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Biomedical subjects

S Wu

Publications and source records attributed to S Wu.

At least 199 records · Page 11Linked to original sources
PubMed1999

Improving support vector machine classifiers by modifying kernel functions.

We propose a method of modifying a kernel function to improve the performance of a support vector machine classifier. This is based on the structure of the Riemannian geometry induced by the kernel function. The idea is to enlarge the spatial resolution around the separating boundary surface, by a conformal mapping, such that the separability between classes is increased. Examples are given specifically for modifying Gaussian Radial Basis Function kernels. Simulation results for both artificial and real data show remarkable improvement of generalization errors, supporting our idea.

Journal Article↗
PubMed1999

Two novel azadirachtin derivatives from azadirachta indica

Two novel compounds, the first 29-oxymethylene azadirachtin analogue, 29-oxymethylene-11- demethoxycarbonyl-11alpha-hydroxyazadirachtin (azadirachtin M) (1) and 22, 23-dihydro-23alpha-hydroxy-3-tigloyl-11-deoxyazadirachtinin (azadirachtin N) (2), together with known compound 11-epi-azadirachtin H were isolated from a methanolic extract of the seed kernels of Azadirachta indica. The structures of 1 and 2 were elucidated on the basis of spectral methods.

Journal Article↗
PubMed1999

Reoxygenation injury of human brain capillary endothelial cells.

1. Many studies have demonstrated that endothelial cells from several species can generate oxygen free radicals when subjected to anoxia and reoxygenation. However, due to the heterogeneity of the endothelium within different organs and species, the effects of superoxide dismutase (SOD), catalase, and allopurinol on reoxygenated cultured cells remain quite controversial. 2. This review outlines the possible sources of oxygen free radicals within brain endothelial cells. 3. We examine the aspects of the effects of SOD catalase and allopurinol on cultured human brain capillary endothelial cells upon reoxygenation. 4. Also, we introduce briefly a method of culturing human brain capillary endothelial cells and present our experimental results on the effects of SOD, catalase, and allopurinol in these cultured cells following anoxia and reoxygenation.

Animals↗
PubMed1999

Study on the hyphal responses of Aspergillus fumigatus to the antifungal agent by Bio-Cell Tracer.

The hyphal responses of an A. fumigatus isolate to a trizole derivative-fluconazole (FCZ) were studied with a Bio-Cell Tracer system. The numerical data were recorded as the original growth rate (Pre-GR), the time needed for FCZ reaching to its target in hypha (tau on), the growth rate under the FCZ effect (Exp-GR) and the growth rate after FCZ was removed (Post-GR). Based on above numerical data, the inhibitory rates in the exposure and post exposure periods were calculated as the Exp-I% and Post-I% values. It was found there were variable inhibitory rate values (I%) in individual hyphae corresponding to different FCZ concentrations. It was shown by correlation analysis of the numerical data that the Pre-GR values were negatively correlated with the tau on values and positively correlated with both the Exp-I% and Post-I% values. Additionally, the tau on values are negatively correlated with the Exp-I% and Post-I% values. Those results suggested that the hyphal growth rate and the susceptibility of the FCZ target be the important factors to determine the hyphal responses to the FCZ effect. Serial morphological alternations were captured while the hyphal growth curves were changing under the FCZ effects. Of the morphological data, the interesting alternations were visualized when the hyphae were affected by 16 micrograms/ml FCZ. As shifting of the hyphal growth curves, the hyphae were repeatedly seen as swollen tips and germination from the swollen sites. It is indicated that the hyphal tips are the most sensitive parts of this mycelia fungus to the FCZ affects. Additionally, because the hyphal regrowth was observed as germination from the swollen tips before FCZ was removed, an adaptation phenomenon could be proposed.

Antifungal Agents↗
PubMed1999

Antisense IRAK-2 oligonucleotide blocks IL-1-stimulated NF-kappaB activation and ICAM-1 expression in cultured endothelial cells.

Phosphorothioate oligodeoxynucleotide (ODN) was designed antisense to sequences of the recently cloned human IL-1 receptor associated kinase-2 (IRAK-2). Antisense IRAK-2 ODN was delivered by lipofectin encapsulation into cultured endothelial cells. The levels of NF-KB, surface expression of intracellular adhesion molecule-1 (ICAM-1), ICAM-1 and IRAK-2 mRNAs were measured by sandwich ELISA, ELISA on cells in situ, and semiquantitative reverse transcription-PCR (RT-PCR), respectively. Antisense IRAK-2 ODN inhibited IL-1-induced NF-KB activation and surface expression of ICAM-1 in a concentration (1-4 microg)- and time (5-24 h)-dependent fashion. A maximum inhibition of NF-KB activation or surface expression of ICAM-1 occurred when the cells were incubated with antisense IRAK-2 ODN 3 microg for 8 h. IL-1-induced ICAM-1 mRNA expression was also inhibited after treatment of cells with antisense IRAK-2 ODN 3 microg for 8 h. The attenuation of the cellular response to IL-1 caused by antisense IRAK-2 ODN correlated with a reduction of IRAK-2 expression. These data suggest that antisense IRAK-2 ODN may share a role in the design of antiinflammatory therapeutics.

Cells, Cultured↗
PubMed1999

Fuzzy segmentation spatiotemporal patterns of cognitive potential into microstates.

Fuzzy c-mean algorithm was applied to segment spatiotemporal patterns of brainwave into microstates and memberships. The optimal clustering number was estimated with both the trends of objective function and the eigenvalue number of microstates. Comparable spatial patterns may occur at different temporal moments in consideration of fuzzy index that is beyond the limit of serial processing. Those techniques were illustrated with multichannel event-related potentials recorded from 9 subjects during Stroop test. Statistical parametric map of F value suggested that significant task (color decision and word decision) effect involve widespread cortical regions after stimulus onset 280 ms and this result supports the hypothesis that Stroop interference derives from response competition during post-perception stage. As significant stimulus (congruent stimulus and incongruent stimulus) effect only involves several separate visual regions within 100 ms after stimulus presentation, it may reflect top-down attentional regulation.

Algorithms↗
PubMed1999

Additive effect of three noradrenergic genes (ADRA2a, ADRA2C, DBH) on attention-deficit hyperactivity disorder and learning disabilities in Tourette syndrome subjects.

Halperin et al. (Halperin JM. Newcorn JH, Koda VH, Pick L, McKay KE, Knott P. Noradrenergic mechanisms in ADHD children with and without reading disabilities: a replication and extension. J Am Acad Child Adolesc Psychiatry 1997: 36: 1688 1696) reported a significant increase in plasma norepinephrine (NE) in attention-deficit hyperactivity disorder (ADHD) children with reading and other cognitive disabilities compared to ADHD children without learning disabilities (LD). We examined the hypothesis that ADHD + LD was associated with NE dysfunction at a molecular genetic level by testing for associations and additive effects between polymorphisms at three noradrenergic genes the adrenergic alpha2A receptor (ADRA2A), adrenergic alpha2C receptor (ADRA2C), and dopamine beta-hydroxylase (DBH) genes. A total of 336 subjects consisting of 274 individuals with Tourette syndrome (TS) and 62 normal controls were genotyped. Regression analysis showed a significant correlation between scores for ADHD, a history of LD, and poor grade-school academic performance that was greatest for the additive effect of all three genes. Combined, these three genes accounted for 3.5% of the variance of the ADHD score (p = 0.0005). There was a significant increase in the number of variant NE genes progressing from subjects without ADHD (A-) or learning disorders (LD-) to A + LD - to A - LD + to A + LD + (p = 0.0017), but no comparable effect for dopamine genes. These data support an association between NE genes and ADHD, especially in ADHD + LD subjects.

Adolescent↗
PubMed1999

Homozygosity at the dopamine DRD3 receptor gene in cocaine dependence.

We examined the hypothesis that the dopamine D3 receptor gene (DRD3) is a susceptibility factor for cocaine dependence. The MscI/BalI polymorphism of the DRD3 gene was examined in 47 Caucasian subjects with cocaine dependence and 305 Caucasian controls. Based on prior studies with a range of psychiatric disorders we hypothesized there would be a decrease in the frequency of the 12 genotype in the patient sample (increased homozygosity). We observed a significant decrease in the frequency of 12 heterozygotes in subjects with cocaine dependence (29.8%) vs controls (46.9%) (P </= 0.028). This percentage was still lower in those who had chronically used cocaine for more than 10 years (25%), or more than 15 years (21.5%). The DRD3 gene accounted for 1.64% of the variance of cocaine dependence. The DRD2 gene had an independent and additive effect on cocaine dependence. These findings support a modest role of the DRD3 gene in susceptibility to cocaine dependence.

Adult↗
PubMed1999

Changes in glomerular thromboxane A2 receptor expression and ligand binding following immune injury.

BACKGROUND: Thromboxane (Tx) A2 is a potent vasoconstrictor eicosanoid that attains high levels within nephritic glomeruli and mediates a drop in glomerular filtration rate (GFR). In the course of nephritis, however, GFR recovers despite high intraglomerular TxA2 levels. We hypothesized that this recovery indicates a reduced responsiveness of the glomerular vasculature to TxA2, and explored whether changes in TxA2 receptor protein expression and receptor-ligand binding are underlying mechanisms. METHODS: Glomerulonephritis was induced in male Sprague-Dawley rats using an antibody raised in rabbits against rat particulate glomerular basement membrane (GBM). Changes in Tx receptor levels were assessed in protein lysates of glomeruli on days 3 and 7 after a single intravenous injection of the anti-GBM antibody. Ligand-binding studies were performed at the same time points using isolated glomeruli and the TxA2 receptor ligand [3H]-SQ-29,548. GFR was measured as the clearance of endogenous creatinine. RESULTS: There was a marked increase in Tx receptor protein in the lysates of nephritic glomeruli on days 3 and 7. In contrast, binding sites (Bmax) of [3H]-SQ-29,548 decreased, indicating that the excess receptor became either inaccessible to its ligand (sequestered) or desensitized. Daily administration of the Tx synthase inhibitor Furegrelate starting prior to injection of anti-GBM antibody prevented the decrease in [3H]-SQ-29,548 binding. Furegrelate treatment starting in an established stage of nephritis had no effect. In these animals, GFR was lower than nephritic controls not treated with Furegrelate. CONCLUSIONS: These observations indicate that in the course of glomerulonephritis, there is a marked increase in glomerular Tx receptor expression. The enhanced intraglomerular TxA2 synthesis causes either a sequestration or desensitization of its receptor. As a result, access of unbound TxA2 to efferent arterioles may become facilitated, and constriction of these arterioles may preserve GFR.

Animals↗
PubMed1999

The effect of a levonorgestrel-releasing intrauterine device on human endometrial oestrogen and progesterone receptors after one year of use.

Thirty-four women bearing a levonorgestrel-releasing intrauterine device, 20 micrograms/day (LNG-IUD-20), for 12-15 months were recruited. Endometrial biopsies were collected during the late proliferative phase of the cycle (on cycle days 10-12) before (control) and after the use of the IUD for 12 months, and assayed for oestrogen receptors (ER) and progesterone receptors (PR). An immunohistochemical technique with the peroxidase-antiperoxidase detection system (PAP method) was employed. D75 and JZB39 were the primary antibodies for ER and PR respectively. The immunostaining semiquantitative analysis was performed with a computerized microscope image processor, and expressed as 'grey value'. Both endometrial ER and PR populations were significantly lower after insertion of the IUD (P < 0.01) than in control biopsies. The intensity of nuclear staining and the percentage of positively stained cells for ER and PR in women with LNG-IUD were each about 50% of those in control biopsies. The results suggested that LNG released locally from the IUD has a depressive action on the ER and PR, which may contribute to the contraceptive effectiveness of this type of IUD and also to the possible causes of LNG-IUD-induced irregular bleeding and amenorrhoea.

Adult↗
PubMed1999

Role of Arg163 in the N-glycosidase activity of neo-trichosanthin.

Three mutant crystals of neo-trichosanthin (n-TCS), R163K, R163H and R163Q, were obtained by the hanging drop vapor diffusion method. Structure determination indicated that there are no significant differences between the mutants and n-TCS except in the active pocket. All of them were also soaked in sodium citrate buffer (pH 4. 5) containing 20% KCl and 10 mg/ml AMP. Structure determination suggests that in the active pocket of the crystals of R163K and R163H, parallel to the aromatic ring of Tyr70, each mutant possesses an adenine. The relationship between structure and function is discussed. Biochemical analysis reveals that the mutants R163K and R163H have N-glycosidase activity, while R163Q does not. This suggests that R163 is a crucial residue for the enzyme activity of n-TCS, and its role is providing proton.

Adenosine Monophosphate↗
PubMed1999

Individual hydrogen bonds play a critical role in MHC class II: peptide interactions: implications for the dynamic aspects of class II trafficking and DM-mediated peptide exchange.

Determination of the crystal structure of class II: peptide complexes has shown that in addition to pocket interactions involving the side chains of the peptide, peptide binding to MHC class II molecules is characterized by a series of hydrogen bonds which are contributed by genetically conserved amino acid residues in the class II molecule to the main chain of the peptide. Our experiments have revealed an unexpectedly large contribution of hydrogen bonds at the periphery of the MHC peptide binding pocket to MHC class II function. Kinetic studies have shown that peptide dissociation rates are profoundly accelerated by loss of a single hydrogen bonding residue. The magnitude of the effects seen with the loss in potential for a single hydrogen bond support a co-operative model in which individual bonds between class II and peptide are dependent on the integrity of neighboring interactions. Collectively our studies have revealed that MHC class II structure, peptide binding and intracellular trafficking events are critically dependent on the integrity of the hydrogen bonding network between class II molecules and its bound peptide.

Animals↗
PubMed1999

Expression of recombinant enterotoxigenic Escherichia coli colonization factor antigen I by Salmonella typhimurium elicits a biphasic T helper cell response.

Protective immunity to enterotoxigenic Escherichia coli (ETEC) is antibody (Ab) dependent; however, oral immunization with purified ETEC fimbriae fails to elicit protective immunity as a consequence of antigenic alteration by the gastrointestinal (GI) tract. Unless unaltered ETEC fimbriae can reach the inductive lymphoid tissues of the GI tract, immunity to ETEC cannot be induced. To produce immunity, live vectors, such as Salmonella typhimurium, can effectively target passenger antigens to the inductive lymphoid tissues of the GI tract. By convention, oral immunizations with Salmonella vectors induce CD4(+) T helper (Th) cell responses by gamma interferon (IFN-gamma)-dominated pathways both to the vector and passenger antigen, resulting in serum immunoglobulin G2a (IgG2a) and modest mucosal IgA Ab responses. In the present study, mice orally immunized with a Salmonella vector engineered to stably express ETEC colonization factor antigen I (CFA/I) showed initially elevated serum IgG1 and mucosal IgA anti-CFA/I Ab responses. As expected, mice orally immunized with an E. coli-CFA/I construct elicited poor anti-CFA/I Ab responses. In fact, the addition of cholera toxin during oral E. coli-CFA/I immunization failed to greatly enhance mucosal IgA Ab responses. Seven days after immunization with the Salmonella-CFA/I construct, cytokine-specific ELISPOT showed induction of predominant Th2-type responses in both mucosal and systemic immune compartments supporting the early IgG1 and IgA anti-CFA/I Abs. By 4 weeks, the Th cell response became Th1 cell dominant from the earlier Th2-type responses, as evidenced by increased mucosal and systemic IFN-gamma-producing T cells and a concomitant elevation of serum IgG2a Ab responses. This biphasic response offers an alternative strategy for directing Salmonella vector-induced host immunity along a Th2 cell-dependent pathway, allowing for early promotion of mucosal and systemic Abs.

Animals↗
PubMed1999

Identification of a third metalloprotease toxin gene in extraintestinal isolates of Bacteroides fragilis.

To further understand the epidemiology of enterotoxigenic Bacteroides fragilis (ETBF), 89 extraintestinal B. fragilis strains from Seoul, Korea, were examined for secretion of B. fragilis toxin (BFT) by the HT29/C1 biologic assay and for the B. fragilis toxin gene (bft) by colony blot hybridization and PCR. Complete agreement between the three techniques was found. Overall, 34 B. fragilis strains (38%) were identified as ETBF. Eleven of the 34 ETBF strains (32%) expressed a new isoform of BFT (Korea-BFT). This new isoform is more related to BFT-2 than to BFT-1. Like BFT-1 and BFT-2, Korea-BFT cleaves E-cadherin, the zonula adherens protein.

Amino Acid Sequence↗
PubMed1999

Molecular evolution of the pathogenicity island of enterotoxigenic Bacteroides fragilis strains.

Enterotoxigenic Bacteroides fragilis (ETBF) strains, which produce a 20-kDa zinc metalloprotease toxin (BFT), have been associated with diarrheal disease in animals and young children. Studying a collection of ETBF and nontoxigenic B. fragilis (NTBF) strains, we found that bft and a second metalloprotease gene (mpII) are contained in an approximately 6-kb pathogenicity island (termed B. fragilis pathogenicity island or BfPAI) which is present exclusively in all 113 ETBF strains tested (pattern I). Of 191 NTBF strains, 100 (52%) lack both the BfPAI and at least a 12-kb region flanking BfPAI (pattern II), and 82 of 191 NTBF strains (43%) lack the BfPAI but contain the flanking region (pattern III). The nucleotide sequence flanking the left end of the BfPAI revealed a region with the same organization as the mobilization region of the 5-nitroimidazole resistance plasmid pIP417 and the clindamycin resistance plasmid pBFTM10, that is, two mobilization genes (bfmA and bfmB) organized in one operon and a putative origin of transfer (oriT) located in a small, compact region. The region flanking the right end of the BfPAI contains a gene (bfmC) whose predicted protein shares significant identity to the TraD mobilization proteins encoded by plasmids F and R100 from Escherichia coli. Nucleotide sequence analysis of one NTBF pattern III strain (strain I-1345) revealed that bfmB and bfmC are adjacent to each other and separated by a 16-bp GC-rich sequence. Comparison of this sequence with the appropriate sequence of ETBF strain 86-5443-2-2 showed that in this ETBF strain the 16-bp sequence is replaced by the BfPAI. This result defined the BfPAI as being 6,036 bp in length and its precise integration site as being between the bfmB and bfmC stop codons. The G+C content of the BfPAI (35%) and the flanking DNA (47 to 50%) differ greatly from that reported for the B. fragilis chromosome (42%), suggesting that the BfPAI and its flanking region are two distinct genetic elements originating from very different organisms. ETBF strains may have evolved by horizontal transfer of these two genetic elements into a pattern II NTBF strain.

Amino Acid Sequence↗
PubMed1999

Prevention of stroke in urban China: a community-based intervention trial.

BACKGROUND AND PURPOSE: Stroke has been the second leading cause of death in large cities in China since the 1980s. Meanwhile, the prevalences of hypertension and smoking have steadily increased over the last 2 decades. Therefore, a community-based intervention trial was initiated in 7 Chinese cities in 1987. The overall goal of the study was to evaluate the effectiveness of an intervention aimed at reducing multiple risk factors for stroke. The primary study objective was to reduce the incidence of stroke by 25% over 3.5 years of intervention. METHODS: In May 1987 in each of 7 the cities, 2 geographically separated communities with a registered population of about 10 000 each were selected as either intervention or control communities. In each community, a cohort containing about 2700 subjects (>/=35 years old) free of stroke was sampled, and a survey was administered to obtain baseline data and screen the eligible subjects for intervention. In each city, a program of treatment for hypertension, heart disease, and diabetes was instituted in the intervention cohort (n approximately 2700) and health education was provided to the full intervention community (n approximately 10 000). A follow-up survey was conducted in 1990. Comparisons of intervention and control cohorts in each city were pooled to yield a single summary. RESULTS: A total of 18 786 subjects were recruited to the intervention cohort and 18 876 to the control cohort from 7 cities. After 3.5 years, 174 new stroke cases had occurred in the intervention cohort and 253 in the control cohort. The 3.5-year cumulative incidence of total stroke was significantly lower in the intervention cohort than the control cohort (0.93% versus 1.34%; RR=0.69; 95% CI, 0.57 to 0.84). The incidence rates of nonfatal and fatal stroke, as well as ischemic and hemorrhagic stroke, were significantly lower in the intervention cohort than the control cohort. The prevalence of hypertension increased by 4.3% in the intervention cohort and by 7.8% in the control cohort. The average systolic and diastolic blood pressures increased more in the control cohort than in the intervention cohort. Among hypertensive individuals in the intervention cohort, awareness of hypertension increased by 6.7% and the percentage of hypertensives who regularly took antihypertensive medication increased 13.2%. All of these indices became worse in the control cohort. The prevalence of heart diseases and diabetes increased significantly in the both cohorts (P<0.01). The prevalence of consumption of alcohol increased slightly, and that of smoking remained constant in both cohorts. CONCLUSIONS: A community-based intervention for stroke reduction is feasible and effective in the cities of China. The reduction, due to the intervention, in the incidence of stroke in the intervention cohort was statistically significant after 3.5 years of intervention. The sharp reduction in the incidence of stroke may be due to the interventions having blunted the expected increase in hypertension that accompanies aging as well as to better and earlier treatment of hypertension, particularly borderline hypertension. Applied health education to all the residents of the community may have prevented some normotensive individuals from developing hypertension and improved overall health awareness and knowledge.

Cerebrovascular Disorders↗