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Biomedical subjects

Kenichi Suzuki

Publications and source records attributed to Kenichi Suzuki.

At least 19 recordsLinked to original sources
PubMed2007

Case of carcinosarcoma of urinary bladder obtained a pathologically complete response by neoadjuvant chemoradiotherapy.

Carcinosarcoma of the bladder is an unusual malignancy characterized by an intimate admixture of malignant epithelial elements (carcinoma) and malignant soft tissue elements (sarcoma). To our knowledge, almost 80 cases have been reported, usually as case reports or small series. Patient with carcinosarcoma usually present with a high stage malignancy. Cystectomy or transurethral resection is the preferred treatment, often followed by radiation therapy, although prognosis is very bad. We herein report a case of carcinosarcoma of bladder obtained pathologically complete response by neoadjuvant chemoradiotherapy. She now shows no evidence of disease 30 months after the operation. To our knowledge, it is the first case where urinary bladder carcinosarcoma obtained a pathologically complete response by chemoradiotherapy.

Antineoplastic Agents↗
PubMed2006

Microelastic mapping of living endothelial cells exposed to shear stress in relation to three-dimensional distribution of actin filaments.

The surface topography and local elastic moduli of endothelial cells exposed to shear stress were measured using atomic force microscopy. Bovine aortic endothelial cells were exposed to shear stress of 2Pa for 6, 12 or 24h. In addition, a confocal laser-scanning microscope used in conjunction with the atomic force microscope was used to observe the actin filament structure of these endothelial cells to elucidate the relationship between mechanical properties and cytoskeletal structure. The elastic modulus, calculated using the Hertz model, was measured at 50x50 points at 1mum intervals within 40min. For endothelial cells sheared for 6h and 12h, the elastic modulus at the upstream region was found to be higher than that at the downstream region. For endothelial cells sheared for 24h, the elastic modulus at both the upstream and downstream regions increased. Fluorescent images showed thick, elongated actin filaments oriented in the direction of flow at the ventral surface of the cells. In the middle plane of the cells, actin filaments developed around the nucleus, while in the upper plane, short, thick actin filaments were observed but thick stress fibers were not present. The high elastic modulus came from the stress fibers. These results indicate that the higher elastic modulus observed in the upstream and downstream regions of sheared endothelial cells is mainly due to the development of stress fibers at the ventral surface and middle plane of the cell.

Actin Cytoskeleton↗
PubMed2006

Shh/BMP-4 signaling pathway is essential for intestinal epithelial development during Xenopus larval-to-adult remodeling.

During amphibian larval-to-adult intestinal remodeling, progenitor cells of the adult epithelium actively proliferate and differentiate under the control of thyroid hormone (TH) to form the intestinal absorptive epithelium, which is analogous to the mammalian counterpart. We previously found that TH-up-regulated expression of bone morphogenetic protein-4 (BMP-4) spatiotemporally correlates with adult epithelial development in the Xenopus laevis intestine. Here, we aimed to clarify the role of BMP-4 in intestinal remodeling. Our reverse transcriptase-polymerase chain reaction and in situ hybridization analyses indicated that mRNA of BMPR-IA, a type I receptor of BMP-4, is expressed in both the developing connective tissue and progenitor cells of the adult epithelium. More importantly, using organ culture and immunohistochemical procedures, we have shown that BMP-4 not only represses cell proliferation of the connective tissue but promotes differentiation of the intestinal absorptive epithelium. In addition, we found that the connective tissue-specific expression of BMP-4 mRNA is up-regulated by sonic hedgehog (Shh), whose epithelium-specific expression is directly induced by TH. These results strongly suggest that the Shh/BMP-4 signaling pathway plays key roles in the amphibian intestinal remodeling through epithelial-connective tissue interactions.

Animals↗
PubMed2005

Toward understanding the dynamics of membrane-raft-based molecular interactions.

The cell membrane is a 2-dimensional non-ideal liquid containing dynamic structures on various time-space scales, and the raft domain is one of them. Existing literature supports the concept that raft dynamics may be important for its formation and function: the raft function may be supported by stimulation-induced raft association/coalescence and recruitment of various raftophilic molecules to coalesced rafts, and, importantly, they both may happen transiently. Thus, one must always consider the limited association time of a raft or a raftophilic molecule with another raft, even when one interprets the results of static experiments, such as immunofluorescence and pull-down assays. Critical considerations on the chemical fixation mechanism and immunocolocalization data suggest that the temporary nature of raft-based molecular interactions may explain why colocalization results are sensitive to subtle variations in experimental conditions employed in different laboratories.

Animals↗
PubMed2005

Rapid hop diffusion of a G-protein-coupled receptor in the plasma membrane as revealed by single-molecule techniques.

Diffusion of a G-protein coupled receptor, mu-opioid receptor (muOR), in the plasma membrane was tracked by single-fluorescent molecule video imaging and high-speed single-particle tracking. At variance with a previous publication, where gold-tagged muOR was found to be totally confined within a domain, which in turn underwent very slow diffusion itself, we found that muOR undergoes rapid hop diffusion over membrane compartments (210-nm and 730-nm nested double compartments in the case of normal rat kidney cell line), which are likely delimited by the actin-based membrane-skeleton "fence or corrals" and its associated transmembrane protein "pickets", at a rate comparable to that for transferrin receptor (every 45 and 760 ms on average, respectively), suggesting that the fence and picket models may also be applicable to G-protein coupled receptors. Further, we found that strong confinement of gold-labeled muOR could be induced by the prolonged on-ice preincubation of the gold probe with the cells, showing that this procedure should be avoided in future single-particle tracking experiments. Based on the dense, long trajectories of muOR obtained by high-speed single-particle tracking, the membrane compartments apposed and adjoined to each other could be defined that are delimited by rather straight boundaries, consistent with the involvement of actin filaments in membrane compartmentalization.

Actins↗
PubMed2005

Paradigm shift of the plasma membrane concept from the two-dimensional continuum fluid to the partitioned fluid: high-speed single-molecule tracking of membrane molecules.

Recent advancements in single-molecule tracking methods with nanometer-level precision now allow researchers to observe the movement, recruitment, and activation of single molecules in the plasma membrane in living cells. In particular, on the basis of the observations by high-speed single-particle tracking at a frame rate of 40,000 frames s(1), the partitioning of the fluid plasma membrane into submicron compartments throughout the cell membrane and the hop diffusion of virtually all the molecules have been proposed. This could explain why the diffusion coefficients in the plasma membrane are considerably smaller than those in artificial membranes, and why the diffusion coefficient is reduced upon molecular complex formation (oligomerization-induced trapping). In this review, we first describe the high-speed single-molecule tracking methods, and then we critically review a new model of a partitioned fluid plasma membrane and the involvement of the actin-based membrane-skeleton "fences" and anchored-transmembrane protein "pickets" in the formation of compartment boundaries.

Actins↗
PubMed2004

Flower color modulations of Torenia hybrida by downregulation of chalcone synthase genes with RNA interference.

Suppression of biosynthetic genes involved in flower color formation is an important approach for obtaining target flower colors. Here we report that flower color of the garden plant Torenia hybrida was successfully modulated by RNA interference (RNAi) against a gene of chalcone synthase (CHS), a key enzyme for anthocyanin and flavonoid biosynthesis. By using each of the coding region and the 3'-untranslated region of the CHS mRNA as an RNAi target, exhaustive and gene-specific gene silencing were successfully induced, and the original blue flower color was modulated to white and pale colors, respectively. Our results indicate that RNAi is quite useful for modulations of flower colors of commercially important garden plants.

Acyltransferases↗
PubMed2004

Risk factors in past histories and familial episodes related to development of testicular germ cell tumor.

BACKGROUND: A retrospective study was conducted to examine the host factors of 240 testicular germ cell tumor patients. This study was performed to address a new theory proposed by Skakkebaek called testicular dysgenesis syndrome which claims that cryptorchism, hypospadias, poor semen quality and testicular germ cell tumors are symptoms of an underlying testicular dysgenesis in uterus. METHODS: The past health histories and familial episodes of 240 testicular germ cell tumor patients were examined. The past health histories included cryptorchism, hypospadias, infertility, atrophic testis and inguinal hernia. RESULTS: Of the 240 patients, 13 (5.4%) had a history of cryptorchism or orchidopexy. Two (0.8%) showed existence of hypospadias or had experienced urethroplasty. Among 129 married couples, 104 (80.6%) couples were fertile. Three (1.3%) patients developed testicular tumors after they were diagnosed as infertile or came to the hospital with the complaints of infertility. Four (1.7%) had contralateral atrophic testis. 19 (7.9%) had experienced inguinal herniorrhaphy before age 15. Three (1.3%) had testicular germ cell tumor patients among their family or relatives. CONCLUSIONS: The testicular germ cell tumor patients showed a considerable incidence of complications such as cryptorchism, hypospadias and incomplete closure of processus vaginalis. Cryptorchism, perinatal factors and familial factors could be risks for developing testicular germ cell tumors.

Adolescent↗
PubMed2004

Molecular dynamics and interactions for creation of stimulation-induced stabilized rafts from small unstable steady-state rafts.

We have evaluated the sizes and lifetimes of rafts in the plasma membrane from the existing literature, with a special attention paid to their intrinsically broad distributions and the limited time and space scales that are covered by the observation methods used for these studies. Distinguishing the rafts in the steady state (reserve rafts) from those after stimulation or unintentional crosslinking of raft molecules (stabilized receptor-cluster rafts) is critically important. In resting cells, the rafts appear small and unstable, and the consensus now is that their sizes are smaller than the optical diffraction limit (250 nm). Upon stimulation, the raft-preferring receptors are clustered, inducing larger, stabilized rafts, probably by coalescing small, unstable rafts or cholesterol-glycosphingolipid complexes in the receptor clusters. This receptor-cluster-induced conversion of raft types may be caused by suppression of alkyl chain isomerization and the lipid lateral diffusion in the cluster, with the aid of exclusion of cholesterol from the bulk domain and the boundary region of the majority of transmembrane proteins. We critically inspected the possible analogy to the boundary lipid concept. Finally, we propose a hypothesis for the coupling of GPI-anchored receptor signals with lipid-anchored signaling molecules in the inner-leaflet raft.

Animals↗
PubMed2004

Ultrafine membrane compartments for molecular diffusion as revealed by single molecule techniques.

Plasma membrane compartments, delimited by transmembrane proteins anchored to the membrane skeleton (anchored-protein picket model), would provide the membrane with fundamental mosaicism because they would affect the movement of practically all molecules incorporated in the cell membrane. Understanding such basic compartmentalized structures of the cell membrane is critical for further studies of a variety of membrane functions. Here, using both high temporal-resolution single particle tracking and single fluorescent molecule video imaging of an unsaturated phospholipid, DOPE, we found that plasma membrane compartments generally exist in various cell types, including CHO, HEPA-OVA, PtK2, FRSK, HEK293, HeLa, T24 (ECV304), and NRK cells. The compartment size varies from 30 to 230 nm, whereas the average hop rate of DOPE crossing the boundaries between two adjacent compartments ranges between 1 and 17 ms. The probability of passing a compartment barrier when DOPE is already at the boundary is also cell-type dependent, with an overall variation by a factor of approximately 7. These results strongly indicate the necessity for the paradigm shift of the concept on the plasma membrane: from the two-dimensional fluid continuum model to the compartmentalized membrane model in which its constituent molecules undergo hop diffusion over the compartments.

Animals↗
PubMed2004

YM-215343, a novel antifungal compound from Phoma sp. QN04621.

Through our screening for novel antifungal compounds, YM-215343 was found in the culture extract of Phoma sp. QN04621. The structure of YM-215343 was determined by several spectroscopic experiments as a novel compound closely related to apiosporamide and fischerin. YM-215343 exhibited antifungal activity against the pathogenic fungi, Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus with MIC values of 2 to approximately 16 microg/ml. It also showed cytotoxicity against HeLa S3 cells with an IC50 of 3.4 microg/ml.

Antifungal Agents↗
PubMed2004

YM-193221, a novel antifungal antibiotic produced by Pseudallescheria ellipsoidea.

A novel antifungal antibiotic, YM-193221, was found in the culture broth of a fungus, Pseudallescheria ellipsoidea. The structure of the antibiotic was determined through several spectroscopic experiments as 2-dimethylamino-1-(4-hydroxyphenyl)-8,10-dimethyl-6-dodecene-3-one. YM-193221 exhibited potent antifungal activity against Candida albicans and also inhibited mannan synthesis in the yeast cell wall.

Antifungal Agents↗
PubMed2003

Actin reorganization and morphological changes in human neutrophils stimulated by TNF, GM-CSF, and G-CSF: the role of MAP kinases.

Stimulation of human neutrophils with tumor necrosis factor-alpha (TNF), granulocyte-macrophage colony-stimulating factor (GM-CSF), or granulocyte CSF (G-CSF) resulted in decreased fluorescence intensity of FITC-phalloidin (actin depolymerization) and morphological changes. Cytokine-induced actin depolymerization was dependent on the concentration of cytokines used as stimuli. The maximal changes were detected at 10 min after stimulation with TNF or GM-CSF and at 20 min after stimulation with G-CSF. Cytokine-induced actin depolymerization was sustained for at least 30 min after stimulation. In contrast, N-formyl-methionyl-leucyl-phenylalanine (FMLP) rapidly (within 45 s) induced an increase in the fluorescence intensity of FITC-phalloidin (actin polymerization) and morphological changes. TNF- and GM-CSF-induced actin depolymerization and morphological changes, but not FMLP-induced responses, were partially inhibited by either PD-98059, an inhibitor of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase, or SB-203580, an inhibitor of p38 MAPK, and were almost completely abolished by these inhibitors in combination. G-CSF-induced responses were almost completely abolished by PD-98059 and were unaffected by SB-203580. These findings are consistent with the ability of these cytokines to activate the distinct MAPK subtype cascade in human neutrophils. Phosphorylated ERK and p38 MAPK were not colocalized with F-actin in neutrophils stimulated by cytokines or FMLP. Furthermore, FMLP-induced polarization and actin polymerization were prevented by cytokine pretreatment. These findings suggest that TNF, GM-CSF, and G-CSF induce actin depolymerization and morphological changes through activation of ERK and/or p38 MAPK and that cytokine-induced actin reorganization may be partly responsible for the inhibitory effect of these cytokines on neutrophil chemotaxis.

Actin Depolymerizing Factors↗