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Biomedical subjects

Yan Lu

Publications and source records attributed to Yan Lu.

At least 91 records · Page 5Linked to original sources
PubMed2005

Receptor for advanced glycation end products and its ligands: a journey from the complications of diabetes to its pathogenesis.

Many studies have suggested that the expression of RAGE (receptor for advanced glycation end products) is upregulated in human tissues susceptible to the long-term complications of diabetes. From the kidneys to the macrovessels of the aorta, RAGE expression is upregulated in a diverse array of cell types, from glomerular epithelial cells (podocytes) to endothelial cells, vascular smooth muscle cells, and inflammatory mononuclear phagocytes and lymphocytes. Although RAGE was first described as a receptor for advanced glycation end products (AGEs), the key finding that RAGE was also a signaling receptor for proinflammatory S100/calgranulins and amphoterin, led to the premise that even in euglycemia, ligand-RAGE interaction propagated inflammatory mechanisms linked to chronic cellular perturbation and tissue injury. Indeed, such considerations suggested that RAGE might even participate in the pathogenesis of type 1 diabetes. Our studies have shown that pharmacological and/or genetic deletion/mutation of the receptor attenuates the development of hyperglycemia in NOD mice; in mice with myriad complications of diabetes, interruption of ligand-RAGE interaction prevents or delays the chronic complications of the disease in both macro- and microvessel structures. Taken together, these findings suggest that RAGE is "at the right place and time" to contribute to the pathogenesis of diabetes and it complications. Studies are in progress to test the premise that antagonism of this interaction is a logical strategy for the prevention and treatment of diabetes.

Animals↗
PubMed2005

[The effect of esmolol on hemodynamic of the myocardial bridging-mural mural coronary artery].

OBJECTIVE: To assess the effect of beta blocker on blood flow velocity and reserve on the intramural coronary artery of patients with myocardial bridging. METHODS: In 8 patients with myocardial bridge, intracoronary Doppler was performed before and after esmolol was given intravenously. The basic average peak velocity (bAPV), hyperaemic average peak velocity (hAPV) of blood flow, and coronary flow reserve (CFR) proximal and distal to the mural myocardial bridging was measured and compared. RESULTS: After esmolol injection, the mural coronary diameter systolic reduction decreased from (58.0 +/- 14.7)% to (26.0 +/- 9.8)% (P < 0.01); the bAPV proximal and distal to myocardial bridging separately decreased from (19.4 +/- 4.9) cm/s and (18.4 +/- 3.6) cm/s to (4.7 +/- 3.9) cm/s (P < 0.01) and (15.1 +/- 1.5) cm/s (P < 0.05). Under hyperemization, esmolol changed the hAPV of proximal and distal to myocardial bridging separately from (54.1 +/- 14.9) cm/s and (44.7 +/- 9.4) cm/s to (49.7 +/- 16.4) cm/s and (48.9 +/- 10.1) cm/s (all P > 0.05); thus, the value of CFR both proximal and distal to myocardial bridge increased separately from 2.8 +/- 0.3 and 2.5 +/- 0.5 to 3.4 +/- 0.5 and 3.2 +/- 0.6 (all P < 0.01). CONCLUSION: Esmolol can decreased the compression of the intramural coronary artery and increased the CFR to normal level of it.

Adrenergic beta-Antagonists↗
PubMed2005

[Relationship between coronary arterial remodeling and plaque composition assessed by intravascular ultrasound imaging].

OBJECTIVE: During progression of atherosclerosis, the vessel may develop either positive or negative remodeling. The pathophysiology of vascular remodeling is not fully understood. This study investigated the relationship between plaque characteristics and arterial remodeling using intravascular ultrasound imaging (IVUS). METHODS: A total of 77 patients (male 53, mean age 58 +/- 10 years) who underwent IVUS imaging (ClearView or Galaxy2, Boston Scientific, USA) of culprit vessel were enrolled in this study. Among the 77 patients, 31 presented with stable angina pectoris and 46 presented with acute coronary syndrome. Qualitative assessment of the lesion and quantitative measurement were performed in both stenotic and reference segments. The lesions were classified into soft plaque and hard plaque (including fibrous plaque, calcified plaque and mixed plaque) according to different ultrasound patterns of tissue reflection. The remodeling index (RI) was defined as the ratio of vessel cross sectional area (EEMcsa) of lesion segment to the mean reference EEMcsa. Positive remodeling was defined as RI > 1.0 and negative remodeling as RI < 1.0. RESULTS: Of 77 lesions, 45 (58%) had undergone positive remodeling, and 32 (42%) had negative remodeling. In comparison to the patients with negative remodeling, patients with positive remodeling presented with more acute coronary syndrome (74% vs. 43%, P = 0.006). Both the plaque area and the vessel area were significantly larger in the lesion with positive remodeling than in lesion with negative remodeling. The lesions with positive remodeling were predominantly soft (71% vs. 34%, P = 0.001) and had less calcification [21% vs. 54%, P = 0.003 and (18 +/- 37) degrees vs. (40 +/- 50) degrees, P = 0.027] compared with lesions with negative remodeling. The difference of clinical presentation and plaque characteristics between the patients with different patterns of remodeling is still significant with binary logistic analysis. CONCLUSIONS: Coronary arterial remodeling pattern is related to the clinical manifestation and the composition of plaque. Lesions presented with positive remodeling have a higher prevalence of soft plaque and less calcification.

Aged↗
PubMed2004

A two-step strategy for detecting differential gene expression in cDNA microarray data.

A mixed-model approach is proposed for identifying differential gene expression in cDNA microarray experiments. This approach is implemented by two interconnected steps. In the first step, we choose a subset of genes that are potentially expressed differentially among treatments with a loose criterion. In the second step, these potential genes are used for further analyses and data-mining with a stringent criterion, in which differentially expressed genes (DEGs) are confirmed and some quantities of interest (such as gene x treatment interaction) are estimated. By simulating datasets with DEGs, we compare our statistical method with a widely used method, the t-statistic, for single genes. Simulation results show that our approach produces a high power and a low false discovery rate for DEG identification. We also investigate the impacts of various source variations resulting from microarray experiments on the efficiency of DEG identification. Analysis of a published experiment studying unstable transcripts in Arabidopsis illustrates the utility of our method. Our method identifies more novel and biologically interesting unstable transcripts than those reported in the original literature.

Arabidopsis↗
PubMed2004

Temperature-sensitive hybrid microgels with magnetic properties.

In the present paper, we report the preparation of hybrid temperature-sensitive microgels which include magnetite nanoparticles in their structure. Polymeric microgels have been prepared by surfactant-free emulsion copolymerization of acetoacetoxyethyl methacrylate (AAEM) and N-vinylcaprolactam (VCL) in water with a water-soluble azo-initiator. The obtained microgels possess a low critical solution temperature (LCST) in water solutions, with a rapid decrease of the particle size being observed at elevated temperatures. Magnetite was deposited directly into microgels, leading to the formation of composite particles which combine both temperature-sensitive and magnetic properties. The influence of magnetite load on microgel size, morphology, swelling-deswelling behavior, and stability is discussed.

Ferrosoferric Oxide↗
PubMed2004

Identification of cell surface and secreted proteins essential for tumor cell survival using a genetic suppressor element screen.

Survival factors play critical roles in regulating cell growth in normal and cancer cells. We designed a genetic screen to identify survival factors which protect tumor cells from apoptosis. A retroviral expression library of random cDNA fragments was constructed from cancer cells and used to transduce the colon carcinoma cell line HCT116. Recipient cells were functionally selected for induction of caspase 3-mediated apoptosis. Analyses of over 10,000 putative genetic suppression elements (GSEs) sequences revealed cognate gene candidates that are implicated in apoptosis. We further analysed 26 genes encoding cell surface and secreted proteins that can potentially serve as targets for therapeutic antibodies. Tetracycline-inducible GSEs from several gene candidates induced apoptosis in stable HCT 116 cell lines. Similar phenotypes were caused by RNAi derived from the same genes. Our data suggest requirement for the cell surface targets IGF2R, L1CAM and SLC31A1 in tumor cell growth in vitro, and suggests that IGF2R is required for xenograft tumor growth in a mouse model.

Animals↗
PubMed2004

Quantifying the relationship between gene expressions and trait values in general pedigrees.

Treating mRNA transcript abundances as quantitative traits and examining their relationships with clinical traits have been pursued by using an analytical approach of quantitative genetics. Recently, Kraft et al. presented a family expression association test (FEXAT) for correlation between gene expressions and trait values with a family-based (sibships) design. This statistic did not account for biological relationships of related subjects, which may inflate type I error rate and/or decrease power of statistical tests. In this article, we propose two new test statistics based on a variance-components approach for analyses of microarray data obtained from general pedigrees. Our methods accommodate covariance between relatives for unmeasured genetic effects and directly model covariates of clinical importance. The efficacy and validity of our methods are investigated by using simulated data under different sample sizes, family sizes, and family structures. The proposed LR method has correct type I error rate with moderate to large sample sizes regardless of family structure and family sizes. It has higher power with complex pedigrees and similar power to the FEXAT with sibships. The other proposed FEXAT(R) method is favorable with large family sizes, regardless of sample sizes and family structure. Our methods, robust to population stratification, are complementary to the FEXAT in expression-trait association studies.

Animals↗
PubMed2004

APOE haplotypes influence bone mineral density in Caucasian males but not females.

Low bone mineral density (BMD) is one of the most important risk factors for osteoporosis. Apolipoprotein E (APOE) has been considered as a candidate gene for osteoporosis because of its influence on osteoblast uptake of lipoprotein-borne vitamin K. Using the quantitative transmission disequilibrium test QTDT, we examined linkage and/or association of APOE and BMD at the lumbar spine and the total hip in a sample of 387 Caucasian nuclear families with 715 parents and 953 children. The children were aged 20-50 years and female offspring were premenopausal as well. Four single nucleotide polymorphisms (SNP1-4) in the APOE gene, 4-locus haplotypes and 2-locus haplotypes (epsilon1, epsilon2, epsilon3, epsilon4 isoforms, reconstructed by SNP3 and SNP4) were analyzed. In the whole sample and the female offspring families we found no evidence of linkage or association for either single SNP or haplotype with BMD at the two studied skeletal sites. In the male offspring families, within-family associations were observed at the haplotypes CGTC (P = 0.001), GGTT (P = 0.002), and GATC (P = 0.006) for the lumbar spine BMD, and GATC (P = 0.008) for the total hip BMD. These data suggested that in our studied Caucasian population, APOE may have effects on BMD variation in males but not females. Further studies with a larger sample size are required to confirm such results.

Absorptiometry, Photon↗
PubMed2004

Isolation and functional characterization of a dynamin-like gene from Plasmodium falciparum.

A novel dynamin-like GTPase gene, Pfdyn1, was cloned from an asexual stage cDNA library of Plasmodium falciparum Dd2 strain. Pfdyn1 contains a highly conserved N-terminal tripartite GTPase domain, a coiled-coil region, and a C-terminal 129 aa unknown function domain. Like yeast Vps1p, it lacks pleckstrin homology domain and proline-rich region. Western blot analysis showed that Pfdyn1 is a Triton X-100 insoluble protein expressed only in the mature sub-stage. Morphological studies indicated that Pfdyn1 is partly co-localized with PfGRP, a known ER-resident protein, and localizes diffusely with several membrane structures and a 60-100 nm vesicle both inside and on surface of the parasites and also in the cytoplasm of infected erythrocytes. The dsRNA originated by C-terminus fragment of Pfdyn1 inhibits markedly the growth of P. falciparum parasite at the erythrocyte stage. Those data showed that Pfdyn1 is a conservative, membrane related protein and plays an essential role for the survival of Plasmodium parasite.

Amino Acid Sequence↗
PubMed2004

Metal-ion interactions with sugars. Crystal structures and FT-IR studies of the LaCl3-ribopyranose and CeCl3-ribopyranose complexes.

Single crystals of LaCl3.C5H10O5.5H2O (1) and CeCl3.C5H10O5.5H2O (2) were obtained from ethanol-water solutions and their structures determined by X-ray. The two complexes are isomorphous. Two configurations of complex 1 or complex 2, as a pair of isomers, were found in each single crystal in a disordered state. The ligand of one of the isomer is alpha-D-ribopyranose in the 4C1 conformation, the ligand of the other is beta-D-ribopyranose in the 1C4 conformation. For complex 1, the alpha:beta anomeric ratio is 51:49, and for complex 2, the ratio is 52:48. Both ligands of the two isomers provide three hydroxyl groups in ax-eq-ax orientation for coordination. The Ln3+ (Ln = La or Ce) ion is nine-coordinated with five Ln-O bonds from water molecules, three Ln-O bonds from hydroxyl groups of the D-ribopyranose, and one Ln-Cl bond from chloride ion. The hydroxyl groups, water molecules, and chloride ions form an extensive hydrogen-bond network. The IR spectral C-C, O-H, C-O, and C-O-H vibrations were observed to be shifted in both the two complexes and the IR results are in accord with those of X-ray diffraction.

Carbohydrates↗
PubMed2004

Tests of linkage and/or association of TGF-beta1 and COL1A1 genes with bone mass.

Transforming growth factor beta 1 (TGF-beta1) is involved in bone metabolism and collagen type I alpha 1 (COL1A1) is the most abundant protein of bone matrix. Both have been considered as candidate genes for osteoporosis. In this study, we employed the transmission disequilibrium test (TDT) to examine the relationship between each of the two genes with bone mineral density (BMD) and bone mineral content (BMC) at the spine and hip in a sample of 1668 subjects from 387 Caucasian nuclear families. For the TGF-beta1 gene, three SNPs, SNP1, SNP2, and SNP4 (located in exon 1, intron 4 and intron 5, respectively) were tested and the minor allele frequencies were 30.9%, 2.1% and 27.0%, respectively. All eight possible haplotypes (TGF1-8) were observed. For the COL1A1 gene, the minor allele frequencies of SNP5, SNP6 and SNP8 (located in exon 1, intron 1, and exon 45, respectively) were 15.2%, 18.7%, 2.0%, respectively, and only six of eight potential haplotypes (COL1-6) were obtained. In the whole sample, total associations were observed between haplotype COL5 with spine BMD (P=0.027), haplotypes COL3 and TGF4 with hip BMC (P=0.002, 0.003, respectively). Within-family associations were found for spine BMD at haplotypes TGF4 (P=0.027) in female offspring families and TGF3 (P=0.021) in male offspring families. Further studies with denser markers and larger sample size are required to eventually define the relationship between these two genes with bone mass at the spine and hip.

Adult↗
PubMed2004

Patterns of linkage disequilibrium and haplotype distribution in disease candidate genes.

BACKGROUND: The adequacy of association studies for complex diseases depends critically on the existence of linkage disequilibrium (LD) between functional alleles and surrounding SNP markers. RESULTS: We examined the patterns of LD and haplotype distribution in eight candidate genes for osteoporosis and/or obesity using 31 SNPs in 1,873 subjects. These eight genes are apolipoprotein E (APOE), type I collagen alpha1 (COL1A1), estrogen receptor-alpha (ER-alpha), leptin receptor (LEPR), parathyroid hormone (PTH)/PTH-related peptide receptor type 1 (PTHR1), transforming growth factor-beta1 (TGF-beta1), uncoupling protein 3 (UCP3), and vitamin D (1,25-dihydroxyvitamin D3) receptor (VDR). Yin yang haplotypes, two high-frequency haplotypes composed of completely mismatching SNP alleles, were examined. To quantify LD patterns, two common measures of LD, D' and r2, were calculated for the SNPs within the genes. The haplotype distribution varied in the different genes. Yin yang haplotypes were observed only in PTHR1 and UCP3. D' ranged from 0.020 to 1.000 with the average of 0.475, whereas the average r2 was 0.158 (ranging from 0.000 to 0.883). A decay of LD was observed as the intermarker distance increased, however, there was a great difference in LD characteristics of different genes or even in different regions within gene. CONCLUSION: The differences in haplotype distributions and LD patterns among the genes underscore the importance of characterizing genomic regions of interest prior to association studies.

Apolipoproteins E↗
PubMed2004

Influence of polymerization temperature on the molecular recognition of imprinted polymers.

This paper aimed at investigating the influence of polymerization temperature on the molecular recognition of molecularly imprinted polymers (MIPs) based on multiple non-covalent interactions. 3-l-Phenylalanylaminopyridine (3-l-PheNHPy) imprinted polymers were prepared using azobisnitriles as either thermal initiators or photoinitiators at various temperatures of 10, 40 and 60 degrees C, respectively. These polymers were subsequently evaluated in the high-performance liquid chromatographic (HPLC) mode for enantioselectivity. An unexpected result shows that polymer prepared at 40 degrees C has the highest enantioselectivity, but not the polymer prepared at lower temperature of 10 degrees C. Further, the effect of elution temperature and sample load on the selectivity of polymers was investigated in detail. In order to get a better understanding of the "exception", the influence of polymerization temperature on the polymerization extent and polymer morphology was studied by FT-IR spectrum test, cross-polarization magic angle spinning (CP-MAS) (13)NMR spectra experiment and pore analysis. Based on these results we attribute this "exception" to that there is a tradeoff between the extent of polymerization and stabilization of the template-functional monomer complexes. And an optimal polymerization temperature can be found for each combination of template and monomer.

Chromatography, High Pressure Liquid↗
PubMed2004

Tests of linkage and/or association of the LEPR gene polymorphisms with obesity phenotypes in Caucasian nuclear families.

Genetic variations in the leptin receptor (LEPR) gene have been conceived to affect body weight in general populations. In this study, using the tests implemented in the statistical package QTDT, we evaluated association and/or linkage of the LEPR gene with obesity phenotypes in a large sample comprising 1,873 subjects from 405 Caucasian nuclear families. Obesity phenotypes tested include body mass index (BMI), fat mass, percentage fat mass (PFM), and lean mass, with the latter three measured by dual-energy X-ray absorptiometry (DXA). Three single nucleotide polymorphisms (SNPs), namely Lys109Arg (A/G), Lys656Asn (G/C), Pro1019Pro (G/A), in the LEPR gene were analyzed. Significant linkage disequilibrium (0.394 < or = |D'| < or = 0.688, P < 0.001) was observed between pairs of the three SNPs. No significant population stratification was found for any SNP/phenotype. In single-locus analyses, evidence of association was observed for Lys656Asn with lean mass (P = 0.002) and fat mass (P = 0.015). The contribution of this polymorphism to the phenotypic variation of lean mass and fat mass was 2.63% and 1.15%, respectively. Subjects carrying allele G at the Lys656Asn site had, on average, 3.16% higher lean mass and 2.71% higher fat mass than those without it. In the analyses for haplotypes defined by the three SNPs, significant associations were detected between haplotype GCA (P = 0.005) and lean mass. In addition, marginally significant evidence of association was observed for this haplotype with fat mass (P = 0.012). No statistically significant linkage was found, largely due to the limited power of the linkage approach to detect small genetic effects in our data sets. Our results suggest that the LEPR gene polymorphisms contribute to variation in obesity phenotypes.

Adult↗
PubMed2004

Marker-assisted selection in segregating generations of self-fertilizing crops.

Computer simulations were used to study the efficiency of MAS for breeding self-fertilizing crops, based on a general model including additive, dominance and epistasis. It was shown that MAS not only gave larger genetic responses but also dramatically increased the frequencies of superior genotypes as compared with phenotypic selection. However, the advantages of MAS over phenotypic selection were considerably reduced when conducting selection in later generations. A modified method combining MAS in early generations with phenotypic selection in later generations was thus proposed from an efficiency standpoint. We also proposed a potential index to measure the probability of an individual showing superior genotypes under selfing. It was apparent that more superior genotypes could be derived from selection by using the potential index than by using other methods. The implications of these findings for plant breeding are discussed.

Breeding↗
PubMed2004

Blockade of receptor for advanced glycation end product (RAGE) attenuates ischemia and reperfusion injury to the liver in mice.

Hepatic ischemia/reperfusion (I/R) injury associated with liver transplantation and hepatic resection is characterized by hepatocellular damage and a deleterious inflammatory response. In this study, we examined whether receptor for advanced glycation end product (RAGE) activation is linked to mechanisms accentuating inflammation on I/R in a murine model of total hepatic ischemia. Animals treated with soluble RAGE (sRAGE), the extracellular ligand-binding domain of RAGE, displayed increased survival after total hepatic I/R compared with vehicle treatment. TUNEL assay and histologic analysis revealed that blockade of RAGE was highly protective against hepatocellular death and necrosis on I/R; in parallel, proliferating cell nuclear antigen was enhanced in livers of mice treated with sRAGE. Rapid activation of p38, p44/42, stress-activated protein kinase and c-Jun N-terminal kinase mitogen-activated protein kinases, signal transducer and activator of transcription-3, and nuclear translocation of activator protein-1 was evident at early times on I/R. In the remnants of sRAGE-treated livers, however, activation of each of these signaling and transcription factor pathways was strikingly decreased. sRAGE-treated remnants displayed enhanced activation of nuclear factor kappaB, in parallel with increased transcripts for the proregenerative cytokine, tumor necrosis factor-alpha. In conclusion, these data suggest that RAGE modulates hepatic I/R injury, at least in part by activation of key signaling pathways linked to proinflammatory and cell death-promoting responses. We propose that blockade of this pathway may represent a novel strategy to attenuate injury in hepatic I/R and to facilitate regeneration.

Animals↗