Biomedical subjects

R Luo

Publications and source records attributed to R Luo.

At least 19 recordsLinked to original sources

PubMed2002

Biomarker study of a municipal effluent dispersion plume in two species of freshwater mussels.

The toxicological effects of a primary-treated municipal effluent plume were investigated in two species of freshwater mussels, Elliptio complanata and Dreissena polymorpha, exposed for 62 days at sites upstream and downstream of an effluent outfall in the St. Lawrence River (Quebec, Canada). Levels of metallothioneins (MT), cytochrome P4501A1 activity, DNA damage, total lipids, relative levels of vitellins, and phagocytic activity (in E. complanata hemocytes) were determined after the exposure period. A parallel analysis measured heavy metals and coprostanol in mussel tissues. The results show that significant levels of coprostanol and some metals (specifically, Cu, Hg, Sb, Se, and Zn) had accumulated in mussels caged 5 km downstream of the effluent plume. Mixed-function oxidase activity, MT in gills, total lipids, DNA damage (in D. polymorpha only), and total hemolymph bacteria (in E. complanata only) had increased in these mussels, while levels of total cadmium (Cd), MT in digestive glands or whole soft tissues, phagocytic activity, and DNA damage in the digestive gland (in E. complanata only) were diminished. The exposure of mussels to surface waters contaminated by a municipal effluent led to many stress responses, depending on both the tissues and the species being examined.

Animals↗

PubMed2001

Interpreting trends in the binding of cyclic ureas to HIV-1 protease.

The design of new HIV protease inhibitors requires an improved understanding of the physical basis of inhibitor/protein binding. Here, the binding affinities of seven aliphatic cyclic ureas to HIV-1 protease are calculated using a predominant states method and an implicit solvent model based upon finite difference solutions of the Poisson-Boltzmann equation. The calculations are able to reproduce the observed U-shaped trend of binding free energy as a function of aliphatic chain length. Interestingly, the decrease in affinity for the longest chains is attributable primarily to the energy cost of partly desolvating charged aspartic and arginine groups at the mouths of the active site. Even aliphatic chains too short to contact these charged groups directly are subject to considerable desolvation penalties. We are not aware of other systems where binding affinity trends have been attributed to long-ranged electrostatic desolvation of ionized groups. A generalized Born/surface area solvation model yields a much smaller change in desolvation energy with chain length and, therefore, does not reproduce the experimental binding affinity trends. This result suggests that the generalized Born model should be used with caution for complex, partly desolvated systems like protein binding sites. We also find that changing the assumed protonation state of the active site aspartyl dyad significantly affects the computed binding affinity trends. The protonation state of the aspartyl dyad in the presence of cyclic ureas is discussed in light of the observation that the monoprotonated state reproduces the experimental results best.

Arginine↗

PubMed2001

An analysis of the interactions between the Sem-5 SH3 domain and its ligands using molecular dynamics, free energy calculations, and sequence analysis.

The Src-homology-3 (SH3) domain of the Caenorhabditis elegans protein Sem-5 binds proline-rich sequences. It is reported that the SH3 domains broadly accept amide N-substituted residues instead of only recognizing prolines on the basis of side chain shape or rigidity. We have studied the interactions between Sem-5 and its ligands using molecular dynamics (MD), free energy calculations, and sequence analysis. Relative binding free energies, estimated by a method called MM/PBSA, between different substitutions at sites -1, 0, and +2 of the peptide are consistent with the experimental data. A new method to calculate atomic partial charges, AM1-BCC method, is also used in the binding free energy calculations for different N-substitutions at site -1. The results are very similar to those obtained from widely used RESP charges in the AMBER force field. AM1-BCC charges can be calculated more rapidly for any organic molecule than can the RESP charges. Therefore, their use can enable a broader and more efficient application of the MM/PBSA method in drug design. Examination of each component of the free energy leads to the construction of van der Waals interaction energy profiles for each ligand as well as for wild-type and mutant Sem-5 proteins. The profiles and free energy calculations indicate that the van der Waals interactions between the ligands and the receptor determine whether an N- or a Calpha-substituted residue is favored at each site. A VC value (defined as a product of the conservation percentage of each residue and its van der Waals interaction energy with the ligand) is used to identify several residues on the receptor that are critical for specificity and binding affinity. This VC value may have a potential use in identifying crucial residues for any ligand-protein or protein-protein system. Mutations at two of those crucial residues, N190 and N206, are examined. One mutation, N190I, is predicted to reduce the selectivity of the N-substituted residue at site -1 of the ligand and is shown to bind similarly with N- and Calpha-substituted residues at that site.

Animals↗

PubMed2001

Purification and properties of three new phospholipase A2 isoenzymes from Micropechis ikaheka venom.

Three new phospholipase A2 (PLA2) isoenzymes were purified from the Micropechis ikaheka venom by successive chromatographies. The homogeneity of them was accessed by capillary zone electrophoresis and mass spectrometry. Their N-terminal sequences showed high identity (94, 88 and 90, respectively) with MiPLA-1, a group IB PLA2 also from this venom. In addition, strong immuno-cross-reaction with anti-MiPLA-1 serum was observed. These results suggested that three newly purified PLA2 belonged to group IB. Beside enzymatic activity, they induced various pharmacological effects, including myotoxic, anticoagulant effects and insulin secretion stimulating effects. Our results indicated that enzymatic activity is essential for their myotoxic and anticoagulant effects. On the other hand, no direct correlation between their insulin secretion stimulating effect and enzymatic activity was observed, suggesting that they may stimulate insulin secretion through a non-enzymatic mechanism.

Amino Acid Sequence↗

PubMed2001

Inhibition of poly(ADP-ribose) polymerase activity is insufficient to induce tetraploidy.

Poly(ADP-ribose) polymerase (PARP) knockout mice are resistant to murine models of human diseases such as cerebral and myocardial ischemia, traumatic brain injury, diabetes, Parkinsonism, endotoxic shock and arthritis, implicating PARP in the pathogenesis of these diseases. Potent selective PARP inhibitors are therefore being evaluated as novel therapeutic agents in the treatment of these diseases. Inhibition or depletion of PARP, however, increases genomic instability in cells exposed to genotoxic agents. We recently demonstrated the presence of a genomically unstable tetraploid population in PARP(-/-) fibroblasts and its loss after stable transfection with PARP cDNA. To elucidate whether the genomic instability is attributable to PARP deficiency or lack of PARP activity, we investigated the effects of PARP inhibition on development of tetraploidy. Immortalized wild-type and PARP(-/-) fibroblasts were exposed for 3 weeks to 20 microM GPI 6150 (1,11b-dihydro-[2H:]benzopyrano[4,3,2-de]isoquinolin-3-one), a novel small molecule specific competitive inhibitor of PARP (K(i) = 60 nM) and one of the most potent PARP inhibitors to date (IC(50) = 0.15 microM). Although GPI 6150 initially decreased cell growth in wild-type cells, there was no effect on cell growth or viability after 24 h. GPI 6150 inhibited endogenous PARP activity in wild-type cells by approximately 91%, to about the residual levels in PARP(-/-) cells. Flow cytometric analysis of unsynchronized wild-type cells exposed for 3 weeks to GPI 6150 did not induce the development of tetraploidy, suggesting that, aside from its catalytic function, PARP may play other essential roles in the maintenance of genomic stability.

Animals↗

PubMed2001

Specific pan-neural crest expression of zebrafish Crestin throughout embryonic development.

Zebrafish crestin was identified in a screen for genes dependent on cyclops function and is a member of a family of retroelements (Rubinstein et al. [2000] Genesis 26:86-97). We report here a detailed description of crestin mRNA expression during zebrafish embryogenesis. Crestin expression was first observed during the onset of somitogenesis in cells of the neural crest domain of the ectoderm. Crestin expression was subsequently observed in premigratory cranial and trunk neural crest cells and then in actively migrating crest cells. Cell counts of crestin-expressing premigratory trunk neural crest cells strongly suggest that crestin is expressed by all neural crest cells at this stage. Crestin expression co-localized with a battery of markers for premigratory neural crest cells, developmentally distinct neural crest-derived precursor sublineages, and overtly differentiated neural crest-derived cell types. Expression of crestin is gradually downregulated in overtly differentiated cells. Our results indicate that crestin is a specific pan-neural crest marker throughout zebrafish embryogenesis.

Animals↗

PubMed2001

The physical basis of nucleic acid base stacking in water.

It has been argued that the stacking of adenyl groups in water must be driven primarily by electrostatic interactions, based upon NMR data showing stacking for two adenyl groups joined by a 3-atom linker but not for two naphthyl groups joined by the same linker. In contrast, theoretical work has suggested that adenine stacking is driven primarily by nonelectrostatic forces, and that electrostatic interactions actually produce a net repulsion between adenines stacking in water. The present study provides evidence that the experimental data for the 3-atom-linked bis-adenyl and bis-naphthyl compounds are consistent with the theory indicating that nonelectrostatic interactions drive adenine stacking. First, a theoretical conformational analysis is found to reproduce the observed ranking of the stacking tendencies of the compounds studied experimentally. A geometric analysis identifies two possible reasons, other than stronger electrostatic interactions, why the 3-atom-linked bis-adenyl compounds should stack more than the bis-naphthyl compounds. First, stacked naphthyl groups tend to lie further apart than stacked adenyl groups, based upon both quantum calculations and crystal structures. This may prevent the bis-naphthyl compound from stacking as extensively as the bis-adenyl compound. Second, geometric analysis shows that more stacked conformations are sterically accessible to the bis-adenyl compound than to the bis-naphthyl compound because the linker is attached to the sides of the adenyl groups, but to the ends of the naphthyl groups. Finally, ab initio quantum mechanics calculations and energy decompositions for relevant conformations of adenine and naphthalene dimers support the view that stacking in these compounds is driven primarily by nonelectrostatic interactions. The present analysis illustrates the importance of considering all aspects of a molecular system when interpreting experimental data, and the value of computer models as an adjunct to chemical intuition.

Adenine↗

PubMed2001

Ligand-receptor docking with the Mining Minima optimizer.

The optimizer developed for the Mining Minima algorithm, which uses ideas from Genetic Algorithms, the Global Underestimator Method, and Poling, has been adapted for use in ligand-receptor docking. The present study describes the resulting methodology and evaluates its accuracy and speed for 27 test systems. The performance of the new docking algorithm appears to be competitive with that of previously published methods. The energy model, an empirical force field with a distance-dependent dielectric treatment of solvation, is adequate for a number of test cases, although incorrect low-energy conformations begin to compete with the correct conformation for larger sampling volumes and for highly solvent-exposed binding sites that impose little steric constraint on the ligand.

Algorithms↗

PubMed2001

Endoplasmic reticulum and cis-Golgi localization of human T-lymphotropic virus type 1 p12(I): association with calreticulin and calnexin.

Human T-lymphotropic virus type 1 (HTLV-1) is a complex retrovirus encoding regulatory and accessory genes in four open reading frames (ORF I to IV) of the pX region. We have demonstrated an important role of pX ORF I expression, which encodes p12(I), in establishment of HTLV-1 infection in a rabbit model and for optimal viral infectivity in quiescent primary lymphocytes. These data indicated that p12(I) may enhance lymphocyte activation and thereby promote virus infection. To further define the role of p12(I) in cell activation, we characterized the subcellular localization of p12(I) in transfected 293T cells and HeLa-Tat cells by multiple methods, including immunofluorescence confocal microscopy, electron microscopy, and subcellular fractionation. Herein, we demonstrate that p12(I) accumulates in the endoplasmic reticulum (ER) and cis-Golgi apparatus. The location of p12(I) was unchanged following treatments with both cycloheximide (blocking de novo protein synthesis) and brefeldin A (disrupting ER-to-Golgi protein transport), indicating that the protein is retained in the ER and cis-Golgi. Moreover, using coimmunoprecipitation assays, we identify the direct binding of p12(I) with both calreticulin and calnexin, resident ER proteins which regulate calcium storage. Our results indicate that p12(I) directly binds key regulatory proteins involved in calcium-mediated cell signaling and suggest a role of p12(I) in the establishment of HTLV-1 infection by activation of host cells.

Biological Transport↗

PubMed2001

[Survey of 3-monochloropropane-1,2-diol in soy sauce and similar products].

A survey of 3-monochloropropane-1,2-diol (3-MCPD) in soy sauce and other similar products available in China has been completed. Thirty samples of soy, oyster sauce and other sauces were purchased from six supermarkets in Beijing during March and April 2000 and analysed using a validated method of analysis by capillary gas chromatography with mass spectrometric detection. The UK Food Advisory Committee (FAC) has advised a level of 0.01 mg/kg for 3-MCPD. Following reports that high levels had been detected in some brands of soy sauce in China. 3-MCPD was undetectable with a detection limit of 0.01 mg/kg in 15 of the 30 samples analyzed in the survey, with a further 4 samples (13.3%) containing very low levels of between 0.01 and 0.02 mg/kg. However, 5 samples (16.7%) contained 3-MCPD levels above 1 mg/kg.

Chemosterilants↗

PubMed2001

[Diagnostic value of five serum markers for liver fibrosis].

OBJECTIVE: To research the diagnostic value of serum hyaluronic acid (HA), type III procollagen (PCIII), type IV collagen (CIV), laminin (LN), and transforming growth factor-beta(1) (TGF-beta(1)) for liver fibrosis in patients with chronic hepatitis. METHODS: Serum levels of HA, PCIII, CIV, LN and TGF-beta(1) in 116 patients with chronic hepatitis and cirrhosis were investigated and compared with hepatic histological findings of 87 patients. RESULTS: The correlation between serum HA and histologically assessed grade of inflammatory activity was weak (r=0.393, P<0.05). The correlation between serum HA, PCIII, LN, TGF-beta(1) and histologically assessed stage of liver fibrosis were all moderate (r=0.584, 0.454, 0.441 and 0.612, respectively, P<0.05), while that between serum CIV and histologically assessed stage of liver fibrosis was weak (r=0.319, P<0.05). As shown by the ROC curves in cases of chronic hepatitis, the ability to differentiate patients with cirrhosis from those without cirrhosis was greater for serum HA than that for serum PCIII, CIV, LN, and TGF-beta(1) (the areas under the curves=0.904 vs 0.784, 0.815, 0.805, 0.828, P<0.05). The ability of serum HA, LN and TGF-beta(1) to differentiate patients with extensive liver fibrosis from those with no or mild liver fibrosis exceeded that of serum PCIII and CIV (the areas under the curves=0.849, 0.819, 0.836 vs 0.702, 0.721, P<0.05). To discriminate the stage of liver fibrosis, serum HA and TGF-beta(1) were selected from the five markers by Bayes discriminate analysis. If S(1), S(2) and S(3) were not required to be discriminated, discrimination between the three stages showed significant difference (P<0.05). The predictive accurate percentage was 72.90%. CONCLUSIONS: The five markers all have the ability not only to judge liver cirrhosis, in which the ability of serum HA is the best, but also to differentiate chronic hepatitis with extensive liver fibrosis from that with no or mild liver fibrosis, in which the ability of serum HA, LN, TGF-beta(1) is stronger than the other two. It is useful for detection of serum HA and TGF-beta(1) at the same time to discriminate the histologically assessed stage of fibrosis. Serum HA and TGF-beta(1) can be helpful in discriminating patients of chronic hepatitis with "no liver fibrosis", "liver fibrosis but no cirrhosis" and "liver cirrhosis", but cannot discriminate them accurately as the histologically assessed stage of fibrosis. They cannot displace liver biopsy for the judgement of liver fibrosis.

Adult↗

PubMed2001

[The experimental study of the anti-enterovirus effects of drugs in vitro].

OBJECTIVE: To screen the safe and effective anti-enterovirus drugs for clinical application. METHODS: The cytotoxicity of Ribavirin, Shuanghuanglian and Garlic were evaluated through MTT colorimetry and cell morphology. The antiviral activity of Ribavirin, Shuanghuanglian and Garlic were studied in HEL and Vero cells infected with CBV3 and ECHO11 by observing cytopathic effect (CPE), MTT colorimetry and plaque-reduction assay. The antiviral activity of these three drugs were compared and that of Shuanghuanglian and Garlic were also compared before and after ECHO11 absorbing by plaque-reduction assay. RESULTS: (1) The cytotoxicity of these three drugs were expressed as TC50(50% toxic concentration). TC50 of Ribavirin was 2 mg/ml, of Shuanghuanglian 5 mg/ml, of Garlic 12.5 micrograms/ml. (2) Ribavirin could inhibit CBV3 and ECHO11 at the concentration ranged from 1 mg/ml to 1.5 mg/ml. Shuanghuanglian could inhibit CBV3 and ECHO11 at the concentration of 0.5 mg/ml and the viral inhibiting effect was concentration-dependent. Garlic could inhibit CBV3 and ECHO11 at the concentration ranged from 2.5 micrograms/ml to 7.5 micrograms/ml and 5 micrograms/ml was the most effective. (3) Plaque-reduction assay was used to test the anti-virus (CBV3 and ECHO11) activity of these three drugs: plaque reduction rate of 1.5 mg/ml Ribavirin was 43.2% and 37.2%, of 2.5 mg/ml Shuanghuanglian was 81.1% and 88.4% and of 5 micrograms/ml Garlic was 66.2% and 77.4% respectively. The plaque reduction rate of Ribavirin was lower than the other two drugs (P < 0.05), between these two showed no significant difference (P > 0.05). The anti-ECHO11 activity of Shanghuanglian before ECHO11 adsorbing was higher than after ECHO11 adsorbing (P < 0.05). There was no significant difference between the plaque reduction rates of Garlic before and after ECHO11 adsorbin. CONCLUSION: All of the three drugs have anti-virus activity in vitro while Shuanghuanglian and Garlic are more effective. Among these three drugs, the cytotoxicity of Shuanghuanglian is the most weak and the anti-virus activity is the strongest. The antiviral activity of Shuanghuanglian adding before virus adsorbing was higher, so it seems that Shuanghuanglian can prevent EV infection.

Animals↗

PubMed2001

Optical coherence tomography in measuring retinal nerve fiber layer thickness in normal subjects and patients with open-angle glaucoma.

OBJECTIVES: To investigate image characteristics and thickness of the retinal nerve fiber layer (RNFL) in normal and glaucomatous eyes using optical coherence tomography (OCT), and analyze the relationship between RNFL thickness and visual field index. METHODS: Eighty-three normal persons (150 eyes) and 83 patients with primary open angle glaucoma (POAG, 149 eyes) underwent OCT examinations with 3.4 mm diameter circle scan to calculate the RNFL thickness. Statistical analysis was used to compare differences in RNFL thickness in quadrants and means between the normal and glaucomatous groups and the different stages of POAG. Linear correlation and regression analysis were used to show the correlation between RNFL thickness and visual field index of 115 eyes in glaucomatous patients. Reproducibility, sensitivity and specificity of RNFL measurements using OCT were evaluated. RESULTS: RNFL thickness measured by OCT in normal subjects was thicker in superior and inferior, less in temporal, and thinnest in nasal quadrants. The curve showed double peaks. RNFL of glaucomatous patients showed local thinning or defect, diffuse thinning, or both. The mean RNFL thicknesses of the normal group in the temporal, superior, nasal and infelor quadrants were 90.1 +/- 10.8 microns, 140.4 +/- 10.5 microns, 85.2 +/- 14.0 microns, and 140.4 +/- 9.7 microns, respectively with a mean of 114.2 +/- 6.0 microns. The numbers for the glaucomatous group were respectively 56.0 +/- 31.0 microns, 81.0 +/- 36.3 microns, 47.1 +/- 27.5 microns, and 73.4 +/- 38.4 microns for the four quadrants, with a mean of 64.6 +/- 28.8 microns. There was a significant difference in RNFL thickness between the normal and glaucomatous groups (P < 0.000), and the three stages (early, developing and late) of glaucomatous groups (P < 0.000). There was a close negative relationship between RNFL thickness and visual field index (r = -0.796, P < 0.0001). The sensitivity and specificity of RNFL thickness in POAG measured using OCT were 93.3% and 92.0%, respectively. CONCLUSIONS: OCT can quantitatively measure RNFL thickness differences between normal persons and glaucomatous patients. RNFL thickness gradually decreases while visual field defect increases with the development of POAG.

Adolescent↗

PubMed2001

[Association between angiotensin-II receptor gene type I polymorphism and diabetic nephropathy in type 2 diabetes mellitus].

OBJECTIVE: To investigate the relationship between angiotensin type I receptor (AGT I R) gene polymorphism and diabetic nephropathy (DN) and its progression. METHODS: PCR technique was used to determine the AGT I R gene polymorphism in 86 patients without DN, 67 with microalbuminuria, 66 with clinical albuminuria and 20 type 2 DM patients with renal insufficiency. RESULTS: In comparing the DN group with the non-DN group, it was found that there was a significant difference of the frequency of AC genotype with DN (chi(2) = 4.30, P < 0.05), and C mutative type was more frequent in the DN group (chi(2) = 3.97, P < 0.05). No significant difference of AGTIR-A1166-C genotype was found in cases with different durations of DN. CONCLUSION: Delete polymorphism of A1166-C gene is associated with DN in type 2 diabetes mellitus. It is suggested that detection of significant AGTIR-A1166-C polymorphism is of help for preventing DN in type 2 diabetes mellitus.

Adult↗

PubMed2001

[A study on susceptibility of different layers of rabbit retina to ocular hypertension].

OBJECTIVE: To investigate the histological damage and its degrees of different layers of rabbit retina induced by ocular hypertension. METHODS: The intraocular pressure (IOP) was elevated by intracameral injection of 0.10 - 0.15 ml of 2% methylcellulose in sixteen gray rabbits. The rabbit eyes were enucleated, fixed, and paraffin-embedded. For histological evaluation, the slides were stained with hematoxylin-eosin, examined by light microscopic and computer automatic image analysis. RESULTS: The quantitative analysis indicated that all of the retinal layers have different degrees of histopathological damage. Among them, the retinal ganglion cells (RGCs) and retinal nerve fiber layer (RNFL) were most severely damaged, with the decrease rate of 74.3% and 61.9%, respectively. The decrease rates of other retinal layers were as follows: the retinal inner layer, 42.4%; the whole sensory layer of the retina, 35.0% and the outer layer, 24.2%. We also found a significant correlation between RGCs loss and RNFL thinning (r = 0.68, P < 0.01), demonstrating a strong correlation between IOP level and RNFL thickness (F = 8.97, P < 0.01). CONCLUSION: All of the anatomic layers of retina can suffer from degeneration and atrophy at different degrees.

Animals↗

PubMed2001

[Level of nerve growth factor protein in cerebellar cortex of rat pups in intrauterine growth retardation model by clamping the uterine vasculature of pregnant rat].

OBJECTIVE: To understand the level of nerve growth factor (NGF) in the brain of rat pups in intrauterine growth retardation (IUGR), explore the mechanism of brain injury. METHODS: Animal models for IUGR pups were established by clamping the uterine vasculature of pregnant rats with 30 minutes in this study. NGF proteins were measured by immunohistochemistry in the cerebellar cortex of rat pups at birth (21 days of gestation), and on the sixth day after birth. RESULTS: 1. The body weight of the 21-day fetuses in IUGR group decreased 16.1% as compared to that in control group (P < 0.0001); 2. The brain weight of the 21-day fetuses in IUGR group decreased to that in control group (P < 0.05) development of their brain retardation during the intrauterine in IUGR fetus period in this model; 3. On the sixth day after birth, there was no statistical difference in body weight between the IUGR and the control groups. But the brain weight difference between these two groups was still there; 4. At birth and on the sixth day after birth, there were statistical differences in NGF proteins in cerebellum between the IUGR and the control groups, which got along with the decrease of their brain weights. CONCLUSION: A successful animal model of IUGR was established by clamping the uterine vasculature of pregnant rats with 30 minutes, and the development of their brain were retarded in IUGR fetus period in this model. Brain retardation in IUGR pups may relate with the decreased level of NGF in brain. This study discovered that quick "catch-up" growth in physical development and slow "catch-up" growth in brain development in IUGR pups.

Animals↗

PubMed2001

[Evaluation of sensorineural hearing loss in childhood].

OBJECTIVE: To explore the clinical and audiological characteristics of sensorineural hearing loss (SHL) with pathological changes both in cochlea and retrocochlear in children and evaluate the relationship between SHL and the lesions in the central nervous system (CNS). METHODS: Three hundred and ten cases (500 ears) of SHL accepted between 1998 and 2000 were studied. The age of patients was ranged from 1 month to 6 years old. According to the evaluation of function of CNS by pediatric neurologist, all cases were divided into two groups: SHL with CNS disease and SHL without CNS disease. Some same age children without hearing loss were subjected as control group. All children were tested using both auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE). RESULTS: 1. The rate of SHL accompanied with CNS diseases was very high in these children. 2. Patients with kernicterus-cerebral palsy usually had serious hearing loss caused by acoustic nerve lesion at retrocochlear, but their cochlea function was injured slightly. Patients with external hydrocephalus had only slight acoustic nerve lesion at retrocochlear, and patients with other CNS diseases usually had no change for their cochlea function. 3. In the group of SHL caused by cochlea lesion, amplitudes of DPOAE decreased obviously when the threshold of wave V of ABR was up to 60 dB nHL, and amplitudes of DPOAE seriously decreased or disappeared when the threshold of wave V was up to above 70 dB nHL. CONCLUSION: The patients with SHL are usually accompanied with CNS diseases in childhood, and their hearing loss appears very difference from audiological characteristics. We suggest that it is necessary to test both ABR and DPOAE in these patients, and it is important that pediatric neurologist join in audiologist team for our clinical study.

Brain Edema↗

PubMed2000

Misregulation of gene expression in primary fibroblasts lacking poly(ADP-ribose) polymerase.

Poly(ADP-ribose) polymerase (PARP) is implicated in the maintenance of genomic integrity, given that inhibition or depletion of this enzyme increases genomic instability in cells exposed to genotoxic agents. We previously showed that immortalized fibroblasts derived from PARP(-/-) mice exhibit an unstable tetraploid population, and partial chromosomal gains and losses in PARP(-/-) mice and immortalized fibroblasts are accompanied by changes in the expression of p53, Rb, and c-Jun, as well as other proteins. A tetraploid population has also now been detected in primary fibroblasts derived from PARP(-/-) mice. Oligonucleotide microarray analysis was applied to characterize more comprehensively the differences in gene expression between asynchronously dividing primary fibroblasts derived from PARP(-/-) mice and their wild-type littermates. Of the 11,000 genes monitored, 91 differentially expressed genes were identified. The loss of PARP results in down-regulation of the expression of several genes involved in regulation of cell cycle progression or mitosis, DNA replication, or chromosomal processing or assembly. PARP deficiency also up-regulates genes that encode extracellular matrix or cytoskeletal proteins that are implicated in cancer initiation or progression or in normal or premature aging. These results provide insight into the mechanism by which PARP deficiency impairs mitotic function, thereby resulting in the genomic alterations and chromosomal abnormalities as well as in altered expression of genes that may contribute to genomic instability, cancer, and aging.

Animals↗