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Hua Gao

Publications and source records attributed to Hua Gao.

11 recordsLinked to original sources
PubMed2003

Photoreceptor degeneration and rd1 mutation in the grizzled/mocha mouse strain.

The mocha mouse is a spontaneous mutant carrying a defective adaptor-like protein complex AP-3delta subunit. We examined retinal function and histology of the mocha mutant. We found that not only mocha homozygotes but also other littermates in the inbred strain are blind due to severe defects in both rod and cone photoreceptors on electroretinogram recordings. The functional deficit was caused by rapid, early postnatal photoreceptor degeneration. Genotyping confirmed the presence of a viral insertion of rd1 gene in the mocha strain. We conclude that rd1 allele contamination is primarily responsible for photoreceptor degeneration, and caution against behavioral tests with visual cues in the present stocks.

Alleles↗
PubMed2003

[Molecular characterization of a new mutation E122G of human ornithine transcarbamylase gene].

OBJECTIVE: To determine the molecular basis of late onset ornithine transcarbamylase (OTC) deficiency in a Chinese family of Han nationality and the exon sequences of OTC gene of this patient. METHODS: Polymerase chain reaction-single strand conformation polymorphism and direct sequencing were used to identify the mutation type. RESULTS: A missense mutation E122G in the conserved residue of exon 4 was identified which is unreported before. CONCLUSION: The E122G mutation in human OTC gene may cause late onset OTC deficiency.

Age of Onset↗
PubMed2003

[Establishment and preliminary application of screening methods for Y chromosome microdeletions in male infertility patients].

OBJECTIVE: To develop a multiplex PCR protocol, which could be suitable for routine screening of microdeletions on the Y chromosome in azoospermic and oligozoospermic male infertility patients. METHODS: Five multiplex sets were established. Eighty-seven azoospermic and oligozoospermic patients undergoing intracytoplasmic sperm injection (ICSI) in the in vitro fertilization (IVF) center and 30 azoospermic men undergoing testicular biopsy in the clinic of Urology Surgery were screened for microdeletions of Y chromosome. RESULTS: A total of 19 (16.2%) cases of microdeletions were found in 117 azoospermic and oligozoospermic patients by screening of Y chromosome microdeletions. Of these, 11 cases (18.0%) were found in 61 oligozoospermic patients, and 8 cases (14.3%) were found in 56 azoospermic patients. CONCLUSION: The multiplex PCR protocol presented in this study is an easy-to-do and reliable method for detecting microdeletions on the Y chromosome. Routine screening of microdeletions on the Y chromosome for azoospermic and oligozoospermic patients is essential.

Chromosome Deletion↗
PubMed2002

Beta-arrestin 2 functions as a G-protein-coupled receptor-activated regulator of oncoprotein Mdm2.

Oncoprotein Mdm2 is a master negative regulator of the tumor suppressor p53 and has been recently shown to regulate the ubiquitination of beta-arrestin 2, an important adapter and scaffold in signaling of G-protein-coupled receptors (GPCRs). However, whether beta-arrestin 2 has any effect on the function of Mdm2 is still unclear. Our current results demonstrated that the binding of Mdm2 to beta-arrestin 2 was significantly enhanced by stimulation of GPCRs. Activation of GPCRs led to formation of a ternary complex of Mdm2, beta-arrestin 2, and GPCRs and thus recruited Mdm2 to GPCRs at plasma membrane. Moreover, the binding of beta-arrestin 2 to Mdm2 suppressed the self-ubiquitination of Mdm2 and consequently reduced the Mdm2-mediated p53 degradation and ubiquitination. Further experiments revealed that overexpression of beta-arrestin 2 enhanced the p53-mediated apoptosis while suppression of endogenous beta-arrestin 2 expression by RNA interference technology considerably attenuated the p53-mediated apoptosis. Our study thus suggests that beta-arrestin 2 may serve as a cross-talk linker between GPCR and p53 signaling pathways.

Animals↗
PubMed2002

Up-regulation of brain-derived neurotrophic factor expression by brimonidine in rat retinal ganglion cells.

OBJECTIVES: Brimonidine tartrate ophth, an alpha(2)-adrenergic agonist, is widely used as an antiglaucoma agent for lowering intraocular pressure. Recent studies suggest that brimonidine may be neuroprotective for retinal ganglion cells (RGCs) following optic nerve crush injury. Brain-derived neurotrophic factor (BDNF), a potent neuroprotective factor present in the RGCs, promotes RGC survival in culture and following optic nerve injury. We tested the hypothesis that a possible mechanism of brimonidine neuroprotection is through up-regulation of endogenous BDNF expression in the RGCs. METHODS: A single dosage of brimonidine tartrate ophth solution (0.85-34 microM) was injected intravitreally into Sprague-Dawley rat eyes. The fellow eyes of each animal were injected with balanced salt solution (BSS) and used as control eyes. To determine BDNF messenger RNA expression, animal eyes were enucleated and processed for in situ hybridization, or retinas were isolated and processed for Northern blot analysis using rat BDNF radiolabeled riboprobes. RESULTS: In the control eyes injected with saline, BDNF was present in a minority of the RGCs. Two days after brimonidine injection, the number of BDNF-positive RGCs was increased from 55% to 166%, depending on brimonidine concentrations, when compared with those in the controls. In addition, the BDNF signal intensities in individual RGCs were elevated 50% in brimonidine-injected eyes compared with control eyes. Northern blot revealed a 28% increase of BDNF expression in the brimonidine group compared with the controls (P <.003). No significant difference was observed in BDNF receptor, trk B, expression between brimonidine, or BSS control groups. CONCLUSIONS: A single dose of a low concentration of intravitreal brimonidine is sufficient to significantly increase endogenous BDNF expression in RGCs. These results suggest that brimonidine neuroprotection may be mediated through up-regulation of BDNF in the RGCs. The BDNF should be further investigated regarding its role in the neuroprotective effects reported with brimonidine. CLINICAL RELEVANCE: Brimonidine may be (potentially) used clinically as a neuroprotective agent in optic neuropathy, including glaucoma, and ischemic and traumatic optic neuropathy.

Adrenergic alpha-Agonists↗
PubMed2002

Enhancement of binary QSAR analysis by a GA-based variable selection method.

Binary quantitative structure-activity relationship (QSAR) is an approach for the analysis of high throughput screening (HTS) data by correlating structural properties of compounds with a "binary" expression of biological activity (1 = active and 0 = inactive) and calculating a probability distribution for active and inactive compounds in a training set. Successfully deriving a predictive binary or any QSAR model largely depends on the selection of a preferred set of molecular descriptors that can capture the chemico-biological interaction for a particular biological target. In this study, a genetic algorithm (GA) was applied as a variable selection method in binary QSAR analysis. This GA-based variable selection method was applied to the analysis of three diverse sets of compounds, estrogen receptor (ER) ligands, carbonic anhydrase II inhibitors, and monoamine oxidase (MAO) inhibitors. Out of a variable pool of 150 molecular descriptors, predictive binary QSAR models were obtained for all three sets of compounds within a reasonable number of GA generations. The results indicate that the GA is a very effective variable selection approach for binary QSAR analysis.

Algorithms↗
PubMed2002

Estimation of aqueous solubility of organic compounds with QSPR approach.

PURPOSE: To derive a QSPR model for estimation of aqueous solubility of organic compounds. METHODS: Solubility data for 930 diverse compounds was investigated with principal component regression analysis. This set of compounds consists of pharmaceuticals, pollutants, nutrients, herbicides, and pesticides. The diversity of this collection was analyzed using MACCS fingerprint and BCUT chemistry space. RESULTS: The training set of the solubility data is as diverse as the Available Chemicals Directory, and more diverse than the MDL Drug Data Report. Forty-six molecular descriptors were screened using a genetic algorithm. A QSPR model with a squared correlation coefficient (r2) of 0.92, a root mean square error of 0.53 log molar solubility (log S(w)), an average absolute estimation error of 0.36 log S(w), and a cross-validated q2 of 0.91 was derived. The QSPR model was validated with a test set of 249 compounds not included in the training set. The absolute estimation error for the test set of compounds was 0.39 log S(w). CONCLUSIONS: A highly predictive QSPR model for estimating aqueous solubility was derived and validated. This model can be used to estimate aqueous solubility for virtual screening and combinatorial library design.

Algorithms↗