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131.
Ogasawara D Suzuki T Mino K Ueda R Khan MN Matsubara T Koseki K Hasegawa M Sasaki R Nakagawa H Mizukami T Miyata N 《Bioorganic & medicinal chemistry》2011,19(12):3702-3708
Optically active (1S,2R)-NCL-1 and (1R,2S)-NCL-1 were synthesized and evaluated for their lysine-specific demethylase 1 inhibitory activity and cell growth inhibitory activity. In enzyme assays, the (1S,2R)-isomer was approximately four times more potent than the (1R,2S)-isomer. In cell growth inhibition assays, the two isomers showed similar activity in HEK293 cells and SH-SY5Y cells, whereas the (1S,2R)-isomer showed approximately four times more potent activity than the (1R,2S)-isomer in HeLa cells. 相似文献
132.
At our research center, cynomolgus monkeys (Macaca fascicularis) are bred by mating or intracytoplasmic sperm injection (ICSI) and embryo transfer. We typically transfer 2 embryos, because the pregnancy rate is better than that for single embryo transfer. In the case we present here, 2 embryos that had been frozen and thawed after ICSI were transplanted into a recipient female macaque, and a multiple pregnancy (3 fetuses) was confirmed. All 3 fetuses were miscarried between days 81 and 85 of pregnancy. One fetus, which was wrapped in the amnion, was expelled along with its own placenta and one other. Because the other placenta had 2 umbilical arteries, 2 fetuses may have shared it. Therefore, we believe this pregnancy was a case of triplets, including a set of twins from an embryo that divided after transfer. 相似文献
133.
Eiichi Imano Ryuzo Kwamori Norimichi Iwama Yutaka Umayahara Yoshimitsu Yamasaki Takenobu Kamada 《生物化学与生物物理学报:疾病的分子基础》1993,1181(2):131-134
An asymmetrical reduction in the levels of the insulin receptor mRNA transcribed from one allele was reported in some patients with severe insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM). To detect this abnormality, we designed the less laborious method; Allele-specific oligonucleotide hybridization of the amplified mRNA (cDNA) by using silent polymorphisms in the insulin receptor gene (nucleotide positions at 1686 and 1698). The allelic frequencies of C-1686 and T-1686 were 0.63 and 0.37, respectively (0.60 and 0.40 in 10 normal subjects, and 0.67 and 0.33 in 20 NIDDMs; n.s.). Similarly, the allelic frequencies of A-1698 and G-1698 were 0.47 and 0.53, respectively (0.50 and 0.50 in the normal subjects, and 0.45 and 0.55 in the NIDDMs; n.s.). These results suggest that these two polymorphisms are very common in Japanese. Nineteen (64%) out of 30 cases are heterozygous at one or two position(s), suggesting that it is possible to distinguish the mRNA transcribed from each of two alleles of the insulin receptor gene with using allele-specific oligonucleotide hybridization. Although we successfully measured the ratio of mRNA expression from two alleles of the gene in 20 NIDDMs, there was not patient whose mRNA transcribed from one allele of the insulin receptor gene was extremely decreased. We showed that allele-specific oligonucleotide hybridization method is useful for the screening of abnormal insulin-receptor gene expression. 相似文献
134.
Motoyuki Sugai Hiroshi Koike Yeong-Man Hong Yoichiro Miyake Ryuzo Nogami Hidekazu Suginaka 《FEMS microbiology letters》1989,61(3):267-272
A bacteriolytic enzyme obtained from the culture fluid of Staphylococcus aureus FDA 209P was purified to homogeneity utilizing dye-ligand affinity column chromatography, hydrophobic interaction high pressure liquid chromatography (HPLC) and hydroxyapatite HPLC. Subsequent characterizations indicated that the purified enzyme acted as endo-beta-N-acetylglucosaminidase. The molecular weight determined by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was 51,000 and the isoelectric point was higher than 10. The optimum pH for the enzyme activity on whole cells of Micrococcus luteus as a substrate was 8.0. Some heavy metal cations (Cu2+ and Zn2+) inhibited the enzyme activity at a concentration of 0.1 mM and others (Ba2+, Mg2+ and Co2+) showed a stimulating effect at a concentration of 1 mM. 相似文献
135.
Yasushi Shida Masami Okabe Tokuyuki Kuroda Makoto Morimotol Ryuzo Ueda Toshitada Takahashi 《Biotherapy》1992,5(2):97-105
Through a linker containing thiocarbomate bound to the 7-N position of mitomycin C (MMC), conjugates with a monoclonal antibody to CD10 (NL-1) were prepared, and their antitumor activities were examined. All five conjugates, except one, showedin vitro cytotoxity to two CD10+ lymphoid cell lines superior to MMC. The conjugate displaying the highest cytotoxicity was selected and further tested against three CD10+ and two CD10 lymphoid cell linesin vitro. The conjugate with NL-1 antibody demonstrated higher cytotoxic activity against CD10+ tumor cells than the control conjugate with normal immunoglobulin, while there was no significant difference, when tested against CD10– tumors. The cytotoxic activity of the NL-1 conjugate to CD10+ tumors was significantly blocked by NL-1 antibody.
In vivo antitumor activity of the NL-1 conjugate was then tested against a CD10+ tumor transplanted to nude mice, and side effects were recorded. The NL-1 conjugate (4 mg/kg) showed anin vivo antitumor effect similar to MMC (2 mg/kg), which is at nearly maximal tolerable dose; the latter induced decreases in numbers of leukocytes and platelets, while the former did not, suggesting less side effect by the NL-1 conjugate. Since MMC demonstrates a broad spectrum of antitumor activity, the conjugate, as such, may be applicable for the treatment of cancer patients. 相似文献
136.
Over expression of receptor tyrosine kinases is responsible for the development of a wide variety of malignancies. Termination of growth factor signaling is primarily determined by the down regulation of active growth factor/receptor complexes. In recent years, considerable insight has been gained in the endocytosis and degradation of growth factor receptors. A crucial player in this process is the EGFR Protein tyrosine kinase Substrate #15, or Eps15. This protein functions as a scaffolding adaptor protein and is involved both in secretion and endocytosis. Eps15 has been shown to bind to AP-1 and AP-2 complexes, to bind to inositol lipids and to several other proteins involved in the regulation of intracellular trafficking. In addition, Eps15 has been detected in the nucleus of mammalian cells. Activation of growth factor receptors induces tyrosine phosphorylation and mono-ubiquitination of Eps15. The role of these post translational modifications of Eps15 is still a mystery. It is proposed that Eps15 and its family members Eps15R and Eps15b are involved in the regulation of membrane morphology, which is required for intracellular vesicle formation and trafficking. 相似文献
137.
In mammals, Sirt1, a member of the sirtuin family of proteins, functions as a nicotinamide adenine dinucleotide-dependent protein deactylase, and has important physiological roles, including the regulation of glucose metabolism, cell survival, and mitochondrial respiration. The initial investigations of Sirt1 deficient mice have revealed a phenotype that includes a reduced lifespan, small size, and an increased frequency of abnormal sperm. We have now performed a detailed analysis of the molecular and functional effects of Sirt1 deficiency in the germ line of Sirt1 knock-out (-/-) mice. We find that Sirt1 deficiency markedly attenuates spermatogenesis, but not oogenesis. Numbers of mature sperm and spermatogenic precursors, as early as d15.5 of development, are significantly reduced ( approximately 2-10-fold less; P=0.004) in numbers in Sirt1-/- mice, whereas Sirt1 deficiency did not effect the efficiency oocyte production following superovulation of female mice. Furthermore, the proportion of mature sperm with elevated DNA damage ( approximately 7.5% of total epididymal sperm; P = 0.02) was significantly increased in adult Sirt1-/- males. Analysis of global gene expression by microarray analysis in Sirt1 deficient testis revealed dysregulated expression of 85 genes, which were enriched (P<0.05) for genes involved in spermatogenesis and protein sumoylation. To assess the function of Sirt1 deficient germ cells, we compared the efficiency of generating embryos and viable offspring in in vitro fertilization (IVF) experiments using gametes from Sirt1-/- and sibling Sirt1+/- mice. While viable animals were derived in both Sirt1-/- X wild type and Sirt1-/- X Sirt1-/- crosses, the efficiency of producing both 2-cell zygotes and viable offspring was diminished when IVF was performed with Sirt1-/- sperm and/or oocytes. Together, these data support an important role for Sirt1 in spermatogenesis, including spermatogenic stem cells, as well as germ cell function. 相似文献
138.
Effect of pH value of freeze-drying solution on the chromosome integrity and developmental ability of mouse spermatozoa 总被引:8,自引:0,他引:8
The nuclei of freeze-dried mouse spermatozoa are able to retain their chromosome integrity and developmental potential. To optimize the conditions of freeze-drying, we examined whether pH values of the freeze-drying solution affect the chromosome integrity and developmental potential of sperm nuclei. The sperm freeze-drying solution we used contained a high concentration (50 mM) of calcium-chelating EGTA. Sperm chromosomes were examined at the metaphase of the first mitosis after injection of freeze-dried spermatozoa into matured oocytes. The developmental potential of sperm nuclei was assessed by examining the development of fetuses in midgestation. The results showed that both sperm chromosomes and sperm developmental potential are maintained better when the freeze-drying solution was slightly alkaline (pH 8.0) rather than near neutral or acidic (pH 7.4-6.0). The data indicated that the chromosome integrity and developmental ability of mouse spermatozoa are affected by the pH value of freeze-drying solution. 相似文献
139.
The Japanese macaque or snow monkey (Macaca fuscata) is an autochthonous monkey in Japan. It has long been assumed that the monkey population was not infected with Cercopithecine herpesvirus 1 (monkey B virus [BV]) since cases of human BV infection have never been reported in Japan. Although serologic testing of captive snow monkeys in Japan revealed antibodies to BV, it was thought that native Japanese macaques had either been infected with herpes simplex virus from humans or with BV from other imported macaque species. To clarify this issue, we performed polymerase chain reaction (PCR) analysis to amplify BV sequences from trigeminal ganglia of 30 Japanese macaque monkeys that were seropositive for BV. Sequences from two BV genes, UL27 (360 bp) and UL19 (1.0 Kbp), from 3 of 30 monkeys were amplified. Results of restriction fragment length polymorphism analysis and DNA sequencing of the fragments provided evidence that native Japanese macaques are infected with BV. Phylogenetic analysis indicated that these monkeys harbor their own genotype of BV that is different from other known BV genotypes, and provided additional evidence supporting the co-evolution of BV and macaques. 相似文献
140.
Tamashiro KL Wakayama T Yamazaki Y Akutsu H Woods SC Kondo S Yanagimachi R Sakai RR 《Experimental biology and medicine (Maywood, N.J.)》2003,228(10):1193-1200
Cloning technology has potential to be a valuable tool in basic research, clinical medicine, and agriculture. However, it is critical to determine the consequences of this technique in resulting offspring before widespread use of the technology. Mammalian cloning using somatic cells was first demonstrated in sheep in 1997 and since then has been extended to a number of other species. We examined development, behavior, physiology, and longevity in B6C3F1 female mice cloned from adult cumulus cells. Control mice were naturally fertilized embryos subjected to the same in vitro manipulation and culture conditions as clone embryos. Clones attained developmental milestones similar to controls. Activity level, motor ability and coordination, and learning and memory skills of cloned mice were comparable with controls. Interestingly, clones gained more body weight than controls during adulthood. Increased body weight was attributable to higher body fat and was associated with hyperleptinemia and hyperinsulinemia indicating that cloned mice are obese. Cloned mice were not hyperphagic as adults and had hypersensitive leptin and melanocortin signaling systems. Longevity of cloned mice was comparable with that reported by the National Institute on Aging and the causes of death were typical for this strain of mouse. These studies represent the first comprehensive set of data to characterize cloned mice and provide critical information about the long-term effects of somatic cell cloning. 相似文献