PubMed Health⌕ Search

Biomedical subjects

M C Yoshida

Publications and source records attributed to M C Yoshida.

At least 19 recordsLinked to original sources
PubMed1992

Genetic linkage between copper accumulation and hepatitis/hepatoma development in LEC rats.

The concentration of copper in the livers of Long-Evans rats with cinnamon-like coat color (LEC), in which hepatitis and then hepatomas develop spontaneously, was recently found to be abnormally high. Therefore, we examined the copper concentrations in the livers of LEC F1 backcrosses (LEC F1 x LEC) to determine the linkage of copper accumulation with development of hepatitis. Consistent with a previously reported ratio of rats with hepatitis to rats without hepatitis of about 1:1, hepatitis developed in 14 of 30 F1 backcrosses. The copper concentrations in the livers of all LEC F1 backcrosses with hepatitis were abnormally high and comparable to those of LEC rats. In contrast, the concentrations in all backcrosses without hepatitis were similar to those in normal Long-Evans with agouti coat color or Brown-Norway rats. Copper accumulation was shown to be closely linked with the development of hepatitis in LEC rats and appeared to be a possible cause of hepatitis. The concentrations of copper in the livers of Fischer 344 rats after carbon tetrachloride treatment were in the range for normal liver, indicating that a high copper concentration in the liver is specific to LEC rats and not a specific characteristic of hepatitis. Furthermore, we found that the size and level of ceruloplasmin mRNA in the livers of LEC rats were the same as those in LEA rats and that the size and level of ceruloplasmin polypeptide in their livers and plasma were almost the same as those in LEA rats. Therefore, these results suggest that the copper accumulation is not due to alteration of expression or to gross alteration of the ceruloplasmin gene.

Animals↗
PubMed1992

Combined use of several mitogens for mitotic stimulation to human lymphocytes.

Several different type of mitogens, such as phytohemagglutinin (PHA) including PHA-P, -M, -W, -C, -L and -E+L, pokeweed mitogen (PWM), Concanavalin A (Con-A), lipopolysaccharide (LPS), wheat germ agglutinin (WGA) and soybean agglutinin (SBA) were compared their mitotic stimulating effects to human lymphocytes in single use and also combined use of these mitogens. In the tests with single use of each mitogen, PHA was confirmed to be the most superior mitogen. Of several different types of PHA, PHA-C, -L and -E+L were not appropriate to stimulate human lymphocytes, though PHA-P, -M and -W induced sufficiently mitoses. The most appropriate concentration of PWM was 50 micrograms/ml, but the highest mitotic index reached at 5 days after the initiation of culture. Con-A did not induce sufficient mitoses, and LPS, WGA and SBA were inadequate to stimulate human lymphocytes in the single use. In the combined use of two mitogens, there was no reliable combination to enhance mitotic stimulation. When three different mitogens were used simultaneously, only one combination with PHA-M, PWM and SBA effectively enhanced the mitotic index when compared to the single use. In the confirmatory experiment for this combination carried out on 5 different donors, the enhanced effect to mitotic index was recognized in two out of three donors with low response to PHA, but the low level of mitotic indices was seen in remaining 2 donors with high response to PHA. This finding suggests that this combination may overcome a disadvantage in some of the low responders to PHA.

Drug Combinations↗
PubMed1992

Recent advances in fluorescence in situ hybridization.

Fluorescence in situ hybridization (FISH) procedures that directly couple molecular and cytological information allow precise visualization of DNA sequences on metaphase chromosomes and interphase nuclei. These techniques can be used to identify chromosomes, detect chromosomal aberrations, and analyze linear and spatial genome organization. FISH procedures are also used to clinical fields for diagnosis of disease-related chromosome changes and tumor biology.

Animals↗
PubMed1992

Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17.

Cytokine LD78 is a member of a newly identified cytokine superfamily. We cloned the third human gene for the LD78, termed LD78 gamma and the sequence analysis showed that it is a 5'-truncated pseudogene. Exons 2 and 3 and the intron between them are highly homologous to those of the LD78 beta gene, hence, the gamma gene was probably derived from the beta gene. Southern blot analysis of human x mouse somatic hybrid cell DNAs and in situ hybridization experiments mapped all the three gene loci on human chromosome 17q21.1-q21.3. Analysis of DNAs from family members supports our previous finding that the beta and gamma genes on each of the paired chromosome 17 vary in copy number and that the LD78 alpha gene is presumably a single copy. In our analyses of cosmid clones, the LD78 beta gene and the second gene for AT744, which is also a member of the superfamily are closely linked in a head-to-head arrangement. The mechanism of generation of the three LD78 genes is discussed.

Base Sequence↗
PubMed1992

Effects of sex hormones on fulminant hepatitis in LEC rats: a model of Wilson's disease.

LEC rats, which have hereditary hepatitis and have recently been proposed as an animal model for Wilson's disease, were examined to determine the effects of sex hormones on fulminant hepatitis. After the rats had undergone ovariectomies or orchidectomies (castration) and were compared with intact rats, the age at the onset of fulminant hepatitis was not substantially altered but the survival rates decreased from 50% to 12.5% for females and 75% to 14.3% for males, indicating that sex hormones did not influence the occurrence of fulminant hepatitis but influenced mortality due to fulminant hepatitis. When testosterone was administered to the ovariectomized or orchidectomized rats, the survival rate increased to over 90% in both sexes. In contrast, estradiol did not affect the survival rate of either sex but affected the onset of fulminant hepatitis. That is, with the administration of estradiol, the age at which serum GPT activity reached its maximum was delayed 4 weeks in ovariectomized rats and 6 weeks in orchidectomized rats as compared with intact rats. A similar but somewhat weaker tendency appeared in rats given progesterone. The results of our study indicate that sex hormones have no effect on the rate of occurrence of hepatitis but affect the progression of hepatitis. In particular, testosterone increased the survival rate of rats with fulminant hepatitis, and exogenous estradiol delayed the onset of hepatitis for several weeks.

Alanine Transaminase↗
PubMed1991

Genetic recombination in a chromosomal translocation t(2;8)(p11;q24) of a Burkitt's lymphoma cell line, KOBK101.

We analyzed a chromosomal translocation, t(2;8)(p11;q24), in a Burkitt's lymphoma cell line, KOBK101. The translocation reciprocally occurred between a site about 150 bp upstream from the J5 segment in the Ig kappa-encoding gene on chromosome 2 and the A-rich end of an Alu repetitive element located far downstream from the c-myc gene on chromosome 8. Short segments of both parental chromosomes were deleted at the rearrangement site. A sequence related to the heptamer recognition signal for the V-J recombination of Ig genes and a topoisomerase I-recognition sequence were detected at the breakpoints. The V-J recombination occurred on both chromosome 2 and the translocated chromosome 2p- at the J3 and J4 segments, respectively. The J region on the translocated chromosomes was mutated, as compared with that on the untranslocated chromosome, while the Alu element and its upstream sequence were conserved. These results suggest the following aspects to the chromosomal translocation of this cell line. A V-J recombination seems to have occurred at the proximal end of the J4 segment first, and then the translocation took place in the region between the J4 and J5 segments. The translocation may have been mediated by the functions of topoisomerase I and the Alu repetitive sequence located at the breakpoint, although the possibility cannot be ruled out that the recombination machinery for Ig gene rearrangements functioned irregularly.

Alleles↗
PubMed1991

Hereditary low level of plasma ceruloplasmin in LEC rats associated with spontaneous development of hepatitis and liver cancer.

Both young (5 weeks old) and old (61-100 weeks old) hereditary hepatitis LEC rats showed a markedly low level of plasma ceruloplasmin (Cp) ferroxidase activity as compared with that of age-matched LEA and BN strain rats. This trait was genetically examined by the use of (BN x LEC) F1 hybrid and (F1 x LEC) backcross rats. The F1 hybrids never developed hepatitis and showed a similar level of Cp to that found in the parental BN rats. Among the backcross rats with about 1:1 segregation rate for hepatitis, affected rats had a remarkably decreased level of Cp, as found in LEC rats, whereas unaffected rats exhibited a similar level of Cp to that of BN, F1 and LEA rats. These results indicate that the low level of Cp is heritable in a single autosomal recessive mode in LEC rats. The observed tight link between the low Cp level and the hepatitis in LEC rats suggests that defective copper metabolism may be associated with the occurrence of hepatitis in LEC rats, since Cp is a copper-binding protein primarily involved in copper transport from the liver.

Age Factors↗
PubMed1991

[Chromosome rearrangements in leukemia].

Information on the presence of specific chromosomal structural abnormalities in certain tumors has been increasing. Although the tumor specific chromosomal abnormalities were deemed important, it was not until the chromosomal location of several oncogenes was determined that the real molecular significance became apparent. It now appears that many of the genes associated with animal tumors are located near specific translocations in human cancers. The specificity of chromosomal changes have not only been used diagnostically and prognostically, but also they present key information for the molecular analysis in determining the nature of the genes of human neoplasia. In recent years, great advances have been made in our understanding of the molecular structure of the specific chromosomal translocations in certain hematologic disorders. The present report will briefly describe chromosomal rearrangements and how oncogenes or cancer related genes involved can be affected.

Chromosome Aberrations↗
PubMed1991

Chromosomal assignments of the human endothelin family genes: the endothelin-1 gene (EDN1) to 6p23-p24, the endothelin-2 gene (EDN2) to 1p34, and the endothelin-3 gene (EDN3) to 20q13.2-q13.3.

Chromosomal assignments of the genes for the human endothelin family, the endothelin-1 gene (EDN1), the endothelin-2 gene (EDN2), and the endothelin-3 gene (EDN3), were accomplished by in situ hybridization to human metaphase chromosomes using a 3H-labeled human preproendothelin cDNA probe for each endothelin. The chromosomal assignment of the EDN2 was also performed by Southern blot analysis of somatic cell hybrid DNAs. EDN1, EDN2, and EDN3 were mapped to 6p23-p24, 1p34, and 20q13.2-q13.3, respectively.

Chromosome Banding↗
PubMed1990

Analysis of a human DNA excision repair gene involved in group A xeroderma pigmentosum and containing a zinc-finger domain.

Xeroderma pigmentosum (XP) is an autosomal recessive disease, characterized by a high incidence of sunlight-induced skin cancer. Cells from people with this condition are hypersensitive to ultraviolet because of a defect in DNA repair. There are nine genetic complementation groups of XP, groups A-H and a variant. We have cloned the mouse DNA repair gene that complements the defect of group A, the XPAC gene. Here we report molecular cloning of human and mouse XPAC complementary DNAs. Expression of XPAC cDNA confers ultraviolet-resistance on several group A cell lines, but not on lines of other XP groups. Almost all group A lines tested showed abnormality or absence of XPAC messenger RNAs. These results indicate that a defective XPAC gene causes group A XP. The human and mouse XPAC genes are located on chromosome 9q34.1 and chromosome 4C2, respectively. Human XPAC cDNA encodes a protein of 273 amino acids with a zinc-finger motif.

Amino Acid Sequence↗
PubMed1990

Joining of the c-myc gene and a line 1 family member on chromosome 8 in a human primary giant cell carcinoma of the lung.

A rearranged c-myc gene found in a human primary giant cell carcinoma of the lung was analyzed. The rearrangement was found in the region about 6 kilobase pairs upstream of the c-myc gene. The breakpoint was joined to a sequence carrying a Line 1 (L1) family member located on chromosome 8. This in vivo rearrangement of the c-myc gene specific to tumor cells may represent one mechanism of activation of a protooncogene during tumorigenesis or tumor progression in human cancer.

Base Sequence↗
PubMed1990

Transcriptional down-regulation of the rearranged C-myc expression in murine cell hybrids between a plasmacytoma and a T-cell lymphoma.

Regulation of the rearranged and non-rearranged c-myc expression was studied in murine cell hybrids (SBWI and SBWII) between plasmacytoma (S194) and T-cell lymphoma (BW5147) cells. Expression of the rearranged c-myc of heterogeneous mRNA sizes (1.8 approximately 2.4 kb) was markedly down-regulated in these hybrids regardless of retention of the gene. On the other hand, expression of the non-rearranged c-myc (2.4 kb) was not significantly affected in these hybrids. Treatment of SBWI hybrid cells with cycloheximide enhanced the non-rearranged c-myc 2- to 4-fold but did not release the down-regulation of the rearranged c-myc at all, suggesting that the down-regulation of the rearranged c-myc in the hybrid cells was mainly at a transcriptional rather than a post-transcriptional level. This was supported by the results of nuclear run-on assay: the high level of run-on transcripts in S194 cells declined in SBWI hybrid cells comparable to the level in BW5147 cells. The rearranged c-myc was hemi-methylated in S194 cells and the pattern was the same in SBWI hybrid cells. Furthermore, down-regulation of the rearranged c-myc in the hybrid was also not restored by treatment with 5-azacytidine (5-AzaC), 12-O-tetradecanoylphorbol-13-acetate (TPA) or forskolin, suggesting no causative involvement of DNA methylation or protein phosphorylation in down-regulation. Higher DNase I sensitivity of the rearranged c-myc in S194 cells decreased to a similar extent to that of the non-rearranged c-myc after cell fusion with BW5147 cells. These results suggest that expression of the rearranged c-myc is down-regulated at the level of transcription in murine cell hybrids between a plasmacytoma and a T-cell lymphoma, probably by changing chromatin configuration around the gene from the open to the closed state.

Animals↗
PubMed1990

Organization of variable region segments of the human immunoglobulin heavy chain: duplication of the D5 cluster within the locus and interchromosomal translocation of variable region segments.

We have studied the organization of variable region (V) genes of the human immunoglobulin heavy chain (H) by cosmid cloning. We isolated two independent immunoglobulin D5 clusters (D5-a and D5-b) from cosmid libraries of the human genome. Restriction maps of these two regions showed that downstream 15 kb portions of the 55 kb overlap were different although upstream 40 kb portions were almost identical. Four more D segments, (DM, DXP, DA and DK) were found around the D5 segment in the conserved region of each cluster. Nucleotide sequences of the corresponding D segments from each cluster were almost identical and they encoded potentially functional D regions. Analysis using human-rodent somatic cell hybrids demonstrated that both clusters were located in the immunoglobulin heavy chain (H) locus on chromosome 14, suggesting that the D5-a and D5-b regions evolved by internal duplication within this locus. We also isolated a 60 kb DNA region carrying four VH segments, designated as VH-F region, which was located on chromosome 16. Nucleotide sequences of the four VH segments were determined. Two of them encoded potentially functional VH segments, and the other two were pseudogenes. Some more VH segments were found to be located outside chromosome 14, by Southern blot hybridization of human-rodent hybrid cell DNAs. These results provide further evidence that the human VH locus has undergone recent reorganization.

Amino Acid Sequence↗
PubMed1990

Cytochrome P-450 and chromosome damage by cyclophosphamide in LEC strain rats predisposed to hereditary hepatitis and liver cancer.

LEC strain rats predisposed to hereditary hepatitis and liver cancer were examined for hepatic drug-metabolizing ability and the inducibility of chromosome damage by cyclophosphamide (CP) in somatic cells. Whereas the hepatic cytochrome P-450 contents and the activities of cytochrome P-450-catalyzed monooxygenases were lower in females than in males of both LEC and control LEA strains, male LEC rats exhibited significantly reduced cytochrome P-450 contents and monooxygenase activities compared with male LEA rats. When exposed to CP, a promutagen/procarcinogen requiring P-450-dependent metabolic activation, the frequencies of chromosome aberrations and sister-chromatid exchanges (SCEs) in bone marrow cells tended to be lower in females than in males of each strain and lower in LEC than in LEA rats of the same sex. In particular, the CP-induced SCEs were substantially lower in LEC rats. However, no such sex and strain differences were found in the SCE frequencies in regenerating hepatocytes of partially hepatectomized rats exposed to CP.

Animals↗
PubMed1990

Superoxide dismutase activity and chromosome damage in cultured chromosome instability syndrome cells.

The basal levels of superoxide dismutase (SOD) activity and chromosome aberration (CA) and sister-chromatid exchange (SCE) frequencies were examined in cultured fibroblasts or Epstein-Barr virus (EBV)-transformed lymphoblastoid cell lines (LCLs). These cells were derived from patients with chromosome instability syndromes (CISs) including Bloom's syndrome (BS), Fanconi's anemia (FA) and ataxia telangiectasia (AT). Embryonal fibroblasts and LCLs from normal subjects served as controls. Although LCLs tended to exhibit a higher SOD level than fibroblasts due to an elevation of Cu/Zn-SOD activity, BS and FA fibroblasts with increased frequencies of CAs and/or SCEs showed abnormally elevated SOD activity due to the manifold increase of Mn-SOD levels compared with control cells. However, BS and AT LCLs with almost control levels of CA and SCE frequencies showed no, or a slightly elevated, SOD activity, suggesting a possible selection of such cells during EBV transformation. The observed parallelism between the SOD activity and the cytogenetic manifestation may imply an involvement of active oxygen species, especially superoxide radicals, in the increased chromosome damage of CIS cells.

Ataxia Telangiectasia↗
PubMed1990

Two-dimensional electrophoretic analysis of hepatitis-associated polypeptides in liver of LEC rats developing spontaneous hepatitis.

High-resolution two-dimensional polyacrylamide gel electrophoresis in combination with silver staining was used to analyze between 800 and 1000 cytosolic and particulate polypeptides from age-matched livers of normal male Long-Evans rat with Agouti coat color (LEA) and Long-Evans rat with Cinnamon-like coat color (LEC) rats with hereditary trait of hepatitis at ages long before, immediately prior to, and just after the onset of hepatitis. Although the electrophoretic patterns of polypeptide expression were very similar with respect to the overall spot patterns, a number of polypeptides which differed either qualitatively or quantitatively were noted. Two constitutively expressed cytosolic polypeptides, P29.5 (Mr 29.5 kDa/pI 6.73) and P30 (30 kDa/6.70), were not detected in livers of LEC animals at any age. In the normal LEA rats both P29.5 and P30 were detected as early as one day after birth and both were expressed at similar concentrations at all ages. In the LEC rats P30-C (30 kDa/6.68) was constitutively expressed in close proximity to the expected position of P30, and P30-C was not detected in the LEA rats. By means of non-equilibrium pH gradient electrophoresis two relatively basic polypeptides were detected in the LEC rats. P18ne was detected immediately prior to and P27ne immediately after the clinical manifestation of hepatitis. Experiments in F1 backcross ([LEA x LEC] x LEC) animals, however, failed to demonstrate any genetic link between either the expression or lack of expression of P29.5, P30, P30-C, or P18ne and hepatitis development. P27ne was detected in all backcross animals exhibiting hepatitis, but was never observed in LEC rats prior to the onset of hepatitis. Although we were unable to identify any unique loss of expression of polypeptides which are genetically linked to hepatitis susceptibility in LEC rats, specific subsets of quantitatively modulated polypeptides were detected.

Animals↗
PubMed1990

Chromosome regional mapping for the human thyroid stimulating hormone beta subunit (TSHB) gene.

The human thyroid stimulating hormone beta subunit (TSHB) gene, located on chromosome 1, was studied to determine its subregional location by in situ hybridization and Southern blot analysis of human x mouse hybrid cells. The results allowed localization of TSHB to the proximal portion of 1p22, which is in the region of localization of the linkage group including amylase (AMY), nerve growth factor beta subunit (NGFB), and NRAS, which are conserved in humans and rodents.

Blotting, Southern↗