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S Kuno

Publications and source records attributed to S Kuno.

At least 37 records · Page 2Linked to original sources
PubMed2001

The effects of cytoplasmic transfer of mtDNA in relation to whole-body endurance performance.

The purpose of this study was to examine the relation between whole-body aerobic capacity and mitochondrial facilities. The mitochondrial enzyme system of oxidative phosphorylation (OXPHOS) is encoded both by mitochondrial DNA (mtDNA) and nuclear DNA. To identify the effect of mtDNA on whole-body aerobic capacity, we fused the platelets of the study subjects that contained mtDNA but that lacked nuclear DNA with rho(0) HeLa cells, which lacked mtDNA, and isolated repopulated cybrids. The mitochondrial respiratory functions of the cybrids, estimated from cell oxygen consumption and cytochrome-c oxidase (CCOX), were compared between endurance athletes and sedentary controls. The oxygen consumption was 18.5 +/- 3.9 and 18.2 +/- 4.1 nmol/min/ml/10(7) cells in athletes and controls, respectively. The CCOX activity was 98.8 +/- 17.5 and 116.7 +/- 9.8%, compared with fibroblasts in athletes and controls, respectively. No significant difference was noted between groups in either cell oxygen consumption or CCOX activity. These results show that the OXPHOS enzymes coded by mtDNA do not strongly influence whole-body aerobic fitness.

Adult↗
PubMed2001

Relationship between mitochondrial DNA polymorphism and the individual differences in aerobic performance.

This study focused on the mitochondrial DNA (mtDNA) as the genetic factor most likely to bring about the individual difference in endurance capacity or its trainability. Platelets contain mtDNA but no nuclear DNA, whereas rho(0)-HeLa cells have nuclear DNA but no mtDNA. The oxidative capacity of mitochondria in the cultured cells, which were fused rho(0)-HeLa cell with platelets obtained from individual subjects (the so-called "cybrids"), reflects the individual mtDNA polymorphism in the gene-coding region. The purpose of this study was to investigate the relationship between the oxidative capacity of cybrids and the individual difference in endurance capacity, or its trainability. Forty-one sedentary young males took part in an 8-week endurance training program. They were determined by using their VO(2 max) as an index of endurance capacity on an ergocycle before and after the endurance training program. The relations between VO(2 max) before endurance training or the change of it by endurance training and the oxidative capacity of cybrids were investigated. There was no relation between them, and two groups were drawn from all subjects, based on one standard division of their initial VO(2 max): the higher pre-VO(2 max) group (n = 6) and the lower pre-VO(2 max) group (n = 5) (51.8 +/- 3.5 ml/min/kg vs. 33.3 +/- 3.8 ml/min/kg, p < 0.01). No significant difference was found between the O(2) consumption of the cybrids in the higher initial VO(2 max) group and that in the lower initial VO(2 max) group (16.3 +/- 4.9 vs. 15.9 +/- 2.0 nmol O(2)/min/10(7) cells, NS). Furthermore, neither the cytochrome c oxidase (COX) activity nor the complex I + III activity of cybrids showed a significant difference between the two groups. The oxidative capacity of cybrids between the high trainability group (n = 6) (Delta VO(2 max) 12.1 +/- 1.6 ml/min/kg) and the low trainability group (n = 9) (Delta VO(2 max) 2.3 +/- 0.5 ml/min/kg) was also similar. Thus the mtDNA polymorphism is very unlikely to relate to the individual difference in endurance capacity or its trainability in young sedentary healthy subjects.

Adult↗
PubMed2000

Selegiline and desmethylselegiline stimulate NGF, BDNF, and GDNF synthesis in cultured mouse astrocytes.

We investigated the effects of selegiline and desmethylselegiline on synthesis of neurotrophic factors in cultured mouse astrocytes. Treatment with 2 mM selegiline for 24 h increased the contents of NGF, BDNF, and GDNF in the culture medium 26-, 1.7-, and 4.2-fold over the control, respectively. With this drug the maximum relative mRNA levels of NGF, BDNF, and GDNF were 6.2-fold at 2 h, 3.4-fold at 6 h, and 2.7-fold at 2 h, respectively. Selegiline at 0.2 mM completely inhibited the MAO activity, but had no effect on the content of neurotrophic factors, suggesting that stimulation of neurotrophic factors by selegiline is independent of MAO-B inhibition. Desmethylselegiline at 1.68 mM for 24 h elevated the NGF, BDNF, and GDNF contents 4.1-, 1.7-, and 2.4-fold over the control, respectively; and the relative transcript levels of NGF, BDNF, and GDNF reached 2.6-fold at 2 h, 1.7-fold at 6 h, and 1.8-fold at 2 h, respectively. These findings suggest that selegiline and desmethylselegiline may protect neurons by up-regulating endogenous NGF, BDNF, and GDNF synthesis.

Amphetamines↗
PubMed2000

Apomorphine up-regulates NGF and GDNF synthesis in cultured mouse astrocytes.

Apomorphine, a D1/D2 dopamine agonist, is an anti-parkinsonian drug. We examined the effects of apomorphine on synthesis of neurotrophic factors in cultured mouse astrocytes. After 24 h incubation with apomorphine, NGF and GDNF contents in the culture medium increased to 122-fold and 1.8-fold of the control, respectively; whereas the BDNF content did not change significantly. In Northern blot analysis, expression of NGF mRNA in astrocytes reached the maximum level at 6 h after addition of the drug. By semiquantitative RT-PCR analysis, the GDNF transcript level was found to reach 2.9-fold of the control level at 15 h. These results suggest that apomorphine may exert neuroprotective effects by stimulation of NGF and GDNF synthesis in astrocytes.

Animals↗
PubMed2000

Influence of interleukin-1beta gene polymorphisms on age-at-onset of sporadic Parkinson's disease.

We studied genetic polymorphisms in the promoter region (position -511) and exon 5 (position +3953) of the interleukin (IL)-1beta gene in 122 Japanese patients with Parkinson's disease (PD) and 112 controls. We also examined polymorphisms in the IL-1alpha and the IL-1 receptor antagonist genes. No significant difference was found in these genetic markers between PD patients and controls. However, PD patients with homozygotes for allele 1 at position -511 of the IL-1beta gene (IL-1B-511*1), a low producer of IL-1beta, were significantly earlier in the disease onset than those with the IL-1B-511*2 homozygotes, a high producer of IL-1beta. This suggests that IL-1beta might play a role, possibly a protective effect for dopaminergic neurons, in PD. Further population and functional studies are necessary to clarify the role of IL-1beta in PD patients.

Age Factors↗
PubMed2000

The use of magnetic resonance images to investigate the influence of recruitment on the relationship between torque and cross-sectional area in human muscle.

The purpose of the present study was to investigate the effect of recruitment on the relationship between peak torque and physiological cross-sectional area (PCSA) in human muscle. A group of 11 healthy men participated in this study. Isokinetic knee extension torques at seven (0, 30, 60, 120, 180, 240, and 300 degrees x s(-1)) velocities were determined. Magnetic resonance imaging (MRI) was performed to calculate PCSA of right quadriceps femoris (QF) muscle. Exercise-induced contrast shifts in spin-spin relaxation time (T2)-weighted MRI were taken at rest and immediately after repetitive knee-extension exercise and T2 of QF were calculated. The MRI pixels with T2 values more than 1 SD greater than the means at rest were considered to represent QF muscle that had contracted. The area of activated PCSA within the total in QF was expressed as percentage activated PCSA and used as an index of muscle recruitment. The PCSA correlated with peak torque at 0 degree x s(-1) (r = 0.615, P<0.05); in contrast, activated PCSA correlated with peak torque at 120 degrees x s(-1) (r = 0.603, P<0.05) and 180 degrees x s(-1) (r = 0.606, P<0.05). Additionally, there was a significant difference in correlation coefficients between the activated PCSA-peak torque relationship and the PCSA-torque relationship (P<0.05). These results suggested that muscle recruitment affects the PCSA-torque relationship.

Adult↗
PubMed2000

Caspase activities and tumor necrosis factor receptor R1 (p55) level are elevated in the substantia nigra from parkinsonian brain.

The activities of caspase-1 and caspase-3 were measured by use of fluoropeptides as substrates for the first time in the brain (substantia nigra, caudate nucleus, putamen, cerebellum, and frontal cortex) from control and parkinsonian patients. The activities of caspases in the brain were significantly higher in the substantia nigra from parkinsonian patients than those in the brain from control patients (p < 0.01). However, the activities of caspases in the caudate nucleus, putamen, cerebellum, and frontal cortex showed no significant difference between parkinsonian and control patients. The tumor necrosis factor (TNF) receptor R1 (TNF-R1, p55) level was also elevated in the substantia nigra of the parkinsonian brain in comparison with that of controls (p < 0.05). Since both caspases and TNF-R1 may play important roles in apoptotic cell death through TNF-alpha-induced signaling pathway, our present data suggest the presence of a proapoptotic environment in the substantia nigra of parkinsonian brain, probably inducing vulnerability of neurons and glias towards a variety of noxious factors.

Adult↗
PubMed2000

Assessment of voiding dysfunction in Parkinson's disease by the international prostate symptom score.

OBJECTIVES: To find the incidence of voiding dysfunction in Parkinson's disease and to examine the relation between the voiding dysfunction and various indices of the disease (disease severity, disease duration, age, sex, and treatment with antiparkisonian drugs), the presence of voiding dysfunction was quantitatively estimated in patients sampled on the unselected (consecutive) basis. METHODS: Using the international prostate symptom score, lower urinary tract symptoms were quantitatively evaluated in all patients with Parkinson's disease visiting this neurological clinic during 1 month. RESULTS: Of the 203 patients who had completed the questionnaire, 55 (27%) were considered to have symptomatic voiding dysfunction. The degree of lower urinary tract symptoms in these patients was well correlated with the severity of the disease rather than with the disease duration or the age. Thirty three (16%) patients had irritative symptoms alone, whereas three (1.5%) patients had obstructive symptoms alone. The irritative and obstructive symptoms were concomitant in 13 (6%) patients. Quality of life was disturbed by lower urinary tract symptoms, and this disturbance paralleled the severity of the disease. The influence of antiparkisonian drugs on the lower urinary tract symptoms was uncertain. The incidence of lower urinary tract symptoms seemed to be independent of sex, but obstructive symptoms were prevalent in male patients. CONCLUSIONS: This study suggests that voiding dysfunction in patients with Parkinson's disease progressively develops at advanced stages (> or =Hoehn and Yahr stage 3 of the disability). The International prostate symptom score is useful in evaluating the voiding dysfunction of neurodegenerative disease in both men and women, not only reflecting prostatic symptoms.

Analysis of Variance↗
PubMed2000

Body sway induced by depth linear vection in reference to central and peripheral visual field.

PURPOSE: A significant correlation between the magnitude of linear vection and the degree of body sway induced by a visual stimulus perceived as moving in depth was previously described (Jpn J Physiol 49: 417-424, 1999). The purpose of this study was to examine the role of the central and peripheral visual fields in inducing vection and body sway. METHODS: Ten healthy volunteer students who had no vestibular or neurological disorders served as subjects. A depth optokinetic stimulus (DOKS) was projected onto a head-mounted display (HMD) and was perceived to move in depth. Different amounts of the central or peripheral visual field were masked independently. The magnitude of the linear vection induced by the DOKS was evaluated by verbal assessment and compared with the magnitude of induced body sway. Body sway was monitored by a video-motion-analyzer that recorded the movement of the head, shoulder, hip, knee and ankle. RESULTS: The magnitude of vection was correlated with the frequency of DOKS and also with the amplitude of body sway (r = 0.74). When the central visual field was restricted by 10 to 30%, there was almost no change in the induced body sway and vection. However, when central occlusion was greater than 40%, depth perception and induced body movement were greatly reduced. With increasing amounts of peripheral field occlusion from 50 to 90%, there was a greater reduction of both vection and body sway. CONCLUSION: Vection is strongly correlated with body movement, and vection and body sway were more dependent on stimulation of the peripheral visual field.

Adult↗
PubMed2000

Voiding dysfunction and Parkinson's disease: urodynamic abnormalities and urinary symptoms.

PURPOSE: We evaluated bladder dysfunction and Parkinson's disease in regard to disease severity and determined whether subjective patient urinary symptoms correlated with urodynamic abnormalities. MATERIALS AND METHODS: We assessed bladder dysfunction in 70 patients with Parkinson's disease and urinary symptoms using the International Prostate Symptom Score and urodynamic tests. RESULTS: Urodynamic evaluation revealed detrusor hyperreflexia in 47 patients (67%), hyporeflexia or areflexia in 11 (16%), hyperreflexia with impaired contractile function in 6 (9%), hyperreflexia with detrusor-sphincter dyssynergia in 2 (3%) and normal function in 4 (6%). The incidence of urodynamic abnormalities appeared to increase with disease severity. However, the only urodynamic parameter that correlated with disease severity was post-void residual urine volume. On the other hand, symptom index scores increased with disease severity. The irritative symptom score correlated with maximum cystometric capacity and volume at initial desire to void, whereas the obstructive symptom score correlated with post-void residual urine volume. Also, irritative and obstructive scores were good predictors of overactivity during the storage and underactivity at the voiding phases. CONCLUSIONS: Bladder function may deteriorate progressively with advancing disease. Symptom scores are fairly accurate for predicting likely urodynamic abnormalities. Our results imply that quantifying subjective urinary symptoms is useful for estimating the severity and type of bladder dysfunction.

Adult↗
PubMed2000

Effects of aging on EMG variables during fatiguing isometric contractions.

The purpose of this study was to evaluate the neuromuscular adaptation that occurred with aging, by comparing young and aged subjects with respect to changes in surface EMG from the tibialis anterior muscle during fatiguing contractions. EMG variables such as the averaged rectified value (ARV), median frequency (MDF), and muscle fiber conduction velocity (MFCV) were calculated during maximal (MVC, 3 sec) and submaximal (60% MVC, 60 sec) isometric contractions. Muscular force, ARV, MDF, and MFCV during MVC were significantly greater in the young than in the elderly (p < 0.05). EMG amplitude increased and the waveform slowed in all subjects during submaximal contractions, indicating the development of local muscle fatigue. As fatigue progressed, the ARV increased and the MDF and MFCV decreased significantly (p < 0.01). The fatigue-induced changes in the MDF and MFCV were significantly smaller in aged than in young subjects (p < 0.05), a trend also seen in the ARV change, which means that the elderly cannot be fatigued as much as the young with contractions of the same relative intensity. These results as a whole suggest that the aged subjects hold an adaptive motor strategy to cope with age-related neuromuscular deteriorations, due to the decline of motor unit activation and selective atrophy of fast twitch muscle fibers.

Adult↗
PubMed1999

A mutation in the microtubule-associated protein tau in pallido-nigro-luysian degeneration.

We detected a missense mutation in exon 10 of tau that causes a substitution at codon 279 (N279K) in a Japanese patient with a familial background of parkinsonism and dementia originally described as pallido-nigro-luysian degeneration. This mutation is the same as one seen in a Caucasian family with pallido-ponto-nigral degeneration. The similarities between these two families suggest a common genetic mechanism that may account for the peculiar distribution of neuroglial degeneration with tauopathy.

Amino Acid Sequence↗
PubMed1999

Exogenous microglia enter the brain and migrate into ischaemic hippocampal lesions.

We compared migration of systemically injected microglia into normal brain vs. ischaemic brain using a model of ischaemic hippocampal lesion. Microglia were labeled by a fluorescent dye using our standard phagocytosis procedure of microscopic particles and then injected intra-arterially into Mongolian gerbils subjected to ischaemia reperfusion neuronal injury. Delayed death of pyramidal neurons was confirmed by conventional histological analysis and dUTP nick end labeling (TUNEL) method. Clusters of dye-tagged cells migrating into the hippocampal ischaemic lesions were confirmed histochemically to be microglia. Since peripherally injected microglia exhibit specific affinity for ischaemic brain lesions and does not exacerbate ischaemic neuronal injury in the present model, we suggest that microglia may have a potential to be used as a piggy-back ride to deliver therapeutic genes and/or drugs for CNS repair following transitory global ischaemic insult.

Animals↗
PubMed1999

Brain-derived growth factor and nerve growth factor concentrations are decreased in the substantia nigra in Parkinson's disease.

Using highly sensitive sandwich enzyme-linked immunosorbent assays (ELISA), we measured for the first time the concentrations of brain-derived growth factor (BDNF) in the brain (substantia nigra, caudate nucleus, putamen, cerebellum, and frontal cortex) from control and parkinsonian patients. BDNF in the human brain (the order of ng/mg protein) was significantly lower specifically in the nigrostriatal dopamine (DA) regions from parkinsonian patients than in those from control patients. The concentration of nerve growth factor (NGF) was also significantly decreased in the substantia nigra of parkinsonian patients in comparison with that in the controls. Since BDNF and NGF may play important roles in survival and differentiation of neuronal cells, the present data indicate that the lack of neurotrophins, especially BDNF, may be involved in the pathogenesis of PD during progress of neurodegeneration of the nigrostriatal DA neurons.

Adult↗