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Biomedical subjects

Toru Maruyama

Publications and source records attributed to Toru Maruyama.

At least 19 recordsLinked to original sources

Impaired filterability of erythrocytes from patients with chronic hepatitis C and effects of eicosapentaenoic acid on the filterability.

Although erythrocyte filterability plays a key role in microcirculation, it is unknown whether the filterability of erythrocytes from patients with chronic hepatitis C (CH-C) is impaired. This study aimed to investigate erythrocyte filterability in CH-C patients in relation to medical treatment. The mean erythrocyte filterability (%) for all 24 patients with CH-C (69.2 +/- 10.8%) was significantly lower than that for 5 normal controls (80.5 +/- 1.7%, P < 0.03). In 8 patients, the combination therapy of ribavirin (RBV) and interferon improved liver function but caused anemia. The filterability after treatment (57.8 +/- 12.8%) was lower than that before treatment (70.8 +/- 9.7%, P < 0.05). Decreased filterability showed no correlation with the mean corpuscular volume or mean corpuscular Hb concentration during treatment, suggesting that the decrease in filterability mainly arises from changes in erythrocyte membrane properties. We investigated the protective effects of eicosapentaenoic acid (EPA) on the RBV-induced anemia. Filterability in 7 responders was markedly improved from 68.4 +/- 4.6% to 77.4 +/- 2.4% (P < 0.001), but not in 3 nonresponders. In the responders, the progression of anemia was restrained. In conclusion, we found an obvious impairment of the filterability of erythrocytes from CH-C patients, further impairment of the filterability induced by oxidative membrane damage caused by RBV leading to hemolytic anemia, and amelioration of the filterability caused by the antioxidative effects of EPA.

Adult↗

Fusionless surgery for scoliosis: 2-17 year radiographic and clinical follow-up.

STUDY DESIGN: Descriptive case series. OBJECTIVE: To determine whether fusionless, multiple vertebral wedge osteotomy can safely obtain correction of the deformity with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: To our knowledge, no such attempts to manage the AIS with fusionless, vertebral osteotomies have been reported. METHODS: A total of 20 consecutive patients were treated since 1987. Deformity correction, complications, respiratory function, and patient-oriented outcome were investigated. RESULTS: There were 20 patients (17 females and 3 males), including 19 with idiopathic and 1 with syringomyelia scoliosis, who underwent surgery at an average age of 16.4 years and were followed for 8.9 years (range 2-17) on average. There were no neurologic complications. One superficial wound infection necessitated debridement. There were 2 patients converted to posterior instrumentation surgery because of deterioration of the deformity. The average Cobb angle of 64.0 degrees before surgery was corrected to 48.2 degrees at 8.9 years after surgery. Decline of the pulmonary function test after surgery was not statistically significant. The patients' responses to questions about function and pain were favorable. CONCLUSION: Deformity with AIS was safely corrected with fusionless, multiple vertebral wedge osteotomy.

Adolescent↗

Recombinant human serum albumin dimer has high blood circulation activity and low vascular permeability in comparison with native human serum albumin.

PURPOSE: Human serum albumin (HSA) is used clinically as an important plasma expander. Albumin infusion is not recommended for critically ill patients with hypovolemia, burns, or hypoalbuminemia because of the increased leakage of albumin into the extravascular spaces, thereby worsening edema. In the present study, we attempted to overcome this problem by producing a recombinant HSA (rHSA) dimer with decreased vascular permeability and an increased half-life. METHODS: Two molecules of rHSA were genetically fused to produce a recombinant albumin dimer molecule. The pharmacokinetics and biodistribution of the recombinant proteins were evaluated in normal rats and carrageenin-induced paw edema mouse model. RESULTS: The conformational properties of this rHSA dimer were similar to those for the native HSA (the HSA monomer), as evidenced by the Western blot and spectroscopic studies. The biological half-life and area under the plasma concentration-time curve of the rHSA dimer were approximately 1.5 times greater than those of the monomer. Dimerization has also caused a significant decrease in the total body clearance and distribution volume at the steady state of the native HSA. rHSA dimer accumulated to a lesser extent in the liver, skin, muscle, and fat, as compared with the native HSA. Up to 96 h, the vascular permeability of the rHSA dimer was less than that of the native HSA in paw edema mouse models. A prolonged plasma half-life of the rHSA dimer was also observed in the edema model rats. CONCLUSIONS: rHSA dimer has a high retention rate in circulating blood and a lower vascular permeability than that of the native HSA.

Animals↗

Involvement of disulfide bonds and histidine 172 in a unique beta-sheet to alpha-helix transition of alpha 1-acid glycoprotein at the biomembrane interface.

Human alpha(1)-acid glycoprotein (AGP), which is comprised of 183 amino acid residues and 5 carbohydrate chains, is a major plasma protein that binds to basic and neutral drugs as well as to steroid hormones. It has a beta-sheet-rich structure in aqueous solution. Our previous findings suggest that AGP forms an alpha-helix structure through an interaction with biomembranes. We report herein on a study of the mechanism of alpha-helix formation in AGP using various modified AGPs. The disulfide reduced AGP (R-AGP) was extensively unfolded, whereas asialylated AGP (A-AGP) maintained the native structure. Intriguingly, reduced and asialylated AGP (RA-AGP) increased the alpha-helix content as observed in the presence of biomembrane models, and showed a significant decrease in ligand binding capacity. This suggests that AGP has an innate tendency to form an alpha-helix structure, and disulfide bonds are a key factor in the conformational transition between the beta-sheet and alpha-helix structures. However, RA-AGP with all histidine residues chemically modified (HRA-AGP) was found to lose the intrinsic ability to form an alpha-helix structure. Furthermore, disulfide reduction of the H172A mutant expressed in Pichia pastoris also caused a similar loss of folding ability. The present results indicate that disulfide bonds and the C-terminal region, including H172 of AGP, play important roles in alpha-helix formation in the interaction of the protein with biomembranes.

Amino Acid Sequence↗

Physical exercises in the treatment of idiopathic scoliosis at risk of brace treatment -- SOSORT consensus paper 2005.

BACKGROUND: Based on a recognized need for research to examine the premise that nonsurgical approaches can be used effectively to treat signs and symptoms of scoliosis, a scientific society on scoliosis orthopaedic and rehabilitation treatment (SOSORT) was established in Barcelona in 2004. SOSORT has a primary goal of implementing multidisciplinary research to develop quantitative, objective data to address the role of conservative therapies in the treatment of scoliosis. This international working group of clinicians and scientists specializing in treatment of scoliosis met in Milan, Italy in January 2005. METHODS: As a baseline for developing a consensus for language and goals for proposed multicenter clinical studies, we developed questionnaires to examine current beliefs, before and after the meeting, regarding (1) the aims of physical exercises; (2) standards of treatment; and (3) the impact of such treatment performed by specialists in the field. RESULTS: The responses to the questionnaires show that, in principle, specialists in scoliosis physiotherapy do not disagree and that several features can be regarded, currently, as standard features in the rehabilitation of scoliosis patients. These features include autocorrection in 3D, training in ADL, stabilizing the corrected posture, and patient education.

Journal Article↗

Indications for conservative management of scoliosis (guidelines).

This guideline has been discussed by the SOSORT guideline committee prior to the SOSORT consensus meeting in Milan, January 2005 and published in its first version on the SOSORT homepage: http://www.sosort.org/meetings.php. After the meeting it again has been discussed by the members of the SOSORT guideline committee to establish the final 2005 version submitted to Scoliosis, the official Journal of the society, in December 2005.

Journal Article↗

Why do we treat adolescent idiopathic scoliosis? What we want to obtain and to avoid for our patients. SOSORT 2005 Consensus paper.

BACKGROUND: Medicine is a scientific art: once science is not clear, choices are made according to individual and collective beliefs that should be better understood. This is particularly true in a field like adolescent idiopathic scoliosis, where currently does not exist definitive scientific evidence on the efficacy either of conservative or of surgical treatments. AIM OF THE STUDY: To verify the philosophical choices on the final outcome of a group of people believing and engaged in a conservative treatment of idiopathic scoliosis. METHODS: We performed a multifaceted study that included a bibliometric analysis, a questionnaire, and a careful Consensus reaching procedure between experts in the conservative treatment of scoliosis (SOSORT members). RESULTS: The Consensus reaching procedure has shown to be useful: answers changed in a statistically significant way, and 9 new outcome criteria were included. The most important final outcomes were considered Aesthetics (100%), Quality of life and Disability (more than 90%), while more than 80% of preferences went to Back Pain, Psychological well-being, Progression in adulthood, Breathing function, Scoliosis Cobb degrees (radiographic lateral flexion), Needs of further treatments in adulthood. DISCUSSION: In the literature prevail outcome criteria driven by the contingent treatment needs or the possibility to have measurement systems (even if it seems that usual clinical and radiographic methods are given much more importance than more complex Disability or Quality of Life instruments). SOSORT members give importance to a wide range of outcome criteria, in which clinical and radiographic issues have the lowest importance. CONCLUSION: We treat our patients for what they need for their future (Breathing function, Needs of further treatments in adulthood, Progression in adulthood), and their present too (Aesthetics, Disability, Quality of life). Technical matters, such as rib hump or radiographic lateral alignment and rotation, but not lateral flexion, are secondary outcomes and only instrumental to previously reported primary outcomes. We advocate a multidimensional, comprehensive evaluation of scoliosis patients, to gather all necessary data for a complete therapeutic approach, that goes beyond x-rays to reach the person and the family.

Journal Article↗

Spine and rib abnormalities and stature in spondylocostal dysostosis.

STUDY DESIGN: A retrospective study of radiographic and clinical findings of spondylocostal dysostosis. OBJECTIVE: To determine the features of spondylocostal dysostosis diagnosed using consistent diagnostic criteria. SUMMARY OF BACKGROUND DATA: To our knowledge, no clear definition of spondylocostal dysostosis exists, and little information is available regarding its clinical or radiographic features. METHODS: We defined spondylocostal dysostosis as a congenital spinal disorder consisting of >or=2 vertebral anomalies associated with rib anomalies, without crab-like chest. For 30 patients, including 12 males and 18 females, who met these criteria, we evaluated vertebral and rib anomalies, birth and present body height, and associated anomalies. There were only 2 familial cases. RESULTS: Features of spondylocostal dysostosis were: (1) anomalies involved the thoracic region in all cases; many also involved the cervical spine; (2) most patients had >or=4 vertebral anomalies; (3) frequent vertebral anomalies were butterfly vertebra, hemivertebra, complete block, and unilateral bar, which were associated with both rib absence and fusion; (4) short stature was not always present at birth; and (5) complete block was 1 factor identified as being related to short stature after 12 years of age. CONCLUSION: Several features of sporadic spondylocostal dysostosis disorder were determined, including new findings related to body height.

Abnormalities, Multiple↗

Oxidation of Arg-410 promotes the elimination of human serum albumin.

The effect of the oxidation of amino acid residues on albumin on its in vivo elimination was investigated using mutants and oxidized HSAs. The single-residue mutants (H146A, K199A, W214A, R218H, R410A, Y411A) and oxidized HSAs were produced by the recombinant DNA techniques and incubation with a metal ion-catalyzed oxidation (MCO) system for 12, 24, 48 or 72 h. Pharmacokinetics were evaluated in mice after labeling with 111In. Structural and functional properties were examined by several spectroscopic techniques. Time-dependent increase in carbonyl group content resulted in increase in the liver clearance of oxidized HSAs. Slight decreases in alpha-helical content as the result of oxidation was induced by the increases in accessible hydrophobic areas and the net negative charge on the HSA molecule. No significant change in the pharmacokinetics and structural properties was observed for the W214A, R218H and Y411A mutants, but the properties for the H146A, K199A and R410A mutants were affected (extent of effect: R410A > K199A > H146A). The liver clearance of these proteins is closely correlated to hydrophobicity (r = 0.929, P < 0.01) and the net charge of the proteins (r=0.930, P < 0.01). The rate of elimination of HSA is closely related to the hydrophobicity and net charge of the molecule. Further, the R410A mutants had a short half-life and structure similar to oxidized HSA after oxidation. Therefore, the modification of Arg-410 via oxidative stress may promote the elimination of HSA.

Amino Acid Sequence↗

Effects of ultrasound energy application on cardiac performance in open-chest Guinea pigs.

BACKGROUND: Although ultrasound (US) is widely used in cardiology, little is known about the effects of US energy on cardiac performance. This study aimed to investigate the mechanical effects of high-intensity continuous US energy (1.0 MHz with 3 different intensities) on cardiac performance. METHODS AND RESULTS: Either left ventricular (LV) pressure or aortic blood flow (ABF) was evaluated in open-chest guinea pigs (n=30) under surface ECG monitoring. LV systolic pressure and ABF increased significantly (ie, maximum percent increases in these parameters were 2.5%, 3.1% and 7.1% for LV systolic pressure and 9.4%, 4.9% and 8.8% for mean ABF at intensities of 0.06, 0.67 and 2.90 W/cm2, respectively). LV end-diastolic pressure was reduced significantly by US (5.3+/-0.9 to 4.8+/-0.8, 5.5 +/-1.3 to 4.8+/-1.0 and 5.8+/-2.0 to 5.0+/-1.2 mmHg, respectively), indicating positive inotropic and lusitropic effects and resultant ABF augmentation. Local temperature was not significantly changed. ECG showed neither chronotropic action nor arrhythmogenesis. CONCLUSIONS: Although the basic mechanisms of these phenomena remain unclear, this pilot study of the short-term effects of US energy on cardiac performance suggests the possibility of physical therapy for heart failure.

Animals↗

Pathophysiological basis for monitoring of whole heart conductance by 2-lead system.

BACKGROUND: The defibrillation threshold (DFT) is elevated during myocardial ischemia, but the underlying mechanism remains to be elucidated. The hypothesis tested by the present study was that whole heart conductance (WHC) is a determinant of DFT. METHODS AND RESULTS: WHC was monitored across the longest diameter of the isolated perfused rat heart, using a 2-electrode instrument under various conditions including ischemia-reperfusion (IR). In the control study, WHC was influenced by the conductivity and flow rate of the solution. In IR, WHC decreased immediately after the onset of perfusion arrest in a single exponential manner, then declined again gradually. The second decrease was augmented and accelerated by pretreatment with 1.0 mmol/L heptanol (p<0.005) or high-[Ca2+]e (p<0.001), and was attenuated and delayed by pretreatment with 1.0 micromol/L verapamil (p<0.01). WHC after reperfusion was greater than the pre ischemic level. The postischemic increase in WHC was proportional to the ischemic interval and tissue water content as assessed by desiccation method. CONCLUSION: Although time-dependent alterations in DFT in ischemic hearts may be attributable at least in part to dynamic changes in WHC, WHC should be interpreted carefully because it reflects many physiological factors such as coronary perfusion, electrical coupling of cardiac myocytes and tissue edema.

Animals↗

Multiple vertebral wedge osteotomy for adolescent idiopathic scoliosis.

19 idiopathic and 1 syringomyelia scoliosis patients (17 females and 3 males) underwent fusionless, multiple vertebral wedge osteotomy and with follow-up for an average of 8.9 years. The average age at surgery was 16.4 years. The average curve magnitude measured by Cobb was 64.0 degrees before surgery, 38.8 degrees after surgery, 43.7 degrees one year after surgery, 46.9 degrees two years after surgery and 48.2 degrees at the latest follow-up. The difference between the Cobb angle two years after surgery and latest follow-up was not significant. There were no major complications such as neurological problems.

Adolescent↗

Validity and reliability of SRSI and SF-36 in Japanese patients with scoliosis.

We have examined the validity and reliability of Japanese SRS-24 and SF-36 in patients with scoliosis. 278 patients with scoliosis were recruited. Their average age was 24.8 years (range 17-84 years) and 83% of patients had idiopathic curves. The major coronal curve averaged 43 degrees (range 10 degrees -114 degrees). Questionnaires surveyed were SRS-24 and SRS-22, and SF-36. Only domains applicable to untreated patients were analyzed. Scale level analysis was evaluated by the ceiling and floor effect. The Cronbach alpha and item-scale correlations were calculated as representatives of internal consistency reliability and item internal consistency, respectively. Most domains of SF-36 had large ceiling effects. Both the SRS questionnaires had limited ceiling/floor effects. SRS-22 had a better internal consistency than SRS-24. Low item-scale correlations (<0.25) were found in question 14, 15, and 18 of SRS-22. The Japanese version of SRS-22 was the most useful measure for patients with scoliosis. However, some questions have low item-scale correlations, lowering reliability of the Function domain.

Adolescent↗

Correction of scoliosis using segmental pedicle screw instrumentation versus hybrid constructs with hooks and screws.

Eighteen consecutive patients with scoliosis surgically treated by posterior correction and fusion were recruited. The major coronal curve averaged 65.8 degrees (range 51 degrees -87 degrees ). Eight patients were treated by hybrid constructs and four of them had anterior release before posterior surgery. Ten patients were treated by posterior correction and fusion alone with pedicle screw instrumentation. Flexibility was assessed by radiographs using the active bending and the fulcrum bending techniques. Two correction indices were not statistically different between the two groups. However, there was a tendency towards better correction in the screw group: mean surgical correction was 62.6+/-11.8% in the hook group and 71.6+/-12.3% in the screw group (p=0.07). Comparable pre- and post-operative radiographic results may indicate the advantages of posterior-only segmental pedicle screw instrumentation over hybrid constructs.

Adolescent↗

The structure and function of oxidized albumin in hemodialysis patients: Its role in elevated oxidative stress via neutrophil burst.

Oxidized albumin is a reliable marker of oxidative stress in hemodialysis (HD) patients. However, oxidized albumin in vivo and its possible clinical significance has been rarely investigated. In the present study, the qualitative modification of albumin in HD patients (n = 20) was examined and their results were compared with healthy age-matched controls (n = 10). The increase in plasma protein carbonyl levels in HD patients was largely due to an increase in oxidized albumin. Human serum albumin (HSA) of HD patients, HSA of HD patients (HD-HSA) and normal subjects (Normal-HSA) were purified on a blue Sepharose CL-6B column. Spectroscopic analysis confirmed that the HD-HSA samples contained higher levels of carbonyls than Normal-HSA. An HPLC analysis also suggested that the state of the purified HSA used throughout the experiments accurately reflects the redox state of albumin in blood. HD-HSA was found to have a decreased the antioxidant activity, and was able to trigger the oxidative burst of human neutrophils, compared to Normal-HSA. HD-HSA was conformationally altered, with its hydrophobic regions more exposed and to have a negative charge. In binding experiments, HD-HSA showed impaired Site II-ligand binding capabilities. Collectively, the oxidation of plasma proteins, especially HSA, might enhance oxidative stress in HD patients.

Adult↗

Cooperative effect of hydrophobic and electrostatic forces on alcohol-induced alpha-helix formation of alpha1-acid glycoprotein.

Alpha1-acid glycoprotein (AGP) is a serum glycoprotein that mainly binds basic drugs. Previous reports have shown that AGP converts from a beta-sheet to an alpha-helix upon interaction with biomembranes. In the current studies, we found that alkanols, diols, and halogenols all induce this conformational change. Increased length and bulkiness of the hydrocarbon group and the presence of a halogen atom promoted this conversion, whereas the presence of a hydroxyl group inhibited it. Moreover, the effect was dependent on the hydrophobic and electrostatic properties of the alcohols. These results indicate that, in a membrane environment, hydrophobic and electrostatic factors cooperatively induce the transition of AGP from a beta-sheet to an alpha-helix.

Alcohols↗

Bucolome, a potent binding inhibitor for furosemide, alters the pharmacokinetics and diuretic effect of furosemide: potential for use of bucolome to restore diuretic response in nephrotic syndrome.

To determine whether bucolome (5-n-butyl-1-cyclohexyl-2,4,6-trioxoperhydropyrimidine), a nonsteroidal anti-inflammatory agent, can reverse diuretic resistance of furosemide in patients with nephrotic syndrome, we examined the inhibitory effect of bucolome on the protein binding of furosemide in serum and urine. Bucolome significantly inhibited the protein binding of furosemide not only in serum but also in urine of preparation albumin (UPA), which mimics urinary albumin concentration in patients with nephrotic syndrome by ultrafiltration method. The binding percentage of furosemide to albumin was approximately 70% in UPA. With coadministration of bucolome to healthy volunteers, renal clearance of furosemide was increased, reflecting the increase of the free fraction of furosemide in serum. Furthermore, coadministration of bucolome caused a significant increase of urine volume and sodium concentration in urine. Even at higher urine levels of furosemide, the inhibitory effect of bucolome on the protein binding of furosemide in UPA remains constant, and changes in pH at weakly acidic pH levels (pH 5.5-6.5) did not alter the inhibitory effect of bucolome. Interestingly, coadministration of bucolome with furosemide in doxorubicin (Adriamycin)-induced nephrotic syndrome model rats alleviated the diuretic resistance. These results suggest that bucolome has a potent inhibitory effect on the protein binding of furosemide in the urine and can partially restore the diuretic response of furosemide in patients with nephrotic syndrome by increasing the free fraction of furosemide at the site of action.

Adult↗