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Biomedical subjects

M Takeichi

Publications and source records attributed to M Takeichi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential expression of cadherin adhesion receptors in neural retina of the postnatal mouse.

PURPOSE: To determine the expression pattern of multiple subtypes of cadherin adhesion receptor in postnatal mouse neural retina. METHODS: The expression of N-cadherin, R-cadherin, cadherin-6, cadherin-8, and cadherin-11 in retinas at postnatal days 0 to 42 was analyzed by in situ hybridization of mRNA as well as by immunohistochemistry. RESULTS: Each cadherin was expressed by different cell populations of the retina, and the following expression patterns were established by postnatal day 14: in the ganglion cell layer, all these molecules were expressed, but each occurred only in a subset of the cells. Likewise, in the inner nuclear layer, R-cadherin and cadherin-6 and -8 were expressed by a restricted population of amacrine cells, and cadherin-8 also by a subpopulation of bipolar cells. All horizontal cells expressed R-cadherin, and Muller cells expressed N-cadherin and cadherin-11. Proteins of R-cadherin and cadherin-6 were concentrated in neuropil layers. CONCLUSIONS: The pattern of differential expression of the five cadherins supports the idea that these molecules may play a role in selective cell interactions within the heterogeneous cell pool of the neural retina.

Animals↗
PubMed1999

Adhesive subdivisions intrinsic to the epithelial somites.

Developing somites express two subtypes of classic cadherin adhesion receptors, N-cadherin and cadherin-11 (cad11). To investigate the role of these adhesion molecules in somite morphogenesis, we analyzed the somites of mice whose N-cadherin and cad11 genes were disrupted. The epithelial somites of N-cadherin null mutant mice were fragmented as reported, whereas those of cad11(-/-) mice showed no structural anomaly. In mice double homozygous for N-cadherin and cad11 mutation, however, somites were further fragmented into smaller clusters than in the N-cadherin-deficient mice, suggesting that these two cadherins cooperate in the maintenance of epithelial somites. Despite the disorganization of epithelial structures, dorsoventral polarity markers were expressed in their correct patterns in all of these mutant somites. Uncx4.1, whose expression is localized only in the caudal region of each somite, was also expressed in a normal pattern in the mutant somites. However, the staining for Uncx4.1 revealed that, in the N-cadherin mutants, each somite tended to be cleaved at the border between the Uncx4. 1-positive and -negative regions and that the cleaved subunits maintained the clustered state, often exhibiting epithelioid morphology. This separation of the rostral and caudal regions was observed as soon as the epithelial somites had been formed. In the N-cadherin/cad11 double-homozygous mutants, this tendency was also observed, although each half of the somite further disintegrated into randomly arranged cell clusters. These results suggest that cells of the rostral and caudal regions of each epithelial somite have an activity to aggregate independently or separate from one another and that one role of N-cadherin and cad11 is to connect the two halves into a single unit.

Animals↗
PubMed1999

Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled.

We identified a seven-pass transmembrane receptor of the cadherin superfamily, designated Flamingo (Fmi), localized at cell-cell boundaries in the Drosophila wing. In the absence of Fmi, planar polarity was distorted. Before morphological polarization of wing cells along the proximal-distal (P-D) axis, Fmi was redistributed predominantly to proximal and distal cell edges. This biased localization of Fmi appears to be driven by an imbalance of the activity of Frizzled (Fz) across the proximal/distal cell boundary. These results, together with phenotypes caused by ectopic expression of fz and fmi, suggest that cells acquire the P-D polarity by way of the Fz-dependent boundary localization of Fmi.

Amino Acid Sequence↗
PubMed1999

p120(ctn) acts as an inhibitory regulator of cadherin function in colon carcinoma cells.

p120(ctn) binds to the cytoplasmic domain of cadherins but its role is poorly understood. Colo 205 cells grow as dispersed cells despite their normal expression of E-cadherin and catenins. However, in these cells we can induce typical E-cadherin-dependent aggregation by treatment with staurosporine or trypsin. These treatments concomitantly induce an electrophoretic mobility shift of p120(ctn) to a faster position. To investigate whether p120(ctn) plays a role in this cadherin reactivation process, we transfected Colo 205 cells with a series of p120(ctn) deletion constructs. Notably, expression of NH2-terminally deleted p120(ctn) induced aggregation. Similar effects were observed when these constructs were introduced into HT-29 cells. When a mutant N-cadherin lacking the p120(ctn)-binding site was introduced into Colo 205 cells, this molecule also induced cell aggregation, indicating that cadherins can function normally if they do not bind to p120(ctn). These findings suggest that in Colo 205 cells, a signaling mechanism exists to modify a biochemical state of p120(ctn) and the modified p120(ctn) blocks the cadherin system. The NH2 terminus-deleted p120(ctn) appears to compete with the endogenous p120(ctn) to abolish the adhesion-blocking action.

Alkaloids↗
PubMed1999

Combinatorial expression of cadherins in the tectum and the sorting of neurites in the tectofugal pathways of the chicken embryo.

The expression of four cadherins (N-cadherin, R-cadherin, cadherin-6B and cadherin-7) was mapped in the developing tectal system of the chicken embryo from four to 19 days of incubation. Each of the cadherins is expressed in a restricted fashion in specific tectal layers, with partial overlap between the cadherins. In some layers, subpopulations of neurons differentially express the cadherins, e.g., in the stratum griseum centrale. Double labeling demonstrates that many of the projection neurons in this layer co-express at least two cadherins. Fibers of the efferent (tectofugal) pathways originating in these neurons also differentially express the cadherins, most prominently at around 1 1 days of incubation. While the different subpopulations of cadherin-expressing projection neurons are dispersed and mixed within the tectum, their neurites sort out and fasciculate according to which cadherin they express, as they collect in the major output of the tectum, the brachium colliculi superioris. From here, cadherin-expressing fascicles follow separate paths to their respective target areas, some of which also express the respective cadherins, in a matching fashion. We propose that the preferentially homophilic binding of cadherins provides a potential adhesive basis for the sorting and selective fasciculation of specific subpopulations of neurites, similar to the well-established sorting and aggregation of cells expressing cadherins. The combinatorial expression of cadherins by the tectal projection neurons may contribute to the complexity and specificity of functional connections in this system.

Animals↗
PubMed1999

Studies on the psychosomatic functioning of ill-health according to Eastern and Western medicine. 1. Visual observation of the sublingual vein for early detection of vital energy stagnation and blood stasis.

Computer-assisted image analyses were performed on the tongue color of 95 medical students without previous history of blood stasis-related condition to clarify the mutual relationship of the color of the tongue proper, the coating, and sublingual vein. The location of the measurement for the tongue proper was the underside of the tongue, and location of the measurement for the tongue coating was the upper surface of the tongue. A linear correlation analysis showed a correlation for each of the different positions for the non-normalized red value and normalized blue value. This analysis also demonstrated a statistically-significant relationship between the tongue proper and the sublingual vein using Red-Green-Blue components and normalized Red-Green-Blue components (r = +0.670 - 0.817, p < 0.0001). The most significant correlation between the tongue proper and the sublingual vein was the normalized red value and the normalized Red-Green-Blue values for minimizing the range of the standard error of the mean (r = +0.745, p < 0.0001), although non-normalized blue had the highest correlation coefficient. Therefore, it seems reasonable to select those normalized red values for the comparison in the tongue color analysis. Correlation of the color between the sublingual vein and the tongue proper strongly suggests that inspection with the naked eye of the sublingual vein is useful for the early detection of vital energy stagnation and blood stasis. Also, because of its close relation to sustained chronic stress, changes in the sublingual vein might be available as one physiological parameter of a stress reaction.

Adult↗
PubMed1999

Studies on the psychosomatic functioning of ill-health according to eastern and Western medicine. 2. Anxiety-affinitive constitution associated with qi, blood, and body fluid--diagnostic and therapeutic methods.

The objective of this investigation was to identify characteristics of psychosomatic function in medical students (N = 62, mean age, 23.3, SD, 1.7 years) whose ill-health was related to unbalanced qi, blood, and body fluid, and to develop a diagnosis and treatment method for these conditions. Our study revealed complicated characteristics. At the psychological level, these characteristics are stress-related emotional disturbances, including anxiety, insomnia and anergy, and the lowering of social function. At the physiological level, these characteristics are associated with high complexity of fractal dimension of eye (horizontal) and respiratory (thoracic) movements correlated to STA1-trait anxiety. Thus, the three psychosomatic characteristics related to unbalanced qi, blood, and body fluid suggest the concept of an anxiety-affinitive constitution, also described as the equivalent of ill-health. This indicates that diagnosis and treatment of this type of constitution has the potential to be useful for both the prevention of stress-related and life-style disease, and the treatment of current disease.

Anxiety↗
PubMed1999

Studies on the psychosomatic functioning of ill-health according to eastern and Western medicine. 3. Two treatment methods using kampo medication for stress-related and lifestyle disease.

In this study, we examine the modality of improvement in psychosomatic function to verify the suitability of two treatment methods previously described. The subjects were nine medical students with no history of blood stasis-related illness (average age, 24.8; SD, 1.4 years) and 21 patients of our outpatient clinic (average age, 54.3; SD, 10.4 years). For purposes of our research, Kampo medication was selected based on the diagnosis and treatment of unbalanced qi, blood, and body fluid developed by the authors in their previous report. As a result, the therapeutic features of the preventive treatment group of nine medical students and the final treatment group of 21 patients of the outpatient clinic were essentially identical. There were two such features: 1. At the psychological level, this consisted an improvement in stress-related emotional reaction, centered on anxiety and depression, and at the physiological level, this consisted of an improvement in peripheral blood circulation (an increase of the fractal dimension of the plethysmogram, p = 0.0357). 2. The improvement of the foregoing psychosomatic function is related to the improvement of blood stasis (strictly speaking, vital energy stagnation and blood stasis) in Oriental medicine, and the improvement of blood rheological abnormalities in Western medicine. Therefore, this research confirmed the significance of two treatment methods proposed by the authors for stress-related illness and lifestyle disease in individuals with an anxiety-affinitive constitution.

Adult↗
PubMed1999

Second opinion behaviour among Japanese primary care patients.

BACKGROUND: Second opinion behaviour is often observed among Japanese primary care patients. These patients secretly visit university-affiliated hospitals without informing their doctors. Research to elucidate the psychosocial determinants of this behaviour in the Japanese primary care setting is needed. AIM: To describe the sociodemographic characteristics of second opinion patients (SOPs), and to determine the factors related to this behaviour. METHOD: Patients from the general medicine clinic answered our original questionnaire and a 30-item General Health Questionnaire (GHQ-30). A random sample of patients was questioned using the Diagnostic Interview Schedule. SOPs were defined as those patients who had visited another medical facility with the same complaint, and 'doctor-shopping' patients (DSPs) were defined as those patients who had visited two or more medical facilities with the same complaint. RESULTS: There were 420 SOPs among 1033 patients (41.0%). The multivariate analysis showed that residence and GHQ-30 were the significant differences between the SOPs and the first-visit patients (FVP) (P < 0.0005 for both factors). Also, the SOPs were anxious and sought advice from anybody, unlike the FVPs. Compared with the DSPs, they had a short duration of illness and they did not feel a worsening of their symptoms (P = 0.0001 for duration of illness; P = 0.006 for condition of illness). CONCLUSION: Our results showed that the SOPs who lived far from the medical school hospital felt anxiety and went to a university-affiliated hospital on the advice of anybody. Determining the reasons for this behaviour will require empirical studies regarding the nature of the patient's anxiety for illness.

Adolescent↗
PubMed1998

Dynamic behavior of the cadherin-based cell-cell adhesion system during Drosophila gastrulation.

During Drosophila gastrulation, morphogenesis occurs as a series of cell shape changes and cell movements which probably involve adhesive interactions between cells. In the present study, we examined the dynamic aspects of cadherin-based cell-cell adhesion in the morphogenetic events to assess its contribution to morphogenesis. DE- and DN-cadherin show complementary expression patterns in the presumptive ectoderm and mesoderm at the mRNA level. We found that switching of cadherin expression from the DE- to the DN-type in the mesodermal germ layer occurred downstream of the mesoderm-determination genes twist and snail. However, examination of their protein expression patterns showed that considerable amounts of DE-cadherin remained on the surfaces of mesodermal cells during invagination, while DN-cadherin did not appear on the cell surfaces at this stage. Further immunocytochemical analysis of the localizations of DE-cadherin and its associated proteins Armadillo (beta-catenin) and Dalpha-catenin revealed dynamic changes in their distributions which were accompanied by changes in cell morphology in the neuroectoderm and mesoderm. Simultaneously, adherens junctions (AJs), based on the cadherin-catenin system, were shown to change their location, size, and morphology. These dynamic aspects of cadherin-based cell-cell adhesion appeared to be associated with the following: (1) initial establishment of the blastoderm epithelium, (2) acquisition of cell motility in the neuroectoderm, (3) cell sheet folding, and (4) epithelial to mesenchymal conversion of the mesoderm. These observations suggest that the behavior of the DE-cadherin-catenin adhesion system may be regulated in a stepwise manner during gastrulation to perform successive cell-morphology conversions. Moreover, the processes responsible for loss of epithelial cell polarity and elimination of preexisting DE-cadherin-based epithelial junctions during early mesodermal morphogenesis are discussed.

Animals↗
PubMed1998

alpha-Catenin-vinculin interaction functions to organize the apical junctional complex in epithelial cells.

alphaE-catenin, a cadherin-associated protein, is required for tight junction (TJ) organization, but its role is poorly understood. We transfected an alphaE-catenin-deficient colon carcinoma line with a series of alphaE-catenin mutant constructs. The results showed that the amino acid 326-509 domain of this catenin was required to organize TJs, and its COOH-terminal domain was not essential for this process. The 326-509 internal domain was found to bind vinculin. When an NH2-terminal alphaE-catenin fragment, which is by itself unable to organize the TJ, was fused with the vinculin tail, this chimeric molecule could induce TJ assembly in the alphaE-catenin-deficient cells. In vinculin-null F9 cells, their apical junctional organization was impaired, and this phenotype was rescued by reexpression of vinculin. These results indicate that the alphaE-catenin-vinculin interaction plays a role in the assembly of the apical junctional complex in epithelia.

Binding Sites↗
PubMed1998

Drosophila synapse formation: regulation by transmembrane protein with Leu-rich repeats, CAPRICIOUS.

Upon reaching the target region, neuronal growth cones transiently search through potential targets and form synaptic connections with only a subset of these. The capricious (caps) gene may regulate these processes in Drosophila. caps encodes a transmembrane protein with leucine-rich repeats (LRRs). During the formation of neuromuscular synapses, caps is expressed in a small number of synaptic partners, including muscle 12 and the motorneurons that innervate it. Loss-of-function and ectopic expression of caps alter the target specificity of muscle 12 motorneurons, indicating a role for caps in selective synapse formation.

Amino Acid Sequence↗
PubMed1998

Cadherin expression in the retina and retinofugal pathways of the chicken embryo.

The expression of two calcium-dependent adhesion molecules of the cadherin superfamily (cadherin-6B and cadherin-7) was mapped in the embryonic neural retina and retinofugal pathways of the chicken embryo and compared with the expression of R-cadherin, N-cadherin, and B-cadherin, studied previously. Whereas B-cadherin is only found in Miller glia, the other four cadherins are each expressed by specific subpopulations of retinal neurons. For example, different (but partly overlapping) populations of bipolar cells express R-cadherin, cadherin-6B, and cadherin-7. Cadherin-6B and cadherin-7 are also expressed by subsets of amacrine cells. In the inner plexiform layer, cadherin-6B and cadherin-7 immunoreactivities are restricted to specific sublaminae associated with synapsin-I-positive nerve terminals. In addition, cadherin-6B and cadherin-7 are expressed by a subset of ganglion cells that project to several retinorecipient nuclei forming part of the accessory optic system (e.g., nucleus of the basal optic root and external pretectal nucleus). Together with their connecting fiber tracts, these nuclei also express cadherin-6B and cadherin-7 in their neurons and neuropile. The expression patterns of the two cadherins overlap but show distinct differences. Some other visual nuclei express cadherin-7 but not cadherin-6B. The expression patterns differ from those previously described for N- and R-cadherin. Together, these results demonstrate that cadherins could provide a system of adhesive cues that specify developing retinal circuits and other functional connections and subsystems in the embryonic chicken visual system.

Animals↗
PubMed1998

Cytoplasmic regulation of the movement of E-cadherin on the free cell surface as studied by optical tweezers and single particle tracking: corralling and tethering by the membrane skeleton.

The translational movement of E-cadherin, a calcium-dependent cell-cell adhesion molecule in the plasma membrane in epithelial cells, and the mechanism of its regulation were studied using single particle tracking (SPT) and optical tweezers (OT). The wild type (Wild) and three types of artificial cytoplasmic mutants of E-cadherin were expressed in L-cells, and their movements were compared. Two mutants were E-cadherins that had deletions in the COOH terminus and lost the catenin-binding site(s) in the COOH terminus, with remaining 116 and 21 amino acids in the cytoplasmic domain (versus 152 amino acids for Wild); these are called Catenin-minus and Short-tailed in this paper, respectively. The third mutant, called Fusion, is a fusion protein between E-cadherin without the catenin-binding site and alpha-catenin without its NH2-terminal half. These cadherins were labeled with 40-nm phi colloidal gold or 210-nm phi latex particles via a monoclonal antibody to the extracellular domain of E-cadherin for SPT or OT experiments, respectively. E-cadherin on the dorsal cell surface (outside the cell-cell contact region) was investigated. Catenin-minus and Short-tailed could be dragged an average of 1.1 and 1.8 micron by OT (trapping force of 0.8 pN), and exhibited average microscopic diffusion coefficients (Dmicro) of 1.2 x 10(-10) and 2.1 x 10(-10) cm2/s, respectively. Approximately 40% of Wild, Catenin-minus, and Short-tailed exhibited confined-type diffusion. The confinement area was 0.13 micron2 for Wild and Catenin-minus, while that for Short-tailed was greater by a factor of four. In contrast, Fusion could be dragged an average of only 140 nm by OT. Average Dmicro for Fusion measured by SPT was small (0.2 x 10(-10) cm2/s). These results suggest that Fusion was bound to the cytoskeleton. Wild consists of two populations; about half behaves like Catenin- minus, and the other half behaves like Fusion. It is concluded that the movements of the wild-type E-cadherin in the plasma membrane are regulated via the cytoplasmic domain by (a) tethering to actin filaments through catenin(s) (like Fusion) and (b) a corralling effect of the network of the membrane skeleton (like Catenin-minus). The effective spring constants of the membrane skeleton that contribute to the tethering and corralling effects as measured by the dragging experiments were 30 and 5 pN/micron, respectively, indicating a difference in the skeletal structures that produce these two effects.

Animals↗
PubMed1998

Cadherin-6 in the developing mouse brain: expression along restricted connection systems and synaptic localization suggest a potential role in neuronal circuitry.

Multiple subtypes of the cadherin homophilic cell-cell adhesion molecule are expressed differentially in developing and mature brains, each being expressed in restricted neuronal groups. Cadherin-6 (cad6) is one of such cadherins. Recent studies of cad6 mRNA expression in the postnatal mouse forebrain showed that it occurs in neurons constituting a specific subset of thalamocortical connections. Here we analyzed the localization of cad6 mRNA as well as its protein in the entire central nervous system and also in cranial ganglia of mice at late embryonic to postnatal stages. Our results showed that cad6 is expressed by a limited population of neurons or their precursors, which are synaptically connected to one another, throughout the perinatal stages, and that this expression delineates restricted neuronal circuits from the central to peripheral nervous systems, which include subpathways of the auditory, somatosensory, solitary, vestibular, and olivocerebellar systems. cad6 proteins were detected in these cad6 mRNA-positive neurons on the surface of their cell bodies or dendrites as well as in the cytoplasm. Confocal microscopic analysis revealed that the cad6 protein distribution overlapped that of synaptotagmin in synapse forming areas, suggesting that homotypic cad6 interactions are involved in synaptic connections between neurons expressing this protein. These findings support the idea that cadherin-mediated cell-cell adhesions take part in specific interneuronal connections.

Age Factors↗
PubMed1998

Cadherin-defined segments and parasagittal cell ribbons in the developing chicken cerebellum.

In the developing chicken cerebellar cortex, three cadherins (Cad6B, Cad7, and R-cadherin) are expressed in distinct parasagittal segments that are separated from each other by ribbons of migrating interneurons and granule cells which express R-cadherin and Cad7, respectively. The segment/ribbon pattern is respected by the expression of other types of molecules, such as engrailed-2 and SC1/BEN/DM-GRASP. The cadherin-defined segments contain young Purkinje cells which are connected to underlying nuclear zones expressing the same cadherin, thereby forming parasagittal cortico-nuclear zones of topographically organized connections. In addition, R-cadherin-positive mossy fiber terminals display a periodic pattern in the internal granular layer. In this layer, Cad7 and R-cadherin are associated with synaptic complexes. These results suggest that cadherins play a pivotal role in the formation of functional cerebellar architecture by providing a three-dimensional scaffold of adhesive information.

Animals↗