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Biomedical subjects

P Furth

Publications and source records attributed to P Furth.

At least 19 recordsLinked to original sources
PubMed1999

Maspin plays an important role in mammary gland development.

Maspin is a unique member of the serpin family, which functions as a class II tumor suppressor gene. Despite its known activity against tumor invasion and motility, little is known about maspin's functions in normal mammary gland development. In this paper, we show that maspin does not act as a tPA inhibitor in the mammary gland. However, targeted expression of maspin by the whey acidic protein gene promoter inhibits the development of lobular-alveolar structures during pregnancy and disrupts mammary gland differentiation. Apoptosis was increased in alveolar cells from transgenic mammary glands at midpregnancy. However, the rate of proliferation was increased in early lactating glands to compensate for the retarded development during pregnancy. These findings demonstrate that maspin plays an important role in mammary development and that its effect is stage dependent.

Animals↗
PubMed1996

Bax and Bcl-xs are induced at the onset of apoptosis in involuting mammary epithelial cells.

Mammary gland involution is a physiological process in which the entire organ is remodeled through the process of apoptosis. Apoptosis of secretory alveolar cells is initiated at the time of weaning, followed by the collapse and disappearance of the entire lobuloalveolar compartment. While apoptotic figures were rare in mammary epithelium of lactating mice, their number increased after weaning and reached a maximum on day 3 of involution. Active cell death continued until day 5 after weaning and only little parenchyma remained on day 8, when remodeling of the gland was completed. Bax mRNA levels increased during the first day of involution independent of the presence or absence of p53. Bax protein was detected in an increasing number of cells after weaning, peaking at day 3 and decreasing thereafter. Low levels of bcl-x mRNA and protein were present during lactation, followed by a sharp increase during the first 2 days of involution. The bcl-xS splice variant of bcl-x can promote cell death, and bcl-xL has a protective function in cell culture. The ratio of bcl-xS versus bcl-xL remained stable in the virgin, pregnant and lactating gland. However, during the first 2 days of involution, bcl-xS expression increased six-fold more than bcl-xL. To further evaluate the role of Bcl-xS which was less abundant in the mammary cells than Bcl-xL, cotransfection studies were performed in cell culture. They confirmed that Bcl-xS protein can facilitate apoptosis even when Bcl-xL is present in excess. These findings point to a significant role for Bax and Bcl-xS in the regulation of apoptosis of secretory alveolar cells during involution.

Animals↗
PubMed1995

Interaction of a peptidomimetic aminimide inhibitor with elastase.

The crystal structure of an aminimide analog of a dipeptide inhibitor of porcine pancreatic elastase bound to its target serine protease has been solved. The peptidomimetic molecule binds in the same fashion as the class of dipeptides from which it was derived, making similar interactions with the subsites on the elastase surface. Because aminimides are readily synthesized from a wide variety of starting materials, they form the basis for a combinatorial chemistry approach to rational drug design.

Amino Acid Sequence↗