Biomedical subjects

Ryoichi Nagatomi

Publications and source records attributed to Ryoichi Nagatomi.

17 recordsLinked to original sources

PubMed2007

Notch2 negatively regulates myofibroblastic differentiation of myoblasts.

Myofibroblasts are one of the key cellular components involved in fibrosis of skeletal muscle as well as in other tissues. Transforming growth factor-beta1 (TGF-beta1) stimulates differentiation of mesenchymal cells into myofibroblasts, but little is known about the regulatory mechanisms of myofibroblastic differentiation. Since Notch2 was shown to be downregulated in TGF-beta1-induced non-muscle fibrogenic tissue, we investigated whether Notch2 also has a distinctive role in myofibroblastic differentiation of myogenic cells induced by TGF-beta1. TGF-beta1 treatment of C2C12 myoblasts led to expression of myofibroblastic marker alpha-smooth muscle actin (alpha-SMA) and collagen I with concomitant downregulation of Notch2 expression. Overexpression of active Notch2 inhibited TGF-beta1-induced expression of alpha-SMA and collagen I. Interestingly, transient knockdown of Notch2 by siRNA in C2C12 myoblasts and primary cultured muscle-derived progenitor cells resulted in differentiation into myofibroblastic cells expressing alpha-SMA and collagen I without TGF-beta1 treatment. Furthermore, we found Notch3 was counter-regulated by Notch2 in C2C12 cells. These findings suggest that Notch2 is inhibiting differentiation of myoblasts into myofibroblasts with downregulation of Notch3 expression.

Actins↗

PubMed2006

Knockdown of hypoxia-inducible factor-1alpha by siRNA inhibits C2C12 myoblast differentiation.

We analyzed the role of Hypoxia-inducible factor (HIF)-1alpha in myoblast differentiation by examining the expression and regulation of HIF-1alpha in proliferating and differentiating C2C12 myoblast, and by knocking down HIF-1alpha of C2C12 myoblasts with small interfering RNA (siRNA), given that HIF-1alpha has been shown to be involved in differentiative process in non-muscle tissues. Although HIF-1alpha mRNA was constantly expressed in C2C12 myoblasts both under growth and differentiating phase, HIF-1alpha protein was hardly detectable in the growth phase but became detectable only during myogenic differentiation even under normoxia. During early stage of C2C12 myogenesis, HIF-1alpha accumulated in the nuclei of myogenin-positive myoblasts. The inhibition of proteasome in the growth phase led to HIF-1alpha protein accumulation, whereas in the differentiation phase the inhibition of Hsp90, which stabilizes HIF-1alpha, suppressed HIF-1alpha accumulation. Therefore, we suggest that the level of HIF-1alpha protein expression is regulated by a proteasome-and chaperon-dependent pathway in C2C12 myoblast. Knockdown of HIF-1alpha effectively blocked myotube formation and myosin heavy chain (MHC) expression. Finally, HIF-1alpha expression in vivo was confirmed in the regenerative muscle tissue of mice after eccentric exercise. We conclude that HIF-1alpha is required for C2C12 myogenesis in vitro, and suggest that HIF-1alpha may have an essential role in regenerative muscle tissue in vivo.

Animals↗

PubMed2006

Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1.

BACKGROUND: Although considerable experimental and animal evidence shows that green tea may possess potent activities of neuroprotection, neurorescue, and amyloid precursor protein processing that may lead to cognitive enhancement, no human data are available. OBJECTIVE: The objective was to examine the association between green tea consumption and cognitive function in humans. DESIGN: We analyzed cross-sectional data from a community-based Comprehensive Geriatric Assessment (CGA) conducted in 2002. The subjects were 1003 Japanese subjects aged > or =70 y. They completed a self-administered questionnaire that included questions about the frequency of green tea consumption. We evaluated cognitive function by using the Mini-Mental State Examination with cutoffs of <28, <26, and <24 and calculated multivariate-adjusted odds ratios (ORs) of cognitive impairment. RESULTS: Higher consumption of green tea was associated with a lower prevalence of cognitive impairment. At the <26 cutoff, after adjustment for potential confounders, the ORs for the cognitive impairment associated with different frequencies of green tea consumption were 1.00 (reference) for < or =3 cups/wk, 0.62 (95% CI: 0.33, 1.19) for 4-6 cups/wk or 1 cup/d, and 0.46 (95% CI: 0.30, 0.72) for > or =2 cups/d (P for trend = 0.0006). Corresponding ORs were 1.00 (reference), 0.60 (95% CI: 0.35, 1.02), and 0.87 (95% CI: 0.55, 1.38) (P for trend = 0.33) for black or oolong tea and 1.00 (reference), 1.16 (95% CI: 0.78, 1.73), and 1.03 (95% CI: 0.59, 1.80) (P for trend = 0.70) for coffee. The results were essentially the same at cutoffs of <28 and <24. CONCLUSION: A higher consumption of green tea is associated with a lower prevalence of cognitive impairment in humans.

Aged↗

PubMed2006

Dietary long-chain n-3 fatty acids of marine origin and serum C-reactive protein concentrations are associated in a population with a diet rich in marine products.

BACKGROUND: Several studies have reported that the intake of n-3 polyunsaturated fatty acids (PUFAs) or fish is inversely associated with serum C-reactive protein (CRP) concentrations, but few studies have evaluated the relations between serum CRP concentrations and consumption of n-3 PUFAs derived from marine products in populations with a diet rich in marine products. Therefore, it is still unclear whether a greater consumption of n-3 PUFAs is associated with lower serum CRP concentrations. OBJECTIVE: The aim of this study was to investigate the relations between n-3 PUFA intake and serum CRP concentration in the Japanese, who have a diet rich in marine products. DESIGN: We designed a cross-sectional survey of 401 men and 570 women aged > or =70 y who were living in Japan. CRP concentrations were measured, and subjects whose serum CRP concentrations were > or =10.0 mg/L were excluded. Dietary intake was assessed with a self-administered diet-history questionnaire. RESULTS: After adjustment for several predictors of inflammation, the odds ratio of high CRP (> or =1.0 mg/L) for increasing quartiles of total n-3 PUFA and eicosapentaenoic acid + docosahexaenoic acid were 1.0, 0.72, 0.57, and 0.44 (P for trend = 0.01) and 1.0, 0.91, 0.76, and 0.54 (P for trend = 0.03), respectively. CONCLUSIONS: Greater intake of n-3 PUFAs derived from marine products, as measured with a self-administered questionnaire, was independently related to a lower prevalence of high CRP concentrations in this older Japanese population with a diet rich in marine products. Our findings suggest that even very high intakes of n-3 PUFAs may lower serum CRP concentrations.

Aged↗

PubMed2006

Exhaustive exercise induces differential changes in serum granulysin and circulating number of natural killer cells.

The circulating number of natural killer (NK) cells largely changes after an acute bout of physical exercise. Granulysin is a cytolytic granule protein with a broad range of antimicrobial and tumoricidal activities produced and released by human NK cells and cytolytic T lymphocytes. Since NK cells constitutively produce granulysin, most serum granulysin in healthy humans is derived from NK cells. Serum graulysin levels in the healthy humans may therefore reflect the size of whole-body NK cell population in the body. The aim of this study was to determine the effect of an acute bout of exhaustive exercise on serum granulysin in comparison with the circulating number of NK cells. Six healthy, young male volunteers participated in the study. Each subject underwent both exhaustive exercise and resting sessions in a random order with at least a seven-day interval. Subjects were asked to run to exhaustion on a treadmill with an incremental graded protocol. Blood samples were collected before, immediately after, and 1 hr, 3 hr, 6 hr, 12 hr and 24 hr after exercise. Serum granulysin levels were measured by enzyme-linked immunosorbent assay (ELISA). NK cells were determined by flow cytometry. Exhaustive exercise induced a 4.8-fold increase in peripheral blood NK cells, but no significant change in serum granulysin. Our results support the hypothesis that exhaustive exercise-induced changes in the circulating number of NK cells represent a redistribution of lymphocytes, rather than the change in the size of whole-body NK cell population.

Adult↗

PubMed2006

[Effectiveness of ability grouping in structured fall prevention exercise program for frail elderly people].

AIM: To assess the effectiveness of ability grouping in a fall prevention structured exercise program for elderly people. METHODS: We enrolled 124 subjects from among 2,582 elderly people aged 70 to 84 years living in the Tsurugaya district in Sendai City. Exclusion criteria were 1) motor fitness scale (MFS) score 9 points or more, 2) severe sensory, cognitive, or 3) physical disorders, and 4) nursing care grade 2 or more. Those ranked in the lower fourth and in the upper 3 fourths of the timed up and go test (TUGT) were each randomly assigned to 3 groups. Subjects in groups A and B had an exercise program for lower and higher fitness subjects separately, whereas all subjects in group C underwent a single exercise program. The exercise program, once a week for 12 weeks, consisted of strength and stability training. TUGT, lateral reach (LR), leg power per body weight and MFS were measured after the intervention and compared with the baseline values. RESULTS: There were no difference in the baseline characteristics among the groups. For group A, no significant changes in physical fitness measures, for group B a small but significant deterioration in LR, and for group C a small but significant deterioration in LR and TUGT were observed. MFS score improved significantly in all groups. CONCLUSION: Ability grouping appeared to be effective for a short-term exercise program in maintaining the physical ability, but the effectiveness did not reach statistical significance in the randomized controlled design.

Accidental Falls↗

PubMed2006

[Comparison of intensive and moderate individual life-style intervention programs for overweight or obese persons with fasting glucose levels of 95-125 mg/dl in Japan].

OBJECTIVES: There are considerable differences in individual health education programs for persons at high risk of type 2 diabetes between ordinary Japanese life-style modification programs and the Diabetes Prevention Program in the US, the former being relatively moderate and the latter more intensive. We therefore compared the effectiveness of intensive and moderate intervention, focusing on the frequency of individual educational classes. METHODS: The subjects were men and women aged 44-69 years living in Nishiaizu town, Fukushima prefecture in Japan. Their fasting plasma glucose concentration was between 95 and 125 mg/dl at health examinations conducted in 2002 or 2003. They also had a body mass index (BMI) of 23.0 or higher, a fasting plasma glucose concentration of 125 mg/dl or lower and a post-load plasma glucose concentration (2 h) of 199 mg/dl or lower in the 2004 survey. We assigned the subjects according to their residences to an intensive life-style intervention group (two education classes per month; n = 11) or a moderate intervention group (one education class per month; n = 14). The main outcome measure was the change in body weight after 6 months of intervention. RESULTS: The loss of body weight was -3.5 kg (P< .0001) in the intensive intervention group and -1.8 kg (P = 0.02) in the moderate group, and the net difference in body weight loss between the groups was -2.0 kg (95% confidence interval -4.0 to -0.05; P = 0.045) after adjustment for age, sex, and baseline body weight. BMI and subcutaneous fat area showed similar results. The post-load plasma glucose concentration (2 h) and other tested values showed no significant net change between the two groups. CONCLUSIONS: Intensive and moderate intervention both reduced body weight in overweight or obese persons at high risk of type 2 diabetes. The intensive intervention, two sessions of individual education classes per month, was significantly more effective than the moderate one for reducing body weight.

Adult↗

PubMed2006

The implication of alterations in leukocyte subset counts on immune function.

Changes elicited by physical exercise in the numbers or the activity of blood T lymphocytes, NK cells and neutrophils are sometimes considered as indicators of altered immunocompetence. By comparing the pathological conditions, in which the changes in the numbers of cells resemble observations in the exercise studies, however we notice large discrepancies in the clinical manifestations. Supplementary information regarding the differences in cytokines and mediators responsible for altered distributions helps to explain this difference and the significance of altered distribution of the cells for immunocompetence. Alterations in the numbers and activities of T lymphocytes, NK cells and neutrophils may serve as markers of sympathetic and glucocorticoid activities, which per se may influence immunocompetence not necessarily deterioration.

Exercise↗

PubMed2005

Effect of foot shock stress on the interferon-gamma production of murine intestinal intraepithelial lymphocytes.

To investigate the effect of stress on interferon (IFN)-gamma production by intestinal intraepithelial lymphocytes (IEL), we exposed male C3H/HeN mice to electric foot shock for 30 min a day for 5 consecutive days. Immediately after the final foot shock stress, IEL from small intestine were isolated by Percoll density gradient. The stress induced a marked suppression of IFN-gamma production by IEL stimulated with immobilized anti-CD3 mAb and a marked decrease in the proportion of IFN-gamma-producing CD3+ IEL or alphabetaTCR+ IEL stimulated with PMA+ionomycin. The alphabetaTCR+ subset was the major cause of stress-induced suppression of IFN-gamma production by IEL. Glucocorticoid induced the suppression of IFN-gamma production by IEL in vitro, which was reversed by mifepristone (RU486), a glucocorticoid receptor antagonist. In vivo administration of RU486 reversed the stress-induced suppression of IFN-gamma production by IEL. In conclusion, repeated foot shock stress suppressed IFN-gamma production of IEL by stress-induced elevation of endogenous glucocorticoid. Substantial suppression of the alphabetaTCR+ subset was the major cause of the suppression.

Animals↗

PubMed2005

Factors associated with suicidal ideation in an elderly urban Japanese population: a community-based, cross-sectional study.

The objective of the present study was to evaluate the association between suicidal ideation and potentially related factors in an elderly urban Japanese population. This was a community-based, cross-sectional study. Urban community residents aged 70 years or more were interviewed regarding suicidal ideation and sociodemographic and health-related variables. Subjects with depressive symptoms underwent further evaluation by psychiatrists using criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Associations were evaluated using univariate and multivariate logistic regression analyses. Of the 1145 eligible participants, 52 (4.5%) reported thoughts of suicide. Of 143 subjects with depressive symptoms (Geriatric Depression Scale, 14+), 22 (15.4%) reported suicidal ideation over a 2-week period. After controlling for depressive symptoms, lack of social support and impaired instrumental activities of daily living were significantly associated with thoughts of suicide. After controlling for the potentially associated factors detected in the univariate analysis, depressive symptoms were strongly associated with thoughts of suicide. In the elderly with depressive symptoms, mental disorders, including depressive and alcohol-related disorders, were significantly associated with suicidal ideation over a 2-week period. In the urban community setting, screening for lack of social support, impaired instrumental activities of daily living, and depressive symptoms, followed by diagnostic evaluation for mental disorders, particularly for depressive syndromes and alcohol-related disorders, may provide a practical and effective means of identifying elders at high risk of suicide.

Aged↗

PubMed2005

Influence of leisure-time physical activity on the relationship between C-reactive protein and hypertension in a community-based elderly population of Japan: the Tsurugaya project.

There are several studies indicating an association between C-reactive protein (CRP) and blood pressure (BP) in the Japanese population, but the influence of physical activity has not been considered. Therefore, we designed a cross-sectional survey to determine whether leisure-time physical activity (LTPA) modifies the relation between CRP and hypertension among Japanese elderly. Our study population comprised 643 subjects aged 70 years and over in whom CRP, home BP, and self-reported LTPA were measured. LPTA was categorized into three levels of intensity--walking, brisk walking, and sports-and a questionnaire was used to estimate the level in each patient. Hypertension was defined as a home systolic BP of 135 mmHg or over and/or home diastolic BP of 85 mmHg or over or current use of antihypertensive agents. LTPA levels were associated with both CRP and hypertension. After adjustment for factors affecting CRP and hypertension, and additional adjustment for LTPA levels, the odds ratio (95% confidence interval) of hypertension by CRP was 2.21 (range: 1.33-3.72), 1.99 (1.17-3.42), and 2.38 (1.36-4.21) times higher in subjects in the second, third, and fourth quartiles of CRP, as compared to subjects in the first quartile, respectively. A multiple regression model showed a positive and significant relation between log-transformed CRP and systolic BP after adjustment for potential confounding factors when participants taking antihypertensive medication were excluded. This is the first study to clarify that the positive significant relation between CRP and hypertension was independent of LTPA levels among Japanese elderly.

Aged↗

PubMed2005

Repeated stress suppresses interferon-gamma production by murine intestinal intraepithelial lymphocytes.

Intestinal intraepithelial lymphocytes (IEL), one of the major effector components in the mucosal immune system, are phenotypically and functionally distinct from thymic and peripheral T cells. To investigate the effect of repeated stress on the number and function of IEL, we exposed male C3H/HeN mice to mild electric foot shock for 30 min/day for 5 consecutive days. Immediately after the final foot shock stress, the blood, spleen, thymus and small intestine of each of the mice were obtained. As a functional measure, we evaluated interferon (IFN)- gamma production by IEL, since IFN-gamma is a key immunomodulating cytokine in mucosal immune responses. Serum corticosterone level was elevated immediately after foot shock stress. There were no significant changes in the number of whole IEL and CD3+ IEL subsets after the stress. In contrast, the stress led to a significant decrease in the total number of thymocytes, particularly the reduction in the number of CD4+CD8+ thymocytes. Thymocytes expressed the highest level of intracellular glucocorticoid receptor (GR), followed by splenocytes and IEL. The foot shock stress induced a marked suppression of IFN-gamma production by IEL, when stimulated with immobilized anti-CD3 monoclonal antibody. Furthermore, corticosterone suppressed the IFN-gamma production by cultured IEL, which was prevented by Mifepristone (RU486), a GR antagonist. In summary, repeated foot shock stress did not alter the numbers of IEL and CD3+ IEL subsets, but suppressed IFN-gamma production by IEL, which was probably mediated by the elevated corticosterone. We therefore propose that stress influences host defense by suppressing the production of IFN-gamma in IEL.

Animals↗

PubMed2004

Comparison of heart rate variability and stroke volume variability.

In order to compare the heart rate variability (HRV) and stroke volume variability (SVV), supine electrocardiographic (ECG) and the time series data of left ventricular (LV) volume recordings were taken in 12 healthy adult male volunteers. The low frequency (LF) and high frequency (HF) peaks of HRV and SVV were evaluated quantitatively by power spectral analysis. The fractal dimension (FD) of the time series data was analyzed by the box-counting method. A LF peak around 0.1 Hz and a HF peak around 0.3 Hz were as clearly observed in the SVV spectrum as in the HRV spectrum. The LF/HF ratio in SVV was significantly lower than that in HRV, while the FD was significantly higher in SVV than in HRV. No significant correlation of HF, LF or FD was observed between HRV and SVV. Our results indicate that SVV provides different information about the activity of the autonomic nervous system than HRV.

Adult↗

PubMed2004

Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress.

The aim of this study was to elucidate the mechanism responsible for lymphopenia after exercise. Seven young healthy men volunteered for this study. Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. To determine the effects of exercise, subjects performed exhaustive cycling exercise. PBMC were cultured with plasma obtained before and after the cycling exercise. Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. We analyzed cortisol- or plasma-treated PBMC to determine their ability to migrate through membrane filters in response to stromal cell-derived factor 1alpha/CXCL12. Cortisol dose- and time-dependently augmented CXCR4 expression on T lymphocytes, with <6 h of treatment sufficient to augment CXCR4 on T lymphocytes. Postexercise plasma also augmented CXCR4 expression. Cortisol or postexercise plasma treatment markedly enhanced migration of T lymphocytes toward CXCL12. Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise.

Acute Disease↗

PubMed2004

Myofibers express IL-6 after eccentric exercise.

BACKGROUND: Interleukin (IL)-6 is locally produced in skeletal muscles and shows a remarkable increase in plasma after eccentric exercises. OBJECTIVE: To elucidate the cell types in the muscles responsible for IL-6 production after eccentric exercises. STUDY DESIGN: Controlled laboratory study. METHODS: An eccentric contraction model was made using electrical stimulation. The authors investigated the muscle damage and regeneration processes after eccentric exercises histologically, and the cell types expressing IL-6 and its subcellular compartimentalization with time immunohistochemically after eccentric exercises. RESULTS: Swollen myofibers were detected from 8 hours to 3 days after exercises. Disrupted myofibers were detected from 24 hours to 7 days, with a peak of 3 days. IL-6 was detected only in the cytoplasm of myofibers until 12 hours; thereafter, it was found in the inflammatory cells and proliferating satellite cells as well. The swollen myofibers were negatively stained for IL-6. The positive ratios of IL-6 in myofibers immediately increased after exercises, peaked in 12 hours, and then decreased. CONCLUSIONS: After eccentric exercises, IL-6 expression increased in myofibers preceding the disruption of myofibers. IL-6 might be closely related to muscle damage caused by strenuous exercises.

Animals↗

PubMed2004

C-reactive protein and peripheral artery disease among Japanese elderly: the Tsurugaya Project.

We investigated the cross-sectional relationship between ankle brachial index and cardiovascular disease risk factors, including C-reactive protein (CRP), among Japanese elderly, a topic which has had little prior epidemiologic study. Our study population comprised 946 subjects aged at least 70 years in whom both CRP and ankle brachial index were measured. The participants were classified into a low (ankle brachial index<0.9) and normal ankle brachial index group. We found that current smoking, high-density lipoprotein cholesterol <40 mg/dl, a low body mass index (continuous variable), hypertension, diabetes and statin use were all significantly related to a lower ankle brachial index. Higher log-transformed CRP level was significantly related to a lower ankle brachial index after adjustment for the cardiovascular risk factors mentioned above (p <0.01). The odds ratios for low ankle brachial index compared to 0-1 risk factors were 5.79 (95% confidence interval [CI]: 2.99-11.20) for 2 risk factors and 17.45 (95% CI: 6.78-49.91) for 3 or more risk factors; independently of other risk factors, the odds ratio for CRP>1.0 mg/l was 2.10 (95% CI: 1.13-3.88) compared to lower CRP values. Thus, a high level of CRP is related to a low ankle brachial index among Japanese elderly as well as Western subjects. This is the first study to report the relationship between CRP and low ankle brachial index among Japanese elderly.

Aged↗

PubMed2003

Effects of exercise training on physical activity in older people: a randomized controlled trial.

BACKGROUND: Recent randomized controlled trials indicated that exercise training for elderly significantly increased their physical fitness. However, very few studies have examined changes in physical activity after exercise training. The purpose of this study was to investigate whether six-month exercise training for older adults can increase and maintain their physical activity in daily life. METHODS: Sixty-two men and women aged 60 to 81 years (mean age 67.1 years), living in communities, were randomly allocated into an exercise group (n = 32) or a control group (n = 33). The intervention started in April 1998 and lasted for 25 weeks. The exercise regimen consisted of endurance training and resistance exercises in a two-hour class conducted at least twice a week. The subjects completed a physical activity diary at each pre-intervention (March 1998), post-intervention (September 1998) and follow-up (April 1999) measurement of physical activity. Physical activity, expressed as total daily energy expenditure, was calculated by multiplying the amount of time spent in each activity and the corresponding METs. RESULTS: Total daily energy expenditure significantly increased from 40.8 kcal/kg/day to 43.5 kcal/kg/day in the exercise group (p = 0.03), but did not change in the control group. At the follow-up measurement, the mean total daily energy expenditure in the exercise group remained significantly higher, by 1.7 kcal/kg/day, than that at the pre-intervention (p = 0.05). CONCLUSIONS: This randomized controlled trial indicated that exercise training for elderly was effective in increasing physical activity in daily life.

Activities of Daily Living↗