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Biomedical subjects

X Yuan

Publications and source records attributed to X Yuan.

At least 19 recordsLinked to original sources
PubMed2006

Regulation of cartilaginous ECM gene transcription by chondrocytes and MSCs in 3D culture in response to dynamic loading.

This study explored the biologic response of chondrocytes and mesenchymal stem cells (MSCs) to a dynamic mechanical loading regime. We developed a time-efficient methodology for monitoring regional changes in extracellular matrix gene transcription using reporter promoter constructs. Specifically, transfected cells were homogenously distributed throughout agarose hydrogel constructs, and spatial and temporal gene expression and the ability to form functional ECM were analyzed in response to dynamic mechanical stimuli. Theoretical analyses were used to predict the physical signals generated within the gel in response to these loading regimes. Using a custom compression bioreactor system, changes in aggrecan and type II collagen promoter activity in transfected chondrocyte-laden cylindrical constructs were evaluated in response to a range of loading frequencies and durations. In general, aggrecan promoter activity increased with increasing duration of loading, particularly in the outer annulus region. Interestingly, type II collagen promoter activity decreased in this annular region under identical loading conditions. In addition, we explored the role of mechanical compression in directing chondrogenic differentiation of MSCs by monitoring short-term aggrecan promoter activity. As an example of long-term utility, a specific loading protocol was applied to MSC-laden constructs for 5 days, and the resultant changes in glycosaminoglycan (GAG) production were evaluated over a 4-week period. This dynamic loading regime increased not only short-term aggrecan transcriptional activity but also GAG deposition in long-term culture. These results demonstrate the utility of a new reporter promoter system for optimizing loading protocols to improve the outcome of engineered chondrocyte- and MSC-laden cartilaginous constructs.

Aggrecans↗
PubMed2006

An online literature mining tool for protein phosphorylation.

A web-based version of the RLIMS-P literature mining system was developed for online mining of protein phosphorylation information from MEDLINE abstracts. The online tool presents extracted phosphorylation objects (phosphorylated proteins, phosphorylation sites and protein kinases) in summary tables and full reports with evidence-tagged abstracts. The tool further allows mapping of phosphorylated proteins to protein entries in the UniProt Knowledgebase based on PubMed ID and/or protein name. The literature mining, coupled with database association, allows retrieval of rich biological information for the phosphorylated proteins and facilitates database annotation of phosphorylation features.

Animals↗
PubMed2006

Identification of potential CSF biomarkers in ALS.

BACKGROUND: The clinical diagnosis of ALS is based entirely on clinical features. Identification of biomarkers for ALS would be important for diagnosis and might also provide clues to pathogenesis. OBJECTIVE: To determine if there is a specific protein profile in the CSF that distinguishes patients with ALS from those with purely motor peripheral neuropathy (PN) and healthy control subjects. METHODS: CSF obtained from patients with ALS, disease controls (patients with other neurologic disorders), and normal controls were analyzed using the surface-enhanced laser desorption/ionization time-of-flight mass spectrometry proteomics technique. Biomarker sensitivity and specificity was calculated with receiver operating characteristic curve methodology. ALS biomarkers were purified and sequence identified by mass spectrometry-directed peptide sequencing. RESULTS: In initial proteomic discovery studies, three protein species (4.8-, 6.7-, and 13.4-kDa) that were significantly lower in concentration in the CSF from patients with ALS (n = 36) than in normal controls (n = 21) were identified. A combination of three protein species (the "three-protein" model) correctly identified patients with ALS with 95% accuracy, 91% sensitivity, and 97% specificity from the controls. Independent validation studies using separate cohorts of ALS (n = 13), healthy control (n = 25), and PN (n = 7) subjects confirmed the ability of the three CSF protein species to separate patients with ALS from other diseases. Protein sequence analysis identified the 13.4-kDa protein species as cystatin C and the 4.8-kDa protein species as a peptic fragment of the neurosecretory protein VGF. CONCLUSION: Additional application of a "three-protein" biomarker model to current diagnostic criteria may provide an objective biomarker pattern to help identify patients with ALS.

Adult↗
PubMed2005

Chondrogenic differentiation and functional maturation of bovine mesenchymal stem cells in long-term agarose culture.

BACKGROUND: The developmental history of the chondrocyte results in a cell whose biosynthetic activities are optimized to maintain the concentration and organization of a mechanically functional cartilaginous extracellular matrix. While useful for cartilage tissue engineering studies, the limited supply of healthy autologous chondrocytes may preclude their clinical use. Consequently, multipotential mesenchymal stem cells (MSCs) have been proposed as an alternative cell source. OBJECTIVE: While MSCs undergo chondrogenesis, few studies have assessed the mechanical integrity of their forming matrix. Furthermore, efficiency of matrix formation must be determined in comparison to healthy chondrocytes from the same donor. Given the scarcity of healthy human tissue, this study determined the feasibility of isolating bovine chondrocytes and MSCs, and examined their long-term maturation in three-dimensional agarose culture. EXPERIMENTAL DESIGN: Bovine MSCs were seeded in agarose and induced to undergo chondrogenesis. Mechanical and biochemical properties of MSC-laden constructs were monitored over a 10-week period and compared to those of chondrocytes derived from the same group of animals maintained similarly. RESULTS: Our results show that while chondrogenesis does occur in MSC-laden hydrogels, the amount of the forming matrix and measures of its mechanical properties are lower than that produced by chondrocytes under the same conditions. Furthermore, some important properties, particularly glycosaminoglycan content and equilibrium modulus, plateau with time in MSC-laden constructs, suggesting that diminished capacity is not the result of delayed differentiation. CONCLUSIONS: These findings suggest that while MSCs do generate constructs with substantial cartilaginous properties, further optimization must be done to achieve levels similar to those produced by chondrocytes.

Animals↗
PubMed2004

p97 and close encounters of every kind: a brief review.

The AAA (ATPase associated with various cellular activities) ATPase, p97, is a hexameric protein of chaperone-like function, which has been reported to interact with a number of proteins of seemingly unrelated functions. For the first time, we report a classification of these proteins and aim to elucidate any common structural or functional features they may share. The interactors are grouped into those containing ubiquitin regulatory X domains, which presumably bind to p97 in the same way as the p47 adaptor, and into non-ubiquitin regulatory X domain proteins of different functional subgroups that may employ a different mode of interaction (assuming they also bind directly to p97 and are not experimental artifacts). Future studies will show whether interacting proteins direct p97 to different cellular pathways or a common one and structural elucidation of these interactions will be crucial in understanding these underlying functions.

Animals↗
PubMed2003

Current and future strategies for the treatment of malignant brain tumors.

Glioblastoma (GB) is the most common subtype of primary brain tumor in adults. These tumors are highly invasive, very aggressive, and often infiltrate critical neurological areas within the brain. The mean survival time after diagnosis of GB has remained unchanged during the last few decades, in spite of advances in surgical techniques, radiotherapy, and also chemotherapy; patients' survival ranges from 9 to 12 months after initial diagnosis. In the same time frame, with our increasing understanding and knowledge of the physiopathology of several cancers, meaningful advances have been made in the treatment and control of several cancers, such as breast, prostate, and hematopoietic malignancies. Although a number of the genetic lesions present in GB have been elucidated and our understanding of the progressions of this cancer has increased dramatically over the last few years, it has not yet been possible to harness this information towards developing effective cures. In this review, we will focus on the classical ways in which GB is currently being treated, and will introduce a novel therapeutic modality, i.e., gene therapy, which we believe will be used in combination with classical treatment strategies to prolong the life-span of patients and to ultimately be able to control and/or cure these brain tumors. We will discuss the use of several vector systems that are needed to introduce the therapeutic genes within either the tumor mass, if these are not resectable, or the tumor bed, after successful tumor resection. We also discuss different therapeutic modalities that could be exploited using gene therapy, i.e., conditional cytotoxic approach, direct cytotoxicity, immunotherapy, inhibition of angiogenesis, and the use of pro-apoptotic genes. The advantages and disadvantages of each of the current vector systems available to transfer genes into the CNS are also discussed. With the advances in molecular techniques, both towards the elucidation of the physiopathology of GB and the development of novel, more efficient and less toxic vectors to deliver putative therapeutic genes into the CNS, it should be possible to develop new rationale and effective therapeutic approaches to treat this devastating cancer.

Animals↗
PubMed2003

Quantitative structure-property relationships for vapor pressures of polybrominated diphenyl ethers.

Based on quantum chemical descriptors, by the use of partial least squares regression, quantitative structure-property relationship models for subcooled liquid vapor pressures (PL) of polybrominated diphenyl ether (PBDE) congeners were developed. The Q2cum value of the optimal model obtained is as high as 0.993, indicating a good predictive ability and robustness of the model. Although disagreements were observed between the predicted log PL values and log PL values of validation set, the model obtained can still be used for estimating PL of other PBDE congeners, considering the fact that accurate PL values for compounds with low volatility are extremely difficult to determine experimentally. Intermolecular dispersive interactions play a leading role in governing the values of PL, followed by electrostatic, dipole-dipole and dipole-induced dipole interactions. Intermolecular dispersive interactions also govern the values of enthalpies of vaporization.

Chemical Phenomena↗
PubMed2002

Seismic images of crust and upper mantle beneath Tibet: evidence for Eurasian plate subduction.

Seismic data from central Tibet have been combined to image the subsurface structure and understand the evolution of the collision of India and Eurasia. The 410- and 660-kilometer mantle discontinuities are sharply defined, implying a lack of a subducting slab beneath the plateau. The discontinuities appear slightly deeper beneath northern Tibet, implying that the average temperature of the mantle above the transition zone is about 300 degrees C hotter in the north than in the south. There is a prominent south-dipping converter in the uppermost mantle beneath northern Tibet that might represent the top of the Eurasian mantle lithosphere underthrusting the northern margin of the plateau.

Journal Article↗
PubMed2002

Regulation of Kv1 subunit expression in oligodendrocyte progenitor cells and their role in G1/S phase progression of the cell cycle.

Proliferative oligodendrocyte progenitor cells (OPs) express large, delayed outward-rectifying K(+) currents (I(K)), whereas nondividing immature and mature oligodendrocytes display much smaller I(K). Here, we show that up-regulation of I(K) occurs in G(1) phase of the cell cycle in purified cultured OPs and is the result of an RNA synthesis-dependent, selective increase of the K(+) channel subunit proteins Kv1.3 and Kv1.5. In oligodendrocyte cells acutely isolated from developing rat brain, a decrease of cyclin D expression is observed as these cells mature along their lineage. This is accompanied by a decrease in Kv1.3 and Kv1.5 subunit expression, suggesting a role for these subunits in the proliferative potential of OPs in situ. I(K) expressed in OPs in subventricular zone and developing white matter in acutely isolated slice preparations were selectively blocked by antagonists of Kv1.3, illustrating the functional presence of this subunit in situ. Interestingly, Kv1.3 block inhibited S-phase entry of both purified OPs in culture and in tissue slice cultures. Thus, we employ both in vitro and in situ experimental approaches to show that (i) RNA-dependent synthesis of Kv1.3 and Kv1.5 subunit proteins occurs in G(1) phase of the OP cell cycle and is responsible for the observed increase in I(K), and (ii) currents through Kv1.3-containing channels play a crucial role in G(1)/S transition of proliferating OPs.

Animals↗
PubMed2002

Sequencing of the putative promoter region of the cocaine- and amphetamine-regulated-transcript gene and identification of polymorphic sites associated with obesity.

OBJECTIVE: We tested the hypothesis that polymorphisms in the cocaine- and amphetamine-regulated-transcript (CART) gene is associated with the development of obesity. SUBJECTS: Five-hundred and twenty-eight subjects (325 men and 203 women) aged 49.6+/-11.0 y with body mass index (BMI) of 26.9+/-5.1. MEASUREMENTS: The 5(')-flanking region of the CART gene was cloned using adaptor-ligated genomic DNA fragments. The CART gene including the 5(')-flanking region was screened for mutation by PCR-single strand conformation polymorphism and direct sequencing. Associations between polymorphisms and obesity were investigated by PCR-restriction fragment length polymorphism analysis and direct sequencing. RESULTS: The 5(')-flanking region of the CART gene up to -1072 bp from the transcription initiation site was sequenced. The region contained a putative cyclic AMP-responsive element and four E-box motifs upstream of a TATA box. Six polymorphic sites were identified in the upstream region; A-->G at -156, T-->C at -390, T-->G at -484, G-->T at -915, G-->C at -929 and C-->T at -962. The nucleotide substitution at -156 was significantly associated with greater BMI (P=0.036). The allele frequency of the -156 variant was significantly higher in obese subjects with BMI > or = 30 than in non-obese subject (0.41 vs 0.32, P=0.0076). The -929 variant allele in linkage disequilibrium with the -156 variant was also more common in obese subjects. No mutation was found in the coding regions. A single nucleotide insertion/deletion polymorphism at +1355 in the 3(') untranslated region was not associated with obesity. CONCLUSION: The 5(')-flanking region of the CART gene was highly polymorphic. The -156 polymorphism or polymorphisms in linkage disequilibrium with the site may be associated with genetic predisposition to obesity.

Base Sequence↗
PubMed2002

Roentgen single-plane photogrammetric analysis (RSPA.) A new approach to the study of musculoskeletal movement.

We present a new approach for the accurate reconstruction of three-dimensional skeletal positions using roentgen single-plane photogrammetric analysis (RSPA). This technique uses a minimum of three markers embedded in each segment which allow continuous, real-time, internal skeletal movement to be measured from single-plane images, provided that the precise distance between the markers is known. A simulation study indicated that the error propagation in this approach is influenced by focus position, object position, the number of control points, the accuracy of the previous measurement of the distance between markers and the accuracy of image measurement. For reconstruction of normal movement of the knee with an input measurement error of SD = 0.02 mm, the rotational and translational differences between reconstructed and original movement were less than 0.27 degrees and 0.9 mm, respectively. Our results showed that the accuracy of RSPA is sufficient for the analysis of most movement of joints. This approach can be applied in combination with force measurements for dynamic studies of the musculoskeletal system.

Computer Simulation↗
PubMed2001

[Monitoring and intervention of infant mortality rate and fetal and infant mortality rate in Beijing, 1992-2000].

OBJECTIVE: To monitor the changing trend of infant mortality rate (IMR) and fetal and infant mortality rate (FIM) in Beijing and to develop proper measures to decrease these two rates. METHODS: Dynamic series analysis was used to analyze the monitoring data of 590,833 cases of live birth, 5,835 cases of infant death, and 10,499 cases of stillbirth in Beijing during 1992-2000. The interventional measures in different phases were analyzed too. RESULTS: The IMR and FIMR in Beijing were 12.42% and 19.43% respectively in 1992 and were reduced to 6.84% and 15.79% respectively in 2000. The IMR and FIMR were declining significantly during the periods of 1992-1994, 1995-1997, and 1998-2001 (P < 0.01). The decrease of IMR by 48% was more remarkable than that of FIMR by 19%. The IMR I rural areas was higher than that in urban area. Pneumonia dropped from the position of the first death cause for infants to the fourth cause and congenital heart disease became the first cause. CONCLUSION: FIMR helps more comprehensively evaluate the effect of maternal and child health care. Monitoring and intervention of congenital heart diseases is very important.

Cause of Death↗
PubMed2001

SRY interacts with and negatively regulates androgen receptor transcriptional activity.

This study investigated interactions between SRY, the Y chromosome encoded male sex determining factor, and the androgen receptor (AR). Coexpression of AR and SRY caused marked repression of AR transcriptional activity on a series of androgen-responsive reporter genes. Mammalian one- and two-hybrid experiments demonstrated an AR-SRY interaction mediated by the AR DNA binding domain. Precipitations with glutathione S-transferase fusion proteins indicated that AR-SRY interactions were direct and mediated by the AR DNA binding domain and the SRY high mobility group box DNA binding domain. Transient expression of SRY in LNCaP prostate cancer cells repressed expression of an androgen-dependent prostate-specific antigen (PSA) reporter gene and stable SRY expression repressed the endogenous PSA gene. SRY protein expression was increased by proteosome inhibitors and by the androgen-liganded AR in transient and stable transfectants. AR transcriptional activity was also repressed by DAX1, and the effects of SRY and DAX1 on the AR were additive. These findings indicate that interactions between the AR, SRY, and DAX1 contribute to normal male development and function and suggest a general role for protein-protein interactions between high mobility group box proteins and steroid hormone receptors in regulating tissue-specific gene expression.

Base Sequence↗
PubMed2001

Expression of the bovine oestrogen receptor-beta (bERbeta) messenger ribonucleic acid (mRNA) during the first ovarian follicular wave and lack of change in the expression of bERbeta mRNA of second wave follicles after LH infusion into cows.

In a previous study, the ERbeta cDNA protein-coding region was utilised to clone bovine ERbeta. The objectives in this study were to examine (1) ERbeta mRNA expression in ovarian follicles throughout the bovine first follicular wave, and (2) effect of LH infusion into cows on bERbeta mRNA expression during the second follicular wave. In experiment 1, heifers (4-5 per time point) were ovariectomized at 12, 24, 36, 48, 60, 72, 84, 96, 144, or 216 h after emergence of the first follicular wave after oestrus. In experiment 2, saline or LH was pulsed hourly (computer-controlled syringe pump) into cows (n = 31; 5-6 per treatment) at wave emergence for 2 or 4 days: wave 1-saline (W1S), wave 2-saline (W2S), or wave 2-LH (25 microg/h; W2LH). Ovaries were removed on day 2 or day 4 after wave emergence. Follicles, 2-19mm in size, were dissected, frozen, and stored at -80 degrees C for in situ hybridisation with two bERbeta cRNA probes. Expression of bERbeta mRNA was localised in granulosa cells of healthy follicles. In experiment 1, bERbeta mRNA expression did not change with time points of the wave showing no association of bERbeta mRNA expression with follicular selection and dominance. However, bERbeta mRNA expression decreased with increase in size of all follicles. Expression of bERbeta mRNA was greater in very small follicles (2-4 mm) than in large (> or = 9 mm) follicles. In experiment 2, expression of bERbeta mRNA in follicles did not differ either between W1S and W2S or between W2S and W2LH. In summary, bERbeta mRNA expression decreased with increasing follicular size. However, neither stage of the wave (selection or dominance), nor pulsatile infusion of LH influenced bERbeta mRNA expression.

Animals↗