Search PubMed⌕ Search

Biomedical subjects

Y Ding

Publications and source records attributed to Y Ding.

At least 109 records · Page 6Linked to original sources

[Simultaneous determination of tryptophan, tyrosine and phenylalanine in injection by derivative fluorescent PLS method].

A new first-derivative fluorescent method by partial least squares (PLS) for the simultaneous determination of tryptophan, tyrosine and Phenylalanine was developed. The determination was carried out in KH2PO4-K2HPO4 buffer solution (pH = 7.4) and at the EX (excite) wavelength of 216.6 nm. The method has been applied to the determination of tryptophan, tyrosine and phenylalanine in compound amino acid injection, and the relative errors are within +/- 7.2%.

Injections↗

[Monte Carlo simulation of FCS in a laser gradient field].

Fluorescence correlation spectroscopy (FCS) is a powerful tool for probing biological process inside living cells. It measures fluorescence fluctuations of small number of molecules and derive information on molecular kinetics and reactions. We have developed a Monte Carlo model to simulate Browning motion of Rayleigh particles in a laser gradient field. The simulation reveals relations between laser field strength and measured parameters from FCS, such as diffusion coefficient and number density of the particles. The simulated results agree qualitatively to the experimental results obtained using fluorescent spheres. Empirical relations from the simulation are also discussed.

Computer Simulation↗

Genetic evidence that lethality in angiotensinogen-deficient mice is due to loss of systemic but not renal angiotensinogen.

Angiotensinogen (AGT)-deficient mice die shortly after birth presumably due to renal dysfunction caused by the presence of severe vascular and tubular lesions in the kidney. Because AGT is expressed in renal proximal tubule cells, we hypothesized that its loss may be the primary mediator of the lethal phenotype. We generated two models to test this hypothesis by breeding transgenic mice expressing human renin with mice expressing human AGT (hAGT) either systemically or kidney-specifically. We then bred double transgenic mice with AGT+/- mice, intercrossed the compound heterozygotes, and examined the offspring. We previously reported that the presence of the human renin and systemically expressed hAGT transgene complemented the lethality observed in AGT-/- mice. On the contrary, we show herein that the presence of the human renin and kidney-specific hAGT transgene cannot rescue lethality in AGT-/- mice. An analysis of newborns indicated that AGT-/- mice were born in normal numbers, and collection of dead 10-day old pups revealed an enrichment in AGT-/-. Importantly, we demonstrated that angiotensinogen protein and functional angiotensin II was generated in the kidney, and the kidney-specific transgene was temporally expressed during renal development similar to the endogenous AGT gene. These data strongly support the notion that the loss of systemic AGT, but not intrarenal AGT, is responsible for death in the AGT-/- mouse model. Taken together with our previous studies, we conclude that the intrarenal renin-angiotensin system located in the proximal tubule plays an important role in blood pressure regulation and may cause hypertension if overexpressed, but may not be required for continued development of the kidney after birth.

Alleles↗

Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors.

ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain. The ATP receptor P2X3 is selectively expressed by nociceptors and is one of seven ATP-gated, cation-selective ion channels. Here we demonstrate that ablation of the P2X3 gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X(2/3) heteromultimers. Null mutants have normal sensorimotor function. Behavioural responses to noxious mechanical and thermal stimuli are also normal, although formalin-induced pain behaviour is reduced. In contrast, deletion of the P2X3 receptor causes enhanced thermal hyperalgesia in chronic inflammation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X3-null mice are unable to code the intensity of non-noxious 'warming' stimuli.

Adenosine Triphosphate↗

Synthesis of the HSA-conjugate of the S-linked thiomimetic of the branched tetrasaccharide repeating unit of the immunostimulant polysaccharide, schizophyllan. Evaluation as potential immunomodulator.

The conjugate with human serum albumin (HSA) of the S-linked thioanalogue of the branched tetrasaccharide repeating unit of the polysaccharide, schizophyllan, was synthesized from 1,2,4,6-tetra-O-acetyl-3-S-[2,4-di-O-acetyl-3,6-di-S-(2,3,4,6-tetra-O-ac etyl-beta-D-glucopyranosyl)-3,6-dithio-beta-D-glucopyranosyl]-3-thio-bet a-D-glucopyranose [M.O. Contour-Galcera et al., Carbohydr. Res., 281 (1996) 119-128] in five steps, and its potential immunomodulatory activity was evaluated in human blood mononuclear cells. The protein glycoconjugate did not effect proliferation or production of IL-4, IL-5 and IFN-g in a significant way.

Adjuvants, Immunologic↗

Transient state of chiral recognition in a binary mixture of cyclodextrins in capillary electrophoresis.

The transient state (as the defined point where no enantioseparation is obtained in a dual chiral selector system) of chiral recognition of aminoglutethimide in a binary mixture of neutral cyclodextrins (CDs) was studied by capillary electrophoresis (CE). The following three dual selector systems were used: alpha-cyclodextrin (alpha-CD) and beta-cyclodextrin (beta-CD); alpha-CD and heptakis(di-O-methyl-beta-cyclodextrin) (DM-beta-CD); alpha-CD and heptakis(tri-O-methyl-beta-cyclodextrin) (TM-beta-CD). The S-(-) enantiomer of the analyte was more strongly retained in the presence of either alpha-CD or TM-beta-CD at pH 2.5, 100 mM phosphate buffer, while the R-(+) enantiomer was more strongly retained in the presence of either beta-CD or DM-beta-CD. In the more simple case, the elution order is invariably kept if the enantiomers have the same elution order in either one of the two hosts of the binary mixture. In contrast, the elution order may be switched by varying the concentration ratio of two hosts that produce opposite elution order for this particular analyte. In such a dual selector system, the enantioselectivity will disappear at the transient state at a certain ratio of host1:host2. Moreover, the migration times of the two enantiomers with host, alone (diluted in buffer) is approximately equal to the migration times at the corresponding concentration of host2 alone (diluted in buffer), where the ratio of concentrations of host1:host2 is the same as in the binary mixture at the transient state. As found by nuclear magnetic resonance experiments, the analyte is forming a 1:1 complex with either one of the CDs applied. From this finding, a theoretical model based on the mobility difference of the two enantiomers was derived that was used to simulate the transient state.

Cyclodextrins↗

A concise synthesis of the 6-O- and 6'-O-sulfated analogues of the sialyl Lewis X tetrasaccharide.

The octyl glycoside of the sialyl Lewis X tetrasaccharide and its 6-O-sulfated and 6'-O-sulfated analogues were chemically synthesized in a concise manner starting from readily accessible monosaccharide intermediates. The synthesis involved formation of an orthogonally protected tetrasaccharide intermediate from which all three materials were prepared. A selective catalytic hydrogenolysis of four O-benzyl ethers in presence of a 4,6-O-benzylidene group was the key step in the synthetic scheme.

Carbohydrate Conformation↗

A new member of the acid-sensing ion channel family.

Acid-sensing ion channels (ASICs) are members of the epithelial sodium channel (ENaC)-degenerin family of two-pass transmembrane segment protein subunits which form multimeric cation channels. Members of the ENaC-degenerin family are gated by stimuli as diverse as protons, peptides and mechanical distension. Here we describe a new member of the family, SPASIC or ASIC 4 (spinal cord ASIC) which is expressed throughout the central nervous system in an overlapping population of neurons that also express the ASIC subunit MDEG2. ASIC-4 which shows 44% identify with ASIC is developmentally regulated and expressed in a subset of sensory neurons as well as in the CNS. However, despite the strong homology with ASIC, the ASIC-4 transcript does not encode a proton gated cation channel.

Acid Sensing Ion Channels↗

ATP, P2X receptors and pain pathways.

A role for ATP in nociception and pain induction was proposed on the basis of human psychophysical experiments shortly after the formulation of the purinergic hypothesis. Following the pharmacological definition of distinct P2X and P2Y purinergic receptor subtypes by Burnstock and his collaborators, molecular cloning studies have identified the gene products that underlie the effects of ATP on peripheral sensory neurons. One particular receptor, P2X(3), is of particular interest in the context of pain pathways, because it is relatively selectively expressed at high levels by nociceptive sensory neurons. Evidence that this receptor may play a role in the excitation of sensory neurons has recently been complemented by studies that suggest an additional presynaptic role in the regulation of glutamate release from primary afferent neurons in the dorsal horn of the spinal cord. In this brief review, we discuss the present state of knowledge of the role of ATP in pain induction through its action on peripheral P2X receptors.

Adenosine Triphosphate↗

Differential biosynthesis of polysialic acid on neural cell adhesion molecule (NCAM) and oligosaccharide acceptors by three distinct alpha 2,8-sialyltransferases, ST8Sia IV (PST), ST8Sia II (STX), and ST8Sia III.

Polysialylated neural cell adhesion molecule (NCAM) is thought to play a critical role in neural development. Polysialylation of NCAM was shown to be achieved by two alpha2,8-polysialyltransferases, ST8Sia IV (PST) and ST8Sia II (STX), which are moderately related to another alpha2,8-sialyltransferase, ST8Sia III. Here we describe that all three alpha2,8-sialyltransferases can utilize oligosaccharides as acceptors but differ in the efficiency of adding polysialic acid on NCAM. First, we found that ST8Sia III can form polysialic acid on the enzyme itself (autopolysialylation) but not on NCAM. These discoveries prompted us to determine if ST8Sia IV and ST8Sia II share the property of ST8Sia III in utilizing low molecular weight oligosaccharides as acceptors. By using a newly established method, we found that ST8Sia IV, ST8Sia II, and ST8Sia III all add oligosialic and polysialic acid on various sialylated N-acetyllactosaminyl oligosaccharides, including NCAM N-glycans, fetuin N-glycans, synthetic sialylated N-acetyllactosamines, and on alpha(2)-HS-glycoprotein. Our results also showed that monosialyl and disialyl N-acetyllactosamines can serve equally as an acceptor, suggesting that no initial addition of alpha2,8-sialic acid is necessary for the action of polysialyltransferases. Polysialylation of NCAM by ST8Sia IV and ST8Sia II is much more efficient than polysialylation of N-glycans isolated from NCAM. Moreover, ST8Sia IV and ST8Sia II catalyze polysialylation of NCAM much more efficiently than ST8Sia III. These results suggest that no specific acceptor recognition is involved in polysialylation of low molecular weight sialylated oligosaccharides, whereas the enzymes exhibit pronounced acceptor specificities if glycoproteins are used as acceptors.

Amino Acid Sequence↗

Reactions of the dirhenium(II) complexes Re2X4(mu-dppm)2 (X = Cl, Br; dppm = Ph2PCH2PPh2) with isocyanides. 21. A comparison with the complexes Re2Cl4(mu-dppE)2 and Re2Cl4(mu-dcpm)2 (dppE = Ph2PC(=CH2)PPh2; dcpm = Cy2PCH2PCy2) and the structural characterization of complexes of the types Re2Cl4(mu-LL)2(CNR), Re2Cl4(mu-LL)2(CNR)2, and [Re2Cl3(mu-LL)2(CNR)3]+ (LL = dppm, dppE, dcpm; R = t-Bu, Xyl).

A study of the reactions between the triply bonded dirhenium(II) complexes Re2Cl4(mu-LL)2, where LL = Ph2PCH2PPh2 (dppm), Ph2PC(=CH2)PPh2 (dppE), or Cy2PCH2PCy2 (dcpm), with the isocyanides t-BuNC and XylNC (Xyl = 2,6-dimethylphenyl) show that complexes of the type Re2Cl4(mu-LL)2(CNR), Re2Cl4(mu-LL)2(CNR)2, and [Re2Cl3(mu-LL)2(CNR)3]+ are formed sequentially. Several of these have been structurally characterized by X-ray crystallography: Re2Cl4(mu-dppm)2(CNXyl) (2), Re2Cl4(mu-dcpm)2(CNXyl) (11), Re2Cl4(mu-dppE)2(CN-t-Bu)2 (6), Re2Cl4(mu-dcpm)2(CN-t-Bu)2 (12), and [Re2Cl3(mu-dppE)2(CN-t-Bu)3]Cl (7). Complex 2 has an A-frame-like structure with a single mu-Cl bridging ligand, whereas for 11 the structure is like that of 2 but without this bridge, viz., Cl2Re(mu-dppm)2ReCl2(CNXyl) with a Re-Cl bond approximately collinear with Re identical to Re. The symmetrical complexes 6 and 12 are essentially isostructural and have an anti-arrangement of the two t-BuNC ligands. Complex 7 has the open bioctahedral structure [(t-BuNC)2ClRe(mu-dppE)2ReCl2(CN-t-Bu)]+, which is quite different from that of the edge-sharing bioctahedron found in salts of the [Re2Cl3(mu-dppm)2(CNXyl)3]+ cation and its neutral congener Re2Cl3(mu-dppm)2(CNXyl)3; preliminary crystallographic data for the latter compound show the structure to be (XylNC)ClRe(mu-Cl)(mu-CNXyl)(mu-dppm)2ReCl(CNXyl) with an all-cis arrangement of XylNC ligands. The Re-Re bond distances of 2, 6, 7, 11, and 12 occur in the range 2.289-2.380 A and are consistent in all instances with the retention of a Re identical to Re bond, albeit weakened by some degree of Re-->CNR(pi*) back-bonding.

Journal Article↗

Attention deficit/hyperactivity disorder children with a 7-repeat allele of the dopamine receptor D4 gene have extreme behavior but normal performance on critical neuropsychological tests of attention.

An association of the dopamine receptor D4 (DRD4) gene located on chromosome 11p15.5 and attention deficit/hyperactivity disorder (ADHD) has been demonstrated and replicated by multiple investigators. A specific allele [the 7-repeat of a 48-bp variable number of tandem repeats (VNTR) in exon 3] has been proposed as an etiological factor in attentional deficits manifested in some children diagnosed with this disorder. In the current study, we evaluated ADHD subgroups defined by the presence or absence of the 7-repeat allele of the DRD4 gene, using neuropsychological tests with reaction time measures designed to probe attentional networks with neuroanatomical foci in D4-rich brain regions. Despite the same severity of symptoms on parent and teacher ratings for the ADHD subgroups, the average reaction times of the 7-present subgroup showed normal speed and variability of response whereas the average reaction times of the 7-absent subgroup showed the expected abnormalities (slow and variable responses). This was opposite the primary prediction of the study. The 7-present subgroup seemed to be free of some of the neuropsychological abnormalities thought to characterize ADHD.

Alleles↗

A single amino acid determines the immunostimulatory activity of interleukin 10.

Cellular interleukin 10s (cIL-10s) of human and murine origin have extensive sequence and structural homology to the Epstein-Barr virus BCRF-I gene product, known as viral IL-10 (vIL-10). Although these cytokines share many immunosuppressive properties, vIL-10 lacks several of the immunostimulatory activities of cIL-10 on certain cell types. The molecular and cellular bases for this dichotomy are not currently defined. Here, we show that the single amino acid isoleucine at position 87 of cIL-10 is required for its immunostimulatory function. Substitution of isoleucine in cIL-10 with alanine, which corresponds to the vIL-10 residue, abrogates immunostimulatory activity for thymocytes, mast cells, and alloantigenic responses while preserving immunosuppressive activity for inhibition of interferon gamma production and prolongation of cardiac allograft survival. Conversely, substitution of alanine with isoleucine in vIL-10 converts it to a cIL-10-like molecule with immunostimulatory activity. This single conservative residue alteration significantly affects ligand affinity for receptor; however, affinity changes do not necessarily alter specific activities for biologic responses in a predictable fashion. These results suggest complex regulation of IL-10 receptor-ligand interactions and subsequent biological responses. These results demonstrate that vIL-10 may represent a captured and selectively mutated cIL-10 gene that benefits viral pathogenesis by leading to ineffective host immune responses. The ability to manipulate the activity of IL-10 in either a stimulatory or suppressive direction may be of practical value for regulating immune responses for disease therapy, and of theoretical value for determining what aspects of IL-10 activity are important for normal T cell responses.

Alanine↗

Anti-tumor and anti-carcinogenic activities of triterpenoid, beta-boswellic acid.

Boswellin (BE), a methanol extract of the gum resin exudate of Boswellia serrata, contains naturally occurring triterpenoids, beta-boswellic acid and its structural related derivatives, has been used as a traditional medicine for the treatment of inflammatory and arthritic diseases. Topical application of BE to the backs of mice markedly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in skin inflammation, epidermal proliferation, the number of epidermal cell layers, and tumor promotion in 7,12-dimethylbenz[a]anthracene (DMBA)-initiated mice. Feeding 0.2% of BE in the diet to CF-1 mice for 10-24 weeks reduced the accumulation of parametrial fat pad weight under the abdomen, and inhibited azoxymethane (AOM)-induced formation of aberrant crypt foci (ACF) by 46%. Addition of pure beta-boswellic acid, 3-O-acetyl-beta-boswellic acid, 11-keto-beta-boswellic acid or 3-O-acetyl-11-keto-beta-boswellic acid to human leukemia HL-60 cell culture inhibited DNA synthesis in HL-60 cells in a dose-dependent manner with IC50 values ranging from 0.6 to 7.1 microM. These results indicate that beta-boswellic acid and its derivatives (the major constituents of Boswellin) have anti-carcinogenic, anti-tumor, and anti-hyperlipidemic activities.

Animals↗

Solubilization of substituted indole compounds by beta-cyclodextrin in water.

The solubilization of four pairs of substituted indole compounds (SICs) by beta-cyclodextrin (beta-CD) in water was investigated. The results show that 1,2,3,4-tetrahydrocarbazole and N-methyl-1,2,3,4-tetrahydrocarbazole form 1:1 inclusion complexes with beta-CD, while the other six SICs form 1:2 inclusion complexes, respectively. To each pair of SICs with similar structures, the differences between their solubilization in beta-CD/water solutions has been explained by the difference of their contact area within the beta-CD cavity, the difference of their molecule polarity, or the presence of hydrogen bond between SIC molecule and beta-CD molecule.

Carbazoles↗

Lead promotes hydroxyl radical generation and lipid peroxidation in cultured aortic endothelial cells.

Early studies by our group have shown that lead-induced hypertension (HTN) is closely related to enhanced activity of reactive oxygen species (ROS). In addition, we have found indirect evidence that hydroxyl radical may be the most likely culprit in lead-exposed animals. In the present study, rat aortic endothelial cells were incubated in the presence of 0, 0.01, 0.1, 0.5, and 1.0 ppm lead acetate for 1, 24, and 48 h. At the conclusion of the incubation period cells were harvested and the media were collected. Lipid peroxidation products were measured as malondialdehyde-thiobarbituric acid (MDA-TBA) in the medium and hydroxyl radical was measured as 2,3-dihydroxybenzoic acid (2,3 DHBA) in the cells. After exposure to lead for 48 h, MDA-TBA generation and 2,3 DHBA formation were significantly increased. These data clearly demonstrate that lead exposure promotes hydroxyl radical generation and induces oxidative stress in isolated endothelial cells, mimicking the effects observed in lead-exposed animals. Enhanced inactivation of endothelium-derived nitric oxide by locally produced oxygen free radicals could contribute to endothelial dysfunction and HTN in lead-exposed animals.

Animals↗

Synthesis and evaluation of 6-[(18)F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine as a PET tracer for nicotinic acetylcholine receptors.

Both ABT-594 ((R)-2-chloro-5-(2-azetidinylmethoxy)pyridine) and A-85380 (3-[2(S)-2-azetidinylmethoxy]pyridine), novel nicotinic agonists that possess potent non-opioid analgesic properties, have high affinity for neuronal nicotinic acetylcholine receptors (nAChR) but do not elicit the pronounced toxicity of epibatidine. 6-[(18)F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (6-[(18)F]fluoro-A-85380), a F-18 labeled analogue of these two compounds, is therefore a promising radioligand for positron emission tomography (PET) studies in humans. The use of trimethylammonium as a leaving group in nucleophilic aromatic substitution reactions has proven to be a versatile and efficient strategy, and offers several advantages over other leaving groups. Here, we report the synthetic strategy for the preparation of a precursor, as a trimethylammonium iodide salt, and its use in the radiosynthesis to 6-[(18)F]fluoro-A-85380. Preliminary compartative PET studies of 6-[(18)F]fluoro-A-85380 and 2-[(18)F]fluoro-A-85380 were carried out in baboon to examine their suitability as tracers for studying nAChR system.

Animals↗