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81.
Choong IC Serafimova I Fan J Stockett D Chan E Cheeti S Lu Y Fahr B Pham P Arkin MR Walker DH Hoch U 《Bioorganic & medicinal chemistry letters》2008,18(21):5763-5765
The identification of a selective CDK2, 7, 9 inhibitor 4 with improved permeability is described. Compound 4 exhibits comparable CDK selectivity profile to SNS-032, but shows improved permeability and higher bioavailability in mice. 相似文献
82.
Choong Hyun Lee In Koo Hwang Ki-Yeon Yoo Jung Hoon Choi Ok Kyu Park Jae-Chul Lee Young-Gil Jeong In Se Lee Moo-Ho Won 《Cellular and molecular neurobiology》2009,29(5):665-672
The hippocampus is associated with learning and memory function and shows neurochemical changes in aging processes. Calbindin
D-28k (CB) binds calcium ion with a fast association rate. We examined age-related changes in CB immunoreactivity and its
protein level in the gerbil hippocampus during normal aging. In the hippocampal CA1 region (CA1) and CA2, CB immunoreaction
was found in some neurons in the stratum pyramidale (SP) at postnatal month 1 (PM 1). CB immunoreactivity in neurons was markedly
increased at PM 3. Thereafter, CB immunoreactivity was decreased with time: CB-immunoreactive (+) neurons were fewest at PM 24. In the CA3, a few CB+ neurons were found only in the SP at PM 1 and in the stratum radiatum at PM 18 and 24. In addition, mossy fibers were stained
with CB at PM 1. CB immunoreactivity in mossy fibers was markedly increased at PM 3, thereafter it was decreased with time.
In the dentate gyrus, many granule cells (GC) in the granule cell layer were stained with CB at PM 1. CB immunoreactivity
in GC was markedly increased at PM 3, thereafter CB immunoreactivity was decreased with time. In Western blot analysis, CB
protein level in the gerbil hippocampus was highest at PM 3, thereafter CB protein levels were decreased with time. This result
indicates that CB in the gerbil hippocampus is abundant at PM 3 and is decreased with age. 相似文献
83.
Ki-Yeon Yoo Ok Kyu Park Jiatian Yu Bingchun Yan Hua Li Choong Hyun Lee Jung Hoon Choi Dae Won Kim In Koo Hwang Moo-Ho Won 《Cellular and molecular neurobiology》2009,29(3):413-421
Oxidative stress is one of predisposing factors to age-related neurodegeneration in the brain. In particular, thiol-containing
groups are susceptible to oxidative stress, which induces the formation of the disulfide bond and/or hyperoxidized form of
thiol-containing proteins. We observed the protein thiol levels in the hippocampal homogenates and also investigated changes
in hyperoxidized form of peroxiredoxin (Prx–SO3) immunoreactivity and proteins levels in the gerbil hippocampal subregions during normal aging. Levels of total thiol, non-protein
thiol, and protein thiol were decreased in the hippocampal homogenates with age. At post-natal month 1 (PM 1), pyramidal and
non-pyramidal cells in the hippocampal CA1 region (CA1) showed Prx–SO3 immunoreactivity. Prx–SO3 immunoreactivity in the cells was decreased by PM 12, thereafter, Prx–SO3 immunoreactivity in the cells increased again with age. In the CA2/3, Prx–SO3 immunoreactivity in pyramidal cells was not significantly changed; however, the immunoreactivity in pyramidal cells was very
low at PM 12. Prx–SO3 immunoreactivity in the dentate gyrus (DG) was distinctly changed during aging. At PM 1, Prx–SO3 immunoreactivity in granule and polymorphic cells was weak and strong, respectively. The immunoreactivity in the neurons
was decreased with age, not shown in any neurons at PM 12. Thereafter, Prx–SO3 immunoreactivity increased again with age. In addition, Prx–SO3 protein level in the hippocampus was lowest at PM 12. These results suggest that thiol-containing proteins are changed during
aging and Prx–SO3 immunoreactivity was different according to cells in the hippocampal subregion during aging. 相似文献
84.
Sina Babazadeh Matthew L Broadhead John L Slavin Peter FM Choong 《International Seminars in Surgical Oncology : ISSO》2009,6(1):18
A presacral mass can present a diagnostic dilemma for the surgical oncologist. Differential diagnoses include congenital causes such as teratoma or chordoma, neurological causes such as neurilemoma or neurofibroma or other malignancies such as lymphoma or sarcoma. Diagnosis usually requires imaging such as CT and MRI and tissue biopsy. We present an unusual cause of a presacral mass being extramedullary haematopoiesis, found incidentally in a 71 year old female. Extramedullary haematopoiesis is defined as the production of myeloid and erythroid elements outside of the bone-marrow. This diagnosis is extremely rare in the presacral area especially in a patient with no haematological abnormalities. A review of the literature is presented. 相似文献
85.
Je Ma C Jung WJ Lee KY Kim YC Sung SH 《Journal of enzyme inhibition and medicinal chemistry》2009,24(3):676-679
The n-butanol (n-BuOH) fraction of Orostachys japonicus A. Berger (Crassulaceae) significantly inhibited calpain activity. Through the activity-guided isolation from the n-BuOH fraction, herbacetin 8-O-alpha-D-ribopyranoside (1), kaempferol (2), quercetin (3), afzelin (4), astragalin (5), isoquercetin (6) and quercitrin (7) were obtained. Their structures were determined by spectroscopic techniques. Among them, compound 3 and 5 had significant calpain inhibitory activities. 相似文献
86.
Sung Eun Sim Yoon Hee Chung Ji Hoon Jeong Sin Weon Yun Hyoun-Sub Lim Daejin Kim Sung Su Kim Won Bok Lee Choong Ik Cha 《Journal of molecular histology》2009,40(2):157-163
In the present study, we performed immunohistochemical studies to investigate the changes of insulin-like growth factor binding
protein 2 (IGFBP2) in the central nervous system of SOD1G93A mutant transgenic mice as an in vivo model of amyotrophic lateral sclerosis (ALS). Decreased immunoreactivity for IGFBP2
was observed in the cerebral cortex, hippocampus and brainstem of SOD1G93A transgenic mice. In the cerebral cortex, the number of IGFBP2-positive cells was decreased in the somatomotor area, somatosensory
area, auditory area, visual area, entorhinal area, piriform area and prefrontal area. In the hippocampal formation, IGFBP2
immunoreactivity was significantly decreased in the CA1-3 areas and the dentate gyrus. In the brainstem, few IGFBP2-immunoreactive
cells were observed in the medullary and pontine reticular formation, vestibular nucleus, trigeminal motor nucleus, facial
nucleus, hypoglossal nucleus and raphe nucleus. In the spinal cord, IGFBP2 immunoreactivity was not significantly decreased
in SOD1G93A transgenic mice. This study showing decreased IGFBP2 in different brain regions of SOD1G93A transgenic mice may provide clues for understanding differential susceptibility of neural structures in ALS.
S. E. Sim and Y. H. Chung have contributed equally to this work. 相似文献
87.
Ingxin Choong Louis Saint‐Amant Shawn M. Sprague Hiromi Hirata Wilson W. Cui Richard I. Hume John Y. Kuwada 《Developmental neurobiology》2010,70(7):508-522
A screen for zebrafish motor mutants identified two noncomplementing alleles of a recessive mutation that were named non‐active (navmi89 and navmi130). nav embryos displayed diminished spontaneous and touch‐evoked escape behaviors during the first 3 days of development. Genetic mapping identified the gene encoding NaV1.6a (scn8aa) as a potential candidate for nav. Subsequent cloning of scn8aa from the two alleles of nav uncovered two missense mutations in NaV1.6a that eliminated channel activity when assayed heterologously. Furthermore, the injection of RNA encoding wild‐type scn8aa rescued the nav mutant phenotype indicating that scn8aa was the causative gene of nav. In‐vivo electrophysiological analysis of the touch‐evoked escape circuit indicated that voltage‐dependent inward current was decreased in mechanosensory neurons in mutants, but they were able to fire action potentials. Furthermore, tactile stimulation of mutants activated some neurons downstream of mechanosensory neurons but failed to activate the swim locomotor circuit in accord with the behavioral response of initial escape contractions but no swimming. Thus, mutant mechanosensory neurons appeared to respond to tactile stimulation but failed to initiate swimming. Interestingly fictive swimming could be initiated pharmacologically suggesting that a swim circuit was present in mutants. These results suggested that NaV1.6a was required for touch‐induced activation of the swim locomotor network. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 70:508–522, 2010 相似文献
88.
Background
The putative promoter of the holocarboxylase synthetase (HLCS) gene on chromosome 21 is hypermethylated in placental tissues and could be detected as a fetal-specific DNA marker in maternal plasma. Detection of fetal trisomy 21 (T21) has been demonstrated by an epigenetic-genetic chromosome dosage approach where the amount of hypermethylated HLCS in maternal plasma is normalized using a fetal genetic marker on the Y chromosome as a chromosome dosage reference marker. We explore if this method can be applied on both male and female fetuses with the use of a paternally-inherited fetal single nucleotide polymorphism (SNP) allele on a reference chromosome for chromosome dosage normalization.Methodology
We quantified hypermethylated HLCS molecules using methylation-sensitive restriction endonuclease digestion followed by real-time or digital PCR analyses. For chromosome dosage analysis, we compared the amount of digestion-resistant HLCS to that of a SNP allele (rs6636, a C/G SNP) that the fetus has inherited from the father but absent in the pregnant mother.Principal Findings
Using a fetal-specific SNP allele on a reference chromosome, we analyzed 20 euploid and nine T21 placental tissue samples. All samples with the fetal-specific C allele were correctly classified. One sample from each of the euploid and T21 groups were misclassified when the fetal-specific G allele was used as the reference marker. We then analyzed 33 euploid and 14 T21 maternal plasma samples. All but one sample from each of the euploid and T21 groups were correctly classified using the fetal-specific C allele, while correct classification was achieved for all samples using the fetal-specific G allele as the reference marker.Conclusions
As a proof-of-concept study, we have demonstrated that the epigenetic-genetic chromosome dosage approach can be applied to the prenatal diagnosis of trisomy 21 for both male and female fetuses. 相似文献89.
Background
Mapping the expression changes during breast cancer development should facilitate basic and translational research that will eventually improve our understanding and clinical management of cancer. However, most studies in this area are challenged by genetic and environmental heterogeneities associated with cancer.Methodology/Principal Findings
We conducted proteomics of the MCF10AT breast cancer model, which comprises of 4 isogenic xenograft-derived human cell lines that mimic different stages of breast cancer progression, using iTRAQ-based tandem mass spectrometry. Of more than 1200 proteins detected, 98 proteins representing at least 20 molecular function groups including kinases, proteases, adhesion, calcium binding and cytoskeletal proteins were found to display significant expression changes across the MCF10AT model. The number of proteins that showed different expression levels increased as disease progressed from AT1k pre-neoplastic cells to low grade CA1h cancer cells and high grade cancer cells. Bioinformatics revealed that MCF10AT model of breast cancer progression is associated with a major re-programming in metabolism, one of the first identified biochemical hallmarks of tumor cells (the “Warburg effect”). Aberrant expression of 3 novel breast cancer-associated proteins namely AK1, ATOX1 and HIST1H2BM were subsequently validated via immunoblotting of the MCF10AT model and immunohistochemistry of progressive clinical breast cancer lesions.Conclusion/Significance
The information generated by this study should serve as a useful reference for future basic and translational cancer research. Dysregulation of ATOX1, AK1 and HIST1HB2M could be detected as early as the pre-neoplastic stage. The findings have implications on early detection and stratification of patients for adjuvant therapy. 相似文献90.
A small library of bivalent α-D-mannopyranosides having rigid linkers was constructed in order to evaluate the effects of inter-saccharide distances upon multivalent binding interactions with plant and bacterial lectins. To this end, iodoaryl and propargyl α-D-mannopyranosides were synthesized and the former treated with TMS-acetylene under palladium chemistry to provide their corresponding ethynylaryl derivatives. A library of 15 dimeric members was then obtained using Lewis acid catalyzed glycosidation, aryl-aryl homocoupling, transition metal catalyzed Sonogashira cross-coupling reactions, and oxidative Glaser homocoupling. 相似文献