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Biomedical subjects

T Okuma

Publications and source records attributed to T Okuma.

At least 19 recordsLinked to original sources
PubMed1999

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.

Amino Acid Sequence↗
PubMed1999

Indications for three-field dissection followed by esophagectomy for advanced carcinoma of the thoracic esophagus.

OBJECTIVE: The aim of this study was to evaluate the indication for 3-field lymphadenectomy (3-field dissection) followed by esophagectomy for locally advanced carcinoma of the thoracic esophagus in the presence of lymph node metastasis. METHODS: From January 1983 to December 1995, 86 patients with thoracic esophageal carcinoma invading muscularis propria or adventitia underwent radical subtotal esophagectomy after preoperative chemotherapy. Forty-six of the 86 patients underwent a 2-field dissection (mediastinal and abdominal nodes, group A), and 40 patients underwent a 3-field dissection (bilateral cervical, mediastinal, and abdominal nodes, group B). Survival curves were compared between the 2 groups after stratification according to the degree of lymph node involvement (number of positive nodes and involvement of intrathoracic or intrathoracic recurrent nerve chain nodes). Potential prognostic factors of these 86 patients were evaluated by means of Cox regression analysis. RESULTS: There were no significant differences in age, sex ratio, depth of tumor invasion, pTNM classification, or number of positive nodes between the 2 groups. Among patients with positive intrathoracic nodes, the 5-year survival of group B (42%) was significantly longer than that of group A (13%, generalized Wilcoxon test P =.02). Among patients with 1 to 4 positive nodes, the 5-year survival of group B (54%) was significantly higher than that of group A (22%, P =.01). Multivariate analysis revealed the number of positive nodes, age, and pT4 stage to be significant predictors of survival in patients with thoracic esophageal carcinoma. CONCLUSIONS: Three-field dissection for advanced carcinoma of the thoracic esophagus is effective in patients with 1 to 4 positive nodes.

Aged↗
PubMed1999

Laterality of delta waves during all-night sleep.

In order to clarify the functional asymmetry of the brain function during sleep, period-amplitude analysis of delta electroencephalogram activity was performed on polysomnograms in 12 right-handed healthy males. Electroencephalograms were recorded from disc electrodes placed at C3, C4, O1 and O2 (10-20 electrode system), using A1 +A2 for reference. Although there were no significant differences in delta counts between O1 and O2, delta counts of C3 were significantly larger than those of C4. These results suggest that there exists distinct laterality in the number of delta waves in the central region, reflecting the functional asymmetry of the brain during sleep.

Adult↗
PubMed1999

The prognostic significance of cell cycle markers in esophageal cancer after neoadjuvant chemotherapy.

Proliferating cell nuclear antigen (PCNA), p27 and cyclin A were analyzed by immunohistochemistry in 89 patients (untreated control n = 40, neoadjuvant chemotherapy n = 49) with esophageal cancer invading the submucosal lesion. The mitotic index (MI) was calculated as the percentage of mitotic cells. In control subjects, the mean PCNA, p27, cyclin A and MI were, respectively, 60.4%, 18.0%, 19.9% and 1.7%; in the chemotherapy group, these values were 46.8%, 15.1%, 18.0% and 1.2% respectively. Neoadjuvant chemotherapy decreased PCNA and the MI significantly. As prognostic indicators, PCNA and the MI were significant in control subjects and p27 and cyclin A were significant in the chemotherapy group. Using multivariate analysis, p27 was a prognostic factor in both groups and cyclin A was prognostic only in the chemotherapy group. Although PCNA and the MI were useful growth and prognostic markers in untreated control subjects, their significance was lost after neoadjuvant chemotherapy. p27 and cyclin A were determined to be significant markers in the neoadjuvant chemotherapy group, especially p27, which was independent in both groups.

Aged↗
PubMed1999

Association between delta waves during sleep and negative symptoms in schizophrenia. Pharmaco-eeg studies by using structurally different hypnotics.

We examined the effects of benzodiazepine (BZD) hypnotics and zopiclone (ZPC), a nonbenzodiazepine hypnotic, on sleep and psychiatric symptoms in schizophrenia, as well as the clinical correlates of these variables. Seven male schizophrenic patients chronically taking neuroleptics together with BZD were studied. We replaced BZD with ZPC and performed polysomnography (PSG) and Brief Psychiatric Rating Scale (BRPS) scoring before and after an 8-week ZPC treatment. The replacement of BZD with ZPC increased the mean amplitude of high-amplitude low-frequency delta waves on the frontal derivation recognized by period-amplitude analysis, and it decreased the BPRS negative-symptom score. Under the BZD treatment, the negative-symptom score correlated inversely with the mean amplitude of high-amplitude low-frequency delta waves. This correlation was weak and not significant under the ZPC treatment. Therefore, delta waves during sleep have a close correlation to negative symptoms in schizophrenia, and such a correlation could be influenced by hypnotics. Although these are preliminary findings, it was suggested that, compared with BZD, ZPC might be a beneficial hypnotic in regard to both sleep and negative symptoms of chronic schizophrenic patients.

Adult↗
PubMed1998

A polysomnographic study of sleep patterns in normal humans with low- or high-anxiety personality traits.

To clarify the effects of anxiety-related personality traits on sleep patterns, polysomnographic examinations (PSG) were performed over 4 consecutive nights on normal humans who tested within the low- or high-anxiety ranges. The subjects consisted of two groups of six male university students who scored either less than 45 points (low-anxiety group) or more than 55 points (high-anxiety group) on the Spielberger's State Trait Anxiety Inventory. Compared to the levels of sleep change in the high-anxiety group, the low-anxiety group exhibited a greater change in REM sleep and stage 2 sleep. The REM sleep in the low-anxiety group was shorter on the first and second nights compared to the third and fourth nights, and the stage 2 sleep was longer on the first night than on the remaining three nights. Thus, the low-anxiety group showed a first-night effect followed by partial recovery on the second night, while the high-anxiety group exhibited no obvious first-night effect. These results suggest that there is a difference in sleep patterns, assessed by consecutive PSG, between those with low- and high-anxiety traits, and that anxiety-related personality traits attenuate the occurrence of the first-night effect, reflecting a lower adaptability to a novel environment.

Adult↗
PubMed1998

A history of investigation on the mood stabilizing effect of carbamazepine in Japan.

A history of investigation on the antimanic and prophylactic effects of carbamazepine in Japan is described. Following the initial open trials in the early 1970s in which the antimanic and prophylactic effects of carbamazepine were indicated for the first time in the world, the mood stabilizing effect was confirmed by the double blind studies which were performed with a multi-institutional cooperation in Japan in the late 1970s. During the course of the double blind trials, the problem of different therapeutic dosages of psychotropic drugs between Japan and Western countries emerged; that is, the doses of chlorpromazine and lithium carbonate, which were used as the control drugs to carbamazepine in the two double-blind group-comparison studies in Japan, were both much lower than the dosage used in most of the Western countries. The low dosage of control drugs made the evaluation of the results of the double blind studies performed in Japan difficult, and caused a delay of publication in the Western journals of the results. Whether the difference is due to biological factors or to psychosocial and cultural factors is an important problem in psychopharmacology and should be investigated further.

Anticonvulsants↗
PubMed1997

Relationship between the effects of a hypnotic drug, zopiclone, on polysomnography and on daytime EEGs.

The correlation between the effects of zopiclone (ZPC), a nonbenzodiazepine hypnotic drug, on sleep polysomnograms and on daytime EEGs was examined in 12 healthy adult male volunteers. Sleep polysomnograms were recorded after a single oral administration of ZPC 10 mg or placebo according to the double-blind crossover method. Daytime EEGs were recorded after the administration of ZPC, 7.5 mg, or placebo in the same manner, and recorded for 3 min with closed eyes at rest. Then, square roots of the absolute power (amplitude) of the delta-, theta-, alpha-, and beta-activities were calculated from the power spectrum obtained by the fast Fourier transform method. As a result, ZPC decreased the percentage of stage 1 sleep in total sleep time, while it increased the percentage of stage 2, total sleep time, and time of slow wave sleep in the first and second sleep cycles (SWS 1 and 2). Changes in SWS 1 and 2 correlated positively with the amplitude changes in daytime resting delta-activity. This indicates that the increase of SWS due to ZPC could be related to the change of delta-activity in the daytime resting EEG.

Adult↗
PubMed1997

Zopiclone versus diazepam effects on EEG power maps in healthy volunteers.

EEG effects of zopiclone (7.5 mg), a cyclopyrrolone derivative with hypnotic action, were compared with effects of diazepam (10 mg). Multichannel EEG recordings, double-blind crossover trials with placebo, and oral single doses were used in healthy volunteers. Vigilance-controlled EEG before and after zopiclone (and placebo), and before and after diazepam (and placebo) were analyzed into FFT power spectra. Effects were assessed as placebo-referred pre-post-medication power differences in four frequency bands. Overall statistics showed significant (P < 0.007) global differences between medication effects in the delta frequency band (0.5-3.5 Hz). After zopiclone, fronto-central delta increased bilaterally, whereas after diazepam delta decreased over centro-parietal to right temporo-occipital regions. These spatially different brain electric effects show that different neuronal populations must have become active in response to zopiclone and diazepam.

Adult↗
PubMed1997

[Study of diazepam with quantitative EEGs taken with eyes opened and topography].

Diazepam is a representative drug of benzodiazepines. The subjects were 9 right-handed healthy male volunteers 21 25 years of age. Double blind crossover trials with placebo control were conducted in a random sequence at an interval of 1 week. Diazepam 10 mg and placebo were administered as single oral doses. Three-minute EEGs were recorded with subjects' eyes opened before and 2 h after drug administration. One-minute out of the 3-minute EEGs was analyzed with FFT, and the absolute amplitude power (microV) was calculated. These results were subjected to Student's t-test (double difference) and displayed with topographic maps (t statistic significance probability mapping). Diazepam decreased the delta absolute amplitude power over left-parietal dominance, theta absolute amplitude power diffusely and alpha absolute amplitude power over parietal region dominance. It also increased the beta absolute amplitude power over left-antero-temporal region dominance. The EEG profiles taken with subjects' eyes open were different from those of diazepam with eyes-closed vigilance controlled concerning the degree of decrease of delta and beta activities and region of the effect on alpha activity.

Adult↗
PubMed1996

Zopiclone pharmacodynamics: by monitoring event-related potentials and psychometric scores.

To investigate the pharmacological effects of zopiclone in the central nervous system, we monitored event-related potentials (ERPs, N100 and P300), the reaction time and the scores for subjective mental and emotional state (by using the Polarity Profile Questionnaire, PPQ) on 10 healthy right-handed male volunteers between 21 and 32 years old. Subjects were randomly allocated to receive a single oral administration of zopiclone 7.5 mg or placebo at the first-session, and the drug was crossed over at the second session 1 week later. ERPs, the reaction time and the psychometric scores were monitored at pre-drug, and 1, 3 and 5 hours after drug administration. In the zopiclone group, the reaction time was prolonged significantly at 1 hour after drug administration, the amplitudes of the ERPs significantly decreased at 1 and 3 hours after, and the PPQ scores showed significant changes. Maximum effects on the psychometric scores appeared later than those on ERPs and reaction time. Zopiclone decreased the arousal level and sensory sensitivity, and induced sedation through changes in subjective mental and emotional states.

Administration, Oral↗
PubMed1995

A quantitative sleep-EEG study on the effects of benzodiazepine and zopiclone in schizophrenic patients.

Polysomnographic examinations (PSG) were performed on 6 male schizophrenic outpatients who were being treated with benzodiazepine (BZD) hypnotics in combination with neuroleptics and 6 healthy male volunteers. In schizophrenic subjects, zopiclone (ZPC), 15 mg/day, was substituted for the BZD hypnotics, and PSGs were recorded again during ZPC therapy. All-night sleep stage scoring was carried out by visual analysis, and computerized period-amplitude analysis of sleep EEG was also performed. The schizophrenics showed marked reduction in the amount of slow-wave sleep (SWS) and in the number of delta half-waves during all-night sleep, especially those with higher amplitude, as compared to the normals. The number of delta half-waves in the patients was markedly reduced during the first sleep cycle. The average amplitude of delta half-waves during all-night sleep in the schizophrenics was significantly lower than that in the normals. The half-wave count of total delta waves in the schizophrenics was higher during treatment with ZPC than with BZDs, although no significant differences were observed in the amount of SWS between the two treatments. Soundness of sleep in the subjective sleep assessment was better evaluated during treatment with ZPC than BZDs. These results suggest that reduction of SWS in schizophrenia may be attributable mainly to the decrease in the number of delta waves with higher amplitude and that ZPC may induce deeper sleep in schizophrenics than BZDs.

Adult↗
PubMed1995

The present and the future of sleep research in Asia.

In recent years, recognition of the importance of sleep, not only as a health problem but also as a social problem, has brought about worldwide growing interest in sleep and sleep research. In Asian countries, the number of sleep researchers is increasing rapidly and as a result the Asian Sleep Research Society (ASRS) was founded in 1994. This paper reviews the main topics of basic and clinical sleep research which have been investigated recently in Japan and in Asian countries. The subjects of sleep research in Asia in the future will be, in principle, similar to those in other countries of the world. However, the author suggests several subjects which are more or less specific to Asia and which should be studied in association, such as epidemiological longitudinal study of sleep disorders in developing countries, characteristics of sleep and dreaming in oriental culture and philosophy, etc. The roles of ASRS in dissemination of information, promotion of training and education, and enlightenment of public and government were also emphasized.

Asia↗
PubMed1995

[Study of zopiclone with quantitative EEG analysis and topography].

Zopiclone is a cyclopyrrolone derivative which possesses hypnotic activity. This drug is known to increase the slow sleep stage compared to benzodiazepines in polysomnography. The subjects were 10 right-handed healthy male volunteers aged 21-23 years. Double-blind crossover trials with placebo control were conducted in a random sequence at intervals of 1 week. Zopiclone 7.5 mg and placebo were administered as single oral doses. Three-minute vigilance controlled EEGs at before and at 1, 3, and 5 h after drug administration, and the response times were recorded. One minute out of the 3-minute EEGs was analyzed with FFT and the power spectrum was obtained. Then the absolute amplitude power (microV) was calculated. These results were subjected to Student's t-test (double difference) and displayed with topographic maps (t statistic significance probability mapping). Zopiclone prolonged the latency of the response time, and increased the amount of delta absolute amplitude power over the right central region, beta 1 absolute amplitude power over the left central region and beta 2 absolute amplitude power over the right central area along with decreased alpha absolute amplitude power over the occipital region and theta power over the left frontal pole area after 1 h, when the peak pharmacological effect was expected. The EEG profiles of zopiclone were different from that of diazepam reported previously concerning the increase in delta activity.

Adult↗
PubMed1994

Effects of zopiclone on sleep and symptoms in schizophrenia: comparison with benzodiazepine hypnotics.

Sleep variables and psychiatric symptoms were investigated in 6 male chronic schizophrenic outpatients. The patients were being treated with benzodiazepine (BZD) hypnotics for more than 8 weeks, and BZDs were replaced with zopiclone (ZPC) 15 mg/day. Polysomnographic examinations, subjective sleep assessments and BPRS scoring were performed during BZD therapy and at the end of 8 weeks of ZPC therapy. The doses of neuroleptics and anticholinergic agents remained fixed throughout the study. The amount of slow-wave sleep (SWS) was markedly small and that of stage 1 sleep was moderately large during BZD therapy. The amount of stage 1 was smaller and that of stage 2 was larger during treatment with ZPC than BZDs. There were no significant change in the amount of SWS between the treatment. Half of the patients exhibited a sleep-onset REM period (SOREMP) during ZPC therapy. Both total BPRS score and negative symptom score were lower during treatment with ZPC than BZDs. These results suggest that ZPC may be more beneficial in treating schizophrenic insomnia than BZD hypnotics and that reduced SWS and SOREMP may be partly involved in the pathophysiology of schizophrenia.

Adult↗
PubMed1994

Preoperative chemotherapy for esophageal cancer based on chemosensitivity testing.

To examine the role and significance of in vitro chemosensitivity testing on cells cultured from endoscopic biopsy specimens, we evaluated outcomes in 57 patients with squamous cell carcinoma of the thoracic esophagus. Over 3 1/2 years, 57 patients were treated with a single course of preoperative combination chemotherapy based on the results of chemosensitivity testing utilizing eight antineoplastic agents. A radiologically evident response (partial response) was seen in 23 patients (40.4%) and histologic effects on grade IIb tumors were seen in six patients (10.5%). The median survival time of all 57 patients was 16.3 months. The median survival time of nine patients who received palliative resection was 4.5 months. The median survival times after curative resection of the 19 patients with a partial response and 29 patients with no response were 27.7 months and 17.3 months, respectively (p < 0.009). The most frequent combination chemotherapy used was cis-dichlorodiammine platinum (II) vindesine/5-fluorouracil, and a high rate of response was noted after therapy with etoposide and 4'-D-tetrahydropyranyl-doxorubicin. Chemosensitivity testing appears to be useful in selecting preoperative chemotherapeutic agents for patients with esophageal cancer, decreasing tumor recurrence after surgery and resulting in more partial responses than conventional chemotherapy.

Adult↗