Search PubMedSearch

Biomedical subjects

Y Tagashira

Publications and source records attributed to Y Tagashira.

At least 19 recordsLinked to original sources

Esophageal cancer in Shanxi Province, People's Republic of China: a case-control study in high and moderate risk areas.

Dietary, smoking, and drinking habits, as well as sociopsychological factors and familial history, were investigated in a case-control study on the etiology of esophageal cancer (EC) in two areas of Shanxi (Yangcheng and Linfen), north central China. Data were analyzed from 326 cases and 396 controls. We identified several factors associated with high or low risk; some were common across the areas and others were area-specific. Consumption of millet gruel was associated positively with EC, in a dose-response relationship. An increase in EC risk was seen for consumption of millet soup with noodles, and also with certain sociopsychological factors, in both areas. A large increase in risk was found with consumption of boiled vegetables in Linfen, with a dose-response relationship. EC risk tended to become greater with the increasing intake of moldy foods and of pickled vegetable juice. A positive association between EC risk and family history of EC was observed only in Yangcheng. Soybean consumption was found to be associated with reduced risk. Dental hygiene (brushing teeth) was associated with reduced risk in Linfen. There was a suggestion of increased risk associated with heavy tobacco smoking, but it was not significant in either area. Alcohol consumption had a marginally significant association with risk in the high risk area, but not in Linfen.

Adult

[Immunohistochemical Study of 3-methylcholanthrene inducible cytochrome P-450 in the stomach and liver--a guide of postoperative chemotherapy in gastric cancer].

Immunohistochemical determination of 3-methylcholanthrene (MC) inducible cytochrome P-450 (MC-P-450) was investigated in rat and human tissue, and its clinical availability was discussed. Induced by MC, MC-P-450 in rat liver and stomach was well stained immunohistochemically, showing clear contrast against control without induction. The staining intensity in the tissue was correlated with the amount of tissue MC-P-450 which was determined previously by electrophoretical and biochemical technics. By the same immunohistochemical method MC-P-450 in human liver and stomach was also detectable. The staining grade of MC-P-450 in human liver and stomach was different from each person. However, its intensities in liver and stomach in the same individual showed clear correlation with p less than 0.02. Since MC-P-450 in liver plays a major role in drug metabolism, the proof of correlation between staining degree of the resected stomach and hepatic tissue would provide useful clue in gastric cancer for postoperative administration of masked compounds activated by MC-P-450.

Animals

Nuclear but not mitochondrial genome involvement in 3-methylcholanthrene-induced expression of tumorigenicity in mouse somatic cells.

The involvement of heritable modifications of mitochondrial DNA (mtDNA) in chemical carcinogenesis was examined by studies on the effects on tumorigenicity of interchange of mtDNA between 3-methylcholanthrene (MCA)-induced mouse tumor cells and nontumorigenic mouse cells by the cytoplast-to-cell fusion technique. The difference in propagating abilities of two types of mouse mtDNA, type 1 mtDNA of B10mtJ strain and type 2 mtDNA of C57BL/10 strain, was applied successfully for complete replacement of the host cell mtDNA by cytoplasmically transmitted mtDNA. Tumorigenicity was assayed in nude mice by inoculating 5 x 10(6) cells s.c. into the backs of the mice. The results showed that tumorigenicity was not induced in nontumorigenic cells by replacement of their mtDNA by that from MCA-induced tumor cells. Moreover, the tumorigenicity of MCA-induced tumor cells was still expressed when their mtDNA was replaced by that from normal cells with a limited life span. These observations suggest that, even if MCA treatment causes heritable modifications of mtDNA, modified mtDNA cannot induce chemical carcinogenesis and that modifications of nuclear DNA alone are sufficient for the expression of tumorigenicity.

Animals

Hybrid origin of Japanese mice "Mus musculus molossinus": evidence from restriction analysis of mitochondrial DNA.

The Japanese mouse, Mus musculus molossinus, has long been considered an independent subspecies of the house mouse. A survey of restriction-site haplotypes of mitochondrial DNA (mtDNA) showed that Japanese mice have two main maternal lineages. The most common haplotype is closely related to the mtDNA of the European subspecies M. m. musculus. The other common haplotype and two minor ones are closely related to each other and to the mtDNA of an Asiatic subspecies, M. m. castaneus. Two other rare variants are probably the result of recent contamination by European M. m. domesticus. The musculus type of mtDNA is found in the southern two-thirds of Japan, whereas the common castaneus type is found in the northern third and the minor variants are found sporadically throughout Japan. The castaneus mtDNA lineage had a few minor variants, whereas the musculus lineage was completely monomorphic. By contrast, the native population of M. m. castaneus and the Chinese and Korean musculus populations were highly polymorphic. These results suggest that M. m. molossinus is a hybrid between ancestral colonies, possibly very small, of M. m. musculus and M. m. castaneus, rather than an independent subspecies.

Animals

[Clinical study on the effect of chemotherapy in the treatment of pancreatic cancer].

The effect of chemotherapy in the treatment of pancreatic cancer was evaluated on the basis of prognosis in 299 patients treated at the Kobe University Hospital and the Interhospital Cooperative Study Group for Multidisciplinary Approaches to Treatment of Pancreatic and Biliary Cancer. One hundred forty-three patients with pancreatic cancer were treated with a number of chemotherapeutic agents, while ninety-eight patients did not receive any chemotherapy. There were no significant differences in clinical characteristics between the two groups. The treated patients had a median survival time of 6 months and a one-year cumulative survival rate of 25.3%. These were significantly different compared with figures of 3 months and 9.5% for non-treated control patients. A chemotherapy regimen consisting of fluoropyrimidines was also confirmed to be effective. These results suggest that the chemotherapeutic approach appears quite promising and is effective for the treatment of pancreatic cancer.

Antineoplastic Combined Chemotherapy Protocols

Mitochondrial genomes in intraspecies mammalian cell hybrids display codominant or dominant/recessive behavior.

A unique type of nonstochastic mitochondrial DNA (mtDNA) segregation was found in mammalian cells. In human cell hybrids isolated from the fusion of HeLa cells with 23, GM639, A549, or 293 cells, HeLa mtDNA was always lost from the hybrids, whereas both parental mtDNAs were maintained in hybrids of HeLa X 143BTK-. Similar phenomena were observed in mouse cell hybrids isolated by the fusion of cells with different mtDNA types. Types 1, 2, and 3, can be distinguished from each other by restriction fragment-length polymorphisms. The mouse cell hybrids between cells with type 1 and type 2 mtDNA always lost type 2 mtDNA, whereas the hybrids between cells with type 2 and type 3 mtDNA retained both types stably. These observations suggest that either a codominant or a dominant/recessive relationship may be present in intraspecies mitochondrial genomes of human and mouse cells. When the mitochondrial genomes in cell hybrids are codominant, stochastic segregation occurs while nonstochastic segregation occurs when they are in the dominant/recessive relationship. These concepts may help elucidate organelle heredity in animals.

Animals

[The role of cytochrome P-450 in chemical carcinogenesis--its application to human cancer epidemiology].

Most chemical carcinogens require metabolic activation before they exert their deleterious effects on an organism. This overview shows the evidence that most chemical carcinogens are metabolically activated by specific P-450 isozymes and the induction of these enzymes plays an important role in chemical carcinogenesis. On the other hand, there is circumstantial evidence from a large number of animal experiments implicating that human susceptibility to environmental cancer may be affected by genetic predisposition for drug metabolism. On the basis of these findings, several problems in application to human cancer epidemiology were pointed out.

Animals

Structure and drug inducibility of the human cytochrome P-450c gene.

A human genomic clone (lambda hP-450mc-1), highly homologous to the rat cytochrome P-450c gene, was isolated and analyzed for the complete nucleotide sequence. The gene structure coincides with that of a recently reported human gene isolated from genomic DNA of a human breast carcinoma cell line, MCF-7 [Jaiswal, A.K., Gonzalez, F.J. & Nebert, D.W. (1985) Nucleic Acids Res. 13, 4503-4520] with notable exceptions in the first intron: a 320-base-pair fragment is inserted and a 650-base-pair fragment is deleted in the gene examined in the present study. The 320-base-pair insert appears to contain a moderately repetitive sequence (approx. 140 copies) in the human genome. The 650-base-pair fragment, present in intron 1 of the reported sequence, is dislocated in the lambda hP-450mc-1 to about 10(4) base pairs upstream from the putative transcription initiation site. The results of Southern blot analysis using human total DNA were compatible with the gene structure of lambda hP-450mc-1. A fusion gene, which was constructed by ligating the 5' flanking region of the gene to the structural gene for prokaryotic chloramphenicol acetyltransferase (CAT), inducibly expressed the CAT activity in mouse Hepa-1 cells in response to administered methylcholanthrene, indicating that the isolated human gene is indeed of methylcholanthrene inducibility.

Acetyltransferases

Sequence search on a supercomputer.

A set of programs was developed for searching nucleic acid and protein sequence data bases for sequences similar to a given sequence. The programs, written in FORTRAN 77, were optimized for vector processing on a Hitachi S810-20 supercomputer. A search of a 500-residue protein sequence against the entire PIR data base Ver. 1.0 (1) (0.5 M residues) is carried out in a CPU time of 45 sec. About 4 min is required for an exhaustive search of a 1500-base nucleotide sequence against all mammalian sequences (1.2M bases) in Genbank Ver. 29.0. The CPU time is reduced to about a quarter with a faster version.

Amino Acid Sequence

Maternal contamination of some NZB sublines and genetic profiles of NZ-strains.

Six sublines of NZB mice bred in Japan were collected and their mitochondrial DNA (mtDNA) was examined by restriction analysis. The phenotypes of at least three of these sublines (NZB/Nrs, NZB/Nga and NZB/KlJms) differed from a standard one (NZB/BlWehi). Since mtDNA is inherited maternally, all sublines of a single inbred strain should share the same mtDNA phenotype. Therefore, b-type of mtDNA should be observed in all NZB sublines. Nevertheless, the above-mentioned sublines showed d-type mtDNA. These results suggested a genetic contamination of these sublines. This was confirmed by the finding that six aberrant alleles were detected also in their nuclear genomes using biochemical markers. For elucidation of the cause of contamination, we characterized the genetic profiles of four standard NZ-strains, NZB/BlWehi NZO/BlWehi, NZC/BlWehi and NZX/BlWehi, and of common inbred strains with black coat color, C57BL/6J, C57BL/10Sn, C57BL/Ks, C58/J and AU/SsJ. We found that five of the six aberrant alleles most strongly corresponded with those of C57BL/Ks. These results suggest that this contamination was ascribable to cross of NZB mice with a certain C56BL strain. We also deduced that NAB/BlPt and NZB/Füll also probably were contaminated strains, suggesting that this contamination was not restricted to Japan.

Alleles

Possible steroid binding site common to adrenal cytochrome P-450scc and prostatic steroid binding protein.

By searching the entire PIR-protein-sequence data base, we have found that a dodecapeptide sequence in bovine adrenal cytochrome P-450scc is closely related to that in rat prostatic steroid binding protein. The two proteins belong to unrelated protein families, but both have steroids as substrates or ligands. Thus, the dodecapeptides may be important for substrate/ligand recognition in the individual proteins.

Adrenal Glands

Absence of extensive recombination between inter- and intraspecies mitochondrial DNA in mammalian cells.

Recombination of mammalian mitochondrial DNA (mtDNA) was examined using mouse X rat somatic cell hybrid clones and rat cybrid clones. The mouse X rat hybrids were isolated by fusion of chloramphenicol-sensitive (CAPs) mouse and CAP-resistant (CAPr) rat cells. The rat cybrids were isolated by fusion of rat cells with type B mtDNA and enucleated cells with type A mtDNA. Genetic and physical analyses showed that the mtDNAs of the hybrids and cybrids were simple mixtures of the two parental mtDNAs except in the following two cases: One was subclone H2-9 of mouse X rat hybrids, which was CAPr even though mtDNA from the CAPs mouse parent was predominantly retained. The other was rat cybrid subclones, Y12-24 and -61, which showed specific loss of one Hinf I fragment of type B mtDNA, B10. These observations suggest that, in contrast to the case with plant mtDNA, recombination of mammalian mtDNA occurs rarely, if at all.

Animals

Titration of mRNAs for cytochrome P-450c and P-450d under drug-inductive conditions in rat livers by their specific probes of cloned DNAs.

By sequence analysis of the cloned cDNA or genomic DNA, we have recently deduced the complete primary structures of two forms of 3-methylcholanthrene-inducible cytochromes P-450 (P-450c and P-450d). Comparing these sequences, we identified two highly conserved regions, amino acid numbers from 35 to 200 and from 340 to 470. The nucleotide sequences corresponding to these homologous regions are also well conserved, whereas other regions have undergone considerable sequence divergence. In RNA blot analysis with unfractionated mRNA isolated from 3-methylcholanthrene-treated rat livers, Probe A (specific to P-450c sequence) hybridized with mRNA around 23 S, while Probe B (specific to P-450d sequence) hybridized with mRNA around 18 S. When common sequence between P-450c and P-450d was used as the probes (Probe C or D), two bands were clearly observed around 23 and 18 S mRNAs. With the common DNA sequence between P-450c and P-450d as a probe (93.7% homology), we studied the induction of specific mRNA for P-450c and P-450d by a single dose of several chemical compounds to rats. 3-Methylcholanthrene increased both P-450c and P-450d mRNA levels by 50 and 10 times above the control at 17 h after the administration, respectively. Despite the lower induction rates, the P-450d mRNA level was constantly higher than or at least similar to that of P-450c mRNA. beta-Naphthoflavone and Kaneclor KC 500 showed similar induction ability to 3-methylcholanthrene. On the other hand, isosafrole induced P-450d mRNA to a much greater extent than P-450c mRNA.

Animals

Isolation and characterization of intraspecific cybrids. Effect of mitochondrial DNA on their cellular properties.

Cybrid clones were obtained by fusing whole cells of rat glioma C6BU-1, resistant to 5-bromodeoxyuridine (BrdU), with cytoplasts of embryonic rat 3Y1CAP cells, resistant to chloramphenicol (CAP), in selective medium with BrdU and CAP. The clones resistant to BrdU and CAP were confirmed to be cybrids by chromosome and mtDNA analyses. More than half the mtDNA of all the cybrid clones was from the 3Y1CAP cells. After cultivation of a cybrid clone Y22 for 3 months in the absence of CAP, subclones were isolated. One subclone Y22-22 contained predominantly mitochondrial DNA (mtDNA) from the 3Y1CAP cells. Using this subclone, the effects of the mitochondrial genome on cellular properties were examined. The growth patterns, expression of glioma-specific beta-adrenergic receptor, and composition of the major proteins of C6BU-1 cells were not affected by transmitted mtDNA from the 3Y1CAP cells. This procedure for isolating cells containing predominantly foreign mtDNA will be useful in studies on the interaction between genomes of the mitochondria and nucleus.

Animals

Coding nucleotide sequence of 3-methylcholanthrene-inducible cytochrome P-450d cDNA from rat liver.

We determined the coding nucleotide sequence of the mRNA for a 3-methylcholanthrene-inducible cytochrome P-450, P-450d, of rat liver by sequence analysis of cloned cDNAs. The predicted amino acid sequence of the cytochrome is composed of 513 amino acids, and its NH2-terminal sequence of 30 amino acids completely coincides with that reported from analysis of the purified cytochrome P-450d. The amino acid composition of the deduced sequence also agrees well with that determined from the purified protein. Computer-aided analysis was carried out to compare the complete primary structures of five species of cytochrome P-450, two molecular species of phenobarbital-inducible rat liver cytochrome P-450 (P-450b and P-450e), phenobarbital-inducible rabbit liver cytochrome P-450LM2, 3-methylcholanthrene-inducible rat liver cytochrome P-450d, and camphor-hydroxylating P-450 of Pseudomonas putida (P-450CAM). It is concluded therefrom that the time of divergence between cytochrome P-450b (P-450e) and P-450d is much earlier than that of branching between phenobarbital-inducible cytochromes P-450 of rat and rabbit. One highly conserved cysteine-containing region that is close to the COOH terminus is found in all of these cytochrome P-450 sequences, indicating that the heme-binding site is the cysteine residue in this region.

Amino Acid Sequence

Effect of mitochondrial DNA transmitted cytoplasmically from nontumorigenic to tumorigenic rat cells on the phenotypic expression of tumorigenicity.

The effect of mitochondrial DNA (mtDNA) on the phenotypic expression of tumorigenicity was examined by its cytoplasmic transmission from nontumorigenic cells to tumorigenic cells. Enucleated cells of the rat embryonic cell line 3Y1CAP, which are nontumorigenic and resistant to chloramphenicol, were fused with whole cells of the rat glioma C6BU-1 line, which are tumorigenic and resistant to 5-bromodeoxyuridine, and the cybrid colonies growing in selective medium with 5-bromodeoxyuridine (30 micrograms/ml) and chloramphenicol (50 micrograms/ml) were isolated clonally. Cytoplasmic transmission of 3Y1CAP mtDNA to C6BU-1 cells was confirmed by quantitative analysis of their mtDNA with restriction endonuclease. Subclones containing various amounts of mtDNA from 3Y1CAP cells were isolated from one cybrid clone, Y22, and their tumorigenicities were examined by inoculating 2 X 10(6) cells s.c. into nude mice. The tumorigenicities of these cybrid cubclones were almost identical to that of the nuclear donor C6BU-1 cells with respect to the tumor incidence (number of animals bearing tumors per number of animals inoculated), latent period, and growth rates of tumors. Moreover, analysis of chromosomes and mtDNAs of the cells recovered from the tumors obtained showed that the tumors were derived from the cells inoculated and that no selective overgrowth of segregants that had lost mtDNA from 3Y1CAP cells occurred in the nude mice. These observations suggest that expression of tumorigenicity of C6BU-1 cells was not suppressed by cytoplasmic transmission of nontumorigenic 3Y1CAP mtDNA.

Animals