Possible association of oestrogen and Cryba4 with masticatory muscle tendon-aponeurosis hyperplasia.

OBJECTIVE: Masticatory muscle tendon-aponeurosis hyperplasia, which is associated with limited mouth opening, progresses very slowly from adolescence. The prevalence rates of this disease are higher among women than among men, suggesting oestrogen involvement. As parafunctional habits are frequently observed, mechanical stress is likely involved in the pathogenesis and advancement of this disease. To elucidate the pathological condition, we examined the effect of oestrogen on tenocyte function and the relationship between mechanical stress and crystallin beta A4 (Cryba4), using murine TT-D6 tenocytes. MATERIALS AND METHODS: Cell proliferation assays, RT-PCR, real-time RT-PCR, Western blot analysis and mechanical loading experiments were performed. RESULTS: The physiological dose of oestrogen increased the levels of scleraxis and tenomodulin in TT-D6 tenocytes. In contrast, forced expression of Cryba4 inhibited scleraxis expression in these cells. Surprisingly, oestrogen significantly promoted cell differentiation in the Cryba4-overexpressing TT-D6 tenocytes. Moreover, tensile force induced Cryba4 expression in these tendon cells. CONCLUSION: Oestrogen and Cryba4 may be associated with the progression of masticatory muscle tendon-aponeurosis hyperplasia.

MLL is essential for NUP98-HOXA9-induced leukemia.

Rearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with mixed lineage leukemia (MLL) via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited. Molecular analyses indicate that MLL is important for the recruitment of NUP98-HOXA9 to the HOXA locus and for NUP98-HOXA9-induced HOXA gene expression. Our data indicate that MLL is crucial for NUP98-HOXA9 leukemia initiation.

A stroke patient with impairment of auditory sensory (echoic) memory.

A 42-year-old man suffered damage to the left supra-sylvian areas due to a stroke and presented with verbal short-term memory (STM) deficits. He occasionally could not recall even a single syllable that he had heard one second before. A study of mismatch negativity using magnetoencephalography suggested that the duration of auditory sensory (echoic) memory traces was reduced on the affected side of the brain. His maximum digit span was four with auditory presentation (equivalent to the 1st percentile for normal subjects), whereas it was up to six with visual presentation (almost within the normal range). He simply showed partial recall in the digit span task, and there was no self correction or incorrect reproduction. From these findings, reduced echoic memory was thought to have affected his verbal short-term retention. Thus, the impairment of verbal short-term memory observed in this patient was "pure auditory" unlike previously reported patients with deficits of the phonological short-term store (STS), which is the next higher-order memory system. We report this case to present physiological and behavioral data suggesting impaired short-term storage of verbal information, and to demonstrate the influence of deterioration of echoic memory on verbal STM.

Molecular phylogenetic analysis of Barley yellow mosaic virus.

Complete nucleotide sequences of three strains (I, III, and IV) of Barley yellow mosaic virus (BaYMV) isolated in Japan were determined. The length of the genome was the same among the three strains; RNA1 was 7,642 nt and RNA2 was 3,585 nt. The molecular phylogenetic analysis showed that strain I was most closely related to the Chinese isolate, and these two strains formed one cluster with European isolates. Strains II, III, and IV, and the Korean isolate formed another cluster. Amino acid sequences of each viral gene product were compared among strains. The sequences of the VPg protein showed less identity among almost strains (less than 92%) than the sequences of other proteins (more than 93%). VPg is thought to be involved in interactions with host factors, especially initiation factor 4E (eIF4E) or eIF(iso)4E, and infection. Therefore, the relationship between amino acid substitutions and infection of host plants is analyzed.

Supramolecular gels formed by amphiphilic low-molecular-weight gelators of N alpha,N epsilon-diacyl-L-lysine derivatives.

Simple L-lysine derivatives, N(alpha)-hexanoyl-N(epsilon)-lauroyl-L-lysine (1), its alkali metal salts (2-4), and two-component compounds that consist of 1 with 2 to 4, were synthesized and their hydrogelation and organogelation properties were studied. Addition of hydrochloric acid to an aqueous solution of the alkali metal salt at room temperature produced a translucent hydrogel. This hydrogelation occurred as a result of a change in nanostructure from micelle-like aggregates to nanofibers, which was induced by partial protonation of the carboxylate to form a carboxylic acid. On the other hand, two-component low-molecular-weight gelators exhibited amphiphilic gelation behavior and functioned as not only hydrogelators, but also as organogelators. FTIR studies revealed that lateral ionic interactions between the carboxylate, alkali metal cation, carboxylic acid, and protons, in addition to hydrogen-bonding and van der Waals interactions play a very important role in hydrogelation. Furthermore, it was found that the water-insoluble carboxylic acid compound underwent a precipitation-dissolution transition with a thermally reversible sol-gel transition in the two-component gelator systems.

Extracellular carbohydrate-signal triggering cAMP-dependent protein kinase-dependent neuronal actin-reorganization.

Cell surface glycoconjugates are thought to mediate cell-cell recognition and to play roles in neuronal development and functions. We demonstrated here that exposure of neuronal cells to nanomolar levels of glyco-chains with an N-acetylgalactosamine (GalNAc) residue at the non-reducing termini (GalNAc-S) such as GalNAcbeta4(Neu5Acalpha3)Galbeta4GlcCer (GM2) ganglioside, its oligosaccharide portion, GalNAcbeta4Galbeta4GlcCer (Gg(3)) Cer, GalNAcalpha3GalNAcbeta3Galalpha4Galbeta4GlcCer (Gb(5)) Cer (Forssman hapten) and alpha1-4 linked oligomers of GalNAc, induced a rapid and transient activation of cAMP-dependent protein kinase (PKA) in subplasmalemma. The treatment was accompanied by peripheral actin polymerization and filopodia formation in NG108-15 cells and primary cultured hippocampal neurons, but not in glial cells. A cAMP-dependent protein kinase (PKA) selective inhibitor and an adenylate cyclase inhibitor blocked both PKA activation and the subsequent filopodia formation. A small GTPase cdc42 was a potential downstream target of GalNAc-S-activated PKA. These results suggest that extracellular GalNAc-S serve as potential regulators of the filopodia formation in neuronal cells by triggering the activation of PKA followed by cdc42 up-regulation via a cell surface receptor-like component. Filopodia formation induced by GalNAc-S may have a physiological relevance because long-term exposure to GalNAc-S enhanced F-actin-rich dendrite generation of primary cultured hippocampal neurons, and PKA-dependent dendritic outgrowth and branch formation of primary cultured cerebellar Purkinje neurons, in which actin isoforms were localized to motile structures in dendrites. These findings provide evidence for a novel GalNAc/PKA-signaling cascade in regulating some neuronal maturation.

Brain lateralization for mismatch response to across- and within-category change of vowels.

Differences in hemispheric predominance between across- and within-category change perception of vowels were assessed using a whole-head magnetoencephalography. The magnetic mismatch responses (MMNm) to pure-tone and vowel within-category changes were significantly predominant in the right hemisphere; on the other hand, vowel across-category MMNm did not differ in power between hemispheres. The results suggest that both hemispheres are symmetrically activated in the preattentive across-category change perception of vowels, while the within-category change of a vowel is analyzed as the change in physical features of the stimuli, thus predominantly activating the right hemisphere. Thus, the relative contribution of the left auditory cortex in the preattentive speech processing may occur only at the level of perception of the vowel across-category change.

Temporal stream of cortical representation for auditory spatial localization in human hemispheres.

We measured human evoked magnetic fields to binaural sounds with an interaural time delay as a cue for auditory localization. By analyzing the topography of auditory-evoked magnetic fields in the middle-latency, we demonstrated that particular cortical regions represent the direction of sound localization by their activity level. Upon presenting a binaural sound, the first representations were found in the middle frontal region as well as the superior temporal region of the right hemisphere approximately 19 ms after the stimulation, but their patterns differed. Other cortical regions including the prefrontal and parietal spatial areas were affected within roughly 60 ms. The results showed that the right hemisphere is dominant even in the preattentive stage of auditory spatial processing of sounds from different directions.

[Recent advances of MEG].

The number of MEG(Magnetoencephalography) channels was rapidly increased from 14 to 306 in the past decade and the detection coil array with the whole-scalp coverage has become fairly common these days. Besides the advances of biomagnetometer itself, there are several important technical advances around MEG measurements. An active shielding technique can reduce the contamination of environmental magnetic noise in the frequency range below 10 Hz. Applying SSP(signal space projection) technique, which is known as a strong tool to resolve multiple current sources, can be another choice to reduce this contamination in the full frequency range. Recently the realistic head model reconstructed from MRI data was accomplished and we can apply this model, instead of the conventional spherical model, to the patients with TLE(temporal lobe epilepsy) expecting further accurate dipole estimation. These advances are quite important for the data acquisition with high S/N(signal to noise) ratio and the reliable three-dimensional localization of current sources in the brain.

Evidence for functional abnormality in the right auditory cortex during musical hallucinations.

Right auditory cortex dysfunction during musical hallucinations occurred in an 88-year-old woman, who was otherwise cognitively intact. We assessed this phenomenon with a combination of neuromagnetic and cerebral blood-flow measurements.

Motor cortical reflex myoclonus: a case study with MEG.

Cortical reflex myoclonus usually depends for its generation on the hyperexcitability of sensory cortex, which manifests itself as an enhanced somatosensory evoked potential (SEP). A 25-year-old female, presenting with involuntary jerky dorsiflexion of the left foot, was found to have cortical reflex myoclonus which was aggravated during intended movements. The jerks were also elicited by electrical stimulation of the posterior tibial nerve, although the SEP evoked by the same stimulus was normal in latency and amplitude. Both the spontaneous spikes and the premyoclonus spike demonstrated by jerk-locked back averaging were localized to the superior frontal gyrus, just anterior to the paracentral sulcus. Paired-pulse magnetic stimulation disclosed lack of inhibition in the right hemisphere leg motor area, whereas the excitability of sensory cortex as studied by paired SEP testing was normal. This suggests that the myoclonus was caused mainly by enhanced excitability of the motor cortex and that this alone was enough for the production of long loop reflexes. We propose to designate this type of cortical myoclonus as motor cortical reflex myoclonus. It is generated in the motor cortex, but is at the same time stimulus-sensitive.

Observation of neural processes of auditory scene analysis by magnetoencephalography.

In order to elucidate the auditory mechanism of sensory cue grouping and stream formation, we used a 37-channel SQUID magnetoencephalographic system to analyze the magnetic fields elicited by spoken sound stimuli consisting of an isolated word, an isolated consonant (/k/) burst, and a concurrent but perceptually segregated version of them. Only the overlapped /k/ burst among the five measured neural activities had a statistically significant difference in the location of the equivalent single-current dipoles in both hemispheres. The result suggests that the neurons activated by the overlapped /k/ burst are at least partially different from those activated by the other sounds: thereby supporting our new hypothesis that concurrent auditory events are spatially represented within the auditory cortex.

Magnetoencephalographic analysis of cortical myoclonic jerks.

We studied the pre-myoclonus spike using magnetoencephalography in patients with cortical myoclonus (6 with cortical reflex myoclonus and one with epilepsia partialis continua). The spike was estimated as a single current dipole on the pre-central gyrus in one patient with epilepsia partialis continua. In contrast, it was estimated as a single dipole on the post-central gyrus in 5 of 6 patients with cortical reflex myoclonus, and as two dipoles on the pre- and post-central gyrus in the remaining patient. We conclude that there are 3 physiological types of cortical myoclonus: (1) abnormal discharges in the motor cortex produce the myoclonus; (2) the source of the myoclonus is mainly the sensory cortex; (3) both the motor and sensory cortices play important roles in the production of myoclonus.

The early component of the visual evoked magnetic field.

Several EEG studies have reported an early component of the visual evoked potential. However, it is controversial whether this component is cortical or subcortical. Our study has aimed to clarify this problem using MEG and EEG in nine normal volunteers. A total of 4000 stimuli were presented to the monocular visual hemifield through a light-proof stimulating goggle and the visual evoked magnetic field and visual evoked potential was measured above the occipital lobe. The early component was observed in three of the nine subjects. The latency ranged from 40 to 45 ms in MEG and from 39 to 47 ms in EEG. The result of dipole localization analysis showed that its origin was cortical, and specifically, the striate cortex.

Pathophysiology of sensorimotor cortex in cortical myoclonus.

We have studied greatly enhanced cortical responses to somatosensory stimuli [giant somatosensory evoked potential (SEP) or magnetic field (SEF)] and cortical activities preceding the myoclonus (premyoclonus spike) in patients with cortical myoclonus, using magnetoencephalographic (MEG) techniques. A P1m component of giant SEF was estimated as a dipole positioned on the postcentral gyrus in all giant SEFs. This indicates that abnormally enhanced responses to sensory stimuli originate from the sensory cortex. In most of the patients with cortical reflex myoclonus, a dipole for the premyoclonus spike was also localized on the postcentral gyrus, which suggests that abnormal activation of the sensory cortex produces the spontaneous myoclonus. In one patient with galactosialidosis, two dipoles, one on the postcentral and the other on the precentral gyrus, could reasonably explain the premyoclonus spike. In the other patient with cortical reflex myoclonus, the premyoclonus spike associated with jerks of the lower limb muscle was estimated to be one dipole on the superior frontal gyrus just anterior to the paracentral lobule. This suggests that both spontaneous myoclonus and enhanced long loop reflex are generated by abnormal activation of the motor cortex in this patient. In a patient with epilepsia partialis continua who had no long loop reflexes, the premyoclonus spike was demonstrated to be positioned on the precentral gyrus, which indicates that abnormal activation of the motor cortex causes the spontaneous myoclonus in this patient. Our MEG studies demonstrated that abnormalities of the sensory or motor cortices contribute differently to the generation of myoclonus in cortical myoclonus, despite the fact that the sensory cortex is the main contributor in most of them.

Hypometabolism and dipole localization in hemimegalencephaly: a case report.

A case of hemimegalencephaly was studied by means of neuroimaging (CT, MRI and PET) and magnetoencephalography (MEG). Hemimegalencephaly (HM) is a neuronal migration disorder. This is the first report of evaluation of HM with the use of PET and MEG from not only the morphological but also the functional point of view. PET with 11C-glucose showed a low radioactive concentration in the affected hemisphere, which suggested a metabolic deficit. MEG proved the epileptic foci existed mainly in the affected hemisphere, especially around a heterotopia and the pachygyric cortex, which was disclosed on MRI.

Giant somatosensory evoked magnetic field in patients with myoclonus epilepsy.

We investigated somatosensory evoked magnetic fields (SEFs) and somatosensory evoked potentials (SEPs) in patients with myoclonus epilepsy. The median nerve was stimulated at the wrist, and responses were recorded over the contralateral hemisphere. The source of the enlarged cortical component of the giant SEF was localized on the post-central sensory cortex. The P1 component of the giant cortical response was composed mainly of a tangentially oriented dipole at area 3b. This is the first magnetoencephalographic analysis of an abnormally enlarged somatosensory cortical response.