Biomedical subjects

Jing Zhang

Publications and source records attributed to Jing Zhang.

At least 55 records · Page 3Linked to original sources

PubMed2006

Surface-plasmon microscopy with a two-piece solid immersion lens: bright and dark fields.

We report bright-field and dark-field surface-plasmon imaging using a modified solid immersion lens and a commercial objective of moderate NA in the epi configuration. The contrast and resolution are extremely good, giving well-resolved images of protein monolayers both in air and in water. We also describe a two-part solid immersion lens that allows the sample to be moved without degrading the image quality in any observable way. The merits of the two-part lens are discussed and compared to commercially available microscope objectives. Finally, we introduce a simple Green's function model that illustrates the key features of both bright-field and dark-field surface-plasmon imaging.

Equipment Design↗

PubMed2006

DQB10301 and DQB10601 modulate narcolepsy susceptibility in Koreans.

The association of narcolepsy with HLA-DQB1*0602 is established in Japanese, African-Americans, European, and North American Caucasians. We examined DRB1, DRB3, DRB4, DRB5, DQA1, and DQB1 in 163 patients with centrally mediated daytime sleepiness (100 with narcolepsy) and 211 Korean controls. In this population, the DQB1*0602 association was always evident in the context of the DRB1*1501-DQA1*0102-DQB1*0602 haplotype. The DQB1*0602 association was highest in cases with hypocretin deficiency (100% vs 13% in controls), most of which had narcolepsy-cataplexy (81%). A weaker DQB1*0602 (45%) association was present in cases without cataplexy. No human leukocyte antigen (HLA) association was present in idiopathic hypersomnia or in cases with normal cerebrospinal fluid (CSF) hypocretin-1. As in other populations, DQB1*0602 homozygosity increased risk in cases with cataplexy and/or hypocretin deficiency (odds ratio = 2.0 vs heterozygotes). Non-DQB1*0602 allelic effects were also observed but could not be interpreted in the context of DQB1*0602 overabundance and linkage disequilibrium. We therefore next analyzed compound heterozygote effects in 77 subjects with either hypocretin deficiency or cataplexy and one copy of DRB1*1501-DQA1*0102-DQB1*0602, a sample constructed to maximize etiologic homogeneity. In this analysis, we found additional predisposing effects of DQB1*0301 and protective effects for DQA1*0103-DQB1*0601. Unexpectedly, the predisposing effects of DQB1*0301 were present in the context of various DQA1-bearing haplotypes. A predisposing effect of DQA1*0303 was also suggested. These results indicate a remarkable consistency in the complex HLA association present in narcolepsy across multiple ethnic groups.

Genetic Predisposition to Disease↗

PubMed2006

The repression of human differentiation-related gene NDRG2 expression by Myc via Miz-1-dependent interaction with the NDRG2 core promoter.

The N-myc downstream-regulated gene 1 (ndrg1) is highly expressed in N-myc knock-out mice through an unknown regulatory mechanism. As one member of the human NDRG gene family, NDRG2 encodes a protein highly homologous to Ndrg1. However, it is uncertain whether the expression of human NDRG2 is regulated by Myc because mouse ndrg2 and -3 are not affected by Myc. In this study, we provide the novel evidence that the expression of human NDRG2 is down-regulated by Myc via transcriptional repression. A high level of NDRG2 was observed as Myc expression was reduced in differentiated cells, whereas a low level of NDRG2 was shown following increased Myc expression upon serum stimulation. The ectopic expression of c-Myc dramatically reduces the cellular Ndrg2 protein and mRNA level. We further identified the core promoter region of NDRG2 that is required for Myc repression on NDRG2 transcription, and we verified the interaction of Myc with the core promoter region both in vitro and in vivo. Moreover, the c-Myc-mediated repression of NDRG2 requires association with Miz-1, and possibly the recruitment of other epigenetic factors, such as histone deacetylases, to the promoter. The regulatory function of Myc on NDRG2 gene expression implicated the role of the Ndrg2 in regulating cell differentiation.

Animals↗

PubMed2006

[Alterations of intermedin and its receptor system in oleic acid-induced acute lung injury of rats].

OBJECTIVE: To investigate the changes of pulmonary IMD and its receptor system-calcitonin receptor-like receptor (CL) and receptor activity modifying proteins (RAMPs) mRNA in acute lung injury(ALI) induced by oleic acid of rats. METHODS: Contents of IMD in plasma and lung homogenates were measured by radioimmunoassay(RIA). The lung mRNA of IMD, CL and RAMPs was determined by semi-quantitative RT-PCR. RESULTS: Compared with control group, in ALI group, the contents of IMD1-53 in plasma and lung homogenates were decreased by 20.8% and 74.5% (all P < 0.05) , respectively. Furthermore , it was found that the levels of IMD, CL, RAMP1 and RAMP2 mRNA in lung were decreased by 30%, 38%, 26% and 37.9% (all P < 0. 05) , respectively. The levels of CL , RAMP1 or RAMP2 mRNA were positively correlated with down-regulations of IMD mRNA in ALI. However, compared with control group, the maximum binding capacity of IMD1-53 to plasma membranes was significantly increased in ALI group, and the affinity of IMD1-53 for its receptor almost had no change. CONCLUSION: The amount of IMD 1-53 is down-regulated and IMD receptor system also down-regulated in Oliec acid induced ALI of rats. These changes suggest that IMD and its receptor system probably are involved in the development of ALI.

Acute Disease↗

PubMed2006

[Difference analysis on proteome of Helicobacter pylori in patients with peptic ulcer, gastritis, and gastric cancer].

OBJECTIVE: To identify the different proteins of Helicobacter pylori (H. pylori) in gastric cancer, peptic ulcer, and gastritis initially. METHODS: H. pylori in the endoscopic biopsy specimens of gastric mucosa of patients with gastric cancer, peptic ulcer, or gastritis, 3 specimens for each disease, were separated and cultured. The whole-cell protein of the H. pylori was extracted by lysis buffer and sonication. The protein concentration of the bacteria cell lysates was measured by the Bradford method. The protein maps of H. pylori were obtained by two-dimensional gel electrophoresis (2-DE) and the different proteins in gastric cancer, peptic ulcer and gastritis were analyzed by Image Master v 5.0. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF-MS) were performed to identify the different proteins. The differential proteins were searched by the Mascot database at www.matrixscience.com. RESULTS: Four protein spots of H. pylori were over-expressed in the protein maps from gastric cancer in comparison with those from peptic ulcer and gastritis. Mass identification showed that the 4 proteins were thioredoxin, adenylate kinase, single-stranded DNA-binding protein, and ribosomal protein 50S L7/L12, with the Mowse scores of 94, 286, 139 and 132, and with the sequence coverage rates of 77%, 33%, 33%, and 28% respectively. CONCLUSION: Anti-oxidant and inhibiting apoptosis, thioredoxin may be related to gastric carcinogenesis induced by H. pylori. Proteomics technology has a widespread perspective in the field of relationship between pathogenic bacteria and gastric cancer.

Adult↗

PubMed2006

Modulatory effects and afferent pathways of gastric electrical stimulation on rat thoracic spinal neurons receiving input from the stomach.

Gastric electrical stimulation (GES) has been suggested as a potential therapy for patients with obesity or gastric motility disorders. The aim of this study was to investigate the spinal mechanism of GES effects on gastric functions. Extracellular potentials of single spinal (T9-T10) neurons were recorded in pentobarbital anesthetized, paralyzed, ventilated male rats (n=19). Gastric distension (GD) was produced by air inflation of a balloon. One pair of platinum electrodes (1.0-1.5cm apart) was sutured onto the serosal surface of the lesser curvature of the stomach. GES with four sets of parameters was applied for 1min: GES-A (6mA, 0.3ms, 40Hz, 2s on, 3s off), GES-B (6mA, 0.3ms, 14Hz, 0.1s on, 5s off), GES-C (6mA, 3ms, 40Hz, 2s on, 3s off), GES-D (6mA, 200ms, 12pulses/min). 62/158 (39%) spinal neurons responded to GD (20, 40, 60mmHg, 20s. Most GD-responsive neurons (n=43) had excitatory responses; the remainder had inhibitory (n=12) or biphasic responses (n=7). GES-A, -B, -C and -D affected activity of 12/33 (36%), 4/31 (13%), 22/29 (76%) and 13/30 (43%) GD-responsive neurons, respectively. Bilateral cervical vagotomy did not significantly alter mean excitatory neuronal responses to GD (n=5) or GES (n=6). Resiniferatoxin (2.0microg/kg, i.v.), an ultrapotent agonist of vanilloid receptor-1, abolished excitatory responses to GD and GES in 4/4 neurons recorded in vagotomized rats. The results suggested that GES mainly had an excitatory effect on T9-T10 spinal neurons with gastric inputs; neuronal responses to GES were strengthened with stimulation at an increased pulse width and/or number of pulses. The modulatory effect of GES involved thoracic spinal (sympathetic) afferent fibers containing vanilloid receptor-1.

Action Potentials↗

PubMed2006

Precision measurement of ultralow losses of an asymmetric optical microcavity.

The losses of the transmission, absorption, and scattering of optical mirrors govern the extraction efficiency of a nonclassical state that is generated inside a cavity. By measuring the reflectivities and transmittances and the matching factors from both sides of a super-mirror-made microcavity at various mode-matching efficiencies, the transmission losses and the unwanted losses, including the absorption and scatter losses, of the left and right cavity mirrors were both determined at the parts-per-million level.

Journal Article↗

PubMed2006

Targeting PKC in multiple myeloma: in vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCl).

In multiple myeloma (MM) protein kinase C (PKC) signaling pathways have been implicated in cell proliferation, survival, and migration. Here we investigated the novel, orally available PKC-inhibitor enzastaurin for its anti-MM activity. Enzastaurin specifically inhibits phorbol ester-induced activation of PKC isoforms, as well as phosphorylation of downstream signaling molecules MARCKS and PKCmu. Importantly, it also inhibits PKC activation triggered by growth factors and cytokines secreted by bone marrow stromal cells (BMSCs), costimulation with fibronectin, vascular endothelial growth factor (VEGF), or interleukin-6 (IL-6), as well as MM patient serum. Consequently, enzastaurin inhibits proliferation, survival, and migration of MM cell lines and MM cells isolated from multidrug-resistant patients and overcomes MM-cell growth triggered by binding to BMSCs and endothelial cells. Importantly, strong synergistic cytotoxicity is observed when enzastaurin is combined with bortezomib and moderate synergistic or additive effects when combined with melphalan or lenalidomide. Finally, tumor growth, survival, and angiogenesis are abrogated by enzastaurin in an in vivo xenograft model of human MM. Our results therefore demonstrate in vitro and in vivo efficacy of the orally available PKC inhibitor enzastaurin in MM and strongly support its clinical evaluation, alone or in combination therapies, to improve outcome in patients with MM.

Administration, Oral↗

PubMed2006

A multistep oriented attachment kinetics: coarsening of ZnS nanoparticle in concentrated NaOH.

Crystal growth of ZnS nanoparticles during hydrothermal coarsened in 4 M NaOH occurs via a two-stage process. In the first stage, the primary particles grow into a size over hundred times of the original volume. The initial growth rate can be fitted by an asymptotic curve. High-resolution transmission electron microscope (HRTEM) data indicate that in this stage, crystal growth mainly occurs via a multistep crystallographically specific oriented attachment (OA). The higher the coarsening temperature, the earlier the first stage ends. In the second stage, an abrupt transition from asymptotic to square parabola growth kinetics occurs. The crystal growth data can be fitted by a standard Ostwald ripening (OR) model consistent with growth controlled by dissolution/precipitation of ions in solution. HRTEM data indicate that a minor amount of OA-based growth also occurs in the early period of the second stage. A new multistep OA kinetics model analogous to the reaction between molecules was proposed to illustrate the asymptotic growth in the first stage of coarsening. The effect of concentrated NaOH was discussed and proved to be the key that hindered the OR process, attributing to the almost exclusive pure OA-based growth of ZnS particles in the first stage.

Journal Article↗

PubMed2006

Primary transcripts and expressions of mammal intergenic microRNAs detected by mapping ESTs to their flanking sequences.

MicroRNAs (miRNAs) are a class of approximately 22-nt small RNAs that regulate posttranscriptional gene expression. Thousands of expressed sequence tags (ESTs) have been identified by using upstream 2500-nt and downstream 4000-nt flanking sequences to BLAST in the dbEST database. The cotranscription of the miRNAs and their flanking sequences covered by the matched ESTs is verified by RT-PCR. It directly reveals that a large portion of mammalian intergenic miRNAs are first transcribed as long primary transcripts (pri-miRNAs). Also, the transcripts' ranges of tens of pri-miRNAs are predicted by the EST-extension method. We then extracted the tissue-specific expression information from the annotations of the matched ESTs and established the expression profile of the studied miRNAs for tens of tissues. This provided a new way to establish the expression profiles of miRNAs. Results show that the human brain, lung, liver, and eye and the mouse brain, eye, and mammary gland are tissues in which enriched numbers of miRNAs are expressed.

3' Flanking Region↗

PubMed2006

Vaccination with viable human umbilical vein endothelial cells prevents metastatic tumors by attack on tumor vasculature with both cellular and humoral immunity.

PURPOSE: Because tumor endothelium is rarely targeted by immunity but is critically important for tumor growth, the immunity against tumor endothelium is to be developed as a novel antitumor strategy. EXPERIMENTAL DESIGN: First, viable human umbilical vein endothelial cells (HUVEC) were immunized to C57BL/6 and BALB/c mice to evoke specific CTLs as well as antibodies against tumor endothelium. Lewis lung carcinoma or myeloma cells were subsequently inoculated to evaluate the effect on tumor growth by vaccination. Second, the effect on tumor metastasis by vaccination was studied using tumor-resected mice receiving HUVEC immunization 3 days after excision. Third, the immune sera and T lymphocytes from HUVEC-immunized mice were transferred to tumor-bearing mice and added to cultured HUVECs to investigate their antiproliferative effect. RESULTS: Viable HUVEC immunization showed potent antitumor effects in Lewis lung carcinoma and myeloma tumor models. Both immune sera and CTL inhibited tumor growth and specifically suppressed proliferation of HUVECs. Particularly, tumors entirely disappeared on day 90 after tumor inoculation in four of six tumor-bearing mice receiving CTL therapy. In a metastatic tumor model, we found that the HUVEC vaccination prolonged life span from 30.9 to 41.5 days after tumor resection compared with PBS-treated mice without apparent side effects. CONCLUSIONS: Vaccination with viable HUVECs evoked both humoral and cellular immunity against tumor microvasculature, and therefore significantly inhibited tumor growth and prolonged life span of tumor-resected mice. This may provide with a novel treatment for metastatic tumors. Moreover, we have established a convenient method to evoke specific CTL against tumor angiogenesis.

Animals↗

PubMed2006

Effect of intestinal lymphatic circulation blockage in two-hit rats.

AIM: To study the effect of blocking intestinal lymphatic circulation in two-hit rats and explore the significance of intestinal lymphatic circulation in two-hit. METHODS: Wistar rats were divided equally into three groups: mesenteric lymph duct ligation group, non-ligation group and sham group. Mesenteric lymph was diverted by ligation of mesenteric lymph duct, and the two-hit model was established by hemorrhage and lipopolysaccharide (LPS) methods. All rats were sampled for serum pre-experiment and 24 h post-experiment. The organs including kidney, liver, lung and heart were collected for pathomorphologic observation and biochemical investigation. The nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD) were determined in serum and tissue homogenate. RESULTS: Pathomorphology study showed that the structures of kidney, lung, liver and heart tissues were normal in sham group; congestion, degeneration and necrosis in non-ligation group; but only mild lesions in ligation group. After two-hits, the contents of AST, ALT, BUN, Cr and LDH-1 in the serum of non-ligation group and ligation group were obviously higher than that in pre-experiment group and sham group, but obviously lower than that in non-ligation group. The contents of NO(2)(-)/NO(3)(-), NOS, iNOS and MDA in the serum of non-ligation group were significantly increased, compared with pre-experiment and sham group, but SOD was significantly lower. These parameters were significantly different in ligation group compared with that in sham group, but NO2-/NO3-, iNOS and MDA in ligation group were significantly lower than that in non-ligation group. CONCLUSION: Ligation of mesenteric lymph duct could improve the disturbance of organic function and morphologic damage in two-hit rats; the lymphatic mechanism in two-hit should be emphasized.

Animals↗

PubMed2006

Pathology of the thyroid in severe acute respiratory syndrome.

The severe acute respiratory syndrome (SARS) epidemic started in November 2002 and spread worldwide. The pathological changes in several human organs of patients with SARS have been extensively described. However, to date, little has been reported about the effects of this infection on the thyroid gland. Femoral head necrosis and low serum triiodothyronine and thyroxine levels, commonly found in patients with SARS, raise the possibility of thyroid dysfunction. We have undertaken this study to evaluate for any potential injury to the thyroid gland caused by SARS on tissue samples obtained from 5 SARS autopsies. The terminal deoxynucleotidyl transferase-mediated dUPT nick end-labeling assay was performed to identify apoptotic cells. The follicular epithelium was found to be damaged with large numbers of cells exfoliated into the follicle. The terminal deoxynucleotidyl transferase-mediated dUPT nick end-labeling assay demonstrated many cells undergoing apoptosis. Follicular architecture was altered and showed distortion, dilatation, and collapse. No distinct calcitonin-positive cells were detectable in the SARS thyroids. In conclusion, both parafollicular and follicular cells were injured. This may provide an explanation both for low serum triiodothyronine and thyroxine levels and the osteonecrosis of the femoral head associated with patients with SARS. Apoptosis may play a role in the pathogenesis of SARS associated coronavirus infection in the thyroid gland.

Adult↗

PubMed2006

Auditory cortical responses evoked by pure tones in healthy and sensorineural hearing loss subjects: functional MRI and magnetoencephalography.

BACKGROUND: Blood oxygen level dependent functional magnetic resonance imaging (fMRI) and magnetoencephalography are new techniques of brain functional imaging which can provide the information of excitation of neurons by measure the changes of hemodynamics and electrophysiological data of local brain tissue. The purpose of this study was to study functional brain areas evoked by pure tones in healthy and sensorineural hearing loss subjects with these techniques and to compare the differences between the two groups. METHODS: Thirty healthy and 30 sensorineural hearing loss subjects were included in this study. In fMRI, block-design paradigm was used. During the active epoch the participants listened to 1000 Hz, sound pressure level 140 dB pure tones at duration 500 ms, interstimulus interval 1000 ms, which presented continuously via a magnetic resonance-compatible audio system. None stimulus was executed in control epoch. In magnetoencephalography study, every subject received stimuli of 1000 Hz tone bursts delivered to the bilateral ear at duration 8 ms, interstimulus intervals 1000 ms. Sound pressure level in healthy subjects was 30 dB; in sensorineural hearing loss subjects was 20 dB above everyone's hearing threshold respectively. All subjects were examined with 306-channel whole-scalp neuromagnetometer. RESULTS: In fMRI, all subjects showed significant activations in bilateral Heschl's gyri, anterior pole of planum temporale, planum temporale, precentral gyri, postcentral gyri, supramarginal gyri, superior temporal gyri, inferior frontal gyri, occipital lobes and cerebellums. The healthy subjects had more intensive activation in bilateral Heschl's gyri, anterior pole of planum temporale, inferior frontal gyri, left superior temporal gyri and right planum temporale than the hearing loss subjects. But in precentral gyri, postcentral gyri and occipital lobes, the activation is more intensive in the hearing loss subjects. In magnetoencephalography study, both in the hearing loss and the healthy subjects, the most evident audio evoked fields activated by pure tone were N100m, which located precisely on the Heschl's gyrus. Compared with the hearing loss subjects, N100m of the healthy subjects was stronger and had longer latencies in right hemisphere. CONCLUSIONS: Under proper pure tone stimulus the activation of auditory cortex can be elicited both in the healthy and the sensorineural hearing loss subjects. Either at objective equivalent stimuli or at subjectively perceived equivalent stimuli, the auditory responses were more intensive in healthy subjects than hearing loss subjects. The tone stimuli were processed in a network in human brain and there was an intrinsic relation between the auditory and visual cortex. Blood oxygen level dependent fMRI and magnetoencephalography could reinforce each other.

Acoustic Stimulation↗

PubMed2006

A new inducible RNAi xenograft model for assessing the staged tumor response to mTOR silencing.

Human xenograft tumor models are widely used for efficacy evaluation of potential cancer targets. siRNA is usually stably introduced into tumor cells prior to transplantation. However, silencing of the cancer therapeutic target usually results in reduced cell growth/survival in vitro and/or failure to establish tumors in vivo, thus hindering tumor response-based efficacy evaluation. The present study explored a new tumor response model based on regulated RNAi, which is more relevant from a clinical standpoint. As a proof of principle, an inducible lentiviral RNAi vector was used to silence the known cancer therapeutic target mTOR upon induction with Doxycycline (DOX). The responses to DOX-induced mTOR silencing were tested both in vitro and in vivo for prostate cancer PC3 models. Significant reduction in cancer cell survival was observed due to cell cycle arrest and apoptosis when mTOR silencing was induced in vitro. mTOR silencing also caused tumor regression for the early-staged PC3 tumors (100% tumor regressed and 45% became tumor-free). The advanced-staged tumors also demonstrated significant responses (100% regressed). Therefore, our results demonstrate the powerful utility of this new inducible xenograft tumor model for efficacy evaluation of cancer targets, and it provides a direct in vivo efficacy validation of mTOR as a cancer therapeutic target.

Animals↗

PubMed2006

Exploring candidate genes for human brain diseases from a brain-specific gene network.

It is believed that large numbers of genes are involved in common human brain diseases. Here, we propose a novel computational strategy for simultaneously identifying multiple candidate genes for genetic human brain diseases from a brain-specific gene network-level perspective. By integrating diverse genomic and proteomic datasets based on Bayesian statistical model, we built a large-scale human brain-specific gene network. Based on this network and minor prior knowledge of a specific brain disease, we can effectively identify multiple candidate genes for this disease. When four known Alzheimer's disease genes were used as the prior knowledge, among the top 46 high-scoring genes that we have found, 37 were previously reported to be associated with Alzheimer's disease. And the higher score a gene has, the more likely this gene is a disease-related one. The results suggest that the proposed method is effective, convenient, and applicable in the future genetic studies.

Alzheimer Disease↗

PubMed2006

High-content screening moves to the front of the line.

High-content screening (HCS) has been used in late-stage drug discovery for a decade. In the past few years, technological advances have expanded the role of HCS into the early stages of drug discovery, including high-throughput screening and hit-to-lead studies. More recently, computational advances in image analysis and technological advancements in general cell biology have extended the utility of HCS into target validation and basic biological studies, including RNAi screening. The use of HCS in target validation is expanding the work that can be done at this stage, especially the range of targets that can be characterized, and putting it into a more biological context.

Biological Assay↗

PubMed2006

Redox-triggered interconversion between piperidine chair conformations in a Cu(I/II) complex.

A redox-induced six-membered ring chair-chair conformational interconversion in a copper-coordinated trans-piperidine tripodal ligand is demonstrated. Each group of the 1,2,3-substituted ring can potentially ligate the metal; two equatorial groups ligate the metal in the Cu(I) state leaving a disassociated, axial group. However, all three groups (two axial and one equatorial) ligate the metal in the Cu(II) state. Exciton-coupled circular dichroism (ECCD) and 2D NMR were used to characterize the structures.

Copper↗