Myoglobin and O2 consumption in exercising human gastrocnemius muscle.
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Adult↗
Biomedical subjects
S Kuno
Publications and source records attributed to S Kuno.
Outgrowth of pseudopodial cables induced by all-trans retinoic acid in micromere-derived cells isolated from sea urchin embryos.
Cultured cells derived from micromeres of sea urchin embryos underwent pseudopodial cable growth without spicule rod formation in the presence of all-trans retinoic acid (tRA) or insulin. Pseudopodial cable growth caused by tRA or insulin was inhibited by genistein, a protein tyrosine kinase inhibitor. Phosphorylation of protein tyrosine residue was augmented in the cells treated with tRA or insulin and was inhibited by genistein. Probably, protein tyrosine kinase takes an indispensable part in signal transduction systems for tRA and insulin in these cells. In tRA-treated cells, augmentation of the phosphorylation of protein tyrosine residue was accompanied by an increase in the activity of protein tyrosine kinase and was inhibited by actinomycin D, inhibiting cable growth. Activation of this enzyme in tRA-treated cells probably depends on RNA synthesis. In insulin-treated cells, augmentation of tyrosine residue phosphorylation occurred without any appreciable change in this enzyme's activity and was hardly affected by actinomycin D. Phosphorylation of protein tyrosine residue seems to be activated by the binding of insulin to an insulin receptor. Pseudopodial cable growth in these cells treated with tRA or insulin was inhibited by wortmannin. Phosphatidylinositol 3 kinase probably participates in tRA and insulin signal transduction systems.
Animals↗
Comparative analysis of NMR and NIRS measurements of intracellular PO2 in human skeletal muscle.
1H NMR has detected both the deoxygenated proximal histidyl NdeltaH signals of myoglobin (deoxyMb) and deoxygenated Hb (deoxyHb) from human gastrocnemius muscle. Exercising the muscle or pressure cuffing the leg to reduce blood flow elicits the appearance of the deoxyMb signal, which increases in intensity as cellular PO2 decreases. The deoxyMb signal is detected with a 45-s time resolution and reaches a steady-state level within 5 min of pressure cuffing. Its desaturation kinetics match those observed in the near-infrared spectroscopy (NIRS) experiments, implying that the NIRS signals are actually monitoring Mb desaturation. That interpretation is consistent with the signal intensity and desaturation of the deoxyHb proximal histidyl NdeltaH signal from the beta-subunit at 73 parts per million. The experimental results establish the feasibility and methodology to observe the deoxyMb and Hb signals in skeletal muscle, help clarify the origin of the NIRS signal, and set a stage for continuing study of O2 regulation in skeletal muscle.
Adult↗
Postural adjustment response to depth direction moving patterns produced by virtual reality graphics.
PURPOSE: Human posture is controlled by a combination of vestibular, somatosensory and visual information. This paper is concerned with postural readjustment responses induced by vection. In the visual control of posture, visually-induced perception of self-motion plays an important role and is called vection. Vection is difficult to measure quantitatively because it is a highly subjective phenomenon. HYPOTHESIS: An optokinetic stimulus that moves in depth induces vection. We hypothesize that the magnitude of the visually-induced body sway is correlated with the degree of vection. METHODS: A depth optokinetic stimulus (DOKS) was projected onto a head-mounted display (HMD) worn by standing subjects. The DOKS consisted of a random dot pattern that was perceived three-dimensionally and moved in depth sinusoidally. Vection was estimated in two ways, a verbal assessment and a joystick maneuver. In addition, visually-induced body sway was measured by monitoring five reference points on the body by two video-motion analyzers. RESULTS: The magnitude of the subjective vection was highly correlated with visually-induced body sway and was strongly dependent on the velocity of the visual stimulus. The ankle joint was pivoted during visually-induced body sway and acted as a motion initiator. When the magnitude of body sway was large, the body movement was adjusted at the hip and head-neck joints. CONCLUSIONS: The high correlation between vection and body sway suggests that vection can be estimated quantitatively by measuring visually-induced body sway.
Adult↗
[Current diagnosis and treatment of Parkinson's disease].
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Adrenal Medulla↗
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↗
Muscle deoxygenation in aerobic and anaerobic exercise.
It has been generally accepted that the use of oxygen is a major contributor of ATP synthesis in endurance exercise but not in short sprints. In anaerobic exercise, muscle energy is thought to be initially supported by the PCr-ATP system followed by glycolysis, not through mitochondrial oxidative phosphorylation. However, in real exercise practice, we do not know how much of this notion is true when an athlete approaches his/her maximal capacity of aerobic and anaerobic exercise, such as during a graded VO2max test. This study investigates the use of oxygen in aerobic and anaerobic exercise by monitoring oxygen concentration of the vastus lateralis muscle at maximum intensity using Near Infra-red Spectroscopy (NIRS). We tested 14 sprinters from the University of Penn track team, whose competitive events are high jump, pole vault, 100 m, 200 m, 400 m, and 800 m. The Wingate anaerobic power test was performed on a cycle ergometer with 10% body weight resistance for 30 seconds. To compare oxygenation during aerobic exercise, a steady-state VO2max test with a cycle ergometer was used with 25 watt increments every 2 min. until exhaustion. Results showed that in the Wingate test, total power reached 774 +/- 86 watt, about 3 times greater than that in the VO2max test (270 +/- 43 watt). In the Wingate test, the deoxygenation reached approximately 80% of the established maximum value, while in the VO2max test resulted in approximately 36% deoxygenation. There was no delay in onset of deoxygenation in the Wingate test, while in the VO2max test, deoxygenation did not occur under low intensity work. The results indicate that oxygen was used from the beginning of sprint test, suggesting that the mitochondrial ATP synthesis was triggered after a surprisingly brief exercise duration. One explanation is that prior warm-up (unloaded exercise) was enough to provide the mitochondrial substrates; ADP and Pi to activate oxidative phosphorylation by the type II a and type I myocytes. In addition, transmural pressure created by the muscle contraction reduces blood flow, causing relative hypoxia.
Adult↗
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↗
Anti-endothelial cell antibody in preeclampsia: clinical findings and serum cytotoxicity to endothelial cell.
BACKGROUND: The role of anti-endothelial cell antibody (AECA) in systemic vasculitis has been reported. One candidate which may disrupt vascular function is AECA. In order to investigate the role of AECA in preeclampsia, the incidence of AECA positive patients, the characteristics of the clinical findings of AECA positive patients and also the cytotoxicity of AECA positive serum for cultured endothelial cells was studied. METHODS: Serum samples were taken from 57 preeclampsia (including 37 severe cases) and 46 normal pregnant women. The AECA were measured by ELISA using human umbilical vein endothelial cells. The cytotoxicity for cultured endothelial cells by test serum was measured by using 51Cr release assay. RESULTS: The incidence of IgG and IgM AECA were revealed in 26.3% and 10.5% of preeclampsia respectively. AECA was detected more frequently in severe (29.7%) than in mild preeclampsia (20.0%). In cases with severe proteinuria of greater than 200 mg/dl we detected a significantly higher incidence of AECA than in mild cases (p < 0.04). The incidence of AECA was not significantly increased in cases with severe hypertension or IUGR. The AECA positive sera had greater cytotoxic activity on endothelial cells than AECA negative sera (p < 0.03). CONCLUSIONS: The appearance of AECA is related to the severity of proteinuria and the cytotoxicity to endothelial cells by AECA positive sera may play a role in causing the endothelial damage in preeclampsia.
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↗
Effects of 20 days of bed rest on physiological cross-sectional area of human thigh and leg muscles evaluated by magnetic resonance imaging.
The present study was to investigate the effects of 20 days of bed rest on morphological characteristics of lower limb skeletal muscles. Ten sedentary volunteers (5 males and 5 females) were participating in this study. Magnetic resonance imaging techniques were used to measure the physiological cross-sectional areas (PCSAs) of the major muscles and muscle groups of the lower limb. Consecutive images were taken from the right thigh and leg of subjects, and muscle volumes (MV), muscle length, and fiber length were calculated. PCSA of each muscle was determined as MV times the cosine of the angle of fiber pennation divided by fiber length. PCSA of knee extensor and flexor muscles were significant reduced during and after bed rest. MV and PCSA of individual muscles in the knee extensors decreased by -5.1 % to -8.0%. In knee flexors, MV and PCSA in biceps femoris (long head), semitendinosus, semimembranosus, and sartorius decreased during and after bed rest. MV and PCSA in medial and lateralis [correction of andateralis] gastrocnemius, and soleus were remarkably reduced by -9.4 to -10.3% after bed rest. The results suggest that there is a great variability of muscle atrophy in the lower limb muscle groups or individual muscle after bed rest and that the plantar flexors primarily affected.
Adult↗