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Biomedical subjects

D Yang

Publications and source records attributed to D Yang.

At least 55 records · Page 3Linked to original sources
PubMed2001

Murine six-transmembrane epithelial antigen of the prostate, prostate stem cell antigen, and prostate-specific membrane antigen: prostate-specific cell-surface antigens highly expressed in prostate cancer of transgenic adenocarcinoma mouse prostate mice.

To identify genes that are differentially up-regulated in prostate cancer of transgenic adenocarcinoma mouse prostate (TRAMP) mice, we subtracted cDNA isolated from mouse kidney and spleen from cDNA isolated from TRAMP-C1 cells, a prostate tumor cell line derived from a TRAMP mouse. Using this strategy, cDNA clones that were homologous to human six-transmembrane epithelial antigen of the prostate (STEAP) and prostate stem cell antigen (PSCA) were isolated. Mouse STEAP (mSteap) is 80% homologous to human STEAP at both the nucleotide and amino acid levels and contains six potential membrane-spanning regions similar to human STEAP. Mouse PSCA (mPsca) shares 65% homology with human PSCA at the nucleotide and amino acid levels. mRNA expression of mSteap and mPsca is largely prostate-specific and highly detected in primary prostate tumors and metastases of TRAMP mice. Both mSteap and mPsca map to chromosome 5. Another known gene coding for mouse prostate-specific membrane antigen (mPsma) is also highly expressed in both primary and metastatic lesions of TRAMP mice. These results indicate that the TRAMP mouse model can be used to effectively identify genes homologous to human prostate-specific genes, thereby allowing for the investigation of their functional roles in prostate cancer. mSteap, mPsca, and mPsma constitute new tools for preventative and/or therapeutic vaccine construction and immune monitoring in the TRAMP mouse model that may provide insights into the treatment of human prostate cancer.

Adenocarcinoma↗
PubMed2001

Macrocyclization in the design of a conformationally constrained Grb2 SH2 domain inhibitor.

Grubbs' olefin metathesis reaction was utilized to prepare a macrocyclic variant of a linear Grb2 SH2 domain antagonist in an attempt to induce a beta-bend conformation known to be required for high affinity binding. In extracellular Grb2 SH2 domain binding assays, the macrocyclic analogue exhibited an approximate 100-fold enhancement in binding potency relative to its linear counterpart. The macrocycle was not as effective in whole cell binding assays as would be expected based on its extracellular binding potency.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Ruthenium-catalyzed oxidative cleavage of olefins to aldehydes.

Three oxidation protocols have been developed to cleave olefins to carbonyl compounds with ruthenium trichloride as catalyst (3.5 mol %). These methods convert olefins that are not fully substituted to aldehydes rather than carboxylic acids. While aryl olefins were cleaved to aromatic aldehydes in excellent yields by using the system of RuCl3-Oxone-NaHCO3 in CH3CN-H2O (1.5:1), aliphatic olefins were converted into alkyl aldehydes with RuCl3-NaIO4 in 1,2-dichloroethane-H2O (1:1) in good to excellent yields. It is noteworthy that terminal aliphatic olefins were cleaved to the corresponding aldehydes in excellent yields by using RuCl3-NaIO4 in CH3CN-H2O (6:1).

Journal Article↗
PubMed2001

Kinetic resolution of acyclic secondary allylic silyl ethers catalyzed by chiral ketones.

Kinetic resolution of acyclic secondary allylic silyl ethers by chiral dioxiranes generated in situ from chiral ketones (R)-1 and (R)-2 and Oxone was investigated. An efficient and catalytic method has been developed for kinetic resolution of those substrates with a CCl(3), tert-butyl, or CF(3) group at the alpha-position. In particular, high selectivities (S up to 100) were observed for kinetic resolutions of racemic alpha-trichloromethyl allylic silyl ethers 7 and 9-15 catalyzed by ketones (R)-2. Both the recovered substrates and the resulting epoxides were obtained in high enantiomeric excess. On the basis of steric and electrostatic interactions between the chiral dioxiranes and the racemic substrates, a model was proposed to rationalize the enantioselectivities and diastereoselectivities in the chiral ketone-catalyzed kinetic resolution process.

Journal Article↗
PubMed2001

First enantioselective syntheses of (+)- and (-)-wilforonide by using chiral auxiliaries derived from the same chiral source.

[see structure]. The first enantioselective syntheses of both (+)-wilforonide (>98% ee) and (-)-wilforonide (>98% ee) have been accomplished by employing chiral auxiliaries derived from the same chiral source, (R)-pulegone. The bicyclic skeleton of wilforonide was constructed by using Mn(III)-based oxidative radical cyclization reactions of chiral beta-keto esters. The absolute configuration of natural wilforonide has been established to be (5aR,9aR).

Chromatography, High Pressure Liquid↗
PubMed2001

Measurement of (13)C(alpha)-(13)C(beta) dipolar couplings in (15)N,(13)C,(2)H-labeled proteins: application to domain orientation in maltose binding protein.

TROSY-based HN(CO)CA 2D and 3D pulse schemes are presented for measurement of (13)C(alpha)-(13)C(beta) dipolar couplings in high molecular weight (15)N,(13)C,(2)H-labeled proteins. In one approach, (13)C(alpha)-(13)C(beta) dipolar couplings are obtained directly from the time modulation of cross-peak intensities in a set of 2D (15)N-(1)HN correlated spectra recorded in both the presence and absence of aligning media. In a second approach 3D data sets are recorded with (13)C(alpha)-(13)C(beta) couplings encoded in a frequency dimension. The utility of the experiments is demonstrated with an application to an (15)N,(13)C,(2)H-labeled sample of the ligand free form of maltose binding protein. A comparison of experimental dipolar couplings with those predicted from the X-ray structure of the apo form of this two-domain protein establishes that the relative orientation of the domains in solution and in the crystal state are very similar. This is in contrast to the situation for maltose binding protein in complex with beta-cyclodextrin where the solution structure can be generated from the crystal state via a 11 degrees domain closure.

Carcinogens↗
PubMed2001

Repetitive nerve stimulation and stimulation single fiber electromyography studies in rats intoxicated with single or mixed insecticides.

The function of the neuromuscular transmission in rats dosed with phoxim (P), methomyl (M), fenvalerate (F), and mixtures of P+M and P+F was studied by using both the stimulation single fiber electromyography (SSFEMG) and repetitive nerve stimulations (RNS) to determine the single muscle fiber action potential and compound muscle action potential (CMAP) respectively. The results showed that the mean consecutive difference (MCD) in SSFEMG was significantly prolonged in P, P+M and P+F intoxicated rats during the presence of myasthenia, but not in rats dosed with F and M when stimuli were given at 10 Hz or 20 Hz, thus indicating a transmission blocking at the neuromuscular junction (NMJ) induced by P. The frequency of neuromuscular transmission abnormalities detected by SSFEMG was significantly higher than those detected by RNS. This study demonstrated that the neuromuscular junction (NMJ) blocking is more frequently seen in P, P+M and P+F poisoning than in M and F poisoning, and that SSFEMG is a more sensitive electrophysiological method than RNS for detecting neuromuscular transmission blockage in myasthenia rats with acute insecticides poisoning.

Acetylcholinesterase↗
PubMed2001

Differential regulation of formyl peptide receptor-like 1 expression during the differentiation of monocytes to dendritic cells and macrophages.

Monocytes are the common precursors for myeloid dendritic cells (DC) and macrophages. Identification of chemotactic receptors expressed by myeloid DC, macrophages, and their precursors in the course of differentiation and maturation is important not only for elucidation of their in vivo trafficking, but also for understanding of the functional distinction between DC and macrophages. We chose to study formyl peptide receptor like-1 (FPRL1), a chemotactic receptor known to interact with several endogenous agonists that are involved in inflammatory and host defense responses. Here we show that FPRL1 is down-regulated as monocytes differentiate into DC. This down-regulation occurs at both mRNA and functional levels. Therefore, the interaction of FPRL1 with its agonists is more likely to regulate the in vivo trafficking of DC precursors than DC. In contrast, FPRL1 expression is maintained at both mRNA and functional levels as monocytes differentiate into macrophages. Thus, our results demonstrate further distinctions between myeloid DC and macrophages, albeit they share a common precursor. The fact that macrophages rather than myeloid DC express functional FPRL1 suggests that this chemotactic receptor may be more involved in inflammatory reactions and innate host defense than in adaptive immune responses.

Animals↗
PubMed2001

Chiral auxiliaries for asymmetric radical cyclization reactions: application to the enantioselective synthesis of (+)-triptocallol.

[figure: see text] A series of epimeric 8-aryl menthyl derivatives 5a-d and 6a-l, prepared from the same chiral source (R)-pulegone, were employed as chiral auxiliaries in the asymmetric radical cyclization reactions of beta-keto esters mediated by Mn(OAc)3. Chiral precursors 8c and 8d provided the cyclization products 10c and 10d, respectively, as single isomers (dr > 99:1), whereas the cyclization of precursor 9k gave 13k with good stereoselectivity (dr = 24:1). Diastereomer 13e was employed as the key intermediate in the enantioselective synthesis of (+)-triptocallol in 90% ee.

Biological Factors↗
PubMed2001

Enhanced apoptosis under low serum conditions in human glioblastoma cells by connexin 43 (Cx43).

Connexin 43 (Cx43), a structural component of gap junctions, is believed to function as a tumor suppressor gene. Previously, we showed that expression of Cx43 suppresses cell proliferation and tumorigenicity of human glioblastoma cells [Huang et al., Cancer Res 58:5089-5096, 1998] and enhances apoptosis in response to chemotherapeutic agents [Huang et al., Int J Cancer 92:130-138, 2001]. In the present study, we demonstrated that expression of Cx43 in human glioblastoma cells potentiated an apoptotic program under low-serum conditions. The Cx43-mediated effect was coupled with a decreased expression of the specific apoptosis-inhibitor bcl-2. Overexpression of bcl-2 in Cx43-transfected cells conferred resistance to apoptosis induced under low-serum conditions, suggesting that the Cx43-mediated apoptosis under low-serum conditions is regulated, in part, through the downregulation of bcl-2 expression. Furthermore, application of the phosphatidylinositol-3'-OH kinase inhibitor LY294002 specifically induced apoptosis in Cx43-transfected cells. Our results demonstrate a new role of Cx43 in the mediation of apoptosis under low serum conditions.

Apoptosis↗
PubMed2001

USPIO-enhanced dynamic MRI: evaluation of normal and transplanted rat kidneys.

To evaluate first-pass renal perfusion with ultrasmall superparamagnetic iron oxide (USPIO) particles by MRI, 40 normal rats (20 Dark Agouti (DA) rats and 20 Brown Norway (BN) rats) and 16 transplanted rats (12 allografts and four isografts) were studied on day 4 post-transplantation with different USPIO doses (3.0-18.1 mg Fe/kg/body weight). All animals underwent 128 consecutive snapshot fast low-angle shot (FLASH) coronal dynamic studies in 43 s. In the normal rats, a larger maximum signal decrease (MSD) in the cortex and the outer medulla is observed with an increasing dose of USPIO particles (P < 0.01). No significant differences were observed between the right and left kidneys at all doses studied. Higher MSD, time of occurrence of MSD (tMSD), and wash-in slope appear with higher doses of USPIO particles. The dynamic curves for DA rats show similar shapes when compared to those for BN rats. In the transplanted rats, allograft kidneys show lower MSD, longer tMSD, and lower wash-in slope compared to those in the normal kidneys. Isograft kidneys show perfusion patterns similar to those of normal kidneys in the cortex and the outer medulla. Histopathology indicates acute vascular rejection in all allografts and normal kidney architecture in all isografts. The results clearly show good agreement between the renal graft perfusion measurements and histopathological changes associated with rejection. This work also introduces a new signal analysis methodology for the automatic detection of transplanted organ rejection. This method compares the dynamics of the intrarenal signal intensities for native and transplanted kidneys. A quantitative measurement to detect significant differences between these signals was developed, and showed that this technique exhibits good performance in identifying renal rejection.

Animals↗
PubMed2001

The role of mammalian antimicrobial peptides and proteins in awakening of innate host defenses and adaptive immunity.

Since we live in a dirty environment, we have developed many host defenses to contend with microorganisms. The epithelial lining of our skin, gastrointestinal tract and bronchial tree produces a number of antibacterial peptides, and our phagocytic neutrophils rapidly ingest and enzymatically degrade invading organisms, as well as produce peptides and enzymes with antimicrobial activities. Some of these antimicrobial moieties also appear to alert host cells involved in both innate host defense and adaptive immune responses. The epithelial cells are a source of constitutively produced beta defensin (HBD1) and proinflammatory cytokine-inducible beta defensins (HBD2 and -3) and cathelicidin (LL37). The neutrophils-derived antimicrobial peptides are released on demand from their cytoplasmic granules. They include the enzymes cathepsin G and chymase, azurocidin, a defensins and cathelicidin. In contrast, C5a and C3b are produced by activation of the serum complement cascade. The antimicrobial moieties direct the migration and activate target cells by interacting with selected G-protein-coupled seven-transmembrane receptors (GPCRs) on cell surfaces. The beta defensins interact with the CCR6 chemokine GPCRs, whereas cathelicidins interact with the low-affinity FPRL-1 receptors. The neutrophil-derived cathepsin G acts on the high-affinity FMLP receptor (GPCR) known as FPR, while the receptors for chymase and azurocidin have not been identified as yet. The serum-derived C5a uses a GPCR known as C5aR to mediate its chemotactic and cell-activating effects. Consequently, all these ligand-receptor interactions in addition to mediating chemotaxis also activate receptor-expressing cells to produce other mediators of inflammation.

Animals↗
PubMed2001

Rice ESTs with disease-resistance gene- or defense-response gene-like sequences mapped to regions containing major resistance genes or QTLs.

The chromosomal locations of 109 rice expressed sequence tags (ESTs) in the rice genome were determined using a doubled haploid mapping population. These ESTs show high similarity to disease resistance genes or to defense response genes. Nine of the ESTs were mapped to three regions that contain genetically defined resistance genes on chromosomes 6 and 11. Clustering of the ESTs in the rice genome was observed at several chromosomal regions. Some of the clusters were located in regions where quantitative trait loci (QTL) associated with partial resistance to rice blast, bacterial blight and sheath blight are known to lie. Three ESTs that were mapped to the regions containing blast resistance genes Pi2 and Pia were chosen for Northern analysis after inoculation of plants with the blast fungus. Two of them, which code for a receptor-like kinase and a putative membrane channel protein, respectively, and were mapped to the Pi2 locus, were induced by rice blast infection as early as 4 h after inoculation. Transcription of another EST, which codes for a homolog of a putative human tumor suppressor and was mapped to the region containing Pia, was repressed after blast infection. These findings demonstrate that the candidate-gene approach is an efficient way of mapping resistance genes or resistance QTLs in rice.

Chromosome Mapping↗
PubMed2001

Status of persistent organic pollutants in the sediment from several estuaries in China.

Sediment samples from three estuaries on the east coast of China were analyzed for persistent organic pollutants. Total PCB, PAH, and DDT concentrations in the sediments from Minjiang, Jiulongjiang, and Zhujiang estuaries ranged from 2 to 14 ng/g, 400 to 1500 ng/g, and 6 to 73 ng/g, respectively, in the sediments from these estuaries. The sources of PAH contamination were inferred from PAH compositions, with pyrogenic PAHs being the dominant source for Minjiang Estuary and petroleum related PAHs being the primary contributors to Jiulongjiang and Zhujiang estuaries. The high concentrations of DDT in the sediments from these estuaries were likely the result of widespread use of DDT in China in the 1960s and 1970s. Butyltin compounds were detected in the sediment from Jiulongjiang Estuary and Victoria Harbor, Hong Kong. Presence of butyltin compounds probably result from the shipping activities in these estuaries. Butyltin compounds were not detected in the sediments from Minjiang and Zhujiang estuaries. Contaminant concentrations were generally below levels expected to affect benthic organisms with the exception of DDTs.

Animals↗
PubMed2001

N-terminal carboxyl and tetrazole-containing amides as adjuvants to Grb2 SH2 domain ligand binding.

High affinity binding of peptides to Src homology 2 (SH2) domains, often requires the presence of phosphotyrosyl (pTyr) or pTyr-mimicking moieties in the N-terminal position of the binding ligand. Several reports have shown that N(alpha)-acylation of the critical pTyr residue can result in increased SH2 domain binding potency. For Grb2 SH2 domains which recognize pTyr-Xxx-Asn-NH(2) motifs, significant potency enhancement can be incurred by N(alpha)-(3-amino)Z derivatization of tripeptides such as pTyr-Ile-Asn-NH(2). Using ligands based on the high affinity pY-Ac(6)c-Asn-(naphthylpropylamide) motif, (where Ac(6)c=1-aminocyclohexanecarboxylic acid), additional reports have shown moderate potentiating effects of N(alpha)-oxalyl derivatization. The current study examined variations of the N(alpha)-oxalyl theme in the context of a Xxx-Ac(6)c-Asn-(naphthylpropylamide) platform, where Xxx=the hydrolytically stable pTyr mimetics phosphonomethyl phenylalanine (Pmp) or carboxymethyl phenylalanine (Cmf). The effects of N(alpha)-(3-amino)Z derivatization were also investigated for this platform, to ascertain whether the large binding enhancement reported for tripeptides such as pTyr-Ile-Asn-NH(2) could be observed. In ELISA-based extracellular Grb2 SH2 domain binding assays, it was found for the Pmp-based series, that extending the oxalyl carboxyl out by one methylene unit or replacing carboxyl functionality with a tetrazole isostere, resulted in binding potency greater than the parent N(alpha)-acetyl-containing compound, with enhancement approximating that observed for the N(alpha)-oxalyl derivative. When Cmf was used as the pTyr mimetic, only modest differences in IC(50) values were observed for the series. Examination of the N(alpha)-(3-amino)Z derivatized Pmp-Ac(6)c-Asn-(naphthylpropylamide), showed that binding affinity was reduced relative to the parent N(alpha)-acetyl analogue, in contrast to the reported significant enhancement of affinity observed with other peptide ligands. Treatment of MDA-453 tumor cells, which are mitogenically driven through erbB-2 tyrosine kinase-dependent pathways, with Pmp-containing inhibitors resulted in growth inhibition, with the N(alpha)-oxalyl and N(alpha)-malonyl-containing compounds exhibiting IC(50) values (4.3 and 4.6 microM, respectively) approximately five-fold lower than the parent N(alpha)-acetyl-containing compound. Tetrazole and N(alpha)-(3-amino)Z-containing inhibitors were from two- to four-fold less potent than these latter analogues in the growth inhibition assays.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Volatiles from Ficus hispida and their attractiveness to fig wasps.

Volatile compositions of receptive (ready to be pollinated), postpollinated, and postparasitized figs. and leaves of Ficus hispida were analyzed. Differences among them were examined, and the specificity of fig wasp attractiveness was investigated. Linalool was the major constituent of steam-distilled oil of either male or female receptive figs, while dibutyl phthalate was the major compound of the oils of postparasitized and postpollinated figs. In petroleum ether extracts, palmitic oil, and 9,12-octadecadienoic acid were the main constituents of male and female receptive figs, while hexadecanoic acid ethyl ester was the major compound of postparasitized and postpollinated figs. In dichloromethane extracts, linalool was the major constituent of male and female receptive figs, 1-hydroxylinalool was the major component of male postparasitized figs, and 1-hydroxylinalool and benzyl alcohol were the major constituents of female postpollinated figs. Bioassays with sticky traps showed that Ceratosolen solmsimarchal was attracted to dichloromethane extracts of male and female receptive figs and to petroleum ether extracts of female receptive figs, but was not attracted to dichloromethane and petroleum ether extracts of male postparasitized and female postpollinated figs. Figs were attractive to pollinating wasps only at the receptive stage. The volatile constituents of receptive figs were different from those of postpollinated or postparasitized figs. From a receptive to a postpollinated state, figs changed in their volatile composition. Some compounds disappeared or decreased in amount. These include linalool, linalool oxide, alpha-terpeneol, and 2,6-dimethyl-1,7-octadiene-3,6-diol, which may act as the attractants of the wasps. Others increased in amount, or several additional chemicals appeared. These include dibutyl phthalate, 1-hydroxylinalool, and benzyl alcohol, which may be repellents of the wasps. That dichloromethane extracts of male and female receptive figs showed similar activities in attracting fig wasps indicates that receptive figs of both sexes are similarly attractive to fig wasps, which is further supported by their similar volatile composition. Leaf extract was not attractive to the wasps.

Animals↗
PubMed2001

Vascular basis of dorsal digital and metacarpal skin flaps.

We studied the vascular anatomy of dorsal digital skin flaps and the vascular anastomoses between the dorsal cutaneous branch of the palmar digital artery (PDA) and the dorsal digital branches (the terminal branches) of the dorsal metacarpal artery (DMA) at the level of the proximal phalanx. Eight fresh cadavers (16 hands) were injected with a lead oxide-gelatin mixture. Our radiographic assessment revealed that there were 2 sources of the arterial supply to the dorsum of the digit, the dorsal digital branches of the DMA, and the dorsal cutaneous branches of the PDA. These branches anastomose with each other. A flap including the territory of the dorsal cutaneous branches of the PDA and a part of the territory of the DMA can be harvested on the dorsal aspect of the proximal and middle phalanges. The extended neurovascular island flap, based on the PDA and the dorsal branch of digital nerve, can be transposed to the volar surface of an adjacent finger resurfacing the entire length of the digit.

Aged↗