Biomedical subjects

S Chen

Publications and source records attributed to S Chen.

At least 55 records · Page 3Linked to original sources

PubMed2006

Allelic distribution of HLA class I genes in the Tibetan ethnic population of China.

Tibetans live in Qinghai-Tibet Plateau rising about 4000 m a.s.l. in south-west China. Archaeological evidences suggested that there have been humans living in Tibet at least 5000 years ago. However, Tibetan earlier history remains elusive. In the present study, allelic distribution of human leucocyte antigen (HLA)-A, -B and -Cw in 158 unrelated Tibetan Chinese was investigated using sequencing-based typing methods, and a total of 25 HLA-A, 45 HLA-B and 20 HLA-Cw alleles were identified. A*24G1 (27.2%), B*51G1 (16.8%), Cw*04G1 (13.3%) and Cw*070201G1 (13.3%) are the most common HLA-A, -B and -Cw alleles. The most frequently detected haplotypes were A*24G1-B*51G1-Cw*140201 (3.6%), A*24G1-B*51G1 (6.8%), A*02G1-Cw*070201G1 (6.5%) and B*51G1-Cw*140201 (5.0%). Chi-squared test suggested that all three loci fitted the Hardy-Weinberg expectations. No evidence for a departure from selective neutrality at the HLA-A and -B loci was observed. However, significant departure of the observed homozygosity from the expected values was found for HLA-Cw. Though the contemporary Tibetans inhabit the south-west China, Nei's genetic distance measure based on frequencies of HLA-A, -B and -Cw indicated that Tibetans were closer to northern Han Chinese, Mongolian Chinese, Koreans and Japanese rather than to southern Han Chinese. The corresponding dendrogram constructed according to the neighbour-joining method supported that Tibetans separated from southern Han and located in North-East Asian cluster which included northern Han Chinese and Mongolian Chinese. These data were in good agreement with language classification and with a recent hypothesis that Tibetan might originate from northern China along Yellow river.

Alleles↗

PubMed2006

Increases in sexually transmitted infections and sexual risk behaviour without a concurrent increase in HIV incidence among men who have sex with men in San Francisco: a suggestion of HIV serosorting?

BACKGROUND: Sexually transmitted infections (STI) and unprotected anal intercourse (UAI) have been increasing among men who have sex with men (MSM) in San Francisco. However, HIV incidence has stabilised. OBJECTIVES: To describe recent trends in sexual risk behaviour, STI, and HIV incidence among MSM in San Francisco and to assess whether increases in HIV serosorting (that is, selective unprotected sex with partners of the same HIV status) may contribute to preventing further expansion of the epidemic. METHODS: The study applies an ecological approach and follows the principles of second generation HIV surveillance. Temporal trends in biological and behavioural measures among MSM were assessed using multiple pre-existing DATA SOURCES: STI case reporting, prevention outreach programmatic data, and voluntary HIV counselling and testing data. RESULTS: Reported STI cases among MSM rose from 1998 through 2004, although the rate of increase slowed between 2002 and 2004. Rectal gonorrhoea cases increased from 157 to 389 while early syphilis increased from nine to 492. UAI increased overall from 1998 to 2004 (p<0.001) in community based surveys; however, UAI with partners of unknown HIV serostatus decreased overall (p<0.001) among HIV negative MSM, and among HIV positive MSM it declined from 30.7% in 2001 to a low of 21.0% in 2004 (p<0.001). Any UAI, receptive UAI, and insertive UAI with a known HIV positive partner decreased overall from 1998 to 2004 (p<0.001) among MSM seeking anonymous HIV testing and at the STI clinic testing programme. HIV incidence using the serological testing algorithm for recent HIV seroconversion (STARHS) peaked in 1999 at 4.1% at the anonymous testing sites and 4.8% at the STI clinic voluntary testing programme, with rates levelling off through 2004. CONCLUSIONS: HIV incidence among MSM appears to have stabilised at a plateau following several years of resurgence. Increases in the selection of sexual partners of concordant HIV serostatus may be contributing to the stabilisation of the epidemic. However, current incidence rates of STI and HIV remain high. Moreover, a strategy of risk reduction by HIV serosorting can be severely limited by imperfect knowledge of one's own and one's partners' serostatus.

Adult↗

PubMed2006

In silico comparison of gene expression levels in ten human tumor types reveals candidate genes associated with carcinogenesis.

Most human cancers are characterized by genomic instability. Changes associated with such may result in altered expression of numerous genes. The sequence information available in the public databases can be used to identify transcripts differentially expressed in cancers. Determining cancer-related genes that are commonly deregulated in different tumor types may facilitate identification of targets for cancer diagnoses and therapeutic treatments. Using a data-mining tool named Digital Differential Display (DDD) from the UniGene database at the NCBI web site, gene expression levels of ten different tumor types and their counterpart normal tissues were analyzed. Unigenes which showed transcriptional regulation in more than five tumor types with > or =2-fold differences from normal tissues were identified. The expression data of selected Unigenes were subjected to clustering analysis. 127 commonly up-regulated genes and 92 commonly down-regulated genes were identified. Clustering analysis using these genes showed that most tumor types can be clustered into a separate branch from most normal tissues. Nineteen genes that have been shown to be involved in carcinogenesis by experimental evidence were also identified. Present computational analyses revealed 219 candidate cancer-related genes that are commonly deregulated in ten human tumor types which may contribute to the progress of carcinogenesis.

Gene Expression↗

PubMed2006

Classification of DNA methylation patterns in tumor cell genomes using a CpG island microarray.

Our group has initiated experiments to epigenetically profile CpG island hypermethylation in genomic DNA from tissue specimens of head and neck squamous cell carcinoma (HNSCC) using a microarray of 12,288 CpG island clones. Our technique, known as a methylation-specific restriction enzyme (MSRE) analysis, is a variation of the differential methylation hybridization (DMH) technique, in that it is not an array comparison of two DNA samples using methylation-specific restriction enzymes. Instead, it is a comparison of a single DNA sample's response to a methylation-sensitive restriction enzyme (HpaII) and its corresponding methylation-insensitive isoschizomer (MspI). Estimation of the reproducibility of this microarray assay by intraclass correlation (ICC) demonstrated that in four replicate experiments for three tumor specimens, the ICC observed for a given tumor specimen ranged from 0.68 to 0.85 without filtering of data. Repeated assays achieved 87% concordance or greater for all tumors after filtering of array data by fluorescence intensity. We utilized hierarchical clustering on a population of 37 HNSCC samples to cluster tumor samples with similar DNA methylation profiles. Supervised learning techniques are now being utilized to allow us to identify associations between specific epigenetic signatures and clinical parameters. Such techniques will allow us to identify select groups of CpG island loci that could be used as epigenetic markers for both diagnosis and prognosis in HNSCC.

Blotting, Southern↗

PubMed2006

Isolation and functional analysis of human HMBOX1, a homeobox containing protein with transcriptional repressor activity.

We have identified and isolated a novel human gene, HMBOX1 (homeobox containing 1) from a pancreatic cDNA library. Human HMBOX1 is widely expressed in 18 tissues, and it is highly expressed in pancreas. According to the genome database, HMBOX1 is located at the boundary of 8p12.3 and 8p21.1. HMBOX1 proteins are highly conserved in human, mouse, rat, chicken and Xenopus laevis. A phylogenetic tree shows that HMBOX1 may represent a distinct group in HNF (Hepatocyte Nuclear Factor) transcriptional factors. Functional HMBOX1::EGFP (enhanced green fluorescent protein) fusion protein revealed that HMBOX1 accumulated more in cytoplasm than in nucleus. Co-transfection of HEK-293T cells with pM-HMBOX1 plasmid and reporter plasmid pGAL4(5)tkLUC indicates that HMBOX1 is a transcription repressor. In situ hybridization on paraffin sections of mouse tissues demonstrated that Hmbox1 is widely expressed in pancreas and the expression of this gene can also be detected in pallium, hippocampus and hypothalamus.

Amino Acid Sequence↗

PubMed2006

Activity corrections for ionization constants in defined media.

Correcting ionization constants for activity effects can have a larger impact on some ionic species than correcting for temperature effects. Computer trials compared two pH calculation methods, and showed that an interpolation algorithm found a precise charge balance quickly but was unstable under certain conditions, while a slower pH search method was stable under all test conditions. The optimal calculation strategy was a hybrid of these two approaches. The hybrid calculation method is stable, quick, includes activity and temperature corrections, does not need kinetic rate constants, allows all known ionic species to be included, and allows for easy addition of new chemical species.

Algorithms↗

PubMed2006

Cheese pH, protein concentration, and formation of calcium lactate crystals.

The occurrence of calcium lactate crystals (CLC) in hard cheeses is a continual expense to the cheese industry, as consumers fail to purchase cheeses with this quality defect. This research investigates the effects of the protein concentration of cheese milk and the pH of cheese on the occurrence of CLC. Atomic absorption spectroscopy was used to determine total and soluble calcium concentrations in skim milk (SM1, 8.7% total solids), and skim milk supplemented with nonfat dry milk (CSM1, 13.5% total solids). Calcium, phosphorus, lactic acid, and citrate were determined in cheeses made with skim milk (SM2, 3.14% protein), skim milk supplemented with ultrafiltered milk (CSM2, 6.80% protein), and nonfat dry milk (CSM3, 6.80% protein). Supplementation with nonfat dry milk increased the initial total calcium in CSM1 (210 mg/100 g of milk) by 52% compared with the total calcium in SM1 (138 mg/100 g of milk). At pH 5.4, soluble calcium concentrations in CSM1 were 68% greater than soluble calcium in SM1. In cheeses made from CSM2 and CSM3, total calcium was 26% greater than in cheeses made from SM2. As the pH of cheeses made from SM2 decreased from 5.4 to 5.1, the concentration of soluble calcium increased by 61.6%. In cheeses made from CSM2 and CSM3, the concentrations of soluble calcium increased by 41.4 and 45.5%, respectively. Calcium lactate crystals were observed in cheeses made from SM2 at and below pH 5.1, whereas CLC were observed in cheeses from CSM2 and CSM3 at and below pH 5.3. The increased presence of soluble calcium can potentially cause CLC to occur in cheese manufactured with increased concentrations of milk solids, particularly at and below pH 5.1.

Animals↗

PubMed2006

Impairment and recovery in inhibitory control after traumatic brain injury in children: effect of age at injury, injury severity and lesion location.

We examined the effect of traumatic brain injury (TBI) on inhibitory control, trajectories of recovery of inhibitory control, and the effect of age at injury, severity, and lesion location on recovery. Participants were 127 children with TBI aged 5-16 years and 117 controls of similar age. Latency of response inhibition was measured with the stop signal task within 1 month of the injury and again at 3, 6, 12, and 24 months. Performance of children with TBI was compared with that of controls. Growth curve analyses showed impairments in response inhibition postinjury. Compared with controls, TBI children improved over time in response inhibition. Younger TBI children recovered better on response inhibition than older TBI children. No significant effect of severity or right frontal lesion on recovery of response inhibition was found. TBI has an acute effect on inhibitory control but which recovers over time.

Adaptation, Physiological↗

PubMed2006

QT prolongation due to aortic aneurysm rupture and amiodarone in a patient with a H558R polymorphism in the cardiac sodium channel gene SCN5A.

The duration of the QT interval is influenced by many pathologic processes and drugs. We report a 74-year-old man who was admitted after syncope. His electrocardiogram (ECG) showed a QT interval of 0.44 s (QTc 0.53 s). After 10 h a ruptured abdominal aortic aneurysm was diagnosed and the patient underwent implantation of an aorto-bi-iliac Y-prosthesis. After surgery QT interval normalized. Under therapy with amiodarone, given because of atrial fibrillation, QT prolongation occurred again and disappeared after discontinuation of amiodarone. The postoperative course was complicated by critical illness polyneuropathy and plexopathy. Whereas amiodarone is a well recognized cause of QT prolongation, aortic aneurysm rupture has not been described previously. Vegetative mechanisms and sudden decrease of cardiac afterload due to the ruptured aneurysm may have altered myocardial repolarisation and thus prolonged QT interval duration. In conclusion in a patient with syncope and QT prolongation, extracardiac causes like rupture or an aortic aneurysm have to be included into the differential diagnosis.

Aged↗

PubMed2005

Identification and quality assessment of Houttuynia cordata injection using GC-MS fingerprint: a standardization approach.

Houttuynia cordata (Saururaceae) injection (HCI) was widely used to treat disease in China. At present, there were about 40 factories producing HCI, but a good quality standard for its quality control was lacking. In this study, an optimized and validated gas chromatography-mass spectrum (GC-MS) method was applied for the fingerprint analysis of 340 batches of HCI from 34 Chinese pharmaceutical factories. The results showed that HCI from the same factory had very similar GC-MS fingerprints, and evident difference existed among different factories. The representative fingerprints from 20 factories whose intra-factory correlation coefficients were over 0.90 and inter-factory correlation coefficients were over 0.75 were used to calculate the mean fingerprint of all samples. Spectral correlative chromatogram (SCC) was adopted to identify common component in different samples. Fifteen main "common components" were obtained. The mean fingerprint containing those 15 components was suggested to be used as characteristic fingerprint for the rapid identification of HCI and evaluation of the consistency of HCI from factory to factory and from batch to batch.

Drugs, Chinese Herbal↗

PubMed2005

The role of Nurr1 in the development of dopaminergic neurons and Parkinson's disease.

Nurr1, a transcription factor belonging to the orphan nuclear receptor superfamily, is critical in the development and maintenance of the dopaminergic system and as such it may have role in the pathogenesis of Parkinson' disease (PD). Human Nurr1 gene has been mapped to chromosome 2q22-23 and Nurr1 protein is predominantly expressed in central dopaminergic neurons. Nurr1 interacts with other factors critical for the survival of mensencephalic dopaminergic neurons and it appears to regulate the expression of tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and l-aromatic amino acid decarboxylase (AADC), all of which are important in the synthesis and storage of dopamine. Experimental studies in Nurr1 knock-out mice indicate that Nurr1 deficiency results in impaired dopaminergic function and increased vulnerability of those midbrain dopaminergic neurons that degenerate in PD. Decreased Nurr1 expression is found in the autopsied PD midbrains, particularly in neurons containing Lewy bodies, as well as in peripheral lymphocytes of patients with parkinsonian disorders. Several variants in Nurr1 gene have been reported in association with PD. All these studies suggest that Nurr1 is not only essential in the development of mensencephalic dopaminergic neurons and maintenance of their functions, but it may also play a role in the pathogenesis of PD.

Animals↗

PubMed2005

Central apnoea after balanced general anaesthesia that included dexmedetomidine.

Dexmedetomidine is an alpha(2)-adrenoreceptor agonist that, in spite of its potent sedative, amnesic, and analgesic properties, has minimal respiratory depressant effect. Even at doses adequate for general anaesthesia, it does not cause central apnoea. Thus, it has been claimed that "combining alpha(2)-agonists with opiate narcotics or non-steroidal anti-inflammatory drugs can enhance the analgesic efficacy without increasing the respiratory depressant effect of the latter" and "the combination of alpha(2)-adrenoceptor agonists with opioids does not lead to further ventilatory depression". We present a case of central apnoea after general anaesthesia that included opioids and dexmedetomidine, and remind the readers that in susceptible patients, dexmedetomidine may cause life-threatening respiratory depression through potentiation of co-administered central nervous system depressants.

Adrenergic alpha-Agonists↗

PubMed2005

Beam-helicity asymmetries in double-charged-pion photoproduction on the proton.

Beam-helicity asymmetries for the two-pion-photoproduction reaction gammap-->ppi(+)pi(-) have been studied for the first time in the resonance region for center-of-mass energies between 1.35 and 2.30 GeV. The experiment was performed at Jefferson Lab with the CEBAF Large Acceptance Spectrometer using circularly polarized tagged photons incident on an unpolarized hydrogen target. Beam-helicity-dependent angular distributions of the final-state particles were measured. The large cross-section asymmetries exhibit strong sensitivity to the kinematics and dynamics of the reaction. The data are compared with the results of various phenomenological model calculations, and show that these models currently do not provide an adequate description for the behavior of this new observable.

Journal Article↗

PubMed2005

Glucose-induced Akt1 activation mediates fibronectin synthesis in endothelial cells.

AIMS/HYPOTHESIS: Increased expression and decreased degradation of extracellular matrix (ECM) proteins are key features of chronic diabetic complications. Fibronectin, a predominant ECM protein, has been shown to be overexpressed in all target organs of diabetic complications and in endothelial cells cultured in high levels of glucose. The present study was designed to elucidate the role of protein kinase B (Akt/PKB) in glucose-induced fibronectin mRNA expression and protein production in vascular endothelial cells. METHODS: Human umbilical vein endothelial cells were cultured in the presence of high glucose to study Akt/PKB activation. The upstream and downstream mediators in the Akt/PKB pathway were also investigated using dominant negative transfections and specific inhibitors of signalling pathways. Cells were subjected to real time RT-PCR, western blotting, and confocal microscopy to assess Akt1/PKBalpha activation and fibronectin mRNA expression and protein production. To detect transcription factor activation, electrophoretic mobility shift assay was carried out. RESULTS: Our data demonstrate that fibronectin mRNA expression and protein production that are induced by high glucose are mediated via activation of Akt/PKB, which is modulated by mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and protein kinase C. Glucose-induced fibronectin mRNA expression and protein production are also mediated by Akt1/PKBalpha-dependent activation of the transcription factors nuclear factor-kappaB and activating protein-1. CONCLUSIONS/INTERPRETATION: Our study provides insight into the mechanical basis of glucose-induced increases in fibronectin mRNA expression and protein production. High levels of glucose may increase fibronectin mRNA expression and protein production by activating Akt/PKB.

Cell Survival↗

PubMed2005

Genetic and physical mapping of Pi36(t), a novel rice blast resistance gene located on rice chromosome 8.

Blast resistance in the indica cultivar (cv.) Q61 was inherited as a single dominant gene in two F2 populations, F2-1 and F2-2, derived from crosses between the donor cv. and two susceptible japonica cvs. Aichi Asahi and Lijiangxintuanheigu (LTH), respectively. To rapidly determine the chromosomal location of the resistance (R) gene detected in Q61, random amplified polymorphic DNA (RAPD) analysis was performed in the F2-1 population using bulked-segregant analysis (BSA) in combination with recessive-class analysis (RCA). One of the three linked markers identified, BA1126(550), was cloned and sequenced. The R gene locus was roughly mapped on rice chromosome 8 by comparison of the BA1126(550) sequence with rice sequences in the databases (chromosome landing). To confirm this finding, seven known markers, including four sequence-tagged-site (STS) markers and three simple-sequence repeat (SSR) markers flanking BA1126(550) on chromosome 8, were subjected to linkage analysis in the two F2 populations. The locus was mapped to a 5.8 cM interval bounded by RM5647 and RM8018 on the short arm of chromosome 8. This novel R gene is therefore tentatively designated as Pi36(t). For fine mapping of the Pi36(t) locus, five additional markers including one STS marker and four candidate resistance gene (CRG) markers were developed in the target region, based on the genomic sequence of the corresponding region of the reference japonica cv. Nipponbare. The Pi36(t) locus was finally localized to an interval of about 0.6 cM flanked by the markers RM5647 and CRG2, and co-segregated with the markers CRG3 and CRG4. To physically map this locus, the Pi36(t)-linked markers were mapped by electronic hybridization to bacterial artificial chromosome (BAC) or P1 artificial chromosome (PAC) clones of Nipponbare, and a contig map was constructed in silico through Pairwise BLAST analysis. The Pi36(t) locus was physically delimited to an interval of about 17.0 kb, based on the genomic sequence of Nipponbare.

Alleles↗

PubMed2005

Atomic-scale imaging of wall-by-wall breakdown and concurrent transport measurements in multiwall carbon nanotubes.

We report the atomic-scale imaging with concurrent transport measurements of the breakdown of individual multiwall carbon nanotubes inside a transmission electron microscope equipped with a piezomanipulator. We found unexpectedly three distinct breakdown sequences: namely, from the outermost wall inward, from the innermost wall outward, and alternatively between the innermost and the outmost walls. Remarkably, a significant amount of current drop was observed when an innermost wall is broken, proving unambiguously that every wall is conducting. Moreover, the breakdown of each wall in any sequence initiates in the middle of the nanotube, not at the contact, proving that the transport is not ballistic.

Journal Article↗

PubMed2005

Neural adhesion molecules L1 and CHL1 are survival factors for motoneurons.

Many neurotrophic factors with survival activity for motoneurons in vivo were first identified using cultures of purified embryonic motoneurons. The L1 neural cell adhesion molecule has multiple roles in brain development. We showed by in situ hybridization and RT-PCR that L1 mRNA was expressed at significant levels in motoneurons of embryonic and postnatal spinal cord. We therefore cultured purified motoneurons from E14 rat embryos in the absence of trophic factors but with L1-Fc and CHL1-Fc fusion proteins. L1-Fc prevented the death of approximately half of the motoneurons that were saved by BDNF in a dose-dependent manner (EC50 = 10 pM). CHL1-Fc saved the same number of motoneurons as did L1-Fc, whereas P0-Fc had little neurotrophic activity at the same concentrations. Survival induced by L1 and CHL1 was completely inhibited by 20 microM LY294002 and PD98059, indicating that both MEK and PI3K pathways are required for signaling by these molecules. L1 can signal in other cell types through the FGF receptor FGFR1. In cultures of motoneurons, effects of suboptimal concentrations of L1 and suboptimal concentrations of FGF-2 were additive, but the effects of optimal concentrations of FGF-2 (50 ng/ml) were not further increased in the presence of L1-Fc. Thus, in this system, too, FGF and L1 may use similar signaling pathways.

Animals↗

PubMed2005

Neurofibromin and its inactivation of Ras are prerequisites for osteoblast functioning.

Skeletal problems and osteoporosis occur in up to 50% affected neurofibromatosis type 1 (NF1) humans. Inactivation of neurofibromin results in deregulation of Ras signal transduction. Little is known of bone biology in humans with NF1. The goal of our work was to determine if loss-of-function of Nf1 gene was associated with altered bone homeostasis and Ras signal transduction. Because homozygous Nf1 mice are embryonically lethal, heterozygote Nf1 (Nf1+/-) male mice were used to investigate skeletal phenotypes and osteoprogenitor functions, using standard in vivo and in vitro assays. We found that bone mass and geometry of Nf1+/- mice did not differ from wild type controls, despite a trend to less bone formation. Nf1+/- committed osteoprogenitors from femur metaphysis exhibited premature apoptosis and higher proliferation. Ras signaling was activated in primary Nf1+/- bone marrow-inducible osteoprogenitors. Inducible osteoprogenitors exhibited lower induction of osteoblast differentiation, assessed as alkaline phosphatase positive CFU-f. A screen of osteoblast marker genes showed a selective increase in osteopontin (OPN) mRNA and protein expression in these cells. OPN protein was increased in Nf1+/- bone, especially in cortical bone matrix. Because bone cell abnormalities in Nf1 haploinsufficiency were detected in vitro, redundant pathways must compensate for the deregulation of Ras signaling in vivo to maintain normal bone mass and function in vivo. Our in vitro data revealed that neurofibromin and its control of Ras signaling are required for osteoprogenitor homeostasis.

Animals↗