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Biomedical subjects

Toru Maruyama

Publications and source records attributed to Toru Maruyama.

At least 37 records · Page 2Linked to original sources
PubMed2005

Oxidation and carboxy methyl lysine-modification of albumin: possible involvement in the progression of oxidative stress in hemodialysis patients.

Hemodialysis (HD) patients are frequently in a state of increased oxidative stress, and hyperglycemia appears to be a major factor. We recently found that oxidized human serum albumin (HSA) is a reliable marker of oxidative stress in HD patients. However, the issue of whether oxidized HSA is associated with the progression of oxidative stress in HD patients with or without diabetes is not clear. In the present study, we examined the effect of a qualitative modification of HSA in HD patients with or without diabetes. Blood samples from 10 HD patients with diabetes, 7 HD patients without diabetes, and 10 healthy age-matched controls were examined. The increase in plasma protein carbonyl content and advanced glycation endproducts (AGEs) in HD patients was largely due to an increase in the levels of oxidized HSA. Furthermore, these increases were greatest in HD patients with diabetes. Purified HSA from HD patients (non-DM-HSA) was carbonylated and AGE-modified. The amount of modified HSA was the highest in HD patients with diabetes (DM-HSA). Carboxy methyl lysine (CML)-modified HSA triggered a neutrophil respiratory burst, and this activity was closely correlated with the increase in the CML/HSA ratio. These findings indicate that uremia plays an important role in the progression of oxidative stress in HD patients via an increase in CML-modified HSA. They also indicate that diabetic complications further exacerbate the progression of oxidative stress by further increasing the amount of these modified HSA molecules.

Adult↗
PubMed2005

Influence of interferon therapy on signal-averaged and ambulatory electrocardiograms in patients with chronic active hepatitis.

Although interferon (IFN) shows cardiotoxicity and arrhythmogenesis, the influence of IFN on signal-averaged electrocardiography remains to be clarified. The aim of this study was to test a clinical hypothesis that IFN therapy for hepatitis C virus may induce ventricular late potentials (LPs) and related arrhythmias in patients with chronic active hepatitis. Signal-averaged and ambulatory electrocardiograms were recorded sequentially in patients with chronic active hepatitis C (n = 22) throughout the entire period of IFN therapy. The filtered QRS duration (fQRS) and low amplitude (< 40 microV) signal duration (LAS40) were significantly increased (95.5 +/- 8.5 to 99.6 +/- 9.4 msec, P < 0.0001, and 32.8 +/- 3.1 to 36.3 +/- 3.0 msec, P < 0.0001, respectively), whereas the root mean square voltage in the terminal 40 msec of the fQRS (RMS40) was significantly decreased (25.5 +/- 5.4 to 22.3 +/- 5.2 microV, P < 0.005) 1 month after starting the IFN therapy. The ventricular LP was negative in all subjects before starting therapy, but became positive in 7 patients after the therapy commenced. There were no differences in clinical baseline characteristics between the LP-positive (n = 7) and LP-negative (n = 15) groups. Significant increases in mean heart rate, fQRS, and LAS40 were observed after starting the therapy, irrespective of the appearance of the ventricular LP, whereas a decrease in RMS40 was observed only in the LP-positive group. No sustained ventricular arrhythmias were documented in the ambulatory electrocardiography and no cardiac events were encountered in the follow-up period. Therefore, the results indicate a reversible and subclinical risk of IFN-induced arrhythmogenesis.

Adult↗
PubMed2005

A unipolar coronary sinus mapping study of patients with left-sided atrioventricular accessory pathways.

So-called unipolar 'PQS pattern' is widely accepted as a hallmark of successful catheter ablation of the left-sided atrioventricular accessory pathway. However, the unipolar nature of the electrogram and the site-dependent appearance of this characteristic pattern are poorly understood. Therefore, unipolar coronary sinus (CS) mapping was performed using a multipolar fine electrode in patients with Wolff-Parkinson-White (WPW) syndrome associated with an antegrade left-sided accessory pathway (case group) and those with a concealed left-sided accessory pathway or atrioventricular nodal reentrant tachycardia (control group) under sinus rhythm and fixed high right atrial, CS ostial, and distal pacing. In both groups, the unipolar CS atrial electrogram showed intrinsic negative deflection (initial positive followed by negative parts) with considerable variation depending on the recording site. This unipolar configuration of the atrial electrogram was not influenced by different activation sequences during pacing at various sites. The case group exhibited a unipolar 'PQS pattern' at successful ablation sites for the left lateral to anterolateral accessory pathway. However, this was not true for the left posteroseptal accessory pathway, possibly because the negative part of the atrial electrogram distorted the 'PQS pattern' as an intervening dip. In conclusion, the site-dependent variations of the unipolar CS atrial electrogram underlie the limited usefulness of the 'PQS pattern' in left posteroseptal accessory pathway localization.

Adolescent↗
PubMed2004

Total synthesis of ingenol.

A total synthesis of the biologically important diterpene ingenol has been completed. Ring-closing olefin metathesis was used to construct the strained "inside-outside" tetracyclic skeleton, and a series of diastereoselective reactions were employed to complete the synthesis. Another naturally occurring ingenane, 20-deoxyingenol, has also been prepared.

Allyl Compounds↗
PubMed2004

Stabilizing mechanisms in commercial albumin preparations: octanoate and N-acetyl-L-tryptophanate protect human serum albumin against heat and oxidative stress.

The capability of octanoate, N-acetyl-L-tryptophanate (N-AcTrp) and other ions of fatty acids and amino acids to stabilize human serum albumin (HSA) against thermal and oxidative stress was studied. Native-PAGE showed that octanoate, and more hydrophobic fatty acids anions, stabilizes the monomeric form of HSA during heating at 60 degrees C for 30 min. Heating in the presence of octanoate did not change the far-UV CD-spectrum. The stabilizing role of octanoate also showed as an increase in denaturation temperature and calorimetric enthalpy, determined by differential scanning calorimetry (DSC). N-AcTrp, which was found to compete with octanoate for a common high-affinity site, has only a minor stabilizing effect. By contrast, no effect was found for l-tryptophanate or N-acetyl-L-cysteinate. Any ligand effect on oxidation was examined by using 2,2' -azobis(2-amidino-propane)dihydrochloride (AAPH) as oxidizing agent. One hour of incubation resulted in the formation of the same number of carbonyl groups, whether octanoate or one of the above mentioned amino acids was present or not. However, the number of groups formed after 24 h of incubation was significantly decreased in the presence of L-tryptophanate and, especially, N-AcTrp. The effect of 1-h incubation with AAPH on the oxidative status of 34-Cys was studied by the HPLC technique. It was found that N-AcTrp, but not octanoate, has a large protecting effect on the sulfhydryl group. Thus, octanoate has the greatest stabilizing effect against heat, whereas the presence of N-AcTrp diminishes oxidation of HSA.

Calorimetry, Differential Scanning↗
PubMed2004

Spatial relations between the vertebral body and the thoracic aorta in adolescent idiopathic scoliosis.

STUDY DESIGN: An analysis of computed tomography images of patients with adolescent idiopathic scoliosis. OBJECTIVES: To evaluate the spatial relations between the vertebral body and the thoracic aorta and to verify the safety of anterior instrumentation surgery. SUMMARY OF BACKGROUND DATA: Recent studies have suggested that the aorta is positioned more laterally and posteriorly in patients with idiopathic scoliosis than in normal patients; however, no study used rib heads as references in the analysis. METHODS: Computed tomography images of the whole thoracic spine of 10 patients with adolescent idiopathic scoliosis were analyzed. A line that passed the anterior edge of the bilateral rib heads was regarded as the virtual passage of the screw used for anterior instrumentation surgery. Whether this line crossed the aorta was investigated. A distance between the vertebral body and the aorta was measured along this line. RESULTS: The aorta was located more posteriorly between T6 and T9. At these levels, the virtual passage of the screw crossed the aorta in 33 of 40 vertebrae (83%). At seven vertebrae in 5 patients, this passage crossed the aorta and the distance was less than 2 mm. Of these, four were T6, two T7, and one T8. CONCLUSION: In some patients with adolescent idiopathic scoliosis, the aorta can be located in the direction of the screw passage and close to the vertebral body. Accordingly, when planning anterior instrumentation surgery for right thoracic curve, surgeons should pay attention to these spatial relations.

Adolescent↗
PubMed2004

Binding of alpha1-acid glycoprotein to membrane results in a unique structural change and ligand release.

Alpha(1)-acid glycoprotein (AGP) consists of 183 amino acid residues and 5 carbohydrate chains and binds to basic and neutral drugs as well as steroid hormones. We investigated the structural properties and ligand-binding capacity of AGP under mild acidic conditions and its interactions with liposomes prepared from neutral or anionic lipids and the neutral drug, progesterone. Interestingly, AGP had a unique structure at pH 4.5, at which the tertiary structure changed, whereas the secondary structure remained intact. Furthermore, the binding capacity of AGP for progesterone did not significantly change under these conditions. It was also observed that AGP was strongly bound to the anionic membrane at pH 4.5, forming an alpha-helix-rich structure from the original beta-sheet-rich structure, which significantly decreased the binding capacity of AGP for progesterone. The structural transitions as well as the membrane binding were suppressed by adding NaCl. These results indicate that AGP has a unique structure on the membrane surface under mild acidic conditions. The conformational change induces binding to the membrane aided by electrostatic interaction, and AGP subsequently takes on a predominantly alpha-helical conformation.

Acids↗
PubMed2004

Characterization of site I of human serum albumin using spectroscopic analyses: locational relations between regions Ib and Ic of site I.

Site I of human serum albumin is an important and complex region for high-affinity binding of drugs. Equilibrium dialysis showed independent binding of dansyl-L-asparagine (DNSA) and n-alkyl p-aminobenzoates (p-ABEs) to regions Ib and Ic, respectively, in the pH range 6.0-9.0. However, individual binding of DNSA increased with pH in the same range. Binding of the four n-alkyl p-ABEs strongly perturbed the circular dichroism spectrum of bound DNSA, and the effect increased with concentration and the number of carbon atoms in the alkyl moiety. A similar effect was observed by increasing pH from 6.0 to 9.0, a pH range in which human serum albumin is known to undergo the neutral-to-base transition. The spectral changes propose spatial orientation changes of DNSA at region Ib. This proposal was supported by increased fluorescence anisotropy values: n-alkyl p-ABEs binding and the pH-dependent conformational change each restricted the mobility of the naphthalene ring of bound DNSA. Despite the similar effects on the spatial orientation of DNSA, clear differences were observed between the effects of n-alkyl p-ABEs and neutral-to-base transition. The former hardly changed the affinity and maximum fluorescence emission wavelength of bound DNSA; in contrast, the latter significantly affected them. The results give new information about site I and, according to our knowledge, represent a new type of ligand interaction, because the binding site of DNSA could be changed by simultaneous binding of the n-alkyl p-ABEs without affecting the binding constant.

Binding Sites↗
PubMed2004

Intravenous iron administration induces oxidation of serum albumin in hemodialysis patients.

BACKGROUND: Intravenous iron administration (IVIR) is effective for correcting anemia in hemodialysis (HD) patients. However, it may also enhance the generation of hydroxyl radicals. Recently, plasma proteins have been demonstrated to be extremely susceptible to oxidative stress. Therefore, we investigated the effect of IVIR on the oxidative status of albumin, a major plasma protein, in HD patients. METHODS: Eleven hemodialysis (HD) patients were treated with 40 mg of saccharated ferric oxide intravenously after every dialysis session for four weeks, and 11 age-/gender-matched HD patients were treated with vehicle. We performed high performance liquid chromatography (HPLC) analysis of serum albumin and determined the levels of reduced and oxidized albumin. Carbonyl formation of plasma proteins were also measured using an anti-2,4 dinitrophenylhydrazine antibody in patients with or without IVIR. RESULTS: IVIR resulted in an increase in both disulfide form (f(HNA-1)) and oxidized form (f(HNA-2)) of albumin in HD patients (36.0 +/- 6.03 vs. 41.7 +/- 6.27; 5.46 +/- 1.50 vs. 8.7 +/- 2.22, respectively, P < 0.05). The findings here also show that IVIR substantially increased plasma protein carbonyl content by oxidizing albumin. In addition, we found a strong correlation between plasma carbonyl content and the levels of oxidized albumin (f(HNA-1) and f(HNA-2)) in HD patients (R= 0.674 and R= 0.724, respectively, P < 0.01). CONCLUSION: The results of this study indicate that the HPLC analysis of serum albumin represents a potentially useful method for the quantitative and qualitative evaluation of oxidative stress in HD patients, and strongly suggest the possibility that oxidative stress, generated by IVIR, enhances the oxidation of albumin in those patients.

Adult↗
PubMed2004

Verapamil prevents impairment in filterability of human erythrocytes exposed to oxidative stress.

Effects of oxidative stress on intact human erythrocytes were investigated using tert-butyl hydroperoxide (tBHP). Exposure of erythrocytes to tBHP caused a marked decrease in filterability in a time-dependent manner. Erythrocytes exposed to tBHP also show an increase in mean corpuscular volume and a remarkable formation of methemoglobin (met-Hb) without any appearance of hemichromes that form Heinz bodies. High performance liquid chromatography demonstrated that the tBHP-treated erythrocytes exhibited an apparent decrease in the membrane phospholipid, phosphatidylethanolamine (PE). The decrease in PE was inhibited by pretreatment with ascorbate, but not with verapamil. SDS-polyacrylamide gel electrophoresis of the tBHP-treated erythrocyte membrane showed a degradation of spectrin, band 3, band 4.2, and band 4.5, accompanied by the appearance of low-molecular-weight products. The degradation of the membrane proteins was not prevented by pretreatment with verapamil or ascorbate. However, the pretreatment with verapamil but not with ascorbate revealed significant inhibition of the tBHP-induced impairment in filterability in the presence of extracellular Ca2+. Thus, the present study shows that verapamil, a potent drug in reperfusion therapy, plays an important role in protection against oxidative injury, based on a close linkage among decreased filterability, met-Hb formation, and impaired membrane integrity.

Calcium Channel Blockers↗
PubMed2004

Extracellular potassium dependent negative dromotropic action of nicorandil in guinea pig myocardium.

Although the antiarrhythmic action of nicorandil is drawing an increasing attention, dromotropic effect of this agent is unclear. Therefore, this was investigated by microelectrode technique to the superfused guinea pig papillary muscle to record the action potential and extracellular potential during conduction. The correlation of myocardial internal longitudinal resistance (r1) assumed to reflect the global gap junctional resistance, maximum rate of rise of the action potential upstroke (Vmax), and conduction velocity was examined under the alterations of external potassium concentrations ([K+]e; ranging from 3.0 to 12.0 mM) in the presence or absence of 100 microM nicorandil. In the minimum [K+]e, nicorandil caused significant (p < 0.05) hyperpolarization and reduction in Vmax. Negative dromotropic action of nicorandil was slight but significant (p < 0.05) in low (3.0 mM) [K+]e but was not evident in physiologic (5.4 mM) or elevated (9.0 to 12.0 mM)[K+]e. In conclusion, nicorandil exerts negative dromotropic action as [K+]e decreased, which was accounted for by the cable analysis and may contribute to the prevention of low [K+]e-induced arrhythmia.

Animals↗
PubMed2003

The effect of glycation on the structure, function and biological fate of human serum albumin as revealed by recombinant mutants.

Recombinant wild-type human serum albumin (rHSA), the single-residue mutants K199A, K439A and K525A and the triple-residue mutant K199A/K439A/K525A were produced using a yeast expression system. Portions of the rHSA were glycated to different degrees (2.5-250 mM D-glucose). As detected by far-UV and near-UV CD, intrinsic tryptophan-fluorescence and probed by 1,1'-bis(4-anilino)naphthalene-5,5-disulfonic acid, the single-residue mutations had no effect on albumin conformation, whereas the triple-residue mutation and glycation caused conformational changes. The triple-residue mutation and glycation had comparable increased effects on high-affinity binding of warfarin (site I), but decreased effects on high-affinity binding of dansylsarcosine (site II) and the esterase-like activity of albumin. The relation between plasma half-lives in rats were found to be glycated rHSA (50 mM glucose)<triple-residue mutated rHSA<rHSA. The opposite trend was found for liver and kidney uptakes in mice. Even though the functional and the in vivo properties of rHSA could be effected differently by the minor conformational changes caused by the triple-residue mutation and glycation, the present findings indicate that the effect of glycation can be partly explained by blockage of the positive charges of lysine at positions 199, 439 and 525.

Animals↗
PubMed2003

Validation of the chloramine-T induced oxidation of human serum albumin as a model for oxidative damage in vivo.

PURPOSE: The validity of using chloramine-T as a model compound for mimicing oxidative stress was examined using human serum albumin (HSA) as a model. Important sites of oxidation were studied by mild treatment with chloramine-T and by mutating 34Cys for a serine (C34S). METHODS: High-performance liquid chromatography (HPLC) combined with fluorescence detection to confirm the validity of chloramine-T as an oxidizing agent was used. Oxidized amino acid residues were detected by reaction with 5,5'-dithiobis(2-nitro benzoic acid), digestion with cyanogen bromide, followed by capillary electrophoresis. Protein conformation was examined by spectroscopic techniques. RESULTS: From the HPLC analysis of human serum, the validity of using chloramine-T as an oxidizing agent was confirmed. At low chloramine-T concentrations (CT0.1-HSA, CT1-HSA), 34Cys and Met residues were oxidized, at medium concentrations (CT10-HSA), the tryptophan residue also appeared to be oxidized, and at the highest concentration (CT50-HSA), the net charge of Site II of HSA was found to be more negative. The two highest levels of oxidation of HSA (CT10-HSA, CT50-HSA) resulted in conformational changes with an increased exposure of hydrophobic regions, decreased high-affinity bindings of warfarin and ketoprofen and a reduced esterase-like activity. The latter protein also has a shorter plasma half-life and an increased liver clearance. CONCLUSIONS: We succeeded in imitating oxidative damage to HSA using chloramine-T and the findings show that Site II is more affected than Site I and 34Cys, when HSA is exposed to oxidative stress.

Animals↗
PubMed2003

Bezold-Jarisch-like reflex during Brockenbrough's procedure for radiofrequency catheter ablation of focal left atrial fibrillation: report of two cases.

Brockenbrough's puncture technique has been widely conducted in the electrophysiologic laboratory. We report here two cases exhibiting a rare complication of this procedure, which arose during the conduct of catheter ablation using radiofrequency energy delivered to the pulmonary vein for the treatment of focal left atrial fibrillation. These cases exhibited marked sinus bradycardia and profound hypotension, suggestive of a Bezold-Jarisch-like reflex, observed immediately after Brockenbrough's procedure but before radiofrequency application. ST elevation in the inferior leads was also observed in spite of normal coronary angiograms. This unanticipated transient complication was treated by intravenous administration of atropine, which had no influence on the ablation procedure or prognosis. This is speculated to be attributable to the elevation of vagal tone caused by the mechanical effects of transseptal puncture on the interatrial vagal network.

Adult↗
PubMed2003

Reentrant atrial tachycardia originating from the superior vena cava.

A 52-years old man with a previous pericardiotomy for idiopathic constrictive pericarditis underwent catheter ablation for drug-resistant atrial tachycardia (AT). The mechanism of the AT was considered as reentry because of resetting response and the entrainment phenomenon during AT. We introduced a 64-electrode basket catheter into the superior vena cava (SVC) during AT to obtain precise mapping. A fractionated potential preceding local atrial electrogram was recorded in the SVC. The earliest activation site of the potential was located at the anterior aspect of the SVC, 2 cm above the SVC-right atrium junction determined fluoroscopically. The fractionated potential at this site preceded the onset of the P wave by 115 msec. Radiofrequency catheter ablation at this site eliminated the tachycardia. At 6 months follow-up, the patient is free of AT. Reentrant AT involving the SVC is a candidate of RF ablation. Multielectrode basket catheter is useful for a detailed mapping of the SVC.

Catheter Ablation↗
PubMed2003

A new quantitative filtration apparatus to evaluate erythrocyte deformability.

We have developed a quantitative filtration apparatus to evaluate erythrocyte deformability, using a precision metal filter which we developed. The test material is sucked into the filter through the action of decreasing negative pressure. The device automatically gives a liquid level (height)-time relation and a pressure-flow rate relation, similar to gravity-based filtration. Unlike the gravity-based system, the experimental performance of this system is very good and reproducible.

Automation↗