Biomedical subjects

M Xiong

Publications and source records attributed to M Xiong.

At least 19 recordsLinked to original sources

PubMed2001

Recursive partitioning for tumor classification with gene expression microarray data.

Precise classification of tumors is critically important for cancer diagnosis and treatment. It is also a scientifically challenging task. Recently, efforts have been made to use gene expression profiles to improve the precision of classification, with limited success. Using a published data set for purposes of comparison, we introduce a methodology based on classification trees and demonstrate that it is significantly more accurate for discriminating among distinct colon cancer tissues than other statistical approaches used heretofore. In addition, competing classification trees are displayed, which suggest that different genes may coregulate colon cancers.

Gene Expression Profiling↗

PubMed2001

The effect that genotyping errors have on the robustness of common linkage-disequilibrium measures.

The rapid development of a dense single-nucleotide-polymorphism marker map has stimulated numerous studies attempting to characterize the magnitude and distribution of background linkage disequilibrium (LD) within and between human populations. Although genotyping errors are an inherent problem in all LD studies, there have been few systematic investigations documenting their consequences on estimates of background LD. Therefore, we derived simple deterministic formulas to investigate the effect that genotyping errors have on four commonly used LD measures-D', r, Q, and d-in studies of background LD. We have found that genotyping error rates as small as 3% can have serious affects on these LD measures, depending on the allele frequencies and the assumed error model. Furthermore, we compared the robustness of D', r, Q, and d, in the presence of genotyping errors. In general, Q and d are more robust than D' and r, although exceptions do exist. Finally, through stochastic simulations, we illustrate how genotyping errors can lead to erroneous inferences when measures of LD between two samples are compared.

Chromosome Mapping↗

PubMed2001

Gene expression profile changes in initiation and progression of squamous cell carcinoma of esophagus.

Tumorigenesis is a complex process involving multiple genes. As a step toward understanding the complicated changes between normal and malignant cells, this report focused on gene expression profile variations among normal and abnormal esophageal epithelium tissues. The cDNA microarray approach was used to investigate gene expression profiles of 5 different stages during initiation and progression of esophageal cancer. According to pathological characteristics, these 5 stages were normal, dysplasia I (mild dysplasia), dysplasia II (moderate dysplasia), carcinoma in situ (CIS) and squamous cell carcinoma of esophagus (SCC). Comparing and analyzing those gene expression profiles, we observed that the expression levels of many genes changed in dysplasia I and some known tumor-related genes were over-expressed or under-expressed in all 4 abnormal stages. Using principle component analysis we identified a set of genes that may play an important role in tumor development. Hybridization data were confirmed by semi-quantitative reverse transcription-polymerase chain reaction and immunohistochemistry. These results suggest that cDNA microarray technology is a useful tool to discover genes frequently involved in esophageal neoplasia and provides novel clues to diagnosis, early detection and intervention of SCC.

Carcinoma in Situ↗

PubMed2001

Feature (gene) selection in gene expression-based tumor classification.

There is increasing interest in changing the emphasis of tumor classification from morphologic to molecular. Gene expression profiles may offer more information than morphology and provide an alternative to morphology-based tumor classification systems. Gene selection involves a search for gene subsets that are able to discriminate tumor tissue from normal tissue, and may have either clear biological interpretation or some implication in the molecular mechanism of the tumorigenesis. Gene selection is a fundamental issue in gene expression-based tumor classification. In the formation of a discriminant rule, the number of genes is large relative to the number of tissue samples. Too many genes can harm the performance of the tumor classification system and increase the cost as well. In this report, we discuss criteria and illustrate techniques for reducing the number of genes and selecting an optimal (or near optimal) subset of genes from an initial set of genes for tumor classification. The practical advantages of gene selection over other methods of reducing the dimensionality (e.g., principal components), include its simplicity, future cost savings, and higher likelihood of being adopted in a clinical setting. We analyze the expression profiles of 2000 genes in 22 normal and 40 colon tumor tissues, 5776 sequences in 14 human mammary epithelial cells and 13 breast tumors, and 6817 genes in 47 acute lymphoblastic leukemia and 25 acute myeloid leukemia samples. Through these three examples, we show that using 2 or 3 genes can achieve more than 90% accuracy of classification. This result implies that after initial investigation of tumor classification using microarrays, a small number of selected genes may be used as biomarkers for tumor classification, or may have some relevance in tumor development and serve as a potential drug target. In this report we also show that stepwise Fisher's linear discriminant function is a practicable method for gene expression-based tumor classification.

Humans↗

PubMed2001

Interaction between the melanocortin-1 receptor and P genes contributes to inter-individual variation in skin pigmentation phenotypes in a Tibetan population.

The melanocortin-1 receptor (MC1R) and P gene product are two important components of the human pigmentary system that have been shown to be associated with red hair/fair skin and cause type II oculocutaneous albinism, respectively. However, their contribution to inter-individual variation at the population level is not well defined. To this end, we genotyped 3 single nucleotide polymorphisms (SNPs) in the MC1R gene (Arg67Gln, Gln163Arg, Val92Met) and 2 SNPs in the P gene (IVS 13-15 and Gly780Gly) in 184 randomly ascertained Tibetan subjects, whose skin color was measured as a quantitative trait by reflective spectroscopy. Single locus analyses failed to demonstrate an association between any of the 5 SNPs and skin pigmentation. However, when an epistatic model was applied to the data, a significant gene-gene interaction was identified between Val92Met in MCIR and IVS13-15 in the P gene (F=2.43; P=0.0105). We also discuss the possible mechanisms of how gene interactions arise in signal transduction pathways.

Adolescent↗

PubMed2001

A polymorphism in the promoter region of catalase is associated with blood pressure levels.

Catalase is an important antioxidant enzyme that detoxifies H2O2 into oxygen and water and thus limits the deleterious effects of reactive oxygen species (ROS). Because chronic exposure to excess ROS may contribute to vascular damage, we investigated whether genetic variation in catalase was associated with susceptibility to essential hypertension (EHYT) in 324 individuals (at least 50 years old) who were randomly sampled from an isolated population living in Xiangchang, China. They were screened for genetic variation in the promoter of catalase by direct sequencing. In total, four single nucleotide polymorphisms (SNPs) were identified. The association between the SNPs and EHYT was investigated by a linear regression model under phenotypic selection; in our analyses, we used both SBP>150 mmHg and SBP>160 mmHg as thresholds. A SNP 844 bp upstream of the start codon (SNP-844) demonstrated strong evidence of association with EHYT (SBP>150 mmHg: F=5.09, P=0.008; SBP>160 mmHg: F=7.13, P=0.002). This is the first study to implicate genetic variation in catalase in susceptibility to EHYT and suggests that polymorphisms in promoter regions may be particularly relevant to the study of complex diseases.

Aged↗

PubMed2001

Haplotypes vs single marker linkage disequilibrium tests: what do we gain?

The genetic dissection of complex diseases represents a formidable challenge for modern human genetics. Recently, it has been suggested that linkage disequilibrium (LD) based methods will be a powerful approach for delineating complex disease genes. Most proposed LD test statistics search for association between a single marker and a putative trait locus. However, the power of a single marker association test may suffer because LD information contained in flanking markers is ignored. Intuitively, haplotypes (which can be regarded as a collection of ordered markers) may be more powerful than individual, unorganised markers. In this study, we derive the analytical tools based on standard chi-square statistics to directly investigate and compare the power between multilocus haplotypes and single marker LD tests. More specifically, novel formulas are obtained in order to calculate expected haplotype frequencies of unlimited size. This study demonstrates that the use of haplotypes can significantly improve the power and robustness of mapping disease genes. Additionally, we detail how the power of haplotype based association tests are affected by important population genetic parameters such as the genetic distance between markers and disease locus, mode of disease inheritance, age of trait causing mutation, frequency of associated marker allele, and level of initial LD. Finally, published data from the Hereditary Hemochromatosis disease region is used to illustrate the utility of haplotypes.

Genetic Diseases, Inborn↗

PubMed2001

Lymphoepithelioma-like carcinoma of the lung with a better prognosis. A clinicopathologic study of 32 cases.

The purpose of our study was to clarify the prognosis of lymphoepithelioma-like carcinoma (LELC) of the lung, which is rare. We analyzed the clinicopathologic features of 32 cases of pulmonary LELC and compared the cases with 84 cases of pulmonary non-LELC with available long-term follow-up information. The results show that LELC of the lung as a distinct entity has a better prognosis than non-LELC. We found a significant difference in the survival rates between patients with LELC and patients with non-LELC in stage II and stages III and IV, respectively. Tumor recurrence and necrosis (5% or more of tumor) are associated with a poor prognosis. It seems that the histologic typing (Regaud type and Schmincke type) of pulmonary LELC is of no clinical value.

Adult↗

PubMed2001

Skin reflectance in the Han Chinese and Tibetan populations.

Genetic and environmental factors are involved in the determination of skin pigmentation in humans. With the recent development of statistical and genetic tools in mapping complex traits in humans, it is becoming feasible to utilize such methods in identifying genes involved in skin pigmentation. Furthermore, the use of new portable reflectance spectroscopy instruments such as the Photovolt ColorWalk colorimeter allows researchers to measure skin reflectance of a large number of subjects with ease and accuracy. We used a new portable instrument (Photovolt ColorWalk) to study the skin reflectance of 372 Han Chinese and 274 Tibetan individuals to establish background reflectance measurements of unexposed skin of the inner upper arm in these two populations. In addition, we explored the effect of various factors such as age and gender on skin reflectance.

Adolescent↗

PubMed2001

[Reconstruction of tissue engineered vascular model in vitro].

OBJECTIVE: To explore the feasibility of reconstructing tissue engineered vessel in vitro. METHODS: Bovine endothelial cells were isolated from calf thoracic aorta by enzyme digestion methods and subcultured and purified. The endothelial cells of the 3rd to 7th passages were seeded into the inner surface of tubular scaffold material by polyglycolic acid(PGA) coated with cross-linked collagen, and cultured in vitro for 10 days using dynamic rotation culture technique. Scanning electron microscopy was used to analyse the morphological characteristics, and prostacyclin released by endothelial cells was measured by radioimmunoassay of 6-keto-prostaglandin F1 alpha. RESULTS: The VIII factor staining of cultured endothelial cells was positive. The endothelial cells adhered well on the inner surface of tubular scaffold material with confluent monolayer covering(91.2 +/- 1.5)%. The endothelialized model released prostacyclin at a rate of (4.6 +/- 0.5) micrograms/cm2.min. There was significant difference to control group (P < 0.05). CONCLUSION: The PGA coating with collagen is an ideal scaffold for endothelial cells, the coverage rate is increased through dynamic rotation culture technique. It will lay a good foundation for architecture of a laminated structure of tissue engineered vessel.

Animals↗

PubMed2001

[Expression of endogenic bone morphogenetic protein in repairing rabbit skull with tissue engineering technique].

OBJECTIVE: To explore the distribution and effect of endogenic bone morphogenetic protein (BMP) in repairing rabbit skull with tissue engineered bone. METHODS: The autologous osteoblast-like cells were instantly implanted onto polyglycolic acid (PGA) matrix coated with collagen. The rabbit skull defect models were established by resection of bilateral 1.5 cm x 1.0 cm full-thickness parietal bone in 18 New Zealand rabbits, which were randomly divided into two groups. In one group, the composite of osteoblast- like cells and PGA matrix were grafted into the defect on one side of the skull as experimental group I, leaving the same defect area on the other side as control group without any graft implanted. In the other group, simply PGA was done in the same way as experimental group II. The tissue samples were harvested at 3, 8 and 14 days postoperatively and examined by histological and immunohistochemistry methods. The concentrations of BMP in different regions of the samples were measured using computer image analysis system. RESULTS: After 3 days of operation, the BMP positive cells were found in the matrix of experimental group I. At 8 days postoperatively, the formation of new bone on experimental group I was prior to that of experimental group II and control group. On the 14th day, bone trabecula was formed on the experimental group I, but there was only fibrous tissue on control group. The concentration of BMP on the experimental group I and II were higher than that of corresponding region on control side. CONCLUSION: The osteoblast-like cells instantly implanted onto PGA matrix can synthesize and secrete BMP. It may be one of the reasons of tissue engineered bone inducing new bone regeneration that localizing endogenic BMP in bone defect area, increasing the concentration of endogenic BMP and improving its distribution by tissue engineering technique.

Animals↗

PubMed2000

Combined linkage and linkage disequilibrium mapping for genome screens.

Linkage analysis and association studies, two major approaches for genetic studies of human diseases, are useful for mapping genes that are highly penetrant, but both use only part of the information that is available for mapping disease genes. Therefore, they provide limited utility when used alone. In this report, we present combined linkage and linkage disequilibrium mapping that simultaneously utilizes linkage and linkage disequilibrium information for mapping human disease genes. Compared with the existing linkage analysis and association study methods, this method has several advantages: 1) it has high statistical power by a joint analysis of linkage and linkage disequilibrium for localizing disease susceptibility loci: 2) it unifies the theory of linkage analysis and linkage disequilibrium mapping, 3) it retains the general framework for linkage analysis and, hence, can be easily incorporated into the existing software for the linkage analysis. The proposed LLDM is applied to familial hemophagocytic lymphohistiocytosis (FHL) disease.

Chromosome Mapping↗

PubMed2000

Effect of c-myc antisense oligodeoxynucleotides on hypoxia-induced proliferation of pulmonary vascular pericytes.

To study the effect of c-myc antisense oligodeoxynucleotides (ODNs) on proliferation of pulmonary vascular pericytes (PC) induced by hypoxia, cell culture, dot hybridization using probe of digoxigenin-11-dUTP-labeled cDNA, 3H-thymidine incorporation, immunocytochemical technique and image analysis methods were used to observe the effect of c-myc antisense ODNs on expression of c-myc gene and proliferating cell nuclear antigen (PCNA), and 3H-thymidine incorporation of PC induced by hypoxia. The results showed that hypoxia could significantly enhance the expression of c-myc and PCNA (P < 0.01), and elevate 3H-thymidine incorporation of PC (P < 0.01), but antisense ODNs could significantly inhibit the expression of c-myc and PCNA (P < 0.05), and 3H-thymidine incorporation of PC (P < 0.01). It was suggested that hypoxia could promote the proliferation of PC by up-regulating the expression of c-myc gene, but c-myc antisense ODNs could inhibit hypoxia-induced proliferation of PC by downregulating the expression of c-myc gene.

Animals↗

PubMed2000

The haplotype linkage disequilibrium test for genome-wide screens: its power and study design.

The focus of human genetics continues to shift toward the dissection of complex phenotypes. Integral to these endeavors is the development of powerful analytical tools. To this end, we propose a novel method designated the haplotype linkage disequibrium (LD) test for identifying diseases genes. The basic structure of the haplotype test statistic is a chi-square in which haplotypes, as opposed to individual marker data, are compared between cases and controls. Specifically, we performed power calculations and demonstrate that the use of haplotypes improves the power of mapping disease genes. We show that this approach can be used for initial genome-wide screens in mapping disease genes. Furthermore, we investigated the factors influencing statistical power of the method and discussed basic principals underlying study design. Published data from the Hereditary Hemochromatosis region was used to illustrate the utility of the haplotype test. Also discussed is its relationship with linkage disequibrium.

Alleles↗

PubMed2000

Association of Epstein-Barr virus with lymphoepithelioma-like carcinoma of the lung in southern China.

Having reviewed the data on 3,663 consecutive cases of primary lung carcinoma in southern China, we found that 32 cases could meet the criteria for lymphoepithelioma-like carcinoma (LELC) of the lung. To study the relationship between pulmonary LELC and Epstein-Barr virus (EBV) infection, we used in situ hybridization and immunohistochemistry techniques to detect the EBV-encoded small nonpolyadenylated RNA (EBER), latent membrane protein 1 (LMP1), and viral capsid antigen (VCA) in 32 cases of LELC and 19 cases of non-LELC lung carcinoma. Of the 32 cases, 30 (94%) showed EBER positivity. Of the 30 EBER-positive pulmonary LELC cases, 16 and 7 expressed LMP1 and VCA, respectively. In contrast with LELC, none of the 19 cases of non-LELC lung carcinoma showed EBER-, LMP1-, or VCA-positive signals in carcinoma cells. The results demonstrate that there is a close relationship between EBV infection and pulmonary LELC. EBV infection may have an essential role in the tumorigenesis of pulmonary LELC. EBV latent infection is the main status in pulmonary LELC except for individual EBV entering into a lytic cycle.

Adult↗

PubMed2000

Computational methods for gene expression-based tumor classification.

Gene expression profiles may offer more or additional information than classic morphologic- and histologic-based tumor classification systems. Because the number of tissue samples examined is usually much smaller than the number of genes examined, efficient data reduction and analysis methods are critical. In this report, we propose a principal component and discriminant analysis method of tumor classification using gene expression profile data. Expression of 2000 genes in 40 tumor and 22 normal colon tissue samples is used to examine the feasibility of gene expression-based tumor classification systems. Using this method, the percentage of correctly classified normal and tumor tissue was 87.0%. The combined approach using principal components and discriminant analysis provided superior sensitivity and specificity compared to an approach using simple differences in the expression levels of individual genes.

Analysis of Variance↗

PubMed1999

Comparison of the power and accuracy of biallelic and microsatellite markers in population-based gene-mapping methods.

Because of their great abundance and amenability to fully automated genotyping, single-nucleotide polymorphisms (SNPs) and simple insertion/deletion are emerging as a new generation of markers for positional cloning. Although the efficiency and cost associated with the markers are important in the mapping of human disease genes, the power to detect the linkage between the marker and the disease locus, as well as the accuracy of the estimation of the map location of the disease gene, dictate the selection of the markers. Both the power and the accuracy depend not only on the type of the markers but also on other factors, such as the age of the disease mutation, the magnitude of the genetic effect, the marker-allele distribution in the population, mutation rates of marker loci, the frequency of the disease allele, the recombination fraction, and the methods for mapping the human disease genes. In this article, we develop a mathematical framework and the analytical formulas for calculation of the power and the accuracy and investigate the impact that the aforementioned factors have on the power and the accuracy, by using two population-based gene-mapping methods-likelihood-based linkage-disequilibrium mapping and the transmission/disequilibrium test, for both biallelic SNPs and microsatellites. These studies provide not only guidance in selection of the markers and in the design of the sample scheme for positional cloning but also insight into the biological bases of the mapping of human disease genes.

Alleles↗

PubMed1999

Y-Chromosome evidence for a northward migration of modern humans into Eastern Asia during the last Ice Age.

The timing and nature of the arrival and the subsequent expansion of modern humans into eastern Asia remains controversial. Using Y-chromosome biallelic markers, we investigated the ancient human-migration patterns in eastern Asia. Our data indicate that southern populations in eastern Asia are much more polymorphic than northern populations, which have only a subset of the southern haplotypes. This pattern indicates that the first settlement of modern humans in eastern Asia occurred in mainland Southeast Asia during the last Ice Age, coinciding with the absence of human fossils in eastern Asia, 50,000-100,000 years ago. After the initial peopling, a great northward migration extended into northern China and Siberia.

Africa↗