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Biomedical subjects

M Kohsaka

Publications and source records attributed to M Kohsaka.

At least 37 records · Page 2Linked to original sources

Functional changes of the brainstem triggering vertex sharp wave with spindle.

A vertex sharp wave followed by spindle (VS-spindle) is one of the hallmarks of human stage 2 sleep. We recorded sleep electroencephalograms (EEG) simultaneously with brainstem auditory evoked potentials (BAEP) from nine healthy male subjects. To investigate the generating mechanism of the VS-spindle, sequentially changing BAEP were analyzed around the VS-spindle. The results revealed the preceding changes of wave-V amplitude to the onset of the VS-spindle. When the generator site of wave-V in the brainstem was considered, the results suggest that the functional changes in the dorsal area of the midbrain-pontine junction participate in the organization of the VS-spindle.

Adolescent↗

Increased prevalence of luteinizing hormone beta-subunit variant in Japanese infertility patients.

To determine the frequency of a common luteinizing hormone variant in a Japanese population and to evaluate its significance in infertility, serum samples were collected from 169 healthy non-pregnant Japanese women, 105 healthy adult Japanese men and 97 female Japanese infertility patients. The luteinizing hormone variant includes two point mutations in the beta-subunit gene (Trp8 to Arg8 and Ile15 to Thr15). DNA from blood cells was studied in 10 healthy women, 10 men and five patients using polymerase chain reaction and direct sequencing. In immunoassays, results with a monoclonal antibody recognizing only the wild-type hormone and a polyclonal antibody recognizing the variant as well were compared as a ratio; ratios in heterozygotes and in individuals with only wild-type alleles ranged from 0.19 to 0.50 and from 0.56 to 1.21, respectively, and 0.50 was considered a 'cut-off' value for identifying individuals with the variant. For the larger subject groups, the frequency of the variant was 9.5% in normals. The mean ratio (0.80 +/- 0.35) in infertility patients was significantly lower (P < 0.01) than in healthy women (1.09 +/- 0.56), and the variant occurred more frequently in infertility patients (16.5%) than in healthy women (8.3%; P < 0.05). The variant was more frequent in patients with ovulatory disorders (43.8%) than other patients (16.0%; P < 0.05).

Adult↗

Gender differences in self-evaluated sleep quality and activity of middle-aged and aged subjects.

In order to investigate the gender difference of sleep and activity in middle-aged and aged individuals, home-based sleep was self-evaluated for sleep quality and activity for 5 nights in 20 healthy adults (50-76 years old; 11 women, nine men). There was no significant gender difference for subjective sleep quality. However, the activity level and movement index at night were significantly higher in men than in women, and the activity level during the day was significantly lower in men than in women. The objective sleep quality of men was significantly worse than that of women, however, subjective sleep quality does not differ.

Activity Cycles↗

Gender differences in the sleep of middle-aged individuals.

The study was designed to investigate gender differences in the sleep-wake patterns of healthy middle-aged individuals in their home environment. Polysomnography showed that daytime napping was more common in men than in women. Men had lower sleep efficiency index and experienced more stage 1 sleep. Males had significantly less stages 3 + 4 sleep, less stage REM sleep, and more transitions to wake from REM sleep. Men could not maintain stage REM as well as women. This study indicates that the gender differences in the sleep-wake patterns have appeared in a group of middle-aged individuals.

Aged↗

Motor activity rhythm in dementia with delirium.

Using an actigraph, the activity patterns in 13 demented patients with delirium were examined. We analyzed the data of the eight patients, wearing the actigraphs for more than 10 days. They were classified into four types: type A, nocturnal delirium type; type B, wandering type; type C, hypobulia type; and type D, lying down type. The day to day activity variation was most prominent in type A and seemingly the least in type B. The dominant period of activity rhythm was nearly 24 h in all cases. Additional 12-h period was observed in type C. Actigraphs might become useful in making therapeutic decisions regarding demented patients with delirium.

Activity Cycles↗

Effects of short duration morning bright light in healthy elderly subjects. I: subjective feeling and ophthalmological examinations.

Seven aged subjects aged 61-78 years were exposed to 6000 lx bright light for 30 min during morning hours at their homes for 1 week. Visual analog scale was recorded before bedtime and after rising to assess subjective feelings. Ophthalmological examinations were made before and after light exposure, to exclude pre-existing ocular disorders and to detect ocular damage. Furthermore, ocular fatigue was self-evaluated immediately before and after exposure. Visual analog scale results indicated that alertness reduced significantly before bedtime. Ophthalmological abnormalities were not found after exposure. These findings suggest that short duration morning bright light exposure reduces night-time vigilance.

Aged↗

Effects of short duration morning bright light in healthy elderly. II: sleep and motor activity.

Subjective sleep feelings and motor activity were measured in seven healthy elderly subjects for 6 days. The subjects were exposed to bright light (6000 lux) for 30 min in the morning or instructed to sit in front of a desktop lighting device without light. The average level of motor activity during the night was significantly decreased in the bright light condition, compared with the controlled condition. However, daytime motor activity did not show significant differences between the two conditions. From these findings, even a short duration of morning bright light is effective in maintaining sleep without changing daytime activity.

Activity Cycles↗

[Non-24-hour sleep-wake syndrome].

The sleep-wake cycle in non-24-hour sleep-wake syndrome is longer than 24 hours. Patients go to bed a little bit later each day and then can not fall asleep and wake up at the usual time. The same sleep patterns and free running rhythms in healthy subjects have been seen in temporal isolation. The mechanism of this syndrome has not been clarified, but several factors have been proposed as follows: 1) the weakness of Zeitgeber 2) decrease of sensitivity to Zeitgeber 3) the period of the circadian system is much longer than 24 hours. Vitamin B12 and melatonin were reported to be effective in treating this syndrome.

Chronotherapy↗

Midday exposure to bright light changes the circadian organization of plasma melatonin rhythm in humans.

Effects of bright light exposure at midday were examined on plasma melatonin rhythm in humans under controlled living conditions. Bright light of 5000 1x was provided from the ceiling at midday (1100-1700 h) for 3 consecutive days and the circadian rhythm in plasma melatonin was determined from the fourth to fifth day. The control study was performed in the same subjects who spend four days under dim light conditions (less than 200 1x). The subjects were allowed to sleep from 2400 to 0800 h. The onset phase, but not the end phase, of plasma melatonin rhythm was significantly phase-advanced by bright light exposure. Furthermore, the area under the curve of nocturnal melatonin rise was significantly larger under bright light exposure than under dim light. These findings indicate that midday exposure to bright light for 3 consecutive days changes the circadian organization of plasma melatonin rhythm in humans.

Adult↗

Vitamin B12 treatment for delayed sleep phase syndrome: a multi-center double-blind study.

The active form of vitamin B12 (methylcobalamin) has been reported to be effective on sleep-wake rhythm disorders. Previous studies, however, were performed under open trial, and the effect of vitamin B12 has not been properly evaluated. The aim of this double-blind study was to investigate the efficacy of methylcobalamin on delayed sleep phase syndrome (DSPS). Methylcobalamin (3 mg/day) or placebo was administered for 4 weeks. The subjects were 50 patients with DSPS aged 13-55 years (26.8 +/- 1.3), 27 of whom received the active drug while 23 received the placebo. No significant differences were observed between the 2 groups in subjective evaluations of mood or drowsiness during the daytime or in night sleep by sleep-log evaluation. These results indicate that 3 mg methylcobalamin administered over 4 weeks is not an effective treatment for DSPS.

Adolescent↗

Vitamin B12 enhances the phase-response of circadian melatonin rhythm to a single bright light exposure in humans.

Eight young males were subjected to a single blind cross-over test to see the effects of vitamin B12 (methylcobalamin; VB12) on the phase-response of the circadian melatonin rhythm to a single bright light exposure. VB12 (0.5 mg/day) or vehicle was injected intravenously at 1230 h for 11 days, which was followed by oral administration (2 mg x 3/day) for 7 days. A serial blood sampling was performed under dim light condition (less than 200 lx) and plasma melatonin rhythm was determined before and after a single bright light exposure (2500 lx for 3 h) at 0700 h. The melatonin rhythm before the light exposure showed a smaller amplitude in the VB12 trial than in the placebo. The light exposure phase-advanced the melatonin rhythm significantly in the VB12 trail, but not in the placebo. These findings indicate that VB12 enhances the light-induced phase-shift in the human circadian rhythm.

Adult↗

Seasonal variation of mood and behaviour in a healthy middle-aged population in Japan.

A population survey of seasonality in six representative cities in Japan was conducted using the Japanese version of the Seasonal Pattern Assessment Questionnaire (SPAQ). The questionnaires were given to 951 parents (male: female ratio 1:1 age range 34-59 years) of high-school students. Significant regional differences in seasonal variations of mood, length of sleep, and weight were observed; the proportion of individuals reporting high seasonality in the two northern cities was significantly higher than that in the other areas. These results provide evidence for a northern predominance in the prevalence of seasonal affective disorder in Japan.

Adult↗

General pharmacology of the new non-xanthine adenosine A1 receptor antagonist (+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl)acryloyl]-2- piperidine ethanol.

FK 453 ((+)-(R)-[(E)-3-(2-phenylpyrazolo[1,5-a]pyridin-3-yl) acryloyl]-2-piperidine ethanol, CAS 121524-18-3) is a potent non-xanthine adenosine A1 receptor antagonist with diuretic and renal vasodilatory activity. The general pharmacology of FK 453 was investigated in mice, rats, guinea-pigs and dogs. In in vivo tests, FK 453 had little effect on the central nervous system (general behaviour, spontaneous motor activity, potentiation of barbiturate anesthesia, anticonvulsant activity, analgesic activity and body temperature), hematological system (bleeding time, coagulation time and recalcification time) and intestinal charcoal transit. FK 453 also did not show any cardiovascular (blood pressure, heart rate and femoral blood flow) or respiratory effects. In in vitro tests, although FK 453 had little effect on noradrenaline-induced contraction in rat vas deferens and histamine-induced contraction in guinea-pig trachea, FK 453 inhibited the acetylcholine-, histamine- and barium-induced contraction in isolated guinea-pig ileum and serotonin-induced contraction in isolated rat stomach. FK 453 also exerted significant inhibitory activity on collagen- and U 46619-induced platelet aggregation. However these effects of FK 453 on isolated tissue and platelet were observed only at high concentrations. These results suggest that FK 453 possesses a selective pharmacological profile, and one promising therapeutic site for this drug is in the kidney.

Analgesics↗

[Changes in biological rhythm and sleep structure during the menstrual cycle in healthy women].

It is well known that clinical symptoms such as psychosis, epileptic seizures and sleep disturbances aggravate around the time of menstruation. In some healthy women, subjective sleep feelings or moods have been reported to change throughout the menstrual cycle, which suggests that sleep structure and sleep-wake rhythm may change during the menstrual cycle. We investigated a circadian pattern of plasma melatonin, sleep-wake rhythm and sleep characteristics in the different phases of the menstrual cycle in young healthy women under controlled environmental conditions. The subjects were seven healthy women, aged 18 to 19, with regular menstrual cycles. They stayed in an experimental facility, where temperature and humidity were kept within a narrow range, for three days in successive five weeks. They got up and went to bed at their preferable time. Polysomnography was performed using ambulatory cassette EEG system on the first and second night. Sleep stages were scored according to Rechtshaffen and Kales' criteria. Plasma melatonin was measured at 1-hour intervals for 24 hours on the third day. The menstrual cycle was divided into four phases (menstruation, follicular, early luteal and late luteal). Although the plasma melatonin level in the late luteal phase tended to be higher than in other phases, no significant difference was observed across four phases. The phase in plasma melatonin level did not change. As for sleep-wake rhythm, the time of getting up on the first day was significantly late in the late luteal phase (p < 0.05), although it showed no significant change on the second day. The time of going to bed did not change. Sleep characteristics changed during the menstrual cycle. There was a significant difference in the amount of stage 3 + 4, slow wave sleep (p < 0.05), which was more abundant in the follicular phase than in the luteal phase. TIB (time in bed), SPT (sleep period time), TST (total sleep time) seemed to increase in the menstrual and follicular phases, while stage W increased in the early and late luteal phases. However, there were no significant differences in these parameters. The other parameters did not show any changes. The changes in amount of stage 3 + 4 throughout the menstrual cycle seem to be due to endogenous factors, because environmental factors were controlled in this experiment. It is possible that the menstrual cycle also affect the plasma melatonin level and sleep-wake rhythm.

Adolescent↗

The induction of interleukin-6 (IL-6) and colony-stimulating factors (CSFs) by FK565 and its thrombopoietic activity following in vivo administration.

The induction of macrophage colony-stimulating factor (M-CSF) in monkey plasma following administration of FK565 was observed within 2 h of injection peaked at 4 h, and remained high after 24 h. Interleukin-6 (IL-6) and M-CSF levels increased in monkeys treated with FK565, even at doses as low as 0.01 mg/kg. Granulocyte CSF (G-CSF) levels increased slightly following a dose of 1 mg/kg, but granulocyte macrophage CSF (GM-CSF) was not detected at any doses of FK565 studied. To examine the thrombopoietic activity of FK565 in vivo, single doses of drug (0.01, 0.1 or 1.0 mg/kg) were administered i.v. to cynomolgus monkeys or normal mice on day 0. The promotes platelet (PLT) count after FK565 injection decreased transiently on days 1 and 2, and then increased in a dose-dependent manner on day 5 and was still high on day 14. The experiment using anti-PLT antibody showed that the increased PLT count was not simply due to a rebound phenomenon after the transient decrease in PLT. The effect of i.v. FK565 was studied in mice myelosuppressed with a single dose of mitomycin C (MMC) (5.6 mg/kg). The fall in PLT count was suppressed on day 7 by 0.1 and 1.0 mg/kg FK565. Although intact cells or tissues are necessary for an increase in PLT following FK565 treatment, FK565 suppressed the impaired hematopoietic function seen after chemotherapy. FK565 is proposed as a drug to restore reduced neutrophil and platelet counts found in AIDS or cancer therapy.

Animals↗

[Effects of a novel orally-active antiallergic drug, quinotolast (FK021), on airway clearance].

The effects of a novel antiallergic drug, quinotolast (FK021, sodium 5-(4-oxo-1-phenoxy-4H-quinolizine-3-carboxamido) tetrazolate monohydrate), on airway clearance was studied in comparison with those of tranilast (an orally-active antiallergic drug). FK021 (10 mg/kg, p.o.) did not influence the rabbit airway secretion, whereas tranilast (100 mg/kg, p.o.) caused a slight suppression. Neither FK021 (10(-10)-10(-5) g/ml) nor tranilast (10(-6), 10(-4) g/ml) had any effect on pulmonary surfactant secretion in rat type II pneumocytes. FK021 (10 mg/kg, p.o.) caused a significant increase in the mucociliary transport rate in quails, whereas tranilast (320 mg/kg, p.o.) had no effect. Antitussive effects were examined in normal guinea pigs and guinea pigs made bronchitic by an exposure to SO2. FK021 (10 mg/kg, p.o.) and tranilast (320 mg/kg, p.o.) significantly depressed the cough reflex induced by citric acid in normal animals. FK021 (32 mg/kg, p.o.), but not tranilast (320 mg/kg, p.o.), showed antitussive effects on citric acid-induced cough in bronchitic animals. These results suggest that FK021 may have favorable effects on expectoration and cough reflex observed in the patients with chronic obstructive pulmonary diseases such as asthma.

Administration, Oral↗