[The alliance of the parent, child and the nurse to challenge medical error].

A group composed of parents, nurses, and physicians involved in pediatric cancerology has reflected on medical errors within the Espace Éthique de l'Assistance publique-Hôpitaux de Paris. Based on narratives and qualitative analysis of histories and testimonies, this discussion aimed at exploring the causes, circumstances, and impacts of medical errors on the relations between these individuals. The study demonstrated that some circumstances actually promote medical errors, such as hard working conditions, mistrust, unreliable control procedures, not listening to parents, and caring for children in extreme situations of pain and suffering.

Modulation of the voltage-gated sodium current in rat striatal neurons by DARPP-32, an inhibitor of protein phosphatase.

DARPP-32 is a cyclic adenosine monophosphate-regulated inhibitor of protein phosphatase 1, highly enriched in striatonigral neurons. Stimulation of dopamine D1 receptors increases phosphorylation of DARPP-32, whereas glutamate acting on N-methyl-D-aspartate receptors induces its dephosphorylation. Yet, to date, there is little direct evidence for the function of DARPP-32 in striatal neurons.

Dephosphorylation of Ser-137 in DARPP-32 by protein phosphatases 2A and 2C: different roles in vitro and in striatonigral neurons.

DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, Mr=32000) is highly expressed in striatonigral neurons in which its phosphorylation is regulated by several neurotransmitters including dopamine and glutamate. DARPP-32 becomes a potent inhibitor of protein phosphatase 1 when it is phosphorylated on Thr-34 by cAMP- or cGMP-dependent protein kinases. DARPP-32 is also phosphorylated on Ser-137 by protein kinase CK1 (CK1), in vitro and in vivo.

Regulation of secretion of Alzheimer amyloid precursor protein by the mitogen-activated protein kinase cascade.

Activation of protein kinase C (PKC) regulates the processing of Alzheimer amyloid precursor protein (APP) into its soluble form (sAPP) and amyloid beta-peptide (A beta). However, little is known about the intermediate steps between PKC activation and modulation of APP metabolism. Using a specific inhibitor of mitogen-activated protein (MAP) kinase kinase activation (PD 98059), as well as a dominant negative mutant of MAP kinase kinase, we show in various cell lines that stimulation of PKC by phorbol ester rapidly induces sAPP secretion through a mechanism involving activation of the MAP kinase cascade.

Characterization of the interaction between DARPP-32 and protein phosphatase 1 (PP-1): DARPP-32 peptides antagonize the interaction of PP-1 with binding proteins.

The catalytic subunit of PP-1 (PP-1C) is potently inhibited (IC50, approximately 1 nM) by DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, M(r) 32,000), inhibitor-1, and inhibitor-2. The NH2-terminal 50 amino acid residues of DARPP-32 and inhibitor-1 are similar, and phosphorylation of a common threonine residue (Thr-34/Thr-35) is necessary for inhibition of PP-1C. We have characterized further the interaction between DARPP-32 and PP-1C.