Biomedical subjects

S Kuno

Publications and source records attributed to S Kuno.

At least 91 records · Page 5Linked to original sources

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

Effects of terguride, a partial D2 agonist, on MPTP-lesioned parkinsonian cynomolgus monkeys.

Behavioral effects of terguride, a partial dopamine D2 agonist, on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned parkinsonian cynomolgus monkeys were compared with those of the dopamine agonist apomorphine and the dopamine antagonist haloperidol. Terguride alone ameliorated the parkinsonism without inducing any sign of excitability, irritability, or aggressiveness (hyperactivity). Apomorphine alone also ameliorated the parkinsonism but induced marked hyperactivity. Haloperidol alone caused worsening of the parkinsonism, inducing transient eyelid closure. In combination with apomorphine, terguride suppressed the hyperactivity induced by apomorphine without reducing its antiparkinsonian effects. Pretreatment with haloperidol suppressed both the antiparkinsonian effects and the hyperactivity induced by apomorphine. Terguride thus exhibits both antiparkinsonian and antihyperactivity effects in a monkey model of Parkinson's disease, suggesting that terguride might be beneficial for treating motor dysfunction and dopaminergic psychosis in advanced Parkinson's disease.

Aggression↗

PubMed1993

Pallidonigroluysian degeneration with iron deposition: a study of three autopsy cases.

In the basal ganglia of three autopsy cases of pallidonigroluysian degeneration, we found marked iron deposition, a finding which has not been mentioned previously in the literature. Besides severe astrogliosis and neuronal loss in the pallidum, Luysian body and nigra, granular deposits of brown pigments were found in the neuropil, microglias, oligodendrocytes and astrocytes in three such the nuclei and the striatum. These brown pigments proved histochemically to be iron. Our histochemical semiquantitative study showed a significantly stronger reaction for iron in the degenerated nuclei in these three cases than in control cases comprising non-degenerative and the other degenerative diseases. Quantitative study with inductively coupled emission spectrometry also demonstrated a markedly higher iron content in the globus pallidus and the striatum in comparison with the control cases. The possibility is discussed that iron deposition plays a role in generating the lesions of pallidonigroluysian degeneration.

Adult↗

PubMed1993

Rotations induced by L-dopa in parkinsonian rats are reduced by an ingestion of amino acids.

We studied the effect of amino acid load on L-dopa-induced rotational behavior in rats with unilateral lesion of the nigrostriatal pathway. Pretreatment of rats with an ingestion of high concentration of amino acids significantly reduced the number of rotations induced by subcutaneously injected L-dopa. These results provide the experimental basis for clinical observations that dietary protein affects the response to L-dopa in parkinsonian patients.

Amino Acids↗

PubMed1993

The dopamine D1 receptor agonist SKF 38393 suppresses detrusor hyperreflexia in the monkey with parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

A pharmacological study using monkeys, in which parkinsonism was induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), was undertaken to elucidate the mechanism underlying urinary bladder dysfunctions in Parkinson's disease. Under ketamine anesthesia, cystometrograms showed that, in MPTP-treated monkeys, a contraction of the urinary bladder was induced with smaller bladder volume than that in normal monkeys. In MPTP-treated monkeys, subcutaneously injected SKF 38393, a dopamine D1 receptor agonist, significantly increased the bladder volume and pressure thresholds for inducing the micturition reflex without affecting those in normal monkeys. In contrast, subcutaneous injections of quinpirole, a dopamine D2 receptor agonist, and apomorphine, a dopamine D1 and D2 receptor agonist, slightly, but significantly reduced the volume threshold of the bladder for the micturition reflex in both normal and MPTP-treated groups. These results indicate that, in parkinsonism, the degeneration of dopaminergic neurons in the substantia nigra leads to the detrusor hyperreflexia, probably due to a failure of activation of dopamine D1 receptors.

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

PubMed1993

Effect of D-penicillamine on pharmacokinetics of levodopa in Parkinson's disease.

A 42-year-old man had suffered from Parkinson's disease for 5 years. Levodopa was effective, but the wearing-off phenomena were severe. Because of relatively low levels of serum copper and ceruloplasmin, D-penicillamine was administered. D-penicillamine increased plasma levodopa concentrations, thereby improving his parkinsonian symptoms. We propose that D-penicillamine facilitates levodopa absorption and, hence, the efficacy of the antiparkinsonian drug.

Absorption↗

PubMed1993

Progress note on Japanese multicenter bromocriptine monotherapy.

The nationwide multicenter collaborative study for evaluating the monotherapy of Parkinson's disease with bromocriptine for a period of 5 years from 1986 was reviewed last year. The present report summarizes the follow-up in its 6th year: it includes 30 patients with Parkinson's disease who continued to receive bromocriptine monotherapy for 6 years and 66 patients who received bromocriptine-levodopa combination therapy during the same period. The mean daily dose of bromocriptine in the 6th year was about the same in the two groups (11.9 and 12.2 mg). In terms of Hoehn-Yahr's severity grade, severity increased in 20% of the patients undergoing bromocriptine monotherapy, whereas of the patients in the bromocriptine-levodopa combination group it was 45%. Wearing-off phenomenon was not seen in the bromocriptine monotherapy group. By contrast, 30% of the patients in the combination therapy group manifested this phenomenon which, when it occurred, invariably followed the administration of levodopa. Absence of the wearing-off phenomenon implies that bromocriptine has a direct protective action on degenerating substantia nigra.

Bromocriptine↗

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↗

PubMed1993

[Parkinsonian tremor, rigidity and flapping tremor].

Tremor occurring at rest (4-6 Hz) is considered to be one of the most characteristic symptoms in patients with Parkinson's disease. Yet, an early stages of the disease only 50% of the patients manifest resting tremor. Indeed, about 15% of Parkinsonian patients never display tremor at any stage of the disease. If tremor is present, its type is essential for differential diagnosis. Pill-rolling movement, for instance, is a hallmark of Parkinson's disease. Parkinsonian patients often show postural tremor associated with certain postures or movement, whereas flapping tremor is indicative of metabolic (ex: hepatic) encephalopathy. Parkinsonian rigidity is unique muscular rigidity. If rigidity is abolished by L-dopa or dopamine agonists, this provides a reliable sign for diagnosis of Parkinson's disease. Pathophysiology of different types of tremor is briefly discussed.

Adult↗

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↗

PubMed1990

Behavioural effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in monkeys.

Subcutaneous injections of a 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), in monkeys induced distinct behavioural changes characterized by head weaving, hindlimb extension and upper limb fluttering. The effects were dose-dependent and were similar to the 5-HT syndrome induced in rats by 8-OH-DPAT. The 5-HT receptor antagonist, metergoline, attenuated the behavioural syndrome seen in response to 8-OH-DPAT. These results suggest that 8-OH-DPAT induces a 5-HT1A receptor-mediated behavioural syndrome in monkeys as well as in rodents.

8-Hydroxy-2-(di-n-propylamino)tetralin↗