Biomedical subjects

Masato Suzuki

Publications and source records attributed to Masato Suzuki.

At least 19 recordsLinked to original sources

PubMed2026

VicMAG, an open-source tool for visualizing circular metagenome-assembled genomes highlighting bacterial virulence and antimicrobial resistance.

Bacterial pathogens spread in clinical and environmental settings, and mobile genetic elements (MGEs), such as plasmids and phages, mediate the transfer of virulence factor genes (VFGs) and antimicrobial resistance genes (ARGs) among bacterial communities. Metagenomic analysis of environmental and wastewater samples using highly accurate long-read sequencing technologies, such as Pacific Biosciences (PacBio) HiFi sequencing, provides valuable insights into monitoring the regional spread of VFGs and ARGs, including dissemination mediated by MGEs. No visualization tool is currently available for the comprehensive display of numerous resulting circular metagenome-assembled genomes (cMAGs) with functional gene annotations. Here, we developed visualization of circular metagenome-assembled genome (VicMAG), a visualization tool for highly complex cMAGs derived from long-read metagenome assemblies annotated using updated databases of VFGs, ARGs, and MGEs. Using 353 cMAGs from PacBio HiFi sequencing of a wastewater sample, we demonstrated the utility of VicMAG for metagenome visualization. VicMAG provides comprehensive, size-aware visualization of cMAGs representing bacterial chromosomes and plasmids, annotated with VFGs, ARGs, and phages. By simultaneously visualizing all cMAGs in a framework, VicMAG facilitates a holistic understanding of the distribution and genomic context of VFGs and ARGs across complex microbial communities. This tool supports integrated surveillance of bacteria associated with virulence and antimicrobial resistance across clinical, environmental, and One Health contexts.

Metagenome↗

PubMed2006

Flow sandwich-type immunoassay in microfluidic devices based on negative dielectrophoresis.

Microparticles have been manipulated in a microfluidic channel by means of negative dielectrophoresis (n-DEP), and the approach applied to a heterogeneous immunoassay system. A microfluidic device, with three-dimensional (3-D) microelectrodes fabricated on two substrates, was used to manipulate particle flow in the channel and to capture the particles in the caged area that was enclosed by the collector electrodes. Polystyrene microparticles (6 microm diameters) modified with anti-mouse immunoglobulin G (IgG) were manipulated and captured in the caged area when surrounded by intense n-DEP electric fields. Specifically, particles were trapped when AC voltages with amplitudes of 6-15 V(peak) and frequencies over 500 kHz were applied to the two facing microelectrodes. A heterogeneous sandwich immunoassay was achieved by successively injecting a sample solution containing mouse antigen (IgG), and a solution containing a secondary antibody with a signal source (FITC-labeled anti-mouse IgG antibody), into the channel. The fluorescence intensity from captured particles in the caged area increased with increasing concentrations (10 ng/ml to 10 microg/ml) of mouse IgG. The described system enables mouse IgG to be assayed in 40 min. Thus, the automatic separation of free fractions from desired analytes and labeled antibodies can be achieved using a microfluidic device based on n-DEP.

Biosensing Techniques↗

PubMed2006

Shigella IpgB1 promotes bacterial entry through the ELMO-Dock180 machinery.

Shigella use a special mechanism to invade epithelial cells called 'the trigger mechanism of entry', which allows epithelial cells to trap several bacteria simultaneously. On contact, Shigella deliver effectors into epithelial cells through the type III secretion system. Here, we show that one of the effectors, IpgB1, has a pivotal role in producing membrane ruffles by exploiting the RhoG-ELMO-Dock180 pathway to stimulate Rac1 activity. Using pulldown assays, we identified engulfment and cell motility (ELMO) protein as the IpgB1 binding partner. IpgB1 colocalized with ELMO and Dock180 in membrane ruffles induced by Shigella. Shigella invasiveness and IpgB1-induced ruffles were less in ELMO- and Dock180-knockdown cells compared with wild-type cells. Membrane association of ELMO-Dock180 with ruffles were promoted when cells expressed an IpgB1-ELMO chimera, establishing that IpgB1 mimics the role of RhoG in producing membrane ruffles. Taken together, our findings show that IpgB1 mimicry is the key to invasion by Shigella.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Adeno-associated virus site-specific integration is regulated by TRP-185.

Adeno-associated virus (AAV) integrates site specifically into the AAVS1 locus on human chromosome 19. Although recruitment of the AAV nonstructural protein Rep78/68 to the Rep binding site (RBS) on AAVS1 is thought to be an essential step, the mechanism of the site-specific integration, particularly, how the site of integration is determined, remains largely unknown. Here we describe the identification and characterization of a new cellular regulator of AAV site-specific integration. TAR RNA loop binding protein 185 (TRP-185), previously reported to associate with human immunodeficiency virus type 1 TAR RNA, binds to AAVS1 DNA. Our data suggest that TRP-185 suppresses AAV integration at the AAVS1 RBS and enhances AAV integration into a region downstream of the RBS. TRP-185 bound to Rep68 directly, changing the Rep68 DNA binding property and stimulating Rep68 helicase activity. We present a model in which TRP-185 changes the specificity of the AAV integration site from the RBS to a downstream region by acting as a molecular chaperone that promotes Rep68 complex formation competent for 3'-->5' DNA helicase activity.

Binding Sites↗

PubMed2006

Microtubule-severing activity of Shigella is pivotal for intercellular spreading.

Some pathogenic bacteria actually invade the cytoplasm of their target host cells. Invasive bacteria acquire the propulsive force to move by recruiting actin and inducing its polymerization. Here we show that Shigella movement within the cytoplasm was severely hindered by microtubules and that the bacteria destroyed surrounding microtubules by secreting VirA by means of the type III secretion system. Degradation of microtubules by VirA was dependent on its alpha-tubulin-specific cysteine protease-like activity. virA mutants did not move within the host cytoplasm and failed to move into adjacent cells.

Actins↗

PubMed2006

Adiponectin is regulated differently by chronic exercise than by weight-matched food restriction in hyperphagic and obese OLETF rats.

This study was intended to investigate the effects of chronic exercise on blood adiponectin level. Male Otsuka Long Evans Tokushima Fatty (OLETF) rats (26 weeks old) were divided to undergo either regular 12-week wheel running exercise (EX) or to have food restriction (FR) that resulted in body weight reduction similar to that in EX. Both EX and FR induced similar reductions in body weight, abdominal fat volume and plasma leptin concentration compared with ad libitum control. At the end of the study, although plasma adiponectin level was increased in FR, the adiponectin level did not change in EX. Plasma testosterone level was higher in EX than in either of the other two groups. A significant inverse relationship existed between plasma levels of adiponectin and testosterone for all groups. Our results suggested that 12-week voluntary wheel running exercise induces different effects on plasma adiponectin level than does food restriction, despite similar reduction in body weight, fat tissue mass and plasma leptin concentration. We speculate that the elevated plasma testosterone concentration might offset any hyperadiponectinemic effect of body weight and fat volume reduction in exercising rats.

Adipocytes↗

PubMed2006

Tamoxifen and the risk of endometrial cancer in Japanese women with breast cancer.

PURPOSE: There is ongoing debate about whether tamoxifen for breast cancer is associated with a risk of endometrial cancer in Japanese women. We conducted a study to investigate this further. METHODS: We conducted a retrospective hospital-based cohort study. A total of 674 consecutive patients underwent surgery for primary breast cancer between January 1989 and December 1998. By December 2003, endometrial cancers had been diagnosed in six of these patients. Based on medical records, we evaluated the potential risk factors for endometrial cancer, including age, menopausal status, obesity, parity, diabetes mellitus, hypertension, and tamoxifen. The 674 patients were divided into three groups based on the cumulative duration of tamoxifen use (A, <2 years vs B, 2-5 years vs C, >5 years). To examine the relationships between endometrial cancer and tamoxifen (and other factors), the hazards ratio (HR), 95% confidence interval (CI), and two-sided P value for endometrial cancer associated with each variable were calculated by the Cox regression method. RESULTS: Endometrial cancer was found in 1/318 (0.31%) patients in group A, 3/247 in group B, and 2/109 in group C. In a multivariate analysis no variable was significant, but tamoxifen use for longer than 5 years (group C) was closely correlated with endometrial cancer (HR = 7.92, CI = 0.69-90.89, P = 0.096). CONCLUSION: Although our data did not reach significance, they support a link between long-term tamoxifen and the development of endometrial cancer in Japanese women with breast cancer.

Aged↗

PubMed2006

Aortic valve myxoma mimicking vegetation: report of a case.

We report a case of cardiac myxoma of the aortic valve. To our knowledge, this represents only the seventh such case ever documented. A 61-year-old woman underwent an echocardiography to screen for hypertensive-diabetic cardiac complications, which showed a mass on her aortic valve. Although she had not experienced a fever, the mass closely resembled a vegetation, resulting in an initial diagnosis of infective endocarditis. We extirpated the mass and repaired the aortic valve with the patient under cardiopulmonary bypass. The postoperative course was uneventful. Histological examination confirmed that the mass was a myxoma.

Aortic Valve↗

PubMed2006

Initial clinical experience with the Heartstring.

OBJECTIVE: The Heartstring is one of the devices that enable proximal anastomosis without clamping the aorta. We have applied the device not only to low-risk patients with normal aortas but also to high-risk patients with diseased aortas. The purpose of this study was to investigate the initial outcomes of using this device. METHODS: The Heartstring was used on 87 patients between January and December 2004. The patients comprised 62 men and 25 women 48-86 years old (mean 68.4 +/- 8.4 years). The ascending aorta was evaluated by computed tomography (CT) scanning before surgery. If a patient's aorta was severely calcified, epiaortic echocardiography was performed. The aortas were ranked into four grades, and the preoperative patient's status were evaluated by the EuroSCORE. Angiography was performed on the third postoperative day. RESULTS: CT scanning revealed that 74 patients had no calcification in the ascending aorta, 10 patients had scattered calcification, and 3 patients had plate-like calcification. The EuroSCORE was 6.86 +/- 1.03. We performed 93 proximal anastomoses and 149 distal anastomoses. The average distal anastomosis was 1.6 +/- 0.6 sites per graft. Of the distal anastomoses, 74.2% were to the circumflex artery territory. Postoperative coronary angiography revealed that all grafts were patent. CONCLUSION: The Heartstring facilitates safe proximal anastomosis, even in high-risk patients. Their short-term outcome was good. The device assists in bypassing circumflex artery territory. Long-term follow-up is necessary.

Aged↗

PubMed2006

Two cases of adenoid cystic carcinoma: preoperative cytological findings were useful in determining treatment strategy.

Adenoid cystic carcinoma (ACC) of the breast is a rare variant of breast malignancy and is known to have an excellent prognosis. We report two cases of ACC diagnosed by preoperative fine-needle aspiration cytology (FNAC), which proved to be very useful in determining the appropriate treatment. The patients were a 57-year-old woman (case 1) and a 71-year-old woman (case 2). On physical examinations and imaging studies both tumors were recognized as lobulated tumors that measured 3.0 x 2.3 cm (case 1) and 3.9 x 3.4 cm (case 2) respectively. FNAC materials showed clusters of malignant cells surrounding globules of mucus, therefore, ACC was diagnosed. Considering the characteristics of ACC, breast-conserving surgeries with axillary dissection and adjuvant radiotherapy were performed instead of primary chemotherapy or mastectomy. Histologically, a distinctive biphasic pattern was observed that consisted of true laminae and pseudocystic spaces. Tumor sizes were 4.0 x 3.3 cm (case 1) and 4.6 x 3.8 cm (case 2), respectively, and surgical margins were negative on microscopic examination. Lymph node metastasis was not present in either case. Even though ACC is very rare, preoperative diagnosis can be made based on its characteristic features. Preoperative diagnosis is extremely useful for determining appropriate treatment.

Aged↗

PubMed2006

Role of protein kinase C in eosinophil function.

Protein kinase C (PKC) isoforms are being elucidated as an increasingly diverse family of enzymes involved in the downstream signal transduction and cell function in various types of cells. To date, 11 PKC isoforms have been identified; they are grouped according to their molecular structure and mode of activation: conventional PKCs (alpha, beta I, beta II, and gamma), novel PKCs (delta, epsilon, mu, theta, and eta), and atypical PKCs (zeta, and iota/lambda). Eosinophils are involved in the pathogenesis of allergic diseases such as bronchial asthma, pollinosis, and atopic dermatitis as well as in the inflammatory response to parasitic infections. Recent studies using selective activators and inhibitors of individual PKC isoforms have revealed that this enzyme is involved in eosinophil dynamics such as cell motility and other functions. However, the role of PKCs in eosinophil functions has been not wholly understood. In this review, we have focused upon and summarized the current knowledge regarding the role of PKC isoforms in eosinophil functions.

Animals↗

PubMed2005

Interaction of CagA with Crk plays an important role in Helicobacter pylori-induced loss of gastric epithelial cell adhesion.

CagA protein is a major virulence factor of Helicobacter pylori, which is delivered into gastric epithelial cells and elicits growth factor-like responses. Once within the cells, CagA is tyrosine phosphorylated by Src family kinases and targets host proteins required to induce the cell responses. We show that the phosphorylated CagA binds Crk adaptor proteins (Crk-II, Crk-I, and Crk-L) and that the interaction is important for the CagA-mediated host responses during H. pylori infection. H. pylori-induced scattering of gastric epithelial cells in culture was blocked by overexpression of dominant-negative Crk and by RNA interference-mediated knockdown of endogenous Crk. H. pylori infection of the gastric epithelium induced disruption of E-cadherin/catenin-containing adherens junctions, which was also dependent on CagA/Crk signaling. Furthermore, inhibition of the SoS1/H-Ras/Raf1, C3G/Rap1/B-Raf, or Dock180/Rac1/Wiskott-Aldrich syndrome protein family verprolin homologous protein pathway, all of which are involved downstream of Crk adaptors, greatly diminished the CagA-associated host responses. Thus, CagA targeting of Crk plays a central role in inducing the pleiotropic cell responses to H. pylori infection that cause several gastric diseases, including gastric cancer.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Photoreactions between [60]fullerene and various aromatic tertiary amines.

The photoreactions of [60]fullerene with aromatic tertiary amines such as N,N-dimethylaniline and N,N-dimethyl-1-naphthylamine gave two or three types of [60]fullerene adducts. The reaction efficiency in the series of p-substituted N,N-dimethylanilines remarkably increased with increasing electron-donating properties of aromatic tertiary amines employed.

Journal Article↗

PubMed2005

Suppression of cell proliferation by inhibition of estrone-3-sulfate transporter in estrogen-dependent breast cancer cells.

PURPOSE: The aim of the study is to suppress the progress of estrogen-dependent breast cancer by inhibiting the membrane transporter, which mediates the internalization of estrone-3-sulfate as estrogen precursor in the cancer cells. METHODS: The uptake of estrone-3-sulfate by estrogen-dependent breast cancer MCF-7 cells was measured, and inhibitory study using various organic anions on estrone-3-sulfate uptake by MCF-7 cells was conducted. The effects of the inhibitor on the transcription of reporter gene and cell proliferation induced by estrone-3-sulfate were examined. RESULTS: The uptake of estrone-3-sulfate by MCF-7 cells was saturable with Km value of 2.32 microM. The uptake was Na+-independent and was inhibited by several anionic compounds such as bromosulfophthalein. Bromosulfophthalein also significantly inhibited the transcription of reporter gene via estrogen response element and cell proliferation induced by estrone-3-sulfate. However, the transcriptional activation or cell proliferation induced by estrone was not inhibited by bromosulfophthalein. Reverse transcription-polymerase chain reaction analysis revealed the expression of mRNA of organic anion transporting polypeptide (OATP)-D and OATP-E as possible candidates to transport estrone-3-sulfate. CONCLUSIONS: The uptake of estrone-3-sulfate is mediated by Na+-independent transporter(s). Inhibitor of estrone-3-sulfate transporter suppressed the transcription and cell proliferation induced by estrone-3-sulfate in MCF-7 cells. The results provide the basis of a novel strategy for breast cancer treatment by focusing on the transporter responsible for the uptake of estrone-3-sulfate.

Alkaline Phosphatase↗

PubMed2005

Catalytic enantioselective synthesis of key intermediates for triazole antifungal agents.

[reaction: see text] A short-step synthesis of versatile chiral building blocks for triazole antifungal agents such as ZD0870 and Sch45450 was developed via catalytic enantioselective cyanosilylation of electron-deficient ketones as the key step. High enantioselectivity was produced using a catalyst prepared from Gd(HMDS)(3) and ligand 5 in a 2:3 ratio. This new catalyst preparation method was superior to the previous method using Gd(O(i)Pr)(3) as a metal source. A rationale for the difference is proposed on the basis of structural studies of the catalyst complexes using ESI-MS.

Antifungal Agents↗

PubMed2005

IpgB1 is a novel Shigella effector protein involved in bacterial invasion of host cells. Its activity to promote membrane ruffling via Rac1 and Cdc42 activation.

Shigella, the causative agent of bacillary dysentery, is capable of inducing the large scale membrane ruffling required for the bacterial invasion of host cells. Shigella secrete a subset of effectors via the type III secretion system (TTSS) into the host cells to induce membrane ruffling. Here, we show that IpgB1 is secreted via the TTSS into epithelial cells and plays a major role in producing membrane ruffles via stimulation of Rac1 and Cdc42 activities, thus promoting bacterial invasion of epithelial cells. The invasiveness of the ipgB1 mutant was decreased to less than 50% of the wild-type level (100%) in a gentamicin protection or plaque forming assay. HeLa cells infected with the wild-type or a IpgB1-hyperproducing strain developed membrane ruffles, with the invasiveness and the scale of membrane ruffles being comparable with the level of IpgB1 production in bacteria. Upon expression of EGFP-IpgB1 in HeLa cells, large membrane ruffles are extended, where the EGFP-IpgB1 was predominantly associated with the cytoplasmic membrane. The IpgB1-mediated formation of ruffles was significantly diminished by expressing Rac1 small interfering RNA and Cdc42 small interfering RNA or by treatment with GGTI-298, an inhibitor of the geranylgeranylation of Rho GTPases. When IpgB1 was expressed in host cells or wild-type Shigella-infected host cells, Rac1 and Cdc42 were activated. The results thus indicate that IpgB1 is a novel Shigella effector involved in bacterial invasion of epithelial cells via the activation of Rho GTPases.

Alkyl and Aryl Transferases↗

PubMed2005

Powder-to-powder polycondensation of natural saccharides. Facile preparation of highly branched polysaccharides.

Solid-state polycondensation of a natural saccharide was found to take place in the presence of H3PO4(5 mol%) at 110 degrees C under a N2 flow, giving a highly branched polysaccharide (conv. 11-84%, Mw = 1400-19000, Mn = 1200-3700); the reaction mixture was powdery throughout the polymerization. Interestingly, alpha- and beta-anomers showed different polymerization behaviour; the former was polymerized more slowly, however, they gave comparable molecular weight polymers. The polysaccharide product was per-O-methylated and subjected to structure analyses. The acid-hydrolysis products, the partially O-methylated monosaccharides, suggested that the polysaccharide products have highly branched structures. MALDI-TOF mass analysis revealed that intramolecular glycosylation and acetal exchange reactions are involved in the polymerization mechanism.

Biopolymers↗

PubMed2005

Dynamics of unidirectional exciton migration to the molecular periphery in a photoexcited compact dendrimer.

We have studied dynamical natures of electronic excited states in a compact series of phenylacetylene dendrimers. So as to clarify the mechanism of unidirectional migration of a photogenerated exciton in a compact dendrimer, we theoretically investigated the temporal behavior of the photogenerated exciton in the molecule by numerically solving the time-dependent Schrodinger equation for the electronic excited states. The structure of the dendrimers is optimized in the ground state, and it is fixed during the calculation of the exciton dynamics. The calculated results show that the exciton generated in the dendrimeric framework tends to migrate toward the outside of the molecule rather than the inside, and to itinerate around the periphery via the through-space interaction between the outer crowding benzene units. This is one of the intrinsic properties that originates from a highly branched treelike structure of the compact dendrimers.

Journal Article↗