PubMed Health⌕ Search

Biomedical subjects

M Takeichi

Publications and source records attributed to M Takeichi.

At least 73 records · Page 4Linked to original sources
PubMed1997

The role of the msh homeobox gene during Drosophila neurogenesis: implication for the dorsoventral specification of the neuroectoderm.

Development of the Drosophila central nervous system begins with the delamination of neural and glial precursors, called neuroblasts, from the neuroectoderm. An early and important step in the generation of neural diversity is the specification of individual neuroblasts according to their position. In this study, we describe the genetic analysis of the msh gene which is likely to play a role in this process. The msh/Msx genes are one of the most highly conserved families of homeobox genes. During vertebrate spinal cord development, Msx genes (Msx1-3) are regionally expressed in the dorsal portion of the developing neuroectoderm. Similarly in Drosophila, msh is expressed in two longitudinal bands that correspond to the dorsal half of the neuroectoderm, and subsequently in many dorsal neuroblasts and their progeny. We showed that Drosophila msh loss-of-function mutations led to cell fate alterations of neuroblasts formed in the dorsal aspect of the neuroectoderm, including a possible dorsal-to-ventral fate switch. Conversely, ectopic expression of msh in the entire neuroectoderm severely disrupted the proper development of the midline and ventral neuroblasts. The results provide the first in vivo evidence for the role of the msh/Msx genes in neural development, and support the notion that they may perform phylogenetically conserved functions in the dorsoventral patterning of the neuroectoderm.

Animals↗
PubMed1997

Neuromuscular target recognition by a homophilic interaction of connectin cell adhesion molecules in Drosophila.

Drosophila Connectin (CON) is a cell surface protein of the leucine-rich repeat family. During the formation of neuromuscular connectivity, CON is expressed on the surface of a subset of embryonic muscles and on the growth cones and axons of the motoneurons that innervate these muscles, including primarily SNa motoneurons and their synaptic targets (lateral muscles). In vitro, CON can mediate homophilic cell adhesion. In this study, we generated transgenic lines that ectopically expressed CON on all muscles. In the transformant embryos and larvae, SNa motoneurons often inappropriately innervated a neighboring non-target muscle (muscle 12) that ectopically expressed CON. Furthermore, the ectopic synapse formation was dependent on the endogenous CON expression on the SNa motoneurons. These results show that CON can function as an attractive and homophilic target recognition molecule in vivo.

Animals↗
PubMed1997

Comment on autogenic training and hypertension.

We comment on a report by Watanabe, et al. regarding the effects of autogenic training on hypertension. Using previous reports in the United States, we mention methodological problems on how to evaluate the effects of autogenic training and express our hope that they would provide further research to clarify the effects of autogenic training on hypertension.

Autogenic Training↗
PubMed1997

In vivo evidence of the critical role of cadherin-5 in murine vascular integrity.

Vascular endothelial cell-cell adhesion is crucial for the regulation of vascular functions and is associated with many circulatory disorders. We isolated a rat monoclonal antibody (VECD1) recognizing the mouse vascular endothelial cell adhesion molecule and found that it inhibited vascular endothelial cell-cell association. We sequenced a full-length cDNA of the antigen that was identical to mouse cadherin-5. L-cells transfected with its cDNA acquired cell-cell adhesiveness, and these transfectants reacted with VECD1 at cell-cell contact areas. We studied the role of mouse cadherin-5 in vascular functions. The addition of VECD1 antibody to a cultured vascular endothelial cell line (F-2) caused the detachment of each cell. Although normal F-2 cells formed tubular structures on Matrigel, VECD1 disturbed the tubulogenesis. VECD1 also increased the permeability through the F-2 cell layer. To clarify the in vivo function of mouse cadherin-5, we intraperitoneally injected the hybridomas producing VECD1 into adult mice. Severe venous stasis and subcutaneous hemorrhage were induced within several days after the injection, resulting in the early death of the animals. These findings are evidence of an essential role of cadherin-5 in the regulation of vascular endothelial cell-cell adhesion in vivo.

Abdominal Muscles↗
PubMed1997

[BUN, Bence Jones protein, and chromosomal aberrations predict survival in multiple myeloma].

The prognostic significance of of some clinical features in 41 patients with multiple myeloma (including 2 patients with plasma cell leukemia) from our institution was analyzed. Out of 14 variables isolated from the univariate analysis (P < 0.05), only three (BUN, Bence Jones protein, and chromosomal aberrations) were significant in the multivariate model (P < 0.05). Derived from these three variables, three subpopulations of patients were identified. The first group included 20 patients with a low risk of death and their median survival has not been reached. In particular, no one died during the first 60 months in this group. The second group also included 14 patients with an intermediate risk of death and a median survival of 49.2 months. The third group comprised seven patients with a high risk of death during 24 months after diagnosis and a median survival of 31.6 months (P < 0.0001). Finally, Durie & Salmon's myeloma staging system was demonstrated in the present series, and it showed prognostic validity for each stage (P < 0.0222). Compared with Durie & Salmon's staging system, our prognostic model for multiple myeloma was more useful to predict prognosis when applied to the present series.

Adult↗
PubMed1996

Cadherins in the developing central nervous system: an adhesive code for segmental and functional subdivisions.

In this review, we describe general features of the expression of cadherins in the developing central nervous system (CNS) of vertebrates. In the early neuroepithelium, the expression of several cadherins is restricted to specific regions corresponding to segmental domains. Segmental boundaries often coincide with changes in cadherin expression, subdividing the primordial CNS into different adhesive domains. In the different neuromeric domains, early neurons are generated which differentially express cadherins. In the mantle layer, these early neurons seem to sort out according to which cadherin they express, and they aggregate into various gray matter regions (brain nuclei and cortical lamina and regions). The gray matter structures expressing a given cadherin become connected to one another to form parts of particular functional systems or neuronal circuits. Together, these findings show that cadherins provide a molecular system reflecting both early embryonic and mature nervous system architecture. The possible roles of cadherins in the formation and maintenance of segmental and functional nervous system structures are discussed.

Animals↗
PubMed1996

Drosophila alpha-catenin and E-cadherin bind to distinct regions of Drosophila Armadillo.

Adherens junctions are multiprotein complexes mediating cell-cell adhesion and communication. They are organized around a transmembrane cadherin, which binds a set of cytoplasmic proteins required for adhesion and to link the complex to the actin cytoskeleton. Three components of Drosophila adherens junctions, analogous to those in vertebrates, have been identified: Armadillo (homolog of beta-catenin), Drosophila E-cadherin (DE-cadherin), and alpha-catenin. We carried out the first analysis of the interactions between these proteins using in vitro binding assays, the yeast two-hybrid system, and in vivo assays. We identified a 76-amino acid region of Armadillo that is necessary and sufficient for binding alpha-catenin and found that the N-terminal 258 amino acids of alpha-catenin interact with Armadillo. A large region of Armadillo, spanning six central Armadillo repeats, is required for DE-cadherin binding, whereas only 41 amino acids of the DE-cadherin cytoplasmic tail are sufficient for Armadillo binding. Our data complement and extend results obtained in studies of vertebrate adherens junctions, providing a foundation for understanding how junctional proteins assemble and a basis for interpreting existing mutations and creating new ones.

Amino Acid Sequence↗
PubMed1996

Zygotic Drosophila E-cadherin expression is required for processes of dynamic epithelial cell rearrangement in the Drosophila embryo.

Dynamic epithelial reorganization is essential for morphogenesis of various organs. In Drosophila embryos, for example the Malpighian tubule is generated by cellular rearrangement of a preexisting epithelium and the tracheal network is formed by outgrowth, branching, and fusion of epithelial vesicles. Here we report that the previously identified locus shotgun (shg) encodes DE-cadherin, an epithelial cell-cell adhesion molecule of the classic cadherin type and that zygotic shg mutations rather specifically impair processes of the dynamic epithelial morphogenesis. In the mutants, the Malpighian tubule disintegrated into small spherical structures, and the tracheal network formation was blocked in selected steps. The malformation of these organs could be rescued by overexpression of DE-cadherin cDNA under a heat shock promoter. Unexpectedly, the zygotic null condition did not severely affect general epithelial organization; most epithelial tissues maintained not only their cell-cell associations but also their apicobasal polarity in the mutants. The zygotic null mutant retained a certain level of maternally derived DE-cadherin molecules until the end of embryogenesis. These results suggest that zygotic DE-cadherin expression is critical for the rearrangement processes of epithelial cells, whereas the maternally derived DE-cadherin may serve only for the maintenance of the static architecture of the epithelia.

Animals↗
PubMed1996

Expression of cadherin-11 delineates boundaries, neuromeres, and nuclei in the developing mouse brain.

Cadherin-11 (cad11 or OB-cadherin) was previously identified as a mesenchymal cell-cell adhesion molecule. Here we studied the expression of cad11 transcripts in developing brains derived from E11.5 to E16.5 mouse embryos. In the brains at these stages, cad11 was expressed in various patterns, which could be grouped into three categories. First, cad11 expression occurred along boundaries between certain brain subdivisions, including those between the ventral and dorsal thalamus and between the mesencephalon and metencephalon. At these boundaries, cad11-positive cells were localized in a narrow, columnar compartment of the neuroepithelium. Second, cad11 expression delineated particular neuromeric compartments at the ventricular zone of the neuroepithelium. A typical example of this pattern was observed in the hypothalamus. Third, cad11 was expressed in differentiating or differentiated brain nuclei. The former included the thalamus, epithalamus, and pretectum; the latter included the mammillary, red, trigeminal motor, facial motor, prepositus hypoglossal, and inferior olive nuclei, as well as the substantia nigra. Furthermore, developing nuclei and the superficial zone of the cerebellum expressed cad11, and the cortical plate of the developing cerebrum also did so. We compared the expression pattern of cad11 with that of R-cadherin in the diencephalon and found that each cadherin delineated a unique set of diencephalic subdivisions. These findings suggest that cad11-mediated specific cell-cell adhesion plays roles in segmentation or compartmentalization of the developing brain in various ways. We also discussed the possibility that cad11 might be involved in neuronal connections between specific nuclei.

Animals↗
PubMed1996

Decreased E-cadherin expression is associated with haematogenous recurrence and poor prognosis in patients with squamous cell carcinoma of the oesophagus.

Reduced expression of E-cadherin is associated with tumour invasiveness and metastasis. To elucidate whether E-cadherin expression correlates with clinical outcome in patients with oesophageal cancer, 62 patients were investigated immunohistochemically using an anti-E-cadherin monoclonal antibody (HECD-1). Eight patients had normal levels of expression in the tumour, 25 had tumours that expressed high levels (50 per cent or more tumour cells staining positive for E-cadherin) and 29 had tumours expressing low levels (less than 50 per cent of cells expressing E-cadherin). Patients with normally expressing tumours had a better prognosis at 3 years than those with low-expressing tumours (P < 0.05). Postoperative death was correlated significantly with lymphatic invasion, lymph node metastasis, E-cadherin expression and depth of invasion (P < 0.05). Furthermore, haematogenous recurrence was correlated with E-cadherin expression (rs = 0.38, P < 0.01) and blood vessel invasion (rs = 0.28, P < 0.05). These results suggest that evaluation of E-cadherin immunoreactivity may predict haematogenous recurrence and poor prognosis in patients with oesophageal cancer.

Adult↗
PubMed1996

Alpha N-catenin expression in the normal and regenerating chick sciatic nerve.

The Ca(2+)-dependent intercellular adhesion molecule cadherin is known to be linked to the cytoskeleton by the protein catenin, an association of which appears to be important for the cell-adhesion function of cadherin. Catenin consists of three subtypes-alpha, beta, and gamma. In our previous study, N-cadherin was shown to be localized on the plasmalemma of normal and regenerating chick peripheral nerve. Thus, as alpha N-catenin is a subtype of alpha-catenin (which is specifically associated with N-cadherin), we investigated the immunolocalization of alpha N-catenin in normal and regenerating chick sciatic nerve. In normal nerve, unmyelinated axons exhibited either intense or weak alpha N-catenin immunoreactivity throughout the axoplasm, whereas myelinated axons were completely immunonegative. Regenerating axons, including those derived from parent myelinated axons, showed alpha N-catenin immunoreactivity of variable intensities in growth cones and axon shafts. Schwann cells were invariably devoid of immunoreactivity. Thus alpha N-catenin is not necessarily bound to the surface plasmalemma, but is distributed throughout the cytoplasm, suggesting that most alpha N-catenin molecules are dissociated from N-cadherin.

Animals↗
PubMed1996

The catenin/cadherin adhesion system is localized in synaptic junctions bordering transmitter release zones.

Molecular mechanisms linking pre- and postsynaptic membranes at the interneuronal synapses are little known. We tested the cadherin adhesion system for its localization in synapses of mouse and chick brains. We found that two classes of cadherin-associated proteins, alpha N- and beta-catenin, are broadly distributed in adult brains, colocalizing with a synaptic marker, synaptophysin. At the ultrastructural level, these proteins were localized in synaptic junctions of various types, forming a symmetrical adhesion structure. These structures sharply bordered the transmitter release sites associated with synaptic vesicles, although their segregation was less clear in certain types of synapses. N-cadherin was also localized at a similar site of synaptic junctions but in restricted brain nuclei. In developing synapses, the catenin-bearing contacts dominated their junctional structures. These findings demonstrate that interneuronal synaptic junctions comprise two subdomains, transmitter release zone and catenin-based adherens junction. The catenins localized in these junctions are likely associated with certain cadherin molecules including N-cadherin, and the cadherin/ catenin complex may play a critical role in the formation or maintenance of synaptic junctions.

Animals↗
PubMed1996

Two cases of panic disorder treated with autogenic training and in vivo exposure without medication.

The aim of this study was to use autogenic training in combination with in vivo exposure in the behavioral treatment of panic disorder without medication. Two cases of panic disorder with agoraphobic avoidance were presented. Case 1 was a 33 year old married female who exhibited mild panic symptoms, and case 2 was a 23 year old single male who had severe panic symptoms. Both subjects were successfully treated with the combination of these two techniques. Treatment effects were maintained for 9 years as a follow up in case 1, and for 4 years in case 2.

Adult↗
PubMed1996

Cadherin-mediated cell adhesion and cell motility in Drosophila trachea regulated by the transcription factor Escargot.

Coordination of cell motility and adhesion is essential for concerted movement of tissues during animal morphogenesis. The Drosophila tracheal network is formed by branching, migration and fusion of tubular ectodermal epithelia. Tracheal tip cells, located at the end of each branch that is going to fuse, extend filopodia to search for targets and later change their cell shape to a seamless ring to allow passage of lumen. The cell adhesion molecule DE-cadherin accumulates at the site of contact to form a ring that marks the site of lumen entry and is essential for the fusion. DE-cadherin expression in tip cells of a subset of branches is dependent on escargot, a zinc finger gene expressed in all tip cells. Such escargot mutant tip cells failed to adhere to each other and continued to search for alternative targets by extending long filopodia. We present evidence indicating escargot positively regulates transcription of the DE-cadherin gene, shotgun. Overexpression of DE-cadherin rescued the defect in one of the fusion points in escargot mutants, demonstrating an essential role of DE-cadherin in target recognition and identifying escargot as a key regulator of cell adhesion and motility in tracheal morphogenesis.

Animals↗
PubMed1996

[Combined effects of sizofiran and rG-CSF on myelosuppression in cancer chemotherapy].

A combination of the antitumor polysaccharide Sizofiran and rG-CSF was investigated for its effects on peripheral blood counts in ovarian cancer patients undergoing chemotherapy. We performed the analysis by using variations in peripheral blood counts and the duration of treatment as variables. In the analysis, effects on decreases in both neutrophils and platelets and their recoveries could be assessed. As a result, the decrease in neutrophils was inhibited and its recovery was promoted, suggesting that the combined use of the drugs may be useful for myelosuppression by chemotherapy for ovarian cancer.

Adult↗
PubMed1995

Increased cell-substratum adhesion, and decreased gelatinase secretion and cell growth, induced by E-cadherin transfection of human colon carcinoma cells.

Metastasis of colon carcinomas is assumed to be caused by multiple steps, which include a loss of cell adhesion that results in the release of carcinoma cells from the original tumor tissue. A human colon carcinoma cell line COKFu was established from a poorly differentiated metastatic adenocarcinoma without cell-cell adhesion and without expression of E-cadherin mRNA and protein. This cell line was co-transfected with mouse E-cadherin cDNA in an expression vector and a neomycin-resistant gene. The parental carcinoma cells had a spindle shape and were scattered, whereas the transfected cells, which expressed exogenous E-cadherin gene, showed a more compact shape with strong cell-cell adhesion and with increased adhesiveness to collagen gel. These cells showed a significantly low anchorage independency (2-7%) and decreased invasiveness (30%) compared to the parental cells. Growth rate of transfectants was decreased both in vitro and in the subcutis of nude mice, with decreased lymphnode metastasis in the case of intravenous injection. It was additionally found that activity of 62 kd gelatinase, secreted from parental cells, was lost or decreased in E-cadherin-transfected cells. These results suggest that E-cadherin is not only involved in the cell-cell adhesion of colon carcinomas, it also has a wider effect, including cell-substratum adhesion and the regulation of proteinase secretion from the cells, resulting in partial suppression of invasiveness and tumorigenic growth.

Animals↗