Biomedical subjects

Hirofumi Tanaka

Publications and source records attributed to Hirofumi Tanaka.

At least 19 recordsLinked to original sources

PubMed2006

Resistance training increases basal limb blood flow and vascular conductance in aging humans.

Age-related reductions in basal limb blood flow and vascular conductance are associated with the metabolic syndrome, functional impairments, and osteoporosis. We tested the hypothesis that a strength training program would increase basal femoral blood flow in aging adults. Twenty-six sedentary but healthy middle-aged and older subjects were randomly assigned to either a whole body strength training intervention group (52 +/- 2 yr, 3 men, 10 women) who underwent three supervised resistance training sessions per week for 13 wk or a control group (53 +/- 2 yr, 4 men, 9 women) who participated in a supervised stretching program. At baseline, there were no significant differences in blood pressure, cardiac output, basal femoral blood flow (via Doppler ultrasound), vascular conductance, and vascular resistance between the two groups. The strength training group increased maximal strength in all the major muscle groups tested (P < 0.05). Whole body lean body mass increased (P < 0.05) with strength training, but leg fat-free mass did not. Basal femoral blood flow and vascular conductance increased by 55-60% after strength training (both P < 0.05). No such changes were observed in the control group. In both groups, there were no significant changes in brachial blood pressure, plasma endothelin-1 and angiotensin II concentrations, femoral artery wall thickness, cardiac output, and systemic vascular resistance. Our results indicate that short-term strength training increases basal femoral blood flow and vascular conductance in healthy middle-aged and older adults.

Aging↗

PubMed2006

Regional hypermethylation and global hypomethylation are associated with altered chromatin conformation and histone acetylation in colorectal cancer.

Regional DNA hypermethylation and global DNA hypomethylation are 2 epigenetic alterations associated with colorectal cancers. However, their correlation with microsatellite instability (MSI) and chromosomal instability (CIN) in colorectal cancer, and their relationship with chromatin conformation and histone modification are not clear. In this study, we analyzed regional and global methylation in 16 cell lines and 64 primary colorectal cancers. We found that MSI and CIN are 2 alternative events in most cell lines and tumors. Furthermore, regional hypermethylation and global hypomethylation are also alternative events in most cases. We also observed a strong correlation between MSI and regional hypermethylation and between CIN and global hypomethylation. We further analyzed chromatin conformation and histone acetylation in cell lines with CIN or MSI. CIN cancers had open chromatin conformation and enriched histone acetylation in repetitive as well as in gene-specific regions. MSI cancers, on the other hand, had closed chromatin conformation and low levels of histone acetylation. After a MSI cell line was treated with 5-aza-2'-deoxycytidine or trichostatin A, the closed chromatin conformation became open, and histone acetylation was enriched. These observations support our hypothesis that in colorectal cancer, regional hypermethylation and global hypomethylation are associated with altered chromatin conformation and histone acetylation, which might have a causal correlation with MSI and CIN, respectively.

Acetylation↗

PubMed2006

BRAF mutation, CpG island methylator phenotype and microsatellite instability occur more frequently and concordantly in mucinous than non-mucinous colorectal cancer.

Mucinous colorectal cancer (CRC) has been reported to have distinct clinicopathological and genetic characteristics. However, the incidence and the relationship among microsatellite instability (MSI), CpG island methylator phenotype (CIMP) and BRAF and KRAS mutations in mucinous and non-mucinous CRC are not known. Activating mutations of BRAF and KRAS and their relationship with MSI and CIMP were examined in 83 sporadic CRC specimens (26 mucinous and 57 non-mucinous CRC). MSI, CIMP, BRAF and KRAS mutation were observed in 17, 24, 25 and 36% of the tumors, respectively. BRAF mutation was highly correlated with MSI (p < 0.001) and CIMP (p < 0.001). A higher incidence of MSI (27% vs. 12%), CIMP (38% vs. 18%, p < 0.05) and BRAF mutation (46% vs. 16%, p < 0.01) was observed in mucinous CRC. KRAS mutation (27% vs. 40%) was observed more frequently in non-mucinous CRC. Significantly higher percentages of mucinous CRC (54%, p < 0.05) had MSI or CIMP or BRAF mutations. Concordant occurrence of 2 or more of these alterations was observed in 39% of mucinous CRC and only 11% of non-mucinous CRC (p < 0.01). The more frequent occurrence and closer association among MSI, CIMP and BRAF mutation in mucinous CRC observed in our study further supports the idea that its pathogenesis may involve distinct genetic and epigenetic changes.

Adenocarcinoma, Mucinous↗

PubMed2006

A novel GTPase, CRAG, mediates promyelocytic leukemia protein-associated nuclear body formation and degradation of expanded polyglutamine protein.

Polyglutamine diseases are inherited neurodegenerative diseases caused by the expanded polyglutamine proteins (polyQs). We have identified a novel guanosine triphosphatase (GTPase) named CRAG that contains a nuclear localization signal (NLS) sequence and forms nuclear inclusions in response to stress. After ultraviolet irradiation, CRAG interacted with and induced an enlarged ring-like structure of promyelocytic leukemia protein (PML) body in a GTPase-dependent manner. Reactive oxygen species (ROS) generated by polyQ accumulation triggered the association of CRAG with polyQ and the nuclear translocation of the CRAG-polyQ complex. Furthermore, CRAG promoted the degradation of polyQ at PML/CRAG bodies through the ubiquitin-proteasome pathway. CRAG knockdown by small interfering RNA in neuronal cells consistently blocked the nuclear translocation of polyQ and enhanced polyQ-mediated cell death. We propose that CRAG is a modulator of PML function and dynamics in ROS signaling and is protectively involved in the pathogenesis of polyglutamine diseases.

Amino Acid Sequence↗

PubMed2006

Resistance training and arterial compliance: keeping the benefits while minimizing the stiffening.

OBJECTIVES: This study aimed to determine the effects of moderate resistance training as well as the combined resistance and aerobic training intervention on carotid arterial compliance. BACKGROUND: Resistance training has become a popular mode of exercise, but intense weight training is shown to stiffen carotid arteries. METHODS: Thirty-nine young healthy men were assigned either to the moderate-intensity resistance training (MODE), the combined resistance training and endurance training (COMBO) or the sedentary control (CONTROL) groups. Participants in the training groups underwent three training sessions per week for 4 months followed by four additional months of detraining. RESULTS: All training groups increased maximal strength in all the muscle groups tested (P < 0.05). Carotid arterial compliance (via simultaneous carotid ultrasound and applanation tonometry) decreased approximately 20% after MODE training (from 0.20 +/- 0.01 to 0.16 +/- 0.01 mm2/mmHg, P < 0.01). No significant changes in carotid arterial compliance were observed in the COMBO (0.20 +/- 0.01 to 0.23 +/- 0.01 mm2/mmHg) and CONTROL (0.20 +/- 0.01 to 0.20 +/- 0.01 mm2/mmHg) groups. Following the detraining period, carotid arterial compliance returned to the baseline level. Peripheral (femoral) artery compliance did not change in any groups. CONCLUSIONS: We concluded that simultaneously performed aerobic exercise training could prevent the stiffening of carotid arteries caused by resistance training in young healthy men.

Adult↗

PubMed2006

Preparation of very reactive thiol-protected gold nanoparticles: revisiting the Brust-Schiffrin method.

The preparation and properties of tert-dodecanethiol protected gold nanoparticles amenable to very rapid surface functionalization by associative mechanism is described. The new material can be easily prepared by controlling the reaction time, because only a limited but enough number of tert-dodecanethiol to stabilize the gold clusters is bond to the surface until about an hour. Accordingly, it can be isolated as a solid and handled much like the highly stabilized Brust-Schiffrin analogues, but reacted very rapidly with any molecular species containing one or multiple functional groups such as thiol, disulfide, pyridine, etc. These characteristics are ideal for the preparation of a variety of new organic-inorganic hybrid nanomaterials by coordinative self-assembly. This possibility was illustrated using meso-tetra(4-pyridyl)porphyrin, which promptly bonded to the reactive protected gold nanoparticles generating a solid that can be grown as thin films with layer-by-layer control on a suitably modified surface.

Adsorption↗

PubMed2006

Electronic properties of a single-walled carbon nanotube/150mer-porphyrin system measured by point-contact current imaging atomic force microscopy.

The electronic properties of a single-walled carbon nanotube/150mer of porphyrin polymer wire system were investigated. Current-voltage (I-V) curves were measured simultaneously along with topographic observations using point-contact current imaging atomic force microscopy. Symmetric I-V curves were obtained at bare single-walled carbon nanotubes but characteristic asymmetrical rectifying behavior was found at the single-walled carbon nanotube/150mer-porphyrin junctions. This finding is of key importance for the development of new nanoscale molecular electronic devices.

Adsorption↗

PubMed2006

Increases in blood flow and shear stress to nonworking limbs during incremental exercise.

PURPOSE: Regular exercise augments endothelium-dependent vasodilatory capacity in the vasculature located in the nonworking limbs. We determined whether blood flow as well as shear stress would change in inactive limbs during acute incremental exercise. METHODS: Eight young healthy female subjects performed graded exercise on arm and leg cycle ergometers that had been modified to minimize the movement of nonworking limbs and to facilitate the placement of Doppler transducers. Both brachial and femoral blood flow was monitored using Doppler ultrasonography. EMG activity was also measured to document that there was no muscular activity in nonworking muscles. RESULTS: During leg exercise, brachial blood flow and calculated shear stress gradually and curvilinearly increased (P < 0.05). At the peak work rate, there was an approximately fourfold increase in blood flow in the brachial artery (19 +/- 6 vs 77 +/- 16 mL x min(-1)). Femoral blood flow and calculated shear stress increased progressively and linearly during arm exercise (P < 0.05). CONCLUSION: We concluded that blood flow to the nonworking limbs increases markedly in proportion to the work intensity. These results suggest that the conduit arteries in the nonworking limbs are exposed to increases in blood flow and shear stress during exercise.

Adult↗

PubMed2005

Molecular junctions composed of oligothiophene dithiol-bridged gold nanoparticles exhibiting photoresponsive properties.

Three oligothiophene dithiols with different numbers of thiophene rings (3, 6 or 9) have been synthesized and characterized. The X-ray single crystal structures of terthiophene 2 and sexithiophene 5 are reported herein to show the exact molecular lengths, and to explain the difference between their UV-visible spectra arising from the different packing modes. These dithiols with different chain lengths were then treated with 2-dodecanethiol-protected active gold nanoparticles (Au-NPs) by means of in situ thiol-to-thiol ligand exchange in the presence of 1 microm gap Au electrodes. Thus the molecular junctions composed of self-assembled films were prepared, in which oligothiophene dithiol-bridged Au-NPs were attached to two electrodes by means of Au-S bonded contacts. The morphologies and current-voltage (I-V) characteristics of these films were studied by SEM and AFM approaches, which suggested that the thickness of the films (3-4 layers) varied within the size of one isolated Au-NP and typical distance-dependent semiconductor properties could be observed. Temperature dependent I-V measurements for these molecular junctions were performed in which the films served as active elements in the temperature range 6-300 K; classical Arrhenius plots and subsequent linear fits were carried out to give the activation energies (deltaE) of devices. Furthermore, preliminary studies on the photoresponsive properties of these devices were explored at 80, 160, and 300 K, respectively. Physical and photochemical mechanisms were used to explain the possible photocurrent generation processes. To the best of our knowledge, this is the first report in which oligothiophene dithiols act as bridging units to link Au-NPs, and also the first report about functionalized Au-NPs exhibiting photoresponse properties in the solid state.

Journal Article↗

PubMed2005

The relationship between global methylation level, loss of heterozygosity, and microsatellite instability in sporadic colorectal cancer.

PURPOSE: The relationship between global hypomethylation, chromosomal instability (CIN), and microsatellite instability (MSI) remains unclear in colorectal cancer. The aim of this study was to investigate the relationship between global methylation status, loss of heterozygosity (LOH), and MSI in sporadic colorectal cancer. EXPERIMENTAL DESIGN: We determined global methylation levels in 80 sporadic colorectal cancers, 51 adjacent normal tissues, and 20 normal tissues using the long interspersed nucleotide elements-combined bisulfite restriction analysis method. We also analyzed 80 colorectal cancers for MSI status and LOH at chromosomes 5q21, 8p12-22, 17p13, and 18q21. RESULTS: We identified 14 cases of MSI (17.5%) and 58 cases of LOH (72.5%). LOH was observed more frequently in microsatellite stable (MSS) cancers than in MSI cancers at all loci. Colorectal cancers showed significantly lower global methylation levels than did normal tissues (41.0+/-9.7% versus 54.3+/-6.5%; P<0.001). MSS cancers showed significantly lower global methylation levels when compared with MSI cancers (39.5+/-9.4% versus 48.2+/-8.2%; P=0.003). Tumors with global hypomethylation (with <or=40% of methylation levels) had a significantly increased number of chromosomal loci with LOH than did tumors without global hypomethylation (1.9 versus 0.9; P<0.001); 11 tumors (13.9%) lacked both MSI and LOH. This subgroup had significantly higher global methylation levels (46.8+/-8.7%) than did MSS cancers with LOH (38.0+/-9.0%; P=0.006). CONCLUSIONS: These data showed a significant association between global hypomethylation and chromosomal instability in sporadic colorectal cancer. This suggests that global hypomethylation plays an important role in inducing genomic instability in colorectal carcinogenesis.

Adult↗

PubMed2005

Arterial compliance of rowers: implications for combined aerobic and strength training on arterial elasticity.

Regular endurance exercise increases central arterial compliance, whereas resistance training decreases it. It is not known how the vasculature adapts to a combination of endurance and resistance training. Rowing is unique, because its training encompasses endurance- and strength-training components. We used a cross-sectional study design to determine arterial compliance of 15 healthy, habitual rowers [50 +/- 9 (SD) yr, 11 men and 4 women] and 15 sedentary controls (52 +/- 8 yr, 10 men and 5 women). Rowers had been training 5.4 +/- 1.2 days/wk for 5.7 +/- 4.0 yr. The two groups were matched for age, body composition, blood pressure, and metabolic risk factors. Central arterial compliance (simultaneous ultrasound and applanation tonometry on the common carotid artery) was higher (P < 0.001) and carotid beta-stiffness index was lower (P < 0.001) in rowers than in sedentary controls. There were no group differences for measures of peripheral (femoral) arterial stiffness. The higher central arterial compliance in rowers was associated with a greater cardiovagal baroreflex sensitivity, as estimated during a Valsalva maneuver (r = 0.54, P < 0.005). In conclusion, regular rowing exercise in middle-aged and older adults is associated with a favorable effect on the elastic properties of the central arteries. Our results suggest that simultaneously performed endurance training may negate the stiffening effects of strength training.

Adaptation, Physiological↗

PubMed2005

Cigarette smoking, regular exercise, and peripheral blood flow.

Acute and chronic smoking reduces peripheral blood flow and shear stress, contributing to the increased incidence of peripheral arterial disease in smokers. Currently, it is not known whether physical activity status influences peripheral blood flow among chronic smokers. Blood flow was measured using Doppler ultrasound on the common femoral artery in nine young otherwise healthy sedentary smokers (eight males/one female) and nine physically-active smokers (six males/three females). Physically-active smokers performed strenuous exercise 4.4 times/week for 8 h/week. No significant differences in body fat, blood pressure, and total cholesterol were observed between groups. Basal femoral artery blood flow was approximately 50% higher in physically-active smokers compared with sedentary smokers (259+/-108 ml min(-1) versus 173+/-47 ml min(-1), P<0.05). The higher basal femoral artery blood flow in physically-active smokers compared with sedentary smokers was associated with a 47% higher femoral artery vascular conductance (2.99+/-1.2 U versus 2.03+/-0.5 U, P<0.05) and a 39% lower vascular resistance (0.38+/-0.13 U versus 0.53+/-0.15 U, P<0.05). Cardiac output, systemic vascular resistance, femoral intima-media thickness, and plasma norepinephrine concentration were not different between the groups. We concluded that smokers who habitually perform physical activity demonstrate greater levels of peripheral blood flow and peripheral vascular conductance. The findings from the present cross-sectional study suggest that chronic smokers may be able to negate, at least in part, the adverse effects of chronic smoking on the peripheral vasculature by performing regular physical activity.

Adult↗

PubMed2005

Lack of age-related decreases in basal whole leg blood flow in resistance-trained men.

Reductions in basal leg blood flow have been implicated in the pathogenesis of metabolic syndrome and functional impairment in humans. We tested the hypothesis that reductions in basal whole leg blood flow with age are either absent or attenuated in those who perform regular strength training. A total of 104 normotensive men aged 20-34 yr (young) and 35-65 yr (middle aged), who were either sedentary or resistance trained, were studied. Mean and diastolic blood pressures were higher (P < 0.05-0.001) in the middle-aged compared with the young men, but there were no significant differences between the sedentary and resistance-trained groups. In the sedentary group, basal whole leg blood flow (duplex Doppler ultrasound) and vascular conductance were lower ( approximately 30 and approximately 38%, respectively; P < 0.01) in the middle-aged compared with the young men. There were no such age-related differences in the resistance-trained group. In the young men, basal whole leg blood flow and vascular conductance were not different between the two activity groups, but, in the middle-aged men, they were higher ( approximately 35 and approximately 36%, respectively; P < 0.01) in the resistance-trained men than in the sedentary men. When blood flow and vascular conductance were expressed relative to the leg muscle mass, the results were essentially the same. We concluded that the age-related reduction in basal whole leg blood flow is absent in resistance-trained men. These results suggest that resistance training may favorably influence leg perfusion in aging humans, independent of its impact on leg muscle mass.

Adult↗

PubMed2005

Retraction.

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Retraction Notice↗

PubMed2005

Acute effects of resistance exercise on arterial compliance.

Decreased central arterial compliance is an emerging risk factor for cardiovascular disease. Resistance training is associated with reductions in the elastic properties of central arteries. Currently, it is not known whether this reduction is from one bout of resistance exercise or from an adaptation to multiple bouts of resistance training. Sixteen healthy sedentary or recreationally active adults (11 men and 5 women, age 27 +/- 1 yr) were studied under parallel experimental conditions on 2 separate days. The order of experiments was randomized between resistance exercise (9 resistance exercises at 75% of 1 repetition maximum) and sham control (seated rest in the exercise room). Baseline hemodynamic values were not different between the two experimental conditions. Carotid arterial compliance (via simultaneous B-mode ultrasound and applanation tonometry) decreased and beta-stiffness index increased (P < 0.01) immediately and 30 min after resistance exercise. Immediately after resistance exercise, carotid systolic blood pressure increased (P < 0.01), although no changes were observed in brachial systolic blood pressure at any time points. These measures returned to baseline values within 60 min after the completion of resistance exercise. No significant changes in these variables were observed during the sham control condition. These results indicate that one bout of resistance exercise acutely decreases central arterial compliance, but this effect is sustained for <60 min after the completion of resistance exercise.

Adaptation, Physiological↗

PubMed2005

Influence of lifestyle modification on arterial stiffness and wave reflections.

Arterial stiffness and wave reflections exert a number of adverse effects on cardiovascular function and disease risk and are associated with a greater rate of mortality in patients with end-stage renal failure and essential hypertension. Accordingly, the prevention and treatment of arterial stiffness are of paramount importance. Because arterial stiffening is being recognized as a critical precursor of cardiovascular disease (CVD), it is essential to understand the role of lifestyle modifications on preventing and reversing arterial stiffening. Available evidence indicates that lifestyle modifications, in particular aerobic exercise and sodium restriction, appear to be clinically efficacious therapeutic interventions for preventing and treating arterial stiffening. Thus, sufficient evidence is available to recommend lifestyle modifications as part of a first-line therapeutic approach for arterial stiffening. However, more information is needed for a full understanding and optimal use of lifestyle modifications in the management of arterial stiffening.

Arteries↗

PubMed2005

Effects of high intensity resistance training on arterial stiffness and wave reflection in women.

BACKGROUND: Cross-sectional studies reported that chronic resistance training is associated with arterial stiffening in men. These findings are in marked contrast to those found with aerobic exercise and may have important clinical relevance with regard to cardiovascular disease risk. However, the effect of resistance training on arterial stiffness has not been confirmed by interventional studies nor has this relation been investigated in women. METHODS: To determine whether a strength training program increases regional and central arterial stiffness in women, 23 healthy young women (29+/-1 years; mean+/-SD) participated in a high-intensity strength and power training program for 11 weeks. Ten other women (27+/-2 years) served as time controls. RESULTS: In the intervention group, one repetition maximal strength increased 12% to 17% (P<.0001), and leg fat-free mass (via DEXA) increased significantly. Brachial blood pressure (BP) and fasting plasma lipid and lipoprotein concentrations did not change across the 11 weeks. Carotid augmentation index, a measure of arterial wave reflection and arterial stiffness, increased from -8%+/-13% to 1%+/-18% (P<.05), and carotid-femoral pulse wave velocity increased (791+/-88 v 833+/-96 cm/sec; P<.05). There were no changes in femoral-ankle pulse wave velocity, a segmental measure of peripheral arterial stiffness. CONCLUSIONS: We concluded that a high-intensity resistance training program increases arterial stiffness and wave reflection in young healthy women. Our present interventional results are consistent with the previous cross-sectional studies in men in which high-intensity strength training is associated with arterial stiffening.

Absorptiometry, Photon↗

PubMed2005

A novel UbcH10-binding protein facilitates the ubiquitinylation of cyclin B in vitro.

UbcH10 is known to act as a ubiquitin-conjugating enzyme (E2) for anaphase-promoting complex/cyclosome. Since some E2s support different ubiquitin ligases (E3), it is possible that UbcH10 interacts with other proteins. We cloned a novel protein named H10BH by using a yeast two-hybrid screening method with UbcH10 as bait. The carboxyl terminus of H10BH showed a weak homology to the HECT (homologous to E6-AP carboxyl terminus) domain, which is conserved in one of the families of E3. H10BH bound UbcH10, and the amino acid sequence between 235 and 257 was necessary for this binding. H10BH showed a self-ubiquitinylation activity in a HECT-like sequence-dependent manner. The carboxyl terminal half (amino acids 188-389) showed stronger activity than the full-length H10BH. Furthermore, the carboxyl terminal half of H10BH was able to bind cyclin B and ubiquitinylate cyclin B in vitro. These results suggest that H10BH functions as an E3 using UbcH10 for its E2.

Amino Acid Sequence↗