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Biomedical subjects

W Chen

Publications and source records attributed to W Chen.

At least 163 records · Page 9Linked to original sources

The N-terminal flanking region of the invariant chain peptide augments the immunogenicity of a cryptic "self" epitope from a tumor-associated antigen.

The N-terminal flanking region of the invariant chain peptide termed CLIP appears to have superagonistic properties interacting with the T cell receptor and the MHC class II molecule at or near the binding site for the bacterial superantigen Staphylococcal enterotoxin B (SEB). The present studies explored the hypothesis that the N-terminal segment of CLIP can augment the immunogenicity of cryptic "self" tumor-associated antigens. A chimeric construct of an MHC class II binding peptide from the c-erb oncogene (Her-2/neu) containing the N-terminal flanking region of CLIP elicited potent antitumor activity against a Her-2/neu-positive tumor in a rat model system. Comparatively, the unmodified parent peptide was ineffective. The induction of effective antitumor immunity, however, required presentation of the chimeric peptide construct on irradiated tumor cells or the peptide construct in concert with a Her-2/neu MHC class I-restricted peptide from Her-2/neu. As revealed by adoptive transfer studies, effective protective antitumor immunity in this setting required the CD4 T helper subset. Additionally, in vitro analysis revealed that immunization with the parent peptide resulted in a weak immune response to the unmodified peptide consisting of both type 1 (IL-2, IFN-gamma) and type 2 (IL-4, IL-10) cytokine-producing cells analyzed by RT-PCR (qualitative and quantitative) and by limiting dilution assay. Comparatively, immunization with the chimeric construct elicited a potent immune response to the parent peptide with predominantly type 1 cytokine-producing cells. Taken together, the results suggest that immunization with the chimeric Her-2/neu peptide induced protective antitumor immunity. Associated with this immunization strategy was the enhancement of a type 1 cytokine response.

Animals↗

Mid-infrared trace gas detection using continuous-wave difference frequency generation in periodically poled RbTiOAsO4.

A tunable mid-infrared continuous-wave (cw) spectroscopic source in the 3.4-4.5 micrometers region is reported, based on difference frequency generation (DFG) in a quasi-phase-matched periodically poled RbTiOAsO4 (PPRTA) crystal. DFG power levels of 10 microW were generated at approximately 4 micrometers in a 20-mm long PPRTA crystal by mixing two cw single-frequency Ti:Al2O3 lasers operating near 713 nm and 871 nm, respectively, using a laser pump power of 300 mW. A quasi-phase-matched infrared wavelength-tuning bandwidth (FWHM) of ~ 12 cm-1 and a temperature tuning rate of 1.02 cm-1/degree C were achieved. Experimental details regarding the feasibility of trace gas detection based on absorption spectroscopy of CO2 in ambient air using this DFG radiation source are also described.

Aluminum Oxide↗

Randomized trials with polyunsaturated fatty acid interventions in preterm and term infants: functional and clinical outcomes.

The role of polyunsaturated fatty acids (PUFA) in infant nutrition has now been well studied through many randomized controlled trials (RCT) that provide us with high-quality evidence, particularly in relation to efficacy. As a result of a systematic search of the literature for RCT of supplementation of formulas of term and preterm infants with long-chain polyunsaturated fatty acids (LC-PUFA), we have identified 21 studies that have physiological responses or growth as outcomes. There have been 11 RCT involving preterm infants, and many of these claim a beneficial effect on visual, neural, or developmental outcomes. There are some reports of negative effects on growth in relation to the addition of n-3 LC-PUFA to preterm formulas but not when AA is added with n-3 LC-PUFA. Small studies have shown no differences in prostanoid formation or peroxidative stress between n-3 LC-PUFA-supplemented and unsupplemented infants. There have been 10 RCT involving term infants; whereas some studies report an effect on visual/neural/developmental outcomes, an equal number report no effect. There have been no reports of negative effects of n-3 LC-PUFA on growth in term infants. In summary, there appear to be few safety concerns relating to the use of LC-PUFA in infant nutrition. The potential medium- and long-term effects of including these compounds in the early diet of infants remain to be assessed.

Dietary Supplements↗

No direct role for Epstein-Barr virus in American hepatocellular carcinoma.

Epstein-Barr virus (EBV) was recently linked to hepatocellular carcinogenesis in Japanese patients. It is not clear whether EBV infection is also associated with hepatocellular carcinoma (HCC) occurring in American patients. We studied 41 cases of HCC from the Los Angeles area for evidence of EBV infection by in situ hybridization, immunohistochemistry, and polymerase chain reaction methods. Of 41 cases, 16 were seropositive for hepatitis B virus surface antigen (39%), 9 of 29 tested were seropositive for hepatitis C virus antibody (31%); in total, 22 cases were seropositive for hepatitis B virus and/or hepatitis C virus (53%). Of 41 cases, 1 was positive for EBV-encoded small nonpolyadenylated RNA (EBER)-1 (2%) by in situ hybridization. By immunohistochemistry, two cases were positive for EBV nuclear antigen (EBNA)-1 (5%), one was positive for the transactivating immediate early BZLF1 (ZEBRA) (2%), and none was positive for latent membrane protein-1. None of the 41 cases was positive for latent membrane protein-1 and EBV nuclear antigen (EBNA)-4 DNAs by polymerase chain reaction assay. All four positive cases showed rare EBER-1-, ZEBRA-, or EBNA-1- positive cells (<0.1%); in none of these cases was there expression of any other EBV viral genes. In the one case each that was positive for EBER-1 and ZEBRA, both of which occurred in patients of non-Asian ethnicity, the staining was limited to infiltrating small lymphocytes, and tumor cells were negative. In the two cases that were positive for EBNA-1, both of which occurred in patients of Asian ethnicity, the staining was limited to tumor cells, and infiltrating small lymphocytes were negative. Our study indicates that rare cases of American HCC may contain EBV-infected cells, but it is unlikely that EBV plays a major role in the carcinogenesis of HCC.

Adolescent↗

Effects of NHE-1 inhibition on cardioprotection and impact on protection by K/Mg cardioplegia.

BACKGROUND: Cardiac sodium hydrogen exchanger isoform-1 (NHE-1) activity during ischemia/reperfusion contributes to myocardial injury. The effects of NHE-1 inhibition during ischemia or reperfusion and on the protection afforded by K/Mg cardioplegia was unknown. METHODS: Rabbit hearts were used for Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia (GI) hearts received 30 minutes normothermic global ischemia and 120 minutes reperfusion. K/Mg hearts received cardioplegia 5 minutes before ischemia. Separate groups of GI and K/Mg hearts received the NHE-1 inhibitor, HOE-642, before ischemia (HOE-642-I), at the immediate start of reperfusion (HOE-642-R), or both before ischemia and at the immediate start of reperfusion (HOE-642-IR). RESULTS: Left ventricular peak developed pressure was significantly increased in HOE-I, HOE-R, and HOE-IR throughout reperfusion (p < 0.05 versus GI). Infarct size was significantly decreased (p < 0.05 versus GI) in all groups, but was significantly increased in HOE-R as compared with HOE-IR (p < 0.05). NHE-1 inhibition with K/Mg cardioplegia significantly decreased left ventricular peak developed pressure after 90 minutes of reperfusion (p < 0.05 versus K/Mg), with no significant effect on infarct size. CONCLUSIONS: NHE-1 inhibition used alone provides cardioprotection with optimal effects being observed with HOE-IR. NHE-1 inhibition with K/Mg cardioplegia decreases postischemic functional recovery during late reperfusion.

Animals↗

Influence of lipoprotein lipase serine 447 stop polymorphism on tracking of triglycerides and HDL cholesterol from childhood to adulthood and familial risk of coronary artery disease: the Bogalusa heart study.

The effects of the lipoprotein lipase (LPL) Serine 447 Stop (S447X) polymorphism on high-density lipoprotein cholesterol (HDLC) and triglycerides (TG) have been demonstrated. However, little is known about its effect on the tracking of HDLC and TG over time and familial risk of coronary artery disease (CAD). This aspect was examined in black and white individuals (n=829) aged 5-18 year at baseline, followed on average 18.8 yr. The frequency of the X447 allele was lower in Blacks than Whites (0.043 vs. 0.087, P=0.002). Carriers vs. noncarriers of the X447 allele had lower TG (99.3 vs 122.1 mg/dl, P<0.01) and higher HDLC (51.1 vs. 49.7 mg/dl, P<0.05) in adulthood, but not in childhood. The trends in genotype-specific means of childhood and adulthood levels of HDLC and TG in sex or race subgroups were similar to those in the total sample. With respect to tracking over time, of those in the bottom quartile of HDLC in childhood, 46.1% of the noncarriers vs. 23.1% of the carriers remained in this lowest quartile into adulthood (P=0.03); corresponding values for the top quartile of HDLC were 37.5% for the noncarriers vs. 57.1% for the carriers (P=0.03). Although TG tended to track better among the carriers in the bottom quartile and among the noncarriers in the top quartile, this trend was not significant. Carriers showed lower prevalence of parental history of CAD than noncarriers (6.9% vs. 14.1%, P=0.02) independently of lipoprotein variables, adiposity, blood pressure, age, sex and race. Thus, the X447 allele of the LPL gene is associated with an increase in HDLC and a decrease in TG in adults, tracking of HDLC since childhood, and a lower family history of CAD.

Adolescent↗

Critical role of dipeptidyl peptidase IV in neuropeptide Y-mediated endothelial cell migration in response to wounding.

Recently, we have discovered that neuropeptide Y (NPY), a sympathetic neurotransmitter, is also present in human umbilical endothelial cells (HUVECs), and is potently chemotactic and angiogenic by acting on one or several of Y1-Y5 receptors. In HUVECs, NPY is co-localized with dipeptidyl peptidase IV (DPPIV) which cleaves Tyr(1)-Pro(2) from NPY(1-36) to form NPY(3-36) resulting in the formation of a non-Y1 receptor agonist, which remains angiogenic. Presently we studied the effects of DPPIV's blockade using monoclonal antibodies (mAbs) on migration of HUVECs in response to NPY(1-36) or NPY(3-36) following cell wounding. Both peptides caused similar dose-dependent increases in cell migration (+80% at 0.1 nM) 12 h after wounding. DPPIV mAbs, E19 and E26, significantly reduced HUVEC's migration below that of the untreated cells, and blocked responses to NPY(1-36) but not NPY(3-36). Enhanced expression of DPPIV was found in the migrating cells and in cells with their protrusions at the edge of the wound (immunostaining and Western blot). Thus, DPPIV's expression is stimulated by endothelial wounding and its enzymatic activity is required for NPY-mediated chemotaxis. Furthermore, this suggests that non-Y1 receptors activated by NPY(3-36) (Y2, Y3 and/or Y5) mediate angiogenic effects of NPY.

Blotting, Western↗

Mechanisms for differences in monozygous twins.

Monozygous (MZ) twins are often described as being physically and genetically identical. Clinical determination of zygosity relies on the assumption that any physical differences between a pair of twins imply they are dizygous. Most twin research relies on the assumption that dizygous twins share approximately 50% of the same genes, whereas monozygous twins share 100%. There is, however, increasing evidence to challenge both these assumptions. In this review, we describe a number of intrauterine effects and genetic mechanisms that may result in phenotypic, genotypic, and epigenetic differences between monozygous twins. Newer molecular techniques are resulting in such differences being increasingly commonly recognised. The potential for differences in monozygotic twin pairs is an important consideration for both clinicians and researchers involved in twin work.

Genetic Variation↗

Expressional profiling of genes related to pollination and fertilization in rice.

Pollination and fertilization are key steps leading to seed and fruit formation. To obtain genes involved in pollination and fertilization in rice, an RNA fingerprinting technique, cDNA-AFLP (amplified fragment length polymorphism), was used to generate transcript profiles related to pollination. Of 15,000 cDNA fragments inspected, 2,100 showed altered expression in the pollinated pistil, of which about 1/5 were up-regulated (URP) and the rest down-regulated (DRP), suggesting that gene repression is a predominant mode of gene regulation in the pollinated pistil. Over 200 URP genes were sequenced and databank searches revealed that 70% of them represented previously unnoticed rice genes. DNA blot analysis of 20 URP genes detected no restriction fragment length polymorphisms (RFLP) between two relatively distant rice varieties, suggesting that the URP genes are highly conserved and likely play important roles in pollination and fertilization. Furthermore, two genes, URP47 and URP63, probably encoding an ADP-ribosylation factor and a membrane transporter, respectively, in relation to pollination were discussed.

DNA, Plant↗

Plasma renin activity and insulin resistance in African American and white children: the Bogalusa Heart Study.

Recent studies have suggested that the renin-angiotensin system is a feature of the insulin resistance syndrome. However, whether such a relationship occurs in childhood and in both African Americans and whites is not clear. We examined this issue in a sample of 264 African American and white children aged 7 to 16 years who participated in a cross-sectional survey of the Bogalusa Heart Study (n = 3,524). Children were selected using a stratified random sampling procedure based on race-, age-, and sex-specific percentiles of diastolic blood pressure. Whites had higher plasma renin activity than African Americans (7.1 +/- 3.6 ng/mL/h v 5.3 +/- 3.5 ng/mL/h, P < .01). Renin activity correlated with blood pressure (BP) (r = 0.21, P < .05) and insulin resistance index defined by post-glucose 1-h insulin X 1-h glucose (r = 0.19, P < .05) only in white children. Other components of insulin resistance syndrome (percent body fat, systolic blood pressure, high-density lipoprotein cholesterol, and triglycerides) showed no relation to renin in both races using univariate analyses. The distribution of insulin resistance index and renin activity among children with elevated BP (above 90th percentile) showed that the percentage of children with both high insulin resistance index and renin values was significantly greater in whites than in African Americans (45.6% v 23.3%, P < .05). A multivariate factor analysis of risk variables of insulin resistance syndrome resulted in clusters of BP/adiposity (factor 1), lipids/adiposity (factor 2), and insulin resistance/renin/adiposity (factor 3) in white children, with adiposity linking the three factors. However, a different pattern emerged in African American children for factor 2 and factor 3, and renin was not part of the cluster in any of the three factors. These observations suggest that renin may be a component of insulin resistance syndrome detectable in early life only in whites.

Adolescent↗

Combined effects of endothelial nitric oxide synthase gene polymorphism (G894T) and insulin resistance status on blood pressure and familial risk of hypertension in young adults: the Bogalusa Heart Study.

Impaired endothelial function with decreased nitric oxide production is shared by insulin resistance and essential hypertension. Although there are limited data on the association between the endothelial nitric oxide synthase (eNOS) G894T polymorphism and hypertension, information is absent on the combined effects of eNOS G894T genotype and insulin resistance status on blood pressure (BP) levels and the familial risk of hypertension. This aspect was examined in a community-based sample of 1021 unrelated African American and white young adults aged 19 to 38 years. African Americans displayed a lower frequency of the T894 allele than whites (0.105 v 0.324, P < .001). After adjusting for sex, age, and body mass index (BMI), noncarriers versus carriers of the T894 allele had significantly higher systolic (SBP), diastolic (DBP) BP and mean arterial pressure (MAP) levels (111.7 v 109.2 mm Hg for SBP; 73.6 v 72.3 mm Hg for DBP; 86.3 v 84.6 mm Hg for MAP), with both African Americans and whites showing similar trends. This association was modulated by insulin resistance status, measured by the homeostasis model assessment of insulin resistance (HOMA IR) using fasting insulin and glucose. Subjects with high insulin resistance (above the median HOMA IR) showed significantly greater differences in BP levels between noncarriers and carriers of the T894 allele. Furthermore, the G894T genotype and insulin resistance also showed a combined effect on the prevalence of parental hypertension, a measure of familial risk, with noncarriers versus carriers in the high insulin resistance group showing higher prevalence (70.5% v 51.3%, P = .006, adjusted for race). Thus, the allelic variation (G894T) in the eNOS gene locus in conjunction with insulin resistance may be one factor contributing to the predisposition to hypertension.

Adolescent↗

Biosensors for direct determination of organophosphate pesticides.

Direct, selective, rapid and simple determination of organophosphate pesticides has been achieved by integrating organophosphorus hydrolase with electrochemical and opitical transducers. Organophosphorus hydrolase catalyzes the hydrolysis of a wide range of organophosphate compounds, releasing an acid and an alcohol that can be detected directly. This article reviews development, characterization and applications of organophosphorus hydrolase-based potentiometric, amperometric and optical biosensors.

Biosensing Techniques↗

Amperometric microbial biosensor for direct determination of organophosphate pesticides using recombinant microorganism with surface expressed organophosphorus hydrolase.

An amperometric microbial biosensor for the direct measurement of organophosphate nerve agents is described. The sensor is based on a carbon paste electrode containing genetically engineered cells expressing organophosphorus hydrolase (OPH) on the cell surface. OPH catalyzes the hydrolysis of organophosphorus pesticides with p-nitrophenyl substituent such as paraoxon, parathion and methyl parathion to p-nitrophenol. The later is detected anodically at the carbon transducer with the oxidation current being proportional to the nerve-agent concentration. The sensor sensitivity was optimized with respect to the buffer pH and loading of cells immobilized using paraoxon as substrate. The best sensitivity was obtained using a sensor constructed with 10 mg of wet cell weight per 100 mg of carbon paste and operating in pH 8.5 buffer. Using these conditions, the biosensor was used to measure as low as 0.2 microM paraoxon and 1 microM methyl parathion with very good sensitivity, excellent selectivity and reproducibility. The microbial biosensor had excellent storage stability, retaining 100% of its original activity when stored at 4 degrees C for up to 45 days.

Aryldialkylphosphatase↗

The magnitude of familial associations of cardiovascular risk factor variables between parents and offspring are influenced by age: the Bogalusa Heart Study.

PURPOSE: Although parent-offspring associations of cardiovascular risk factor variables are known, the age-specific nature of this familial relationship is not clear. METHODS: This aspect was examined in 727 unrelated children (mean age: 11.2 years) and their parents who participated in the Bogalusa Heart Study during their childhood (mean age: 11.3 years) and adulthood (mean age: 25.5 years). RESULTS: After adjusting for covariates, the mothers' childhood-offspring correlations were consistently higher than mothers' adulthood-offspring correlations for body mass index (BMI) [r = 0.45 vs. 0.32], systolic blood pressure (SBP) [r = 0.30 vs. 0.10], diastolic blood pressure (DPB) [r = 0.22 vs. 0.13] and low-density lipoprotein cholesterol (LDLC) [r = 0.20 vs. 0.11]. In contrast, high-density lipoprotein cholesterol (HDLC) and triglycerides did not show such age-specific trends in mother-offspring correlations. Corresponding father-offspring correlations showed similar patterns, but the differences were of lesser magnitude. Multiple regression analyses using offspring's risk factor variables as dependent variables revealed that parents' childhood obesity, blood pressure and LDLC levels were better predictors of the corresponding variables in the young offspring than parents' adulthood values. Further, sex of either parents or offspring made no difference in the above findings. CONCLUSIONS: The magnitude of the familial associations of cardiovascular risk factor variables between parents and offspring are influenced by age. Intrinsic genetic make-up, duration of exposure to environment and gene-environment interactions may play a role in this association.

Adolescent↗

TGF-beta released by apoptotic T cells contributes to an immunosuppressive milieu.

T cell apoptosis is critical to development and homeostasis of the immune system. The most salient feature of apoptosis is the lack of an attendant inflammatory response or tissue damage. Here, we present evidence that apoptotic T cells release TGF-beta, thereby contributing to an immunosuppressive milieu. Apoptotic T cells released not only latent but also bio-active TGF-beta. Nonetheless, TGF-beta transcription was not upregulated, suggesting release of existing rather than synthesis of new TGF-beta. Localized within the intracellular membrane-bound compartment, which includes mitochondria, TGF-beta was redistributed into the cytosol following loss of mitochondrial membrane potential. TGF-beta secreted from apoptotic T cells inhibited proinflammatory cytokine production by activated macrophages to foster immune suppression. These findings broaden the potential mechanisms whereby induction of immune tolerance or deficiency occurs through T cell deletion.

Animals↗

Structural change of mesoporous silica with sonochemically prepared gold nanoparticles in its pores.

Ultrasonic irradiation of mesoporous silica soaked in a mixture of chloroauric acid and isopropanol for 120 min in Ar atmosphere at room temperature yielded Au/SiO2 mesoporous composite, which was characterized by high resolution transmission electron microscopy and optical absorption measurement. The structure of mesoporous silica after sonochemical preparation of gold (Au) nanoparticles within its pores was studied by nitrogen adsorption technique. It has been shown that the structural parameters, such as specific surface area (SSA), porosity (P), the mean pore diameter (lp) were increased significantly after ultrasonic irradiation. It is suggested that the collision of Au nanoparticles with pore walls and localized erosion induced by the asymmetric implosive collapse of cavities on the extensive liquid-solid interface that are responsible for the structural change in the mesoporous solid.

Journal Article↗