Biomedical subjects

M Xiong

Publications and source records attributed to M Xiong.

At least 19 recordsLinked to original sources

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

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↗

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↗

PubMed1999

Factors limiting adenovirus-mediated gene transfer into human lung and pancreatic cancer cell lines.

Adenoviral vectors are a widely used means of gene transfer. However, transgene expression after adenoviral administration varies among different carcinoma cell lines. We hypothesized that this variation is attributable, in part, to the presence of cell surface molecules involved in adenoviral infection. To test this, we first assessed adenovirus-mediated transgene expression in four human lung carcinoma cell lines and four human pancreatic carcinoma cell lines in terms of luciferase activities and found it to vary from 4.8 x 10(4) to 6.1 x 10(7) relative light units/microg of protein. Then, to determine whether the molecules involved in the entry of adenovirus into host cells were responsible for this variation, we evaluated the expression of alpha(v)beta5, alpha(v), beta3, alpha5, and beta1 integrins and that of coxsackievirus and adenovirus receptor (CAR) in these cell lines. Statistical analysis revealed that the levels of beta3 were associated with the levels of transgene expression. Blocking analysis showed that adenovirus-mediated gene transfer could be blocked by antibodies against these six molecules but not by the antibodies against alpha2 or alpha3 integrins, thus suggesting that the integrins alphavbeta5, alpha(v), beta3, alpha5, and beta1 and CAR molecules could limit adenovirus-mediated gene transfer when their levels fell below a certain threshold. Furthermore, cells expressing low levels of beta3 and resistant to conventional adenoviral vectors were susceptible to a vector containing the heparin-binding domain in its fiber, thus suggesting that redirecting vectors to receptors other than CAR may bypass the integrin pathway. These findings may have implications for improving the efficiency of adenovirus-mediated gene transfer and developing novel adenoviral vectors.

Adenoviruses, Human↗

PubMed1999

Evaluation of recombinant chitinase antigen in serological diagnosis and surveillance of lymphatic filariasis.

Apply recombinant chitinase fusion protein antigen, enzyme-linked immunosorbent assays examined anti-filarial antibodies and evaluated of useful value in serological diagnosis and surveillance of lymphatic filariasis. The test jirds were immunized and infected by chitinase and B. malayi third stage larvae respectively. Functional protein molecular of chitinase was analyzed by SDS-PAGE, Western blot. The result shown that jirds from microfilaremia (mf) and donors with Mf were directly to react with chitinase antigen that positive rate was 100%, but Mf-xt antigen was only 80%. Normal jirds and persons sera from unepidemic control donors all were negative. False positives of 5% and 20% reacted with chitinase and Mf-xt antigens respectively. The results indicate that recombinant chitinase antigen is suitable for detection of active occult or patent lymphatic filariasis with daytime blood samples in residents of endemic areas, is easy to be performed and inexpensive.

Animals↗

PubMed1998

Production of vascular endothelial growth factor by murine macrophages: regulation by hypoxia, lactate, and the inducible nitric oxide synthase pathway.

Murine thioglycolate-induced peritoneal macrophages (MPMs) and the murine RAW264.7 macrophage-like cell line (RAW cells) constitutively produce vascular endothelial growth factor (VEGF). VEGF production is increased under hypoxic conditions or after cell activation with interferon-gamma (IFNgamma) and endotoxin (lipopolysaccharide, LPS). In contrast, tumor necrosis factor-alpha is produced only by IFNgamma/LPS-activated cells. Lactate (25 mmol/L) does not increase VEGF production by these cells. However, hypoxia, lactate, and IFNgamma/LPS-activated MPMs express angiogenic activity, whereas normoxic, nonactivated MPMs do not. Lack of angiogenic activity is not due to an antiangiogenic factor(s) in the medium of these cells. Angiogenic activity produced by hypoxia and lactate-treated MPMs is neutralized by anti-VEGF antibody, which also neutralizes most of the angiogenic activity produced by IFNgamma/LPS-activated MPMs. The inducible nitric oxide synthase inhibitors Ng-nitro-L-arginine-methyl ester (1.5 mmol/L) and aminoguanidine (1 mmol/L) block production of angiogenic activity by MPMs and RAW cells. In RAW cells, Ng-nitro-L-arginine-methyl ester and AG block IFNgamma/LPS-activated, but not constitutive, VEGF production, whereas in MPMs, neither constitutive nor IFNgamma/LPS-activated VEGF synthesis is affected. Synthesis of tumor necrosis factor-alpha is also unaffected. In contrast to normoxic, nonactivated MPMs, inducible nitric oxide synthase-inhibited, IFNgamma/LPS-activated MPMs produce an antiangiogenic factor(s). We conclude that VEGF is a major contributor to macrophage-derived angiogenic activity, and that activation by hypoxia, lactate, or IFNgamma/LPS switches macrophage-derived VEGF from a nonangiogenic to an angiogenic state. This switch may involve a posttranslational modification of VEGF, possibly by the process of ADP-ribosylation. ADP-ribosylation by MPM cytosolic extracts or by cholera toxin switches rVEGF165 from an angiogenic to a nonangiogenic state. In IFNgamma/LPS-activated MPMs, the inducible nitric oxide synthase-dependent pathway also regulates the expression of an antiangiogenic factor(s) that antagonizes the bioactivity of VEGF and provides an additional regulatory pathway controlling the angiogenic phenotype of macrophages.

Animals↗

PubMed1998

Linkage and association of adrenergic and dopamine receptor genes in the distal portion of the long arm of chromosome 5 with systolic blood pressure variation.

Elevated blood pressure is an important risk factor for renal-, cerebro- and cardiovascular diseases. We used an efficient discordant sib-pair ascertainment scheme to investigate the impact of the distal end of the long arm of human chromosome 5 (chromosomal region 5q31.1-qter) containing genes for the alpha1B and beta2 adrenergic receptors and the dopamine receptor type 1A on variation of systolic blood pressure in young Caucasians. We measured eight highly polymorphic markers spanning this positional candidate gene-rich region in 427 individuals from 55 three-generation pedigrees containing 69 discordant sibling pairs, and calculated multipoint identity by descent (MIBD) probabilities. The results of genetic linkage and association tests indicate that the region between markers D5S2093 and D5S462 is significantly linked to one or more polymorphic genes influencing interindividual variation in systolic blood pressure levels. Since the alpha1B adrenergic receptor and dopamine receptor type 1A genes are located close to these markers, these data suggest that genetic variation in one or both of these G protein-coupled receptors, which participate in the control of vascular tone, plays an important role in influencing interindividual variation in systolic blood pressure levels.

Adolescent↗

PubMed1998

[An experimental study of prevention of peridural adhesion following laminectomy].

In order to find an ideal biological material to prevent peridural adhesion following laminectomy, 30 rabbits were used as animal model, in each of which 2 defects with a size of 1 cm x 0.5 cm were made following laminectomy of L3, L5 spine. One of the defects was covered extradurally with chitosan, gelatin foam or PLA membrane respectively, while the other defect was exposed as control. All of these animals were sacrificed on the 2nd, 4th, 6th, 8th and 10th week after operation, and the extradural fibrosis and adhesion of every animal were evaluated by gross observation and histological examinations. It was revealed that in the chitosan and PLA membrane groups, the extradural tissue was smooth without thickening and there was no fibrous proliferation or adhesion in the epidural cavity, and that in the chitosan group, the growth of fibroblast was restrained but the growth of the epithelial cells was promoted significantly, thus, wound healing was rapid. In the control group and gelatin foam group, obvious extradural fibrosis and adhesion were observed and the extradural space had almost disappeared. Therefore, it was concluded that the biodegradable PLA membrane and chitosan were both an ideal material in the prevention of postoperative epidural adhesion.

Animals↗

PubMed1997

Fine-scale genetic mapping based on linkage disequilibrium: theory and applications.

Linkage-disequilibrium mapping (LDM) recently has been hailed as a powerful statistical method for fine-scale mapping of disease genes. After reviewing its historical background and methodological development, we present a general, mathematical, and conceptually coherent framework for LDM that incorporates multilocus and multiallelic markers and mutational processes at the marker and disease loci. With this framework, we address several issues relevant to fine-scale mapping and propose some efficient computational methods for LDM. We implement various LDM methods that incorporate population growth, recurrent mutation, and marker mutations, on the basis of a general framework. We demonstrate these methods by applying them to published data on cystic fibrosis, Huntington disease, Friedreich ataxia, and progressive myoclonus epilepsy. Since the genes responsible for these diseases all have been cloned, we can evaluate the performance of our methods and can compare ours with that of other methods. Using the proposed methods, we successfully and accurately predicted the locations of genes responsible for these diseases, on the basis of published data only.

Chromosome Mapping↗

PubMed1997

Fine-scale mapping of quantitative trait loci using historical recombinations.

With increasing popularity of QTL mapping in economically important animals and experimental species, the need for statistical methodology for fine-scale QTL mapping becomes increasingly urgent. The ability to disentangle several linked QTL depends on the number of recombination events. An obvious approach to increase the recombination events is to increase sample size, but this approach is often constrained by resources. Moreover, increasing the sample size beyond a certain point will not further reduce the length of confidence interval for QTL map locations. The alternative approach is to use historical recombinations. We use analytical methods to examine the properties of fine QTL mapping using historical recombinations that are accumulated through repeated intercrossing from an F2 population. We demonstrate that, using the historical recombinations, both simple and multiple regression models can reduce significantly the lengths of support intervals for estimated QTL map locations and the variances of estimated QTL map locations. We also demonstrate that, while the simple regression model using historical recombinations does not reduce the variances of the estimated additive and dominant effects, the multiple regression model does. We further determine the power and threshold values for both the simple and multiple regression models. In addition, we calculate the Kullback-Leibler distance and Fisher information for the simple regression model, in the hope to further understand the advantages and disadvantages of using historical recombinations relative to F2 data.

Algorithms↗

PubMed1997

The activity of the scs and scs' insulator elements is not dependent on chromosomal context.

Sequence elements that protect a reporter gene from chromosomal position effects or that block enhancer-activated transcription are called insulators. Using a plasmid-based microinjection assay with Xenopus laevis oocytes, we show that the heterologous Drosophila melanogaster scs and scs' insulator elements do not require chromosomal context to block enhancer-activated transcription. A single insulator element partially blocks enhancer-activated transcription, indicating that each element operates independently rather than as part of a pair. Deletion analysis of the 1.8-kb scs element identified a 220-bp fragment from one of the DNase I-hypersensitive regions that has full blocking activity in the oocyte assay. This fragment corresponds to the critical region of the scs mapped in previous studies with Drosophila. A time course of transcription shows that the scs blocks enhancer-activated transcription as early as transcription can be detected, about 30 min after injection. Complete assembly of the DNA template into nucleosomes requires 4 h. The scs and scs' sequences do not block site-specific recombination by FLP recombinase, implying that insulators do not operate by a general mechanism that physically sequesters the DNA. These data are most consistent with a model for insulator action in which direct interaction between the insulator and either the enhancer or promoter confers directionality to enhancer-activated transcription.

Animals↗

PubMed1997

[Association of epstein-barr virus with lymphoepithelioma-like carcinoma of the lung].

OBJECTIVE: To study the relationship between pulmonary lymphoepithelima-like carcinoma (LELC) and Epstein-Barr virus (EBV). METHODS: 30 cases of LELC and 19 cases of non LELC pulmonary pulmonary specimens were studied by in situ hybridization and immunohistochemistry techniques to detect EB virus small RNA (EBERs), latent menbrane protein-1 (LMP-1) and virus capsid antigen (VCA). RESULTS: The detection rates for EBER, LMP-1 and VCA were 93.3% (28/30), 53.3% (16/30) and 23.3% (7/30) respectively. LMP-1 positive carcinoma cells were not found in the 19 non-LELC specimens, which were used as the controls. CONCLUSION: Pulmonary LELC is closely associated with latent EBV infection and may be an important factor involved in the development and progression of LELC. In addition, EBV lytic gene products may sometimes be found in a small portion of LELC cells.

Adult↗

PubMed1996

What do developmental mapping rules optimize?

Convergence ratios between pre- and postsynaptic cells in the visual system vary widely between cell classes, areas of the visual field, between individuals and between species. Proper stabilization of the convergence and divergence of single visual neurons is critical for visual integration generally, and for specific functions such as those of rod and cone pathways, or the center and peripheral regions of the visual field. In early development, retinal ganglion cells, target cells and all their processes are produced in excess and stabilize at certain mature values. The intent of the investigations described here is to determine what features of cell connectivity are stabilized over normal variability by these developmental processes and how such stabilization is accomplished, using the developing mammalian retinotectal system as an example. Orderly compression of the retinotopic map into a half tectum was induced by a partial tectal ablation at birth in hamsters, increasing the ratio of retinal ganglion cells to superior colliculus target cells. The convergence problem is solved in this case by undersampling the spatial array with respect to normal, preserving local spatial resolution, but potentially reducing sensitivity or introducing aliasing artifacts. Receptive field sizes of single neurons are indistinguishable from normal, and reduction of branching of presynaptic axon arbors is the mechanism of the remapping. Behaviorally, though the entire visual field is still represented in the remaining colliculus, the solution has a cost in decreased probability and increased latency to orient to visual stimuli, particularly in the peripheral visual field. The generality of this solution for retinal and other central convergence regulation problems is evaluated.

Animals↗

PubMed1996

Central implants of dilute estradiol enhance the satiety effect of CCK-8.

The following studies evaluated whether direct placement of estradiol into different brain areas could increase the satiating potency of CCK in female rats. In Experiment 1, estradiol implants in the PVN, but not in the VMN or third ventricle, significantly enhanced the satiety actions of CCK (5.0 micrograms/kg). In Experiment 2, a lower dose of CCK (0.5 micrograms/kg) suppressed food intake in females with estradiol implants in the PVN but not in animals with implants in the VMN or preoptic area. In both experiments, estradiol implants in the PVN significantly lowered food intake and body weight during the 2-day period of hormone treatment. Implants in other areas had no significant effects on feeding or body weight. These data support the hypothesis that the satiety effect of CCK is enhanced by estradiol and suggest that the PVN is involved in the interaction between CCK and estradiol.

Animals↗

PubMed1996

On the consistency of a physical mapping method to reconstruct a chromosome in vitro.

During recent years considerable effort has been invested in creating physical maps for a variety of organisms as part of the Human Genome Project and in creating various methods for physical mapping. The statistical consistency of a physical mapping method to reconstruct a chromosome, however, has not been investigated. In this paper, we first establish that a model of physical mapping by binary fingerprinting of DNA fragments is identifiable using the key assumption-for a large randomly generated recombinant DNA library, there exists a staircase of DNA fragments across the chromosomal region of interest. Then we briefly introduce epi-convergence theory of variational analysis and transform the physical mapping problem into a constrained stochastic optimization problem. By doing so, we prove epi-convergence of the physical mapping model and epi-convergence of the physical mapping method. Combining the identifiability of our physical mapping model and the epi-convergence of a physical mapping method, finally we establish strong consistency of a physical mapping method.

Aspergillus nidulans↗

PubMed1996

Study on insulin resistance in TCM treatment of noninsulin-dependent diabetes mellitus.

In the present paper, it is advanced that in TCM treatment of noninsulin-dependent diabetes mellitus (NIDDM), insulin resistance must be studied; and it is held that reversing or relieving of insulin resistance is the ultimate aim for treating NIDDM, and looking for the prescriptions of reversing the insulin resistance is an urgent task. Therefore, establishing the indexes of comprehensive assessment for the insulin resistance and the related models of the disease is the basis and prerequisite for the study.

Animals↗