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Biomedical subjects

A Okamoto

Publications and source records attributed to A Okamoto.

At least 163 records · Page 9Linked to original sources
PubMed1992

[Genetic alterations in the genesis and development of ovarian cancer].

Genetic alterations of various cancers have been clarified by recent development of molecular biology. Multiple genetic alterations occur through the development of cancer. Both activation of proto-oncogenes and inactivation of tumor suppressor genes are important for the development of cancer. Alterations of oncogenes such as K-ras, c-erbB-2/HER-2/neu and c-myc, and those of tumor suppressor genes such as p53, RB and DCC have been reported in ovarian cancer. Allelic losses of the specific chromosomes, which suggest the existence of tumor suppressor genes on those chromosomes, also have been reported in ovarian cancer. Further studies on genetic alterations of ovarian cancer will clarify the mechanisms for the development of ovarian cancer and also will develop new methods for prevention, diagnosis and treatment in clinical.

Female↗
PubMed1992

Effects of metallothionein on mutagenicity and oxidation of quercetin.

The effects of four types of Zn/Cd-metallothioneins on the mutagenicity of quercetin in Salmonella typhimurium TA98 were studied. The four types of Zn/Cd-metallothionein used in this experiment were metallothionein I, metallothionein I/II and metallothionein II from rabbit liver and metallothionein I/II from horse kidney. All four of the metallothioneins enhanced the mutagenicity of quercetin. Metallothionein II from rabbit liver, in which Zn content was the highest of the four metallothioneins, enhanced the mutagenicity of quercetin most effectively. Metallothioneins as well as Zn/Cu-SOD prevented quercetin oxidation under aerobic conditions. The action of these metallothioneins, which enhances the mutagenicity of quercetin, was fairly proportional to the activity which prevents quercetin from being oxidized. Reduced glutathione did not enhance the mutagenicity of quercetin although it did inhibit the quercetin oxidation. These results suggest that metallothioneins have superoxide (O2-) scavenging ability and act as "SOD-like" proteins in vivo. A simple and reliable system to detect biological substances which have antioxidant activity for the superoxide (O2-) was devised.

Animals↗
PubMed1991

Allelic loss on chromosome 17p and p53 mutations in human endometrial carcinoma of the uterus.

To understand the involvement of allelic losses and inactivation of tumor suppressor genes for the development of endometrial carcinoma of the uterus (EC), 24 cases of EC were examined for loss of heterozygosity (LOH) using a total of 57 polymorphic DNA markers covering all 23 pairs of chromosomes. LOH was observed at 27 loci on 10 different chromosomes, i.e., chromosomes 1, 3, 6, 11, 13, 15, 17, 18, 20, and 21, but was not detected at loci on chromosomes 4, 5, 7, 9, 10, 12, 14, 16, and X. It was observed only in seven of 24 cases, and the other 19 cases did not show LOH at any loci examined, including five cases of tumors with a high proportion of adenomatous hyperplasia. Among seven tumors with LOH at one or more loci, five tumors showed LOH at loci on the short arm of chromosome 17. Furthermore, mutations of the p53 gene, which is located on the short arm of chromosome 17, were detected in three of these 24 tumors by a polymerase chain reaction-single strand conformation polymorphism analysis and subsequent DNA sequencing. In two of these three tumors, p53 mutations were accompanied by the loss of wild-type p53 alleles. These results suggest that inactivation of the p53 gene is involved in the development of EC as in the case of several other types of human cancers.

Alleles↗
PubMed1991

Frequent allelic losses and mutations of the p53 gene in human ovarian cancer.

The p53 gene on chromosome 17p is considered to be a tumor suppressor gene, and frequent mutations of the p53 gene have been found in a wide variety of human cancers. We examined 31 ovarian cancers for allelic losses and mutations of the p53 gene by polymerase chain reaction-single strand conformation polymorphism analysis as well as restriction fragment length polymorphism analysis. Allelic loss of the p53 gene was detected in 16 of 20 cases (80%). Mutations were detected in 9 of 31 cases (29%): 2 cases in exon 4; 5 cases in exons 5-6; and 2 cases in exons 7-8. In 8 of 9 cases, p53 mutations were accompanied by losses of the normal allele. These alterations of the p53 gene were commonly detected from stage I to stage IV. These results suggest that alterations of the p53 gene play an important role in the development of human ovarian cancers.

Base Sequence↗
PubMed1991

Site-directed mutagenesis of Escherichia coli aspartate aminotransferase: role of Tyr70 in the catalytic processes.

Site-directed mutagenesis of Tyr70 in the active site of Escherichia coli aspartate aminotransferase (AspAT) followed by kinetic studies has elucidated the roles of the hydroxyl group and benzene ring of Tyr70. X-ray crystallographic analysis showed that replacement of Tyr70 by Phe did not alter the active-site conformation of the enzyme. Comparison of the kinetic parameters of the four half-transamination reactions (the pyridoxal 5'-phosphate form of the enzyme with L-aspartate or L-glutamate and the pyridoxamine 5'-phosphate form with oxalacetate or 2-oxoglutarate) between the wild-type and [Tyr70----Phe]AspATs showed that the mutation increases the energy level of the transition state by 2 kcal.mol-1 for all the four substrates, suggesting some contribution of the hydroxyl group of Tyr70 to the transition state. When Phe70 was further replaced by Ser, the energy level of the transition state for L-glutamate or 2-oxoglutarate, but not for L-aspartate or oxalacetate, was further increased by 2-3 kcal.mol-1, suggesting that the presence of a benzene ring at position 70 is essential for recognizing the L-glutamate-2-oxoglutarate pair as substrates.

Amino Acid Sequence↗
PubMed1991

Thermostable aspartate aminotransferase from a thermophilic Bacillus species. Gene cloning, sequence determination, and preliminary x-ray characterization.

The gene encoding aspartate aminotransferase of a thermophilic Bacillus species, YM-2, has been cloned and expressed efficiently in Escherichia coli. The primary structure of the enzyme was deduced from nucleotide sequences of the gene and confirmed mostly by amino acid sequences of tryptic peptides. The gene consists of 1,176 base pairs encoding a protein of 392 amino acid residues; the molecular mass of the enzyme subunit is estimated to be 42,661 daltons. The active site lysyl residue that binds the coenzyme, pyridoxal phosphate, was identified as Lys-239. Comparison of the amino acid sequence with those of aspartate aminotransferases from other organisms revealed very low overall similarities (13-14%) except for the sequence of the extremely thermostable enzyme from Sulfolobus solfataricus (34%). Several amino acid residues conserved in all the compared sequences include those that have been reported to participate in binding of the coenzyme in three-dimensional structures of the vertebrate and E. coli enzymes. However, the strictly conserved arginyl residue that is essential for binding of the distal carboxyl group of substrates is not found in the corresponding region of the sequences of the thermostable enzymes from the Bacillus species and S. solfataricus. The Bacillus aspartate aminotransferase has been purified from the E. coli clone cell extracts on a large scale and crystallized in the buffered ammonium sulfate solution by the hanging drop method. The crystals are monoclinic with unit cell dimensions a = 121.2 A, b = 110.5 A, c = 81.8 A, and beta = 97.6 degrees, belonging to space group C2, and contain two molecules in the asymmetric unit. The crystals of the enzyme-alpha-methylaspartate complex are isomorphous with those without the substrate analog.

Amino Acid Sequence↗
PubMed1991

Enhancement of mutagenicity of 1-nitropyrene by water as a diluent.

The mutagenicity of 1-nitropyrene was strongly enhanced in the Salmonella mutagenicity test with the preincubation modification when it was dissolved in dimethylsulfoxide and diluted with water. The enhancement of mutagenicity was not found in the plate incorporation method and seemed to be common to chemicals which have low solubilities in water. The indications were that the effectiveness of preincubation modification was due to the increased absorption of test chemicals by the Salmonella cells, and that the absorption depends primarily on the solubility of test chemicals in the assay mixture.

Air Pollutants↗
PubMed1991

Lymphoplasmacytic sclerosing pancreatitis with cholangitis: a variant of primary sclerosing cholangitis extensively involving pancreas.

Pancreatic involvement in primary sclerosing cholangitis (PSC) is an extremely rare condition, and its pathologic features are poorly documented. We report two cases of an unusual lymphoplasmacytic sclerosing inflammatory disease involving the total pancreas, common bile duct, gallbladder, and, in one patient, the lip. Two elderly men presented with waxing and waning obstructive jaundice, and exhibited radiologic and ultrasonographic findings highly suggestive of pancreatic carcinoma. Gross appearance of the pancreas showed firm and mass-like enlargement with regional lymph node swelling. Histologic findings were characterized by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis and acinar atrophy, obliterated phlebitis of the pancreatic veins, and involvement of the portal vein. Similar inflammatory processes involved the bile duct and the gallbladder. Lymphoplasmacytic sclerosing pancreatitis with cholangitis is thought to be a more appropriate term for this condition, of which a similar lesion has been previously noted in a single case of "PSC involving pancreas". Differences in age, radiologic appearance, and the negative history of ulcerative colitis exist, but the two cases in this study could be considered as a variant of PSC extensively involving pancreas, which can readily be mistaken for pancreatic carcinoma.

Aged↗
PubMed1991

Genotoxicity of beryllium, gallium and antimony in short-term assays.

The genotoxicity of beryllium, gallium and antimony compounds was studied with the rec, Salmonella mutagenicity and SCE assays. In the rec assay, all the salts of the metals, BeCl2, Be(NO3)2, GaCl3, Ga(NO3)3, SbCl3, SbCl5, and an oxide, Sb2O3, had DNA-damaging activity. None of the compounds was mutagenic to Salmonella. In the SCE assays using V79 cells, 2 antimony(III) compounds, SbCl3 and Sb2O3, and 2 beryllium compounds, BeCl2 and Be(NO3)2, induced SCEs significantly. Sb2O3, slightly soluble in water, was positive in both the rec assay and the SCE assay at very low doses.

Animals↗
PubMed1991

Tyr225 in aspartate aminotransferase: contribution of the hydrogen bond between Tyr225 and coenzyme to the catalytic reaction.

Tyr225 in the active site of Escherichia coli aspartate aminotransferase (AspAT) was replaced by phenylalanine or arginine by site-directed mutagenesis. X-ray crystallographic analysis of Y225F AspAT showed that the benzene ring of Phe225 was situated at the same position as the phenol ring of Tyr225 in wild-type AspAT. The mutations resulted in a great decrease in the rate of the transamination reaction, suggesting that Tyr225 is important for efficient catalysis. The kinetic analysis of half-transamination reactions of Y225F AspAT with four substrates (aspartate, glutamate, oxalacetate, and 2-oxoglutarate) and some analogues (2-methylaspartate, succinate, and glutarate) revealed a considerable increase in the affinities for all these compounds. In contrast, affinity for the amino acid substrates was decreased by mutation to arginine, but affinities for the keto acid substrates and the two dicarboxylates (succinate and glutarate) were increased. The electrostatic interaction between O(3') of the coenzyme [pyridoxal 5'-phosphate (PLP)] and the residue at position 225 affected the pKa value of the Schiff base, which is formed between the epsilon-amino group of Lys258 and the aldehyde group of PLP; based on the spectrophotometric titration the pKa values were determined to be 6.8 for wild-type AspAT, 8.5 for Y225F AspAT, and 6.1 for Y225R AspAT in the absence of substrate. The absorption spectra of the three AspATs were almost identical in the acidic pH region, but the spectrum of Y225F AspAT differed from that of wild-type or Y225R AspAT in the alkaline pH region.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Structure and organization of the mouse acrosin gene.

The genomic region carrying the mouse acrosin gene, including the 5'-flanking sequence, has been isolated and characterized. The acrosin gene consists of five exons separated by four introns. Organization of this gene is very similar to those of the genes for other typical serine proteases, except for the phase class of the first intron. Riboprobe mapping and primer extension analyses showed that the start site of transcription initiation in the acrosin gene is heterogeneous, including three major sites. Thus, the structure and organization of the mouse acrosin gene are different from those of the human gene [Keime, S., Adham, I.M., & Engel, W. (1990) Eur. J. Biochem. 190, 195-200] in two respects: the number of transcription initiation sites and the phase class of the third intron. The putative promoter regions of the mouse and human acrosin genes lack typical sequences of TATA, CAAT, and GC boxes, but contain a consensus sequence, GGGTGGG, known to be specific for the phosphoglycerate kinase-2 gene, and the protamine-1 and 2 genes that are uniquely expressed during spermatogenesis.

Acrosin↗
PubMed1991

Metabolism of sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate in hamsters.

Metabolism of sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate, the sulfonate derivative of chenodeoxycholic acid, was studied in hamsters. In bile fistula hamsters, the sulfonate analogue was efficiently absorbed from the ileum and secreted rapidly into the bile without any modification such as conjugation. However, absorption from the jejunum was smaller than that observed for the ileum. After oral administration, the sulfonate analogue of chenodeoxycholic acid was recovered quantitatively in the feces as the unchanged form in contrast to simultaneously administered chenodeoxycholic acid, which was entirely converted to lithocholic acid during its passage through the intestinal tract. These results demonstrate that the sulfonate analogue is absorbed mainly from the ileum by active transport, enters the enterohepatic circulation like the endogenous conjugated bile acids, and completely resists bacterial degradation.

Animals↗
PubMed1991

Postoperative magnetic resonance imaging in patients with cervical myelopathy.

Magnetic resonance imaging using T1-weighted sagittal images was performed on 81 postoperative patients with cervical myelopathy. Cord compression was observed after surgery in 32 (40%) of the patients. Compression was demonstrated in the decompressed area in 9 patients, at the upper or lower edge of decompression in 11 patients, and at adjacent levels of fusion in 11 patients. The remaining patient had cord compression in both the decompressed area and at the adjacent level. From their operative results, cord compression was proved to be functionally innocuous in 13 (41%) patients and the cause of neurologic deterioration in 3 (9%); it was not clear whether or not the compression was innocuous in the remaining 16 (50%) patients.

Adult↗
PubMed1991

Intraoperative monitoring for tethered spinal cord syndrome.

Functions of the lower extremities and bowel and bladder must be monitored during releasing surgery for tethered spinal cord syndrome, because neural elements are embedded in lipoma or anomalous tissues. Evoked muscle action potentials of the external anal sphincter muscle, external urethral sphincter muscle, and lower extremity muscles can indicate promptly whether or not neural elements are involved before the surgeon releases or cuts the tissue for cord release. It is also important to monitor vesical pressure because of different types of innervation from the external urethral and anal sphincters, in spite of slow reaction times of vesical pressure elevation. Evoked muscle action potentials indicate only motor function; therefore, it is more appropriate to record evoked spinal cord potentials from the spinal cord above a lumbosacral operative field, because sensory function can also be monitored. Evoked muscle action potentials are an easy and extremely sensitive monitoring system; nevertheless, monitoring of vesical pressure and evoked spinal cord potentials should also be done to achieve optimum monitoring. For the past 5 years, 10 patients have undergone cord-release surgery with such a monitoring system, and the results indicate no exacerbating case.

Adolescent↗
PubMed1991

Relation between nucleolar size and growth characteristics in small cell lung cancer cell lines.

Relationships among cytological features, doubling time, S-phase percentage, expression of myc-family oncogenes, DNA ploidy and biochemical properties were studied in thirteen small cell lung cancer cell lines. Six cell lines that grew slowly (average doubling time 99 h) and had lower S-phase percentages (average 32%) showed inconspicuous nucleoli (average area of 1.5 microns 2), and the remaining seven cell lines that grew quickly (average doubling time 45 h) and had higher S-phase percentages (average 44%) showed large and prominent nucleoli (average area of 6.1 microns 2). DNA index value obtained from flow cytometric DNA histograms showed that all cell lines except for H-69 cell line displayed aneuploidy. Ribbon-like cell arrangements were observed in the 7 cell lines that grew quickly, and in 1 cell line that grew slowly. Biochemically, six slow-growing cell lines and four fast-growing cell lines showed high levels of aromatic L-amino acid decarboxylase activity, while in the remaining three fast-growing cell lines its level was low. A high level of c-myc or N-myc oncogene expression was observed in all 7 cell lines that grew quickly, but not in any of the 6 cell lines that grew slowly. It appears that small cell lung cancer cell lines that grow quickly can be expected to have large nucleoli and ribbon-like cell arrangements and to express high levels of myc-family oncogenes, and that nucleolar size is a good indicator for growth characteristics.

Animals↗
PubMed1991

Preparations, solution conformation and molecular structures of N,N'-ethylene-bridged dipeptides and their derivatives.

The solution conformations of novel dipeptides, methyl (2S, 3'S)-3-methyl-2-(2'-oxo-3'-isopropyl-1'-piperazinyl)-butanoate (EVV-OCH3), methyl (2S, 3'S)-3-phenyl-2-(2'-oxo-3'-benzyl-1'-piperazinyl) propionate (EFF-OCH3), and their derivatives (Boc-Gly-EVV-OH, Boc-Gly-EVV-Gly-OH, and Boc-Gly-EFF-OH), were studied by 1H NMR measurements and molecular mechanics calculations (1). The molecular structures of Boc-Gly-EVV-OH, Boc-Gly-EFF-OH, and the hydrochloride of EVV-OCH3 were determined by X-ray analyses. The conformations of the piperazinone rings and the side chains of these oligopeptides were clarified.

Chemical Phenomena↗