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P Farnham

Publications and source records attributed to P Farnham.

10 recordsLinked to original sources

Expression patterns of the E2F family of transcription factors during mouse nervous system development.

The E2F family of transcription factors consists of two subgroups termed E2F and DP. E2F is required for cell proliferation, and is necessary for fruit fly development. E2F activity is a target for regulation by the retinoblastoma gene family, which includes pRB, p107 and p130. Mutant RB-/-, RB-/-:p107-/- and p107-/-:p130-/- mice develop abnormally, probably as a result of dysregulation in the activity of E2F, indicating the importance of E2F in mammalian development. To investigate the role of E2F in murine development, we have examined the patterns of expression of E2F-1 through E2F-5, and DP-1 in the developing nervous system by in situ hybridization. E2F-1, E2F-2 and E2F-5 are first detected in the 9.5 days post-coitus (dpc) forebrain. Expression of these E2F forms extends caudally thereafter and includes the developing brain and the upper half of the 10.5 dpc spinal cord. By 11.5 dpc, these E2F factors are expressed throughout the central nervous system. In 12.5 dpc embryos, E2F-1, E2F-2 and E2F-5 are highly expressed in proliferating, undifferentiated neuronal precursors. As neurons differentiate and migrate to the outer marginal zones in the nervous system, expression of these E2F members is extinguished. In the developing retina, another neuronal tissue, E2F-1 expression is also confined to the proliferating, undifferentiated retinoblastic layer. In contrast, E2F-3 expression is up-regulated as retinoblasts differentiate into the ganglion cell layer. In non-neuronal tissues, high E2F-4 transcript levels are present in regions corresponding to proliferative chondrocytes, whereas E2F-2 and E2F-4 transcripts are very abundant in the thymic cortex, which contains immature thymocytes. We conclude that individual E2F forms are differentially regulated during the development of distinct tissues, and especially during neuronal development.

3T3 Cells↗

Computer simulated cost effectiveness of care management strategies on reduction of long-term sequelae in patients with non-insulin dependent diabetes mellitus.

Systems dynamics and computer "microworlds" offer a window on the long-term benefit of investing in aggressive care management for patients with non-insulin dependent diabetes mellitus. This article describes how clinicians, planners, payment specialists, and patients collaborated to make the business case for aggressive management of this disease.

Blood Glucose↗

Expression patterns of the E2F family of transcription factors during murine epithelial development.

The E2F family of transcription factors includes five E2F and three DP forms. E2F is involved in the regulation of cell proliferation, but little is known about E2F function during vertebrate development. We have explored the regulation of E2F expression during mouse organogenesis by in situ hybridization. We find selective up-regulation of E2F-2, E2F-4, and E2F-5 transcripts in epidermis and intestinal epithelium at important developmental stages. E2F-4 transcript levels are high in early, undifferentiated single-cell-layer ectoderm, and later in 13.5-14.5-day-postcoitus (dpc) embryo epithelium, which contains several layers of proliferating cells. E2F-2 is up-regulated following the onset of E2F-4 expression and is first apparent in undifferentiated epithelium at 13.5-14.5 days of gestation. In contrast, E2F-5 transcripts are detected later in gestation, once the epidermis shows evidence of stratification. Stratification of the epidermis into basal, proliferating cells and suprabasal, terminally differentiating cells at 15.5-19.5 days of gestation coincides with expression of E2F-2 and E2F-4 in basal cells and of E2F-5 in suprabasal cells. Similarly, in intestinal epithelium, E2F-4 up-regulation in pseudostratified epithelium at 13.5 days of gestation precedes appearance of E2F-2 transcripts, in 14.5-dpc embryos, in the proliferating, intervillus epithelium. In 16.5-19.5-dpc embryos, no E2F-2 transcripts were detected at the tip of the developing villi, which contain terminally differentiating cells. In contrast, E2F-5 transcripts were limited to the upper half of the villi and were absent in the intervillus epithelium. This suggests that E2F-2 and E2F-4 may participate in maintaining epithelial cells in a proliferative, undifferentiated phenotype, whereas E2F-5 may be important to maintain the differentiated state. Thus, selective regulation of E2F forms occurs during murine epithelial development, irrespective of the ectodermal or endodermal origin of such epithelia.

Amino Acid Sequence↗

Potential and actual workdays lost among patients with HIV.

How many more potential and actual workdays are lost by HIV patients than persons without HIV? To answer this question, we assessed differences in the number of workdays among a panel of AIDS patients, patients who were HIV positive but did not yet have AIDS, and comparison patients. The patients included persons who were employed and unemployed. Information on 1,346 patients was gathered from January 1, 1990, to December 31, 1992, as part of the ongoing ATHOS (AIDS Time-Oriented Health Outcome Study) study. Data were collected every 3 months on AIDS and HIV-positive patients and every 6-12 months on the comparison patients. At the end of the study (December 31, 1992), 856 people were still enrolled. A total of 5,507 panel data points covering 3 years were available. Data were analyzed with a linear regression model. We found that patients with AIDS reported 29-32 and HIV-positive patients reported 9-13 more potential and actual workdays lost out of the previous 90 than the comparison patients, other variables being equal. All p values were < 0.005, and most were < 0.0001. We conclude that (a) while the AIDS patients showed substantially more workdays lost than the comparison group, the HIV-positive group showed only a modest number of more days lost than the comparison group and (b) that previous estimates exaggerated indirect morbidity costs.

Absenteeism↗