Further evidence for excitability changes in human primary motor cortex during ipsilateral voluntary contractions

The present study aimed to further investigate whether the intracortical neural circuits within the primary motor cortex (M1) are modulated during ipsilateral voluntary finger movements. Single- and paired-pulse (interstimulus intervals, ISIs; 3 ms and 12 ms) transcranial magnetic stimulations of the left M1 were applied to elicit motor evoked potential (MEP) in the right first dorsal interosseous (Rt-FDI) muscle during voluntary contractions (10% and 30% maximum voluntary contraction) of the left FDI (Lt-FDI) muscle. F-waves of Rt-FDI muscle were recorded under these left index-finger conditions for ensuring that the excitability changes occur at the supraspinal level. MEPs were also recorded during motor imagery of the left index-finger abduction instead of overt movement. The results showed that, in single-pulse transcranial magnetic stimulation (TMS) paradigm, MEPs in Rt-FDI muscle were markedly enhanced during voluntary contractions of Lt-FDI muscle compared with the complete resting state. In paired-pulse TMS paradigm, the short intracortical inhibition was significantly reduced in proportion to increments of the ipsilateral muscle contraction, whereas the intracortical facilitation had no change. F-wave of Rt-FDI muscle was unchanged under these conditions, while MEP in Rt-FDI muscle was also enhanced during motor imagery of the left index-finger abduction. Based on the present results, it is suggested that the intracortical inhibitory neural circuits may be modulated in the transition from rest to activity of the ipsilateral homonymous muscle. The excitability changes in M1 might be induced by overflows of voluntary drive given to the ipsilateral limb, probably via the transcallosal pathway.     

Topical application of FK506 (tacrolimus) ointment inhibits mite antigen-induced dermatitis by local action in NC/Nga mice

BACKGROUND: FK506 ointment (tacrolimus ointment, protopic) is a new drug therapeutically effective for patients with atopic dermatitis (AD). However, the mechanism of action of FK506 ointment on AD is not fully understood. METHODS: We examined the effect of FK506 ointment on mite antigen-induced dermatitis in NC/Nga mice. Clinical symptoms and ear thickness were recorded, and histopathological studies and in vitro analyses were performed. RESULTS: Topical application of FK506 ointment (0.03-0.3%) suppressed the development of dermatitis. In the lesional skin, both interleukin (IL)-4 and interferon (IFN)-gamma were detected, even though the IL-4+/IFN-gamma- T helper 2 (Th2) population was predominant in the regional lymph nodes (LNs). Topical application of FK506 treatment reduced the elevated level of both IL-4 and IFN-gamma in the skin, but did not decrease the expansion of the Th2 population in the LNs. CONCLUSIONS: Topical application of FK506 ointment suppresses dermatitis by inhibiting the activation of inflammatory cells locally, without systemic immune suppression, in this AD model.     

Ebselen prevents noise-induced excitotoxicity and temporary threshold shift

This investigation tested the hypothesis that a noise-induced temporary threshold shift (TTS) can be attenuated by a peroxynitrite scavenger, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one). Guinea pigs received an oral dose of the vehicle or 10 mg/kg ebselen 1 h before exposure to 115 dB SPL 4-kHz octave band noise for 3 h. In controls, auditory brainstem response (ABR) thresholds increased by 25–45 dB immediately after noise and returned to pre-exposure baseline thresholds 7 days later. Ebselen eliminated this ABR threshold shift following noise exposure. In controls, swelling of the afferent dendrites beneath the inner hair cells was evident immediately after noise, whereas ebselen significantly reduced this pathology. These findings suggest that scavenging peroxynitrite can attenuate noise-induced excitotoxicity and, thereby, TTS.     

A new gene encoding tRNAPro (GGG) is present in the chloroplast genome of black pine: a compilation of 32 tRNA genes from black pine chloroplasts

The chloroplast genome of black pine (Pinus thumbergii), a gymnosperm, contains 32 different tRNA genes, 30 of which correspond to those previously identified in tobacco and rice chloroplast genomes. Two additional genes encode tRNA^Pro (GGG) and tRNA^Arg (CCG); the former is newly identified while the latter is present in liverwort, Physcomitrella patens and Angiopteris lygodiifolia, chloroplast genomes. Moreover, a partial copy of the split tRNA^Gly (UCC) gene and full copies of tRNA^His (GUG), tRNA^Thr (GGU) and tRNA^Ser (GCU) genes are present in the large single-copy region of the genome, suggesting extensive rearrangements of the chloroplast genome during evolutio. No tRNA genes whose tRNA products can recognize codons CUU/C (Leu) and GCU/C (Ala) have been found. We propose that the 32 tRNAs are sufficient to read all the 61 sense codons in the black pine system using the two-out-of-three and the U:N wobble mechanisms.     

Cohesin release is required for sister chromatid resolution,but not for condensin-mediated compaction,at the onset of mitosis

The establishment of metaphase chromosomes is an essential prerequisite of sister chromatid separation in anaphase. It involves the coordinated action of cohesin and condensin, protein complexes that mediate cohesion and condensation, respectively. In metazoans, most cohesin dissociates from chromatin at prophase, coincident with association of condensin. Whether loosening of cohesion at the onset of mitosis facilitates the compaction process, resolution of the sister chromatids, or both, remains unknown. We have found that the prophase release of cohesin is completely blocked when two mitotic kinases, aurora B and polo-like kinase (Plx1), are simultaneously depleted from Xenopus egg extracts. Condensin loading onto chromatin is not affected under this condition, and rod-shaped chromosomes are produced that show an apparently normal level of compaction. However, the resolution of sister chromatids within these chromosomes is severely compromised. This is not because of inhibition of topoisomerase II activity that is also required for the resolution process. We propose that aurora B and Plx1 cooperate to destabilize the sister chromatid linkage through distinct mechanisms that may involve phosphorylation of histone H3 and cohesin, respectively. More importantly, our results strongly suggest that cohesin release at the onset of mitosis is essential for sister chromatid resolution but not for condensin-mediated compaction.     

No evidence of PEG1/MEST gene mutations in Silver‐Russell syndrome patients

Silver‐Russell syndrome (SRS) is characterized by prenatal and postnatal growth retardation with morphologic anomalies. Maternal uniparental disomy 7 has been reported in some SRS patients. PEG1/MEST is an imprinted gene on chromosome 7q32 that is expressed only from the paternal allele and is a candidate gene for SRS. To clarify its biological function and role in SRS, we screened PEG1/MEST abnormalities in 15 SRS patients from various standpoints. In the lymphocytes of SRS patients, no aberrant expression patterns of two splice variants (α and β) of PEG1/MEST were detected when they were compared with normal samples. Direct sequence analysis failed to detect any mutations in the PEG1/MEST α coding region, and there were no significant mutations in the 5′‐flanking upstream region containing the predicted promoter and the highly conserved human/mouse genomic region. Differential methylation patterns of the CpG island for PEG1/MEST α were normally maintained and resulted in the same pattern as in the normal control, suggesting that there was no loss of imprinting. These findings suggest that PEG1/MEST can be excluded as a major determinant of SRS. © 2001 Wiley‐Liss, Inc.     

Further insight into the task-dependent excitability of motor evoked potentials in first dorsal interosseous muscle in humans

We have reexamined the contradictory evidence in which task-dependent excitation of motor evoked potentials (MEPs) in the first dorsal interosseous (FDI) muscle was stronger with increasingly more complex finger tasks than with individual finger movement tasks. In the first step of the experiment, based on previous findings, we investigated remarkable functional differences between intrinsic and extrinsic hand muscles during complex finger tasks (precision and power grip). During the performance of the tasks, the optimal stimulus intensity of the transcranial magnetic stimulation (TMS) was applied to the contralateral motor cortex. MEPs of the FDI, extensor carpi radialis (ECR), and flexor carpi radialis (FCR) muscles were recorded simultaneously with increased background EMG activity step by step in both tasks. The intensity threshold of TMS was lower in the precision grip. Furthermore, the MEP amplitudes of FDI muscle dependent on the background EMG activity were different between these two tasks, i.e., MEP amplitudes and regression coefficients in a precision grip were larger than those in a power grip. Although our results for MEP amplitude and threshold in the FDI muscle were similar to previous reported evidence, the different contributions of a synergistic muscle (in particular, the ECR muscle) during performance in these tasks was new evidence. Since there were no differences in cutaneous afferent effects on both tasks, corticomotoneuronal (CM) cells connected to FDI motoneurons seemed generally to be more active during precision than power gripping, and there were different contributions from synergistic muscles during the performance of these tasks. In the second part of the experiment, the results obtained from the complex tasks were compared with those from a simple task (isolated index finger flexion). MEP amplitudes, dependent on the background EMG activity during isolated index finger flexion, varied among subjects, i.e., the relationship between the MEP amplitude and the background EMG of the FDI muscle showed individual, strategy-dependent modulation. There were several kinds of individual motor strategies for performing the isolated finger movement. The present results may explain the previous contradictory evidence related to the contribution of the CM system during coordinated finger movement.     

Characteristics affecting cervical sagittal alignment in patients with chronic low back pain

BackgroundSagittal spino-pelvic malalignment in patients with chronic low back pain (CLBP) have been reported in the past, which may also affect cervical spine lesions. The purpose of this study is to investigate the cervical alignment in patients with CLBP.MethodOf the patients who visited an orthopedic specialist due to low back pain lasting more than three months, 121 cases (average 71.5-years-old, 46 male and 75 female) with whole standing spinal screening radiographs were reviewed (CLBP group). Cervical parameters included cervical lordosis (CL), C2–C7 sagittal vertical axis (C2-7 SVA), and the T1 slope minus CL (T1S-CL). Cervical spine deformity was defined as C2-7 SVA >4 cm, CL <0°, or T1S-CL ≧20°. We compared the cervical alignment of these patients with 121 age and gender matched volunteers (control group).ResultsThe prevalence of cervical spine deformity was significantly higher in the CLBP group than in the control group (20.7% vs. 10.7%, P = 0.034). The mean CL was smaller in the CLBP group than in the control group (16.1° vs. 21.4°, P = 0.002). The mean C2-7 SVA was 17.6 mm vs. 18.7 mm in the CLBP group and in the control group, respectively (P = 0.817). The mean T1S-CL was larger in the CLBP group than in the control group (9.1° vs. 3.5°, P < 0.001). Multivariate analysis showed that people with CLBP were more likely to have cervical deformities than people without CLBP (odds ratio 2.16, 95% confidence interval 1.006 to 4.637).ConclusionsThis study results suggest that people with CLBP present with worse cervical sagittal alignment and higher prevalence of cervical spine deformities than age and gender matched volunteers with no CLBP. This means CLBP impacts cervical spine lesions negatively.Level of evidenceⅣ