Testicular involvement in mantle cell lymphoma: An analysis of 16 patients.

Mantle cell lymphoma (MCL) with testicular involvement is a rare presentation and only a few cases have been described in the literature. We present a case of MCL with testicular involvement and the first analysis of all previously reported cases assessing trends in immunohistochemical features, prognostic indicators, and survival. Our data suggest that among all MCL, testicular MCL is more likely to present with aggressive features: blastoid/pleomorphic morphology, high Ki-67 proliferative index, and CNS involvement. Testicular MCL is also associated with shorter overall survival.

Multiple Non-Equivalent Interfaces Mediate Direct Activation of GABAA Receptors by Propofol.

BACKGROUND: Propofol is a sedative agent that at clinical concentrations acts by allosterically activating or potentiating the γ-aminobutyric acid type A (GABAA) receptor. Mutational, modeling, and photolabeling studies with propofol and its analogues have identified potential interaction sites in the transmembrane domain of the receptor. At the "+" of the ß subunit, in the ß-α interface, meta-azipropofol labels the M286 residue in the third transmembrane domain. Substitution of this residue with tryptophan results in loss of potentiation by propofol. At the "-" side of the ß subunit, in the α-ß interface (or ß-ß interface, in the case of homomeric ß receptors), ortho-propofol diazirine labels the H267 residue in the second transmembrane domain. Structural modeling indicates that the ß(H267) residue lines a cavity that docks propofol with favorable interaction energy. METHOD: We used two-electrode voltage clamp to determine the functional effects of mutations to the "+" and "-" sides of the ß subunit on activation of the α1ß3 GABAA receptor by propofol. RESULTS: We found that while the individual mutations had a small effect, the combination of the M286W mutation with tryptophan mutations of selected residues at the α-ß interface leads to strong reduction in gating efficacy for propofol. CONCLUSION: We conclude that α1ß3 GABAA receptors can be activated by propofol interactions with the ß-ß, α-ß, and ß-α interfaces, where distinct, non-equivalent regions control channel gating. Any interface can mediate activation, hence substitutions at all interfaces are required for loss of activation by propofol.