Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 91 records · Page 5Linked to original sources

PubMed2004

Algorithmic generation of freely jointed hard sphere chains and properties of their inertial tensors.

A statistical algorithm, capable of generating a large number of freely jointed hard sphere chains, is presented. This is the first of a series of algorithms being developed to model unfolded proteins by different modes of hard sphere chains. The aim of these studies is to systematically investigate the effects of different factors, such as atomic radii, bond angles, torsion angles, chain length, etc., on the conformation of unfolded proteins and other random polymers. As continuous models, various types of hard sphere chains enable one to isolate the aforementioned factors one at a time for investigation and thus are advantageous over discrete lattice models. In particular, the freely jointed hard sphere chain model allows one to evaluate the excluded volume effect. As a first step in this endeavor, the average determinant D(N, r) and the average trace T(N, r) of the inertial tensor A of the random chains were calculated at various sphere radii r and chain lengths N. It is found that both the average determinant D(N, r) and the average trace T(N, r) scale linearly with chain length N after logarithmic transformation. However, the critical exponent of D(N, r) increases with r faster than that of T(N, r) as a result of the non-commutativity between the det operator and the average operator < >. The significance of the algorithm and the results obtained on understanding random polypeptide chains are discussed.

Algorithms↗

PubMed2004

Immune modulation of the pulmonary hypertensive response to bacterial lipopolysaccharide (endotoxin) in broilers.

The lungs of broilers are constantly challenged with lipopolysaccharide (LPS, endotoxin) that can activate leukocytes and trigger thromboxane A2 (TxA2)- and serotonin (5HT)-mediated pulmonary vasoconstriction leading to pulmonary hypertension. Among broilers from a single genetic line, some individuals respond to LPS with large increases in pulmonary arterial pressure, whereas others fail to exhibit any response to the same supramaximal dose of LPS. This extreme variability in the pulmonary hypertensive response to LPS appears to reflect variability in the types or proportions of chemical mediators released by leukocytes. Our research has confirmed that TxA2 and 5HT are potent pulmonary vasoconstrictors in broilers and that broilers hatched and reared together consistently exhibit pulmonary hypertension after i.v. injections of TxA2 or 5HT. Previous in vitro studies conducted using macrophages from different lines of chickens demonstrated innate variability in the LPS-stimulated induction of nitric oxide synthase (iNOS) followed by the onset of an LPS-refractory state. The NOS enzyme converts arginine to citrulline and nitric oxide (NO). It is known that NO produced by endothelial NOS serves as a key modulator of flow-dependent pulmonary vasodilation, and it is likely that NO generated by iNOS also contributes to the pulmonary vasodilator response. Accordingly, it is our hypothesis that the pulmonary hypertensive response to LPS in broilers is minimal when more vasodilators (NO, prostacyclin) than vasoconstrictors (TxA2, 5HT) are generated during an LPS challenge. Indeed, inhibiting NO production through pharmacological blockade of NOS with the inhibitor Nomega-nitro-L-arginine methyl ester modestly increased the baseline pulmonary arterial pressure and dramatically increased the pulmonary hypertensive response to LPS in all broilers evaluated. Innate differences in the effect of LPS on the pulmonary vasculature may contribute to differences in susceptibility of broilers to pulmonary hypertension syndrome (ascites).

Animals↗

PubMed2004

Component and whole-system respiration fluxes in northern deciduous forests.

We measured component and whole-system respiration fluxes in northern hardwood (Acer saccharum Marsh., Tilia americana L., Fraxinus pennsylvanica Marsh.) and aspen (Populus tremuloides Michx.) forest stands in Price County, northern Wisconsin from 1999 through 2002. Measurements of soil, leaf and stem respiration, stem biomass, leaf area and biomass, and vertical profiles of leaf area were combined with biometric measurements to create site-specific respiration models and to estimate component and whole-system respiration fluxes. Hourly estimates of component respiration were based on site measurements of air, soil and stem temperature, leaf mass, sapwood volume and species composition. We also measured whole-system respiration from an above-canopy eddy flux tower. Measured soil respiration rates varied significantly among sites, but not consistently among dominant species (P < 0.05 and P > 0.1). Annual soil respiration ranged from 8.09 to 11.94 Mg C ha(-1) year(-1). Soil respiration varied linearly with temperature (P < 0.05), but not with soil water content (P > 0.1). Stem respiration rates per unit volume and per unit area differed significantly among species (P < 0.05). Stem respiration per unit volume of sapwood was highest in F. pennsylvanica (up to 300 micro mol m(3) s(-1)) and lowest in T. americana (22 micro mol m(3) s(-1)) when measured at peak summer temperatures (27 to 29 degrees C). In northern hardwood stands, south-side stem temperatures were higher and more variable than north-side temperatures during leaf-off periods, but were not different statistically during leaf-on periods. Cumulative annual stem respiration varied by year and species (P < 0.05) and averaged 1.59 Mg C ha(-1) year(-1). Leaf respiration rates varied significantly among species (P < 0.05). Respiration rates per unit leaf mass measured at 30 degrees C were highest for P. tremuloides (38.8 nmol g(-1) s(-1)), lowest for Ulmus rubra Muhlenb. (13.1 nmol g(-1) s(-1)) and intermediate and similar (30.2 nmol g(-1) s(-1)) for T. americana, F. pennsylvanica and Q. rubra. During the growing season, component respiration estimates were dominated by soil respiration, followed by leaf and then stem respiration. Summed component respiration averaged 11.86 Mg C ha(-1) year(-1). We found strong covariance between whole-ecosystem and summed component respiration measurements, but absolute rates and annual sums differed greatly.

Acer↗

PubMed2004

A theta-defensin composed exclusively of D-amino acids is active against HIV-1.

The ability of certain theta-defensins, including retrocyclin-1, to protect human cells from infection by HIV-1 marks them as potentially useful molecules. Theta-defensins composed of L-amino acids are likely to be unstable in environments that contain host and microbial proteases. This study compared the properties of two enantiomeric theta-defensins, retrocyclin-1, and RC-112. Although these peptides have identical sequences, RC-112 is composed exclusively of D-amino acids, whereas retrocyclin-1 contains only L-amino acids. We compared the ability of these peptides to protect JC53-BL human cells from infection by 30 primary HIV-1 isolates. JC53-BL cells are modified HeLa cells that express surface CD4, CXCR4, and CCR5. They also contain reporter cassettes that are driven by the HIV-1 LTR, and express beta-galactosidase and luciferase. The HIV-1 isolates varied in co-receptor specificity and included subtypes A, B, C, D, CRF01-AE, and G. RC-112 was several fold more potent than retrocyclin-1 across the entire HIV-1 panel. Although RC-112 bound immobilized gp120 and CD4 with lower affinity than did retrocyclin-1, surface plasmon resonance experiments performed with 1 microg/mL of RC-112 and retrocyclin-1 revealed that both glycoproteins were bound to a similar extent. The superior antiviral performance of RC-112 most likely reflected its resistance to degradation by surface-associated or secreted proteases of the JC53-BL target cells. Theta-defensins composed exclusively of D-amino acids merit consideration as starting points for designing microbicides for topical application to the vagina or rectum.

Amino Acids↗

PubMed2004

The expression of thrombospondin-1 in benign prostatic hyperplasia and prostatic intraepithelial neoplasia is decreased in prostate cancer.

OBJECTIVE: To evaluate the immunohistochemical expression of thrombospondin (TSP), a potent inhibitor of angiogenesis, in human benign prostatic hyperplasia (BPH) and prostate cancer. MATERIALS AND METHODS: The expression of TSP-1, TSP-2 and CD36 receptor was assessed in 73 tissue specimens using immunohistochemistry; specimens were from 32 patients with BPH, seven with prostatic intraepithelial neoplasia (PIN) and 34 with cancer. RESULTS: Immunohistochemistry showed that all 39 patients with BPH and PIN had TSP-1-positive glands. In contrast, none of the 34 patients with cancer had positive TSP-1 staining in the cancer tissue. All 73 patients were positive for TSP receptor CD36 and negative for TSP-2. CONCLUSIONS: TSP is expressed in BPH, down-regulated in PIN and absent in prostate cancer tissue. This may indicate that TSP is important in prostate cancer progression. Further studies are needed to understand the significance of these findings for the malignant transformation of the prostate gland.

Humans↗

PubMed2004

Peptide deformylase inhibitors as antibacterial agents: identification of VRC3375, a proline-3-alkylsuccinyl hydroxamate derivative, by using an integrated combinatorial and medicinal chemistry approach.

Peptide deformylase (PDF), a metallohydrolase essential for bacterial growth, is an attractive target for use in the discovery of novel antibiotics. Focused chelator-based chemical libraries were constructed and screened for inhibition of enzymatic activity, inhibition of Staphylococcus aureus growth, and cytotoxicity. Positive compounds were selected based on the results of all three assays. VRC3375 [N-hydroxy-3-R-butyl-3-(2-S-(tert-butoxycarbonyl)-pyrrolidin-1-ylcarbonyl)propionamide] was identified as having the most favorable properties through an integrated combinatorial and medicinal chemistry effort. This compound is a potent PDF inhibitor with a K(i) of 0.24 nM against the Escherichia coli Ni(2+) enzyme, possesses activity against gram-positive and gram-negative bacterial pathogens, and has a low cytotoxicity. Mechanistic experiments demonstrate that the compound inhibits bacterial growth through PDF inhibition. Pharmacokinetic studies of this drug in mice indicate that VRC3375 is orally bioavailable and rapidly distributed among various tissues. VRC3375 has in vivo activity against S. aureus in a murine septicemia model, with 50% effective doses of 32, 17, and 21 mg/kg of body weight after dosing by intravenous (i.v.), subcutaneous (s.c.), and oral (p.o.) administration, respectively. In murine single-dose toxicity studies, no adverse effects were observed after dosing with more than 400 mg of VRC3375 per kg by i.v., p.o., or s.c. administration. The in vivo efficacy and low toxicity of VRC3375 suggest the potential for developing this class of compounds to be used in future antibacterial drugs.

Algorithms↗

PubMed2004

Stress and dysmenorrhoea: a population based prospective study.

BACKGROUND: Dysmenorrhoea is the most common gynaecological disorder in women of reproductive age. Despite the association between stress and pregnancy outcomes, few studies have examined the possible link between stress and dysmenorrhoea. AIMS AND METHODS: Using a population based cohort of Chinese women, the independent effect of women's perceived stress in the preceding menstrual cycle on the incidence of dysmenorrhoea in the subsequent cycle was investigated prospectively. The analysis included 1160 prospectively observed menstrual cycles from 388 healthy, nulliparous, newly married women who intended to conceive. The perception of stress and the occurrence of dysmenorrhoea in each menstrual cycle were determined from daily diaries recorded by the women. RESULTS: After adjustment for important covariates, the risk of dysmenorrhoea was more than twice as great among women with high stress compared to those with low stress in the preceding cycle (OR = 2.4; 95% CI 1.4 to 4.3). The risk of dysmenorrhoea was greatest among women with both high stress and a history of dysmenorrhoea compared to women with low stress and no history of dysmenorrhoea (OR = 10.4, 95% CI 4.9 to 22.3). Stress in the follicular phase of the preceding cycles had a stronger association with dysmenorrhoea than stress in the luteal phase of the preceding cycles. CONCLUSION: This study shows a significant association between stress and the incidence of dysmenorrhoea, which is even stronger among women with a history of dysmenorrhoea.

Adult↗

PubMed2004

Accurate classification of protein structural families using coherent subgraph analysis.

Protein structural annotation and classification is an important problem in bioinformatics. We report on the development of an efficient subgraph mining technique and its application to finding characteristic substructural patterns within protein structural families. In our method, protein structures are represented by graphs where the nodes are residues and the edges connect residues found within certain distance from each other. Application of subgraph mining to proteins is challenging for a number reasons: (1) protein graphs are large and complex, (2) current protein databases are large and continue to grow rapidly, and (3) only a small fraction of the frequent subgraphs among the huge pool of all possible subgraphs could be significant in the context of protein classification. To address these challenges, we have developed an information theoretic model called coherent subgraph mining. From information theory, the entropy of a random variable X measures the information content carried by X and the Mutual Information (MI) between two random variables X and Y measures the correlation between X and Y. We define a subgraph X as coherent if it is strongly correlated with every sufficiently large sub-subgraph Y embedded in it. Based on the MI metric, we have designed a search scheme that only reports coherent subgraphs. To determine the significance of coherent protein subgraphs, we have conducted an experimental study in which all coherent subgraphs were identified in several protein structural families annotated in the SCOP database (Murzin et al, 1995). The Support Vector Machine algorithm was used to classify proteins from different families under the binary classification scheme. We find that this approach identifies spatial motifs unique to individual SCOP families and affords excellent discrimination between families.

Algorithms↗

PubMed2004

Mainland Chinese students' concept of health.

This investigation, which was part of a larger project, was to describe and explain the concept of health as perceived by Chinese students. Data were collected through a questionnaire from students from two primary schools, two high schools and two universities (N=946) in Shanghai, China. The results showed that Chinese students not only considered themselves healthy but also viewed adolescents as the healthiest people in comparison with children, the middle and the old-aged. Their health concept consisted of components relating to physical, psychological, and social/moral dimensions. There were more boys than girls who considered mental health to be part of general health and a tendency for boys to perceive health status as poorer along with the increase in age. The categories of the concept of health and students' views on how to enhance health status are presented.

Adolescent↗

PubMed2004

The regulation of glucose-excited neurons in the hypothalamic arcuate nucleus by glucose and feeding-relevant peptides.

Glucosensing neurons in the hypothalamic arcuate nucleus (ARC) were studied using electrophysiological and immunocytochemical techniques in neonatal male Sprague-Dawley rats. We identified glucose-excited and -inhibited neurons, which increase and decrease, respectively, their action potential frequency (APF) as extracellular glucose levels increase throughout the physiological range. Glucose-inhibited neurons were found predominantly in the medial ARC, whereas glucose-excited neurons were found in the lateral ARC. ARC glucose-excited neurons in brain slices dose-dependently increased their APF and decreased their ATP-sensitive K+ channel (KATP channel) currents as extracellular glucose levels increased from 0.1 to 10 mmol/l. However, glucose sensitivity was greatest as extracellular glucose decreased to <2.5 mmol/l. The glucokinase inhibitor alloxan increases KATP single-channel currents in glucose-excited neurons in a manner similar to low glucose. Leptin did not alter the activity of ARC glucose-excited neurons. Although insulin did not affect ARC glucose-excited neurons in the presence of 2.5 mmol/l (steady-state) glucose, they were stimulated by insulin in the presence of 0.1 mmol/l glucose. Neuropeptide Y (NPY) inhibited and alpha-melanocyte-stimulating hormone stimulated ARC glucose-excited neurons. ARC glucose-excited neurons did not show pro-opiomelanocortin immunoreactivity. These data suggest that ARC glucose-excited neurons may serve an integrative role in the regulation of energy balance.

Alloxan↗

PubMed2004

De novo satellited 21q associated with corpus callosum dysgenesis, colpocephaly, a concealed penis, congenital heart defects, and developmental delay.

De novo satellited 21q associated with corpus callosum dysgenesis, colpocephaly, a concealed penis, congenital heart defects, and developmental delay: We present clinical and cytogenetic data on an infant with de novo satellited 21 q. A 3-month-old boy was found to have microcephaly, developmental delay, hypertelorism, down-slanting palpebral fissures, large low-set ears, a prominent nose, a broad philtrum, a concealed penis, interventricular septal defects, corpus callosum dysgenesis, colpocephaly, ventriculomegaly, and a de novo karyotype of 46,XY,21qs. Standard Ag-NOR staining and FISH studies confirmed a satellite and a deletion on the long arm of a chromosome 21. Quantitative-fluorescent polymerase chain reaction using the polymorphic small tandem repeat markers specific for chromosome 21 determined a maternal origin of the deletion and the breakpoint between D21S156 (21q22.1) (present) and D21S53 (21q22.3) (absent), centromeric to the known minimal holoprosencephaly critical region, D21S13-21qter. The present case provides evidence of the correlation of a distal region of chromosome 21 to the phenotypic effects of monosomy 21.

Abnormalities, Multiple↗

PubMed2004

Discrepancy between the fetus and extra-embryonic tissues in prenatally detected mosaic distal 5p deletion.

Discrepancy between the fetus and extra-embryonic tissues in prenatally detected mosaic distal 5p deletion: We present clinical and cytogenetic data on a second-trimester fetus with mosaic del(5)(p15.1) and the extra-embryonic tissues with a normal karyotype. A 34-year-old woman, gravida 2, para 0, underwent genetic amniocentesis at 20 weeks' gestation because of advanced maternal age. Cytogenetic analysis of the cultured amniocytes revealed mosaicism for a distal 5p deletion, mos 46,XY,del(5)(p15.1)[4]/46,XY[26]. The pregnancy was terminated subsequently. Postnatally, the fetus displayed a triangular face, hypertelorism, epicanthal folds, low-set ears, and micrognathia. A karyotype of mos 46,XY,del(5)(pl 5.1)/46,XY was found in the liver, lungs, skin, and cord blood, whereas, the placenta, amnion, and umbilical cord had a karyotype of 46,XY. Our observation of fetoplacental, fetoamniotic, and fetoumbilical discrepancies shows a limitation of using placenta, amnion, and umbilical cord as confirmatory tools for prenatally detected mosaic distal 5p deletion. Our case also reinforces the notion that amniocentesis offers a more reliable diagnosis, compared to chorionic villus sampling.

Adult↗

PubMed2004

Effect of corporal fibroids on outcome following embryo transfer in donor-oocyte recipients.

PURPOSE: To evaluate the effect of intramural or subserosal fibroids in the uterine fundus or corpus on pregnancy outcome following transfer of embryos formed from donated oocytes methods. METHODS: Leiomyomata were measured in three dimensions by transvaginal sonography. Scanning was performed in two planes (sagittal and coronal) at the level of maximal width. The location was categorized by depth in the uterus. RESULTS: There was no difference in pregnancy rates in those with or without fibroids. However, there was a significantly higher miscarriage rate in the former group. CONCLUSION: Women with fibroids are generally older. Thus conclusions about the effect on miscarriage rates are complicated by the effect of the aging oocyte on miscarriages. This study eliminated the oocyte factor by using only younger donated oocytes.

Abortion, Spontaneous↗

PubMed2003

Alpha-substituted hydroxamic acids as novel bacterial deformylase inhibitor-based antibacterial agents.

We report the synthesis and biological activity of analogues of VRC3375 (N-hydroxy-3-R-butyl-3-[(2-S-(tert-butoxycarbonyl)-pyrrolidin-1-ylcarbonyl]propionamide), an orally active peptide deformylase inhibitor. This study explores the structure-activity relationship of various chelator groups, alpha substituents, P(2)' and P(3)' substituents in order to achieve optimal antibacterial activity with minimal toxicity liability.

Amidohydrolases↗

PubMed2003

Effects of c-fos antisense oligodeoxynucleotide on 5-HT-induced upregulation of preprodynorphin, preproenkephalin, and glutamic acid decarboxylase mRNA expression in cultured rat spinal dorsal horn neurons.

Effects of c-fos antisense oligodeoxynucleotide (ASO) on serotonin (5-HT)-induced upregulation of preprodynorphin (ppDyn), preproenkephalin (ppEnk), and glutamic acid decarboxylase (GAD), a special chemical marker for gamma-aminobutyric acid (GABA) neurons, mRNAs in cultured spinal dorsal horn neurons were investigated in order to extend our understanding of expressions of opioid peptides and GABA in spinal cord regulated by the descending serotonergic efferents. Reverse transcription-polymerase chain reaction analysis revealed a time-course increase in the expression of mRNAs encoding c-fos, ppDyn, ppEnk, and GAD after administration of 5-HT (100 nM). Administration of c-fos ASO (0.02 nM) 30 min prior to 5-HT application markedly blocked the expression of c-fos gene. Moreover, c-fos ASO pretreatment significantly decreased the 5-HT-induced upregulation of ppDyn and ppEnk mRNAs, but failed to affect the expression level of GAD mRNA. These results suggest that the serotoningic raphe-spinal efferents might play an important role in regulating the synthesis of enkephalin, dynorphin, and GABA in the spinal dorsal horn neurons. The immediate early oncogene c-fos might be involved in the 5-HT-induced increase in ppDyn and ppEnk expression. However, under the present experimental conditions, c-fos does not seem to be associated with the upregulation of GAD mRNA induced by 5-HT.

Animals↗

PubMed2003

Oxygen partial pressure in outer layers of skin of human finger nail folds.

To gain insight into oxygen transport by the cutaneous microcirculation, we have developed oxygen-sensitive microelectrodes (tip diameter approximately 5 micro m) to measure the distribution of PO2 in dermal papillae of the finger nail folds of healthy human subjects. Oxygen entry into the tissue was minimised by covering the skin with a layer of paraffin oil. The finger was held under a dissecting microscope and microelectrodes were guided into position. PO2 varied from 5-25 % of its atmospheric value, Pair (approximately 160 mmHg), depending on the location within the papilla. Along the axis of a papillary loop, PO2 decreased from 40.0 +/- 4.8 mmHg (mean +/- S.E.M., n = 6) at the base to 30.4 +/- 5.2 mmHg (n = 6) at the tip. The lowest values of PO2, in the range of 5 % of Pair, were measured in the epidermis where the metabolism of cells was highest and the steepest PO2 gradients were recorded in the vicinity of the epidermal-dermal boundary. When the local circulation was abruptly reduced or stopped, PO2 fell exponentially with time, with a time constant of 8.4 +/- 1.5 s (n = 7). When flow was reinstated, PO2 rose exponentially to a new value with a time constant of 4.8 +/- 0.8 s (n = 6). The steady state PO2 following reperfusion was approximately 23 % higher than the pre-occlusion value (P < 0.05, ANOVA and two-tailed Student's t test) indicating localised reactive hyperaemia.

Adult↗

PubMed2003

Constitutive nuclear factor-kappa B mRNA, protein overexpression and enhanced DNA-binding activity in thymidylate synthase inhibitor-resistant tumour cells.

In this study, the gene copy number, mRNA and protein expression levels and nuclear DNA-binding activity of nuclear factor kappa B (NF-kappa B) were compared in a panel of five pairs of thymidylate synthase (TS) inhibitor-resistant and wild-type parent cancer cell lines. High constitutive NF-kappa B DNA-binding activity was detected in all chemoresistant cell lines. The upregulated NF-kappa B activity was composed of NF-kappa B subunits p50 and p65. Four out of five resistant cell lines constitutively overexpressed NF-kappa B p50 and p65 mRNA and protein. One resistant cell line with the highest NF-kappa B DNA-binding activity showed normal p50 and p65 protein expression. No NF-kappa B gene amplification was detected in resistant cell lines. Transient exposure of wild-type RKO(WT) and H630(WT) cells to 5-FU induced NF-kappa B DNA-binding activity but had no effect on NF-kappa B protein expression in these cells. Our results indicate that high constitutive NF-kappa B activity caused by its gene overexpression is an intrinsic character of TS inhibitor-resistant cells. NF-kappa B can antagonise anticancer drug-induced apoptosis. High NF-kappa B expression and nuclear activity in TS inhibitor-resistant cancer cells may play an important role in the chemoresistance.

Cell Division↗

PubMed2003

Aquaporin expression in developing human teeth and selected orofacial tissues.

The aquaporin (AQP) family of membrane channel proteins function as selective pores through which water, glycerol, and other small solutes cross the cell plasma membrane. To date, 11 members of this transporter family, designated AQP0-10, have been cloned and characterized in humans. The AQPs are differentially expressed in temporospatial patterns, where different AQPs demonstrate distinct tissue distributions that may reflect differing cell membrane transport functions. The purpose of this study was to evaluate AQP expression in the developing human teeth by RT-PCR and Western blot analysis. To access the generality of AQP expression, selected other orofacial tissues were studied by RT-PCR. The presence of all eleven human AQPs was screened in each tissue by RT-PCR. Positive amplification products were verified by direct DNA sequencing. AQPs 1, 3, 4, 5, 6, and 10 were identified by RT-PCR in developing teeth, and AQP1, 3, 5, and 6 were confirmed by Western blot analysis. AQP 4 was not detected by Western blot analysis, and we were unable to test for the recently identified AQP10 due to unavailability of antibodies. AQPs detected in other orofacial tissues by RT-PCR included gingiva (AQP3, 7, 10); Meckel's cartilage (AQP1, 3, 4, 5, 6); submandibular gland (AQP1, 3, 4, 5, 6, 7); masseter muscle (AQP1, 3, 4, 7, 8, 9,10); and infrahyoid muscle (AQP1, 3, 4,10). These results demonstrate that multiple aquaporins are expressed in developing teeth and in selected orofacial tissues.

Adolescent↗