The mitogen-activated protein kinase (MAPK) cascade is required for mitogenesis in somatic mammalian cells and is activated by a wide variety of oncogenic stimuli. Specific roles for this signaling module in growth were dissected by inhibiting MAPK kinase 1 (MAPKK1) activity in highly synchronized NIH 3T3 cells. In addition to the known role of this kinase in cell-cycle entry from G 0 , the level of MAPKK activity was observed to affect the kinetics of progression through both the G 1 and G 2 phases of the cell cycle in NIH 3T3 cells. Ectopic expression of dominant-negative forms of MAPKK1, which was previously shown to inhibit G 0 /G 1 progression, was found to also delay progression of cells through G 2 . In addition, treatment of cells with the specific MAPKK inhibitor PD 98059 during a synchronous S phase arrested the cells in the following G 2 phase. These data demonstrate a novel role for the MAPK cascade in progression from G 2 into mitosis in NIH 3T3 cells.

BackgroundMethamphetamine use is associated with HIV acquisition and transmission among men who have sex with men (MSM). Contingency management (CM), providing positive reinforcement for drug abstinence and withholding reinforcement when abstinence is not demonstrated, may facilitate reduced methamphetamine use and sexual risk. We compared CM as a stand-alone intervention to a minimal intervention control to assess the feasibility of conducting a larger, more definitive trial of CM; to define the frequency of behavioral outcomes to power such a trial; and, to compute preliminary estimates of CM's effectiveness.MethodsWe randomly assigned 127 MSM from Seattle, WA who use methamphetamine to receive a 12-week CM intervention (n = 70) or referral to community resources (n = 57).ResultsRetention at 24 weeks was 84%. Comparing consecutive study visits, non-concordant UAI declined significantly in both study arms. During the intervention, CM and control participants were comparably likely to provide urine samples containing methamphetamine (adjusted relative risk [aRR] = 1.09; 95%CI: 0.71, 1.56) and to report non-concordant UAI (aRR = 0.80; 95%CI: 0.47, 1.35). However, during post-intervention follow-up, CM participants were somewhat more likely to provide urine samples containing methamphetamine than control participants (aRR = 1.21; 95%CI: 0.95, 1.54, P = 0.11). Compared to control participants, CM participants were significantly more likely to report weekly or more frequent methamphetamine use and use of more than eight quarters of methamphetamine during the intervention and post-intervention periods.ConclusionsWhile it is possible to enroll and retain MSM who use methamphetamine in a trial of CM conducted outside drug treatment, our data suggest that CM is not likely to have a large, sustained effect on methamphetamine use.Trial RegistrationClinicalTrials.gov Identifier NCT01174654