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D M Nelson

Publications and source records attributed to D M Nelson.

117 records · Page 7Linked to original sources

The kinase p38 regulates peroxisome proliferator activated receptor-gamma in human trophoblasts.

Deficiency of either the mitogen-activated protein kinase p38 or the nuclear receptor PPARgamma results in disrupted vasculogenesis and abnormal development of the murine placenta. In addition, PPARgamma regulates differentiation of human trophoblasts. Here we tested the hypothesis that p38 plays an important role in the regulation of PPARgamma in primary human trophoblasts. We initially confirmed that cultured trophoblasts derived from normal term human placentas express p38 as well as its functional phosphorylated form. Whereas PPARgamma did not alter p38 expression, p38 inhibitors diminished the transcriptional activity of PPARgamma in primary trophoblasts. In addition, inhibition of p38 resulted in marked attenuation of PPARgamma-stimulated hCG production by cultured trophoblast. Our data support an effect of p38 on PPARgamma protein stability because p38 inhibition led to reduced expression of PPARgamma protein without a significant effect on PPARgamma mRNA, and this reduction was blocked by the protease inhibitor MG-132. Together, these data indicate that p38 regulates PPARgamma expression and activity in term human trophoblasts. Cross talk between p38 and PPARgamma signaling may play a role in modulating differentiation and function of the human placenta.

Cells, Cultured↗

Paracellular permeability pathways in the human placenta: a quantitative and morphological study of maternal-fetal transfer of horseradish peroxidase.

Physiological data indicate that both a transcellular and a paracellular pathway are available for transfer across the human placenta but the morphological correlate of the latter is uncertain. We measured the permeability of the dually perfused human placental cotyledon to the predominantly cationic protein horseradish peroxidase (MW 40,000), to the neutral polymer 14C-dextran (MW 50-70,000) and to the extracellular space marker creatinine (MW 113). Following fixation and cytochemistry, we used brightfield microscopy to localize peroxidase reaction product within the same tissue. Steady state unidirectional maternofetal clearance (Kmf) for the peroxidase (0.90 +/- 0.27 microliters/min/g, n = 9) was not significantly different from that for 14C-dextran (0.95 +/- 0.07 microliters/min/g, n = 3) suggesting that charge does not markedly influence peroxidase permeability. The Kmf for creatinine was 13.1 +/- 2.5 microliters/min/g (n = 9); these permeability data are similar to those reported for the placenta in vivo. Microscopically, peroxidase reaction product was localized to the microvillous surface of the syncytiotrophoblast of most villi and to the trophoblastic basement membrane and connective tissue cells of the villous core in a few villi. The reaction product was also associated with fibrin-containing deposits attached to the villous core at sites of discontinuity of the syncytial epithelium. The staining pattern within the deposits was consistent with a diffusion gradient of the peroxidase. These fibrin-containing deposits at discontinuities in the syncytiotrophoblast may provide one paracellular route for peroxidase diffusion from the intervillous space into the villous core.

Cell Membrane Permeability↗

Differentiation and secretory activities of cultured human placental cytotrophoblast.

Ultrastructural, autoradiographic, immunofluorescent and biochemical techniques were used to characterize primary cultures of term placental cytotrophoblast in order to gain insight into the differentiation and secretory capacities of the cellular component of human trophoblast. Trypsin treatment of placental villi allowed isolation of a predominantly cytotrophoblast cell population that maintained viability up to 13 weeks in monolayer culture. Autoradiographic studies of tritiated thymidine incorporation identified a smaller diameter mononucleated cell population that was mitotically active and developed into larger diameter mononucleated cells and into multinucleated cells during culture. Ultrastructurally, cultured cells formed desmosomes, had an extensive network of cytoplasmic microfilaments and contained the organelles for hormone synthesis and secretion. These cells secreted steroid hormones, secreted Schwangerschafts protein I, actively incorporated tritiated glycoprotein precursors and expressed surface immunoreactivity for the beta-subunit of human chorionic gonadotrophin (hCG). However, medium concentrations of hCG and human placental lactogen dropped rapidly to undetectable levels after 14 days in primary culture. Cells grown beyond confluence differentiated into 1 to 2 mm structures with a villus-like histology. Our studies indicate that cytotrophoblast can secrete steroids, cytotrophoblast differentiation occurs in vitro in the absence of maternal tissues, hCG synthesis occurs in cultured cytotrophoblast and medium concentrations of placental protein hormones are not the best indicators of cell viability for cultures of cytotrophoblast.

Autoradiography↗

Central regional profile of dental hygiene students.

PURPOSE: This study was designed to identify personal, familial, academic, and employment characteristics of dental hygiene students from the central region of the United States to develop a comprehensive student profile for research and recruitment purposes. METHODS: In fall 1990, 25 dental hygiene program directors in ten states in the central region of the United States and 475 students enrolled in these programs were mailed surveys to develop program and student profiles. Data were analyzed using measures of central tendency and frequency. RESULTS: Directors and students from 24 of 25 dental hygiene programs responded. Data are reported from these 24 directors and 422 of 464 (91%) of the students enrolled in the programs. Dental hygiene students in the central region of the United States are similar in personal, parental, and academic backgrounds to the general population of college students nationally. Unlike the general college population, the regional dental hygiene population tends to be singularly female. Students chose to major in dental hygiene for economic and personal reasons. The availability of employment opportunities, the flexibility to work full- or part-time, and the prospects of making a better income and becoming a professional influenced their decision. Students identified dentists, dental hygienists, and relatives as being influential in their becoming interested in the dental hygiene profession. Previous dental office employment experience also influenced many students in their career choice. CONCLUSION: The study findings provide information for dental hygiene educators and others interested in student characteristics and factors that influence the selection of dental hygiene as a career.

Adult↗