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Y Shimauchi

Publications and source records attributed to Y Shimauchi.

At least 19 recordsLinked to original sources

FGF signals are involved in the differentiation of notochord cells and mesenchyme cells of the ascidian Halocynthia roretzi.

Differentiation of notochord cells and mesenchyme cells of the ascidian Halocynthia roretzi requires interactions with neighboring endodermal cells and previous experiments suggest that these interactions require fibroblast growth factor (FGF). In the present study, we examined the role of FGF in these interactions by disrupting signaling using the dominant negative form of the FGF receptor. An FGF receptor gene of H. roretzi (HrFGFR) is expressed both maternally and zygotically. The maternally expressed transcript was ubiquitously distributed in fertilized eggs and in early embryos. Zygotic expression became evident by the neurula stage and transcripts were detected in epidermal cells of the posterior half of embryos. Synthetic mRNA for the dominant negative form of FGFR, in which the intracellular tyrosine kinase domain was deleted, was injected into fertilized eggs to interfere with the possible function of HRFGFR: Injected eggs cleaved and gastrulated the same as the control embryos. Analyses of the expression of differentiation markers in the experimental embryos indicated that the differentiation of epidermal cells, muscle cells and endodermal cells was not affected significantly. However, manipulated embryos showed downregulation of notochord-specific Brachyury expression and failure of notochord cell differentiation, resulting in the development of tailbud embryos with shorted tails. The expression of an actin gene that is normally expressed in mesenchyme cells was also suppressed. These results suggest that FGF signals are involved in differentiation of notochord cells and mesenchyme cells in Halocynthia embryos. Furthermore, the patterning of a neuron-specific tubulin gene expression was disturbed, suggesting that the formation of the nervous system was directly affected by disrupting FGF signals or indirectly affected due to the disruption of normal notochord formation.

Amino Acid Sequence↗

Synergistic action of HNF-3 and Brachyury in the notochord differentiation of ascidian embryos.

In vertebrate embryos, the class I subtype forkhead domain gene HNF-3 is essential for the formation of the endoderm, notochord and overlying ventral neural tube. In ascidian embryos, Brachyury is involved in the formation of the notochord. Although the results of previous studies imply a role of HNF-3 in notochord differentiation in ascidian embryos, no experiments have been carried out to address this issue directly. Therefore the present study examined the developmental role of HNF-3 in ascidian notochord differentiation. When embryos were injected with a low dose of HNF-3 mRNA, their tails were shortened and when embryos were injected with a high dose of HNF-3 mRNA, which was enough to inhibit differentiation of epidermis and muscle, no obvious ectopic differentiation of endoderm or notochord cells was observed. However, co-injection of HNF-3 mRNA along with Brachyury mRNA resulted in ectopic differentiation of notochord cells in the animal hemisphere, suggesting that HNF-3 acts synergistically with Brachyury in ascidian notochord differentiation. Notochord differentiation of the A-line precursor cells depends on inducing signal(s) from endodermal cells, which can be mimicked by bFGF treatment. Treatment of notochord precursor cells isolated from the 32-cell stage embryoswith bFGF resulted in upregulation of both the HNF-3 and Brachyury genes.

Amino Acid Sequence↗

Clinical characteristics of patients in their 40s with HCV antibody-positive hepatocellular carcinoma.

BACKGROUND: We investigated the clinical characteristics of hepatitis C virus (HCV) antibody-positive hepatocellular carcinoma (HCC) patients who developed HCC at a relatively young age. METHODS: Clinical characteristics of patients in their 40s were investigated and were compared with those of patients 50 years and older. The subjects were 648 HCC patients, 469 men (72%) and 179 women (28%), who were treated at our hospital between 1991 and 1997. RESULTS: No patient was under 40 years of age. Eighteen patients (3%) were in their 40s, 137 patients (21%) were in their 50s, 338 patients (52%) were in their 60s, 143 patients (22%) were in their 70s, and 12 patients (2%) were in their 80s. Fifteen of the patients (83%) in their 40s were male. The proportion of men in their 40s was higher than that of all men. Eight of the 15 men in their 40s (53%) were heavy drinkers, and 2 (14%) were habitual drinkers. Three of the 15 men (20%) were HBV carriers, and these 3 HBV carriers were not drinkers. The proportion of heavy drinkers and HBV carriers was significantly higher among the patients in their 40s than in the 60 patients randomly sampled from the patients 50 years of age and older. The mean ages of male patients with HCC who were heavy drinkers, habitual drinkers, occasional drinkers, or nondrinkers were 52.3, 58.9, 62.0, and 61.7 years, respectively. HCC occurred significantly earlier in heavy drinkers than in the other 3 groups. We compared laboratory data of the patients in their 40s with data of all of the patients of 50 years and older. Serum total bilirubin, prothrombin time, and platelet counts were significantly worse in the patients in their 40s. CONCLUSIONS: Logistic regression analysis revealed that heavy drinking and presence of HBV infection were independently related to HCV antibody-positive HCC development at a younger age.

Adult↗

Increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 with tumor dedifferentiation in hepatocellular carcinomas.

Destruction of the extracellular matrices is required for tumor invasion and metastasis. Matrix metalloproteinase-2 degrades type IV collagen and laminin, major components of the basement membrane. Membrane type 1 matrix metalloproteinase activates the latent form of matrix metalloproteinase-2. We studied changes in membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 expression in relation to the tumor differentiation of hepatocellular carcinomas. Activity of matrix metalloproteinase-2 was also evaluated in hepatocellular carcinomas and noncancerous tissues. Overall, 37 hepatocellular carcinomas were studied. Expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was determined by either immunohistochemistry (n=37) or in situ hybridization (n=6). Changes in membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 expression were evaluated in relation to tumor differentiation. Gelatinolytic activities were analyzed by gelatin zymography (n=4). Membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 were detected in hepatoma cells and stromal cells. In addition, these matrix metalloproteinases were detected in the same hepatoma cells. Increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was associated with tumor dedifferentiation. The active form of matrix metalloproteinase-2 was more strongly expressed by hepatocellular carcinomas than by noncancerous tissues. These findings indicate that increased expression of membrane type 1 matrix metalloproteinase and matrix metalloproteinase-2 was associated with tumor dedifferentiation, suggesting that these matrix metalloproteinases are intimately involved in the invasion of hepatocellular carcinomas.

Adult↗

Children in Japan and multimedia.

Many parents in Japan today are very concerned and have daily problems with their children over the following kind of issues concerning video games, multimedia, and similar devices. 1) Is children's enthusiasm for video games actually harming their growth (physically or mentally)? 2) Is there any way that video games can help children in the future? For example, will playing these games help children learn to use computers or develop their power of thought? 3) Will excessive enthusiasm for TV games undermine our basic lifestyle? Is the time they spend studying at home or playing outside actually decreasing? 4) Will the methods of communication brought about by computers, pagers, and cellular phones weaken human relations among children? 5) Will being immersed in a virtual world created by computers result in a diminished sense of reality? The causes of this uneasiness may be traced to parents' own anxieties and concerns about the exceedingly rapid growth of the "information society" of today, together with the fact that their children are directly caught up in the deluge of this information and multimedia society. The development of media has coincided with the growth of today's adults, but children are immersed in a media-filled environment from the day they are born. In Japan, there are now children who can play video games before even learning to write. No one can predict what kind of adults these children will grow to be in the future, and it is fair to say that the most parents and children in Japan are being tossed about on the waves of this information explosion. At this international symposium, we hope to hear the many views that are held around the world concerning children and multimedia.

Adult↗

Usefulness of ED036 kit for measuring serum PIVKA-II levels in small hepatocellular carcinoma.

As a tumor marker for hepatocellular carcinoma (HCC), serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) has high specificity, yet its sensitivity is relatively low, marking it less suitable to serve as an adjunct in the diagnosis of small HCC. Recently, the ED036 kit (Eisai, Tokyo, Japan), whose detection limit is approximately ten times superior to that of a conventional kit (Eitest MONOP II, Eisai) has been developed. In this study, serum PIVKA-II levels in serum samples from 83 patients with benign chronic liver diseases (CLD) and 129 patients with HCC were measured with those two kits. With the ED036 kit, the cut-off value was set at 40 mAU/ml. For PIVKA-II measured with the ED036 kit, sensitivity was 45.0%, specificity 92.8%, and accuracy 63.7%, when we discriminated patients with HCC from those with CLD without HCC. While maintaining a high specificity, of 92.8%, the ED036 kit showed a significantly higher sensitivity than the conventional kit (45.0% versus 27.9%; P < 0.0001). With patients who had HCC consisting of a single nodule 30 mm or less in diameter, the positivity rate for serum PIVKA-II with the ED036 kit was significantly greater than the rate with the conventional kit (21.4% versus 9.5%; P < 0.005). Thus, the ED036 kit was thought to be more useful than the conventional kit as a tumor marker for small HCC.

Adult↗

Autonomy of ascidian fork head/HNF-3 gene expression.

We have characterized the expression pattern of a class I fork head/HNF-3 gene (HrHNF3-1) of the ascidian Halocynthia roretzi. Zygotic HrHNF3-1 expression was detectable as early as the 16-cell stage, and the transcript was evident in blastomeres of the endoderm, notochord and mesenchyme lineages of the early embryos. After the late gastrula stage, HrHNF3-1 was also expressed in the presumptive spinal cord cells and some brain cells. The spinal cord of the ascidian tadpole consists of four layers of cells; the dorsal layer, two lateral layers and the ventral layer, the latter of which simply lies on the notochord. Cross-sections of in situ hybridized specimens showed that HrHNF3-1 was expressed in cells of the ventral layer, reminiscent of the floor plate of vertebrate embryos. In addition, we found autonomy in the initiation of early HrHNF3-1 expression, because the gene was expressed in blastomeres continuously dissociated from the first cleavage until the 16-cell stage.

Amino Acid Sequence↗

The ascidian genome contains another T-domain gene that is expressed in differentiating muscle and the tip of the tail of the embryo.

The vertebrate Brachyury (T) gene is transiently expressed in nascent and migrating mesoderm, in the differentiating notochord, and in the tail bud, reflecting its independent functions. In contrast, the expression of an ascidian Brachyury gene (As-T) is restricted to differentiating notochord. The present study revealed that the genome of Halocynthia roretzi contains another T-domain gene (As-T2) which encodes a divergent T-domain protein. The transient expression of As-T2 was detected in the endoderm- and muscle-lineage blastomeres of the early embryo and the transcript was retained by involuting and differentiating muscle cells until it became undetectable by the mid-tailbud stage. In addition, As-T2 was expressed transiently in cells that form the tip of the newly forming tail. Interestingly, the combined pattern of spatial expression of As-T and As-T2 appears to correspond to that of a single vertebrate Brachyury gene.

Amino Acid Sequence↗

A patient with hepatocellular carcinoma who underwent resection of the primary lesion 10 years ago and resection of a giant adrenal metastasis 8 and a half years later.

A 56-year-old male consulted us because of a palpable mass and pain of the left flank 8 and a half years after resection of hepatocellular carcinoma of the left lobe about 3 cm in diameter. Ultrasound examination of the abdomen demonstrated a tumor about 10 cm in diameter showing a mosaic of hyperechoic and hypoechoic areas on the upper pole of the left kidney. By angiography, the tumor was found to be supplied mainly by the inferior adrenal artery. PIVKA-II was increased. Adrenal metastasis of hepatocellular carcinoma was suspected, and adrenalectomy was carried out. No intrahepatic metastasis was noted. The tumor was histopathologically identified as a pseudo-glandular type of moderately differentiated hepatocellular carcinoma with a trabecular pattern similar to the primary lesion. In this patient, a resectable giant metastasis was observed only in the left adrenal gland and no intrahepatic metastasis was demonstrated 8 and a half years after resection of hepatocellular carcinoma. The patient has survived 10 years after the first operation. This case is considered to be important for evaluation of the treatment for distant metastasis of hepatocellular carcinoma.

Adrenal Gland Neoplasms↗

Ultrastructure of intracellular membranous system and intracellular transport of asialoglycoproteins in rat hepatocytes.

The ultrastructure of the intracellular membranous system in rat hepatocytes was observed three dimensionally with a scanning electron microscope using the aldehyde prefix osmium-dimethyl sulfoxide-osmium method. Intracellular organelles were clearly observed in three dimensions, and direct connection of tubular structures with the bile canalicular membrane was clearly seen. The transcellular pathway of asialoglycoproteins in isolated cultured rat hepatocytes was also investigated, by affinity cytochemistry, using gold-conjugated asialofetuin, under a transmission electron microscope. Gold particles were clearly seen not only in vesicles, endosomes and lysosomes, but also in the tubular structures. These results suggest that the tubular structures in rat hepatocytes directly participate in the transcellular transport of macromolecules. In addition, the frequent connections of tubular structures with the bile canalicular membrane indicate that these structures around the bile canaliculus may supply membrane components to the bile canalicular membrane.

Animals↗

Chemical modification of anthracycline antibiotics IV. Synthesis of new anthracyclines with trisaccharide.

The glycosidation products of O-alpha-L-cinerulosyl-(1 leads to 4)-O-(3-O-acetyl-2-deoxy-alpha-L-fucosyl)-(1 leads to 4)-alpha, beta-L-rhodosamine with aklavinone, daunomycinone, adriamycinone and carminomycinone were synthesized and the resulting products were deacylated, yielding anthracyclines having the trisaccharide. We further synthesized N-monomethyl and N-didemethyl derivatives of daunomycinone trisaccharide by photolysis with sunlight. 3"-O-Acyl derivatives of daunomycinone, carminomycinone and aklavinone glycosides showed a marked antitumor activity against L1210 leukemia in mice with ILS 110, 86 and 86%, respectively, while 3"-O-acetyladriamycinone glycoside was highly toxic with a ILS of 44%.

Animals↗