Biomedical subjects
G Ichikawa
Publications and source records attributed to G Ichikawa.
[Involvement of adhesion molecules in experimental otitis media in rats--an in vitro evaluation].
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[Auditory screening of newborn and young infants].
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In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2.
The SUMO-1 has been identified as a protein that is highly similar to ubiquitin and shown to conjugate to RanGAP1, PML, Sp200 and I kappa B alpha. The conjugation steps are thought to be similar to those of ubiquitination; and human Ubc9, which is homologous to the E2 enzyme for the ubiquitin conjugation step, was identified and shown to be necessary for the conjugation of SUMO-1 to its target protein. Other essential enzymes involved in this modification, however, remain to be clarified. Here we cloned human Sua1 (SUMO-1 activating enzyme) and hUba2, which are human homologs of yeast Saccharomyces cerevisiae Aos1 and Uba2, respectively. The recombinant proteins, Sua1p and hUba2p, formed a complex. In this complex, hUba2 bound SUMO-1 and this complex had the activity of the SUMO-1 activating enzyme. Furthermore, in an in vitro system, RanGAP1 was modified by SUMO-1 in the presence of Sua1p/Uba2p and hUbc9p, showing that the modification of SUMO-1 could be catalyzed by two enzyme steps, although ubiquitination usually requires three enzyme steps.
Equivalent dipoles for middle latency auditory evoked potentials using the dipole tracing method.
During the last decade, new dipole localization techniques have prompted the search for the neuronal generators of evoked potentials. In this study we have reported the equivalent dipoles for the middle latency auditory evoked potentials (MAEPs) by the mean of these localization using the dipole tracing method. MAEPs that were recorded from 19 normal human subjects attending to random binaural clicks were analyzed using the dipole tracing method. Equivalent dipoles (EDs) were found, using both the single-dipole model and the two-dipole model, for components occurring from 0 to 60 ms after stimulus onset. The dipole analysis accounted for the real head geometry based on three-dimensional digitization of measured head shape, and the results were experimentally correlated to those of magnetic resonance imaging to increase the accuracy of ED localization. For components in the first 15 ms latency (P0 and Na), neither model provided EDs with reproducible high dipolality. Na was particularly difficult to analyze, as this component was often contaminated by myogenic potentials. The results provided by the two-dipole model for the Pa component (20-30 ms) showed three variations: in three subjects, one ED was located in each supratemporal cortex; in another three, one ED was located in the right temporal cortex and the other in the midbrain; and in the remaining thirteen subjects, both EDs were in the midbrain. The single-dipole model and the two-dipole model both found EDs in the midbrain for Nb. Further study is necessary to determine the cause or causes of the variety in our results. And it is also necessary to try the study using unilateral ear stimulation with/without contralateral masking noise for understanding the mechanism of the binaural interaction.
Solitary polypoid xanthoma in the larynx.
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A clinical study on the magnetic stimulation of the facial nerve.
OBJECTIVES: A clinical study on the usefulness of magnetic stimulation of the facial nerve, with special attention paid to the selection of the coil shape and stimulation procedures. STUDY DESIGN: The subjects consisted of 55 patients with Bell's palsy, 1 patient with a cerebellopontine angle (CPA) tumor, 1 patient with multiple sclerosis (MS), and 30 normal subjects. Three types of coils were used in this study; a 90-mm large single coil, a 40-mm small single coil, and a 20-mm small double coil. METHODS: The compound muscle action potentials (CMAPs) and long latency response were evoked by transcranial magnetic stimulation (TMS) with a 90-mm large single coil. The 40-mm small single coil was used to test blink reflex by aiming it at the supraorbital nerve as the target site. The subcutaneous activation of the infra-auricular facial nerve was performed with the 20-mm double coil. RESULTS: The reproducible CMAP and long latency responses were obtained from normal subjects with TMS. However, responses were observed only in patients with relatively mild Bell's palsy. The magnetic stimulation-evoked responses reflected the brainstem function in the patients with a CPA tumor and MS. CONCLUSION: Although magnetic stimulation remains inferior to conventional electric stimulation in some sense and requires further study, this method is potentially useful because it can stimulate the facial nerve continuously from the cortex to the periphery and can effectively evoke responses reflecting the brainstem function.
Leiomyoma with atypical cells (atypical leiomyoma) in the larynx.
AIMS: To report and confirm the identity of laryngeal leiomyoma with many atypical cells, which has not been described previously. CASE DETAILS: A 53-year-old man was found to have a polypoid tumour in the larynx. The tumour was excised and the patient has shown no evidence of recurrence over a 5-year period. The tumour tissue comprised intersecting fascicles of spindle-shaped tumour cells with blunt-ended nuclei. Many of the tumour cells showed marked atypia. Mitotic activity in the tumour cells was low, and no atypical mitoses were found. Immunohistochemically, the tumour cells were positive for smooth muscle actin and desmin. p53 overexpression was identified in many tumour cells; the p53 labelling index of the tumour cells was 45%. DNA from tumour cells showed loss of heterozygosity on chromosomes 3p, 5q, 8p, 9p, 10q, 17p and 18q. We diagnosed this case as leiomyoma with atypical cells (atypical leiomyoma) based on the clinical course and pathological and genetic findings. CONCLUSION: This is the first report of atypical leiomyoma in the larynx. The clinical course and pathological findings indicate that although laryngeal atypical leiomyoma contains numerous atypical cells, it is a benign neoplasm.
[Effect of adrenaline on vagus nerve reflexes].
INTRODUCTION: Dizziness or syncope may occur during treatment of nasal disease. These symptoms are considered imputable to the vagovagal reflex, which is partly involved in neurogenic syncope. In response to trigeminal nerve stimulation, the vagus nerve causes a sudden fall in heart rate and blood pressure. Elevation in blood adrenaline level during pain or tension was noted, and its effects on vagovagal reflexes were studied. MATERIALS AND METHODS: Ten cats were used in the experiment. The vagus nerve was exposed on the right side of the neck by making an incision in the trachea, and a platinum electrode was attached to the vagus nerve on nerve's distal side. The head was tilted a 30 degree angle. The cats were divided into control and adrenaline-treated groups, and changes in cerebral blood flow, heart rate, and arterial pressure were compared between the two groups after electric stimulation of the vagus nerve. Cerebral blood flow was measured by the hydrogen clearance method. 1) Control group The vagus nerve was electrically stimulated for 1 minute. 2) Adrenaline-treated group The vagus nerve was electrically stimulated for 1 minute following 30 seconds of intravenous administration of adrenaline. RESULTS: Cerebral blood flow was significantly decreased in both the control and adrenaline-treated groups after electric stimulation, but the decrease was significantly greater in the latter group at all sites of measurement. Whereas heart rate and arterial pressure were significantly decreased in the control group, these variables in the adrenaline-treated group showed no significant change despite the greater decrease in cerebral blood flow. DISCUSSION: Heart rate, blood pressure, and cerebral blood flow were all significantly decreased after electric stimulation of the vagus nerve. These changes were considered owing to a fall in blood pressure due to vasodilation resulting from bradycardia and a relative decrease in sympathetic nervous tension resulting from electric stimulation. On the other hand, in the adrenaline-treated group, neither heart rate nor blood pressure showed any significant change, but cerebral blood flow was significantly decreased at all sites of measurement despite an adrenaline load. This contradictory results may be accounted for by the powerful beta 2-activity of adrenaline. The greater decrease in cerebral blood flow in the adrenaline-treated than in the control group can be attributed to decreased peripheral vascular resistance by its beta 2-activity. In the field of otorhinolaryngology the trigeminal region is often involved in the treatment of nasal disorders so that vagovagal reflexes are often encountered. The results of this study counsels caution in the treatment involving the trigeminal region.
Quantitative analysis of ERD during odorous sensation.
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[Late phase II clinical study of RP56976 (docetaxel) in patients with advanced/recurrent head and neck cancer].
A late phase II clinical study of RP56976 (docetaxel), a new anticancer agent for advanced/recurrent head and neck cancer, was conducted in 29 institutions all over Japan as a multi-institutional cooperative study. Docetaxel was administered by 1 to 2-hour intravenous infusion at a dose of 60 mg/m2 every 3 to 4 weeks. Of 63 patients eligible in this study, 59 were judged as complete cases. Complete response (CR) was observed in 1 patient, partial response (PR) in 13, no change (NC) in 25, and progressive disease (PD) in 20, for an overall response rate of 22.2% (14/63, 95% CI: 12.7-34.5%) in eligible cases, and 23.7% (14/59, 95% CI: 13.6-36.6%) in complete cases. Previously treated patients showed a 17.9% (10/56) response rate, whereas treatment--naive patients showed a 57.1% (4/7) response rate. Among 46 patients who received prior chemotherapy, one CR and 7 PR were observed with a 17.4% response rate. Major hematological toxicities were leucopenia in 95.1% (> or = grade 3, 59.7%) and neutropenia in 90.3% (> or = grade 3, 79.0%). Other severe toxicities (> or = grade 3) included anorexia in 9.7% (6 cases), diarrhea in 3.2% (2 cases), dyspnea in 3.2% (2 cases), and fatigue in 3.2% (2 cases). One patient had a grade 3 interstitial pneumonia; however, symptoms were resolved by the administration of corticosteroids. During this study, one patient died due to multiple organ failure (MOF) caused by disseminated intravascular coagulation (DIC), and this case was reported as a therapy-related death. Based on these results, docetaxel is an active agent for treatment of head and neck cancer.
[The role and expression of CD27/CD70 in tonsil].
We studied the expression and function of CD27 and CD70, which are reported to play an important role in the T-B cell interaction in tonsillar lymphocytes of patients with chronic tonsillitis. In comparison of CD27 and CD70 in peripheral lymphocytes of each patients, no significant difference was found. Furthermore, CD27 and CD70 in T-B cell interaction and antibody production in the tonsil was studied. Our findings was confirmed that CD27 and CD70 are involved in interactions between T/T, T/B and B/B cells. A comparative study of CD27- CD4+ cells and CD70+ CD4 cells, so-called memory cells in the T cell subset, was made in tonsillar lymphocytes and peripheral lymphocytes. No significant difference was found in the presence of CD27+ CD4+ cells, but the CD27- CD4+ cells increased in tonsillar lymphocytes. This suggests recurrent antigenic stimulation and the presence of memory cells in tonsillar lymphocytes. Localization of CD27 and CD70 in tonsillar tissue was also investigate.
Effect of erythromycin on otitis media with effusion in experimental rat model.
To understand the mechanism of erythromycin (EM) on otitis media with effusion, we examined its effects on leukocyte accumulation and expression of adhesion molecules L-selectin and Mac-1, using a rat experimental model Administration of EM inhibited leukocyte (neutrophil) accumulation in the middle ear cavity after LPS stimulation. Moreover, EM downregulated L-selectin expression and inhibited interleukin (IL)-8-induced upregulation of Mac-1 on peripheral blood neutrophils. These finding suggests that EM may improve otitis media with effusion by inhibiting neutrophil accumulation in the middle ear cavity through modulating the expression of adhesion molecules L-selectin and Mac-1 on peripheral blood neutrophils.
[Changes in adhesion molecule expressions in neutrophils caused by new macrolide administration].
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Electrically evoked potentials of the auditory pathway.
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[Evaluation of methods of macrolide antibiotic administration in experimental otitis media of rats].
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Reactive arthritis induced by pseudomonas aeruginosa.
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[Evaluation of the effect of erythromycin on otitis media with effusion in experimental rat models].
The clinical efficacy of erythromycin (EM) therapy has been demonstrated in otitis media with effusion (OME). However, the mechanism of action of this drug is not clear. In this study, to elucidate the possible mechanism of action of EM, we examined the effect of the drug on the expression of neutrophil adhesion molecules such as L-selectin and Mac-1. Furthermore, we examined production of leukotrienes B4, C4 (LTB4, C4) and prostaglandin E2 (PGE2) in rat OME induced by injection of a lipopolysaccharide. EM down-regulated L-selectin expression, and inhibited up regulation of Mac-1 expression on peripheral blood neutrophils. Also it inhibited the accumulation of inflammatory cells such as neutrophils and macrophages in middle ear effusion (MEE). Furthermore, EM suppressed the exudation of plasma protein and the production of LTB4, C4 and PGE2, in OME. These results suggest that EM may exert the antiinflammatory effect on MEE through suppression of leukocyte accumulation the middle ear by affecting the expression of adhesion molecules on leukocytes and inhibiting the production of arachidonic acid metabolitis.