Biomedical subjects

T Nguyen

Publications and source records attributed to T Nguyen.

At least 91 records · Page 5Linked to original sources

PubMed2000

Incremental reduction of serum total cholesterol and low-density lipoprotein cholesterol with the addition of plant stanol ester-containing spread to statin therapy.

This study compares the effect of plant stanol ester spread with a placebo spread on cholesterol in patients taking statin therapy, but who still had elevated low-density lipoprotein (LDL) cholesterol. This was a randomized, double-blind, placebo-controlled clinical trial, with 67 women and 100 men with LDL cholesterol >/=130 mg/dl and triglycerides </=350 mg/dl who had been taking a stable dose of a statin drug for at least 90 days before the start of the study. For 8 weeks, participants consumed 3 servings/day of the plant stanol ester spread that provided 5.1 g/day of plant stanol ester or a placebo. The addition of plant stanol ester spread significantly reduced total cholesterol and LDL cholesterol at 2, 4, and 8 weeks when compared with placebo spread. Plant stanol ester spread reduced total cholesterol at 8 weeks by 12% compared with a placebo reduction of 5% (-7% difference; p <0.0001). Plant stanol ester spread reduced LDL cholesterol at 8 weeks by 17% compared with a 7% reduction in the placebo group (-10% difference, p <0.0001). The absolute reduction in LDL cholesterol at 8 weeks was 24 and 10 mg/dl in the stanol ester and placebo groups, respectively. The plant stanol ester spread group also had greater reductions in both serum total cholesterol and LDL cholesterol than the placebo group at 2 and 4 weeks (p <0.001 for all comparisons). Both spreads were well tolerated by study participants, and no significant adverse events were noted. Consumption of spread that provided 5.1 g/day of plant stanol esters effectively reduced elevated total and LDL cholesterol levels in participants on a stable regimen of a statin.

Administration, Oral↗

PubMed2000

Ectopic noradrenergic hyperinnervation does not functionally compensate for neonatal forebrain acetylcholine lesion.

Adult rats who have undergone neonatal 192 IgG-saporin induced lesions of forebrain acetylcholine (ACH) neurons are normal on many behavioral tasks. In this study we determined whether ectopic hippocampal ingrowths, a documented consequence of these neonatal cholinergic lesions, functionally compensate for ACH denervation in these rats. Neonatal rats underwent systemic 6-hydroxydopamine (6-OHDA) injections on postnatal days (PND) 1-3 to prevent the ingrowths, and/or intraventricular 192 IgG-saporin injections on PND 7. The 192 IgG-saporin profoundly reduced basal forebrain p75 neurotrophin receptor (p75(NTR)) immunoreactive (IR) neurons. The 6-OHDA treatment abolished hippocampal and cortical dopamine-beta-hydroxylase (DBH) IR terminals, indicating the absence of normal norepinephrine (NE) innervation. Ectopic DBH IR and p75(NTR) IR varicosities which occurred in the hippocampus of 192 IgG-saporin treated rats were also eliminated by 6-OHDA treatment. Behavioral testing in adulthood indicated no effect of the treatments on the Morris water maze. 192 IgG-saporin treatment caused perseveration during delayed spatial alternation (DSA) and increased working but not reference memory errors on the radial arm maze (RAM). The 6-OHDA plus 192 IgG-saporin treated rats did not differ from the 192 IgG-saporin only rats on any task. These results indicate that ectopic hippocampal NE ingrowths do not functionally compensate for neonatal ACH lesions. Neonatal forebrain ACH lesion impairs working memory on the RAM but the absence of an effect on DSA contraindicates a basic dysfunction of short term memory. Despite severe combined neonatal loss of forebrain ACH and NE innervation, behavior is remarkably intact.

Acetylcholine↗

PubMed2000

Influence of live respiratory syncytial virus priming on the immune response generated by a recombinant vaccine candidate, BBG2Na.

Respiratory syncytial virus is one of the major respiratory pathogens for infants and immunocompromized children. With the exception of young children, all the population has encountered RSV and is seropositive. Recent reports have demonstrated however that the virus also affects the elderly and represents a major cause of illness associated with an excess of morbidity and mortality. We have generated a recombinant RSV vaccine, BBG2Na, which is highly protective in rodents against RSV infection. The aim of this study was to evaluate the ability of the vaccine to increase anti-RSV protection in RSV-primed mice and to characterize the induced immune responses. Immunization with BBG2Na increased the anti-RSV-A serum antibody titers of RSV-primed mice with induction of both IgG1 and IgG2a antibodies attesting for a mixed Th response. Moreover, the level of the induced anti-G2Na antibodies was greater in seropositive mice. Finally, sera from RSV-primed mice displayed a higher protective efficacy after transfer into naive mice following subsequent immunization with BBG2Na than sera of mice immunized with RSV-A only. Our results demonstrate that BBG2Na is immunogenic and increases the protective efficacy of serum antibodies in RSV-primed mice; they support the possibility of performing clinical trials in the seropositive human population.

Animals↗

PubMed2000

Structure of the liquid-crystal ferrielectric phases as determined by ellipsometry

The unit cell structures of two ferrielectric liquid-crystal phases are determined from ellipsometric studies of freestanding films in a nondistorting rotatable electric field. A highly biaxial mode with out-of-plane distortions describes all of the data from two different compounds. Qualitative and quantitative features of the data rule out alternate models. We also present a detailed explanation for apparent inconsistencies between previous resonant x-ray and optical experiments.

Journal Article↗

PubMed2000

Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK.

The antioxidant response element (ARE) mediates the transcriptional activation of many genes encoding phase II drug-metabolizing enzymes in response to oxidative stress. Recent studies using knockout mice suggest that NF-E2-related factor 2 (Nrf2), along with small Maf proteins, binds and activates the ARE. In this study, using in vitro binding assays, Nrf2/MafK heterodimers were found to interact with high affinity to the ARE. However, distinct differences were observed when this interaction was compared with that formed with nuclear proteins from H4II EC3 or HepG2 cells. Overexpression of Nrf2 activated ARE-mediated transcription in HepG2 cells, and this activation was further increased by tert-butylhydroquinone. In HeLa cells, overexpression of Nrf2 resulted in activation of the ARE, but this activation was no longer induced by tert-butylhydroquinone. Using ARE constructs with point mutations in the core sequence, we found that only mutations at the T or G nucleotides within the core (TGAC) render the ARE unresponsive to Nrf2. Overexpression of MafK led to dose-dependent repression of ARE activity. Activation of the ARE by Nrf2 was similarly antagonized by MafK. These data suggest that Nrf2 plays an important role mediating basal activity of the ARE but that small Maf proteins are repressors and not activators of ARE-mediated transcription.

Animals↗

PubMed2000

Differential localization and regulation of death and decoy receptors for TNF-related apoptosis-inducing ligand (TRAIL) in human melanoma cells.

Induction of apoptosis in cells by TNF-related apoptosis-inducing ligand (TRAIL), a member of the TNF family, is believed to be regulated by expression of two death-inducing and two inhibitory (decoy) receptors on the cell surface. In previous studies we found no correlation between expression of decoy receptors and susceptibility of human melanoma cells to TRAIL-induced apoptosis. In view of this, we studied the localization of the receptors in melanoma cells by confocal microscopy to better understand their function. We show that the death receptors TRAIL-R1 and R2 are located in the trans-Golgi network, whereas the inhibitory receptors TRAIL-R3 and -R4 are located in the nucleus. After exposure to TRAIL, TRAIL-R1 and -R2 are internalized into endosomes, whereas TRAIL-R3 and -R4 undergo relocation from the nucleus to the cytoplasm and cell membranes. This movement of decoy receptors was dependent on signals from TRAIL-R1 and -R2, as shown by blocking experiments with Abs to TRAIL-R1 and -R2. The location of TRAIL-R1, -R3, and -R4 in melanoma cells transfected with cDNA for these receptors was similar to that in nontransfected cells. Transfection of TRAIL-R3 and -R4 increased resistance of the melanoma lines to TRAIL-induced apoptosis even in melanoma lines that naturally expressed these receptors. These results indicate that abnormalities in "decoy" receptor location or function may contribute to sensitivity of melanoma to TRAIL-induced apoptosis and suggest that further studies are needed on the functional significance of their nuclear location and TRAIL-induced movement within cells.

Amino Acid Chloromethyl Ketones↗

PubMed2000

The human homolog of insect-derived growth factor, CECR1, is a candidate gene for features of cat eye syndrome.

Cat eye syndrome (CES) is a developmental disorder with multiple organ involvement, associated with the duplication of a 2-Mb region of 22q11.2. Using exon trapping and genomic sequence analysis, we have isolated and characterized a gene, CECR1, that maps to this critical region. The protein encoded by CECR1 is similar to previously identified novel growth factors: IDGF from Sarcophaga peregrina (flesh fly) and MDGF from Aplysia californica (sea hare). The CECR1 gene is alternatively spliced and expressed in numerous tissues, with most abundant expression in human adult heart, lung, lymphoblasts, and placenta as well as fetal lung, liver, and kidney. In situ hybridization of a human embryo shows specific expression in the outflow tract and atrium of the developing heart, the VII/VIII cranial nerve ganglion, and the notochord. The location of this gene in the CES critical region and its embryonic expression suggest that the overexpression of CECR1 may be responsible for at least some features of CES, particularly the heart defects.

Abnormalities, Multiple↗

PubMed2000

Cloning and characterization of additional members of the G protein-coupled receptor family.

A search of the expressed sequence tag (EST) database retrieved a human cDNA sequence which partially encoded a novel G protein-coupled receptor (GPCR) GPR26. A human genomic DNA fragment encoding a partial open reading frame (ORF) and a rat cDNA encoding the full length ORF of GPR26 were obtained by library screening. The rat GPR26 cDNA encoded a protein of 317 amino acids, most similar (albeit distantly related) to the serotonin 5-HT(5A) and gastrin releasing hormone BB2 receptors. GPR26 mRNA expression analysis revealed signals in the striatum, pons, cerebellum and cortex. HEK293 and Rh7777 cells transfected with GPR26 cDNA displayed high basal cAMP levels, slow growth rate of clonal populations and derangements of normal cell shape. We also used a sequence reported only in the patent literature encoding GPR57 (a.k.a. HNHCI32) to PCR amplify a DNA fragment which was used to screen a human genomic library. This resulted in the cloning of a genomic fragment containing a pseudogene, psiGPR57, with a 99.6% nucleotide identity to GPR57. Based on shared sequence identities, the receptor encoded by GPR57 was predicted to belong to a novel subfamily of GPCRs together with GPR58 (a.k.a. phBL5, reported only in the patent literature), putative neurotransmitter receptor (PNR) and a 5-HT(4) pseudogene. Analysis of this subfamily revealed greatest identities (approximately 56%) between the receptors encoded by GPR57 and GPR58, each with shared identities of approximately 40% with PNR. Furthermore, psiGPR57, GPR58, PNR and the 5-HT(4) pseudogene were mapped in a cluster localized to chromosome 6q22-24. PNR and GPR58 were expressed in COS cells, however no specific binding was observed for various serotonin receptor-specific ligands.

1-Methyl-3-isobutylxanthine↗

PubMed2000

Ligand-, cell-, and estrogen receptor subtype (alpha/beta)-dependent activation at GC-rich (Sp1) promoter elements.

17beta-Estradiol (E2) induces expression of several genes via estrogen receptor (ER)-Sp1 protein interactions with GC-rich promoter elements in which Sp1 but not ER binds DNA. This study reports the ligand- and cell context-dependent ER(alpha)/Sp1 and ER(beta)/Sp1 action using an E2-responsive construct (pSp1) containing a GC-rich promoter. Both ER(alpha) and ER(beta) proteins physically interact with Sp1 (coimmunoprecipitation) and preferentially bind to the C-terminal region of this protein in pull-down assays. E2- and antiestrogen-dependent transcriptional activation of ER(alpha)/Sp1 was observed in MCF-7, MDA-MB-231, and LnCaP cells, but not in HeLa cells. E2 did not affect or significantly decrease ER(beta)/Sp1 action, and antiestrogens had minimal effects in the same 4 cell lines. Exchange of activation function-1 (AF-1) domains of ER subtypes gave chimeric ER(alpha/beta) (AF-1alpha/AF-2beta) and ER(beta/alpha) (AF-1beta/AF-2alpha) proteins that resembled wild-type ER (alpha or beta) in terms of physical association with Sp1 protein. Transcriptional activation studies with chimeric ER(beta/alpha) and ER(alpha/beta) showed that only ER(alpha/beta) can activate transcription from an Sp1 element, not ER(beta/alpha). This indicates that the AF-1 domain from ER(alpha) is responsible for activation at an Sp1 element, independent of ER subtype context. In order to further characterize this observation, deletion constructs in the AF-1 domain of both ER(alpha) and ER(alpha/beta) were made, and transactivation studies indicated that the region between amino acids 79 and 117 of this domain is important for activation at an Sp1 element.

Cloning, Molecular↗

PubMed2000

Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart.

BACKGROUND: IGF-1 has been shown to protect myocardium against death in animal models of infarct and ischemia-reperfusion injury. In the present study, we investigated the role of the IGF-1-regulated protein kinase Akt in cardiac myocyte survival in vitro and in vivo. METHODS AND RESULTS: IGF-1 promoted survival of cultured cardiomyocytes under conditions of serum deprivation in a dose-dependent manner but had no effect on cardiac fibroblast survival. The cytoprotective effect of IGF-1 on cardiomyocytes was abrogated by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor wortmannin. Wortmannin had no effect on cardiomyocyte viability in the absence of IGF-1. IGF-1-mediated cytoprotection correlated with the wortmannin-sensitive induction of Akt protein kinase activity. To examine the functional consequences of Akt activation in cardiomyocyte survival, replication-defective adenoviral constructs expressing wild-type, dominant-negative, and constitutively active Akt genes were constructed. Transduction of dominant-negative Akt blocked IGF-1-induced survival but had no effect on cardiomyocyte survival in the absence of IGF-1. In contrast, transduction of wild-type Akt enhanced cardiomyocyte survival at subsaturating levels of IGF-1, whereas constitutively active Akt protected cardiomyocytes from apoptosis in the absence of IGF-1. After transduction into the mouse heart in vivo, constitutively active Akt protected against myocyte apoptosis in response to ischemia-reperfusion injury. CONCLUSIONS: These data are the first documentation that Akt functions to promote cellular survival in vivo, and they indicate that the activation of this pathway may be useful in promoting myocyte survival in the diseased heart.

Animals↗

PubMed2000

CC chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte-derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo.

Isolated peripheral blood CD4 cells from allergic individuals express CC chemokine receptor (CCR)3 and CCR4 after expansion in vitro. In addition, human T helper type 2 (Th2) cells polarized in vitro selectively express CCR3 and CCR4 at certain stages of activation/differentiation and respond preferentially to the ligands eotaxin and monocyte-derived chemokine (MDC). However, controversy arises when the in vivo significance of this distinct expression is discussed. To address the functional role of CCR3/eotaxin and CCR4/MDC during the in vivo recruitment of Th2 cells, we have transferred effector Th cells into naive mice to induce allergic airway disease. Tracking of these cells after repeated antigen challenge has established that both CCR3/eotaxin and CCR4/MDC axes contribute to the recruitment of Th2 cells to the lung, demonstrating the in vivo relevance of the expression of these receptors on Th2 cells. We have shown that involvement of the CCR3/eotaxin pathway is confined to early stages of the response in vivo, whereas repeated antigen stimulation results in the predominant use of the CCR4/MDC pathway. We propose that effector Th2 cells respond to both CCR3/eotaxin and CCR4/MDC pathways initially, but that a progressive increase in CCR4-positive cells results in the predominance of the CCR4/MDC axis in the long-term recruitment of Th2 cells in vivo.

Adoptive Transfer↗

PubMed2000

Acetophenone-based linker for solid-phase peptide synthesis.

A new and cost-effective linker for the generation of carboxylic acid end groups on Multipin supports (SynPhase crowns) has been developed. Synthesis of the linker was based on modification of grafted polystyrene (PS) crowns to generate a hydroxyethyl moiety which is acid labile in 10-20% trifluoroacetic acid (TFA) in dichloromethane (DCM). Solid-phase syntheses of model decapeptides using this linker are described.

Acetophenones↗

PubMed2000

Solid phase synthesis of C-terminal peptide amides: development of a new aminoethyl-polystyrene linker on the Multipin solid support.

A new aminoethyl-polystyrene linker, stable at low concentrations of TFA, has been developed for the solid phase synthesis of peptide amides. The described linker is stable under conditions which remove Bu(t) protecting groups (30-50% TFA in DCM) and the desired product can be finally cleaved off the solid support in 95% TFA (5% H2O). Model peptide amides and other N-alkylated peptide amides have been successfully synthesized in good yield and purity.

Amides↗

PubMed2000

IL-12 enhances IL-2 function by inducing CD25 expression through a p38 mitogen-activated protein kinase pathway.

We previously showed that an IL-2 mutant, Q126D, could induce T cells to proliferate to the same extent as wild-type IL-2 but was unable to sensitize T cells to activation-induced cell death (AICD). Here we show that the partial signaling of Q126D is attributable to its inability to up-regulate the IL-2 receptor alpha chain (CD25). IL-12, which can up-regulate CD25 expression, enhances the ability of Q126D to induce AICD sensitivity and proliferation. IL-12 synergism with Q126D is dependent on CD25 up-regulation because the synergism is absent in CD25-deficient T cells. Inhibition of IL-12-induced up-regulation of CD25 by a p38 mitogen-activated protein (MAP) kinase inhibitor, SB203580, also ablates the synergism between IL-12 and Q126D. Although CD25 is important for IL-2-induced proliferation and AICD sensitivity, it is not absolutely required because a high concentration of IL-2 can overcome the requirement for CD25. Under physiological concentrations of IL-2, CD25 expression is critical for the function of IL-2. IL-12 can enhance the function of IL-2 by up-regulating CD25 in a p38 MAP kinase-dependent manner.

Animals↗

PubMed2000

Driving reaction time before and after anterior cruciate ligament reconstruction.

Driving reaction time was studied in 73 patients under anterior cruciate ligament (ACL) reconstruction using a computer-linked automobile simulator. Each patient was tested pre-operatively and 2, 4, 6 and 8 weeks after surgery. Stepping and standing tests were studied at each time point. Twenty-five normal subjects were also tested as controls. Pre-operative test results did not differ significantly between groups on any of the tests. Post-operatively it took 6 weeks for driving reaction time of the right ACL group to be equivalent to that of the controls, compared to 2 weeks in the left ACL group. There was a strong correlation between the stepping and standing tests and the driving reaction time; this made them good clinical tests to monitor patients' progress and to suggest the appropriate time to resume driving.

Adult↗

PubMed2000

The in vitro efficacy of varidase versus streptokinase or urokinase for liquefying thick purulent exudative material from loculated empyema.

Patients with loculated parapneumonic effusion or empyema are sometimes treated with streptokinase or urokinase in an attempt to facilitate pleural fluid drainage by liquefying the pleural exudate and destroying the fibrin membranes producing the loculation. This study evaluated the effectiveness of streptokinase, urokinase, and Varidase (the combination of streptokinase and streptodornase) in liquefying gummy, purulent, exudative material from loculated empyemas. An empyema was created by injecting 10(8) Pasteurella multocida bacteria into the pleural space of New Zealand white rabbits. Twenty specimens, each containing 0.5 g of purulent material obtained 5 days after empyema induction, were placed in test tubes. Streptokinase (15,000 IU), urokinase (10,000 IU), Varidase (4,000-15,000 IU streptodornase + 15,000 IU streptokinase) or saline was added to five sets of four test tubes each. The amount of nonliquefied material that remained after incubation with the fibrinolytic agents was quantitated. Over the 6-h incubation period, the amount of nonliquefied material decreased from 0.5 g to 0.02 g in the Varidase group but never decreased to less than 0.4 g in any of the other three treatment groups. Liquefaction of thick pleural exudates from rabbits with empyema can be achieved with Varidase but not with streptokinase or urokinase.

Animals↗

PubMed2000

Outcome of thoracoabdominal aortic operations using deep hypothermia and distal exsanguination.

BACKGROUND: Operation of the descending and thoracoabdominal aorta may be affected by a significant perioperative morbidity, mainly because of ischemic damage of the spinal cord and malperfusion of the abdominal organs. METHODS: A comparative analysis was performed on two consecutive series of patients operated between 1982 and 1998. Group 1 consisted of 90 patients operated with moderate hypothermic left heart bypass. Group 2 included 38 patients operated using deep hypothermic cardiopulmonary bypass and a period of circulatory arrest while performing the proximal anastomosis and distal exsanguination during confection of the distal anastomosis. RESULTS: Main demographic factors and causes of the aortic disease were similar in both groups. Early mortality was significantly higher in the group of patients with aortic cross-clamping (15 of 90, 16%) than in those operated with circulatory arrest (2 of 38, 5.2%), p < 0.001. Paraplegia occurred in 8 patients in the group operated with mild hypothermia (8.8%) but in only 1 patient (2.6%) when deep hypothermia had been used. CONCLUSIONS: In our experience, deep hypothermia combined with distal exsanguination significantly improved the early postoperative outcome after operation of the descending and thoracoabdominal aorta. This technique allowed easy confection of proximal and distal anastomoses, and the duration of the operation was not prolonged significantly through this approach.

Aorta↗

PubMed2000

Functional interleukin 4 receptor and interleukin 2 receptor common gamma-chain on human non-small cell lung cancers: novel targets for immune therapy.

OBJECTIVE: The interleukin 4 receptor has been demonstrated on the surface of human non-small cell lung carcinoma cell lines and tumor specimens. Interleukin 4 causes G1-phase cell-cycle arrest of non-small cell lung cancer cell lines expressing the interleukin 4 receptor; the effect directly correlates with the expression of the interleukin 4 receptor and is seen within 48 hours after treatment. We examined signal transduction pathways used by the interleukin 4 receptor that may account for growth arrest of the cell line LUst but had no effect on another non-small cell lung cancer cell line, SK-MES-1. METHODS: Western blot analysis was performed on both LUst and SK-MES-1 cell lines cultured in the presence of interleukin 4 (500 U/mL). Cells were lysed, protein extracted, and electroblotted; blots were then probed with murine monoclonal antibodies to specific intracellular proteins. RESULTS: Western blotting of the cell lines with antiphosphotyrosine antibody (4G10) demonstrated multiple (140 kd, 100-130 kd, and 65 kd) phosphoproteins seen only in the interleukin 4-treated LUst cell line and not observed in the SK-MES-1 cell lines. Immunoprecipitation and blotting of the LUst cell line with specific secondary antibodies demonstrated that the 140-kd phosphoprotein was the interleukin 4 receptor, the 130-kd phosphoprotein was Janus kinase 1, the 116-kd phosphoprotein was Janus kinase 3, and the 65-kd phosphoprotein was the interleukin 2 receptor gamma-chain. Specific binding was not observed in the non-small cell lung cancer cell line SK-MES-1, suggesting that a functional interleukin receptor gamma-chain was not present. Southern blotting with complementary DNA probes to interleukin 2 receptor gamma-chain confirmed the absence of this receptor on cell line SK-MES-1. CONCLUSIONS: These results suggest that non-small cell lung cancer cells may express functional cytokine receptors, including the interleukin 2 receptor gamma-chain commonly found in association with the lymphocyte interleukin 2 receptor. These receptors may be novel targets for directing cytokine-based immune therapy.

Carcinoma, Non-Small-Cell Lung↗