Hypoxia initiates pulmonary vasoconstriction (HPV) by inhibiting one or more voltage-gated potassium channels (Kv) in the pulmonary artery smooth muscle cells (PASMCs) of resistance arteries. The resulting membrane depolarization increases opening of voltage-gated calcium channels, raising cytosolic Ca 2 ϩ and initiating HPV. There are presently nine families of Kv channels known and pharmacological inhibitors lack the specificity to distinguish those involved in control of resting membrane potential (E m ) or HPV. However, the Kv channels involved in E m and HPV have characteristic electrophysiological and pharmacological properties which suggest their molecular identity. They are slowly inactivating, delayed rectifier currents, inhibited by 4-aminopyridine (4-AP) but insensitive to charybdotoxin. Candidate Kv channels with these traits (Kv1.5 and Kv2.1) were studied. Antibodies were used to immunolocalize and functionally characterize the contribution of Kv1.

Mammalian target of rapamycin (mTOR), a serine/threonine kinase, regulates cell growth and proliferation in part via the activation of p70 S6 kinase (S6K). Rapamycin is an antineoplastic agent that, in complex with FKBP12, is a specific inhibitor of mTOR through interaction with its FKBP12-rapamycin binding domain, thereby causing G 1 cell cycle arrest. However, cancer cells often develop resistance to rapamycin, and alternative inhibitors of mTOR are desired. 2-(4-Morpholinyl)-8-phenyl-

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A report is given on two neutropenic patients with staphylococcal septicemia caused by Staphylococcus haemolyticus and Staphylococcus aureus (both strains methicillin-resistant) who failed to respond to therapy with teicoplanin. Both strains were resistant to teicoplanin (MIC 16 and 8 mg/l respectively), but remained sensitive to vancomycin (MIC 2 and 4 mg/l respectively). Replacement of teicoplanin with vancomycin led to full recovery of both patients and their discharge from hospital. These two cases emphasize the importance of clinical and microbiological monitoring of patients with staphylococcal septicemia, even when glycopeptides are used for treatment.

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