Effects of aortic valve replacement on left ventricular dyssynchrony in aortic stenosis with narrow QRS complex.

BACKGROUND: The presence and determinants of left ventricular (LV) dyssynchrony in patients with aortic stenosis (AS) are not clear. The aims of this study were to (1) investigate the presence and determinants of LV dyssynchrony and (2) assess if LV dyssynchrony could improve after aortic valve replacement (AVR) in patients with AS with narrow QRS complexes. METHODS: Twenty healthy subjects and 30 consecutive patients with AS were retrospectively studied. AVR was performed in 19 patients. The time to peak systolic velocity with reference to the QRS complex (Ts), the standard deviation of Ts (Ts-SD), and maximal difference of Ts were measured as the index of LV dyssynchrony in 12 LV segments on Doppler tissue imaging. RESULTS: Ts-SD (25 ± 17 vs 52 ± 15 msec) and the maximal difference of Ts (70 ± 47 vs 148 ± 38 msec) were significantly greater (P < .001) in patients with AS than in healthy subjects. Early after AVR (11 ± 4 days), LV dyssynchrony significantly improved with the shortening of Ts-SD (29 ± 14 msec) and the maximal difference of Ts (91 ± 42 msec) (P < .001). Ts-SD was significantly correlated with estimated LV systolic pressure (r = 0.53, P < .001) and LV mass index (r = 0.28, P = .02). CONCLUSIONS: LV dyssynchrony is not uncommon in patients with AS with narrow QRS complexes and is reversible early after AVR, suggesting the favorable effect of afterload reduction on dyssynchronous LV contraction.

Interatrial septum pacing decreases atrial dyssynchrony on strain rate imaging compared with right atrial appendage pacing.

BACKGROUND: Interatrial septum pacing (IAS-P) decreases atrial conduction delay compared with right atrial appendage pacing (RAA-P). We evaluate the atrial contraction with strain rate of tissue Doppler imaging (TDI) during sinus activation or with IAS-P or RAA-P. METHODS: Fifty-two patients with permanent pacemaker for sinus node disease were enrolled in the study. Twenty-three subjects were with IAS-P and 29 with RAA-P. The time from end-diastole to peak end-diastolic strain rate was measured and corrected with RR interval on electrocardiogram. It was defined as the time from end-diastole to peak end-diastolic strain rate (TSRc), and the balance between maximum and minimum TSRc at three sites (ΔTSRc) was compared during sinus activation and with pacing rhythm in each group. RESULTS: There were no significant differences observed in general characteristics and standard echocardiographic parameters except the duration of pacing P wave between the two groups. The duration was significantly shorter in the IAS-P group compared with the RAA-P group (95 ± 34 vs 138 ± 41; P = 0.001). TSRc was significantly different between sinus activation and pacing rhythm (36.3 ± 35.7 vs 61.6 ± 36.3; P = 0.003) in the RAA-P group, whereas no significant differences were observed in the IAS-P group (25.4 ± 12.1 vs 27.7 ± 14.7; NS). During the follow-up (mean 2.4 ± 0.7 years), the incidence of paroxysmal atrial fibrillation (AF) conversion to permanent AF was not significantly different between the two groups. CONCLUSIONS: IAS-P decreased the contraction delay on atrial TDI compared to RAA-P; however, it did not contribute to the reduction of AF incidence in the present study.

The first clinical pilot study of intravenous adrenomedullin administration in patients with acute myocardial infarction.

Adrenomedullin (AM) is a 52-amino-acid vasodilator peptide that was originally isolated from human pheochromocytoma. In the previous experimental study with rat ischemia/reperfusion model, AM reduced infarct size and inhibited myocyte apoptosis. AM also suppressed the production of oxygen-free radicals. The present study was designed to evaluate the feasibility of intravenous administration of AM in patients with acute myocardial infarction. We studied 10 patients with first acute myocardial infarction [male to female ratio: 9 to 1, age: 65 ± 9 (mean ± SD) years, peak creatine phosphokinase level: 4215 ± 1933 (SD) U/L], who were hospitalized within 12 hours of symptom onset. Proceeding reperfusion therapy, AM infusion was initiated and continued at concentration of 0.0125-0.025 µg·kg·min for 12 hours. Follow-up coronary angiography and left ventriculography were performed at 3 months. Cardiac magnetic resonance was examined at 1 month and 3 months after AM therapy. During infusion of AM, hemodynamics kept stable except 2 patients. Wall motion index in the infarct area at 3 months was significantly improved compared with that at baseline, and infarct size evaluated by cardiac magnetic resonance was significantly decreased at 3 months. In conclusion, intravenous administration of AM, which possesses a variety of potential cardiovascular protective actions, can be adjunctive to percutaneous coronary intervention.

In vivo evaluation of hydroxyapatite nanocoating on polyester artificial vascular grafts and possibility as soft-tissue compatible material.

The efficacy of hydroxyapatite (HAp) nanocoating on polyester vascular grafts was investigated in animal experiments. The HAp nanocrystals were covalently bonded separately between hydroxyl groups on a nanocrystal and alkoxysilyl groups in gamma-methacryloxypropyl triethoxysilane graft polymerized on a polyester substrate. Twelve HAp-coated polyester grafts and 10 control grafts of 20, 30, or 50 mm in length were implanted in canine common carotid arteries. Serious complications or occlusions were not observed in any of the dogs after implantation. A histologic evaluation was conducted by staining with hematoxylin and eosin (HE), the von Willebrand factor (vWf), and alpha-smooth muscle actin (alpha-SMA) around the inner lumen of the grafts. The number of inflammation cells and giant cells in the HAp-coated group was significantly lower than that in the group receiving noncoated grafts (p < 0.05).

A case of Mikulicz's disease with Th2-biased cytokine profile: possible feature discriminable from Sjögren's syndrome.

This article concerns a male patient with Mikulicz's disease (MD) accompanied with marked elevation of serum immunoglobulin (Ig)G4 and IgE levels. His peripheral blood mononuclear cells (PBMC) showed markedly enhanced in vitro production of interleukin (IL)-4, IL-5, IL-13, but not interferon gamma (IFN-gamma) compared with patients with Sjögren's syndrome (SS) and healthy donors, suggesting distinct Th2 bias in this MD patient. Besides the prominent infiltration of IgG4-producing plasma cells, the enhanced expression of both CD40 and CD40 ligand (CD40L) were observed in the swollen salivary gland of the MD patient, suggesting enhanced signaling pathways for the induction of IgG4 and IgE switching. Possible differences between MD and SS in light of their underlying pathogenesis are discussed.

Repolarization spatial-time current abnormalities in patients with coronary heart disease.

BACKGROUND: Magnetocardiography (MCG) is a new technique for visualizing a current distribution in the myocardium. In recent years, current distribution parameters (CDPs) have been developed based on the distribution. The CDPs reflect spatial-time current abnormalities in patients with coronary heart disease (CHD). However, the criteria and scoring method of the abnormalities using CDPs are still controversial. METHOD: We measured MCG signals for 101 normal controls and 56 CHD patients (single-, double-, and triple-vessel diseases) using a MCG system. The CDPs (maximum current vector [MCV], total current vector [TCV], current integral map, and current rotation) during ventricular repolarization were analyzed. To evaluate the CDPs that are effective in distinguishing between normal controls and CHD patients, the areas under the receiver operating characteristic curve (A(z)) are calculated. Furthermore, the total scores ("0" to "4") of four CDPs with high A(z) values are also calculated. RESULTS: MCV and TCV angles at the T-wave peak had the highest A(z) value. Furthermore, TCV angular differences between the ST-T segment also had high A(z) values. Using the four CDPs, the averaged total score for patients with triple-vessel disease was the highest ("2.67") compared to the other groups (normal controls: 0.53). Furthermore, based on the assumption that subjects with a total score over "1" were suspected of having CHD, sensitivity and specificity were 85.7% and 74.3%, respectively. CONCLUSION: We concluded that the score and criteria using MCV and TCV during repolarization in CHD patients can reflect lesion areas and time changes of electrical activation dispersion due to ischemia.

Right atrial spontaneous echo contrast indicates a high incidence of perfusion defects in pulmonary scintigraphy in patients with atrial fibrillation.

This study investigated the relationship between right atrial SEC (RA-SEC) and silent pulmonary embolism (PE) in patients with nonvalvular atrial fibrillation (NVAF). Spontaneous echo contrast (SEC) within the cardiac chambers is associated with an increased risk of thromboembolism. However, most studies have examined the relationship between left atrial SEC and systemic thromboembolic disease. Transesophageal echocardiography (TEE) was performed in 210 patients with NVAF to assess a risk of thromboembolism. Right atrial SEC was detected in 37 patients, and 35 of these patients with RA-SEC and 29 patients without RA-SEC were enrolled in this study. However, patients with a history of symptomatic PE or deep vein thrombosis were excluded. Spontaneous echo contrast was diagnosed by TEE as the presence of smoke-like echoes that swirled in a circular pattern. PE was diagnosed by pulmonary scintigraphy. Thrombotic and thrombolytic parameters, including serum concentrations of plasmin-alpha-plasmin inhibitor complex (PIC), thrombin-antithrombin complex (TAT), D-dimer, and fibrinogen were measured in all patients. Left ventricular dimension, cardiac function, and hematologic parameters were similar in the two groups. Nevertheless, the incidence of perfusion defects in pulmonary scintigraphy was significantly higher in the group with RA-SEC (40%) than in the group without RA-SEC (7%; chi-square, P=0.006). The increased incidence of perfusion defects in pulmonary scintigraphy in patients with RA-SEC indicates that right atrial SEC may be a predictable factor at a high risk of PE.

An accordion phenomenon with ST-segment elevation of electrocardiogram and anginal chest pain: a case report.

Tortuous coronary arteries frequently make percutaneous coronary intervention (PCI) difficult by causing less accessibility of guidewire toward the target lesion. After guidewire has been passed through the target lesion, it often assists a balloon catheter and stent system insertion along the stiff guidewire. However, artificial kinking and wrinkling might induce pseudo-narrowing of coronary arteries, which has been recognized as an "accordion phenomenon." We describe an educational case of an accordion phenomenon with ST-segment elevation of electrocardiogram and anginal chest pain when the stiff guidewire which had been withdrawn was advanced again into the distal site after deploying stents.

Comparison of the effects of telmisartan and olmesartan on home blood pressure, glucose, and lipid profiles in patients with hypertension, chronic heart failure, and metabolic syndrome.

We compared the effects of telmisartan and olmesartan in 20 patients with chronic heart failure and metabolic syndrome. The subjects underwent once-daily 40 mg telmisartan for at least 3 months before switching to once-daily 20 mg olmesartan for the next 3 months (post 1). They were then treated with 3 months of once-daily 40 mg telmisartan (post 2). Systolic and diastolic blood pressure in the early morning, plasma B-type natriuretic peptide, serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels were increased at post 1 (p < 0.005, p < 0.05, p < 0.05, p < 0.05, p < 0.05, and p < 0.005 vs. baseline, respectively) before returning to their baseline values at post 2. The changes in plasma B-type natriuretic peptide levels correlated significantly with the shifts in systolic and diastolic blood pressure in the early morning at posts 1 and 2. Meanwhile, there were no fluctuations in either blood pressure in the late evening or in the outpatient room; nor were there fluctuations in heart rate. Simultaneously, neither serum high-density lipoprotein cholesterol nor fasting blood sugar levels differed significantly between posts. Moreover, telmisartan had more beneficial effects on glucose and lipid profiles in patients with relatively high HbA1c, serum total and low-density lipoprotein cholesterol, and triglyceride levels. Therefore, we concluded that telmisartan was more beneficial than olmesartan for controlling blood pressure in the early morning, as well as for improving glucose and lipid profiles in patients with hypertension, chronic heart failure, and metabolic syndrome.

Abundant expression of tetraspanin CD9 in activated osteoclasts in ovariectomy-induced osteoporosis and in bone erosions of collagen-induced arthritis.

Tetraspanin CD9 has been shown to be critically involved in multinucleation and cell fusion during osteoclastogenesis, however, its in vivo pathophysiological role in bone-resorbing disorders such as osteoporosis and rheumatoid arthritis, has not been elucidated. To investigate the involvement of tetraspanin CD9 in bone destruction in such diseases, we examined the expression and distribution of tetraspanin CD9 using murine experimental models of osteoporosis and arthritis. In results, CD9 protein is abundantly expressed on the activated osteoclasts in the bone tissues whose trabeculae are severely reduced in ovariectomy-induced osteoporosis. The expression of CD9 is also detected at the sites of bone erosion in arthritic lesions of collagen-induced arthritis (CIA), where tartate-resistant acid phosphatase (TRAP) staining-positive activated osteoclasts are present. These data suggest that tetraspanin CD9 play important roles in bone destructions in osteoporosis and arthritis, and therefore, functional alterations of tetraspanin CD9 may have therapeutic potential in such bone-resorptive disorders.

Preparation of hydroxyapatite-nanocrystal-coated stainless steel, and its cell interaction.

Calcined nanocrystals of hydroxyapatite (HAp) having spherical or rod-shaped morphologies were coated through covalent linkage on a type 316L stainless steel substrate, which was chemically modified by the graft polymerization of gamma-methacryloxypropyl triethoxysilane (MPTS) at 70-110 degrees C. The grafting of poly(MPTS) on the substrate was confirmed by X-ray photoelectron spectroscopy (XPS) and attenuated total reflection Fourier transform infrared spectroscopy (ATR FT-IR). In order to coat the substrate with the HAp crystals through covalent linkage, the reactionbetween the alkoxysilyl groupsin the poly (MPTS) grafted on the substrate and the OH groups on the HAp crystals was conducted at 80 degrees C. The poly(MPTS)-grafted substrate was strongly coated with the HAp nanocrystals, although the HAp crystals adsorbed physically on the original substrate without poly(MPTS) grafting were removed by ultrasonic treatment. Human umbilical vein endothelial cells (HUVEC) adhered in larger numbers on the HAp-coated stainless steel substrate as compared with the original substrate after 24 h of initial incubation. The number of HUVEC adhered on the rod-shaped HAp-coated substrate was not significantly different from that on the spherical HAp-coated substrate under the present conditions.

Different time course of changes in tricuspid regurgitant pressure gradient and pulmonary artery flow acceleration after pulmonary thromboendarterectomy: implications for discordant recovery of pulmonary artery pressure and compliance.

BACKGROUND: Pulmonary artery pressure (PAP) is reduced dramatically after pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension (CTEPH). However, it is unclear whether pulmonary artery compliance increases in conjunction with the reduction in PAP. Pulmonary artery compliance may affect right ventricular afterload and prognosis. METHODS AND RESULTS: In 33 patients with CTEPH (9 men, 22-76 years), changes in the tricuspid regurgitation pressure gradient (TRPG) and the acceleration time (ACT) of pulmonary artery flow (a surrogate parameter of pulmonary artery compliance) were examined before and after pulmonary thromboendarterectomy using echocardiography to clarify factors affecting the changes. At 6 months, both TRPG and ACT normalized (or=100 ms, respectively) in 25 patients (group A) but not in 8 (group B). In group B, there were 5 with normal TRPG and shortened ACT at 6 months that normalized at 17+/-3 months. Group A patients showed shorter disease period and shorter period without anticoagulation than group B patients (p=0.04, 0.02 respectively). All patients in group A had the proximal type, and 2 patients of group B had the distal type (p=0.05). Clinical improvement was more remarkable in group A. CONCLUSIONS: The recovery of PAP and the ACT of pulmonary artery flow was not always concordant after pulmonary thromboendarterectomy, suggesting a presence of a time lag in the recovery between pressure and compliance in some patients. A long period of CTEPH, a long period without anticoagulation and the distal embolism type may be predictive factors of an unfavorable operative result with reduced pulmonary artery compliance, and hence poor recovery of clinical performance.

Expression and function of transmembrane-4 superfamily (tetraspanin) proteins in osteoclasts: reciprocal roles of Tspan-5 and NET-6 during osteoclastogenesis.

BACKGROUND: Osteoclasts are bone-resorbing multinuclear polykaryons essential for bone remodeling, formed through cell fusion of mononuclear macrophage/monocyte lineage precursor cells upon stimulation by the RANK/RANKL system. Recent studies have revealed that a family of tetraspanin proteins, such as CD9, is critically involved in the cell fusion/polykaryon formation of these cell types. Until now, however, there is limited knowledge about the types of tetraspanins expressed in osteoclasts and their precursors. METHODS: The expression of different tetraspanin proteins in a monocyte/macrophage-lineage osteoclast precursor cell line, RAW264.7, was cyclopedically investigated using RT-PCR with specific primers and quantitative real-time RT-PCR. The function of two kinds of tetraspanins, Tspan-5 and NET-6, whose expression pattern was altered by RANKL stimulation, was examined by transfecting gene-specific short-interfering RNAs into these cell types. RESULTS: Of the 17 tetraspanins in mammalian hematopoietic cells, RAW264.7 cells express mRNA for 12 different kinds of tetraspanins, namely, CD9, CD37, CD53, CD63, CD81, CD82, CD151, NAG-2, NET-6, SAS, Tspan-3, and Tspan-5. Interestingly, during their maturation into osteoclasts upon RANKL stimulation, the transcript for Tspan-5 is up-regulated, whereas that for NET-6 is down-regulated. Targeted inhibition of Tspan-5 by using gene-specific RNA interference suppressed RANKL-induced cell fusion during osteoclastogenesis, whereas inhibition of NET-6 augmented the osteoclastogenesis itself. These results suggest that Tspan-5 and NET-6 have a reciprocal function during osteoclastogenesis, i.e., positive and negative regulation by Tspan-5 and NET-6, respectively. RANKL regulates osteoclastogenesis by altering the balances of these tetraspanin proteins. CONCLUSIONS: These data indicate that a diversity of tetraspanins is expressed in osteoclast precursors, and that cell fusion during osteoclastogenesis is regulated by cooperation of distinct tetraspanin family proteins such as Tspan-5 and NET-6. This study indicates that functional alterations of tetraspanin family proteins may have therapeutic potential in diseases where osteoclasts play a major role, such as rheumatoid arthritis and osteoporosis.

RGS18 acts as a negative regulator of osteoclastogenesis by modulating the acid-sensing OGR1/NFAT signaling pathway.

UNLABELLED: We showed that RGS18, a myeloid lineage-specific RGS protein that is inhibited after activation of the RANK/RANKL system, is a negative regulator of osteoclastogenesis. RGS18 acts through an external acidosis-sensing osteoclastogenic mechanism through the OGR1/NFAT pathway. INTRODUCTION: Osteoclasts are bone-resorbing multinuclear giant cells that are differentiated from mononuclear macrophage/monocyte lineage precursors stimulated by the RANK/RANKL system. The regulators of G-protein signaling (RGS) family is a diverse group of proteins that accelerate intrinsic GTP hydrolysis on heterotrimeric G-protein alpha subunits and play crucial roles in physiological regulation of G-protein-mediated cell signaling in various tissues and organs. We examined the expression and function of RGS18, a myeloid lineage-specific RGS protein, during osteoclastogenesis. MATERIALS AND METHODS: A macrophage/monocyte lineage cell line, RAW264.7, and primary osteoclast precursor monocytes derived from mouse bone marrow cultured with macrophage-colony stimulating factor (M-CSF) (bone marrow-derived monocytes [BMMs]) were used in this study. Both cell types differentiate into osteoclast-like cells on activation by RANKL. Expression of different RGS proteins, including RGS18, was assessed by gene-specific RT-PCR. The subcellular distribution of RGS18 on native osteoclasts in bone tissues, as well as in RAW264.7 cells, was examined by immunohistochemistry using a specific polyclonal antibody. Short interfering RNA against RGS18 was used to inhibit the function endogenous RGS18 in these cell types. Activation of NFATc1, an osteoclastogenic transcription factor, on external acidosis was assessed by visualizing the nuclear localization of NFATc1 visualized with anti-NFATc1 antibody. RESULTS: RAW264.7 and BMM cells both expressed mRNA for 10 different mammalian RGS proteins, including RGS18. Expression of RGS18 is significantly inhibited by RANKL both cell types, and inhibition of RGS18 function using RNA interference prominently enhanced osteoclastogenesis on stimulation with RANKL. The effect of RGS18 inhibition was reversed by blocking of proton-sensing OGR1 signaling, and overexpression of exogenous RGS18 inhibited extracellular acidosis-mediated NFATc1 activation. Immunohistochemical studies of mouse bone tissues revealed expression of RGS18 in osteoclasts in vivo. CONCLUSIONS: RGS18 acts as a negative regulator of the acidosis-induced osteoclastogenic OGR1/NFAT signaling pathway, and RANKL stimulates osteoclastogenesis by inhibiting expression of RGS18. Therefore, the results suggest a novel control mechanism of osteoclastogenesis by RGS proteins.

Initial experiences with the HeartMate vented electric left ventricular assist system in Japan.

We report three consecutive cases of long-term circulatory support using the HeartMate vented electric (VE) left ventricular assist system (LVAS). The HeartMate VE LVAS dramatically improved the functional status and quality of life of these three patients with end-stage heart failure, and all were successfully bridged to transplantation after 659, 995, and 1055 days of support on the device. Only an antiplatelet agent was used for anticoagulation therapy, and no cerebrovascular event occurred. Although the pump stopped in two of these three patients 665 days and 491 days after implantation, both were supported by the backup pneumatic driver thereafter. The drive-line exit site became infected in one patient and thinning of the left ventricular wall due to an unknown cause occurred in one patient.

Autoantibodies to cyclic citrullinated peptide 2 (CCP2) are superior to other potential diagnostic biomarkers for predicting rheumatoid arthritis in early undifferentiated arthritis.

We evaluated the diagnostic value of anti-cyclic citrullinated peptide 2 (anti-CCP2) antibodies and other potential diagnostic biomarkers (IgM rheumatoid factor, anti-agalactosyl IgG antibodies, matrix metalloproteinase 3, C-reactive protein) for predicting early development of rheumatoid arthritis (RA). Patients were defined as having recent-onset undifferentiated arthritis (UA) if they had developed arthritis in two or more joints within the previous 2 years and could not be classified with a well-defined arthropathy. Baseline levels of biomarkers were measured in blood samples collected at the entry of the study and the patients were followed for 1 year to monitor development of RA. Diagnoses of RA and non-RA arthropathies were made according to individual standard diagnostic criteria. A total of 146 patients were enrolled in the study. In the follow-up year, 18 patients developed RA, 54 developed non-RA arthropathies, and 60 remained in the UA category. The sensitivity and specificity of the presence of anti-CCP2 antibodies for the diagnosis of RA were 83.3 and 93.0%, respectively. The positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of anti-CCP2 antibodies for RA (65.2, 97.2, and 91.7%, respectively) were higher than for any other biomarker. Combination of anti-CCP2 with any other biomarker only slightly improved each diagnostic value compared to the presence of anti-CCP2 alone. Among the anti-CCP2-positive patients, the average titer was significantly higher in those with RA than in non-RA or UA patients (163.7 +/- 138.4 vs 55.2 +/- 72.0 U/ml, p = 0.017). Anti-CCP2 antibodies are superior to any other single biomarker for predicting early development of RA in patients with recent-onset UA and the diagnostic value of anti-CCP2 alone is similar to that for biomarker combinations. Moreover, the anti-CCP2 antibody titer is useful to discriminate between patients at high risk for early developing RA from those at risk of developing non-RA arthropathies.

Evaluation of transmural distribution of viable muscle by myocardial strain profile and dobutamine stress echocardiography.

Transmural distribution of viable myocardium in the ischemic myocardium has not been quantified and fully elucidated. To address this issue, we evaluated transmural myocardial strain profile (TMSP) in dogs with myocardial infarction using a newly developed tissue strain imaging. TMSP was obtained from the posterior wall at the epicardial left ventricular short-axis view in 13 anesthetized open-chest dogs. After control measurements, the left circumflex coronary artery was occluded for 90 min to induce subendocardial infarction (SMI). Subsequently, latex microbeads (90 microm) were injected in the same artery to create transmural infarction (TMI). In each stage, measurements were done before and after dobutamine challenge (10 microg.kg(-1).min(-1) for 10 min) to estimate transmural myocardial viability. Strain in the subendocardium in the control stage increased by dobutamine (from 53.6 +/- 17.1 to 73.3 +/- 21.8%, P < 0.001), whereas that in SMI and TMI stages was almost zero at baseline and did not increase significantly by dobutamine [from 0.8 +/- 8.8 to 1.3 +/- 7.0%, P = not significant (NS) for SMI, from -3.9 +/- 5.6 to -1.9 +/- 6.0%, P = NS for TMI]. Strain in the subepicardium increased by dobutamine in the control stage (from 23.9 +/- 6.1 to 26.3 +/- 6.4%, P < 0.05) and in the SMI stage (from 12.4 +/- 7.3 to 27.1 +/- 8.8%, P < 0.005), whereas that in the TMI stage did not change (from -1.0 +/- 7.8 to -0.7 +/- 8.3%, P = NS). In SMI, the subendocardial contraction was lost, but the subepicardium showed a significant increase in contraction with dobutamine. However, in TMI, even the subepicardial increase was not seen. Assessment of transmural strain profile using tissue strain imaging was a new and useful method to estimate transmural distribution of the viable myocardium in myocardial infarction.

Increase in cell adhesiveness on a poly(ethylene terephthalate) fabric by sintered hydroxyapatite nanocrystal coating in the development of an artificial blood vessel.

Nano-scaled sintered hydroxyapatite (HAp) crystals were covalently linked onto a poly(ethylene terephthalate) (PET) fabric substrate chemically modified by graft polymerization with gamma-methacryloxypropyl triethoxysilane (MPTS) for development of an artificial blood vessel. The weight gain of graft polymerization with poly(MPTS) on PET in benzyl alcohol containing H2O2 as an initiator increased as increasing the reaction time and finally reached a plateau value of about 3.5 wt%. The surface characterization of surface modification with poly(MPTS)-grafting was conducted by x-ray photoelectron spectroscopy. HAp nanocrystals of approximately 50 nm in diameter, monodispersed in pure ethanol, were coupled with alkoxysilyl groups of the poly(MPTS)-grafted PET substrate. The HAp nanocrystals were uniformly and strongly coated on the surface of the PET fabrics, although HAp particles adsorbed physically on the original PET without poly(MPTS) grafting were almost removed by ultrasonic wave treatment. More human umbilical vein endothelial cells adhered to the HAp/PET composite fabric compared with original PET after only 4 hours of initial incubation, and the same was observed on the collagen-coated PET. The coating of sintered HAp nanocrystals imparted bioactivity to the polyester substrate, which is a widely used biomedical polymer, without a coating of adhesion proteins derived from animals, such as collagen or gelatin. A prototype of an artificial blood vessel was finally fabricated by use of HAp/PET composite.

RANKL-induced expression of tetraspanin CD9 in lipid raft membrane microdomain is essential for cell fusion during osteoclastogenesis.

UNLABELLED: We showed that CD9, a member of tetraspanin superfamily proteins, is expressed in a specific membrane microdomain, called "lipid raft," and is crucial for cell fusion during osteoclastogenesis after activation of the RANK/RANKL system. INTRODUCTION: Osteoclasts are bone-resorbing multinuclear polykaryons that are essential for bone remodeling and are formed through cell fusion of mononuclear macrophage/monocyte lineage precursors. Although osteoclastogenesis has been shown to be critically regulated by the RANK/RANKL system, the mechanism how precursor cells fuse with each other remains unclear. We examined the function of CD9, a member of tetraspanin superfamily, which has previously been shown to form macromolecular membrane microdomains and to regulate cell-cell fusion in various cell types. MATERIALS AND METHODS: We used RAW264.7, a macrophage/monocyte lineage cell line, which can differentiate into osteoclast-like polykaryons on the application of RANKL. Expression and distribution of CD9 was assessed by Western blotting, fluorescence-assorted cell sorting (FACS) and immunohistochemistry with light and electron microscopy. A specific neutralizing antibody and RNA interference were used to inhibit the function of CD9, and green fluorescent protein (GFP)-CD9 was exogenously expressed to enhance the effect of CD9. The distribution of CD9 in lipid microdomain was examined by biochemical (sucrose density gradient) isolation and imaging technique. RESULTS: CD9 is expressed on cell surfaces of RAW264.7, which is enhanced by RANKL. Targeted inhibition of CD9 decreases the number of osteoclast-like cells. On the other hand, overexpression of CD9 promotes spontaneous cell fusion even in the absence of RANKL. CD9 is localized in detergent-insoluble "lipid raft" microdomain in RANKL stimulation, and disruption of lipid rafts markedly reduces the formation of osteoclast-like polykaryons. Immunohistochemical studies of bone tissues revealed the expression of CD9 in osteoclasts in vivo. CONCLUSIONS: These data suggest that function of tetraspanin CD9 and its expression in lipid rafts are crucial for cell fusion during osteoclastogenesis.