Naoki Satoh

Endogenous components of event-related potential appearing during NREM stage 1 and REM sleep in man

Information processing in the brain during sleep was studied by analyzing the evoked cortical response to auditory stimulations presented in the odd-ball paradigm. Eight subjects were examined in different sleep stages. The subjects could provide the correct behavioral response to the auditory stimulation by pressing a key button in the light part of stage 1 of NREM sleep, just succeeding to the waking state, but none of the subjects could give the correct behavioral response in the other sleep stages. In the deep part of stage 1 of NREM sleep and REM sleep, a cortical potential corresponding to P300, the endogenous component of the event-related potential (ERP) recorded in the waking state, was recorded in 6 of the 8 subjects in spite of the absence of the behavioral response. In stages 2, 3 and 4 of NREM sleep, emergence of this endogenous component of ERP could not be confirmed. The present findings provide electrophysiological evidence indicating that selective information processing corresponding to sensory discrimination of auditory stimuli is actively performed in stage 1 of NREM sleep and REM sleep.

Electrophysiological evidence suggesting that sensory stimuli of unknown origin induce spontaneous K-complexes

The present study was performed to determine whether or not spontaneous K-complexes are induced by sensory stimuli. In the first part of the present study, sound stimuli were prescribed during sleep in 7 healthy, young, adult subjects. EEG segments in stage 2 sleep were averaged separately according to the presence or absence of an evoked K-complex appearing after each stimulus. The sound stimulus induced N100 and P200 components in averaged EEGs regardless of K-complex appearance. The appearance of N100 and P200 components was considered to be an indicator of the presence of sensory stimuli. In the second part of the present study, EEG segments in stage 2 sleep containing an evoked K-complex or spontaneous K-complex were separately averaged with respect to the peak of N300, one of the main components constituting the K-complex. Small negative and positive components were found just before the main components of spontaneous K-complexes in averaged EEGs. These two components were judged to correspond to N100 and P200 components induced by the sound stimulus, as they appeared just before the main components of the spontaneous K-complex with almost the same lag time between the two components, or between each of the two components and the main components of K-complex, as in the case of N100 and P200 appearing just before the evoked K-complex. The present findings suggest that the spontaneous K-complex is not a spontaneous phenomenon, but that it is induced by sensory stimuli, probably of extracerebral origin.

Suppression of Experimental Autoimmune Uveoretinitis by Dietary Calorie Restriction

To investigate the inhibitory effect of dietary calorie restriction on experimental autoimmune uveoretinitis (EAU) in rats, and its mechanism. Lewis rats were maintained on a 50% calorie-restricted diet for 2 months or 6 months. The control group was maintained on a 90% ad libitum intake for the same length of time. Experimental autoimmune uveoretinitis was elicited in both groups by immunization with an inter-photoreceptor retinoid-binding protein or its peptide. Rats in both groups were examined clinically, histopathologically, and immunologically. The severity of EAU was milder in the restricted diet group than in the control group. In EAU rats, production of interferon-gamma (IFN-gamma) in eyes and of IFN-gamma and tumor necrosis factor-alpha in draining lymph node cells was significantly lower in the restricted diet group than in the control group. Our results indicate that a calorie-restricted diet suppresses the development of EAU. The suppressed Th1-dependent immunological response is one of the reasons for the mildness of EAU in the calorie-restricted diet group of rats.

A negative component on event related potential recorded in the drowsy state

Abstract Behavior of event related potential (ERP) components in the drowsy state was examined in nine subjects using oddball paradigm. A component with peak latency of 300 msec, N300, was superimposed on ERP in the drowsy state. N300 appeared also in stage 1 of NREM sleep and closely resembled vertex sharp wave evoked by sound stimulation in both scalp distribution and peak latency. It was suggested that N300 recorded in the drowsy state and vertex sharp wave recorded in stage 1 of NREM sleep are generated by the identical synchronizing mechanism in the brain.

Analysis of uveitogenic sites in phosducin molecule.

PURPOSE Phosducin, a retinal photoreceptor protein, induces experimental autoimmune uveitis (EAU). In this study, we attempted to determine the numbers of uveitogenic sites in phosducin using synthetic peptides. METHODS Antigen peptides were synthesized according to the amino acid sequence of the rat-derived phosducin with a peptide-synthesizer and purified by reversed-phase HPLC. First, 13 peptides covering the entire sequence of phosducin were synthesized, and each was injected into the hind footpad of Lewis rats for immunization, and induction of EAU was examined clinically and histologically. Next, peptides that appeared to contain sequences of a uveitogenic site were newly synthesized and examined clinically and immunologically. RESULTS Of the 13 peptides used in the first immunization, 7 induced inflammation. Similar to other EAU antigens, clinical changes began with fibrin deposition in the anterior segment and posterior synechia, followed by posterior chamber hypopyon. Histologically, inflammation was observed mainly in the outer segment of photoreceptor cells and outer nuclear layer, and serous retinal detachment was found in cases of severe inflammation. Infiltration of inflammatory cells in the pineal gland was also observed. In experiments designed to further specify the uveitogenic sites, the presence of inflammation-inducing sequences was inferred for amino acid sequences 1-20, 23-37, 79-91, 127-142 and 198-212. The rats immunized with these peptides also exhibited high value on lymphocyte proliferation assay. CONCLUSION Phosducin has 5 uveitogenic sites. Among others, one of them has potent and others weak uveitogenicity.

Two cases of malignant lymphoma complicated by hemophagocytosis resembling orbital cellulitis

Two patients with malignant lymphoma complicated by hemophagocytic syndrome (HPS) are reported. Their clinical signs at onset were similar to those of orbital cellulitis. Lymphoma complicated by hemophagocytosis is called lymphoma-associated hemophagocytic syndrome (LAHS) and its prognosis is reported to be very poor. As far as we know, this is the first report in the ophthalmological field. In our patients, we suspected that the lesions occurred from the orbit or skin of this area. The first patient was a 22-year-old man and the second patient a 16-year-old girl. The diagnosis was very difficult at the onset of disease. They died within 6 months after the first ophthalmological examination. When orbital cellulitis is suspected and antibiotic therapy is ineffective, we should suspect HPS and should examine serum ferritin, which is a good marker of HPS. Early biopsy and consultation with a hematologist are very important.

Uveitopathogenic sites in recoverin.

Purpose. This study was carried out in order to determine the most potent and novel uveitopathogenic sites of recoverin using synthetic peptides. Methods. Several synthetic peptides containing the recoverin sequence plus adjuvants were injected into Lewis rats, and the uveitopathogenic sequence was defined, clinically, histologically, and immunologically. Results. Peptides containing of amino acids 57–85 and 136–167 induced severe EAU, and the lowest doses to induce EAU were 20 µg and 10 µg, respectively. Lymphocyte proliferative reactions were also positive for peptides 57–85 and 136–167. The core sequences within the uveitopathogenic site were 65–79 and 153–164. Peptides of amino acids 65–79 within 57–85 and 149–167 within 136–167 were the smallest in the recoverin sequence, respectively, that could induce severe EAU. Conclusion. We found recoverin has some novel potent uveitopathogenic sites, 149–167. These findings of the uveitopathogenic sites in recoverin may lead to improved understanding of the pathogenesis of uveitis and the means to design specific treatment.

Fas Expression and Apoptosis in Rats with Experimental Autoimmune Uveoretinitis

PURPOSE To evaluate Fas expression on CD4 and CD8 T cells in each organ at each stage of experimental autoimmune uveoretinitis (EAU) and apoptotic cells within EAU eyes. METHODS Rats were immunized with the uveitopathogenic peptide derived from interphotoreceptor retinoid-binding protein. Flow cytometry was performed in ocular cells, draining lymph nodes cells and splenic cells of EAU rats to investigate Fas expression by CD4 and CD8 lymphocytes. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining of apoptotic nuclei was performed on sections of EAU eyes. RESULTS Fas expression by both ocular and splenic CD4 and CD8 lymphocytes was significantly higher than in lymph nodes at each stage. In EAU eyes, there was a relatively large population of lymphocytes with Fas expression (19.6-25.6% of CD4 and 33.2-53.4% of CD8). Apoptotic cells were more prominent in the EAU eyes with established disease than in those with early or resolving disease. CONCLUSIONS These results suggest that the relatively large population of lymphocytes with Fas expression in EAU eyes reflects the activation of lymphocytes in these eyes, and that the increase in apoptotic inflammatory cells at the peak of established disease may participate in the spontaneous disappearance of EAU.

Some sensory stimuli generate spontaneous K-complexes

Abstract The present study was performed in order to determine whether spontaneous K‐complex are induced by sensory stimuli. Electroencephalogram (EEG) segments in stage 2 sleep containing an evoked K‐complex or spontaneous K‐complex were separately averaged with respect to the peak of N300, one of the main components constituting the K‐complex. Small negative and positive components were found immediately before the main components of spontaneous K‐complex in averaged EEG. These two components were judged to correspond to N100 and P200 induced by the sound stimulus. The present findings suggest that the spontaneous K‐complex is not a spontaneous phenomenon but that it is induced by sensory stimuli.

Decreased Serum Melatonin Levels in Rats with Experimental Autoimmune Uveitis/Pinealitis and in Patients with Uveitis

The authors measured serum levels of the pineal hormone melatonin to investigate the possibility of pineal dysfunction in both rats with experimental autoimmune uveitis/pinealitis (EAU/EAP) and uveitis patients. The serum melatonin concentrations of EAU/EAP rats were measured by radioimmunoassay over a 24-hour (h) period, and in uveitis patients at night (0200 h). Melatonin concentrations were assayed in six patients with Behçets disease, four with Vogt-Koyanagi-Harada (VKH) disease, three with sarcoidosis, three with Kirisawa-type uveitis, and one with tubulointerstitial nephritis and uveitis syndrome. Nocturnal serum melatonin levels were significantly lower in Lewis rats with EAU/EAP (2200 h: 33.6±20.4 pg/ml, 0200 h: 43.2±13.9 pg/ml) than in the controls (2200 h: 117.5±25.3 pg/ml, 0200 h: 132.4±20.2 pg/ml) (p>0.01, at 2200 h and 0200 h). Melatonin levels were significantly lower in VKH disease (20.7±10.5 pg/ml) (p>0.01) and Behçets disease (42.1±42.5 pg/ml) (p>0.05) than in the controls (79.4±36.7 pg/ml). These results suggest that there is a decrease in pineal gland function due to pinealitis in EAU/EAP rats. The markedly decreased nocturnal serum melatonin levels may also be related to the presence of retinal uveitogenic antigens in uveitis patients.