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H W Deng

Publications and source records attributed to H W Deng.

At least 37 records · Page 2Linked to original sources
PubMed2001

Elevated serum endogenous inhibitor of nitric oxide synthase and endothelial dysfunction in aged rats.

1. The purpose of the present study was to determine the relationship between endothelial dysfunction and the endogenous inhibitor of nitric oxide synthase NG,NG'-asymmetric dimethylarginine (ADMA) in aged rats. 2. Studies were performed in male adult Sprague-Dawley rats (6 months old; n = 8) and in aged rats (20 months old; n = 8). Serum levels of ADMA and L-arginine were measured by high-performance liquid chromatography and responses of endothelium-intact aortic rings to acetylcholine (ACh) were tested. Nitric oxide synthase activity in kidney tissue and serum concentrations of nitrite, a stable end-product of nitric oxide, were assayed and serum contents of malondialdehyde, derived from lipid peroxidation and serum lipid and creatinine level were determined. 3. Serum levels of ADMA increased significantly in aged rats compared with adult rats (P < 0.01), whereas serum levels of L-arginine were similar in both groups (P = NS). Accordingly, the ratio of L-arginine/ADMA in old rats was lower than that in young rats (P < 0.01). Endothelium-dependent relaxation responses to ACh in aortic rings from aged rats were impaired and these impaired responses were improved by pre-incubation of aortic rings with L-arginine. 4. Nitric oxide synthase activity in the kidney, together with serum concentration of nitrite, was significantly decreased and serum contents of malondialdehyde, cholesterol and triglycerides were increased in old compared with young rats. However, the serum creatinine level was not significantly different between adult and aged rats. 5. Endogenous ADMA may be a contributor to age-related endothelial dysfunction and increases in endogenous ADMA may be linked to lipid peroxidation in aged rats.

Acetylcholine↗
PubMed2001

Effect of asymmetric dimethylarginine on osteoblastic differentiation.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS) that accumulates in renal insufficiency and may be a uremic toxin. To determine whether ADMA inhibits bone metabolism, we investigated the in vitro effect of ADMA on osteoblastic differentiation in mouse bone marrow-derived mesenchymal stem cells (BMSCs). METHODS: The effect of ADMA on nitric oxide (NO) production was determined by measuring the stable end product of NO, nitrite, in the culture medium using commercial NO kit. The temporal sequence of osteoblastic differentiation in BMSCs was assessed in the presence and absence of ADMA by measuring alkaline phosphatase (ALP) activity, mineralization, and osteoblast gene expression at 0, 4, 8, 12 days of culture. RESULTS: ADMA (5, 50, 500 micromol. L-1) resulted in a dose-dependent decrease in nitrite formation in conditioned media of BMCS cultures, consistent with inhibition of NOS. ADMA treatment was associated with reduced ALP activity, calcium deposition and osteoblast-related gene expression in BMSCs cultures. Concurrent treatment with l-arginine (3600 micromol. L-1) reversed the ADMA (500 micromol. L-1)-mediated decrease in NO production, restored the differentiation potential of BMSCs, and significantly attenuated the down-regulation of Cbfa1 and osteocalcin gene expression by ADMA. CONCLUSIONS: ADMA inhibition of the NO-NOS pathway in BMSCs impairs osteoblastic differentiation of mouse BMSC cultures. These studies further support a role of NO in the local regulation of bone metabolism and the possibility that ADMA may act as uremic toxin on bone through its effect to inhibit NO actions in osteoblasts.

Alkaline Phosphatase↗
PubMed2001

Population admixture: detection by Hardy-Weinberg test and its quantitative effects on linkage-disequilibrium methods for localizing genes underlying complex traits.

In association studies searching for genes underlying complex traits, the results are often inconsistent, and population admixture has been recognized qualitatively as one major potential cause. Hardy-Weinberg equilibrium (HWE) is often employed to test for population admixture; however, its power is generally unknown. Through analytical and simulation approaches, we quantify the power of the HWE test for population admixture and the effects of population admixture on increasing the type I error rate of association studies under various scenarios of population differentiation and admixture. We found that (1) the power of the HWE test for detecting population admixture is usually small; (2) population admixture seriously elevates type I error rate for detecting genes underlying complex traits, the extent of which depends on the degrees of population differentiation and admixture; (3) HWE testing for population admixture should be performed with random samples or only with controls at the candidate genes, or the test can be performed for combined samples of cases and controls at marker loci that are not linked to the disease; (4) testing HWE for population admixture generally reduces false positive association findings of genes underlying complex traits but the effect is small; and (5) with population admixture, a linkage disequilibrium method that employs cases only is more robust and yields many fewer false positive findings than conventional case-control analyses. Therefore, unless random samples are carefully selected from one homogeneous population, admixture is always a legitimate concern for positive findings in association studies except for the analyses that deliberately control population admixture.

Alleles↗
PubMed2001

An amplified fragment length polymorphism map of the silkworm.

The silkworm (Bombyx mori L.) is a lepidopteran insect with a long history of significant agricultural value. We have constructed the first amplified fragment length polymorphism (AFLP) genetic linkage map of the silkworm B. mori at a LOD score of 2.5. The mapping AFLP markers were genotyped in 47 progeny from a backcross population of the cross no. 782 x od100. A total of 1248 (60.7%) polymorphic AFLP markers were detected with 35 PstI/TaqI primer combinations. Each of the primer combinations generated an average of 35.7 polymorphic AFLP markers. A total of 545 (44%) polymorphic markers are consistent with the expected segregation ratio of 1:1 at the significance level of P = 0.05. Of the 545 polymorphic markers, 356 were assigned to 30 linkage groups. The number of markers on linkage groups ranged from 4 to 36. There were 21 major linkage groups with 7-36 markers and 9 relatively small linkage groups with 4-6 markers. The 30 linkage groups varied in length from 37.4 to 691.0 cM. The total length of this AFLP linkage map was 6512 cM. Genetic distances between two neighboring markers on the same linkage group ranged from 0.2 to 47 cM with an average of 18.2 cM. The sex-linked gene od was located between the markers P1T3B40 and P3T3B27 at the end of group 3, indicating that AFLP linkage group 3 was the Z (sex) chromosome. This work provides an essential basic map for constructing a denser linkage map and for mapping genes underlying agronomically important traits in the silkworm B. mori L.

Animals↗
PubMed2001

Population admixture may appear to mask, change or reverse genetic effects of genes underlying complex traits.

Association studies using random population samples are increasingly being applied in the identification and inference of genetic effects of genes underlying complex traits. It is well recognized that population admixture may yield false-positive identification of genetic effects for complex traits. However, it is less well appreciated that population admixture can appear to mask, change, or reverse true genetic effects for genes underlying complex traits. By employing a simple population genetics model, we explore the effects and the conditions of population admixture in masking, changing, or even reversing true genetic effects of genes underlying complex traits.

Genetics, Population↗
PubMed2001

Toward high-throughput genotyping: dynamic and automatic software for manipulating large-scale genotype data using fluorescently labeled dinucleotide markers.

To efficiently manipulate large amounts of genotype data generated with fluorescently labeled dinucleotide markers, we developed a Microsoft database management system, named. offers several advantages. First, it accommodates the dynamic nature of the accumulations of genotype data during the genotyping process; some data need to be confirmed or replaced by repeat lab procedures. By using, the raw genotype data can be imported easily and continuously and incorporated into the database during the genotyping process that may continue over an extended period of time in large projects. Second, almost all of the procedures are automatic, including autocomparison of the raw data read by different technicians from the same gel, autoadjustment among the allele fragment-size data from cross-runs or cross-platforms, autobinning of alleles, and autocompilation of genotype data for suitable programs to perform inheritance check in pedigrees. Third, provides functions to track electrophoresis gel files to locate gel or sample sources for any resultant genotype data, which is extremely helpful for double-checking consistency of raw and final data and for directing repeat experiments. In addition, the user-friendly graphic interface of renders processing of large amounts of data much less labor-intensive. Furthermore, has built-in mechanisms to detect some genotyping errors and to assess the quality of genotype data that then are summarized in the statistic reports automatically generated by. The can easily handle >500,000 genotype data entries, a number more than sufficient for typical whole-genome linkage studies. The modules and programs we developed for the can be extended to other database platforms, such as Microsoft SQL server, if the capability to handle still greater quantities of genotype data simultaneously is desired.

Alleles↗
PubMed2001

Is population bone mineral density variation linked to the marker D11S987 on chromosome 11q12-13?

Our purpose is to test linkage of human chromosome 11q12-13 to BMD variation. Chromosome 11q12-13 has been linked to three BMD-related phenotypes that are inherited as Mendelian traits in human pedigrees: an autosomal dominant high bone mass trait, autosomal recessive osteoporosis pseudoglioma, and autosomal recessive osteopetrosis. A sibling pair study with 374 sibships showed significant linkage of D11S987 to normal BMD variation, with a maximum logarithm of odds score of 3.5. However, a subsequent linkage study with a total of 595 sibling pairs demonstrated reduced significance for linkage of D11S987 to bone mineral density variation, with a logarithm of odds score less than 2.2. We genotyped five markers in a genomic region of approximately 27 cM centering on D11S987 and measured bone mineral density and other traits (weight, etc.) for 635 individuals from 53 human pedigrees. Each of these pedigrees was ascertained through a proband with bone mineral density Z-scores less than -1.28 at the hip or spine. Adjusting for age, sex, and weight as covariates, we performed two-point and multipoint linkage analyses using the variance component linkage analysis method implemented in Sequential Oligogenic Linkage Analysis Routines. We found little evidence of linkage of these five markers to bone mineral density at the spine, hip, wrist and total body bone mineral content. The maximum logarithm of odds score at these five markers was 0.25, and the maximum logarithm of odds score at D11S987 was 0.15. Therefore, although we cannot exclude the linkage of D11S987 region to bone mineral density variation, there is no evidence for linkage of the marker D11S987 on human chromosome 11q12-13 to bone mineral density variation in our study population.

Adult↗
PubMed2001

Characterization of genetic and lifestyle factors for determining variation in body mass index, fat mass, percentage of fat mass, and lean mass.

In this study, we simultaneously characterized genetic and lifestyle factors (exercise, smoking, and alcohol consumption) in determining variation in body mass index (BMI), fat mass, percentage of fat mass (PFM), and lean mass while adjusting for the effects of age and sex. Six hundred fifty-eight Caucasian individuals from 48 pedigrees were studied for BMI. Among these individuals, 289 from 38 pedigrees were studied for fat mass, PFM, and lean mass measured by dual X-ray absorptiometry (DXA). After adjusting for age, sex, and lifestyle factors, the heritabilities (h(2)) of BMI, fat mass, PFM, and lean mass ranged from 0.52 to 0.57 with associated standard errors ranging from 0.09 to 0.14. After accounting for significant sex and age effects, exercise had significant effects for all the phenotypes studied, and the effects of smoking and alcohol consumption were not significant. Therefore, significant proportions of variation in BMI, fat mass, PFM, and lean mass were under genetic control, and exercise had a significant effect in reducing BMI, fat mass, and PFM and in increasing lean mass. This study warrants further genetic linkage analyses to search for genes for the obesity-related phenotypes measured by DXA in our population.

Absorptiometry, Photon↗
PubMed2001

Role of calcitonin gene-related peptide in prostaglandins-mediated ischemic preconditioning in guinea pig hearts.

AIM: To examine the role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning induced by prostaglandins in isolated guinea pig hearts. METHODS: The isolated guinea pig hearts were perfused in a Langendorff model. The heart rate, coronary flow, left ventricular pressure, and its first derivatives (+/-dp/dt(max)) were recorded and the calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and 6-keto-PGF(1 alpha) were measured. RESULTS: Endothelin-1 (200 pmol in 1 mL K-H buffer) reduced the left ventricular developed pressure and its first derivatives (+/-dp/dt(max)), heart rate, and coronary flow. Preconditioning with two cycles of 5-min global ischemia and 5-min reperfusion attenuated endothelin-1 induced myocardial injury, and concentrations of both CGRP and 6-keto-PGF(1alpha) in the coronary effluent were markedly raised in the preconditioning periods. Pretreatment with capsaicin, which depletes endogenous CGRP, abolished the elevated level of CGRP concomitantly with loss of the cardioprotection induced by ischemic preconditioning. CGRP(8-37) (100 nmol/L), a selective CGRP1 receptor antagonist, also abolished the protective effects of ischemic preconditioning. After pretreatment with indometacin (10 micromol/L), an inhibitor of cyclooxygenase, the protective effects of ischemic preconditioning were abolished and the release of 6-keto-PGF1alpha was no longer elevated. Pretreatment with indometacin abolished the elevated level of CGRP in the coronary effluent. CONCLUSION: Endogenous prostaglandins are involved in the protective effects of ischemic preconditioning, and the beneficial effects of prostaglandins are mediated by CGRP in the guinea pig heart.

6-Ketoprostaglandin F1 alpha↗
PubMed2001

Involvement of calcitonin gene-related peptide in nitroglycerin induced improvement of preservation with cardioplegic solution.

AIM: To study improvement of preservation with cardioplegic solution induced by nitroglycerin was related to stimulation of calcitonin gene-related peptide (CG RP) release. METHODS: The isolated rat heart was arrested using St Thomas Hospital cardioplegic solution and then was reperfused with normothermic Krebs-Henseleit solution for 40 min after the 4-h hypothermic ischemic period. Hear t rate, coronary flow, left ventricular pressure (LVP), and its first derivative (+/- dp/dtmax) were recorded, and the calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and the release of creatine kinase (CK) were measured. RESULTS: Nitroglycerin (0.1 or 1 micro;mol/L) or CGRP (5 or 10 nmol/L) caused an improvement of cardiac function (LVP and +/- dp/dtmax) and a decrease in the release of creatine kinase during reperfusion. The protection induced by nitroglycerin was abolished by CGRP(8-37), the selective CGRP receptor antagonist, or pretreatment wit h capsaicin to deplete sensory nerves neurotransmitter content, but was unaltered by treatment w ith glibenclamide, the blocker of the ATP-sensitive potassium channel (KATP). The protection induced by exogenous CGRP was not also blocked by glibenclamide. Levels of CGRP-LI in the coronary effluent were significantly increased in the hearts treated with nitroglycerin. However, the elevated level of CGRP-LI by nitroglycerin was abolished by pretreatment with capsaicin. CONCLUSION: The improvement of preservation with cardioplegic solution induced by nitroglycerin was related to stimulation of CGRP release in the rat heart, and the effect is not related to the activation of the KATP channel.

Animals↗
PubMed2001

Role of calcitonin gene-related peptide in nitric oxide-mediated myocardial delayed preconditioning induced by head stress.

AIM: To study the role of calcitonin gene-related peptide (CGRP) in nitric oxide (NO)-mediated myocardial delayed preconditioning induced by heat stress. METHODS: The isolated rat heart was perfused in a Langendorff model. Hearts for all groups were subjected to 4 h hypothermia (4 degrees C) and 40 min reperfusion (37 degrees C). In the hyperthermia-treated group, rats were subjected to whole-body hyperthermia (rectal 42 degrees C, 15 min) 24 h before the experiment. Heart rate, coronary flow, left ventricular pressure, and its derivative (+/- dp/dtmax) were recorded, and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in plasma and the activity of creatine kinase (CK) in the coronary effluent were measured. RESULTS: Pretreatment with hyperthermia significantly improved the recovery of cardiac protection, reduced the release of CK, and increased plasma concentrations of CGRP. Pretreatment with L-NAME, an inhibitor of NOS, or capsaicin, which selectively depleted sensory neurotransmitter content, abolished the protective effects and the increased level of CGRP elicited by hyperthermia. CONCLUSION: Endogenous NO is involved in the cardioprotection afforded by heat stress, and the beneficial effects of NO are mediated by CGRP in the rat.

Animals↗
PubMed2000

Inhibition of cardiac tumor necrosis factor-alpha production by calcitonin gene-related peptide-mediated ischemic preconditioning in isolated rat hearts.

Previous investigations have demonstrated that calcitonin gene-related peptide (CGRP) plays an important role in the mediation of ischemic preconditioning in rats. In the present study, we examined signal transduction pathways of CGRP-mediated ischemic preconditioning. Thirty minutes of global ischemia and 40 min of reperfusion caused a dramatic decrease in myocardial function, and a significant increase in the release of cardiac creatine kinase in the coronary effluent and in the content of tumor necrosis factor-alpha (TNF-alpha) in myocardial tissues. However, ischemic preconditioning (three cycles of 5-min ischemia and 5-min reperfusion) or pretreatment with CGRP for 5 min dramatically improved the recovery of cardiac function, and reduced the release of cardiac creatine kinase and the TNF-alpha content. The effect of ischemic preconditioning was abolished by CGRP-(8-37), the selective CGRP receptor antagonist, and by capsaicin, which depletes sensory nerve neurotransmitter content, but was unaltered by treatment with glibenclamide, a blocker of the ATP-sensitive potassium (K(ATP)) channel. The protective effects of exogenous CGRP-induced preconditioning were also not blocked by glibenclamide. These results suggest that the cardioprotective effects afforded by CGRP-mediated ischemic preconditioning are related to inhibition of cardiac TNF-alpha production, but not to activation of the K(ATP) channel.

Animals↗
PubMed2000

Determination of bone mineral density of the hip and spine in human pedigrees by genetic and life-style factors.

In 40 human pedigrees with 563 subjects, we evaluated the contribution of genetic and life-style factors (exercise, smoking, and alcohol consumption) and the interactions between non-genetic factors in determining bone mineral density (BMD) of the hip and spine. In our analysis, we adjusted for age, weight, height, menopausal status in females, life-style factors, and the significant interactions among these factors. For the spine and hip BMD, heritabilities (h(2)) (+/- SE) were, respectively, 0.68 (0.21) and 0.86 (0.28) in males and 0.64 (0.13) and 0.67 (0.14) in females. Exercise had significant beneficial effects for male spine BMD and female hip BMD. Alcohol consumption experienced in our sample had significant beneficial effects on hip BMD in both sexes. Although the main effect of smoking was not significant, there were significant interaction effects between smoking and other important factors (e.g., exercise, weight, alcohol consumption). For example, for female spine BMD, exercise had significant beneficial effects in smokers; however, its effect in non-smokers was non-significant. This result indicates that exercise may reduce deleterious effects of smoking (if any) on BMD, but may have minor effects in increasing BMD in non-smokers. The various interaction effects among risk factors explicitly revealed here for the first time indicate that the detailed effects and direction of individual risk factors may depend on the presence and magnitude of other factors. Weight invariably affected BMD of the hip and spine in both sexes. Age effects were significant for hip BMD, but not for male spine BMD.

Alcohol Drinking↗
PubMed2000

Protective effects of calcitonin gene-related peptide on guinea-pig cardiac anaphylaxis.

Anaphylactic events occurring in cardiac tissues can result in cardiac dysfunction via vasoconstriction and arrhythmias. Calcitonin gene-related peptide (CGRP) is the most potent vasodilator and possesses anti-arrhythmic action. We examined the influence of CGRP on cardiac anaphylaxis in guinea-pigs. In the Langendorff-perfused heart of passively sensitized guinea-pigs, antigen challenge evoked a decrease in coronary flow, left ventricular pressure and its maximum first derivatives (+/-dP/dtmax) and an increased heart rate. Antigen challenge also induced atrioventricular conduction block. Treatment with CGRP (1 or 3 nM) significantly improved the recovery of cardiac function and reduced the incidence and duration of atrioventricular block without influencing the increased heart rate. Pretreatment with capsaicin caused effects similar to those of CGRP and markedly elevated the content of CGRP in coronary effluent. Ischaemic preconditioning, induced by two cycles each of 5 min global ischaemia and 5 min reperfusion, also improved cardiac function and raised the level of CGRP in coronary effluent. The protective effects of ischaemic preconditioning were abolished in the presence of the CGRP receptor antagonist CGRP8-37. Histamine release did not differ significantly during any of the interventions. The findings of the present study indicate that, in guinea-pig hearts, CGRP protects against cardiac anaphylaxis and that the cardioprotection by CGRP is independent of histamine release.

Anaphylaxis↗
PubMed2000

QTL fine mapping by measuring and testing for Hardy-Weinberg and linkage disequilibrium at a series of linked marker loci in extreme samples of populations.

It has recently been demonstrated that fine-scale mapping of a susceptibility locus for a complex disease can be accomplished on the basis of deviations from Hardy-Weinberg (HW) equilibrium at closely linked marker loci among affected individuals. We extend this theory to fine-scale localization of a quantitative-trait locus (QTL) from extreme individuals in populations, by means of HW and linkage-disequilibrium (LD) analyses. QTL mapping and/or linkage analyses can establish a large genomic region ( approximately 30 cM) that contains a QTL. The QTL can be fine mapped by examination of the degree of deviation from HW and LD at a series of closely linked marker loci. The tests can be performed for samples of individuals belonging to either high or low percentiles of the phenotype distribution or for combined samples of these extreme individuals. The statistical properties (the power and the size) of the tests of this fine-mapping approach are investigated and are compared extensively, under various genetic models and parameters for the QTL and marker loci. On the basis of the results, a two-stage procedure that uses extreme samples and different tests (for HW and LD) is suggested for QTL fine mapping. This two-step procedure is economic and powerful and can accurately narrow a genomic region containing a QTL from approximately 30-1 cM, a range that renders physical mapping feasible for identification of the QTL. In addition, the relationship between parameterizations of complex diseases, by means of penetrance, and those of complex quantitative traits, by means of genotypic values, is outlined. This means that many statistical genetic methods developed for searching for susceptibility loci of complex diseases can be directly adopted and/or extended to QTL mapping for quantitative traits.

Alleles↗
PubMed2000

Estimation of parameters of deleterious mutations in partial selfing or partial outcrossing populations and in nonequilibrium populations.

The Deng-Lynch method was developed to estimate the rate and effects of deleterious genomic mutations (DGM) in natural populations under the assumption that populations are either completely outcrossing or completely selfing and that populations are at mutation-selection (M-S) balance. However, in many plant and animal populations, selfing or outcrossing is often incomplete in that a proportion of populations undergo inbreeding while the rest are outcrossing. In addition, the degrees of deviation of populations from M-S balance are often not known. Through computer simulations, we investigated the robustness and the applicability of the Deng-Lynch method under different degrees of partial selfing or partial outcrossing and for nonequilibrium populations approaching M-S balance at different stages. The investigation was implemented under constant, variable, and epistatic mutation effects. We found that, generally, the estimation by the Deng-Lynch method is fairly robust if the selfing rate (S) is <0.10 in outcrossing populations and if S > 0.8 in selfing populations. The estimation may be unbiased under partial selfing with variable and epistatic mutation effects in predominantly outcrossing populations. The estimation is fairly robust in nonequilibrium populations at different stages approaching M-S balance. The dynamics of populations approaching M-S balance under various parameters are also studied. Under mutation and selection, populations approach balance at a rapid pace. Generally, it takes 400-2000 generations to reach M-S balance even when starting from homogeneous individuals free of DGM. Our investigation here provides a basis for characterizing DGM in partial selfing or outcrossing populations and for nonequilibrium populations.

Genetics, Population↗