Picomolar concentrations of lead stimulate brain protein kinase C

Recent growth studies in children suggest that there is no threshold for adverse effects from the universal exposure to inorganic lead. The biochemical mechanisms mediating low-level toxicity are unclear, but in several biological systems, lead alters calcium-mediated cellular processes and may mimic calcium in binding to regulatory proteins. Here we present evidence that lead stimulates diacylglycerol-activated calcium and phospholipid-dependent protein kinase, protein kinase C, partially purified from rat brain. Picomolar concentrations of lead are equivalent to micromolar calcium in kinase activation, so this regulatory enzyme is sensitive to the lead levels expected from current environmental exposure.     

Common sequence variants on 20q11.22 confer melanoma susceptibility

We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.     

Etude comparative de l'effet de la thymosine et d'un extrait de cultures cellulaires épithéliales thymiques sur la production d'anticorps

Summary A thymic extract (TE) was preparated from supernatant of mice thymic epithelial cultures according to the purification of thymosin. TE and thymosin stimulated, in vitro, the immune response of mouse against sheep red blood cells.

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Les auteurs remercient Mademoiselle Condemine Florence pour son aide technique durant ce travail.     

Population genetic structure of variable drug response.

Geographic patterns of genetic variation, including variation at drug metabolizing enzyme (DME) loci and drug targets, indicate that geographic structuring of inter-individual variation in drug response may occur frequently. This raises two questions: how to represent human population genetic structure in the evaluation of drug safety and efficacy, and how to relate this structure to drug response. We address these by (i) inferring the genetic structure present in a heterogeneous sample and (ii) comparing the distribution of DME variants across the inferred genetic clusters of individuals. We find that commonly used ethnic labels are both insufficient and inaccurate representations of the inferred genetic clusters, and that drug-metabolizing profiles, defined by the distribution of DME variants, differ significantly among the clusters. We note, however, that the complexity of human demographic history means that there is no obvious natural clustering scheme, nor an obvious appropriate degree of resolution. Our comparison of drug-metabolizing profiles across the inferred clusters establishes a framework for assessing the appropriate level of resolution in relating genetic structure to drug response.     

A method for the separation and estimation of catechol amines in urine

Zusammenfassung Es wird eine neue Methode zur Bestimmung der Katecholamine im Harn beschrieben. Die Katecholamine werden im Harn acetyliert und die Acetylderivate papierchromatographisch im Bush-?C?-System getrennt. Nach erfolgter Trennung werden die einzelnen Katecholamine mit ?thylendiamin kondensiert und fluorimetrisch untersucht. Eine Spezifit?tserh?hung der Methode durch Anwendung doppelt markierter Isotopen wird in Betracht gezogen.      

A radioassay for dopamine-β-hydroxylase activity

Zusammenfassung Es wurde eine Isotopenmethode zur Bestimmung der Dopamine--hydroxylase-Aktivität beschrieben, die auch zur Bestimmung der enzymatischen-Hydroxylierung sämtlicher Substrate der Dopamine--hydroxylase verwendet werden kann. Die Methode bewährte sich für Aktivitätsbestimmungen in Neuroblastoma-und Pheochromocytoma-Tumoren.