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Biomedical subjects

S Kuno

Publications and source records attributed to S Kuno.

At least 19 recordsLinked to original sources

No association between apolipoprotein E alleles and olivopontocerebellar atrophy.

Apolipoprotein E (apo E) epsilon4 is a risk factor for sporadic and late-onset familial Alzheimer's disease, but it is not well known whether the apo E is associated with spinocerebellar degeneration. We studied the frequency of apo E allele in 59 olivopontocerebellar atrophy (OPCA) patients, including 13 pathologically confirmed cases. The distribution of the apo E allele frequency did not differ between OPCA patients and controls. Apo E allele does not influence the development of OPCA.

Alleles

Mutual link among the approaches to clipping of basilar aneurysms.

The pterional approach for basilar aneurysm clipping, has become the most common approach among surgeons, since it was advocated by Yasargil in 1982. However, other approaches aiming at an adequate but less invasive surgery to meet conditions of peripheral blood vessels (including aneurysmal size, direction and perforating arteries and arteriosclerosis) and the direction of clip insertion have also been developed. The approaches will be recommended to be expanded according to situations of the actual intra-operative findings in the future. The mutual link among the approaches to clipping of basilar aneurysms was investigated.

Adult

Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus monkeys.

The effects of dopamine receptor agonists on urinary bladder function were evaluated in normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys to investigate the therapeutic efficacy in the treatment of urinary symptoms in Parkinson's disease. Under ketamine anesthesia, cystometrograms exhibited significant reduction in the volume threshold for the micturition reflex in MPTP-lesioned parkinsonian monkeys when compared with those of normal monkeys. The selective dopamine D2 receptor agonist bromocriptine significantly reduced the bladder volume threshold for the micturition reflex by 25 to 30% in both normal and MPTP-lesioned animals. The nonselective D1/D2 receptor agonist pergolide significantly reduced the bladder volume threshold by 22% in normal monkeys, but increased the volume threshold by 50% in MPTP-lesioned parkinsonian monkeys. Another D1/D2 agonist (5R,8R,10R)-6-methyl-8-(1,2,4-triazol-1-ylmethyl) ergoline maleate (BAM-1110) also increased the bladder volume threshold (by 80%) in parkinsonian monkeys without significant effects on the micturition reflex in normal monkeys. The reduction in the volume threshold by bromocriptine in both normal and MPTP-treated groups and by pergolide in normal monkeys was suppressed by pretreatment with the selective D2 antagonist sulpiride, whereas the increment in the volume threshold by pergolide and BAM-1110 in parkinsonian monkeys was antagonized by pretreatment with the selective D1 antagonist SCH 23390, but not by sulpiride. These findings suggest that concurrent activation of D1/D2 receptors, rather than selective stimulation of D2 receptors, might be beneficial for treating urinary symptoms caused by detrusor hyperreflexia in Parkinson's disease.

Animals

Effects of tolcapone, a catechol-O-methyltransferase inhibitor, on motor symptoms and pharmacokinetics of levodopa in patients with Parkinson's disease.

The effects of tolcapone, a catechol-O-methyltransferase inhibitor, on the bioavailability and efficacy of levodopa were evaluated in 12 patients with Parkinson's disease (PD), 8 of whom showed signs of daily motor fluctuations (wearing-off phenomenon). Motor disabilities were assessed in 12 patients at 7 time points before and after the chronic administration of tolcapone using the Unified Parkinson's Disease Rating Scale (UPDRS). The UPDRS score was improved at all points of determination. Eight patients with wearing-off phenomenon on levodopa showed symptomatic improvement on the combination. The area under the curve (AUC) for levodopa increased by 34% (p = 0.0059) after the administration of tolcapone. The elimination half-life (T1/2) of levodopa was significantly prolonged by 81% (p = 0.0001) after the treatment. The AUC of 3-O-methyldopa, a metabolite of levodopa, was decreased by 79% (p = 0.0001) and the Cmax (maximum concentration) was also decreased by 80%d after the administration (p = 0.0001) of tolcapone. The combination of tolcapone and levodopa was well tolerated. Our findings suggest that tolcapone improves the pharmacokinetics of levodopa in plasma and motor symptoms of fluctuating PD patients. It is suggested that tolcapone may be useful drug adjunct to levodopa in treating patients with PD with wearing-off phenomena.

Aged

Muscle architecture and function in humans.

The present study focused on architectural factors which are considered to influence the linkage of muscle fiber and joint actions. By means of real-time ultrasonography we can observe clearly and noninvasively in vivo the movement of fascicle and aponeurosis in human muscle and measure directly the changes in pennation angle and length of fascicle during muscle contraction. During dorsi and plantar flexion without load the movement of tendinous tissue in human tibialis anterior muscle (TA) appeared to synchronize with the displacement of the ankle joint, indicating that the muscle tendon complexes are stiff relative to the applied force, which is fairly small in the case of foot shaking motion. On the other hand, when the ankle joint was fixed and the TA contracted 'statically' the ultrasonic echo from deep aponeurosis in the TA was observed to move proximally, indicating the elastic component (i.e. mainly tendinous tissue) was stretched significantly by the contraction force of muscle. In the case of the kneejoint, a length of fascicle in vastus lateralis decreased by 18% with the extension of the knee passively from a 100 degrees flexed position. When the knee extensors contracted 'statically' the fascicle length decreased at every joint angles and its magnitude was greater (30%) when the knee was closer to full extension than (5%) at the flexed positions. The present results clearly show that the architecture of actively contracting muscle fibers differ considerably than that which occurs when movement is passively induced. The use of cadaver data in the study of architecture and modeling of muscle functions would result in inaccurate, and in some cases even erroneous results.

Animals

Effects of anti-endothelial cell antibody in pre-eclampsia on endothelin-1 release from cultured endothelial cells.

In order to investigate the pathophysiological significance of anti-endothelial cell antibody (AECA) in pre-eclampsia, the effects of AECA on endothelin-1 (ET-1) and prostaglandin I2 (PGI2) release from cultured human umbilical vein endothelial cells (HUVEC) was evaluated. Serum samples were taken from 85 pre-eclamptic and 20 normal pregnant women. Anti-endothelial cell antibody was measured by ELISA using HUVEC. The release of ET-1 and 6-keto PGF1-alpha, a stable metabolite of PGI2, from HUVEC were evaluated after incubation with IgG-AECA-positive sera and IgG isolated from AECA-positive sera. The incidence of IgG- and IgM-AECA was 24.7 and 8.2%, respectively. The release of ET-1, in the medium containing IgG-AECA-positive sera was significantly greater than in the medium containing IgG-AECA-negative sera. There was significant correlation between the levels of IgG-AECA and the release of ET-1 from endothelial cells. The ET-1 release by IgG isolated from AECA-positive sera was greater than that from AECA-negative sera. However, the release of 6-keto PGF1-alpha by AECA-positive sera was not significantly different from that of AECA-negative sera. It is concluded that IgG-AECA in pre-eclampsia increases ET-1 release from endothelial cells and that AECA may affect local vascular function in this disorder.

6-Ketoprostaglandin F1 alpha

Nine-year follow-up study of bromocriptine monotherapy for Parkinson's disease.

A 9-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Eleven patients were on bromocriptine monotherapy, 35 patients were on combined treatment of bromocriptine and levodopa for a certain time during a 9-year period. Maintenance doses of bromocriptine at the end of the 9th year in the two groups were 11.1 mg/day in the monotherapy and 12.7 mg/day in the combination therapy group with levodopa. Changes in Hoehn and Yahr's grading between the time of trial start and the end of 108 months' treatment revealed that 5 of 11 cases in the monotherapy group remained in the same stages, the other 2 cases improved in condition from stage II to I, and another 4 deteriorated compared with pretreatment grade. On the other hand, 20 of 35 cases in the combination-therapy group reached more advanced stages, 3 patients moving to stage V. Four of them, however, improved, and 11 did not change at the end of 9 years of treatment. Although it is difficult to prove the neuroprotective effect of a dopamine receptor agonist, our long-term nation-wide collaborative studies will help us to answer the question of how bromocriptine works in pharmacokinetic aspects.

Aged

Differential therapeutic effects of dopamine D1 and D2 agonists in MPTP-induced parkinsonian monkeys: clinical implications.

L-DOPA, the precursor of dopamine, remains most effective in the treatment of patients with Parkinson's disease, but prolonged L-DOPA treatment often produces adverse effects, including dyskinesia and psychosis. Dopamine receptors can be divided into two major subtypes, D1 and D2. Might both subtypes of the dopamine receptor be equally relevant to amelioration of parkinsonian symptoms and responsible for the adverse side effects? To address this question, the effects of D1 or D2 receptor agonists alone and in joint administration were examined in MPTP-induced parkinsonian monkeys. The parkinsonian symptoms, such as tremor, bradykinesia and rigidity, and the adverse side effects, such as hyperactivity and aggressiveness, were evaluated independently using different behavioral criteria. The results showed that antiparkinsonian effects can be exerted either by the D1 agonist (SKF 82958) alone or by the D2 agonist (quinpirole) alone, whereas hyperactivity and aggressiveness manifested by dopamine agonists require coactivation of the D1 and D2 receptors. Thus, the antiparkinsonian effect can be dissociated from the adverse effect by therapeutic strategy. It is implied that imbalances in activation of the D1 and D2 receptors may provide a favorable approach for long-term treatment of parkinsonian patients with dopamine drugs.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Nationwide multicenter prospective study on the long-term effects of bromocriptine for Parkinson's disease. Final report of a ten-year follow-up.

A 10-year nationwide multicenter prospective study on the long-term efficacy of bromocriptine for Parkinson's disease is reported. Six patients remained on bromocriptine monotherapy for 10 years, while 22 patients achieved good disease control with bromocriptine plus levodopa (added during the course of the study). In the 6 patients on bromocriptine alone, the disease remained in Hoehn and Yahr stage I or II for 10 years. In the other 22 patients on bromocriptine plus levodopa therapy, disease progression was very slow for 7-8 years. None of the 6 patients remaining on bromocriptine monotherapy experienced adverse reactions like the wearing-off phenomenon, dyskinesia, or the on-off phenomenon. Among the 22 patients who started levodopa therapy during the course of the study, these adverse reactions to levodopa were infrequent (10, 3, and 3 patients, respectively). Thus, early introduction and long continuation of bromocriptine therapy with restricted concomitant use of levodopa may have led to very slow disease progression and the suppression of adverse reactions. Although the patients who could be maintained long-term on bromocriptine monotherapy might represent a population who have very slowly progressive disease, their adequate disease control and the low incidence of adverse reactions in the patients who later started concomitant levodopa suggest that the unwanted effects of levodopa may be reduced by early and sustained treatment with bromocriptine. Introduction of bromocriptine monotherapy at an early stage of Parkinson's disease or with restricted use of additional levodopa therapy to bromocriptine when necessary may be a useful strategy for achieving adequate and sustained disease control.

Aged

Neuroleptic malignant syndrome in parkinsonian patients: risk factors.

A syndrome resembling the neuroleptic malignant syndrome (NMS) is known to develop occasionally following interruption of dopaminergic medications in patients with Parkinson's disease. However, NMS can develop even without withdrawal of antiparkinsonian drugs. In parkinsonian patients who continually received dopaminergic medications, the development of NMS occurred exclusively in warm seasons, May to August. The development of NMS could occur at any season in association with the cessation of dopaminergic drugs. A female parkinsonian patient showed two episodes of NMS during the premenstrual period. It is suggested that hot weather or dehydration and aggravation of parkinsonism premenstrually constitute risk factors for the development of NMS, in addition to withdrawal of antiparkinsonian drugs.

Aged

[Treatment of Parkinson's disease with multiple drugs].

All major symptoms of Parkinson's disease, i.e., rigidity, tremor, hypokinesia and postural instability are induced by an impaired dopaminergic neurotransmission in the nigro-striatal pathway. Levodopa pioneered the symptomatic therapy of Parkinson's disease. While it is effective on the motor symptoms, long-term levodopa therapy often results in dyskinesia, motor fluctuations and psychosis. Coadministration of levodopa and dopamine agonists, bromocriptine and pergolide, decreases these adverse side effects. Anticholinergics and amantadine are often effective as adjuvant drugs for the early stage of patients with Parkinson's disease. Furthermore, L-threo-DOPS, nor-adrenergic precursor drug, is sometimes effective for the advanced stage of Parkinson's disease. Thus coadministration of multiple antiparkinsonian drugs, rather than single therapy of levodopa, is useful for the long-term treatment of Parkinson's disease.

Amantadine

Combined effects of cabergoline and L-dopa on parkinsonism in MPTP-treated cynomolgus monkeys.

The behavioral effects of L-dopa or cabergoline alone were compared with those of the joint administration of the two drugs in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention to the induction of hyperactivity and dyskinesia. Cabergoline alone at 0.2 mg/kg or less improved in a dose-dependent fashion the parkinsonism without inducing hyperactivity and dyskinesia following a single subcutaneous injection. L-dopa alone improved the parkinsonism, but induced hyperactivity and dyskinesia, depending on the dose applied. Doses required for 50% amelioration by L-dopa and cabergoline were 10 and 0.038 mg/kg, s.c., respectively. With low doses (50%-amelioration doses), cabergoline or L-dopa alone improved the parkinsonism without induction of hyperactivity and dyskinesia, but the duration of action was brief. Cabergoline in combination with L-dopa was highly effective in improving motor disability without induction of hyperactivity and dyskinesia. Moreover, the duration of action was more prolonged with the coadministration than with the single administration of each drug. These findings suggest that the combined therapy with low doses of L-dopa and cabergoline is beneficial for treating patients with advanced Parkinson's disease.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Influence of two different modes of resistance training in female subjects.

In resistance training, it has been empirically accepted that muscle hypertrophy is developed by low intensity and high volume training, while muscle strength and power are developed by high intensity and low volume training. The purpose of the present study was to investigate the influence of two different modes of resistance training on isokinetic strength and muscle cross-sectional area (CSA) in females. Eleven females, who had no experience in resistance training, participated in this study and were randomly divided into two groups. The former consisted of 4-5 sets of 15-20 RM (repetition maximum) with sufficient rest between sets (Group H), while the latter consisted of 8-9 sets of 4-6R M with 90 s of rest between sets (Group S). The former was assumed to be appropriate for muscle hypertrophy and the latter muscle strength, respectively. All subjects completed isotonic knee extension exercise three times a week for 8 weeks. Measurements were made on quadriceps muscle cross-sectional area (CSA) and isokinetic torques at 0, 60, 180, and approximately 300 degrees before training, at the fifth week and the end of training period. Muscle CSA was defined as the sum of CSA measured at 30, 50 and 70% of femur length. After training, muscle CSA had significantly increased in both groups: 3.3 +/- 0.7% (p < .05) for group H and 3.6 +/- 1.1% (p < .05) for group S, respectively. While the changes in isokinetic torque were 43.4 +/- 47.5% (p < .05) for group H and 27.4 +/- 31.3% (p < .05) for group S, respectively. In both groups the percentage changes of the isokinetic strength were significantly higher than those of the CSA. No significant difference in these variables were found between the two groups. These results suggest that during the early phase of resistance training two different modes of resistance training may have similar effects on muscle CSA and isokinetic strength in untrained females.

Adult

Tendinous movement of a human muscle during voluntary contractions determined by real-time ultrasonography.

The degree of shortening or lengthening of muscles during joint actions has not been clarified in humans, although such information is essential in understanding human muscle functions. In this study, the tendinous movement of a muscle was determined by real-time ultrasonography during voluntary contractions. The tibialis anterior muscle (TA) was tested in five healthy men who performed dorsi- and plantar flexion movements (shortening and lengthening of TA) at two frequencies (0.1 and 1.5 Hz). The insertion point (eta) of fascicles onto the aponeurosis was clearly visualized on the ultrasonogram, and its position relative to a fixed marker moved proximally and distally according to dorsi- and plantar flexion of ankle joint. The movement of eta occurred in phase with the angular change of ankle joint, giving high correlations (r = 0.93 to 0.97) between the displacement of eta and the angle. The displacement of eta for one radian of joint angle change, 46.5 +/- 1.7 (SD) mm, was comparable to the reported moment arm of TA. The present method has many potential applications in the field of muscle physiology and biomechanics in humans.

Adult

Eight-year follow-up study of bromocriptine monotherapy for Parkinson's disease.

An 8-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Fifteen patients were on bromocriptine monotherapy, and 44 patients on bromocriptine combined with levodopa for a certain time during an 8-year period. By judging from Hoehn and Yahr's grading, 4 of the 15 patients in the monotherapy group were in a better condition than before treatment, while 7 cases remained in the same grading, and only 4 showed deterioration. On the other hand, 26 of 44 patients on combination therapy showed more advanced grading at the end of 8 years compared to the stage at the onset of the trial. Maintenance doses of bromocriptine in the two groups were 12-13 mg per day, and levodopa doses were kept at a relatively low level (310-370 mg per day) during this study period. Whether dopamine receptor agonists have neuroprotective effect or not is extremely difficult to prove in human subjects, but this type of long-term follow-up study might give some clues as to these important questions.

Aged

Measurement of muscle fibre displacement during contraction by real-time ultrasonography in humans.

The contact point (P) made by both the echoes of the aponeurosis and from interspaces among fascicles of the tibialis anterior muscle was detected by real-time ultrasound scanning in 12 adults. Movement in the location of P was observed during muscle contraction and its displacement was related to changes in ankle joint angles (r = 0.81, P < 0.01), i.e., P shifted proximally when the ankle joint was dorsiflexed. There was also a significant positive correlation between the degree of dorsiflexion and the velocity related to the change in location of P (r = 0.84, P < 0.01). Ultrasound measurements of the displacement and the velocity of P were reproducible as there was no variation noticed among measurements on different days. It is suggested from these results that the displacement of P reflected changes in muscle length during contraction and that this amount of change corresponded to changes in joint angles.

Adult

Muscle metabolism during exercise using phosphorus-31 nuclear magnetic resonance spectroscopy in adolescents.

Very little has been reported on muscle energetics during exercise in adolescents. This is attributable to the difficulty of subjecting children to muscle biopsy. The purpose of this study was to investigate the characteristics of muscle metabolism during exercise in vivo in adolescents by comparing firstly, with adults and secondly, the differences resulting from physical activity using phosphorus-31 nuclear magnetic resonance (31P NMR) spectroscopy. The subjects were boys aged 12 to 15 years, comprising 21 trained boys and 23 control boys, and 6 adults controls. The ratio of phosphocreatine (PCr):(PCr + P(i)), where P(i) is inorganic phosphate intracellular pH at exhaustion and the time constant of PCr during recovery were measured in all the subjects using 31P NMR. Both groups of children showed higher values of PCr:(PCr + P(i)) and intracellular pH at exhaustion than did the adult control group (P < 0.01 or P < 0.05). However, no significant differences were found between the trained boys and the control boys with respect to PCr:(PCr + P(i)) and intracellular pH at exhaustion. On the other hand, we found the same values for PCr time constant in all groups. This result suggested no differences of the muscle oxidative capacity between children and adults. We concluded that the adolescents, aged 12 to 15 years in both the trained and control groups, had less glycolytic ability during exercise than the adults.

Adolescent