Biomedical subjects

H Lan

Publications and source records attributed to H Lan.

At least 19 recordsLinked to original sources

PubMed2006

The Mcs7 quantitative trait locus is associated with an increased susceptibility to mammary cancer in congenic rats and an allele-specific imbalance.

Identification of high-penetrance breast cancer genes such as Brca1 has been accomplished by analysing familial cases. However, these genes occur at low frequency and do not account for the majority of genetic risk. Identification of low-penetrance alleles that occur commonly in populations may benefit from unbiased genome-wide screening. One such approach uses linkage studies in rodent models to identify homologous human candidates. The Wistar Kyoto (WKy) rat is resistant to mammary carcinomas induced with 7,12-dimethybenz[a]anthracene (DMBA), whereas the Wistar Furth (WF) strain is susceptible. Previous genome-wide linkage studies in crosses of these strains identified three WKy resistance quantitative trait loci, Mcs5, Mcs6 and Mcs8, and one predicted to increase susceptibility, Mcs7. The Mcs7 region on rat chromosome 10 (RNO10) is orthologous to human 17q, a common site of genetic aberrations in breast cancer. Here, we establish the independent phenotype conferred by Mcs7 using congenic rats carrying the WKy Mcs7 locus on a WF background. Tumor multiplicity was significantly higher ( approximately 50%) in DMBA-treated congenics homozygous and heterozygous for the WKy allele at the Mcs7 locus, compared to controls. We also investigated allelic imbalance (AI) in mammary carcinomas from (WKy x WF)F1 rats and Mcs7 heterozygous congenics. Of the four known WKy Mcs loci tested, only Mcs7 displayed AI. The pattern of AI in carcinomas from both F1 and Mcs7 congenic rats was similar, suggesting a WF allelic loss. Together, these data suggest that one or more breast cancer-related genes are located within the dominantly acting WKy allele at the Mcs7 locus.

Alleles↗

PubMed2006

Unrelated donor bone marrow transplantation for beta-thalassemia major: an experience from China.

Although related bone marrow transplantation (BMT) is effective for thalassemia, less than 30% of patients have sibling donors. Here, we report unrelated BMT in nine thalassemic children using a high-resolution HLA typing technique to identify donors. HLA mismatches between donors and recipients were 0, 1 and 2 in 2, 5 and 2 cases, respectively. The results showed that white blood cells, platelets and hemoglobin all returned to normal at various time points, and blood transfusion was eliminated from 13 to 62 days after transplantation. Full engraftment was achieved in eight patients while ABO blood types were replaced with that of donors in five of the six ABO mismatched recipients. Acute skin GVHD was found in seven patients and acute liver GVHD in one. One patient with acute intestinal GVHD eventually developed chronic GVHD. One patient died of pulmonary hemorrhage in spite of having a fully functional graft. We conclude that this is the first successful application of unrelated BMT for thalassemia major in Chinese people and that the results will certainly expand donor resources and greatly enhance the survival and quality of life of thalassemic patients.

ABO Blood-Group System↗

PubMed2006

Statistical methods for expression quantitative trait loci (eQTL) mapping.

Traditional genetic mapping has largely focused on the identification of loci affecting one, or at most a few, complex traits. Microarrays allow for measurement of thousands of gene expression abundances, themselves complex traits, and a number of recent investigations have considered these measurements as phenotypes in mapping studies. Combining traditional quantitative trait loci (QTL) mapping methods with microarray data is a powerful approach with demonstrated utility in a number of recent biological investigations. These expression quantitative trait loci (eQTL) studies are similar to traditional QTL studies, as a main goal is to identify the genomic locations to which the expression traits are linked. However, eQTL studies probe thousands of expression transcripts; and as a result, standard multi-trait QTL mapping methods, designed to handle at most tens of traits, do not directly apply. One possible approach is to use single-trait QTL mapping methods to analyze each transcript separately. This leads to an increased number of false discoveries, as corrections for multiple tests across transcripts are not made. Similarly, the repeated application, at each marker, of methods for identifying differentially expressed transcripts suffers from multiple tests across markers. Here, we demonstrate the deficiencies of these approaches and propose a mixture over markers (MOM) model that shares information across both markers and transcripts. The utility of all methods is evaluated using simulated data as well as data from an F(2) mouse cross in a study of diabetes. Results from simulation studies indicate that the MOM model is best at controlling false discoveries, without sacrificing power. The MOM model is also the only one capable of finding two genome regions previously shown to be involved in diabetes.

Animals↗

PubMed2003

On parametric empirical Bayes methods for comparing multiple groups using replicated gene expression profiles.

DNA microarrays provide for unprecedented large-scale views of gene expression and, as a result, have emerged as a fundamental measurement tool in the study of diverse biological systems. Statistical questions abound, but many traditional data analytic approaches do not apply, in large part because thousands of individual genes are measured with relatively little replication. Empirical Bayes methods provide a natural approach to microarray data analysis because they can significantly reduce the dimensionality of an inference problem while compensating for relatively few replicates by using information across the array. We propose a general empirical Bayes modelling approach which allows for replicate expression profiles in multiple conditions. The hierarchical mixture model accounts for differences among genes in their average expression levels, differential expression for a given gene among cell types, and measurement fluctuations. Two distinct parameterizations are considered: a model based on Gamma distributed measurements and one based on log-normally distributed measurements. False discovery rate and related operating characteristics of the methodology are assessed in a simulation study. We also show how the posterior odds of differential expression in one version of the model is related to the ratio of the arithmetic mean to the geometric mean of the two sample means. The methodology is used in a study of mammary cancer in the rat, where four distinct patterns of expression are possible.

Animals↗

PubMed2003

The efficiency of pooling mRNA in microarray experiments.

In a microarray experiment, messenger RNA samples are oftentimes pooled across subjects out of necessity, or in an effort to reduce the effect of biological variation. A basic problem in such experiments is to estimate the nominal expression levels of a large number of genes. Pooling samples will affect expression estimation, but the exact effects are not yet known as the approach has not been systematically studied in this context. We consider how mRNA pooling affects expression estimates by assessing the finite-sample performance of different estimators for designs with and without pooling. Conditions under which it is advantageous to pool mRNA are defined; and general properties of estimates from both pooled and non-pooled designs are derived under these conditions. A formula is given for the total number of subjects and arrays required in a pooled experiment to obtain gene expression estimates and confidence intervals comparable to those obtained from the no-pooling case. The formula demonstrates that by pooling a perhaps increased number of subjects, one can decrease the number of arrays required in an experiment without a loss of precision. The assumptions that facilitate derivation of this formula are considered using data from a quantitative real-time PCR experiment. The calculations are not specific to one particular method of quantifying gene expression as they assume only that a single, normalized, estimate of expression is obtained for each gene. As such, the results should be generally applicable to a number of technologies provided sufficient pre-processing and normalization methods are available and applied.

Animals↗

PubMed2001

Distribution of paclitaxel and its congeners in Taxus mairei.

Concentrations of paclitaxel and its congeners 10-deacetylpaclitaxel, cephalomannine, 10-deacetylcephalomannine, baccatin III and 10-deacetylbaccatin III in Taxus mairei were determined by HPLC. It was found that paclitaxel is abundant in roots and stem bark. The concentrations of paclitaxel and its congeners in the plants growing in one area may vary to a great extent from those growing in another area.

Antineoplastic Agents, Phytogenic↗

PubMed2001

Genetic loci controlling breast cancer susceptibility in the Wistar-Kyoto rat.

In this study, the Wistar-Kyoto (WKy) rat was genetically characterized for loci that modify susceptibility to mammary carcinogenesis. We used a genetic backcross between resistant WKy and susceptible Wistar-Furth (WF) rats as a panel for linkage mapping to genetically identify mammary carcinoma susceptibility (Mcs) loci underlying the resistance of the WKy rat. Rats were phenotyped for DMBA-induced mammary carcinomas and genotyped using microsatellite markers. To detect quantitative trait loci (QTL), we analyzed the genome scan data under both parametric and nonparametric distributional assumptions and used permutation tests to calculate significance thresholds. A generalized linear model analysis was also performed to test for interactions between significant QTL. This methodology was extended to identify interactions between the significant QTL and other genome locations. Chromosomes 5, 7, 10, and 14 were found to contain significant QTL, termed Mcs5, Mcs6, Mcs7, and Mcs8, respectively. The WKy alleles of Mcs5, -6, and -8 are associated with mammary carcinoma resistance; the WKy allele of Mcs7 is associated with an increased incidence of mammary cancer. In addition, we identified an interaction between Mcs8 and a region on chromosome 6 termed Mcsm1 (modifier of Mcs), which had no significant main effect on mammary cancer susceptibility in this genetic analysis.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2001

Detection of sporadic cases of hepatitis E virus (HEV) infection in China using immunoassays based on recombinant open reading frame 2 and 3 polypeptides from HEV genotype 4.

We reported previously on the complete sequence of hepatitis E virus (HEV) genotype 4, isolated from patients with sporadic cases of acute HEV infection in China. At least eight HEV genotypes have now been described worldwide, and further isolates await classification. Current immunoassays for the detection of anti-HEV antibodies are based on polypeptides from genotypes 1 and 2 only and may be inadequate for the reliable detection of other genotypes. Because genotypes 1 and 4 predominate in China, we wished to investigate the antigenic reactivities of HEV genotype 4 proteins. Four overlapping regions of open reading frame 2 (ORF2) (FB5, amino acids [aa] 1 to 130; E4, aa 67 to 308; F2-2, aa 288 to 461; E5, aa 414 to 672) and the entire ORF3 product were expressed in Escherichia coli as fusion proteins. Enzyme immunoassays based on each of the five purified polypeptides were evaluated with sera from patients with sporadic cases of acute HEV infection. Individual immunoassays derived from HEV genotype 4 detected more cases of acute hepatitis E than a commercial assay. Some serum samples, which were positive for anti-HEV immunoglobulin G only by assays based on HEV genotype 4, were positive for HEV RNA by reverse transcription-PCR. Polypeptide FB5, from the N terminus of ORF2, had the greatest immunoreactivity with sera from patients with acute hepatitis E. These data indicate that the N terminus of ORF2 may provide epitopes which are highly reactive with acute-phase sera and that assays based on genotypes 1 and 2 alone may be inadequate for the detection of HEV infection in China, where sporadic cases of HEV infection are caused predominantly by HEV genotypes 4 and 1.

Acute Disease↗

PubMed2001

Genotype and allele frequency of the 27-bp tandem repeat polymorphism in the endothelial nitric oxide synthase gene in Chinese population.

Genotype and allele frequency of the polymorphic 27-bp repeat, a variable number of tandem repeats (VNTR) located in intron 4 of the endothelial nitric oxide synthase gene, were analyzed in 316 healthy Chinese individuals. Four genotypes, namely 6/5-repeats heterozygous, 5/5-repeats homozygous, 5/4-repeats heterozygous and 4/4-repeats homozygous, were identified. Both observed genotype and allele frequencies of this VNTR in Chinese were similar to those of Japanese, while the 4/4-repeats genotype differed significantly from that of Caucasians in Spain, and all ones did from those of African-American in United States.

Alleles↗

PubMed2000

Effects of aprotinin on serum interleukin-2 and soluble interleukin-2 receptor during cardiopulmonary bypass.

Interleukin-2 and its receptor are of importance in regulating immunity responses. The changes of interleukin-2 (IL-2) and soluble interleukin-2 receptor (IL-2R) during heart valve (s) replacement operation and effects of aprotinin on them were observed. Twenty patients undergoing heart valve(s) replacement were randomly divided into two groups: control group (n = 10) and aprotinin group (n = 10). In aprotinin group, 1,000,000 KIU aprotinin was given by vein injection and then 2,000,000 KIU was given as a bolus in prime. Blood samples were collected before CPB, right after CPB and on the 1st, 3rd and 7th postoperative day (POD) for serum IL-2 and sIL-2R determination. Results showed that after CPB, IL-2 was reduced and sIL-2R increased. Meanwhile, serum IL-2R was lower in aprotinin group than that of control. It is concluded that the immunity depression after CPB is associated with low level of IL-2 and high level of sIL-2R and aprotinin can ameliorate the situation.

Aprotinin↗

PubMed2000

Rapid and parallel chromosomal number reductions in muntjac deer inferred from mitochondrial DNA phylogeny.

Muntjac deer (Muntiacinae, Cervidae) are of great interest in evolutionary studies because of their dramatic chromosome variations and recent discoveries of several new species. In this paper, we analyze the evolution of karyotypes of muntjac deer in the context of a phylogeny which is based on 1,844-bp mitochondrial DNA sequences of seven generally recognized species in the muntjac subfamily. The phylogenetic results support the hypothesis that karyotypic evolution in muntjac deer has proceeded via reduction in diploid number. However, the reduction in number is not always linear, i.e., not strictly following the order: 46-->14/13-->8/9-->6/7. For example, Muntiacus muntjak (2n = 6/7) shares a common ancestor with Muntiacus feae (2n = 13/14), which indicates that its karyotype was derived in parallel with M. feae's from an ancestral karyotype of 2n >/= 13/14. The newly discovered giant muntjac (Muntiacus vuquangensis) may represent another parallel reduction lineage from the ancestral 2n = 46 karyotype. Our phylogenetic results indicate that the giant muntjac is relatively closer to Muntiacus reevesi than to other muntjacs and may be placed in the genus Muntiacus Analyses of sequence divergence reveal that the rate of change in chromosome number in muntjac deer is one of the fastest in vertebrates. Within the muntjac subfamily, the fastest evolutionary rate is found in the Fea's lineage, in which two species with different karyotypes diverged in around 0.5 Myr.

Animals↗

PubMed1999

Phylogenetic study of complete cytochrome b genes in musk deer (genus Moschus) using museum samples.

As an endangered animal group, musk deer (genus Moschus) are not only a great concern of wildlife conservation, but also of special interest to evolutionary studies due to long-standing arguments on the taxonomic and phylogenetic associations in this group. Using museum samples, we sequenced complete mitochondrial cytochrome b genes (1140 bp) of all suggested species of musk deer in order to reconstruct their phylogenetic history through molecular information. Our results showed that the cytochrome b gene tree is rather robust and concurred for all the algorithms employed (parsimony, maximum likelihood, and distance methods). Further, the relative rate test indicated a constant sequence substitution rate among all the species, permitting the dating of divergence events by molecular clock. According to the molecular topology, M. moschiferus branched off the earliest from a common ancestor of musk deer (about 700,000 years ago); then followed the bifurcation forming the M. berezovskii lineage and the lineage clustering M. fuscus, M. chrysogaster, and M. leucogaster (around 370,000 years before present). Interestingly, the most recent speciation event in musk deer happened rather recently (140,000 years ago), which might have resulted from the diversified habitats and geographic barriers in southwest China caused by gigantic movements of the Qinghai-Tibetan Plateau in history. Combining the data of current distributions, fossil records, and molecular data of this study, we suggest that the historical dispersion of musk deer might be from north to south in China. Additionally, in our further analyses involving other pecora species, musk deer was strongly supported as a monophyletic group and a valid family in Artiodactyla, closely related to Cervidae.

Animals↗

PubMed1999

The effects of lower intensity anticoagulation therapy on coagulation system in patients with mechanical prosthetic valves.

To evaluate the effect of lower intensity anticoagulation therapy in patients with mechanical prosthetic valves, laboratory-based hematological assays including prothrombin time (PT), activity of factor X, antithrombin III (AT III), D-dimer, fibrinogen (Fg) and platel et al pha-granular membrane protein (GMP-140) were performed in 65 patients who had been on warfarin treatment for over one month. The patients were assigned to 3 groups on the basis of their International Normalized Ratios (INR), ranging from 2.00 to 2.50; 2.51 to 3.00; 3.01 to 4.50, respectively. The results showed that the D-dimer, Fg, GMP-140 levels were higher after mechanical valve replacement than those before operation, indicating the activation of coagulation and fibrinolysis system and the damage of platelets. Lower intensity anticoagulation therapy (INR 2.00 to 2.50) could effectively inhibit the activity of factor X and increase the level of AT III. There were no appreciable differences among D-dimer, Fg, GMP-140 and AT III in the 3 anticoagulation intensity groups. These results suggest that in patients with new generation mechanical prosthetic valves, target anticoagulation level (INR 2.00 to 2.50) may result in good protection from thrombo-embolism.

Adolescent↗

PubMed1999

Linkage mapping of rat chromosome 5 markers generated from chromosome-specific libraries.

Seventy-six novel microsatellite markers with various simple sequence repeat (SSR) motifs are reported in this paper. They were generated on the basis of non-radioactive library screening procedures from flow-sorted rat Chromosome (Chr) 5-specific DNA, and were mapped in three rat backcross populations. Fifty-four of these markers mapped to Chr 5, while the other 22 mapped to other chromosomes of the rat genome. The marker D3Uwm8 is a new microsatellite marker for the rat syndecan 4 (ryudocan) gene. A genotyping protocol based on agarose gel electrophoresis is also provided in this paper.

Animals↗

PubMed1998

Effect of aprotinin on the red cell immunity in cardiopulmonary bypass.

To investigate the effects of aprotinin on red cell (RC) immune function in the patients undergoing cardiopulmonary bypass (CPB), 20 patients who received valve replacement procedure were prospectively studied. The patients were randomly assigned to aprotinin group and control group. Red blood cell C3b receptor ratio (RC3bRR), red blood cell immune-component ratio (RICR), plasma C3, C4, CH50 and IgG level were determined before operation, at the end of CPB and 1st, 3rd, 7th postoperative days. Our results showed that: (1) The blood requirement was reduced in aprotinin group. (2) After bypass, plasma C3, C4, CH50 was maintained in aprotinin group, while they declined in control group. (3) Plasma level IgG fell in both groups, but at 7th postoperative day it recovered in aprotinin group while the level stayed at low level in control group. (4) The RC3bRR and RICR was mildly inhibited in aprotinin group. It is concluded that the impairment of RC immune function caused by CPB can be mitigated by aprotinin, which may be related to the effects of aprotinin in blood sparing, restriction of complement activation, and reduction of blood requirement which could mitigate the non-specific inflammatory reaction.

Adjuvants, Immunologic↗

PubMed1998

Left to right extracardial shunt to control hemorrhage of ascending aorta and left ventricle: a report of 3 cases.

Presented in this paper are 3 cases of hemorrhage of ascending aorta and left ventricle after open heart surgery treated by extracardial bypass in our hospital from Oct. 1994 to Dec. 1995. Remained aneurysmal wall enclosing conduit graft was used as a sac bypassed to right atrium to form a extracardial left-to-right shunt in order to control bleeding and the results turned out to be satisfactory. The bypass and hemodynamically ignorable shunt can close spontaneously without complications with recovery of coagulation system. The technique may find wide application in clinical practice.

Adult↗

PubMed1998

Mapping of 55 new rat microsatellite markers from chromosome-specific libraries.

Fifty-five novel rat microsatellite markers were isolated from libraries specific for rat chromosomes (Chrs) 1, 2, and 7. The markers were mapped in three backcross rat populations. Thirty of these markers mapped to Chrs 1, 2, or 7, while the other 25 mapped to other chromosomes. New markers for two genes, liver-specific transporter gene (Livtr) and insulin-responsive glucose transporter (Glut4), were also mapped to rat Chrs 9 and 10, respectively. Three provisionally assigned markers from previous studies were also confirmed. Detailed methodologies for the generation and enrichment of clones containing repeat sequences and for the isolation of chromosome-specific markers are presented, since they represent unique combinations and modifications of previous protocols. Such methods and the newly presented markers should be useful for both specific and general mapping studies in the rat.

Animals↗

PubMed1998

Genetic identification of multiple loci that control breast cancer susceptibility in the rat.

We have used a rat model of induced mammary carcinomas in an effort to identify breast cancer susceptibility genes. Using genetic crosses between the carcinoma-resistant Copenhagen (COP) and carcinoma-sensitive Wistar-Furth rats, we have confirmed the identification of the Mcs1 locus that modulates tumor number. We have now also identified two additional loci, Mcs2 and Mcs3. These three loci map to chromosomes 2, 7, and 1, respectively, and interact additively to suppress mammary carcinoma development in the COP strain. They are responsible for a major portion of the tumor-resistant phenotype of the COP rat. No loss of heterozygosity was observed surrounding the three loci. A fourth COP locus, Mcs4, has also been identified on chromosome 8 and acts in contrast to increase the number of carcinomas. These results show that mammary carcinoma susceptibility in the COP rat is a polygenic trait. Interestingly, a polymorphism in the human genomic region homologous to the rat Mcs4 region is associated with an increased breast cancer risk in African-American women. The isolation of the Mcs genes may help elucidate novel mechanisms of carcinogenesis, provide information important for human breast cancer risk estimation, and also provide unique drug discovery targets for breast cancer prevention.

Alleles↗