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Biomedical subjects

Toshiki Ohta

Publications and source records attributed to Toshiki Ohta.

At least 19 recordsLinked to original sources
PubMed2007

(--)-epigallocatechin gallate enhances prostaglandin F2alpha-induced VEGF synthesis via upregulating SAPK/JNK activation in osteoblasts.

Catechin, one of the major flavonoids presented in plants such as tea, reportedly suppresses bone resorption. We previously reported that prostaglandin F(2alpha) (PGF(2alpha)) stimulates the synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase in osteoblast-like MC3T3-E1 cells. To clarify the mechanism of catechin effect on osteoblasts, we investigated the effect of (--)-epigallocatechin gallate (EGCG), one of the major green tea flavonoids, on the VEGF synthesis by PGF(2alpha) in MC3T3-E1 cells. The PGF(2alpha)-induced VEGF synthesis was significantly enhanced by EGCG. The amplifying effect of EGCG was dose dependent between 10 and 100 microM. EGCG did not affect the PGF(2alpha)-induced phosphorylation of p44/p42 MAP kinase. SB203580, a specific inhibitor of p38 MAP kinase, and SP600125, a specific inhibitor of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), reduced the PGF(2alpha)-induced VEGF synthesis. EGCG markedly enhanced the phosphorylation of SAPK/JNK induced by PGF(2alpha) without affecting the PGF(2alpha)-induced phosphorylation of p38 MAP kinase. SP600125 markedly reduced the amplification by EGCG of the SAPK/JNK phosphorylation. In addition, the PGF(2alpha)-induced phosphorylation of c-Jun was amplified by EGCG. These results strongly suggest that EGCG upregulate PGF(2alpha)-stimulated VEGF synthesis resulting from amplifying activation of SAPK/JNK in osteoblasts.

Animals↗
PubMed2007

Negative regulation by p70 S6 kinase of FGF-2-stimulated VEGF release through stress-activated protein kinase/c-Jun N-terminal kinase in osteoblasts.

UNLABELLED: To clarify the mechanism of VEGF release in osteoblasts, we studied whether p70 S6 kinase is involved in basic FGF-2-stimulated VEGF release in osteoblast-like MC3T3-E1 cells. In this study, we show that p70 S6 kinase activated by FGF-2 negatively regulates VEGF release through SAPK/JNK in osteoblasts. INTRODUCTION: Vascular endothelial growth factor (VEGF) plays an important role in bone metabolism. We have previously reported that fibroblast growth factor-2 (FGF-2) stimulates the release of VEGF through p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells and that FGF-2-activated p38 MAP kinase negatively regulates VEGF release. However, the mechanism behind VEGF release in osteoblasts is not precisely known. MATERIALS AND METHODS: The levels of VEGF released from MC3T3-E1 cells were measured by enzyme immunoassay. The phosphorylation of each protein kinase was analyzed by Western blotting. To knock down p70 S6 kinase in MC3T3-E1 cells, the cells were transfected with siRNA to target p70 S6 kinase. RESULTS: FGF-2 time-dependently induced the phosphorylation of p70 S6 kinase. Rapamycin significantly enhanced the FGF-2-stimulated VEGF release and VEGF mRNA expression. The FGF-2-induced phosphorylation of p70 S6 kinase was suppressed by rapamycin. Rapamycin markedly enhanced the FGF-2-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p44/p42 MAP kinase or p38 MAP kinase. SP600125, a specific inhibitor of SAPK/JNK, suppressed the amplification by rapamycin of the FGF-2-stimulated VEGF release similar to the levels of FGF-2 with SP600125. Finally, downregulation of p70 S6 kinase by siRNA significantly enhanced the FGF-2-stimulated VEGF release and phosphorylation of SAPK/JNK. CONCLUSIONS: These results strongly suggest that p70 S6 kinase limits FGF-2-stimulated VEGF release through self-regulation of SAPK/JNK, composing a negative feedback loop, in osteoblasts.

Animals↗
PubMed2007

[Development of the Telephone Interview for Cognitive Status (TICS) in Japanese].

In recent years, population of elder people has increased in Japan, following augmentation of the number of people with dementia in Japan. Then it is important to detect cognitive impairment in early stage for adequate treatment, care and prevention. We studied 135 subjects, 49 patients with Alzheimer's disease (AD) and 86 healthy controls using Telephone Interview for Cognitive Status (TICS), and developing Japanese version of the TICS (TICS-J). The sensitivity and the specificity of the TICS-J to differentiate AD patients from healthy controls was 98.0% and 90.7%, respectively. Pearson's correlation coefficiency between the TICS-J and Mini-Mental State Examination (MMSE) was 0.858 (p < 0.001). On the receiver operating curves, the area under the curve for the TICS-J was 98.7% (95% CI: 97.5%-100%). These results indicate that TICS-J is sensitive and specific instrument for differentiating AD patients from healthy controls.

Aged↗
PubMed2006

Phosphatidylinositol 3-kinase/Akt auto-regulates PDGF-BB-stimulated interleukin-6 synthesis in osteoblasts.

It has been reported that platelet-derived growth factor (PDGF)-BB stimulates the synthesis of interleukin (IL)-6 in osteoblasts. In the present study, we investigated whether the phosphatidylinositol 3-kinase (PI3K)/Akt is involved in the PDGF-BB-induced IL-6 synthesis in osteoblast-like MC3T3-E1 cells. PDGF-BB markedly induced the phosphorylation of Akt and GSK-3beta. Akt inhibitor, 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, significantly amplified the synthesis of IL-6 by PDGF-BB. The PDGF-BB-induced GSK-3beta phosphorylation was suppressed by the Akt inhibitor. The IL-6 synthesis stimulated by PDGF-BB was markedly enhanced by LY294002 and wortmannin, inhibitors of PI3K. Wortmannin and LY294002 suppressed the PDGF-BB-induced phosphorylation of Akt and GSK-3beta. Taken together, these results strongly suggest that PI3K/Akt negatively regulates the PDGF-BB-stimulated IL-6 synthesis in osteoblasts.

3T3 Cells↗
PubMed2006

Up-regulation by zinc of FGF-2-induced VEGF release through enhancing p44/p42 MAP kinase activation in osteoblasts.

We previously reported that basic fibroblast growth factor (FGF-2) activates stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42 mitogen-activated protein (MAP) kinase resulting in the stimulation of vascular endothelial growth factor (VEGF) release in osteoblast-like MC3T3-E1 cells. In the present study, we investigated whether zinc affects the VEGF release by FGF-2 in MC3T3-E1 cells. The FGF-2-induced VEGF release was significantly enhanced by ZnSO(4) but not Na(2)SO(4). The enhancing effect of ZnSO(4) was dose-dependent between 1 and 100 muM. ZnSO(4) markedly enhanced the FGF-2-induced phosphorylation of p44/p42 MAP kinase while having little effect on the SAPK/JNK phosphorylation. PD98059 significantly reduced the amplification by ZnSO(4) of the FGF-2-stimulated VEGF release. Taken together, our findings strongly suggest that zinc enhances FGF-2-stimulated VEGF release resulting from up-regulating activation of p44/p42 MAP kinase in osteoblasts.

Animals↗
PubMed2006

Involvement of p44/p42 MAP kinase in insulin-like growth factor-I-induced alkaline phosphatase activity in osteoblast-like-MC3T3-E1 cells.

It has been shown that insulin-like growth factor-I (IGF-I) stimulates the activity of alkaline phosphatase, a marker of mature osteoblast phenotype, in osteoblasts. In the present study, we investigated the involvement of the mitogen-activated protein (MAP) kinase superfamily in the IGF-I-stimulated alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells. IGF-I-stimulated alkaline phosphatase activity dose dependently in the range between 1 nM and 0.1 microM. IGF-I induced the phosphorylation of p44/p42 MAP kinase and p38 MAP kinase but not stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK). PD98059 and U0126, specific inhibitors of the upstream kinase that activates p44/p42 MAP kinase, significantly suppressed the IGF-I-induced alkaline phosphatase activity. On the contrary, SB203580 and PD169316, specific inhibitors of p38 MAP kinase, failed to affect the activity induced by IGF-I. Specific inhibitors for phosphatidylinositol 3-kinase (PI3K)/Akt pathway (LY294002 and wortmannin) also had no significant effect on IGF-I-induced p44/p42 MAP kinase phosphorylation. The phosphorylation of p44/p42 MAP kinase induced by IGF-I was reduced by U0126. These results strongly suggest that p44/p42 MAP kinase among the MAP kinase superfamily plays a role in the IGF-I-stimulated alkaline phosphatase activity in osteoblast-like MC3T3-E1 cells.

3T3 Cells↗
PubMed2005

The effects of Tai Chi Chuan on physiological function and fear of falling in the less robust elderly: an intervention study for preventing falls.

The aim of this report is to investigate the effects of 8 weeks of intensive Tai Chi Chuan (TCC) training on physiological function and fear of falling (FOF) in the less-robust elderly. Forty-nine community-dwelling elderly, aged 60 or older, were classified randomly into a TCC training or control group. Physical performance measures (including one-leg stance, trunk flexion, and walking speed) and interviews were conducted before and after the intervention. The TCC group showed significant improvements in balance and flexibility, and a reduced FOF, when compared with the control group after the intervention. However, walking speed did not change significantly. The results suggest that a high-frequency, short-term TCC training program can improve balance, flexibility, and increase the confidence of less-robust elderly. These suggest the effectiveness of TCC for intervention as a means to prevent falling among high-risk elderly populations.

Accidental Falls↗
PubMed2005

[Non-pharmacological treatment of hypertension in the elderly].

We reviewed non-pharmacological treatment of hypertension in the elderly. Although hypotensive effect of salt restriction was evident, severe salt restriction might result in impairment of QOL by decrease in appetite and consequent nutritional deterioration. Hypotensive effect of mild to moderate aerobic exercise was also evident. Our previous report indicated that decrease in blood pressure was less in older subjects than in younger group. Another study showed that blood pressure decreased even during 3 to 9 months after the beginning of exercise therapy. These findings might indicate that decrease in blood pressure in the elderly was slower than in younger subjects.

Aged↗
PubMed2005

[Nonpharmacological prevention and treatment for osteoporosis].

Treatment of osteoporosis includes prevention for further bone loss, treatment of fracture-related pain, building bone mass, and modifying behavior to prevent fracture and/or falls. Improvement of nutritional intake to prevent bone loss, increasing physical activity or exercise training to prevent bone loss or occurrence of falls and/or fracture, and modifying environmental risk factors are essential as nonpharmacological treatment for osteoporosis. The combination of pharmacologic and nonpharmacologic intervention is fundamental to the management of osteoporosis.

Aged↗
PubMed2004

Japanese orthopedists' interests in prevention of fractures in the elderly from falls.

The aim of the present study was to survey the interest of Japanese orthopedists in preventing fractures in the elderly, and investigate their awareness with regard to main prevention strategies such as medications and hip protectors. From the list of 20,899 members of the Japanese Orthopedic Association, we randomly selected a sample of 2035 people. Each orthopedist was sent an anonymous survey consisting of 12 questions during July to August 2001. At that time, risedronate, raloxifene, and parathyroid hormone had not been approved for clinical use in Japan, and even alendronate had just been approved. Of the survey forms sent, 1011 responses were received, for a response rate of 50%. Analysis of these responses showed a very high interest in osteoporosis, fractures in the elderly from falls, and the prevention of such fractures. This interest was associated with physician age, with those above the age of 50 years being 2.3 times more likely to have an interest in each of these than physicians below that age. The respondents considered the most promising measure for the prevention of fractures in the elderly from falls to be fall prevention, followed by exercise and osteoporosis medications. The medication considered to be effective as a monotherapy by the overwhelming number of respondents was bisphosphonates, followed by vitamin D3 and calcitonin. Combination agents cited were vitamin D3, bisphosphonates, and calcitonin, in that order. Forty-two percent of respondents had some knowledge of hip protectors, but confidence in them as a means to prevent fractures was still low. The practical information from our survey should serve as a starting point for comparison to periods when new bisphosphonates or hip protectors become commonly available to Japanese orthopedists. The overall results indicate that Japanese orthopedists are very positive toward fracture prevention.

Accidental Falls↗
PubMed2004

[Present condition and future direction of osteoporosis in Japan].

The purpose of this special issue is to clarify the problems in the prevention, the treatment and the care of osteoporotic patients in Japan. Herein, we presented the accumulating evidence about the epidemiology, the prevention, the screening and the therapy of osteoporosis. We also introduced the countermeasures for osteoporosis through the life and the medical financial studies etc. The government, the medical societies and the foundations support the studies for osteoporosis and have proposed the guidelines for osteoporosis. We overviewed the prospective of osteoporosis and fracture prevention. For the establishment of healthy longevity society, we should continue the effort to solve the problems in osteoporosis in Japan.

Humans↗
PubMed2004

[Cost-effectiveness of osteoporosis treatment].

With Japan's rapidly aging population, a remarkable increase in fragility fractures due to osteoporosis and exhaustion of medical care resources is anticipated. Therefore, the cost-effectiveness of osteoporosis treatment will be more important than ever before. Because the outcome is estimated in terms of gain of life time and improvement in quality of living, a treatment is judged to be cost-effective when its cost per quality adjusted life year (QYALY) gained is below an acceptable threshold. According to studies in Western countries, medicines in use today including alendronate, risedronate, calcium plus vitamin D, calcitonin and raloxifene are cost-effective. However, studies on the cost-effectiveness of osteoporosis treatment based on Japanese data are thought to be needed for Japanese patients.

Aged↗
PubMed2003

Effects of daily activity recorded by pedometer on peak oxygen consumption (VO2peak), ventilatory threshold and leg extension power in 30- to 69-year-old Japanese without exercise habit.

The relationships among walk steps, exercise habits and peak oxygen consumption (VO2peak), ventilatory threshold (VT) and leg extension power (LEP) were examined in 709 apparently healthy Japanese subjects (male 372, female 337) aged 30-69 years. Walk steps were evaluated using a pedometer. VO2peak and VT were assessed by a cycle ergometer test, while LEP was measured with an isokinetic leg extension system (Combi, Anaero Press 3500, Japan). Subjects who participated in exercise three times or more a week demonstrated significantly greater VO2peak and VT when compared with subjects without exercise habits. When a separate analysis was conducted on subjects who exercised fewer than three times per week, we found that the subgroup with the highest number of walk steps showed significantly greater VT in all male subjects and female subjects aged 30-49 years, but a significantly greater VO2peak only in females aged 30-49 years, when compared to the subgroup with the fewest walk steps. These results suggest that although some people exercise less than three times a week, if they are quite active in daily life, such activities might also confer benefits upon their fitness.

Activities of Daily Living↗
PubMed2003

How much exercise is required to reduce blood pressure in essential hypertensives: a dose-response study.

BACKGROUND: Regular aerobic exercise is widely recommended for essential hypertensives. However, it is not clear how much exercise is needed to reduce blood pressure (BP). METHODS: The dose-response relation of exercise training and BP was determined using an 8-week exercise intervention study involving 207 untreated subjects with stage 1 or 2 essential hypertension. Subjects were divided into five groups based on the duration and frequency/week of exercise (sedentary control, 30 to 60 min/wk, 61 to 90 min/wk, 91 to 120 min/wk, and >120 min/wk). Age, gender, height, body mass, body mass index, dietary intake, and baseline BP were not different among the groups. RESULTS: Both systolic and diastolic BP at rest did not change in the nonexercising control group. All four exercise groups demonstrated significant reductions in both systolic and diastolic BP at rest. The magnitude of reductions in systolic BP was greater in the 61 to 90 min/wk group compared with the 30 to 60 min/wk group. There were no greater reductions in systolic BP with further increases in exercise volume. The magnitude of reductions in diastolic BP was not significantly different among four exercise groups. There were no obvious relations between exercise frequency per week and the magnitude of BP decreases with exercise training. CONCLUSIONS: In previously sedentary hypertensive subjects, clinically significant decreases in BP can be achieved with relatively modest increases in physical activity above sedentary levels and that the volume of exercise required to reduce BP may be relatively small that should be reasonably attainable by a sedentary hypertensive population.

Adult↗
PubMed2003

[Preservation of quality of life and its relation to lifestyle in centenarians in Japan: a visitation interview survey].

PURPOSE: To investigate quality of life (QOL) and associated factors in centenarians, we conducted a visitation interview survey for all male and one half of the female centenarians living in Japan, and studied QOL, lifestyle and health status. METHODS: All the male centenarians and a randomly-sampled half of the female centenarians living in Japan were included in the study based on the National Census. Finally, 556 male and 1341 female centenarians participated in the present visitation interview survey and were studied using a structured questionnaire. QOL was assessed from 3 aspects; activities of daily life (ADL), cognitive function (CF) and mental health (MH). RESULTS: Individuals having superior ADL accounted for 30.9% of the male and 13.6% of the female centenarians, those with superior CF were 58.1% and 35.6%, respectively, and those with superior MH were 39.2% and 26.8%, providing evidence that superior QOL was more dominant in males than in females. There were no effects of residential areas (north, east, middle, west, southwest and south of Japan) on the prevalence of ADL, CF and MH. Multiple logistic regression analyses conducted independently, for ADL, CF and MH as dependent valuables revealed that habitual exercise, less decline in visual ability and preservation of masticating ability were associated with better results for these 3 aspects of male centenarians' QOL, and that habitual exercise, less decline in visual ability, spontaneous awakening in the morning, good appetite and having cohabitating family members were associated with superior QOL in the females, suggesting that more factors are operating in the latter. CONCLUSIONS: Several lifestyle factors were found to be associated with preservation of QOL in centenarians in Japan. These results should facilitate establishing a public health and welfare policy for the most senior citizens, a group that has been increasing in Japan.

Aged↗
PubMed2002

[The effects of daily physical activity on QOL in the elderly].

OBJECTIVE: To ascertain the meaning and the influence of daily physical activity on QOL among the elderly, we surveyed their lifestyle exercise habits, cross-sectionally and longitudinally. METHODS: The subjects of this study were all residents living in a certain suburb of Nagoya-city, aged 63, 68, 73, 78, 83 years of age. They answered questionnaires regarding their exercise, physical activity, and QOL with six categories. The same questionnaire survey was conducted again 3 years later, and 958 people who answered both of them were examined in this study. The three-year-trend for physical activities, exercise habits and QOL scores, were analyzed and a comparison of QOL was made between the first and third year data based on the primary physical-activity-scores. In addition we applied logistic regression analysis to investigate the influence of physical activity changes (independent variable) on maintaining or improving of QOL scores (dependent variable). RESULTS: Daily physical activities were well maintained, but the percentage of feasible activities decreased by 5-10% as the sample population aged. On the other hand, 20 to 30% of the subjects increased their physical activity. The more people moved, the higher the QOL scores they had in both cross-sectional and longitudinal analyses. According to the logistic regression analysis, baseline physical activity habits positively contributed to most QOL change, increase in exercise tending to maintain or improve the QOL scores. CONCLUSIONS: Daily physical activity was relatively well maintained among the sample population, and some increased their physical activity scores over the period studied. Those with high values had better physical conditions and a consistently high QOL. These results suggest that maintaining or increasing physical activity positively influences QOL in the elderly.

Activities of Daily Living↗