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Biomedical subjects

K Kurata

Publications and source records attributed to K Kurata.

At least 127 records · Page 7Linked to original sources

Meige's syndrome during long-term neuroleptic treatment.

Two patients developed difficulties in eyelid opening following long-term neuroleptic treatment of more than 6-8 years. Tardive dyskinesia and dystonia apart from the face were not found in either case. The symptoms fluctuated in their severities on a daily basis and were easily aggravated by various stimuli, e.g., stress, walking, reading and watching television. Electromyographic studies of their faces clearly indicated that the symptoms resulted from spontaneous blepharospasm and were analogous to idiopathic Meige's syndrome. Therefore, the patients' difficulties in opening their eyes were considered to be the so-called drug-induced Meige's syndrome and/or facial tardive dystonia. It must be stressed that this syndrome is extremely distressing to patients and is a severe complication accompanying a long-term neuroleptic treatment.

Adult↗

Changes in amitriptyline distribution in rat brain during a 14-day continuous infusion.

The amitriptyline (ATL) distribution in 12 rat brain regions was examined during 2-, 7- and 14-day continuous ATL infusion, starting with 18 mg/kg/day on the first day. The concentration of nortriptyline, a demethylated metabolite of ATL, in brain and serum was very low in comparison with ATL. The brain/serum concentration ratio of ATL and absolute ATL concentration in the brain were lower on the 2nd day than on the other 2 days. On the other hand, the ATL serum level on the 2nd day was higher than on the other 2 days. The ATL distribution in brain was heterogeneous on each of the three days and there were changes with time in its distribution in two brain portions, the anterior basal ganglia and the medulla oblongata + pons.

Amitriptyline↗

Heterogeneous distribution of mianserin in rat brain during chronic continuous infusion.

The mianserin (MIS) distribution in 12 brain regions was investigated after 2- and 14-day continuous MIS infusion, starting with 19 mg/kg/day on the first day. There was no significant difference between the 2nd and 14th day with respect to MIS concentration, brain/serum concentration ratio in whole brain or MIS serum level. The MIS distribution was heterogeneous on the 2nd and 14th day and did not change with time. The concentrations were highest in cortex and hippocampus and lowest in cerebellum, hypothalamus, and bulbus olfactorious and septum. This distribution pattern differs from those found with tricyclic antidepressant drugs.

Animals↗

Effects of endolymphatic mastoid shunt operation for patients with Menière's disease.

During the past 10 years, the endolymphatic mastoid shunt operation was carried out on 108 patients with Meniere's disease: 54 men and 54 women between 22 and 72 years old. According to criteria AAOO proposed in 1972, 86 cases (79.6%) belonged to class A, 19 cases (17.7%) to class B and 3 cases (2.7%) to class C. Forty patients took the body sway test before and after the operation. Four of the 40 patients were found to have Meniere's disease on the contralateral side within 12 months after the operation and one patient was found to have a complicating psychogenic disease. The abnormal body sway had recovered 2 to 9 months after the operation, but the medical treatment could not be stopped during this period. The average hearing gain after the operation was 21.3 +/- 14.4 dB; that for the patients with a short period of illness (within 23 months of the first onset to the operation) was 25.2 +/- 14.5 dB and that for the patients with a longer period of illness (over 24 months) was only 13.8 +/- 10.6 dB.

Adult↗

Set-related activity in the premotor cortex of rhesus monkeys: effect of triggering cues and relatively long delay intervals.

"Set-related activity" has been defined as a significant alteration in neuronal discharge rate during an "instructed delay period," a period when a previously instructed movement is being withheld. It has been argued that set-related activity in the primate premotor cortex, or at least a significant proportion of it, reflects motor preparation. In most previous investigations, however, in which visual stimuli have triggered the movement and simultaneously indicated its target, set-related activity might reflect either the anticipation of or attention to the trigger stimulus. The present report shows that set-related activity is robust and can be directionally selective when trigger stimuli do not indicate the target and when a trigger stimulus is absent. Another feature of previous studies has been the relatively brief intervals between the instruction and trigger stimuli (typically 3 sec or less). In the present study, we were able to observe the activity of a small number of cells during longer delay periods. Set-related activity persists, although it becomes less consistent, for as much as 7.5 sec after an instruction stimulus. These results support the hypothesis that set-related activity reflects the preparation for specific limb movements.

Animals↗

[Mathematical analysis of equilibrium on 2-site immunoradiometric assay using anti-human TSH monoclonal antibody].

A mathematical analysis of equilibrium was adapted on a practical 2-site immunoradiometric assay (IRMA) using 10 murine monoclonal antibodies (Mabs) to human TSH. The affinity constant of 10 Mabs was from 2.5 x 10(8) to 3.3 x 10(10) M-1. The dose-response curves using appropriate combinations of Mab-coated bead and 125I-labeled Mab were compared with the theoretical curves calculated from mathematical analysis of equilibrium. Theoretical curves were directly affected by the affinity constants in which antibodies with higher affinity constants showed higher binding activity of tracer. However, the curves which antibodies have more than 1 x 10(9) M-1 and 1 x 10(10) M-1 for capture antibody and tracer antibody did not show remarkable change, but were similar with the curve obtained from unlimited affinity constant. From these curve, the maximum and minimum detectable dose were approx. 2 x 10(-10) M and 4 x 10(-14) M, respectively. Seven out of 10 experimental curves for TSH showed good consistency with the corresponding theoretical curves which indicated that a mathematical analysis of equilibrium was useful to presume experimental results using monoclonal antibody.

Antibodies, Monoclonal↗

Structural characteristics of endogenous sugar acids and relations to feeding modulation.

Structural specificity among short-chain organic acids for effects on feeding behavior, blood glucose and insulin was investigated by infusion of 1 exogenous and 6 endogenous derivatives into the rat third cerebral ventricle. Glyceric acid (GEA) (1.0 mumol), 3,4-dihydroxybutanoic acid gamma-lactone (3,4-DB) and 3,4,5-trihydroxypentanoic acid gamma-lactone (3,4,5-TP) (2.50 mumol) decreased food intake for, at most, 24 h. These acids depressed the size of the first meal after infusion, but did not affect latency to the first meal, eating speed, drinking or ambulation. Infusion of 2,4-dihydroxybutanoic acid gamma-lactone (2,4-DB) (1.25 mumol), 2,4,5-trihydroxypentanoic acid gamma-lactone (2,4,5-TP), and an exogenous compound, 2,4,5,6-tetrahydroxyhexanoic acid gamma-lactone (2,4,5,6-TH) (2.50 mumol), induced transient initial feeding which was not necessarily accompanied by periprandial drinking. Ambulation was concomitantly increased. Of these organic acids, 3,4-DB and 2,4,5-TP were most potent in their effects on feeding. Hyperglycemia was induced by 2.50 mumol 3,4-DB leaving insulin unaffected; 2.50 mumol 2,4,5-TP caused hypoglycemia, with a persistent but not significant rise in insulin. The results suggest that slight structural differences of endogenous organic acids, in particular the positions of hydroxyl groups on the lactone ring of 4-butanolide, may be important in feeding modulation by conveying intrinsically reciprocal signals to neurons involved in feeding and satiety.

Animals↗

Effect of an amino group at carbon 2 of 1-deoxyglucose analogues on anorexia in the rat.

A steric hindering group at carbon 2 of 1-deoxyglucose analogues was introduced by epimerization, deoxidation and substitution of a hydroxyl group with either an acetamido or a fluoro group. Injection of this analogue into the rat third cerebroventricle attenuated the feeding suppression produced by 1-deoxyglucose. In contrast, the replacement of a hydroxyl group at carbon 2 with an amino group produced anorexia of the same magnitude as that produced by 1-deoxyglucose. Amination at carbon 2 was more potent than that at carbon 3, 4 or 6. These results indicate that an amino group at carbon 2 of the glucose molecule is important to reinforce the feeding suppression caused by 1-deoxyglucose analogues.

Animals↗

Detection of patients with cancer by monoclonal antibody directed to lactoneotetraosylceramide (paragloboside).

A hybridoma producing monoclonal antibody (H11) directed to lactoneotetraosylceramide (paragloboside) has been established from spleen cells of a mouse immunized with paragloboside. The monoclonal antibody H11 (immunoglobulin M type) was selected from five clones showing different reactivities with paragloboside. The monoclonal antibody was highly specific to paragloboside and lacked reactivity with other glycolipids including glucosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, gangliotriaosylceramide, gangliotetraosylceramide, and GalNAc beta 1-4[NeuAc alpha 2-3]Gal beta 1-4Glc beta 1-1Cer. However, the monoclonal antibody (H11) was found to bind to lactosamine-containing glycolipids at their terminals, such as i- and I-type glycolipids as well as paragloboside. A two-step sandwich radioimmunoassay method for paragloboside antigen in serum was established by using the monoclonal antibody. The mean paragloboside antigen concentration in the sera from 20 normal individuals was 25.3 ng/ml. If the cutoff value was set at 80.9 ng/ml [25.3 + 2 x 27.8 (SD)], only 1 of 20 healthy controls had an elevated paragloboside value in the serum, whereas sera from 9 of 12 (75.0%) hepatoma, 4 of 10 (40%) pancreatic cancer, 16 of 40 (40.0%) stomach cancer, and 6 of 10 (60%) lung cancer patients had elevated paragloboside values. Sera from 3 of 8 hepatitis patients and 7 of 10 liver cirrhosis patients were estimated to be positive but sera from 16 patients with benign disease had paragloboside levels lower than the cutoff value. A larger amount of the antigen was found in liver metastases from colorectal carcinoma compared to the normal counterpart. The antigen was also detected in the medium of various human cancer cells and meconium. However, the antigen in the sera, medium, meconium, and cancer tissue seemed to be associated with glycoprotein or lipoprotein, because most of the antigen activity was eluted in the void volume fraction on high-performance liquid chromatography with a gel filtration column.

Antibodies, Monoclonal↗

Extension of nasopharyngeal carcinoma and otitis media with effusion.

In 35 patients with nasopharyngeal carcinoma that occupied the fossa of Rosenmüller, the relationship of the tumor, assessed by computed tomographic scans, to otitis media with effusion and ventilatory function of the eustachian tube was examined. Incidence of otitis media with effusion was low when the tumor was limited to the fossa of Rosenmüller (stage I), and high when the tumor extended from the fossa to the parapharyngeal space (stage II). Passive opening of the eustachian tube remained normal until the tumor occupied the parapharyngeal space (stage III). However, active tubal opening was impaired in stage I and the impairment increased with the tumor stage. These results indicate that tumor extension from the fossa of Rosenmüller to the parapharyngeal space and resultant poor active tubal opening cause the development of otitis media with effusion in patients with nasopharyngeal carcinoma.

Adult↗

Distribution of clomipramine in various brain regions of rats under steady-state serum concentrations.

The clomipramine (CMP) distribution in 12 regions of rat brain was investigated 2 and 7 days after subcutaneous minipump implantation. The results of serial blood samplings during 7 days indicated that steady-state CMP serum levels were achieved from experimental day 2. The regional CMP distributions in the brains were uneven on both the 2nd and 7th experimental days. On both test days the CMP concentrations were higher in the cerebral cortex and hippocampus than those in the other regions, and those in the cerebellum and bulbus olfactorius and septum were lower. When the serial fluctuations of the CMP levels were examined in 12 brain regions, there were significant differences between days 2 and 7 in the following four regions: the anterior basal ganglia, hypothalamus, bulbus olfactorius + septum and amygdala.

Animals↗

Premotor cortex of rhesus monkeys: set-related activity during two conditional motor tasks.

We compared set-related premotor cortex activity in two conditional motor tasks. In both tasks, a rhesus monkey moved its forelimb to one of two possible targets on the basis of visuospatial instruction stimuli. One target was located to the left of the limb's starting position, the other to the right. In the directional task, a white light situated within the target provided the instruction. In the arbitrary task, colored instruction stimuli equidistant from the targets established an arbitrary relationship between stimulus and response. One hypothesis about set-related premotor cortex activity is that it contributes to the preparation for limb movement on the basis of sensory instruction stimuli. If set-related activity differed profoundly in the arbitrary and directional tasks, then that hypothesis would be untenable. Out of 403 task-related premotor cortex neurons in two monkeys, 130 neurons showed set-related activity, and we studied 118 cells in detail. The vast majority (81%) of these 118 neurons showed no significant difference between the two tasks in set-related activity. When set-related activity did differ, the greatest activity usually occurred after arbitrary instructions; the opposite being the case for only 5% of our sample. Differences in activity during the two tasks, even when statistically significant, were generally small. The present results accord with the hypothesis that set-related premotor cortex activity reflects aspects of motor preparation.

Animals↗

Premotor and supplementary motor cortex in rhesus monkeys: neuronal activity during externally- and internally-instructed motor tasks.

We compared neuronal activity in the premotor (PM) and supplementary motor cortex (SM) of two rhesus monkeys as they performed two tasks. In an externally-instructed task, a visuospatial instruction stimulus indicated which of two touch pads should be the target of a forelimb movement. In an internally-instructed task, the visuospatial stimulus was either irrelevant or not presented, but in either case the target alternated between the two touch pads in blocks of 20 trials each. In both tasks, the monkey withheld movement for a self-timed delay period. Neuronal activity modulation during the delay period (set-related activity) and immediately before movement (movement-related activity) was comparable in PM and SM, both in terms of the proportion of cells with both of those activity patterns and their depth of modulation. Thus, our findings do not provide strong support for a clear-cut functional division between PM and SM regarding the control of externally- and internally-instructed limb movements. Within PM, 57 out of 96 cells with set-related activity showed similar modulation during the two tasks, supporting the proposition that such activity contributes to the preparation for a limb movement. In 32 of the 39 PM set-related neurons that showed a significant activity difference between the two tasks, activity was greater in the externally-instructed task. This finding supports the hypothesis that set-related activity in PM contributes more to sensorially-instructed than to other movements.

Animals↗

Episodic twilight state with severe autonomic symptoms in an epileptic patient.

A boy suffering from epileptic seizures experienced five episodes of a twilight state. His twilight states continued for at least two weeks, and were characterized by behavioral disorders and severe autonomic symptoms. Sometimes functional ileus was present. The electroencephalographic finding in the first episode was 6-per-second phantom spike and wave complex (PSW). For treatment, a combination of carbamazepine and sodium valproate was useful in preventing the reappearance of the episode of the twilight state and in suppressing PSW. From the clinical and electroencephalographic findings and therapeutic response to antiepileptics, the episodes were considered to have originated in localized epileptic discharges in the hippocampal, amygdaloidal and hypothalamic regions.

Amygdala↗

A relationship between clomipramine brain concentration and its effect on serotonin metabolism.

The relationship between clomipramine (CMP) brain concentration and its inhibitory effect on serotonin (5HT) turnover was investigated in rats treated with a single dose and multiple doses of CMP. CMP reduced the 5-hydroxyindole acetic acid (5HIAA) brain levels in two groups of rats. Concerning the 5HT turnover measured by the probenecid (PBC) technique, there were significant correlations between the CMP brain level (x) and 5HIAA brain level (y) after PBC injections in both acute and chronic experiments. The regression lines for the respective groups were y = 764 - 117 log x (r = 0.84, P less than 0.001) and y = 770 - 97.7 log x (r = 0.68, P less than 0.001). The regression coefficient for the acute experiment was greater than that for the chronic one (p less than 0.001), indicating a less dose-response in the latter. From these findings, the acute dosing with CMP seemed to reduce the 5HT turnover without reference to the dose but a prolonged administration seemed to vary in its effect. This may be due to a compensatory mechanism in the 5HT system induced by chronic CMP-treatment.

Animals↗

Neuronal activity preceding directional and nondirectional cues in the premotor cortex of rhesus monkeys.

Pre-cue activity, the neuronal modulation that precedes a predictable stimulus, was studied in the premotor cortex of three rhesus monkeys. In one condition, a directional cue dictated the timing and target of a forelimb movement. In another condition, a nondirectional cue provided identical timing information but did not indicate the target. Of 501 task-related neurons recorded in premotor cortex, 168 showed pre-cue activity. The onset time of pre-cue activity varied markedly from trial to trial and cell to cell, ranging from trial initiation to 4.8 sec later. No pre-cue activity reflected the direction of limb movement; thus, the data argue against the hypothesis that pre-cue activity reflects preparation for specific limb movements. A small number of cells showed greater pre-cue activity before directional than before nondirectional cues, and this difference may reflect anticipation of the cue's directional information. However, the vast majority (84%) of neurons lacked such differences. We therefore hypothesize that most pre-cue activity reflects or contributes to a facet of behavior common to the two conditions: anticipation of the time and/or nature of events.

Animals↗