Biomedical subjects

Jie Huang

Publications and source records attributed to Jie Huang.

At least 73 records · Page 4Linked to original sources

PubMed2004

Quasi-group-velocity matching using integrated-optic structures.

We propose a device to compensate for group-velocity mismatch (GVM) effects that limit the efficiency-bandwidth product in nonlinear frequency-mixing devices. Integrated wavelength-dependent delay lines are introduced periodically in a waveguide containing a series of quasi-phase-matching (QPM) gratings. Appropriate choice of the time delays can compensate for GVM. We have demonstrated a two-stage device in a periodically poled lithium niobate waveguide. Two approximately 150-fs-long pulses generated 6 ps apart by second-harmonic generation in two QPM gratings were resynchronized by a fixed delay line, and their relative phase was fine controlled by temperature tuning. This technique, which can be iterated to more than two segments, permits optical frequency mixers with a higher efficiency-bandwidth product than would be possible in a single grating short enough to avoid GVM effects.

Journal Article↗

PubMed2004

Precision ranger for measuring large mechanical components.

We present a precision laser ranger system for the measurement of large manufactured components and structures. The system was developed based on a beat-wave interferometry principle. The light source of this system is a frequency-stabilized laser with a frequency stability of 1 x 10(-7) (in open air) or 10(-8) (in the laboratory). The laser operates in two longitudinal modes, and the two modes are generated in common resonator; therefore the two beams are naturally coaxial. The precision ranger system does not need a long guide or any heavy machinery. In this system an adaptive filter and a wavelet-transform program are used to improve the measurement accuracy. The system described here has a measuring range of 0-20 m and a measuring uncertainty of 30 microm/10 m.

Journal Article↗

PubMed2004

Regulation of flowering time in Arabidopsis by K homology domain proteins.

The transition from vegetative growth to reproductive development in Arabidopsis is regulated by multiple floral induction pathways, including the photoperiodic, the autonomous, the vernalization, and the hormonal pathways. These pathways converge to regulate the expression of a small set of genes critical for floral initiation and different signal transduction pathways can interact to govern the time to flower. One important regulator of floral initiation is the MADS-box transcription factor FLC, which acts as a negative regulator of flowering in response to both endogenous and environmental signals. In this report, we describe a study of the flowering-time gene, FLK [flowering locus K homology (KH) domain] that encodes a putative RNA-binding protein with three KH domains. The flk mutations cause delayed flowering without a significant effect on the photoperiodic or vernalization responses. FLK functions primarily as a repressor of FLC expression, although it also modestly affects expression of genes associated with the photoperiodic pathway. In addition to FLK, the expression of two other KH domain genes are modestly affected by the flk mutation, suggesting a possible involvement of more than one KH domain protein in the regulation of flowering time in Arabidopsis.

Arabidopsis↗

PubMed2004

GRK2 is an endogenous protein inhibitor of the insulin signaling pathway for glucose transport stimulation.

G protein-coupled receptor kinases (GRKs) represent a class of proteins that classically phosphorylate agonist-activated G protein-coupled receptors, leading to uncoupling of the receptor from further G protein activation. Recently, we have reported that the heterotrimeric G protein alpha-subunit, Galphaq/11, can mediate insulin-stimulated glucose transport. GRK2 contains a regulator of G protein signaling (RGS) domain with specificity for Galphaq/11. Therefore, we postulated that GRK2 could be an inhibitor of the insulin signaling cascade leading to glucose transport in 3T3-L1 adipocytes. In this study, we demonstrate that microinjection of anti-GRK2 antibody or siRNA against GRK2 increased insulin-stimulated insulin-responsive glucose transporter 4 (GLUT4) translocation, while adenovirus-mediated overexpression of wild-type or kinase-deficient GRK2 inhibited insulin-stimulated GLUT4 translocation as well as 2-deoxyglucose uptake. Importantly, a mutant GRK2 lacking the RGS domain was without effect. Taken together, these results indicate that through its RGS domain endogenous GRK2 functions as a negative regulator of insulin-stimulated glucose transport by interfering with Galphaq/11 signaling to GLUT4 translocation. Furthermore, inhibitors of GRK2 can lead to enhanced insulin sensitivity.

3T3-L1 Cells↗

PubMed2004

Oncogenic Ras promotes butyrate-induced apoptosis through inhibition of gelsolin expression.

Activation of Ras promotes oncogenesis by altering a multiple of cellular processes, such as cell cycle progression, differentiation, and apoptosis. Oncogenic Ras can either promote or inhibit apoptosis, depending on the cell type and the nature of the apoptotic stimuli. The response of normal and transformed colonic epithelial cells to the short chain fatty acid butyrate, a physiological regulator of epithelial cell maturation, is also divergent: normal epithelial cells proliferate, and transformed cells undergo apoptosis in response to butyrate. To investigate the role of k-ras mutations in butyrate-induced apoptosis, we utilized HCT116 cells, which harbor an oncogenic k-ras mutation and two isogenic clones with targeted inactivation of the mutant k-ras allele, Hkh2, and Hke-3. We demonstrated that the targeted deletion of the mutant k-ras allele is sufficient to protect epithelial cells from butyrate-induced apoptosis. Consistent with this, we showed that apigenin, a dietary flavonoid that has been shown to inhibit Ras signaling and to reverse transformation of cancer cell lines, prevented butyrate-induced apoptosis in HCT116 cells. To investigate the mechanism whereby activated k-ras sensitizes colonic cells to butyrate, we performed a genome-wide analysis of Ras target genes in the isogenic cell lines HCT116, Hkh2, and Hke-3. The gene exhibiting the greatest down-regulation by the activating k-ras mutation was gelsolin, an actin-binding protein whose expression is frequently reduced or absent in colorectal cancer cell lines and primary tumors. We demonstrated that silencing of gelsolin expression by small interfering RNA sensitized cells to butyrate-induced apoptosis through amplification of the activation of caspase-9 and caspase-7. These data therefore demonstrate that gelsolin protects cells from butyrate-induced apoptosis and suggest that Ras promotes apoptosis, at least in part, through its ability to down-regulate the expression of gelsolin.

Alleles↗

PubMed2004

NADPH oxidase contributes to angiotensin II signaling in the nucleus tractus solitarius.

Angiotensin II (AngII), acting through angiotensin type 1 (AT1) receptors, exerts powerful effects on central autonomic networks regulating cardiovascular homeostasis and fluid balance; however, the mechanisms of AngII signaling in functionally defined central autonomic neurons have not been fully elucidated. In vascular cells, reactive oxygen species (ROS) generated by the enzyme NADPH oxidase play a major role in AngII signaling. Thus, we sought to determine whether NADPH oxidase is present in central autonomic neurons and, if so, whether NADPH oxidase-derived ROS are involved in the effects of AngII on these neurons. The present studies focused on the intermediate dorsomedial nucleus of the solitary tract (dmNTS) because this region receives autonomic afferents via the vagus nerve and is an important site of AngII actions. Using double-label immunoelectron microscopy, we found that the essential NADPH oxidase subunit gp91phox is present in somatodendric and axonal profiles containing AT1 receptors. The gp91phox-labeled dendrites received inputs from large axon terminals resembling vagal afferents. In parallel experiments using patch clamp of dissociated NTS neurons anterogradely labeled via the vagus, we found that AngII potentiates the L-type Ca2+ currents, an effect mediated by AT1 receptors and abolished by the ROS scavenger Mn(III) tetrakis (4-benzoic acid) porphyrin chloride. The NADPH oxidase assembly inhibitor apocynin and the peptide inhibitor gp91phox docking sequence, but not its scrambled version, also blocked the potentiation. The results provide evidence that NADPH oxidase-derived ROS are involved in the effects of AngII on Ca2+ influx in NTS neurons receiving vagal afferents and support the notion that ROS are important signaling molecules in central autonomic networks.

Angiotensin II↗

PubMed2004

Characterization of recombinant soluble carcinoembryonic antigen cell adhesion molecule 1.

Carcinoembryonic antigen cell adhesion molecule 1 (CEACAM1) is a type 1 transmembrane, homotypic cell adhesion protein expressed on epithelial and hematopoietic cells. CEACAM1 has four major isoforms with three or four immunoglobulin (Ig)-like ectodomains and either long or short cytoplasmic domains. In a 3D model of breast epithelial cell morphogenesis, CEACAM1 plays an essential role in lumen formation [J. Cell Sci. 112 (1999) 4193]. Two soluble ectodomain isoforms of CEACAM1 expressed in myeloma cells were immunologically active and highly glycosylated. The molecular weights of the 3-ecto- and 4-ectodomain isoforms were 90 and 110kDa, respectively, and monomers by sedimentation equilibrium centrifugation. Both isoforms were prolate ellipsoids with axial ratios of 6 for the 3-ecto- and 8 for 4-ectodomain isoforms, respectively, by size exclusion chromatography and analytical ultracentrifugation. Both isoforms caused a significant reduction in lumen formation when tested in the 3D model culture system.

Animals↗

PubMed2004

Requirement of histone deacetylase activity for signaling by STAT1.

STAT1 is a transcription factor that plays a crucial role in signaling by interferons (IFNs). In this study we demonstrated that inhibitors of histone deacetylase (HDAC) activity, butyrate, trichostatin A, and suberoylanilide hydroxamic acid, prevented IFNgamma-induced JAK1 activation, STAT1 phosphorylation, its nuclear translocation, and STAT1-dependent gene activation. Furthermore, we showed that silencing of HDAC1, HDAC2, and HDAC3 through RNA interference markedly decreased IFNgamma-driven gene activation and that overexpression of HDAC1, HDAC2, and HDAC3 enhanced STAT1-dependent transcriptional activity. Our data therefore established the essential role of deacetylase activity in STAT1 signaling. Induction of IRF-1 by IFNgamma requires functional STAT1 signaling and was abrogated by butyrate, trichostatin A, suberoylanilide hydroxamic acid, and STAT1 small interfering RNA. In contrast, silencing of STAT1 did not interfere with IFNgamma-induced expression of STAT2 and caspase-7, and HDAC inhibitors did not preclude IFNgamma-induced expression of STAT1, STAT2, and caspase-7, suggesting that HDAC inhibitors impede the expression of IFNgamma target genes whose expression depends on STAT1 but do not interfere with STAT1-independent signaling by IFNgamma. Finally, we showed that inhibitors of deacetylase activity sensitized colon cancer cells to IFNgamma-induced apoptosis through cooperative negative regulation of Bcl-x expression, demonstrating that interruption of the balance between STAT1-dependent and STAT1-independent signaling significantly alters the biological activity of IFNgamma.

Active Transport, Cell Nucleus↗

PubMed2004

White spot syndrome virus (WSSV) detected by PCR in rotifers and rotifer resting eggs from shrimp pond sediments.

White spot syndrome virus (WSSV) was detected by PCR-dot blot hybridization in rotifer resting eggs from shrimp Penaeus chinensis culture-pond sediments. It was also detected in rotifers hatched from those eggs. Surface disinfection before analysis indicated that WSSV was probably present within the resting eggs. Results suggested that rotifer resting eggs may be an overwintering reservoir for WSSV in shrimp ponds.

Animals↗

PubMed2004

Cisplatin resistance is associated with deregulation in protein kinase C-delta.

Proteolytic activation of protein kinase C (PKC)-delta has been associated with cell death induced by the DNA damaging agent cisplatin. In the present study, we have examined if PKCdelta is affected when cells acquire resistance to cisplatin. The level of PKCdelta was elevated in cisplatin-resistant HeLa (HeLa/CP) cells compared to parental HeLa cells. Prolonged cellular exposure to the PKC activator phorbol-12,13-dibutyrate (PDBu), caused downregulation of PKCdelta in HeLa cells but not in HeLa/CP cells. Treatment of HeLa cells with PDBu resulted in the translocation of PKCdelta from the cytosol to the membrane but it failed to induce PKCdelta translocation in HeLa/CP cells. PDBu, however, induced translocation and downregulation of PKCalpha in both HeLa and HeLa/CP cells. The ability of PDBu to enhance cisplatin-induced cell death was attenuated in cisplatin-resistant HeLa cells. Thus, a deregulation in PKCdelta was associated with reduced cellular sensitivity to cisplatin.

Antineoplastic Agents↗

PubMed2004

Mode multiplexing in optical frequency mixers.

Asymmetric Y junctions allow the development of a new class of optical frequency mixers that utilize higher-order waveguide modes for signal processing. We measure high-contrast (>30 dB) mode sorting in asymmetric Y junctions by use of a novel technique: efficient TM00, TM10, and TM20 mode mixing in a periodically poled lithium niobate waveguide. We also demonstrate an odd-to-even mode wavelength converter capable of spectral inversion without offset or bidirectional wavelength conversion.

Journal Article↗

PubMed2004

Annexin II is a thiazolidinedione-responsive gene involved in insulin-induced glucose transporter isoform 4 translocation in 3T3-L1 adipocytes.

The target genes of peroxisomal proliferator-activated receptor-gamma ligands that lead to insulin sensitization are not fully understood. In this study, we have found that the thiazolidinedione, troglitazone, increases expression of annexin II at both the mRNA and protein levels, raising the possibility that annexin II plays a role in insulin-stimulated glucose transporter isoform 4 (GLUT4) translocation and glucose transport. To assess this, we microinjected annexin II antibody or annexin II small interfering RNA into 3T3-L1 adipocytes and found that insulin-stimulated GLUT4 translocation was inhibited by 54 and 60%, respectively. Furthermore, microinjection of annexin II antibody inhibited constitutively active Galphaq (Q209L-Galphaq)-induced but not osmotic shock-induced GLUT4 translocation. When cells were cotransfected with wild-type annexin II, along with an enhanced green fluorescent protein-cmyc-GLUT4 construct, and the percentage of cells expressing cmyc-GLUT4 at the cell surface was measured by immunofluorescence microscopy, there was a marked increase in the ability of insulin to stimulate recruitment of cmyc-GLUT4 protein to the cell surface. In summary, our results show that annexin II is a newly described thiazolidinedione response gene involved in insulin-induced GLUT4 translocation in 3T3-L1 adipocytes.

3T3 Cells↗

PubMed2004

A randomized clinical trial of a psychoeducational intervention to improve outcomes in systemic lupus erythematosus.

OBJECTIVE: In a cross-sectional study, we previously identified 2 potentially modifiable risk factors for adverse outcomes in systemic lupus erythematosus (SLE): self-efficacy and social support. The goal of this study was to evaluate in a randomized controlled trial a theory-based intervention to improve patient self-efficacy and partner support to manage SLE. METHODS: Patients with SLE ages 18 years and older who met the American College of Rheumatology criteria and were able to identify a partner (spouse or family member) were recruited from 2 academic medical centers and randomized into an experimental group or a control group. Patients in the experimental group and their partners received an intervention designed to enhance self-efficacy, couples communication about lupus, social support, and problem solving, in the form of a 1-hour session with a nurse educator followed by monthly telephone counseling for 6 months. Patients in the control group and their partners received an attention placebo, including a 45-minute video presentation about lupus, and monthly telephone calls. Measures of physical and mental health status, disease activity, and psychosocial factors were collected at baseline, 6 months, and 12 months. The effect of the intervention on physical and mental health and disease activity at 6 and at 12 months was modeled with linear regression and adjusted for baseline health status, disease activity, sociodemographic factors, treatment change, and psychosocial factors. RESULTS: One hundred twenty-two patients (plus their partners) were enrolled and randomized as follows: 64 to the experimental intervention and 58 to the attention control group. The participants were predominantly white, approximately half were college educated, and the groups were balanced for sociodemographic factors. At 6 months, significantly higher scores for couples communication (P = 0.01) and problem-focused coping (P = 0.03) were seen in the experimental group compared with the control group. At 12 months (6 months after the intervention ended), social support was higher (4.4 versus 4.1; P = 0.03), self-efficacy was higher (7.2 versus 6.2; P = 0.02), couples communication was higher (3.5 versus 3.1; P = 0.03), and fatigue was lower (5.1 versus 6.3; P = 0.02) in the experimental group compared with the control group. Global mental health status at 12 months, as measured by the Short Form 36 survey, was 69 points in the experimental group compared with 58 points in the control group (P = 0.04). In multivariate models, adjusting for baseline covariates, scores for couple communication (P = 0.01) were significantly higher at 6 months, and scores for self-efficacy (P = 0.004) and global mental health status (P = 0.03) were significantly higher at 12 months in the experimental group compared with the control group, and the mean score for global physical function was higher by 7 points, which was a clinically meaningful change (P = 0.2). The mean score for fatigue was also significantly lower in the experimental group than in the control group (P = 0.05). SLE disease activity was unchanged by this intervention. CONCLUSION: This randomized, controlled trial of a theory-based educational intervention in SLE demonstrated significantly higher scores for couple communication, self-efficacy, and mental health status, and lower fatigue scores in the experimental group compared with the control group. Because couple communication and self-efficacy appear to be modifiable risk factors, they may also be potential targets in more disadvantaged populations.

Adult↗

PubMed2004

Dimension reduction in the linear model for right-censored data: predicting the change of HIV-I RNA levels using clinical and protease gene mutation data.

With rapid development in the technology of measuring disease characteristics at molecular or genetic level, it is possible to collect a large amount of data on various potential predictors of the clinical outcome of interest in medical research. It is often of interest to effectively use the information on a large number of predictors to make prediction of the interested outcome. Various statistical tools were developed to overcome the difficulties caused by the high-dimensionality of the covariate space in the setting of a linear regression model. This paper focuses on the situation, where the interested outcomes are subjected to right censoring. We implemented the extended partial least squares method along with other commonly used approaches for analyzing the high-dimensional covariates to the ACTG333 data set. Especially, we compared the prediction performance of different approaches with extensive cross-validation studies. The results show that the Buckley-James based partial least squares, stepwise subset model selection and principal components regression have similar promising predictive power and the partial least square method has several advantages in terms of interpretability and numerical computation.

HIV Infections↗

PubMed2004

Quantitative real-time polymerase chain reaction measurement of regulators of G-protein signaling mRNA levels in mouse tissues.

Regulators of G-protein signaling (RGS) play a critical role in G-protein-coupled receptor signaling in mammalian cells. RGS proteins are GTPase-accelerating proteins (GAPs) for alpha subunits of heterotrimeric G proteins of the Gi and Gq class. RGS GAPs can modulate the frequency and duration of G-protein signaling and may constitute a new family of therapeutic targets. Identifying the tissue distribution and cellular localization of RGS proteins has been hindered by the lack of effective antibodies for immunodetection. The measurement of mRNA levels for RGS proteins, however, can provide insight into their tissue specificity and regulation. This article describes the use of a highly sensitive and rapid method for measuring RGS mRNA in mouse tissues. This quantitative real-time polymerase chain reaction method is established for the 19 reported mouse RGS genes and is used to study the tissue distribution of the R4 family of RGS genes and the diurnal regulation of RGS16 in mouse liver.

Animals↗

PubMed2004

beta-arrestin-1 competitively inhibits insulin-induced ubiquitination and degradation of insulin receptor substrate 1.

beta-arrestin-1 is an adaptor protein that mediates agonist-dependent internalization and desensitization of G-protein-coupled receptors (GPCRs) and also participates in the process of heterologous desensitization between receptor tyrosine kinases and GPCR signaling. In the present study, we determined whether beta-arrestin-1 is involved in insulin-induced insulin receptor substrate 1 (IRS-1) degradation. Overexpression of wild-type (WT) beta-arrestin-1 attenuated insulin-induced degradation of IRS-1, leading to increased insulin signaling downstream of IRS-1. When endogenous beta-arrestin-1 was knocked down by transfection of beta-arrestin-1 small interfering RNA, insulin-induced IRS-1 degradation was enhanced. Insulin stimulated the association of IRS-1 and Mdm2, an E3 ubiquitin ligase, and this association was inhibited to overexpression of WT beta-arrestin-1, which led by decreased ubiquitin content of IRS-1, suggesting that both beta-arrestin-1 and IRS-1 competitively bind to Mdm2. In summary, we have found the following: (i) beta-arrestin-1 can alter insulin signaling by inhibiting insulin-induced proteasomal degradation of IRS-1; (ii) beta-arrestin-1 decreases the rate of ubiquitination of IRS-1 by competitively binding to endogenous Mdm2, an E3 ligase that can ubiquitinate IRS-1; (iii) dephosphorylation of S412 on beta-arrestin and the amino terminus of beta-arrestin-1 are required for this effect of beta-arrestin on IRS-1 degradation; and (iv) inhibition of beta-arrestin-1 leads to enhanced IRS-1 degradation and accentuated cellular insulin resistance.

Acetylcysteine↗

PubMed2004

[Osteogenesis characteristics of cultured rat mesenchymal stem cells under bone induction condition].

OBJECTIVE: To investigate the osteogenesis characteristics of cultured rat mesenchymal stem cells (MSCs) under bone induction condition. METHODS: MSCs were isolated from adult rat by using density gradient separation method. The osteogenic inducers were compounds of Dexone, beta-glycerophosphate sodium and vitamin C. RESULTS: The MSC attachment formed soon after the seeding and grew into colonies with the appearance of fibroblastic cells. The osteogenic inducer with low dose of Dexone could promote the osteogenic differentiation of MSC. In the group of osteogenic inducer with low dose of Dexone, the expression of alkaline phosphatase (ALP) was remarkably increased after one week's induction, and the number of positive cells was (15.1 +/- 2.6), significantly higher than that of the control group (12.0 +/- 3.5) (P < 0.01). The calcified deposits began to appear in the group of osteogenic inducer with low dose of Dexone after one week's induction and was increased remarkably after three weeks, and the number of calcified deposits was (9.0 +/- 1.7), significantly higher than that of the control group (2.0 +/- 1.8) (P < 0.01). CONCLUSION: MSC can differentiate into osteogenesis by osteogenic induction and may be used to provide seed cells for bone tissue engineering.

Alkaline Phosphatase↗

PubMed2004

Down-regulation of Bcl-2 is associated with cisplatin resistance in human small cell lung cancer H69 cells.

Overexpression of the anti-apoptotic protein Bcl-2 has been associated with several malignancies, including small cell lung cancer (SCLC). In the present study, we have investigated if Bcl-2 contributes to the emergence of cisplatin resistance in SCLC H69 cells. The ability of cisplatin to induce apoptosis was decreased in H69 cells that acquired resistance to cisplatin (H69/CP). The level of Bcl-2 was, however, substantially reduced in H69/CP cells compared to parental H69 cells. There was little change in Bcl-2 content in H69 cells that were resistant to etoposide (VP-16) or Taxol. Bcl-2 was constitutively phosphorylated at serine 70 in H69 cells but not in H69/CP cells and cisplatin had little effect on Bcl-2 phosphorylation. The level of procaspase-3 was elevated in H69/CP cells but the ability of cisplatin to induce mitochondrial depolarization, caspase-9 activation, and poly(ADP-ribose) polymerase (PARP) cleavage was compromised in H69/CP cells. The level of the anti-apoptotic protein Bcl-x(L) and the pro-apoptotic protein Bax was slightly reduced in H69/CP cells but the ratio of pro-apoptotic and anti-apoptotic Bcl-2 family proteins was not sufficient to explain cellular resistance to cisplatin. These results suggest that the acquisition of cisplatin resistance by H69 cells was not due to an increase in the level/phosphorylation status of the anti-apoptotic protein Bcl-2.

Acetophenones↗