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Biomedical subjects

Yan Liang

Publications and source records attributed to Yan Liang.

At least 55 records · Page 3Linked to original sources

ERK-dependent signaling pathway and transcriptional factor Ets-1 regulate matrix metalloproteinase-9 production in transforming growth factor-beta1 stimulated glomerular podocytes.

The unregulated synthesis of glomerular basement membrane (GBM) components, extracelluar matrix (ECM) proteins, or the secretion of ECM-degradation enzymes, matrix metalloproteinases (MMPs), by podocytes under pathological conditions might be major factors in GBM damage. The present study examined the effects and the underlying molecular mechanism of transforming growth factor beta1 (TGFbeta1) on the production of gelatinase in cultured murine podocytes. Our results showed that TGFbeta1 is the most potent inducer of MMP-9 secretion in both a dose- and time-dependent manner, but has very little effect on MMP-2 secretion. TGFbeta1 upregulated MMP-9 mRNA levels, but did not affect the expression of matrix mettaloproteinases TIMP-1 mRNA. TGFbeta1 induced activation of both Smad2 and extracellular signal-regulated kinases (ERK1/2). However, blockade of Smad2 signaling pathway by Staurosporine did not affect the TGFbeta1-stimulated secretion of MMP-9, whereas inhibition of activation of ERK1/2 by PD98059 abolished TGFbeta1-stimulated secretion of MMP-9 and expression of MMP-9 mRNA. Protein levels of the transcriptional factor Ets-1 increased and were sustained for 12 h by TGFbeta1-stimulation. Our data also showed that blockage of ERK1/2 activation by PD98059 led to a reduction in the level of Ets-1 protein and to a consequent decrease in MMP-9 mRNA levels. These results demonstrate that TGFbeta1 can induce the production of MMP-9 in podocytes through the ERK1/2 MAPK pathway, and suggested that an increase in MMP-9 enzymatic activities may be involved in the damage of the GBM in response to inflammatory factors, ultimately leading to glomerulosclerosis.

Animals↗

[Risk factors of sudden death and death from arrhythmia in patients with non-ST elevation acute coronary syndromes in China].

OBJECTIVE: To analyze the relationship between sudden death and death from arrhythmia and multiple risk factors in patients with non-ST elevation acute coronary syndromes in two years of follow-up in China. METHODS: This study was a part of an international multicentre registry-Organization to Assess Strategies for Ischemic Syndromes (OASIS). The patients admitted to the hospital with non-ST elevation acute coronary syndrome were enrolled. No particular intervention was given for the treatment. All patients had been followed-up for two years. The patients' clinical characteristics, therapeutic regimes and major events during hospitalization and two years' follow-up period were recorded by filling in Case Report Forms according to the protocol offered by Canadian Cardiovascular Collaboration. Cox regression model was used to analyze the association with the most common causes of death and multiple factors recorded. RESULTS: From April 1999 to December 2001, 2294 cases were enrolled in 38 hospitals in China nationwide. Among them 2188 patients two years follow-up was accomplished. The mean age of the patients was (62.8+/-8.1) years. Male gender was dominant (62.3%). The clinical diagnosis at admission was unstable angina in 88.5% of the patients and non Q-wave myocardial infarction(MI) in the remaining 11.5%. The mortality was 7.6% with total deaths of 174 by the end of 24-month follow up. The most common cause of death was severe arrhythmias or sudden death (92 cases, 52.9%). More than 70 factors were analyzed by Cox regression model in order to determine which were the predominant factors of death. Major risk factors that predisposed to death were: number of episodes of MI during follow-up period, re-MI within 24 hours during hospitalization, heart failure during hospitalization, previous history of MI, recurrent angina pectoris during hospitalization, the duration of hospitalization, and patient age. Protective factors that reduced the chance of death were: the frequency of using nitrate, frequency of taking anti-platelet medicine or beta-blocker during follow-up period. CONCLUSION: In China, the most common cause of death in patients with non-ST elevation acute coronary syndromes is severe arrhythmias or sudden death, and it is related with the severity of coronary artery disease and the age of patients in majority of cases. Some factors that influence survival are similar to those established by previous evidence based medicine.

Acute Coronary Syndrome↗

[Marker chromosome analysis in Chinese patients with Turner syndrome by fluorescence in situ hybridization].

OBJECTIVE: To identify the origin of marker chromosome of patients with Turner syndrome, and to provide the information for genetic counseling and treatment. METHODS: The karyotypes of 32 patients with Turner syndrome from 2001 to 2003 at the Center for Diagnosis of Genetic Metabolic Diseases were reviewed. Metaphase chromosome analyses of peripheral blood lymphocytes, G-band and C-band were performed using standard methods. Fluorescence in situ hybridization (FISH) was performed to identify the origin of marker chromosome by using two probes: sex-determining region Y (SRY) for band region Yp11.3 and chromosome enumeration probe for X(CEPX) for band region Xp11.1-q11.1. RESULTS: 3/32(9.4%) patients with Turner syndrome had marker chromosome, the karyotype being 45,X/46,X,mar. Among the 3 marker chromosomes, 2 originated from chromosome X or Y, as identified by the FISH. The origin of the third marker chromosome could not be identified by CEPX and SRY probes. CONCLUSION: The presence of a marker chromosome in Turner syndrome generally implicates a sex chromosome origin. It may also originate from a non-sex chromosome. Therefore, it is necessary to apply X and Y probes simultaneously for marker chromosome detection in Turner patients with monosomy X.

Adolescent↗

[Study on adherence and interrelated factors of acquired immunedeficiency syndrome patients receiving antiretroviral treatment].

OBJECTIVE: To study on the compliance antiretroviral(ARV) drugs and interrelated factors of HIV/AIDS patients undertaking highly active antiretroviral therapy(HAART) to improve clinical treatment. METHODS: 3 counties in Henan province were selected including 2 counties from China Cares Program points and one county where HIV/AIDS was serious. All cases studied had already received antiretroviral therapy (ART) for 2-12 months. Several indicators through questionnaire were studied including drug adherence, side effect, symptoms status before and after treatment and ART measures etc. At the same time, blood was collected to analyze CD4+ T-lymphocyte, the virus loads of HIV and drug genotype resistance by reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In the therapy group, most patients had taken ARV drugs for 4-8 months, which accounted for 78.24% of the total number, with the adherence rate above 90% as 67.51%. The main reason for the patients not listening to their doctor's advice was due to ART drug's side effects (66.95%), including queasiness, vomiting and tetter. In the therapy group, 82.57% of patients' symptoms were obvious. Adherence had a great impact on the improvement (P < 0.05). After therapy, the total count of patients' CD4+ T-lymphocyte's kept stable or improved with slow speed. At the time of 3 months and 6 months after ART, the rates of improvement were 55.1% and 50.8%. However CD4+ count did not show much difference between the twe group. The prevalence rate of HIV drug resistance strain roise from 13.9% in non-remedial group to 45.4% at the time of 3 months after therapy and 62.7% at the time of 6 months after therapy. The resistance against non-nucleoside reverse transcriptase inhibitors (NNRTI) had improved obviously. CONCLUSION: Patients with HIV/AIDS receiving HAART, compliance seemed directly affect the curative effect and the implementation of therapy schedule and should be improved to avoid drug resistance.

Acquired Immunodeficiency Syndrome↗

Genetic association study of PINK1 coding polymorphisms in Parkinson's disease.

Parkinson's disease (PD) is the most common neurodegenerative movement disorder with a substantial genetic component (which is more pronounced in earlier onset cases). In addition to three well-confirmed PD genes (SNCA, parkin and DJ-1), mutations in the PTEN Induced Kinase (PINK1) gene have recently been identified in families with recessive early onset PD. We tested the hypothesis that three common coding variations (Leu63Leu, Ala340Thr and Asn521Thr) could increase the risk of PD. We performed a case control association study in a series of 91 PD cases (Caucasian of Canadian origin) and 182 normal controls. The patients were largely pre-selected for having an early age of onset (<50 years) and/or a positive family history. Our results did not reveal any evidence of association between PD and any of the three SNPs at the allelic or genotypic levels (p > 0.25). Furthermore, we did not detect a modifying effect for any genotype upon the age of onset in the PD group (p > 0.19). Nevertheless, it remains to be evaluated whether PINK1 variations contribute to the risk of common late onset sporadic PD.

Adult↗

Rhodopsin signaling and organization in heterozygote rhodopsin knockout mice.

Rhodopsin (Rho) resides within internal membrane structures called disc membranes that are found in the rod outer segments (ROS) of photoreceptors in the retina. Rho expression is essential for formation of ROS, which are absent in knockout Rho-/- mice. ROS of mice heterozygous for the Rho gene deletion (Rho+/-) may have a lower Rho density than wild type (WT) membranes, or the ROS structure may be reduced in size due to lower Rho expression. Here, we present evidence that the smaller volume of ROS from heterozygous mice is most likely responsible for observed electrophysiological response differences. In Rho+/- mice as compared with age-matched WT mice, the length of ROS was shorter by 30-40%, and the average diameter of ROS was reduced by approximately 20%, as demonstrated by transmission and scanning electron microscopy. Together, the reduction of the volume of ROS was approximately 60% in Rho+/- mice. Rho content in the eyes was reduced by approximately 43% and 11-cis-retinal content in the eye was reduced by approximately 38%, as determined by UV-visible spectroscopy and retinoid analysis, respectively. Transmission electron microscopy of negatively stained disc membranes from Rho+/- mice indicated a typical morphology apart from the reduced size of disc diameter. Power spectra calculated from disc membrane regions on such electron micrographs displayed a diffuse ring at approximately 4.5 nm(-1), indicating paracrystallinity of Rho. Atomic force microscopy of WT and Rho+/- disc membranes revealed, in both cases, Rho organized in paracrystalline and raftlike structures. From these data, we conclude that the differences in physiological responses measured in WT and Rho+/- mice are due to structural changes of the whole ROS and not due to a lower density of Rho.

Animals↗

The G protein-coupled receptor rhodopsin in the native membrane.

The higher-order structure of G protein-coupled receptors (GPCRs) in membranes may involve dimerization and formation of even larger oligomeric complexes. Here, we have investigated the organization of the prototypical GPCR rhodopsin in its native membrane by electron and atomic force microscopy (AFM). Disc membranes from mice were isolated and observed by AFM at room temperature. In all experimental conditions, rhodopsin forms structural dimers organized in paracrystalline arrays. A semi-empirical molecular model for the rhodopsin paracrystal is presented validating our previously reported results. Finally, we compare our model with other currently available models describing the supramolecular structure of GPCRs in the membrane.

Animals↗

[Transforming growth factor beta 1 modulates connective tissue growth factor expression via Smad2 signaling pathway in podocyte in vitro].

OBJECTIVE: To assess the expression of connective tissue growth factor (CTGF), and the signaling pathway for the regulation of CTGF by transforming growth factor beta1 (TGF beta(1)) in podocytes. METHODS: In this study, we observed the effects of three potent profibrotic growth factors-TGF beta(1), Platelet-derived growth factor (PDGF), and Angiotensin II (AngII) on the expression of CTGF protein by Western blot analysis in cultured mouse podocytes, which is one of the most important cell construction of glomerular filter barrier, and we also investigated the underlying ERK and Smads signaling pathway through which TGF beta(1) regulates CTGF expression. The levels of CTGF mRNA were assayed by RT-PCR. RESULTS: Basal levels of CTGF protein were observed in cultured podocytes, treatment with 20 ng/ml PDGF and 10(-6) mol/L Ang. II for 24 h did not stimulate the expression of CTGF protein compared with control (P > 0.05), but significantly increase in levels of CTGF protein were seen in 1 ng/ml TGF beta(1) treated cells compared with with control (P < 0.05), and the levels of CTGF were up-regulated in a TGF beta(1) dose-dependent manner; The level of CTGF mRNA was also stimulated by 1 ng/ml TGF beta(1) at 12 h. 1 ng/ml TGF beta(1) induced phosphorylation of Smad(2) and ERK(1/2), and both reached the peak at 30 min; suppression of phosphorylation of Smad(2) with Staurosporine, a Serine/Threonine kinase inhibitor, diminished TGF beta(1)-triggered expression of CTGF protein, while blockade of phosphorylation of ERK(1/2) with PD98059, a specific ERK(1/2) activation inhibitor, did not decrease the TGF beta(1)-triggered expression of CTGF protein. CONCLUSION: TGF beta(1) stimulated the expression of CTGF protein via Smad(2)-dependent and ERK(1/2)-independent signaling pathway in podocyte in vitro.

Angiotensin II↗

A concept for G protein activation by G protein-coupled receptor dimers: the transducin/rhodopsin interface.

G protein-coupled receptors (GPCRs) are ubiquitous and essential in modulating virtually all physiological processes. These receptors share a similar structural design consisting of the seven-transmembrane alpha-helical segments. The active conformations of the receptors are stabilized by an agonist and couple to structurally highly conserved heterotrimeric G proteins. One of the most important unanswered questions is how GPCRs couple to their cognate G proteins. Phototransduction represents an excellent model system for understanding G protein signaling, owing to the high expression of rhodopsin in rod photoreceptors and the multidisciplinary experimental approaches used to study this GPCR. Here, we describe how a G protein (transducin) docks on to an oligomeric GPCR (rhodopsin), revealing structural details of this critical interface in the signal transduction process. This conceptual model takes into account recent structural information on the receptor and G protein, as well as oligomeric states of GPCRs.

Animals↗

Analysis of the PINK1 gene in a large cohort of cases with Parkinson disease.

BACKGROUND: Mutations in the PTEN-induced kinase (PINK1) gene located within the PARK6 locus on chromosome 1p35-p36 have recently been identified in patients with recessive early-onset Parkinson disease. OBJECTIVE: To assess the prevalence of PINK1 mutations within a series of early- and late-onset Parkinson disease patients living in North America. DESIGN: All coding exons of the PINK1 gene were sequenced in a series of 289 Parkinson disease patients and 80 neurologically normal control subjects; the mutation frequencies were evaluated in additional controls (100 white and 50 Filipino subjects). RESULTS: We identified 27 variants, including the first reported compound heterozygous mutation (Glu240Lys and Leu489Pro) and a homozygous Leu347Pro mutation in 2 unrelated young-onset Parkinson disease patients. CONCLUSION: Autosomal recessive mutations in PINK1 are a rare cause of young-onset Parkinson disease.

Adolescent↗

Combined MR spectroscopic imaging and diffusion tensor MRI visualizes corticospinal tract degeneration in amyotrophic lateral sclerosis.

Motor neuron damage and cortical spinal tract (CST) degeneration are pathological features of amyotrophic lateral sclerosis (ALS). We combined whole-brain diffusion tensor imaging (DTI) and three-dimensional magnetic resonance spectroscopic imaging (MRSI) to study the CST at different locations. Eight ALS patients were compared with normal controls. Fractional anisotropy (FA) and mean diffusivity (MD), and the ratio of N-acetyl-aspartate (NAA) to creatine (Cr) were measured at various locations in the CST, including the subcortical white matter (SWM), centrum semiovale (CS), periventricular white matter (PV), posterior limb of the internal capsule (PIC) and cerebral peduncle (CP). Patients showed significantly lower FA than controls in the CST, including the SWM, CS, PV and PIC. Although there was a trend towards elevated MD in ALS patients, this did not reach statistical significance. NAA/Cr ratios were also decreased in ALS patients compared with normal controls, with significant differences in the SWM and PV but not in PIC. Combined whole-brain DTI and MRSI can detect axonal degeneration in ALS. Measurements of FA obtained in the SWM, CS, PV and PIC, and NAA/Cr ratios in the SWM and PV yield the most robust results.

Adult↗

Three-dimensional expression of adhesion molecules on the superficial synovial intima of LPS-induced arthritis of the mouse knee analyzed by immuno-SEM.

Three-dimensional microlocalization of adhesion molecules, i.e. ICAM-1 (intercellular adhesion molecule), VCAM-1 (vascular adhesion molecule), LFA-1 (lymphocyte function-associated antigen), Mac-1 (macrophage differentiation antigen) and VLA-4 (very late activation antigen), expressed on type-A synoviocyte (macrophage-like cell) and type-B synoviocyte (fibroblast-like cell), were detected by immuno-scanning electron microscopy (SEM) to investigate the immunoreactive microenvironment of the superficial synovial intima in lipopolysaccharide (LPS)-induced arthritis of the mouse knee. Type-B synoviocytes extended rich slender processes from the periphery and constructed a cytoplasmic network, to which ICAM-1 was restricted. VCAM-1 was expressed only in the LPS-stimulated group and was relatively limited to the microvilli of type-B synoviocytes. Type-A synoviocytes were located randomly among the network with a smoother surface and expressed Mac-1 and LFA-1, which were counter-receptors for ICAM-1, and VLA-4 for VCAM-1 on the microvilli or lamellipodia. Three-dimensional microlocalization of adhesion molecules suggests that the network constructed by cytoplasmic processes and microvilli of type-B synoviocytes forms the pathway for the migration or the foothold for the fixation of type-A synoviocytes and takes part in forming an immunoreactive environment in the articular cavity.

Animals↗

[Quantification of isopimpinellin in root of Toddalia asiatica by HPLC].

OBJECTIVE: To determine the content of isopimpinellin in root of Toddalia asiatica. METHODS: A HPLC method was set up. Using Hypersil C18 column and methanol-water (70:30) as mobile phase, with the detection wavelength at 306 nm. RESULT: The linear range of isopimpinellin was 0.004 20 approximately 0.420 microg. The average recovery was 99.7% and the RSD 2.8%. CONCLUSION: The method is simple and accurate, with good reproducibility, and can be used as a quantitative analysis method for isopimpinellin.

Chromatography, High Pressure Liquid↗

[Application of fetal DNA in maternal plasma for non-invasive prenatal diagnosis of fetal sex].

To investigate the feasibility and possibility of application of fetal DNA from maternal plasma for noninvasive prenatal diagnosis of fetal sex, plasma DNAs in blood samples of 73 pregnant women at the gestational period of 26 to 41 weeks were extracted by column separation and nested polymerase chain reaction were employed to amplify the SRY gene. A comparison was made between the amplification results and the real sex of the fetus after their delivery. The concordance rate of SRY gene amplification results of plasma free DNA with real fetal sex was 91.78% (67/73), the sensitivity rate was 97.37% (37/38), and the specific rate was 85.71% (30/35). The cell-free fetal DNA in maternal blood can be one of the valuable material sources for noninvasive prenatal diagnosis and the method of nested PCR could be useful for fetal sex determination. The specific rate of the test was 91.78%. It is of significance to prevent sex-linked inheritant diseases.

Adult↗

[Clinical study of subcutaneous administration of gonadotropin-releasing hormone agonist every six weeks in girls with idiopathic central precocious puberty].

OBJECTIVE: Gonadotropin-releasing hormone agonist (GnRHa) is widely used for the treatment of precocious puberty, but there was no identical regime for the dosage and the interval of administration. The aim of this study was to assess the feasibility of subcutaneous administration of Triptorelin with a prolonged interval (six weeks) for the suppression of pituitary-gonadal axis and clinical signs in girls with idiopathic central precocious puberty (ICPP). METHODS: Forty-six girls with ICPP were enrolled in this trial and were divided into two groups at random, with 26 patients in group A and 20 in group B. There were no significantly differences in chronological age, height, weight, age at clinical onset of puberty and bone age between the two groups before treatment. Triptorelin (Decapeptyl, 3.75 mg) was administered subcutaneously (SC) at 6 weeks intervals in group A or intramuscularly (IM) at 4 weeks intervals in group B. Both forms were given for more than 12 months consecutively. During the period of treatment, the clinical parameters including height, weight, pubertal stage, bone age, uterine volume and ovarian size were documented. The serum levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and estradiol (E(2)) were monitored using immunoenzymometric assay. RESULTS: Both treatment regimes can completely suppressed the pituitary-gonadal axis. The clinical signs of pubertal development regressed or stabilized in all patients. Breast developments, as reflected by Tanner staging, were regressed. Uterine volume decreased after treatment, however, this decrease did not reach statistical significance. Mean ovarian volume did not change significantly during treatment. The height velocity was significantly decreased from a pretreatment value of 6.3 +/- 1.4 cm/year to 5.8 +/- 1.2 cm/year in group A and 6.7 +/- 1.3 cm/year to 5.4 +/- 1.0 cm/year in group B, respectively. The rate of skeletal maturation was reduced significantly during treatment. The ratio of bone age/chronological age was 1.2 +/- 0.2 or 1.3 +/- 0.3 at the onset of therapy and decreased significantly after the treatment to 0.7 +/- 0.2 or 0.9 +/- 0.1, respectively. The predicted adult height increased significantly and progressively during therapy. The levels of serum LH, FSH and E(2) were returned to the prepubertal condition after 6 - 8 weeks treatment and remained suppressed for the duration of treatment. No significantly side effects of therapy were noted. The most common adverse event during SC treatment was that a non-irritating, 1 cm in diameter mass can be palpated at the site of subcutaneous injection in the abdominal wall of group A patients. It gradually decreased in size, and disappeared after 8 - 12 weeks. Two girls had minimal withdrawal virginal bleeding episodes after the first injection. CONCLUSION: Both IM and SC triptorelin administration were clinically effective. They can induce profound suppression of hypothalamic-pituitary-gonadal axis while stabilizing height velocity, slowing bone maturation and increasing predicted adult height. These results suggest that subcutaneous injection of triptorelin in 6 weeks intervals at a dosage of 3.75 mg was a safe and acceptable regime for ICPP with good efficacy.

Body Height↗

[Genetic polymorphisms of five STR loci on chromosome 21 in Chinese Han population].

To elucidate the genetic polymorphisms of five STR loci on chromosome 21 in Chinese Han population and construct a preliminary database, EDTA-blood specimens were collected from unrelated individuals in Beijing. The DNAs were extracted with Chelex method and were amplified by PCR. The PCR products were analyzed by the PAG electrophoresis or by the approach of the automated fluorescent detection. The five STR loci consist of simple repeat motif and its distributions of genotypes are agreement with Hardy-Weinberg equation. Its polymorphism information content is all over 0.50. The obtained data can not only be used as evidences for genetic diagnosis of Down Syndrome, but also for calculating the probabilities in the paternity test and individual identification.

Alleles↗