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Biomedical subjects

A Suzuki

Publications and source records attributed to A Suzuki.

At least 37 records · Page 2Linked to original sources

Evaluation of interface wave velocity, reflection coefficients and interfacial stiffnesses of contacting surfaces.

The phase velocity of the antisymmetric-mode interface wave as well as the longitudinal and shear wave reflection coefficients have been measured for contacting poly(methyl methacrylate) (PMMA) surfaces subjected to different contact pressures. It has been found that while the reflection coefficients decrease as the contact pressure is increased, the phase velocity of the interface wave increases from that of the Rayleigh wave toward that of the bulk shear wave. From these measurements, the normal and tangential interfacial stiffnesses of the contacting PMMA surfaces have been evaluated as functions of the contact pressure. As a result, the two independent procedures to evaluate the tangential stiffness, namely, from the interface wave velocity and from the shear wave reflection measurements, have yielded mutually consistent results. Furthermore, it has been found that the tangential/normal stiffness ratio and the shear/longitudinal reflection ratio of the contact interface are consistent with the predictions of an existing theoretical model for kissing bond interfaces.

Journal Article↗

CUL1, a component of E3 ubiquitin ligase, alters lymphocyte signal transduction with possible effect on rheumatoid arthritis.

Ubiquitination affects various immune processes and E3 ubiquitin ligases (E3) play an important role in determining substrate specificity. We identified 11 human E3 ligase genes of potential importance in pathogenesis of autoimmune diseases by search of public databases and screened them for candidacy of biological investigation with case-control linkage disequilibrium tests on multiple SNPs in the genes using rheumatoid arthritis (RA) as a model of autoimmune diseases. Significant association with RA was observed in an SNP in intron 3 of Cullin 1 (CUL1) that affected transcriptional efficiency of the promoter activity in lymphocytic cell lines. Quantitative expression analysis revealed that CUL1 mRNA was highly detected in lymphoid tissues including spleen and tonsil, and was specifically expressed in T and B lymphocytes in fractionated peripheral leukocytes. Histological evaluation of tonsils indicated that CUL1 protein expression was relatively specific for maturing germinal centers. Suppression of CUL1 expression had influence on the phenotype of T-cell line, that is, it inhibited IL-8 induction, which is known to play an important role in the migration of inflammatory cells into the affected area seen in RA. Our data suggest that the regulation of CUL1 expression in immunological tissues may affect the susceptibility of RA via altering lymphocyte signal transduction.

Arthritis, Rheumatoid↗

Probiotic Lactobacillus-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines in lamina propria mononuclear cells.

IL-6/STAT-3 signals play key roles in inflammatory bowel disease (IBD). It is known that Lactobacillus casei strain Shirota (LcS) improves inflammatory disorders. This study aimed to elucidate the effect of LcS on murine chronic IBD and to clarify the mechanism. We focused the inhibitory effect of LcS on the production of IL-6 in lipopolysaccharide (LPS)-stimulated large intestinal lamina propria mononuclear cells (LI-LPMC) isolated from mice with chronic colitis and in RAW264.7 cells in vitro. We also determined in vivo the effect of LcS on murine chronic IBD models induced with dextran sodium sulphate and SAMP1/Yit mice. Finally, we examined the cellular determinants of LcS for the down-regulation of IL-6 secretion by LI-LPMC, RAW264.7 cells and peripheral blood mononuclear cells (PBMC) derived from patients with ulcerative colitis (UC). LcS, but not other strains of Lactobacillus, inhibited the production of IL-6 in LPS-stimulated LI-LPMC and RAW264.7 cells, down-regulating the nuclear translocation of NF-kappaB. The LcS-diet-improved murine chronic colitis is associated with the reduction of IL-6 synthesis by LI-LPMC. LcS also improved chronic ileitis in SAMP1/Yit mice. The release of IL-6 in vitro in LPS-stimulated LI-LPMC, RAW 264.7 cells and UC-PBMC was inhibited by a polysaccharide-peptidoglycan complex (PSPG) derived from LcS. This probiotic-induced improvement in murine chronic inflammatory bowel disease is associated with the down-regulation of pro-inflammatory cytokines such as IL-6 and IFN-gamma production in LPMC. Therefore, LcS may be a useful probiotic for the treatment of human inflammatory bowel disease.

Animals↗

Diminished cytokine signalling against bacterial components in mononuclear leucocytes from ulcerative colitis patients after leukocytapheresis.

Infiltration by circulating inflammatory cells is a prominent local inflammatory feature of ulcerative colitis (UC). Several trials have suggested that leukocytapheresis by filtration can benefit patients with active UC. We investigated how this therapy might modulate the inflammatory response. Patients with active UC who were beginning repeated filtration leukocytapheresis were studied. Mononuclear cell preparations were obtained from blood before and after the first treatment, and expression of cytokine signalling components and the cell-proliferative response were analysed in vitro. Leukocytapheresis reduced lipopolysaccharide-induced production of proinflammatory cytokines (interleukin-1, -6, -8 and tumour necrosis factor-alpha, P < 0.05 for all) and activation of intracellular signalling components (nuclear factor-kappaB, mitogen-activated protein kinases, and signal transducer and activator of transcription-3), as well as surface expression of toll-like receptor-4 (P < 0.05) in mononuclear cells. The therapy also reduced the cell-proliferative response by mononuclear cells stimulated with sonicated bacterial preparations from autologous intestine (P < 0.05). These results indicate that activated mononuclear cells in the peripheral blood of patients with active UC are removed by leukocytapheresis and replaced by cells with a lower activation status. This replacement may partly explain the therapeutic benefit.

Adult↗

Overexpression of anti-apoptotic Mcl-1 in testicular germ cell tumours.

AIMS: To determine the expression of Mcl-1 in testicular germ cell tumours in order to clarify the role of this anti-apoptotic factor in these tumours. Various members of the Bcl-2 family have been implicated in the apoptotic mechanisms regulating germ cell apoptosis. Mcl-1 is an anti-apoptotic Bcl-2 family member and has recently been reported to be related to the progression of malignancy; however, the involvement of Mcl-1 in the development of germ cell tumours is still unknown. METHODS AND RESULTS: Mcl-1 expression in testicular germ cell tumours was investigated by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR). By immunohistochemistry, overexpression of Mcl-1 was present in all germ cell tumours that were studied, including embryonal carcinoma and yolk sac tumour, as well as choriocarcinoma and teratoma. In teratomas, Mcl-1 was widely distributed in the epithelial, myogenic, neural and mesenchymal components. RT-PCR analysis after microdissection revealed high levels of Mcl-1 mRNA in all tumour variants compared with non-neoplastic germ cells. CONCLUSION: Overexpression of anti-apoptotic Mcl-1 may function to enhance the viability of testicular germ cells, thereby leading to tumorigenesis.

Adolescent↗

Fibrocartilaginous embolism in a chondrodystrophoid breed dog.

An 8-year-old intact male Shih Tzu dog was admitted with acute-onset tetraplegia. Magnetic resonance imaging showed an abnormality of the cervical intramedullary spinal cord. Histopathological examination of a spinal biopsy confirmed the presence of intravascular cartilaginous emboli. This is the first report of an antemortem diagnosis of fibrocartilaginous embolism in a chondrodystrophoid breed dog.

Animals↗

[Lung carcinomas with interstitial pneumonia; detection of lung cancers by CYFRA and selection of surgical procedure].

Interstitial pneumonia (IP) may occur with the chest radiographic abnormality at the bilateral, predominantly basal and subpleural area of the lower lobe. And the incidence of lung cancer are markedly increased among patients with IP. From 1993 to 2003, 15 cases (male 14, female 1; average age 65.9-year-old), who were complicated IP, underwent surgical treatment in our hospital. Concerning detective tumor markers of lung cancers with IP, CYFRA showed very high sensitivity (92.3%) for any type of carcinoma. There were no case of perioperative death, however, 3 cases occurred severe deterioration of IP within 1 month and 6 cases died of respiratory failure. The risk factors, which aggravated IP at the postoperative period, were administration of prednisolone or immunosuppressive drugs from pre-operation and resection of the relatively non-fibrotic and non-honeycomb lobe which was affected with cancer. If it is possible to prognosticate the postoperative deterioration of IP, segmentectomy should be considered.

Aged↗

[Surgical treatment for locally advanced lung cancer; therapeutic response of induction chemotherapy and postoperative chemotherapy].

The current chemotherapy has been able to give us many options to treat for lung cancer and recent studies have showed that perioperative chemotherapy may improve survival. In this study, we compared 2 groups with locally advanced lung cancers (stage III, T3N0M0, inclusive of ipsilateral PM2, D1 and D2) ; group A, which had been treated by chemotherapy for downstaging prior to surgery (n = 23), and group B, which had been treated by surgery alone (n = 48). The postoperative 3- and 5-year overall survival rates analyzed using the Kaplan-Meier method were 64.7 and 29.4% for group A, 32.5 and 10% for group B, respectively. And there was a significant difference between 2 groups. Further on patients with pN2, 3-year survival rate was 60% for group A and 36.7% for group B. In view of the progress of chemotherapy, even if the locally advanced lung cancer, which may be suspected of invasion to pulmonary artery, pulmonary vein and central bronchus, is not classified as T4, a patient with it should be performed an induction chemotherapy for downstaging and an operation for complete resection of the tumor and preserving lung function.

Aged↗

Retiming of picosecond pulses by a cascaded second-order nonlinear process in quasi-phase-matched LiNbO3 waveguides.

A new technique for reducing timing jitter by using a cascaded second-order nonlinear process in quasi-phase-matched (QPM) LiNbO3 waveguides is proposed. It was found that the timing jitter of a signal at QPM wavelength is not transferred to the converted pulses during cascading in a 30-mm-long LiNbO3 QPM waveguide. Timing-jitter transfer characteristics in QPM LiNbO3 waveguides are evaluated by calculation of pulse evolution, and retiming of 1.5-ps pulses in 10- and 30-mm-long waveguides is demonstrated experimentally.

Journal Article↗

Evaluation of genitofemoral nerve block, in addition to ilioinguinal and iliohypogastric nerve block, during inguinal hernia repair in children.

BACKGROUND: Ilioinguinal and iliohypogastric (IG-IH) nerve block has been widely used in children undergoing inguinal hernia repair. This technique may provide insufficient analgesia for intraoperative management as the inguinal region may receive sensory innervation from genitofemoral nerve. We proposed that addition of a genitofemoral nerve block might improve the quality of analgesia. METHODS: Ninety-eight children undergoing inguinal hernia repair were assigned randomly to receive either IG-IH nerve block (Group I) or IG-IH and genitofemoral nerve blocks (Group II). Systolic arterial pressure (SAP) and heart rate (HR) were recorded before surgery (control), after skin incision, at sac traction and at the end of surgery. Postoperative analgesic requirements and incidence of complications were recorded until discharge. RESULTS: At sac traction, SAP and HR were significantly higher in Group I (P<0.05), and the incidence of episodes of increased HR was also significantly higher in Group II (29 vs 12%, respectively, P<0.05). There were no significant differences in SAP and HR at other time points, postoperative analgesic requirements or incidence of complications between the groups. CONCLUSIONS: The benefit of the additional genitofemoral nerve block to IG-IH nerve block was limited only to the time of sac traction without any postoperative effect. This suggests there is little clinical benefit in the addition of a genitofemoral nerve block.

Analgesics↗

The inhibition of antithrombin by peptidylarginine deiminase 4 may contribute to pathogenesis of rheumatoid arthritis.

OBJECTIVE: The gene for peptidylarginine deiminase 4 (PADI4) has been found to be closely associated with rheumatoid arthritis (RA). Peptidylarginine deiminase (PADI) catalyses the post-translational modification of peptidylarginine to citrulline, a reaction known as citrullination. PADI extracted from rabbit muscle has been reported to citrullinate antithrombin, a principal plasma inhibitor of thrombin. Thrombin is known to induce angiogenesis, fibrin formation and inflammation, the primary events of the RA joint. Here, we investigate whether human PADI4 can inhibit antithrombin by catalysing antithrombin citrullination and how the enzyme is involved in RA pathogenesis. METHODS: Antithrombin was incubated with recombinant PADI4 protein, and the inactivation of antithrombin was determined by reduction of its thrombin-inhibiting activity. Citrullination of antithrombin was detected by western blotting and enzyme-linked immunosorbent assay (ELISA). In addition, the citrullination level, activity and concentration of antithrombin in RA plasma were investigated by sandwich ELISA. RESULTS: Incubation of antithrombin with PADI4 resulted in loss of thrombin-inhibitory activity and in citrullination of antithrombin. RA plasma showed higher levels of citrullinated antithrombin than controls with non-arthritis disease and healthy individuals. CONCLUSION: The results indicate that PADI4 could inactivate antithrombin through citrullination. The abnormal expression or activation of PADI4 in RA synovium is suggested to be responsible for the high level of citrullinated antithrombin in RA plasma. Local inhibition of antithrombin activity in RA synovium might lead to the excessive angiogenesis, fibrin deposition and inflammation of the tissue.

Animals↗

Localization of peptidylarginine deiminase 4 (PADI4) and citrullinated protein in synovial tissue of rheumatoid arthritis.

OBJECTIVES: Peptidylarginine deiminases (PADIs) convert peptidylarginine into citrulline via post-translational modification. Anti-citrullinated peptide antibodies are highly specific for rheumatoid arthritis (RA). Our genome-wide case-control study of single-nucleotide polymorphisms found that the PADI4 gene polymorphism is closely associated with RA. Here, we localized the expression of PADI4 and the citrullinated protein product in synovial RA tissue. METHODS: We used immunohistochemistry, double immunofluorescent labelling and western blotting. RESULTS: We found that PADI4 is extensively expressed in T cells, B cells, macrophages, neutrophils, fibroblast-like cells and endothelial cells in the lining and sublining areas of the RA synovium. We also found extracellular and intracellular expression of PADI4 in fibrin deposits with loose tissue structures where apoptosis was widespread. Unlike PADI4, citrullinated protein generally appeared in fibrin deposits that were abundant in the RA synovium. The citrullinated fibrin aggregate was immunoreactive against immunoglobulin (Ig) A and IgM, but not IgG and IgE. Although a little PADI4 was expressed in osteoarthritic and normal synovial tissues, significant citrullination was undetectable. CONCLUSIONS: The results showed that PADI4 is mainly distributed in cells of various haematopoietic lineages and expressed at high levels in the inflamed RA synovium. The co-localization of PADI4, citrullinated protein and apoptotic cells in fibrin deposits suggests that PADI4 is responsible for fibrin citrullination and is involved in apoptosis. The immunoreactivity of citrullinated fibrin with IgA and IgM in the RA synovium supports the notion that citrullinated fibrin is a potential antigen of RA autoimmunity.

Apoptosis↗

Search for electron neutrino appearance in a 250 km long-baseline experiment.

We present a search for electron neutrino appearance from accelerator-produced muon neutrinos in the K2K long-baseline neutrino experiment. One candidate event is found in the data corresponding to an exposure of 4.8 x 10(19) protons on target. The expected background in the absence of neutrino oscillations is estimated to be 2.4+/-0.6 events and is dominated by misidentification of events from neutral current pi(0) production. We exclude the nu(micro) to nu(e) oscillations at 90% C.L. for the effective mixing angle in the 2-flavor approximation of sin((2)2theta(microe)( approximately 1/2sin((2)2theta(13))>0.15 at Deltam(2)(microe)=2.8 x 10(-3) eV(2), the best-fit value of the nu(micro) disappearance analysis in K2K. The most stringent limit of sin((2)2theta(microe)<0.09 is obtained at Deltam(2)(microe)=6 x 10(-3) eV(2).

Journal Article↗

Inhibition of the metabolism of etizolam by itraconazole in humans: evidence for the involvement of CYP3A4 in etizolam metabolism.

OBJECTIVE: To clarify the involvement of cytochrome P450 (CYP) 3A4 in the metabolism of etizolam. METHODS: The effects of itraconazole, a potent and specific inhibitor of CYP3A4, on the single oral dose pharmacokinetics and pharmacodynamics of etizolam were examined. Twelve healthy male volunteers received itraconazole (200 mg/day) or placebo for 7 days in a double-blind randomized crossover manner, and on the 6th day they received a single oral 1-mg dose of etizolam. Blood samplings and evaluation of psychomotor function using the Digit Symbol Substitution Test and Stanford Sleepiness Scale were conducted up to 24 h after etizolam dosing. Plasma concentration of etizolam was measured by means of high-performance liquid chromatography. RESULTS: Itraconazole treatment significantly increased the total area under the plasma concentration-time curve (AUC; 213+/-106 ng rectangle h/ml versus 326+/-166 ng rectangle h/ml, P<0.001) and the elimination half-life (12.0+/-5.4 h versus 17.3+/-7.4 h, P<0.01) of etizolam. The 90% confidence interval of the itraconazole/placebo ratio of the total AUC was 1.38-1.68, indicating a significant effect of itraconazole. No significant change was induced by itraconazole in the two pharmacodynamic parameters. CONCLUSION: The present study suggests that itraconazole inhibits the metabolism of etizolam, providing evidence that CYP3A4 is at least partly involved in etizolam metabolism.

Adult↗

Fundamental study on diffuse reflective optical tomography.

We report a simulation study on diffuse reflective optical computed tomography, in which continuous-wave sources and detectors are placed on the plane surface of a semi-infinite body. We adopted a simple Tikhonov regularization in the inverse problem and demonstrated the feasibility of three-dimensional reconstruction of the absorption coefficient change. The spatial resolution of the reconstructed image was shown to be degrading markedly with the depth. The regularization parameter should be chosen appropriately considering the trade-off between the reconstructed image noise and the spatial resolution. We analysed the dependence of the spatial resolution of the reconstructed image on the regularization parameter and the depth, and also the behaviour of the reconstructed image noise on the regularization parameter and the depth.

Absorption↗

High sensitivity search for nu;e's from the sun and other sources at KamLAND.

Data corresponding to a KamLAND detector exposure of 0.28 kton yr has been used to search for nu;(e)'s in the energy range 8.3<E(nu;(e))<14.8 MeV. No candidates were found for an expected background of 1.1+/-0.4 events. This result can be used to obtain a limit on nu;(e) fluxes of any origin. Assuming that all nu;(e) flux has its origin in the Sun and has the characteristic 8B solar nu(e) energy spectrum, we obtain an upper limit of 3.7 x 10(2) cm(-2) s(-1) (90% C.L.) on the nu;(e) flux. We interpret this limit, corresponding to 2.8 x 10(-4) of the standard solar model 8B nu(e) flux, in the framework of spin-flavor precession and neutrino decay models.

Journal Article↗