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Biomedical subjects

F Zheng

Publications and source records attributed to F Zheng.

At least 19 recordsLinked to original sources
PubMed2003

Metabotropic glutamate and muscarinic cholinergic receptor-mediated preferential inhibition of N-methyl-D-aspartate component of transmissions in rat ventral tegmental area.

Presynaptic inhibition is one of the major control mechanisms in the CNS. Our laboratory recently reported that presynaptic GABA(B) and adenosine A(1) receptors mediate a preferential inhibition on N-methyl-D-aspartate receptor-mediated excitatory postsynaptic currents recorded in rat midbrain dopamine neurons. Here we extended these findings to metabotropic glutamate and muscarinic cholinergic receptors. Intracellular voltage clamp recordings were made from dopamine neurons in rat ventral tegmental area in slice preparations. (+/-)-1-Aminocyclopentane-trans-1,3-dicarboxylic acid (agonist for groups I and II metabotropic glutamate receptors) and L(+)-2-amino-4-phosphonobutyric acid (L-AP4; agonist for group III metabotropic glutamate receptors) were significantly more potent for inhibiting N-methyl-D-aspartate receptor-mediated excitatory postsynaptic currents, as compared with inhibition of excitatory postsynaptic currents mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Such preferential inhibition of the N-methyl-D-aspartate component was also observed for muscarine (agonist for muscarinic cholinergic receptors). Inhibitory effects of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid, L-AP4, and muscarine were blocked reversibly by their respective antagonists [(RS)-alpha-methyl-4-carboxyphenylglycine, (RS)-alpha-methyl-4-phosphonophenylglycine, and 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide]. In addition, all three agonists increased the ratio of excitatory postsynaptic currents in paired-pulse studies and did not reduce currents induced by exogenous N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. Interestingly, the glutamate release stimulator 4-aminopyridine (30 microM) and the glutamate uptake inhibitor L-anti-endo-3,4-methanopyrrolidine dicarboxylate (300 microM) preferentially increased the amplitude of N-methyl-D-aspartate excitatory postsynaptic currents.Thus, agonists for metabotropic glutamate and muscarinic cholinergic receptors act presynaptically to cause a preferential reduction in the N-methyl-D-aspartate component of excitatory synaptic transmissions. Together with the evidence for GABA(B) and adenosine A(1) receptor-mediated preferential inhibition of the N-methyl-D-aspartate component, the present results suggest that limiting glutamate spillover onto postsynaptic N-methyl-D-aspartate receptors may be a general rule for presynaptic modulation in midbrain dopamine neurons.

Animals↗
PubMed2003

Dual modulation of gabaergic transmission by metabotropic glutamate receptors in rat ventral tegmental area.

The effects of metabotropic glutamate receptor (mGluR) activation on non-dopamine (putative GABAergic) neurons and inhibitory synaptic transmission in the ventral tegmental area were examined using intracellular recordings from rat midbrain slices. Perfusion of (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD; agonist for group I and II mGluRs), but not L-amino-4-phosphonobutyric acid (L-AP4; agonist for group III mGluRs), produced membrane depolarization (current clamp) and inward current (voltage clamp) in non-dopamine neurons. The t-ACPD-induced depolarization was concentration-dependent (concentration producing 50% maximal depolarization [EC(50)]=6.1+/-2.5 microM), and was blocked by the antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine, but not by tetrodotoxin and ionotropic glutamate-receptor antagonists. The t-ACPD-evoked responses were mimicked comparably by selective group I mGluR agonist (RS)-3,5-dihydroxyphenylglycine (DHPG). Furthermore, the DHPG-induced depolarization in non-dopamine neurons was greatly reduced by mGluR1-specific antagonist 7(hydroxyimino)cyclopropachromen-1a-carboxylate ethyl ester. When recorded in dopamine neurons, the frequency of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic potentials was increased by t-ACPD but not L-AP4. However, the amplitude of evoked inhibitory postsynaptic currents in dopamine neurons was reduced by all three group mGluR agonists. These results reveal a dual modulation of mGLuR activation on inhibitory transmission in midbrain ventral tegmental area: enhancing putative GABAergic neuronal excitability and thus potentiating tonic inhibitory synaptic transmission while reducing evoked synaptic transmission at inhibitory terminals.

Anesthetics, Local↗
PubMed2002

Thermophoresis of spherical and non-spherical particles: a review of theories and experiments.

Thermophoresis is an important mechanism of micro-particle transport due to a temperature gradient in the surrounding medium and has found numerous applications, especially in the field of aerosol technology. Extensive studies, both theoretical and experimental, have been done to understand the nature of this phenomenon. However, it is clear that a lot more of work needs to be done before we can predict thermophoresis accurately for any given gas-particle system as well as particle shape and orientation in any flow regime. This paper reviews the existing theories and data in two major categories, for spherical particles and for non-spherical particles, as well as the various techniques in making thermophoresis measurements. The current state of development for thermophoresis studies is that for spheres the theories and experimental data agree with each other fairly well but for non-spherical particles in the transition regime the theories are yet to be developed and experimental data showing the effect of particle shape are much needed in all Knudsen number range. The best techniques of thermophoretic force measurements involve the use of electrodynamic balances to work on single micro-particles and the use of microgravity to minimize the effect of convection. A combination of the above two has not been attempted and should provide the most accurate data.

Journal Article↗
PubMed2001

Glycine receptor-mediated inhibition of dopamine and non-dopamine neurons of the rat ventral tegmental area in vitro.

Dopaminergic and non-dopaminergic neurons of the ventral tegmental area (VTA) were recorded intracellularly in slices of rat midbrain. Glycine (0.1-3 mM) caused a strychnine-sensitive and chloride-dependent reduction in membrane input resistance in both types of neuron. However, glycine also reduced the frequency of spontaneous bicuculline-sensitive inhibitory postsynaptic potentials (IPSPs) when recorded in dopaminergic cells. We conclude that glycine inhibits both types of VTA neuron by activating a strychnine-sensitive chloride conductance. Our data also raise the possibility that glycine could increase dopamine output from the VTA by a mechanism of disinhibition.

Action Potentials↗
PubMed2001

[Establishment of model of aristolochic acid-induced chronic renal interstitial fibrosis in rats].

OBJECTIVE: To study chronic renal interstitial fibrosis induced by aristolochic acid (AA) in animal models. METHODS: Female Wistar rats were divided into two groups: AA group (n = 42) peritoneally injected with AA (5 mg.kg-1.d-1) for 16 weeks and control group (n = 5) peritoneally injected with normal saline (2 ml/d) for 16 weeks. The body weight of rats was taken. At week 8, 12, 16, and 24 six rats were killed in the AA group. The five rats in the control group were killed at week 24. Specimens of lood and urine were taken before the animals were killed. Specimens of renal tissue were taken after the animals were killed. Twenty-four hour urine protein, urine beta 2 microglobulin (beta 2-MG), and renal function were tested regularly. Pathological examination, including tubulo-interstitial area calculation, was made to the renal specimens. RESULTS: The body weight of rats in AA group became significantly lower than that of the control rats after 16 weeks' AA injection (P < 0.01). The blood urea nitrogen (BUN) and serum creatinine (Scr) in AA group increased significantly than those of the control group at the 16th, 20th, and 24th weeks (P < 0.05). Optical microscopy showed tubular-interstitial damage in AA group in 16 weeks. Renal tubular atrophy and multifocal renal interstitial fibrosis were shown in 24 weeks. The area of renal tubule increased and the area of the lumen remarkably decreased at week 16 compared with those in the control group. The area of renal tubule decreased remarkably and the area of renal interstitial greatly in the AA group at week 24. Electrical microscopy showed increase of primary and secondary lysosomes and diasappearence of part of brush border of tubular endothelial cells at week 16, and accumulation of secondary lysosome in cytoplasm at weeks 20 and 24 in the AA group. Histoimmunofluorescence showed that IgG, IgA, IgM, C3, and C1q were negative in the renal tissue of experimental animals. CONCLUSION: Animal models with chronic renal tubuloointerstitial nephropathy induced by aristolochic acid were successfully established. Aristolochic acid may have chronic toxicity to renal tissues, and cause chronic renal interstitial fibrosis in rats.

Animals↗
PubMed2001

The 2-norbornyl cation via the fragmentations of exo- and endo-2-norbornyloxychlorocarbenes: distinction without much difference.

exo- and endo-2-norbornyloxychlorocarbenes (7) were generated photochemically from the corresponding diazirines (6). Both carbenes fragmented to [2-norbornyl cation (carbon monoxide) chloride] ion pairs in MeCN or 1,2-dichloroethane solutions. Products included exo-norbornyl chloride (8), endo-norbornyl chloride (9), norbornene (10), and nortricyclene (11). Fragmentation activation energies were very low (< approximately 4 kcal/mol) and, as a result, the (laser flash photolytic) rate constants for fragmentation were essentially identical for exo-7 and endo-7 ( approximately 5 x 10(5) s(-1) in MeCN). Due to chloride return within the ion pairs, product distributions from exo- and endo-7 differed, with more endo-chloride formed from the endo-carbene: the 8/9 product ratio in MeCN was approximately 41 from exo-7, but only 4.6 from endo-7. Norbornene, formed by proton transfer to Cl(-) within the ion pairs, was a major product in both cases (44% from exo-7 and 62% from endo-7). In MeOH/MeCN, up to 28% of exo-2-norbornyl methyl ether formed at the expense of some of the norbornene, but even in 100% MeOH, the norbornyl chloride products of ion pair return still accounted for 46% and 31% of the exo-7 and endo-7 product mixtures (accompanied by 26-32% of norbornene). Electronic structure calculations on the ground states and fragmentation transition states of exo-7 and endo-7 are presented.

Journal Article↗
PubMed2001

Development of an internally quenched fluorescent substrate and a continuous fluorimetric assay for Streptococcus pneumoniae signal peptidase I.

Signal peptidase (SPase) I is responsible for the cleavage of signal peptides of many secreted proteins in bacteria and serves as a potential target for the development of novel antibacterial agents due to its unique physiological and biochemical properties. In this paper, we describe a novel fluorogenic substrate, KLTFGTVK(Abz)PVQAIAGY(NO2)EWL, in which 2-aminobenzoic acid (Abz) and 3-nitrotyrosine (Y(NO2)) were used as the fluorescent donor and acceptor, respectively. The substrate can be cleaved by both Streptococcus pneumoniae and Escherichia coli SPase I. Upon cleavage of the fluorogenic substrate by SPase I, the fluorescent intensity increases and can be monitored continuously by spectrofluorometer. Kinetic analysis with S. pneumoniae SPase I demonstrated that the K(m) value for the substrate is 118.1 microM, and the k(cat) value is 0.032 s(-1). Mass spectrometric analysis and peptide sequencing of the two cleaved products confirmed that the cleavage occurs specifically at the predicted site. More interestingly, the positively charged lysine in the N-terminus of the substrate was demonstrated to be important for effective cleavage. Phospholipids were found to stimulate the cleavage reaction. This stimulation by phospholipids is dependent upon the N-terminal charge of the substrate, indicating that the interaction of the positively charged substrate with anionic phospholipids is important for maintaining the substrate in certain conformation for cleavage. The substrate and assay described here can be readily automated and utilized for the identification of potential antibacterial agents.

Amino Acid Sequence↗
PubMed2001

Rearrangement kinetics of spiropentylchlorocarbene, [3]triangulylchlorocarbene, and related species.

[structure: see text] Absolute rate constants were measured for the 1,2-CH(2), 1,2-cyclopropyl, and 1,2-CMe(2) rearrangements of spiropentylchlorocarbene (5), [3]triangulylchlorocarbene (6), and tetramethylcyclopropylchlorocarbene (7). The factors responsible for the observed relative migratory aptitudes (cyclopropyl > CH(2) > CMe(2)) were analyzed with the aid of electronic structure calculations.

Journal Article↗
PubMed2001

First computational evidence for a catalytic bridging hydroxide ion in a phosphodiesterase active site.

Phosphodiesterases are clinical targets for a variety of biological disorders, because this superfamily of enzymes regulates the intracellular concentration of cyclic nucleotides that serve as the second messengers playing a critical role in a variety of physiological processes. Understanding the structure and mechanism of a phosphodiesterase will provide a solid basis for rational design of the more efficient therapeutics. Although a three-dimensional X-ray crystal structure of the catalytic domain of human phosphodiesterase 4B2B was recently reported, it is uncertain whether a critical bridging ligand in the active site is a water molecule or a hydroxide ion. The identity of this bridging ligand is theoretically determined by performing first-principles quantum chemical calculations on models of the active site. All the results obtained indicate that this critical bridging ligand in the active site of the reported X-ray crystal structure is a hydroxide ion, rather than a water molecule, expected to serve as the nucleophile to initialize the catalytic degradation of the intracellular second messengers.

Binding Sites↗
PubMed2001

Selective destruction of medial septal cholinergic neurons attenuates pyramidal cell suppression, but not excitation in dorsal hippocampus field CA1 induced by subcutaneous injection of formalin.

Using extracellular recording techniques in urethane- (1g/kg, i.p.) anaesthetized rats, we investigated the influence exercised by medial septal cholinergic neurons on dorsal hippocampus field CA1 neural responses to a hind paw injection of formalin (5%, 0.05 ml, s.c.). Cholinergic neurons of the medial septal region were destroyed by local microinjection of the immunotoxin 192 IgG-saporin. Compared to control vehicle microinjected animals, immunotoxin-treatment attenuated the amplitude, but not frequency, of CA1 theta induced by intraseptal injection of carbachol. This suggested a selective destruction of medial septal cholinergic neurons by the immunotoxin. Such destruction also abolished; (i) intraseptal carbachol-induced suppression of CA1 population spike, and (ii) stimulation-intensity dependent increase in amplitude, but not frequency, of theta evoked on electrical stimulation in the region of oral part of pontine reticular nucleus. Further, in comparison to vehicle-treated animals, selective cholinergic destruction attenuated formalin-induced; (i) theta activation, (ii) suppression of CA1 pyramidal cell population spike and dendritic field excitatory post-synaptic potential, (iii) inhibition of complex spike cell extracellular activity, and (iv) excitation and theta-rhythmicity of local putative GABAergic interneurons. However, pretreatment with the immunotoxin did not alter the strength and proportion of complex spike cells excited following injection of formalin. From these findings we suggest that medial septal cholinergic neurons mediate, at least partly, the amplitude of theta and pyramidal cell suppression via an inhibitory network involving CA1 interneurons. The data also indicates that during formalin theta, the cholinergic-mediated inhibitory processing does not modulate the strength and selectivity of complex spike cell excitation. This points to formalin-induced, non-overlapping inhibitory and excitatory processes that might have different functional relevance.

Animals↗
PubMed2001

Electron and light microscopy of neutrophil responses in mice vaccinated and challenged with third-stage infective hookworm (Ancylostoma caninum) larvae.

The role of neutrophils in mediating host inflammation was examined in mice vaccinated with living third-stage infective hookworm larvae (L3). Mice were vaccinated by oral immunization with 500 L3 (Ancylostoma caninum) once every 2 weeks for a total of three immunizations. The vaccinated mice were then challenged intraperitoneally with 2000 L3) 1 week after the final immunization. To stimulate peritoneal production of neutrophils, 2 ml of 2% glycogen were injected intraperitoneally at 16 h prior to the challenge infection. Neutrophils were found to comprise 85% of the peritoneal cell population. L3 from the challenge infection were collected and then examined at timed intervals by inverted light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Greater than a fivefold increase in the total numbers of peritoneal cells was noted in the vaccinated mice as compared to unvaccinated mice. In the peritoneal cavity of vaccinated mice, the neutrophils adhered to the L3 within 2 h, and over 55% of the L3 were surround by clusters of neutrophils to form a sausage-like sheath 4 h later. At 24-72 h after challenge, almost all of the L3 recovered from the vaccinated mice were covered with thick clusters of cells. Both SEM and TEM demonstrated extensive ultrastructural damage to the L3. In contrast, the L3 recovered from the unvaccinated mice appeared to be unaffected by neutrophils. These studies suggest that neutrophils, like macrophages, can have an important role as effector cells in L3-vaccinated mice.

Ancylostoma↗
PubMed2001

An HphI polymorphism in the E-selectin gene is associated with premature coronary artery disease.

An increased expression of E-selectin has been observed in the arterial endothelium interacting with lymphocytes and macrophages in human atherosclerotic lesions. We examined whether a polymorphism in the E-selectin gene, due to a G to T mutation (G98T) in the untranslated region of exon 2, was associated with premature coronary artery disease (CAD). Other lipid and nonlipid risk factors including a Ser to Arg (S128R) substitution in the E-selectin gene were also assessed. In patients with premature CAD (men < or = 45 years old and women < or =55 years old, N = 51) who underwent an elective diagnostic coronary arteriography, the frequency of the mutation was significantly higher than in controls (N = 50, 0.22 vs. 0.10, p = 0.024). After controlling for other CAD risk factors (plasma total cholesterol, triglyceride, LDL-apolipoprotein B. cigarette smoking and the S128R mutation) by multiple logistic analysis, the G98T mutation in the E-selectin gene was still a significant predictor of premature CAD [p = 0.022, odds ratio (95%, CI)= 3.58 (1.20-10.67)].

Alleles↗
PubMed2001

Allosteric interaction between the amino terminal domain and the ligand binding domain of NR2A.

Fast desensitization is an important regulatory mechanism of neuronal NMDA receptor function. Only recombinant NMDA receptors composed of NR1/NR2A exhibit a fast component of desensitization similar to neuronal NMDA receptors. Here we report that the fast desensitization of NR1/NR2A receptors is caused by ambient zinc, and that a positive allosteric interaction occurs between the extracellular zinc-binding site located in the amino terminal domain and the glutamate-binding domain of NR2A. The relaxation of macroscopic currents reflects a shift to a new equilibrium due to increased zinc affinity after binding of glutamate. We also show a similar interaction between the ifenprodil binding site and the glutamate binding site of NR1/NR2B receptors. These data raise the possibility that there is an allosteric interaction between the amino terminal domain and the ligand-binding domain of other glutamate receptors. Our findings may provide insight into how zinc and other extracellular modulators regulate NMDA receptor function.

Allosteric Regulation↗
PubMed2001

GDNF acutely modulates excitability and A-type K(+) channels in midbrain dopaminergic neurons.

Glial cell line-derived neurotrophic factor (GDNF) prevents lesion-induced death of midbrain dopaminergic neurons, but its function in normal brain remains uncertain. Here we show that GDNF acutely and reversibly potentiated the excitability of cultured midbrain neurons by inhibiting transient A-type K(+) channels. The effects of GDNF were limited to large, tyrosine hydroxylase (TH)-positive dopaminergic neurons, and were mediated by mitogen associated protein (MAP) kinase. Application of GDNF also elicited a MAP kinase-dependent enhancement of the excitability in dopaminergic neurons in midbrain slice. These results demonstrate an acute regulation of GDNF on ion channels and its underlying signaling mechanism, and reveal an unexpected role of GDNF in normal midbrain dopaminergic neurons.

4-Aminopyridine↗
PubMed2001

Predictors of functional outcome in elderly patients undergoing posterior lumbar spine surgery.

To ascertain the predictors of functional outcome in elderly patients undergoing posterior lumbar spinal decompression and fusion, a modified low back outcome score questionnaire survey in 83 elderly patients (49 men, 34 women) was carried out at our hospital. The average follow-up was 35.8 months (range: 22-57 months). The outcomes were as follows: excellent to good, 83%; fair, 7%; and poor, 10%. Multiple regression analysis revealed that significant predictors of unfavorable outcome included coexistence of other bone and joint degenerative disorders (p < 0.001) and history of heart disease (p < 0.01). Patients who had undergone previous lumbar surgery had significantly lower modified low back outcome score than those without previous lumbar spine surgery (p < 0.05). The modified low back outcome score questionnaire system is a reliable method in elderly patients.

Aged↗
PubMed2001

Species-specific identification of human hookworms by PCR of the mitochondrial cytochrome oxidase I gene.

Significant differences in the life histories of the human hookworms Ancylostoma duodenale and Necator americanus necessitate their differentiation for epidemiological studies and the design of control programs. Current methods of identification require time-consuming, labor-intensive techniques. A polymerase chain reaction (PCR)-based method that enables rapid species identification is described. The mitochondrial cytochrome oxidase I genes of both species were sequenced, and species-specific primer sets were designed. The primers were used in PCR to amplify 585-bp fragments of the cytochrome oxidase gene from individual hookworm eggs, larvae, and adults. The technique was also able to identify mixed infections containing equal amounts of eggs from each species. The technique is rapid, technically simple, and sensitive and will permit the accurate identification of human hookworms in epidemiological field studies.

Ancylostoma↗