PubMed Health⌕ Search

Biomedical subjects

Xiaofei Wang

Publications and source records attributed to Xiaofei Wang.

47 records · Page 3Linked to original sources
PubMed2003

Overexpression of lipoprotein lipase in transgenic Watanabe heritable hyperlipidemic rabbits improves hyperlipidemia and obesity.

Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of the triglyceride-rich lipoproteins and plays a critical role in lipoprotein and free fatty acid metabolism. Genetic manipulation of LPL may be beneficial in the treatment of hypertriglyceridemias, but it is unknown whether increased LPL activity may be effective in lowering plasma cholesterol and improving insulin resistance in familial hypercholesterolemic patients. To test the hypothesis that stimulation of LPL expression may be used as an adjunctive therapy for treatment of homozygous familial hypercholesterolemia, we have generated transgenic (Tg) Watanabe heritable hyperlipidemic (WHHL) rabbits that overexpress the human LPL transgene and compared their plasma lipid levels, glucose metabolism, and body fat accumulation with those of non-Tg WHHL rabbits. Overexpression of LPL dramatically ameliorated hypertriglyceridemia in Tg WHHL rabbits. Furthermore, increased LPL activity in male Tg WHHL rabbits also corrected hypercholesterolemia (544 +/- 52 in non-Tg versus 227 +/- 29 mg/dl in Tg, p < 0.01) and reduced body fat accumulation by 61% (323 +/- 27 in non-Tg versus 125 +/- 21ginTg, p < 0.01), suggesting that LPL plays an important role in mediating plasma cholesterol homeostasis and adipose accumulation. In addition, overexpression of LPL significantly suppressed high fat diet-induced obesity and insulin resistance in Tg WHHL rabbits. These results imply that systemic elevation of LPL expression may be potentially useful for the treatment of hyperlipidemias, obesity, and insulin resistance.

Adipose Tissue↗
PubMed2003

How do statistical properties influence findings of tracking (maintenance) in epidemiologic studies? An example of research in tracking of obesity.

There is great interest in studying the tracking (maintenance) of health conditions and risk factors over the life span. Tracking is often defined as the maintenance of a distribution position (e.g., quintile or percentile) in a study population over time. This study investigated how statistical properties might influence research findings of tracking with a special attention on the tracking of extreme ranking. Our results show that when repeated measures over time were positively correlated, the probability of tracking in extreme rankings was greater than other rankings and this was closely influenced by the overall correlation (r) and by the categorization. For example, when r = 0.4, 38% remained in the bottom and upper quintile (Q1, Q5) respectively, while only 22% remained in the middle quintile (Q3); when r = 0.8, the figure became 65% vs. 32%. When r = 0.4 and 0.8, 19 and 50% remained in the upper 95th percentile (or under the 5th percentile), respectively. Our real data show that children in the upper body mass index (= weight(kg)/height(m)(2)) quintile were more likely to maintain their ranking (54%) than others (about 30%), but not significantly higher than the expected (47%, p > 0.05). In conclusion, the overall correlation should be considered when studying tracking. Our proposed methods and predicted probabilities of tracking can help test whether one's observed tracking patterns are different from the statistically predicted ones.

Body Mass Index↗
PubMed2003

Oxidative damage to human lens epithelial cells in culture: estrogen protection of mitochondrial potential, ATP, and cell viability.

PURPOSE: Epidemiologic studies demonstrate a higher incidence of cataracts in estrogen-deprived postmenopausal women, but the mechanism for the increased risk of cataracts is unclear. An elevated level of H(2)O(2) in aqueous humor and whole lenses has been associated with cataractogenesis. In the present study, for the first time, the protective effect of estrogens against oxidative stress were tested in cultured human lens epithelial cells (HLECs). METHODS: To investigate the involvement of 17beta-estradiol (17beta-E(2)) in protection against oxidative stress, HLECs were exposed to insult with H(2)O(2) at a physiological level (100 microM) over a time course of several hours, with and without pretreatment with 17beta-E(2). Cell viability was measured by calcein AM assay, and 2',7'-dichlorofluorescein diacetate (DCFH-DA) was used to determine intracellular reactive oxygen species (ROS). Intracellular adenosine triphosphate (ATP) level was quantified with a luciferin- and luciferase-based assay and mitochondrial potential (deltapsi(m)) was monitored by a fluorescence resonance energy-transfer technique. RESULTS: H(2)O(2) caused a dose-dependent decrease in mitochondrial membrane potential, intracellular ATP levels, and cell viability. Dose-dependent increases in cell viability and intracellular ATP level were observed with pretreatment of 17beta-E(2) for 2 hours before oxidative insult. At 1 nM, 17beta-E(2) increased cell viability from 39% +/- 4% to 75% +/- 3%, and at 100 nM or higher, it increased survival to greater than 95%. The level of intracellular ATP approached normal with 17beta-E(2) at 100 nM or higher. Pretreatment with 17beta-E(2) did not diminish intracellular ROS accumulation after exposure to H(2)O(2). Moreover, two nonfeminizing estrogens, 17alpha-E(2) and ent-E(2), both of which do not bind to either estrogen receptor alpha or beta, were as effective as 17beta-E(2) in the recovery of cell viability. The estrogen receptor antagonist, ICI 182,780, did not block protection by 17beta-E(2). Both 17beta- and 17alpha-E(2) moderated the collapse of deltapsi(m) in response to either H(2)O(2) or excessive Ca(2+) loading. CONCLUSIONS: The present study indicates that both 17alpha- and 17beta-E(2) can preserve mitochondrial function, cell viability, and ATP levels in human lens cells during oxidative stress. Although the precise mechanism responsible for protection by the estradiols against oxidative stress remains to be determined, the ability of nonfeminizing estrogens, which do not bind to estrogen receptors, to protect against H(2)O(2) toxicity indicates that this conservation is not likely to be mediated through classic estrogen receptors.

Adenosine Triphosphate↗
PubMed2002

Mycoplasma genitalium infections in asymptomatic men and men with urethritis attending a sexually transmitted diseases clinic in New Orleans.

We report the results of a study of Mycoplasma genitalium (detected with a modified polymerase chain reaction [PCR] assay) in men with urethritis and in asymptomatic control subjects at a sexually transmitted diseases clinic in New Orleans. Data for 97 men with urethritis and 184 asymptomatic men were available for analysis. M. genitalium infection rates in symptomatic and asymptomatic men who were negative for Chlamydia trachomatis and Neisseria gonorrhoeae were 25% and 7%, respectively (P=.006). M. genitalium coinfection rates among men with chlamydial and gonococcal urethritis were 35% and 14%, respectively. Men with M. genitalium urethritis resembled those with C. trachomatis in that both groups were younger and more likely to experience milder urethral symptoms. Among men with urethritis, the sensitivities of PCR of urine and swab specimens for the detection of M. genitalium were 87% and 91%, respectively. M. genitalium is associated with nongonococcal urethritis in this population.

Adolescent↗
PubMed2002

Lipoprotein(a) enhances advanced atherosclerosis and vascular calcification in WHHL transgenic rabbits expressing human apolipoprotein(a).

High lipoprotein(a) (Lp(a)) levels are a major risk factor for the development of atherosclerosis. The risk of elevated Lp(a) concentration is increased significantly in patients who also have high levels of low density lipoprotein (LDL) cholesterol. To test the hypothesis that increased plasma levels of Lp(a) may enhance the development of atherosclerosis in the setting of hypercholesterolemia, we generated Watanabe heritable hyperlipidemic (WHHL) transgenic (Tg) rabbits expressing human apolipoprotein(a) (apo(a)). We report here that Tg WHHL rabbits developed more extensive advanced atherosclerotic lesions than did non-Tg WHHL rabbits. In particular, the advanced atherosclerotic lesions in Tg WHHL rabbits were frequently associated with calcification, which was barely evident in non-Tg WHHL rabbits. To investigate the molecular mechanism of Lp(a)-induced vascular calcification, we examined the effect of human Lp(a) on cultured rabbit aortic smooth muscle cells and found that smooth muscle cells treated with Lp(a) showed increased alkaline phosphatase activity and enhanced calcium accumulation. These results demonstrate for the first time that Lp(a) accelerates advanced atherosclerotic lesion formation and may play an important role in vascular calcification.

Alkaline Phosphatase↗
PubMed2002

Increased expression of lipoprotein lipase in transgenic rabbits does not lead to abnormalities in skeletal and heart muscles.

Lipoprotein lipase (LPL) plays an important role in plasma lipoprotein metabolism and the uptake of free fatty acid in muscle. Previous studies using transgenic mice showed that increased LPL leads to myopathies, but these results were controversial. To examine this hypothesis, we studied LPL transgenic rabbits, and our results refute the suggested role of LPL in the pathogenesis of myopathies.

Animals↗
PubMed2002

Partially inverted tandem repeat isolated from pericentric region of chicken chromosome 8.

The majority of chicken repetitive sequence is nuclear-membrane-associated sequence (CNM), which resides in a large number of microchromosomes (chromosomes 11-39) and is absent from macrochromosomes 1-5, ZW, and some of the intermediate chromosomes 6-10. Two repetitive families, EcoRI/XhoI, are confined to the female-specific W chromosome. The core repeat units of the three families are 21 bp, containing (A)3-5 and (T)3-5 clusters separated by 5-7-bp sequences. In this article, we describe the isolation and initial characterization of a novel repeat family that is related to CNM/EcoRI/XhoI families. The novel family, designated as PIR, consists of multiple types of partially inverted repeat units of about 1.2, 1.4 and 1.6 kb. The PIR sequence is restricted to chicken chromosome 8, and accounts for about 3.8 mb, or 2500 copies of the 1.4-kb units, of the chicken genome. The evolution of PIR and related sequences is discussed.

Animals↗
PubMed2002

Activation of the p38 MAP kinase pathway is required for foam cell formation from macrophages exposed to oxidized LDL.

Endocytosis of oxidized low density lipoproteins (oxLDL) by macrophages, mediated by scavenger receptors, is thought to play a central role in foam cell formation and, thus, in the pathogenesis of atherosclerosis. OxLDL activates several MAP kinases, including the ERK, JNK and p38 MAP kinases, but the role of these activations in oxLDL uptake has not been studied. In the present investigation, we find that SB203580, a specific inhibitor of p38, blocks oxLDL-exposed J774 cells from becoming foam cells. Inhibition of foam cell formation by blockade of the p38 pathway is, at least in part, due to inhibition of oxLDL-induced up-regulation of the scavenger receptor CD36. Using pharmaceutical inhibitors and dominant active MAP kinase kinases, we demonstrated that activation of the p38 pathway, but not the ERK or JNK pathways, is necessary and sufficient to transactivate PPARgamma, a nuclear receptor that has recently been shown to play a pivotal role in oxLDL-induced CD36 expression. Our results for the first time demonstrate a regulation of CD36 by p38, and the importance of the p38 pathway in regulation of foam cell formation.

Animals↗
PubMedDate not supplied

The Tennessee Mouse Genome Consortium: identification of ocular mutants.

The Tennessee Mouse Genome Consortium (TMGC) is in its fifth year of a ethylnitrosourea (ENU)-based mutagenesis screen to detect recessive mutations that affect the eye and brain. Each pedigree is tested by various phenotyping domains including the eye, neurohistology, behavior, aging, ethanol, drug, social behavior, auditory, and epilepsy domains. The utilization of a highly efficient breeding protocol and coordination of various universities across Tennessee makes it possible for mice with ENU-induced mutations to be evaluated by nine distinct phenotyping domains within this large-scale project known as the TMGC. Our goal is to create mutant lines that model human diseases and disease syndromes and to make the mutant mice available to the scientific research community. Within the eye domain, mice are screened for anterior and posterior segment abnormalities using slit-lamp biomicroscopy, indirect ophthalmoscopy, fundus photography, eye weight, histology, and immunohistochemistry. As of January 2005, we have screened 958 pedigrees and 4800 mice, excluding those used in mapping studies. We have thus far identified seven pedigrees with primary ocular abnormalities. Six of the mutant pedigrees have retinal or subretinal aberrations, while the remaining pedigree presents with an abnormal eye size. Continued characterization of these mutant mice should in most cases lead to the identification of the mutated gene, as well as provide insight into the function of each gene. Mice from each of these pedigrees of mutant mice are available for distribution to researchers for independent study.

Animals↗