Inhibitory and excitatory intracortical circuits across the human sleep-wake cycle using paired-pulse transcranial magnetic stimulation.

Studies using single-pulse transcranial magnetic stimulation (TMS) have shown that excitability of the corticospinal system is systematically reduced in natural human sleep as compared to wakefulness with significant differences between sleep stages. However, the underlying excitatory and inhibitory interactions on the corticospinal system across the sleep-wake cycle are poorly understood. Here, we specifically asked whether in the motor cortex short intracortical inhibition (SICI) and facilitation (ICF) can be elicited at all in sleep using the paired-pulse TMS protocol, and if so, how SICI and ICF vary across sleep stages. We studied 28 healthy subjects at interstimulus intervals of 3 ms (SICI) and 10 ms (ICF), respectively. Magnetic stimulation was performed over the hand area of the motor cortex using a focal coil and evoked motor potentials were recorded from the contralateral first dorsal interosseus muscle (1DI). Relevant data was obtained from 13 subjects (NREM 2: n=7; NREM 3/4: n=7; REM: n=7). Results show that both SICI and ICF were present in NREM sleep. SICI was significantly enhanced in NREM 3/4 as compared to wakefulness and all other sleep stages whereas in NREM 2 neither SICI nor ICF differed from wakefulness. In REM sleep SICI was in the same range as in wakefulness, but ICF was entirely absent. These results in humans support the hypothesis derived from animal experiments which suggests that intracortical inhibitory mechanisms are involved in the control of neocortical pyramidal cells in NREM and REM sleep, but along different intraneuronal circuits. Further, our findings suggest that cortical mechanisms may additionally contribute to the inhibition of spinal motoneurones in REM sleep.

Influence of retrovirally transduced human tumor-necrosis-factor-alpha on the expression of C-myc, k-ras, C-jun, p53, tgf-alpha, and cea in human colon-carcinoma cell-lines.

Northern slot blot hybridization and immunohistochemical staining were applied for the characterization of tumor necrosis factor alpha (TNF)-transduced human colon carcinoma cell lines. A significant decrease in the CEA-specific mRNA and protein was observed in TNF-transduced tumor cells LS174T and LoVo while other probes (c-myc, K-ras, c-jun, p53, TGF alpha) as well as anti-K-ras- and anti-p53-antibodies failed to detect differences between cytokine-transduced and parental tumor cells.