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At least 325 records · Page 18Linked to original sources
PubMed1994

Cortical reflex negative myoclonus.

Three patients with progressive myoclonic epilepsy (PME), two of them clinically manifesting only negative myoclonus and the other manifesting both positive and negative myoclonus, were electrophysiologically investigated, and compared with two other patients with PME presenting with only positive myoclonus. Electric stimulation of the median nerve during sustained active wrist extension in the three patients with negative myoclonus often elicited a short lapse of the posture in the stimulated hand associated with a silent period in the muscle discharge with or without being preceded by an abrupt increase in the muscle discharge (C reflex). The occurrence of the stimulus-induced silent period was significantly correlated with that of the giant somatosensory evoked potentials (SEPs), and in two patients the silent period was elicited also in the opposite (non-stimulated) hand when the giant SEP was recorded at the hemisphere ipsilateral to the stimulus as well. In one patient, the duration of the silent period was positively correlated with the amplitude of the cortical SEP. Furthermore, the duration of the induced silent period was closely related to the recovery function of SEP in each individual case. In contrast, in the two patients manifesting only positive myoclonus, the silent period was not elicited by the peripheral stimulation, and the somatosensory cortex was hyperexcitable immediately after the peripheral stimulus. Thus, this stimulus-sensitive negative myoclonus is mediated by a transcortical reflex mechanism, and corresponds to the negative form of the cortical reflex myoclonus ('cortical reflex negative myoclonus').

Adult↗
PubMed1999

Brain structures related to active and passive finger movements in man.

A PET study was performed in six normal volunteers to elucidate the functional localization of the sensory afferent component during finger movement. Brain activation during the passive movement driven by a servo-motor was compared with that during an auditory-cued active movement which was controlled kinematically in the same way as the passive one. A newly developed device was used for selectively activating proprioception with a minimal contribution from tactile senses. Active movement was associated with activation of multiple areas, including the contralateral primary sensorimotor cortex, premotor cortex, supplementary motor area (SMA), bilateral secondary somatosensory areas and basal ganglia and ipsilateral cerebellum. In contrast, only the contralateral primary and secondary somatosensory areas were activated by the passive movement. It is likely that the contribution of proprioceptive input to the activation of the premotor cortex, SMA, cerebellum and basal ganglia, if any, is small. However, the present results do not rule out the possibility that the cutaneous afferent input or the combination of cutaneous and proprioceptive input participates in the activation of those areas during the active movement.

Acoustic Stimulation↗
PubMed1999

Functional coupling of human cortical sensorimotor areas during bimanual skill acquisition.

Bimanual co-ordination of skilled finger movements is a high-level capability of the human motor system and virtually always requires training. Little is known about the physiological processes underlying successful bimanual performance and skill acquisition. In the present study, we used task-related coherence (TRCoh) and task-related power (TRPow) analysis of multichannel surface EEG to investigate the functional coupling and regional activation of human sensorimotor regions during bimanual skill acquisition. We focused on changes in interhemispheric coupling associated with bimanual learning. TRCoh and TRPow were estimated during the fusion of two overlearned unimanual finger-tapping sequences into one novel bimanual sequence, before and after a 30-min training period in 18 normal volunteers. Control experiments included learning and repetition of complex and simple unimanual finger sequences. The main finding was a significant increase in interhemispheric TRCoh selectively in the early learning stage (P < 0.0001). Interhemispheric TRCoh was also present during the unimanual control tasks, but with lower magnitude, even if learning was involved. Training improved bimanual sequence performance (from 58.3+/-24.1 to 83.7+/-15.3% correct sequences). After training, interhemispheric (bimanual) TRCoh decreased again, thereby approaching levels similar to those in the unimanual controls. We propose that the initial increase in TRCoh reflects changes in interhemispheric communication that are specifically related to bimanual learning and may be relayed through the corpus callosum. The present data might also offer a neurophysiological explanation for the clinical observation that patients with lesions of the corpus callosum may show deficits in the acquisition of novel bimanual tasks but not necessarily in the execution of previously learned bimanual activities.

Adult↗
PubMed2004

Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer's cramp.

Writer's cramp, or focal hand dystonia, is characterized by involuntary coactivation of antagonist or unnecessary muscles while writing or performing other tasks. Although the mechanism underlying this muscle overactivation is unknown, recent studies of changes in cerebral blood flow during writing have demonstrated a reduction in the activation of the primary motor cortex (MC) and hyperactivity of parts of the frontal non-primary motor areas. Therefore, any measures that decrease the activities of non-primary motor areas such as the premotor cortex (PMC) and the supplementary motor area (SMA) might improve dystonic symptoms. To explore this possibility, we studied nine patients with writer's cramp and seven age-matched control subjects, using subthreshold low-frequency (0.2 Hz) repetitive transcranial magnetic stimulation (rTMS), which exerts an inhibitory action on the cortex. Previous studies have demonstrated shortened cortical silent periods in dystonia, suggesting deficient cortical inhibition in the MC. We compared the silent periods and computer-assisted ratings of handwriting before and after rTMS applied to the MC, SMA or PMC. We also used the sham coil for control runs. Stimulation of the PMC but not the MC significantly improved the rating of handwriting (mean tracking error from the target, P = 0.004; pen pressure, P = 0.01) and prolonged the silent period (P = 0.02) in the patient group. rTMS over the other sites or using a sham coil in the patient group or trials in the control group revealed no physiological or clinical changes. This increased susceptibility of the PMC in dystonia suggests that the lack of inhibition in the MC is secondary to the hyperactivity of PMC neurons. Inhibition of the PMC using rTMS could provide a therapeutic measure of writer's cramp.

Adult↗
PubMed2006

Isolation and expression profiling of genes upregulated in the peripheral blood cells of systemic lupus erythematosus patients.

We have identified the genes whose expressions are augmented in the blood cells of the patients with systemic lupus erythematosus (SLE) using the 'stepwise subtraction' technique along with microarray analysis. The expression levels of these genes were assessed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) in 31 SLE patients and 30 healthy controls. We found that the transcription levels of following eight genes were significantly increased in SLE patients; interferon (IFN)-alpha-inducible protein 27 (IFI27), IFN-alpha-inducible protein IFI-15K (G1P2), IFN stimulated gene 20 kDa (ISG20), epithelial stromal interaction 1 (EPSTI1), defensin-alpha (DEFA3), amphiregulin (AREG) and two genes of unknown function (BLAST accession nos AL050290 and AY358224 = SLED1). In comparison with idiopathic thrombocytopenic purpura (ITP), an organ-specific autoimmune disease, IFI27, G1P2 and SLED1 were preferentially upregulated in SLE. In contrast, AREG and AL050290 were more highly expressed in ITP than in SLE. We correlated changes in gene expression and clinical/laboratory features of SLE and found that expression of ISG20, EPSTI1 and SLED1 are significantly correlated with lymphocyte counts. Genes linked to IFN are well known to influence SLE, but several other novel genes unrelated to IFN signaling we report here would be useful to understand the pathophysiology of SLE.

Female↗
PubMed2003

Induction of mexCD-oprJ operon for a multidrug efflux pump by disinfectants in wild-type Pseudomonas aeruginosa PAO1.

Induction of the MexCD-OprJ multidrug efflux pump was investigated in wild-type Pseudomonas aeruginosa PAO1. MexCD-OprJ was induced by clinically important disinfectants such as benzalkonium chloride and chlorhexidine gluconate, and by some cytotoxic agents such as tetraphenylphosphonium chloride, ethidium bromide and rhodamine 6G. MexCD-OprJ was not induced by norfloxacin, tetracycline, chloramphenicol, streptomycin, erythromycin or carbenicillin, although they are substrates for the pump. Cells of PAO1 showed increased resistance to norfloxacin when grown in the presence of the inducers of the mexCD-oprJ operon mentioned above. These results indicate that MexCD-OprJ plays an important role in intrinsic multidrug resistance in wild-type P. aeruginosa in hospitals where disinfectants are used frequently.

Bacterial Proteins↗
PubMed2003

A new member of the tripartite multidrug efflux pumps, MexVW-OprM, in Pseudomonas aeruginosa.

OBJECTIVES: Multidrug efflux pumps are thought to be involved in mediating multidrug resistance in Pseudomonas aeruginosa. Here we aim to characterize hitherto uncharacterized multidrug efflux pumps from P. aeruginosa. MATERIALS AND METHODS: We isolated a mutant, YM442, which showed elevated resistance to several antimicrobial agents from P. aeruginosa YM44 lacking four major multidrug efflux pumps, MexAB, MexCD-OprJ, MexEF-OprN and MexXY. We cloned genes responsible for the resistance from chromosomal DNA of YM442 using YM44 as host. RESULTS: We designated the genes mexVW. Introduction of a recombinant plasmid pTAJ2 carrying the mexVW into YM44 cells conferred resistance to fluoroquinolones, tetracycline, chloramphenicol, erythromycin, ethidium bromide and acriflavine. Elevated ethidium bromide extrusion was observed with cells of YM442 and of YM44/pTAJ2. An outer membrane protein OprM was able to cooperate with MexVW. Elevated expression of the mexV gene was observed with YM442 compared with YM44. CONCLUSIONS: MexV (membrane fusion protein)-MexW (RND-type membrane protein)-OprM is a tripartite multidrug efflux pump. It is suggested that other outer membrane component(s) could cooperate with MexVW.

Bacterial Outer Membrane Proteins↗
PubMed2006

Development of a gas injection/specimen heating holder for use with transmission electron microscope.

A new gas injection/specimen heating holder is developed for the purpose of in situ observation of gas reaction of materials at high temperatures in a transmission electron microscope at near-atomic resolution. A fine tungsten wire is employed as a heating element of the holder and a battery is used as the power source. Gas was injected onto specimens in the form of particles lying on the heating element via a nozzle. The maximum pressure near specimens was middle of 10(-2) Pa, while the pressure in the electron-gun chamber was kept to 2 x 10(-4) Pa. This gas injection/specimen heating holder was applied to observe solid-gas reactions. The reactions observed include oxidation of pure In into In2O3, reduction of SiO2 into Si and re-oxidation of Si into SiO2.

Journal Article↗
PubMed2002

Overexpression and functional characterization of a serine carboxypeptidase inhibitor (I(C)) from Saccharomyces cerevisiae.

Carboxypeptidase Y (CPY) inhibitor, I(C), a cytoplasmic inhibitor of vacuolar proteinases in yeast, Saccharomyces cerevisiae, was purified by means of a high-level expression system using a proteinase-deficient strain, BJ2168, and an expression vector with the promoter GAL1. The purified I(C) exists as a monomeric beta-protein in solution with a mole-cular weight of 24,398.4 as determined by gel filtration chromatography, MALDI-TOF mass spectrometry, and far-UV CD spectroscopy. The acetylated N-terminal methionine residue is the sole posttranslational modification. I(C) specifically inhibits both the peptidase and anilidase activities of CPY with inhibitor constants (K(i)) of approximately 1.0 x 10(-9) M. The chemical modification of I(C) with sulfhydryl reagents indicated that it lacks disulfide bonds and has two free SH groups, which are responsible, not for the inhibitory function, but, apparently, for the folding of the overall structure. The formation of a complex of I(C) with CPY was highly specific, as evidenced by no detectable interaction with pro-CPY. Chemical modification studies of the CPY-I(C) complex with specific reagents demonstrated that the catalytic Ser146 and S1 substrate-binding site of CPY are covered in the complex.

Cathepsin A↗
PubMed1998

Partial agonistic activity of naloxone on the opioid receptors expressed from complementary deoxyribonucleic acids in Chinese hamster ovary cells.

UNLABELLED: Naloxone is a widely used opioid antagonist. To analyze the cellular responses induced by naloxone in the absence of opioid agonists, Chinese hamster ovary (CHO) cells, which do not endogenously express the opioid receptors, have been permanently transfected with the cloned complementary DNAs to produce the mu-, delta-, and kappa-opioid receptors. Naloxone dose-dependently reduced forskolin-stimulated cyclic adenosine monophosphate (cAMP) formation in the cells expressing the mu- and kappa-opioid receptors, although the effect was less than that of opioid agonists [D-Ala2, N-Me-Phe4, Gly-ol5]enkephalin and U50,488, respectively. The naloxone-induced cAMP reduction was abolished by pretreatment of the cells with pertussis toxin, which suggests that pertussis toxin-sensitive G proteins (Gi and/or Go) are involved in the response. Cellular guanosine triphosphatase activity was significantly increased by naloxone in the cells expressing the mu- and kappa-opioid receptors, which suggests that the application of naloxone to these receptors induces activation of the G proteins. We conclude that naloxone possesses partial agonistic activity on the mu- and kappa-opioid receptors expressed from complementary DNAs in CHO cells. IMPLICATIONS: In this study, we examined whether naloxone has agonistic activity on the opioid receptors by using cultured cells transfected with delta-, mu-, and kappa-opioid receptor complementary DNAs. Our data indicate that naloxone is a partial agonist on the mu- and kappa-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed2002

Midazolam induces expression of c-Fos and EGR-1 by a non-GABAergic mechanism.

UNLABELLED: Gene expression changes induced by general anesthetics have not been extensively examined. In this investigation, we treated rat pheochromocytoma PC12 cells with IV anesthetics, and assessed expression of immediate early gene products, c-Fos and EGR-1, by immunoblot analysis. Thiopental, ketamine, propofol, and diazepam did not significantly change the expression level of c-Fos and EGR-1. In contrast, midazolam dose- and time-dependently induced expression of c-Fos and EGR-1, which was not affected by antagonists of the benzodiazepine receptors, flumazenil and PK11195. The midazolam-induced c-Fos and EGR-1 expression was abolished by PD98059, an inhibitor for mitogen- activated protein kinase/extracellular signal-regulated kinase kinase, suggesting the involvement of extracellular signal-regulated kinases (ERKs). Immunoblot analysis demonstrated that midazolam induces phosphorylation and activation of ERKs. These results indicate that midazolam induces the expression of c-Fos and EGR-1, by activation of ERKs through a mechanism independent from gamma-aminobutyric acid(A) receptors, in PC12 cells, and suggest the possibility that midazolam can induce long-term changes of neural functions by changing gene expression. IMPLICATIONS: Gene expression changes induced by anesthetics in neuronal cells have not been noticed. We demonstrate that a large concentration of midazolam can induce expression of immediate early genes by a non-GABAergic mechanism in PC12 cells, suggesting that the administration of midazolam might lead to long-term changes of neural functions by changing gene expression.

Anesthetics, Intravenous↗
PubMed2001

Activation of mu-opioid receptor induces expression of c-fos and junB via mitogen-activated protein kinase cascade.

BACKGROUND: Opioid-induced long-term functional alterations of the nervous system, such as tolerance, addiction, and dependence, conceivably involve changes in gene expression. The authors have previously reported that opioid receptors are functionally coupled to extracellular signal-regulated kinase, a class of the mitogen-activated protein kinase. To address whether activation of the opioid receptor induces changes in gene expression through the activation of extracellular signal-regulated kinase, the authors examined mu-opioid receptor (MOR)-induced immediate early gene expression. METHODS: Chinese hamster ovary cells stably expressing MOR were used. Cells were stimulated by MOR agonists after 24-h serum starvation. Expression of c-fos and junB genes was analyzed by RNA blot hybridization. To explore the mechanism of MOR-mediated c-fos and junB expression, activity of a transcription factor, Elk-1, was assessed by reporter assay. Furthermore, to investigate the functional consequences of c-fos and junB induction, MOR-mediated formation of the functional transcription factor complex AP-1 was examined by reporter assay and electrophoretic mobility shift assay. RESULTS: Mu-opioid receptor activation induced c-fos and junB messenger RNAs, which were inhibited by pretreatment of the cells with pertussis toxin and PD98059, an inhibitor of extracellular signal-regulated kinase cascade. MOR stimulation elevated Elk-1-mediated transcriptional activity by about 10-fold. AP-1-mediated transcriptional activity was stimulated by MOR agonists by about twofold. Electrophoretic mobility shift assay revealed that AP-1 binding activity in the nuclear extract was elevated by MOR activation and further showed that products of c-fos and junB genes are involved in formation of AP-1 complex. CONCLUSIONS: Mu-opioid receptor activation induces c-fos and junB expression and elevates AP-1-mediated transcriptional activities via the mitogen-activated protein kinase cascade.

Animals↗
PubMed1997

Functional localization of pain perception in the human brain studied by PET.

To elucidate the functional localization and somatotopic organization of pain perception in the human cerebral cortex, we studied the regional cerebral blood flow using positron emission tomography during selective painful stimulation in six normal subjects. Response to a painful stimulus was elicited using a special CO2 laser, which selectively activates nociceptive receptors, to the hand and foot. Multiple brain areas, including bilateral secondary somatosensory cortices (SII) and insula, and the frontal lobe and thalamus contralateral to the stimulus side, were found to be involved in the response to painful stimulation. While our data indicate that the bilateral SII play an important role in pain perception, they also indicate that there is no pain-related somatotopic organization in the human SII or insula.

Adult↗
PubMed1999

Somesthetic function of supplementary motor area during voluntary movements.

To clarify the somesthetic functions of the supplementary motor area (SMA), we recorded the cortical potentials following the median nerve electric stimulation directly from the SMA and investigated the modulation caused by voluntary movements in two patients with intractable SMA seizures. The evoked potentials over the SMA consisted of positive (61.5ms) and negative (100.0 ms) peaks, which were enlarged by voluntary movements of the stimulated hand. The present finding is in strong contrast with the attenuation (gating) of the response at the primary sensorimotor area (SM1) and suggests that the voluntary movements differently modulate the somatosensory functions of SMA and SM1.

Adult↗
PubMed2005

Involvement of V5/MT+ in object substitution masking: evidence from repetitive transcranial magnetic stimulation.

The visibility of a briefly presented target can be reduced by a subsequent weak mask that does not touch it, when the target is encoded in low spatiotemporal resolution. This phenomenon, called object substitution masking, has recently been proposed to reflect information updating in object-level representation, with perception of the target and the mask belonging to a single object through apparent motion. We investigated this issue by applying repetitive transcranial magnetic stimulation over V5/MT+, specialized in visual motion processing. The transient functional disruption of V5/MT+ produced by repetitive transcranial magnetic stimulation attenuated object substitution masking, while sham stimulation did not. Our results suggest that object substitution masking is mediated by normal functioning of V5/MT+. We conclude that repetitive transcranial magnetic stimulation of V5/MT+ impaired perceived object continuity and reduced object substitution masking accordingly.

Adult↗
PubMed1999

Corticomuscular coherence: a review.

Corticomuscular coherence measured between electroencephalography (EEG), magnetoencephalography, or local field potentials and electromyography (EMG) should be helpful in understanding the cortical control of movement. EEG-EMG coherence and phase spectra depend on the types of EEG derivation and current source density function of EEG appears to be the most appropriate for computation of EEG-EMG coherence. A new model for the interpretation of the phase spectra ("constant phase shift plus constant time lag model") shows that cortical surface negative potentials are phase-locked to EMG firing. There are functional differences of EEG-EMG coherence among the alpha, beta, and gamma bands suggesting differences in their possible generator mechanisms. Since corticomuscular coherence is a noninvasive measure of corticomotoneuronal function in a specific frequency range, clinical application of this method might be very fruitful in tremor research.

Electroencephalography↗
PubMed1989

Endothelin-1 acts in cerebral arteries from the adventitial but not from the luminal side.

The in vivo vasoconstrictor effect of endothelin-1 (ET-1) was investigated on feline and canine basilar arteries. The basilar artery caliber was angiographically measured after either vertebral artery perfusion or cisternal injection of the peptide. In both cats and dogs, ET-1 (5-500 pmol) induced a dose-dependent basilar artery contraction in vivo when applied intracisternally. The vasoconstriction was extremely long lasting; no significant recovery of vessel caliber was observed up to 12 h after injection. In contrast, bolus injection of ET-1 up to 3 nmol into the vertebral artery had no appreciable effect on the basilar artery caliber. These observations suggest that ET-1 acts in cerebral vessels from the adventitial but not from the luminal side, possibly due to the presence of the blood-brain barrier. The long-lasting nature of the ET-1-induced constriction of the cerebral arteries in vivo suggests that the peptide might be involved in the pathogenesis of cerebral vasospasm.

Animals↗