Effects of protein kinase C activators on phorbol ester-sensitive and - resistant EL4 thymoma cells

Phorbol ester-sensitive EL4 murine thymoma cells respond to phorbol 12- myristate 13-acetate with activation of ERK mitogen-activated protein kinases, synthesis of interleukin-2, and death, whereas phorbol ester- resistant variants of this cell line do not exhibit these responses. Additional aspects of the resistant phenotype were examined, using a newly-established resistant cell line. Phorbol ester induced morphological changes, ERK activation, calcium-dependent activation of the c-Jun N-terminal kinase (JNK), interleukin-2 synthesis, and growth inhibition in sensitive but not resistant cells. A series of protein kinase C activators caused membrane translocation of protein kinase C's (PKCs) alpha, eta, and theta in both cell lines. While PKC eta was expressed at higher levels in sensitive than in resistant cells, overexpression of PKC eta did not restore phorbol ester-induced ERK activation to resistant cells. In sensitive cells, PKC activators had similar effects on cell viability and ERK activation, but differed in their abilities to induce JNK activation and interleukin-2 synthesis. PD 098059, an inhibitor of the mitogen activated protein (MAP)/ERK kinase kinase MEK, partially inhibited ERK activation and completely blocked phorbol ester-induced cell death in sensitive cells. Thus MEK and/or ERK activation, but not JNK activation or interleukin-2 synthesis, appears to be required for phorbol ester-induced toxicity. Alterations in phorbol ester response pathways, rather than altered expression of PKC isoforms, appear to confer phorbol ester resistance to EL4 cells.      

Perinatal stimulation and adaptation of the neonate

The present report describes psychobiological studies of behavior around the time of birth. An adaptive, ecological perspective is presented in which stimulation of the fetus and newborn is purported to instigate adaptive postpartum behavior. Studies describing the perinatal sensory environment are reviewed, with a consideration of emergent sensory function of the fetus. It is asserted that afferent input associated with parturition perturbs the fetus and neonate, producing a general arousal state that facilitates breathing, suckling, and early learning. The view developed herein is that perinatal sensory input induces and canalizes the newborn's behavior, thereby regulating adaptive postpartum function. Deviations in afferent input may alter ontogenetic trajectories and compromise developmental outcome by reducing availability of conditions necessary for adequate postpartum adaptation.     

Cricoid pressure impedes placement of the laryngeal mask airway and subsequent tracheal intubation through the mask

We have studied 40 patients to see if cricoid pressure affectsthe success rate of ventilation through, and the position of,the laryngeal mask and subsequent fibrescope-aided trachealintubation. Adequate ventilation of the lungs was produced throughthe laryngeal mask in 19 of 20 patients in the control group,but in only 10 of 20 patients in the cricoid pressure group(P < 0.002). The laryngeal mask was positioned correctlyin 16 patients in the control group, but in only two patientsin the cricoid pressure group (P < 0.001). Tracheal intubationwas accomplished in 19 patients in the control group, but inonly three patients in the cricoid pressure group (P < 0.001).Release of cricoid pressure after placement of the laryngealmask improved the view of the glottis, but tracheal intubationwas still difficult because of laryngeal deviation. These resultsshow that cricoid pressure impedes placement of the laryngealmask and subsequent fibrescope-aided tracheal intubation. (Br.J. Anaesth. 1994; 72: 47–51)