Biomedical subjects

Hui Kong

Publications and source records attributed to Hui Kong.

13 recordsLinked to original sources

PubMed2007

Palladin regulates cell and extracellular matrix interaction through maintaining normal actin cytoskeleton architecture and stabilizing beta1-integrin.

Cell and extracellular matrix (ECM) interaction plays an important role in development and normal cellular function. Cell adhesion and cell spreading on ECM are two basic cellular behaviors related to cell-ECM interaction. Here we show that palladin, a novel actin cytoskeleton-associated protein, is actively involved in the regulation of cell-ECM interaction. It was found that palladin-deficient mouse embryonic fibroblasts (MEFs) display decreased cell adhesion and compromised cell spreading on various ECMs. Disorganized actin cytoskeleton architecture characterized by faint stress fibers, less lamellipodia and focal adhesions can account for the weakened cell-ECM interaction in palladin(-/-) MEFs. Furthermore, decreased polymerized filament actin and increased globular actin can be observed in palladin(-/-) MEFs, strongly suggesting that palladin is essential for the formation or stabilization of polymerized filament actin. Elevated phospho-cofilin level and proper responses in cofilin phosphorylation to either Rho signal agonist or antagonist in palladin(-/-) MEFs indicate that disrupted stress fibers in palladin(-/-) MEFs is not associated with cofilin phosphorylation. More interestingly, the protein level of ECM receptor beta1-integrin is dramatically decreased in MEFs lacking palladin. Down-regulation of beta1-integrin protein can be restored by proteasome inhibitor MG-132 treatment. All these data implicate that palladin is essential for cell-ECM interaction through maintaining normal actin cytoskeleton architecture and stabilizing beta1-integrin protein.

Actins↗

PubMed2006

Isobolographic analysis of the antinociceptive interactions between ketoprofen and paracetamol.

The present study was undertaken to evaluate the antinociceptive interaction between paracetamol and ketoprofen. The antinociceptive effect of oral administration of the drugs alone or in combination was evaluated using the mouse abdominal constriction test. The data were interpreted by isobolographic analysis to establish the nature of the interaction. The effective dose that produced 50% antinociception (ED(50,mix)) was calculated from the log dose-response curve of fixed-ratio combinations of paracetamol with ketoprofen. This ED(50,mix) was compared to the theoretical additive ED(50,add) by isobolographic analysis. The experimental ED(50,mix) was found to be significantly smaller than the theoretically calculated ED(50,add), indicating a synergistic antinociceptive interaction between ketoprofen and paracetamol. Pharmacokinetic studies were carried out with mice treated with combined ketoprofen (12 mg/kg) and paracetamol (36 mg/kg). Plasma levels of ketoprofen were not changed by concurrent paracetamol treatment, and similarly no statistically significant difference was observed between paracetamol alone and the combination with ketoprofen. The pharmacokinetic analysis revealed that the combination of ketoprofen with paracetamol exerted a synergistic (supra-additive) interaction that was not associated with a pharmacokinetic interaction. The results of this study demonstrate significant synergism between ketoprofen and paracetamol.

Acetaminophen↗

PubMed2006

Wnt pathway is involved in pleomorphic adenomas induced by overexpression of PLAG1 in transgenic mice.

Pleomorphic adenoma gene 1 (PLAG1) was found frequently rearranged and activated in human salivary gland pleomorphic adenomas. It encodes a developmentally regulated transcription factor. Ectopic overexpression of PLAG1 has been proposed to play a crucial role in tumorigenesis of salivary gland pleomorphic adenomas. It was reported that PLAG1 can activate the transcription of insulin-like growth factor 2 (IGF2), functioning as a protooncogene. In this report, we show that the salivary gland tumors developed in PLAG1 transgenic mice share major histopathologic features with human pleomorphic adenomas. It was found that beta-catenin, the key component of Wnt signaling pathway, was upregulated at transcriptional level in tumors developed in 3 independent transgenic mouse lines. Immunohistochemical staining revealed that expression of beta-catenin as well as c-myc, downstream of beta-catenin in Wnt signaling pathway, was highly upregulated with overexpression of PLAG1 transgene in tumor and normal transgenic salivary gland tissues. Moreover, we found that PLAG1 can activate the transcription of mouse but not human beta-catenin in the 3T3 cells cotransfected with reporter constructs. Sequence analysis shows there are 4 PLAG1 consensus binding sites in mouse beta-catenin promoter region but not in human. Our findings provide the first in vivo evidence for the oncogenic activity of PLAG1 in pleomorphic adenoma tumorigenesis, reveal a valued animal model for human salivary gland tumors and suggest that Wnt signaling pathway may also contribute to the development of pleomorphic adenomas in transgenic mice.

3T3 Cells↗

PubMed2005

Disruption of palladin results in neural tube closure defects in mice.

Palladin is a newly identified actin-associated protein which was proposed to be involved in actin cytoskeleton organization and nervous system development. Here, we show that inactivation of palladin leads to embryonic lethality due to severe defects of cranial neural tube closure and herniation of liver and intestine. It was found that palladin(-/-) embryos died around E15.5 and developed cranial neural tube closure defects (NTDs) with 100% penetrance. Whole mount in situ hybridization revealed that expression of palladin in early wild type embryos (E8.5) was specifically restricted in the elevating cranial neural folds where the neural tube closure is initiated. Palladin expression closely mirrors the phenotypic defects observed in palladin(-/-) mutants. While in E 9.5 and E10.5 embryos palladin was ubiquitously expressed. In vitro study revealed that formation of stress fibers in cytoplasm, cell adherent ability to extra-cellular matrix protein fibronectin and cell migration were dramatically disturbed in palladin(-/-) murine embryonic fibroblast cells (MEFs). Our findings suggest that palladin plays important roles in actin stress fiber formation, cell adhesion and migration. We propose that palladin is required for the initiation of neural tube closure and provides an important new candidate that may be implicated in the etiology of human NTDs.

Animals↗

PubMed2005

[The significance and expression of EGF and its receptor in nasal inverted papillomas and the correlation with malignant phenotype].

OBJECTIVE: To determine the expression of epidermal growth factor (EGF) and its receptor in nasal inverted papillomas (NIP) and to clarify the function of EGF in the establishment of NIPs and the correlation with malignant phenotype. METHOD: The expression of EGF and its receptor EGFR were examined by immunohistochemistry using LSAB method in sections of NIP from 24 patients and squamous carcinoma from 4 patients. RESULT: Showed that all the epithelium in NIPs together with vascular and stroma adjacent to the epithelium, expressed different degree of EGF. The EGF, EGFR expression in epithelium was significantly stronger in severe atypical hyperplasia of NIP than that in mild atypical hyperplasia of NIP (P < 0.01). CONCLUSION: The results suggest that EGF, EGFR participate in the growth of NIPs, part of which shows the characteristics of containing plenty of blood vessels and being bloody in operation. The enhanted EGF, EGFR in the epithelium may be identified as one of the parameters of judging the propensity of NIPs malignant transformation.

Aged↗

PubMed2005

[Cloning and transcriptional regulation analysis of amelogenin promoter in different cells].

PURPOSE: To clone different promoter region of amelogenin gene and analyze their transcriptional activity. METHODS: The upstream regulation sequences of amelogenin gene were retrieved and analyzed. Amplified by PCR from the genomic DNA of mouse C57BL/6J and digested with restriction endonucleases enzyme, different transcriptional regulation sequences of 5'flanking of amelogenin gene including the basal promoter were cloned and ligated with luciferase gene in PGL3-Basic vector. These report vectors were transiently transfected into CHO, Hela and UMR-106 cells and luciferase assay was performed to analyse the transcription activation of these promoters. RESULTS: 6 promoters different in length were cloned. The activity of luciferase was very strong in Hela cells. On the contrary, the CHO and UMR-106 cells showed weak fluorescence. Luciferase activity fluctuated with the different promoter lengths in Hela cell as well as in CHO and UMR-106 cells. 975 bp and 532 bp of amelogenin 5'flanking DNA had a strong transcriptional activation, but 285 bp of amelogenin 5'flanking DNA had a weaker transcriptional activation. CONCLUSION: The sequence of amelogenin promoter can be activated in Hela cell. Hela cell can be used as a good model to study the transcriptional regulation of amelogenin promoter. According to the different activities of different lengths, it is suggested that there were some potential siliencer located between -975 and -532, and some potential activator in the region between -532 and -285.

Amelogenin↗

PubMed2004

[HUP98-HOXA9 transgenic mice are susceptible to N-ethyl-N-nitrosourea stimulation in leukemogenesis].

OBJECTIVE: In order to investigate the leukemogenic potential of NUP98-HOXA9 fusion gene in vivo. METHODS: Molecular cloning technology was used to construct NUP98-HOXA9 transgenic plasmid and NUP98-HOXA9 transgenic mice were generated. The genotype and phenotype of the NUP98-HOXA9 transgenic mice were analyzed by PCR, RT-PCR and colony-forming assay. The effect of N-ethyl-N-nitrosourea (ENU) stimulation on the transgenic mice was analyzed by peripheral blood count, bone marrow (BM) cells morphology pathological examination. RESULTS: The transgenic expression was detected in 5 independent lines of NUP98-HOXA9 transgenic mice, but no expected phenotypes was found in 2 year follow-up. Upon ENU stimulation, 2 of 10 transgenic mice developed myeloid leukemia, suggesting that NUP98-HOXA9 transgenic mice have increased susceptibility to ENU mutagenesis in leukemogenesis. CONCLUSION: The fusion gene expressed in BM cells of NUP98-HOXA9 transgenic mice. It seems that the expression of the fusion gene is insufficient to trigger leukemogenesis. However, the increased susceptibility to ENU mutagenesis suggests that NUP98-HOXA9 fusion gene might play a potential role in leukemogenesis.

Animals↗

PubMed2004

[Development of human myeloid leukemia-like phenotype in NUP98-PMX1 transgenic mice].

OBJECTIVE: In order to investigate the leukemogenic potential of NUP98-PMX1 fusion gene in vivo. METHODS: NUP98-PMX1 transgenic mice were generated, in which the fusion gene was driven by hCG promoter and expressed in myeloid cells at early stage of differentiation. Molecular cloning technology was used to construct NUP98-PMX1 transgenic plasmid. The genotype and phenotype of the NUP98-PMX1 transgenic mice were analyzed by PCR, RT-PCR, peripheral blood count (PBC), bone marrow (BM) cells morphology and pathological examination. RESULTS: NIH3T3 cells transfected with NUP98-PMX1 fusion gene grew faster, formed colonies in soft agar, and developed tumors in 10 inoculated nude mice. Among 8 disordered NUP98-PMX1 transgenic mice, 4 developed myeloid leukemia-like phenotype, including 3 resembling human chronic myeloid leukemia. CONCLUSION: NUP98-PMX1 has oncogenic activity and plays a crucial role in leukemogenesis.

Animals↗

PubMed2003

[Preliminary study of correlation factor in surgery effect of nasal polyps].

OBJECTIVE: To study the relation between nasal polyp pathology, cellular expression of CD45 RO, CD20, CD68, proliferating cell nuclear antigen (PCNA) in nasal polyps and the response to surgery. METHOD: Nasal polyp tissues from 50 patients were evaluated for cellular expression of CD45 RO, CD20, CD68, PCNA using immunohistochemistry SP by counting the average number in 5 chosen high-power fields, histopathological observations were combined with clinic and postoperative dates. Analyses were performed on SPSS10.0. RESULT: Significant correlation was found between CD68+ cells and eosinophils or PCNA positive cells on epithelium. PCNA positive cells on epithelium has significant correlation on fibroblast (P < 0.05). The nasal polyps dominated with CD68+ and high polyp score have significant correlation to cure. CONCLUSION: Extent of inflammatory cells infiltration especially CD68+ or eosinophilia or lymphocytes and polyp score have significant effect on cure rate.

Adolescent↗

PubMed2003

[Development of salivary gland tumors in pleomorphic adenoma gene 1 transgenic mice].

OBJECTIVE: Activation and overexpression of pleomorphic adenoma (PLAG1) gene due to t(3;8)(p21;q12) translocation are associated with the development of human pleomorphic adenomas of the salivary glands. This study was conducted to generate ubiquitously-expressed or tissue-specific expressed PLAG1 transgenic mice and to elucidate the role of PLAG1 gene in tumorigenesis in vivo. METHODS: Human PLAG1 cDNA was cloned from salivary gland tumor or placenta tissues by RT-PCR. Ubiquitous expression vector pCMV-EGFP/PLAG1 driven by CMV promoter and tissue-specific expression vector pMMTV-PLAG1 driven by MMTV LTR were constructed. NIH3T3 cells transiently transfected with pCMV-EGFP/PLAG1 showed high expression of PLAG1 in nucleus. Transgenes were microinjected into pronucleus of zygotes to generate transgenic mice. RESULTS: It was found that the human PLAG1 cDNA cloned from several salivary gland tumor and normal placenta tissues consistently showed a variation of a single nucleotide at the same position when compared with the human PLAG1 cDNA sequence in Genbank (Accession No. U65002), which led to T458P at protein level. It might be a single nucleotide polymorphism (SNP)locus. Fused EGFP/PLAG1 protein was found to be localized in the nucleus of NIH3T3 cells transiently transfected with pCMV-EGFP/ PLAG1. Several pCMV-EGFP/PLAG1 and pMMTV-PLAG1 transgenic mouse lines were obtained respectively. As might be expected, pMMTV-PLAG1 transgenic mice spontaneously developed salivary gland tumors in three independent lines, among which, line 42 showed tumorigenic phenotype in 100% of transgenic mice within three months after birth. CONCLUSION: Overexpression of PLAG1 gene plays a crucial role in tumorigenesis of salivary gland tumors.

Animals↗

PubMed2003

[Establishment of transgenic mice for HRX-EEN fusion gene].

OBJECTIVE: To study the biological function of fusion gene HRX-EEN and its role in leukemogenesis, and to provide an ideal animal model for anti-leukemia drug screening. METHODS: HRX-EEN fusion gene was constructed by use of three different DNA fragments, and it was inserted into hCG transgenic vector. G(0) transgenic mice were obtained by microinjection of the recombined DNA into the pronucleus of zygotes, followed by implantation of the injected zygotes into pseudopregnant mice. The integration of the transgene was tested by PCR and its expression by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: The sequence of recombined HRX-EEN gene was confirmed by sequencing. PCR testing revealed a total of 7 G(0) transgenic mice, these mice were then mated with C57 wild type mice. Except mouse No. 35 that died, the others all had their F1 offsprings. From these 6 lines of transgenic mice, HRX-EEN gene was found to be stably expressed in 3 lines by RT-PCR. Up to now, all transgenic mice expressing the fusion gene have no obvious abnormal phenotypes. CONCLUSION: A transgenic mice model in which the HRX-EEN fusion gene can be stably expressed has been established.

Animals↗

PubMed2002

[Construction and tumorigenic study on a novel fusion gene AML1-MTG16].

OBJECTIVE: To test whether splicing overlapping extension(SOE) method can be a tool for obtaining rare fusion gene's transcripts and to study the tumorigenic capacity of a novel fusion gene AML1-MTG16. METHODS: SOE method was used to obtain AML1- MTG16 fusion gene's transcripts. MTG16, AML1-MTG16 and AML1-MTG16 without III,VI conserved domains of MTG16 segment were inserted into pEGFP- C1,pDsRed-N1 vector respectively,then transfected NIH3T3 cell line by lipofection. Forty-eight hours later, the transfected cells were examined by laser-scanning confocal microscopy. Stable transfected cells were obtained by G418 500ug/ul selection for one month. Growth curve, soft agar colonies formation tumorigenesis in nude mice were done to compare the difference between stable transfected cells. RESULTS: Recombined AML1-MTG16 by SOE contained its CDS. NIH3T3 expressing AML1-MTG16 had a faster proliferation in medium, colony growth in soft agar. AML1-MTG16 expression cells also induced tumors formation following injection into nude mouse. MTG16,AML1-MTG16 and AML1-MTG16 without III,VI conserved domains of MTG16 were colocalized in the nucleus of cotransfected NIH3T3 cells under the examination of laser-scanning confocal microscope. CONCLUSION: SOE is an effective method to get rare fusion gene's transcripts. AML1-MTG16 plays an important role in leukemogenesis. MTG16 may also have a carcinogenic property within the AML1-MTG16 fusion gene. Carcinogenic property of AML1-MTG16 is restricted to its localization in the nuclear matrix. N terminal of MTG16 may play an important part in the carcinogenic activity of AML1-MTG16.

3T3 Cells↗

PubMedDate not supplied

Generalized 2D principal component analysis for face image representation and recognition.

In the tasks of image representation, recognition and retrieval, a 2D image is usually transformed into a 1D long vector and modelled as a point in a high-dimensional vector space. This vector-space model brings up much convenience and many advantages. However, it also leads to some problems such as the Curse of Dimensionality dilemma and Small Sample Size problem, and thus produces us a series of challenges, for example, how to deal with the problem of numerical instability in image recognition, how to improve the accuracy and meantime to lower down the computational complexity and storage requirement in image retrieval, and how to enhance the image quality and meanwhile to reduce the transmission time in image transmission, etc. In this paper, these problems are solved, to some extent, by the proposed Generalized 2D Principal Component Analysis (G2DPCA). G2DPCA overcomes the limitations of the recently proposed 2DPCA (Yang et al., 2004) from the following aspects: (1) the essence of 2DPCA is clarified and the theoretical proof why 2DPCA is better than Principal Component Analysis (PCA) is given; (2) 2DPCA often needs much more coefficients than PCA in representing an image. In this work, a Bilateral-projection-based 2DPCA (B2DPCA) is proposed to remedy this drawback; (3) a Kernel-based 2DPCA (K2DPCA) scheme is developed and the relationship between K2DPCA and KPCA (Scholkopf et al., 1998) is explored. Experimental results in face image representation and recognition show the excellent performance of G2DPCA.

Algorithms↗