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Biomedical subjects

A Ikeda

Publications and source records attributed to A Ikeda.

At least 91 records · Page 5Linked to original sources

Detection of antibody to sialyl-i, a possible antigen in patients with Meniere's disease.

An autoimmune hypothesis for the etiology of Meniere's disease has been proposed. In this study, we focused on gangliosides as potential antigens for autoantibodies in Meniere's disease patients. In an attempt to investigate ganglioside antigens which respond to the serum of patients with Meniere's disease, we analyzed gangliosides of human acoustic neurinomas, and used them as antigens to broadly explore gangliosides that react to serum. All the acoustic neurinoma samples used in the present study showed a similar ganglioside profile on TLC (thin-layer chromatography). For the microscale ganglioside analysis, a newly developed TLC blotting/secondary ion mass spectrometry (SIMS) system together with TLC immunostaining method was employed. Most of the ganglioside bands could be analyzed, and they were identified as GM3, GM2, SPG, GM1a, GD3, S-i (sialyl-i ganglioside) and GD1a. GD1a was the predominant ganglioside and many neolactoseries gangliosides were recognized by immunological analysis. Next, the immune reactivity of serum samples, from patients with Meniere's disease, with the acoustic neurinoma gangliosides was studied by TLC immunostaining. The result showed that five of 11 patients with Meniere's disease and one of eight normal subjects reacted with a specific band, which was identified as S-i by the TLC blotting/SIMS system. The findings of the present study indicate that S-i ganglioside is an autoantigen and possibly involved in the pathogenesis of Meniere's disease.

Autoantibodies↗

p300/CBP-dependent and -independent transcriptional interference between NF-kappaB RelA and p53.

p53 and NF-kappaB RelA are activated by various genotoxic agents and mutually suppress each other's ability to activate transcription, most likely through competition for transcriptional coactivators such as CBP or p300. However, we found that the inhibition by RelA of p53 transcriptional activity is not completely restored by CBP/p300 overexpression and that a p53 mutant can not suppress RelA activity despite of its ability to bind CBP/p300. In the present study, we further present evidence that these two transcriptional factors directly interact both in vivo and in vitro. These results therefore indicate that the cross transcriptional interference between p53 and RelA is partly caused by the direct interaction between these two transcription factors which is mediated by their dimerization/tetramerization domains and results in inhibition of each other's transcriptional activity. Finally, cells derived from RelA knockout mice showed enhanced p53 transcriptional activity, suggesting that this cross transcriptional interference is physiologically important in cellular response to genotoxic stress.

Animals↗

The Epstein-Barr virus latent membrane protein 2A PY motif recruits WW domain-containing ubiquitin-protein ligases.

Latent membrane protein 2A (LMP2A) is expressed in latent Epstein-Barr virus (EBV) infection. LMP2A functions to downregulate B-cell signal transduction and viral reactivation from latency in EBV-immortalized B cells in vitro, and acts to provide B cells with both a survival and developmental signal in vivo. Identification of proteins associated with LMP2A is important for elucidation of the mechanism that LMP2A employs to regulate B-cell signal transduction and EBV latency. LMP2A is constitutively tyrosine phosphorylated and is associated with protein tyrosine kinases such as Lyn and Syk when specific LMP2A tyrosines are phosphorylated. The amino-terminal domain of LMP2A includes multiple proline-rich regions, which may provide binding sites for proteins containing SH3 or WW domains. In this study, we demonstrate that four cellular proteins bind specifically to two PPPPY (PY) motifs present within the LMP2A amino-terminal domain. Protein microsequence analysis determined that three of these proteins were AIP4, WWP2/AIP2, and Nedd4. All of these proteins are members of the Nedd4-like ubiquitin-protein ligases family and have conserved domains including the C2, WW, and ubiquitin-protein ligase domain. The mutation of both PY motifs completely abolished binding activity of these proteins to LMP2A and the interaction of AIP4 and WWP2 with LMP2A was confirmed in cell lines expressing LMP2A, WWP2, and AIP4. Furthermore, a reduction in the level of Lyn and the rapid turnover of LMP2A and Lyn were observed in LMP2A-expressing cells. These findings suggest that LMP2A recruits Nedd4-like ubiquitin-protein ligases and B-cell signal transduction molecules, resulting in the degradation of LMP2A and Lyn by a ubiquitin-dependent mechanism. This provides a new means by which LMP2A may modulate B-cell signal transduction.

Amino Acid Motifs↗

Primary somatosensory cortex is actively involved in pain processing in human.

We recorded somatosensory evoked magnetic fields (SEFs) by a whole head magnetometer to elucidate cortical receptive areas involved in pain processing, focusing on the primary somatosensory cortex (SI), following painful CO(2) laser stimulation of the dorsum of the left hand in 12 healthy human subjects. In seven subjects, three spatially segregated cortical areas (contralateral SI and bilateral second (SII) somatosensory cortices) were simultaneously activated at around 210 ms after the stimulus, suggesting parallel processing of pain information in SI and SII. Equivalent current dipole (ECD) in SI pointed anteriorly in three subjects whereas posteriorly in the remaining four. We also recorded SEFs following electric stimulation of the left median nerve at wrist in three subjects. ECD of CO(2) laser stimulation was located medial-superior to that of electric stimulation in all three subjects. In addition, by direct recording of somatosensory evoked potentials (SEPs) from peri-Rolandic cortex by subdural electrodes in an epilepsy patient, we identified a response to the laser stimulation over the contralateral SI with the peak latency of 220 ms. Its distribution was similar to, but slightly wider than, that of P25 of electric SEPs. Taken together, it is postulated that the pain impulse is received in the crown of the postcentral gyrus in human.

Adult↗

Retinal degeneration but not obesity is observed in null mutants of the tubby-like protein 1 gene.

The tub gene is a member of a small, well conserved neuronal gene family of unknown function. Mutations within this gene lead to early-onset blindness and deafness, as well as late-onset obesity and insulin resistance. To test the hypothesis that mutations within other members of this gene family would lead to similar phenotypes as observed in tubby mice, and hence have similar functional properties, we have generated null mutants of the tubby-like protein ( Tulp ) 1 gene by homologous recombination. Similarly to tubby mice, Tulp1 (-/-)mice exhibit an early-onset retinal degeneration with a progressive, rapid loss of photoreceptors, further supporting the notion that previously identified mutations within the human TULP1 gene are indeed causative of retinitis pigmentosa. However, in contrast to tubby mice, Tulp1 (-/-)mice exhibited normal hearing ability and, surprisingly, normal body weight despite the fact that both TUB and TULP1 are expressed in the same neurons within the hypothalamus in areas known to be involved in feeding behavior and energy homeo stasis. However, TUB and TULP1 show a distinctly different staining pattern in the nucleus of these neurons, perhaps explaining the difference in body weight between the Tulp1 (-/-)and tubby mutant mice.

Animals↗

Implication of sensorimotor integration in the generation of periodic dystonic myoclonus in subacute sclerosing panencephalitis (SSPE).

To clarify the mechanism of periodic dystonic myoclonus in subacute sclerosing panencephalitis (SSPE), a 22-year-old patient with a clinical diagnosis of SSPE was electrophysiologically investigated. Involuntary movements consisted of generalized dystonic posturing which occurred quasiperiodically once every 4 to 8 seconds. Effects of sensory stimuli and voluntary movements were studied by means of polygraphic recording of surface electromyogram (EMG), scalp electroencephalogram (EEG), and magnetoencephalogram (MEG). EEG showed quasi-periodic, generalized, transient complexes synchronous to each dystonic myoclonus, which were preceded by a slow negative EEG shift at the parietal region by approximately 5 seconds. Neither external stimuli nor self-paced movements alone influenced the periodicity of dystonic myoclonus or EEG complexes. In the reaction time task, however, the external stimuli given as an imperative cue to execute a motor task elicited dystonic myoclonus and generalized EEG complexes only if they were presented in the latter segment of the interval between the two successive EEG complexes while the slow negative EEG shift appeared. These findings suggest that EEG complexes and periodic movements spontaneously occur when cortical excitability reaches a certain critical level, but both phenomena are elicited even before if the sensory stimuli as an imperative signal requiring motor execution are presented. This finding most likely implies involvement of the sensorimotor integration mechanism in these periodic phenomena.

Adult↗

Additive effects of prednisolone and beclomethasone dipropionate in patients with stable chronic obstructive pulmonary disease.

It remains unclear whether inhaled corticosteroids can produce the maximum benefits of corticosteroids in patients with chronic obstructive pulmonary disease (COPD). To assess the additive effects of 30 mg/day prednisolone to high-dose, inhaled beclomethasone dipropionate (BDP), we conducted a randomised double-blind, placebo-controlled cross-over trial. The study population consisted of 21 men with stable COPD. The mean age of the patients was 69.1 +/- 6.8 years, and FEV(1)was 0.86 +/- 0.28 l. Seventeen out of the 21 patients (81%) were considered susceptible to steroids in a previous trial (FEV(1)increased at least 15% from baseline after receiving 14 days of 30 mg/day prednisolone). All of the patients had been on 1600 microg/day BDP for more than 3 months. Spirometry was performed before the entry, and at the end of 3-week placebo and prednisolone periods. The peak expiratory flow (PEF), symptoms, and Guyatt's Chronic Respiratory Disease Questionnaire (CRQ) as a disease specific health-related quality of life over the last seven days of each period were also evaluated. Although a marginal increase in PEF was found during the prednisolone period, no significant differences in FEV(1), FVC, symptoms or CRQ scores were observed between the two treatment periods. We conclude that the therapeutic effects of steroid therapy may be achieved by the long-term use of high-dose, inhaled corticosteroid in some patients with stable COPD.

Administration, Inhalation↗

Desynchronization and synchronization of central 20-Hz rhythms associated with voluntary muscle relaxation: a magnetoencephalographic study.

To clarify the cortical mechanisms involved in motor inhibition, modulation of cortical rhythms around 20 Hz during voluntary muscle relaxation was compared to that during muscle contraction in ten normal volunteers, using a whole head type neuromagnetometer. Each subject relaxed or contracted the right forearm muscles, from which electromyograms were recorded. After bandpass filtering magnetoencephalographic signals into frequency bands of 6-10, 10-14, 14-18, 18-22, 22-26, and 26-30 Hz, the signals of each frequency band were rectified and averaged with respect to the onset of motor trial. The relaxation task showed movement-related 20-Hz desynchronization over bilateral central areas beginning a few seconds before the termination of muscle contraction. Twenty-hertz desynchronization was present also for the contraction task at the same location within each subject. The two tasks had a positive correlation among subjects in both the percent decrease (r2=0.76, P<0.01) and the peak time (r2=0.61, P<0.05) for the contralateral 20-Hz desynchronization. After the muscle relaxation, desynchronization was followed by conspicuous movement-related synchronization of the 20-Hz passband in the contralateral central areas, which was significantly larger than that after the contraction (P<0.001). The results suggest that the voluntary muscle relaxation involves the modulation of central rhythms starting a few seconds before the actual event, and the 20-Hz desynchronization has a similar temporal property in the muscle relaxation and contraction. The 20-Hz synchronization in the contralateral central area after the muscle relaxation may be associated with the temporally arrayed termination of the ongoing muscle contraction.

Adult↗

Different activation of presupplementary motor area, supplementary motor area proper, and primary sensorimotor area, depending on the movement repetition rate in humans.

In order to clarify the functional role of the supplementary motor area (SMA) and its rostral part (pre-SMA) in relation to the rate of repetitive finger movements, we recorded movement-related cortical potentials (MRCPs) directly from the surface of the mesial frontal lobe by using subdural electrode grids implanted in four patients with intractable partial epilepsy. Two subregions in the SMA were identified based on the anatomical location and the different response to cortical stimulation. In three of the four subjects, we also recorded MRCPs from the surface of the lateral convexity covering the primary sensorimotor areas (SI-MI), which were defined by cortical stimulation and SEP recording. The subjects extended the middle finger or opposed the thumb against other fingers of the same hand at a self-paced rate of 0.2 Hz (slow) and 2 Hz (rapid), each in separate sessions. As a result, pre-and postmovement potentials were clearly seen at the SI-MI in both slow- and rapid-rate movements. By contrast, in the SMA, especially in the pre-SMA, premovement potentials were not seen and postmovement potentials were seldom seen in the rapid rate movement. In the slow-rate condition, pre- and postmovement potentials were clearly seen in both the pre-SMA and the SMA proper. In conclusion, the SMA, especially the pre-SMA, is less activated electrophysiologically in the rapid-rate movements, while the SI-MI remains active regardless of the movement rate.

Adolescent↗

Human presupplementary motor area is active before voluntary movement: subdural recording of Bereitschaftspotential from medial frontal cortex.

Bereitschaftspotential (BP) was recorded directly from the right supplementary motor area proper (SMA-proper) and its rostral part by chronically implanted subdural electrodes in three patients with intractable focal motor seizure. Cortical electrical stimulation of the SMA-proper revealed the somatotopy as previously reported, and the supplementary negative motor area (SNMA) was identified just anterior to the SMA-proper in two of three cases. In patient 1, eight kinds of simple movements, i.e., left and right middle finger extension, left arm abduction, left and right foot dorsiflexion, left knee extension, tongue protrusion and saccadic eye movement, were studied to record BP. In patient 2, three kinds of movements, i.e., left and right middle finger extension and left foot dorsiflexion, were adopted as movement tasks. In patient 3, four kinds of movements, i.e., left and right middle finger extension and left and right foot dorsiflexion, were adopted. In the SMA-proper, somatotopically distributed BP preceding movements were observed in all three patients. In the SNMA and its rostrally adjacent areas, "SNMA-plus" BPs were generated invariably regardless of the sites of movement. There was no significant difference in the onset time of BPs between the SMA-proper and the SNMA-plus. The present findings suggest that the SNMA-plus is more consistently involved in the preparation for various simple movements than the SMA-proper. This functionally independent region (SNMA-plus) just rostral to the SMA-proper most likely corresponds to a part of the presupplementary motor area which was originally defined in nonhuman primates. Since a part of this area elicited the inhibition of various movements by cortical stimulation, and since it generated BPs regardless of the sites of movement, it may play a higher role in the movement preparatory process than the SMA-proper.

Adult↗

Adult mesoblastic nephroma with ciliated epithelium. A case report.

A case of renal pelvic tumors occurring in a 44-year-old man is reported. There were two polypoid renal pelvic tumors which consisted of glandular and stromal components. Some glands in the tumors had ciliated epithelium and were quite similar to the epididymal tubules. Other glands in the tumors resembled the collecting duct or the mesonephric remnant seen in female genitalia. Immunohistochemistry and electron microscopy revealed smooth muscle differentiation of the stromal cells of these tumors. Some psammoma bodies were seen in the glands of the tumors. We diagnosed these tumors as adult mesoblastic nephroma (MN). The patient has been followed up for 14 months, showing no evidence of recurrence. Differentiation of the tumors from angiomyolipoma, leiomyoma, and nephrogenic adenofibroma is discussed. Adult renal tumors that consist of epithelial and stromal components have been reported under various names. They constitute clinicopathologically different entities originating from pediatric MN. We suggest that these tumors should be termed "adult MN".

Adult↗

Electrocorticogram-electromyogram coherence during isometric contraction of hand muscle in human.

OBJECTIVE: To clarify how the primary sensorimotor and supplementary motor areas are involved in the generation of the rhythmicity of electromyogram (EMG) activity during continuous muscle contraction. METHOD: We analyzed the coherence between subdurally recorded cortical electroencephalograms (EEG) and EMGs of the contralateral wrist extensor muscle during continuous isometric contraction in 8 patients with medically intractable epilepsy. RESULTS: In all subjects, a significant coherence between the primary motor area (M1) and EMG was observed at the peak frequency of 15+/-3 Hz (means+/-SD). In the primary somatosensory area (S1) of 7 subjects and the supplementary motor area proper (SMA proper) of 4 subjects, significant coherence with EMG was observed at 12+/-5 and 15+/-4 Hz, respectively. The time lags revealed by cross-correlogram were 10+/-3, 7+/-1 and 22+/-8 ms in the M1, S1 and SMA proper, respectively, with the EMG lagging in all areas. CONCLUSION: These findings suggest that the rhythmic activity in the SMA proper, as well as in the S1 and M1, is related to the generation of the rhythmicity of EMG activity.

Electromyography↗

Purification and characterization of a ferredoxin from Haloarcula japonica strain TR-1.

A ferredoxin (Fd) was purified from the extremely halophilic archaeon, Haloarcula japonica strain TR-1, to electrophoretic homogeneity. The apparent molecular weight (Mr) of the Fd was estimated to be 24,000 on SDS-polyacrylamide gel electrophoresis. The amino acid composition analysis revealed that the Fd composed of a number of acidic amino acids (uncorrected for amides). The N-terminal amino acid sequence (30 residues) was determined to be: PTVEYLNYEVVDDNGWDMYDDDVFAEASDM. The iron content was 3.42+/-0.04 mol/mol-Fd on the basis of the apparent Mr value. The absorption and ESR spectra of the Fd showed similarity to those of Fds from plant and Halobacterium halobium. These results led us to conclude that the H. japonica Fd contained a [2Fe-2S] cluster.

Amino Acid Sequence↗

Stages of disease severity and factors that affect the health status of patients with chronic obstructive pulmonary disease.

BACKGROUND: We hypothesized that the factors which may influence health status would differ in patients at different disease stages of chronic obstructive pulmonary disease (COPD). The present study investigated how impairments in health status were distributed in male patients at each disease stage according to the British Thoracic Society (BTS) guidelines, and analysed the contribution of the clinical indices, the dyspnoea rating and the psychological status to the health status of patients at the three disease stages of COPD. METHODS: A total of 218 consecutive male patients with stable COPD were recruited from our outpatient clinic. All eligible patients completed pulmonary function testing, progressive cycle ergometry, a dyspnoea rating [Medical Research Council (MRC) dyspnoea scale], an assessment of their anxiety and depression [Hospital Anxiety and Depression Scale (HADS)], and an assessment of their health status [the St. George's Respiratory Questionnaire (SGRQ)]. The patients were categorized into three groups: mild COPD with a FEV1 at 60-79% of the predicted value, moderate COPD at 40-59% of the predicted value, and severe COPD at below 40% of the predicted value. RESULTS: Twenty-five patients (11%) had mild COPD, 72 patients (33%) had moderate COPD, and 121 patients (56%) had severe COPD. Significant differences were observed for the total score and for three components on the SGRQ among patients at the three stages (one-way ANOVA, P<0.05). The scores for the total SGRQ and for the activity component were significantly higher for patients with severe COPD than for patients with moderate COPD [Fisher's least-significant-difference (LSD) method, P<0.05], and also significantly higher for moderate COPD patients than for mild COPD patients. The maximal oxygen uptake (VO2 max) correlated significantly with the total SGRQ score in the mild patients [Pearson's correlation coefficient (r) = -0.67], but not in the moderate or severe patients. The MRC dyspnoea scale had strong correlations with the SGRQ in all patient groups (r = 0.53 to approximately 0.70). Anxiety and depression on the HADS showed moderate correlations with the SGRQ score in the mild and severe patients (r = 0.51 to approximately 0.57). Multiple regression analysis showed that in patients with mild COPD, the MRC and VO2 max accounted for the total score on the SGRQ. Anxiety on the HADS plus the MRC scale accounted for the total score on the SGRQ in patients with moderate COPD, and anxiety on the HADS, the MRC scale and the FEV1 significantly influenced the SGRQ severe COPD patients. CONCLUSIONS: The disease staging proposed by the BTS guidelines can separate patients with COPD according to impairments in their health status. Furthermore, the factors that influence health status differed in patients at the three disease stages. Our findings support the boundaries used in disease staging and some recommendations from the BTS guidelines.

Aged↗

Movement-related change of electrocorticographic activity in human supplementary motor area proper.

We investigated movement-related change in the cortical EEG signal by simultaneous recording from the primary sensorimotor area (S1-M1) and the supplementary motor area proper (SMA proper) in four patients with intractable partial epilepsy. By the use of temporal spectral evolution (TSE) analysis, the change in background cortical activity in relation to self-paced finger/wrist extension was compared among the SMA proper, S1 and M1. All three areas showed a decrease in the amount of activity for the frequency range between 10 and 40 Hz before the onset of movement [event-related desynchronization (ERD)]. The SMA proper showed earlier onset of ERD for 18-22 Hz activity (-3.4 +/- 0.5 s, mean +/- standard deviation) than M1 (-1.7 +/- 0.7 s) and S1 (-1.4 +/- 0.5 s). The degree of ERD in S1 was greatest for 10-14 Hz and that in M1 for 18-22 Hz, whereas in the SMA proper ERD was observed throughout the frequency bands from 10 to 40 Hz. Neither the degree nor the onset time of ERD in the SMA proper was lateralized to either the ipsilateral or the contralateral side with respect to the movement. A transient increase in activity after movement [event-related synchronization (ERS)] was observed in all three areas. In the SMA proper, two out of four subjects showed ERS for frequency bands below 40 Hz with both ipsilateral and contralateral movements. By contrast, in S1 and M1, ERS was recorded for frequency bands between 20 and 90 Hz, and was predominantly associated with the contralateral movement. The present study suggests that the background cortical activity in the SMA proper has a specific temporal pattern with respect to self-paced movement, and that the SMA proper is involved in motor preparation earlier than S1-M1 in a bilaterally organized manner.

Adult↗

Role of primary sensorimotor cortices in generating inhibitory motor response in humans.

To clarify the mechanism by which inhibitory motor responses such as cortical negative myoclonus are generated in humans, three patients with medically intractable partial epilepsy (two with frontal lobe epilepsy and one with parietal lobe epilepsy) were studied by means of direct cortical stimulation with a single electric pulse through subdural electrodes. All underwent chronic long-term video/EEG monitoring, cortical mapping by 50 Hz electric cortical stimulation and recording of cortical somatosensory evoked potentials with chronically implanted subdural grid electrodes (3 mm in diameter and centre-to-centre distance of 1 cm) to map both epileptogenic and functional zones. After these clinical evaluations, cortical stimulation by single electric pulse (0.3 ms duration, 1 Hz) was carried out through pairs of subdural electrodes located at the primary sensorimotor area (MI-SI), pre-supplementary motor area (pre-SMA) and lateral negative motor area (lateral NMA), while surface EMG was recorded from the muscles of the contralateral hand. The results showed that (i) in all subjects, single pulse stimulation of MI-SI elicited a motor evoked potential (MEP) followed by a silent period (SP) in the contralateral distal hand muscles, the latter lasting 300 ms after the stimulus. The duration of SP was proportional to the size of the preceding MEP. In one subject, SP without any preceding MEP was elicited, and, in another subject, there was a short SP immediately before MEP in the contralateral thenar muscle. (ii) Following the stimulation of either pre-SMA or lateral NMA, no SP was observed. It is concluded that the inhibitory mechanism within the MI-SI, but probably not in the non-primary motor areas, either closely linked to or completely independent of excitation, most likely plays an important role in eliciting brief negative motor phenomena such as cortical negative myoclonus or SP.

Adult↗

Abnormal premovement gating of somatosensory input in writer's cramp.

One characteristic of focal dystonia is the sensory trick, by which sensory input to a certain area of the body can reduce abnormal contractions in muscles nearby. This suggests that adjusting the link between sensory input and movement allows motor commands to be issued more effectively from the brain. To explore this sensorimotor link, we studied the attenuation (gating) of somatosensory evoked potentials (SEPs) before and during hand movements in patients with writer's cramp. For premovement gating, 10 patients and 11 age-matched normal subjects were given a warning sound followed 1s later by an electric stimulus to the right median nerve at the wrist. The latter served both as a reaction signal to start a finger extension task and as the input to evoke SEPs over the scalp. Because reaction times always exceeded 70 ms, short-latency SEPs thus obtained were unaffected by the afferents activated by the movement. The amplitudes of frontal N30 components were significantly decreased over the frontal leads compared with SEPs elicited at rest (P: < 0.002) in the normal group, whereas significant gating was found not for N30 but for frontal P22 (P: = 0. 002) in the patient group. For midmovement gating studies, SEPs to the right median nerve stimulation were recorded in 16 patients and 12 age-matched normal subjects at rest, and during active and passive finger extension-flexion movements. In contrast to the premovement SEPs, the frontal N30 was equally gated during active and passive movements both in the patient (P: < or = 0.002) and the normal group (P: < or = 0.003). These findings indicate that in writer's cramp the sensitivity of sensory input channels from the hand is wrongly set by the central command to move. Perhaps the sensory trick, by supplying additional input not usually present during unobstructed movement, is a manoeuvre to correct this imbalance. Dystonia may result not only from abnormalities in the central motor command but also from disturbed central processing of sensory input.

Adult↗