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Biomedical subjects

M Sun

Publications and source records attributed to M Sun.

At least 91 records · Page 5Linked to original sources
PubMed2000

The forward EEG solutions can be computed using artificial neural networks.

Study of electroencenphalography (EEG) is the one of the most utilized methods in both basic brain research and clinical diagnosis of neurological disorders. Recent technological advances in computer and electronic systems have allowed the EEG to be recorded from large electrode arrays. Modeling the brain waves using a head volume conductor model provides an effective method to localize functional generators within the brain. However, the forward solutions to this model, which represent theoretical potentials in response to current sources within the volume conductor, are difficult to compute because of time-consuming numerical procedures utilized in either the boundary element method (BEM) or the finite element method (FEM). This paper presents a novel computational approach using an artificial neural network (ANN) to map two vectors of forward solutions. These two vectors correspond to different head models but with respect to the same current source. The input vector to the ANN is based on the spherical head model, which can be computed efficiently but involves large errors. The output vector from the ANN is based on the spheroidal model, which is more precise, but difficult to compute directly using the traditional means. Our experiments indicate that this ANN approach provides a remarkable improvement over the BEM and FEM methods: 1) the mean-square error of computation was only approximately 0.3% compared to the exact solution; 2) the online computation was extremely efficient, requiring only 168 floating point operations per channel to compute the forward solution, and 10.2 K-bytes of storage to represent the entire ANN. Using this approach it is possible to perform real-time EEG modeling accurately on personal computers.

Biomedical Engineering↗
PubMed2000

Mechanism of action of camptothecin.

Camptothecin (CPT) class of compounds has been demonstrated to be effective against a broad spectrum of tumors. Their molecular target has been firmly established to be human DNA topoisomerase I (topo I). CPT inhibits topo I by blocking the rejoining step of the cleavage/religation reaction of topo-I, resulting in accumulation of a covalent reaction intermediate, the cleavable complex. The primary mechanism of cell killing by CPT is S-phase-specific killing through potentially lethal collisions between advancing replication forks and topo-I cleavable complexes. Collisions with the transcription machinery have also been shown to trigger the formation of long-lived covalent topo-I DNA complexes, which contribute to CPT cytotoxicity. Two novel repair responses to topo-I-mediated DNA damage involving covalent modifications of topo-I have been discovered. The first involves activation of the ubiquitin/26S proteasome pathway, leading to degradation of topo-I (CPT-induced topo-I downregulation). The second involves SUMO conjugation to topo-I. The potentials roles of these new mechanisms for repair of topo-I-mediated DNA damage in determining CPT sensitivity/resistance in tumor cells are discussed.

Animals↗
PubMed2000

Cytochrome P4501A1-inhibitory action of antimutagenic anthraquinones in medicinal plants and the structure-activity relationship.

We have earlier found that flavones and flavonols in vegetables specifically inhibited one of the carcinogenesis-related enzymes, cytochrome P450 (CYP) 1A1, and subsequently suppressed the mutagenicity of food-derived carcinogens. In this study, we explored other candidates for the enzyme inhibitor in Chinese medicinal plants. Some of them were antimutagenic toward 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2). For example, Rheum officinale contained large amounts of anthraquinones as the active compounds, 3.4 mg of emodin, 2.1 mg of chrysophanol and 1.8 mg of rhein in 10 g of dry matter. Anthraquinones showed similar IC50 values for antimutagenicity against Trp-P-2 to those for inhibition of the N-hydroxylation activity of CYP1A1 toward Trp-P-2, indicating that the antimutagenicity was attributable to CYP inhibition. The structure-activity relationships were then examined with 14 commercial chemicals, and it was found that the interaction with an enzyme required three rings and an oxygen group in the side ring. This characteristic is similar to that of flavones and flavonols.

Anthraquinones↗
PubMed2000

Dietary antioxidants fail in protection against oxidative genetic damage in in vitro evaluation.

Carcinogenesis is believed to be induced through the oxidative damage of DNA, and antioxidants are expected to suppress it. So, the polyphenolic antioxidants in daily foods were investigated to see whether they protect against genetic damage by active oxygen. In the evaluation, we used a bioassay and a chemical determination, a Salmonella mutagenicity test for mutation by a N-hydroxyl radical from one of the dietary carcinogens 3-amino-1-methyl-5H-pyrido[4,3-b]indole and the formation of 8-hydroxyl (8-OHdG) from 2'-deoxyguanosine (2'-dG) in a Fenton OH-radical generating system. Thirty-one antioxidants including flavonoids were compared in terms of radical-trapping activity with bacterial DNA and 2'-dG. Antioxidants inhibited the mutation but the IC50 values were in the mM order. Against 8-OHdG formation, only alpha-tocopherol had a suppressive effect with an IC50 of 1.5 microM. Thus, except alpha-tocopherol, the dietary antioxidants did not scavenge the biological radicals faster than bacterial DNA and intact 2'-dG, indicating that they failed to prevent oxidative gene damage and probably carcinogenesis.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2000

Aerobic fitness, not energy expenditure, influences subsequent increase in adiposity in black and white children.

BACKGROUND: Low levels of energy expenditure and aerobic fitness have been hypothesized to be risk factors for obesity. Longitudinal studies to determine whether energy expenditure influences weight gain in whites have provided conflicting results. To date, no studies have examined this relationship in blacks or whether aerobic fitness influences weight gain in white or black children. METHODS: One hundred fifteen children, 72 white (55 girls and 17 boys) and 43 black (24 girls and 19 boys) were recruited for this study. Aerobic fitness, resting, total, and activity-related energy expenditure and body composition were measured at baseline. The children returned annually for 3 to 5 repeated measures of body composition. The influence of the initial measures of energy expenditure and fitness on the subsequent rate of increase in adiposity was examined, adjusting for initial body composition, age, ethnicity, gender, and Tanner stage. Because 20 children did not attain maximum oxygen consumption, the sample size for the combined analysis was 95. RESULTS: Initial fat mass was the main predictor of increasing adiposity in this cohort of children, with greater initial fat predicting a higher rate of increase of adiposity. There was also a significant negative relationship between aerobic fitness and the rate of increasing adiposity (F(1,82) = 3.92). With every increase of.1 L/minute of fitness, there was a decrease of.081 kg fat per kg of lean mass gained. None of the measures of energy expenditure significantly predicted increasing adiposity in white or black children. CONCLUSIONS: Initial fat mass was the dominant factor influencing increasing adiposity; however, aerobic fitness was also a significant independent predictor of increasing adiposity in this cohort of children. Resting, total, or activity-related energy expenditure did not predict increasing adiposity. It seems that aerobic fitness may be more important than absolute energy expenditure in the development of obesity in white or black children. energy expenditure, fitness, longitudinal, obesity.

Adipose Tissue↗
PubMed2000

Localization of prostaglandin synthase type-1 (PGHS-1) mRNA and prostaglandin synthase type-2 (PGHS-2) mRNA in ovine myometrium and endometrium throughout gestation.

Increased prostaglandin production by tissues in the sheep uterus and placenta are thought to be important for the onset of parturition. In the sheep placenta, this is most likely due to increased expression of prostaglandin synthase type-2 (PGHS-2) rather than prostaglandin synthase type-1 (PGHS-1). However, there is no information concerning expression of PGHS isoenzymes in maternal uterine tissues during pregnancy. Therefore, the purpose of the present study was to examine the expression of PGHS-1 and PGHS-2 in the sheep myometrium and endometrium during late gestation using in situ hybridization and immunohistochemistry. Using (35)S-labelled oligonucleotide probes, which give specific hybridization signals in other tissues, we localized PGHS-2 mRNA to endometrial epithelium, and apparently to other cells in both endometrium and myometrium. This artefactual signal was still present with 100-fold excess unlabelled oligonucleotide probe and with sense probes, but was resolved with the use of (33)P-oligonucleotides. Using (33)P-labelled oligonucleotide probes we could not detect either PGHS-1 or PGHS-2 mRNA in myometrium, and found expression only of PGHS-2 mRNA in endometrium. PGHS-2 mRNA localized to the endometrial epithelium and was undetectable in glandular epithelium. The level of PGHS-2 expression rose significantly between days 80 and 85 of pregnancy and term, and this corresponded to the appearance of immunoreactive PGHS-2 protein, measured by immunohistochemistry, in the endometrial epithelium. Therefore we conclude that (33)P-labelled probes are preferred for detection of mRNAs encoding PGHS-2 in ovine uterine tissues. Expression of PGHS-2 mRNA is greater than that of PGHS-1, increases during gestation, and predominates in the endometrial epithelium, consistent with the site of PGHS-2 protein localization.

Animals↗
PubMed2000

Molecular profiling of sporadic colorectal tumors by microsatellite analysis.

To investigate the prognostic value of multiple genetic alterations, individual molecular tumor profiles were established in 79 sporadic colorectal carcinomas (41 stage II and 38 stage III). Tumors were analyzed for allelic loss (LOH) and genetic instability (MSI) using 14 microsatellites intragenic to or associated with tumor suppressor or DNA mismatch repair genes. Molecular profiling identified tumors with LOH at multiple loci without microsatellite instability (MSS), tumors with high levels of LOH and low level microsatellite marker instability (MSI-L), and tumors with high levels of MSI (MSI-H), but rare LOH. K-ras mutations occurred more frequently in MSS/MSI-L carcinomas (26%) than in MSI-H colorectal tumors (10%), the latter showing a high frequency of TGFbeta type II frameshift mutations (82%). Correlation of molecular and clinical data revealed a better prognosis for stage III tumor patients displaying 5q12 loss rather than retention of heterozygosity. Thus, molecular profiling allows the identification of new prognostic markers and might facilitate the stratification of colorectal cancer patients.

Adult↗
PubMed2000

[Computer modeling and experimental research of interactions between two anti-hTNF alpha monoclonal antibody variable regions and hTNF alpha].

On SGI workstation, we constructed two anti-hTNF alpha McAbs by means of homologous protein-structure-prediction method. And then, on the basis of relative experimental results and the surface properties of hTNF alpha and two McAbs, we performed the docking of hTNF alpha into two anti-hTNF alpha McAbs. In order to confirm the models, we prepared two hTNF alpha mutants designed according to the binding models, analysed and predicted the possible changes in complexes resulted from hTNF alpha mutations. The experimental analysis results proved these complex models. This will make the base of our next antibody humanization and/or reshape work.

Antibodies, Monoclonal↗
PubMed2000

[Cloning of plasmid pBMB2062 in Bacillus thuringiensis strain YBT-1520 and construction of plasmid vector with genetic stability].

A small plasmid pBMB2062 in Bacillus thuringiensis strain YBT-1520 was cloned and sequenced. Its 2,062 bp sequence contains two potential open reading frames (orfs). The orf1 and orf2 encode a tentative replication initial protein consisting of 289 amino acid residues and a tentative replication protein consisting of 80 amino acid residues, respectively. Two homological plasmids were found by Blast searching. There are 23 nucleotides difference occurring among three of the plasmids. The difference occurred in the orf1 causes different encoding capability. Comparing with the orf1 in pBMB2062, the orf1 in the homological plasmids are truncated, one at the N-terminal and another at the C-terminal. cDNA synthesis and PCR detection showed that the mRNA corresponding to orf1 in pBMB2062 really occurs. Shuttle vectors were constructed based on pBMB2062 and showed the ability to express insecticidal crystal gene. Under nonselective condition, recombinant plasmids based on pBMB2062 were genetically stable.

Amino Acid Sequence↗
PubMed2000

Modest increases in the titers of helper virus-free herpes simplex virus 1 (HSV-1) vectors by packaging in a cell line with inducible expression of HSV-1 VP16 or by treatment with N,N'-hexamethylene-bis-acetamide.

A recently developed helper virus-free HSV-1 vector system has potential for both gene therapy and physiological studies, but relatively low vector titers have complicated use of this system. In this report, we explored improving the vector titers by isolating a Vero cell line that uses the tetracycline-regulated promoter system to induce HSV-1 VP16 at the beginning of the packaging procedure. We isolated the required cell line and demonstrated that it supports enhanced expression from a HSV-1 immediate early (IE) promoter. However, use of this cell line in helper virus-free vector packaging results in only a modest, approximately 2-fold increase in the vector titers. Additionally, treating the packaging cells with N,N'-hexamethylene-bis-acetamide (HMBA), which is known to induce HSV-1 IE promoters, also supports only modest increases in the vector titers. These results suggest that the lack of VP16 is not the rate limiting factor in the packaging procedure.

Acetamides↗
PubMed2000

[Characterization of the insecticidal crystal protein genes of Bacillus thuringiensis YBT-1520].

The insecticidal crystal protein genes of highly toxic Bacillus thuringiensis YBT-1520 were analyzed. Southern hybridization and PCR analysis indicated that this strain bears cry1Aa, cry1Ab, cry1Ac and cry2 genes. The copy number of three cry1A genes is different and cry1Ac gene (here named cry218) is the highest. The restriction location of three genes is different from that in typical strains, such as HD-1 and HD-73 strains. 4190 bp nucleotide sequence of cry218 gene was determined and this gene was named cry1Ac10 in the recently published gene nomenclature.

Bacillus thuringiensis↗
PubMed2000

[A new resolution vector with cry1Ac10 gene based on Bacillus thuringiensis transposon Tn4430].

A new resolution vector with cry1Ac10 gene based on TnpI-mediated site-specific recombination system of Bacillus thuringiensis(Bt) transposon Tn4430 was developed. The gene cry1Ac10, encoding a protoxin against plutella xylostella larvae, and the gene ori1030, from a plasmid of wide type Bacillus thuringiensis, were inserted into two copy sets of RES sites, named pBMB801. When pBMB801 was introduced into crystal negative Bt host BMB171, antibiotic resistance genes and other non-Bt DNA can be selectively eliminated. This recombinant plasmid was found very stable without antibiotic selection. The resulting strain only contained Bt DNA and is free of antibiotic resistance genes. This strategy should facilitate regulatory approval for its development as a commercial biopesticide.

Bacillus thuringiensis↗
PubMed2000

[Construction of plasmids expressing hepatitis E virus antigen fragments and their combinations].

OBJECTIVE: Several different regions of the HEV antigen were expressed in Escherichia coli and their immunological characteristics were simply evaluated. METHODS: Three coding sequences of immunodominant antigenic regions in structural protein of the hepatitis E virus (ORF2.1: 6287-6403nt, ORF2.2: 6743-7126nt, ORF3: full length of ORF3) were amplified by RT-PCR from the fecal supernatants of macaques experimentally infected with HEV. These three fragments were inserted into the pThioHisC expression vector separately or fused in line by (Gly)n short arms. After identified by DNA sequence analysis, these six recombinant plasmids were transformed into Escherichia coli, and immunology characteristics of expressed antigen fragments were evaluated by Western blotting. RESULTS: All six genes were successfully expressed in Escherichia coli. Western blotting assay showed that the recombinant proteins specifically reacted with the serum antibody from hepatitis E patient in various degrees. CONCLUSION: Artificial antigen based on strung epitopes provides a promising strategy for detection and prevention of HEV infection.

Antigens, Viral↗