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Biomedical subjects

Yukio Ozaki

Publications and source records attributed to Yukio Ozaki.

At least 19 recordsLinked to original sources
PubMed2007

Impact of cutting balloon angioplasty (CBA) prior to bare metal stenting on restenosis.

BACKGROUND: While stent restenosis and late thrombosis still occur even with drug-eluting-stents (DES), there remains a need to explore other strategies for preventing restenosis. METHODS AND RESULTS: Five hundred and twenty-one patients were randomized: 260 to cutting-balloon angioplasty (CBA) before bare-metal stent (CBA-BMS) and 261 to balloon-angioplasty (BA) before BMS (BA-BMS). Intravascular ultrasound (IVUS)-guided procedures were performed in 279 (54%) patients and angiographic guidance was used in the remainder. Minimal lumen diameter was significantly greater in CBA-BMS than BA-BMS (2.65+/-0.40 mm vs 2.52+/-0.4 mm, p<0.01) and % diameter stenosis (%DS)-post was less in CBA-BMS than BA-BMS (14.0+/-5.9% vs 16.3+/-6.8%, p<0.01). %DS-follow-up was subsequently less in CBA-BMS than BA-BMS (32.4+/-15.1% vs 35.4+/-15.3%, p<0.05) associated with lower rates of restenosis in CBA-BMS than BA-BMS (11.8% vs 19.6%, p<0.05) and less target lesion revascularization (TLR) in CBA-BMS than BA-BMS (9.6% vs 15.3%, p<0.05). Patients were divided into 4 groups based on the device used before stenting and IVUS use (IVUS-CBA-BMS: 137 patients; Angio-CBA-BMS: 123; IVUS-BA-BMS: 142; and Angio-BA-BMS: 119). At follow-up IVUS-CBA-BMS had a significantly lower restenosis rate (6.6%) than Angio-CBA-BMS (17.9%), IVUS-BA-BMS (19.8%) and Angio-BA-BMS (18.2%, p<0.05). CONCLUSIONS: Restenosis and TLR were significantly lower in CBA-BMS than BA-BMS. This favorable outcome was achieved because of the lower restenosis rate conferred by the IVUS-guided-CBA-BMS strategy (6.6%). The restenosis rates obtained with this strategy were comparable to those achieved with DES.

Aged↗
PubMed2006

Involvement of Src kinases and PLCgamma2 in clot retraction.

The integrin alpha(IIb)beta(3) plays a critical role in mediating clot retraction by platelets which is important in vivo in consolidating thrombus formation. Actin-myosin interaction is essential for clot retraction. In the present study, we demonstrate that the structurally distinct Src kinase inhibitors, PP2 and PD173952, significantly reduced the rate of clot retraction, but did not prevent it reaching completion. This effect was accompanied by abolition of alpha(IIb)beta(3)-dependent protein tyrosine phosphorylation, including PLCgamma2. A role for PLCgamma2 in mediating clot retraction was demonstrated using PLCgamma2-deficient murine platelets. Furthermore, platelet adhesion to fibrinogen leads to MLC phosphorylation through a pathway that is inhibited by PP2 and by the PLC inhibitor, U73122. These results demonstrate a partial role for Src kinase-dependent activation of PLCgamma2 and MLC phosphorylation in mediating clot retraction downstream of integrin alpha(IIb)beta(3).

Animals↗
PubMed2006

Relation between platelet microaggregates and ankle brachial index in patients with peripheral arterial disease.

INTRODUCTION: Peripheral arterial disease is one of the systemic atherosclerotic diseases, and patients with the disorder are classified in the high risk group of coronary artery disease. A lower ankle brachial index is a frequent finding in peripheral arterial disease. While platelet microaggregates are a significant predictor of adverse clinical outcome in coronary artery disease, the significance of platelet aggregability in peripheral arterial disease has not been elucidated. MATERIALS AND METHODS: Small platelet aggregates measured using laser-light scattering and ankle brachial index were determined in 42 patients with both coronary artery disease and peripheral arterial disease (peripheral group), 56 patients with only coronary artery disease (coronary group) and 32 patients without both (control group). RESULTS: The level of small platelet aggregates was increased significantly in the peripheral group (4.3 x 10(4) [range 2.2 x 10(4) to 7.4 x 10(4)]) compared with both the coronary (1.1 x 10(4) [range 0.3 x 10(4) to 5.0 x 10(4)]) and control groups (0.5 x 10(4) [range 0.1 x 10(4) to 0.9 x 10(4)]). There was a significant inverse correlation between log small platelet aggregates and ankle brachial index (n=130, r=-0.422, p<0.001). Multivariate logistic regression analysis revealed that a lower ankle brachial index (<0.90) was an independent determinant of increased levels of small platelet aggregates. CONCLUSIONS: Platelet aggregability was increased in patients with peripheral arterial disease with the degree of platelet aggregation being closely associated with ankle brachial index. It is possible that this change in platelet activity may be one mechanism to explain why a lower ankle brachial index is a predictor of poor prognosis in patients with peripheral arterial disease.

Aged↗
PubMed2006

Analysis of prognostic factors in therapeutic responses to interferon in patients with chronic hepatitis C.

The genotype of hepatitis C virus (HCV) and the amount of HCV RNA are often used to predict the efficacy of interferon (IFN) therapy on chronic hepatitis C. In addition to these factors, there may be several factors related to the host. Therefore, the authors undertook a retrospective study in which physical findings and laboratory data before therapy were evaluated by multiple logistic analysis. Two-hundred and five cases with chronic hepatitis C treated with interferon were analyzed in this study. Sustained virological response was observed with 68 cases. Multiple logistic analysis was performed with 29 explanatory variables including HCV genotype, HCV RNA, IFN types, and total dose, along with gender, age, alcohol consumption, body mass index (BMI), histological findings of liver biopsy, platelet counts, and laboratory data of serum enzymes. Analysis on the factors that correlated well with therapeutic efficacy revealed that genotype 2a, 2b showed higher therapeutic responses than genotype 1b with reference to HCV genotypes, and higher IFN dose or lower HCV RNA levels gave better results. With reference to host factors, higher total protein level, lower levels of BMI, total bilirubin, and aspartate aminotransferase were highly correlated with therapeutic efficacy. HCV genotypes and HCV RNA levels have been already identified as prognostic factors. However, the high correlation values of BMI and the total protein level are new findings. It is suggested that probability estimation of therapeutic effects using the logistic regression equation may be a good tool for predicting therapeutic efficacy of IFN therapy on individual cases.

Adult↗
PubMed2006

Impact of angiotensin II receptor blockers on the progression and regression of coronary atherosclerosis: an intravascular ultrasound study.

BACKGROUND: Although angiotensin II receptor blockers (ARB) have been found to reduce the coronary atherosclerotic plaque burden in animal models, it is unknown whether ARB have a similar effect on human coronary arteries. METHODS AND RESULTS: Serial intravascular ultrasound (IVUS) studies of the left main (LM) coronary artery were performed in 64 patients at baseline and after 7-month follow-up. All patients were divided into 2 groups (ARB group: 23 patients; non-ARB group: 41 patients). Three-dimensional volumetric analysis was done throughout the LM coronary artery, and the volume index (VI; volume/length) was calculated for the vessel (VVI), lumen (LVI), and plaque (PVI). No significant difference was found between the 2 groups in baseline clinical characteristics, including age, gender, blood pressure levels, serum cholesterol levels, the presence of diabetes and smoking status. At baseline VVI, LVI and PVI were similar between the groups. In the non-ARB group, VVI, LVI, and PVI did not change between baseline and follow-up. In the ARB group, PVI significantly decreased during follow-up (9.9 +/-3.1 mm2 vs 9.1+/-2.7 mm2, p<0.01), whereas VVI and LVI were unaffected. CONCLUSIONS: This preliminary IVUS study suggests that ARB could cause regression of coronary atherosclerosis in humans.

Aged↗
PubMed2006

Japan assessment of pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS): rationale and design.

BACKGROUND: Many trials have shown that 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce the incidence of cardiovascular events and mortality. One method of decreasing the incidence of cardiovascular events could be to reduce the progression of coronary atherosclerosis, and a recent study found that atorvastatin can cause coronary plaque to regress. To generalize this finding, using conventional HMG-CoA reductase inhibitors at many Japanese centers, randomized trials of pitavastatin and atorvastatin will be conducted with patients with acute coronary syndrome (ACS). METHODS AND RESULTS: Patients with ACS who have undergone successful percutaneous coronary intervention under intravascular ultrasound guidance will be studied. They will be randomly allocated to pitavastatin or atorvastatin groups and followed up for 8-12 months. The primary endpoint will be the percent change in coronary plaque volume, and secondary endpoints will include absolute changes in coronary plaque volume, serum lipid levels and inflammatory markers. The safety profile will also be evaluated. CONCLUSIONS: This study will examine the ability of HMG-CoA reductase inhibitors to regress coronary plaque in Japanese patients with ACS and the findings should help to improve the prognosis of such patients and clarify the involved mechanisms.

Atorvastatin↗
PubMed2006

[Regression of a large lipid-rich pool in the coronary artery during treatment with statin detected by intravascular ultrasound: a case report].

A 54-year-old man with unstable angina presented with severe stenosis of the middle segment of the left anterior descending coronary artery. Percutaneous coronary stent implantation and serial intravascular ultrasound (IVUS) were performed. IVUS detected a non-culprit coronary plaque with a large lipid-rich pool in the proximal segment of the left anterior descending coronary artery. Atorvastatin 10 mg/day was given to reduce his cholesterol level for 2 years after the stent implantation. This patient had no cardiac events, and the low-density lipoprotein-cholesterol level reduced from 171 to 88 mg/dl at follow-up. Two-year follow-up IVUS examination revealed the reduction of plaque burden associated with regression of the lipid-rich pool size. This case may indicate that statin could contribute to the regression of lipid-rich plaque and to the stability of coronary plaque.

Angina, Unstable↗
PubMed2006

[Attempts for aspirin monitoring with a new assay system, Ultegra Rapid Platelet Function Assay (RPFA), based on turbidimetric platelet agglutination of whole blood samples].

Platelet aggregation measured by the optical density method has been applied for the assessment of platelet functions. However, as the method has to use platelet-rich plasma, it requires centrifugation of blood samples, which takes a considerable period of time. Using whole blood as samples has advantage because there is no pre-treatment of samples before measurement of platelet functions. Additionally, it would be desirable to have a bedside assay that reflects hyper-function of platelets and can monitor inhibitory effects of anti-platelet drugs. Rapid Platelet Function Assay (RPFA) is a qualitative test to aid the detection of platelet dysfunction due to anti-platelet drug ingestion, which uses citrated whole blood for sample in point of care or laboratory settings. The RPFA is a turbidimetric analysis, based on an optical detection system which measures platelet agglutination as an increase in light transmission. The aim of this study is to assess the accuracy and reproducibility of RPFA and to determine whether RPFA can monitor the effects of anti-platelet drugs. During the first 30 minutes after blood collection, Aspirin Reaction Units (ARU) determined with RPFA gradually increased, and reached its plateau after 30 minutes. The ARU values remained almost constant thereafter until 6 hours after blood collection (Fig. 3). These findings suggest that platelet function is unstable immediately after blood collection. Therefore, in this study ARU measurement was performed 60 minutes after blood collection. The reproducibility of ARU is very good both before and after aspirin intake. Seven days after daily uptake aspirin, ARU was decreased as compared with the control (440.8 +/- 39.4 vs. 663.4 +/- 2.4 ARU). RPFA measurement provides rapid information on platelet function that mirrors turbidimetric platelet agglutination and reflects COX1-depedent platelet activity.

Aspirin↗
PubMed2006

[Promising efficacy of the sirolimus-eluting stent in patients with acute myocardial infarction].

OBJECTIVES: This study investigated the safety and efficacy of sirolimus-eluting stents (SESs) on early and late outcomes in patients with acute myocardial infarction. METHODS: A series of 100 consecutive patients (September 2004 to November 2005)with acute myocardial infarction undergoing primary stenting using SES ptember 24 hr) was compared with 100 consecutive patients (September 2003 to August 2004) treated with bare metal stent (BMS). The frequency of major adverse cardiac events (MACE) and stent thrombosis, and status of ticlopidine administration were assessed at 270 days. RESULTS: The rates of premature discontinuation of ticlopidine (SES group <3 months: 11%, BMS group <1 month: 11%, p = NS) and stent thrombosis (SES group: 1%, BMS group: 0%, p = NS) were similar in the two groups. At follow-up, restenosis rate and target vessel revascularization rate were lower in the SES group(4% vs 19%, p < 0.001 and 4% vs 10%, p = 0.149, respectively). Furthermore, the occurrence of MACE at 270 days was significantly less frequent in the SES group compared with the BMS group (6% vs. 17%, p = 0.038). Multivariate analysis showed SES use tended to predict 270-day MACE (hazard ratio 0.37, 95% confidence interval 0.14-1.02, p = 0.055). Culprit lesion located in the left main trunk was identified as an independent predictor of 270-day MACE (hazard ratio 5.43, 95% confidence interval 1.07-27.59, p = 0.041). CONCLUSIONS: The use of a SES was not associated with increased risk of stent thrombosis compared with a BMS. With lower rates of restenosis and subsequent target vessel revascularization, SES placement could provide superior outcomes in patients with acute myocardial infarction.

Aged↗
PubMed2005

Short photoperiod induces dormancy in Lotus (Nelumbo nucifera).

BACKGROUND AND AIMS: Lotus (Nelumbo nucifera) has been cultivated as an ornamental and food plant in Japan for more than 1000 years. As large areas are required for its cultivation (approximately 2 m2 per plant), physiological research, such as into the effect of environmental factors on dormancy, has not been well studied until recently. In this paper, seedlings were used to examine environmental factors affecting dormancy induction. METHODS: In a first experiment, seeds were sown from 6 April to 6 October at 2-month intervals, and cultivated for 2 months in an unheated greenhouse. In a second experiment, seeds were prepared for germination on 16 November and 16 May and the seedlings were grown at 25 or 30 degrees C under natural daylength in phytotron growth rooms. After 1 month, the seedlings were cultivated at 20, 25 or 30 degrees C for a further month. The number of leaves and rhizome branches on the main stem were counted, and growth of rhizomes on the main stem was calculated using a rhizome enlargement index (= maximum internode diameter/internode length) after 2 months of culture in both experiments. KEY RESULTS: Rhizomes elongated without enlargement when the seeds were sown in April and June. Sowing the seeds in August and October resulted in rhizome enlargement from the tenth and fifth internodes, respectively. Rhizomes enlarged in the November-sowing but elongated in the May-sowing irrespective of temperature treatments under natural daylength in the phytotron rooms. The seedlings cultivated from May at 25-30 degrees C for 2 months had more leaves, and more rhizome branches and nodes than those cultivated from November. CONCLUSIONS: Short days led to induced dormancy in lotus.

Nelumbo↗
PubMed2005

Laminin stimulates spreading of platelets through integrin alpha6beta1-dependent activation of GPVI.

The extracellular matrix protein, laminin, supports platelet adhesion through binding to integrin alpha6beta1 In the present study, we demonstrate that human laminin, purified from placenta, also stimulates formation of filopodia and lamellipodia in human and mouse platelets through a pathway that is dependent on alpha6beta1 and the collagen receptor GPVI. The integrin alpha6beta1 is essential for adhesion to laminin, as demonstrated using an alpha6-blocking antibody, whereas GPVI is dispensable for this response, as shown using "knockout" mouse platelets. On the other hand, lamellipodia formation on laminin is completely inhibited in the absence of GPVI, although filopodia formation remains and is presumably mediated via alpha6beta1 Lamellipodia and filopodia formation are inhibited in Syk-deficient platelets, demonstrating a key role for the kinase in signaling downstream of GPVI and integrin alpha6beta1 GPVI was confirmed as a receptor for laminin using surface plasmon resonance spectroscopy and by demonstration of lamellipodia formation on laminin in the presence of collagenase. These results identify GPVI as a novel receptor for laminin and support a model in which integrin alpha6beta1 brings laminin to GPVI, which in turn mediates lamellipodia formation. We speculate that laminin contributes to platelet spreading in vivo through a direct interaction with GPVI.

Animals↗
PubMed2005

Docking protein Gab2 positively regulates glycoprotein VI-mediated platelet activation.

Gab2, a recently identified docking protein, contains a pleckstrin homology domain and potential binding sites for SH2 and SH3 domain-containing proteins. Gab2 has been shown to support growth, differentiation, and function in a number of haematopoietic cells, although its role in platelets remains to be determined. Here we report that cross-linking of the collagen receptor GPVI by the snake venom toxin convulxin stimulates tyrosine phosphorylation of Gab2. Furthermore, platelet aggregation induced by submaximal concentrations of convulxin is attenuated in the absence of Gab2, although recovery is seen with higher concentrations of the toxin. Consistent with this, tyrosine phosphorylation of Fc receptor gamma-chain, Syk, Btk, and phospholipase Cgamma2 by convulxin is reduced in the absence of Gab2. In comparison, the G protein-coupled receptor agonist, thrombin, does not induce phosphorylation of Gab2 and aggregation is unaltered in the absence of the toxin. These findings provide evidence for a functional role of Gab2 in supporting platelet activation by GPVI.

Adaptor Proteins, Signal Transducing↗
PubMed2005

A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2.

The snake venom rhodocytin has been reported to bind to integrin alpha2beta1 and glycoprotein (GP) Ibalpha on platelets, but it is also able to induce activation independent of the 2 receptors and of GPVI. Using rhodocytin affinity chromatography, we have identified a novel C-type lectin receptor, CLEC-2, in platelets that confers signaling responses to rhodocytin when expressed in a cell line. CLEC-2 has a single tyrosine residue in a YXXL motif in its cytosolic tail, which undergoes tyrosine phosphorylation upon platelet activation by rhodocytin or an antibody to CLEC-2, but not to collagen, thrombin receptor agonist peptide (TRAP), or convulxin. Tyrosine phosphorylation of CLEC-2 and other signaling proteins by rhodocytin is inhibited by the Src family kinase inhibitor PP2. Further, activation of murine platelets by rhodocytin is abolished in the absence of Syk and PLCgamma2, and partially reduced in the absence of LAT, SLP-76, and Vav1/Vav3. These findings define a novel signaling pathway in platelets whereby activation of CLEC-2 by rhodocytin leads to tyrosine phosphorylation of its cytosolic tail, binding of Syk and initiation of downstream tyrosine phosphorylation events, and activation of PLCgamma2. CLEC-2 is the first C-type lectin receptor to be found on platelets which signals through this novel pathway.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Usefulness of preprocedural platelet aggregation to predict restenosis after percutaneous coronary intervention.

We investigated whether the assessment of small platelet aggregates before percutaneous coronary intervention (PCI) could predict restenosis after PCI. This was a prospective cohort study that enrolled 189 consecutive patients who had coronary artery disease. In multiple logistic regression analysis, higher levels of preprocedural small platelet aggregates were independently associated with restenosis after PCI. Measurement of small platelet aggregates may serve as a useful clinical variable for stratifying patients who present for PCI.

Aged↗
PubMed2005

Prognostic value of serum concentration of heart-type fatty acid-binding protein relative to cardiac troponin T on admission in the early hours of acute coronary syndrome.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is proposed as an early biomarker for acute myocardial infarction (AMI), but its prognostic value is unclear in acute coronary syndrome (ACS). We evaluated the prognostic value of the H-FABP concentration relative to cardiac troponin T (cTnT) in the early hours of ACS. METHODS: Serum concentrations of H-FABP and cTnT were measured on admission in 328 consecutive patients hospitalized for ACS within 6 h after the onset of chest pain [AMI, 241 (73.5%) patients; ST-segment elevation myocardial infarction, 154 (47.0%) patients; and emergent coronary angiography within 24 h after admission, 287 (87.5%) patients]. Cardiac events, which were defined as cardiac death or subsequent nonfatal AMI, were monitored for 6 months after admission. RESULTS: During the 6-month follow-up period, there were 25 cardiac events, including 15 cardiac deaths and 10 subsequent nonfatal AMIs. Stepwise multivariate analyses including clinical, electrocardiographic, and biochemical variables revealed that increased H-FABP (above the median of 9.8 microg/L), but not increased cTnT (above the median of 0.02 microg/L), was independently associated with cardiac events in all patients [relative risk (RR) = 8.96; P = 0.0004], the subgroup of patients with ST-segment elevation myocardial infarction (RR = 11.3; P = 0.02), and the subgroup of patients with unstable angina and non-ST-segment elevation myocardial infarction (RR = 8.31; P = 0.007). The area under the ROC curve was higher for H-FABP than for cTnT (0.711 vs 0.578; P = 0.08), suggesting that H-FABP concentrations have a greater predictive capacity for cardiac events than cTnT. CONCLUSION: Serum H-FABP is a potential independent predictor of cardiac events within 6 months of patient admission and may provide prognostic information superior to cTnT in the early hours of ACS.

Acute Disease↗
PubMed2005

Is the size of an abdominal aortic aneurysm associated with coagulopathy?

Abdominal aortic aneurysm (AAA) volume and intraluminal thrombi were analyzed with respect to the number and function of platelets, blood cells, and coagulation factors. A group of 43 patients who underwent repair of an AAA were enrolled in this study. The maximum diameter and volume of the AAA, and the volume of intraluminal thrombi and lumen were measured by computed tomography with planimetry. The platelet count and platelet function, prothrombin time, activated partial thromboplastin time, fibrinogen, plasminogen, antithrombin 3, fibrin degradation products (FDP), D-dimer, and blood cell counts were measured. Spontaneous platelet aggregation and the FDP, and D-dimer levels were elevated; all other factors remained within the normal range. Intraluminal thrombus volume was strongly correlated with the volume and diameter of the AAA. However, no correlation was observed between the size of the AAA and coagulating factors, including the number and aggregation value of platelets. AAAs are frequently associated with a coagulating disorder. However, its size and thrombus volume are not correlated with coagulation changes. Although an intraluminal thrombus increases along with fee enlargement of the AAA, the clinical manifestation of bleeding is rarely associated with an AAA. Therefore coagulopathy in patients with an AAA is not fully explained by its morphology.

Aged↗
PubMed2005

Evaluation of platelet function under high shear condition in the small-sized collagen bead column.

We previously reported that platelet retention rates as measured with collagen-coated bead columns (the conventional column) reflect the processes of platelet adhesion and aggregation under low shear stress, and that this system could serve as an easy-to-use platelet aggregometry. With this column, platelet glycoprotein (GP) VI and GPIIb/IIIa, but not the GPIb-von Willebrand factor (VWF) interaction, play major roles in platelet activation. To develop a system that can better reflect the GPIb-VWF interaction under high shear stress, we designed a column containing small-sized beads (125-212 microm) coated with porcine collagen type I. As expected, the GPIb-VWF interaction played a crucial role in platelet retention rates at higher flow rates. Adenosine 5'-diphosphate, but not thromboxane A2, appears to support platelet activation in this system. The platelet retention rates among healthy individuals with the new columns are in the range wider than the conventional columns, and this diversity could be attributed to the broad range of the VWF antigen and/or its activity. It is suggested that this new column can serve as an easy-to-use method for evaluating the VWF antigen levels and its activity and for monitoring patients with thrombotic or bleeding disorders related to the VWF-GPIb interaction.

Antibodies↗