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Biomedical subjects

M E Dodge

Publications and source records attributed to M E Dodge.

4 recordsLinked to original sources

Stress-mediated signaling in PC12 cells - the role of the small heat shock protein, Hsp27, and Akt in protecting cells from heat stress and nerve growth factor withdrawal.

We have investigated the role of stress-activated signaling pathways and the small heat shock protein, Hsp27, in protecting PC12 cells from heat shock and nerve growth factor (NGF) withdrawal-induced apoptosis. PC12 cells and a stable cell line overexpressing Hsp27 (HSPC cells) were subjected to heat shock. This resulted in the rapid activation of Akt followed by p38 mitogen-activated protein kinase (MAPK) signaling, with phosphorylation and intracellular translocation of Hsp27 also detectable. Hsp27 was found to form an immunoprecipitable complex with Akt and p38 MAPK in both non-stimulated and heat shocked cells, although after heat shock there was a gradual dissociation of Akt and p38 from the Hsp27. Cells were differentiated with NGF and then subjected to NGF withdrawal, a treatment which results in substantial cell death over 24-72 h. Hsp27 was shown to be protective against this treatment, since HSPC cells which overexpress Hsp27 showed significantly less cell death than the parental PC12 cells. In addition, we observed that phosphorylation of Akt was maintained in HSPC cells subjected to heat shock and NGF withdrawal compared with the parental cells. Taken together, our results suggest that Hsp27 may protect Akt from dephosphorylation and may also act in stabilizing Akt.

Active Transport, Cell Nucleus↗

Glucose perturbation in experimental hyperviscosity.

Hyperviscosity was produced in one member of each of 7 sets of twin newborn lambs by an exchange transfusion with 500 ml maternal packed red blood cells. The remaining seven control twin lambs underwent an identical exchange with maternal whole blood. Postexchange hematocrits were 63 +/- 6 and 29.0 +/- 3% (mean +/- S.E.), respectively (P less than 0.01). Whole blood viscosity measured at 3 rpm increased from 3.2 +/- 0.4 centipoise (cps) to 14.4 +/- 6.1 cps in the lambs made hyperviscous (P less than 0.01) and remained unchanged in the control lambs (2.2 +/- 0.1 versus 2.8 +/- 0.3 cps). A 2-hr steady state glucose infusion was performed on each lamb before and after the packed cell or whole blood exchange transfusion. Mean steady state plasma glucose concentrations were significantly decreased from pre-exchange steady state glucose infusion levels in the same lambs made hyperviscous (P less than 0.05), whereas steady state glucose levels increased from preexchange levels in the twin lambs exchanges with maternal whole blood. Mean plasma insulin and glucagon values for the hyperviscous and control lambs remained unchanged during the glucose infusion.

Animals↗

Pulmonary and circulatory function in preterm lambs treated with hydrocortisone in utero.

The effects of the in utero intravenous administration of hydrocortisone on postnatal lung function and pulmonary and systemic hemodynamics were studied in preterm fetal lambs and compared with those of non-treated animals of similar gestational ages. The results indicate that steroid-induced changes in lung pressure volume curves, although statistically significant, did not render the pretreated fetuses capable of surviving without ventilatory assistance. In addition, the ductus arteriosus in the steroid-treated lambs at 2 h of age was functionally closed or constricted regardless of gestational age. In contrast, in the untreated lambs the ductus arteriosus was widely patent and, especially in lambs of less than 120 days gestation, there was invariably a large left-to-right ductal shunt.

Animals↗

Early functional closure of the ductus arteriosus associated with decreased severity of respiratory distress syndrome in preterm infants.

It has been shown that a patent ductus arteriosus may complicate the course of the respiratory distress syndrome (RDS) in preterm infants. In this study, an attempt is made to answer the question: Is there any relationship between RDS and patency of the ductus arteriosus in preterm infants, that is, do preterm infants without the RDS have early functional closure of the ductus arteriosus? Clinical observations were made on 144 preterm infants 25 to 34 weeks' gestation. Infants were included in the study if the status of the ductus arteriosus (open or closed) could be established either by clinical examination or retrograde aortography. The ductus arteriosus was closed in 59 infants within 48 hours of birth and open in 85. None of the infants with a closed ductus had severe RDS and only three had mild RDS. In contrast, 50% (43 of 85) of infants with open ductus had severe RDS. These findings suggest that early functional closure of the ductus can occur even in very immature infants, and this early closure appears to be associated with a decreased incidence of RDS.

Aortography↗