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Biomedical subjects

C Sato

Publications and source records attributed to C Sato.

At least 271 records · Page 15Linked to original sources
PubMed1990

Changes in levels of microtubule-associated proteins in relation to the outgrowth of neurites from PC12D cells, a forskolin- and nerve growth factor-responsive subline of PC12 pheochromocytoma cells.

Immunoblotting analysis and immunofluorescence studies of proteins that react with MAP1- and MAP2-specific antibodies in PC12 rat pheochromocytoma cells were carried out. When cells of the PC12D subline of PC12 cells, which rapidly extend neurites in response to NGF or drugs that elevate intracellular levels of cyclic AMP, were examined, they were found to contain a relatively higher level of MAP1 or of a MAP1-like protein than conventional PC12 cells. Immunoblotting study showed that levels of MAP1 and MAP2 or of MAP1 or MAP2-like proteins increased in PC12D cells, but not in conventional PC12 cells, in response to forskolin. Immunofluorescence studies also revealed increases in levels of MAP1 and MAP2 or of MAP1 or MAP2-like proteins in conjunction with the outgrowth of neurites from the cells. These results support the hypothesis that the induction of MAPs may be one of the first steps required for outgrowth of neurites from PC12 cells. Furthermore, PC12D cells may contain a sufficiently high level of MAP1 or MAP1-like protein to permit the extension of neurites in the absence of the lag period normally required by PC12 cells. The MAP1 or a MAP1-like protein was localized in the cell soma and neurites. An increase of MAP2-specific immunoreactivity in perikarya was observed in the differentiated cells. After immunostaining with a monoclonal antibody that reacted with phosphorylated MAP1, intense fluorescence was seen in the growth cones of neurites. This observation supports the hypothesis that the phosphorylation of MAP1 or of a MAP1-like protein may play a regulatory role in the formation of neurites in growth cones.

Adrenal Gland Neoplasms↗
PubMed1990

Molecular nature of chromosome 5q loss in colorectal tumors and desmoids from patients with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP), which includes familial polyposis coli (FPC) and the Gardner syndrome (GS), is a genetically determined premalignant disease of the colon inherited by a locus (APC) mapping within 5q15-q22. To elucidate the role of 5q loss in FAP tumorigenesis, we analysed 51 colorectal tumors and seven desmoids from 19 cases of FPC and five GS patients, as well as 15 sporadic colon cancers. RFLP analysis revealed a high incidence of allelic deletion in hereditary colon cancers as well as in sporadic colon cancers with a peak at the APC locus. APC loss resulted primarily from interstitial deletion or mitotic recombination. Combined tumor and pedigree analysis in a GS family revealed loss of normal 5q alleles in three tumors, including a desmoid tumor, which suggests the involvement of hemizygosity or homozygosity of the defective APC gene in colon carcinogenesis and, possibly, in extracolonic neoplasms associated with FAP.

Adenomatous Polyposis Coli↗
PubMed1990

Effect of neonatal undernutrition upon cerebroside sulfate degradation in the developing rat brain.

In order to find out if the decreased accumulation of cerebroside sulfates observed in 21-d-old undernourished rats was in part the result of an increased rate of catabolism of these galactolipids, the in vivo degradation of brain cerebroside sulfates was studied in 18-d-old normal and undernourished rats. Two hours after the intracranial injection of the precursor (0 time), the animals were injected intraperitoneally with unlabeled sodium sulfate. Labeled cerebroside sulfates were measured in the brain up to 48 h after the chase. In normal animals, the radioactivity decreased at 24 h and 48 h to 55% and 41%, respectively, of the value obtained at 0 time. In undernourished animals, degradation was negligible, since the radioactivity attained at 0 time remained almost constant up to 48 h. The lack of in vivo degradation of cerebroside sulfates observed in the starved rats cannot be explained by a deficiency of Arylsulfatase A, since the pattern of activity of the enzyme was similar in both groups of animals.

Aging↗
PubMed1990

Cloning and nucleotide sequence of cDNA for Ki antigen, a highly conserved nuclear protein detected with sera from patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) produce autoantibodies against a variety of nuclear antigens including Ki antigen. Although anti-Ki autoantibodies were found in a significant number of SLE patients, the nature of Ki antigen is poorly characterized. By using anti-Ki serum as a probe we have cloned a bovine cDNA directing the synthesis in Escherichia coli of a polypeptide immunologically indistinguishable from the authentic Ki antigen. A homologous human cDNA was also cloned and its nucleotide sequence predicted the entire primary structure of a novel nuclear protein with a molecular weight of 29 508 and with highly hydrophilic and weakly acidic character. The gene is highly conserved not only in the coding region but also in the 3'-untranslated region. The bacterially produced Ki antigen would be valuable for diagnosis of SLE.

Amino Acid Sequence↗
PubMed1990

Heterosis for brain cerebroside synthesis in mice.

The (C57BL/6J X DBA/2J) F1 or B6D2F1 hybrid mice are known to exhibit a transitory hypermyelinating activity compared with their parental strains B6 and D2. These mice exhibit an elevated accumulation of cerebrosides in the brain which can be explained by an increase in their synthesis. Analysis of the two major cerebroside species indicated that the elevated content of total cerebrosides in the cerebellum and cerebrum of B6D2F1, as well as D2B6F1 hybrids, reflected an increased accumulation of the hydroxylated species. The UDP-galactose:ceramide galactosyltransferase (CgalT) activities in B6, D2 and hybrid mice were studied using as substrates alpha-hydroxy fatty acid (HFA)-containing ceramides or normal fatty acid (NFA)-containing ceramides (HFA- and NFA-CgalT activities, respectively). Both CgalT activities were found to be about 2 times higher in the cerebellum than in the cerebrum for all the strains studied. Before 20 days of age, the HFA-CgalT activities in B6D2F1, D2B6F1 and D2 mice were higher than in B6. However, at 20 days, there was no difference between B6 and D2 while the HFA-CgalT activity in the hybrids remained about 20% higher than in the parental strains. In contrast, no strain differences could be detected for the NFA-CgalT activity at all ages. The data suggest that the increased synthesis of brain cerebrosides in the B6D2F1 and D2B6F1 strains of mice could be largely accounted for by an increased HFA-CgalT activity.

Animals↗
PubMed1989

Establishment of a human malignant meningioma cell line with amplified c-myc oncogene.

A new cell line (KT21-MG1) has been established from a human malignant meningioma transplanted into nude mice. The cultured cells showed epithelial cell-like morphology and were positive immunohistochemically for vimentin as the original tumor. They have been grown continuously in vitro for more than 2 years. The population doubling time was about 24 hours at the 30th passage. The cells are capable of proliferating in soft agar medium and produced tumors in nude mice, the histologies of which were similar to the original patient-derived tumor. Analysis of cellular oncogenes showed that myc and fps were amplified approximately tenfold and threefold, respectively, in this cell line, whereas N-myc, L-myc, N-ras, K-ras, H-ras, abl, erbB2, Blym, src, raf-1, myb, and sis were not changed significantly. The amplification of myc was accompanied by an enhanced expression. Chromosome studies of cultured cells showed the monosomy of chromosome 22 that has been reported to be a specific abnormality in meningiomas.

Animals↗
PubMed1989

Ca2+-dependent deimination-induced disassembly of intermediate filaments involves specific modification of the amino-terminal head domain.

Peptidylarginine deiminase (proteinarginine iminohydrolase, EC 3.5.3.15) converted some arginine residues to citrulline residues in soluble vimentin, in a micromolar Ca2+-dependent manner and resulted in the loss of polymerization competence of the intermediate filament protein. When about 8 mol of residues/mol of vimentin were deiminated, there was a complete loss of filament forming ability. This enzyme also deiminated vimentin filaments which had been polymerized, and deimination of vimentin filaments resulted in filament disassembly. Similar results were obtained with other intermediate filaments such as desmin and glial filaments. High performance liquid chromatography and amino acid analyses of lysine-specific protease-generated fragments from deiminated vimentin (about 8 mol of citrulline/mol of vimentin) showed a differential deimination of three structural domains. The head domain was predominant. These observations suggest that the head domain strongly influences integrity of the intermediate filament.

Amino Acids↗
PubMed1989

Loss of constitutional heterozygosity in colorectal tumors from patients with familial polyposis coli and those with nonpolyposis colorectal carcinoma.

Familial polyposis coli (FPC) is an autosomal dominant tumorigenic disorder, the major gene of which is mapped to chromosome 5q. We searched for a gene loss in colorectal tumors from FPC patients, as related to tumorigenesis by inactivation of tumor suppression genes, using restriction fragment length polymorphism analysis. The findings were compared with those in the case of nonpolyposis colorectal carcinomas (NPCC). We examined specimens from 39 FPC patients, including 21 adenocarcinomas and 49 adenomas, and 23 colorectal carcinomas from 22 NPCC patients. For this, we used 53 polymorphic DNA markers on all autosomes. Frequent loss of heterozygosity in colorectal carcinoma from FPC patients was observed on chromosomes 5 (24%), 14 (20%), 17 (31%), 18 (40%), and 22 (35%) and also on chromosomes 5 (32%), 14 (30%), 17 (27%), 18 (20%), and 22 (19%) in NPCC. Although loss of heterozygosity in adenoma from FPC patients was observed on nine chromosomes, the frequencies were less than 7%. As we fractionated tumors only macroscopically, actual frequencies of loss of heterozygosity are probably somewhat higher. However, these results do suggest that tumor suppression genes for colorectal carcinoma may locate on chromosomes 5, 14, 17, 18, and 22 and that they may play a critical role in carcinogenesis in both FPC and NPCC patients.

Adenoma↗
PubMed1989

Protein kinase C phosphorylation of desmin at four serine residues within the non-alpha-helical head domain.

We reported that phosphorylation by either cAMP-dependent protein kinase or protein kinase C (Ca2+/phospholipid-dependent enzyme) in vitro induces disassembly of the desmin filaments (Inagaki, M., Gonda, Y., Matsuyama, M., Nishizawa, K., Nishi, Y., and Sato, C. (1988) J. Biol. Chem. 263, 5970-5978). For this subunit protein, Ser-29, Ser-35, and Ser-50 within the non-alpha-helical head domain were shown to be the sites of phosphorylation for cAMP-dependent protein kinase (Geisler, N., and Weber, K. (1988) EMBO J. 7, 15-20). In the present work, we identified the sites of desmin phosphorylated in vitro by other protein kinase which affects the filament structure. The protein kinase C-phosphorylated desmin was hydrolyzed with trypsin, and the phosphorylated peptides were isolated by reverse-phase chromatography. Sequential analysis of the purified phosphopeptides, together with the known primary sequence, revealed that Ser-12, Ser-29, Ser-38, and Ser-56 were phosphorylated by protein kinase C. All four sites are located within the non-alpha-helical head domain of desmin. Ser-12, Ser-38, and Ser-56, specifically phosphorylated by protein kinase C, have arginine residues at the carboxyl-terminal side (Arg-14, Arg-42, and Arg-59, respectively). Ser-29 phosphorylated by both protein kinase C and cAMP-dependent protein kinase has arginine residues at the amino and carboxyl termini (Arg-27 and Arg-33). These findings support the view that the head domain-specific phosphorylation strongly influences desmin filament structure; however, each protein kinase differed with regard to site recognition on this domain.

Amino Acid Sequence↗
PubMed1989

Domain- and sequence-specific phosphorylation of vimentin induces disassembly of the filament structure.

We reported that stoichiometric phosphorylation by either cAMP-dependent protein kinase or protein kinase C induces disassembly of vimentin filaments [Inagaki, M., Nishi, Y., Nishizawa, K., Matsuyama, M., & Sato, C. (1987) Nature 328, 649-652; Inagaki, M., Gonda, Y., Matsuyama, M., Nishizawa, K., Nishi, Y., & Sato, C. (1988) J. Biol. Chem. 263, 5970-5978]. In the present work, we attempted to identify the sites of vimentin phosphorylated by each protein kinase. Sequential analysis of the purified phosphopeptides, together with the known primary sequence, revealed that Ser-8, Ser-9, Ser-20, Ser-25, Ser-33, and Ser-41 were specifically phosphorylated by protein kinase C, whereas Ser-46 was phosphorylated preferentially by cAMP-dependent protein kinase. Both kinases reacted with Ser-6, Ser-24, Ser-38, Ser-50, and Ser-65. Specific phosphorylation sites for protein kinase C are mostly located close to the amino-terminal side of arginine while those for cAMP-dependent protein kinase are located close to the carboxyl-terminal side of arginine. The phosphorylation sites exclusively occur in the amino-terminal non-alpha-helical head domain, particularly at the beta-turn region. These results provide clues to the molecular mechanisms of phosphorylation-dependent disassembly of vimentin filaments.

Amino Acid Sequence↗
PubMed1989

Kg, a new low-frequency red cell antigen responsible for hemolytic disease of the newborn.

Hemolytic disease of the newborn in a Japanese infant led to studies which indicate that an antibody detected in the maternal serum is recognizing a hitherto unknown red cell antigen. The antigen, which we have named Kg, was found in two generations of the family and it is inherited as a Mendelian dominant character. The maternal serum failed to react with the red cells of more than 600 random Japanese blood donors, 64 red cell samples known to possess low-frequency antigens and all but one of 75 red cell samples known to lack high-frequency antigens without recognized low-frequency antigens. The father's red cells were tested extensively for established low-frequency antigens; only Dia was demonstrated and the maternal antibody was shown not to contain anti-Dia.

ABO Blood-Group System↗
PubMed1989

Resistance to oncogenic transformation in revertant R1 of human ras-transformed NIH 3T3 cells.

A flat revertant, R1, was isolated from human activated c-Ha-ras-1 (hu-ac-Ha-ras) gene-transformed NIH 3T3 cells (EJ-NIH 3T3) treated with mutagens. R1 contained unchanged transfected hu-ac-Ha-ras DNA and expressed high levels of hu-ac-Ha-ras-specific mRNA and p21 protein. Transfection experiments revealed that NIH 3T3 cells could be transformed by DNA from R1 cells but R1 cells could not be retransformed by Kirsten sarcoma virus, DNA from EJ-NIH 3T3 cells, hu-ac-Ha-ras, v-src, v-mos, simian virus 40 large T antigen, or polyomavirus middle T antigen. Somatic cell hybridization studies showed that R1 was not retransformed by fusion with NIH 3T3 cells and suppressed anchorage independence of EJ-NIH 3T3 and hu-ac-Ha-ras gene-transformed rat W31 cells in soft agar. These results suggest that the reversion and resistance to several oncogenes in R1 is due not to cellular defects in the production of the transformed phenotype but rather to enhancement of cellular mechanisms that suppress oncogenic transformation.

Animals↗
PubMed1989

Melanin production in cultured albino melanocytes transfected with mouse tyrosinase cDNA.

An attempt was made in the present study to express mouse tyrosinase cDNAs fused with the authentic genomic 5' non-coding flanking sequence in cultured albino melanocytes. One of the cDNA sequences, which expressed successfully and produced melanin pigments, was analyzed with respect to deduced amino acid sequence. Sequencing of the tyrosinase genomic gene revealed the existence of several sets of a characteristic structure which consists of a chain of two successive stem structures, CCAAT-homology and TATA box at its 5' non-coding region. It seems possible that this region represents the regulatory element of the tyrosinase gene. Unusually long GA cluster at 5' upstream region was also found.

Amino Acid Sequence↗
PubMed1989

[The effects of the viewpoints and observers' traits on the observational learning of altruistic behavior].

This study was to examine the changes of altruistic responses through observational learning (OL) in elementary school children (4th graders) with the conditions of the different viewpoints and observers' traits. The OL was the symbolic modeling of altruistic behavior by presentation of pictures with narration. All the stories had the same situation, but differed whether the actor behaved himself in an altruistic fashion to the object, or not. Observers' viewpoints were determined by the instruction: they were told to observe the story as if they were one of the characters and to pay attention to emotional responses or behavior of the character. The emphasis of each story corresponded to the viewpoint. Out of these eight combined experimental conditions six were performed. Traits were concerned with observers' impression, empathy, and evaluation of the story. The response measure was the change of rating between pre- and post-questionnaires through observation. The effect of OL was higher significantly when the viewpoint directed to the characters' emotion. Observers who reacted strongly to empathy and impression items showed higher altruistic changes.

Altruism↗
PubMed1989

Mechanism of increased hepatotoxicity of acetaminophen by the simultaneous administration of caffeine in the rat.

The simultaneous administration of caffeine has been shown to potentiate acetaminophen-induced hepatotoxicity. In the present study, the mechanisms of this effect were studied. Male Sprague-Dawley rats, fasted for 18 hr, were given acetaminophen (0.5 g/kg) and/or caffeine (0.1 g/kg) i.p. Two hours later, the depletion of hepatic reduced glutathione (GSH) induced by acetaminophen was more pronounced by the concomitant administration of caffeine, although the effect of caffeine alone on the hepatic GSH content was minimal at this dose. Covalent binding of a reactive metabolite of acetaminophen to hepatic proteins was increased by caffeine although the free acetaminophen content in the liver was not affected. In isolated rat hepatocytes prepared from normal animals, caffeine enhanced acetaminophen-induced GSH depletion and potentiated covalent binding of the reactive metabolite to cellular proteins. The extracellular release of GSH + oxidized glutathione was decreased by acetaminophen, and this decrease was potentiated further by the addition of caffeine. In the cells, the production of acetaminophen-GSH conjugate also was increased in the presence of caffeine, whereas that of glucuronide conjugate was decreased. In microsomes, NADPH-dependent production of acetaminophen-GSH conjugate was increased in the presence of caffeine. Thus, caffeine appears to potentiate acetaminophen-induced hepatotoxicity mainly by enhancing the production of a reactive metabolite of acetaminophen by mixed function oxidases. To what extend caffeine-induced GSH depletion plays a role is to be clarified.

Acetaminophen↗
PubMed1988

Increased formation of unintegrated viral DNA in skin fibroblasts from patients with familial polyposis coli shortly after infection with Kirsten murine sarcoma virus.

Skin fibroblasts from patients with familial polyposis coli (FPC) exhibit increased frequency of morphological transformation, anchorage-independent growth, and enhanced production of viral RNA and viral particles after infection with murine sarcoma virus(murine leukemia virus), MSV(MLV). These FPC fibroblasts form greater amounts of unintegrated viral DNA as compared to normal fibroblasts during the first 4 to 24 hr after infection with Kirsten MSV(KiMLV), suggesting that increased susceptibility of FPC cells to MSV is determined at an early stage of viral transformation. Several MSV-transformed clones of both FPC and normal fibroblasts, isolated from agarose gel, were non-producers having integrated viral genome which was expressed into viral RNA and rescued by infection with MLV.

Adenomatous Polyposis Coli↗