A comparison of the pharmacological activity in man of intravenously administered 1368-11368-11368-1, cannabinol,and cannabidiol

Resumen Se hizo un estudio comparativo de la actividad del ⁹-tetrahidrocannabinol, cannabinol, y cannabidiol en producir efectos similares a la marihuana cuando son inyectados i.v. a humanos. Estas substancias son los componentes predominantes de la marihuana o del hashish. Se encontro que a las dosis inyectados cannabidiol no tiene ninguna potencia, y que cannabinol es capaz de producir efectos tipicos de la marihuana, aunque a dosis varias veces mas grandes que las del ⁹-tetrahidrocannabinol.     

Pharmacogenetic factor in the convulsive responses of mice to flurothyl

Résumé La sensibilité convulsive a été determinée dans 6 groupes de souris par les réactions de l'ether hexafluorodiéthyle, convulsivant chimique. La lignée DBA/2 fut très sensible, tandis que les lignées C57BL/6 et BALB/c se montrèrent les moins sensibles. La sensibilité convulsive ne présenta pas de corrélation positive avec l'activité locomotrice.     

Two-step binding mechanism for T-cell receptor recognition of peptide MHC

T cells probe a diverse milieu of peptides presented by molecules of the major histocompatibility complex (MHC) by using the T-cell receptor (TCR) to scan these ligands with high sensitivity and specificity. Here we describe a physical basis for this scanning process by studying the residues involved in both the initial association and the stable binding of TCR to peptide-MHC, using the well-characterized TCR and peptide-MHC pair of 2B4 and MCC-IE(k) (moth cytochrome c, residues 88 103). We show that MHC contacts dictate the initial association, guiding TCR docking in a way that is mainly independent of the peptide. Subsequently, MCC-IE(k) peptide contacts dominate stabilization, imparting specificity and influencing T-cell activation by modulating the duration of binding. This functional subdivision of the peptide-MHC ligand suggests that a two-step process for TCR recognition facilitates the efficient scanning of diverse peptide-MHC complexes on the surface of cells and also makes TCRs inherently crossreactive towards different peptides bound by the same MHC.