Biomedical subjects

W Wang

Publications and source records attributed to W Wang.

At least 433 records · Page 24Linked to original sources

PubMed2000

Fast repair of dAMP radical anions by phenylpropanoid glycosides and their analogs.

Repair effect on 2'-deoxyadenosine-5'-monophosphate (dAMP) radical anions by phenylpropanoid glycosides (PPGs) and their analogs, isolated from Chinese folk medicinal herb, was studied using pulse radiolysis technique. The radical anion of dAMP was formed by the reaction of hydrated electron with dAMP. On pulse irradiation of nitrogen-saturated dAMP aqueous solution containing 0.2 M t-BuOH and one of PPGs or their analogs, the transient absorption spectrum of the radical anion of dAMP decayed with the formation of that of the radical anion of PPGs or their analogs within several decades of microseconds after electron pulse irradiation. The results indicated that dAMP radical anions can be repaired by PPGs or their analogs. The rate constants of the repair reactions were deduced to be 1.6-4.5 x 10(8) M(-1) s(-1).

Anions↗

PubMed2000

Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease.

We identified zonulin, a novel human protein analogue to the Vibrio cholerae derived Zonula occludens toxin, which induces tight junction disassembly and a subsequent increase in intestinal permeability in non-human primate intestinal epithelia. Zonulin expression was raised in intestinal tissues during the acute phase of coeliac disease, a clinical condition in which tight junctions are opened and permeability is increased.

Adult↗

PubMed2000

[Chemically induced (streptozotocin-alloxan) diabetes mellitus in dogs].

To evaluate the efficiency and toxic and side effect of the combined chemical inducer for Type I diabetes mellitus, Type I diabetes in 9 adult dogs were induced with alloxan(50 mg.kg-1) and streptozotocin (30 mg.kg-1) with vein injection. After 7-14 days, the blood glucose of 5 male dogs was kept on high levels [mean value was (22.7 +/- 3.2) mmol.L-1], exogenous insulin was (21.4 +/- 2.4) U.day-1. Three female dogs died in 7 days after they had been injected with the combined inducers. Alloxan-streptozotocin combination administration reduced the dosage of each drug, and decreased the toxic and side effect of each drug. The results suggest that this method has a high rate of success to induce Type I diabetes male dogs.

Alloxan↗

PubMed2000

Matrix metalloproteinase-2 contributes to ischemia-reperfusion injury in the heart.

BACKGROUND: Matrix metalloproteinases (MMPs) contribute to collagen degradation and remodeling of the extracellular matrix after myocardial infarction; however, their role in myocardial dysfunction immediately after ischemia and reperfusion is unknown. METHODS AND RESULTS: We measured the release of MMPs into the coronary effluent of isolated, perfused rat hearts during aerobic perfusion and reperfusion after ischemia. Aerobically perfused control hearts expressed pro-MMP-2 and MMP-2, as well as an unidentified 75-kDa gelatinase. These enzymes were also detected in the coronary effluent. After 20 minutes of global no-flow ischemia, there was a marked increase in pro-MMP-2 in the coronary effluent that peaked within the first minute of reperfusion. The release of pro-MMP-2 into the coronary effluent during reperfusion was enhanced with increasing duration of ischemia and correlated negatively with the recovery of mechanical function during reperfusion (r(2)=0.99). MMP-2 antibody (1.5 to 15 microg/mL) and the inhibitors of MMPs doxycycline (10 to 100 micromol/L) and o-phenanthroline (3 to 100 micromol/L) improved whereas MMP-2 worsened the recovery of mechanical function during reperfusion. CONCLUSIONS: These results show that acute release of MMP-2 during reperfusion after ischemia contributes to cardiac mechanical dysfunction. The inhibition of MMPs may be a novel pharmacological strategy for the treatment of ischemia-reperfusion injury.

Analysis of Variance↗

PubMed2000

Modulation of focal and global Ca2+ release in calsequestrin-overexpressing mouse cardiomyocytes.

1. Focal and global Ca2+ releases were monitored in voltage-clamped control and hypertrophied calsequestrin (CSQ)-overexpressing mouse cardiomyocytes, dialysed with fluo-3, using rapid (120-240 frames s-1) two-dimensional confocal imaging. 2. Spontaneous focal Ca2+ releases (Ca2+ sparks) were absent or significantly reduced in frequency in hypertrophied myocytes of CSQ-overexpressing mice compared to their age-matched controls. Sporadic Ca2+ sparks seen in CSQ-overexpressing myocytes had intensities and durations similar to those of controls although quantitative analysis showed a trend towards more diffuse focal releases. 3. Activation of Ca2+ current (ICa) failed to produce the typical sarcomeric Ca2+ striping pattern consistently seen in control myocytes. Instead, focal Ca2+ releases appeared as a disorganized patchwork of diffuse or 'woolly' fluorescence signals, resulting in slowly developing and reduced global Ca2+ transients. 4. Although the density of ICa in CSQ-overexpressing myocytes was only slightly smaller than that of controls, the inactivation kinetics of the current were greatly reduced, consistent with the much smaller rate of rise of cytosolic Ca2+. 5. Enhancement of ICa by elevation of [Ca2+]o from 2 to 10 mM or addition of 3 microM isoproterenol (isoprenaline) failed to normalize the frequency of spontaneous Ca2+ sparks at rest or the pattern and the magnitude of ICa-gated Ca2+ transients. Isoproterenol was somewhat more effective than elevation of [Ca2+]o. 6. In sharp contrast, low (0.5 mM) caffeine concentrations that produced no measurable effects on ICa or Ca2+ transients in control myocytes, re-established spontaneous focal Ca2+ releases in CSQ-overexpressing cells, triggered large ICa-gated cellular Ca2+ transients, and strongly enhanced the kinetics of inactivation of ICa. 7. Our data suggest that impaired Ca2+ signalling in CSQ-overexpressing myocytes results from reduced co-ordination and decreased frequency of Ca2+ sparks. The impaired Ca2+ signalling could not be restored by procedures that increased ICa, but was mostly restored in the presence of caffeine, which may alter the Ca2+ sensitivity of the ryanodine receptor.

Adrenergic beta-Agonists↗

PubMed2000

Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC).

We recently reported the identification of a chemokine (CTACK), which has been renamed CCL27 according to a new systematic chemokine nomenclature. We report that CCL27 binds the previously orphan chemokine receptor GPR-2, as detected by calcium flux and chemotactic responses of GPR-2 transfectants. We renamed this receptor CCR10. Because of the skin-associated expression pattern of CCL27, we focused on the expression of CCL27 and CCR10 in normal skin compared with inflammatory and autoimmune skin diseases. CCL27 is constitutively produced by keratinocytes but can also be induced upon stimulation with TNF-alpha and IL-1beta. CCR10 is not expressed by keratinocytes and is instead expressed by melanocytes, dermal fibroblasts, and dermal microvascular endothelial cells. CCR10 was also detected in T cells as well as in skin-derived Langerhans cells. Taken together, these observations suggest a role for this novel ligand/receptor pair in both skin homeostasis as well as a potential role in inflammatory responses.

Amino Acid Sequence↗

PubMed2000

Chemosensitivity of non-respiratory rat CNS neurons in tissue culture.

Neurons from many brainstem nuclei involved in respiratory control increase their firing rate in response to acidosis in vitro, suggesting that they are central chemoreceptors. This property has been considered to be either unique to neurons involved in respiratory control, or at least very unusual for non-respiratory neurons. However, recordings of intrinsic pH responses of neurons have not been made from enough non-respiratory regions of the CNS to be certain this assumption is true. Here, we have quantified changes in firing rate of neurons cultured from the hippocampus (n=43), neocortex (n=33), and cerebellum (n=29) in response to changes in CO(2) between 3% and 9% (pH approximately 7.6-7.2) after blockade of glutamatergic and GABAergic transmission. The responses of neurons from these three regions were similar, with a subset of neurons (12% of the total 105) inhibited by acidosis, decreasing their firing rate to a mean of 70% of control in response to a decrease in pH of 0.2. Some neurons (5% of total) were stimulated by acidosis, with an increase in firing rate to a mean of 175% of control in response to a decrease in pH of 0.2. We previously quantified chemosensitivity of neurons from the medullary raphe using the same methods [W. Wang, J.H. Pizzonia, G.B. Richerson, Chemosensitivity of rat medullary raphe neurones in primary tissue culture, J. Physiol., 511 (1998) 433-450]. Compared to these non-respiratory neurons, more raphe neurons were stimulated by acidosis (22%), and the average response was greater (to 300% of control) in response to the same stimulus. Thus, over a physiologically relevant pH range, stimulation by acidosis occurs in a significant percentage of neurons not involved in respiratory chemoreception. However, the degree of chemosensitivity of these neurons was less than medullary raphe neurons under the same conditions. Chemosensitivity is not an all-or-none neuronal property, and the degree of chemosensitivity may be relevant to the role neurons play in sensing pH in vivo.

2-Amino-5-phosphonovalerate↗

PubMed2000

Phase order in chaotic maps and in coupled map lattices

By defining a direction phase as the direction of two sequential iterations of the logistic map, a transition of a net direction phase M from zero to a finite value as the parameter &mgr; increases is found. Near the transition point &mgr;(0) a scaling M approximately (&mgr;-&mgr;(0))(alpha) with alpha = 0.5 is obtained. The order state of the direction phases in a coupled map lattice is also studied. A phase synchronization of the direction phases is found although the lattices still remain chaotic.

Journal Article↗

PubMed2000

Synthesis and structure of the cluster ion pair [Ru3(CO)9[mu-P(NPri2)2]3][Ru6(CO)15(mu 6-C)[mu-P(NPri2)2]]. A theoretical overview of M3(mu-PR2)3 frameworks.

The compound [Ru3(CO)9[mu-P(NPri2)2]3][Ru6(CO)15(mu 6-C)[mu-P(NPri2)2]] (1), obtained via the addition of PCl(NPri2)2 to K2[Ru4(CO)13], crystallizes in the monoclinic space group P2l/c with a = 15.537(8) A, b = 36.151(16) A, c = 19.407(5) A, beta = 91.14(2) degrees, Z = 4, and R = 0.069 for 8006 observed reflections. The unit cell is unusual in that it contains both a typical octahedral Ru6 cluster anion (1a), featuring an encapsulated carbide, and a symmetrical phosphido bridge, in addition to a 50-electron trinuclear cluster cation [Ru3(CO)9[mu-P(NPri2)2]3]+ (1c). The latter, with approximate D3h symmetry, exhibits long Ru-Ru distances (> or = 3.15 A). Among the family of clusters with M3(mu-PR2)3 cores and different numbers of both electrons (TEC) and terminal ligands (LxLyLz), 1c is unique in that it is a 333 stereotype with 50 valence electrons. MO calculations permit us to predict the existence of redox congeners of 1c clusters and related 48e Re3 clusters. This work also presents a summary of the relationships between the electronic and the geometric structures for all known M3LxLyLz(mu-PR2)3 species. The basic stereochemical features are influenced by the total-electron count and, hence, by the degree of M-M bonding, as well as the remarkable flexibility of the phosphido bridging ligands. The mu-PR2 ligands need not necessarily lie in the M3 plane, and a wide range of M-P-M angles (as small as 72 degrees or as large as 133 degrees) have been observed.

Journal Article↗

PubMed2000

Rat testicular Src: normal distribution and involvement in ethylene glycol monomethyl ether-induced apoptosis.

Kinase activities were previously proposed to be central to germ cell apoptosis induced by ethylene glycol monomethyl ether (EGME) and its active metabolite methoxyacetic acid (MAA). We evaluated the role of tyrosine kinase pp60(c-src) in control and EGME-treated adult rat testis in vivo, as well as in vitro using cultured adult rat seminiferous tubules treated with MAA. In normal testicular tissue, immunoreactivity of Src was mostly detected in Sertoli cell cytoplasm and reached the maximum level around the lumen at spermiation. Src localization was confirmed by immunostaining of cocultures of Sertoli and germ cells and was further confirmed by electron microscopic observation that immunoreactivity was predominant in Sertoli cell cytoplasm as well as occasionally at the Sertoli/germ cell junctions. A single dose of 200 mg/kg EGME induced an increase of Src immunoexpression in both epithelium and interstitium in rat testis. Eight hours after treatment, an intensive immunostaining of Src began to be observed specifically in the cytoplasm of the dying spermatocytes. The apoptotic changes were replicated by exposure of 5 mM MAA in the adult rat seminiferous tubule culture model. Furthermore, spermatocyte degeneration was significantly prevented by cotreatment with 0.1 microM geldanamycin, 10 microM herbimycin A, or 10 microM PP2, which are inhibitors of Src activity. These data collectively suggest that pp60(c-src) mediates Sertoli-germ cell interaction in physiological events, and may play an important role in EGME/MAA-induced germ cell apoptosis.

Animals↗

PubMed2000

A coumarin-based prodrug strategy to improve the oral absorption of RGD peptidomimetics.

In recent years, major progress has been made in the design and synthesis of fibrinogen antagonists, which are peptidomimetic Arg-Gly-Asp (RGD) analogs. These RGD analogs are very promising antiplatelet agents. However, the clinical development of orally active RGD analogs has been hindered by the low oral bioavailability of many such RGD analogs. Aimed at enhancing their oral bioavailability, we have synthesized several coumarin-based cyclic prodrugs of RGD analogs, which have the two most polar functional groups, a carboxyl and an amino group, masked as an ester and an amide, respectively. As expected, these cyclic prodrugs have higher membrane interaction potentials as estimated by determining their partitioning between aqueous buffer and an immobilized artificial membrane than the corresponding RGD analogs. Consequently, these cyclic prodrugs are 5-6-fold more able to permeate monolayers of Caco-2 cells, an in vitro cell culture model of the intestinal mucosa barrier. Preliminary studies using dog also indicate the promising potential of using this coumarin-based prodrug strategy to improve the oral bioavailability of such RGD analogs.

Animals↗

PubMed2000

The C3(1)/SV40 T-antigen transgenic mouse model of mammary cancer: ductal epithelial cell targeting with multistage progression to carcinoma.

The 5' flanking region of the C3(1) component of the rat prostate steroid binding protein (PSBP) has been used to successfully target the expression of the SV40 large T-antigen (Tag) to the epithelium of both the mammary and prostate glands resulting in models of mammary and prostate cancers which histologically resemble the human diseases. Atypia of the mammary ductal epithelium develops at about 8 weeks of age, progressing to mammary intraepithelial neoplasia (resembling human ductal carcinoma in situ [DCIS]) at about 12 weeks of age with the development of invasive carcinomas at about 16 weeks of age in 100% of female mice. The carcinomas share features to what has been classified in human breast cancer as infiltrating ductal carcinomas. All FVB/N female mice carrying the transgene develop mammary cancer with about a 15% incidence of lung metastases. Approximately 10% of older male mice develop anaplastic mammary carcinomas. Unlike many other transgenic models in which hormones and pregnancy are used to induce a mammary phenotype, C3(1)/Tag mice develop mammary tumors in the mammary epithelium of virgin animals without hormone supplementation or pregnancy. Although mammary tumor development appears hormone-responsive at early stages, invasive carcinomas are hormone-independent, which corresponds to the loss of estrogen receptor-alpha expression during tumor progression. Molecular and biologic factors related to mammary tumor progression can be studied in this model since lesions evolve over a predictable time course. Genomic alterations have been identified during tumor progression, including an amplification of the distal portion of chromosome 6 containing ki-ras and loss of heterozygosity (LOH) in other chromosomal regions. We have demonstrated that stage specific alterations in the expression of genes which are critical regulators of the cell cycle and apoptosis are functionally important in vivo. C3(1)/Tag mice appear useful for testing particular therapies since growth of the mammary tumors can be reduced using chemopreventive agents, cytokines, and an anti-angiogenesis agent.

Androgen-Binding Protein↗

PubMed2000

Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor.

Peptide deformylase (PDF) is essential in prokaryotes and absent in mammalian cells, thus making it an attractive target for the discovery of novel antibiotics. We have identified actinonin, a naturally occurring antibacterial agent, as a potent PDF inhibitor. The dissociation constant for this compound was 0.3 x 10(-)(9) M against Ni-PDF from Escherichia coli; the PDF from Staphylococcus aureus gave a similar value. Microbiological evaluation revealed that actinonin is a bacteriostatic agent with activity against Gram-positive and fastidious Gram-negative microorganisms. The PDF gene, def, was placed under control of P(BAD) in E. coli tolC, permitting regulation of PDF expression levels in the cell by varying the external arabinose concentration. The susceptibility of this strain to actinonin increases with decreased levels of PDF expression, indicating that actinonin inhibits bacterial growth by targeting this enzyme. Actinonin provides an excellent starting point from which to derive a more potent PDF inhibitor that has a broader spectrum of antibacterial activity.

Amidohydrolases↗

PubMed2000

Trp1, a candidate protein for the store-operated Ca(2+) influx mechanism in salivary gland cells.

The trp gene family has been proposed to encode the store-operated Ca(2+) influx (SOC) channel(s). This study examines the role of Trp1 in the SOC mechanism of salivary gland cells. htrp1, htrp3, and Trp1 were detected in the human submandibular gland cell line (HSG). HSG cells stably transfected with htrp1alpha cDNA displayed (i) a higher level of Trp1, (ii) a 3-5-fold increase in SOC (thapsigargin-stimulated Ca(2+) influx), determined by [Ca(2+)](i) and Ca(2+)-activated K(+) channel current measurements, and (iii) similar basal Ca(2+) permeability, and inhibition of SOC by Gd(3+) but not by Zn(2+), as compared with control cells. Importantly, (i) transfection of HSG cells with antisense trp1alpha cDNA decreased endogenous Trp1 level and significantly attenuated SOC, and (ii) transfection of HSG cells with htrp3 cDNA did not increase SOC. These data demonstrate an association between Trp1 and SOC and strongly suggest that Trp1 is involved in this mechanism in HSG cells. Consistent with this suggestion, Trp1 was detected in the plasma membrane region, the proposed site of SOC, of acinar and ductal cells in intact rat submandibular glands. Based on these aggregate data, we propose Trp1 as a candidate protein for the SOC mechanism in salivary gland cells.

Animals↗

PubMed2000

Cell cycle-dependent regulation of N-acetylglucosaminyltransferase-III in a human colon cancer cell line, Colo201.

The mechanism for cell-cycle-dependent regulation of N-acetylglucosaminyltransferase III (GnT-III) activity was investigated using synchronized culture of Colo201, a human colon cancer cell line. In the synchronized culture, it was found that GnT-III activity rapidly increased in the M phase and the maximal activity was five times higher than the basal level found in the G1 phase. Northern blot and Western blot analyses revealed that the increase in the activity is due not to an increase in expression level of its mRNA but, rather, to the level of protein. Furthermore, it was shown by a pulse-chase experiment that the increased protein level of GnT-III is the result of its prolonged turnover rate. Lectin blotting with erythroagglutinating phytohemagglutinin showed that the content of bisecting N-acetylglucosamine structure in glycoproteins was transiently increased during the M phase in conjunction with the increased activity of GnT-III. These results suggest that GnT-III activity undergoes a cell-cycle-dependent regulation and thereby oligosaccharide structures of N-glycans vary specifically during the M phase of the cell cycle. Thus, it is possible that the cell-cycle-dependent alteration of N-glycans by GnT-III might play a role in biological events, such as the progression of cell cycle and cell division.

Aphidicolin↗

PubMed2000

Reaction behaviors of decomposition of monocrotophos in aqueous solution by UV and UV/O processes.

The decomposition of monocrotophos (cis-3-dimethoxyphosphinyloxy-N-methyl-crotonamide) in aqueous solution by UV and UV/O(3) processes was studied. The experiments were carried out under various solution pH values to investigate the decomposition efficiencies of the reactant and organic intermediates in order to determine the completeness of decomposition. The photolytic decomposition rate of monocrotophos was increased with increasing solution pH because the solution pH affects the distribution and light absorbance of monocrotophos species. The combination of O(3) with UV light apparently promoted the decomposition and mineralization of monocrotophos in aqueous solution. For the UV/O(3) process, the breakage of the >C=C< bond of monocrotophos by ozone molecules was found to occur first, followed by mineralization by hydroxyl radicals to generate CO(3)(2-), PO4(3-), and NO(3)(-) anions in sequence. The quasi-global kinetics based on a simplified consecutive-parallel reaction scheme was developed to describe the temporal behavior of monocrotophos decomposition in aqueous solution by the UV/O(3) process.

Absorption↗

PubMed2000

A family of chromatin remodeling factors related to Williams syndrome transcription factor.

Chromatin remodeling complexes have been implicated in the disruption or reformation of nucleosomal arrays resulting in modulation of transcription, DNA replication, and DNA repair. Here we report the isolation of WCRF, a new chromatin-remodeling complex from HeLa cells. WCRF is composed of two subunits, WCRF135, the human homolog of Drosophila ISWI, and WCRF180, a protein related to the Williams syndrome transcription factor. WCRF180 is a member of a family of proteins sharing a putative heterochromatin localization domain, a PHD finger, and a bromodomain, prevalent in factors involved in regulation of chromatin structure.

Adenosine Triphosphatases↗

PubMed2000

[Effects of tea on aberrant crypt foci and colorectal tumors in rats].

The present study was designed to investigate the chemopreventive effects of green tea and tea pigments (the main component of black tea) on 1,2-dimethylhydrazine (DMH)-induced rat colorectal carcinogenesis. Compared with the positive control group, green tea and tea pigments groups had less numbers of aberrant crypt foci (ACF) (P < 0.01) at the end of week 16. At the end of week 32, all rats in the positive control group developed colorectal tumors with an average of 2.6 tumors per rat, and a mean volume of 294.7 mm3 per tumor, while in the groups drinking green tea and tea pigments, the average numbers of colorectal tumors per rat were only 47.1% and 43.1% of controls respectively, and the mean tumor volume was inhibited by 77.1% and 68.1% respectively. It was concluded that tea pigments had a chemopreventive effect on colorectal tumor and ACF formation can be used as a useful intermediate end point to study chemopreventive effects on colorectal cancer.

1,2-Dimethylhydrazine↗