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Biomedical subjects

Jingbo Zhang

Publications and source records attributed to Jingbo Zhang.

At least 19 recordsLinked to original sources

Imaging of bladder cancer.

Bladder cancer is a heterogeneous and frequently multifocal disease with a variable clinical course. The management of bladder cancer is therefore challenging and complicated. CT and MR imaging have replaced the traditional excretory urography and are emerging as the imaging modalities of choice for work-up of patients who have bladder cancer. Imaging provides essential diagnostic information for detection, staging, and post-treatment follow-up of bladder cancer.

Adult↗

Imaging of kidney cancer.

Advances in molecular genetics have expanded the understanding of renal cell tumors. Now it is understood that renal cortical tumors are a family of neoplasms with distinct cytogenetics and molecular defects, unique histopathologic features, and different malignant potentials. Imaging contributes to clinical management of patients with renal tumors in providing diagnostic information for tumor detection, characterization, staging, treatment planning, and follow-up.

Adult↗

Incremental value of multiplanar cross-referencing for prostate cancer staging with endorectal MRI.

OBJECTIVE: The purpose of this study was to assess whether use of the PACS cross-referencing tool in 3D MRI improves tumor staging of prostate cancer when pathologic findings are used as the reference standard. MATERIALS AND METHODS: The institutional review board granted a waiver of informed consent for the study. Endorectal MRI at 1.5 T was performed before radical prostatectomy in 255 consecutive patients. Two radiologists unaware of the clinical data retrospectively and independently interpreted MR images without and with cross-referencing to predict the presence of extracapsular extension (ECE) and seminal vesicle invasion (SVI). Histopathologic findings were used as the reference standard. Area under the receiver operating characteristics curve (AUC), sensitivity and specificity, and weighted kappa statistics were calculated. RESULTS: At histologic examination, 68 (27%) of the patients were found to have ECE and 13 (5%) of the patients to have SVI; the latter all had ECE. In detecting ECE, both reviewers had a higher AUC using cross-referencing (p < 0.001 for both). The weighted kappa value was 0.56 for MRI alone and 0.76 for MRI with cross-referencing, indicating fair to good interobserver agreement. Sensitivity and specificity for ECE with MRI alone and with cross-referencing were 43% and 94% and 57% and 100% for reviewer 1 and 40% and 93% and 59% and 98% for reviewer 2, respectively. In detecting SVI, both reviewers had a higher AUC with cross-referencing (p = 0.007 and p = 0.056 for reviewers 1 and 2, respectively). Reviewer 1 benefited much more from cross-referencing than did reviewer 2. The weighted kappa statistic was 0.69 for MRI alone and the same with cross-referencing, indicating good interobserver agreement. Sensitivity and specificity for SVI with MRI alone and with cross-referencing, respectively, were 23% and 83% and 46% and 93% for reviewer 1 and 31% and 91% and 54% and 95% for reviewer 2. CONCLUSION: PACS cross-referencing significantly improves tumor staging of prostate cancer with 3D MRI. Some reviewers benefit more than others from use of this tool.

Adult↗

Combined T2* and T1 measurements for improved perfusion and permeability studies in high field using dynamic contrast enhancement.

This study analyzed the T2* effect of extracellularly distributed gadolinium contrast agents in arterial blood during tumor studies using T1-weighted sequences at high field strength. A saturation-prepared dual echo sequence with echo times of 1.5 and 3.5 ms was employed at 3 T to simultaneously characterize T1 and T2* of arterial blood during bolus administration of Gd-DTPA in 28 patients with body tumors. T2* effect and T1 effect of Gd-DTPA on image intensity of whole blood were calibrated in human blood samples with different concentrations of contrast agent. T2* was used to estimate concentration near the peak of the bolus. T1 was used to measure lower concentrations when T2* was not significant. T2* was measurable on calibration curves for Gd-DTPA concentrations higher than 4 mM. This concentration was exceeded in 18 patients. The mean signal intensity reduction because of T2* effect was estimated at 22+/-14% of the T2* compensated signal. Using T2* measurements reduced underestimations of peak arterial Gd-DTPA concentration (59 +/- 38%) and overestimation of permeability Ktrans (58%). The T2* effect of gadolinium contrast agents should therefore be accounted for when performing tumors study with T1-weighted sequences at high field strength.

Aorta↗

Isotropic 3D T2-weighted MR cholangiopancreatography with parallel imaging: feasibility study.

OBJECTIVE: The aim of this study was to compare the quality of images obtained with fast 3D T2-weighted turbo spin-echo (TSE) MR cholangiopancreatography (MRCP) sequences and 1-mm isotropic voxels with the quality of conventional 2D MRCP images. SUBJECTS AND METHODS: Thirty consecutively registered patients (14 women, 16 men; average age, 60.2 years; age range, 32-87 years) underwent imaging at 1.5 T with a 6-element body array coil. All imaging was performed with three MRCP techniques: free-breathing 3D T2-weighted TSE (TR/TE, 1,300/680; flip angle, 180 degrees; field of view, 250-300 mm; matrix size, 256 x 256; slice thickness, 1 mm; parallel acquisition technique factor, 2); breath-hold 3D T2-weighted TSE (same parameters as the free-breathing 3D technique); breath-hold coronal and oblique coronal thick-slab 2D TSE without parallel acquisition technique (2,800/1,100; flip angle, 150-180 degrees). Quantitative measures of image signal and contrast were evaluated by analysis of variance and paired Student's t tests. A 5-point scale (1, nondiagnostic, to 5, high diagnostic confidence) was used to compare the 3D and 2D data sets for image quality and definition of biliary and pancreatic ductal anatomic features. Friedman's nonparametric and Wilcoxon's rank sum tests were performed for statistical analysis of the qualitative assessments. RESULTS: Quantitative results showed free-breathing and breath-hold 3D TSE images had significantly higher relative signal intensity and contrast than 2D TSE images (p < 0.0001). The qualitative findings showed that both free-breathing and breath-hold 3D TSE techniques gave better delineation of biliary anatomy (p < 0.0001) than the 2D technique. The overall quality of 3D images was better than that of 2D images, and 3D imaging was better at depicting pancreatic ducts, although the difference did not reach statistical significance. CONCLUSION: Three-dimensional volumetric MRCP images are of superior quality and give better delineation of pancreaticobiliary anatomy than conventional 2D images and have the added advantage of multiplanar and postprocessing capabilities.

Adult↗

Time-resolved 3D MR angiography with parallel imaging for evaluation of hemodialysis fistulas and grafts: initial experience.

OBJECTIVE: We optimized a time-resolved 3D contrast-enhanced MR angiography sequence with integrated parallel imaging technique that can provide a large field of view with high temporal and spatial resolution, by which the hemodialysis access and the entire course of the inflow and outflow vessels can be imaged at a single anatomic station. Our objective was to evaluate the feasibility and usefulness of this method in the evaluation of patients referred for possible abnormalities in hemodialysis access. CONCLUSION: Time-resolved contrast-enhanced 3D MR angiography with parallel imaging has the potential to provide a rapid and comprehensive evaluation for the surveillance and diagnosis of hemodialysis access malfunctions. This technique may function as an important complement to conventional digital subtraction angiography and may be able to help guide medical management. The MR angiography protocol we present is a noninvasive, versatile, and time-efficient technique, without the need of direct graft puncture or flow interruption, and can be performed using a single injection of contrast material at a single station.

Aged↗

Expression of B7-H1 in inflammatory renal tubular epithelial cells.

BACKGROUND: Renal tubular epithelial cells (TECs) function as antigen-presenting cells (APCs) as they constitutively express MHC-II molecules and have the capacity to present peptide antigen to T cells. Nevertheless, co-stimulatory signals provided by TECs for regulating T cell activation have not been fully characterized. We therefore investigated the expression of B7-H1, a member of the B7 superfamily, on TECs under normal or pathologic conditions in vivo and analyzed the regulation and functional role of it after proinflammatory factors treatment in vitro. METHODS: Immunohistological staining for B7-H1 on cryostat sections of core needle biopsies from patients with different renal diseases was examined. Furthermore, we also detected B7-H1 protein expression on cultured human TECs stimulated by various inflammatory factors and performed TEC/T-cell co-cultured experiment to determine TEC-associated B7-H1 in regulating CD4+ T cell activation as well as antigen presentation. RESULTS: Significant B7-H1 protein was detected in TECs of diseased renal samples. Although the presence of B7-H1 does not have any correlation with clinicopathological variables, marked B7-H1 expression on sections without interstitial inflammation revealed that B7-H1 has some protective function. In vitro, the expression of B7-H1 on TECs was increased after TECs were stimulated with IL-1alpha, LPS, TNF-alpha, IFN-gamma or anti-CD40. Co-cultured experiments revealed that TEC-related B7-H1 was identified as a strong inhibitor of CD4+ T-cell activation as assessed by increased cytokine production (interleukin-2 and interferon-gamma) and expression levels of the T cell activation marker (CD69) in the presence of a neutralizing antibody against B7-H1 (clone MIH1). Interestingly, IL-2 production by C10 T cells after antigen presentation by murine TECs was also enhanced when the B7-H1/PD-1 pathway was interrupted. CONCLUSION: This study clearly shows that B7-H1 is an inducible renal tubular epithelial antigen that inhibits T cell activation. It is speculated that B7-H1/PD-1 pathway might play a role in protecting tubular epithelium from immune-mediated damage and active delivery of the B7-H1 inhibitory signal represents a novel therapeutic strategy in autoimmune renal diseases.

Animals↗

Triptolide inhibits B7-H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-kappaB transcription.

Triptolide has been used extensively in China for the treatment of autoimmune diseases and tumor for many centuries. Nevertheless, little is known about its exact immunosuppressive and anti-inflammatory properties. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether triptolide can regulate TEC activity. In this study, various cultured human and murine TECs were exposed to tumor necrotic factor-alpha (TNF-alpha) and triptolide, followed to examine the expression of B7-H1 and B7-DC. Flow cytometric analysis revealed that B7-H1 but not B7-DC constitutively expresses on TECs, and the B7-H1 protein expression was profoundly up-regulated by the stimulation of TNF-alpha with a dose-dependent manner. However, triptolide under non-cytotoxic concentration could down-regulate B7-H1 expression on activated TECs at both mRNA and protein level. This effect was transcription factor NF-kappaB dependent. Interestingly, the significant damping effect of triptolide on B7-H1 signal could promote interleukin-2 production by T cell hybridoma (C10) after antigen presentation and enhance cytokine (IFN-gamma and IL-2) secretion by anti-CD3 activated T cells. Our results indicated that triptolide could regulate TEC activity via B7-H1, in addition to previously reported it directly affects the production of some inflammatory factors by T cells, tumor cells and peripheral blood mononuclear cells.

Animals↗

Subclavian steal syndrome: diagnosis with perfusion metrics from contrast-enhanced MR angiographic bolus-timing examination--initial experience.

PURPOSE: To retrospectively determine whether differential temporal changes in signal intensity of the vertebral arteries, measured at a bolus-timing examination with a test dose of a gadolinium-based contrast agent, are present in patients with subclavian steal syndrome. MATERIALS AND METHODS: Institutional review board exemption was obtained, and informed consent was not required for this retrospective study. The study complied with the Health Insurance Portability and Accountability Act. Twenty-five patients with known or clinically suspected atherosclerotic disease of the aortic arch and branch vessels underwent breath-hold contrast material-enhanced magnetic resonance (MR) angiography with circulation time derived from a timing examination by using a test bolus of a gadolinium-based contrast agent. Eight patients (three men and five women aged 54-80 years; mean, 70 years) had subclavian stenosis or occlusion with retrograde vertebral artery flow confirmed with time-of-flight MR angiography, nine patients (eight men and one woman aged 31-91 years; mean, 70 years) had mild to severe ostial stenosis of a single vertebral artery, and eight patients (including four men and four women aged 53-86 years; mean, 73 years) had normal vertebral arteries. The difference in time to peak signal intensity between the right and left vertebral arteries was compared among the three groups by using Fisher exact and Cochran-Mantel-Haenszel tests. RESULTS: The delay in peak enhancement in the ipsilateral vertebral artery ranged from 2 to 4 seconds (mean, 2.5 seconds) in all eight patients with subclavian steal syndrome. In eight of nine patients with ostial vertebral artery stenosis and eight controls, both vertebral arteries filled simultaneously. The presence of unilateral delayed vertebral artery enhancement was significantly associated with retrograde flow in patients with subclavian steal syndrome, compared with patients with normal flow (P < .01) and those with ostial vertebral artery stenosis (P < .01). CONCLUSION: A bolus-timing examination performed with a test bolus of the gadolinium-based contrast agent via the neck vessels that demonstrates at least a 2-second delay in peak contrast enhancement in the right or left vertebral arteries may, in the appropriate clinical setting, indicate subclavian steal syndrome.

Aged↗

Sinomenine inhibits B7-H1 and B7-DC expression on human renal tubular epithelial cells.

Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact mechanisms of action. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether sinomenine can regulate TEC activity. In this study, cultured human TECs were exposed to proinflammatory factors interferon-gamma (IFN-gamma) and tumor necrotic factor-alpha (TNF-alpha) in presence or absence of sinomenine for 72 h, followed by analysis of surface expression of costimulatory molecules. Flow cytometric analysis revealed that various costimulatory molecules were expressed on TECs and that they were significantly up-regulated by the simulation of IFN-gamma and TNF-alpha. However, sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell. Our results indicated that sinomenine could regulate TECs activity via B7-H1 and B7-DC, in addition to previously reported its effects on some pro-inflammatory factors production by macrophages and peripheral blood mononuclear cells.

Antigens, CD↗

H-2 Kd-restricted hepatitis B virus-derived epitope whose specific CD8+ T lymphocytes can produce gamma interferon without cytotoxicity.

It is necessary to evaluate the cytokine secretion status of CD8+ T lymphocytes and elucidate the factors influencing cytokine secretion, because the secretion of cytokines is also an important feature of CD8+ T lymphocytes, and the cytokines usually play critical roles in the outcome of diseases. We showed here that peptide AYRPPNAPI, derived from the core antigen of hepatitis B virus (HBV), could bind to H-2 Kd and induce primed splenocytes from HBcAg expression plasmid-immunized mice to produce gamma interferon (IFN-gamma) in H-2 Kd- and CD8-dependent manners instead of in a CD4-dependent manner. The induced cells were mainly CD3 and CD8 positive but had no cytotoxic effect on the corresponding target cells. When administered into HBV transgenic mice, these cells can decrease the serum HBV load without causing liver damage. These results suggest that this peptide is a special kind of CD8+ T-cell epitope, for which specific CD8+ T cells can produce IFN-gamma when antigenic stimulation is encountered but which have no cytotoxic effect on the corresponding target cells both in vitro and in HBV transgenic mice. This phenomenon indicates initially that the functional mechanisms of CD8+ T cells can be determined by their epitope specificity, which may be associated with the development of epitope-based immunotherapeutic approaches for infectious diseases and tumors.

Animals↗

Protective immunity against Q fever induced with a recombinant P1 antigen fused with HspB of Coxiella burnetii.

The gene fragments encoding outer membrane protein 1 (P1) and heat-shock protein B (HspB) amplified from genomic DNA of Coxiella burnetii Xinqiao by PCR were inserted into prokaryotic expression vector pQE30 to construct recombinant expression plasmids pQE30/p1 and pQE30/hspB, respectively. The p1 fragment from pQE30/p1 was ligated with hspB of pQE30/hspB to construct pQE30/p1-hspB. Recombinant proteins, P1, HspB, and P1-HspB, were expressed in Escherichia coli cells transformed with pQE30/p1, pQE30/hspB, and pQE30/p1-hspB, respectively. The purified recombinant proteins and whole-cell antigen (WCA) of C. burnetii were used to immunize BALB/c mice. The antibody detection, T-cell proliferation assay, and cytokine detection demonstrated that the animals immunized with P1-HspB or WCA exhibited stronger humoral and cellular immune responses compared with animals immunized with P1 or HspB individually. Seven days after challenge of 10-fold 50% infection dose of C. burnetii, mice were euthanized and their spleens were collected. The splenic weights of mice immunized with P1-HspB or WCA were significantly lighter than that of mice immunized with P1 or HspB. By real-time PCR assay, the coxiella loads of spleens of mice immunized with P1-HspB or WCA were also significantly lower than that of mice immunized with P1 or HspB. The data from this study indicate that fusion antigen P1-HspB is a good immunogen for eliciting immunoresponses against C. burnetii, and it may be a more suitable candidate for preparing subunit vaccine against Q fever.

Animals↗

Balb/c mouse model and real-time quantitative polymerase chain reaction for evaluation of the immunoprotectivity against Q fever.

The Balb/c mice were infected with Coxiella burnetii and samples of blood and major organs from the infected mice were collected on days 1 to 14 after infection. The DNAs extracted from the samples were detected by a developed real-time quantitative PCR specific for C. burnetii and high loads of C. burnetii were found in spleens, livers, and lungs, particularly in spleens. The Balb/c mice were immunized with whole cell antigen (WCA) of C. burnetii and coxiella loads in spleens of mice were assessed by the real-time quantitative PCR on day 7 after challenge with C. burnetii. The analysis suggested that phase I whole cells were excellent immunogen that elicited complete protection against coxiella infection by two-booster but not one-booster immunization. The results suggest that the combination of Balb/c model and the real-time quantitative PCR assay is a reliable and sensitive way to evaluate the efficiency of vaccines against Q fever.

Animals↗

Frequencies of epitope-specific cytotoxic T lymphocytes in active chronic viral hepatitis B infection by using MHC class I peptide tetramers.

Hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) are thought to play key roles in viral control and liver damage. We have used HLA-A*02 tetramer complex to human HBV core 18-27 (Tc 18-27), envelope 183-191 (Te 183-191), envelope 335-343 (Te 335-343), and polymerase 575-583 (Tp 575-583) epitopes to characterize HLA class I-restricted CD8+ T cells in active chronic HBV infection. The frequencies of specific epitopes circulating tetramer+ cells were determined in whole-blood samples by analysis of flow cytometry. The correlation of HBV epitope-specific CTL, between viral replication and liver damage, was analyzed by multiple regression. Our data shown that HBV-specific CD8+ T cells can be easily detected in peripheral blood of active chronic HBV infections. No significant correlation was found between either the frequency of HBV-specific CD8+ T cells and the viral load, or the frequency of HBV-specific CD8+ T cells and the levels of alanine transaminase. These results suggest that the existence of epitope-specific HBV CTLs are not directly correlated to hepatocyte injury, and the frequencies of HBV-specific T cells are not determinant of immune-mediated protection in chronic HBV infection.

Epitopes, T-Lymphocyte↗

Iron-containing nodules of cirrhosis.

In the absence of genetic hemochromatosis and systemic hemosiderosis, patients with cirrhosis can accumulate focal iron within regenerative or dysplastic hepatic nodules, commonly referred to as 'siderotic nodules'. Siderotic dysplastic nodules are premalignant lesions while siderotic regenerative nodules are a marker for severe viral or alcoholic cirrhosis. The relationship of hepatic iron deposition to hepatic cirrhosis and neoplasia has not been fully clarified. This article will review the current literature regarding selective iron accumulation in siderotic nodules in chronic liver disease, followed by a discussion of current MR imaging techniques for detection and characterization of these nodules.

Animals↗

Identification and characterization of 177 unreported genes associated with liver regeneration.

The mammalian liver has a very strong regeneration capacity after partial hepatectomy (PH). To further learn the genes participating in the liver regeneration (LR), 551 cDNAs selected from subtracted cDNA libraries of the regenerating rat liver were screened by microarray, and their expression profiles were studied by cluster and generalization analyses. Among them, 177 genes were identified unreported and up- or down-regulated more than twofold at one or more time points after PH, of which 62 genes were down-regulated to less than 0.5; 99 genes were up-regulated to 2-10 folds, and 16 genes were either up- or down-regulated at different time points during LR. By using BLAST and GENSCAN, these genes were located on responsible chromosomes with 131 genes on the long arms of the chromosomes. The cluster and generalization analyses showed that the gene expression profiles are similar in 2 and 4, 12 and 16, 96 and 144 h respectively after PH, suggesting that the actions of the genes expressed in the same profiles are similar, and those expressed in different profiles have less similarity. However, the types, characteristics and functions of the 177 genes remain to be further studied.

Animals↗

Identification of a nuclear protein that promotes NF-kappaB activation.

Receptor-interacting protein (RIP) is a serine/threonine protein kinase that is critically involved in tumor necrosis factor receptor-1 (TNF-R1)-induced NF-kappaB activation. In a yeast two-hybrid screening for potential RIP-interacting proteins, we identified a novel protein designated as NKAP. Although NKAP interacts with RIP in yeast, NKAP does not interact with RIP in mammalian cells in co-immunoprecipitation experiments. When overexpressed in 293 cells, NKAP activated NF-kappaB in a dose-dependent manner. Moreover, down-regulation of NKAP by antisense RNA significantly inhibited TNF- and IL-1-induced NF-kappaB activation. Immunofluorescent staining indicated that NKAP was localized in the nucleus. Our findings suggest that NKAP is a novel nuclear regulator of TNF- and IL-1-induced NF-kappaB activation.

Amino Acid Sequence↗

Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105.

Casper/c-FLIP is a caspase-8-related molecule critically involved in regulation of death receptor-induced apoptosis. It has been shown that Casper can either promote or antagonize apoptosis and can activate the transcription factor NF-kappaB. The exact functions of Casper are controversial. To further understand how Casper signals, we searched Casper-interacting proteins by yeast two-hybrid screening. This effort identified NF-kappaB1 (p105), an atypical IkappaB molecule and the precursor of NF-kappaB subunit p50. Co-immunoprecipitation experiments indicated that Casper interacted with p105 in 293 cells and this interaction was mediated through the C-terminal IkappaB-like domain (IkappaBgamma). Overexpression of p105 and IkappaBgamma inhibited Casper-induced NF-kappaB activation and potentiated Casper-induced apoptosis. Furthermore, Casper and its C-terminal caspase-like domain inhibited p105 processing into p50. Our findings suggest that p105 is involved in Casper-mediated regulation of apoptosis and NF-kappaB activation.

CASP8 and FADD-Like Apoptosis Regulating Protein↗