Biomedical subjects

D G Chen

Publications and source records attributed to D G Chen.

At least 19 recordsLinked to original sources

PubMed2007

Dose-time-response cumulative multinomial generalized linear model.

In toxicological and pharmaceutical experiments, a type of quantal bioassay experiment is designed in which a response, such as mortality, in a group of animals is recorded over time points under different dose levels in the course of the experiment. The application of the typical logit and probit analyses is no longer valid in this situation because it neglects the dependency on time and also the possible interaction of time and dose concentration on the response in the experiment. In this paper, a dose-time-response model is proposed for this type of experiment and a cumulative multinomial generalized linear model that incorporates time and the other experimental conditions as covariates is developed by the theory of maximum likelihood estimation. Both the point estimator and confidence bands for ED50(t), the concentration of a toxicant that will kill 50% of the animals by a specific time, t; as well as LT50(d), the time to 50% mortalities for a specific concentration, d, is then formulated in closed form from the newly proposed dose-time-response model. Finally, the newly proposed model is considered for a real data set to demonstrate the application.

Algorithms↗

PubMed2000

[Study of helical CT low-contrast resolution and its influencing factors].

This paper studies the helical CT low-contrast resolution and its influencing factors by experimental analysis. The CT low-contrast resolution increased with mA, kV, slice thickness, scan time and FOV, and decreased with matrix, pitch and thickness of the scanned objective. The reconstruction algorithm of high resolution results lower low-contrast resolution. Mostly helical image low-contrast resolution is slightly lower than axial image. It's very important for us to understand CT low-contrast resolution and its influencing factors for the correct evaluation of the performance of CT scanner.

Algorithms↗

PubMed1999

Empirical Bayes estimation for combinations of multivariate bioassays.

This article presents a new empirical Bayes estimator (EBE) and a shrinkage estimator for determining the relative potency from several multivariate bioassays by incorporating prior information on the model parameters based on Jeffreys' rules. The EBE can account for any extra variability among the bioassays, and if this extra variability is 0, then the EBE reduces to the maximum likelihood estimator for combinations of multivariate bioassays. The shrinkage estimator turns out to be a compromise of the prior information and the estimator from each multivariate bioassay, with the weights depending on the prior variance.

Algorithms↗

PubMed1999

Effects of perindopril, propranolol, and dihydrochlorothiazide on cardiovascular remodelling in spontaneously hypertensive rats.

AIM: To investigate the effects of perindopril, propranolol, and dihydrochlorothiazide on artery wall thickening, left ventricular hypertrophy, and cardiac fibrosis in spontaneously hypertensive rats (SHR). METHODS: After measurement of systolic blood pressure (SBP), 16-wk-old Male SHR were randomly divided into 3 groups (each n = 10), given perindopril (Per, 5 mg.kg-1.d-1), propranolol (Pro, 40 mg.kg-1.d-1), dihydrochlorothiazide (DCT, 100 mg.kg-1.d-1) respectively by gavage for 12 wk. Sex-, age-, and number-matched untreated SHR and normotensive Wistar Kyoto rats (WKY) served as controls. When the treatment finished, body weights (BW) and SBP were measured before decapitation of the rats. The heart was excised rapidly, the left ventricle was weighed and then subjected to collagen content analysis. Vascular wall and lumen ratio from aorta, renal arteries and branch III vessels of mesenteric arteries were determined morphometrically. RESULTS: Treated rats in 3 groups showed a lower SBP and the ratio of left ventricle weight to body weight (LVW/BW) compared with WKY. Artery wall thickening was similarly inhibited in the treated groups. Per and Pro inhibited cardiac fibrosis, but collagen concentration increased in DCT treated SHR [collagen volume fraction (CVF): 19 +/- 4 vs SHR 14 +/- 4, P < 0.05; perivascular collagen fraction(PVCF): 84 +/- 7 vs SHR 79 +/- 5, P < 0.05]. CONCLUSION: Per and Pro inhibited, but DCT promoted, cardiac fibrosis.

Adrenergic beta-Antagonists↗

PubMed1998

A nonlinear isobologram model with Box-Cox transformation to both sides for chemical mixtures.

The linear logistical isobologram is a commonly used and powerful graphical and statistical tool for analyzing the combined effects of simple chemical mixtures. In this paper a nonlinear isobologram model is proposed to analyze the joint action of chemical mixtures for quantitative dose-response relationships. This nonlinear isobologram model incorporates two additional new parameters, Ymin and Ymax, to facilitate analysis of response data that are not constrained between 0 and 1, where parameters Ymin and Ymax represent the minimal and the maximal observed toxic response. This nonlinear isobologram model for binary mixtures can be expressed as [formula: see text] In addition, a Box-Cox transformation to both sides is introduced to improve the goodness of fit and to provide a more robust model for achieving homogeneity and normality of the residuals. Finally, a confidence band is proposed for selected isobols, e.g., the median effective dose, to facilitate graphical and statistical analysis of the isobologram. The versatility of this approach is demonstrated using published data describing the toxicity of the binary mixtures of citrinin and ochratoxin as well as a new experimental data from our laboratory for mixtures of mercury and cadmium.

Algorithms↗

PubMed1998

Inhibitory effects of captopril on c-myc expression during left ventricular hypertrophy.

AIM: To study the molecular mechanism of captopril (Cap) on the inhibition of left ventricular hypertrophy (LVH), disclose the expression and distribution of c-myc in different cell types in left ventricle (LV) in spontaneously hypertensive rats (SHR). METHODS: Cap 100 mg.kg-1.d-1 was given p.o. to SHR. Systolic blood pressure (SBP), left ventricular weight (LVW), and body weight (BW) were measured at 16-wk old. The level of angiotensin II (Ang II), c-myc mRNA, and oncoprotein were determined by immunohistochemical method, Northern blot, and Western blot, respectively. RESULTS: Cap reduced SBP, LVW/BW in SHR, with a decrease of Ang II and c-myc expression in LV. Local cardial Ang II mainly distributed in cardiomyocytes. Cap inhibited cardial Ang II production and c-myc expression (histochemical staining intensity index, 0.49 +/- 0.04 vs 0.83 +/- 0.24, P < 0.01). The c-myc oncoprotein was prevailingly located in cardiac fibroblasts. The c-myc oncoprotein in Cap treated SHR was lower than that of WKY. CONCLUSION: High expression of c-myc in fibroblasts played an important role in the development of LVH in SHR. Inhibitory effects of Cap on LVH was associated with a decreased myocardial Ang II and interstitial fibroblasts c-myc expression. The c-myc oncoprotein post-transcriptional translation was also interrupted by Cap.

Angiotensin II↗

PubMed1996

Disparate effects of captopril on hypertension and blood vessel.

AIM: To study whether the effect of captopril (Cap) on vascular structure and function may be seperated from its effect on blood pressure. METHODS: Captopril treatment (group Cap A and B, 20 and 100 mg.kg-1.d-1) was given to SHR rats during pregnancy, weaning, and up to 16 wk of age. Study performed at 40 wk. Blood pressure (BP) was measured by tail-cuff sphygmomanometer, and wall/lumen ratio of mesenteric artery 3rd grade branch was assessed by morphometric assay. Resistance vessel properties were determined by hindquarter perfusion pressure responses to incremental doses of phenylephrine, in the presence of N omega nitro-L-arginine methyl ester (L-NAME) or the L-arginine, the precursor of nitric oxide synthesis. RESULTS: Both doses of Cap prevented hypertrophy of blood vessels to an extent comparable to that of the untreated WKY rats (wall/lumen ratio of mesenteric artery, Cap A: 0.38 +/- 0.08, Cap B: 0.29 +/- 0.05 vs WKY: 0.34 +/- 0.11, P > 0.05, respectively). The parameters derived from hindquarter perfusion pressure curves in Cap treated group were almost identical to that of WKY, significantly different from that of untreated SHR (EC50, Cap B 4.05 +/- 2.58 vs SHR 1.15 +/- 0.96 mL.L-1, P < 0.01; vs WKY 5.13 +/- 1.97 mL.L-1, P > 0.05). Addition of L-NAME or L-arginine in the perfusate augmented or attenuated the vasoconstriction responses in the Cap treated group. CONCLUSION: Cap initiated from intrauterine period normalized the vascular structure and vasoconstrictive responses in SHR when BP still sustained at a higher level vs WKY.

Animals↗

PubMed1996

Effect of chronic captopril treatment on circulating and tissue renin-angiotensin system in SHR rats.

AIM: To study the effect of captopril treatment and its withdrawal on the circulating and tissue peptidyl-dipeptidase A, angiotensinogen (AGT), and angiotensin II (A II), in relation to left ventricular hypertrophy (LVH) and systolic blood pressure (SBP). METHODS: SHR male rats were given captopril 100 mg.kg-1.d-1 [SHRcap, number (n) = 43] orally in mixture with milk powder as vehicle from intrautero period of 16 wk of age. Rats were killed at 16 (n = 19) and 40 (n = 24) wk of age, respectively. Male, age-matched untreated SHR and WKY rats served as controls. SBP, left ventricular mass/body weight (LVM/BW) ratio, left ventricular (LV) myocardium and plasma A II concentration, aortic and serum peptidyl-dipeptidase A activity, AGT mRNA level in kidney and liver, renal renin mRNA level were determined. RESULTS: Captopril treatment decreased SBP and reduced LVM/BW at 16 and 40 wk of age, and persistently inhibited LV myocardium A II, aortic peptidyl-dipeptidase A activity, and AGT gene expression in kidney even after the treatment was removed. Nevertheless, no changes were found in plasma A II concentration, serum peptidyl-dipeptidase A activity, and AGT mRNA level in liver by captopril therapy. Renal renin mRNA level was low in SHR and WKY rats, but it was increased by captopril treatment. Tissue renin-angiotensin system (RAS) such as AGT mRNA in kidney, aortic peptidyl-dipeptidase A activity, and LV myocardium A II, rather than circulating RAS (AGT mRNA in liver, renin mRNA in kidney, serum peptidyl-dipeptidase A activity and plasma A II), were persistently inhibited by early captopril treatment, even after the withdrawal of the treatment. CONCLUSION: The long-term inhibition of tissue RAS is one of the mechanisms of the persistent hypotensive effect of captopril treatment.

Angiotensin II↗

PubMed1995

Mechanisms responsible for sustained hypotension after captopril treatment.

OBJECTIVE: To investigate new aspects of the relationship between sustained reduction of blood pressure and alteration of cardiovascular structure and function after cessation of early captopril treatment. METHODS: Spontaneously hypertensive rats (SHR) were given captopril 20 mg/kg per day (n = 13) or 100 mg/kg per day (n = 12) from the intra-uterine period to age 16 weeks and then the treatment was stopped. Age-matched untreated SHR (n = 16) and Wistar-Kyoto (WKY) rats (n = 17) served as controls. The experiments were carried out at 40 weeks. RESULTS: Withdrawal of captopril treatment resulted in a rapid rebound of SBP to a level close to that of untreated SHR in the low-dose group, whereas a persistently lower SBP was maintained in the high-dose group. Both doses of captopril treatment completely prevented wall hypertrophy either of arteriolar resistance vessels or of muscular vessels. Captopril decreased left ventricular mass:body weight ratio dose-dependently. High-dose captopril improved the resting and stress systolic and diastolic function. Thoracic angiotensin converting enzyme levels were dose-dependently reduced by captopril treatment. The curves of perfusion pressure response to incremental doses of phenylephrine shifted to the right in both captopril treatment groups compared with those of the control SHR. Addition of L-NAME and L-arginine to the perfusate augmented or attenuated the vasoconstrictor activity in all of the rats, whereas high-dose captopril totally restored the abnormal hypersensitivity to L-NAME and caused less attenuation in response to L-arginine in the control SHR. CONCLUSIONS: The persistent lower blood pressure caused by early captopril treatment was ascribed mainly to its sustained normalization of structure and function of resistance vessels, which may be partly mediated by the improvement of endothelial cell function. The persistent reduction of angiotensin converting enzyme activity in blood vessel wall attenuated left ventricular hypertrophy, and the improvement of cardiac systolic and diastolic function may also contribute to the sustained hypotensive effect.

Animals↗

PubMed1995

Inhibition of left ventricular hypertrophy and expression of proto-oncogenes c-myc other than c-fos in myocardium by early captopril treatment in SHR rats.

AIM: To explore the mechanisms by which angiotensin converting enzyme inhibitor (ACEI) prevents the development of left ventricular hypertrophy (LVH). METHODS: Captopril (Cap 100 mg.kg(-1).d(-1)) was given orally to male spontaneously hypertensive rats from intrauterine period to 16 wk of age. Experiments were performed at 40 wk of age. SBP, left ventricular weight to body weight ratio (LVW/BW) were assessed. The levels of c-myc and c-fos mRNA in the left ventricle were measured by Northern blot. RESULTS: Early-onset Cap therapy significantly decreased SBP. After discontinuance of treatment for 24 wk, SBP of SHRcap was still maintained at a lower level. LVW/BW in SHRcap was markedly reduced. The expression of myocardial c-myc mRNA was decreased by 72% in SHRcap compared with that in the untreated SHR, but the expression of myocardial c-fos mRNA was not different between the untreated SHR, SHRcap, and WKY rats. CONCLUSION: Early Cap treatment may permanently prevent the development of hypertension, inhibit LVH. Furthermore, the prevention of LVH is associated with a decrease in c-myc mRNA levels, and the development and regression of left ventricular hypertrophy may be irrelevant to c-fos expression.

Animals↗

PubMed1995

[Mechanism of inhibition in left ventricular hypertrophy by captopril treatment in spontaneously hypertensive rats].

To explore the mechanisms by which angiotensin converting enzyme inhibitor (ACEI) prevents the development of left ventricular hypertrophy (LVH), captopril (Cap 100 mg.kg-1/d was administered orally to male spontaneously hypertensive rats from intrauterine period to 16 weeks of age. Male and age-matched untreated WKY rats and SHR were used as controls. Experiments were performed at 40 weeks of age. SBP, left ventricular weight to body weight ratio (LVW/BW), myocardial hydroxyproline (Hypro) and norepinephrine (NE) were determined. The levels of c-myc and c-fos mRNA in the left ventricle were measured by Northern blot. Early-onset Cap therapy significantly decreased SBP at 16 weeks of age. After discontinuance of treatment for 24 weeks, SBP of SHRcap was still maintained at a level lower than that of untreated SHR. LVW/BW and Hypro in SHR cap were markedly reduced. The expression of myocardial c-myc mRNA (n = 5) was decreased by 72% in SHRcap compared with that in the untreated SHR, but the expression of c-fos mRNA (n = 7) and NE was not different between the untreated SHR, SHRcap and WKY rats. These results indicate that early Cap treatment may permanently prevent the development of hypertension, inhibit myocardial hypertrophy (MH), and interstitial fibrosis. Furthermore, the prevention of MH is associated with a decrease in myocardial c-myc mRNA levels, and the development and regression of MH may be irrelevant to proto-oncogene c-fos expression.

Animals↗

PubMed1995

[Relationship between CENP-B gene expression and the cell cycle].

The centromere/kinetochore is a specialized structure at the primary constriction of mammalian chromosomes. It participates in and is necessary for the mitotic chromosome movement. Centromere Protein B(CENP-B) is a highly conserved protein located at the centromere/kinetochore region. In this article, we explore the relationship between CENP-B expression and cell proliferation. HeLa cells were synchronized at different phases of the cell cycle and the synchronized cells were examined by flow cytometry and 3H-TdR labelling. ACA immunostaining showed the discrete single spots in nuclei of the cells at G1 and S phase, and spots in pairs mostly in those at G2 phase. Dot blot and Northern blot indicated that CENP-B gene was expressed at all phases of the cell cycle, but the expression level very much different with the highest at G2 phase and the lowest at S phase. Interestingly relatively high expression of CENP-B gene was also found in M phase, showing the continuity of the CENP-B gene expression during the cell cycle. This continuity implies a possibility that the assembly of the new centromere/kinetochore can not occur until centromere proteins reach a critical concentration when cells enter S phase and G 2 phase. Also, the continuous expression of centromere proteins may be necessary for the centromere/kinetochore function. In addition, the relationship between CENP-B gene expression and the nuclear skeleton was investigated. The nuclear skeleton-associated DNA extracted after Bam HI digestion were hybridized with 32P-labelled cDNA of CENP-B gene by means of Southern blot technique. The results that there stronger positive hybridization reaction in G 2 phase than in S phase indicated that CENP-B gene was more closely associated with the nuclear skeleton in G 2 phase cells than in S phase cells, which was in consistence with the level of the CENP-B gene expression at G 2 and S phase cells.

Autoantigens↗

PubMed1994

Effects of captopril and clonidine on resting and stress cardiac performance of left ventricle in spontaneously hypertensive rats.

Captopril (Cap) 20 mg.kg-1.d-1 and clonidine (Clo) 300 micrograms.kg-1.d-1 were given po to SHR from their parents mating day to 24 wk of age, with untreated, age-matched SHR and WKY as controls. Stress cardiac function was assessed by the development of LVdp/dtmax in response to incremental pressure load (phenylephrine, Phe) and volume load (dextran, Dex). The slope of delta HR/delta MAP relationship curve was used as an index of baroceptor sensitivity. Results showed that both Cap and Clo caused decreases in BP in SHR. Cap not only reduced markedly the left ventricular mass/body weight (LVM/BW), (mg.g-1, 2.7 +/- 0.4 vs SHR 3.5 +/- 0.3, P < 0.01), but also normalized the LVdp/dtmax, -LVdp/dtmax, T value, and the stress cardiac function. Clo neither decreased the LVM/BW (mg.g-1, 3.4 +/- 0.5 vs SHR 3.5 +/- 0.3, P > 0.05), nor improved the resting and stress cardiac function. The results suggested that attenuation of the left ventricular hypertrophy (LVH) is beneficial not only to the resting but also stress cardiac performance.

Animals↗

PubMed1994

Sympatholytic effect of captopril in regression of cardiovascular remodeling in spontaneously hypertensive rats.

Fifty-eight spontaneously hypertensive rats (SHR) at 12 wk of age were divided into 3 groups: A) captopril (Cap) 20 mg.kg-1.d-1; B) clonidine (Clo) 30 micrograms.kg-1.d-1; C) Clo 30 micrograms.kg-1.d-1 + Cap 20 mg.kg-1.d-1 orally for 24 wk. Concomitant administration of Cap and Clo did not result in more lowering of the systolic blood pressure (SBP) than that by Cap alone. Regression of left ventricular hypertrophy (LVH) were remarkable in Groups A and C, but not to the extent in that of WKY. No significant difference between these two groups was found. Cap alone resulted in a greater decrease of myocardial norepinephrine (NE) than that of Groups B and C. The wall/lumen ratio and the number of smooth muscle cell (SMC) layers of renal artery decreased in Groups A and C, but little difference was found between them. It seemed that combined blockade of renin-angiotensin-aldosterone (RAA) system and sympathetic nervous system (SNS) did not produce more significant BP reduction and reversal of cardiovascular remodeling than Cap alone did. The sympathetic inhibitory effect of angiotensin converting enzyme inhibitor (ACEI) was not enhanced by sympatholytic treatment.

Animals↗

PubMed1993

Increased pressor responsiveness of femoral arteries to exogenous norepinephrine in renal hypertensive dogs mediated through alpha 2 adrenoceptors.

Changes of perfusion pressure induced by femoral arterial perfusion of norepinephrine (NE) were studied in renal hypertensive dogs made with the method of wrapping both kidneys. The NE threshold dose which induced perfusion pressure increase was lower in hypertensive dogs than that in normotensive dogs. The NE pressor response in low concentration (1, 2, 10 ng.kg-1) was increased in hypertensive dogs, after alpha 2 adrenoceptors antagonized by idazoxan this increased response had been eliminated. These suggested that increased vasoconstriction by exogenous NE in hypertensive dogs was mediated through the increased reactivity of postsynaptic alpha 2 adrenoceptors to NE.

Adrenergic alpha-Antagonists↗

PubMed1993

[Possible involvement of atrial natriuretic factor and vasopressin in antihypertensive mechanism of clonidine in humans].

To appreciate the role of some neuropeptides in the antihypertensive mechanism of clonidine, 17 patients with essential hypertension were given po clonidine 150 micrograms tid for 3 d. Plasma atrial natriuretic factor (ANF), vasopressin (Vas), and dynorphin A (Dyn A) were measured by radioimmunoassay. After the treatment, mean blood pressure (MBP), heart rate and 24 h urine norepinephrine, epinephrine were decreased, but no change was found in plasma Dyn A. The magnitudes of increased ANF and decreased Vas were correlated with the decreased MBP (r = -0.57 and 0.53, respectively, P < 0.05). These results suggest that both ANF and Vas are involved in the antihypertensive mechanism of clonidine.

Adult↗

PubMed1993

[Effects of clonidine on estrus, estradiol, gonadotropin, graafian follicle, and corpus luteum in rats].

Effects of clonidine (Clo) on female reproductive system were studied in rats. Blood FSH, LH, progesterone, testosterone, and estradiol were measured by radioimmunoassay and the development of secondary follicles and corpus luteum in ovary were investigated by morphometry. After Clo po 0.3 mg.kg-1.d-1 x 14 d, the estrus of rats was prolonged; FSH, LH, and progesterone increased significantly; while estradiol reduced. The development of secondary follicles in ovary was blocked at the stage of prematuration and the numerical density of corpus luteum decreased. After clonidine po 28 d, FSH and LH sustained at high levels, but the estrous cycle, estradiol and progesterone recovered.

Animals↗

PubMed1992

A point mutation in the MyoD basic domain imparts c-Myc-like properties.

MyoD and c-Myc, members of the large "basic-helix-loop-helix" family of proteins, regulate diverse aspects of both normal and neoplastic growth and specific gene regulation. These two proteins differ at 9 of the 14 amino acids that comprise the basic domains necessary for DNA binding and transcriptional control. Individual amino acids in the MyoD basic domain were mutated to those found at the analogous positions in c-Myc. Four classes of mutants were obtained: (i) those with no effects on MyoD-site binding or activation of MyoD-responsive genes, (ii) those with no effect on MyoD-site binding but with a loss of activation potential, (iii) those with a loss of both DNA binding and activation potential, and (iv) one mutant (mut 9, Leu122----Arg) that left MyoD-site binding unaffected but imparted a new c-Myc-site binding capability. mut 9 competed with wild-type protein for the activation of MyoD-responsive reporter genes but could, like c-Myc, also suppress the adenovirus major-late promoter, which contains a c-Myc binding site. Our studies thus identify specific amino acid residues in the MyoD basic domain that are important for its activity as a DNA-binding transcriptional activator. Most significantly, our results with mut 9 indicate that Leu122 of MyoD is a critical determinant of specific DNA binding and that mutation at this residue can alter this specificity.

Amino Acid Sequence↗