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Biomedical subjects

M Gao

Publications and source records attributed to M Gao.

At least 19 recordsLinked to original sources
PubMed2006

Fibroblast growth factor-10 prevents H2O2-induced cell cycle arrest by regulation of G1 cyclins and cyclin dependent kinases.

We studied the effects of fibroblast growth factor (FGF-10) on H2O2-induced alveolar epithelial cell (AEC) G1 arrest and the role of G1 cyclins. FGF-10 prevented H2O2-induced AEC G1 arrest. FGF-10 induced 2-4-fold increase in cyclin E, cyclin A and CDKs (2,4) alone and in AEC treated with H2O2. H2O2 downregulated cyclin D1; FGF-10 blocked these effects. FGF-10 prevented H2O2-induced upregulation of CDK inhibitor, p21. SiRNAp21 blocked H2O2-induced downregulation of cyclins, CDKs and AEC G1 arrest. Accordingly, we provide first evidence that FGF-10 regulates G1 cyclins and CDKs, and prevents H2O2-induced AEC G1 arrest.

Cell Cycle↗
PubMed2006

Effect of Akt inhibition on scatter factor-regulated gene expression in DU-145 human prostate cancer cells.

The cytokine scatter factor (SF) (hepatocyte growth factor) transduces various biologic actions, including cell motility, invasion, angiogenesis and apoptosis inhibition. The latter is relevant to understanding the role of SF in promoting tumor cell survival in different contexts, for example, detachment from basement membrane, growth in metastatic sites and responses to chemo- and radiotherapy. Previously, we showed that SF protects cells against apoptosis owing to DNA damage, by a mechanism involving phosphoinositol-3-kinase/c-Akt signaling. Here, we used DNA microarray assays to identify c-Akt-regulated genes that might contribute to cell protection. DU-145 human prostate cancer cells were transfected+/-a dominant-negative mutant Akt, treated+/-SF and analysed for gene expression using Affymetrix arrays. These studies identified SF-regulated genes for which induction was c-Akt-dependent vs -independent. Selected microarray findings were confirmed by semiquantitative and quantitative reverse transcription-polymerase chain reaction. We tested the contribution of four SF-inducible/c-Akt-dependent genes (AMPD3, EPHB2, MX1 and WNT4) to protection against adriamycin (a DNA topoisomerase IIalpha inhibitor) using RNA interference. Knockdown of each gene except EPHB2 caused a small but significant reduction in the SF cell protection. The lack of effect of EPHB2 knockdown may be due to the fact that DU-145 cells contain a single-mutant EPHB2 allele. A combination of three small interfering RNAs blocked most of the protection by SF in both DU-145 and T47D cells. These findings identify novel c-Akt-regulated genes, some of which contribute to SF-mediated cytoprotection.

Doxorubicin↗
PubMed2006

Gain of 1q25-32, 12q23-24.3, and 17q12-22 facilitates tumorigenesis and progression of human squamous cell lung cancer.

To explore the genetic changes involved in the stepwise development of lung cancer, we have determined the genetic events associated with the histological progression from normal bronchial epithelium to squamous cell carcinoma. Comparative genomic hybridization was used to identify chromosomal imbalances in 54 microdissected samples, including squamous metaplasia, dysplasia, carcinoma in situ, and invasive tumour derived from 23 patients with squamous cell carcinoma of the lung. Histopathological progression was accompanied by an increased number of chromosomal abnormalities. Gains of 1q25-32, 12q23-24.3, and 17q12-22, in particular, were detected at high frequencies in both carcinoma in situ and invasive tumours and were found more often in the cases with lymph node metastases than in those without. Our previous expression profiling of squamous cell carcinomas had identified overexpression of laminin5 gamma2, a gene located at 1q25-31. Therefore, this was investigated at the protein level by immunohistochemical analysis in 336 samples of squamous cell carcinoma of the lung. Consistent with the genomic data for this region, the expression level of laminin5 gamma2 was higher in the primary tumours with lymph node metastases than in tumours without metastases (p = 0.012). These data suggest that gains of genes from 1q25-32, 12q23-24.3, and 17q12-22 facilitate tumorigenesis and progression of squamous cell carcinoma of the lung, and may serve as potential predictors for this disease.

Aged↗
PubMed2006

Genetic heterogeneity in acrokeratosis verruciformis of Hopf.

BACKGROUND: Acrokeratosis verruciformis of Hopf (AKV) is a rare genodermatosis characterized by multiple flat-topped, flesh-coloured papules on the dorsa of hands and feet, and punctuate keratoses on the palms and soles. A mutation in the ATP2A2 gene has been shown to be associated with AKV and with Darier's disease (DD). OBJECTIVES: To explore the molecular aetiology of AKV and DD. METHODS: We investigated the clinical and histological information in two families and a sporadic case with AKV and one family and a sporadic case with DD in China. Mutation analysis of ATP2A2 was performed by PCR and direct sequencing, and genotyping and linkage analysis performed using six polymorphic microsatellite markers spanning the locus at 12q23-12q24 containing ATP2A2. RESULTS: Mutational analysis showed no mutation in ATP2A2 among the AKV patients, but we found two novel mutations (p.C318F and p.M719fs) in the DD patients. The genotyping and linkage analysis results revealed no linkage evidence of the locus at 12q23-12q24 in a large AKV family. CONCLUSIONS: Our findings provide evidence for the genetic heterogeneity of AKV and demonstrate that mutations in genes other than ATP2A2 are responsible for AKV in a proportion of the Chinese population.

Acrodermatitis↗
PubMed2006

MHC haplotypic association in Chinese Han patients with vitiligo.

BACKGROUND: Serological typing of the human leucocyte antigen (HLA) has shown discrepancies in HLA associations with vitiligo in different ethnic populations. OBJECTIVE: To evaluate the distributions of HLA at class I and II loci that may contribute to the genetic susceptibility of vitiligo patients in Chinese Hans population. METHODS: We analysed the allelic frequencies of HLA class I and II by using the polymerase chain reaction sequence-specific primer (PCR-SSP) method in 187 patients with vitiligo and 273 controls in Chinese Hans. The linkage disequilibrium was calculated from a 2 x 2 table. RESULTS: Two-locus haplotypes including HLA-A25-B13, HLA-A25-B27, HLA-A25-Cw*0602, HLA-A25-DQA1*0302, HLA-A25-DQA1*0601, HLA-A25-DQB1*0303, HLA-B13-Cw*0602, HLA-B13-DQA1*0302, HLA-B13-DQA1*0601, HLA-B27-Cw*0602, HLA-B27-DQA1*0302, HLA-B27-DQA1*0601, HLA-B27-DQB1*0303, HLA-B27-DQB1*0503, HLA-Cw*0602-DQA1*0302, HLA-Cw*0602-DQA1*0601, HLA-Cw*0602-DQB1*0303, HLA-Cw*0602-DQB1*0503 and HLA-DQA1*0302-DQB1*0503 were associated with all types of vitiligo in Chinese Hans. The extended haplotypes HLA-A25-B13-Cw*0602, HLA-A25-B27-Cw*0602, HLA-DQA1*0302-DQB1*0303-Cw*0602 and HLA-B13-DQB1*0303-Cw*0602 were found to be associated with all types of vitiligo in Chinese Hans, whereas the frequency of HLA-A25-Cw*0602-DQA1*0302 was significantly increased in generalized vitiligo but not in localized vitiligo. The frequencies of HLA-A25-DQA1*0302-DQB1*0503 and HLA-A30-DQA1*0302-DQB1*0303 were higher in childhood vitiligo than in adult vitiligo, and the frequency of HLA-A25-B13-DQB1*0303-Cw*0602 was shown to be associated with adult vitiligo but not childhood vitiligo. CONCLUSION: This study demonstrates not only the differential association between HLA markers and types of vitiligo according to distribution or age at onset but also newly found high-risk haplotypes in Chinese vitiligo patients.

Adolescent↗
PubMed2006

An estrogen receptor alpha-dependent regulation of estrogen receptor-related receptor alpha in the proliferation of endometrial carcinoma cells.

Estrogen receptor-related receptor alpha (ERRalpha) was reported to compete with estrogen receptor alpha (ERalpha) in a constitutive manner as an orphan nuclear closely related to (ERalpha). To discuss the role of ERRalpha in the endometrial carcinoma cells, this study was performed. ER-responsive endometrial carcinoma cells Ishikawa and ER-nonresponse HEC-1A cells were treated with different concentration of 17beta-E2 or E2 plus ICI 182780. Semiquantitative reverse transcription-polymerase chain reaction and western blot were performed to analysis the expression of human estrogen receptor-related receptor alpha (hERRalpha). Plasmid PLXSN-hERRalpha was constructed and transfected into cells. Selected in the medium containing high-dose G418, the Ishikawa and HEC-1A cells with stable overexpression of hERRalpha were constructed and renamed as Ishikawa/hERRalpha and HEC-1A/hERRalpha, respectively. To discuss the effect of overexpression of hERRalpha in the cell biological behavior (3-[4,5-dimethylth-lazol-2yl]-2,5-diphenyltetrazolium bromid) (MTT) cell assay was performed. Estrogen downregulates ERRalpha expression in ER-positive Ishikawa cells, while upregulates the expression of ERRalpha in ER-negative HEC-1A cells. In Ishikawa cells, the downregulation of 17beta-E2 in ERRalpha expression cells could be blocked by ICI 182780. A decreasing expression of hERalpha was observed in the ER-responsive cells with overexpression of ERRalpha (Ishikawa/hERRalpha). Overexpression of hERRalpha inhibits the cell proliferation in the ERalpha-responsive Ishikawa cells and stimulated the cell proliferation in the ERalpha-nonresponsive HEC-1A cells. Function of hERRalpha depends on the expression and function of hERalpha. ER-mediated signaling might be the important factor resulting in the hormone-dependent endometrial carcinoma, whereas ERRalpha-mediated pathway might act as the vital role in hormone-independent endometrial carcinoma.

Blotting, Western↗
PubMed2005

Reliability of the AccuSens Taste Kit(c) in patients with eating disorders.

Zinc deficiency is a putative risk factor for anorexia nervosa (AN). Detecting zinc deficiency may therefore be important in treatment. However, serum zinc is not a good measure of total body zinc. An alternative test for zinc deficiency is taste testing because zinc deficiency is known to impair taste (dysgeusia). To determine whether taste testing could be used in this way, we measured the reliability of the only commercially available taste test in 16 patients with eating disorders. The results were analyzed graphically and with the kappa statistic (K). The taste test was found to be unreliable and should not be used to determine zinc status.

Adult↗
PubMed2005

Refined localization of a punctate palmoplantar keratoderma gene to a 5.06-cM region at 15q22.2-15q22.31.

BACKGROUND: Punctate palmoplantar keratoderma (PPK) is a rare autosomal dominant cutaneous disorder characterized by numerous hyperkeratotic papules distributed on the palms and soles. Two loci for punctate PPK were recently found to be located on 8q24.13-8q24.21 and 15q22-15q24. However, no genes for this disease have been identified to date. Objectives To refine the previously mapped regions and to identify the disease gene locus in a four-generation Chinese family with punctate PPK. METHODS: Genetic linkage analysis was carried out in this family using microsatellite markers on chromosomes 8q and 15q. Two-point linkage analysis was performed using Linkage programs version 5.10 and the haplotype was constructed using Cyrillic version 2.02 software. RESULTS: We failed to confirm our previous locus at 8q24.13-8q24.21, but significant evidence for linkage was observed in the region of 15q with a maximum two-point LOD score of 5.38 at D15S153 (theta = 0.00). Haplotype analysis localized the punctate PPK locus within the region defined by D15S651 and D15S988. This region overlaps by 5.06 cM with the previously reported punctate PPK region. CONCLUSIONS: This study refines a disease gene causing punctate PPK to a 5.06-cM interval at 15q22.2-15q22.31.

Adolescent↗
PubMed2005

Glass rod detectors for small field, stereotactic radiosurgery dosimetric audit.

This paper demonstrates the feasibility of using glass rod detectors for quality assurance audit of radiosurgery units. Five radiosurgery units (3 Gamma Knife model C, 1 Gamma Knife model U and 1 Cyberknife) located in California participated in the study. At each center glass rod detectors were used to measure a number of dosimetric parameters including relative collimator output factor and absolute dose rate. The Gamma Knife data obtained is in excellent agreement with the commissioning data generated by the manufacturer for each unit and the Cyberknife data is in general agreement with the data published by other centers. In particular the output factor of the 4 mm Gamma Knife helmet factor, a subject of abundant debate, was measured in the range 0.863-0.872 with an accuracy of better than 1% across the four participating centers. It is hoped that this pilot study will facilitate a nationwide postal audit of stereotactic radiosurgery units.

Calibration↗
PubMed2005

Comparison of nitrification performance and microbial community between submerged membrane bioreactor and conventional activated sludge system.

A submerged membrane bioreactor (SMBR) and a conventional activated sludge system (CAS) were compared in parallel over a period of more than 260 days on treating synthetic ammonia-bearing inorganic wastewater without sludge purge under decreased hydraulic retention times (HRTs). Conversion of NH4(+)-N to NO3(-)-N was achieved with an efficiency of over 98% at an HRT > or = 10 h in the SMBR, while similar performance was obtained at an HRT > or = 20 h in the CAS. Denaturing gradient gel electrophoresis (DGGE) of polymerase chain reaction (PCR) amplified 16S rDNA was used to monitor variations of community structures in the two systems. With the prolongation of operation, the number of DGGE bands in the SMBR gradually increased from the initial 11 bands to the final 22 bands, whereas that in the CAS varied in a range between 13 and 183 Sequence analysis indicates that Nitrosomonas sp. and Nitrospira sp. were the dominating nitrification species responsible for ammonia and nitrite oxidation, respectively. Heterotrophic bacteria like Pseudomonas sp. and Flavobacteria sp. existed in both of the systems although only inorganic wastewater was fed. Substantive accumulation of extracellular polymeric substances (EPS) in the SMBR was confirmed by scanning electron microscopy and EPS analysis.

Ammonia↗
PubMed2004

Coherent nano-area electron diffraction.

We describe the new coherent nano-area electron diffraction (NED) and its application for structure determination of individual nanostructures. The study is motivated by the challenge and the general lack of analytical techniques for characterizing nanometer-sized, heterogeneous phases. We show that by focusing electrons on the focal plane of the pre-objective lens using a 3rd condenser lens and a small condense aperture, it is possible to achieve a nanometer-sized highly parallel illumination or probe. The high angular resolution of diffraction pattern from the parallel illumination allows over-sampling and consequently the solution of phase problem based on the recently developed ab initio phase retrieval technique. From this, a high-contrast and high-resolution image can be reconstructed at resolution beyond the performance limit of the image-forming objective lens. The significance of NED for nanostructure characterization will be exemplified by single-wall carbon nanotubes and small metallic clusters. Imaging from diffraction patterns, or diffractive imaging, will be demonstrated using double-wall carbon nanotubes.

Computer Simulation↗
PubMed2004

Refined localization of dyschromatosis symmetrica hereditaria gene to a 9.4-cM region at 1q21-22 and a literature review of 136 cases reported in China.

BACKGROUND: Dyschromatosis symmetrica hereditaria (DSH) is an autosomal dominant pigmentary genodermatosis characterized by hyperpigmented and hypopigmented macules on the extremities, which has recently been mapped to an 11.6-cM interval on chromosome 1q11-21. So far, most cases of DSH have been reported in Japan and dermatologists around the world might think this disorder mainly occurs in Japan. In fact, there are 17 DSH families including 136 cases reported in China since 1980, but most of them are described in Chinese. OBJECTIVES: To refine the previously mapped region that facilitates the identification of the DSH gene and to delineate the clinical and genetic features of Chinese DSH cases by a literature review of 136 cases reported in China. METHODS: We performed genotyping and linkage analysis using polymorphic microsatellite markers at 1q11-22 in two Chinese DSH families, and reviewed all of the DSH cases reported in China since 1980. RESULTS: A cumulative maximum two-point lod score of 3.68 was produced with marker D1S506 at a recombination frequency of theta = 0.00 in these two families. Haplotype analysis refined the DSH locus to a 9.4-cM interval flanked by D1S2343 and D1S2635. The genetic and clinical features of Chinese cases with DSH were summarized. In some Chinese cases, hyperpigmented and hypopigmented macules were scattered on the neck and chest, but among Japanese patients there were no similar skin lesions to be reported on these sites. CONCLUSIONS: This study confirms linkage of DSH to a previously mapped region and refines the DSH gene to a 9.4-cM interval at 1q21-22. Likewise, the literature review indicates that DSH is not an uncommon disorder in China and the differences in the distribution of skin lesions could be related to race and environment.

Adult↗
PubMed2004

The genetic epidemiology of alopecia areata in China.

BACKGROUND: Alopecia areata (AA) is hypothesized to be an organ-specific autoimmune disease with genetic predisposition and an environmental trigger. There are few clinical data in Asians. OBJECTIVES: To describe the genetic epidemiological features of AA patients in China and to determine the possible genetic model for AA. METHODS: Data for 1032 patients with AA were obtained by questionnaire in the Institute of Dermatology of Anhui Medical University in China from 2001 to 2003. Complex segregation analysis and heritability analysis were performed using Falconer's method, EPI INFO 6.0 and SAGE-REGTL programs. RESULTS: In total, 1032 AA patients (male/female ratio 1.1 : 1) were enrolled, representing 0.94% of the total number of cases seen in our outpatient clinic during that time. The mean +/- SD age of onset was 28.98 +/- 13.43 years. The difference between the mean age of onset in males and females was not significant. Most patients (82.6%) experienced their first episode of AA within the first four decades of life. A positive family history of AA was obtained in 87 patients (8.4%). The prevalence of AA in first-, second- and third-degree relatives of the proband with AA was 1.6%, 0.19% and 0.03%, respectively. These figures were higher than those in controls. A greater severity and longer duration of AA were seen in the early onset group than in the late-onset group. The early onset group also had more affected first- and second-degree relatives. The heritability of AA in first-, second- and third-degree relatives was 47.16%, 42.53% and 22.29%, respectively. Based on the REGTL results, the best model was a polygenic additive model for AA. CONCLUSIONS: The effect of genetic factors is strong in AA, but environmental factors such as infection and psychological stress may still play an important role. Our findings on the genetics of AA are consistent with a polygenic additive mode of inheritance.

Adolescent↗
PubMed2004

Haplotype associations of the MHC with psoriasis vulgaris in Chinese Hans.

Summary Haplotype associations of the major histocompatibility complex (MHC) with psoriasis vulgaris (PV) have been demonstrated in different racial or ethnic populations. The objective of this study was to demonstrate the different haplotype associations of the MHC in Chinese patients with psoriasis according to the type of onset and their sex. One hundred and thirty-eight patients with PV and 149 normal control subjects without psoriasis were typed for HLA-A, -B, -C, -DQA1, -DQB1 and -DRB1 by using the PCR with sequence-specific primers. The results showed: (i) HLA-A*26 (26.1% vs. 12.1%, Pc < 1 x 10(-5)), -B*27 (17.03% vs. 1.01%, Pc < 1 x 10(-7)), -Cw*0602 (15.58% vs. 5.03%, Pc < 1 x 10(-2)), -DQA1*0104 (19.93% vs. 9.40%, Pc < 1 x 10(-3)), -DQA1*0201 (22.40% vs. 10.74%, Pc < 1 x 10(-3)), -DQB1*0303 (18.12% vs. 9.73%, Pc < 1 x 10(-7)), and -DRB1*0701/02 (26.09% vs. 9.73%, Pc < 1 x 10(-7)) were significantly increased in PV patients, while HLA-B*57, -DQB1*0201 were slightly increased in PV patients. HLA-Cw*0304 (5.07% vs. 14.43%, Pc < 1 x 10(-3)), -DQA1*0501 (5.79% vs. 14.09%, Pc < 0.05) were found to be negatively associated with PV, but HLA-A*2 (2.54% vs. 6.38%, Pc < 0.5) was decreased in PV patients without statistical significance. (ii) HLA-A*26-B*27 [P < 0.0001, odds ratio (OR) = 48.38], -A*26-Cw*0602 (P < 0.0001, OR = 11.84), -B*27-Cw*0602 (P < 0.0001, OR = undefined), -DRB1*0701/02-B*27 (P < 0.0001, OR = 22.62), -DRB1*0701/02-DQA1*0104 (P < 0.0002, OR = 3.59), -DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 5.63), -DQA1*0201-DQB1*0303 (P < 0.0002, OR = 7.77), -A*26-B*27-Cw*0602 (P < 0.0004, OR = undefined), -A*26-DRB1*0701/02-DQA1*0201-DQB1*0303 (P < 0.01, OR = undefined) were identified as risk haplotypes for patients with PV in China. (iii) HLA-A*26 -B*27 (P < 0.0001, OR = 58.47), -DQA1*0201-DQB1*0303 (P < 0.0001, OR = 8.62), -DRB1*0701/02 -DQA1*0104 (P < 0.0002, OR = 4.13), -DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 6.68) and -A*26-DRB1*0701-DQA1*0201 -DQB1*0303 (P < 0.006, OR = undefined) were only significantly associated with type I psoriasis compared with controls, while others showed no differences in either type I or type II psoriasis. (iv) These associated haplotypes with PV were not different by sex, except that the frequency of DRB1*0701/02-DQB1*0303 (P < 0.0001, OR = 10.14) was higher in male patients with psoriasis. To summarize, this study demonstrated a differential association of HLA and identified some special risk haplotypes in Chinese patients with PV compared with other ethnic or racial populations.

Adolescent↗
PubMed2004

A novel mutation of the DSRAD gene in a Chinese family with dyschromatosis symmetrica hereditaria.

Dyschromatosis symmetrica hereditaria (DSH) is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal aspects of the hands and feet. It is caused by mutations of the RNA-specific adenosine deaminase gene. We report the identification of a Chinese family with a three-generation pedigree of DSH, in whom a novel tyrosine substitution mutation in DSRAD was demonstrated: a heterozygous nucleotide A-->G transition at position 2879 in exon 10 of the DSRAD gene was detected.

Adenosine Deaminase↗
PubMed2004

Marie Unna hereditary hypotrichosis: report of a Chinese family and evidence for genetic heterogeneity.

Marie Unna hereditary hypotrichosis (MUHH) is a rare autosomal dominant disorder with progressive hair loss starting in early childhood and aggravating at puberty. Several studies have mapped the MUHH gene to chromosome 8p21. Here we report a Chinese MUHH family with variable phenotypes. All affected individuals have anomalies affecting both hair density and hair shafts. Major clinical characteristics, disease history and histological examination support the diagnosis of MUHH, but the features of scarring in this kindred are modest and none of the patients have vertex hair loss, which is in contrast with typical MUHH. We now report genotyping and linkage analysis using 11 polymorphic microsatellite markers spanning the MUHH locus at 8p. Two-point linkage analysis using these markers revealed significant exclusion of this locus (log of the odds scores < - 2) at Theta = 0 indicating that there is a range of clinical presentations in MUHH, and that more than one genetic locus is responsible for the disorder.

Adult↗
PubMed2004

Heterogeneity of narrowing in normal and asthmatic airways measured by HRCT.

Asthmatic airway narrowing is heterogeneous and contributes to airway hyperresponsiveness. The present study compared heterogeneity of narrowing during methacholine challenge in asthmatics and normal subjects using high-resolution computed tomography (HRCT). The current authors defined heterogeneity as variability in narrowing greater than the repeatability of measurement. Airways of <2 mm diameter were compared with larger airways from baseline and postmethacholine HRCT of the right lower lung in 13 normals (seven had repeat baseline scans) and seven asthmatics. The coefficient of repeatability was calculated from repeat scans (RepAi) and was compared with heterogeneity of narrowing measured by the variability in narrowing from pre versus postmethacholine scans (VardeltaAi). Forced expiratory volume in one second decreased 27+/-6% and 24+/-8% in normals and asthmatics, respectively. Airways >2 mm narrowed more heterogeneously in asthmatics (VardeltaAi=+/-0.85 mm) compared with normals (VardeltaAi=+/-0.67 mm), with both being greater than the measure of repeatability (RepAi=+/-0.16 mm). Small airway narrowing was not heterogeneous in asthmatics (VardeltaAi=+/-0.59 mm) or normals (VardeltaAi=+/-0.53 mm) compared with repeatability (RepAi=0.51 mm). It is possible to study heterogeneity of airway narrowing in small and large airways using high resolution computed tomography. Airway narrowing is heterogeneous in the large airways of asthmatics and normals, being greater in asthmatics.

Adult↗