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Biomedical subjects

Takeshi Yamashita

Publications and source records attributed to Takeshi Yamashita.

At least 19 recordsLinked to original sources
PubMed2007

Stress distribution in the supraspinatus tendon after tendon repair: suture anchors versus transosseous suture fixation.

BACKGROUND: The stress concentration at the site of supraspinatus tendon repair, either by suture anchor fixation or by transosseous suture fixation, has not been fully clarified. HYPOTHESIS: Suture anchor fixation showed higher stress concentrations in the tendon than did transosseous suture fixation. STUDY DESIGN: Controlled laboratory study. METHODS: Three finite element models were developed based on a previously published model of normal supraspinatus tendon (0 degrees abduction). Single-row fixation, double-row fixation, and transosseous suture fixation were simulated. A tensile force was applied to the proximal end of the supraspinatus tendon to simulate its contraction force. RESULTS: In the single-row model, the stress appeared from the site of the anchor and extended into the proximal tendon. The highest stress concentration was observed on the bursal surface of the tendon. The double-row model showed a similar pattern to the single-row model except that the stress concentration was observed only around the medial anchor. In the transosseous model, the stress appeared from the attachment site to a bony trough, which extended proximally into the tendon substance. No significant stress concentration was observed inside the tendon. CONCLUSION: Both single-row and double-row fixations showed higher stress concentration inside the tendon than did transosseous suture fixation. CLINICAL RELEVANCE: A high stress concentration might be a cause of the rerupture often observed after arthroscopic cuff repair using suture anchors.

Adaptation, Physiological↗
PubMed2006

A method for the simultaneous analysis of mRNA levels of multiple cardiac ion channels with a multi-probe RNase protection assay.

AIMS: Various pathological conditions can alter cardiac electrophysiological properties not only by physiological responses but also by modifying the gene expression of ion channels (electrical remodelling). To investigate the underlying mechanisms of the latter, electrophysiological alterations would require a simultaneous and comprehensive analysis of the mRNA level of the ion channel genes. METHODS AND RESULTS: We designed 19 cardiac ion channel cDNA templates to analyse the corresponding mRNAs and classified them into three template sets. Those sets were a voltage-dependent K(+) channel series (rat erg, KvLQT1, Kv4.3, Kv4.2, Kv2.1, Kv1.5, Kv1.4, Kv1.2), an inwardly rectifying K(+) channel series (rat Kir6.2, SUR2A/B, Kir3.4, Kir3.1, Kir2.2, Kir2.1), and an inward cationic ion channel series (rat SCN5A, alpha1C, beta2, alpha2delta2 of cardiac L-type Ca(2+) channel and alpha1G). These cDNA templates were used to synthesize antisense digoxigenin-labelled RNA probes. An amount of the total RNA of 25 microg was adequate to analyse simultaneously the mRNA levels of the ion channel genes with the use of multi-probe RPA, and these three multi-probe template sets enabled us to evaluate the profile of the spatial and temporal transcripts of the cardiac ion channels. CONCLUSION: The newly developed ion channel multi-probe RPA templates provide an aid in the comprehensive analysis of the electrical remodelling of the heart.

Animals↗
PubMed2006

What are arrhythmogenic substrates in diabetic rat atria?

INTRODUCTION: Diabetes mellitus is one of the significant independent risk factors for the development of atrial fibrillation (AF). However, the pathophysiological mechanisms of the relationship have not been fully elucidated. METHODS AND RESULTS: The genetic type II diabetes (GK) rats and their original (Wistar) ones were subjected to electrophysiological (n = 8 per group) and histological (n = 7 per group) studies. At 40 weeks old, when GK rats had significantly (P < 0.01) more increased plasma glucose and HbA(1c) values than Wistar rats, atrial electrical stimuli in the isolated-perfused hearts induced significantly greater number of repetitive atrial responses in GK rats than in Wistar rats (47.9 +/- 17.5 vs 3.1 +/- 1.3 beats, respectively, P < 0.01). GK rats showed significantly longer intra-atrial activation time than Wistar rats (18.3 +/- 0.4 ms vs 15.9 +/- 0.5 ms, P < 0.01) without any significant difference in the atrial refractoriness. The histological examination revealed significantly increased diffuse fibrotic deposition in GK rats atria compared with Wistar ones (P < 0.01). CONCLUSION: The present diabetic GK rat showed increased atrial arrhythmogenicity with intra-atrial conduction disturbance, and thus indicated that the structural remodeling of atrium characterized by diffuse interstitial fibrosis would be a major substrate for diabetes-related AF.

Animals↗
PubMed2006

Regulation of CaMKII by alpha4/PP2Ac contributes to learning and memory.

Ca(2+)-dependent CaMKIIalpha activation with autophosphorylation plays an essential role in learning and memory. The regulation of CaMKIIalpha by dephosphorylation by protein phosphatase 1 (PP1) has been demonstrated. We addressed whether the protein phosphatase 2A (PP2A) that is abundant in the brain could be involved in the regulation of CaMKIIalpha. CaMKIIalpha was associated with the catalytic subunit of PP2A (PP2Ac) and alpha4, a regulator of PP2A. To investigate whether alpha4 plays an important role in the CNS, we established a neuron specific Cre transgenic mouse and a neuron specific alpha4 deficient mouse (N-alpha4 KO mouse). This N-alpha4 KO mouse showed impaired learning and memory in a water maze and also shuttle-box avoidance test. The activity of CaMKIIalpha also increased in hippocampus. An overexpression of alpha4 in the neuronal cell line demonstrated the activity of CaMKIIalpha to be regulated by alpha4. alpha4 and PP2Ac were localized in the cytoplasm but not in the postsynaptic density (PSD), thus suggesting that the dephosphorylation of CaMKIIalpha by alpha4/PP2Ac occurred in the cytoplasm. These results suggest that alpha4 and PP2A may thus play an important role in CaMKIIalpha regulation and thereby also influence learning.

Adaptor Proteins, Signal Transducing↗
PubMed2006

An in vivo study of a growth-factor enhanced, cell free, two-layered collagen-tricalcium phosphate in deep osteochondral defects.

Focal osteochondral defects are still a challenging problem in joint surgery. We have developed a two-layered implant consisting of a basal porous beta-tricalcium phosphate (TCP) for bone reconstruction and a superficial fibrous collagen type I/III layer for cartilage regeneration. Fifty-four osteochondral defects in the trochlear groove of 27 Göttinger Minipigs were created and either left untreated, treated with the implant alone, or the implant augmented with an additional growth factor mixture, which was assumed to stimulate cell and tissue differentiation. Follow-up was 6, 12 and 52 weeks with n=6 for each group. The repair tissue was evaluated for its gross appearance and biomechanical properties. Histological sections were semi-quantitatively scored for their histomorphological structure. Treatment with the two-layered implant improved defect filling and subchondral bone repair at 6 and 12 weeks follow-up. The TCP was replaced by cancellous bone at 52 weeks. Cartilage repair tissue mainly consisted of fibrocartilage and showed a moderate cell density up to the joint surface. Growth factor treatment improved the mechanical and histomorphological properties of the cartilage repair tissue at 12, but not at 52 weeks postoperatively. In conclusion, the two-layered collagen-TCP implant augmented with chondroinductive growth factors seems a promising new option for the treatment of deep osteochondral defects in joint surgery.

Animals↗
PubMed2006

Randomized study of angiotensin II type 1 receptor blocker vs dihydropiridine calcium antagonist for the treatment of paroxysmal atrial fibrillation in patients with hypertension.

BACKGROUND: Mega trials of rhythm vs rate control could not demonstrate the usefulness of available antiarrhythmic drugs, so a more effective and safer therapy for atrial fibrillation (AF) is now required. One candidate is the so-called "upstream therapy", which refers to the blockade of upstream modifying elements (renin - angiotensin system, cathecholamines, oxidative stress etc) that contribute to the arrhythmogenic substrate. METHODS AND RESULTS: The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is a randomized comparative evaluation of an angiotensin II type 1 blocker (candesartan) and a dihydropiridine calcium blocker (amlodipine), both combined with antithrombotic therapy, as an antiarrhythmic therapy for the treatment of paroxysmal AF (PAF) associated with hypertension. To test the usefulness of this therapy, this study will reveal the recurrence rate of asymptomatic as well as symptomatic PAF during 1-year of treatment with candesartan or amlodipine, using daily transtelephonic monitoring. CONCLUSIONS: The J-RHYTHM II study will follow 400 patients with PAF and hypertension who were treated at approximately 50 sites throughout Japan, and will provide clinically important information.

Amlodipine↗
PubMed2006

Critical level of cerebral oxygenation during exercise in patients with left ventricular dysfunction.

BACKGROUND: In a recent study the indexes of cerebral oxygenation decreased during maximal exercise in nearly half of all patients with left ventricular dysfunction. Whether these levels decrease severely enough to influence mental status or level of consciousness was evaluated in the present study. METHODS AND RESULTS: Forty-two patients with idiopathic dilated cardiomyopathy (IDC) and 29 healthy subjects underwent a symptom-limited maximal exercise test. The cerebral oxyhemoglobin (O(2)Hb) and tissue oxygenation index (TOI) were continuously monitored using near-infrared spectroscopy. The changes in O(2)Hb and TOI were also measured in 7 subjects: 2 who experienced episodes of reduced consciousness caused by sudden decreases in blood pressure during exercise recovery and 5 who exhibited sustained ventricular tachycardia during an electrophysiological study. The change in cerebral O(2)Hb during exercise in patients with IDC averaged 0.38+/-3.39 micromol/L, significantly lower than in the normal subjects (4.30+/-4.47 micromol/L, p<0.0001). The cerebral O(2)Hb decreased during exercise in 18 of 42 patients with IDC. The change in cerebral TOI in the IDC patients during exercise was significantly less than that in the normal subjects (-2.0+/-4.7 vs 2.1+/-5.8%, p=0.002). The mean decreases in cerebral O(2)Hb and TOI were -5.34 micromol/L and -9.7%, respectively, in the patients with reduced consciousness during exercise recovery, and -2.52 micromol/L and -16.5%, respectively, in those with ventricular tachycardia. CONCLUSION: The indexes of cerebral oxygenation may drop severely enough during maximal exercise in some patients with severe IDC that consciousness is affected.

Aged↗
PubMed2006

Molecular and electrophysiological differences in the L-type Ca2+ channel of the atrium and ventricle of rat hearts.

BACKGROUND: Many pathological conditions induce electrical remodeling, possibly through intracellular Ca2+ overload, but the currently available L-type Ca2+ channel blockers may be detrimental because of their global negative inotropic effects. METHODS AND RESULTS: To determine whether the L-type Ca2+ channel is identical throughout the heart, the distribution of the mRNAs and proteins comprising the L-type Ca2+ channel and its electrophysiological properties were analyzed in rat atria and ventricles. The mRNA of alpha2delta-2 (Cacna2d2) was more abundantly expressed in the atrium (approximately 5-fold) than in the ventricle. In contrast, alpha1C (Cacna1c) (Cav1.2) mRNA was significantly less abundant in the atrium. The level of the alpha1C (Cacna1c) (Cav1.2) protein was decreased (approximately 0.5-fold) and that of alpha2 delta-1 (Cacna2d1) was increased (approximately 2-fold) in the atrium compared with the ventricle. Although the peak ICa,L density showed no significant differences, voltage dependence of inactivation and activation of the current showed a more depolarized shift in the atrium than in the ventricle. CONCLUSION: These results indicate that in the rat heart the L-type Ca2+ channel differs between the atrium and ventricle with regard to gene expression and electrophysiological properties.

Animals↗
PubMed2006

Rate control and quality of life in patients with permanent atrial fibrillation: the Quality of Life and Atrial Fibrillation (QOLAF) Study.

BACKGROUND: The present study aimed to determine whether quality of life (QOL) in permanent atrial fibrillation (AF) patients would be improved by monotherapy with beta-blocker (BB) or calcium antagonist (CAA) as compared with digitalis. METHODS AND RESULTS: Twenty-nine patients with permanent AF under digitalis were randomized into BB (bisoprolol, atenolol or metoprolol) or CAA (verapamil) monotherapy treatment group. Twenty-five were men and the mean age was 67+/-8 years. After the assigned monotherapy, 12 patients received the other monotherapy in a cross-over fashion. Under each treatment, efficacy of rate control was determined by Holter electrocardiogram (ECG), treadmill testing and QOL questionnaire (Short Form-36 (SF-36) and Quality of Life of Atrial Fibrillation (AFQLQ)), and compared with the baseline digitalis treatment. CAA significantly increased mean and minimum heart rate (HR) in Holter ECG as compared with digitalis, whereas BB increased only minimum HR. Exercise duration in treadmill testing was significantly prolonged by CAA treatment, although it only tended to be prolonged by BB treatment. CAA but not BB improved role function-physical score of SF-36, and frequency and severity of symptoms of AFQLQ. CONCLUSION: These results indicate that CAA is preferable to digitalis when monotherapy is selected for short-term improvement of QOL and exercise tolerance in patients with permanent AF.

Adrenergic beta-Antagonists↗
PubMed2006

[Magnetic resonance imaging of repair cartilage].

In recent years, several MR imaging techniques that enable detailed morphological and qualitative evaluations of repair cartilage have been developed. We perform fat-suppressed three-dimensional spoiled gradient-recalled (3D-SPGR) magnetic resonance (MR) imaging and delayed gadolinium-enhanced MR imaging of cartilage (dGEMRIC) for the evaluation of repair cartilage. Evaluation of the time course changes in signal intensity of repair cartilage by use of 3D-SPGR MR imaging was thought to be useful for the assessment of histological change in repair cartilage. Moreover, evaluation of the glycosaminoglycan concentration in repair cartilage by use of dGEMRIC was thought to be useful to assess the quality and function of repair cartilage. These new MR imaging techniques may be useful for evaluating repair cartilage and for assessing the treatment effect and the long-term durability of repair cartilage.

Cartilage, Articular↗
PubMed2005

The heterodimer of alpha4 and PP2Ac is associated with S6 kinase1 in B cells.

Alpha4 is a signal transduction molecule that is required for B cell activation. Alpha4 associates with the catalytic subunit of protein phosphatase 2A (PP2Ac) and regulates its enzymatic activity. We examined the interaction of alpha4/PP2Ac with S6 kinase1 (S6K1) as a potential downstream signal transduction molecule because both alpha4/PP2Ac association and S6K1 activity were rapamycin-sensitive. Stimulation of spleen B cells with lipopolysaccharide induced the interaction of alpha4/PP2Ac and S6K1. Pull-down assay demonstrated that alpha4 interacts with S6K1 through PP2Ac. S6K1 and alpha4 bind to the different regions of PP2Ac as S6K1 to the region from amino acid 88th to 309th of PP2Ac and alpha4 to the two separated regions of the amino-terminal (from amino acid 19th to 22nd) and the middle (from 150th to 164th) portions of PP2Ac. These results suggest that alpha4 regulates S6K1 activity through PP2Ac in B cell activation.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Stabilization of guanine quadruplex DNA by the binding of porphyrins with cationic side arms.

Many aromatic ligands, including tetra-(N-methyl-4-pyridyl)porphyrin (TMPyP4), have been reported to bind and stabilize quadruplex structure of telomeric DNA. We synthesized novel quadruplex-interacting porphyrins with cationic pyridinium and trimethylammonium arms at para- or meta-position of all phenyl groups of tetratolyl porphyrin. An antiparallel quadruplex structure was found to be stabilized more greatly by the meta-isomers than by the para-isomers and well-studied TMPyP4, as revealed by the increase in melting temperature of the quadruplex. One mole equivalent of the isomers was sufficient to stabilize the quadruplex. From the results of absorption, induced circular dichroism, and fluorescence resonance energy transfer spectroscopic methods, the unique site for the porphyrin binding is suggested to be the external guanine tetrad or groove of the quadruplex. The cationic side arms played a key role in the stabilization of the quadruplex structure.

Cations↗
PubMed2005

Associations of plasma C-reactive protein levels with the presence and extent of coronary stenosis in patients with stable coronary artery disease.

Prospective studies showed plasma high sensitivity C-reactive protein (hsCRP) levels to be a powerful predictor of cardiac events. However, the association between hsCRP levels and the extent of coronary stenosis in patients with coronary artery disease (CAD) remains controversial. We investigated the association between hsCRP levels and the extent of coronary stenosis in 273 patients undergoing elective coronary angiography. Plasma hsCRP levels were higher in patients with CAD than in those without CAD (0.70 mg/l versus 0.56 mg/l, P < 0.02), but hsCRP levels did not correlate with the number of >50% stenotic vessels and were not a significant factor for CAD. However, after the exclusion of 76 patients taking statins, a step-wise increase in hsCRP levels was found depending on the number of >50% stenotic vessels: 0.50 in CAD(-), 0.68 in 1-vessel, 0.77 in 2-vessel, and 0.88 mg/l in 3-vessel disease (P < 0.01). The hsCRP levels also correlated with the numbers of >50% and >25% stenotic segments (r = 0.30 and 0.32, P < 0.001). Multivariate analysis revealed the hsCRP levels to be a significant factor for CAD. Thus, after the exclusion of patients with statins, plasma hsCRP levels were found to be associated with the presence and extent of coronary stenosis in patients with stable CAD.

Aged↗
PubMed2005

Hangover susceptibility in relation to aldehyde dehydrogenase-2 genotype, alcohol flushing, and mean corpuscular volume in Japanese workers.

BACKGROUND: A study of Asian-American students suggested a positive association between inactive ALDH2*2 and susceptibility to hangover. A biomarker for moderate-to-heavy drinking in persons with inactive aldehyde dehydrogenase-2 (ALDH2) is increased mean corpuscular volume (MCV). METHODS: Associations between hangover and ALDH2 genotype, alcohol flushing, and MCV were examined for 251 Japanese workers (139 men, 112 women). RESULTS: Inactive ALDH2*1/2*2 heterozygotes drank less alcohol than active ALDH2*1/2*1 homozygotes (p < 0.0001), but the frequency of hangover did not significantly differ between the two groups for either gender. The amount of drinking reported to lead to hangover was significantly less for male and female ALDH2*1/2*2 heterozygotes than for their ALDH2*1/2*1 homozygous counterparts (p < 0.005). The proportion of men who had hangover three times or more during the past year increased significantly with increased daily alcohol consumption in men with the ALDH2*1/2*2 genotype (p = 0.0002) but not in those with the ALDH2*1/2*1 genotype. For men who usually consumed <44 g of ethanol/day, the median amount of drinking before hangover was significantly lower for ALDH2*1/2*2 men than for ALDH2*1/2*1 men reporting the same level of consumption. Hangover occurred with consistently high frequency among ALDH2*1/2*1 men, regardless of their daily consumption. Similar findings were observed in a comparison of men who never flushed and those who reported current or former flushing, a surrogate marker of inactive ALDH2. Assessment of hangover risk by quartiles of MCV showed that men with MCV of > or =96 had a significantly higher risk of hangover than did men with MCV of <91 (odds ratio = 5.56; 95% confidence interval = 1.69-18.25). CONCLUSIONS: Inactive heterozygous ALDH2, alcohol flushing, and increased MCV were positively associated with hangover susceptibility in Japanese workers, suggesting that acetaldehyde is etiologically linked to the development of hangover.

Adult↗
PubMed2005

Premature atrial complex with P'R prolongation indicates multiple atrioventricular nodal pathways.

BACKGROUND: The goal of the present study was to test if ambulatory Holter recordings can predict the electrophysiologic study (EPS) findings in patients with supraventricular tachycardia (SVT). METHODS AND RESULTS: The study involved 110 patients with SVT who underwent Holter recording, and then EPS. The hypotheses were that (1) a P'R interval of premature atrial complexes (PACs) between 280 and 400 ms in the Holter recordings predicted dual atrioventricular nodal (AVN) pathways, (2) P'R interval >400 ms predicted triple or more AVN pathways, and (3) SVT initiated by a single PAC suggested easy SVT induction during the EPS. The EPS revealed dual AVN pathways in 14 (93%) of 15 patients with P'R intervals between 280 and 400 ms on the Holter recordings, and triple or more AVN pathways in 18 (90%) of 20 patients with P'R intervals >400 ms. In addition, a single extrastimulus easily induced SVT during the EPS in 11 (85%) of 13 patients in whom SVT was initiated by a single PAC during Holter recording. CONCLUSION: The ambulatory Holter recording criteria specifically predicted the EPS findings, thereby providing useful advance information.

Aged↗
PubMed2005

Pilsicainide-induced coronary vasospasm in a patient with Brugada-type electrocardiogram.

A 65-year-old man with Brugada-type electrocardiogram (ECG) was admitted to our hospital for chest pain, palpitation and faintness. In the cardiac electrophysiological study, no ventricular tachyarrthymia was induced either at baseline or after pilsicainide (50 mg) infusion. Intravenous administration of pilsicainide exaggerated ST-segment elevation in V(1-4) and converted it to the coved type in V(1), accompanied by severe chest pain. Coronary angiography revealed the vasospasm of the right coronary artery was induced by pilsicainide, not by ergonovine. This is the first case report of coronary vasospasm induced by a pure sodium channel blocker in a patient with Brugada-type ECG.

Aged↗