Search PubMed⌕ Search

Biomedical subjects

Jia Li

Publications and source records attributed to Jia Li.

At least 73 records · Page 4Linked to original sources
PubMed2005

Genetic determinants of cardiovascular disease risk in familial hypercholesterolemia.

OBJECTIVE: To investigate the contribution of polymorphisms in multiple candidate genes to cardiovascular disease (CVD) risk in a large cohort of patients with heterozygous familial hypercholesterolemia (FH). METHODS AND RESULTS: We genotyped 1940 FH patients for 65 polymorphisms in 36 candidate genes. During 91.451 person-years, 643 (33.1%) patients had at least 1 cardiovascular event. Multifactorial Cox survival analysis revealed that the G20210A polymorphism in the prothrombin gene was strongly associated with a significantly increased CVD risk (GA versus GG; P<0.001). CONCLUSIONS: In a large cohort of FH patients, we found that the G20210A polymorphism in the prothrombin gene is strongly associated with CVD risk. Our results constitute a step forward in the unraveling of the hereditary propensity toward CVD in FH and might lead to better risk stratification and hence to more tailored therapy for CVD prevention.

Adult↗
PubMed2005

Inhibitors of type I MetAPs containing pyridine-2-carboxylic acid thiazol-2-ylamide. Part 1: SAR studies on the determination of the key scaffold.

Systematic SAR studies on the HTS hit pyridine-2-carboxylic acid thiazol-2-ylamide (PACT) analogues revealed that the scaffold of PCAT is indispensable for the inhibition of type I MetAP. For effective inhibition of the enzyme, the most suitable position to modify is the 3-position of the pyridine ring of PCAT, and the best substituents are those containing O or N atoms connected directly with the pyridine ring. These findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.

Amides↗
PubMed2005

Inhibitors of type I MetAPs containing pyridine-2-carboxylic acid thiazol-2-ylamide. Part 2: SAR studies on the pyridine ring 3-substituent.

Systematic SAR studies on the pyridine ring 3-substituent of PCAT, an inhibitor of EcMetAP1 and ScMetAP1, revealed that 3-substituents have different selectivity for EcMetAP1 and ScMetAP1. The selective inhibitors of type I MetAP are useful tools for investigating the detailed interactions between the enzymes and their inhibitors. In addition, these findings provide useful information for the design and discovery of more potent inhibitors of type I MetAPs.

Aminopeptidases↗
PubMed2005

Regulation of CHK2 by DNA-dependent protein kinase.

Chk2 is a critical mediator of diverse cellular responses to DNA damage. Activation of Chk2 by DNA damage requires phosphorylation at sites including Thr68. In earlier work, we found that an activity present in rabbit reticulocyte lysates phosphorylates and activates Chk2. We now find that hypophosphorylated Chk2 can be phosphorylated at Thr68 by various subcellular fractions of HEK293 cells. This activity is sensitive to the phosphatidylinositol 3'-kinase-like kinase inhibitor wortmannin, but not to caffeine. DNA enhances the Chk2 phosphorylation by cellular fractions in vitro. The wortmannin-sensitive Chk2 kinase activity is present in fractions from ATM-deficient cells. In contrast, Chk2 was not efficiently phosphorylated at Thr68 in vitro by fractions from cells with a defective DNA-dependent protein kinase (DNA-PK) catalytic subunit. Chk2 is phosphorylated by purified DNA-PK in vitro. Endogenous Chk2 coimmunoprecipitates Ku70 and Ku80. In a series of matched cell lines having and lacking functional DNA-PK, Chk2 activation by exposure of cells to ionizing radiation, or to camptothecin was consistently diminished in the absence of DNA-PK. Down-regulation of DNA-PK(cs) by either siRNA or a chemical inhibitor attenuated radiation-induced Chk2 phosphorylation. Ionizing radiation-induced Chk2 phosphorylation was wortmannin-sensitive in ATM-defective cells with depleted ATR. These results suggest that DNA-PK augments ATM and ATR in activation of Chk2 by DNA damage.

Androstadienes↗
PubMed2005

Activation of the WUS gene induces ectopic initiation of floral meristems on mature stem surface in Arabidopsis thaliana.

A gain-of-function Arabidopsis mutant was identified via activation tagging genetic screening. The mutant exhibited clustered ectopic floral buds on the surface of inflorescence stems. The mutant was designated as sef for stem ectopic flowers. Our detailed studies indicate that the ectopic flower meristems are initiated from the differentiated cortex cells. Inverse PCR and sequence analysis indicated that the enhancer-containing T-DNA from the activation tagging construct, SKI015, was inserted upstream of the previously cloned WUS gene encoding a homeodomain protein. Studies from RT-PCR, RNA in situ hybridization and transgenic plant analysis further confirmed that the phenotypes of sef are caused by the overexpression of WUS. Our results suggest that overexpression of WUS could trigger the cell pluripotence and reestablish a new meristem in cortex. The type of new meristems caused by WUS overexpression was dependent upon the developmental and physiological stages of a plant. With the help of some undefined factors in the reproductive organs the new meristems differentiated into floral buds. In a vegetative growth plant, however, only the new vegetative buds can be initiated upon the overexpression of WUS. These studies provide new insights of WUS on flower development.

Arabidopsis↗
PubMed2005

A tribute to Giancarlo Rastelli.

Giancarlo Rastelli (1933-1970) was a pioneer cardiac surgeon who developed a classification of atrioventricular canal and a novel surgical procedure that revolutionized the management of children with congenital heart disease. Rastelli lived a short, yet fascinating life. His work was ahead of its time and laid the foundation for the treatment of complex congenital cardiac anomalies.

Heart↗
PubMed2005

Mutations profile in Chinese patients with hypertrophic cardiomyopathy.

BACKGROUND: There are more than 1 million patients with hypertrophic cardiomyopathy (HCM) in China, but the genetic basis is presently unknown. METHODS: We investigated 100 independent patients with HCM (proband 51, sporadic 49) by sequencing the three most frequent HCM-causing genes (MYH7, MYBPC3, TNNT2). RESULTS: Thirty-four patients (34%) carried 25 types of mutations in the selected genes, most (14/25) were newly identified. MYH7 and MYBPC3 accounted for 41% and 18% of the familial HCM, respectively. TNNT2 mutations only caused 2% of the familial HCM. These results suggested that MYH7 and MYBPC3 were the predominant genes responsible for HCM, and TNNT2 mutation less proportionally contributed to Chinese HCM. MYH7 mutations caused HCM at younger age, more frequent syncope and ECG abnormalities compared with MYBPC3 mutations. The patients carrying R663C, Q734P, E930K in MYH7 and R130C in TNNT2 expressed malignant phenotype. R403Q in MYH7, the most common hot and malignant mutation in Caucasians, was not identified in Chinese. CONCLUSION: We confirmed the diversity of mutation profile in different populations and suggest that a global registry of HCM mutations and their phenotypes is necessary to correlate genotype with phenotype.

Adolescent↗
PubMed2005

Isovolumic but not ejection phase Doppler tissue indices detect left ventricular dysfunction caused by coronary stenosis.

BACKGROUND: Isovolumic acceleration (IVA) obtained by tissue Doppler echocardiography (TDE) is a sensitive and relatively load-independent index for assessing systolic ventricular function. IVA also has the ability to describe the force-frequency relationship during incremental atrial pacing in vivo. OBJECTIVE: We sought to assess the ability of IVA to detect global left ventricular (LV) dysfunction induced by coronary constriction. METHODS: In 6 open-chest anesthetized pigs we examined right ventricular and LV long-axis function by TDE (4-chamber view) with simultaneous invasive measurements of intraventricular pressure, maximum dP/dt, minimum dP/dt, and tau by microtip catheter. A pneumatic cuff was placed around the proximal portion of left anterior descending coronary artery (LAD) and distal flow was monitored by transonic flow probe. Mean arterial pressures were monitored by indwelling cannula. Baseline studies assessed force-frequency relationships with TDE and invasive measurements during incremental pacing from 100 to 200/min (20/min increments every 10 minutes). The protocol was repeated 10 minutes after balloon inflation to reduce LAD blood flow by 50%. RESULTS: Compared with baseline, LV pressure decreased significantly (P = .03, 2-way analysis of variance) as did maximum dP/dt (P < .004) with LAD constriction. At the same time IVA and isovolumic velocity at the LV free wall were significantly reduced (P < .002 and P = .04, respectively) and both IVA and isovolumic velocity were correlated with dP/dt (r = 0.45, P < .002, and r = 0.35, P < .02, respectively). TDE systolic indices were unchanged in the right ventricle. CONCLUSION: IVA detects changes in global LV systolic function during LAD constriction and may be a useful clinical tool to diagnose ischemia.

Animals↗
PubMed2005

The remote ischemic preconditioning stimulus modifies gene expression in mouse myocardium.

BACKGROUND: We have recently demonstrated that remote ischemic preconditioning reduces ischemia-reperfusion injury in animal models. The mechanisms by which the remote ischemic preconditioning stimulus exerts its effect remain to be fully defined, and its effect on myocardial gene expression is unknown. We tested the hypothesis that remote ischemic preconditioning modifies myocardial gene expression immediately after the remote ischemic preconditioning stimulus (early phase) and 24 hours later (late phase). METHODS: Twenty male (C57BL/6) 10- to 12-week-old mice were randomized into 4 groups: group 1 (control, early phase; n = 5), group 2 (remote ischemic preconditioning, early phase; n = 5), group 3 (control, late phase; n = 5), and group 4 (remote ischemic preconditioning, late phase; n = 5). Groups 2 and 4 underwent remote ischemic preconditioning induced by 6 cycles of 4 minutes of occlusion and 4 minutes of reperfusion of the femoral artery. Groups 1 and 2 were killed 15 minutes after completion of sham procedure or remote ischemic preconditioning, and the hearts were removed and frozen in liquid nitrogen. Groups 3 and 4 were killed 24 hours after remote ischemic preconditioning, and the hearts were harvested in the same fashion. Gene expression was assessed by using the Affymetrix MG-430A chip (Affymetrix, Santa Clara, Calif). RESULTS: Data filtering (P < .05, analysis of variance) and hierarchic 2-way clustering identified significant differences in gene expression among the 4 groups. Genes involved in protection against oxidative stress (eg, Hadhsc, Prdx4, and Fabp4) and cytoprotection (Hsp73) were upregulated, whereas many proinflammatory genes (eg, Egr-1 and Dusp 1 and 6) were suppressed. CONCLUSION: A simple remote ischemic preconditioning stimulus modifies myocardial gene expression by upregulating cardioprotective genes and suppressing genes potentially involved in the pathogenesis of ischemia-reperfusion injury.

Animals↗
PubMed2005

Genetic determinants of plasma HDL-cholesterol levels in familial hypercholesterolemia.

The objective of this study was to determine the extent to which common genetic variants can explain the variation of high-density lipoprotein cholesterol (HDL-C) plasma levels in familial hypercholesterolemia (FH). FH is characterized by elevated low-density lipoprotein cholesterol levels and premature cardiovascular disease (CVD). Although low HDL-C levels have been shown to affect the severity of the clinical phenotype, little is known about the factors that determine HDL-C levels in these patients. A cohort of 1002 heterozygous FH patients was genotyped for polymorphisms in the genes encoding for ATP-binding cassette transporter A1, apolipoprotein (apo) AIV, apoCIII, apoE, cholesteryl transfer ester protein, hepatic lipase, lipoprotein lipase, and two paraoxonases. Multiple linear regression showed that, together, these polymorphisms explain only 3.9% of the variation of HDL-C plasma levels. When significant two-way interactions between the polymorphisms were also taken into account, the explained variation rose to 12.5%. In a regression model that also incorporated sex, smoking, alcohol use, body mass index, and concomitant beta-blocker use as covariates, the explained variation of HDL-C plasma levels even increased to 32.5%. This study provides direct evidence that multiple, modestly penetrant, but highly prevalent, polymorphisms can explain a substantial part of the variation of HDL-C plasma levels in a representative large cohort of heterozygous FH patients.

ATP Binding Cassette Transporter 1↗
PubMed2005

PTP1B inhibitors from Ardisia japonica.

In bioassay-directed isolation from the whole plant of Ardisia japonica, sixteen known compounds: chrysophanol (1), physcion (2), oleanolic acid (3), euscaphic acid (4), tormentic acid (5), quercetin (6), quercitrin (7), myricitrin (8), kaempferol 3-O-alpha-L-rhamnopyranoside (9), cyclamiretin A 3-O-alpha--rhamnopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->2)-[beta-D-glucopyranosyl(1-->4)]-alpha-L-arabinopyranoside (10), (7E)-9-hydroxymegastigma-4, 7-dien-3-on-9-O-beta-D-glucopyranoside (11), bergenin (12), norbergenin (13), rutin (14), kaempferol 3,7-O-alpha-L-dirhamnopyranoside (15), (-)-epigallacatechin 3-O-gallate (16) were obtained. Compounds 1-5, 9, 11 and 14-16 have not been reported previously from this plant. Among these isolates, 2, 3, 6 and 12 showed moderate bioactivity against PTP1B in vitro with IC50 values of 121.50, 23.90, 28.12 and 157 microM, respectively.

Ardisia↗
PubMed2005

Furostanoside from Asparagus filicinus.

A new furostanoside, named aspafilioside D (1), together with the five known compounds officinalisnin-II (2), Asp-IV' (3), (+)-4'-O-methyl-nyasol (4), (+)-nyasol (5) and tormentic acid (6), have been isolated from the roots of Asparagus filicinus. The structure of 1 has been elucidated on the basis of spectral data.

Asparagus Plant↗
PubMed2005

Effect of carbon dioxide on systemic oxygenation, oxygen consumption, and blood lactate levels after bidirectional superior cavopulmonary anastomosis.

OBJECTIVE: We sought to assess the effects of four different CO2 tensions on systemic oxygenation, oxygen consumption, and arterial blood lactate levels early after bidirectional superior cavopulmonary anastomosis. DESIGN: Prospective study. SETTING: Quaternary pediatric cardiac critical care unit. PATIENTS: Nine children aged 2-23 months (median, 7 months). INTERVENTIONS: All patients were sedated, muscle relaxed, and mechanically ventilated. Baseline Paco2 was adjusted to 35 mm Hg by changing tidal volume. CO2 was added via the inlet port of the ventilator to maintain the Paco2 at 45 and 55 mm Hg. Measurements were repeated after discontinuing additional CO2 gas at a Paco2 of 40 mm Hg. Arterial blood gases and lactate were measured at each level of Paco2. We measured oxygen consumption continuously by respiratory mass spectrometry. MEASUREMENTS AND MAIN RESULTS: Mean (95% confidence interval) Paco2 increased from 35 (34-36) to 45 (44-46) to 55 (54-56) mm Hg (4.7 [4.5-4.9] to 6 [5.7-6.3] to 7.3 [7.2-7.4] kPa), arterial pH decreased from 7.43 (7.39-7.47) to 7.35 (7.31-7.39) to 7.28 (7.24-7.32). Pao2 increased from 36 (32-40) to 44 (40-48) to 50 (45-55) mm Hg (4.8 [4.3-5.3] to 5.9 [5.4-6.4] to 6.7 [6.2-7.2] kPa), and oxygen saturation increased from 72% (67-79%) to 77% (73-81%) to 80% (76-84%). Oxygen consumption decreased significantly, with each increase in Paco2, from 146 (125-167) to 132 (112-152) to 126 (107-145) mL.min.m (p = .0001), and lactate decreased from 1.5 (1-2.0) to 1.2 (0.8-1.6) to 0.8 (0.5-1.1) mmol/L (p < .01). These changes returned toward baseline at a Paco2 of 40 mm Hg. CONCLUSIONS: Moderate hypercapnia with respiratory acidosis improved arterial oxygenation and reduced oxygen consumption and arterial lactate levels, thus improving overall oxygen transport in children after bidirectional superior cavopulmonary anastomosis.

Carbon Dioxide↗
PubMed2005

Evidence for a significant myocardial contribution to total metabolic burden during hypothermic cardiopulmonary bypass: a study of continuously measured oxygen consumption and arterial lactate levels in pigs.

OBJECTIVE: We assessed the causes of imbalance of oxygen transport by continuously measuring oxygen consumption (VO2) during hypothermic cardiopulmonary bypass (CPB) in pigs. METHODS: Six pigs (17.2+/-1.6 kg) underwent hypothermic (32 degrees C) CPB for 180 min with 120 min of aortic crossclamping (ACC). An AMIS 2000 mass spectrometer was adapted for the on-line measurement of VO2. Arterial lactate was measured at the beginning of CPB, the end of hypothermia, before and 10 min after ACC release, 20 min later, and at the end of CPB. RESULTS: Arterial lactate increased from 1.8+/-0.7 to 5.1+/-1.8 mmol/L during CPB. Hypothermia reduced VO2 by 0.63+/-0.29 mlmin/kg per degrees C, but lactate increased to 4.2+/-1.5 mmol/L (p <0.05). The most rapid rise of VO2 and lactate occurred during the first 10 min after ACC removal, accounting for 26% and 68%, respectively, of the total rise during rewarming. CONCLUSIONS: Inadequate tissue oxygenation persists throughout hypothermic CPB. The rise in systemic VO2 and lactate immediately after ACC release may reflect inadequate oxygen transport within the myocardium during ischemia and manifest on reperfusion. This simple technique may be used to provide important information regarding the dynamic balance of systemic and myocardial oxygen transport during ischemia-reperfusion.

Animals↗
PubMed2005

Research of blastocyte-like structure in chicken.

The chicken embryo is a classic model used to investigate embryonic development, gene expression, and tissue differentiation, and is also an important research tool in studying the animal functional genomics. The whole blastoderms of fresh unincubated eggs from White Leghorn chickens were collected with a paper ring, mechanically broken into small pieces and cultured in medium. Then the small pieces would develop into blastocyte-like structures (BLS), which could be facilitated by an addition of fetal bovine serum (FBS) to the primary culture and their diameter was nearly doubled from 12 to 24 h. The additional yolk had no positive effect on the development in the first 12 h but encouraged the BLSs attaching and inner cells differentiating instead in 24 h. The inner cells of the BLS showing a high alkaline-phosphatase activity similar to those in mouse embryonic stem (ES) cells and also expressing a large amount of the specific stage embryonic antigen-1 (SSEA-1) on the surface, which was known to be the characteristic of non-differentiated mouse and avian ES cells, could finally differentiate into nerve-like cells, fibroblast cells and so on in the medium. Leukemia inhibitory factor (LIF) facilitated the cells' proliferation and prevented differentiation in the suspended culture of the BLSs. So we drew the conclusion that the BLS obtained from broken blastoderm can be used to amplify avian ES cells so as to initiate a new method of producing transgenic chickens.

Animals↗
PubMed2005

Electrochemical study of breast cancer cells MCF-7 and its application in evaluating the effect of diosgenin.

The electrochemical behavior of breast cancer cells was studied on a graphite electrode by cyclic voltammetry (CV) and potentiometric stripping analysis (PSA). In both cases, only one oxidative peak at approximately +0.75 V was observed. The peak area in PSA was used to study the growth of the cells and the effect of diosgenin on MCF-7 cells. The results showed that diosgenin can effectively inhibit the viability and proliferation of the breast cancer cells.

Antineoplastic Agents↗