Biomedical subjects

K Furukawa

Publications and source records attributed to K Furukawa.

At least 37 records · Page 2Linked to original sources

PubMed2004

Risk factors associated with perioperative myocardial damage in patients with severe aortic stenosis.

AIM: Few studies have been performed about the risk factors associated with perioperative myocardial damage in patients undergoing valve surgery for severe aortic stenosis. METHODS: To assess the prevalence of perioperative myocardial damage, we studied 103 consecutive patients with aortic stenosis. Perioperative myocardial damage (PMD) was diagnosed by both enzymatic data of peak creatine kinase iso-enzyme (CK-MB) and new appearance of electrocardiographic abnormality. PMD was noticed in 16 patients, and PMD was not noticed in 87 patients. A stepwise multiple logistic regression model was used to investigate predictors of PMD in several categorized parameters such as preoperative data, cardioplegic delivery method, and aortic clamping time. RESULTS: A multivariate analysis identified that cardioplegic delivery method, preoperative left ventricular (LV) wall thickness, and aortic clamping time were independent predictors of PMD. The incidence of PMD in the combined antegrade and continuous retrograde delivery method was significantly lower than that in antegrade delivery method (odds ratio 0.11, CI 0.02-0.61, p=0.011). The peak CK-MB value of the combined antegrade and retrograde method was significantly lower than that of the antegrade method (48+/-24 vs 71+/-50 IU/L; p=0.009). The peak lactate-dehydrogenase value of the combined method was significantly lower than that of the antegrade method (590+/-249 vs 1058+/-656 IU/L; p<0.001). The combined method decreased the incidence of PMD in patients with increased total wall thickness. CONCLUSION: Cardioplegic delivery method, LV total wall thickness, and aortic clamping time were independent predictors for PMD. Combined antegrade and continuous retrograde delivery method may be an important factor to obtain adequate myocardial protection.

Adult↗

PubMed2003

Measurement of time-dependent CP-violating asymmetries in B0-->phiK(0)S, K+K-K0(S), and eta'K0(S) decays.

We present an improved measurement of CP-violation parameters in B0-->phiK(0)(S), K(+)K(-)K(0)(S), and eta(')K(0)(S) decays based on a 140 fb(-1) data sample collected at the Upsilon(4S) resonance with the Belle detector at the KEKB energy-asymmetric e(+)e(-) collider. One neutral B meson is fully reconstructed in one of the specified decay channels, and the flavor of the accompanying B meson is identified from its decay products. CP-violation parameters for each of the three modes are obtained from the asymmetries in the distributions of the proper-time intervals between the two B decays. We find that the observed CP asymmetry in the B-->phiK(0)(S) decay differs from the standard model (SM) expectation by 3.5 standard deviations, while the other cases are consistent with the SM.

Journal Article↗

PubMed2003

Observation of B-->K*l+l-.

We report the observation of the flavor-changing neutral current decay B-->K(*)l(+)l(-) and an im-proved measurement of the decay B-->Kl(+)l(-), where l represents an electron or a muon, with a data sample of 140 fb(-1) accumulated at the Upsilon(4S) resonance with the Belle detector at KEKB. The results for the branching fractions are B(B-->K(*)l(+)l(-))=(11.5(+2.6)(-2.4)+/-0.8+/-0.2)x10(-7) and B(B-->Kl(+)l(-))=(4.8(+1.0)(-0.9)+/-0.3+/-0.1)x10(-7), where the first error is statistical, the second is systematic and the third is from model dependence.

Journal Article↗

PubMed2003

Evidence for B0-->pi0pi0.

We report evidence for the decay B0-->pi(0)pi(0). The analysis is based on a data sample of 152x10(6) BBmacr; pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB e(+)e(-) storage ring. We detect a signal for B0-->pi(0)pi(0) with a significance of 3.4 standard deviations, and measure the branching fraction to be [1.7+/-0.6(stat)+/-0.2(syst)]x10(-6).

Journal Article↗

PubMed2003

Observation of a narrow charmoniumlike state in exclusive B+/--->K+/-pi+pi-J/psi decays.

We report the observation of a narrow charmoniumlike state produced in the exclusive decay process B+/--->K+/-pi(+)pi(-)J/psi. This state, which decays into pi(+)pi(-)J/psi, has a mass of 3872.0+/-0.6(stat)+/-0.5(syst) MeV, a value that is very near the M(D0)+M(D(*0)) mass threshold. The results are based on an analysis of 152M B-Bmacr; events collected at the Upsilon(4S) resonance in the Belle detector at the KEKB collider. The signal has a statistical significance that is in excess of 10sigma.

Journal Article↗

PubMed2003

Effect of AD-5423 on animal models of schizophrenia: phencyclidine-induced behavioral changes in mice.

The antipsychotic efficacy of AD-5423, which has the properties of both a serotonin 5-HT(2) and a dopamine D(2) receptor antagonist, was evaluated using animal models of schizophrenia. Sensitization to phencyclidine (PCP)-induced hyperlocomotion is considered a model of the positive symptoms of schizophrenia, and was significantly antagonized by AD-5423 and haloperidol. The PCP-induced enhancement of immobility induced by the forced swimming test, a model of the negative symptoms of schizophrenia, was attenuated by AD-5423 but not by haloperidol. Since this attenuated effect of AD-5423 was antagonized by DOI, a serotonin 5-HT(2) receptor agonist, it is postulated to be mediated by serotonin 5-HT(2) receptors. These findings suggest that AD-5423 would be clinically effective against both the positive and negative symptoms of schizophrenia.

Animals↗

PubMed2003

Measurement of positron production efficiency from a tungsten monocrystalline target using 4- and 8-GeV electrons.

Intense positron sources are being widely investigated for the next-generation linear colliders and B factories. A new method utilizing an axially oriented crystal as a positron-production target is one of the bright schemes, since it provides a powerful photon source through channeling and coherent bremsstrahlung processes when high-energy electrons penetrate the target. A series of positron-production experiments with tungsten crystals hit by 4- and 8-GeV single-bunch electron beams were carried out at the KEKB 8-GeV injector linac. Three tungsten crystals with different thicknesses (2.2, 5.3, and 9.0 mm) and those combined with amorphous tungsten plates were tested on a precise goniometer. The positron-production yields were measured with a magnetic spectrometer in the positron momentum (P(e(+))) range from 5 to 20 MeV/c. The angle of the <111> crystal axis with respect to the electron-beam direction was controlled by measuring the relative intensities of the produced positrons as a function of the rotational angle of the goniometer. The results show that the enhancements of the positron yield from crystal targets compared to amorphous targets of the same thickness at P(e(+))=20 MeV/c are from 1.5 to 3.7 and from 1.8 to 5.1, depending upon the target thickness for 4- and 8-GeV electrons, respectively.

Journal Article↗

PubMed2003

Heterogeneity of endocytic proteins: distribution of clathrin adaptor proteins in neurons and glia.

Clathrin adaptor protein (AP)180 is a synaptic protein that regulates the assembly of clathrin-coated vesicles. Several endocytic proteins including AP2, CALM, and epsin 1 have functions or molecular structures similar to AP180. We determined if AP180 associates with functional synapses in cultured hippocampal neurons. We also compared the expression pattern of AP180 with the other endocytic proteins. The distribution of AP180 corresponded with the synaptic vesicle-associated protein synapsin I, and with functional presynaptic terminals labeled with the styryl dye FM1-43. Synaptic AP2 colocalized with AP180, but the distribution of AP2 was not limited to synapses of neurons and it was also expressed in glia. CLAM and epsin 1 immunoreactivities were also detected in both neurons and glia. Unlike AP180, the neuronal immunoreactivity of CALM was not intense in the synaptic puncta. Epsin 1 immunoreactivity was found in both synaptic and extrasynaptic sites, and its synaptic distribution only partially overlapped with that of AP180. These results support roles for AP180 in synaptic function in neurons. The findings also provide information on the distribution of AP2, CALM, and epsin 1 in cells of the nervous system that suggest different roles for these endocytic proteins in the biology of these cells.

Adaptor Proteins, Vesicular Transport↗

PubMed2003

Transplantation of skin fibroblasts expressing BMP-2 promotes bone repair more effectively than those expressing Runx2.

We investigated the osteogenic potential of skin fibroblasts that overexpressed BMP-2 or Runx2 by using adenoviral vectors. In in vitro experiments, skin fibroblasts infected with adenovirus vector encoding BMP-2 (AdBMP-2) released substantial levels of BMP-2 proteins into culture media, and those infected with adenovirus vector encoding Runx2 (AdRunx2) produced its protein. Transduction of BMP-2 or Runx2, respectively, increased alkaline phosphatase (ALP) activity and induced expression of mRNAs of ALP, osteocalcin, and osterix in skin fibroblasts. In in vivo experiments, we investigated the bone induction activity by transplantation of a complex composed of carrier [poly-D,L-lactic-co-glycolic acid/gelatin sponge (PGS)] and skin fibroblasts (PGS/SF complex). Transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdBMP-2-induced ectopic bone formation when transplanted into the subfascia of back muscle, unlike those infected with AdRunx2. Transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdBMP-2 into craniotomy defects induced bone formation from 2 weeks after transplantation, and almost all PGS was replaced by newly synthesized bone at 6 weeks. To investigate the fate of the transplanted cells, we transplanted skin fibroblasts isolated from green fluorescence protein transgenic mice into craniotomy defects. Transplantation of these skin fibroblasts transfected with AdBMP-2 generated green fluorescence protein-positive osteoblasts and osteocytes, indicating that the transplanted skin fibroblasts differentiated into osteoblastic lineage cells during bone repair. In contrast, transplantation of PGS/SF complexes composed of skin fibroblasts transduced with AdRunx2 induced a few ALP-positive cells at 1 week after transplantation, but their number decreased depending on time after transplantation. In addition, transplantation of these complexes was insufficient to induce bone repair. Taken together, our results suggest that skin fibroblasts expressing BMP-2 are more suitable for cell-mediated therapy of bone repair than those expressing Runx2.

Adenoviridae↗

PubMed2003

Responses to serotonin (5HT) in isolated corpus cavernosum penis of rabbit.

This study was aimed at determining serotonin (5-hydroxytryptamine: 5HT) receptor subtypes participating in 5HT-induced response in the isolated corpus cavernosum penis (CCP) of rabbits. 5HT contracted the CCP in a concentration-dependent manner. Both WAY100635 (5HT(1A) antagonist) and LY53857 (5HT(2) antagonist) concentration-dependently suppressed the 5HT-induced contraction. The suppression of the 5HT-induced contraction by ketanserin (5HT(2A) antagonist) was weaker than that by LY53857. LY278584 (5HT(3) antagonist) did not affect the 5HT-induced contraction. SDZ205557 (5HT(4) antagonist) showed a tendency to potentiate the 5HT-induced contraction. The above results suggest that 5HT(1A) and 5HT(2) receptor subtypes partially participate in the contractile response to 5HT in rabbit CCP, and the potentiation by SDZ205557 of the 5HT-induced contraction implies the existence of dual contractile and relaxing responses to 5HT via 5HT(1) and 5HT(2), and 5HT(4) receptors, respectively. The relaxing response to 5HT(4) receptor stimulation may be masked by 5HT-induced contraction.

4-Aminobenzoic Acid↗

PubMed2002

The usefulness of prevention consolidation therapy of esophageal varices using an argon plasma coagulation technique.

BACKGROUND AND STUDY AIM: esophageal variceal ligation (EVL) has been spread widely as a simple and effective method for treating esophageal varices. However, in view of the unacceptably high rate of recurrence associated with this technique, the availability of other supplemental consolidation therapies has been earnestly desired. Under these circumstances, attempts such as endoscopic injection sclerotherapy (EIS) have been made for this particular therapeutic purpose. In the current study, we tested the clinical usefulness and safety of the argon plasma coagulation technique (APC). PATIENTS AND METHODS: 11 patients with imminent signs of esophageal varix rupture in our hospital were subjects in the present study. Before APC was performed, these patients underwent EVL with consequent improvement of esophageal varices from F3 (largest sized varices) to disappear or F1 (straight). RESULTS: the patients were followed up for a mean post-treatment period of 637.4 (SD +/-56.5) days, and no obvious recurrence of varices in the so-called critical area was noted. In addition, no serious complications were observed. CONCLUSION: our current clinical study has demonstrated that APC may be an effective prevention consolidation therapy after EVL without serious complications.

Journal Article↗

PubMed2002

[Combined carotid endarterectomy and off-pump coronary artery bypass grafting].

Patients with angina undergoing carotid endarterectomy have a high mortality. A 74-yaer-old man who has severe carotid stenosis was performed combined carotid endarterectomy and off-pump coronary artery bypass grafting successfully. At first, carotid endarterectomy was performed with Jamieson's specially designed dissector, which allow simultaneous dissection and removal blood from the surgical field. Secondly, then off-pump CABG was performed. Skeletonized internal mammary artery was harvested with ultrasound dissector. The advantage of that the dissected artery is not only long and greater blood flow, but also less damage to sternal blood flow which prevent infection and complications. Then internal mammary artery was anastomosed to left anterior discending artery with Octopus II stabilizer. After the operation, he recovered uneventfully without neurological complication. Combined single staged carotid endarterectomy and off-pump CABG appears to be a safe method.

Aged↗

PubMed2001

A 30-base-pair element in the first intron of SOX9 acts as an enhancer in ATDC5.

SOX9 is a transcription factor that is essential for chondrogenesis and testis differentiation, and haploinsufficiency of SOX9 causes campomelic dysplasia, severe skeletal malformation syndrome with variably penetrant XY sex reversal. Here we demonstrate that in several cell lines that express SOX9, 30-bp element in the first intron of human SOX9 gene act as a potential enhancer in the ATDC5 chondroprogenitor cell line, despite the apparent absence of cell-specific regulatory elements within a 5.5-kb promoter region. Deletion and site-specific mutational analyses reveal that the last 12 bp of the 30-bp element are critical for transcriptional activity, while 5'-half sequences are necessary for full transactivation. Gel retardation assays indicate the possible involvement of several binding factors along the length of this element. These results suggest that functionally interdependent elements in the 30-bp enhancer region of the first intron account for basal expression levels of Sox9 in ATDC5.

3T3 Cells↗

PubMed2001

Lactosylceramide is essential for the osteoclastogenesis mediated by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand.

Glycosphingolipids and their metabolites play important roles in a variety of biological processes. Several signal molecules are localized in a glycolipid-enriched microdomain on the cell surface, and their signals are regulated by the glycolipid composition. However, the function of glycolipids in osteoclastogenesis has not been clearly understood. We found that D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), a glucosylceramide synthase inhibitor, completely inhibits the osteoclast formation induced by macrophage-colony-stimulating factor and receptor activator of nuclear factor-kappa B ligand (RANKL) in a dose-dependent manner. Expression of RANK, the receptor of RANKL, induced by macrophage colony-stimulating factor, was reduced markedly in D-PDMP-treated cells. d-PDMP also inhibited the phosphorylation of the inhibitor of nuclear factor-kappa B and extracellular signal-regulated kinase 1/2 induced by RANKL. In several experiments with the addition of glycolipids to D-PDMP-treated purified bone marrow cells, lactosylceramide (LacCer) strongly affected the differentiation into tartrate-resistant acid phosphatase mononucleated cells, but not positive multinucleated cells. GM3 and GM1 also recovered, but less effectively compared with LacCer. Moreover, exogenous LacCer recovered the reduced expression of RANK and the phosphorylation of inhibitor of NF-kappa B and extracellular signal-regulated kinase 1/2 after stimulation by RANKL at the same level of cells without D-PDMP treatment. Our data suggest that glycosphingolipids, especially LacCer, are necessary for the initiation step of RANKL-induced osteoclastogenesis.

Animals↗

PubMed2001

Determination of fluvastatin and its five metabolites in human plasma using simple gradient reversed-phase high-performance liquid chromatography with ultraviolet detection.

A simple gradient reversed-phase high-performance chromatographic method with ultraviolet detection for the determination of fluvastatin (FV) and its five metabolites, (M-2, M-3, M4, M-5 and M-7) in human plasma was developed and validated. The limit of quantification of FV and its five metabolites in human plasma was 10 ng ml(-1). The assay had satisfactory selectivity, recovery, linearity and precision accuracy. Stability studies showed that FV and its five metabolites were stable in plasma up to at least 1 month of storage at -30 degrees C.

Anticholesteremic Agents↗

PubMed2001

Increased cytotoxic effects of photodynamic therapy in IL-6 gene transfected cells via enhanced apoptosis.

PDT has been reported to induce cancer cell expression of cytokines, such as IL-6 and TNF-alpha, but it has been unclear whether cytokine expression by cancer cells is directly related to the antitumor effect of PDT. We treated Lewis lung carcinoma (LLC) cells with a new photosensitizer, mono-L-aspartyl chlorin e6 (NPe6) and light from a diode laser and found that expression of the mRNA of IL-2, IL-6, and TNF-alpha was increased by NPe6-mediated-PDT 6 hr later. To elucidate the mechanism of the direct anti-tumor effect of cytokine expression, we examined the photosensitivity of cytokine-gene-transfected cells, namely LLC-IL-2, LLC-IL-6, and LLC-TNF-alpha cells, by MTT assay. The IL-6 gene transfected, LLC-IL-6 cells were significantly more sensitive to cytotoxic effects than the parent LLC cells and other cytokine gene-transfected cells. This finding indicates that IL-6 expression modulates cellular sensitivity to PDT and that IL-2 and TNF-alpha expressions does not. In addition, the apoptosis of LLC-IL-6 cells induced by NPe6-PDT was greater than in the other cells as determined by DNA fragmentation and staining of apoptotic nuclei. Because IL-6 has been reported to induce apoptosis by downregulating expression of Bcl-2, we analyzed the expression of apoptosis-related Bcl-2, Bax, and cytochrome C by Western blot analysis. Decreased expression of Bcl-2 and cytochrome C was observed in both LLC cells and LLC-IL-6 cells. Bax protein increased in a time-dependent manner, and the ratio of Bax to Bcl-2 rose markedly after PDT in LLC-IL-6 cells. These results suggest that the increased sensitivity of LLC-IL-6 cells to PDT-induced cytotoxicity results from the high ratio of Bax to Bcl-2 in the IL-6-dependent apoptotic pathway. In conclusion, IL-6 expression plays a role in cellular sensitivity to PDT, and combination of IL-6 and PDT may provide a new strategy for cancer treatment.

Animals↗

PubMed2001

Functional analyses of Bph-Tod hybrid dioxygenase, which exhibits high degradation activity toward trichloroethylene.

Biphenyl dioxygenase (BphDox) in Pseudomonas pseudoalcaligenes KF707 is a multicomponent enzyme consisting of an iron-sulfur protein (ISP) that is composed of alpha (BphA1) and beta (BphA2) subunits, a ferredoxin (FD(BphA3)), and a ferredoxin reductase (FDR(BphA4)). A recombinant Escherichia coli strain expressing hybrid Dox that had replaced BphA1 with TodC1 (alpha subunit of toluene dioxygenase (TolDox) of Pseudomonas putida) exhibited high activity toward trichloroethylene (TCE) (Furukawa, K., Hirose, J., Hayashida, S., and Nakamura, K. (1994) J. Bacteriol. 176, 2121-2123). In this study, ISP, FD, and FDR were purified and characterized. Reconstitution of the dioxygenase components consisting of purified ISP(TodC1BphA2), FD(BphA3), and FDR(BphA4) exhibited oxygenation activities toward biphenyl, toluene, and TCE. Native polyacrylamide gel electrophoresis followed by the Ferguson plot analyses demonstrated that ISP(TodC1BphA2) and ISP(BphA1A2) were present as heterohexamers, whereas ISP(TodC1C2) was present as a heterotetramer. The molecular activity (k(0)) of the hybrid Dox for TCE was 4.1 min(-1), which is comparable to that of TolDox. The K(m) value of the hybrid Dox for TCE was 130 microm, which was lower than 250 microm for TolDox. These results suggest that the alpha subunit of ISP is crucial for the determination of substrate specificity and that the change in the alpha subunit conformation of ISP from alpha(2)beta(2) to alpha(3)beta(3) results in the acquisition of higher affinity to TCE, which may lead to high TCE degradation activity.

Electrophoresis, Polyacrylamide Gel↗

PubMed2001

A role of the third complementarity-determining region in the affinity maturation of an antibody.

We recently found that there are two distinct antibody maturation pathways for the immune response of C57BL/6 mice to (4-hydroxy-3-nitrophenyl) acetyl and that a junctional amino acid introduced at a point far in advance of somatic hypermutation determined which pathway of affinity maturation was used. We describe here the structural basis for this aspect of maturation using recently developed H3 rules, which allow for reliable identification of the conformation of the third complementarity-determining region of the heavy chain (CDR-H3) from the primary amino acid sequences only. By the application of these rules, the anti-(4-hydroxy-3-nitrophenyl) acetyl antibodies examined here were classified into two major groups on the basis of their CDR-H3 structure, and these groups were found to be consistent with the maturation pathways. In addition, circular dichroism measurements revealed that the versatile nature of the antigen binding of the antibodies was significantly influenced by the pathway employed. We postulated in this study that flexibility in the CDR-H3 structure in the antigen-combining site could facilitate efficient antibody maturation supported by a plurality of possible antigen binding modes.

Animals↗