Comparison of IMP-single photon emission computed tomography findings to Wechsler Intelligence Scale and Benton Visual Memory Scale.
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Adult↗
Biomedical subjects
M Watabe
Publications and source records attributed to M Watabe.
The X-gene of human hepatitis B virus transactivates the c-jun and alpha-fetoprotein genes.
The X-gene product of human hepatitis B virus is a transacting transcriptional factor which activates a variety of heterologous viral and host promoters/enhancers. We have found that the X-gene product can significantly transactivate the regulatory sequences located at the 5'-upstream of the c-jun oncogene when a reporter plasmid containing the sequences was co-transfected to HepG2 cells with an X-gene expression plasmid. The results of mutational analysis indicate that the X-gene activation requires the AP-1 sequence of the c-jun gene. Furthermore, we also found that the X-gene is capable of activating the 5'-upstream sequence of the alpha-fetoprotein gene. There are at least two elements that respond to the X-gene transactivation. One is located in the sequences between -5,100 and -2,900, and the other is at the C/EBP site. Therefore, the X-gene activates the c-jun and alpha-fetoprotein genes through different host factors, namely AP-1 and C/EBP, respectively. The results of c-jun activation by the X-gene strongly support the previous hypothesis that the X-gene may play a critical role in the development of hepatocellular carcinoma.
Base Sequence↗
Induction of polarized cell-cell association and retardation of growth by activation of the E-cadherin-catenin adhesion system in a dispersed carcinoma line.
PC9 lung carcinoma cells cannot tightly associate with one another, and therefore grow singly, despite their expression of E-cadherin, because of their lack of alpha-catenin, a cadherin-associated protein. However, when the E-cadherin is activated by transfection with alpha-catenin cDNA, they form spherical aggregates, each consisting of an enclosed monolayer cell sheet. In the present work, we examined whether the alpha-catenin-transfected cell layers expressed epithelial phenotypes, by determining the distribution of various cell adhesion molecules on their surfaces, including E-cadherin, ZO-1, desmoplakin, integrins, and laminin. In untransfected PC9 cells, all these molecules were randomly distributed on their cell surface. In the transfected cells, however, each of them was redistributed into a characteristic polarized pattern without a change in the amount of expression. Electron microscopic study demonstrated that the alpha-catenin-transfected cell layers acquired apical-basal polarity typical of simple epithelia; they formed microvilli only on the outer surface of the aggregates, and a junctional complex composed of tight junction adherens junction, and desmosome arranged in this order. These results indicate that the activation of E-cadherin triggered the formation of the junctional complex and the polarized distribution of cell surface proteins and structures. We also found that, in untransfected PC9 cells, ZO-1 formed condensed clusters and colocalized with E-cadherin, but that other adhesion molecules rarely showed such colocalization with E-cadherin, suggesting that there is some specific interaction between ZO-1 and E-cadherin even in the absence of cell-cell contacts. In addition, we found that the activation of E-cadherin caused a retardation of PC9 cell growth. Thus, we concluded that the E-cadherin-catenin adhesion system is essential not only for structural organization of epithelial cells but also for the control of their growth.
Cadherins↗
Serial changes of n-isopropyl-p-iodoamphetamine single photon emission computed tomography in two epileptic psychotics.
Serial changes of single photon emission computed tomography (SPECT) in two epileptic psychotics are reported. One patient had a decreased blood flow of the left temporal lobe with schizophrenia-like symptoms, and the other patient had a decreased blood flow of the right temporal lobe with depressive symptoms. In each case, these abnormal findings disappeared following recovery from a psychotic state. It might be suggested that the psychotic state of an epileptic patient influences the SPECT findings.
Adult↗
Cadherin-dependent organization and disorganization of epithelial architecture.
Epithelial cell layers exhibit an ordered polarized architecture. However, such structures are disrupted during malignant transformation, which generally coincides with a loss of regulate cell growth. We are investigating how the cadherin cell adhesion system controls these processes. Cadherins form a molecular complex with alpha-catenin, and beta-catenin or plakoglobin at the cytoplasmic side in normal cells. Lung carcinoma PC9 cells express E-cadherin. Although they express other catenins, they lack alpha-catenin and cannot firmly aggregate, suggesting that their E-cadherin is inactive. Transfection of the PC9 cells with alpha-catenin cDNA leads to activation of the E-cadherin, inducing their compact aggregation. In these aggregates, an almost complete epithelial-specific architecture is organized, including the formation of microvilli and a junctional complex. We also studied the effect of hepatocyte growth factor/scatter factor (HGF/SF) on cell-cell contacts in keratinocyte cell lines, and found that this growth factor can disrupt desmosomal cell-cell contacts. HGF/SF, and also epidermal growth factor, enhance tyrosine phosphorylation of beta-catenin or plakoglobin in human carcinoma lines as they induce scattering of these cells. These findings suggest that the cadherin adhesion system is central in organizing epithelial structures and that tyrosine phosphorylation of catenins may modulate this organization process.
Cadherins↗
Characterization of the 5'-flanking region of the hepatocyte growth factor gene.
The Hepatocyte growth factor is the most potent mitogen for hepatocytes in primary culture and is involved in liver regeneration. The expression of the gene appears to be tightly controlled by various humoral factors. To understand the molecular mechanism of the gene expression, we cloned and determined the nucleotide sequence of the 5'-flanking region of the gene. In this region, there are sequences homologous to responding elements of P53, Rb, IL-1, IL-6, glucocorticoids, TPA and TGF-beta. We also identified three major transcriptional initiation sites by primer extension analysis of this region. Functional analyses of this region by constructing CAT reporter plasmids indicate that the sequence functions in a tissue specific manner and there is a negative regulatory region which suppresses the gene expression in rat transformed kidney cells.
Animals↗
Carbamazepine and carbamazepine-10, 11-epoxide concentrations in rat brain and blood evaluated by in vivo microdialysis.
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Animals↗
Effect of hepatocyte growth factor on cadherin-mediated cell-cell adhesion.
Hepatocyte growth factor (HGF) is known to induce the dispersion of epithelial cells, as scatter factor. On the other hand, cadherins play a crucial role in connecting cells together. Two groups of cadherins are involved in epithelial cell adhesion, those locating in adherens junctions (AJ) and in desmosomes. Here, we examined the effect of HGF on the function of these cadherins in keratinocyte cell lines F and 308R, which expressed E- and P-cadherin in AJ (referred to as AJ cadherins) and desmoplakin in desmosomes. In the presence of HGF, these cells spread more extensively than in control cultures and their associations apparently loosened. However, they maintained cell-cell contacts where cadherins and desmoplakin concentrated, although the level of the concentration was reduced by HGF treatment. When antibodies to E- and P-cadherins were added to cultures of these cells without HGF, AJ cadherins were redistributed into non-junctional areas of the cells, but desmoplakin still localized at cell-cell boundaries. When HGF was added together with anti-AJ cadherin antibodies to the cultures, cell-cell contacts were now disrupted. In these cultures, not only AJ cadherins but also desmoplakin were lost at cell-cell contact sites, indicating that HGF can disrupt desmosomal cell-cell adhesion when AJ cadherins are inactive. These results suggest that, although HGF cannot block cadherin-mediated cell-cell adhesion when the entire cadherin system is intact, it might modulate the activities of cadherins, especially, of desmosomal cadherins.
Animals↗
Dynamic control of cell-cell adhesion for multicellular organization.
Cadherin cell-cell adhesion molecules are associated with cytoskeletal proteins, including alpha and beta catenin, and plakoglobin. This cadherin-catenin complex plays an indispensable role in construction of ordered multicellular structures such as polarized epithelium. alpha-catenin is crucial for the cell binding function of cadherins; without it, cells cannot use the cadherin adhesion system for their adhesion. beta-catenin and plakoglobin possibly play more regulatory roles, as it was shown that their tyrosine phosphorylation correlated with modified cadherin activities. The expression of some cadherin-associated proteins is controlled by the wingless/Wnt-1 signal in embryos. These regulatory mechanisms of cadherin function and expression may be involved in dynamic control of cell-cell contacts during morphogenesis, and even in certain processes of cell growth and differentiation.
Animals↗
Organ distribution and stability of phosphorothioated oligodeoxyribonucleotides in mice.
Results of recent studies in our laboratory have suggested a potential role for antisense oligodeoxyribonucleotides (oligo(dN)s) as therapeutic agents in the treatment of human hepatitis B virus infection. As a first step towards assessing the potential utility of oligo(dN) in therapy, we have examined the organ distribution, stability and toxicity of a phosphorothioated oligo(dN) (S-oligo) of 20 nucleotides in length which was administered to mice via different routes. Among the various organs analysed, the liver retained the highest amount of S-oligo (1.3-2 per cent of the total injection) at the peak time (10-30 min) regardless of the route of injection. However, the S-oligo appeared to be degraded in the liver to about 40 per cent of its original length within 30 min of injection, presumably by the action of 3' exonucleases. Injection of doses of up to 5 mg kg-1 of S-oligo had no apparent toxic effects on the mice.
Animals↗
Serial changes of SPECT in periodic synchronous discharges in a case with Creutzfeldt-Jakob disease.
We conducted serial EEG and SPECT studies on one female with Creutzfeldt-Jakob disease (CJD). In an analysis of EEG, a periodic synchronous discharge (PSD) was observed in the middle of the third stage (terminal stage) of Bernoulli's classification. The frequency of PSD was the highest at the beginning of the third stage, followed by a gradual decrease and disappeared at the end of the third stage. In the middle of the third stage, SPECT disclosed blood flow differences between the cerebrum and other regions (the cerebellum and the brainstem), while no such difference was observed by SPECT at the end of the third stage. It was suggested that the appearance of PSD requires the presence of a pathological change in the cerebrum precedent to other regions.
Aged↗
Hepatocellular carcinoma in children with hepatitis B surface antigen.
This study discusses four children of hepatocellular carcinoma (HCC) who were asymptomatic HBsAg carriers or had HBsAg-positive chronic hepatitis for 3 to 11 years before the occurrence of the carcinoma. Three of these four patients were positive for anti-HBe at 3 to 5 years before the diagnosis of hepatocellular carcinoma. Autopsy findings disclosed liver cirrhosis in all the four patients. To the best of our knowledge few reports have documented children in HBsAg carrier status or with HBsAg-positive hepatitis prior to the development of hepatocellular carcinoma. It is emphasized that HBsAg-positive children, with or without detectable hepatic lesions in routine examinations, have a possibility of developing HCC, and should be carefully monitored for long periods.
Adolescent↗
Binding of oligonucleotides to cell membranes at acidic pH.
Antisense oligodeoxynucleotides [oligo(dN)] have the ability to enter living cells and block the expression of specific genes. However, little is known about the mechanism of cellular uptake of oligo(dN). We have found that oligo(dN) can bind to the cell membranes of eukaryotic cells with much greater efficiency under acidic conditions (pH 4.0-4.5) than at neutral pH. The binding appears to be specific to poly nucleic acids since various sizes of oligo(dN), DNA and RNA, but not mononucleotides, compete for the binding. We have identified a 34 kDa membrane protein from T-cells, which binds to oligo(dT) cellulose at pH 4.5 and can be eluted at pH 7.5. This protein fraction blocked the binding of oligo(dN) to living T-cells in a competitive fashion. Our results suggest that eukaryotic cells have a receptor for oligo(dN) at acidic pH and that the 34 kDa dalton protein on the cell membrane may mediate such binding.
Binding Sites↗
Chronic pancreatitis in a child with glycogen storage disease type 1.
A case of chronic pancreatitis in an 8-year-old boy with glycogen storage disease type 1a (GSD 1a) is presented. This patient had a history of hyperlipidaemia unresponsive to dietary therapy, e.g., a carbohydrate-rich diet, uncooked cornstarch, and nocturnal intragastric tube feedings. He had recently suffered bouts of abdominal pain and diarrhoea. Serum amylase and trypsin were elevated, abdominal CT revealed the presence of a pseudocyst of the pancreas. The presence of chronic pancreatitis was confirmed by endoscopic retrograde cholangiopancreatography and an infected pseudocyst was removed at laparotomy.
Child↗
Abnormal results of biochemical liver function tests in breast-fed infants with prolonged indirect hyperbilirubinaemia.
To clarify the relationship between hyperbilirubinaemia and abnormal results of biochemical liver function tests in infants with breast milk jaundice (BMJ), 58 breast-fed infants with indirect hyperbilirubinaemia were enrolled in this study. Sera obtained from the above infants were subjected to routine liver function tests. Although serum transaminases were within normal limits in all 58 patients, serum alkaline phosphatase levels were abnormally increased in 13, gamma-glutamyltranspeptidase in 8 and total bile acids in 11 out of all patients examined. A total of 18 (31%) patients had abnormal results in at least one item of the liver function tests. The intrinsic bile acid loading test showed postprandial increases in bile acids in 5 of 16 (31%) patients examined at either 60 or 120 min, while all 13 breast-fed, age-matched controls had no abnormal results. The decrease in rate of serum bilirubin levels after the 3-day discontinuation of breast-feeding was significantly less in patients with increased fasting bile acids than in patients with normal fasting levels of serum bile acids. These results may suggest that mild hepatic dysfunction or cholestasis is associated with indirect hyperbilirubinaemia in some infants with BMJ.
Alkaline Phosphatase↗
Mutational analysis of enhancer domains responsive to trans-activation by the X gene of human hepatitis B virus.
The X gene product of human hepatitis B virus (HBV) trans-activates the HBV enhancer. In order to identify domains responsive to trans-activation by the X gene, we introduced a series of mutations into the HBV enhancer and assayed the enhancer activities in the presence of the X gene product. Our results suggest that the EP domain of the enhancer is essential for trans-activation by the X gene.
Base Sequence↗
Organ-specific distribution of isozymes of 5'-nucleotide phosphodiesterase in mouse.
1. The distribution of isozymes of 5'-nucleotide phosphodiesterase (E.C.3.1.4.1) was examined in various organs of mouse, including liver, spleen, pancreas, heart, lung, kidney, brain and blood. 2. Five isozymes were identified and designated as isozymes I through V. 3. These isozymes are distributed unevenly with respect to the various organs and clear differences were observed in the patterns of distribution among the organs examined. 4. The level of these isozymes was compared in serum of neonate and adult mice, and a higher level of isozyme I and a lower level of isozyme IV were found in neonates compared to adults. 5. These results suggest that each isozyme has different functional roles in individual organs and that these isozymes may be involved in proliferation and development of cells.
Animals↗
Fall and rise variations of serum GGTP in preoperative infants with biliary atresia.
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Biliary Atresia↗