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Biomedical subjects

T Kawasaki

Publications and source records attributed to T Kawasaki.

At least 19 recordsLinked to original sources

Effects of epidural anaesthesia on surgical stress-induced immunosuppression during upper abdominal surgery.

BACKGROUND: Previously, we have demonstrated that surgical stress rapidly induced transient hyporesponsiveness of blood cells to endotoxin and that monocyte mCD14 and HLA-DR expression decreased soon after the start of surgery under general anaesthesia. This study was designed to investigate the effects of epidural anaesthesia on surgical stress-induced immunosuppression in patients undergoing upper abdominal surgery. METHODS: After having obtained informed consent, patients were randomly allocated to receive general anaesthesia (Group G) or general anaesthesia with epidural anaesthesia (Group E). Perioperative changes in neutrophil phagocytic activity, neutrophil respiratory burst activity, monocyte mCD14 and HLA-DR expression, plasma IL-10 concentration, and the LPS-induced TNF-alpha production in whole blood were measured. RESULTS: Surgical stress rapidly depressed neutrophil phagocytic activity, monocyte mCD14 and HLA-DR expression, and LPS-induced TNF-alpha production ex vivo (P < 0.05 vs preoperation) in both Group G and Group E. In contrast, the plasma IL-10 concentration increased significantly 2 h after the start of surgery (P < 0.05) in both groups. There were no significant differences between the two groups. The neutrophil respiratory burst activity did not change during the operation in either group. CONCLUSION: This study showed that the innate immune system is suppressed from the early period of upper abdominal surgery. Subgroup analysis suggested that epidural anaesthesia to T4 dermatome as well as general anaesthesia may not protect patients from this immunosuppression. These results in part explain the impairment of host-defense mechanisms seen in the perioperative period.

Anesthesia, Epidural↗

Observation of B+ --> Lambda c+ Lambda c- K+ and B0 --> Lambda c+ Lambda c- K0 decays.

We report the first measurements of the doubly charmed baryonic B decays B --> Lambda c+ Lambda c- K. The B+ --> Lambda c+ Lambda c- K+ decay is observed with a branching fraction of (6.5(-0.9)(+1.0)+/-1.1+/-3.4)x10(-4) and a statistical significance of 15.4sigma. The B0 --> Lambda c+ Lambda c- K0 decay is observed with a branching fraction of (7.9(-2.3)(+2.9)+/-1.2+/-4.1)x10(-4) and a statistical significance of 6.6sigma. The branching fraction errors are statistical, systematic, and the error resulting from the uncertainty of the Lambda c+ --> pK- pi+ decay branching fraction. The analysis is based on 357 fb(-1) of data accumulated at the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+ e- collider.

Journal Article↗

Study of J/psi-->pp[over],LambdaLambda[over] and observation of eta(c)-->LambdaLambda[over] at Belle.

We study the baryonic charmonium decays of B mesons B+-->etacK+ and B+-->J/psiK+, where the etac and J/psi subsequently decay into a pp[over] or LambdaLambda[over] pair. We measure the J/psi-->pp[over] and LambdaLambda[over] anisotropy parameters alphaB=-0.60+/-0.13+/-0.14 (pp[over]), -0.44+/-0.51+/-0.31 (LambdaLambda[over ]) and compare to results from e;{+}e;{-}-->J/psi formation experiments. We also report the first observation of etac-->LambdaLambda[over]. The measured branching fraction is B(etac-->LambdaLambda[over ])=(0.87(+0.24)/(-0.21)(stat)(+0.09/-0.14) (syst)+/-0.27(PDG))x10-3. This study is based on a 357 fb-1 data sample recorded on the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+ e- collider.

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Observation of new states decaying into Lambda(c)(+)Kappa(-)pi(+) and Lambda(c)(+)Kappa(0)/(s)pi(-).

We report the first observation of two charmed strange baryons that decay into Lambda(c)(+)Kappa(-)pi(+). The broader of the two states is measured to have a mass of 2978.5+/-2.1+/-2.0 MeV/c2 and a width of 43.5+/-7.5+/-7.0 MeV/c2. The mass and width of the narrow state are measured to be 3076.7+/-0.9+/-0.5 MeV/c;{2} and 6.2+/-1.2+/-0.8 MeV/c2, respectively. We also perform a search for the isospin partner states that decay into Lambda(c)(+)Kappa(0)/(s)pi(-) and observe a significant signal at the mass of 3082.8+/-1.8+/-1.5 MeV/c2. The data used for this analysis were accumulated at or near the Upsilon(4S) resonance, using the Belle detector at the e+ e- asymmetric-energy collider KEKB. The integrated luminosity of the data sample used is 461.5 fb(-1).

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Observation of a near-threshold D(0)D[over](0)pi(0) enhancement in B-->D(0)D[over](0)pi(0)Kappa decay.

We report the first observation of a near-threshold enhancement in the D(0)D[over](0)pi(0) system from B-->D(0)D[over](0)pi(0)Kappa decays using a 414 fb(-1) data sample collected at the Upsilon(4S) resonance. The enhancement peaks at a mass M=3875.2+/-0.7(+0.3)/(-1.6) +/-0.8 MeV/c2 and the branching fraction for events in the peak is B(B-->D(0)D[over](0)pi(0)Kappa)=(1.22+/-0.31(+0.23)/(-0.30))x10(-4). The data were collected with the Belle detector at the KEKB energy-asymmetric e+ e- collider.

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Measurement of the quark mixing parameter cos2phi1 using time-dependent Dalitz analysis of B0 -->D[KS(0)pi + pi-]h0.

We present a measurement of the angle phi1 of the Cabibbo-Kobayashi-Maskawa unitarity triangle using a time-dependent Dalitz analysis of D-->KS(0)pi + pi- decays produced in neutral B meson decay to a neutral D meson and a light meson (B0-->D*h0). The method allows a direct extraction of 2phi1 and, therefore, helps to resolve the ambiguity between 2phi1 and pi-2phi1 in the measurement of sin2phi1. We obtain sin2phi1= 0.78 +/- 0.44 +/- 0.22 and cos2varphi1 = 1.87(-0.53-0.32)(+0.40 + 0.22). The sign of cos2phi1 is determined to be positive at 98.3% C.L.

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Measurement of D0-->pilnu(Klnu) form factors and absolute branching fractions.

Using a 282 fb-1 data sample collected by the Belle experiment at the KEKB e+e- collider, we study D0 decays to K-l+nu and pi-l+nu final states. The D0 flavor and momentum are tagged through a full reconstruction of the recoiling charm meson and additional mesons from fragmentation. The reconstruction method provides very good resolution in neutrino momentum and in q2=(pl+pnu)2. Normalizing to the total number of D0 tags, we measure the absolute branching fractions to be B(D0-->Klnu)=(3.45+/-0.07stat+/-0.20syst)% and B(D0-->pilnu)=(0.255+/-0.019stat+/-0.016syst)% and the semileptonic form factors (within the modified pole model) f+K(0)=0.695+/-0.007stat+/-0.022syst and f+pi(0)=0.624+/-0.020stat+/-0.030syst.

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Evidence for B-->eta'pi and improved measurements for B-->eta'K.

We report evidence for the exclusive two-body charmless hadronic B meson decay B-->eta'pi, and improved measurements of B-->eta'K. The results are obtained from a data sample of 386x10(6) BB pairs collected at the Upsilon(4S) resonance, with the Belle detector at the KEKB asymmetric-energy e+e- collider. We measure B(B+-->eta'pi+)=[1.76(-0.62)(+0.67)(stat)(-0.14)(+0.15)(syst)]x10(-6) and B(B0-->eta'pi0)=[2.79(-0.96)(+1.02)(stat)(-0.34)(+0.25)(syst)]x10(-6). We also find the ratio of B(B+-->eta'K+)/B(B0-->eta'K0)=1.17+/-0.08(stat)+/-0.03(syst) and measure the direct CP asymmetries for the charged modes.

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Evidence for large direct CP violation in B+/- --> rho(770)0K+/- from analysis of three-body charmless B+/- --> K+/-pi+/-pi+/- decays.

We report results on a Dalitz analysis of three-body charmless B+/- --> K+/-pi+/-pi+/- decay including searches for direct CP violation. We report the first observation of the decay B+/- --> f2(1270)K+/- with a statistical significance above 6sigma. We also observe first evidence for large direct CP violation in the B+/- --> rho(770)0K+/- channel. The results are obtained with a data sample that contains 386 10(6) BB pairs collected at the Y(4s) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider.

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Measurement of forward-backward asymmetry and Wilson coefficients in B --> K*l+l-.

We report the first measurement of the forward-backward asymmetry and the ratios of Wilson coefficients and in A9/A7 and A10/A7 in B --> K*l+l-, where l represents an electron or a muon. We find evidence for the forward-backward asymmetry with a significance of 3.4sigma. The results are obtained from a data sample containing 386 x 10(6) BB pairs that were collected on the Y(4S) resonance with the Belle detector at the KEKB asymmetric-energy e+e- collider.

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Measurement of azimuthal asymmetries in inclusive production of hadron pairs in e(+)e(-) annihilation at Belle.

The Collins effect connects transverse quark spin with a measurable azimuthal dependence in the yield of hadronic fragments around the quark's momentum vector. Using two different reconstruction methods, we find evidence of statistically significant azimuthal asymmetries for charged pion pairs in e(+)e(-) annihilation at a center-of-mass energy of 10.52 GeV, which can be attributed to a transverse polarization of the primordial quarks. The measurement was performed using a sample of 79 x 10(6) hadronic events collected with the Belle detector.

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Observation of b-->dgamma and determination of /Vtd/Vts/.

We report the observation of the flavor-changing neutral current process b-->dgamma using a sample of 386 x 106 B meson pairs accumulated by the Belle detector at the KEKB e+e- collider. We measure branching fractions for the exclusive modes B--->rho-gamma, B0rho0gamma, and B0omegagamma. Assuming that these three modes are related by isospin, we find B(B-->(rho,gamma)gamma)=[Formula: See Text] with a significance of 5.1sigma. This result is used to determine the ratio of Cabibbo-Kobayashi-Maskawa matrix elements /Vtd/Vts/ to be [Formula: See Text].

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Measurement of the branching fraction, polarization, and asymmetry for decays, and determination of the Cabibbo-Kobayashi-Maskawa phase.

We have measured the branching fraction , longitudinal polarization fraction f(L), and CP asymmetry coefficients A and S for B(0) --> rho(+) rho(-) decays with the Belle detector at the KEKB e(+) e(-) collider using 253 Fb(-1) of data. We obtain B = [22.8 +/- 3.8(stat)(+2.3)(-2.6)(syst)] x 10(-6), f(L) = 0.941 (+0.034)(-0.040)(stat) +/- 0.030(syst). A = 0.00 +/- 0.30(stat) +/- 0.09(syst) and S = 0.08 +/- 0.09(syst). These values are used to constrain the Cabibbo-Kobayashi-Maskawa phase ; the solution consistent with the standard model is phi(2) = (88 +/- 17) degrees or 59 degrees < phi(2) < 115 degrees at 90% C.L.

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Improved constraints on D0-D0 mixing in D0 --> K+ pi- decays from the Belle detector.

We report the results of a search for D0-D0 mixing in D0 --> K+ pi- decays based on 400 fb(-1) of data accumulated by the Belle detector at KEKB. Both assuming CP conservation and allowing for CP violation, we fit the decay-time distribution for the mixing parameters x and y, as well as for the parameter R(D), the ratio of doubly Cabibbo-suppressed decays to Cabibbo-favored decays. The 95% confidence level region in the (x'2,y') plane is obtained using a frequentist method. Assuming CP conservation, we find x'2 < 0.72 x 10(-3) and -9.9 x 10(-3) < y' < 6.8 x 10(-3) at the 95% confidence level; these are the most stringent constraints on the mixing parameters to date. The no-mixing point (0,0) has a confidence level of 3.9%. Assuming no mixing, we measure R(D) = (0.377 +/- 0.008 +/- 0.005)%.

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Observation of a chi(c2)' candidate in gamma gamma --> DD production at belle.

We report on a search for new resonant states in the process gamma gamma --> DD. A candidate C-even charmonium state is observed in the vicinity of 3.93 GeV/c2. The production rate and the angular distribution in the gamma gamma center-of-mass frame suggest that this state is the previously unobserved chi(c2)', the 2(3)P2 charmonium state.

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CpG island methylator phenotype (CIMP) of colorectal cancer is best characterised by quantitative DNA methylation analysis and prospective cohort studies.

BACKGROUND: The concept of CpG island methylator phenotype (CIMP) is not universally accepted. Even if specific clinicopathological features have been associated with CIMP, investigators often failed to demonstrate a bimodal distribution of the number of methylated markers, which would suggest CIMP as a distinct subtype of colorectal cancer. Previous studies primarily used methylation specific polymerase chain reaction which might detect biologically insignificant low levels of methylation. AIM: To demonstrate a distinct genetic profile of CIMP colorectal cancer using quantitative DNA methylation analysis that can distinguish high from low levels of DNA methylation. MATERIALS AND METHODS: We developed quantitative real time polymerase chain reaction (MethyLight) assays and measured DNA methylation (percentage of methylated reference) of five carefully selected loci (promoters of CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 460 colorectal cancers from large prospective cohorts. RESULTS: There was a clear bimodal distribution of 80 microsatellite instability-high (MSI-H) tumours according to the number of methylated promoters, with no tumours showing 3/5 methylated loci. Thus we defined CIMP as having >or=4/5 methylated loci, and 17% (78) of the 460 tumours were classified as CIMP. CIMP was significantly associated with female sex, MSI, BRAF mutations, and wild-type KRAS. Both CIMP MSI-H tumours and CIMP microsatellite stable (MSS) tumours showed much higher frequencies of BRAF mutations (63% and 54%) than non-CIMP counterparts (non-CIMP MSI-H (0%, p<10(-5)) and non-CIMP MSS tumours (6.6%, p<10(-4)), respectively). CONCLUSION: CIMP is best characterised by quantitative DNA methylation analysis. CIMP is a distinct epigenotype of colorectal cancer and may be less frequent than previously reported.

Colorectal Neoplasms↗

Down-regulation of p21 (CDKN1A/CIP1) is inversely associated with microsatellite instability and CpG island methylator phenotype (CIMP) in colorectal cancer.

p21 (CDKN1A/CIP1/WAF1), one of the cyclin-dependent kinase inhibitors, plays a key role in regulating the cell cycle and is transcriptionally regulated by p53. Down-regulation of p21 is caused by TP53 mutations in colorectal cancer. CpG island methylator phenotype (CIMP) appears to be a distinct subtype of colorectal cancer with concordant methylation of multiple gene promoters and is associated with a high degree of microsatellite instability (MSI-H) and BRAF mutations. However, no study to date has evaluated the relationship between p21 expression and CIMP in colorectal cancer. The purpose of this study was to examine the inter-relationships between p21, p53, CIMP, MSI and KRAS/BRAF status in colorectal cancer. We utilized 737 relatively unbiased samples of colorectal cancers from two large prospective cohort studies. Using quantitative real-time PCR (MethyLight), we measured DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16/INK4A), CRABP1, MLH1 and NEUROG1]. CIMP-high (>or=4/5 methylated promoters) was diagnosed in 118 (16%) of the 737 tumours. We also assessed expression of p21 and p53 by immunohistochemistry. Among the 737 tumours, 371 (50%) showed p21 loss. Both p21 loss and p53 positivity were inversely associated with CIMP-high, MSI-H and BRAF mutations. The associations of p21 with these molecular features were still present after tumours were stratified by p53 status. In contrast, the associations of p53 positivity with the molecular features were no longer present after tumours were stratified by p21 status. When CIMP-high and non-CIMP-high tumours were stratified by MSI or KRAS/BRAF status, CIMP-high and MSI-H (but not BRAF mutations) were still inversely associated with p21 loss. In conclusion, down-regulation of p21 is inversely correlated with CIMP-high and MSI-H in colorectal cancer, independent of TP53 and BRAF status.

Colorectal Neoplasms↗

Prevention of abdominal aortic aneurysms by simultaneous inhibition of NFkappaB and ets using chimeric decoy oligonucleotides in a rabbit model.

Abdominal aortic aneurysm (AAA) is one of the major vascular diseases caused by atherosclerosis. Because treatment for AAA mainly consists of surgery to prevent deaths from AAA rupture and there is a conspicuous absence of alternative therapeutic strategies, the development of minimally invasive treatment is needed. To develop a novel therapeutic approach, we examined the simultaneous inhibition of the transcription factors NFkappaB and ets, which regulate inflammation and matrix degradation, in a rabbit AAA model. In this study, we employed chimeric decoy oligodeoxynucleotides (ODN), containing the consensus sequences of both the NFkappaB- and ets-binding sites, to inhibit both the transcription factors simultaneously. Using a delivery sheet, we examined the inhibitory effect of chimeric decoy ODN on aortic dilatation. Ultrasound and angiographic analysis demonstrated that treatment with chimeric decoy ODN significantly prevented the progression of elastase-induced aortic dilatation. The inhibitory effect of chimeric decoy ODN on aortic dilatation was also confirmed by histological studies. Treatment with chimeric decoy ODN reduced the activities of matrix metalloproteinase (MMP)-2 and MMP-9 and markedly inhibited the proteolysis of elastin as compared to scrambled decoy ODN. Interestingly, treatment with chimeric decoy ODN also suppressed VCAM-1 and MCP-1 gene expression, leading to inhibition of macrophage infiltration in the adventitia and media. The present study in a rabbit model provides a novel strategy to treat AAA by the simultaneous inhibition of both NFkappaB and ets using chimeric decoy ODN. Further modification of chimeric decoy ODN would be useful to treat AAA as a decoy-based therapy.

Animals↗