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Biomedical subjects

N Fujiki

Publications and source records attributed to N Fujiki.

At least 55 records · Page 3Linked to original sources

Influence of unilateral deafness on auditory evoked magnetic field.

To investigate the effect of unilateral deafness on central auditory mechanisms, we examined patients with unilateral deafness of various durations. Auditory evoked magnetic fields (AEF) were recorded using a whole-head neuromagnetometer. In patients who had unilateral deafness for more than 3 weeks, the average N100m latency in the ipsilateral hemisphere did not differ from that in the contralateral hemisphere. In addition, in some patients with congenital or early onset deafness, the equivalent current dipole (ECD) moment was larger in the ipsilateral hemisphere than in the contralateral hemisphere. These findings suggest that unilateral deafness may cause reorganization of the central auditory pathway. They also suggest that central auditory pathway in adults has some plasticity, though not as much as in childhood.

Adult↗

Influence of speech-coding strategy on cortical activity in cochlear implant users: a positron emission tomographic study.

The effects of a speech-coding strategy of cochlear implant (CI) on cortical activity were evaluated using positron emission tomography. The CIs used in the present study were those of a 22-channel system using the Multipeak speech-coding strategy (MPEAK) and the spectral peak strategy (SPEAK). On comparing the 2 groups, it was found that the speech-tracking performance was significantly higher in the SPEAK group than in the MPEAK group. Regional cerebral blood flow (rCBF) was measured during the silent resting, noise stimulus and speech stimulus periods. The increase in rCBF was localized mainly in the primary auditory area during the noise stimulus period. The increase in rCBF in the auditory association area during the speech stimulus period was stronger in the SPEAK group than in the MPEAK group. This finding suggests that the SPEAK strategy activates more speech processing neuronal networks in the auditory association area than the MPEAK strategy.

Acoustic Stimulation↗

Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450 reductase coexpressed in insect cells using baculovirus.

Human fetal CYP3A7 and human NADPH-cytochrome P450 reductase were coexpressed in insect cells, TN-5, infected with a recombinant baculovirus carrying both cDNAs. The expression of reductase in TN-5 cells was shown to be sufficient for the CYP3A7 dependent 16 alpha-hydroxylation of dehydroepiandrosterone. However, the extra addition of cytochrome b5 and phospholipid was necessary to obtain a maximal activity of CYP3A7 catalyzing the reaction. CYP3A7 expressed in TN-5 cells was capable of metabolizing testosterone, cortisol and dehydroepiandrosterone 3-sulfate as well as dehydroepiandrosterone. The apparent Vmax for 6 beta-hydroxylations of testosterone was similar to that obtained for 6 beta-hydroxylation of cortisol (2.9 versus 2.5 nmol/nmolP450/min). In contrast, the apparent Vmax for 16 alpha-hydroxylation of dehydroepiandrosterone and its 3-sulfate were 20 and 2 times greater than those observed for steroid 6 beta-hydroxylations, respectively (67.5 and 5.8 versus 2.5-2.9 nmol/nmol P450/min). On the other hand, the apparent K(m) for 6 beta-hydroxylations of testosterone and cortisol were greater than those for 16 alpha-hydroxylations (120 and 860 versus 46-58 microM). Thus, CYP3A7 was active for steroid 6 beta-hydroxylations and 16 alpha-hydroxylations, but there were greater differences in Vmax/K(m) ratios between these reactions.

Animals↗

Characteristics of DPOAE audiogram in tinnitus patients.

To investigate cochlear activity in tinnitus, the DPOAE (distortion product otoacoustic emission) audiograms (DP-gram) of tinnitus patients were measured. Nine tinnitus patients (15 ears) with normal hearing and 55 tinnitus patients (75 ears) with hearing impairment were included in this study. Significant decreases in DPOAE amplitude over a limited frequency range were observed in 93.3% of the normal hearing tinnitus group and in 96% of the hearing-impaired tinnitus group. The averaged DP-gram of the normal hearing tinnitus group was significantly different from that of the normal subject (repeated-measures ANOVA, P < 0.01). These results imply that tinnitus may be evaluated objectively by DPOAE.

Adult↗

Efficacy of transmeatal low power laser irradiation on tinnitus: a preliminary report.

Thirty-eight patients suffering from tinnitus resistant to several medical therapies for more than 6 months were treated by low power laser irradiation. A 40 mW laser with a wavelength of 830 nm was irradiated via their external auditory meatus toward the cochlea for 9 min once a week, 10 times or more. Patients were asked to score their symptoms on a 5 point scale before and after the treatment for a subjective evaluation of the effect. The results were estimated by the change of the loudness and duration of tinnitus, and the degree of annoyance due to tinnitus. Although only 26% of the patients had improved duration, loudness and degree of annoyance were relieved in up to 58 and 55%, respectively, without major complication. Laser therapy seemed to be worth trying on patients with intractable tinnitus.

Adult↗

The effect of intravenous lidocaine injection on hearing thresholds.

The effect of intravenous injection of lidocaine on hearing thresholds was studied in normal subjects. Continuous and intermittent tones at 1, 4 and 8 kHz were used as stimuli and the threshold change with lidocaine injection was measured using a self-recording audiometer (Békésy audiometer). Both increases and decreases in the threshold were observed. The former occurred more frequently than the latter. In cases of a threshold increase, lidocaine injection exhibited a frequency specific effect; the higher the frequency, the more often the threshold was increased by lidocaine injection. There was no significant difference in threshold changes between continuous and intermittent tones. The present results suggest that lidocaine may act on the inner ear hair cells.

Adult↗

Sound-induced activation of auditory cortices in cochlear implant users with post- and prelingual deafness demonstrated by positron emission tomography.

Changes of regional cerebral blood flow (rCBF) in the auditory cortices induced by sound stimulation were examined in nine postlingually and five prelingually deaf cochlear implant (CI) users by 15O-labeled water Positron Emission Tomography, and the results were compared with those of eight normal volunteers. Speech stimulation caused significantly greater rCBF increase compared with noise stimulation in the auditory association area in normal and postlingually deaf subjects. In prelingually deaf subjects, however, speech activation of the auditory association area was much less than that found in either of the other two groups. Neuronal networks for speech sound processing in the auditory association area in postlingually deaf individuals are thought be similar to those in normal subjects, while those in prelingually deaf patients who received CI after the speech acquisition period may not develop completely.

Acoustic Stimulation↗

Tinnitus remission by lidocaine demonstrated by auditory-evoked magnetoencephalogram. A preliminary report.

An auditory-evoked magnetic field was recorded before and during tinnitus remission induced by an intravenous lidocaine injection. One and 4 kHz probe tones were presented monaurally in four tinnitus patients, and the responses were recorded using a 122-channel magnetometer. Three normal volunteers were also examined as controls. In tinnitus patients, the N100 m peak became sharper, while there was no marked change except for slight reduction in amplitude in normal subjects. Tinnitus remission by lidocaine may be related to attenuation of a masking-like effect of tinnitus on the sound-evoked responses.

Aged↗

[Herpes viruses--herpes simplex virus, varicella-zoster virus, EB virus, cytomegalovirus].

Herpes simplex encephalitis is the commonest viral encephalitis among individuals, and the mortality has been markedly decreased by the use of vidarabine and acyclovir. Early diagnoses and immediate treatment are essential for favorable prognoses. Neuro-imagings, such as MRI and SPECT, and PCR technique for detection of HSV-DNA in CSF, are useful for early diagnoses, without requiring brain biopsy. Varicella and herpes zoster viruses are complicated, only rarely, with neurological manifestations, such as meningoencephalitis, myelitis, or peripheral neuropathy. Acyclovir is mostly effective in these cases. Neurological complications of Epstein-Barr virus infections are variable, including meningitis, cerebellar ataxia, cranial neuropathy, and Guillain-Barré syndrome. Their prognoses are generally good. Cytomegalovirus encephalitis is one of the common complications in AIDS patients. Its clinical diagnosis is difficult and the prognosis is considered to be poor.

AIDS-Related Opportunistic Infections↗

[Bioethics on DNA diagnosis].

Through the applications of medical genetic knowledges, early diagnosis, neonatal screening, prenatal diagnosis followed by selective abortion, carrier detection and genetic counselling has become more effective. Since 1960, we performed over 3,500 cases with its followup study in Kyoto, Aichi, and Fukui, according to guidelines emphasizing non-directive counselling, informed consent, autonomous decision-making and confidentiality. New bioethical problems using DNA diagnosis has been arisen on justification of presymptomatic diagnosis of trinucleotide repeat diseases, carrier detection of thalassemia as well as possibility for genetic discrimination, susceptibility and testing. We should provide knowledges of science and technology with bioethical considerations, in order to protect the human genome and right as well as biosphere, as shown in the activities of IBC, UNESCO and MURS.

Bioethics↗

Ganglioside GM1 binds to the Trk protein and regulates receptor function.

Several lines of evidence have suggested that ganglioside GM1 stimulates neuronal sprouting and enhances the action of nerve growth factor (NGF), but its precise mechanism is yet to be elucidated. We report here that GM1 directly and tightly associates with Trk, the high-affinity tyrosine kinase-type receptor for NGF, and strongly enhances neurite outgrowth and neurofilament expression in rat PC12 cells elicited by a low dose of NGF that alone is insufficient to induce neuronal differentiation. The potentiation of NGF activity by GM1 appears to involve tyrosine-autophosphorylation of Trk, which contains intrinsic tyrosine kinase activity that has been localized to the cytoplasmic domain. In the presence of GM1 in culture medium, there is a > 3-fold increase in NGF-induced autophosphorylation of Trk as compared with NGF alone. We also found that GM1 could directly enhance NGF-activated autophosphorylation of immunoprecipitated Trk in vitro. Monosialoganglioside GM1, but not polysialogangliosides, is tightly associated with immunoprecipitated Trk. Furthermore, such tight association of GM1 with Trk appears to be specific, since a similar association was not observed with other growth factor receptors, such as low-affinity NGF receptor (p75NGR) and epidermal growth factor receptor (EGFR). Thus, these results strongly suggest that GM1 functions as a specific endogenous activator of NGF receptor function, and these enhanced effects appear to be due, at least in part, to tight association of GM1 with Trk.

Animals↗

1-Methyl-4-phenylpyridinum kills differentiated PC12 cells with a concomitant change in protein phosphorylation.

1-Methyl-4-phenylpyridinum (MPP+), a selective neurotoxin, destroys the dopaminergic nigrostriatal pathway and results in a parkinsonian syndrome. Exposure of differentiated PC12 cells with nerve growth factor for 5 days to MPP+ (100 microM) for 4 h induced DNA fragmentation which is typical for the programmed cell death. MPP+ treatment (100 microM) concomitantly stimulates S6 kinase activity and resultant phosphorylation of S6 protein of 40S ribosomal subunits in the cells. Cycloheximide treatment prevents the MPP(+)-induced DNA fragmentation and enhancement of the phosphorylation of S6 protein. The present data demonstrate that neurotoxin, MPP+, kills differentiated PC12 cells by the apparent involvement of apoptotic process. Furthermore, the data strongly suggest that a change in protein phosphorylation might be involved in the signal transduction of MPP+ neurotoxicity and/or the protection from its toxicity.

1-Methyl-4-phenylpyridinium↗

High prevalence of neutralizing activity to Helicobacter pylori cytotoxin in serum of gastric-carcinoma patients.

Helicobacter pylori infection is causally related to chronic type-B gastritis, and may also be associated with an increased risk of gastric carcinoma. Vacuolating cytotoxin, which is an 87-kDa protein secreted by H. pylori, induces eukaryotic cell vacuolation in vitro. To determine whether there is an association between H. pylori vacuolating cytotoxin and gastric carcinoma, we investigated several characteristics of H. pylori infection, i.e., isolation of H. pylori from gastric biopsies, antibodies specific for H. pylori, detection of neutralizing activity to vacuolating cytotoxin in serum and immunological detection of cytotoxin by serum. Out of 6 sera from gastric-carcinoma patients, all showed the neutralizing activity to vacuolating cytotoxin, in contrast to 3 of 5 sera from peptic-ulcer patients. Normal individuals showed no neutralizing activity. All sera possessing the neutralizing activity recognized an 87-kDa protein band by Western blot analysis. Our results confirmed that cytotoxin-neutralizing activity in human sera was associated with immunodetection of an 87-kDa protein. To further evaluate neutralizing activity in serum from gastric-carcinoma patients, we retrospectively analyzed frozen-stocked serum samples from 22 gastric-carcinoma patients. Sera from 21 of these 22 patients exhibited neutralizing activity. These sera were also checked for antibodies to H. pylori, using an ELISA; 16 sera showed positive results. Our results indicate that detection of cytotoxin-neutralizing activity in sera is strongly associated with H. pylori infection, and probably with gastric carcinoma, and is also of interest in the diagnosis of H. pylori infection.

Adult↗

Influence of ammonia solution on gastric mucosa and acetic acid induced ulcer in rats.

Aqueous ammonia in concentrations of 0.02 or 0.1% was continuously administered to rats to study its effect on the gastric mucosa histologically and cell kinetically. Furthermore, acetic acid ulcer, which is a model of chronic gastric ulcer, was experimentally induced in the stomachs of rats to assess the influence of 0.02% ammonia on the course of this ulcer. Male Donryu rats were divided into three groups given 0.02% ammonia, 0.1% ammonia or tap water. On several occasions (1, 3 and 5 days and 1, 4, 8, 12 and 24 weeks from the beginning of the experiment), the gastric mucosa in the fundic gland region and the antrum was examined histologically, and from the viewpoint of cell kinetics. The assessment in the 8th and 24th weeks employed the double labeling technique with bromodeoxyuridine and 3H-thymidine. The assessment on the other occasions used the flash labeling technique with bromodeoxyuridine. Both the 0.02% and 0.1% ammonia treatment groups showed a decrease in PAS-positive mucus and an enhanced cell cycling in the early stage of the experiment. After long periods of treatment, these groups showed a reduction in the gland height, a recovery in PAS-positive mucus and a suppression of cell cycle, suggesting direct toxicity of ammonia on the gastric mucosa. Although glandular atrophy was observed in these animals, infiltration of inflammatory cells was not observed. Thus, the relationship between ammonia and gastritis remained obscure. No ulcer developed in any group. Subsequently, we experimentally induced Ul-IV or Ul-V acetic acid ulcers in the stomachs of rats, according to the method of Okabe et al. (1971, 1972). These rats were divided into two groups given 0.02% ammonia or tap water. In the 4th and 8th weeks of the experiment, the stomachs of these rats were examined histologically and from the viewpoint of cell kinetics. The 0.02% ammonia treatment group showed a significant increase in the ulcer index (long diameter x short diameter; mm2) in the 4th and 8th weeks. This group also showed suppressed cell cycling of the regenerative epithelium and fibroblasts in the ulcer margin, suggesting direct toxicity of ammonia. Thus, healing of peptic ulcer was delayed by continuous administration of 0.02% ammonia.

Acetates↗

Early progression stage of malignancy as revealed by immunohistochemical demonstration of DNA instability; I, Human gastric adenomas.

The degree of DNA-instability as revealed by the immunohistochemical staining with monoclonal anti-single-stranded DNA antibody after acid hydrolysis (DNA-instability test) was used as the marker of malignancy. This was applied to human gastric regenerative epithelium in chronic peptic ulcer (5 cases), adenoma (35 cases), and well differentiated tubular adenocarcinoma (5 cases). Proliferative activity was evaluated by proliferating cell nuclear antigen (PCNA) immunohistochemistry, and the quantitative analyses of the mean number and mean area of silver-stained nucleolar organizer regions (AgNORs) per one nucleus were performed for all these cases. All cancers and adenomas were positively stained by the DNA-instability test diffusely, indicating the malignant character of the latter from the view point of DNA-instability, in contrast to the negative stainability of all regenerative epithelium. The percent number of PCNA-positive cells and mean number and mean area of AgNORs tended to be larger in adenoma and cancer than in regenerative epithelium, although the differences were not usually statistically significant. Supporting the malignant character of adenoma, single cell necroses and abnormal mitoses were almost always present in the lesion. In conclusion, all adenoma lesions were regarded as malignant in nature, namely, in-situ carcinoma, existing at an early stage of progression of malignancy.

3,3'-Diaminobenzidine↗