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T Miyata

Publications and source records attributed to T Miyata.

At least 757 records · Page 42Linked to original sources

Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes.

Immunoglobulin class switch involves a unique recombination event that takes place at the region 5' to each heavy chain constant region gene during B lymphocyte differentiation. Such regions that are responsible for the class-switch recombination are defined as S regions (Kataoka et al., Proc. Natl. Acad. Sci. USA 77, 919, 1980). We have cloned a rearranged gamma 2b gene from a mouse myeloma (MPC11) and compared its structure with the germ line counterparts. The rearranged gamma 2b gene contained the 5' flanking region of the gamma 3 gene (S gamma 3 region) which are linked to the 5' flanking region of the gamma 2b gene (S gamma 2b region). We have determined nucleotide sequences surrounding the recombination site of the rearranged and germ line gamma 2b genes, which include the S gamma 2b and S gamma 3 regions. Both gamma 2b and S gamma 3 regions comprise tandem repetition of conserved units of 49 bp. Similar 49 bp repeating units are also found in the previously determined sequence of the S gamma 1 region in which class-switch recombination took place in MC101 myeloma. The nucleotide sequences of the S gamma 1, S gamma 2b and S gamma 3 repeating units share significant homology with each other. The S mu region, partial nucleotide sequence of which was previously determined, contains abundant short sequences such as AGCT, TGGG and AGCTGGGG which are shared in common by repeating sequences in S gamma regions. These results suggest that the recombination responsible for class switch from mu to gamma or from a gamma to another gamma, may be facilitated directly or indirectly by homology of repeating sequences in S regions.

Animals↗

Rapidly evolving mouse alpha-globin-related pseudo gene and its evolutionary history.

The nucleotide sequences of a mouse pseudo alpha-globin gene and two adult alpha-globin genes from mouse and rabbit were compared. A close examination of sequence differences among the three genes revealed that the mouse pseudo alpha-globin gene was derived from one of the mouse alpha-globin genes about 24 million years ago by gene duplication and lost its original function, presumably due to loss of both the intervening sequences or frameshift mutations that prevented production of a functional globin polypeptide, and eventually became an inactive gene about 17 million years ago. After this event, this gene evolved at a very high rate, approximately 1.9 times the rate of synonymous codon change in productive genes. This suggests the presence of functional constraints against synonymous codon changes in normally functioning genes and also suggests that the "nucleotide arrangements" serve almost no important functions beside protein coding ability in the greater part of this gene, except for a very limited number of nucleotides. A continuous stretch of the pseudo alpha-globin gene consisting of a third exon and a 5' half of the 3' noncoding region shows marked sequence homology to the alpha-globin gene, suggesting transfer from one of the globin or globin-like genes by recombination very recently.

Animals↗

Novel models for RNA splicing that involve a small nuclear RNA.

Nucleotide sequences of mammalian small nuclear RNAs (snRNAs) have been analyzed with a computer program for complementarity with sequences around a splice junction of various eukaryotic mRNA precursors (pre-mRNAs). A region in U2 RNA or some other snRNAs can form base pairs with both exons surrounding an intron of certain pre-mRNAs and, thereby, can align the two junctions leading to correct splicing of the pre-mRNA. These findings suggest that a snRNA such as U2 can be involved in splicing certain pre-mRNAs by pairing with exons, which we we call an "exon model" for splicing, as compared with the model involving U1 RNA presented by Lerner et al. [Lerner, M. R., Boyle, J. A., Mount, S. M., Wolin, S. L. & Steitz, J. A. (1980) Nature (London) 283, 220-224]. We constructed a secondary structure model of U1 RNA and studied the capacity of base pairing with pre-mRNAs on the basis of both primary and secondary structures of U1 RNA. We present an alternative model for splicing that involves U1 RNA, which assumes base pairing of noncontiguous regions of U1 RNA with an intron of a pre-mRNA. Pairing of an snRNA with exons could explain correct matching of the two junctions that bound one and the same intron, which is not explained by pairing with consensus sequences at the ends of an intron as proposed by Lerner et al. Pairing of an intron with U1 RNA and pairing of the surrounding exons with another snRNA such as U2 RNA could take place at the same time to insure specificity of splicing.

Animals↗

Extraordinarily high evolutionary rate of pseudogenes: evidence for the presence of selective pressure against changes between synonymous codons.

Comparisons of nucleotide sequences of several pseudogenes described to date, including alpha- and beta-globin and immunoglobulin kappa-type variable domain pseudogenes, with those of functional counterparts revealed that pseudogenes accumulate mutations at an extremely high rate uniformly over their entirety. It is remarkable that the evolutionary rate exceeds the rate of changes between synonymous codons, the highest known rate, in functional genes. Because no pseudogenes appear to function, this result strongly supports the neutral theory. In addition this result apparently indicates the presence of selective pressure against changes between synonymous codons in functional genes. Close examinations of codon utilization patterns in pseudogenes and functional genes revealed a significant correlation between the rate of changes at synonymous codon sites and the strength of bias in code word usage. This implies that even synonymous codon changes are not completely free from selective pressure but are constrained in part, although presumably weakly, depending on the degree of bias in code word usage. We also reexamined alignment between mouse beta h3 (pseudogene) and beta maj sequences and found a unique structure of the beta h3 that is homologous in sequence to the beta maj gene overall but contains a long deletion (about 150 base pairs) in the middle of the gene.

Animals↗

Effects of cyclodextrins on chlorpromazine-induced haemolysis and central nervous system responses.

Cyclodextrins (CyDs) protected the human erythrocytes from haemolysis induced with chlorpromazine (CPZ) in isotonic solution, depending upon the magnitude of the stability constant of CPZ-CyD complexes (beta-greater than-gamma-greater than alpha-CyD). From the observations of CPZ uptake into erythrocytes and changes in surface activity of CPZ, the protective effects of CyDs in vitro appeared to be due to the decrease in effective haemolytic concentration of CPZ through inclusion complex formation rather than the direct interaction of CyDs with the erythrocyte membrane. The effect of beta-CyD on some central nervous system (c.n.s.) actions of CPZ in rats was also investigated to see if there were any advantages in the use of beta-CyD complexes given by injection. The results suggest that beta-CyD does not after the time-course or magnitude of the effects of CPZ on the c.n.s.

Animals↗

Mass fragmentographic analysis of piperidine levels in tissues of rats during development.

Piperidine levels in the brain and adrenal gland of rats during development were determined by mass fragmentography with deuterium-labeled piperidine as an internal standard. The levels in both organs showed distinct developmental changes, and two peaks were observed in association with the development of each organ. The initial peaks appeared in the early stage of development, that is, at the 19th day of gestation for the brain and 1 week after birth for the adrenal gland. The second peaks appeared at the age of sexual maturation (10 weeks after birth). The significance of the finding is discussed with respect to a presumed role of piperidine as a neuroendocrine modulator.

Adrenal Glands↗

Seasonal and activity-dependent variations of piperidine levels in the amphibian brain.

Piperidine is one of biogenic amines possessing nicotine-like synaptotropic actions on the nervous systems. Since piperidine produces multiplex physiological actions, a role for the amine as a modulator in neuroendocrine as well as neuronal functions has been supposed. In the present study, piperidine levels in the amphobian brains during activity and hibernation were examined by use of a mass fragmentographic technique and it was found that the brain piperidine concentrations significantly increased in the cold season especially during hibernation. The significance of the findings is discussed with respect to the hypnogenic effect of piperidine.

Animals↗

Electrophoretic study of pipecolic acid, a biogenic imino acid, in the mammalian brain.

Pipecolic acid (PA), one of the imino acids, is a normal constituent in the mammalian brain. It is said that PA is a major intermediate of lysine metabolism in the rat brain. Biochemical studies have suggested that PA may be involved in the regulation of synaptic mechanism in the CNS. Moreover, the pathophysiological significance of PA has been also suggested by some investigators. However, there has so far been no good evidence based on the comprehensive electrophysiological experiments. Using unit recording and microelectrophoretic technique, the action of PA on single neuron activities in the rat brain was examined. PA depressed the firing of 88 out of 115 cortical neurons tested. Only 2 were excited and 25 remained unaffected. All the identified hippocampal pyramidal neurons examined were uniformly inhibited. It has been reported that PA inhibits the uptake of GABA into the brain slices and enhances the release of GABA from the slices. Thus, it is likely that the inhibitory response due to PA may have some connections with GABAergic transmission. On the other hand, it remains to be clarified whether the specific PA sensitive receptors exist in the brain. Our findings provide a clue to the elucidation of the presumed synaptic involvement of PA in the CNS.

Animals↗

On the antisymmetry of the amino acid code table.

Antisymmetry of the amino acid code table in terms of codon degeneracy is pointed out, and it is related to a physico-chemical problem of codon-anticodon interaction energy. A strong negative correlation between molecular weight of an amino acid and its codon degeneracy is point out, and its implication to the origin of the amino acid code table is discussed. Finally, an earlier form of the amino acid code table is proposed.

Amino Acids↗

Molecular evolution of mRNA: a method for estimating evolutionary rates of synonymous and amino acid substitutions from homologous nucleotide sequences and its application.

A method for estimating the evolutionary rates of synonymous and amino acid substitutions from homologous nucleotide sequences is presented. This method is applied to genes of phi X174 and G4 genomes, histone genes and beta-globin genes, for which homologous nucleotide sequences are available for comparison to be made. It is shown that the rates of synonymous substitutions are quite uniform among the non-overlapping genes of phi X174 and G4 and among histone genes H4, H2B, H3 and H2A. A comparison between phi X174 and G4 reveals that, in the overlapping segments of the A-gene, the rate of synonymous substitution is reduced more significantly than the rate of amino acid substitution relative to the corresponding rate in the non-overlapping segment. It is also suggested that, in the coding region surrounding the splicing points of intervening sequences of beta-globin genes, there exist rigid secondary structures. It is in only these regions that the beta-globin genes show the slowing down of evolutionary rates of both synonymous and amino acid substitutions in the primate line.

Amino Acid Sequence↗

Nucleotide sequence divergence and functional constraint in mRNA evolution.

Comparison of about 50 pairs of homologous nucleotide sequences for different genes revealed that the substitutions between synonymous codons occurred at much higher rates than did amino acid substitutions. Furthermore, five pairs of mRNA sequences for different genes were compared in species that had diverged at the same time. The evolutionary rate of synonymous substitution was estimated to be 5.1 X 10(-9) per site per year on the average and is approximately constant among different genes. It also is suggested that this property would be suitable for a molecular clock to determine the evolutionary relationships and branching order of duplicated genes. Each functional block of the noncoding region evolves with a rate that is almost constant, regardless of the types of genes. The intervening sequence and the 5' portion of the 3' noncoding region show considerable divergence, the extent of which is almost comparable to that in the synonymous codon sites, whereas the other blocks consisting of the 5' noncoding region and the 3' portion of the 3' noncoding region are strongly conserved, showing approximatley half of the divergence of the synonymous sites. This strong sequence preservation might be due to the functional requirements for transcription and modification of mRNA.

Amino Acid Sequence↗

Nucleotide sequence divergence of mouse immunoglobulin gamma 1 and gamma 2b chain genes and the hypothesis of intervening sequence-mediated domain transfer.

The nucleotide sequences of the constant portions of mouse immunoglobulin gamma 1 and gamma 2b genes were compared. A remarkable homology was found in a long (about 500 nucleotides) continuous segment including the entire CH1 coding region and about the first half of the first intervening sequence. Furthermore, comparison of amino acid sequences of four gamma-class chains revealed that the CH1 domain shows limited divergence among gamma 1, gamma 2a, and gamma 2b. Interestingly, the homology region extends to the CH2 domain in gamma 2a and gamma 2b. These findings suggest that, during their evolution, a double unequal crossing-over event has taken place at different intervening sequences, resulting in the transfer of the DNA segment coding for the CH1 domain or CH1-CH2 domains. A possible evolutionary implication for such an "intervening sequence-mediated domain transfer" event is discussed.

Amino Acid Sequence↗

Spread of varicella in hospitalized children having no direct contact with an indicator zoster case and its prevention by a live vaccine.

Varicella spread from a child with zoster to a total of 3 susceptible infants in another room in a children's ward, although they had been strictly isolated. To prevent spread of the disease, the staffs and patients were doing their own washing and no source of natural infection could be found. The cases indicate that it is difficult to predict nosocomial varicella infection or to prevent spread of the disease simply by isolation in a children's ward. A total of 11 other children without history of varicella in the ward were given live varicella vaccine before or immediately after this event. None of these children developed symptoms of varicella and all the susceptible children who were vaccinated showed an antibody response.

Adolescent↗