Biomedical subjects

Qing Wang

Publications and source records attributed to Qing Wang.

At least 127 records · Page 7Linked to original sources

PubMed2004

Premature myocardial infarction novel susceptibility locus on chromosome 1P34-36 identified by genomewide linkage analysis.

The most frequent causes of death and disability in the Western world are atherosclerotic coronary artery disease (CAD) and acute myocardial infarction (MI). This common disease is thought to have a polygenic basis with a complex interaction with environmental factors. Here, we report results of a genomewide search for susceptibility genes for MI in a well-characterized U.S. cohort consisting of 1,613 individuals in 428 multiplex families with familial premature CAD and MI: 712 with MI, 974 with CAD, and average age of onset of 44.4+/-9.7 years. Genotyping was performed at the National Heart, Lung, and Blood Institute Mammalian Genotyping Facility through use of 408 markers that span the entire human genome every 10 cM. Linkage analysis was performed with the modified Haseman-Elston regression model through use of the SIBPAL program. Three genomewide scans were conducted: single-point, multipoint, and multipoint performed on of white pedigrees only (92% of the cohort). One novel significant susceptibility locus was detected for MI on chromosomal region 1p34-36, with a multipoint allele-sharing P value of <10(-12) (LOD=11.68). Validation by use of a permutation test yielded a pointwise empirical P value of.00011 at this locus, which corresponds to a genomewide significance of P<.05. For the less restrictive phenotype of CAD, no genetic locus was detected, suggesting that CAD and MI may not share all susceptibility genes. The present study thus identifies a novel genetic-susceptibility locus for MI and provides a framework for the ultimate cloning of a gene for the complex disease MI.

Adult↗

PubMed2004

Analysis of the allele-specific expression of the mismatch repair gene MLH1 using a simple DHPLC-Based Method.

Quantitative measures of allele-specific gene expression allow the indirect detection of mutations or sequence variants in regulatory elements or in other non-coding regions that may result in significant physiological or pathological changes of gene expression and may contribute to Mendelian or multifactorial disorders. We have devised a simple method, based on RT-PCR and single nucleotide primer extension (SNuPE) with unlabelled dideoxynucleotides, followed by DHPLC (denaturing high performance liquid chromatography). We established optimal conditions for separation of the extended products corresponding to the alleles of the c.655A>G (p.Ile219Val) SNP, which is the most frequent exonic polymorphism of MLH1. We then genotyped 99 unrelated control subjects and measured the allele-specific MLH1 expression in the 40 heterozygous controls found in this group. This method allowed us to define a narrow range of normal biallelic expression of MLH1, each allele contributing between 44.7% and 55.3% of the total expression. We then measured the allele-specific expression in hereditary nonpolyposis colorectal cancer (HNPCC) patients with MLH1 mRNAs bearing different stop-codon or frame-shift mutations, or in-frame deletions, in order to detect the effects of nonsense-mediated mRNA decay (NMD). Defects that induce mRNA instability were identified unambiguously and the data were consistent with current models of NMD. This study provides a sensitive tool to identify indirectly MLH1 defects that may escape detection in genomic DNA screenings but result in a quantitative change at the mRNA level.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Identification and molecular characterization of a de novo supernumerary ring chromosome 18 in a patient with Klippel-Trenaunay syndrome.

Klippel-Trenaunay syndrome (KTS) is a congenital vascular disorder comprised of capillary, venous and lymphatic malformations associated with overgrowth of the affected tissues. In this study, we report the identification of a de novo supernumerary ring chromosome in a patient with mild mental retardation, long tapering fingers, elongated, thin feet and Klippel-Trenaunay syndrome (KTS). The ring marker chromosome was found to be mosaic, present in 24% of cells, and was later shown to be derived from chromosome 18, r(18). Fluorescence in situ hybridization (FISH) was used to define the breakpoints involved in the formation of r(18). The chromosome 18p breakpoint was localized between the markers WI-9619 and D18S1150, which is less than 10 cM to the centromere. The 18q breakpoint was localized between the centromere and BAC clone 666n19, which is a region of less than 40 kb. These data suggest that the r(18) mostly originated from 18p, with an estimated size of less than 10 cM. These studies identify and characterize a new marker chromosome 18, provide insights into the understanding of the relationships between the clinical phenotypes and marker chromosomes, and establish a framework for finding a potential vascular and/or overgrowth gene located on chromosome 18.

Adult↗

PubMed2004

Renal endothelin receptor type B upregulation in rats with low or high renin hypertension.

OBJECTIVES: To evaluate the role of endothelin-1 (ET-1) in hypertension, we investigated density and distribution of ETA and ETB receptors in hearts and kidneys of deoxycorticosterone acetate (DOCA)-salt and 1 kidney -- 1 clip (1K1C) hypertensive rats. METHODS: Five groups of uninephrectomized Wistar rats were put on a low salt diet. Three groups of rats drank tap water and two groups received saline. One group of each regimen received DOCA subcutaneously and two corresponding groups without DOCA served as controls. The fifth group of rats had the renal artery clipped to induce 1K1C hypertension. At 6 weeks, mean arterial pressure (MAP) was recorded and membrane binding assays using 125I-ET-1 were carried out. RESULTS: MAP was increased from control 122 +/- 3 to 155 +/- 6 and 218 +/- 11 mmHg in DOCA-salt and 1K1C rats, respectively, and cardiac weight index was increased. ETA receptors were predominantly expressed in the heart, whereas ETB receptors were predominant in the kidney. In the kidneys, the density of the ETB receptor subtype was upregulated in DOCA-salt and 1K1C rats from 160 +/- 8 to 217 +/- 12 and 190 +/- 2 fmol/mg (P < 0.05), respectively, and ETA tended to be downregulated (P = 0.057). Plasma renin activity was decreased in DOCA-salt rats from 17 +/- 3 to 0.17 +/- 0.01 ng/ml per h and increased in 1K1C rats on low salt diet to 30 +/- 5 ng/ml per h. CONCLUSIONS: Since ETB is the predominant endothelin receptor in the kidneys, upregulation of the ETB receptor mediating vasodilation and downregulation of the ETA receptor mediating vasoconstriction would be compatible with a mainly renal counter-regulatory effect of endothelin-1 to hypertension. Both low and high renin models of hypertension may be affected.

Animals↗

PubMed2004

Expression profiling of cardiovascular disease.

Cardiovascular disease is the most important cause of morbidity and mortality in developed countries, causing twice as many deaths as cancer in the USA. The major cardiovascular diseases, including coronary artery disease (CAD), myocardial infarction (MI), congestive heart failure (CHF) and common congenital heart disease (CHD), are caused by multiple genetic and environmental factors, as well as the interactions between them. The underlying molecular pathogenic mechanisms for these disorders are still largely unknown, but gene expression may play a central role in the development and progression of cardiovascular disease. Microarrays are high-throughput genomic tools that allow the comparison of global expression changes in thousands of genes between normal and diseased cells/tissues. Microarrays have recently been applied to CAD/MI, CHF and CHD to profile changes in gene expression patterns in diseased and non-diseased patients. This same technology has also been used to characterise endothelial cells, vascular smooth muscle cells and inflammatory cells, with or without various treatments that mimic disease processes involved in CAD/MI. These studies have led to the identification of unique subsets of genes associated with specific diseases and disease processes. Ongoing microarray studies in the field will provide insights into the molecular mechanism of cardiovascular disease and may generate new diagnostic and therapeutic markers.

Animals↗

PubMed2004

[Frequency of transfusion transmitted virus in healthy infants in Jiujiang city Jiangxi province].

OBJECTIVE: Transfusion transmitted virus (TTV) DNA was detected in serum samples obtained from healthy infants and volunteer blood donors living in Jiujiang city in an attempt to shed light on the prevalence of TTV infection and the transmission route of TTV infection in infants. METHODS: Modified untranslated region, polymerase chain reaction (UTR PCR) and N22 PCR were performed to test TTV DNA in serum samples from 86 infants and 58 blood donors. RESULTS: TTV DNA was detected by UTR PCR in 51 (53.5%) infants and 58 (100%) in blood donors, while that tested by N22 PCR was 14 (16.3%) and 22 (37.3%) in infants and blood donors, respectively. Among infants younger than 30 days, 1 - 6 months and 7 - 12 months of age, TTV DNA was detected by UTR PCR and N22 PCR at rates of 0, 33.3%, 95.0% and 0, 7.4%, 30.0%, respectively. CONCLUSION: The prevalence rates of TTV DNA detected by UTR PCR were 95% in infants of 7 - 12 months after birth and 100% in healthy blood donors in Jiujiang city. However the results obtained by N22 PCR were much less frequently in the same population. Results showed that significant difference did exist in the prevalence of TTV DNA detected by the two different PCR systems. Age-dependent increase of TTV infection was observed in early childhood, while environmental sources were considered to be the most common route of TTV acquisition as the primary infection in infants. However, the prevalence of TTV in infants of 7 - 12 months was similar to that in healthy adults in the same region.

Base Sequence↗

PubMed2004

[A randomized controlled Multi-center clinical trial on mosapride in the treatment of functional dyspepsia].

OBJECTIVE: To evaluate the effectiveness and safety of mosapride on treatment of functional dyspepsia. METHODS: Randomized controlled clinical trial was conducted and patients suffered from functional dyspepsia were included. 5 mg mosapride was given three times daily for 4 weeks in the treatment group. 10 mg domperidone was given three times daily for 4 weeks as control. Changes on symptom score, gastric empty or new occurring events were included as outcomes. RESULTS: 231 patients suffered from functional dyspepsia were selected by inclusion and exclusion criteria from August 15 to Oct 22, 1999. Of these, 108 (46.8%) were males, versus 123 (53.2%) females and 118 (51.2%) in the treatment group and 113 (48.9%) as controls. 222 (96.1%) patients were followed up. Results showed that the total efficacy rates in early satiety and abdominal distension were 84.5% and 90.1% in mosapride after the 2 weeks of treatment. Mosapride seemed to be more effective in improving symptoms of belching and heartburn than that in controls (P < 0.05). In 4 weeks, the total efficacy in improving symptoms of abdominal distention and belching showed more effective in mosapride than that in controls (P < 0.05). Decrease of symptoms score was more in mosapride than that in controls (P < 0.05). Mosapride was less effective in controls in improving the gastric empty in terms of proportion (46.2% vs. 25.9%, P = 0.020) and range (46.2% vs. 24.0%, P = 0.003). Side effects would include diarrhea, constipation, headache, dizziness, insomnia, skin scare and the like. There was no significant difference between the two groups (9.6% in mosapride vs. 14.0% in controls). CONCLUSION: Mosapride was safe and effective in improving the symptoms and gastric empty of functional dyspepsia.

Adult↗

PubMed2004

[The effect of coronal preflaring on the working length measurement of root canals in molars].

PURPOSE: To study the influence of coronal preflaring of root canal on the working length measurement in molars. METHODS: 48 molars from 47 adult patients with pulpitis were divided into two groups randomly. 74 root canals of 24 molars were examined in Group 1. After preparing an access cavity, the root canal orifices were located. A 15# K-type file was inserted into root canal to detect resistance at the apical region. 75 root canals of 24 molars were examined in Group 2. Before testing the apical resistance,a size 25# and 20# ProFile.06 taper NiTi rotary instrument was used to enlarge the canal orifice and flare the coronal portion of the root canal. After placing 15# K-type files, a radiograph was taken with the bisecting-angle technique. The distance between the tip of the file and the radiographic apex was measured on the radiographs. Statistical analysis of univariate and multiple logistic regression were carried out for analysis. RESULTS: There was a significant difference between the two groups (P<0.05), there were more accurate measurements in Group 2 than in Group 1. No statistical correlation was found between X-ray measurements and age, sex and the position of molars,while there was significant correlation between maxillary molars and mandibular molars (P<0.05). CONCLUSION: Preflaring the coronal portion of the root canals could significantly increase the accurate measurements of the working length of root canals in molars.

Adult↗

PubMed2004

[The clinical features of acute pancreatitis in 10 cities in Shandong Province].

OBJECTIVE: To investigate and obtain a more comprehensive view of the etiology and clinical features of acute pancreatitis (AP) in Shandong Province. METHODS: 1471 cases admitted to hospital for AP were studied and collected from the ten cities of Shandong Province from January 1992 to December 2002 retrospectively. Data of each enrolled patient was recorded in a standardized form. RESULTS: In the 1471 patients, the ratio of male: female was 854:617, and also the mean age of them and the range was 43.3 and from 13 - 82 years old. 1280 had mild AP, and 191 had sever AP. Cholelithiasis (20.2%), alcohol (17.3%) and diet-induced (12.4%) were the most frequent etiologic factors, followed by biliary tract infections (5.6%), hyperlipemia (2.3%), other factors (5.1%). But in about 36.1% cases, the etiology of AP still remains unexplained. In coastal regions, cholelithiasis is the most frequent factor but in interior regions alcohol ranked first. In male, a small predominance of alcohol over cholelithiasis was seen (27.4 vs.14.3%, P < 0.01); and in female, there was a clear predominance of cholelithiasis over alcohol (28.4 vs. 3.2%, P < 0.01). The complications of AP were pancreatic pseudocyst, ascites and peritonitis, pulmonary infections, multiple organ failure, diabetes mellitus-2 and shock, etc. according to their frequencies. CONCLUSIONS: Cholelithiasis, alcohol and diet-induced factor were main etiologic factors in Shandong Province, whereas cholelithiasis alone predominated in the females. In about 36.1% cases, the etiology remains unknown. So that more attention should be paid to study the etiology of AP.

Acute Disease↗

PubMed2004

[Effect of natural killer cell on hematopoiesis and immunity recovery in mouse allogeneic bone marrow transplantation].

OBJECTIVE: To study the effect of natural killer (NK)-cell on reconstitution of hematopoiesis and immunity in mouse allogeneic bone marrow transplantation (allo-BMT). METHODS: Lethally irradiated BALB/c (H-2(d)) mice were transplanted with C57BL/6 (H-2(b)) bone marrow plus peripheral T cells and/or NK cells. Recipients CD34(+) cells and H-2K(b+), CD3(+) and CD19(+) cells were detected by flow cytometry, peripheral white blood cell (WBC) by auto-cytometry, and the survival rates, engraftment, hematopoietic and immune recovery were observed. RESULTS: In the transplantation with NK cell infusion group, the survival rates, the WBC and CD34(+) cell counts, and the H-2(b+) and CD19(+) cells were significantly higher than that in without NK cell infusion group (P < 0.01). Twenty-eight days after transplantation, the CD3(+) cells in the NK cell infusion group [(33.69 +/- 3.36)%] were lower than that in without [(50.4 +/- 5.06)%] (P < 0.01), and there was no longer difference between these groups 60 days after transplantation (P > 0.05). CONCLUSION: In mouse allo-BMT, alloreactive NK cell enhances engraftment, promotes reconstitution of hematopoiesis and immunity and increases survival rates.

Animals↗

PubMed2003

Genetic linkage analysis of longitudinal hypertension phenotypes using three summary measures.

BACKGROUND: Longitudinal data often have multiple (repeated) measures recorded along a time trajectory. For example, the two cohorts from the Framingham Heart Study (GAW13 Problem 1) contain 21 and 5 repeated measures for hypertension phenotypes as well as epidemiological risk factors, respectively. Direct modelling of a large number of serially and biologically correlated traits in the context of linkage analysis can be prohibitively complex. Alternatively, we may consider using univariate transformation for linkage analysis of longitudinal repeated measures. RESULTS: We evaluated the utility of three conventional summary measures (mean, slope, and principal components) for genetic linkage analysis of longitudinal phenotypes by analyzing the chromosome 10 data of the Framingham Heart Study. Except for the temporal slope, all of the summary methods and the multivariate analysis identified the previously reported region, marker GATA64A09, for systolic blood pressure or high blood pressure. Further analysis revealed that this region may harbor gene(s) affecting human blood pressure at multiple stages of life. CONCLUSION: We conclude that mean and principal components are feasible alternatives for genetic linkage analysis of longitudinal phenotypes, but the slope might have a separate genetic basis from that of the original longitudinal phenotypes.

Adult Children↗

PubMed2003

Multivariate sib-pair linkage analysis of longitudinal phenotypes by three step-wise analysis approaches.

BACKGROUND: Current statistical methods for sib-pair linkage analysis of complex diseases include linear models, generalized linear models, and novel data mining techniques. The purpose of this study was to further investigate the utility and properties of a novel pattern recognition technique (step-wise discriminant analysis) using the chromosome 10 linkage data from the Framingham Heart Study and by comparing it with step-wise logistic regression and linear regression. RESULTS: The three step-wise approaches were compared in terms of statistical significance and gene localization. Step-wise discriminant linkage analysis approach performed best; next was step-wise logistic regression; and step-wise linear regression was the least efficient because it ignored the categorical nature of disease phenotypes. Nevertheless, all three methods successfully identified the previously reported chromosomal region linked to human hypertension, marker GATA64A09. We also explored the possibility of using the discriminant analysis to detect gene x gene and gene x environment interactions. There was evidence to suggest the existence of gene x environment interactions between markers GATA64A09 or GATA115E01 and hypertension treatment and gene x gene interactions between markers GATA64A09 and GATA115E01. Finally, we answered the theoretical question "Is a trichotomous phenotype more efficient than a binary?" Unlike logistic regression, discriminant sib-pair linkage analysis might have more power to detect linkage to a binary phenotype than a trichotomous one. CONCLUSION: We confirmed our previous speculation that step-wise discriminant analysis is useful for genetic mapping of complex diseases. This analysis also supported the possibility of the pattern recognition technique for investigating gene x gene or gene x environment interactions.

Adult Children↗

PubMed2003

Chfr inactivation is not associated to chromosomal instability in colon cancers.

Numerous observations suggest that chromosome instability is caused by mitotic abnormalities such as errors in the partitioning of chromosomes. Chfr was recently defined as a central component of a new mitotic checkpoint that delays chromosome condensation in response to mitotic stress. Chfr was shown to be frequently inactivated in several human neoplasms, including colon, lung and esophageal cancers. To test whether Chfr inactivation may lead or participate to chromosomal instability (CIN), we analysed the genetic and epigenetic status of the gene in a large panel of primary colon and breast cancers, as well as in colon and breast cancer cell lines displaying either a microsatellite instability or a CIN. Our results confirm that Chfr is frequently inactivated in colon cancers, through a mechanism of hypermethylation of the promoter sequences. In contrast, the loss of Chfr expression appears to be a rare event in breast cancers. Furthermore, our data demonstrate that Chfr inactivation is not associated with CIN in these frequent types of human cancers.

Cell Cycle Proteins↗

PubMed2003

Mutation of MEF2A in an inherited disorder with features of coronary artery disease.

The early genetic pathway(s) triggering the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) remain largely unknown. Here, we describe an autosomal dominant form of CAD/MI (adCAD1) that is caused by the deletion of seven amino acids in transcription factor MEF2A. The deletion disrupts nuclear localization of MEF2A, reduces MEF2A-mediated transcription activation, and abolishes synergistic activation by MEF2A and by the transcription factor GATA-1 through a dominant-negative mechanism. The MEF2A protein demonstrates strong expression in the endothelium of coronary arteries. These results identify a pathogenic gene for a familial vascular disease with features of CAD and implicate the MEF2A signaling pathway in the pathogenesis of CAD/MI.

Aged↗

PubMed2003

Identification of new genes differentially expressed in coronary artery disease by expression profiling.

Genetic factors increase the risk to coronary artery disease (CAD). To date, a limited number of genes that potentially contribute to development of CAD have been identified. In this study, we have performed large-scale gene expression analysis of approximately 12,000 human genes in nine severely atherosclerotic and six nonatherosclerotic human coronary arteries using oligonucleotide microarrays. Fifty-six genes showed differential expression in atherosclerotic coronary artery tissues; expression of 55 genes was increased in atherosclerotic coronary arteries, whereas only one gene, GST, encoding a reducing agent, showed downregulated expression. The expression data of selected genes were validated by quantitative RT-PCR analysis as well as immunostaining. The associations of 49 genes with CAD appear to be novel, and they include genes encoding ICAM-2, PIM-2, ECGF1, fusin, B cell activator (BL34, GOS8), Rho GTPase activating protein-4, retinoic acid receptor responder, beta2-arrestin, membrane aminopeptidase, cathepsins K and H, MIR-7, TNF-alpha-induced protein 2 (B94), and flavocytochrome 558. In conclusion, we have identified 56 genes whose expression is associated with CAD, and 49 of them may represent new genes linked to CAD.

Apoptosis↗

PubMed2003

Determination of cardiac contractility in awake unsedated mice with a fluid-filled catheter.

Today, cardiac contractility in mice is exclusively measured under anesthesia or in sedated animals because the catheters available are too rigid to be used in awake mice. We therefore developed a new catheter (Pebax 03) to measure cardiac contractility in conscious mice. In this study, we evaluated the accuracy and utility of this new catheter for assessment of cardiac contractility in anesthetized and conscious mice. With the use of a balloon-pop test, the Pebax catheter with an inner diameter of 0.3 mm was found to exhibit a high natural frequency, a low damping coefficient, and a flat frequency of up to 50.5 +/- 0.6 Hz. Under anesthesia (0.5% or 1.0% halothane), no difference was found in heart rate (HR), left ventricular (LV) systolic pressure (LVSP), the maximum rates of LV pressure rise and fall (LV dP/dt(max) and LV dP/dt(min), respectively), ejection time (ET), and isovolumic relaxation time constant (tau) when measured with either the 1.4-Fr Millar or Pebax 03 catheter. However, when HR, LVSP, LV dP/dt(max), and LV dP/dt(min) were recorded with the Pebax catheter in awake mice, values were significantly higher, and ET and tau were lower, than under anesthesia, suggesting a major impact of anesthesia on these parameters. The Pebax catheter was also used in a normotensive one-renin gene mouse model of cardiac hypertrophy induced by DOCA and salt. In this model, DOCA-salt induced a severe decrease in cardiac contractility in the absence of changes in blood pressure. These data demonstrate that cardiac contractility can be measured very accurately in conscious mice. This new device can be of great help in the investigation of cardiac function in normal and genetically engineered mice.

Anesthesia, General↗

PubMed2003

Novel deletion in the pre-mRNA splicing gene PRPF31 causes autosomal dominant retinitis pigmentosa in a large Chinese family.

We report the identification of a novel 12 bp deletion of the pre-mRNA splicing gene PRPF31 in a large Chinese family with autosomal dominant retinitis pigmentosa (adRP). This mutation results in the deletion of four amino acids (DeltaH(111)K(112)F(113)I(114)) including H(111), an amino acid residue that is highly conserved throughout evolution. The 12 bp deletion co-segregates with the disease phenotype in 19 RP patients in the family, but is not present in unaffected relatives or 100 normal individuals. Our data indicate that the novel 12 bp deletion in PRPF31 causes retinitis pigementosa in this Chinese adRP family. In contrast to the incomplete penetrance observed in most adRP families linked to chromosome band 19q13.4 (RP11), the 12 bp PRPF31 deletion identified in this study appears to show high penetrance. These data expand the spectrum of PRPF31 mutations causing adRP, and confirm the role of PRPF31 in the pathogenesis of RP.

Alleles↗

PubMed2003

Jun N-terminal kinase pathway enhances signaling of monocytic differentiation of human leukemia cells induced by 1,25-dihydroxyvitamin D3.

Recent studies revealed that the MEK/ERK module of the mitogen-activated protein kinase (MAPK) signaling cascades is up-regulated in the early stages of 1alpha,25-dihydroxyvitamin D(3) (1,25D(3))-induced monocytic differentiation of human leukemia cells HL60. In the present study, we investigated whether another MAPK module, the JNK pathway, also participates in this form of differentiation. We found that the dependence on the concentration of the inducer, the vitamin-hormone 1,25D(3), in two types of human leukemia cells, HL60 and U937, and the kinetics of monocytic differentiation in HL60 cells, parallel the degree of the activation of the JNK pathway. A blockade of JNK signaling by a stable expression of dominant negative (dn) JNK1 mutant in U937 cells resulted in reduced c-jun phosphorylation, and the differentiation of these cells was markedly decreased. Similarly, inhibition of JNK1 and JNK2 activities by the selective inhibitor SP600125 led to both dose-dependent reduction of c-jun and ATF-2 phosphorylation, and of the differentiation of HL60 cells. In addition, we found that JNK activity is essential for the AP-1 DNA binding induced by 1,25D(3) in HL60 and U937 cells. The results indicate that in cultured human leukemia cells, the JNK pathway participates in the induction of monocytic differentiation by 1,25D(3), probably by activating the AP-1 transcription factor.

Anthracenes↗