The sleep spindle has been implicated in thalamic sensory gating, cortical development, and memory consolidation. These multiple functions may depend on specific spatiotemporal emergence and interactions with other spindles and other forms of brain activity. Therefore, we measured sleep spindle cortical distribution, regional heterogeneity, synchronization, and phase relationships with other electroencephalographic components in freely moving primates. Transcortical field potentials were recorded from Japanese monkeys via telemetry and were analyzed using the Hilbert-Huang transform. Spindle (12–20 Hz) current sources were identified over a wide region of the frontoparietal cortex. Most spindles occurred independently in their own frequency, but some appeared concordant between cortical areas with frequency interdependence, particularly in nearby regions and bilaterally symmetrical regions. Spindles in the dorsolateral prefrontal cortex appeared around the surface-positive and depth-negative phase of transcortically recorded slow oscillations (< 1 Hz), whereas centroparietal spindles emerged around the opposite phase. The slow-oscillation phase reversed between the prefrontal and central regions. Gamma activities increased before spindle onset. Several regional heterogeneities in properties of human spindles were replicated in the monkeys, including frequency, density, and inter-cortical time lags, although their topographic patterns were different from those of humans. The phase-amplitude coupling between spindle and gamma activity was also replicated. Spindles in widespread cortical regions are possibly driven by independent rhythm generators, but are temporally associated to spindles in other regions and to slow and gamma oscillations by corticocortical and thalamocortical pathways.
<i>Background:</i> Retinoic acids, a group of natural and synthetic vitamin A derivatives, have potent anti-proliferative, anti-inflammatory and anti-fibrotic properties. We investigated the therapeutic effect of all-<i>trans</i>-retinoic acid (ATRA) on unilateral ureteral obstruction (UUO) model mice. <i>Methods:</i> First, to evaluate the prophylactic effect, we administered 0.5 mg of ATRA for 3 days before UUO (UUO ATRA). Then, to evaluate the therapeutic effects, we administered 0.5 mg of ATRA 3 days after UUO (Day3 ATRA). We compared the histological changes and immunostaining of macrophages, α-smooth muscle actin (α-SMA) and collagen I, and mRNA expression of monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-β<sub>1</sub> and TGF-β R-II by RT-PCR 7 days after UUO. <i>Results:</i> In the UUO ATRA and Day3 ATRA groups, we observed a significant improvement in histological and immunological findings, including macrophage infiltration and improved expression of MCP-1, TGF-β<sub>1</sub>, α-SMA and collagen I compared with the UUO Day7 group. <i>Conclusion:</i> ATRA treatment is not only an effective prophylactic strategy, but also a therapeutic strategy for the treatment of progressive renal fibrosis in diseased kidneys.
We demonstrate that in the macaque monkey there is robust, short-latency facilitation by ventral premotor cortex (area F5) of motor outputs from primary motor cortex (M1) to contralateral intrinsic hand muscles. Experiments were carried out on two adult macaques under light sedation (ketamine plus medetomidine HCl). Facilitation of hand muscle electromyograms (EMG) was tested using arrays of fine intracortical microwires implanted, respectively, in the wrist/digit motor representations of F5 and M1, which were identified by previous mapping with intracortical microstimulation. Single pulses (70–200 μA) delivered to F5 microwires never evoked any EMG responses, but small responses were occasionally seen with double pulses (interval: 3 ms) at high intensity. However, both single- and double-pulse stimulation of F5 could facilitate the EMG responses evoked from M1 by single shocks. The facilitation was large (up to 4-fold with single and 12-fold with double F5 shocks) and occurred with an early onset, with significant effects at intervals of only 1–2 ms between conditioning F5 and test M1 stimuli. A number of possible pathways could be responsible for these effects, although it is argued that the most likely mechanism would be the facilitation, by cortico-cortical inputs from F5, of corticospinal I wave activity evoked from M1. This facilitatory action could be of considerable importance for the coupling of grasp-related neurons in F5 and M1 during visuomotor tasks.
To predict the response of patients with rheumatoid arthritis (RA) to infliximab, patient profile and laboratory findings were compared to determine whether there was any association with the clinical course of the disease, and the clinical significance of serum rheumatoid factor (RF) in the response to this treatment was considered. Sixty-two RA patients were treated with infliximab, 87.9% of whom were positive for RF. At baseline and 12 months after the start of treatment, RF titers were significantly lower in the low-CRP group (CRP at 12 months<0.3 mg/dl) compared with that in the high-CRP group (CRP at 12 months >1.5 mg/dl). Furthermore, at baseline and 12 months, RF titers were significantly lower in the good-CRP-response group (DeltaCRP>or=1.5 mg/d) compared with the poor-CRP-response group (DeltaCRP
