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Biomedical subjects

Akira Nagasaki

Publications and source records attributed to Akira Nagasaki.

14 recordsLinked to original sources
PubMed2006

Clinical characteristics and outcome of Wilms tumors with a favorable histology in Japan: a report from the Study Group for Pediatric Solid Malignant Tumors in the Kyushu Area, Japan.

BACKGROUND/PURPOSE: Since 1996, the standard treatment of Wilms tumors in Japan has been based on the regimen of the Japanese Wilms Tumor Study. However, in Japan, there have been no reports about Wilms tumors that analyzed the clinical features and patient outcome in a large series until now. This study aims to assess the clinical characteristics of patients with Wilms tumor with a favorable histology from a retrospective standpoint in the Kyushu area in Japan and, furthermore, to analyze the historical changes of clinical features and outcome from the 1980s to the 1990s. METHODS: Between 1982 and 1996, 90 cases of Wilms tumors with a favorable histology were registered in the Kyushu area. Regarding the clinical feature and outcome, they were divided into 2 groups (group A, 1982-1989, n = 50; group B, 1990-1996, n = 40). The outcome was analyzed based on the 5-year overall survival rate. RESULTS: The clinical features (age, sex, initial symptom, location, stage) demonstrated no definite differences between group A and group B. Regarding the operation, the rate of an initial complete resection in the early stages was significantly higher in group B than in group A. All stage V cases in group B undewent a bilateral tumor biopsy instead of a radical nephrectomy as the initial operation. The 5-year overall survival rate throughout the whole period was 87.8%, whereas the rates were 84.0% for group A and 90.0% for group B (P = NS), respectively. Of particular note, the outcome of patients with stage I and stage V in group B substantially improved in comparison to that in group A. However, in advanced cases, no significant improvement in the outcome was noted. CONCLUSIONS: This is the first report about the clinical features and outcome for Wilms tumors with a favorable histology in Japan from the 1980s to the 1990s. The present study suggested that in the early-stage cases, an initially complete resection followed by standard postoperative chemotherapy substantially improved the outcome of the patients in group B. In the stage V cases, the performance of renal salvage surgery may have positively contributed to the improvement in the outcome in group B. However, in the advanced stage cases, no definite improvement was noted. In the future, an improved efficacy of the treatments for Wilms tumors based on the standard protocol established by the Japanese Wilms Tumor Study in 1996 is expected in Japan.

Child, Preschool↗
PubMed2005

Multiple myosin II heavy chain kinases: roles in filament assembly control and proper cytokinesis in Dictyostelium.

Myosin II filament assembly in Dictyostelium discoideum is regulated via phosphorylation of residues located in the carboxyl-terminal portion of the myosin II heavy chain (MHC) tail. A series of novel protein kinases in this system are capable of phosphorylating these residues in vitro, driving filament disassembly. Previous studies have demonstrated that at least three of these kinases (MHCK A, MHCK B, and MHCK C) display differential localization patterns in living cells. We have created a collection of single, double, and triple gene knockout cell lines for this family of kinases. Analysis of these lines reveals that three MHC kinases appear to represent the majority of cellular activity capable of driving myosin II filament disassembly, and reveals that cytokinesis defects increase with the number of kinases disrupted. Using biochemical fractionation of cytoskeletons and in vivo measurements via fluorescence recovery after photobleaching (FRAP), we find that myosin II overassembly increases incrementally in the mutants, with the MHCK A(-)/B(-)/C(-) triple mutant showing severe myosin II overassembly. These studies suggest that the full complement of MHC kinases that significantly contribute to growth phase and cytokinesis myosin II disassembly in this organism has now been identified.

Animals↗
PubMed2005

Adhesion-dependent and contractile ring-independent equatorial furrowing during cytokinesis in mammalian cells.

Myosin II-dependent contraction of the contractile ring drives equatorial furrowing during cytokinesis in animal cells. Nonetheless, myosin II-null cells of the cellular slime mold Dictyostelium divide efficiently when adhering to substrates by making use of polar traction forces. Here, we show that in the presence of 30 microM blebbistatin, a potent myosin II inhibitor, normal rat kidney (NRK) cells adhering to fibronectin-coated surfaces formed equatorial furrows and divided in a manner strikingly similar to myosin II-null Dictyostelium cells. Such blebbistatin-resistant cytokinesis was absent in partially detached NRK cells and was disrupted in adherent cells if the advance of their polar lamellipodia was disturbed by neighboring cells. Y-27632 (40 microM), which inhibits Rho-kinase, was similar to 30 microM blebbistatin in that it inhibited cytokinesis of partially detached NRK cells but only prolonged furrow ingression in attached cells. In the presence of 100 microM blebbistatin, most NRK cells that initiated anaphase formed tight furrows, although scission never occurred. Adherent HT1080 fibrosarcoma cells also formed equatorial furrows efficiently in the presence of 100 microM blebbistatin. These results provide direct evidence for adhesion-dependent, contractile ring-independent equatorial furrowing in mammalian cells and demonstrate the importance of substrate adhesion for cytokinesis.

Amides↗
PubMed2004

Keratocyte-like locomotion in amiB-null Dictyostelium cells.

Starved Dictyostelium amoebae continuously change their shape and they are elongated along the front-rear axis during locomotion. In contrast, we found that disruption of the amiB gene, which had been identified as a gene required for the aggregation process during development, caused these cells to move in a manner similar to fish keratocytes. Starved amiB- cells were elongated laterally and had one large lamellipodium along the front side arc of the cell. These cells moved unidirectionally for long distances maintaining the half-moon shape, and this movement followed the predictions of the graded radial extension model, which was originally developed to describe the keratocyte movements. Furthermore, the distributions of actin, Arp2, and myosin II in amiB- cells were similar to those in keratocytes. Therefore, locomotion by keratocytes and amiB- cells appears to be driven by similar mechanisms of cytoskeletal regulation. Double knockout cells lacking both AmiB and myosin II were still able to move unidirectionally in a keratocyte-like manner, although the frequency of those movements was lower. Thus, myosin II is dispensable for the unidirectional movement, though it likely functions in the maintenance of the characteristic half-moon shape. This mutant cell can be a useful tool for further molecular genetic analysis of the mechanism of cell locomotion.

Animals↗
PubMed2004

Variations on a theme: the many modes of cytokinesis.

Animal cell division is believed to be mediated primarily by the 'purse-string' mechanism, which entails furrowing of the equatorial region, driven by the interaction of actin and myosin II filaments within contractile rings. However, myosin II-null Dictyostelium cells on substrates divide efficiently in a cell cycle-coupled manner. This process, termed cytokinesis B, appears to be driven by polar traction forces. Data in the literature can be interpreted as suggesting that adherent higher animal cells also use a cytokinesis B-like mechanism for cytokinesis. An additional chemotaxis-based cytokinesis that involves a 'midwife' cell has also been reported. Collectively, these findings demonstrate an unexpected diversity of mechanisms by which animal cells carry out cytokinesis.

Animals↗
PubMed2004

Multiple parallelisms in animal cytokinesis.

The process of cytokinesis in animal cells is usually presented as a relatively simple picture: A cleavage plane is first positioned in the equatorial region by the astral microtubules of the anaphase mitotic apparatus, and a contractile ring made up of parallel filaments of actin and myosin II is formed and encircles the cortex at the division site. Active sliding between the two filament systems constricts the perimeter of the cortex, leading to separation of two daughter cells. However, recent studies in both animal cells and lower eukaryotic model organisms have demonstrated that cytokinesis is actually far more complex. It is now obvious that the three key processes of cytokinesis, cleavage plane determination, equatorial furrowing, and scission, are driven by different mechanisms in different types of cells. In some cases, moreover, multiple pathways appear to have redundant functions in a single cell type. In this review, we present a novel hypothesis that incorporates recent observations on the activities of mitotic microtubules and the biochemistry of Rho-type GTPase proteins and postulates that two different sets of microtubules are responsible for the two known mechanisms of cleavage plane determination and also for two distinct mechanisms of equatorial furrowing.

Actin Cytoskeleton↗
PubMed2004

Double atresia of hindgut with ileal stenosis: a case report.

An unusual case of imperforate anus with sigmoid colonic atresia and ileal stenosis is described. Only six cases of imperforate anus associated with colonic atresia have previously been reported in Japan. The possibility of other alimentary obstructions should thus be considered when anorectal anomalies are observed.

Abnormalities, Multiple↗
PubMed2004

Dictyostelium discoideum talin A is crucial for myosin II-independent and adhesion-dependent cytokinesis.

Cytokinesis in myosin II-null (mhcA-) cells of Dictyostelium discoideum requires adhesion to a substratum. Moreover, such myosin II-independent, adhesion-dependent cytokinesis can be divided into two distinct classes: a cell cycle-coupled form (cytokinesis B) and a cell cycle-independent form (cytokinesis C). To better understand the mechanisms underlying cytokinesis B and C, we introduced mutations into mhcA- cells and isolated clones that consistently gave rise to large, multinucleated cells. One such clone was found to have a disrupted talA gene, which codes for one of two Dictyostelium homologues of talin. Time-lapse observation revealed that cytokinesis B is partially impaired in mhcA-/talA- cells and that cytokinesis C is completely blocked. MhcA-/talA- cells took significantly longer to complete cytokinesis B than mhcA- cells on regular polystyrene surfaces, but not on a more adhesive surface. During cytokinesis B in mhcA- cells, GFP-TalA localized in the cortex and in dot-like structures on the ventral surface. Like vertebrate talin, these TalA dots may be involved in substrate adhesion and provide the traction needed to efficiently carry out cytokinesis B. During cytokinesis C in mhcA- cells, GFP-TalA was localized in the cortex of future furrow regions, and was highly enriched in cytoplasmic bridges that formed as the furrowing proceeded. Analysis of furrows in which GFP-TalA concentrations were asymmetric suggested that cortical TalA prevents formation of leading edges in regions where its concentration is high and indirectly promotes formation of leading edges elsewhere, which causes passive furrowing of the TalA-rich regions.

Actins↗
PubMed2003

DWWA, a novel protein containing two WW domains and an IQ motif, is required for scission of the residual cytoplasmic bridge during cytokinesis in Dictyostelium.

We have identified a novel gene, dwwA, which is required for cytokinesis of Dictyostelium cells on solid surfaces. Its product, Dd WW domain containing protein A (DWWA), contains several motifs, including two WW domains, an IQ motif, a C2 domain, and a proline-rich region. On substrates, cells lacking dwwA were multinucleated and larger and flatter than wild-type cells due to their frequent inability to sever the cytoplasmic bridge connecting daughter cells after mitosis. When cultured in suspension, however, dwwA-null cells seemed to carry out cytokinesis normally via a process not driven by the shearing force arising from agitation of the culture. GFP-DWWA localized to the cell cortex and nucleus; analysis of the distributions of various truncation mutants revealed that the N-terminal half of the protein, which contains the C2 domain, is required for the cortical localization of DWWA. The IQ motif of DWWA binds calmodulin in vitro. Given that the scission process is also defective in calmodulin knockdown cells cultured on substrates (Liu et al., 1992), we propose that DWWA's multiple binding domains enable it to function as an adaptor protein, facilitating the scission process through the regulation of Ca(2+)/calmodulin-mediated remodeling of the actin cytoskeleton and/or modulation of membrane dynamics.

Amino Acid Motifs↗
PubMed2003

Intestinal obstruction caused by congenital cytomegalovirus infection: report of a case.

We report a case of coexistent congenital cytomegalovirus (CMV) infection with pseudo-Hirschsprung's disease in a female infant born at 39 weeks' gestation. The serologic data, urinary viral culture, and gene expression by in situ hybridization all suggested a CMV infection, and the pathologic findings of resected bowel specimens showed aganglionosis. Thus, congenital CMV infection may be etiologically associated with Hirschsprung's disease in some children.

Cytomegalovirus Infections↗
PubMed2002

Confirmation by FRET in individual living cells of the absence of significant amyloid beta -mediated caspase 8 activation.

When cells are exposed to death-inducing molecules such as tumor necrosis factor-alpha or Fas, caspase 8 is activated and cleaves an apoptotic facilitator, Bid, that is a member of the Bcl-2 family. After additional modification, the C-terminal moiety of Bid is translocated to the mitochondria and induces the release of cytochrome c into the cytoplasm. In an attempt to directly observe the cleavage of Bid and the following events in living cells, we constructed a vector that encoded Bid fused with yellow fluorescent protein (YFP) and cyan fluorescent protein (CFP) (YFP-Bid-CFP). On expression of YFP-Bid-CFP in mammalian cells, we were able to observe the efficient transfer of energy from excited CFP to YFP within the YFP-Bid-CFP molecule and, importantly, the fusion protein YFP-Bid-CFP was fully functional in cells. When YFP-Bid-CFP was cleaved by caspase 8, on activation by anti-Fas Abs but not by Abeta or tunicamycin, no such transfer of energy was detected. To our knowledge, this is the first report of (i) visualization of the activation of Bid by proteolytic cleavage, with direct observation of the cleavage of YFP-Bid-CFP in the cytoplasm and subsequent translocation of the cleaved Bid to mitochondria and (ii) the absence of Abeta- or tunicamycin-mediated significant activation of caspase 8 in individual living cells.

3T3 Cells↗
PubMed2002

Genetic and morphological evidence for two parallel pathways of cell-cycle-coupled cytokinesis in Dictyostelium.

Myosin-II-null cells of Dictyostelium discoideum cannot divide in suspension, consistent with the dogma that myosin II drives constriction of the cleavage furrow and, consequently, cytokinesis (cytokinesis A). Nonetheless, when grown on substrates, these cells exhibit efficient, cell-cycle-coupled division, suggesting that they possess a novel, myosin-II-independent, adhesion-dependent method of cytokinesis (cytokinesis B). Here we show that double mutants lacking myosin II and either AmiA or coronin, both of which are implicated in cytokinesis B, are incapable of cell-cycle-coupled cytokinesis. These double mutants multiplied mainly by cytokinesis C, a third, inefficient, method of cell division, which requires substrate adhesion and is independent of cell cycle progression. In contrast, double mutants lacking AmiA and coronin were no sicker than each of the single mutants, indicating that the severe defects of myosin II(-)/AmiA(-) or myosin II(-)/coronin(-) mutants are not simple additive effects of two mutations. We take this as genetic evidence for two parallel pathways both of which lead to cell-cycle-coupled cytokinesis. This conclusion is supported by differences in morphological changes during cytokinesis in the mutant cell lines.

Animals↗
PubMed2002

Novel myosin heavy chain kinase involved in disassembly of myosin II filaments and efficient cleavage in mitotic dictyostelium cells.

We have cloned a full-length cDNA encoding a novel myosin II heavy chain kinase (mhckC) from Dictyostelium. Like other members of the myosin heavy chain kinase family, the mhckC gene product, MHCK C, has a kinase domain in its N-terminal half and six WD repeats in the C-terminal half. GFP-MHCK C fusion protein localized to the cortex of interphase cells, to the cleavage furrow of mitotic cells, and to the posterior of migrating cells. These distributions of GFP-MHCK C always corresponded with that of myosin II filaments and were not observed in myosin II-null cells, where GFP-MHCK C was diffusely distributed in the cytoplasm. Thus, localization of MHCK C seems to be myosin II-dependent. Cells lacking the mhckC gene exhibited excessive aggregation of myosin II filaments in the cleavage furrows and in the posteriors of the daughter cells once cleavage was complete. The cleavage process of these cells took longer than that of wild-type cells. Taken together, these findings suggest MHCK C drives the disassembly of myosin II filaments for efficient cytokinesis and recycling of myosin II that occurs during cytokinesis.

Amino Acid Motifs↗