Biomedical subjects

J Du

Publications and source records attributed to J Du.

At least 19 recordsLinked to original sources

PubMed2007

Chronic ethanol feeding alters the epithelial cell proliferation and apoptosis in rat gastric mucosa.

We developed a chronic drinking rat model to investigate the long-term effects of ethanol feeding on cell proliferation and apoptosis in rat stomach. Adult male Sprague-Dawley (SD) rats received either an isocaloric control or drinking water containing 6% (v/v) ethanol as their only water intake for 1, 3, 7, 14 and 28 days. At the end of each feeding period, animals were sacrificed and the stomach was dissected for the sample preparation. The cell proliferation and apoptosis in gastric mucosa of rats in different groups were analyzed by flow cytometer, immunohistochemistry and computer image analysis. In the flow cytometric study, compared with the control, the cell apoptosis in gastric mucosa of the rats was enhanced during the exposure to the ethanol in 3rd to 28th day. Otherwise the cell proliferation was increased in 3rd to 14th days, and decreased in 28th days, respectively. The results were confirmed by immunohistochemistry and computer image analysis studied. This finding suggested that short-term chronic adequate alcohol intake may enhance the cell turnover of gastric mucosa. Long-term stimulus with the low concentration ethanol may cause the impairment of the cell turnover function of the gastric mucosa and may be one of the mechanisms underlying the gastric pathology associated with alcohol abuse.

Alcohol Drinking↗

PubMed2006

Intra-ethnic differences in genetic variants of the UGT-glucuronosyltransferase 1A1 gene in Chinese populations.

Variants within the human UGT1A1 gene are associated with irinotecan induced severely adverse reactions and hyperbilirubinemia. Intra-ethnic differences in the genetic variation and haplotypes of UGT1A1 gene have been analyzed in the present study. Relationship between the concentrations of total serum bilirubin (T-bil) and haplotype structure of UGT1A1 in healthy people were also evaluated. We genotyped five functional polymorphisms including -3279T>G and -3156G>A in the enhancer region, (TA)6>7 in the TATA box, and 211G>A (G71R), 686C>A (P229Q) in the exon1 region of UGT1A1 in three groups of healthy Chinese ethnic populations, consisting of 264 subjects of She origin, 539 of Han origin and 273 of Dong origin. The distribution of -3279T>G, (TA)6>7, 211G>A of UGT1A1 differed greatly as between the three ethnic groups. All of six haplotypes differed considerably between at least two of the three groups, which highlighted the need to analyze clinically irinotecan toxicity relevant SNPs and haplotypes in a variety of different racial groups within the Chinese population. Total bilirubin concentration in homozygous carriers of the -3279G and (TA)7 allele were significantly higher than those in heterozygous carriers or homozygous carriers of wild-type alleles. Carriers of the variant haplotypes (-3279G; -3156A; (TA)7; 211G; 686C) had higher serum T-Bil concentrations compared with the other groups. Our results indicate that heterogeneity among different ethnic populations is possibly the result of microevolution and is relevant to studies into the effect of tailored drug treatment.

Adult↗

PubMed2006

A point mutation (R192H) in the C-terminus of human cardiac troponin I causes diastolic dysfunction in transgenic mice.

Cardiac troponin I (cTnI) mutations have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. We modeled one mutation in human cTnI C-terminus, arginine192-->histidine (R192H) by cardiac specific expression of the mutated protein (cTnI(193His) in mouse sequence) in transgenic mice. Heart tissue sections revealed neither significant hypertrophy nor ventricular dilation in cTnI(193His) mice. The main functional alteration detected in cTnI(193His) mice by ultrasound cardiac imaging examinations was impaired cardiac relaxation manifested by a decreased left ventricular end diastolic dimension (LVEDD) and an increased end diastolic dimension in both atria. The cardiac ejection fraction (EF) was not significant changed in 6- to 8-week-old cTnI(193His) mice, however, the EF was significantly decreased in cTnI(193His) mice at age of 11 months. These data indicate that individual genetic conditions and environmental factors participate together in the development of the cTnI mutation based-cardiac muscle disorders. This mouse model provides us with a tool to further investigate the pathophysiology and the development of RCM.

Animals↗

PubMed2006

Family-based association studies of the TCP1 gene and schizophrenia in the Chinese Han population.

A previous case-control study by Yang et al. indicated that the TCP1 gene in 6q25 was associated with schizophrenia in the Han population. To replicate this result, we selected eight SNPs (rs2273828, rs3818298, rs1547094, rs1547093, rs2295898, rs2295899, rs4832, rs15982) spanning the whole gene and performed a family-based study using 325 trios samples. Our transmission disequilibrium test showed neither allele nor haplotype association with schizophrenia, and suggests that the TCP1 locus is not associated with schizophrenia in the Chinese population. Since 6q25 has consistently been found to be a susceptible region for schizophrenia, we suggest that other genes within this region should be the focus of attention.

Adult↗

PubMed2006

Transmission disequilibrium test provides evidence of association between promoter polymorphisms in 22q11 gene DGCR14 and schizophrenia.

Recent research has suggested that the DiGeorge syndrome critical region gene 14 (DGCR14) exhibits activity differences of more than 1.5 fold between the haplotypes of the variants in the promoter region. DGCR14 is located at 22q11.21, an acknowledged region for susceptibility to schizophrenia. To test the hypothesis that DGCR14 may be involved in the etiology of the disease, we carried out a family-based association study between the reported functional markers and schizophrenia in 235 Chinese Han trios. We found significant evidence of preferential transmission of the promoter variants of DGCR14 across all the trios (Best p-value = 0.00038, Global p-value = 0.0008). The positive results have suggested that DGCR14 is likely to play an important role in the etiology of schizophrenia in the Chinese Han population.

Adult↗

PubMed2006

High-resolution, time-resolved MRA provides superior definition of lower-extremity arterial segments compared to 2D time-of-flight imaging.

PURPOSE: To evaluate a novel time-resolved contrast-enhanced (CE) projection reconstruction (PR) magnetic resonance angiography (MRA) method for identifying potential bypass graft target vessels in patients with Class II-IV peripheral vascular disease. MATERIALS AND METHODS: Twenty patients (M:F = 15:5, mean age = 58 years, range = 48-83 years), were recruited from routine MRA referrals. All imaging was performed on a 1.5 T MRI system with fast gradients (Signa LX; GE Healthcare, Waukesha, WI). Images were acquired with a novel technique that combined undersampled PR with a time-resolved acquisition to yield an MRA method with high temporal and spatial resolution. The method is called PR hyper time-resolved imaging of contrast kinetics (PR-hyperTRICKS). Quantitative and qualitative analyses were used to compare two-dimensional (2D) time-of-flight (TOF) and PR-hyperTRICKS in 13 arterial segments per lower extremity. Statistical analysis was performed with the Wilcoxon signed-rank test. RESULTS: Fifteen percent (77/517) of the vessels were scored as missing or nondiagnostic with 2D TOF, but were scored as diagnostic with PR-hyperTRICKS. Image quality was superior with PR-hyperTRICKS vs. 2D TOF (on a four-point scale, mean rank = 3.3 +/- 1.2 vs. 2.9 +/- 1.2, P < 0.0001). PR-hyperTRICKS produced images with high contrast-to-noise ratios (CNR) and high spatial and temporal resolution. 2D TOF images were of inferior quality due to moderate spatial resolution, inferior CNR, greater flow-related artifacts, and absence of temporal resolution. CONCLUSION: PR-hyperTRICKS provides superior preoperative assessment of lower limb ischemia compared to 2D TOF.

Aged↗

PubMed2006

Technique for rapid in vitro single-cell elastography.

Statistically meaningful assays require scanning a large number of cells in a short time. Here we present a technique for rapid in vitro single-cell elastography. The technique is based on atomic force acoustic microscopy but (1) requires only a few minutes of scan time, (2) can be used on live cells briefly removed from most of the nutrient fluid, (3) does negligible harm or damage to the cell, (4) provides semiquantitative information on the distribution of modulus across the cell and (5) yields data with 1- to 10-nm resolution. We describe the new technique in detail, apply it to baby hamster kidney cells, verify the results and calibrate the images with atomic force microscope force-distance measurements. The technique enables rapid assessment of physical/biochemical signals on the cell modulus and contributes to current understanding of cell mechanics.

Animals↗

PubMed2006

A proposed alternative to phase-space recycling using the adaptive kernel density estimator method.

We have implemented a nonparametric density estimation technique, the adaptive kernel density estimator (AKDE), to generate additional phase space (PS) variables in the vicinity of simulated PS points in Monte Carlo linear accelerator simulation. The method involves the placement of kernels at simulated PS points that have a "window width" that depends on the density of simulated PS points. This method has been tested on known one-dimensional (1-D) and two-dimensional (2-D) probability density functions (PDFs) and has been used to sample (photons only) from PS files generated from accelerator simulations. The original simulated PS vector (x, y, u, v, E) was reduced to a rotationally invariant PS vector (r, theta, alpha, E) that takes advantage of the azimuthal symmetry (phi) above the collimating jaws. The new PS vector (r', theta', alpha', E') is sampled in the vicinity of the sampled PS vector (r, theta, alpha, E). The first step in assessing the accuracy of the method was a correlation analysis among the AKDE generated PS variables compared with correlations among the original PS variables. "In-air" particle fluence distributions between AKDE samples and the original PS distribution showed agreement within 2% (-8.8% to 6.8%) across the entire phase space plane. Central axis energy distributions and angular distributions agreed on average to within 1.5% (range = -1.5% to 6.6%) and 0.1% (range = 0 to 3.0%), respectively. Dose profiles were calculated for field sizes 3 x 3 cm2, 10 x 10 cm2, and 30 x 30 cm2 for AKDE and compared against calculations performed with PS recycling. AKDE calculated depth doses and profiles were within 2% and 2%/1 mm, respectively, of those computed using PS recycling.

Algorithms↗

PubMed2006

A novel mutation in ALK-1 causes hereditary hemorrhagic telangiectasia type 2.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant bleeding disorder and has two variants, HHT1 and HHT2, associated with mutations in the ENG and ALK-1 genes, respectively. We identified one Chinese HHT2 family to investigate the pathogenic gene and its possible mechanism of action by mutation screening and functional study. One substitution mutation (1717C>T) in exon 10 of the ALK-1 was found by sequencing of all exons of ENG and ALK-1 and caused a R479X mutation in the ALK-1 protein. ALK-1 mRNA and plasma thrombomodulin were measured by real-time quantitative PCR and ELISA, respectively. There was no significant difference in the expression levels of ALK-1 mRNA between patients and healthy individuals. A significantly higher level of thrombomodulin was found in HHT patients. These findings indicate that the mutation causes truncation of the ALK-1 protein at the post-transcriptional level; the plasma thrombomodulin may provide an easy diagnostic indicator in HHT patients.

Activin Receptors, Type II↗

PubMed2006

Artifact simulating subarachnoid and intraventricular hemorrhage on single-shot, fast spin-echo fluid-attenuated inversion recovery images caused by head movement: A trap for the unwary.

BACKGROUND AND PURPOSE: Single-shot, fast spin-echo, fluid attenuated inversion recovery (SS-FSE-FLAIR) images are frequently used to detect disease in the brain and subarachnoid space in confused or uncooperative patients who may move during the examination. In some of these patients, high signal intensity areas are seen on good-quality images in the subarachnoid space and ventricular system in locations not associated with high CSF flow. These artifacts may simulate hemorrhage or leptomeningeal disease. The purpose of this article was to determine the cause of these artifacts, describe ways to recognize them, and find methods to reduce or eliminate them. METHODS: Healthy volunteers were studied on 6 occasions with conventional multisection FSE-FLAIR images and SS-FSE-FLAIR images while at rest and while nodding and rotating their heads at different speeds. In addition, SS-FSE-FLAIR images with different section widths of the initial inverting pulse and a non-section-selective initial inversion pulse were performed with the subjects moving their heads in the same way. The scans of 30 successive patients with acute neurologic syndromes who had been studied with SS-FSE-FLAIR sequences were reviewed for evidence of high signal intensity in the CSF in regions not associated with high CSF flow. RESULTS: Each of the volunteers showed areas of increased signal intensity in CSF at sites apart from those associated with rapid pulsatile CSF flow on SS-FSE-FLAIR images acquired during head motion. The images were otherwise virtually free of motion artifact. The use of a wider initial inversion pulse section and a non-section-selected initial inversion pulse reduced the extent of these artifacts. Nineteen of the 30 patients showed areas of high signal intensity in the CSF in regions not associated with highly pulsatile CSF flow. Six of these patients had negative lumbar punctures for blood and xanthochromia and normal CSF protein levels. CONCLUSION: High signal intensity artifacts may be seen in CSF as a result of head movement on otherwise artifact-free images when imaging uncooperative patients with SS-FSE-FLAIR sequences. These artifacts have a different mechanism and distribution from those caused by CSF pulsation and may simulate subarachnoid and intraventricular hemorrhage. Artifact recognition is aided by signs of patient motion during the examination. The artifacts can be reduced by use of increased section width and non-section-selective initial inversion pulses. Recognition of these artifacts is important, because the circumstances in which the SS-FSE-FLAIR sequence is used and the particular properties of the sequence may conspire to produce a trap for the unwary.

Adult↗

PubMed2005

Kainate-induced excitation and sensitization of nociceptors in normal and inflamed rat glabrous skin.

This study investigates contributions of peripheral kainate receptors to acute nociception and persistent inflammatory pain in rat. Immunohistochemical analysis of kainate receptor expression using antibodies recognizing glutamate receptor subunits 5, 6, and 7 demonstrates that 28% of unmyelinated axons in normal digital nerve are positively labeled. Following intraplantar injection of complete Freund's adjuvant, a significant increase in glutamate receptor subunits 5, 6, and 7-labeled axons occurs at 2 days (40%), but not 7 (31%) or 14 days (28%) post-complete Freund's adjuvant. In behavioral studies, we confirm an increased mechanical sensitivity in complete Freund's adjuvant-injected hind paws. Furthermore, activation of kainate receptors following intraplantar injection of 1.0 mM kainate in normal animals results in a mechanical sensitivity similar to that observed in inflamed animals. A 1.0 mM kainate injection into inflamed hind paws further enhances the mechanical sensitivity. Injection of the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (0.1 mM) reverses complete Freund's adjuvant-induced mechanical sensitivity through a local effect. In single unit recordings from nociceptors in a glabrous skin-nerve preparation, mechanical sensitization is present in inflamed skin evidenced by a decrease in mechanical threshold and an increase in discharge rate during a suprathreshold, constant force stimulus. Thermal sensitization is also present evidenced by a decrease in heat threshold. There is a dose-dependent increase in kainate-induced nociceptor activity in both normal and inflamed skin but the kainate required to induce activation is reduced in inflamed skin. Although proportions of kainate-activated nociceptors are the same in normal and inflamed skin, the kainate-induced mean discharge rate is significantly enhanced in inflamed skin. Exposure of normal and inflamed nociceptors to 0.3 mM kainate sensitizes fibers to re-application of kainate and heat. This sensitization is blocked in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione or the glutamate receptor subunit 5 selective antagonist 3S,4aR,6S,8aR-6-[4-carboxy-phenyl] methyl-1,2,3,4,4a,5,6,7,8,8a-deca-hydroisoquinoline-3-carboxylic acid. The data indicate that peripheral kainate receptors not only play an important role in normal nociception but also contribute to mechanical sensitivity and heat sensitization accompanying inflammatory pain.

Animals↗

PubMed2005

Failure to find association between TRAR4 and schizophrenia in the Chinese Han population.

The TRAR4 gene locates in SCZD5 (MIM 603175), which a number of studies have linked with schizophrenia. One recent study suggested that three TRAR4 variants (M1: rs4305745, P=0.0014; M2: rs6903874, P=0.0026; M3: rs6937506, P=0.0052) in the 3'-UTR were associated with schizophrenia. To replicate these findings, we conducted a family-based association study within a sample of 235 Chinese Han trios. However, we didn't find significant evidence of preferential transmission of the three variants across all the trios (all P values>0.2). Thus, we conclude that TRAR4 is not a major or independent determinant in the occurrence of schizophrenia in the Chinese Han population.

Adult↗

PubMed2005

Cell-based gene therapy experiments in murine experimental autoimmune encephalomyelitis.

With the ultimate goal of developing a novel treatment for multiple sclerosis (MS), we have developed a cell-based gene therapy protocol for the treatment of murine experimental autoimmune encephalomyelitis (EAE), a powerful animal model for MS. We have determined that transduced fibroblasts secreting encephalogenic epitopes, when injected into mice with EAE, cause a striking abrogation of disease. Both myelin basic protein (MBP) and proteolipid protein mini-gene constructs expressed in syngeneic fibroblast cells were capable of ameliorating ongoing EAE induced by MBP protein. These experiments are crucial since they suggest that not all encephalogenic epitopes need be secreted for the control of disease. We also demonstrate the success of this protocol when transduced syngeneic, and most importantly, allogeneic cells are sequestered within an implantable chamber. Furthermore, we find that through modifying antigen expression by changing the signal sequence of the mini-gene construct, we were able to significantly reduce the dose of cells required for treatment. These improvements to the mini-gene delivery system are critical for the eventual translation of our protocol to the clinic.

Amino Acid Sequence↗

PubMed2005

Molecular mechanisms activating muscle protein degradation in chronic kidney disease and other catabolic conditions.

Muscle atrophy is a prominent feature of chronic kidney disease (CKD) and is frequent in other catabolic conditions. Results from animal models of these conditions as well as patients indicate that atrophy is mainly owing to accelerated muscle proteolysis in the ubiquitin-proteasome (Ub-P'some) proteolytic system. The Ub-P'some system, however, rapidly degrades actin or myosin but cannot breakdown actomyosin or myofibrils. Consequently, another protease must initially cleave the complex structure of muscle. We identified caspase-3 as an initial and potentially rate-limiting proteolytic step that cleaves actomyosin/myofibrils to produce substrates degraded by the Ub-P'some system. In rodent models of CKD and other catabolic conditions, we find that caspase-3 is activated and cleaves actomyosin to actin, myosin and their fragments. This initial proteolytic step in muscle leaves a characteristic footprint, a 14-kDa actin band, providing a potential diagnostic tool to detect muscle catabolism. We also found that stimulation of caspase-3 activity depends on inhibition of IRS-1-associated phosphatidylinositol 3-kinase (PI3K) activity; inhibiting PI3K in muscle cells also leads to expression of a critical E3-ubiquitin-conjugating enzyme involved in muscle protein breakdown: atrogin-1/MAFbx. Thus, protein breakdown by caspase-3 and the ubiquitin-proteasome system in muscle are stimulated by the same signal: a low PI3K activity. These responses could yield therapeutic strategies to block muscle atrophy.

Caspase 3↗

PubMed2004

Resistance to apoptosis of HPV 16-infected laryngeal cancer cells is associated with decreased Bak and increased Bcl-2 expression.

Human papillomavirus type 16 (HPV 16) plays an etiological role in human laryngeal carcinoma. Apoptosis is closely associated with various biological processes including oncogenesis. This study investigated how HPV 16 oncoproteins E6 and E7 affect apoptosis in human laryngeal cancer cells. We established two human laryngeal cancer cell lines that expressed HPV 16 E6 and E7, respectively. Using these two cell lines, we found that both E6 and E7 exhibited an inhibitive effect on apoptosis induced by tumor necrosis factor alpha and cycloheximide. In both transfected cell lines, the expression of pro-apoptotic Bak was reduced and that of anti-apoptotic Bcl-2 was over-expressed. However, the expression of caspase-3 and caspase-8 was not significantly different between the E6- and E7-transfected cells and the control cells without HPV 16. p53 Protein was not detected in either the transfected or the non-transfected cells. Our study indicates that: (1) HPV 16 E6 and E7 oncoproteins are capable of inhibiting apoptosis in laryngeal squamous carcinoma cells; (2) the mechanism modulated by E6 and E7 involves the over-expression of Bcl-2 and the down-regulation of Bak; (3) the anti-apoptotic pathway is not related to the level of p53, caspase-3, or caspase-8. These results suggest that the dysregulation of apoptotic molecules Bak and Bcl-2 by HPV 16 E6 and E7 plays a role in the prolongation of cell survival, which may subsequently contribute to the development of human laryngeal cancer.

Animals↗

PubMed2004

Artifact reduction in undersampled projection reconstruction MRI of the peripheral vessels using selective excitation.

The projection reconstruction (PR)-HyperTRICKS (time resolved imaging of contrast kinetics) acquisition integrates the benefits of through-plane Cartesian slice encoding and in-plane undersampled PR. It provides high spatial resolution both in-plane (about 1 mm(2)) and through-plane (1-2 mm), as well as relatively high temporal resolution (about 0.25 frames per second). However, undersampling artifacts that originate from anatomy superior or inferior to a coronal imaging FOV may severely degrade the image quality. In coronal MRA acquisitions, the slice coverage is limited in order to achieve high temporal resolution. In this report we describe an artifact reduction method that uses selective excitation in PR-HyperTRICKS. This technique significantly reduces undersampling streak artifacts while it increases the slice coverage.

Artifacts↗

PubMed2004

High-resolution multistation peripheral MR angiography using undersampled projection reconstruction imaging.

A novel protocol for three-station MR angiography (MRA) of the lower extremities is described. A time-resolved undersampled projection reconstruction (PR) acquisition was used to image the calf station during a first injection, and non-time-resolved PR acquisitions were used with the bolus-chase technique to image the abdomen and thigh stations during a second injection. The streak artifacts resulting from undersampling the PR data were reduced with the use of a spatial Fermi filter based on the sensitivity of each coil element in a peripheral vascular phased-array coil. This novel technique provided high spatial resolution and a broad range of coverage, and depicted the contrast dynamics in the most distal station of the lower extremities.

Abdomen↗

PubMed2004

Alteration of heme-oxygenase-carbon monoxide pathway in calcified rat vascular smooth muscle cells.

OBJECTIVE: The aim of the present study was to investigate the changes in heme-oxygenase (HO)-carbon monoxide (CO)-cyclic guanosine monophosphate (cGMP) pathway in clacified rat vascular smooth muscle cells (VSMCs). METHODS: Calcification of cultured rat VSMCs was induced by incubation of VSMCs with beta-glycerophosphate. Cellular calcium content, ALP activities and (45)Ca uptake were measured. HO activity, HbCO formation and content of cGMP in VSMCs were determined. Immunocytochemistry for HO-1 expression was observed. RESULTS: In comparison of control VSMCs, the cellular calcium content, ALP activity and (45)Ca uptake in calcified VSMCs were obviously increased. Immunocytochemistry showed that HO-1 expression was weak and not well distributed in calcified cells as compared to non-calcified VSMCs, but interestingly, there was stronger staining in calcified nodules than in VSMCs. Compared with VSMCs, HO-1 activity in calcified cells decreased by 42.7% [36.4 +/- 2.8 pmol (mg Pr x h)(-1) vs 63.5 x 5.3 pmol (mg Pr x h)(-1), p < 0.01], and HbCO formation decreased by 39.2% (3.38 x 0.69 micromol/mg Pr vs 5.56 +/- 0.48 micromol/mg Pr, p < 0.05). The cGMP content in calcified VSMCs was 78.1% lower than that of non-calcified VSMCs (4.3 +/- 0.51 vs 19.6 +/- 1.2 pmol/mg, p < 0.01). CONCLUSION: The results showed that HO-CO-cGMP pathway in calcified vascular cells obviously changed, which might contribute to disturbance of vascular function.

Animals↗