Nuclear import of PKCdelta is required for apoptosis: identification of a novel nuclear import sequence.

We have shown previously that protein kinase Cdelta (PKCdelta) is required for mitochondrial-dependent apoptosis. Here we show that PKCdelta is imported into the nucleus of etoposide-treated cells, that nuclear import is required for apoptosis and that it is mediated by a nuclear localization signal (NLS) in the C-terminus of PKCdelta. Mutation of the caspase cleavage site of PKCdelta inhibits nuclear accumulation in apoptotic cells, indicating that caspase cleavage facilitates this process.

Photochemical synthesis of aldehydes in the solid phase.

A substituted anthraquinone (AQ), previously shown to photochemically generate benzaldehyde in methanol solution, was attached to a commercially available resin via an 11 carbon tether and an amide bond. Photolysis of the polymer-bound AQ with visible or 350 nm UV light resulted in the formation of benzaldehyde in yields of 50-55% as determined by HPLC. The phenolic positions in the polymer were then alkylated using benzyl bromide and 1-iodo-3-(4-nitrophenyl)propane in a coupling reaction with K(2)CO(3) as a base and a solution-phase proton shuttle.

Activation of atypical protein kinase C zeta by caspase processing and degradation by the ubiquitin-proteasome system.

Atypical protein kinase C zeta (PKCzeta) is known to transduce signals that influence cell proliferation and survival. Here we show that recombinant human caspases can process PKCzeta at three sites in the hinge region between the regulatory and catalytic domains. Caspase-3, -6, -7, and -8 chiefly cleaved human PKCzeta at EETD downward arrowG, and caspase-3 and -7 also cleaved PKCzeta at DGMD downward arrowG and DSED downward arrowL, respectively.

The impact of restrictive entry criterion during the placebo lead-in period.

In the study of depression, most randomized clinical trials have design features that attempt to sample from a stable patient population. One commonly used design feature is to require patients to maintain some minimum baseline symptom severity score during a placebo lead-in period. One intent of this design feature is to evaluate the behavior of patients prior to administration of active medication.

Caffeine based measures of CYP1A2 activity correlate with oral clearance of tacrine in patients with Alzheimer's disease.

Aims: To study the potential utility of caffeine based probes of CYP1A2 enzyme activity in predicting the pharmokinetics of tacrine in patients with Alzheimer's disease.

Methods: The pharmokinetics of a single 40 mg oral dose of tacrine were measured in 19 patients with Alzheimer's disease. Each patient also received 2 mg kg(-1) [13C-3-methyl] caffeine orally and had breath and urine samples collected.

Quantitative analysis of a presence/absence microbiological assay: the hard surface carrier test of disinfectant efficacy.

The Hard Surface Carrier Test (HSCT) is a presence/absence assay for determining the extent to which chemical disinfectants kill bacteria. The disinfectants are marketed for cleaning surfaces in hospitals, restaurants, the home, etc. In the HSCT, a presence response (or equivalently, a positive carrier) is recorded if one or more bacteria survive among M bacteria attached to a glass carrier and exposed to the chemical disinfectant; otherwise, the response is absence.

Inhibition of tacrine oral clearance by cimetidine.

Plasma tacrine, 1-hydroxytacrine, 2-hydroxytacrine, and 4-hydroxytacrine concentrations were measured in 12 healthy elderly subjects in this nonblinded two-period study to assess the effect of multiple doses of cimetidine on single-dose tacrine pharmacokinetics. Subjects received 40 mg tacrine (Cognex) alone and during multiple-dose cimetidine (300 mg four times a day) administration. Overall, tacrine and cimetidine were well tolerated by healthy elderly subjects.

Hard surface carrier test as a quantitative test of disinfection: a collaborative study.

The hard surface carrier test (HSCT) recently was proposed as a qualitative test for disinfectant efficacy. A collaborative study of HSCT led to a suggested performance standard of < or = 2 or 3 positive carriers out of 60 tested. Subsequently, it was discovered that HSCT can be used as a quantitative test, because the HSCT protocol requires measurement of inoculum level on some carriers.