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Biomedical subjects

Min Gao

Publications and source records attributed to Min Gao.

86 records · Page 5Linked to original sources
PubMed2003

Role of BRCA1 in heat shock response.

The heat shock response is an evolutionarily conserved response to heat and other stresses that promotes the maintenance of key metabolic functions and cell survival. We report that exposure of human prostate (DU-145) and breast (MCF-7) cancer cells to heat (42 degrees C) caused a rapid disappearance of the breast cancer susceptibility gene-1 (BRCA1) protein, starting at approximately 1 h after the onset of heating and slightly lagging behind the increase in heat shock protein 70 (HSP70) levels. The heat-induced loss of BRCA1 occurred at the protein level, since: (1) BRCA1 mRNA expression was unaffected; and (2) the BRCA1 protein loss was also observed in DU-145 cells that expressed exogenous wild-type BRCA1 (wtBRCA1). In addition to heat regulation of BRCA1 protein levels, we also found that BRCA1 could modulate the heat shock response. Thus, wtBRCA1 overexpressing DU-145 cell clones showed significantly decreased sensitivity to heat-induced cytotoxicity; and Brca1 mutant mouse embryo fibroblasts showed increased sensitivity to heat. The DU-145 wtBRCA1 clones also showed increased expression of the small heat shock protein HSP27; and reporter assays revealed that wtBRCA1 stimulated a two to four-fold increase in HSP27 promoter activity, consistent with its ability to upregulate HSP27 mRNA and protein levels. In studies using epitope-tagged truncated BRCA1 proteins, the ability to stimulate the HSP27 promoter and to mediate heat-induced degradation required the amino-terminus but not the carboxyl-terminus of BRCA1. Although the heat-induced loss of BRCA1 appeared to be due to protein degradation, various protein metabolic agents (or combinations) failed to block this event, including: MG132 (a 26S proteasomal inhibitor), N-acetyl-leucyl-leucyl-norleucinal (a calpain inhibitor), z-VAD-fmk (a pan-caspase inhibitor), and ammonium chloride and chloroquine (which stabilize lysosomes). These findings suggest that in addition to its other functions, BRCA1 may participate in mammalian heat shock response pathways.

BRCA1 Protein↗
PubMed2003

Association of HLA class I alleles with psoriasis vulgaris in southeastern Chinese Hans.

BACKGROUND: Predisposing genetic factors in psoriasis include associations with human leukocyte antigen (HLA). Accumulative evidence has shown that certain HLA at class I locus, especially HLA-Cw6, are associated closely with psoriasis. OBJECTIVE: To evaluate the association of HLA class I alleles with susceptibility to psoriasis in the southeastern Chinese Han population. METHODS: We performed genotype for HLA-A, -B and -C loci in 166 patients with psoriasis vulgaris by means of polymerase chain reaction with sequence-specific primers technique. The distribution of HLA allelic frequencies was further analyzed according to age of onset, i.e. under 35-y and beyond 35-y groups. These data were compared with the healthy controls of 204 unrelated Hans. RESULTS: The frequencies of HLA-A*26 (24.7% vs. 13.1%, OR=2.36, Pc<0.01), -B*13 (27.2% vs. 14.8%, OR=2.34, Pc<0.01), -B*27 (12.2% vs. 4.0%, OR=3.49, Pc<0.01) and -Cw*0602 (17.9% vs. 5.3%, OR=4.20, Pc<0.001) were significantly increased in psoriasis patients, whereas HLA-Cw*0304 frequency (4.9% vs. 13.4%, OR=0.32, Pc<0.01) was highly decreased, when compared to the controls. HLA-A*26-B*27-Cw*0602 was identified as a high-risk haplotype of HLA class I in developing psoriasis in the test. HLA-Cw*0602 was found to be strongly associated with the early-onset psoriasis (age of onset <35 y). CONCLUSION: This study demonstrated the positive associations of HLA class I markers with psoriasis vulgaris, of which HLA-Cw*0602 was the strongest susceptibility determinant for development of early-onset psoriasis, in the southeastern Chinese Han population.

Adult↗
PubMed2003

Identification of a locus for dyschromatosis symmetrica hereditaria at chromosome 1q11-1q21.

Dyschromatosis symmetrica hereditaria is a rare autosomal dominant cutaneous disorder characterized by a mixture of hyperpigmented and hypopigmented macules of various sizes on the face and the dorsal aspects of the extremities. The genetic basis for this disease is unknown. We performed a genome-wide search in two large Chinese families to map the chromosome location of the responsible gene. We identified a locus at chromosome 1q11-1q21 with a cumulative maximum two-point LOD score of 8.85 at marker D1S2343 (at recombination fraction=0.00). Haplotype analyses indicated that the disease gene is located within the 11.6 cM region between markers D1S2696 and D1S2635. This is the first locus identified for dyschromatosis symmetrica hereditaria. This study provides a map location for isolation of a disease gene causing dyschromatosis symmetrica hereditaria.

China↗
PubMed2003

In vitro anticancer activities of Leonurus heterophyllus sweet (Chinese motherwort herb).

OBJECTIVES: To investigate the anticancer activities of Chinese motherwort herb (Leonurus heterophyllus Sweet; LHS). DESIGN: Dried LHS was extracted and reconstituted in phosphate-buffered saline. The in vitro antiproliferation activities of the extract were tested against seven human cancer cell lines. The DNA ladder assay and cell morphologic studies were performed to verify the drug's apoptotic activities. The possible pathway by which LHS induced apoptosis was also explored by examining mitochondrial depolarization, cytochrome c release, and caspase-3 activation. RESULTS: The LHS extract was effective in inhibiting the growth of all seven cancer cell lines tested. The IC(50) (50% inhibition concentrations, milligrams of raw material per milliliter) were in the range of 8.0-40.0 when the drug exposure time was 48 hours. The inhibitory action of the herbal extract was time- and dose-dependent. A significant decrease in activity was seen when the drug exposure time was shortened. Microscopic examination of the LN CaP and other cancer cell lines after treatment with LHS revealed morphologic changes that are typical of cells undergoing apoptosis. DNA fragmentation was obvious in the DNA latter assay and this confirmed the induction of apoptosis of the cancer cells by LHS. The mitochondria of the LHS-treated cells were found to undergo depolarization. Cytochrome c was released into the cytosol from the LHS-treated cells but not from the control cells. Cells treated with LHS showed cleavage of the full-length poly[ADP(ribose)] polymerase (PARP; 112 kd) to generate the 85-kd cleaved PARP fragment indicating the activation of caspase-3. CONCLUSIONS: LHS was able to induce apoptosis of all the tumor cell lines tested. The antiproliferation effect was dose- and time-dependent. The mitochondrion was found to be involved in the apoptosis induced by the LHS extract.

Antineoplastic Agents, Phytogenic↗
PubMed2003

Specific inhibition of bovine viral diarrhea virus replicase.

Compound-1453 was identified and characterized as a specific inhibitor of bovine viral diarrhea virus (BVDV). The concentration of compound-1453 which results in 50% protection from virus-induced cytopathic effect is approximately 2.2 microM, with a therapeutic index of 60, and it is not active against a panel of RNA and DNA viruses. A time-of-addition experiment suggested that compound-1453 targets a stage of the viral life cycle after viral entry. To determine the target of compound-1453, resistant virus was generated. Resistant variants grew efficiently in the presence or absence of 33 micro M compound-1453 and exhibited replication efficiency in the presence of compound-1453 approximately 1,000-fold higher than that of the wild-type (wt) virus. Functional mapping and sequence analysis of resistant cDNAs revealed a single amino acid substitution (Glu to Gly) at residue 291 in the NS5B polymerase in all eight independently generated cDNA clones. Recombinant virus containing this single mutation retained the resistance phenotype and a replication efficiency similar to that of the original isolated resistant virus. Since compound-1453 did not inhibit BVDV polymerase activity in vitro (50% inhibitory concentration > 300 microM), we developed a membrane-based assay that consisted of a BVDV RNA replicase complex isolated from virus-infected cells. Compound-1453 inhibited the activity of the wt, but not the drug-resistant, replicase in the membrane assay at concentrations similar to those observed in the viral infection assay. This work presents a novel inhibitor of a viral RNA-dependent RNA replicase.

Amino Acid Sequence↗
PubMed2002

The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements.

HeLa cytoplasmic extracts contain both 3'-5' and 5'-3' exonuclease activities that may play important roles in mRNA decay. Using an in vitro RNA deadenylation/decay assay, mRNA decay intermediates were trapped using phosphothioate-modified RNAs. These data indicate that 3'-5' exonucleolytic decay is the major pathway of RNA degradation following deadenylation in HeLa cytoplasmic extracts. Immunodepletion using antibodies specific for the exosomal protein PM-Scl75 demonstrated that the human exosome complex is required for efficient 3'-5' exonucleolytic decay. Furthermore, 3'-5' exonucleolytic decay was stimulated dramatically by AU-rich instability elements (AREs), implicating a role for the exosome in the regulation of mRNA turnover. Finally, PM-Scl75 protein was found to interact specifically with AREs. These data suggest that the interaction between the exosome and AREs plays a key role in regulating the efficiency of ARE-containing mRNA turnover.

Base Composition↗
PubMed2002

[Virtual colonoscopy in diagnosis of colorectal neoplasia]

OBJECTIVE: To evaluate the value of virtual colonoscopy in diagnosis of colorectal neoplasia. METHODS: Virtual colonoscopy was performed in 29 patients with colorectal neoplasia confirmed by colonoscopy. The results were compared with colonoscopy for each case. RESULTS: Virtual colonoscopy was successfully performed in each patient without any complications. All colorectal carcinomas detected by colonoscopy were identified by virtual colonoscopy. Twenty-five polyps were detected with colonoscopy, whereas only 16 identified by virtual colonoscopy. Compared with the results of colonoscopy, detection rate of polyps greater than 1.0 cm between 0.5 approximate, equals 0.9 cm and less than 0.5 cm in size was 90.0% 62.5% and 28.6% respectively. CONCLUSION: Virtual colonoscopy is fast, minimal invasive and well tolerated. This technique is a valuable clinical method in diagnosis of colorectal cancer and polyps larger than 0.5 cm in size.

Journal Article↗
PubMed2002

[Study of the association between HLA-DQA1 alleles and environmental factors in psoriasis].

OBJECTIVE: To study of the HLA-DQA(1) alleles and environment interaction in type I psoriasis. METHODS: Using case-control study, 144 type I psoriatics and 273 healthy people were investigated. The HLA-DQA(1) alleles were examined by PCR-SSP. RESULTS: (1) HLA-DQA(1)*0104 and DQA(1)*0201 alleles were positively associated with type I psoriasis (P(c) < 0.002); HLA-DQA(1)*0501 allele was negatively associated with type I psoriasis (P(c) < 0.000 5). (2) The HLA-DQA(1)*0104 allele and moisture was interaction in type I psoriasis (P = 0.023 8, OR = 5.29). (3) There were no interactions between the HLA-DQA(1)*0201 allele and 10 environmental factors in type I psoriasis. (4) The HLA-DQA(1)*0501 allele, moisture (P = 0.002 4, OR = 7.50), eating fish and shrimp (P = 0.000 4, OR = 12.92), drugs (P = 0.043 3, OR = 9.43) or vaccination (P = 0.043 3, OR = 9.43) were interacted in type I psoriasis. CONCLUSIONS: (1) HLA-DQA(1)*0104 and DQA(1)*0201 alleles might be the susceptible genes or it may have close linkage with the susceptible gene. HLA-DQA(1)*0501 allele had protective effect against the development of type I psoriasis. (2) The HLA-DQA(1)*0104 and DQA(1)*0501 alleles increased risk possibility of environmental factors in type I psoriasis.

Adolescent↗
PubMed2002

[Synthesis and characterization of a time-resolved fluorescence analysis chelate reagent-BCPDA].

In this paper, we report on a solid phase time-resolved fluorescence immunoassay chelate reagent-4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid (BCPDA), which is suitable as a fluorescent labeling agent. The five step synthesis product of BCPDA was presented for improving the purity of the product based on the three step synthesis product. The approach involves chlorization, hydrolyzing the ester, preparing disodium, carboxylate to diacid, sulfonation. The yield of five step product is 99%, 45%, 94%, 95%, 80% respectively. The structure and purity of product was characterized by the melting point, IR, 1H NMR, UV spectrum, element analysis, and proved to be consistent with the structure predictal.

Chelating Agents↗
PubMedDate not supplied

The challenge of defining normality for human mitral and aortic valves: geometrical and compositional analysis.

Advances in digital imaging technology and in tools for obtaining detailed quantitation of morphological features have facilitated a new approach to pathological assessment of many tissues, including heart valves. In the present study, we quantitatively examined the tissue geometry and composition of structurally normal mitral and aortic valves removed at autopsy or surgery from patients aged 15-84 years. Through univariate analyses of quantitative variables, we have determined which features change distinctively with age. The anterior mitral valve leaflet (AMV) underwent a statistically significant decrease in area of the valve proper and an increase in the number of superficial tissue accumulations called onlays as the patients aged. For all geometric variables measured in the aortic valve, increases were seen with age, leading to a thicker valve, with enlargement of the valve proper and onlays, and with changes in the number of onlays. The mitral valve proper, composed largely of collagen in younger individuals, showed significant increases in glycosaminoglycans and elastin and a relative decrease in collagen with age. The compositional characteristics of the aortic valve proper were similar to those of the mitral valve, with a dramatic relative increase in elastin and a decrease in collagen with age. Valve onlays, when present, were similar in composition to the valve proper for both valves. Our findings regarding normal valve tissue composition, when taken in the context of geometrical features, and together with evidence of age-related changes in the relative amounts of specific constituents, provide a basis on which to analyze human heart valves affected by various known or putative diseases.

Adolescent↗
PubMedDate not supplied

Quantitative analysis of human heart valves: does anorexigen exposure produce a distinctive morphological lesion?

The need for more detail regarding the clinical and morphological features of human heart valves has become evident due to recent controversy regarding anorexigen-associated valvular dysfunction. In the present study, we used quantitative digital image analysis of geometric and compositional features to compare the histopathology of cardiac valves excised from patients treated with anorexigens as compared to normal, floppy, rheumatic and carcinoid valves. Anorexigen-exposed valves had the greatest number of onlays/valve (P<.0001), while rheumatic valves showed the greatest average onlay size and thickness of the comparison groups studied (P=.01). The valve onlays from anorexigen-exposed, carcinoid and floppy valves contained a greater percentage of glycosaminoglycans (GAGs) as compared to normal and rheumatic valves (P=.01). The anorexigen-exposed valve propers contained more GAGs than any other comparison group (P=.02). Vessels were prominent in both onlay and valve proper regions of carcinoid valves, in the anorexigen-exposed valve onlays and in rheumatic valve propers. Thus, the number of onlays, their size, the degree of GAG deposition, and the presence and location of vessels and leukocytes were important features distinguishing anorexigen-exposed valves from normal valves. Discriminant analyses, based on geometry, color composition or color composition, and vessel and leukocyte counts combined, were able to separate the valves into distinguishable groups. Our findings demonstrate that specific microscopic features can be used to separate anorexigen-associated heart valve lesions from normal valves and valve lesions associated with other pathologies, and suggest that a distinctive pathological process may exist in many anorexigen-exposed valves.

Adolescent↗
PubMedDate not supplied

The epidemiology of childhood alopecia areata in China: a study of 226 patients.

To study the clinical and epidemiologic profile of childhood alopecia areata, we performed a survey in which a total of 226 childhood patients less than 16 years old were enrolled. Statistical analysis and heritability were performed using EPI INFO 6.0, SPSS10.0, and the Falconer method. The median age of onset was 10 years. The majority of patients (84.96%) presented with limited alopecia. The male : female ratio was 1.4:1. Boys appeared to have more severe involvement. The earlier the age of onset, the greater the severity of the disease. Sixty-seven patients (29.65%) had previous episodes of alopecia areata. Greater severity and longer duration were seen in the relapsing patients than in the primary patients. Six patients (2.65%) had an associated disease. A positive family history was reported in 25 patients (11.06%). The prevalence figures for alopecia areata in first-, second-, and third-degree relatives of the probands were 2.87%, 0.40%, and 0.13%, respectively. The heritabilities of AA in first-, second-, and third-degree relatives were 51.20%, 46.25%, and 25.65%, respectively. It can be speculated that the effect of genetic factors is important in the occurrence of this disease.

Adolescent↗
PubMedDate not supplied

Aortic arch reconstruction: safety of moderate hypothermia and antegrade cerebral perfusion during systemic circulatory arrest.

BACKGROUND AND AIM: The ideal strategy for cerebral protection during aortic arch (AA) reconstructive surgery remains undefined. Antegrade cerebral perfusion (ACP) during systemic circulatory arrest (SCA) may provide superior results; however, optimal systemic temperature is undetermined. Our objective was to determine whether "deep" hypothermia is necessary during ACP with SCA, and whether the degree of hypothermia is associated with neurologic outcomes postoperatively. METHODS: Retrospective series of 72 consecutive patients (aged 65.9 +/- 3.2 years) who underwent AA reconstructive surgery at Vancouver General Hospital using a cerebral protection strategy of ACP with SCA between December 1995 and December 2002. Patients were divided into two groups according to lowest systemic temperature: <22 degrees C (n = 52) and > or =22 degrees C (n = 20). RESULTS: ACP was via right axillary or innominate artery, +/- left common carotid cannulation. Median SCA time with ACP was not different between groups. There were four hospital deaths (5.6%) (three from the <22 degrees C group). Eight patients (11.2%) had major neurologic injuries (seven from the <22 degrees C group): 4 (5.6%) permanent (1 fatal) and 4 (5.6%) temporary. There was a trend toward a significantly higher incidence of delirium in the <22 degrees C group than the > or =22 degrees C group (30.8 vs 10.0%, respectively, p = 0.07). CONCLUSIONS: In our experience, SCA with ACP was a safe technique for AA reconstructive surgery. The observation of a larger number of major neurologic injuries, and a trend toward a higher incidence of delirium in the <22 degrees C group, suggests that systemic temperatures below 22 degrees C may not be necessary and may be associated with a higher incidence of neurologic injury when using ACP during SCA.

Aged↗