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At least 253 records · Page 14Linked to original sources

Short-term high-frequency transcutaneous electrical nerve stimulation decreases human motor cortex excitability.

Several previous studies have shown that periods of changed sensory input can have after effects on the excitability of the corticospinal system. Here we test whether the parameters of peripheral stimulation conventionally used to treat pain with transcutaneous electrical nerve stimulation (TENS: 90 Hz) also have modulatory effects on the motor system. We measured the amplitude of motor evoked potentials (MEPs) elicited by the focal transcranial magnetic stimulation in the right abductor pollicis brevis and first dorsal interosseous muscles before and after 30 min TENS over the right thenar eminence. In addition, we evaluated tactile and 2-point discrimination thresholds at the same site. TENS transiently reduced MEPs and increased sensory thresholds. This suggests that short-term TENS might have an inhibitory effect on both the sensory and motor systems.

Adult↗

Neuronal cell type-specific promoter of the alpha CaM kinase II gene is activated by Zic2, a Zic family zinc finger protein.

To understand the neuronal cell type-specific expression of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), we investigated binding proteins that specifically activated the promoter of the alpha isoform of CaM kinase II (alpha CaM kinase II). Proteins that bind the promoter sequence were found in rat brain nuclear extract by electrophoretic mobility shift assay. Then, we screened for binding proteins in a mouse brain cDNA library using the yeast one-hybrid system. Zic2, a Zic family zinc finger transcription factor, was identified as one of the binding proteins. To investigate the effect of Zic2 on the promoter activity, Zic2 cDNA was expressed with a luciferase reporter gene containing a neuronal cell type-specific promoter of alpha CaM kinase II in neuronal and non-neuronal cells. The promoter activity of alpha CaM kinase II was enhanced 1.3-5-fold in cultured neuronal cells by Zic2. The activation was varied among neuronal cell types. Zic2 also increased the promoter activity in non-neuronal cells, although the relative luciferase activites in non-neuronal cells were lower than those in neuronal cell lines. These results indicated that Zic2 was one of the proteins binding to, and regulating the activity of, the promoter of alpha CaM kinase II.

Animals↗

Cortical mechanisms of unilateral voluntary motor inhibition in humans.

While motor control is very often a goal-oriented event, little is known about the mechanisms underlying the termination of motor performance. To investigate what type of cortical activation underlies the muscle relaxation required to terminate the act, we performed single- and double-pulse transcranial magnetic stimulation (TMS) studies during voluntary muscle relaxation in nine normal volunteers. Subjects maintained a weak isometric contraction of the right first dorsal interosseous muscle (FDI), and either increased the level of contraction (Contraction), terminated the contraction (Relaxation), or maintained it (No-go) depending on a visual cue. Motor evoked potentials (MEP) and the silent period (SP) were recorded from the FDI during motor activity. To measure intra-cortical inhibition (ICI), we also performed double-pulse TMS, applying subthreshold conditioning stimuli at interstimulus intervals of 2 ms. When single-pulse TMS was given just prior to muscle relaxation (-21 to -70 ms), the MEP was reduced while the SP was unchanged. Intra-cortical inhibition was smaller just prior to the muscle relaxation. Unilateral voluntary muscle relaxation may not be associated with activation of the intracortical inhibitory system, but rather with the possible excitation of the corticospinal system, which can inhibit motoneurons disynaptically. These findings suggest that multiple inhibitory mechanisms act in diverse ways to achieve motor inhibition.

Adult↗

Effects of angiotensin and vasopressin V(1) receptors on water and sodium intake induced by injection of vasopressin into lateral septal area.

The specific arginine(8)-vasopressin (AVP) V(1) receptors antagonist (AAVP) was injected (20, 40 and 80 nmol) into the lateral septal area (LSA) to determine the effects of selective septal V(1) receptor on water and 3% sodium intake in rats. Was also observed the effects of losartan and CGP42112A (select ligands of the AT(1) and AT(2) ANG II receptors, respectively) injected into LSA prior AVP on the same appetites. Twenty-four hours before the experiments, the rats were deprived of water. The volume of drug solution injected was 0.5 microl. Water and sodium intake were measured at 0.25, 0.5, 1.0 and 2.0 h. Injection of AVP reduced the water and sodium ingestion vs. control (0.15 M saline). Pre-treatment with AAVP (40, 80 and 160 nmol) did not alter the decrease in the water ingestion induced by AVP, whereas AAVP abolished the action of AVP-induced sodium intake. Losartan (40, 80 and 160 nmol) did not alter the effect of AVP on water and sodium intake, whereas CGP42112A (20, 40 and 60 nmol) at the first 30 min increased water ingestion. Losartan and CGP42112A together increased the actions of AVP, showing more pronounced effects than when the two antagonists were injected alone. The results showed that AVP inhibited the appetites and these effects were increased by the AAVP. The involvement of angiotensinergic receptors in the effects of AVP is also suggested.

Angiotensin II Type 1 Receptor Blockers↗

Assessment of coronary artery and cardiac function using multidetector CT.

Multidetector CT is able to reconstruct artifact-less cardiac images due to improved temporal resolution. In this article, we review the potential benefits of the cardiac application of multidetector CT in the assessment of coronary artery and cardiac function, such as wall motion and systolic thickening. By applying retrospective ECG-gating, 10 phases throughout 1 cardiac cycle are extracted for functional analysis. Animated movies are generated by paging through these 2D and 3D images in cardiac phase order. Left ventricular end-diastolic volume, end-systolic volume, and ejection fraction can also be generated. Using the data acquired during a single breath hold, coronary artery and cardiac function can be assessed by multidetector CT.

Contrast Media↗

Serial processing of the somesthetic information revealed by different effects of stimulus rate on the somatosensory-evoked potentials and magnetic fields.

In order to evaluate information processing in the somatosensory cortex, the effect of two different stimulus rates was investigated by simultaneously recording somatosensory-evoked potentials (SEPs) and magnetic fields (SEFs) in nine healthy adults. During electric stimulation of the median nerve at the wrist, SEFs were recorded with the helmet-shaped whole-head coverage magnetometer array with 122 first-order planar gradiometers while SEPs were simultaneously recorded from seven scalp positions. Interstimulus intervals (ISIs) of 0.9 s and 4 s were compared. In all subjects, N20 as well as its magnetic counterpart, N20m, was clearly demonstrated over the contralateral somatosensory area. Subsequent deflections around 80-200 ms did not make any clear peak and were smaller than those at 20-60 ms (P30m, P40m, N50m and P60m). After 200 ms, SEFs were negligible, whereas SEPs had larger amplitude than those of shorter latencies, constituting a peak around 250 ms (P250). Both SEF and SEP deflections later than 40 ms were decreased in responses at the shorter ISI; this diminution was most prominent for P250. Therefore, it is concluded that the tangential currents in the somatosensory cortex (area 3b) mainly contribute to responses during the first 200 ms after the stimulus, whereas the radially oriented currents (most likely in the crown of the postcentral gyrus) take over for subsequent information processing.

Adult↗

Adaptations to chronic agonist exposure of mu-opioid receptor-expressing Chinese hamster ovary cells.

To investigate cellular adaptation responses induced by chronic agonist treatment of the mu-opioid receptor, Chinese hamster ovary (CHO) cells were stably transfected with the rat mu-opioid receptor cDNA. Chronic treatment with agonists selective for the mu-opioid receptor, [D-Ala2, N-MePhe4, Gy-ol5]enkephalin (DAMGO), morphine and fentanyl, time- and dose-dependently induced down-regulation of the mu-opioid receptor. The down-regulation was not significantly affected by pretreatment with pertussis toxin, but was completely blocked by treatment with hypertonic sucrose, suggesting that receptor internalization mediated by clathrin-coated vesicles is an essential step in the mu-opioid receptor down-regulation. On the other hand, forskolin-stimulated cyclic AMP formation was increased by chronic DAMGO treatment, which was inhibited by pertussis toxin pretreatment. These results indicate that two adaptation responses induced by chronic agonist treatment of the mu-opioid receptor-expressing CHO cells, down-regulation of the mu-opioid receptor and supersensitization of adenylate cyclase, are mediated by distinct mechanisms.

Animals↗

Nociceptin receptor-mediated Ca2+ channel inhibition and its desensitization in NG108-15 cells.

It has been shown that the membrane of hybrid NG108-15 neuroblastoma x glioma cells contains a high-affinity binding site for nociceptin. In the present study, we first demonstrated the expression of nociceptin receptor mRNA in NG108-15 cells. Application of nociceptin to NG108-15 cells produced a concentration-dependent (EC50 = 29 nM) inhibition of Ca2+ channel currents in a pertussis toxin-sensitive fashion. This nociceptin-induced inhibition of Ca2+ channel currents was prevented in the presence of omega-conotoxin GVIA, a blocker of the N-type Ca2+ channel, and had both voltage-dependent and -independent components. Prolonged application of nociceptin elicited homologous desensitization of the inhibition with a time constant of 5.3 min. These results indicate that the nociceptin receptor is coupled to the N-type Ca2+ channel via pertussis toxin-sensitive G proteins in NG108-15 cells and that this coupling is associated with rapid and homologous desensitization.

Animals↗

N-terminal acetyl group is essential for the inhibitory function of carboxypeptidase Y inhibitor (I(C)).

Carboxypeptidase Y (CPY) inhibitor, I(C), a yeast cytoplasmic inhibitor in which the N-terminal amino acid is acetylated, was expressed in Escherichia coli and produced as an unacetylated form of I(C) (unaI(C)). Circular dichroism and fluorescence measurements showed that unaI(C) and I(C) were structurally identical and produce identical complexes with CPY. However, the K(i) values for unaI(C) for anilidase and peptidase activity of CPY were much larger, by 700- and 60-fold, respectively, than those of I(C). The reactivities of phenylmethylsulfonyl fluoride and p-chloromercuribenzoic acid toward the CPY-unaI(C) complex were considerably higher than those toward the CPY-I(C) complex. Thus, the N-terminal acetyl group of I(C) is essential for achieving a tight interaction with CPY and for its complete inactivation.

Acetylation↗

In vitro growth suppression of vascular smooth muscle cells using adenovirus-mediated gene transfer of a truncated form of fibroblast growth factor receptor.

Vascular smooth muscle cell (VSMC) proliferation associated with arterial injury causes restenosis, which remains to be resolved in cardiovascular and ischemic cerebrovascular disease, especially after balloon angioplasty. Fibroblast growth factor (FGF) is a potent mitogen and a trophic factor for a variety of cells, including VSMCs. We constructed a replication-deficient adenovirus vector, designated AxCA delta FR, coding a truncated form of fibroblast growth factor receptor-1 (FGFR-1) gene lacking the intracellular domain to interrupt receptor-mediated FGF signaling, and examined its effect on the proliferation of primary-cultured rat VSMCs. We transferred the truncated form of the FGFR-1 gene to the VSMCs and confirmed its expression and localization in infected cells by Western blotting and immunofluorescence study. The VSMCs infected with AxCA delta FR degenerated and the proliferation of these cells was suppressed markedly by the infection with this virus in vitro. Our results suggest that the receptor-mediated signal of FGFs has an important role in VSMC proliferation and gene transfer of a truncated form of FGFR using adenoviral vector may be useful for the treatment of the diseases caused by excessive proliferation of VSMCs like restenosis after percutaneous transluminal angioplasty or carotid endoarterectomy.

Adenoviridae↗

Interaction of metallopyrazoliumylporphyrins with calf thymus DNA.

The interaction of transition metal complexes of cationic porphyrins bearing five membered rings, meso-tetrakis(1,2-dimethylpyrazolium-4-yl)porphyrin (MPzP, M=Mn(III), Ni(II), Cu(II) or Zn(II)), with calf thymus DNA (ctDNA) has been studied. Metalloporphyrins NiPzP and CuPzP are intercalated into the 5'GC3' step of ctDNA. MnPzP is bound edge-on at the 5'TA3' step of the minor groove of ctDNA, while ZnPzP is bound face-on at the 5'TA3' step of the major groove of ctDNA. The binding constants of the metalloporphyrins to ctDNA range from 1.05x10(5) to 2.66x10(6) M(-1) and are comparable to those of other reported cationic porphyrins. The binding process of the metallopyrazoliumylporphyrins to ctDNA is endothermic and entropically driven. These results have revealed that the kind of central metal ions of metalloporphyrins influences the binding characteristics of the porphyrin to DNA.

Animals↗

Combined argatroban and edaravone caused additive neuroprotection against 15 min of forebrain ischemia in gerbils.

We investigated whether or not a combination of the selective thrombin inhibitor, argatroban, and the free radical scavenger, edaravone (MCI-186), ameliorates postischemic hypoperfusion and decreases mortality after 15 min of forebrain ischemia in the gerbil. Argatroban or edaravone alone significantly increased postischemic cerebral blood flow and attenuated brain edema after reperfusion. However, only the combination increased the survival ratio (P<0.05 by Mantel-Cox) and protected the damage of neuronal cells. The present study indicates that anticoagulants and free radical scavengers reciprocally function to inhibit the progression of ischemic cell damage and that a combination of these types of drugs will help to improve the outcomes after cerebral ischemia.

Animals↗

Afferent mechanism of cortical myoclonus studied by proprioception-related SEPs.

Proprioception-related somatosensory evoked potentials (SEPs) to passive flexion movement of the middle finger at proximal interphalangeal joint were recorded in 7 patients with myoclonus of cortical origin who demonstrated enlarged electrical SEPs (giant SEPs). In 3 out of the 7 patients, the proprioception-related SEPs were also enlarged. The remaining 4 patients showed giant electrical SEPs without enhancement of proprioception-related SEPs. Long loop electromyographic response was recorded during the resting condition in all of the 3 patients with enlarged proprioception-related SEPs. We have previously reported that proprioception-related SEPs are mainly generated by muscle afferent inputs, though electrical SEPs are thought to reflect mostly cutaneous inputs with some contribution from muscle afferents. Therefore, it is concluded that hyperexcitability of the sensorimotor cortex in cortical myoclonus is modality-specific. Cortical excitability is exaggerated to both cutaneous and deep receptor inputs in some patients, but only to cutaneous input in others.

Adult↗

Modality-specific organization for cutaneous and proprioceptive sense in human primary sensory cortex studied by chronic epicortical recording.

Modality specificity of human primary somatosensory cortex was studied by recording somatosensory evoked potentials (SEPs) from subdural electrodes in a patient with intractable focal motor seizure. A newly developed device was used for selectively activating proprioception. The spatial and temporal distributions of proprioception-related SEPs elicited by brisk passive flexion movement at the proximal interphalangeal (PIP) joint of the middle finger (4 degrees in 25 ms) were quite different from those to cutaneous sense evoked by electric stimulation of the digital nerve at the same site. It was for the first time demonstrated that proprioception-related SEPs following passive finger movement do not originate in area 3b, which was clearly activated by cutaneous stimulation, and that other sites at the sensorimotor cortex such as areas 2, 3a and 4 possibly contribute to the cortical processing of proprioception.

Adult↗

Detection of precore/core-mutant hepatitis B virus genome in patients with acute or fulminant hepatitis without serological markers for recent HBV infection.

To confirm the possibility that some hepatitis B virus (HBV) variants do not induce HB s antigen (HBsAg), anti-HB core antibody (anti-HBc) and anti-HBc IgM in a transient infection, polymerase chain reaction (PCR) was performed in 20 patients with acute hepatitis and 7 patients with fulminant hepatitis. Patients were diagnosed with non-A, non-B hepatitis by serological markers at admission. PCR successfully amplified the precore/core gene in 5 (25%) of the patients with acute hepatitis and 2 (29%) of the patients with fulminant hepatitis. Subsequent sequencing revealed frequent mutations including precore-defects in the precore/core gene.

Acute Disease↗

Doxorubicin, an RNA synthesis inhibitor, prevents vasoconstriction and inhibits aberrant expression of endothelin-1 in the cerebral vasospasm model of the rat.

A vasoconstrictor peptide, endothelin-1 (ET-1), has been identified as one of the causative substances in cerebral vasospasm after subarachnoid hemorrhage. We investigated whether doxorubicin, an RNA synthesis inhibitor, effectively suppresses induction of ET-1 in the rat vasospasm model. Blood was injected around the right femoral artery and the left one was used as an internal control. Seven days later (day 7), diameters of the right femoral arteries narrowed to about 60% and this vasoconstriction was prevented by clinical dose (0.6 mg/kg) or one third of its dose of doxorubicin injected on day 1. Reverse transcriptase-polymerase chain reaction analysis demonstrated that expression of ET-1 mRNA in the vasospastic artery was not detected in doxorubicin-treated rats. It is concluded that doxorubicin effectively inhibits aberrant expression of ET-1 in the vasospasm-destined artery in the rat.

Animals↗