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Biomedical subjects

Lin He

Publications and source records attributed to Lin He.

At least 109 records · Page 6Linked to original sources
PubMed2005

A family-based study of the association between the G72/G30 genes and schizophrenia in the Chinese population.

Studies have shown a strong positive association between schizophrenia and G72/G30, demonstrated by both individual markers and haplotypes. A further functional study also supports the role of G72 in the etiology of schizophrenia. In this study, we have replicated these results of transmission/disequilibrium testing (TDT) and haplotype analysis in the Han Chinese population, showing P values of 0.0018 and 0.00007 for individual markers and haplotypes, respectively. Hence, our data supports the hypothesis that G72/G30 are important candidate genes for explaining schizophrenia in the Han Chinese population.

Adult↗
PubMed2005

Case-control association study of the close homologue of L1 (CHL1) gene and schizophrenia in the Chinese population.

The close homolog of L1 (CHL1), located on human chromosome 3p26.1, is a newly identified member of the L1 family of cell adhesion molecules which play important roles in cell migration, axonal growth, and synaptic remodeling. A positive association has been reported between a missense polymorphism in CHL1 gene and schizophrenia in the Japanese population [Sakurai, K., Migita, O., Toru, M., Arinami, T., 2002. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. Mol. Psychiatry 7, 412-415]. An association between a missense polymorphism in the close homologue of L1 (CHL1, CALL) gene and schizophrenia. In order to test this finding, we genotyped four SNPs in the gene in the Han Chinese population using a sample of 560 cases and 576 controls. Analysis of allele frequencies in both samples also showed strong association between SNP rs2272522 (the same marker studied by K. Sakurai) and the disease (X2=31.591, P<0.000001, OR=1.745, 95% CI=1.435-2.121). Our results confirm the positive association between CHL1 gene and schizophrenia and indicate that CHL1 may be involved in the etiology of schizophrenia.

Adult↗
PubMed2005

A family-based association study of the MOG gene with schizophrenia in the Chinese population.

Recently the expression of human myelin/oligodendrocyte glycoprotein (MOG) has been found to be significantly downregulated in the brain tissue of subjects with schizophrenia, suggesting that the MOG gene resides within a high-susceptibility locus for schizophrenia. In order to test this prediction, we analyzed three microsatellites from MOG in the Han Chinese population using a sample of 532 trios. Analysis of allele, genotype and haplotype frequencies showed weak positive association between the markers and the disease (p=0.01982). Our results would indicate that the MOG gene may play a significant role in schizophrenia in the Han Chinese. However, further study is required using other methods and involving other populations.

Asian People↗
PubMed2005

Ordered silicon nanocavity arrays in surface-assisted desorption/ionization mass spectrometry.

We report here a simple method to generate ordered nanocavity arrays on a Si wafer and use it in surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS). A close-packed SiO2 nanosphere array was first deposited on a low-resistivity Si wafer using a convective self-assembly method. The nanoparticle array was then used as a mask in a reactive ion etching (RIE) process to selectively remove portions of the Si surface. Subsequent sonication removed those physically adsorbed SiO2 nanoparticles and exposed an ordered nanocavity array underneath. The importance of this approach is its capability of systematically varying surface geometries to achieve desired features, which makes detailed studies of the impacts of surface features on the desorption/ionization mechanism feasible. We demonstrated that the in-plane width and out-of-plane depth of the cavities were adjustable by varying etching times, and the intercavity spacing was controllable by varying the number of particle layers deposited. MS detection of small peptides on these substrates showed comparable sensitivity to conventional porous Si substrates (DIOS, desorption/ ionization on porous silicon). The desorption and ionization efficiency of these roughened surfaces exhibited a nonmonotonic relationship to the increased total surface area. Several possible factors contributing to the observed phenomenon are speculated upon. The application of this arrayed surface in metabolite detection of Arabidopsis thaliana root extracts is also demonstrated.

Arabidopsis↗
PubMed2005

Synthesis of alkyl and aryl C-pyranosides using organozinc reagents via a Ferrier-type rearrangement.

The reaction of 1,2-dihydropyranyl acetates with dimethylzinc, diethylzinc and diphenylzinc in the presence of CF3COOH gave the corresponding alky and aryl C-pyranosides via a Ferrier rearrangement in excellent yields. Use of the organozinc species, CF3CO2ZnPh, reacted with high stereoselectivity to give the phenyl C-glycosides. Arylzinc chlorides could also be successfully applied to this reaction in the presence of BF3.OEt2.

Alkanes↗
PubMed2005

A case-control study of the relationship between the metabotropic glutamate receptor 3 gene and schizophrenia in the Chinese population.

Recent studies of the association between the metabotropic glutamate receptor 3 gene (GRM3) and schizophrenia have produced conflicting results, although GRM3 is a promising candidate gene. Fujii et al. found a single nuclear polymorphism (SNP) for within this gene, rs1468412 to have a positive association to schizophrenia in Japanese patients. To investigate this further, we genotyped 7 SNPs around GRM3 including rs1468412, in 752 Chinese patients with schizophrenia and 752 controls using Taqman technology. We did not detect any association between rs1468412 and schizophrenia, however we found differences in the allele frequency distribution of SNP rs2299225 (p=0.0297, odds ration [OR]=1.44, 95% confidence interval 1.05-1.99) between cases and controls. Moreover, the overall frequency of haplotypes constructed from three SNPs including rs2299225 showed significant differences between cases and controls (p=0.0017). Our results partially support the previous studies in other ethnic groups and indicate that the GRM3 gene may play an important role in the etiology of schizophrenia in the Han Chinese.

Adult↗
PubMed2005

Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis.

BACKGROUND: A common functional polymorphism (Val/Met) in the catechol-O-methyltransferase gene (COMT) that markedly affects enzyme activity has been shown to affect executive cognition and the physiology of the prefrontal cortex in humans. It is hypothesized that the high activity Val allele slightly increases risk for schizophrenia through its effect on dopamine-mediated prefrontal information processing. METHODS: We compared the allele/genotype frequencies of the Val/Met polymorphism in a large independent patient-control sample (862 patient and 928 healthy control subjects) from Han Chinese population, and an update meta-analysis was performed to assess the collective evidence across individual studies. RESULTS: No statistically significant differences were found in allele or genotype frequencies between patient and normal control subjects, although a nonsignificant overrepresentation of the Val allele in schizophrenia patients (odds ratio [OR] = 1.09, 95% confidence interval [CI] = .94-1.26) was suggested. Comparatively, the meta-analysis of all published population-based association studies showed statistically significant evidence for heterogeneity among the group of studies. Stratification of the studies by ethnicity of the samples yielded no significant evidence for an association with the Val allele in Asian population (OR = .96, 95% CI = .85-1.09), nor in European population (OR = 1.06, 95% CI = .95-1.19). CONCLUSIONS: Our data provide minimal evidence that the Val allele is a susceptibility factor for schizophrenia in either European or Asian populations.

Amino Acid Substitution↗
PubMed2005

A family-based association study of schizophrenia with polymorphisms at three candidate genes.

Clinical researches have shown that there is a genetic contribution to the pathogenesis of schizophrenia. Recent studies have suggested that three genes neuropeptide Y (NPY), phosphoinositide-3-kinase class 3 (PIK3C3) and 14-3-3 eta chain gene (YWHAH) are probably associated with schizophrenia. To replicate these findings, we carried out a family-based study on a sample of 235 trios. Our results suggest that the polymorphisms at the NPY and YWHAH genes are unlikely to be linked with genetic susceptibility to schizophrenia. However, we found significant evidence of preferential transmission of the -432C allele of the PIK3C3 gene in the entire trios (Z=2.91, d.f.=1, P=0.0036) and the male probands trios (Z=2.66, d.f.=1, P=0.0079).

14-3-3 Proteins↗
PubMed2005

Pioglitazone inhibits MMP-1 expression in vascular smooth muscle cells through a mitogen-activated protein kinase-independent mechanism.

Antidiabetic drug thiazolidinedione (TZD) also has anti-atherogenic effects. Among these effects, inhibition of smooth muscle cell (SMC) migration is considered to be essential. However, the mechanism whereby TZD inhibits SMC migration is not well understood. Since it is known that matrix metalloproteinases (MMPs) play a permissive role for SMC migration, we determined if TZD inhibits the upregulation of MMP-1 expression in SMCs by oxidized LDL (oxLDL), a potent stimulator for atherogenesis. Results showed that oxLDL markedly stimulated MMP-1 secretion, mRNA expression, and MMP-1 promoter activity, but pioglitazone significantly inhibited the oxLDL-upregulated MMP-1 expression. In an attempt to explore the signaling mechanism by which pioglitazone inhibits the oxLDL-upregulated MMP-1 expression, we found that extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK) pathways were required for the oxLDL-stimulated MMP-1 expression, but pioglitazone failed to antagonize the activation of ERK and JNK by oxLDL. Finally, our AP-1 activity assay showed that pioglitazone inhibited oxLDL-stimulated c-Jun activity. Taken together, the present study indicates that pioglitazone inhibits oxLDL-stimulated MMP-1 expression in VSMCs by inhibiting c-Jun transcriptional activity through a mitogen-activated protein kinase (MAPK)-independent mechanism.

Aorta↗
PubMed2005

Antitumor effects of radioiodinated antisense oligonuclide mediated by VIP receptor.

A 15-mer phosphorothioate antisense oligonuclide (ASON) complementary to the translation start region of the C-myc oncogene mRNA was radioiodinated to enhance its antitumor activity, and vasoactive intestinal peptide bound covalently polylysine (VIP-polylysine) was used as a carrier to deliver the oligonucleotide into VIP receptor-positive tumor cells. The antitumor activity of radioiodinated ASON conjugated to VIP-polylysine(VIP-131I-ASON) was investigated in athymic mice bearing HT29 tumor xenografts in comparison with unconjugated radioiodinated ASON(131I-ASON), unlabelled ASON (VIP-ASON) and scrambled oligonucleotide (VIP-131I-MON) conjugated to VIP-polylysine. Conjugation 125I-ASON to VIP-polylysine resulted in a 5.6-fold decrease in the plasma clearance and a 3.4-fold increase in tumor uptake of the radiopharmaceutical. Athymic mice bearing HT29 tumor xenografts were treated with 4 weekly doses of VIP-131I-ASON and the antitumor effects were assessed by use of the slope of the tumor growth curve. VIP-131I-ASON exhibited strong antitumor effects against HT29 xenografts, decreasing tumor growth rate 9.67-, 7.90-fold more effectively than 131I-ASON and VIP-ASON at equivalent doses of ASON. Conversely, 131I-ASON, VIP-ASON or VIP-131I-MON caused no significant effect compared with the normal saline. These data indicated that use of a VIP-polylysine carrier greatly increased HT29 tumor uptake of ASON and treatment with the VIP-131I-ASON complexes resulted in tumor growth delay in human colon cancer xenograft.

Animals↗
PubMed2005

SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci.

In multiloci-based genetic association studies of complex diseases, a powerful and high efficient tool for analyses of linkage disequilibrium (LD) between markers, haplotype distributions and many chi-square/p values with a large number of samples has been sought for long. In order to achieve the goal of obtaining meaningful results directly from raw data, we developed a robust and user-friendly software platform with a series of tools for analysis in association study with high efficiency. The platform has been well evaluated by several sets of real data.

Genetic Predisposition to Disease↗
PubMed2005

An association study of the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B) in schizophrenia with universal DNA microarray.

Dysfunction of the N-methyl-D-aspartate (NMDA) receptors has been implicated in the etiology of schizophrenia based on psychotomimetic properties of several antagonists and on observation of genetic animal models. To conduct association analysis of the NMDA receptors in the Chinese population, we examined 16 reported SNPs across the NMDA receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B), five of which were identified in the Chinese population. In this study, we combined universal DNA microarray and ligase detection reaction (LDR) for the purposes of association analysis, an approach we considered to be highly specific as well as offering a potentially high throughput of SNP genotyping. The association study was performed using 253 Chinese patients with schizophrenia and 140 Chinese control subjects. No significant frequency differences were found in the analysis of the alleles but some were found in the haplotypes of the GRIN2B gene. The interactions between the GRIN1 and GRIN2B genes were evaluated using the multifactor-dimensionality reduction (MDR) method, which showed a significant genetic interaction between the G1001C in the GRIN1 gene and the T4197C and T5988C polymorphisms in the GRIN2B gene. These findings suggest that the combined effects of the polymorphisms in the GRIN1 and GRIN2B genes might be involved in the etiology of schizophrenia.European Journal of Human Genetics (2005) 13, 807-814. doi:10.1038/sj.ejhg.5201418 Published online 20 April 2005.

Adult↗
PubMed2005

The case for strategic international alliances to harness nutritional genomics for public and personal health.

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries.

Animals↗
PubMed2005

Controlling pathological pain by adenovirally driven spinal production of the anti-inflammatory cytokine, interleukin-10.

Gene therapy for the control of pain has, to date, targeted neurons. However, recent evidence supports that spinal cord glia are critical to the creation and maintenance of pain facilitation through the release of proinflammatory cytokines. Because of the ability of interleukin-10 (IL-10) to suppress proinflammatory cytokines, we tested whether an adenoviral vector encoding human IL-10 (AD-h-IL10) would block and reverse pain facilitation. Three pain models were examined, all of which are mediated by spinal pro-inflammatory cytokines. Acute intrathecal administration of rat IL-10 protein itself briefly reversed chronic constriction injury-induced mechanical allodynia and thermal hyperalgesia. The transient reversal caused by IL-10 protein paralleled the half-life of human IL-10 protein in the intrathecal space (t(1/2) approximately 2 h). IL-10 gene therapy both prevented and reversed thermal hyperalgesia and mechanical allodynia, without affecting basal responses to thermal or mechanical stimuli. Extra-territorial, as well as territorial, pain changes were reversed by this treatment. Intrathecal AD-h-IL10 injected over lumbosacral spinal cord led to elevated lumbosacral cerebrospinal fluid (CSF) levels of human IL-10, with far less human IL-10 observed in cervical CSF. In keeping with IL-10's known anti-inflammatory actions, AD-h-IL10 lowered CSF levels of IL-1, relative to control AD. These studies support that this gene therapy approach provides an alternative to neuronally focused drug and gene therapies for clinical pain control.

Adenoviridae↗
PubMed2005

Use of nanobarcodes particles in bioassays.

We have developed striped metal nanoparticles, Nanobarcodes particles, which can act as encoded substrates in multiplexed assays. These particles are metallic, encodeable, machine-readable, durable, submicron-sized tags. The power of this technology is that the particles are intrinsically encoded by virtue of the difference in reflectivity of adjacent metal stripes. This chapter describes protocols for the attachment of biological molecules, and the subsequent use of the Nanobarcodes particles in bioassays.

Animals↗
PubMed2005

Predicting protein subcellular location using digital signal processing.

The biological functions of a protein are closely related to its attributes in a cell. With the rapid accumulation of newly found protein sequence data in databanks, it is highly desirable to develop an automated method for predicting the subcellular location of proteins. The establishment of such a predictor will expedite the functional determination of newly found proteins and the process of prioritizing genes and proteins identified by genomic efforts as potential molecular targets for drug design. The traditional algorithms for predicting these attributes were based solely on amino acid composition in which no sequence order effect was taken into account. To improve the prediction quality, it is necessary to incorporate such an effect. However, the number of possible patterns in protein sequences is extremely large, posing a formidable difficulty for realizing this goal. To deal with such difficulty, a well-developed tool in digital signal processing named digital Fourier transform (DFT) [1] was introduced. After being translated to a digital signal according to the hydrophobicity of each amino acid, a protein was analyzed by DFT within the frequency domain. A set of frequency spectrum parameters, thus obtained, were regarded as the factors to represent the sequence order effect. A significant improvement in prediction quality was observed by incorporating the frequency spectrum parameters with the conventional amino acid composition. One of the crucial merits of this approach is that many existing tools in mathematics and engineering can be easily applied in the predicting process. It is anticipated that digital signal processing may serve as a useful vehicle for many other protein science areas.

Algorithms↗
PubMed2005

[Mutation detection of COL1A1 gene in a pedigree with osteogenesis imperfecta].

Osteogenesis imperfecta (OI) is heritable bone fragility,which is inherited as an autosomal dominant trait clinical presentation. Clinical symptom, in general, is dominantly inherited OI with blue sclerae, hearing loss and mild-moderate skeletal deformity. Genetic loci of OI have been mapped to17q21.31-q22 and 7q22.1, in which COL1A1 and COL1A2 are known to be the causal genes. In this work,we performed linkage analysis in a kindred with autosomal dominant hereditary OI. A tight linkage to the markers on chromosome 17q21.31-q22 (maximum two-point lod score: 9.31 at theta = .00) was observed. Sequence analysis of COL1A1 revealed a single-base mutation that converted the consensus sequence at the 5' end of intron 26 from GT to AT to form an abnormal splicing site leading to OI.

Adolescent↗