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Biomedical subjects

Akira Kamiya

Publications and source records attributed to Akira Kamiya.

At least 19 recordsLinked to original sources

Arterioles' contribution to oxygen supply to the skeletal muscles at rest.

We tested the hypothesis that oxygen is supplied to the resting skeletal muscle by arterioles rather than by capillaries. This hypothesis was evaluated in rats and rabbits by combining different approaches (1) determination of the intravascular oxygen tension (PO2) in arterioles of different diameters, (2) measurement of the perfused capillary number in response to changes in tissue PO2, and (3) estimation of the optimum capillary number to provide oxygen efficiently to the surrounding tissue. The intravascular PO2 values of arterioles along the vessels decreased downstream, suggesting that a significant amount of oxygen diffuses from the arterioles to the surrounding tissue. The perfused capillary number decreased as the tissue PO2 level was elevated, and this mutual relationship displayed a nonlinear correlation. The results suggest that a boundary PO2 level affecting the capillary recruitment exists for tissue PO2 of less than 40 mmHg with the capillary blood-flow stops above that PO2 level. At a high PO2 level, therefore, the oxygen is supplied from the arterioles. Furthermore, an estimation of optimum capillary number reveals that the capillary arrangement is constructed to achieve sufficient oxygen supply to the muscle during exercise, rather than at rest. These results suggest that oxygen is supplied from arterioles to the resting skeletal muscle, whereas the oxygen is supplied from the capillaries during exercise.

Animals↗

Shear stress induces hepatocyte PAI-1 gene expression through cooperative Sp1/Ets-1 activation of transcription.

Partial hepatectomy causes hemodynamic changes that increase portal blood flow in the remaining lobe, where the expression of immediate-early genes, including plasminogen activator inhibitor-1 (PAI-1), is induced. We hypothesized that a hyperdynamic circulatory state occurring in the remaining lobe induces immediate-early gene expression. In this study, we investigated whether the mechanical force generated by flowing blood, shear stress, induces PAI-1 expression in hepatocytes. When cultured rat hepatocytes were exposed to flow, PAI-1 mRNA levels began to increase within 3 h, peaked at levels significantly higher than the static control levels, and then gradually decreased. The flow-induced PAI-1 expression was shear stress dependent rather than shear rate dependent and accompanied by increased hepatocyte production of PAI-1 protein. Shear stress increased PAI-1 transcription but did not affect PAI-1 mRNA stability. Functional analysis of the 2.1-kb PAI-1 5'-promoter indicated that a 278-bp segment containing transcription factor Sp1 and Ets-1 consensus sequences was critical to the shear stress-dependent increase of PAI-1 transcription. Mutations of both the Sp1 and Ets-1 consensus sequences, but not of either one alone, markedly prevented basal PAI-1 transcription and abolished the response of the PAI-1 promoter to shear stress. EMSA and chromatin immunoprecipitation assays showed binding of Sp1 and Ets-1 to each consensus sequence under static conditions, which increased in response to shear stress. In conclusion, hepatocyte PAI-1 expression is flow sensitive and transcriptionally regulated by shear stress via cooperative interactions between Sp1 and Ets-1.

Animals↗

Vascular wall energetics in arterioles during nitric oxide-dependent and -independent vasodilation.

The objective of this study was to evaluate whether the nitric oxide (NO) released from vascular endothelial cells would decrease vessel wall oxygen consumption by decreasing the energy expenditure of mechanical work by vascular smooth muscle. The oxygen consumption rate of arteriolar walls in rat cremaster muscle was determined in vivo during NO-dependent and -independent vasodilation on the basis of the intra- and perivascular oxygen tension (Po2) measured by phosphorescence quenching laser microscopy. NO-dependent vasodilation was induced by increased NO production due to increased blood flow, whereas NO-independent vasodilation was induced by topical administration of papaverine. The energy efficiency of vessel walls was evaluated by the variable ratio of circumferential wall stress (amount of mechanical work) to vessel wall oxygen consumption rate (energy cost) in the arteriole between normal and vasodilated conditions. NO-dependent and -independent dilation increased arteriolar diameters by 13 and 17%, respectively, relative to the values under normal condition. Vessel wall oxygen consumption decreased significantly during both NO-dependent and -independent vasodilation compared with that under normal condition. However, vessel wall oxygen consumption during NO-independent vasodilation was significantly lower than that during NO-dependent vasodilation. On the other hand, there was no significant difference between the energy efficiency of vessel walls during NO-dependent and -independent vasodilation, suggesting the decrease in vessel wall oxygen consumption produced by NO to be related to reduced mechanical work of vascular smooth muscle.

Animals↗

Staphylococcus aureus contamination on the surface of working tables in ward staff centers and its preventive methods.

We investigated Staphylococcus aureus (S. aureus) contamination on the surface of working tables in ward staff centers and the effects of disinfection by wiping with 80% (v/v) ethyl alcohol on this contamination. When working tables were not regularly disinfected or washed, S. aureus [methicillin-sensitive S. aureus (MSSA) and/or methicillin-resistant S. aureus (MRSA)] was detected in 29 (51.8%) of 56 tables in 6 wards investigated. MRSA was detected in 17 (30.4%) of 56 tables and in all investigated wards. The S. aureus contamination density on the entire surface of the S. aureus-contaminated tables was 2081+/-8915 (mean+/-S.D.) colony-forming units (cfu) (n=29, range, 10-4.8x10(4) cfu), and the MRSA contamination density on the entire surface of the MRSA-contaminated tables was 158+/-200 cfu (n=17, range, 10-7.4x10(2) cfu). The second investigation was performed immediately after working tables not regularly disinfected or washed were disinfected by wiping once with 80% (v/v) ethyl alcohol, and MRSA was detected in 5 (8.9%) of 56 tables. The contamination density on the entire surface of the MRSA-contaminated tables was 36+/-30 cfu (n=5, range, 10-80 cfu). The third investigation was performed immediately after working tables not regularly disinfected or washed were disinfected by wiping with 80% (v/v) ethyl alcohol twice with a 1-min interval, and no S. aureus contamination was observed in any of 56 tables. These results suggest that disinfection by wiping once with 80% (v/v) ethyl alcohol could not completely eliminate MRSA in particulates. For the disinfection of the MRSA-contaminated surface of working tables and the removal of particulates, regular disinfection by wiping with 80% (v/v) ethyl alcohol is necessary.

Anti-Bacterial Agents↗

Particulate and microbial contamination in in-use admixed intravenous infusions.

We compared particulate and microbial contamination in residual solutions of peripheral intravenous admixtures after the termination of drip infusion between intravenous fluids admixed with glass ampoule drugs and those admixed with pre-filled syringe drugs. The mean number of particles>or=1.3 microm in diameter per 1 ml of residual solution was 758.4 for fluids (n=60) admixed with potassium chloride in a glass ampoule (20 ml volume), 158.6 for fluids (n=63) admixed with potassium chloride in a pre-filled syringe (20 ml volume), 736.5 for fluids (n=66) admixed with sodium chloride in a glass ampoule (20 ml volume), 179.2 for fluids (n=15) admixed with sodium chloride in a pre-filled syringe (20 ml volume), 1884.5 in fluids (n=30) admixed with dobutamine hydrochloride in 3 glass ampoules (5 ml volume), and 178.9 (n=10) in diluted dobutamine hydrochloride in pre-filled syringes (50 ml volume: For these samples alone, particulate and microbial contamination were evaluated in sealed products.) Thus, for potassium chloride or sodium chloride for injection, the number of particles>or=1.3 microm in diameter in the residual intravenous solution was significantly higher for fluids admixed with glass ampoule drugs than for those admixed with pre-filled syringe drugs (p<0.0001). For dobutamine hydrochloride for injection, the number of particles>or=1.3 microm in diameter in the residual intravenous solution was estimated to be higher for fluids admixed with its glass ampoule drug than for those admixed with its pre-filled syringe drug. Observation of the residual solutions of fluids admixed with potassium chloride, sodium chloride, or dobutamine hydrochloride in glass ampoules using an electron microscope with an X-ray analyzer showed glass fragments in each residual solution. Therefore, for the prevention of glass particle contamination in peripheral intravenous admixtures, the use of pre-filled syringe drugs may a useful method. No microbial contamination was observed in any of the residual solutions of 5 types of admixture.

Dobutamine↗

Microbial contamination of nebulization solution and its measures.

We evaluated the microbial contamination of nebulization solutions in medication cups from a total of 76 ultrasonic nebulizers in use in 10 hospitals. In addition, an interview survey was given to nurses to evaluate the disinfection methods of these ultrasonic nebulizers. Of a total of 76 nebulization solution samples, 11 (14.5%) were contaminated with 10-10(2) colony-forming units (CFU)/ml and 9 (11.8%) with 10(3)-10(5) CFU/ml. The major contaminants were glucose non-fermentative bacilli such as Burkholderia cepacia, CDC gr.IV C-2, and Sphingomonas paucimobilis. Comparison of microbial contamination between the frequencies of disinfection showed a significantly lower number of contaminated samples when the cups were disinfected once daily than when disinfected once at intervals of 2-7 d (p=0.00037). In addition, comparison between the presence and absence of preservatives contained in the nebulization solution showed a significantly lower number of contaminated samples in the presence, rather than in the absence, of preservatives (p=0.00001). These results show that disinfection of ultrasonic nebulizers at 24-h intervals is desirable. In particular, when nebulization solutions not containing preservatives are used, disinfection at 24-h intervals is indispensable.

Bacteria↗

[COPE trial].

Explore the source record for details and available documents.

Adrenergic beta-Antagonists↗

Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice.

The structure and function of blood vessels adapt to environmental changes such as physical development and exercise. This phenomenon is based on the ability of the endothelial cells to sense and respond to blood flow; however, the underlying mechanisms remain unclear. Here we show that the ATP-gated P2X4 ion channel, expressed on endothelial cells and encoded by P2rx4 in mice, has a key role in the response of endothelial cells to changes in blood flow. P2rx4(-/-) mice do not have normal endothelial cell responses to flow, such as influx of Ca(2+) and subsequent production of the potent vasodilator nitric oxide (NO). Additionally, vessel dilation induced by acute increases in blood flow is markedly suppressed in P2rx4(-/-) mice. Furthermore, P2rx4(-/-) mice have higher blood pressure and excrete smaller amounts of NO products in their urine than do wild-type mice. Moreover, no adaptive vascular remodeling, that is, a decrease in vessel size in response to a chronic decrease in blood flow, was observed in P2rx4(-/-) mice. Thus, endothelial P2X4 channels are crucial to flow-sensitive mechanisms that regulate blood pressure and vascular remodeling.

Acetylcholine↗

[Influence of respiratory motion in body diffusion weighted imaging under free breathing (examination of a moving phantom)].

Diffusion weighted imaging (DWI) theoretically aims to detect random motion over small distances, such as Brownian motion. Therefore, breath-hold scanning has been considered the only way to acquire DWI in the body without artifacts from bulk motion. Recent reports suggest that non-breath-hold scanning is feasible. The purpose of this study was to evaluate the influence of respiratory motion on DWI using a moving phantom model. Our results showed that the difference in apparent diffusion coefficient (ADC) was less than 10% between a static phantom and a moving phantom. There was no relation between the speed and stroke of the moving phantom and the calculated ADC. The results indicate that stable motion such as calm respiration does not cause signal loss on DWI, in contrast to intra-voxel incoherent motion (IVIM). The images obtained using this method showed high resolution and signal-to-noise ratio (SNR), suitable for three-dimensional display of the lesion.

Diffusion Magnetic Resonance Imaging↗

Nitric oxide modulates oxygen consumption by arteriolar walls in rat skeletal muscle.

To study the role of nitric oxide (NO) in regulating oxygen consumption by vessel walls, the oxygen consumption rate of arteriolar walls in rat cremaster muscle was measured in vivo during flow-induced vasodilation and after inhibiting NO synthesis. The oxygen consumption rate of arteriolar walls was calculated based on the intra- and perivascular PO2 values measured by phosphorescence quenching laser microscopy. The perivascular PO2 value of the arterioles during vasodilation was significantly higher than under control conditions, although the intravascular PO2 values under both conditions were approximately the same. Inhibition of NO synthesis, on the other hand, caused a significant increase in arterial blood pressure and a significant decrease in arteriolar diameter. Inhibition of NO synthesis also caused a significant decrease in both the intra- and perivascular PO2 values of the arterioles. Inhibition of NO synthesis increased the oxygen consumption rate of the vessel walls by 42%, whereas enhancement of flow-induced NO release decreased it by 34%. These results suggest that NO plays an important role not only as a regulator of peripheral vascular tone but also as a modulator of tissue oxygenation by reducing oxygen consumption by vessel walls. In addition, enhancement of NO release during exercise may facilitate efficient oxygen supply to the surrounding high metabolic tissue.

Animals↗

Effects of the muscle pump and body posture on cardiovascular responses during recovery from cycle exercise.

The purpose of the study was to characterize the effects of muscular contractions (the muscle pump) and body posture on cardiovascular responses during recovery from moderate exercise in the upright-sitting or supine positions. Heart rate (HR), stroke volume (SV), and cardiac output (CO) were measured in seven young male subjects at rest and during 10-min of cycle exercise at 60% of peak oxygen uptake (VO2peak). This was followed by either complete rest for 5 min (inactive recovery) or cycling at VO2peak for 5 min (active recovery) in the upright or supine positions. In the upright position, an initial rapid decrease in HR was followed by a gradual decrease in HR, and this response was similar when comparing inactive and active recoveries. Upright SV during inactive recovery decreased gradually to the pre-exercise resting level, whereas upright SV during active recovery remained significantly elevated. In contrast, in the supine position, the HR during active recovery decreased, but remained significantly higher than that during inactive recovery. Changes in supine SV were similar when comparing inactive and active recovery. Thus, maintenance of SV and HR resulted in significantly greater CO during active recovery than during inactive recovery, regardless of body position. HR was greater during supine active-recovery than during supine inactive-recovery, and there was no difference in SV. These data suggest that the muscle pump is less important in facilitating venous return and vagal resumption in the supine position as compared to the upright position.

Adult↗

Nonlinear regulation of capillary perfusion in relation to ambient pO(2) changes in skeletal muscle.

To study the process of O(2) transport to tissue, we investigated how capillary perfusion is controlled in response to changes in tissue O(2) levels in skeletal muscle. Capillary red blood cell (RBC) velocity and perfused capillary recruitment were measured in rabbit tenuissimus muscle at various ambient oxygen tensions (pO(2)) by intravital microscopy. Both RBC velocity and capillary recruitment significantly decreased as the pO(2) level of the suffusate was increased, and the relationship between capillary perfusion, calculated from the velocity and recruitment data, and the pO(2) level of the suffusate clearly yielded a nonlinear correlation that fitted a sigmoidal curve. Capillary perfusion dramatically decreases or increases above or below a suffusate pO(2) level of around 40 Torr, where the O(2) dissociation curve of hemoglobin changes slope. These findings support the hypothesis that microvasculature possesses an intrinsic, effective flow-control mechanism by sensing the metabolic demands of tissue, intimately related to the O(2) saturation of hemoglobin.

Animals↗

Estimating oxygen consumption rates of arteriolar walls under physiological conditions in rat skeletal muscle.

To examine the effects of vascular tone reduction on O2 consumption of the vascular wall, we determined the O2 consumption rates of arteriolar walls under normal conditions and during vasodilation induced by topical application of papaverine. A phosphorescence quenching technique was used to quantify intra- and perivascular PO2 in rat cremaster arterioles with different branching orders. Then, the measured radial PO2 gradients and a theoretical model were used to estimate the O2 consumption rates of the arteriolar walls. The vascular O2 consumption rates of functional arterioles were >100 times greater than those observed in in vitro experiments. The vascular O2 consumption rate was highest in first-order (1A) arterioles, which are located upstream, and sequentially decreased downstream in 2A and 3A arterioles under normal conditions. During papaverine-induced vasodilation, on the other hand, the O2 consumption rates of the vascular walls decreased to similar levels, suggesting that the high O2 consumption rates of 1A arterioles under normal conditions depend in part on the workload of the vascular smooth muscle. These results strongly support the hypothesis that arteriolar walls consume a significant amount of O2 compared with the surrounding tissue. Furthermore, the reduction of vascular tone of arteriolar walls may facilitate an efficient supply of O2 to the surrounding tissue.

Animals↗

Contamination of environmental surfaces by Staphylococcus aureus in a dermatological ward and its preventive measures.

We investigated contamination of environmental surfaces by Staphylococcus aureus from April 1 to the end of June in 2002 in the dermatological ward (37 beds) of a university hospital. For surfaces contaminated by high levels of S. aureus, disinfection methods were evaluated. 100-10(5) colony forming units (cfu) of methicillin-resistant S. aureus (MRSA) or methicillin-sensitive S. aureus (MSSA) were detected on items such as an immersion bathtub (examined area, about 900 cm2), foot washbowl, stretcher for an immersion bath, and chair for the shower. After disinfection, no S. aureus was detected on smooth surfaces such as the immersion bathtub and foot washbowl; however, S. aureus was detected even after disinfection on porous surfaces made of sponge-like materials (polyethylene foam) such as the stretcher for the immersion bath and the shower chair. Scanning electron microscopy of the porous surfaces showed formation of a large amount of coccus and bacillus biofilms on the walls of pores in the multi-pore structure. Material that is porous should not be used in patient care settings because it is not possible to disinfect it properly.

Dermatology↗

Particulate and microbial contamination in in-use admixed parenteral nutrition solutions.

We evaluated particulate and microbial contamination in a total of 192 samples of in-use admixed and unadmixed parenteral nutrition solutions remaining in infusion bags in 10 hospitals. The mean numbers (range) of drug glass ampoules, plastic ampoules, and vials used in a total of 192 admixed solutions were 3.38 (1-13), 0.79 (0-7), and 1.2 (0-8), respectively. The mean number of particles (range) contained in the 192 samples according to the particle size (diameter) was 960.9 (30-9,539)/ml for particles >or=1.3 microm, 42.8 (0-587)/ml for those >or=5 microm, 6.4 (0-146)/ml for those >or=10 microm, and 0.09 (0-1)/ml for those >or=50 microm. The number of particles >or=1.3 microm in diameter was significantly higher in the 192 samples than in 7 samples (controls) of solutions not mixed with any ampoule or vial (p<0.0001). In addition, the number of particles >or=1.3 microm in diameter was significantly higher in samples of solutions mixed with 4-13 glass ampoules than in those of solutions mixed with 1-3 glass ampoules (p<0.01). On the other hand, none of the 199 samples showed bacteria or fungi/5 ml residual solution. Measures against particulate contamination of admixed parenteral nutrition solutions are necessary.

Biofilms↗

The combination therapy of hypertension to prevent cardiovascular events (COPE) trial: rationale and design.

A number of major clinical trials have demonstrated the clinical benefits of lowering blood pressure and have indicated that a majority of patients with hypertension will require more than one drug to achieve optimal blood pressure control. However, there is little data showing which antihypertensive combination best protects patients from cardiovascular events and which best achieves the target blood pressure with the fewest adverse events. The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial is the first large-scale investigator-initiated multicenter study with a prospective, randomized, open, blinded endpoint evaluation (PROBE) design to directly compare cardiovascular mortality and morbidity, incidence of adverse drug reaction, and degree of blood pressure reduction in Japanese hypertensive patients for a combination of angiotensin receptor blockers, beta-blockers or thiazide diuretics in addition to a calcium antagonist, benidipine hydrochloride, with a response-dependent dose titration scheme. The COPE trial is being conducted with the cooperation of more than 100 centers and clinics in Japan and involves 3,000 patients, who will be followed for 3 years. Eligible patients are being enrolled from May 2003 until May 2006. Results from the COPE trial should provide new evidence for selecting optimal combination therapies for hypertensive patients.

Antihypertensive Agents↗

Fluid shear stress induces differentiation of Flk-1-positive embryonic stem cells into vascular endothelial cells in vitro.

Pluripotent embryonic stem (ES) cells are capable of differentiating into all cell lineages, but the molecular mechanisms that regulate ES cell differentiation have not been sufficiently explored. In this study, we report that shear stress, a mechanical force generated by fluid flow, can induce ES cell differentiation. When Flk-1-positive (Flk-1(+)) mouse ES cells were subjected to shear stress, their cell density increased markedly, and a larger percentage of the cells were in the S and G(2)-M phases of the cell cycle than Flk-1(+) ES cells cultured under static conditions. Shear stress significantly increased the expression of the vascular endothelial cell-specific markers Flk-1, Flt-1, vascular endothelial cadherin, and PECAM-1 at both the protein level and the mRNA level, but it had no effect on expression of the mural cell marker smooth muscle alpha-actin, blood cell marker CD3, or the epithelial cell marker keratin. These findings indicate that shear stress selectively promotes the differentiation of Flk-1(+) ES cells into the endothelial cell lineage. The shear stressed Flk-1(+) ES cells formed tubelike structures in collagen gel and developed an extensive tubular network significantly faster than the static controls. Shear stress induced tyrosine phosphorylation of Flk-1 in Flk-1(+) ES cells that was blocked by a Flk-1 kinase inhibitor, SU1498, but not by a neutralizing antibody against VEGF. SU1498 also abolished the shear stress-induced proliferation and differentiation of Flk-1(+) ES cells, indicating that a ligand-independent activation of Flk-1 plays an important role in the shear stress-mediated proliferation and differentiation by Flk-1(+) ES cells.

Animals↗

In vitro bactericidal activity of antimicrobial agents against enterohaemorrhagic Escherichia coli.

OBJECTIVES: In vitro bactericidal activity of four antimicrobial agents was determined against nine strains of enterohaemorrhagic Escherichia coli. METHODS: Pulsed-field gel electrophoresis was carried out with the Bio-Rad Gene Path system. Each antimicrobial agent was added to logarithmic phase of enterohaemorrhagic E. coli (four strains of E. coli O157:H7, two of E. coli O26, two of E. coli O111, and one of E. coli O165) in broth to obtain a concentration of 10 or 50 mg/L, and viable cells were counted after 1, 2, 6 and 24 h. RESULTS: All nine strains were confirmed to differ in their DNA pattern by pulsed-field gel electrophoresis. Norfloxacin at concentrations of 10 and 50 mg/L had bactericidal effects on all nine strains of enterohaemorrhagic E. coli. However, cefoperazone, kanamycin and fosfomycin had no bactericidal effects on some strains. In particular, after addition of 10 mg/L fosfomycin or kanamycin, four of the nine strains showed proliferation. CONCLUSIONS: Norfloxacin had marked bactericidal effects on enterohaemorrhagic E. coli. This information could be of value in planning randomized clinical trials of antimicrobial agents as treatment for enterohaemorrhagic E. coli infection.

Anti-Bacterial Agents↗