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Biomedical subjects

M Takeichi

Publications and source records attributed to M Takeichi.

At least 163 records · Page 9Linked to original sources
PubMed1990

Localization of specificity determining sites in cadherin cell adhesion molecules.

Cadherins are a group of homophilic intercellular adhesion molecules; each member of this family exhibits binding specificity. Here, we attempted to map the sites for the specificities of these molecules by analyzing adhesives selectivities of the cells that express chimeric and point-mutated E- and P-cadherin. The results showed that the amino-terminal 113 amino acid region is essential to determine the specificities, and within this region we could identify especially important sites in which amino acid substitutions altered the binding specificity of cadherins. We also found that the epitopes for antibodies capable of blocking cadherin action are located in this amino-terminal region.

Amino Acid Sequence↗
PubMed1990

Prospective trial for early detection of pancreatic cancer by elevated serum immunoreactive elastase.

Early detection of pancreatic cancer was prospectively evaluated by measuring serum immunoreactive elastase (IRE) in 722 patients in two hospitals during the past 18 months. Patients included in the study were over 40 years of age and had symptoms suggestive of pancreatic disease such as upper abdominal pain, discomfort or mass, jaundice, weight loss, or diabetes. Among the 722 patients, 171 exhibited elevation of serum IRE. Pancreatic diseases were subsequently found in 42% of the 171 patients. Pancreatic cancer was found in 22 patients, among which 17 had elevated serum IRE. Among the 17 pancreatic cancer patients with elevated IRE, 10 underwent radical resection of the cancer but in none of the five patients with normal serum IRE could radical resection be carried out. Three of the 10 patients had a small cancer less than 2 cm in diameter and two of them survived for more than three years. Patients over 40 or 45 years of age complaining of upper abdominal pain of recent onset that cannot be explained by diseases other than that of the pancreas would be candidates for measurement of serum elastase, and this is an effective way to detect pancreatic cancer at an early stages.

Adult↗
PubMed1990

Activation of protein kinase C triggers premature compaction in the four-cell stage mouse embryo.

During mouse preimplantation development, the cells of the mouse embryo undergo a progressive subcellular reorganization at compaction, which eventually results in the formation of two distinct cell types. We have investigated the effect that activators of the Ca2(+)-phospholipid-dependent protein kinase (PKC) have on mouse compaction. Phorbol ester activation of PKC caused premature compaction of four-cell embryos within a few minutes of addition followed by a prolonged decompaction phase after 1 hr. This response was dose-dependent to concentrations as low as 250 pg/ml. Diacylglycerides also caused compaction; however, it was more sustained than with phorbol esters and was not followed by a phase of decompaction. Inhibition of PKC with sphingosine blocks induced compaction in a dose-dependent manner and also blocks normal compaction of eight-cell embryos. A monoclonal antibody to the cell adhesion molecule, E-cadherin, which mediates mouse embryo compaction, completely blocks compaction induced by these activators of PKC. Indirect immunofluorescence with a monoclonal antibody to E-cadherin indicates that PKC activation causes a rapid shift in the localization of this cell adhesion molecule, which coincides with the observed compaction. These results suggest that PKC plays a role in the initiation of compaction through its effect either directly or indirectly on E-cadherin.

Animals↗
PubMed1990

Nerve growth cone migration onto Schwann cells involves the calcium-dependent adhesion molecule, N-cadherin.

The role of calcium-dependent adhesion molecules in the migration of nerve growth cones onto the top of Schwann cells was probed by examination of sensory growth cone-Schwann cell interactions in medium containing either 1.0 mM Ca2+ or 0.1 mM Ca2+. In the presence of 1.0 mM Ca2+ growth cones rapidly migrated onto Schwann cells, spread, and remained for extended periods. However, in 0.1 mM Ca2+ growth cones still made frequent contacts with Schwann cells, but migration onto the upper cell surface was much reduced. This contrast in growth cone-Schwann cell interactions could be switched rapidly by changing the Ca2+ concentration of the culture medium. Growth cones of retinal neurons showed similar calcium-dependence in their migration onto Schwann cells. Antibodies to the calcium-dependent adhesion molecule, N-cadherin, also blocked growth cone migration onto Schwann cells, but antibodies to another neuronal adhesion molecule, L1, had no effect on growth cone-Schwann cell interactions. Immunocytochemical staining for N-cadherin and L1 indicated that growth cones and Schwann cells have N-cadherin on their surfaces, while L1 is present only on axons and growth cones. These results provide two kinds of evidence that N-cadherin is important in the initial interactions of growth cones and Schwann cells.

Animals↗
PubMed1990

Cadherin-mediated cell-cell adhesion and neurogenesis.

Cadherins constitute a molecular family which confers adhesive specificities on cells. Their expression is spatio-temporally regulated in embryos and the multiple types of cadherins are expressed in the nervous system. The inhibition of cadherin action with antibodies resulted in the perturbation of the histogenesis of neural tissues. The sites for determining the binding specificities of cadherins reside in their amino terminal 113 amino acid region. Possible roles of cadherins associated with these properties in neurogenesis are discussed.

Animals↗
PubMed1990

Cadherin subclasses: differential expression and their roles in neural morphogenesis.

Cadherins homophilically bind cells. Thus, cells expressing identical cadherins adhere selectively to each other, and they do not randomly intermix with the cells expressing other types of cadherins in vitro. Neural tissues express multiple types of cadherins, and the expression of each cadherin type is spatiotemporally regulated within a tissue during development. This molecular family therefore could operate for the sorting of different cell types in the nervous system. The regulation of N-cadherin expression is also important for the early development of the neural tube. The ectopic expression of N-cadherin in Xenopus embryos, which was induced by mRNA injection, led to the disorganization of neural tube structures or the fusion of the neural tube to the epidermis. These results suggest that the precise regulation of cadherin expression at the quantitative as well as at the qualitative level si crucial for neural morphogenesis.

Animals↗
PubMed1990

Effects of intraventricular implantation of crystalline estradiol benzoate on the sleep-wakefulness circadian rhythm of ovariectomized rats.

The effect of estrogen on the sleep-wakefulness circadian rhythm was examined in ovariectomized rats. Implantation of crystalline estradiol benzoate (EB) into the third cerebral ventricle reduced the slow wave sleep (SWS) and paradoxical sleep (PS) appearances within the dark period. This result was similar to that obtained by a systemic administration of 20 micrograms of EB. The inhibition of sleep during the nighttime was more remarkable in PS than in SWS. The reduction of SWS was due to a shorter duration of SWS episodes and the reduction of PS to a fewer number of PS episodes. These results indicate that ovariectomized rats treated with estrogen develop an inability to sustain episodes of SWS and initiate PS episodes.

Animals↗
PubMed1990

Ectopic expression of N-cadherin perturbs histogenesis in Xenopus embryos.

Xenopus embryos express N-cadherin in a pattern similar to that observed in other species, and cells expressing Xenopus N-cadherin can bind to cells expressing chicken N-cadherin in vitro. To investigate the developmental role of this molecule, we injected mRNA encoding chicken N-cadherin into one blastomere of 2-cell-stage Xenopus embryos and examined the effect of its expression on their development. The ectopic expression of N-cadherin occurred in various regions of the injected embryos and induced abnormal histogenesis, such as thickening, clumping or fusion of cell layers. These results suggest that the precise quantitative and qualitative regulation of the expression of cadherins is essential to embryonic morphogenesis.

Animals↗
PubMed1990

[Long-term follow-up study of alcoholic liver disease].

Two hundred seventy-one patients with various forms of alcoholic liver disease were followed up for an average of 87.9 months. The survival was the lowest for alcoholic cirrhosis (average 10-year survival: 23.8%). Prognosis was grave especially in cirrhotic patients who continued drinking, owing mainly to the increased death due to gastrointestinal bleeding. The development of hepatocellular carcinoma (HCC) was observed during the first six years only in cirrhosis. The average 5-year probability rate of developing HCC for cirrhosis was 16.3%. The rate was significantly higher for the cirrhotic patients who abstained than for those who continued drinking. Serial biopsies were performed on 66 non-cirrhotic patients who continued drinking. The mean duration of histological follow-up 46.0 months. Cirrhosis developed eventually in 30.3% of the cases. In conclusion, the present study indicates that continued drinking causes progressive liver damage and a poor prognosis. Our data also suggest that abstinence is associated with an increased risk of HCC in cirrhosis. Thus, it is important to recover from alcoholism before cirrhosis develops.

Adult↗
PubMed1989

Neural cadherin: role in selective cell-cell adhesion.

Cadherins are a family of Ca2+-dependent intercellular adhesion molecules. Complementary DNAs encoding mouse neural cadherin (N-cadherin) were cloned, and the cell binding specificity of this molecule was examined. Mouse N-cadherin shows 92 percent similarity in amino acid sequence to the chicken homolog, while it shows 49 percent and 43 percent similarity to epithelial cadherin and to placental cadherin of the same species, respectively. In cell binding assays, mouse N-cadherin did not cross-react with other mouse cadherins, but it did cross-react with chicken N-cadherin. The results indicate that each cadherin type confers distinct adhesive specificities on different cells, and also that the specificity of N-cadherin is conserved between mammalian and avian cells.

Amino Acid Sequence↗
PubMed1989

Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas.

Two distinct calcium-sensitive cell-cell adhesion molecules were identified in human epithelial tissues and carcinomas using two monoclonal antibodies raised against vulvar epidermoid carcinoma A-431 and human mammary carcinoma MCF-7 and selected on the basis of their activities to disrupt cell-cell adhesion. In immunoblot analysis, these antibodies, designated NCC-CAD-299 and HECD-1, detected main bands of Mr 118,000 and 124,000, respectively. Purified tryptic fragments of the antigen recognized by NCC-CAD-299 showed cross-reactivity with a rabbit antiserum against mouse P-cadherin, indicating that this molecule was the human homologue of P-cadherin. On the other hand, the antigen recognized by HECD-1 showed essentially the same tissue distribution pattern as E-cadherin in the mouse, suggesting that this molecule is the human homologue of E-cadherin. Availability of these monoclonal antibodies to human P- and E-cadherin allowed us to examine their distributions in human tissues immunohistochemically. Both antigens were detected in epithelial tissues, but they showed distributions that were distinct from each other. The antigen recognized by HECD-1 was expressed in almost all epithelial tissues, while distribution of the other one recognized by NCC-CAD-299 was restricted to the basal or lower layers of stratified epithelia in which both antigens were coexpressed. Moreover, immunohistochemical examination of 44 lung carcinomas showed that both molecules were coexpressed in all of them, and suggested that expression of P-cadherin was closely related to the differentiation of carcinoma cells.

Antibodies, Monoclonal↗
PubMed1989

Cadherin-mediated specific cell adhesion and animal morphogenesis.

Cadherins are a family of transmembrane glycoproteins which are responsible for Ca2+-dependent cell-cell adhesion. Each member of the family displays a unique pattern of tissue distribution. The expression of cadherin molecules in an embryo is spatiotemporally regulated so as to be associated with a variety of morphogenetic events. Antibodies against cadherins perturb the morphogenesis of tissues, indicating their importance in tissue formation. When cells were transfected with cDNAs encoding cadherins, they expressed the exogenous cadherin molecules and these were functional. Using these transfected cells, we tested whether each member of the cadherin family has a binding specificity, and found that cells preferentially adhere to those expressing the identical cadherin type. The cadherin-mediated specific adhesion also occurred in the attachment of neurites to the surface of other cells. These observations suggest that cadherins are crucial for the selective adhesiveness of cells, and thus for the embryonic morphogenetic processes in which specific adhesive interactions of cells are involved.

Animals↗
PubMed1989

Serum insulin-like growth factor II in chronic liver disease.

Insulin-like growth factor II is secreted primarily by the liver and is reported to be transcribed in many primary hepatocellular carcinoma (PHC) cell lines. We have studied diagnostic significance of serum IGF-II in chronic liver diseases using specific enzyme immunoassay. Serum IGF-II levels (mean +/- SE) were decreased in chronic hepatitis (538 +/- 51 ng/ml; N = 29), liver cirrhosis (427 +/- 45; 50) and PHC (260 +/- 41; 17) compared to controls (830 +/- 49; 57). Serum IGF-II was not different from controls in any of nonhepatic diseases such as diabetes (1032 +/- 97; 19) pancreatic cancer (1413 +/- 282; 8), chronic pancreatitis (999 +/- 126; 17), peptic ulcer (1186 +/- 43; 11), irritable bowel syndrome (1002 +/- 109; 12), gastrointestinal tract cancer (1250 +/- 216; 21) and chronic renal failure (733 +/- 135; 14). In liver diseases serum IGF-II showed a significant correlation with liver function test (negative with retention of indocyanine green and total bile acids; positive with albumin, thrombo-test, and cholinesterase). These results suggest that serum IGF-II reflects a reduced production of IGF-II in the liver and that it can be an index for the residual capacity of liver function.

Adult↗
PubMed1989

Monoclonal antibodies to chicken iodopsin.

The protein moiety of chicken iodopsin, R-photopsin, was purified from the chicken retina using a sucrose flotation method followed by two steps of column chromatography. Apparent molecular weights of R-photopsin and scotopsin (the protein moiety of chicken rhodopsin), which was partly purified in the process of purification of R-photopsin, were estimated to be 34,000 and 36,000, respectively, by sodium docecylsulfate-polyacrylamide gel electrophoresis. Using the purified R-photopsin as an antigen, four kinds of hybridoma cells which secreted monoclonal antibodies specific for R-photopsin and iodopsin were prepared. The antibodies thus obtained reacted with neither other chicken cone visual pigments nor rhodopsin as analyzed by immunoblots and immunoprecipitation methods. All the monoclonal antibodies stained the majority of the cone outer segments in chicken retina, while an antiserum raised against cattle rhodopsin stained the rod outer segments as well as some cone outer segments in the retina.

Animals↗
PubMed1989

Transmembrane control of cadherin-mediated cell adhesion: a 94 kDa protein functionally associated with a specific region of the cytoplasmic domain of E-cadherin.

Cadherins are a family of transmembrane glycoproteins which play a key role in Ca(2+)-dependent cell-cell adhesion. Cytoplasmic domains of these molecules are anchored to the cell cytoskeleton and are required for cadherin function. To elucidate how the function of cadherins is controlled through their cytoplasmic domains, we deleted five different regions in the cytoplasmic domain of E-cadherin. After transfecting L cells with cDNA encoding the mutant polypeptides, we assayed aggregating activity of these transfectants; all these mutant proteins were shown to have an extracellular domain with normal Ca(2+)-sensitivity and molecular weight. Two mutant polypeptides with deletions in the carboxy half of the cytoplasmic domain, however, did not promote cell-cell adhesion and had also lost the ability to bind to the cytoskeleton, whereas the mutant molecules with deletions of other regions retained the ability to promote cell adhesion and to anchor to the cytoskeleton. Thus, the cytoplasmic domain contains a subdomain which was involved in the cell adhesion and cytoskeleton-binding functions. When E-cadherin in F9 cells or in L cells transfected with wild-type or functional mutant cadherin polypeptides was solubilized with nonionic detergents and immunoprecipitated, two additional 94 and 102 kDa components were coprecipitated. The 94 kDa component, however, was not detected in the immunoprecipitates from cells expressing the mutant cadherins which had lost the adhesive function. These results suggest that the interaction of the carboxy half of the cytoplasmic domain with the 94 kDa component regulates the cell binding function of the extracellular domain of E-cadherin.

Animals↗
PubMed1989

Unstable expression of E-cadherin adhesion molecules in metastatic ovarian tumor cells.

E-Cadherin is a member of the cadherin family, which plays a key role in intercellular adhesion in various tumors as well as in normal tissues. Here, we examined the expression of this adhesion molecule in a murine ovarian tumor line OV2944, whose sublines show different degrees of spontaneous metastasis from subcutaneous sites; sublines LM-1 and LM-3 exhibit a low metastatic activity but a variant subline HM-1 has a high metastatic activity. When the expression of E-cadherin in these cells was examined by immunoblot analysis, the highly metastatic HM-1 cells was found to express an extremely small amount of this molecule, as compared with a high level of E-cadherin expression in the weakly metastatic LM-1 and LM-3 cells. Northern blot analysis showed that the amount of tanscripts from the E-cadherin gene is proportional to the amount of proteins detected in these cells. Immunofluorescence staining revealed that cells of the highly metastatic line were heterogeneous, that is, their cultures contained both E-cadherin-positive and negative cells. In contrast, cells of the weakly metastatic lines homogeneously expressed E-cadherin. When the highly metastatic line was subcloned, all the subclones consisted of E-cadherin-positive and negative cells. These results suggest that the expression of E-cadherin gene is not stably controlled in the highly metastatic line.

Animals↗