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F Zhou

Publications and source records attributed to F Zhou.

169 records · Page 10Linked to original sources
PubMedDate not supplied

Glucocorticoid mediated transcriptional repression of c-myc in apoptotic human leukemic CEM cells.

Suppression of c-myc has been implicated as a critical event in some glucocorticoid-evoked apoptotic systems. It is therefore of interest to understand the mechanism of glucocorticoid-regulation of the c-myc gene. In the present study, a detailed analysis of dexamethasone (Dex)-evoked regulation of the human c-myc gene in human leukemic CEM-C7 cells has been performed. Dex suppresses c-myc mRNA and immunoreactive protein expression in clone CEM-C7 and subclone CEM-C7-14 cells. Nuclear run-on assays suggested that the regulation occurred at the level of transcription initiation. The half-life of c-myc mRNA was approximately 30 min and its stability was not affected by Dex treatment. In addition, Dex suppressed luciferase gene expression driven by -2052 to +34 bp c-myc promoter in transfected CEM-C7-14 cells. This result further supports that c-myc gene is suppressed by Dex at the transcriptional level in apoptotic human leukemic cells.

Apoptosis↗
PubMedDate not supplied

Glucocorticoids, oxysterols, and cAMP with glucocorticoids each cause apoptosis of CEM cells and suppress c-myc.

In clones of the CEM human acute lymphoblastic leukemic cell line, glucocorticoids, oxysterols and activators of the cAMP pathway acting synergistically with glucocorticoids, each can cause apoptotic cell death. Morphologically and kinetically, these deaths resemble one another. The kinetics are striking: in each case, after addition of the lethal compound(s), an interval of approximately 24 h follows, during which cell growth continues unabated. During this "prodromal" period, removal of the apoptotic agent leaves the cells fully viable. We hypothesize that a sequence of biochemical events occurs during the prodrome which eventually results in the triggering of the full apoptotic response as evidenced by the activation of caspases and DNA fragmentation. At some point, the process is irreversible and proceeds relatively rapidly to cell death. Suppression of c-Myc seems a universal early event evoked by each of these lethal compounds or combinations, and we conclude that the negative regulation of this proto-oncogene is an important aspect of the critical pre-apoptotic events in these cells.

Apoptosis↗
PubMedDate not supplied

Paradigm to test a drug-induced aversion to ethanol.

The screening of new agents for aversive therapy of alcoholism requires a simple animal model. Animals trained to ingest ethanol solutions and subsequently administered a drug known to produce an aversion to ethanol in humans, do not readily make the association between the malaise induced by the aversive drug-ethanol reaction and the consumption of the same ethanol-containing solution that has been consumed previously without ill effects. An experimental paradigm is reported in which the malaise of the drug-ethanol reaction is quickly recognized by rats as derived from ethanol. Disulfiram was used as the model drug. Lewis rats were deprived of water for 18 h after which 6% (v/v) ethanol was offered as the only fluid. During the first hour of ethanol access, both controls (vehicle) and disulfiram (100 mg/kg)-treated animals consumed intoxicating amounts of ethanol (0.7-0.9 g ethanol/kg). Plasma acetaldehyde levels developed were 3-5 microM and 40-50 microM in the two groups respectively. After this time, disulfiram-treated animals virtually ceased consuming alcohol (90% inhibition), indicating that the disulfiram-ethanol reaction is associated with alcohol ingestion. Control animals continued consuming the alcohol solution for the additional 4-5 h tested. This model should be of value in the testing of new agents that reduce aldehyde dehydrogenase levels for prolonged periods for their potential as an aversive treatment in alcoholism.

Acetaldehyde↗
PubMedDate not supplied

The internal ventricular venting loop catheter. A new, simplified, single cannulation approach for a ventricular assist system.

The internal ventricular venting loop (IVVL) catheter is a coaxial, two lumen, bidirectional flow cannula introduced peripherally and advanced intraluminally to the pulmonary artery by its flow directed, balloon tipped inner tubing in a right ventricular assist system (RVAS), or to the left ventricle over a guide wire under fluoroscopy in a left ventricular assist system (LVAS). Its use was successfully tested in six acute canine experiments using a small IVVL catheter. Hemodynamic responses to increasing roller pump flow rates, to a maximum of 1 L/min, were initially measured. Then, hemodynamic changes to 600 ml/min, after left anterior descending artery ligation (in IVVL-LVAS) and 300 ml/min after right coronary artery ligation (in IVVL-RVAS) were regularly recorded every 15 min until cardiac arrest. The IVVL-LVAS was able to significantly decrease the pulmonary capillary wedge pressure, while the IVVL-RVAS was able to significantly decrease the central venous pressure. The IVVL system was able to partially unload the ventricles and restore about 33-60% of the cardiac output. However, it could not effectively support the heart during arrest. Thus, the IVVL catheter can facilitate simple and effective single cannulation for either RVAS or LVAS. This approach may enable ordinary cardiac centers to make use of already available blood pumps for temporary, inexpensive, and less invasive application of partially assisted circulation when intra aortic balloon pump assistance fails.

Animals↗