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51.
Koizumi A Matsuura N Inoue S Utsunomiya M Nozaki J Inoue K Takasago Y;Mass Screening Group 《Genetic testing》2003,7(1):29-35
Lysinuric protein intolerance (LPI:MIM 222700) is an autosomal recessive disease characterized by defective transport of the dibasic amino acids. We recently reported a local cluster of LPI in the northern part of Japan (Koizumi et al., 2000). Mutational analysis of the LPI patients in this local cluster revealed they were exclusively homozygous for the R410X mutation. The effectiveness of early intervention with citrulline therapy (200 mg/kg per day) and protein restriction (1.5 g/kg per day) was confirmed in these patients. Mass screening was conducted in 4,568 newborn babies between 1999 and 2002, which was estimated to cover 100% of almost all newborns delivered in the screened area. Forty heterozygous newborns were found (0.88%), leading to an estimated incidence of LPI of 1:51,984. The number of people that required screening to detect one case was 51,984, and the cost for mass screening was 30 cents/person (a total of dollars 15,600). This is comparable to, or even less than, the cost of currently screened diseases in Japan. Therefore, we conclude that a mass screening program for LPI can be introduced effectively and economically into an area where an LPI cluster is located as the result of a founder mutation. 相似文献
52.
53.
An alpha-helical coiled-coil structure is one of the basic structural units in proteins. Hydrophilic residues at the hydrophobic positions in the coiled-coil structure play important roles in structures and functions of natural proteins. We reported here a peptide that formed a triple stranded alpha-helical coiled-coil showing the pH-dependent structural change. The peptide was designed to have two His residues at the hydrophobic positions of the center of the coiled-coil structure. The peptide folded into a triple stranded coiled-coil at neutral pH, while it unfolded at acidic pH. This construct is useful to create a protein that the structure or function is controlled by pH. 相似文献
54.
Imamura N Ishikawa T Ohtsuka T Yamamoto K Dekura M Fukami H Nishida R 《Bioscience, biotechnology, and biochemistry》2000,64(10):2216-2217
An antibiotic-producing Penicillium sp. strain was isolated from cocoons of the leaf-rolling moth, Dactylioglypha tonica. An antibacterial compound was isolated from the cultured broth, and the chemical structure of the principle was determined by spectroscopic data to be a derivative of isocoumarincarboxylate. 相似文献
55.
Troponin T (TnT) isoforms of chicken fast skeletal muscle are classified into two types, breast-muscle-type (B-type) and leg-muscle-type (L-type) isoforms. These isoforms are produced from a single gene by differential alternative splicing of pre-mRNA. We investigated immunohistochemically the distribution of B-type TnT isoforms in chicken leg muscle (musculus biceps femoris), using anti-exon x3 that was raised against a synthetic peptide corresponding to exon x3 and recognized B-type, but not the L-type, TnT isoforms. Mosaic patterns of immunostaining showing locally different expression of B-type TnT isoforms in a single fiber were observed among fibers, and the non-uniform distribution of the isoforms was also detected in sectioned fibers and myofibrils from the muscle. The results indicated that regulation of pre-mRNA splicing of fast skeletal muscle TnT was different not only among the muscle fibers but also within a single fiber, suggesting that heterogeneous myonuclei in regulation of alternative splicings occur in a single muscle fiber. 相似文献
56.
Function of 90-kDa heat shock protein in cellular differentiation of human embryonal carcinoma cells
Yamada T Hashiguchi A Fukushima S Kakita Y Umezawa A Maruyama T Hata J 《In vitro cellular & developmental biology. Animal》2000,36(2):139-146
Summary Heat shock proteins (HSPs) have been recognized as molecules that maintain cellular homeostasis during changes in the environment.
Here we report that HSP90 functions not only in stress responses but also in certain aspects of cellular differentiation.
We found that HSP90 slowed remarkably high expression in undifferentiated human embryonal carcinoma (EC) cells, which were
subsequently dramatically down-regulated during in vitro cellular differentiation, following retinoic acid (RA) treatment,
at the protein level. Surprisingly, heat shock treatment also triggered the down-regulation of HSP90 within 48 h at the protein
level. Furthermore, the heat treatment induced cellular differentiation into neural cells. This down-regulation of HSP90 by
heat treatment was shifted to an up-regulation attern after cellular differentiation in response to RA treatment. In order
to clarify the functions of HSP90 in cellular differentiation, we conducted various experiments, including overexpression
of HSP90 via gene transfer. We showed that the RA-induced differentiation of EC cells into a neural cell lineage was inhibited
by overexpression of the HSP90α or-β isoform via the gene transfer method. On the other hand, the overexpression of HSP90β
alone impaired cellular differentiation into trophoectoderm. These results show that down-regulation of HSP90 is a physiological
critical event in the differentiation of human EC cells and that specific HSP90 isoforms may be involved in differentiation
into specific cell lineages. 相似文献
57.
Jun-Ichi Sasaki Masanori Hashimoto Satoshi Yamaguchi Yoshihiro Itoh Itsumi Yoshimoto Takuya Matsumoto Satoshi Imazato 《PloS one》2015,10(6)
The development of technologies to promote vascularization of engineered tissue would drive major developments in tissue engineering and regenerative medicine. Recently, we succeeded in fabricating three-dimensional (3D) cell constructs composed of mesenchymal stem cells (MSCs). However, the majority of cells within the constructs underwent necrosis due to a lack of nutrients and oxygen. We hypothesized that incorporation of vascular endothelial cells would improve the cell survival rate and aid in the fabrication of biomimetic bone tissues in vitro. The purpose of this study was to assess the impact of endothelial cells combined with the MSC constructs (MSC/HUVEC constructs) during short- and long-term culture. When human umbilical vein endothelial cells (HUVECs) were incorporated into the cell constructs, cell viability and growth factor production were increased after 7 days. Furthermore, HUVECs were observed to proliferate and self-organize into reticulate porous structures by interacting with the MSCs. After long-term culture, MSC/HUVEC constructs formed abundant mineralized matrices compared with those composed of MSCs alone. Transmission electron microscopy and qualitative analysis revealed that the mineralized matrices comprised porous cancellous bone-like tissues. These results demonstrate that highly biomimetic bone tissue can be fabricated in vitro by 3D MSC constructs incorporated with HUVECs. 相似文献
58.
Shoichiro Ozaki Etsuko Ebisui Kozo Hamada Jun-Ichi Goto Akinobu Z. Suzuki Akiko Terauchi Katsuhiko Mikoshiba 《Bioorganic & medicinal chemistry letters》2010,20(3):1141-1144
Aryl β-aminoethyl ketones were discovered as potent inhibitors of tissue transglutaminase. Heteroaryl-like thiophene groups and N-benzyl N-t-butyl aminoethyl group are critical to the strong inhibitory activity of aryl β-aminoethyl ketones. 相似文献
59.
Takanori Matsui Masayoshi Takeuchi Kei Fukami 《Biochemical and biophysical research communications》2010,398(2):326-5124
There is a growing body of evidence that advanced glycation end products (AGEs) and their receptor (RAGE) interaction evokes oxidative stress generation and subsequently elicits inflammatory and fibrogenic reactions, thereby contributing to the development and progression of diabetic nephropathy. We have previously found that nifedipine, a calcium-channel blocker (CCB), inhibits the AGE-induced mesangial cell damage in vitro. However, effects of nifedipine on proximal tubular cell injury remain unknown. We examined here whether and how nifedipine blocked the AGE-induced tubular cell damage. Nifedipine, but not amlodipine, a control CCB, inhibited the AGE-induced up-regulation of RAGE mRNA levels in tubular cells, which was prevented by the simultaneous treatment of GW9662, an inhibitor of peroxisome proliferator-activated receptor-γ (PPARγ). GW9662 treatment alone was found to increase RAGE mRNA levels in tubular cells. Further, nifedipine inhibited the AGE-induced reactive oxygen species generation, NF-κB activation and increases in intercellular adhesion molecule-1 and transforming growth factor-beta gene expression in tubular cells, all of which were blocked by GW9662. Our present study provides a unique beneficial aspect of nifedipine on diabetic nephropathy; it could work as an anti-oxidative and anti-inflammatory agent against AGEs in tubular cells by suppressing RAGE expression via PPARγ activation. 相似文献
60.
Acetylated YY1 regulates Otx2 expression in anterior neuroectoderm at two cis-sites 90 kb apart
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The mouse homeobox gene Otx2 plays essential roles at each step and in every tissue during head development. We have previously identified a series of enhancers that are responsible for driving the Otx2 expression in these contexts. Among them the AN enhancer, existing 92 kb 5' upstream, directs Otx2 expression in anterior neuroectoderm (AN) at the headfold stage. Analysis of the enhancer mutant Otx2(DeltaAN/-) indicated that Otx2 expression under the control of this enhancer is essential to the development of AN. This study demonstrates that the AN enhancer is promoter-dependent and regulated by acetylated YY1. YY1 binds to both the AN enhancer and promoter region. YY1 is acetylated in the anterior head, and only acetylated YY1 can bind to the sequence in the enhancer. Moreover, YY1 binding to both of these two sites is essential to Otx2 expression in AN. These YY1 binding sites are highly conserved in AN enhancers in tetrapods, coelacanth and skate, suggesting that establishment of the YY1 regulation coincides with that of OTX2 function in AN development in an ancestral gnathostome. 相似文献