[A case report of congenital liver fibrosis tolerated 3 normal deliveries].
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Adult↗
Biomedical subjects
H Yonekawa
Publications and source records attributed to H Yonekawa.
Elimination of paternal mitochondrial DNA in intraspecific crosses during early mouse embryogenesis.
To examine whether mtDNA is uni- or biparentally transmitted in mice, we developed an assay that can detect sperm mtDNA in a single mouse embryo. In intraspecific hybrids of Mus musculus, paternal mtDNA was detected only through the early pronucleus stage, and its disappearance co-incided with loss of membrane potential in sperm-derived mitochondria. By contrast, in interspecific hybrids between M. musculus and Mus spretus, paternal mtDNA was detected throughout development from pronucleus stage to neonates. We propose that oocyte cytoplasm has a species-specific mechanism that recognizes and eliminates sperm mitochondria and mtDNA. This mechanism must recognize nuclearly encoded proteins in the sperm midpiece, and not the mtDNA or the proteins it encodes, because sperm mitochondria from the congenic strain B6.mtspr, which carries M. spretus mtDNA on background of M. musculus (B6) nuclear genes, were eliminated early by B6 oocytes as in intraspecific crosses. We conclude that cytoplasmic genomes are transmitted uniparentally in intraspecific crosses in mammals as in Chlamydomonas and that leakage of parental mtDNA is limited to interspecific crosses, which rarely occur in nature.
Animals↗
Detection of host DNA sequences including the H-2 locus of the major histocompatibility complex in schistosomes.
The mouse type 2 Alu (B2) sequence was detected in both DNAs of Schistosoma mansoni and S.japonicum except for the cercarial stage by the polymerase chain reaction (PCR). Using several kinds of mouse STMS (sequence tagged microsatellite site) primer sets, PCR products related to the host were found in the DNAs of S. mansoni as well as of S.japonicum. Products could be detected only in the DNA of S. japonicum using certain STMS primer sets. The fact that no products could be amplified from the DNAs of both parasites when other kinds of STMS primer sets were used suggests unequal incorporation of the host DNA into the schistosomes. Furthermore, the sequence of the N-terminal domain of H-2, the mouse major histocompatibility complex (MHC), was detected in the DNAs from S. mansoni miracidium, male adult and S. japonicum adults, whereas the sequence of the C2 domain of H-2 was found only in the DNAs of S. japonicum adults. This evidence that host DNA sequences, including the class I MHC, exist heterogeneously in the DNAs of schistosomes might provide an important insight for further understanding of host-parasite immune interactions.
Animals↗
Mutational and LOH analyses of p53 alleles in colon tumors induced by 1,2-dimethylhydrazine in F1 hybrid mice.
To elucidate the role of p53 in colon tumorigenesis in mice, we examined allele loss and mutational alteration of the p53 gene in colon tumors induced by 1,2-dimethylhydrazine (DMH) in F1 hybrid mice. Intragenic polymorphism of the p53 gene among parental strains enabled us to assess allele loss of the p53 gene and also to determine parental origin of mutated and/or lost alleles. Allele loss was detected in two of 163 tumors heterozygous for the p53 gene. Polymerase chain reaction-single-strand conformation polymorphism analysis of p53 exons 5-8 revealed 33 mutations in 20 of 182 colon tumors, the incidence being lower than that in human colon cancers. The majority of these mutations were of transition type: G:A transitions at non-CpG sites were most prevalent, while those at CpG sites were less common. Distribution of the mutations along p53 amino acid sequence revealed a difference in the location of 'hot spots' between mice and humans. Incidence of p53 alterations did not differ among alleles of different parental origins, suggesting that genetic changes in DMH-induced mouse colon tumors had occurred independently of parental origin and DMH susceptibility. Detailed analysis of p53 mutations on each allele revealed intratumoral heterogeneity in mouse colon tumors. The low incidence of p53 mutations and rare allele loss suggest that p53 alteration plays only a minor role in colon tumorigenesis in mice.
1,2-Dimethylhydrazine↗
Nuclear but not mitochondrial genome involvement in human age-related mitochondrial dysfunction. Functional integrity of mitochondrial DNA from aged subjects.
The role of mtDNA and nuclear genome in human aging was examined by their intercellular transfer using skin fibroblasts and mtDNA-less HeLa cells (rho o-HeLa cells). We found in vivo age-related reductions in the activity of cytochrome c oxidase in human skin fibroblasts obtained from 16 donors of various ages (0-97 years). The abnormality in mitochondria of the aged donors was not attributable to either decrease in the copy number of mtDNA molecules or increase in the copy number of deletion mutant mtDNA molecules, but to significant decrease in overall polypeptide synthesis in the mitochondria. However, intercellular mtDNA transfer experiments showed that fibroblast mtDNA from elderly donors is functionally intact. By contrast, intercellular transfer of HeLa nuclei to fibroblasts from aged donors restored cytochrome c oxidase activity, suggesting that the age-related phenotype was nuclear recessive. However, during subsequent cultivation of these hybrids, the activity gradually reduced again, associated with gradual chromosome loss. These observations support the idea that accumulation of nuclear recessive somatic mutations, but not mtDNA mutations, is responsible for the in vivo age-related mitochondrial dysfunction observed in human skin fibroblasts.
Aged↗
Characterization of three different transgenic mouse lines that carry human poliovirus receptor gene--influence of the transgene expression on pathogenesis.
Three transgenic mouse lines, ICR-PVRTg1, ICR-PVRTg5, and ICR-PVRTg21, which are susceptible to poliovirus, have been established by introducing the human gene for poliovirus receptor (PVR) into the genome of mouse strain ICR. Genetic characterizations of the PVR gene were carried out on these mouse lines to define the approximate copy number, insertion site, and expression of the transgene in the central nervous system (CNS). The transgene was integrated in the chromosome 4, 12, and 13 of ICR-PVRTg1, ICR-PVRTg5 and ICR-PVRTg21 mice, respectively, and was stably transmitted to progeny mice. ICR-PVRTg1 appeared to have the most abundant copy numbers of the transgene and showed the highest level of PVR mRNA and membrane associated PVR protein in the CNS among the three mouse lines. Those in ICR-PVRTg21 and ICR-PVRTg5 were at intermediate and lowest levels, respectively. In the CNS, PVR mRNA was detected at high levels only in neurons of the spinal cord and brain stem where poliovirus can replicate, suggesting that the PVR mRNA expression confers cell specificity to poliovirus in the CNS. ICR-PVRTg1 and ICR-PVRTg5 showed the highest and the lowest sensitivity to poliovirus, respectively, whereas ICR-PVRTg21 was in-between. These results may suggest that poliovirus sensitivity of the mice is attributed to relative levels of PVR expression.
Animals↗
Mitochondrial DNA differentiation of Japanese diploid and triploid Paragonimus westermani.
Restriction endonuclease analysis of mitochondrial DNA was carried out in order to differentiate diploid and triploid types of Paragonimus westermani originating from Japan. It was found that out of 16 restriction enzymes. PstI, HaeIII and RsaI revealed consistently different cleavage patterns between the two types.
Animals↗
Novel mouse microsatellites: primer sequences and chromosomal location.
Sixty-nine sequences containing microsatellites were determined by analysis of clones from a pUC118 library of total genomic mouse DNA. These sequences were examined for size variation using polymerase chain reaction and gel electrophoresis. Fifty-one of them showed allelic variations between C57BL/6 and MSM, the two strains used for genetic mapping. Hence, their chromosomal location was determined using a panel consisting of 131 backcross mice that had been typed with 85 anchor loci. The microsatellites were distributed to most chromosomes except for chromosomes 16 and 19. These novel markers with defined locations are useful in linkage and genome mapping studies.
Animals↗
Noise content analysis in clinical digital images.
Most digital modalities in radiology use 12 bits precision to store the digital images. To determine whether all these bits contain useful information, a statistical method called the Moran test was used to measure the noise level in computed tomographic, magnetic resonance, and digital radiographic images. The test was performed on the bit planes of each pixel. After the noise level was estimated, the pixel data were separated into signal bits and noise bits, and image enhancement techniques were applied on the noise-bits-removed images to demonstrate that the removal of noise bits did not affect image quality. Preliminary results showed no noticeable difference between the original images and the noise-bits-removed images.
Algorithms↗
[The effect of induction chemotherapy with CBDCA, 5-FU and UFT in head and neck cancer].
Induction chemotherapy of low-dose CBDCA, 120-hour continuous infusion 5-FU and UFT was applied to 22 patients with untreated head and neck cancer. CBDCA 75 mg/m2 was given on day 1 and, subsequently, 5-FU 1,500 mg/m2/day for 120-hour continuous infusion was started. UFT was administered every day orally at 400-600 mg/day as biochemical modulation. If tumors were reduced and side effects were mild, these schedules were repeated after two weeks. Three patients (14%) achieved a CR and 11 (50%) a PR, for an overall response rate of 64%. Anorexia, nausea, vomiting and stomatitis were the predominant toxicities. They were mild and well tolerable, although severe diarrhea was observed in one case. Good general conditions of patients were kept because of low grade of toxicities. They were important factors for the tolerance of subsequent radiotherapy and surgery. Based on these results, we conclude that the combination of low-dose CBDCA, 5-FU and UFT as biochemical modulation is effective in head and neck cancer.
Administration, Oral↗
No allelic loss at the p53 locus in 1,2-dimethylhydrazine-induced mouse colon tumours: PCR-SSCP analysis with sequence-tagged microsatellite site primers.
We examined allelic loss in colon tumors induced by 1,2-dimethylhydrazine (DMH) in F1 hybrid mice, using sequence-tagged microsatellite site (STMS) primers derived from the chromosomal region closely linked to the p53 locus. Polymerase chain reaction--single-strand conformation polymorphism (PCR-SSCP) analysis of 155 colonic tumors with two STMS markers revealed that no genetic alterations had occurred in these tumors, except for one case where one of the markers detected an increase of one CA repeat unit in one allele. No allelic loss at the loci closely linked to the p53 locus strongly suggests that allelic loss at the p53 locus is not involved in DMH-induced colon carcinogenesis in mice.
1,2-Dimethylhydrazine↗
Mitochondrial DNA polymorphisms in subterranean mole-rats of the Spalax ehrenbergi superspecies in Israel, and its peripheral isolates.
Patterns of mitochondrial DNA (mtDNA) variation were examined in 133 mole-rats constituting all four chromosomal species (2n = 52, 2n = 54, 2n = 58, and 2n = 60) of the Spalax ehrenbergi superspecies in Israel, as well as the peripheral isolates of 2n = 60. In the main range of the complex, a total of 28 mtDNA haplotypes were found in 64 mole-rats, with most haplotypes being unique to either a single chromosomal species or population. mtDNA divergence increased from low to high diploid number in a north-to-south direction in Israel. Overall levels of mtDNA diversity were unexpectedly the highest in the 2n = 60, the youngest species of the complex. The mtDNA haplotypes can be separated into two major groups, 2n = 52-54 and 2n = 58-60, and a phylogenetic analysis for each group revealed evidence of a few haplotypes not sorted by diploid number. The overall patterns of mtDNA divergence seen within and among the four chromosomal species are consistent with the parapatric mode of speciation as suggested from previous studies of allozyme and DNA hybridization. In a separate data set the patterns of mtDNA variation were examined across the main geographic range and across peripheral semi-isolates and isolates of the 2n = 60 chromosomal species. Fifteen haplotypes were found in 69 mole-rats. High levels of mtDNA diversity characterized the main range, semi-isolated, and even some desert isolated populations. The peripheral isolates contain much mtDNA diversity, including novel haplotypes.
Animals↗
[A three-dimensional reconstruction of the temporal bone by the helical scanning CT and its clinical application].
The current availability of 3 dimensional (3-D) imaging from Computed Tomography (CT) has yielded new anatomical information and pre-and postoperative evaluations. However, little discussion as to the 3-D structural image of the temporal bone has been reported because conventional CT does provide sufficient data to produce such images. The Helical scanning CT gathers continuous and multiple slice image data since it consists of an X-ray tube that continuously rotates around the patient while the patient moves continuously into the CT scanner. Thus, application of the Helical scanning CT has made it possible to reconstruct 3-D images of the minute and complicated structure of the temporal bone. We evaluated 3-D images from 9 typical cases, examined from February to October 1992. As a result, we found that the 3-D images reconstructed with this system are useful for evaluation of the postoperative state of tympanoplasty, the diagnosis of anomalies of the bony labyrinth, and examining the extent of bone destruction induced by trauma, cholesteatoma, etc.
Adolescent↗
Poliovirus-sensitive transgenic mice as a new animal model.
Transgenic mice susceptible to poliovirus infection were produced by introducing a human gene encoding cellular receptors for poliovirus into the mouse genome. Expression of receptor mRNAs in tissues of the transgenic mice was analysed using Northern blot hybridization. The results indicate that the human gene is expressed in many tissues of the transgenic mice just as in human tissues, and that the amount of the receptor mRNAs varies from tissue to tissue. The transgenic mice inoculated with poliovirus by any of the routes tested in this study show clinical symptoms similar to those in humans and monkeys, although the sensitivity of the mice depended on the inoculation route. In any route, the virulent Mahoney strain of type 1 poliovirus is much more virulent than the attenuated Sabin 1 strain in the transgenic mice. These observations suggest that the transgenic mice become an excellent new animal model for studying molecular mechanisms of pathogenesis of poliovirus and for assessing oral poliovirus vaccines.
Administration, Oral↗
[Establishment of the transgenic mouse strains susceptible to poliovirus].
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Animals↗
A second gene for the African green monkey poliovirus receptor that has no putative N-glycosylation site in the functional N-terminal immunoglobulin-like domain.
Using cDNA of the human poliovirus receptor (PVR) as a probe, two types of cDNA clones of the monkey homologs were isolated from a cDNA library prepared from an African green monkey kidney cell line. Either type of cDNA clone rendered mouse L cells permissive for poliovirus infection. Homologies of the amino acid sequences deduced from these cDNA sequences with that of human PVR were 90.2 and 86.4%, respectively. These two monkey PVRs were found to be encoded in two different loci of the genome. Evolutionary analysis suggested that duplication of the PVR gene in the monkey genome had occurred after the species differentiation between humans and monkeys. The NH2-terminal immunoglobulin-like domain, domain 1, of the second monkey PVR, which lacks a putative N-glycosylation site, mediated poliovirus infection. In addition, a human PVR mutant without N-glycosylation sites in domain 1 also promoted viral infection. These results suggest that domain 1 of the monkey receptor also harbors the binding site for poliovirus and that sugar moieties possibly attached to this domain of human PVR are dispensable for the virus-receptor interaction.
Amino Acid Sequence↗
Genetical control on lentinan-induced acute phase responses and vascular responses.
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Acute-Phase Reaction↗