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Biomedical subjects

N Tian

Publications and source records attributed to N Tian.

15 recordsLinked to original sources

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

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

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

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

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

[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

Spectral characteristics of electroretinogram in X-linked dichromats--a preliminary study.

Spectral characteristics of X-linked Dichromats (13 protanopes, 20 deuteranopes) were studied with spectral ERG. The results are as follows: The maximal spectral response of the b-wave in protanopes tended to shift toward the short wavelength side and the sensitivity to long wavelengths decreased obviously. The ratio value of the amplitude in 500 nm and in 620 nm (500/620) was greater in the protanope than that in the normal subject. Like the normals, the maximal response of the b-wave in deuteranopes appeared at 550-570 nm. Though the differences between the normals and deuteranopes in the ratio values (600/620 and b/a at 520 nm) were found by means of analysing a, b wave responses at each wavelength, most of the ratio values (600/620 or b/a at 520 nm) overlapped between the normals and deuteranopes. We established the discriminant function or score made up by the combination of two ratios basing on Fisher's rule, which can raise the diagnostic rate for deuteranopes.

Adolescent

Contrast sensitivity in amblyopia.

Contrast sensitivity function (CSF) for sinusoid gratings of varying spatial frequencies was determined for each eye of 21 cases with unilateral amblyopia. The CSF of all amblyopic eyes, except one, showed reduced sensitivity when compared with the non-amblyopic eye of the same person. The curve showed reduction more significantly at middle and high spatial frequencies. The cut-off frequency was shifted toward lower spatial frequencies. The relationship between CSF and various degree of amblyopia was also discussed.

Adolescent

[Contrast sensitivity in open-angle glaucoma].

The contrast sensitivity function (CSF) was determined with vertical stationary sinusoidal gratings of 6 spatial frequencies of 0.5, 1, 3, 6, 11.4 and 22.8 cycles/degree in 31 patients (50 eyes) with open-angle glaucoma. The data of CSF were compared with visual acuity and visual field determinations. It was found that CSF could be abnormal in subjects with visual acuities of 1.0 or better and normal visual fields; the patterns of CSF loss were varied, and there was a linear correlation between the area of the visual field and the CSF value. The results suggested that the measurement of CSF provided basis for the judgment of visual functional changes in the clinical observation of glaucoma.

Adolescent

Functional properties of a metabotropic glutamate receptor at dendritic synapses of ON bipolar cells in the amphibian retina.

Perforated patch-voltage and current-clamp recordings were obtained from ON bipolar cells in the amphibian retinal slice preparation. The currents produced by the photoreceptor transmitter were compared to the currents produced by selective metabotropic glutamate agonists: L-2-amino-4-phosphonobutyrate (L-AP4, APB) and IS,3R 1-amino-1,3 cyclopentanedicarboxylic acid (1S, 3R ACPD). Both agonists produced currents that were very similar to that produced by the photoreceptor transmitter in terms of conductance and reversal potential. The similarities suggest that the metabotropic glutamate receptors are functionally localized to the synaptic region of ON bipolar dendrites. The synaptic conductance rarely exceeded the non-synaptic conductance. The mean input resistance of ON bipolar neurons was 770 M omega in the light and 1.2 G omega in the dark. The average light-regulated synaptic conductance was 57% of the non-synaptic conductance. The L-AP4 regulated conductance averaged 77% of the non-synaptic conductance, while the 1S, 3R ACPD regulated conductance averaged 95% of the non-synaptic conductance. This balance between synaptic and non-synaptic conductance indicates that the synapse will not shunt the cell and the conductance ratio serves to maximize incremental gain at the photoreceptor to ON bipolar synapse. This conductance mechanism makes the ON bipolar cell well equipped to relay rod signals.

Aminobutyrates