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Biomedical subjects

X Gu

Publications and source records attributed to X Gu.

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

Renal artery embolization with diluted hot contrast medium: an experimental study.

PURPOSE: To evaluate the safety and efficacy of diluted hot contrast medium to embolize the renal arteries in a canine model. MATERIALS AND METHODS: Transcatheter embolization was performed in 15 dogs (five dogs in each phase: I, II, and control). The diluted hot contrast medium was heated to 90 degrees C--100 degrees C and 30--60 mL were injected into a renal artery of each dog in phase I (optimization studies) and II (efficacy studies). In the control group, balloon inflation was performed without injection of diluted hot contrast medium. The temperature measurement was performed on one dog in phase I by temperature probe. Follow-up angiography was performed immediately (n = 15), at 1 week (n = 9), at 1 month (n = 9), and after 3 months (n = 5). All dogs were killed and kidneys were removed for histologic examination. RESULTS: The procedure was performed successfully in all dogs. Follow-up angiography showed complete obstruction of the injected renal arteries in phases I and II. The microscopic findings showed acute full-thickness necrosis of the renal cortex and renal artery in phase I, and complete coagulative necrosis of the cortex, medulla, and intrarenal blood vessels in phase II. There were no histologic changes of renal veins, inferior vena cava (IVC), and aorta. There were nonspecific findings in the control group. CONCLUSION: This preliminary experimental study suggests that diluted hot contrast medium may be a safe agent for renal ablation without thrombus formation in the renal vein or IVC.

Animals↗
PubMed2001

Suppression of the early and late cutaneous allergic responses using fexofenadine and montelukast.

BACKGROUND: The relative contribution of histamine and the cysteinyl leukotrienes to the early and late cutaneous allergic responses (ECAR and LCAR) can be studied using antagonists of these mediators. OBJECTIVE: To determine the relative suppression of the ECARs and LCARs using standard doses of an H1-receptor antagonist, a cysteinyl leukotriene1-receptor antagonist, and the two antagonists administered concurrently. METHODS: We carried out a prospective, randomized, double-blind, placebo-controlled, four-way crossover study in 12 highly allergic participants. Intradermal tests with standardized allergen, and with histamine phosphate, LTD4, and saline controls were performed on 5 different test days as follows: pretreatment baseline and at steady state immediately after the seventh and last dose of a 1-week course of treatment with once-daily fexofenadine, 120 mg; montelukast, 10 mg; fexofenadine and montelukast administered concurrently; or placebo. On each test day, the skin test results were read at intervals from 0.25 to 24 hours after the intradermal injections were performed. RESULTS: After allergen injection, compared with baseline, all treatment regimens significantly decreased the ECAR and LCAR. After allergen injection, compared with placebo, fexofenadine significantly decreased the ECAR and the LCAR from 0.25 to 2 hours and at 8 hours. Montelukast did not significantly decrease the ECAR or LCAR. Fexofenadine and montelukast administered concurrently were not more effective than fexofenadine alone at any time. In the control skin tests, compared with placebo, fexofenadine, but not montelukast, significantly decreased the histamine-induced response, and montelukast, but not fexofenadine, significantly decreased the LTD4-induced response. CONCLUSIONS: Fexofenadine and montelukast administered concurrently were not significantly more effective than fexofenadine alone in decreasing the ECAR and LCAR. Montelukast does not need to be discontinued before allergen skin testing. Further studies of the effect of concurrent treatment with higher doses of a histamine antagonist and a leukotriene modifier on the allergic response in the skin are needed.

Acetates↗
PubMed2001

Skin concentrations of H1-receptor antagonists.

BACKGROUND: H1-receptor antagonists are widely used in the treatment of allergic skin disorders. OBJECTIVE: We sought to evaluate the extent of fexofenadine and diphenhydramine distribution into the skin concomitantly with their peripheral H1-receptor antagonist activity. METHODS: In a prospective, randomized, double-blind, parallel-group study, 7 men received 120 mg of fexofenadine, and 7 received 50 mg of diphenhydramine. Before dosing; at 1, 3, 6, 9, and 24 hours after the first dose; and at 168 hours (steady-state), 12 hours after the seventh and last daily dose, blood samples and skin punch biopsy specimens were obtained, and epicutaneous tests with histamine phosphate, 1 mg/mL, were performed. RESULTS: Fexofenadine penetrated the skin to a significantly greater extent than diphenhydramine at 6, 9, 24, and 168 hours (P < or = .05). Maximum skin/plasma ratios of both the H1-antagonists (41.3 +/- 7.8 for fexofenadine and 8.1 +/- 4.4 for diphenhydramine) were obtained at 24 hours. Fexofenadine also produced significantly greater suppression of wheals at 3, 6, and 9 hours and of flares at 3, 6, 9, and 168 hours compared with diphenhydramine (P < or = .05). CONCLUSION: In disorders in which the presence and the effects of H1-receptor antagonists in the skin are clinically relevant, our results support the use of fexofenadine and indicate the need to re-examine the role of diphenhydramine.

Adult↗
PubMed2001

Epinephrine absorption in adults: intramuscular versus subcutaneous injection.

We report a prospective, randomized, blinded, placebo-controlled, 6-way crossover study of intramuscular versus subcutaneous injection of epinephrine in young men. Peak plasma epinephrine concentrations were significantly higher (P < .01) after epinephrine was injected intramuscularly into the thigh than after epinephrine was injected intramuscularly or subcutaneously into the upper arm. We recommend intramuscular injection of epinephrine into the thigh as the preferred route and site of injection of this life-saving medication in the initial treatment of anaphylaxis.

Absorption↗
PubMed2001

Epinephrine for the out-of-hospital (first-aid) treatment of anaphylaxis in infants: is the ampule/syringe/needle method practical?

BACKGROUND: Little information is available about administration of an accurate epinephrine dose to infants experiencing anaphylaxis outside the hospital setting. OBJECTIVE: Our purpose was to perform a prospective, controlled study of (1) the time needed by parents to draw up an infant epinephrine dose from an ampule and (2) the dose accuracy. METHODS: We gave 18 parents written instructions and asked them to draw up epinephrine 0.09 mL. We timed them by means of a stopwatch and measured the epinephrine content (in micrograms) in each dose by using HPLC-UV. Eighteen resident physicians, 18 general duty nurses, and 18 emergency department nurses served as controls. RESULTS: The parents took significantly longer (P < .05) than the controls to draw up the dose; the mean (+/- SEM) times were 142 +/- 13 seconds (range, 83-248) for the parents, 52 +/- 3 seconds (range, 30-83) for the physicians, 40 +/- 2 seconds (range, 26-71) for the general duty nurses, and 29 +/- 0.09 seconds (range, 27-33) for the emergency department nurses. The control groups did not differ significantly from each other in speed (P > .05). The epinephrine content of the doses drawn up by the parents ranged 40-fold in contrast to the physicians' doses (7- to 8-fold), general duty nurses' doses (3-fold), and emergency department nurses' doses (2-fold). The mean epinephrine content did not differ significantly (P > .05) among the 4 groups. CONCLUSIONS: Most parents were unable to draw up an infant epinephrine dose rapidly or accurately. Most health care professionals drew up the dose rapidly; however, their accuracy was compromised by inherent variations of epinephrine concentrations in the ampules (United States Pharmacopeia compendial limits, 90% to 115%) and the inherent difficulty of measuring low volumes (<0.1 mL) of epinephrine. User-friendly premeasured epinephrine doses suitable for infants should be developed.

Anaphylaxis↗
PubMed2001

Mathematical modeling for functional divergence after gene duplication.

In this paper, I present a statistical framework for modeling the functional divergence after gene duplication. A rate-component model to describe the rate covariation among homologous genes of a gene family is implemented when a phylogenetic tree is known. The Markov chain model is rigorous but may require a huge amount of computational time when the number of sequences is large. On the other hand, the Poisson-based model is mathematically analytical so that computation is very fast even for a large dataset. Moreover, under the posterior framework, we have developed a site-specific profile for predicting important amino acid residues responsible for these functional differences between member genes of a gene family. Our study may have great potential for functional genomics because it is cost-effective, and these predictions can be further tested by biological experimentation.

Biological Evolution↗
PubMed2001

Determination of the number of conserved chromosomal segments between species.

Genomic divergence between species can be quantified in terms of the number of chromosomal rearrangements that have occurred in the respective genomes following their divergence from a common ancestor. These rearrangements disrupt the structural similarity between genomes, with each rearrangement producing additional, albeit shorter, conserved segments. Here we propose a simple statistical approach on the basis of the distribution of the number of markers in contiguous sets of autosomal markers (CSAMs) to estimate the number of conserved segments. CSAM identification requires information on the relative locations of orthologous markers in one genome and only the chromosome number on which each marker resides in the other genome. We propose a simple mathematical model that can account for the effect of the nonuniformity of the breakpoints and markers on the observed distribution of the number of markers in different conserved segments. Computer simulations show that the number of CSAMs increases linearly with the number of chromosomal rearrangements under a variety of conditions. Using the CSAM approach, the estimate of the number of conserved segments between human and mouse genomes is 529 +/- 84, with a mean conserved segment length of 2.8 cM. This length is <40% of that currently accepted for human and mouse genomes. This means that the mouse and human genomes have diverged at a rate of approximately 1.15 rearrangements per million years. By contrast, mouse and rat are diverging at a rate of only approximately 0.74 rearrangements per million years.

Animals↗
PubMed2001

Functional divergence in the caspase gene family and altered functional constraints: statistical analysis and prediction.

In this article, we explore the pattern of type I functional divergence (i.e., altered functional constraints or site-specific rate difference) in the caspase gene family that is important for apoptosis (programmed cell death) and cytokine maturation. By taking advantage of substantial experimental data from caspases, the functional/structural basis of our posterior predictions from sequence analysis was extensively studied. Our results are as follows: (1) Phylogenetic analysis shows that the evolution of major caspase-mediated pathways has been facilitated by gene duplications, (2) type I functional divergence (altered functional constraints) is statistically significant between two major subfamilies, CED-3 and ICE, (3) 4 of 21 predicted amino acid residues (for site-specific rate difference between CED-3 and ICE) have been verified by experimental evidence, and (4) we found that some CED-3 caspases may inherit more ancestral functions, whereas other members may employ some recently derived functions. Our approach can be cost effective in functional genomics to make statistically sound predictions from amino acid sequences.

Amino Acid Sequence↗
PubMed2001

Motor unit properties of nerve-intact extensor digitorum longus muscle grafts in young and old rats.

Impaired reinnervation has been implicated as the cause of the threefold disparity in the recovery of maximum force (P0) of standard muscle grafts in old compared with young rats. The specific, null hypothesis of this study is that compared with age-matched control extensor digitorum longus (EDL) muscles, nerve-intact EDL muscle grafts in young and old rats show no evidence of an age-related impairment in reinnervation. Nerve-intact grafts were performed in 3-month-old and 23-month-old rats and were evaluated 60 days postoperatively. Compared with age-matched control EDL muscles, nerve-intact grafts in young and old rats showed no difference in muscle mass or motor unit numbers. The mean motor unit P0 for nerve-intact graft muscles in both age groups was significantly lower than that of age-matched control muscles. These data support our hypothesis that if axons are allowed to regenerate in an endoneurial environment, there is no evidence of an age-related impairment in muscle reinnervation.

Aging↗
PubMed2001

Maximum-likelihood approach for gene family evolution under functional divergence.

According to the observed alignment pattern (i.e., amino acid configuration), we studied two basic types of functional divergence of a protein family. Type I functional divergence after gene duplication results in altered functional constraints (i.e., different evolutionary rate) between duplicate genes, whereas type II results in no altered functional constraints but radical change in amino acid property between them (e.g., charge, hydrophobicity, etc.). Two statistical approaches, i.e., the subtree likelihood and the whole-tree likelihood, were developed for estimating the coefficients of (type I or type II) functional divergence. Numerical algorithms for obtaining maximum-likelihood estimates are also provided. Moreover, a posterior-based site-specific profile is implemented to predict critical amino acid residues that are responsible for type I and/or type II functional divergence after gene duplication. We compared the current likelihood with a fast method developed previously by examples; both show similar results. For handling altered functional constraints (type I functional divergence) in the large gene family with many member genes (clusters), which appears to be a normal case in postgenomics, the subtree likelihood provides a solution that is computationally feasible and robust against the uncertainty of the phylogeny. The cost of this feasibility is the approximation when frequencies of amino acids are very skewed. The potential bias and correction are discussed.

Amino Acid Sequence↗
PubMed2001

Structural analysis of free and enzyme-bound amaranth alpha-amylase inhibitor: classification within the knottin fold superfamily and analysis of its functional flexibility.

The three-dimensional structure of the amaranth alpha-amylase inhibitor (AAI) adopts a knottin fold of abcabc topology. Upon binding to alpha-amylase, it adopts a more compact conformation characterized by an increased number of intramolecular hydrogen bonds, a decreased volume and in addition a trans to cis isomerization of Pro20. A systematic analysis of the 3-D structural databanks revealed that similar proteins and domains share with AAI the characteristic presence of proline residues, many of which are in a cis backbone conformation. As these proteins fulfil a variety of functional roles and are expressed in very different organisms, we conclude that the structure of the knottin fold, including the propensity of the cis bond, are the result of convergent evolution.

Algorithms↗
PubMed2001

Effects of phytoestrogens and synthetic combinatorial libraries on aromatase, estrogen biosynthesis, and metabolism.

Approximately 60% of breast cancer patients have hormone-dependent breast cancer containing estrogen receptors and requiring estrogen for tumor growth. The extent of estrogen biosynthesis and metabolism in the breast cancer tissue microenvironment influences breast-tumor development and growth, and endogenous and exogenous agents may alter the levels of hormonally active estrogens and their metabolites. Isoflavonoid phytoestrogens such as genistein exhibit numerous biochemical activities; however, their effects on estrogen biosynthesis and metabolism in breast cancer cells have not been fully examined. MCF-7 cells (hormone-dependent) and MBA-MB-231 cells (hormone-independent) were treated with genistein (100 nM) for five days and then incubated with radiolabeled estradiol (100 nM, 2.5 microCi) for 0 to 48 h. Media were extracted with ethyl acetate, and the organic residues analyzed by reverse-phase HPLC with a radioactivity flow detector. The major metabolite formed in all cases is estrone, although differences were observed between the cell lines and the various drug treatments. The formation of estrone in untreated MCF-7 cells (approximately 9.3% of radioactivity at 24 h) is relatively limited, in contrast to untreated MDA-MB-231 cells (approximately 32.0% of radioactivity at 24 h). Treatment of MCF-7 cells with 100 nM genistein increased the conversion of estradiol to estrone up to 19.5% in 24 h. The effect of genistein on estrone formation in MDA-MB-231 cells resulted in 37.7% of the radioactivity being estrone. Thus, genistein treatment of breast cancer cells resulted in increased 17-betahydroxysteroid dehydrogenase activity and elevated formation of estrone. Increased levels of oxidative 17-betahydroxysteroid dehydrogenase activity (Type II) were confirmed by Western blots. Therefore, exposure of breast cancer cells to genistein results in elevated conversion of estradiol to estrogenically weaker or inactive metabolites. The regulation of breast-tissue aromatase by exogenous agents such as drugs and environmental agents is being investigated. The benzopyranone-ring system is a molecular scaffold of considerable interest, and this scaffold is found in flavonoid natural products that have weak aromatase inhibitory activity. Medicinal chemistry efforts focus on diversifying the benzopyranone scaffold and utilizing combinatorial chemistry approaches to construct small benzopyranone libraries as potential aro- matase inhibitors. Several compounds in the initial libraries have demonstrated moderate aromatase inhibitory activity in screening assays.

Antineoplastic Agents, Phytogenic↗
PubMed2001

On reporting fold differences.

As we enter an age in which genomics and bioinformatics make possible the discovery of new knowledge about the biological characteristics of an organism, it is critical that we attempt to report newly discovered "significant" phenotypes only when they are actually of significance. With the relative youth of genome-scale gene expression technologies, how to make such distinctions has yet to be better defined. We present a "mask technology" by which to filter out those levels of gene expression that fall within the noise of the experimental techniques being employed. Conversely, our technique can lend validation to significant fold differences in expression level even when the fold value may appear quite small (e.g. 1.3). Given array-organized expression level results from a pair of identical experiments, our ID Mask Tool enables the automated creation of a two-dimensional "region of insignificance" that can then be used with subsequent data analyses. Fundamentally, this should enable researchers to report on findings that are more likely to be in nature truly meaningful. Moreover, this can prevent major investments of time, energy, and biological resources into the pursuit of candidate genes that represent false positives.

Computational Biology↗
PubMed2001

Identification of IgE-binding proteins in soy lecithin.

BACKGROUND: Soy lecithin is widely used as an emulsifier in processed foods, pharmaceuticals and cosmetics. Soy lecithin is composed principally of phospholipids; however, it has also been shown to contain IgE-binding proteins, albeit at a low level. A few clinical cases involving allergic reactions to soy lecithin have been reported. The purpose of this investigation is to better characterize the IgE-binding proteins typically found in lecithin. METHODS: Soy lecithin proteins were isolated following solvent extraction of lipid components and then separated on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The separated lecithin proteins were immunoblotted with sera from soy-sensitive individuals to determine the pattern of IgE-binding proteins. The identity of IgE-reactive bands was determined from their N-terminal sequence. RESULTS: The level of protein in six lecithin samples obtained from commercial suppliers ranged from 100 to 1,400 ppm. Lecithin samples showed similar protein patterns when examined by SDS-PAGE. Immunoblotting with sera from soy-sensitive individuals showed IgE binding to bands corresponding to 7, 12, 20, 39 and 57 kD. N-terminal analysis of these IgE-binding bands resulted in sequences for 3 components. The 12-kD band was identified as a methionine-rich protein (MRP) and a member of the 2S albumin class of soy proteins. The 20-kD band was found to be soybean Kunitz trypsin inhibitor. The 39-kD band was matched to a soy protein with unknown function. CONCLUSIONS: Soy lecithin contains a number of IgE-binding proteins; thus, it might represent a source of hidden allergens. These allergens are a more significant concern for soy-allergic individuals consuming lecithin products as a health supplement. In addition, the MRP and the 39-kD protein identified in this study represent newly identified IgE-binding proteins.

Adolescent↗
PubMed2001

Bone marrow stromal cells mediate androgenic suppression of B lymphocyte development.

Castration of normal male mice induces expansion of the bone marrow B cell population, an effect that can be reversed by androgen replacement. We employed in vitro cultures and two in vivo models to investigate whether androgens exert these effects directly on marrow lymphoid precursors or whether actions on marrow stromal elements are required. Immature B cells from normal mouse bone marrow were not responsive to the suppressive effect of androgens unless they were cocultured with marrow stromal cells or with supernatants from androgen-treated stromal cells, suggesting that the androgen effects are exerted through marrow stromal elements by production of a diffusible mediator. Further experiments revealed that bone marrow stromal cells produced TGF-beta in response to dihydrotestosterone (DHT), and neutralization of TGF-beta in the DHT-treated stromal cells reversed the suppressive effects. The stromal cell requirement for androgen-mediated effects was confirmed in vivo by experiments using chimeric animals created by bone marrow transplantation in which androgen receptor expression was restricted to either the stromal or lymphoid cells of the bone marrow. Androgens only affected B cell development in chimeric mice with androgen-sensitive stromal cells. These experiments suggest that effects of androgens on developing B cells are mediated through androgen receptors in bone marrow stromal cells. TGF-beta is a candidate mediator for these hormonal effects.

Animals↗
PubMed2001

Androgen receptors in thymic epithelium modulate thymus size and thymocyte development.

Castration of normal male rodents results in significant enlargement of the thymus, and androgen replacement reverses these changes. Androgen-resistant testicular feminization (Tfm) mice also show significant thymus enlargement, which suggests that these changes are mediated by the androgen receptor (AR). The cellular targets of androgen action in the thymus are not known, but may include the lymphoid cells (thymocytes) as well as nonlymphoid epithelial cells, both of which have been believed to express AR. In the present study immunohistochemical analysis and hormone binding assays were used to demonstrate the presence of AR in thymic epithelial cells. The physiological significance of this epithelial cell AR expression was defined by further studies performed in vivo using chimeric mice, produced by bone marrow transplantation, in which AR expression was limited to either lymphoid or epithelial components of the thymus. Chimeric C57 mice engrafted with Tfm bone marrow cells (AR(+) epithelium and AR(-) thymocytes) had thymuses of normal size and showed the normal involutional response to androgens, whereas chimeric Tfm mice engrafted with C57 bone marrow cells (AR(-) epithelium and AR(+) thymocytes) showed thymus enlargement and androgen insensitivity. Furthermore, phenotypic analyses of lymphocytes in mice with AR(-) thymic epithelium showed abrogation of the normal responses to androgens. These data suggest that AR expressed by thymic epithelium are important modulators of thymocyte development.

Animals↗
PubMed2001

Reduced severity of oxygen-induced retinopathy in eNOS-deficient mice.

PURPOSE: Exposure of premature human infants to hyperoxia results in the obliteration of developing retina capillaries, leading to a vision-threatening retinopathy termed retinopathy of prematurity (ROP). The authors hypothesized that this process may be mediated in part by endothelial nitric oxide (NO)-derived oxidants such as peroxynitrite and tested this hypothesis in a mouse model of ROP. METHODS: Normal mice, mice treated with the nitric oxide synthase (NOS) inhibitor N:(G)-nitro-L-arginine (L-NNA), and knockout mice carrying a homozygous targeted disruption of the gene for endothelial NOS (eNOS) were studied in an experimental model of ROP. Retinas were compared for extent of capillary obliteration in hyperoxia, vascular endothelial growth factor (VEGF) expression, nitrotyrosine formation, and vitreous neovascularization. RESULTS: Oxygen-induced retinal vaso-obliteration was significantly reduced by L-NNA treatment (43% decrease from controls). The eNOS-deficient mice showed a similar reduction in vaso-obliteration (46% decrease from controls), and vitreous neovascularization was also substantially reduced (threefold decrease). Retinal nitrotyrosine formation, a measure of in situ peroxynitrite modification of proteins, was significantly elevated in normal mice during hyperoxia, in a spatial and temporal pattern consistent with a role in oxygen-induced vaso-obliteration. This was not seen in eNOS-deficient mice. VEGF expression was similar in both groups of mice, although suppression in hyperoxia was slightly blunted in eNOS-deficient mice. CONCLUSIONS: These data suggest a role for NO and peroxynitrite in the pathogenesis of ROP. Therapies aimed at modulation of eNOS activity may have therapeutic potential for preventing ROP.

Animals↗