PubMed Health⌕ Search

Biomedical subjects

W Gan

Publications and source records attributed to W Gan.

13 recordsLinked to original sources
PubMed2003

Apolipoprotein E isoform-specific regulation of dendritic spine morphology in apolipoprotein E transgenic mice and Alzheimer's disease patients.

Dendritic spines are postsynaptic sites of excitatory input in the mammalian nervous system. Apolipoprotein (apo) E participates in the transport of plasma lipids and in the redistribution of lipids among cells. A role for apoE is implicated in regeneration of synaptic circuitry after neural injury. The apoE4 allele is a major risk factor for late-onset familial and sporadic Alzheimer's disease (AD) and is associated with a poor outcome after brain injury. ApoE isoforms are suggested to have differential effects on neuronal repair mechanisms. In vitro studies have demonstrated the neurotrophic properties of apoE3 on neurite outgrowth. We have investigated the influence of apoE genotype on neuronal cell dendritic spine density in mice and in human postmortem tissue. In order to compare the morphology of neurons developing under different apoE conditions, gene gun labeling studies of dendritic spines of dentate gyrus (DG) granule cells of the hippocampus were carried out in wild-type (WT), human apoE3, human apoE4 expressing transgenic mice and apoE knockout (KO) mice; the same dendritic spine parameters were also assessed in human postmortem DG from individuals with and without the apoE4 gene. Quantitative analysis of dendritic spine length, morphology, and number was carried out on these mice at 3 weeks, 1 and 2 years of age. Human apoE3 and WT mice had a higher density of dendritic spines than human E4 and apoE KO mice in the 1 and 2 year age groups (P<0.0001), while at 3 weeks there were no differences between the groups. These age dependent differences in the effects of apoE isoforms on neuronal integrity may relate to the increased risk of dementia in aged individuals with the apoE4 allele. Significantly in human brain, apoE4 dose correlated inversely with dendritic spine density of DG neurons cell in the hippocampus of both AD (P=0.0008) and aged normal controls (P=0.0015). Our findings provide one potential explanation for the increased cognitive decline seen in aged and AD patients expressing apoE4.

Aged↗
PubMed2001

The sequence of the human genome.

A 2.91-billion base pair (bp) consensus sequence of the euchromatic portion of the human genome was generated by the whole-genome shotgun sequencing method. The 14.8-billion bp DNA sequence was generated over 9 months from 27,271,853 high-quality sequence reads (5.11-fold coverage of the genome) from both ends of plasmid clones made from the DNA of five individuals. Two assembly strategies-a whole-genome assembly and a regional chromosome assembly-were used, each combining sequence data from Celera and the publicly funded genome effort. The public data were shredded into 550-bp segments to create a 2.9-fold coverage of those genome regions that had been sequenced, without including biases inherent in the cloning and assembly procedure used by the publicly funded group. This brought the effective coverage in the assemblies to eightfold, reducing the number and size of gaps in the final assembly over what would be obtained with 5.11-fold coverage. The two assembly strategies yielded very similar results that largely agree with independent mapping data. The assemblies effectively cover the euchromatic regions of the human chromosomes. More than 90% of the genome is in scaffold assemblies of 100,000 bp or more, and 25% of the genome is in scaffolds of 10 million bp or larger. Analysis of the genome sequence revealed 26,588 protein-encoding transcripts for which there was strong corroborating evidence and an additional approximately 12,000 computationally derived genes with mouse matches or other weak supporting evidence. Although gene-dense clusters are obvious, almost half the genes are dispersed in low G+C sequence separated by large tracts of apparently noncoding sequence. Only 1.1% of the genome is spanned by exons, whereas 24% is in introns, with 75% of the genome being intergenic DNA. Duplications of segmental blocks, ranging in size up to chromosomal lengths, are abundant throughout the genome and reveal a complex evolutionary history. Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems. DNA sequence comparisons between the consensus sequence and publicly funded genome data provided locations of 2.1 million single-nucleotide polymorphisms (SNPs). A random pair of human haploid genomes differed at a rate of 1 bp per 1250 on average, but there was marked heterogeneity in the level of polymorphism across the genome. Less than 1% of all SNPs resulted in variation in proteins, but the task of determining which SNPs have functional consequences remains an open challenge.

Algorithms↗
PubMed2001

[Evaluation on the effect of cardiovascular prevention program in Fangshan, Beijing].

OBJECTIVE: To evaluate the effect of cardiovascular prevention program in Fangshan, Beijing (BFCP) from 1991-1999. METHODS: BFCP was a comprehensive community trial covering 120,000 residents in five communities, including three as intervention communities (IC), and two as control communities (CC), in Fangshan, suburb of Beijing. The program was implemented under both population and high risk individual strategies, focusing on health education and hypertension control. The main intervention measures were as follows: (1) network setup; (2) health education and promotion; (3) health professional training; (4) detection and management of hypertensive patients. RESULTS: Baseline, midterm and final cross-sectional surveys were conducted in the year 1991, 1995 and 1999, respectively. After 9-year intervention, improvement was found in population of IC versus CC (P < 0.01 or P < 0.05) for knowledge, attitude and behavior of CVD prevention, awareness on hypertension, treatment and control rates, as well as the quantity of dietary intake of protein, potassium and calcium. Risk factors such as systolic blood pressure, diastolic blood pressure, rates of smoking and alcohol drinking declined in the population in IC versus CC (P < 0.01). The average morbidity and mortality of stroke were 18.7% (u = 2.81, P < 0.01) and 17.7% (u = 2.91, P < 0.01), significantly lower in the IC versus CC. No significant difference was identified on the morbidity and mortality of coronary heart diseases between IC and CC. CONCLUSION: The comprehensive community prevention approach was feasible and effective in the prevention and control of cardiovascular diseases in rural populations in China.

Adult↗
PubMed2001

[An epidemiological study on pesticide poisoning with mixed preparation].

OBJECTIVE: To investigate the incidence of pesticide poisoning with mixed preparation and risk factors contributing to it. METHODS: Twenty-five administrative villages were studied in three townships of Jiangsu and Shandong Provinces with cluster sampling. The sampled villages were divided into study group (12 villages) and control group (13 villages) with approximately equal number of people each. Pesticide sprayers in the study group applied mixed preparation containing organophosphorous and dimethrin and those in the control group applied single organophosphorous preparation. All the sprayers in sampled villages were interviewed with a same questionnaire about their situation of pesticide spraying during the observation period. Cases of pesticide poisoning were ascertained by seniors physicians in occupational diseases after group discussion. RESULTS: Incidence of pesticide poisoning was higher in 2 179 sprayers of the study group (10.10 %) than that in 2 615 of the control group (2.29%), with a highly statistically difference (chi(2) = 12.46, P < 0.01) and an risk ratio (RR) of 4.45 (95% CI = 1.94 approximately 10.05) adjusted for other risk factors by logistic regression. Other risk factors for pesticide poisoning with mixed preparation were smoking or taking food during spraying, leaking or breakdown of sprayers, without washing their whole body as soon as possible after spraying, poor personal protection, spraying for a long time, spraying by women and spraying pesticide on cotton. CONCLUSIONS: If toxicity of mixed preparation of single pesticide showed a synergistic or additional effect, risk of poisoning by spraying mixed preparation increased. Health education and technical training should be strengthened for pesticide sprayers.

Adult↗
PubMed2000

The human gene for gammaS-crystallin: alternative transcripts and expressed sequences from the first intron.

PURPOSE: gammaS-crystallins are major components of adult vertebrate lenses. Here we examine the population of gammaS transcripts in adult human lens and the structure of the human CRYGS genes. METHODS: Adult lens human transcripts were obtained from NEIBANK, an Expressed Sequence Tag (EST) analysis of human eye tissues. The human CRYGS gene was isolated as a PAC clone and sequenced by direct and PCR-based methods. RESULTS: As judged by EST frequency, gammaS is one of the most abundant transcripts in the adult human lens, ranking just behind betaB2-, alphaB- and alphaA-crystallins. EST analysis reveals two transcript sizes resulting from alternative AATAAA and ATTAAA polyadenylation signals. In addition, one cDNA clone was found to contain a novel insert sequence that disrupted the open reading frame. Gene sequencing confirmed that this insert comes from intron 1 and is part of a sequence corresponding to a cluster of unidentified human transcripts in dbEST. Human and mouse gammaS gene proximal promoter sequences were compared and showed a high degree of evolutionary conservation, including consensus binding sites for transcription factors of the maf and SOX families. CONCLUSIONS: The human CRYGS gene can give rise to at least two transcripts through alternative polyadenylation. A minor transcript results from alternative splicing into sequences in intron 1. These sequences form part of a transcription unit (Mys) expressed in several non-lens tissues. The identity and function Mys of is not yet known, however, the cryptic splicing of CRYGS could produce a defective protein product, with potentially deleterious results for the adult human lens.

Adult↗
PubMed2000

Cloning, modeling, and chromosomal localization for a small leucine-rich repeat proteoglycan (SLRP) family member expressed in human eye.

PURPOSE: To examine a highly abundant novel transcript from human iris. METHODS: Expressed sequence tag (EST) analysis of an adult human iris cDNA library revealed an abundant (>0.7%) transcript for a novel member of the small leucine-rich proteoglycan (SLRP) family. Other 3' ESTs from retina were also detected in dbEST. The structure of the leucine-rich repeat (LRR) domain was investigated by molecular modeling. Antisera were raised against a specific peptide and used in western blots of human and rat eye tissues. RESULTS: From its prevalence in the eye and its superfamily relationships, this SLRP protein has been given the names oculoglycan or opticin (Optc). Sequence analysis suggests that Optc has a signal peptide and two structural domains, the larger of which is the LRR domain. Modeling of the LRR domain reveals structural variability in the repeat motifs, forming potential interaction sites for binding partners. Antiserum to a specific peptide detected a protein of approximately 48 kDa, in human iris, ciliary body and retina while the major protein detected in rat ocular tissues was 37 kDa in size. This may reflect a species difference in post-translational modification. Radiation hybrid mapping shows that the gene for OPTC is located on chromosome 1q31, close to the inherited eye diseases ARMD1 and AXPC1. CONCLUSIONS: Optc is a newly identified SLRP family member, which appears to have eye-preferred expression. Molecular modeling reveals local deviations from the familiar LRR structure, which are candidates for specific interaction sites. Western blotting with a specific peptide antibody detects Optc in iris, ciliary body and retina in the human eye and suggests that the protein is post-translationally modified. In rat, the antibody detects Optc in several eye tissues and in brain but the protein appears to have undergone much less modification, suggesting that this is not essential for all aspects of function. Considering its eye-preferred expression, the OPTC gene has the potential for involvement in inherited eye disease. Indeed, it maps close to at least two disease loci for which no gene has so far been identified.

Adolescent↗
PubMed1999

Protein synthesis initiation factor 4G.

eIF4G is a member of the class of translational initiation factors involved in mRNA recruitment to the 43S initiation complex. The proteins from yeast to mammals are present in multiple isoforms of 82-176 kDa. Mammalian eIF4G-1 is synthesized by internal initiation of translation and is specifically degraded by viral and host proteases activated by stress conditions. The role of eIF4G in protein synthesis is inferred from the presence of binding sites for other initiation factors that serve to co-localize the 5'- and 3'-termini of mRNA with RNA-helicase activity and the 40S ribosomal subunit. Growth-regulated mRNAs are preferentially translated under conditions of accentuated eIF4E-eIF4G interaction. Proteolysis of eIF4G or expression of competitor proteins interferes with its binding to either the 5'- or 3'-termini, changing the spectrum of mRNAs translated. Elevated eIF4G levels correlate with malignant cell transformation and diminished eIF4G levels, with nutritional deprivation and anoxia.

Animals↗
PubMed1999

[Analysis of chiral compounds by micelle electrokinetic capillary chromatography].

An overview on applications of micelle electrokinetic capillary chromatography (MECC) in chiral compounds analysis is presented. Ionic chiral surfactants such as bile salts, long-alkyl-chain surfactants and high-molecular-weight surfactants, which can migrate with electroosmosis and its electrophoretic mobility, and interact with the solutes, are employed as chiral selectors. Addition of electrically neutral chiral selectors such as cyclodextrins is also successful in MECC separation. Theory of MECC enantiomer separation is briefly described.

Bile Acids and Salts↗
PubMed1999

[Determination of cadmium in soil slurry samples by GFAAS using ammonium oxalate as disperstant].

A method for the determination of trace cadmium in soil slurry samples by GFAAS was optimized. The factors that influence the performances of cadmium at different chemical modifier were investigated. The effect of background has also been studied. It is found that the slurry of soil samples was most stable with ammonium oxalate as disperstant. The results show that the determination of trace cadmium in soil slurry samples could performed.

Cadmium↗
PubMed1998

Functional characterization of the internal ribosome entry site of eIF4G mRNA.

The eIF4 group initiation factors are required for cap-dependent translation initiation. Infection of mammalian cells by picornaviruses results in proteolytic cleavage of one of these factors, eIF4G, which severely restricts cap-dependent initiation but permits cap-independent initiation to proceed from an internal ribosome entry site (IRES) in picornaviral RNAs. The first 357 nucleotides (nt) of the 5'-untranslated region of eIF4G mRNA also contains an IRES. Using bicistronic constructs for expression in K562 cells, we have now shown that progressive deletions of the 5'-untranslated region can have either stimulatory or inhibitory effects. Furthermore, a 101-nt segment exhibits full IRES activity, and an 81-nt segment exhibits detectable IRES activity. A polypyrimidine tract (PPT) at the 3' terminus is essential for internal initiation, a property which is characteristic of picornaviral IRESs but not the other host cellular IRESs studied to date. IRES activity does not require sequences beyond 357 nt. Out-of-frame AUGs have no effect on IRES-driven luciferase expression when introduced upstream of the PPT but markedly decrease expression when introduced at sites between the PPT and the authentic initiation codon at nt 369. These results suggest that the ribosomal subunit enters at or near the PPT and then scans downstream for the initiation codon.

Codon, Initiator↗
PubMed1996

Internal initiation of translation directed by the 5'-untranslated region of the mRNA for eIF4G, a factor involved in the picornavirus-induced switch from cap-dependent to internal initiation.

The eIF4 group initiation factors carry out recognition of the mRNA cap, unwinding of mRNA secondary structure, and binding of mRNA to the 43 S preinitiation complex. Infection by picornaviruses results in proteolytic cleavage of one of these factors, eIF4G, an event that severely restricts cap-dependent translation but permits cap-independent initiation to proceed from internal ribosome entry sequences in picornaviral RNAs. The 5'-untranslated region (5'-UTR) of eIF4G mRNA resembles such picornaviral sequences in being unusually long and containing multiple open reading frames and a polypyrimidine tract. When inserted upstream of a luciferase reporter gene, this 5'-UTR served as a translational enhancer in four different cell lines. Mutation of all four upstream ATG codons to AAG did not alter the translational enhancement. The presence of the eIF4G 5'-UTR between an RNA hairpin and the luciferase cistron stimulated expression 119-fold. Similarly, the presence of the 5'-UTR between the two cistrons of a bicistronic mRNA stimulated expression of the downstream cistron 42-fold. These results indicate that the eIF4G 5'-UTR directs internal initiation. The ability to continue synthesis of eIF4G when the cell is unable to carry out normal cap-dependent translation may represent an autoregulatory mechanism or be part of the cellular response to stresses that interrupt cap-dependent translation.

Base Sequence↗