Biomedical subjects

Yun Xia

Publications and source records attributed to Yun Xia.

33 records · Page 2Linked to original sources

PubMed2004

Metabotropic signal transduction for bradykinin in submucosal neurons of guinea pig small intestine.

Intracellular recording methods with "sharp" microelectrodes were used to study signal transduction mechanisms underlying the excitatory action of bradykinin (BK) in morphologically identified neurons in the small intestinal submucosal plexus. Exposure to BK evoked slowly activating membrane depolarization and enhanced excitability associated with increased input resistance in AH-type and decreased input resistance in S-type neurons. Preincubation with pertussis toxin did not affect the BK-evoked responses. Pretreatment with the cyclooxygenase inhibitors indomethacin or piroxicam suppressed or abolished the BK-evoked responses. Application of prostaglandin (PG) E(2) or PG analogs evoked BK-like depolarizing responses in the submucosal plexus with a potency order of PGE(2) > PGE(1) > 17-phenyl trinor-PGE(2) > PGI(2) > sulprostone > PGF(2alpha). Depolarizing responses to bradykinin or PGE(2) in S-type neurons were suppressed in the presence of the phospholipase C inhibitor U73122 [(1-6-[([17beta]-3-methoxyestra-1,3,5[10]-tren-17-71)amino]hexyl)-1H-pyrrole-2,5-dione)], but not the inactive analog U73343 [(1-6-[([17beta]-3-methoxyestra-1,3,5[10]trien-17yl)amino]hexyl)-2,5-pyrrolidinedione)]. The inositol-1,4,5-trisphosphate receptor antagonist 2-aminoethoxy-diphenylborane and the calmodulin inhibitor W-7, but not ryanodine, suppressed both bradykinin- and PGE(2)-evoked responses. KN-62, an inhibitor of calmodulin kinases, or GF109203X, a specific protein kinase C inhibitor, suppressed both BK- and PGE(2)-evoked depolarizing responses. Selective protein kinase A inhibitors did not alter BK- or PGE(2)-evoked depolarizing responses in S neurons. The results suggest that BK stimulates synthesis and release of PGE(2), which acts at EP(1) receptors to evoke depolarizing responses in submucosal neurons. The postreceptor transduction cascade includes activation of phospholipase C, inositol-1,4,5-trisphosphate production, intraneuronal Ca2+ mobilization, activation of protein kinase C and/or calmodulin kinases, and phosphorylation of cationic channels.

Animals↗

PubMed2004

The characterization of cationic fusogenic liposomes mediated antisense oligonucleotides into HeLa cells.

Antisense oligonucleotides (ODNs) are potential therapeutic agents, but their development is still limited due to poor cellular uptake and high degradation rate in biological media. To resolve these problems, we propose to attach the Sendai virus to cationic liposomes. Cationic-fusogenic liposomes (CFLs) were prepared by reverse-phase evaporation and fused with the Sendai virus. The mean diameter was about 186 nm, determined by photon correlation laser light scattering method. The cytotoxicity of CFLs and the ODN loading efficiency depended on the +/- charge ratio. The fluorescence intensity in cytoplasm was enhanced with the increasing of DC-Chol content and +/- charge ratio. We also investigated the mechanism of cellular uptake using temperature shifts and lysosomotropic agent. The results indicated that the vector was introduced into the cells, not via endocytosis but membrane fusion. The preliminary experiment showed that CFLs are a promising formulation for ODN delivery with high levels of transfection and minimal cytotoxicity.

Deoxyribonuclease I↗

PubMed2004

[The anti-cancer effect of siRNA targeting human telomerase reverse transcriptase in SMMC-7721 cells].

OBJECTIVE: To explore the anti-cancer effects of siRNAs targeting hTERT in SMMC-7721 cells. METHODS: Two siRNAs targeting hTERT mRNA were designed and synthesized by T7 transcription system in vitro. MMT, RT-PCR and Western blot were applied to evaluate effects on inhibiting cell growth, hTERT mRNA and protein expression in SMMC-7721 cells. RESULTS: siRNAs decreased cell proliferation in a dose-dependent manner. At a concentration of 100 nmol/L, siRNAs exhibited obvious effects on inhibiting hTERT mRNA and protein expression in SMMC-7721 cells. CONCLUSION: siRNAs targeting hTERT have significant inhibitory effects on hTERT gene expression in SMMC-7721 cells. siRNA has the possibility to become a new anti-cancer agent

DNA-Binding Proteins↗

PubMed2003

Actions of galanin on neurotransmission in the submucous plexus of guinea pig small intestine.

Electrophysiologic recording methods were used to study the actions of galanin on synaptic transmission in the submucous plexus of guinea pig ileum. Exposure to galanin resulted in concentration-dependent suppression of slow noradrenergic inhibitory postsynaptic potentials and fast nicotinic excitatory postsynaptic potentials in the majority of neurons. Failure of galanin to suppress nicotinic depolarizing responses to micropressure pulses of acetylcholine and failure to suppress hyperpolarizing responses to micropressure pulses of norepinephrine suggested that galanin acted at presynaptic inhibitory receptors to suppress release of acetylcholine and norepinephrine. Galanin suppressed slow excitatory postsynaptic potentials in eight of eight neurons with AH (after-hyperpolarization) type electrical behavior and in none of 26 neurons with S (synaptic) type electrical behavior. Suppression of excitatory neurotransmission in AH neurons was always associated with membrane hyperpolarization. Excitatory responses caused by experimentally applied substance P were also inhibited by galanin. Galanin-(1-16) and galanin-like peptide mimicked the inhibitory actions of galanin on neurotransmission. The selective galanin GAL2 receptor agonist [D-Trp(2)]galanin was inactive. The chimeric peptides, galanin-(1-13)-spantide I, galantide, galanin-(1-13)-neuropeptide Y(25-36) amide, galanin-(1-13)-bradykinin-(2-9)amide and galanin-(1-13)-Pro-Pro-Ala-Leu-Ala-Leu-Ala amide all produced varying degrees of suppression of the synaptic potentials. The evidence suggests that the galanin GAL1 receptor, but not the galanin GAL2 receptor, mediated the presynaptic and postsynaptic inhibitory actions of galanin.

Animals↗

PubMed2003

Differential acute effects of fluoxetine on frontal and auditory cortex networks in vitro.

Primary cultures of neuronal networks grown on microelectrode arrays were used to quantify acute effects of fluoxetine (Prozac) on spontaneous spike and burst activity. For frontal cortex cultures, fluoxetine showed consistent inhibitory effects and terminated activity at 10-16 microM. IC(50) mean+/-S.E. for spike rates was 5.4+/-0.7 microM (n=15). For auditory cortex cultures, fluoxetine caused excitation at 1-10 microM, initial inhibition at 15 microM, and activity cessation at 20-25 microM. The spike rate IC(50) was 15.9+/-1.0 microM (n=11). Fluoxetine did not change the action potential waveform shape. However, at high concentrations, it caused total cessation of spike activity on all channels. The inhibition caused by fluoxetine was reversible for both tissues. Based on the results, we conclude that cultures showed repeatable, concentration-dependent sensitivities to fluoxetine but demonstrated tissue-specific responses for frontal and auditory cortex networks. These responses may not be due to the interference with serotonin reuptake, but may be due to a secondary effect on ionic channels.

Action Potentials↗

PubMed2003

Actions of cysteinyl leukotrienes in the enteric nervous system of guinea-pig stomach and small intestine.

Conventional intracellular microelectrodes, neuronal tracer injection techniques and immunohistochemistry were used to study the actions of cysteinyl leukotrienes (CysLTs) on electrical and synaptic behavior of enteric neurons in guinea-pig stomach and small intestine. Bath application of leukotriene C(4), leukotriene D(4) or leukotriene E(4) evoked a slowly activating depolarizing response in most of the myenteric and submucous plexus neurons in the small intestine while no effect was observed in gastric neurons. The depolarization evoked by cysteinyl leukotrienes in intestinal neurons was associated with increased input resistance and enhanced excitability. Suppression of hyperpolarizing after-potentials occurred in AH type neurons. The depolarizing action of cysteinyl leukotrienes was resistant to tetrodotoxin and cyclooxygenase inhibitors. Neither the CysLT(1) receptor antagonists (E)-3-[[[3-[2-(7-chloro-2-quinolinyl)ethenyl]phenyl][[3-dimethylamino)-3-oxopropyl]thio]methyl]thio]-propanoic acid (MK 571), 1-[2-hydroxy-3-propyl-4-[4-(1H-tetrazol-5-yl)butoxy]phenyl]-ethanone (LY 171883) and alpha-pentyl-3-(2-quinolinylmethoxy)-benzenemethanol (REV 5901), nor the dual CysLT(1)/CysLT(2) receptor antagonist 6(R)-(4'-carboxyphenylthio)-5(S)-hydroxy-7(E),9(E),11(Z),14(Z)-eicosatetraenoic acid (BAY u9773) significantly altered the depolarizing action of the cysteinyl leukotrienes. Neurotransmission was unaffected by the cysteinyl leukotrienes. The results suggested involvement of cysteinyl leukotrienes in enteric immuno-neural communication through excitatory actions on enteric neurons. The receptor mediating these effects was distinct from currently recognized cysteinyl leukotriene receptor subtypes (CysLT(1) and CysLT(2) receptors) and may represent a new receptor subtype.

Acetophenones↗

PubMed2003

Histiotypic electrophysiological responses of cultured neuronal networks to ethanol.

Embryonic murine neuronal networks cultured on substrate-integrated microelectrode arrays were used to quantify acute electrophysiological effects of ethanol by using extracellular, multichannel recording of action potentials. Spontaneously active frontal cortex cultures showed repeatable, concentration-dependent sensitivities to ethanol, with initial inhibition at 20 mM and a spike rate 50% effective concentration (EC50) of 48.8+/-5.4 mM. Ethanol concentrations of greater than 100 mM led to cessation of activity. The ethanol inhibitions up to the maximum tested 160 mM were reversible. Although ethanol did not change the shape of action potentials, unit-specific spike pattern effects were found. At 40 mM, ethanol decreased neuronal firing in 71%, increased firing in 20%, and generated no effect in 9% of all units observed (14 cultures, 200 discriminated units). The effects of combined application of ethanol and fluoxetine were additive. Excellent agreement with findings obtained from experimental studies with animals validates the use of these in vitro systems for alcohol research.

Action Potentials↗

PubMed2003

Actions of bradykinin on electrical and synaptic behavior of neurones in the myenteric plexus of guinea-pig small intestine.

1. Electrophysiologic methods were used to study actions of bradykinin (BK) in neurones of the myenteric plexus of guinea-pig small intestine in vitro. Exposure to BK depolarized the membrane potential and elevated excitability in AH- and S-type neurones. Neuronal input resistance associated with the depolarizing responses was either decreased or unchanged in S-type and increased in AH-type neurones. 2. The selective B(2) BK receptor antagonist HOE-140, but not the selective B(1) receptor antagonist des-arg(10)-HOE-140, suppressed the BK-evoked responses. RT-PCR confirmed the expression of B(2) receptor mRNA, but not B(1) receptor mRNA. 3. Binding of fluorescently- labeled HOE-140 (HOE741) was localized to ganglion cells in whole-mount preparations. BK B(2) receptors were coexpressed with immunoreactivity for calbindin or nitric oxide synthase. 4. Exposure to BK suppressed the amplitude of both fast and slow excitatory postsynaptic potentials. Depolarizing responses evoked by application of serotonin or substance P and nicotinic responses to acetylcholine were not reduced by BK. This suggested that BK action on neurotransmission was presynaptic suppression of neurotransmitter release. Presence of HOE-140 in the bathing solution suppressed or abolished the presynaptic inhibitory action of BK. 5. The cyclooxygenase inhibitor, piroxicam, suppressed both the direct excitatory action of BK and its presynaptic inhibitory action. Application of prostaglandin E(2), D(2), F(2alpha) or I(2) mimicked the BK-evoked responses. 6. The results suggest that BK acts at B(2) BK receptors on myenteric neurones to stimulate the formation of prostaglandins. Once formed and released, the prostaglandins act to elevate the excitability of ganglion cells in the myenteric plexus and to suppress the synaptic release of neurotransmitters.

Animals↗

PubMed2003

[Effects of the adsorbent CAA for hemopurification on normal components of human plasma in removing methylene blue].

Virus inactivation of plasma can be achieved by phototreatment with methylene blue (MB). Subsequently, elimination of MB may reduce the adverse effects of MB. This study examined the effects of adsorbing MB with the use of cross-linked agar bead entrapped attapulgite clay (CAA) on normal ingredients in MB-treated plasma units. The biomedical characteristics of CAA were assessed by determination of partial biochemical indexes, coagulation potency and some cationic concentration in a control sample and the MB-treated plasma eluted from CAA column. The biochemistry indexes or K+, Na+ in plasma were almost unaltered before and after CAA adsorption. In contrast, the concentrations of CA2+ and Mg2+ increased and the blood ammonium decreased obviously. The activated partial thromboplastin time (APTT) was prolonged from 42 s to 53 s, and prothrombin time (PT) from 13 s to 14 s. The result indicates that CAA as an adsorbent for hemopurification retains the most important characters of human plasma. CAA can be useful for the elimination of MB in MB-treated plasma and does not bring on harmful alteration in clinical significance.

Adsorption↗

PubMed2002

Neuroimmune interactions in guinea pig stomach and small intestine.

Enteric neuroimmune interactions in gastrointestinal hypersensitivity responses involve antigen detection by mast cells, mast cell degranulation, release of chemical mediators, and modulatory actions of the mediators on the enteric nervous system (ENS). Electrophysiological methods were used to investigate electrical and synaptic behavior of neurons in the stomach and small intestine during exposure to beta-lactoglobulin in guinea pigs sensitized to cow's milk. Application of beta-lactoglobulin to sensitized preparations depolarized the membrane potential and increased neuronal excitability in small intestinal neurons but not in gastric neurons. Effects on membrane potential and excitability in the small intestine were suppressed by the mast cell stabilizing drug ketotifen, the histamine H(2) receptor antagonist cimetidine, the cyclooxygenase inhibitor piroxicam, and the 5-lipoxygenase inhibitor caffeic acid. Unlike small intestinal ganglion cells, gastric myenteric neurons did not respond to histamine applied exogenously. Antigenic exposure suppressed noradrenergic inhibitory neurotransmission in the small intestinal submucosal plexus. The histamine H(3) receptor antagonist thioperamide and piroxicam, but not caffeic acid, prevented the allergic suppression of noradrenergic inhibitory neurotransmission. Antigenic stimulation of neuronal excitability and suppression of synaptic transmission occurred only in milk-sensitized animals. Results suggest that signaling between mast cells and the ENS underlies intestinal, but not gastric, anaphylactic responses associated with food allergies. Histamine, prostaglandins, and leukotrienes are paracrine signals in the communication pathway from mast cells to the small intestinal ENS.

Anaphylaxis↗

PubMed2002

Chemical coding and electrophysiology of enteric neurons expressing neurofilament 145 in guinea pig gastrointestinal tract.

Electrophysiologic recording and indirect immunofluorescence were combined to study localization of the medium-sized neurofilament 145 (NF145) component of the cytoskeleton in morphologically identified neurons in the myenteric and submucosal plexuses of the guinea pig enteric nervous system. Neuronal localization of chemical markers, including calbindin DK28, calretinin, nitric oxide synthase, choline-acetyltransferase, neuropeptide Y, serotonin, neurokinin 1 receptor protein, and somatostatin, was integrated with electrophysiologic and morphologic results for a more complete assessment. NF145 immunoreactivity (-IR) was present in ganglion cells with Dogiel type I morphology in the myenteric plexus of the stomach and small and large intestine. NF145-IR was not found in myenteric ganglion cells with Dogiel type II morphology. NF145-IR was not present in any of the ganglion cells in the submucosal plexus. NF145 was expressed in nerve fibers in both myenteric and submucosal plexuses. The majority of these fibers were identified as sympathetic postganglionic axons based on their disappearance in organotypic culture and on their expression of tyrosine hydroxylase. The myenteric ganglion cells with NF145-IR had electrophysiologic properties of S-type enteric neurons. NF145-IR was found in neurons with vasoactive intestinal peptide, serotonin, nitric oxide synthase, somatostatin, and neurokinin 1 receptor but not with neuropeptide Y or calbindin. The results in general suggest that NF145 is localized to distinct subsets of myenteric motor neurons and interneurons. Absence of NF145 from ganglion cells in the submucosal plexus is an example of differences between myenteric and submucosal components of the enteric nervous system.

Action Potentials↗

PubMed2002

Comparison of effects of lidocaine hydrochloride, buffered lidocaine, diphenhydramine, and normal saline after intradermal injection.

STUDY OBJECTIVE: To evaluate pain and the spread of analgesia when local anesthetics are given as an intradermal injection into the dorsal aspect of the hand. DESIGN: Randomized, double-blinded, placebo-controlled study. SETTING: University medical center. PATIENTS: 40 consenting adult volunteers. INTERVENTIONS: Volunteers were randomly assigned to receive a 0.25-mL injection of either lidocaine hydrochloride (1%), buffered lidocaine, diphenhydramine (1%), or placebo (0.9% sodium chloride solution) into the dorsal aspect of both hands. MEASUREMENTS: The volunteers used a visual analog scale to compare the pain of needle insertion and solution injection. Then at 1, 2, 5, 10, 20, and 30 minutes after intradermal injection, the extent of the analgesic area was marked on a strip of tape placed horizontally across the hand. Then at 32 minutes after intradermal injection, the extent of the analgesic area was marked on a strip of tape placed vertically across the hand. The volunteers were called each day and asked the duration of their numbness or hyperesthesia until their hands were no longer numb or sore. MAIN RESULTS: Buffered lidocaine during intradermal infiltration was found to be significantly (p < 0.05) less painful than either lidocaine hydrochloride or diphenhydramine and equivalent to placebo. Diphenhydramine and lidocaine hydrochloride during intradermal infiltration induced significantly (p < 0.05) more pain than buffered lidocaine or placebo. Lidocaine hydrochloride displayed a significantly (p < 0.05) larger diameter of analgesia than placebo by 1 minute after the injection, buffered lidocaine by 2 minutes after injection, and diphenhydramine by 5 minutes after injection. By 20 minutes after injection, diphenhydramine diameter of analgesia was significantly (p < 0.05) larger than placebo but significantly less than buffered lidocaine. By 30 minutes after injection, diphenhydramine diameter of analgesia was equivalent to placebo whereas buffered lidocaine and lidocaine diameters were still significantly (p < 0.05) larger than placebo. Diphenhydramine injection resulted in numbness that lasted significantly (p < 0.05) longer than other study solutions whereas buffered lidocaine and lidocaine injections resulted in numbness that lasted significantly longer than placebo. Diphenhydramine injection resulted in hyperesthesia that lasted for 2 or more days in 12 of the volunteers. CONCLUSION: There is a reduction of infiltration pain using buffered lidocaine as opposed to lidocaine and diphenhydramine. Although lidocaine injection resulted in a slightly faster spread of analgesic diameter, buffered lidocaine was equivalent to lidocaine from minute 2 until minute 30. Therefore, to obtain optimal anesthetic conditions, we recommend that buffered lidocaine be given 2 minutes before performing catheterization, whereas diphenhydramine should be given 5 minutes before catheterization, but only when buffered lidocaine cannot be used.

Adult↗

PubMed2002

Serine proteases excite myenteric neurons through protease-activated receptors in guinea pig small intestine.

BACKGROUND & AIMS: Serine proteases are postulated to influence gastrointestinal function by stimulating protease-activated receptors (PARs). This study identified the effects on myenteric neurons of activating PARs and investigated underlying mechanisms of action. METHODS: Intracellular electrophysiologic methods were used to study the effects of proteases on electrical and synaptic behavior of morphologically identified neurons in the guinea pig enteric nervous system. Fluorescent immunohistochemistry was used to study the chemical coding of neurons that responded to PARs stimulation. RESULTS: Application of thrombin, trypsin, or mast cell tryptase evoked slowly activating excitatory responses reminiscent of slow synaptic excitation in enteric neurons. Synthetic activating peptides for PAR-1, -2, and -4 receptors mimicked the actions of the proteases. The depolarizing responses evoked by PARs were insensitive to cyclooxygenase inhibitors and were suppressed by agents that inhibit phospholipase C (PLC) or block intraneuronal receptors for inositol triphosphate. A majority of PAR-sensitive uniaxonal neurons expressed immunoreactivity for nitric oxide synthase. Most of the PAR-sensitive AH Dogiel morphologic type II neurons were immunoreactive for calbindin. CONCLUSIONS: Excitatory responses to the serine proteases are mediated by PAR-1, -2, and -4 receptors. The mechanism of signal transduction involves stimulation of PLC and intraneuronal calcium mobilization and is independent of prostanoid formation.

Animals↗

PubMed2002

[Plate theory model under non-ideal chromatography].

The mobile phase in chromatography is regarded as to be composed of many continual plates, whose height is the same as that of one plate in the stationary phase. The solute in initial concentration of mobile phase is seen to be concentrated in the first plate. The solute is exchanged dynamically between the mobile phase and stationary phase. When the mobile phase passes the distance of one plate in the stationary phase, the solute cannot be immediately released from the stationary phase to mobile phase, because of the dynamic factors of chromatographic system. The solute distribution between mobile and stationary phases is controlled by two factors, i.e. the equilibrium coefficient P, which represents chromatographic thermodynamic properties, and release probability factor alpha, which represents chromatographic dynamic properties. This process is considered as non-ideal chromatography. In the view of statistics, authors studied the influences integrated of the release property factor and equilibrium coefficient factor upon chromatographic distribution, and simulated the chromatographic distribution curve by means of computer. As a result, a new distribution model has been established, the distribution equation under the non-ideal chromatography was deduced and, the integrative action of the release probability and the equilibrium coefficient was revealed. The release probability factor can be regarded as an index in chromatography and the peak width can be deduced and hence the resolution can be calculated through this index.

Chromatography↗

PubMed1996

The Rapid Identification of Protein Through Its Amino Acid Composition.

This paper described a method for the identification of protein through its composition. The basic idea is as follows: A database for lengths, compositions and molecular weights of all known proteins is easily derived from a protein sequence database and by comparing the composition, length and molecular weight of the protein in question with each array of data in the composition database, proteins with similar length, composition and molecular weight may be found; as such a tentative identification for the said protein may be made. In some cases, it can be perfectly accurate to predict the right protein(s) from the composition database. A computer program applying this method was developed and used to search for the compositions of human insulin precursor and other proteins. The results are good, which proves that it is a fast and economic way to identify a protein based on its amino acid composition.

Journal Article↗