Non-specific in vivo inhibition of CK1 by the pyridinyl imidazole p38 inhibitors SB 203580 and SB 202190.

Small-molecule inhibitors of protein kinases have contributed immensely to our understanding of biological signaling pathways and have been exploited therapeutically for the treatment of cancers and other disease states. The pyridinyl imidazole compounds SB 203580 and SB 202190 were identified as ATP competitive antagonists of the p38 stress-activated protein kinases and have been widely used to elucidate p38-dependent cellular processes. Here, we identify SB 203580 and SB 202190 as potent inhibitors of stress-induced CREB phosphorylation on Serine 111 (Ser-111) in intact cells.

ATR activation necessary but not sufficient for p53 induction and apoptosis in hydroxyurea-hypersensitive myeloid leukemia cells.

Hydroxyurea (HU) is a competitive inhibitor of ribonucleotide reductase that is used for the treatment of myeloproliferative disorders. HU inhibits DNA replication and induces apoptosis in a cell type-dependent manner, yet the relevant pathways that mediate apoptosis in response to this agent are not well characterized. In this study, we employed the human myeloid leukemia 1 (ML-1) cell line as a model to investigate the mechanisms of HU-induced apoptosis.

Distortion product otoacoustic emission response characteristics in older adults.

Objective: The primary purpose of this study was to determine the distortion product otoacoustic emission (DPOAE) and noise response characteristics in a large sample of older adults. Another purpose was to evaluate how specific absolute DPOAE levels or DPOAE/Noise ratios differentiated hearing status in these individuals.

Design: A cross-sectional design was utilized for this study.

Otoacoustic emission, evoked potential, and behavioral auditory thresholds in the rhesus monkey (Macaca mulatta).

Distortion product otoacoustic emission (DPOAE), auditory brainstem evoked response (ABR), and behavioral thresholds were recorded in a group of 15 adult rhesus monkeys with normal auditory function. DPOAE thresholds were recorded with stimulus parameters selected to maximize signal-to-noise ratio. Additional averaging at the lowest frequencies ensured comparable noise levels across frequencies.

Nonlinear functional modeling of scalp recorded auditory evoked responses to maximum length sequences.

The purpose of this study was to model the adult human's scalp recorded evoked response to auditory pulses separated by varying inter pulse intervals (IPIs). The responses modeled probably reflect auditory nerve and brainstem generators. The subjects were 10 young adult humans with normal hearing.

Hearing loss in survivors of neonatal extracorporeal membrane oxygenation (ECMO) therapy and high-frequency oscillatory (HFO) therapy.

Survivors of extracorporeal membrane oxygenation (ECMO) therapy and high-frequency oscillatory (HFO) therapy during the newborn period were followed to evaluate their hearing. Eleven of the 66 ECMO survivors (16.7%) were diagnosed with significant hearing loss after being discharged from the neonatal intensive care unit (NICU).

Rate and adaptation effects on the auditory evoked brainstem response in human newborns and adults.

Auditory evoked brainstem response (ABR) latencies increased and amplitudes decreased with increasing stimulus repetition rate for human newborns and adults. The wave V latency increases were larger for newborns than adults. The wave V amplitude decreases were smaller for newborns than adults.