Biomedical subjects

S Kuno

Publications and source records attributed to S Kuno.

At least 19 recordsLinked to original sources

PubMed1995

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↗

PubMed1995

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↗

PubMed1995

Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA).

An unstable expansion of CAG repeat in the coding region of the DRPLA gene on chromosome 12p is the mutation specific for hereditary dentatorubral-pallidoluysian atrophy (DRPLA). We studied the CAG expansion in brain and other tissues from six unrelated DRPLA patients. The CAG repeat lengths showed distinct differences between tissues. The sizes of the CAG expansion in various regions of the brain except the cerebellum were generally larger by several repeats than in other peripheral tissues. Brain samples showed greater variation of the expansion compared with other tissues, but neither the size of the CAG expansion nor the degree of CAG repeat variation parallels the detailed findings of neuropathological involvement. We conclude that somatic instabilities of the CAG repeat cause tissue variability of the CAG repeat size in DRPLA but other region or cell type-specific factors would be involved to explain the selectivity of cell damage in DRPLA.

Adult↗

PubMed1995

Behavioral involvement of central dopamine D1 and D2 receptors in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys.

To clarify the roles of dopamine D1 and D2 receptors in behavioral symptoms of Parkinson's disease, antiparkinsonian effects of various dopamine agonists in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian monkeys were investigated with regard to induction of hyperactivity such as excitability, irritability and aggressiveness. The non-selective dopamine agonist apomorphine ameliorated the parkinsonism, but induced marked hyperactivity dose-dependently. Pretreatment with either the dopamine D1 antagonist SCH 23390 or the dopamine D2 antagonist sulpiride markedly suppressed the apomorphine-induced hyperactivity with slight attenuation of the antiparkinsonian effects. Both the dopamine D2-receptor agonist quinpirole and the dopamine D1-receptor agonist SKF 82958 ameliorated the parkinsonism in a dose-dependent manner with a slight induction of hyperactivity. Combination treatment of a threshold dose of quinpirole with that of SKF 82958 augmented the antiparkinsonian effects without a marked induction of hyperactivity. However, the combination treatment at higher doses induced marked hyperactivity accompanied by augmented antiparkinsonian effects. These results suggest that stimulation of either central dopamine D1 or D2 receptors is requisite for the antiparkinsonian effects and concurrent strong stimulation of both central dopamine D1 and D2 receptors causes marked hyperactivity which may be predictive of dopaminergic psychiatric side effects.

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

PubMed1995

Combination treatment of the partial D2 agonist terguride with the D1 agonist SKF 82958 in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinsonian cynomolgus monkeys.

The optimal combination of a dopamine D2 agonist and a D1 agonist was evaluated for symptomatic treatment of Parkinson's disease. Behavioral effects of combination treatment of the full D2 agonist quinpirole or the partial D2 agonist terguride with the full D1 agonist SKF 82958 [(I) 6-Chloro-7, 8-dihydroxy-3-allyl-1-phenyl-2, 3, 4, 5-tetra-hydro-1H-3-benzazepine] were investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys with attention to the induction of hyperactivity such as irritability, excitability and aggressiveness and of dyskinesias such as licking of paws, chewing and biting. Both quinpirole and SKF 82958 alone improved the parkinsonism with a slight induction of the hyperactivity and dyskinesias. Terguride also improved the parkinsonism but did not induce the hyperactivity and dyskinesias. Combination treatment of quinpirole with SKF 82958 not only showed a tendency to augment the antiparkinsonian effects but also induced the marked hyperactivity and dyskinesias. On the other hand, combination treatment of terguride with SKF 82958 also augmented the antiparkinsonian effects but did not induce any hyperactivity and dyskinesias. These findings suggest that combination therapy with a partial D2 agonist and a full D1 agonist or monotherapy with a dopamine agonist that has both partial D2 and full D1 agonist properties might be beneficial for treating motor dysfunction in Parkinson's disease without inducing dopaminergic side effects.

Animals↗

PubMed1994

In vivo human myocardial metabolism during aerobic exercise by phosphorus-31 nuclear magnetic resonance spectroscopy.

A few studies have been made in vivo on human myocardial energy metabolism. Hence, no discussion has taken place on metabolism during exercise or of training effects on metabolism. We examined human myocardial energy metabolism at rest and during exercise, and also training effects on the metabolism by phosphorus-31 nuclear magnetic resonance (31P NMR)-spectroscopy. Six sedentary male students (Cont) and six male long distance runners (Tr) were the subjects. Energy metabolism data were obtained from myocardium during rest and exercise by the region selection method using 31P NMR. Rotation of the legs while riding a bicycle, which was fitted with an ergometer we had made ourselves for NMR, imposed given exercise intensities. The heart rate was measured in a stationary phase during exercise. Although the heart rate at rest in the Tr group was significantly lower [Tr, 52.5 (SD 3.1) beat.min-1; Cont, 67.1 (SD 2.9) beat.min-1], no significant difference was observed in myocardial energy metabolism using the 31P NMR method [Tr, phosphocreatine/beta-adenosine 5'-triphosphate (PCr/beta-ATP); 1.51 (SD 0.02); Cont, 1.51 (SD 0.01)]. When NMR measurements were investigated at two different intensities of exercise, heart rates in the Cont group were significantly higher by about 20 beat.min-1 than those in the Tr group at both exercise intensities, while no difference in energy metabolism was observed between the groups or between rest and exercise [Tr, 75.9 (SD 3.6), 88.3 (SD 3.7) beat.min-1; PCr/beta-ATP 1.51 (SD 0.03), 1.51 (SD 0.03); Cont, 95.9 (SD 2.4), 115.1 (SD 3.5) beat.min-1, PCr/beta-ATP 1.51 (SD 0.01), 1.51 (SD 0.04)].(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1994

Muscle energetics in short-term training during hypoxia in elite combination skiers.

Four well-trained combination skiers were studied through pre- and post-training for the effects of short-term intermittent training during hypoxia on muscle energetics during submaximal exercise as measured by Phosphorus-31 nuclear magnetic resonance and maximal aerobic power (VO2max). The hypoxia and training in the cold was conducted in a hypobaric chamber and comprised 60-min aerobic exercise (at an intensity equivalent to the blood lactate threshold), using a cycle ergometer or a treadmill twice a day for 4, consecutive days at 5 degrees C, in conditions equivalent to an altitude of 2000 m (593 mm Hg). No change in VO2max was observed over the training period, while in the muscle energetics during submaximal exercise, the values of phosphocreatine/(phosphocreatine+inorganic phosphate) and intracellular pH were found to be significantly increased by training during hypoxia. During recovery, the time constant of phosphocreatine was found to have been significantly reduced [pre, 27.9 (SD 6.7) s; post, 22.5 (SD 4.7) s, P < 0.01]. The observed inhibition of phosphocreatine as well as that of intracellular pH changes after training during hypoxia and quicker recovery of phosphocreatine in submaximal exercise tests, may indicate improved oxidative capacity (i.e. a high adenosine 5'-triphosphate formation rate) despite the short-term hypoxia training.

Adult↗

PubMed1994

Changes in magnetic resonance images in human skeletal muscle after eccentric exercise.

To investigate the time-course of changes in transverse relaxation time (T2) and cross-sectional area (CSA) of the quadriceps muscle after a single session of eccentric exercise, magnetic resonance imaging was performed on six healthy male volunteers before and at 0, 7, 15, 20, 30 and 60 min and 12, 24, 36, 48, 72 and 168 h after exercise. Although there was almost no muscle soreness immediately after exercise, it started to increase 1 day after, peaking 1-2 days after the exercise (P < 0.01). Immediately after exercise, T2 increased significantly in the rectus femoris, vastus lateralis and intermedius muscles (P < 0.05) and decreased quickly continuing until 60 min after exercise. At and after the 12th h, a significant increase was perceived again in the T2 values of the vastus lateralis and intermedius muscles (P < 0.01) [maximum 9.3 (SEM 2.8)% and 10.9 (SEM 2.2)%, respectively]. The maximal values were exhibited at 24-36 h after exercise. In contrast, the rectus femoris muscle showed no delayed-stage increase. Also, in CSA, an increase after 12 h was observed in addition to the one immediately after exercise in the vastus lateralis, intermedius and medialis and quadriceps muscles as a whole (P < 0.01), reaching the maximal values at 12-24 h after exercise. The plasma creatine kinase activity remained unchanged up to 24 h after and then increased significantly 48 h after exercise (P < 0.05). Beginning 12 h after exercise, the subjects whose T2 and CSA increased less than the others displayed a faster decrease in muscle soreness.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Dilemma in the treatment of Parkinson's disease with L-dopa.

L-Dopa pioneered the symptomatic therapy of Parkinson's disease. While this treatment proved effective in the treatment of parkinsonian akinesia, rigidity and tremor, prolonged L-dopa treatment was often noted to result in dyskinesia, psychosis and 'on-off' phenomena. This increasing disability of L-Dopa-treated parkinsonian patients, however, is not correlated with the duration of L-dopa treatment. Mortality due to Parkinson's disease has decreased significantly after the introduction of L-dopa treatment. The development of D1-selective dopamine agonists and the introduction of neuroprotective rather than symptomatic therapy are required for treating Parkinson's disease.

Humans↗

PubMed1994

Seven-year follow-up study of bromocriptine therapy for Parkinson's disease.

A 7-year nationwide study of bromocriptine monotherapy and combination therapy with bromocriptine and levodopa in Parkinson's disease is reported. Of 22 patients who had been on bromocriptine monotherapy for 7 years (group B), 16 remained improved or remained in the same stages of Hoehn and Yahr, and no wearing-off phenomenon or dyskinesia was observed. In another 56 patients who were started on bromocriptine alone, but in whom combination therapy with levodopa was instituted at some time in the 7 years (group BL), disease progressed faster than in group B. A wearing-off phenomenon and dyskinesia occurred in 34% and 5.4% of the patients, respectively. These manifestations appeared only after initiation of levodopa. The favorable course of group B suggests possible neuroprotective effects of bromocriptine or may be due to the inevitable selection of patients who had a favorable course originally.

Adult↗

PubMed1994

Pharmacological characterization of the novel anxiolytic beta-carboline abecarnil in rodents and primates.

beta-Carboline abecarnil was behaviorally and biochemically characterized as a new anxiolytic agent in rodents and primates in comparison with the benzodiazepine (BZ) anxiolytics. Oral treatment with abecarnil (0.5-10 mg/kg) showed a potent anticonflict activity in the water-lick test in rats. The minimal effective dose was lower than those of BZ anxiolytics, such as etizolam, diazepam, clotiazepam and tofisopam. Abecarnil also showed taming effects to suppress fighting and aggressive behaviors in mice and monkeys with little sedative and ataxic effects, in contrast to the BZ anxiolytics producing marked sedative and ataxic effects. Furthermore, abecarnil suppressed both the sedative and ataxic effects induced by diazepam. Abecarnil bound to rat cerebellar BZ1 receptors (Ki = 0.24 nM) with higher affinity than to rat spinal cord BZ2 receptors (Ki = 1.3 nM), whereas BZ derivatives bound to both the receptors with a low and equal affinity. GABA-ratios of abecarnil were 1.9 for the BZ1 receptors and 2.8 for the BZ2 receptors, and they were smaller than those of diazepam and flunitrazepam. Thus, in contrast to the BZ derivatives, abecarnil may act as a selective partial agonist at central BZ1 receptors, resulting in its potent anticonflict and taming effects with little sedative and ataxic effects.

Aggression↗

PubMed1993

Neuroleptic malignant syndrome in a parkinsonian woman during the premenstrual period.

A 45-year-old woman with Parkinson's disease developed neuroleptic malignant syndrome (NMS) despite lack of levodopa withdrawal. She experienced two episodes characterized by indomethacin-resistant hyperthermia, hyperhidrosis, and aggravation of parkinsonism. The symptoms, however, disappeared during menstruation. We suggest that the development of NMS may depend, in part, upon the hormonal state.

Body Temperature↗

PubMed1992

Therapeutic effects of arotinolol, a beta-adrenergic blocker, on tremor in MPTP-induced parkinsonian monkeys.

The effect of arotinolol, a peripherally acting beta-adrenergic-blocking agent, on postural or kinetic tremor was studied in monkeys with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism. Male cynomolgus monkeys (Macaca fascicularis) were treated with three injections of MPTP hydrochloride (0.3 mg/kg, i.v.) at an interval of 3-4 days, followed by several injections of the same dose every 7 days. Four monkeys with persistent parkinsonian symptoms manifested for greater than 1 year were used. The animals developed mild to moderate degrees of postural or kinetic tremor, and their motor activity was reduced. Arotinolol (20-30 mg/kg, s.c.) significantly suppressed postural tremor in a dose-dependent manner. Propranolol (20-30 mg/kg) was also effective in suppressing the tremor. However, the application of propranolol induced emesis, whereas arotinolol had no adverse effects. These results suggest that arotinolol is a useful adjunct to dopaminergic therapy for tremor in Parkinson's disease.

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

PubMed1992

Muscle energetics during exercise by 31P NMR.

Previous studies have shown that a decrease in muscle tension is not proportional to decrease in the ATP concentration and free energy for ATP degradation but is proportional to the decrease in ATP consumption during muscle contraction, and that the free ADP concentration in the cell can be estimated using the Pi/PCr ratio obtained by 31P NMR. From this view, we discuss findings on muscle energetics during exercise that have been clarified by 31P NMR and its future problems.

Animals↗

PubMed1992

[The intraocular pressure lowering effects of UF-021, a novel prostaglandin related compound, in animals].

The ophthalmic solution of UF-021, a novel prostaglandin (PG) related compound, was investigated for its intraocular pressure (IOP) reducing activity and local ocular side effects in different species of animals. UF-021 ophthalmic solution (0.03 to 0.24%), when topically applied to the eyes of rabbits, caused dose-dependent IOP reduction (2.8 to 5.2 mmHg), without transient IOP rise. Both in cats and monkeys, UF-021 ophthalmic solution (0.12%) elicited rapid, significant IOP reduction (ca. 9 mmHg and 2 mmHg, respectively), without any controversial, local ocular side effects being revealed. On the other hand, PGE2, PGF2 alpha-isopropyl ester all brought about marked increases in IOP prior to development of their IOP reducing activities. In addition, these primary PGs showed intense local ocular irritation, which presented a striking contrast with UF-021. Enhancement of IOP reducing activity, coupled with freedom from any significant ocular side effects, as described above, suggests that UF-021 ophthalmic solution could be promising as a new anti-glaucoma agent.

Animals↗

PubMed1991

Evidence for binding of at least two factors, including T-rich strand-binding factor(s) to the single-stranded ARS1 sequence in Saccharomyces cerevisiae.

To study the mechanism of initiation of eukaryotic chromosomal replication, we examined protein factors interacting with the ARS1 region located near the centromere of chromosome IV in Saccharomyces cerevisiae. Using the gel shift assay, we found protein factor(s) which specifically bound to the T-rich strand of the region containing the core consensus and its flanking sequences in ARS1, but not to the opposite strand. We designated this factor ATS (ARS1, T-rich strand-binding factor(s]. Similar specific complexes were also detected with oligonucleotide probes specific for the H4 or C2G1 ARS. As we have previously identified another binding factor, we conclude that at least two factors bind to the single-stranded ARS1 sequence.

Base Sequence↗

PubMed1991

Tears of cruciate ligaments and menisci: evaluation with cine MR imaging.

A cine magnetic resonance (MR) imaging technique, involving the acquisition of kinematic sagittal images during knee movement, was used to evaluate 52 symptomatic knee joints. Results were compared with those obtained by means of static three-dimensional (3D) MR imaging. Twenty-seven of the 28 anterior cruciate ligament (ACL) tears and 22 of 24 normal ligaments were correctly identified at cine MR imaging for a sensitivity of 96% and a specificity of 92%. Static 3D MR imaging yielded a sensitivity of 71% and a specificity of 88%. All four posterior cruciate ligament tears were identified at cine and 3D MR imaging. For meniscal tears, cine MR imaging yielded a sensitivity of 48% and a specificity of 96%; the sensitivity and specificity for 3D MR imaging were 71% and 96%, respectively. Cine MR imaging proved to be more useful than static MR imaging in assessing the tightness of cruciate ligaments, especially of those that were partially torn, and in assessing the movement of meniscal-free fragments. The increased information obtained with cine MR imaging may warrant continued investigation and clinical application.

Adult↗

PubMed1990

Single-strand-binding factor(s) which interact with ARS1 of Saccharomyces cerevisiae.

Since plasmids containing autonomously replicating sequence(s) (ARS) can transform Saccharomyces cerevisiae cells at high frequency, ARS are considered to be the replication origins of chromosomes. To study the mechanism of initiation of eukaryotic chromosomal replication, we examined protein factors which interact with the ARS1 region located near the centromere of chromosome IV in S. cerevisiae. Using the gel-shift assay, we found protein factors which bound to a single-stranded, 97-bp fragment of the ARS1 region containing the core consensus. Competition experiments with various oligodeoxyribonucleotides (oligos) suggest that a site recognized by the factor(s) was within the element containing the core consensus and adjacent close matches to the core consensus of the minus strand. Indeed, when the oligo containing the minus strand of this element was used as a probe, two oligo-protein complexes were detected. Mutations in the core consensus reduced these binding activities. When the plus-strand oligo of the same region was used as a probe, a retarded band was also detected, but with less specific binding. Considering the fact that the core consensus and close matches to the core consensus are important for ARS function, these results imply that the protein factors detected in this experiment may participate in DNA replication.

Base Sequence↗