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111.
112.
Atsushi Ohashi PhD Hirohisa Kotera BS Hideo Hori BS Makoto Hibiya PhD Koji Watanabe MD PhD Kazutaka Murakami MD PhD Midori Hasegawa MD PhD Makoto Tomita MD PhD Yoshinobu Hiki MD PhD Satoshi Sugiyama MD PhD 《Journal of artificial organs》2005,8(4):252-256
Polyvinyl chloride (PVC) tubing is an indispensable medical material for extracorporeal circulation therapy. However, di(2-ethylhexyl)phthalate
(DEHP), a suspected endocrine disruptor, can be eluted from PVC, suggesting that an alternative material that does not contain
DEHP is needed for clinical applications. First, we evaluated the endocrine disrupting risks of the plasticizers contained
in PVC tubes by investigating their binding affinities for the human estrogen receptor alpha (ERα). Our results revealed that,
while DEHP has some binding affinity for ERα, neither epoxidized soybean oil nor tris(2-ethylhexyl)trimellitate (an alternative
to DEHP) has any affinity for ERα. Second, we evaluated the endocrine disrupting risks of a tube made of newly developed plasticizer-free
(PF) materials. We confirmed the presence of DEHP and detected several unidentified substances in plasma stored within the
PVC tube. This plasma's competitive binding affinity for ERα was significantly higher than that of control plasma (P < 0.01). In contrast, the profile of plasma stored in the PF tube was similar to that of the control, both in terms of high-performance
liquid chromatography chromatograms and competitive binding capacity for ERα, suggesting that the PF tube is biocompatible
and is useful for reducing the elution of substances capable of binding to ERα.
Presented in part at the 42nd Congress of the Japanese Society for Artificial Organs, October 5–7, 2004, Tokyo, Japan 相似文献
113.
Yamazaki K McGovern D Ragoussis J Paolucci M Butler H Jewell D Cardon L Takazoe M Tanaka T Ichimori T Saito S Sekine A Iida A Takahashi A Tsunoda T Lathrop M Nakamura Y 《Human molecular genetics》2005,14(22):3499-3506
The inflammatory bowel diseases (IBDs), Crohn's disease (CD) and ulcerative colitis, are chronic inflammatory disorders of the digestive tract. The pathogenesis of IBD is complicated, and it is widely accepted that immunologic, environmental and genetic components contribute to its etiology. To identify genetic susceptibility factors in CD, we performed a genome-wide association study in Japanese patients and controls using nearly 80,000 gene-based single nucleotide polymorphism (SNP) markers and investigated the haplotype structure of the candidate locus in Japanese and European patients. We identified highly significant associations (P = 1.71 x 10(-14) with odds ratio of 2.17) of SNPs and haplotypes within the TNFSF15 (the gene encoding tumor necrosis factor superfamily, member 15) genes in Japanese CD patients. The association was confirmed in the study of two European IBD cohorts. Interestingly, a core TNFSF15 haplotype showing association with increased risk to the disease was common in the two ethnic groups. Our results suggest that the genetic variations in the TNFSF15 gene contribute to the susceptibility to IBD in the Japanese and European populations. 相似文献
114.
Kobayashi M Hirano A Kumano T Xiang SL Mihara K Haseda Y Matsui O Shimizu H Yamamoto K 《Genes to cells : devoted to molecular & cellular mechanisms》2004,9(4):291-303
The Rad17-replication factor C (Rad17-RFC) and Rad9-Rad1-Hus1 complexes are thought to function in the early phase of cell-cycle checkpoint control as sensors for genome damage and genome replication errors. However, genetic analysis of the functions of these complexes in vertebrates is complicated by the lethality of these gene disruptions in embryonic mouse cells. We disrupted the Rad17 and Rad9 loci by gene targeting in the chicken B lymphocyte line DT40. Rad17-/- and Rad9-/- DT40 cells are viable, and are highly sensitive to UV irradiation, alkylating agents, and DNA replication inhibitors, such as hydroxyurea. We further found that Rad17-/- and Rad9-/- but not ATM-/- cells are defective in S-phase DNA damage checkpoint controls and in the cellular response to stalled DNA replication. These results indicate a critical role for chicken Rad17 and Rad9 in the cellular response to stalled DNA replication and DNA damage. 相似文献
115.
Significant association between nonsyndromic oral clefts and arylhydrocarbon receptor nuclear translocator (ARNT) 总被引:1,自引:0,他引:1
Kayano S Suzuki Y Kanno K Aoki Y Kure S Yamada A Matsubara Y 《American journal of medical genetics. Part A》2004,(1):40-44
The etiology of nonsyndromic oral clefts (cleft lip, cleft palate, or cleft lip and palate) is still controversial, but is considered to involve both genetic and environmental factors. One of suspected environmental factors is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) found in tobacco, herbicides, contaminated soil, and food. TCDD administered during organogenesis in mice causes a high incidence of CP in fetuses. There is ample evidence that aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), and cytochrome P450 1A1 (CYP1A1) are involved in TCDD metabolism. We assessed whether there is any association in the Japanese population of nonsyndromic oral clefts with single nucleotide polymorphisms (SNPs) in the AHR, ARNT, and CYP1A1 genes using transmission disequilibrium test (TDT) and case-control study. We identified and investigated three SNPs in ARNT; 567G/C (V189V), IVS12-19T/G, and 2117C/T (P706L). Two amino acid substitutions, R554L in AHR and I462V in CYP1A1, were also investigated. In the TDT, the C allele of ARNT 567G/C was preferentially transmitted to patients (P = 0.033). When a haplotype consisting of 567G/C and IVS12-19T/G in ARNT was considered, the preferential transmission of the CT (567C-IVS12-19T) haplotype was observed (P = 0.0012). In a case-control study, a significant association of IVS12-19T/G in ARNT was observed (P = 0.021). The SNPs studied in AHR and CYP1A1 were not associated with the disease. Our results suggest that ARNT is involved in the development of nonsyndromic oral clefts in the Japanese population. 相似文献
116.
Caenorhabditis elegans RBX1 is essential for meiosis, mitotic chromosomal condensation and segregation, and cytokinesis 总被引:1,自引:0,他引:1
Sasagawa Y Urano T Kohara Y Takahashi H Higashitani A 《Genes to cells : devoted to molecular & cellular mechanisms》2003,8(11):857-872
BACKGROUND: The RING-H2 finger protein RBX1 (ROC1/HRT1) is a common subunit of SKP1-CDC53/CUL1-F-box (SCF), other cullins and von Hippel-Lindau (VHL) tumour suppressor E3 ubiquitin ligase complexes. RBX1 protein sequences are highly conserved in various species, including yeasts, Drosophila melanogaster, mice and humans. In Saccharomyces cerevisiae, RBX1 is essential for the G1/S transition. RESULTS: Caenorhabditis elegans RBX1 is strongly expressed in early embryos and in the gonad, including meiotic cells. Depletion of RBX1 by RNA-mediated interference (RNAi) caused pronounced defects in the first meiotic division. Several irregular phenotypes were identified in embryos that escaped from meiotic arrest: defects in mitotic chromosomal condensation and segregation, abnormal chromosome bridges, giant nuclei, abnormal cortical protrusion, multinucleate cells and defects in germ cell proliferation. Moreover, histone H3 phosphorylation at Ser10 and Ser28 was significantly reduced in these embryos. The histone H3 phosphorylation defect of embryos was rescued by the additional depletion of protein phosphatase 1 (GLC7alpha/beta) by RNAi. CONCLUSION: These results indicate that the RBX1 protein participates in diverse functions relevant to chromosome metabolism and cell cycle control. 相似文献
117.
Fukushima A Funaki H Yaoeda K Tanaka T Shirakashi M Yoshida Y Yaoita E Abe H Yamamoto T 《Archives of histology and cytology》2003,66(5):445-452
The localization and expression in the rat cornea of chondromodulin-I (ChM-I), an inhibitory angiogenesis factor, were examined by immunohistochemistry, Western blot analysis, ribonuclease protection assay, and real-time PCR assay. We found immunoreactivity for ChM-I in the epithelial layer but not the stromal layer or endothelial layer in the cornea, in addition to the positive ChM-I immunoreactivity in other sites in the eye such as the sclera, retina, and ciliary body. The ChM-I immunoreactivity was most intense at the outside of the basal cells and in their cytoplasm while the intensity of the immunoreactivity decreased gradually from the wing cells to the superficial cells in the corneal epithelial layer. No reactivity however, was detected in the Bowman's membrane or conjunctival epithelial cells which had continuity with the corneal epithelial cells. The expression of ChM-I mRNA was demonstrated in the cornea at one-third less intensity than that in the sclera with choroids and retinal pigment epithelium by ribonuclease protection assay and real-time PCR. ChM-I in the corneal epithelial layer may prevent neovascularization and maintain avascularity in the cornea. 相似文献
118.
Tsukamoto K Suzuki H Harada D Namba A Abe S Usami S 《European journal of human genetics : EJHG》2003,11(12):916-922
Molecular diagnosis makes a substantial contribution to precise diagnosis, subclassification, prognosis, and selection of therapy. Mutations in the PDS (SLC26A4) gene are known to be responsible for both Pendred syndrome and nonsyndromic hearing loss associated with enlarged vestibular aqueduct, and the molecular confirmation of the PDS gene has become important in the diagnosis of these conditions. In the present study, PDS mutation analysis confirmed that PDS mutations were present and significantly responsible in 90% of Pendred families, and in 78.1% of families with nonsyndromic hearing loss associated with enlarged vestibular aqueduct. Furthermore, variable phenotypic expression by the same combination of mutations indicated that these two conditions are part of a continuous category of disease. Interestingly, the PDS mutation spectrum in Japanese, including the seven novel mutations revealed by this study, is very different from that found in Caucasians. Of the novel mutations detected, 53% were the H723R mutation, suggesting a possible founder effect. Ethnic background is therefore presumably important and should be noted when genetic testing is being performed. The PDS gene mutation spectrum in Japanese may be representative of those in Eastern Asian populations and its elucidation is expected to facilitate the molecular diagnosis of a variety of diseases. 相似文献
119.
Asuka Iwanaga Tokiharu Sato Kazushi Sugihara Atsushi Hirao Nobuyuki Takakura Hiroshi Okamoto Masahide Asano Katsuji Yoshioka 《Neuroscience letters》2007
We previously identified c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1, also known as JNK-interacting protein 3) as a scaffolding factor for JNK intracellular signaling pathways. Targeted gene-disruption studies have shown that JSAP1-null mice are unable to breathe and die shortly after birth. Although neural defects might be responsible for their death, there has been no convincing evidence for this. Here we first generated genetically engineered mice carrying a loxP-flanked (floxed) jsap1 gene. To evaluate the validity of this deletion as a jsap1 conditional knockout (KO), we created mice in which the same exon was deleted in all cell lineages, and compared their phenotypes with those of the jsap1 conventional KO mice reported previously. The two KO lines showed indistinguishable phenotypes, i.e., neonatal death and morphological defects in the telencephalon, indicating that the conditional deletion was a true null mutation. We then introduced the floxed jsap1 deletion mutant specifically into the neural lineage, and found that the jsap1 conditional KO mice showed essentially the same phenotypes as the JSAP1-null mice. These results strongly suggest that the neonatal death of jsap1-deficient mice is caused by defects in the nervous system. 相似文献
120.
Fujio Murakami Yasushi Kobayashi Takashi Uratani Atsushi Tamada 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1993,96(2):181-193
The corticorubral projections in adult cats are primarily uncrossed. However, early in development and after early unilateral lesions of the sensorimotor cortex, crossed corticorubral projections are also observed. The present study was performed to disclose (1) whether the crossed projections originate from neuronal subpopulations different from those producing uncrossed ones and (2) how the neurons that give rise to the crossed projections in the lesioned animals are related to those occurring in normal development. We injected fluorescent latex microspheres into the red nucleus of two groups of animals: (1) intact kittens at postnatal week 3 and (2) kittens that had received unilateral ablation of the cerebral cortex at this stage and were then allowed to survive for at least 4 weeks. Red fluorescing microspheres were injected on one side and green ones on the other. In both normal and lesioned kittens, a number of cells in the cortex were labeled as a result of the contralateral as well as the ipsilateral injections, and no difference in size or distribution was found between the cells labeled from contralateral and ipsilateral injections. More than half of the cells labeled from contralateral injections were double-labeled in both groups of animals. These results indicate that individual corticorubral cells project bilaterally in normal development as well as following unilateral lesions of the cortex. With respect to the cells producing crossed projections, they were similar in both laminar and regional distributions between the intact and lesioned animal, suggesting that the crossed projections arise from the same neuronal subpopulation before and after cortical lesions. This view was supported by sequential injections of the tracers, which indicated that cells normally projecting contralaterally maintained the crossed projection after the lesions. Taking into account our previous observations that growth and proliferation of crossed corticorubral axons took place in the red nucleus (Murakami et al. 1991a), it is likely that growth and proliferation of the axons in denervated targets play a major role in lesion-induced establishment of aberrant projections. 相似文献