Biomedical subjects

Frank Schroeder

Publications and source records attributed to Frank Schroeder.

3 recordsLinked to original sources

PubMed2003

A chemical genetic screen identifies inhibitors of regulated nuclear export of a Forkhead transcription factor in PTEN-deficient tumor cells.

The PI3K/PTEN/Akt signal transduction pathway plays a key role in many tumors. Downstream targets of this pathway include the Forkhead family of transcription factors (FOXO1a, FOXO3a, FOXO4). In PTEN null cells, FOXO1a is inactivated by PI3K-dependent phosphorylation and mislocalization to the cytoplasm, yet still undergoes nucleocytoplasmic shuttling. Since forcible localization of FOXO1a to the nucleus can reverse tumorigenicity of PTEN null cells, a high-content, chemical genetic screen for inhibitors of FOXO1a nuclear export was performed. The compounds detected in the primary screen were retested in secondary assays, and structure-function relationships were identified. Novel general export inhibitors were found that react with CRM1 as well as a number of compounds that inhibit PI3K/Akt signaling, among which are included multiple antagonists of calmodulin signaling.

Active Transport, Cell Nucleus↗

PubMed2003

Hydroxyethyl starch (HES) 130/0.4 provides larger and faster increases in tissue oxygen tension in comparison with prehemodilution values than HES 70/0.5 or HES 200/0.5 in volunteers undergoing acute normovolemic hemodilution.

UNLABELLED: Stable hemodynamics and improved rheology are important effects of hemodilution with hydroxyethyl starch (HES) infusions. One clinical indicator of improved rheology is increased tissue oxygen tension (tpO(2)). In this prospective, randomized, double-blinded, crossover study, we examined the effects of acute normovolemic hemodilution with HES 130/0.4 on hemodynamics and skeletal muscle tpO(2) in comparison with conventional HES solutions. Twelve healthy volunteers were randomly enrolled in each group. At an interval of >8 days, volunteers donated 18% of their calculated blood volume within 30 min and randomly received 6% HES 130/0.4, 6% HES 70/0.5, or 6% HES 200/0.5 (crossover design) in a 1:1.2 ratio to their blood loss. Hemodynamic variables, tpO(2) in the quadriceps muscle, hematocrit, plasmatic HES concentrations, plasma viscosity, colloid osmotic pressures, and platelet aggregation were measured until 6 h after the infusion of HES. No differences were found among groups with respect to changes of hemodynamics, hematocrit, or platelet aggregation. With HES 200, colloid osmotic pressures and plasma viscosities were larger than after HES 70 (P < 0.05). HES 130 in comparison with HES 70 and 200 caused the fastest (30 min versus 90 min and 150 min after hemodilution; P < 0.05) and largest increase of tpO(2) in comparison to baseline (+93% versus +33% and 40%; P < 0.05). In healthy volunteers undergoing acute normovolemic hemodilution, the newly designed HES 130/0.4 showed a more pronounced and earlier increase of skeletal muscle tpO(2) in comparison with prehemodilution values than HES 70/0.5 or 200/0.5. IMPLICATIONS: The effects of three different hydroxyethyl starch (HES) solutions on hemodynamics, rheology, and skeletal muscle tissue tension after acute normovolemic hemodilution were examined in awake volunteers. With HES 130/0.4, increases of tissue oxygen tension in comparison to baseline were larger and more rapid than with HES 70/0.5 or HES 200/0.5.

Adult↗

PubMed2002

Active warming during cesarean delivery.

UNLABELLED: We tested the hypothesis that 15 min of forced-air prewarming, combined with intraoperative warming, prevents hypothermia and shivering in patients undergoing elective cesarean delivery. We simultaneously tested the hypothesis that maintaining maternal normothermia increases newborn temperature, umbilical vein pH, and Apgar scores. Thirty patients undergoing elective cesarean delivery were randomly assigned to forced-air warming or to passive insulation. Warming started 15 min before the induction of epidural anesthesia. Core temperature was measured at the tympanic membrane, and shivering was graded by visual inspection. Patients evaluated their thermal sensation with visual analog scales. Rectal temperature and umbilical pH were measured in the infants after birth. Results were compared with unpaired, two-tailed Student's t-tests and chi(2) tests. Core temperatures after 2 h of anesthesia were greater in the actively warmed (37.1 degrees C +/- 0.4 degrees C) than in the unwarmed (36.0 degrees C +/- 0.5 degrees C; P < 0.01) patients. Shivering was observed in 2 of 15 warmed and 9 of 15 unwarmed mothers (P < 0.05). Babies of warmed mothers had significantly greater core temperatures (37.1 degrees C +/- 0.5 degrees C vs 36.2 degrees C +/- 0.6 degrees C) and umbilical vein pH (7.32 +/- 0.07 vs 7.24 +/- 0.07). IMPLICATIONS: Perioperative forced-air warming of women undergoing cesarean delivery with epidural anesthesia prevents maternal and fetal hypothermia, reduces maternal shivering, and improves umbilical vein pH.

Adult↗