Delay in initiation and termination of muscle contraction, motor impairment, and physical disability in upper limb hemiparesis

The purpose of this study was to describe the relationship between the delay in initiation and termination of muscle contraction and clinical measures of motor impairment and physical disability in the affected upper limb of patients with hemiparesis. Electromyographic (EMG) activity of 26 long-term survivors of stroke was recorded during isometric wrist flexion and extension. Upper limb motor impairment and disability were assessed with the Fugl-Meyer motor assessment (FMA) and arm motor ability test (AMAT), respectively. Delay in initiation and termination of muscle contraction was significantly prolonged in the paretic arm. However, the delay was not significantly affected by stroke type, stroke level, side of hemiparesis, or presence of aphasia. Delay in initiation and termination of muscle contraction correlated significantly with FMA and AMAT. Abnormally delayed initiation and termination of muscle contraction may contribute to hemiparetic upper limb motor impairment and physical disability in hemiparetic patients.     

Mutation analysis of MECP2 and clinical characterization in Korean patients with Rett syndrome

Rett syndrome is a progressive neurodevelopmental disorder occurring predominantly in females. Recently, mutations in the MECP2 gene on Xq28, which encodes methyl-CpG binding protein 2, were identified as responsible for some cases of Rett syndrome. In the present study, we analyzed the entire coding sequence of the MECP2 gene in 20 sporadic cases of Rett syndrome in Korea. Of the 20 patients, 14 (70%) had pathogenic mutations, which included 10 different mutations. Altogether, there were five missense mutations (D97Y, L100V, R133C, T158M, R306C), four nonsense mutations (R168X, R255X, R270X, R294X), and one frameshift mutation (a 41-bp deletion at 1157-1197). Two of these were novel mutations (D97Y, L100V). Most of the nucleotide substitutions involved C to T transitions at CpG hotspots. We could find no clear phenotype-genotype correlation according to the type of mutation. However, there was a tendency for patients with no MECP2 mutation (30%) to show more severe symptoms and more rapid clinical progression than patients with mutations. Further studies are necessary to identify the other possible genetic causes of Rett syndrome.     

Vagus nerve stimulation (VNS) synchronized BOLD fMRI suggests that VNS in depressed adults has frequency/dose dependent effects

Stimulation of the vagus nerve in the neck can reduce seizures in epilepsy patients, and may be helpful in treating depression. PET studies have shown that vagus nerve stimulation (VNS) in epilepsy patients causes acute dose (intensity) dependent changes in regional cerebral blood flow. We sought to use the newly developed VNS synchronized fMRI technique to examine whether VNS BOLD signal changes depend on the frequency of stimulation. Six adults with recurrent depression were scanned inside a 1.5 T MR scanner. Data were acquired at rest, with the VNS device on for 7 s, and also, for comparison, while the patient listened to a tone for 7 s. In two separate back-to-back sessions, the VNS stimulation frequency was set to either 5 or 20 Hz. Data were transformed into Talairach space and then compared by condition. Compared to 5 Hz, 20 Hz VNS produced more acute activity changes from rest in regions similar to our initial VNS synchronized fMRI feasibility study in depression. Brain regions activated by hearing a tone were also greater when VNS was intermittently being applied at 20 Hz than at 5 Hz. In depressed adults, left cervical VNS causes regional brain activity changes that depend on the frequency of stimulation or total dose, or both. In addition to the acute immediate effects of VNS on regional brain activity, this study suggests further that VNS at different frequencies likely has frequency or dose dependent modulatory effects on other brain activities (e.g. hearing a tone).     

Homocysteine induces oxidative cytotoxicity in Cu,Zn-superoxide dismutase mutant motor neuronal cell

Mutations in human Cu,Zn-superoxide dismutase (SOD1) cause approximately 20% of familial amyotrophic lateral sclerosis (FALS) cases. The mechanism of late-onset disease manifestation despite the innate mutation has no clear explanation. The relationship between homocysteine (HC) and amyotrophic lateral sclerosis (ALS) has not been investigated, in spite of the similarity in their pathogenesis. We investigated the effect of HC on the motor neuronal cell-line transfected with SOD1 of either wild-type or one of two mutant forms (G93A and A4V). In the MTT assay, HC induced significant cytotoxicity in A4V, but not in G93A, as compared with wild-type, even at the physiological concentration of 10 microM. This HC-induced cytotoxicity was inhibited by the antioxidant trolox and the Cu (I) chelator bathocuproinedisulfonate. Here we show that the vulnerability of the A4 V mutant involves the cytotoxic copper-mediated pathway, and that HC may be a lifelong precipitating factor in some forms of FALS, suggesting the possible treatment modality with vitamin supplements.     

Human leukocyte antigen alleles in patients with bipolar disorder in the Korean population

We performed an association study between human leukocyte antigen (HLA) alleles and bipolar disorder to evaluate the potentiality of HLA as a genetic marker in bipolar disorder. HLA class I and class II allele frequencies were assessed in 87 bipolar patients and were compared with those of 206 normal controls in the Korean population. HLA class I typing was performed using the microlymphocytotoxicity method, whereas class II (DRB1 and DQB1) genotyping was performed with polymerase chain reaction-sequence specific oligonucleotide probes. When the allele frequency of HLA in bipolar patients was compared with that in normal controls, there were some significant differences. Bipolar patients showed statistically significant increased allele frequencies of HLA-A29 and B54. Allele frequencies of HLA-B51 and DRB1*02 were significantly higher in normal controls. However, these results were no longer significant after correcting for the number of alleles. The results of the present study suggest that HLA alleles may not confer susceptibility to bipolar disorder in the Korean population. To clarify the genetic influence of HLA on bipolar disorder, we should conduct a consecutive study with a larger cohort of subjects.     

NDP kinase 2 interacts with two oxidative stress-activated MAPKs to regulate cellular redox state and enhances multiple stress tolerance in transgenic plants

NDP kinases (NDPKs) are multifunctional proteins that regulate a variety of eukaryotic cellular activities, including cell proliferation, development, and differentiation. However, much less is known about the functional significance of NDPKs in plants. We show here that NDPK is associated with H(2)O(2)-mediated mitogen-activated protein kinase signaling in plants. H(2)O(2) stress strongly induces the expression of the NDPK2 gene in Arabidopsis thaliana (AtNDPK2). Proteins from transgenic plants overexpressing AtNDPK2 showed high levels of autophosphorylation and NDPK activity, and they have lower levels of reactive oxygen species (ROS) than wild-type plants. Mutants lacking AtNDPK2 had higher levels of ROS than wild type. H(2)O(2) treatment induced the phosphorylation of two endogenous proteins whose molecular weights suggested they are AtMPK3 and AtMPK6, two H(2)O(2)-activated A. thaliana mitogen-activated protein kinases. In the absence of H(2)O(2) treatment, phosphorylation of these proteins was slightly elevated in plants overexpressing AtNDPK2 but markedly decreased in the AtNDPK2 deletion mutant. Yeast two-hybrid and in vitro protein pull-down assays revealed that AtNDPK2 specifically interacts with AtMPK3 and AtMPK6. Furthermore, AtNDPK2 also enhances the myelin basic protein phosphorylation activity of AtMPK3 in vitro. Finally, constitutive overexpression of AtNDPK2 in Arabidopsis plants conferred an enhanced tolerance to multiple environmental stresses that elicit ROS accumulation in situ. Thus, AtNDPK2 appears to play a previously uncharacterized regulatory role in H(2)O(2)-mediated MAPK signaling in plants.