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Biomedical subjects

Naoki Matsuda

Publications and source records attributed to Naoki Matsuda.

At least 19 recordsLinked to original sources

Mild and short recurrence of type II amiodarone-induced thyrotoxicosis in three patients receiving amiodarone continuously for more than 10 years.

Although there are two types of amiodarone-induced thyrotoxicosis (AIT), only type II AIT has been seen at our institution in Japan so far. There have been few case reports of AIT recurrence, probably because of the fact that amiodarone is immediately discontinued once AIT has developed. Our own policy is not to discontinue amiodarone in all AIT patients, unless severe adverse effects such as pulmonary fibrosis develop. Among more than 50 patients with type II AIT we have encountered, three with arrhythmogenic right ventricular cardiomyopathy showed AIT recurrence. In these patients, the first episode of AIT developed 3, 4, and 2 years after the start of amiodarone administration, and recurrence was observed 5, 6, and 8 years after the first episode, respectively. The AIT resolved spontaneously in all cases while the patients continued to take amiodarone. In comparison with the first AIT episode, the second was milder and resolved within a shorter period. These three cases suggest that recurrence of type II AIT may not be rare in iodine-sufficient areas, and that it is relatively mild and may resolve spontaneously. Furthermore, at least in Japan, it may be possible for patients with recurrent type II AIT to continue taking amiodarone.

Aged↗

Significance of 8-hydroxy-2'-deoxyguanosine levels in patients with idiopathic dilated cardiomyopathy.

BACKGROUND: Although oxidative stress mediated by reactive oxygen species plays an important role in the pathogenesis of heart failure (HF), good clinical markers for reactive oxygen species in patients with HF have not been established. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is formed from deoxyguanosine in DNA by hydroxyl free radicals and might serve as a sensitive biomarker of intracellular oxidative stress in vivo. Thioredoxin (TRX) is known to be induced in cells as a radical scavenger against oxidative stress. The aim of this study is to evaluate the clinical significance of the serum 8-OHdG and TRX of patients with chronic HF with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We estimated serum 8-OHdG and TRX levels using enzyme-linked immunosorbent assay in 32 patients with DCM and investigated the impact of these markers to the clinical characteristics of these patients. Serum levels of 8-OHdG, but not TRX were significantly correlated with New York Heart Association functional class, left atrial diameters, left ventricular end-diastolic diameters, left ventricular end-systolic diameters, and plasma levels of brain natriuretic peptide. CONCLUSION: These data suggest oxidative DNA damage is increased in patients with DCM according to the severity of HF. Serum levels of 8-OHdG may represent clinically useful markers of left ventricular remodeling.

8-Hydroxy-2'-Deoxyguanosine↗

[Cardiac resynchronization therapy].

Despite recent advances in pharmacologic treatment for heart failure, the prognosis of patients with chronic heart failure remains poor. One third of patients with chronic heart failure have intraventricular conduction delay. The ventricular mechanical dyssynchrony based on intraventricular conduction delay worsen ventricular systolic dysfunction. Cardiac resynchronization therapy(CRT) through biventricular pacing significantly improves symptoms, exercise tolerance, hemodynamics, hospitalization for heart failure and mortality. However, it is estimated that 30 % of patients do not respond to CRT. A direct assessment of mechanical dyssynchrony with echocardiography seems more important than QRS duration in selecting appropriate patients for CRT.

Cardiac Pacing, Artificial↗

[Implantable cardioverter-defibrillator in patients with chronic heart failure].

Sudden cardiac death (SCD) is a major cause of death in patients with chronic heart failure. The implantable cardioverter-defibrillator (ICD) effectively treats malignant ventricular tachyarrhythmias and reduces significantly the total mortality as well as the incidence of SCD in heart failure patients. It is evident that ICD is indicated for the secondary prevention of SCD. There is growing evidence for the use of the ICD for the primary prevention of SCD in patients with LV systolic dysfunction without documented arrhythmia. However, the efficacy of ICD seems to be modest in patients with advanced heart failure. Individualized combined therapies such as ICD plus amiodarone and ICD plus cardiac resynchronization therapy are necessary for advanced heart failure patients. It is doubtful whether ICD is indicated for MADIT II and SCD -HeFT population in Japan, where the incidence of SCD is thought to be lower than the Western countries.

Defibrillators, Implantable↗

[Long-term outcome and tolerability of carvedilol therapy in Japanese patients with chronic heart failure].

OBJECTIVES: Randomized controlled clinical studies in western countries have shown that the beta-blockers improve the survival of patients with chronic heart failure and are highly tolerable. The tolerability of beta-blocker therapy and the long-term prognosis for patients with chronic heart failure receiving beta-blockers remain unclear in Japan. In the present study, carvedilol was employed for the treatment of mild to severe chronic heart failure and the long-term prognosis of the patients was monitored to evaluate the tolerability and chronic efficacy of beta-blocker therapy in Japanese patients. METHODS: Three hundred and twenty-seven patients with chronic heart failure [Classes II to IV according to the New York Heart Association (NYHA) classification] were studied. Carvedilol was started at a dose of 1.25 to 5 mg/day and then increased to the final target dose of 20 mg/day, depending on its tolerability in each patient. The patients were monitored with respect to their NYHA classification, daily mean heart rate (evaluated by Holter electrocardiography), changes of the plasma brain natriuretic peptide level, and prognosis. They were followed up for a mean period of 4.4 +/- 1.8 years. RESULTS: Carvedilol was not tolerated by 21 of the 327 patients (6.4%), and was discontinued during the follow-up period in 38 patients (11.6%). The mean maintenance dose for the remaining 268 patients (82.0%), in whom treatment could be continued over the long term, was 14.1 +/- 7.5 mg. The NYHA classification and plasma brain natriuretic peptide level were significantly improved, and the daily mean heart rate was also significantly reduced in the 268 patients. Significant improvement was also observed in patients with severe heart failure (classes III or IV of the NYHA classification). The five-year survival rate of patients continuously treated with carvedilol was 83%, and their outcome was significantly better than that of those who could not tolerate the drug (49%; p < 0.001) or those who discontinued treatment prematurely (68%; p < 0.001). The treated group also had a significantly lower cardiac death rate than the intolerant group or discontinued group. CONCLUSIONS: Carvedilol was well tolerated by Japanese patients with chronic heart failure. Treatment with low-dose carvedilol may improve the symptoms and prognosis of patients with mild to severe chronic heart failure over the long term.

Adrenergic beta-Antagonists↗

Echocardiographic characteristics predicting efficacy of drug therapy in patients with hypertrophic obstructive cardiomyopathy.

BACKGROUND: The efficacy of long-term drug therapy for patients with hypertrophic obstructive cardiomyopathy (HOCM) remains unclear. This study was performed to characterize the echocardiographic findings of patients responsive to drug therapy. METHODS: Left ventricular outflow tract (LVOT) gradient and morphologic characteristics of the septum, posterior wall, and mitral valve were measured echocardiographically in 35 Japanese patients. The mean follow-up time was 41+/-22 months. RESULTS: Long-term drug therapy was effective in 14 patients and ineffective in 21 patients. Five of the refractory patients required mitral valve replacement to become free of symptoms. Only 5 of 21 patients whose LVOT gradient was 100 mm Hg were responsive to drug therapy, whereas 9 of 14 patients whose LVOT gradient was <100 mm Hg were responsive to drug therapy. Seven of eight patients with an asymmetric septal hypertrophy (ASH) ratio >==1.3 and LVOT gradient <100 mm Hg were responsive to drug therapy. Only 3 of 16 patients with an ASH ratio <1.3 were responsive to drug therapy. There was no correlation between the efficacy of drug therapy and the morphology of the mitral valve or the width of the LVOT. CONCLUSION: Our results demonstrate that drug therapy effectively reduces the LVOT gradient in patients with asymmetric septal hypertrophy and a less severe LVOT gradient.

Adult↗

Emergency treatment with nifekalant, a novel class III anti-arrhythmic agent, for life-threatening refractory ventricular tachyarrhythmias: post-marketing special investigation.

BACKGROUND: Because class I anti-arrhythmic drugs sometimes suppress cardiac function caused by their negative inotropic effects, they are not adequate for use in patients with severe heart failure, even as emergency treatment for life-threatening ventricular tachyarrhythmias (ventricular tachycardia (VT)/ventricular fibrillation (VF)). METHODS AND RESULTS: An objective evaluation committee re-evaluated the effect of nifekalant in 191 patients with refractory VT/VF. The attack termination was achieved in 45 out of 93 patients (48.4%). Nifekalant was administered to 39 patients with direct-current (DC) shock-resistant VT/VF and directly terminated VT/VF in 9 patients. In 15 of the remaining 29 patients (51.7%), VT/VF was successfully cardioverted by additional DC shock after nifekalant administration. Prevention of recurrence was achieved in 60 out of 99 patients (60.6%). Corrected QT interval (QTc) was significantly prolonged after initial administration of nifekalant (0.463+/-0.056 to 0.504 +/-0.072), and during maintenance infusion (0.470 +/-0.056 to 0.547+/-0.070). As an adverse reaction, excess prolongation of QTc was noted in 11 patients including 3 patients with torsades de pointes. Hemodynamic parameters tended to improve after maintenance infusion of nifekalant. CONCLUSION: Nifekalant is effective and useful for life-threatening refractory ventricular tachyarrhythmias, although careful observation of the QT interval is required.

Aged↗

Ampulla cardiomyopathy after hypoglycemia in three young female patients with anorexia nervosa.

Ampulla cardiomyopathy is named after the echocardiographic abnormalities occurring in this condition, characterized by extensive akinesis (ballooning ) of the apical region with hypercontraction of the basal segment of the ventricle. We describe 3 young female anorexia nervosa patients showing evidence of this cardiac complication after hypoglycemia. One case was complicated by echocardiographically confirmed ampulla cardiomyopathy while the other 2 patients showed increases in myocardial enzymes and transient electrocardiographic abnormalities consistent with this complication. The precipitating event for all three patients was hypoglycemic coma, and this is the first case report in which this factor lead to the complication of ampulla cardiomyopathy in anorexia nervosa patients.

Adolescent↗

A novel function of N-cadherin and Connexin43: marked enhancement of alkaline phosphatase activity in rat calvarial osteoblast exposed to sulfated hyaluronan.

In this study, we examined the interaction of the osteoblast which forms bone and sulfated hyaluronan (SHya). For the purpose of the creation of a new functional polysaccharide, we introduced a sulfate group in hyaluronan (Hya) of high molecular weight, and SHya of high molecular weight could be obtained for the first time. When rat calvarial osteoblast (rOB) cells were cultured with a high concentration of SHya, they formed aggregated spheroids after 4h and the spheroids grew to about 200microm after 24h. We examined the expression of cell adhesion molecules in order to clarify the mechanism of aggregate formation. The N-cadherin (N-cad) and Connexin43 (Cx43) expression level of rOB cells cultured with SHya remarkably increased after 2h. A difference in the expression of Integrin beta1 (Intbeta1) could not be observed between the SHya addition and control group. The alkaline phosphatase (ALPase) activity of rOB cells cultured with SHya after 8h was significantly enhanced in comparison with control. Therefore, the sulfate group of SHya seems to enhance expression of cell adhesion protein such as N-cad and Cx43, resulting in aggregate formation and further remarkable induction of the ALPase activity of rOB cells.

Alkaline Phosphatase↗

In situ monitoring of metal nanoparticle self-assembly on protein-functionalized glass by broadband optical waveguide spectroscopy.

Broadband, time-resolved optical waveguide (OWG) spectroscopy has been used for in situ, real-time investigation into the self-assembly of metal nanoparticle monolayers. The OWG spectroscopy makes it possible to use the transverse electric (TE) and transverse magnetic (TM) modes to measure surface plasmon absorption of immobilized metal nanoparticles in two directions, parallel and normal to the waveguide surface. Therefore, this technique can provide direction-dependent information on the metal nanoparticles at the interface. In this paper, a 50-microm-thick glass plate was used as a slab waveguide and the kinetics of Au nanoparticle adsorption on a hemoglobin-functionalized glass substrate was examined in the early stage of self-assembly. The findings show that with the TE mode the surface plasmon resonance (SPR) behavior for immobilized Au nanoparticles is different from that with the TM mode.

Glass↗

In situ investigation of coadsorption of myoglobin and methylene blue to hydrophilic glass by broadband time-resolved optical waveguide spectroscopy.

Recently, we have developed a broadband optical waveguide (OWG) spectrometer by using commercially available glass plates of tens of micrometers in thickness as the substrate-free multimode waveguides (Qi et al. Opt. Lett. 2002, 27, 2001-2003). The spectrometer having a bandwidth from 360 to 800 nm is capable of simultaneously detecting the Soret-band absorption of heme proteins and the visible absorption of organic dyes. In this article, the spectrometer was used to in situ investigate coadsorption of methylene blue (MB) and myoglobin from the mixed aqueous solution onto bare glass. Both MB and myoglobin in the mixed solution are positively charged, which makes them not only avoid the chemical interaction between each other but also easy to adsorb to hydrophilic glass. It was found that the coadsorption of MB and myoglobin occurred just in the early stage and the glass surface was finally occupied by myoglobin. The OWG spectroscopic investigation into the respective MB and myoglobin adsorptions shows that MB adsorption is reversible to some degree but that of myoglobin is irreversible. It reveals that the electrostatic binding of myoglobin to bare glass is stronger than the case of MB. Therefore, the adsorbed MB can be substituted by myoglobin. Moreover, via the electrostatic repulsion the tightly immobilized myoglobin prevents bulk MB from occupying the empty surface sites. It is the reason MB is absent from the hydrophilic glass coated with a submonolayer of myoglobin. In the article, we explained both the strong dimerization of MB at the interface and a slow decrease with time of the Soret-band absorbance after its maximum was reached. We also estimated the myoglobin coverage based on the waveguide theory. The study shows the distinguished applicability of the broadband OWG spectroscopy for in situ, real-time monitoring of the dye-protein coadsorption to silica from the mixed solution.

Journal Article↗

Involvement of reactive oxygen species (ROS) in the induction of genetic instability by radiation.

Radiation generates reactive oxygen species (ROS) that interact with cellular molecules, including DNA, lipids, and proteins. To know how ROS contribute to the induction of genetic instability, we examined the effect of the anti-ROS condition, using both ascorbic acid phosphate (APM) treatment or a low oxygen condition, on the induction of delayed reproductive cell death and delayed chromosome aberrations. The primary surviving colonies of mouse m5S-derived cl. 2011-14 cells irradiated with 6 Gy of X-rays were replated and allowed to form secondary colonies. The anti-ROS treatments were applied to either preirradiation culture or postirradiation cultures for primary or secondary colony formation. Both anti-ROS conditions relieved X-ray-induced acute cell killing to a similar extent. These anti-ROS conditions also relieved genetic instability when those conditions were applied during primary colony formation. However, no effect was observed when the conditions were applied during preirradiation culture and secondary colony formation. We also demonstrated that the amounts of ROS in X-ray-irradiated cells rapidly increase and then decrease at 6 hr postirradiation, and the levels of ROS then gradually decrease to a baseline within 2 weeks. The APM treatment kept the ROS production at a lower level than an untreated control. These results suggest that the cause of genetic instability might be fixed by ROS during a 2-week postirradiation period.

Animals↗

Colloidal gold submonolayer-coated thin-film glass plates for waveguide-coupled surface plasmon resonance sensors.

A novel optical sensor based on spectroscopic measurement of the plasmon absorption of a colloidal gold submonolayer immobilized upon a planar waveguide has been developed for label-free detection of biomolecular interactions at the sensor's surface. We fabricated the sensor by locally modifying a 50-microm-thick glass plate with hemoglobin (Hb) and then self-assembling gold colloids from the aqueous solution onto the Hb-modified area of the glass plate. Polychromatic light from a xenon-arc lamp was launched into the thin-film glass plate by use of a broadband fiber-coupling method. With the use of a CCD detector to monitor the light beam emitted from an end face of the glass plate, the plasmon absorption spectrum of the colloidal gold submonolayer was determined to depend on the polarization states of the guided light and to change with the refractive index of the medium in contact with the colloids. In addition to simplicity of fabrication and the ease of use, the sensor yields a larger absorbance sensitivity than the normal transmission measurement.

Journal Article↗

Enhanced DNA synthesis accompanied by constitutive phosphorylation of the ERK pathway in human fibroblasts cultured on a polyelectrolyte complex.

In this study, we examined the cellular and molecular responses of fibroblasts cultured on a polyelectrolyte complex (PEC) derived from sulfated chitin as a polyanion and chitosan as a polycation. On PEC-coated dishes, the fibroblasts aggregated and then developed spheroid-like structures. At earlier stages of culture, DNA synthesis of cells cultured on PEC was stimulated approximately 75% higher than control cells. Among various signaling molecules examined, including mitogen-activated protein kinases, Akt/PKB and p53, an extracellular-signal-regulated kinase (ERK) was selectively and constitutively phosphorylated in cells cultured on PEC. The constitutive phosphorylation of ERK was derived from an activation of the ERK kinase MEK, but not from an inactivation of the ERK phosphatase MKP-1. Furthermore, ERK phosphorylation was almost abolished by a membrane receptor tyrosine kinase inhibitor. The enhanced phosphorylation of focal adhesion kinase, a downstream molecule of integrins, was also observed in cells cultured on PEC. These results suggest that fibroblasts recognize PEC as a continuous mitogenic stimulant which results in the constitutive activation of the MEK-ERK pathway toward mitogenesis. Further, PEC interacts with the cell membrane leading to activation of membrane molecules, including integrins and receptor tyrosine kinases. These responses may account, at least in part, for the potential use of PEC as a biomaterial for tissue regeneration.

Cell Aggregation↗