We previously published evidence that oocytes exposed to doxorubicin (DXR), a widely used chemotherapeutic agent, rapidly undergo morphological and biochemical changes via discrete effector signaling pathways consistent with the occurrence of apoptosis. In this report, we elucidated the molecular requirements for actions of this drug in oocytes. Our results indicate that within 1 h of exposure DXR causes rapid DNA damage, and commits the oocyte to cytoplasmic fragmentation by the fourth hour, followed by delayed oocyte activation and execution of cytoplasmic fragmentation. Inhibitors that interfere with oocyte activation consistently rescue cytoplasmic fragmentation, but fail to suppress DNA damage. There was evidence of depletion of Bax, Caspase-2, MA-3 and Bcl-x transcripts, suggesting that modulations by DXR caused recruitment of these maternal transcripts into the translation process. Furthermore, sphingolipids such as sphingosine-1-phosphate and ceramide modulate DXR actions by, respectively, altering its intracellular trafficking, or by sustaining the drug's contact with DNA.

Animals↗
PubMed2001

Consumer-directed home and community services programs in eight states: policy issues for older people and government.

This study assesses consumer-directed home and community services for older persons by examining public programs that serve this population in eight states. These programs give beneficiaries, rather than agencies, the power to hire, train, supervise, and fire workers. Most stakeholders interviewed, in addition to the quantitative research, indicate that many older beneficiaries want to and can manage their services, although significant issues arise for persons with cognitive impairments. Research results suggest better, or, at least, no worse, quality of life for beneficiaries when they direct their services, although quality of services remains a contentious issue. For workers, consumer-directed care has some disadvantages, including fewer fringe benefits. With exceptions, state agencies have not provided extensive consumer or worker support or aggressively regulated quality of care.

Aged↗
PubMed1996

Requirement of basement membrane for the suppression of programmed cell death in mammary epithelium.

Apoptosis is an active mechanism of cell death required for normal tissue homeostasis. Cells require survival signals to avoid the engagement of apoptosis. In the mammary gland, secretory epithelial cells are removed by apoptosis during involution. This cell loss coincides with matrix metalloproteinase activation and basement membrane degradation. In this paper we describe studies that confer a new role for basement membrane in the regulation of cell phenotype. We demonstrate that the first passage epithelial cells isolated from pregnant mouse mammary gland die by apoptosis in culture, but that cell death is suppressed by basement membrane. The correct type of extracellular matrix was required, since only a basement membrane, not plastic or a collagen I matrix, lowered the rate of apoptosis. Attachment to a matrix per se was not sufficient for survival, since apoptotic cells were observed when still attached to a collagen I substratum. Experiments with individually isolated cells confirmed the requirement of basement membrane for survival, and demonstrated that survival is enhanced by cell-cell contact. A function-blocking anti-beta1 integrin antibody doubled the rate of apoptosis in single cells cultured with basement membrane, indicating that integrin-mediated signals contributed to survival. We examined the cell death-associated genes bcl-2 and bax in mammary epithelia, and found that although the expression of Bcl-2 did not correlate with cell survival, increased levels of Bax were associated with apoptosis. We propose that basement membrane provides a survival stimulus for epithelial cells in vivo, and that loss of interaction with this type of matrix acts as a control point for cell deletions that occur at specific times during development, such as in mammary gland involution.

Animals↗