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Biomedical subjects

N Tian

Publications and source records attributed to N Tian.

At least 19 recordsLinked to original sources
PubMed2006

Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension.

The goal of this study was to test the hypothesis that renal infiltration of immune cells in Dahl S rats on increased dietary sodium intake contributes to the progression of renal damage, decreases in renal hemodynamics, and development of hypertension. We specifically studied whether anti-immune therapy, using mycophenolate mofetil (MMF), could help prevent increases in renal NF-kappaB activation, renal infiltration of monocytes/macrophages, renal damage, decreases in glomerular filtration rate (GFR) and renal plasma flow, and increases in arterial pressure. Seventy-four 7-to 8-wk-old Dahl S, Rapp strain rats were maintained on an 8% Na, 8% Na + MMF (20 mg.kg(-1).day(-1)), 0.3% Na, or 0.3% Na + MMF diet for 5 wk. Arterial and venous catheters were implanted at day 21. By day 35, renal NF-kappaB in 8% Na rats was 47% higher than in 0.3% Na rats and renal NF-kappaB was 41% lower in 8% Na + MMF rats compared with the 8% Na group. MMF treatment significantly decreased renal monocyte/macrophage infiltration and renal damage and increased GFR and renal plasma flow. In high-NA Dahl S rats mean arterial pressure increased to 182 +/- 5 mmHg, and MMF reduced this arterial pressure to 124 +/- 3 mmHg. In summary, in Dahl S rats on high sodium intake, treatment with MMF decreases renal NF-kappaB and renal monocyte/macrophage infiltration and improves renal function, lessens renal injury, and decreases arterial pressure. This suggests that renal infiltration of immune cells is associated with increased arterial pressure and renal damage and decreasing GFR and renal plasma flow in Dahl salt-sensitive hypertension.

Animals↗
PubMed2003

Renal and vascular oxidative stress and salt-sensitivity of arterial pressure.

Oxidative stress occurs in a tissue or in the whole body when the total oxidant production exceeds the antioxidant capacity. Recent studies in human essential hypertension indicate that free radical production is increased and antioxidant levels are decreased, and more than one-half of these hypertensives have a salt-sensitive type of hypertension with progressive renal damage. Increased oxidative stress may also play a critical role in animal models of salt-sensitive hypertension. The stroke-prone spontaneously hypertensive rats (SHRSP) exhibits salt-sensitivity, vascular release of superoxide is increased, and total plasma antioxidant capacity is decreased. The superoxide release in the SHRSP rats inactivates nitric oxide, and superoxide dismutase (SOD) administration returns the bioactive nitric oxide levels to normal. The deoxycorticosterone acetate (DOCA)-salt hypertensive rat is salt-sensitive, aortic superoxide production is increased, and renal inflammation is significant. Treatment of the DOCA-salt rats with apocynin, an NADPH oxidase inhibitor, decreased aortic superoxide production and decreased arterial pressure. The Dahl salt-sensitive (S) rat has increased mesenteric microvascular and renal superoxide production and increased plasma levels of H2O2. The renal protein expression of SOD is decreased in the kidney of Dahl S rats, and long-term administration of Tempol, a superoxide mimetic, significantly decreased arterial pressure and renal damage. In conclusion, both human hypertension and experimental models of salt-sensitive hypertension have increased superoxide release, decreased antioxidant capacity and elevated renal damage.

Animals↗
PubMed2001

Visual deprivation alters development of synaptic function in inner retina after eye opening.

Visual deprivation impedes refinement of neuronal function in higher visual centers of mammals. It is often assumed that visual deprivation has minimal effect, if any, on neuronal function in retina. Here we report that dark rearing reduces the light-evoked responsiveness of inner retinal neurons in young mice. We also find that 1 to 2 weeks after eye opening, there is a surge (>4-fold) in the frequency of spontaneous excitatory and inhibitory synaptic events in ganglion cells. Dark rearing reversibly suppresses this surge, but recovery takes >6 days. Frequency changes are not accompanied by amplitude changes, indicating that synaptic reorganization is likely to be presynaptic. These findings indicate there is a degree of activity-dependent plasticity in the mammalian retina that has not been previously described.

Animals↗
PubMed2001

A potent PPARalpha agonist stimulates mitochondrial fatty acid beta-oxidation in liver and skeletal muscle.

The proposed mechanism for the triglyceride (TG) lowering by fibrate drugs is via activation of the peroxisome proliferator-activated receptor-alpha (PPARalpha). Here we show that a PPARalpha agonist, ureido-fibrate-5 (UF-5), approximately 200-fold more potent than fenofibric acid, exerts TG-lowering effects (37%) in fat-fed hamsters after 3 days at 30 mg/kg. In addition to lowering hepatic apolipoprotein C-III (apoC-III) gene expression by approximately 60%, UF-5 induces hepatic mitochondrial carnitine palmitoyltransferase I (CPT I) expression. A 3-wk rising-dose treatment results in a greater TG-lowering effect (70%) at 15 mg/kg and a 2.3-fold elevation of muscle CPT I mRNA levels, as well as effects on hepatic gene expression. UF-5 also stimulated mitochondrial [3H]palmitate beta-oxidation in vitro in human hepatic and skeletal muscle cells 2.7- and 1.6-fold, respectively, in a dose-related manner. These results suggest that, in addition to previously described effects of fibrates on apoC-III expression and on peroxisomal fatty acid (FA) beta-oxidation, PPARalpha agonists stimulate mitochondrial FA beta-oxidation in vivo in both liver and muscle. These observations suggest an important mechanism for the biological effects of PPARalpha agonists.

Animals↗
PubMed2000

BDNF-Induced potentiation of spontaneous twitching in innervated myocytes requires calcium release from intracellular stores.

Brain-derived neurotrophic factor (BDNF) can potentiate synaptic release at newly developed frog neuromuscular junctions. Although this potentiation depends on extracellular Ca(2+) and reflects changes in acetylcholine release, little is known about the intracellular transduction or calcium signaling pathways. We have developed a video assay for neurotrophin-induced potentiation of myocyte twitching as a measure of potentiation of synaptic activity. We use this assay to show that BDNF-induced synaptic potentiation is not blocked by cadmium, indicating that Ca(2+) influx through voltage-gated Ca(2+) channels is not required. TrkB autophosphorylation is not blocked in Ca(2+)-free conditions, indicating that TrkB activity is not Ca(2+) dependent. Additionally, an inhibitor of phospholipase C interferes with BDNF-induced potentiation. These results suggest that activation of the TrkB receptor activates phospholipase C to initiate intracellular Ca(2+) release from stores which subsequently potentiates transmitter release.

Action Potentials↗
PubMed1999

The role of the synthetic enzyme GAD65 in the control of neuronal gamma-aminobutyric acid release.

We have studied GABAergic synaptic transmission in retinal ganglion cells and hippocampal pyramidal cells to determine, at a cellular level, what is the effect of the targeted disruption of the gene encoding the synthetic enzyme GAD65 on the synaptic release of gamma-aminobutyric acid (GABA). Neither the size nor the frequency of GABA-mediated spontaneous inhibitory postsynaptic currents (IPSCs) were reduced in retina or hippocampus in GAD65-/- mice. However, the release of GABA during sustained synaptic activation was substantially reduced. In the retina both electrical- and K(+)-induced increases in IPSC frequency were depressed without a change in IPSC amplitude. In the hippocampus the transient increase in the probability of inhibitory transmitter release associated with posttetanic potentiation was absent in the GAD65-/- mice. These results indicate that during and immediately after sustained stimulation the increase in the probability of transmitter release is not maintained in GAD65-/- mice. Such a finding suggests a decrease in the size or refilling kinetics of the releasable pool of vesicles, and various mechanisms are discussed that could account for such a defect.

Animals↗
PubMed1999

Multiplex inheritance of component phenotypes in a murine model of lupus.

We analyzed the linkage of GN and a wide spectrum of serological phenotypes associated with systemic lupus erythematosus in a (NZM2410 x C57BL/6)F2 cross. Some phenotypes, such as glomerulonephritis (GN) and anti-chromatin IgG antibody production, were more penetrant in females, but others, such as anti-dsDNA antibody production, did not show a gender bias. These results suggest that gender bias affects only a subset of SLE-component phenotypes, and that NZM2410 can be used to dissect the genetic basis of this phenomenon. Genome scanning linked six chromosomal intervals with the expression of one or more component phenotypes. These loci included two Sle loci previously identified in an (NZM2410 x B6)F1 x NZM2410 backcross, loci identified by others in the NZB/W model. Our analysis also suggested two new intervals on chromosomes (Chrs.) 10 and 11. Detailed analysis of the segregation of different phenotypes within these intervals suggests that they encompass more than one susceptibility locus. This clustering has been a common finding in several murine polygenic traits. Each of NZM2410 susceptibility loci can be aligned with a specific genetic pathways contributing to SLE pathogenesis on the basis of the spectrum of component phenotypes expressed.

Animals↗
PubMed1998

Analysis of excitatory and inhibitory spontaneous synaptic activity in mouse retinal ganglion cells.

Spontaneous inhibitory and excitatory postsynaptic currents (sIPSCs and sEPSCs) were identified and characterized with whole cell and perforated patch voltage-clamp recordings in adult mouse retinal ganglion cells. Pharmacological dissection revealed that all cells were driven by spontaneous synaptic inputs mediated by glutamate and gamma-aminobutyric acid-A (GABAA) receptors. One-half (7/14) of the cells also received glycinergic spontaneous synaptic inputs. Both GABAA and glycine receptor-mediated sIPSCs had rise times (10-90%) of < 1 ms. The decay times of the GABAA receptor-mediated sIPSCs were comparable with those of the glycine receptor-mediated sIPSCs. The average decay time constant for monoexponentially fitted sIPSCs was 63.2 +/- 74.1 ms (mean +/- SD, n = 3278). Glutamate receptor-mediated sEPSCs had an average rise time of 0.50 +/- 0.20 ms (n = 109) and an average monoexponential decay time constant of 5.9 +/- 8.6 ms (n = 2705). Slightly more than two-thirds of the spontaneous synaptic events were monoexponential (68% for sIPSCs and 76% for sEPSCs). The remainder of the events was biexponential. The amplitudes of the spontaneous synaptic events were not correlated with rise times, suggesting that the electrotonic filtering properties of the neurons and/or differences in the spatial location of synaptic inputs could not account for the difference between the decay time constants of the glutamate and GABAA/glycine receptor-mediated spontaneous synaptic events. The amplitudes of sEPSCs were similar to those recorded in tetrodotoxin (TTX), consistent with the events measured in control saline being the response to the release of a single quantum of transmitter. The range of the sIPSC amplitudes in control saline was wider than that recorded in TTX, consistent with some sIPSCs being evoked by presynaptic spikes having an average quantal size greater than one. The rates of sIPSCs and sEPSCs were determined under equivalent conditions by recording with perforated patch electrodes at potentials at which both types of event could be identified. Two groups of ganglion cell were observed; one group had an average sEPSCs/sIPSCs frequency ratio of 0.96 +/- 0.77 (n = 28) and another group had an average ratio of 6.63 +/- 0.82 (n = 7). These findings suggest that a subset of cells is driven much more strongly by excitatory synaptic inputs. We propose that this subset of cells could be OFF ganglion cells, consistent with the higher frequency of spontaneous action potentials found in OFF ganglion cells in other studies.

2-Amino-5-phosphonovalerate↗
PubMed1998

Neuronal discriminator formed by metabotropic gamma-aminobutyric acid receptors.

Neuronal discriminator formed by metabotropic gamma-aminobutyric acid receptors. J. Neurophysiol. 80: 3365-3368, 1998. Neurotransmitters function in one of two modes, promoting either inhibition or excitation. However, the metabotropic gamma-aminobutyric acid receptor (GABABR) system can switch between these modes. In the presence of a small excitatory stimulus, the GABABR mediates a shunting inhibition that suppresses excitation. However, in the presence of a strong excitatory stimulus, the GABABR potentiates the response. This bipartite action is accomplished by linking the GABABR to two electrogenic mechanisms; one activates an outward current and another reduces an outward current. As a consequence, the GABABR serves as a discriminator that reduces the influence of weak signals while augmenting responses to strong signals. In retinal ganglion cells, this mechanism acts to promote the communication of phasic information.

Ambystoma↗
PubMed1997

Functional dissection of systemic lupus erythematosus using congenic mouse strains.

We describe the in vivo phenotypes associated with three genomic intervals containing systemic lupus erythematosus (SLE)-susceptibility genes derived from the SLE-prone NZM2410 strain on a C57BL/6 genome. These intervals were identified previously via a genome-wide analysis of SLE susceptibility in a (NZM2410 x C57BL/6)F1 x NZM2410 backcross, and transferred independently on a C57BL/6 background to produce three congenic strains: B6.NZMc1 carrying Sle1, B6.NZMc4 carrying Sle2, and B6.NZMc7 carrying Sle3. B6.NZMc1 develops high titers of IgG anti-nuclear autoantibodies in the absence of any severe nephritis. B6.NZMc4 spontaneously develops elevated levels of IgM, but not IgG Abs against several Ags, indicative of polyclonal activation or polyreactivity affecting the B cell lineage. B6.NZMc7 causes the production of IgM and IgG Abs against both nuclear and non-nuclear Ags and the development of severe lupus nephritis. Therefore, our results show that three defined genomic intervals from the NZM2410 SLE-prone strain each contribute specific component phenotypes that have been associated with SLE, which in combination can mediate severe disease.

Animals↗
PubMed1997

[The study of ICAM-1 expression after brain ischemia-reperfusion injury in rats].

Intercellular adhesion molecule-1 (ICAM-1) expression was studied with rat transient cerebral ischemic model. The results showed that the expression of ICAM-1 markedly increased after 1 h ischemia following 6 h reperfusion. Laser confocal microscope demonstrated that the FITC quantum on blood vessels after reperfusion was more than 47% compared to that of pure ischemia. MPO activity and light microscope observation showed that leukocytes accumulated in injured tissue 9 h after reperfusion. The local IL-1 content in brain tissue changed with different period of reperfusion time. Our data indicated that after brain ischemia-reperfusion injury ICAM-1 expression was in time-dependent increase, the local IL-1 secretion might up regulate the ICAM-1 expression, there were large amount of leukocytes accumulated in surrounding tissue, the increase of ICAM-1 expression was the prerequisite for leukocyte adhesion and migration.

Animals↗
PubMed1997

[Image analysis of the microvascular permeability to various molecular weight of flucrescein in rat mesentery].

An intravital fluorescence microscopic method and digital image analysis were established for measuring the changes of fluorescein sodium (FINa, MW 376) and FITC-Dextrans (FD-4, MW4000, FD-150, MW150000) permeability in mesenteric microvessels. The transport of various molecular fluorescent tracer within the blood vessels and through the vessel walls into the perivascular tissue of the rat mesentery was studied using a highly sensitive CCD camera, the fluorescence intensities were transformed into video signals and recorded for subsequent analysis. The results showed that FINa could pass through the wall of microvessels very quickly. The diffusion constant was 3.362 x 10(-8) cm2/s with FINa, and FD-4 was 1.718 x 10(-8) cm2/s, FD-150 was 0.0486 x 10(-8) cm2/s. The diffusion constant depended very strongly on the molecular weight and showed no difference between capillary and vessels of the venous part of the microcirculation, but in vessels of the arterial part of microcirculation no diffusion was found. That was to say that diffusion occurred in capillary and microvenous, but not in microarterial. It is expected that this method would be very useful for the quantitive analysis in various molecular weights and in monolayer endothelial cell permeability.

Animals↗
PubMed1995

Correlation of dynamic responses in the ON bipolar neuron and the b-wave of the electroretinogram.

2-Amino-4-phosphonobutyrate (APB) is known to selectively suppress the light response of ON bipolar cells in the vertebrate retina, and reduce the b-wave of the electroretinogram (ERG) as a consequence. Using slow drug application, the progressive effect of APB was used to compare the relative response amplitudes of the b-wave and the ON bipolar cell. Simultaneous ERG recordings and ON bipolar intracellular recordings were performed in the amphibian retina. The results indicate that there is a strong positive correlation between these two waveforms. This supports the possibility that the b-wave of the ERG is the direct result of ON bipolar cell activity.

Ambystoma↗
PubMed1994

Pharmacology of the GABAB receptor in amphibian retina.

Amacrine and ganglion cells in the amphibian retina contain GABAB, as well as GABAA, receptors. Baclofen, a GABAB agonist, hyperpolarizes the dark membrane potential of these third order neurons and makes their light responses more transient. GABAB receptors in the retina have a similar agonist profile to GABAB receptors described at other sites in the brain. Namely, preferential activation by the R-enantiomer of baclofen, and agonist sensitivity in the order 3-aminopropylphosphinic acid > baclofen >> 3-aminopropylphosphonic acid. The GABAB receptor was not activated by 4-aminobutylphosphonic acid. Several antagonists, such as phaclofen, saclofen, and 2-hydroxysaclofen, were ineffective in the amphibian retina. However, CGP35348 blocked the action of applied baclofen and produced effects on the light response that were opposite to those of baclofen. Applied agonists and antagonists support the hypothesis that GABAB receptors serve to regulate the balance of sustained and transient signals to the inner retina.

Ambystoma↗
PubMed1994

Pharmacological similarity between the retinal APB receptor and the family of metabotropic glutamate receptors.

1. We performed current-clamp and voltage-clamp experiments in the amphibian retina to examine the effects of 1-amino-1,3-cyclopentanedicarboxylic acid (1S,3R ACPD), which is a selective agonist for the family of metabotropic glutamate receptors. 2. 1S,3R ACPD was found to selectively block the light responses of ON bipolar cells. It did not suppress the responses of horizontal cells of OFF bipolar cells. It blocked ON but not OFF responses of third-order retinal neurons. 3. 1S,3R ACPD mimicked the effect of the photoreceptor transmitter at the ON bipolar synapse. It reduced an inward current by a decrease in conductance. 4. The action of 1S,3R ACPD was very similar to that of 2-amino-4-phosphonobutyrate (APB) both in terms of effects on the ON bipolar cell potential and conductance and in terms of the retinal network. This suggests that the APB receptor is a predominant synaptic metabotropic glutamate receptor in the retina. 5. The rank-order potency at the retinal APB receptor is APB > 1S,3R ACPD > ibotenate. Quisqualate appears to be inactive at this receptor. The pharmacology of the retinal APB receptor matches that of the cloned mGluR4 and mGluR6 metabotropic glutamate receptors. On the basis of the in situ localization of mGluR6 to the inner nuclear layer of the retina, the retinal APB receptor may be this cloned receptor protein. 6. The effects of the three other ACPD stereo isomers were examined. 1S,3S ACPD was a weak agonist at the APB receptor. 1R,3R ACPD was a potent agonist in the inner retina, but inactive in the outer retina. This fits the profile of N-methyl-D-aspartate agonists. 1R,3S ACPD was inactive.

Ambystoma↗
PubMed1994

A study of spectral electroretinogram of color vision defects due to macular diseases.

Studies of spectral electroretinograms in central serous retinopathy (CSR) and hereditary macular degeneration (HMD) showed that the b-wave amplitudes of most wavelengths of CSR were significantly decreased as compared with normal controls, and those of HMD were obviously lower than the normal values. Patients of HMD with type-A color vision defects (CVD) had primarily a reduction of b-wave amplitudes in the full spectrum of 480-620 nm, and patients with type-I CVD a reduction of b-wave amplitudes wave-lengths of 480-560 nm. These differences might reflect differences in damages to the medium-and long-wave length.

Adolescent↗
PubMed1993

[A study of spectral electroretinograms of color vision defects due to macular diseases].

Studies of spectral electroretinograms in central serous chorioretinopathy (CSC) and hereditary macular degeneration (HMD) found that the b-wave amplitudes of CSC for most wavelengths were significantly decreased as compared with normal controls, and the b-wave amplitudes of HMD for most wavelengths were obviously lower than the normal values. Patients of HMD with type-A color vision defects (CVD) showed primarily a reduction of b-wave amplitudes for the full spectrum of 480-620 nm, and patients with type-I CVD a reduction of b-wave amplitudes for wavelengths of 480-560 nm. These differences might reflect differences in damages to the medium-and long-wave length cones.

Adolescent↗