Biomedical subjects

Tao Wang

Publications and source records attributed to Tao Wang.

At least 73 records · Page 4Linked to original sources

PubMed2006

Separation of phospholipids by capillary zone electrophoresis with indirect ultraviolet detection.

A simple method for separation of different anionic and zwitterionic phospholipid classes by capillary zone electrophoresis (CZE), using indirect UV detection with adenosine monophosphate (AMP) as background electrolyte and the UV-absorbing additive, was successfully developed in this study. The separation conditions including apparent pH (pH*) of running buffer, concentration of AMP, organic solvent, applied voltage and capillary temperature were systematically optimized. The application of this method to human blood sample was also briefly examined.

Adenosine Monophosphate↗

PubMed2006

Real-time endpoint monitoring and determination for a pharmaceutical salt formation process with in-line FT-IR spectroscopy.

An application of Fourier transform infrared (FT-IR) spectroscopy equipped with an attenuated total reflectance (ATR) probe for in-line monitoring of a hydrochloride (HCl) salt formation process of 4-{1-methyl-2-piperidin-4-yl-4-[3-(trifluorometryl)phenyl]-1H-imidazol-5-yl}-N-[(1S)-1-phenylethyl]pyridine-2-amine (freebase), an active pharmaceutical ingredient as a P38 MAP kinase inhibitor, is described. The freebase forms both mono- and bis-HCl salts due to its structural features. The mono-HCl salt is the desired product but the bis-salt is an impurity. The key to maximizing the product yield and minimizing the impurity level is to monitor the salt-forming reaction and to terminate it at the correct HCl charge amount. The process analytical technology (PAT) provided real-time data for process control and overcame the limitations that had been previously encountered by other analytical instrumentations, such as high-performance liquid chromatography and titration. Two qualitative approaches for reaction endpoint determination were employed. In the first approach, changes in the concentration of the freebase and bis-salt were monitored via the first derivative concentration profiles. The flat point in the freebase profile and the rise in the bis-salt profile were used as a detection bracket for the endpoint of HCl charging. In the second approach, principal component analysis (PCA) was used to classify the status of the process based on a spectral library consisting of spectra collected around the endpoint. Results indicated that both methods provided adequate accuracy for endpoint control in a small window between 1.0 and 1.05 HCl to freebase mole ratio. Both methods were used to support a scaled up process. Three batches of MAP mono-HCl salt formation were successfully controlled and prepared.

Calibration↗

PubMed2006

QSAR study of 1,4-dihydropyridine calcium channel antagonists based on gene expression programming.

The gene expression programming, a novel machine learning algorithm, is used to develop quantitative model as a potential screening mechanism for a series of 1,4-dihydropyridine calcium channel antagonists for the first time. The heuristic method was used to search the descriptor space and select the descriptors responsible for activity. A nonlinear, six-descriptor model based on gene expression programming with mean-square errors 0.19 was set up with a predicted correlation coefficient (R2) 0.92. This paper provides a new and effective method for drug design and screening.

Algorithms↗

PubMed2006

[Value of carbon-11 choline positron emission tomography in patients with pulmonary abnormalities].

OBJECTIVE: To assess the value of carbon-11 choline (CH) positron emission tomography (PET) in patients with pulmonary nodules. METHODS: From September 2002 to December 2004, 39 patients with pulmonary nodules were imaged with CH-PET. CH-PET data was analyzed by visual method and semiquantitative method. When pulmonary nodules with abnormal CH uptake appeared in PET scans confirmed by visual method, their maximum and mean standard uptake value (SUVmax and SUVmean) were measured using semiquantitative method. Diagnoses were confirmed by surgery or biopsy and follow-up survey. RESULTS: Twenty-four cancerous and 3 inflammatory nodules and 1 bronchogenic cyst were detected by CH-PET and were diagnosed malignant with visual method. Three bronchial alveolar carcinoma, 2 metastatic tumor from kidney and colon, 3 fibrous nodules, 1 cryptococcosis, 1 hamartoma and 1 sclerosing hemangioma showed nothing abnormal in PET scans. For identification of pulmonary nodules with CH-PET, the sensitivity was 89% (24/29), the specificity was 60% (6/10), and the accuracy was 77% (30/39). There were differences in SUV between 8 squamous cell carcinomas and 9 adenocarcinomas (Z = -2.937, -2.887, P < 0.01). In diagnosing 70 resected enlarged lymph nodes beyond 1 cm in 17 lung cancer patients, CH-PET had the sensitivity of 86% (25/29), the specificity of 90% (37/41), and the accuracy of 89% (62/70). CH-PET confirmed 7 distant metastases in 25 lung cancer patients. In 5 cases suspected brain metastases CH-PET identified 2 cases positive correctly. CONCLUSIONS: CH-PET can confirm malignant pulmonary nodules, but still there were false positive and false negative cases. CH-PET can evaluate N stage effectively in patients with lung cancer. CH-PET can depict brain metastases accurately.

Adult↗

PubMed2006

Assembly of HIV-1 Vif-Cul5 E3 ubiquitin ligase through a novel zinc-binding domain-stabilized hydrophobic interface in Vif.

APOBEC3G (A3G) and related cytidine deaminases are potent inhibitors of retroviruses. HIV-1 Vif hijacks the cellular Cul5-E3 ubiquitin ligase to degrade APOBEC3 proteins and render them ineffective against these viruses. Here, we report that HIV-1 Vif is a novel zinc-binding protein containing an H-x(5)-C-x(17-18)-C-x(3-5)-H motif that is distinct from other recognized classes of zinc fingers. Zinc-binding stabilized a conserved hydrophobic interface within the HCCH motif that is critical for Vif-Cul5 E3 assembly and Vif function. An N-terminal region in the first Cullin repeat of Cul5, which is dispensable for adaptor ElonginC binding, was required for interaction with Vif. This region is the most divergent sequence between Cul2 and Cul5, a factor that may contribute to the selection of Cul5 and not Cul2 by Vif. This is the first example of a zinc-binding substrate receptor responsible for the assembly of a Cullin-RING ligase, representing a new target for antiviral development.

Amino Acid Motifs↗

PubMed2006

A microdeletion in Xp11.3 accounts for co-segregation of retinitis pigmentosa and mental retardation in a large kindred.

In a previous report, Aldred et al. [1994] described a 5-generation family in which severe retinitis pigmentosa (RP) co-segregates with mild-moderate mental retardation as an X-linked recessive phenotype mapping to the broad interval between Xp21-q21. We re-examined this family, initially analyzing RP2, a gene in the disease interval that was identified as a cause of RP after the initial report of this family. We found that the male propositus lacked the 5' three exons of RP2 and that RP2 marks the centromeric boundary of a 1.27 Mb deletion that includes two other annotated genes (SLC9A7, CHST7), one predicted transcript encoding a zinc finger protein (FLJ20344) and two highly conserved miRNAs (mir221, mir222). We conclude that this family is segregating a contiguous gene deletion and that the absence of a functional RP2 accounts, at least in part, for the retinal degeneration while deletion of one or more of the other genes is likely responsible for the mental retardation phenotype.

Antiporters↗

PubMed2006

Models and partition of variance for quantitative trait loci with epistasis and linkage disequilibrium.

BACKGROUND: A genetic model about quantitative trait loci (QTL) provides a basis to interpret the genetic basis of quantitative traits in a study population, such as additive, dominance and epistatic effects of QTL and the partition of genetic variance. The standard quantitative genetics model is based on the least squares partition of genetic effects and also genetic variance in an equilibrium population. However, over years many specialized QTL models have also been proposed for applications in some specific populations. How are these models related? How to analyze and partition a QTL model and genetic variance when both epistasis and linkage disequilibrium are considered? RESULTS: Starting from the classical description of Cockerham genetic model, we first represent the model in a multiple regression setting by using indicator variables to describe the segregation of QTL alleles. In this setting, the definition of additive, dominance and epistatic effects of QTL and the basis for the partition of genetic variance are elaborated. We then build the connection between this general genetic model and a few specialized models (a haploid model, a diploid F2 model and a general two-allele model), and derive the genetic effects and partition of genetic variance for multiple QTL with epistasis and linkage disequilibrium for these specialized models. CONCLUSION: In this paper, we study extensively the composition and property of the genetic model parameters, such as genetic effects and partition of genetic variance, when both epistasis and linkage disequilibrium are considered. This is the first time that both epistasis and linkage disequilibrium are considered in modeling multiple QTL. This analysis would help us to understand the structure of genetic parameters and relationship of various genetic quantities, such as allelic frequencies and linkage disequilibrium, on the definition of genetic effects, and will also help us to understand and properly interpret estimates of the genetic effects and variance components in a QTL mapping experiment.

Algorithms↗

PubMed2006

Foxf1 and Foxf2 control murine gut development by limiting mesenchymal Wnt signaling and promoting extracellular matrix production.

Development of the vertebrate gut is controlled by paracrine crosstalk between the endodermal epithelium and the associated splanchnic mesoderm. In the adult, the same types of signals control epithelial proliferation and survival, which account for the importance of the stroma in colon carcinoma progression. Here, we show that targeting murine Foxf1 and Foxf2, encoding forkhead transcription factors, has pleiotropic effects on intestinal paracrine signaling. Inactivation of both Foxf2 alleles, or one allele each of Foxf1 and Foxf2, cause a range of defects, including megacolon, colorectal muscle hypoplasia and agangliosis. Foxf expression in the splanchnic mesoderm is activated by Indian and sonic hedgehog secreted by the epithelium. In Foxf mutants, mesenchymal expression of Bmp4 is reduced, whereas Wnt5a expression is increased. Activation of the canonical Wnt pathway -- with nuclear localization of beta-catenin in epithelial cells -- is associated with over-proliferation and resistance to apoptosis. Extracellular matrix, particularly collagens, is severely reduced in Foxf mutant intestine, which causes epithelial depolarization and tissue disintegration. Thus, Foxf proteins are mesenchymal factors that control epithelial proliferation and survival, and link hedgehog to Bmp and Wnt signaling.

Animals↗

PubMed2006

A quantitative linkage score for an association study following a linkage analysis.

BACKGROUND: Currently, a commonly used strategy for mapping complex quantitative traits is to use a genome-wide linkage analysis to narrow suspected genes to regions on a scale of centiMorgans (cM), followed by an association analysis to fine map the genetic variation in regions showing linkage. Two important questions arise in the design and the resulting inference at the association stage of this sequential procedure: (1) how should we design an efficient association study given the information provided by the previous linkage study? and (2) can an association in a linkage region explain, in part, the detected linkage signal? RESULTS: We derive a quantitative linkage score (QLS) based on Haseman-Elston regression (Haseman and Elston 1972) and make use of this score to address both questions. In designing an association study, the selection of a subsample from the linkage study sample can be guided by the linkage information summarized in the QLS. When heterogeneity exists, we show that selection based on the QLS can increase the proportion of sample individuals from the subpopulation affected by a disease allele and therefore greatly improves the power of the association study. For the resulting inference, we frame as a hypothesis test the question of whether a linkage signal in a region can be in part explained by a marker allele. A simple one sided paired t-statistic is defined by comparing the two sets of QLSs obtained with/without modeling a marker association: a significant difference indicates that the marker can at least partly account for the detected linkage. We also show that this statistic can be used to detect a spurious association. CONCLUSION: All our results suggest that a careful examination of QLSs should be helpful for understanding the results of both association and linkage studies.

Alleles↗

PubMed2006

In vitro permeation of repellent DEET and sunscreen oxybenzone across three artificial membranes.

DEET and oxybenzone are two essential active ingredients in repellent and sunscreen products. We performed a series of in vitro diffusion studies to evaluate the transmembrane permeation of DEET and oxybenzone across three artificial membranes, low-density polyethylene (LDPE), low fouling composite (LFC) and mixed cellulose esters (MCE), from concurrent use of commercial repellent and sunscreen preparations. Permeation of DEET and oxybenzone across the test membranes was synergistically increased when both the repellent and the sunscreen formulations were applied simultaneously. Different application sequences and formulation types also resulted in variable permeation profiles of DEET and oxybenzone. Compared to biological piglet epidermis under the identical experimental conditions, transmembrane permeation of DEET was suppressed in LDPE and LFC membranes, but enhanced in MCE membrane; transmembrane permeation of oxybenzone was reduced in LFC membrane, but increased in LDPE and MCE membranes. Permeability coefficients of DEET and oxybenzone in all three artificial membranes were significantly different from those in piglet skin. It was concluded that the permeation profiles of the compounds were dependent upon physicochemical characteristics of the membranes and the formulations.

Animals↗

PubMed2006

[Fluorine-18 fluorodeoxyglucose uptake in patients with benign pulmonary nodules].

OBJECTIVE: To assess the features of fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with benign pulmonary nodules. METHODS: From October 1998 to July 2004, 47 patients with benign pulmonary nodules were imaged with FDG-positron emission tomography (PET). Diagnoses were confirmed by surgery. FDG-PET data was analyzed by visual method and semi-quantitive method. When pulmonary nodules with abnormal FDG intake appeared in PET scans confirmed by visual method, their maximum and mean standard uptake value (SUVmax and SUVmean) and SUV of normal lung (SUVlung) were measured using semiquantitative method. RESULTS: Twenty-one cases showed nothing abnormal in PET scans, including 17 calcification and fibrosis, 2 hamartomas and 2 sclerosing hemangiomas. 26 pulmonary nodules were detected by FDG-PET (17 active tuberculous, 6 inflammatory pseudotumors, 3 cryptococcosis). FDG uptake of these 26 nodules was higher than that of normal lung (SUVmax, SUVmean and SUVlung were 3.04 +/- 1.65, 2.48 +/- 1.35 and 0.40 +/- 0.07, respectively, P < 0.001). Correlations were not found between FDG uptake and nodule size or SUV of normal lung or age or blood glucose level in these 26 patients (P > 0.05). SUV in 9 cases (9/26, 35%) were beyond 2.5. CONCLUSIONS: Some benign pulmonary nodules were FDG avid.

Adult↗

PubMed2006

Resveratrol, a natural ingredient of grape skin: antiarrhythmic efficacy and ionic mechanisms.

Resveratrol has been demonstrated to produce a variety of biological actions. Accumulating line of evidence supported the view that resveratrol may exert protective effect on the cardiovascular system. The aim of the study was to assess the antiarrhythmic profile as well as electrophysiological properties of resveratrol. We observe the antiarrhythmic effect of resveratrol on aconitine induced rat arrhythmia, ouabain induced guinea pig arrhythmia, and coronary ligation induced rat arrhythmia animal models. Resveratrol significantly and dose-dependently increased the doses of aconitine and ouabain required to induce the arrhythmia indexes. In coronary ligation induced rat arrhythmia model, resveratrol shortened duration of arrhythmia, decreased incidence of ventricular tachycardia and mortality. Electrophysiological experiment revealed that resveratrol could shorten APD through inhibition of ICa and selective enhancement of IKs without an effect on IKr.

Animals↗

PubMed2006

Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa.

Age-related macular degeneration (ARMD) is the leading cause of irreversible visual loss in the Western world, affecting approximately 25 million people worldwide. The pathogenesis is complex and missense mutations in FBLN5 have been reported in association with ARMD. We have investigated the role of fibulin 5 in ARMD by completing the first European study of the gene FBLN5 in ARMD (using 2 European cohorts of 805 ARMD patients and 279 controls) and by determining the functional effects of the missense mutations on fibulin 5 expression. We also correlated the FBLN5 genotype with the ARMD phenotype. We found two novel sequence changes in ARMD patients that were absent in controls and expressed these and the other nine reported FBLN5 mutations associated with ARMD and two associated with the autosomal recessive disease cutis laxa. Fibulin 5 secretion was significantly reduced (P<0.001) for four ARMD (p.G412E, p.G267S, p.I169 T, and p.Q124P) and two cutis laxa (p.S227P, p.C217R) mutations. These results suggest that some missense mutations associated with ARMD lead to decreased fibulin 5 secretion with a possible corresponding reduction in elastinogenesis. This study confirms the previous work identifying an association between FBLN5 mutations and ARMD and for the first time suggests a functional mechanism by which these mutations can lead to ARMD. It further demonstrates that FBLN5 mutations can be associated with different phenotypes of ARMD (not limited to the previously described cuticular drusen type). Such knowledge may ultimately lead to the development of novel therapies for this common disease.

Age Factors↗

PubMed2006

Trichostatin A regulates hGCN5 expression and cell cycle on Daudi cells in vitro.

The expression of human general control of amino acid synthesis protein 5 (hGCN5) in human Burkitt's lymphoma Daudi cells in vitro, effects of Trichostatin A (TSA) on cell proliferation and apoptosis and the molecular mechanism of TSA inhibiting proliferation of Daudi cells were investigated. The effects of TSA on the growth of Daudi cells were studied by 3-(4, 5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. The effect of TSA on the cell cycle of Daudi cells was assayed by a propidium iodide method. Immunochemistry and Western blot were used to detect the expression of hGCN5. The proliferation of Daudi cells was decreased in TSA-treated group with a 24 h IC50 value of 415.3979 microg/L. TSA induced apoptosis of Daudi cells in a time- and dose-dependent manner. Treatment with TSA (200 and 400 microg/L) for 24 h, the apoptosis rates of Daudi cells were (14.74+/-2.04) % and (17.63+/-1.25) %, respectively. The cell cycle was arrested in G0/G1 phase (50, 100 microg/L) and in G2/M phase (200 microg/L) by treatment with TSA for 24 h. The expression of hGCN5 protein in Daudi cells was increased in 24 h TSA-treated group by immunochemistry and Western blot (P<0.05). It was suggested that TSA as HDACIs could increase the expression of hGCN5 in Daudi cells, and might play an important role in regulating the proliferation and apoptosis of B-NHL cell line Daudi cells.

Apoptosis↗

PubMed2006

Factors affecting the long-term results of hypospadias repairs.

PURPOSE: The aim of this study was to explore the relationships between the short- and long-term results of hypospadias repair and identify the factors that could affect the long-term results of hypospadias repair. MATERIALS AND METHODS: Between 1982 and 1988, 142 patients were operated for hypospadias and completed their treatment at Tongji Hospital (Wuhan, China). Their records were analyzed retrospectively, and a detailed questionnaire was mailed to them. RESULTS: One hundred two patients returned the questionnaire. Patients in the proximal hypospadias group, those using Denis-Browne technique, and those with early complications were markedly dissatisfied with the overall results of hypospadias repair and penile appearance. Moreover, their dissatisfaction grew with the number of operations they had. Thirty-nine (95.1%) of 41 patients using the Denis-Browne technique had voiding problems. Forty-nine (48%) of 102 patients felt inhibited in seeking girlfriends or sexual contacts. Moreover, there was a positive correlation between the level of sexual inhibition and operation times. A highly positive correlation was found between the age at the time hypospadias surgery was completed and the extent of being sexually inhibited. The patients in proximal hypospadias group had more erection and ejaculation problems. CONCLUSIONS: The short-term results of hypospadias repair could affect the long-term results significantly, and good short-term results also predict long-term ones. The types of hypospadias, procedures, and complications have significant influences on predicting the long-term results of hypospadias repairs.

Adolescent↗

PubMed2006

Decreased inhibitory activity of prothrombin to calcium oxalate crystallization by specific chemical modification of its gamma-carboxyglutamic acid residues.

OBJECTIVES: To investigate the inhibitory role of gamma (gamma)-carboxyglutamic acid (Gla) in the Gla domain of urinary prothrombin in the formation of calcium oxalate crystals. METHODS: Morpholine and formaldehyde at different concentrations were added to the solution of prothrombin to cause the conversion of Gla to gamma-methyleneglutamic acid (MGlu). The extent of the modification was controlled by the relative amount of modification reagents to prothrombin. The 100-fold molar excess of modification reagents to prothrombin produced the prothrombin molecule containing 2gamma-MGlu residues, and the 10,000-fold molar excess produced the molecule containing 8gamma-MGlu residues. The inhibitory activities of prothrombin and modified prothrombin to calcium oxalate crystallization were evaluated by the seeded crystallization technique. RESULTS: The inhibitory index of Gla prothrombin to calcium oxalate crystallization was 14.2%, that of 2gamma-MGlu prothrombin was 12.8%, decreased by about 10%, and that of 8gamma-MGlu prothrombin was 5.0%, decreased by about 65%. CONCLUSIONS: The Gla in the Gla domain of urinary prothrombin may play an important role in inhibiting the formation of renal calcium oxalate calculus.

1-Carboxyglutamic Acid↗

PubMed2006

Menu suggestion: an effective way to improve dietary compliance in peritoneal dialysis patients.

OBJECTIVE: Poor compliance with the dietary prescriptions is quite common in dialysis patients. We believe that most of the noncompliance is caused by the patient's poor understanding of the dietary prescription. Therefore, in the present study, we tried to investigate the role of menu suggestion in improving the patient's compliance with the dietary prescription. DESIGN AND SETTING: A longitudinal cohort study conducted at an outpatient dialysis clinic. PATIENTS: Seventy clinically stable patients on peritoneal dialysis were included in this prospective study during April 1, 2004, to November 31, 2004, in a single center. Patients who had significant cognitive impairment and thus did not understand the food contents during the training course were not eligible for enrollment. INTERVENTION: All the patients were randomly assigned to 1 of 2 groups. Group 1 patients received the traditional patient education method. Group 2 patients additionally received individualized menu suggestions based on their food preferences and education on how to exchange the foods at equivalent amounts according to the exchange list. MAIN OUTCOME MEASURES: At present, there are no clear optimal dietary protein intake levels for peritoneal dialysis patients. Our experience is that a dietary protein intake level of 0.8 to 1.2 g/kg/d can maintain our patients in a good nutritional status. Thereafter, in this study we prescribed the dietary protein intake level at 0.8 to 1.2 g/kg/d and defined compliance as meeting this target protein intake level. RESULTS: There were 35 patients in each group. The compliance was 22.9% in group 1 and 57.1% in group 2 (P < .05). CONCLUSIONS: Our study suggests that menu suggestion may be an effective way of improving the compliance with the diet in peritoneal dialysis patients. It improves the patient's understanding of the dietary prescription.

Adult↗

PubMed2006

The role of erythrocytes phosphatidylserine exposure in anemia in peritoneal dialysis patients.

BACKGROUND: An increased red blood cell (RBC) phosphatidylserine (PS) exposure in uremic patients was found that could promote macrophage recognition and decrease RBC survival time. Furthermore, a reduced red cell life span was found to contribute anemia in patients with renal failure. It is therefore possible to hypothesize that increased PS externalization of RBC may influence renal anemia. The present study preliminarily explored the role of erythrocytes' PS exposure in anemia in uremic patients. METHOD: Erythrocyte PS exposure was measured in 67 stable patients on continuous ambulatory peritoneal dialysis (CAPD). An investigation was conducted in the relationship between the level of erythrocyte PS exposure and hemoglobin concentration. A flow-cytometric assay based on FITC-Annexin V was used to measure the PS exposure of erythrocytes. RESULTS: An inverse correlation was found between the percentage of PS-positive RBCs and hemoglobin concentration (r = -0.2601, p < 0.05). Logistic regression analysis revealed that the percentage of PS-positive RBCs was identified as a risk factor for anemia (Hazards ratio = -0.421, p < 0.05). CONCLUSION: This study found that elevated PS exposure in erythrocytes might be a risk factor for anemia and contribute to the development of anemia in peritoneal dialysis patients.

Anemia↗