Biomedical subjects

Tong Xu

Publications and source records attributed to Tong Xu.

At least 19 recordsLinked to original sources

PubMed2024

Transcriptome analysis reveals that PRV XJ delgE/gI/TK protects against intestinal damage in nose-dropping-infected mice by regulating ECM-ITGA/ITGB-P-FAK.

Pseudorabies virus (PRV) is an ideal model for mechanistic investigations into α-herpesvirus. The neurotropism and latent infection of PRV have been extensively studied. Apart from neurological symptoms, diarrhea caused by PRV infection is also an essential cause of mortality in newborn and weaned piglets. However, little research has been done on PRV invasion of the gut. To fill this gap, a nasal drip PRV-infection mouse model was developed, consisting of three groups: the challenged group (Group A), the immunization-challenged group (Group B), and a mock group (Group C). The results showed that immunization with PRV XJ delgE/gI/TK successfully prevented intestinal damage caused by PRV drop-nose infection. Subsequently, intestines were collected for transcriptional analysis. Differentially expressed genes analysis revealed that PRV XJ delgE/gI/TK was effective in reducing the organismal intestinal transcriptional activity caused by PRV. The Group A vs Group C and Group A vs Group B had similar Kyoto Encyclopedia of Genes and Genomes (KEGG)-enriched signaling pathways and the differentially expressed genes were primarily enriched in pathways, such as cell adhesion molecules, focal adhesion kinase, and actin cytoskeleton regulation. Notably, transcriptome analysis indicated that genes associated with the focal adhesion kinase (FAK) signaling pathway (ECM-ITGA/ITGB-p-FAK) were significantly more highly expressed in Group A than in Group B and Group C. The results of quantitative real-time PCR (RT-qPCR) and western blotting were consistent with KEGG analysis. Therefore, we hypothesized that PRV promotes self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway and that PRV XJ delgE/gI/TK immunization could attenuate the intestinal damage caused by PRV by inhibiting the activation of this pathway.IMPORTANCEPseudorabies virus (PRV) poses a significant threat to the swine industry and public health due to its ability to infect multiple species, including humans, leading to substantial economic losses and potential health risks. This study addresses a critical gap in understanding the impact of PRV infection on the gut, which has been less explored compared to its neurological effects. By developing a drip-nose PRV-infection mouse model, the research indicated that PRV might promote self-infection through activation of the ECM-ITGA/ITGB-p-FAK signaling pathway, and PRV XJ delgE/gI/TK immunization effectively prevents intestinal damage by significantly reducing the expression of genes in the ECM-ITGA/ITGB-p-FAK signaling pathway. The research has important implications for the swine industry and public health by contributing to the development of better vaccines and treatments, ultimately helping to control PRV and prevent its cross-species transmission.

Animals↗

PubMed2006

Dual-energy cardiac imaging: an image quality and dose comparison for a flat-panel detector and x-ray image intensifier.

This study presents a comparison of dual-energy imaging with an x-ray image intensifier and flat-panel detector for cardiac imaging. It also investigates if the wide dynamic range of the flat-panel detector can improve dual-energy image quality while reducing patient dose. Experimental contrast-to-noise (CNR) measurements were carried out in addition to simulation studies. Patient entrance exposure and system tube loading were also recorded. The studied contrast objects were calcium and iodine. System performance was quantified with a figure-of-merit (FOM) defined as the image CNR(2) over patient entrance exposure. The range of thickness studied was from 10 to 30 cm of Lucite (PMMA). Detector dose was initially set to 140 nGy (16 microR)/frame. The high-energy 120 kVp beam was filtered by an additional 0.8 mm silver filter. Keeping the same filament current, the kVp for the low-energy beam was adjusted as a function of thickness until 140 nGy was achieved. System performance was found to be similar for both systems, with the x-ray image intensifier performing better at lower thicknesses and the flat-panel detector performing better at higher thicknesses. This requirement of fixed detector entrance exposure was then relaxed and the kVp for the low-energy beam was allowed to vary while the mAs of the x-ray tube remained fixed to study changes in dual-energy image quality, patient dose and FOM with the flat-panel detector. It was found that as the kVp for the low-energy beam was reduced, system performance would rise until reaching a maximum while simultaneously lowering patient exposure. Suggested recommendations for optimal dual-energy imaging implementation are also provided.

Bone and Bones↗

PubMed2006

Acute respiratory distress syndrome induced by avian influenza A (H5N1) virus in mice.

RATIONALE AND OBJECTIVE: The acute respiratory distress syndrome (ARDS) caused by avian influenza H5N1 viral infection has been reported in many humans since this virus was found to infect humans in Hong Kong in 1997, but no studies regarding an animal model of ARDS with H5N1 viral infection have been found in the literature. Here we present a mouse model of ARDS induced by H5N1 virus. METHODS: Six- to 8-wk-old BALB/c mice were inoculated intranasally (50 micro l) with 1 x 10(2) 50% mouse infectious doses of A/Chicken/Hebei/108/2002 (H5N1) virus. Lung injury was assessed by observation of lung water content and histopathology. Arterial blood gas, white blood cell count in bronchial alveolar lavage fluid, and tumor necrosis factor-alpha and interleukin-6 in bronchoalveolar lavage fluid and serum were measured at the indicated time points. RESULTS: Our data showed that H5N1 viral infection in mice resulted in typical ARDS, which was characterized by the following features: (1) about 80% of mice (13 of 16) dead on Days 6 to 8 postinoculation; (2) highly edematous lungs and dramatically increased lung wet:dry weight ratios and lung wet weight:body weight ratios; (3) inflammatory cellular infiltration, alveolar and interstitial edema, and hemorrhage in lungs; (4) progressive and severe hypoxemia; and (5) significant increase in neutrophils, tumor necrosis factor-alpha, and interleukin-6 in BALF. CONCLUSION: These results suggested that we successfully established a mouse model of ARDS with H5N1 viral infection, which may benefit further investigation into the pathogenesis of human ARDS induced by H5N1 virus.

Animals↗

PubMed2006

Positron autoradiography for intravascular imaging: feasibility evaluation.

Approximately 70% of acute coronary artery disease is caused by unstable (vulnerable) plaques with an inflammation of the overlying cap and high lipid content. A rupturing of the inflamed cap of the plaque results in propagation of the thrombus into the lumen, blockage of the artery and acute ischaemic syndrome or sudden death. Morphological imaging such as angiography or intravascular ultrasound cannot determine inflammation status of the plaque. A radiotracer such as 18F-FDG is accumulated in vulnerable plaques due to higher metabolic activity of the inflamed cap and could be used to detect a vulnerable plaque. However, positron emission tomography (PET) cannot detect the FDG-labelled plaques because of respiratory and heart motions, small size and low activity of the plaques. Plaques can be detected using a miniature particle (positron) detector inserted into the artery. In this work, a new detector concept is investigated for intravascular imaging of the plaques. The detector consists of a storage phosphor tip bound to the end of an intravascular catheter. It can be inserted into an artery, absorb the 18F-FDG positrons from the plaques, withdrawn from the artery and read out. Length and diameter of the storage phosphor tip can be matched to the length and the diameter of the artery. Monte Carlo simulations and experimental evaluations of coronary plaque imaging with the proposed detector were performed. It was shown that the sensitivity of the storage phosphor detector to the positrons of 18F-FDG is sufficient to detect coronary plaques with 1 mm and 2 mm sizes and 590 Bq and 1180 Bq activities in the arteries with 2 mm and 3 mm diameters, respectively. An experimental study was performed using plastic tubes with 2 mm diameter filled with an FDG solution, which simulates blood. FDG spots simulating plaques were placed over the surface of the tube. A phosphor tip was inserted into the tube and imaged the plaques. Exposure time was 1 min in all simulations and experiments. Experiments showed that detecting the coronary plaques using the proposed technique is possible. The proposed technique has the potential for fast and accurate detection of vulnerable coronary and other intravascular plaques.

Autoradiography↗

PubMed2006

Automated technique for angiographic determination of coronary blood flow and lumen volume.

RATIONALE AND OBJECTIVES: Visual interpretation of angiographic images has been shown to be inadequate for assessing the severity of intermediate coronary stenoses. An approach for evaluating both the anatomic and functional impact of a stenosis is needed. An automated technique for determining both coronary blood flow and lumen volume based on a first-pass analysis (FPA) of coronary angiograms and a template matching algorithm was evaluated. MATERIALS AND METHODS: Coronary angiograms of a swine animal model were obtained during power injections of contrast material into the left coronary ostium. Background anatomy was subtracted with an automated phase matching program. A template matching algorithm and first-pass analysis were then used to quantify coronary blood flow and lumen volume. Coronary blood flow and lumen volume measurements were validated with a transit-time ultrasound flow probe and a polymer cast of the coronary arteries, respectively. RESULTS: In 14 independent comparisons, the mean coronary blood flow measured with FPA showed strong correlation with the mean flow measured with the ultrasound flow probe (Q(FPA) = 0.88Q(probe) - 1.99; r = 0.977; standard error of estimate = 3.23 mL/minute). The lumen volumes determined with FPA and cast measurements demonstrated excellent correlation and can be related to each other by V(FPA) = 0.95V(C) - 0.01 (r = 0.997; standard error of estimate = 0.01 mL). CONCLUSIONS: The proposed automated method for accurate determination of coronary blood flow and lumen volume can supplement visual evaluation of coronary anatomy with quantitative physiologic data. This automated technique potentially offers a clinically feasible method of quantifying coronary blood flow and lumen volume in conjunction with routine cardiac catheterization.

Algorithms↗

PubMed2006

Evaluation of the diagnostic value of serum tumor markers, and fecal k-ras and p53 gene mutations for pancreatic cancer.

OBJECTIVE: To evaluate the diagnostic value for pancreatic cancer of four serum tumor markers, carbohydrate antigen (CA) 199, CA242, CA50 and carcino-embryonic antigen (CEA), and fecal k-ras and p53 gene mutations. METHODS: From February 2002 to March 2004, 136 patients were consecutively diagnosed with pancreatic cancer in the three participating medical centers. The diagnosis was confirmed by pathology in 53 patients, of whom five were excluded because they did not have measurement of serum tumor marker. The remaining 48 patients comprised the case group in the study. Ninety-six patients with benign digestive diseases diagnosed during the same period were recruited as control subjects. They were matched by sex and age. In both groups, serum CA199, CA242, CA50 and CEA were measured by ELISA, and fecal k-ras and p53 gene mutations were measured by PCR-restriction fragment length polymorphism and PCR-single strand conformational polymorphism, respectively. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to compare their diagnostic value, as well as the sensitivity, specificity and likelihood ratio. Moreover, independent and sensitive tests from these non-invasive approaches were selected to form a parallel test that may have further improved sensitivity for diagnosis of pancreatic cancer. RESULTS: The AUC of serum CA199 and CA242 were 0.821 (95%CI 0.725-0.917) and 0.821 (95%CI 0.723-0.919), respectively. The optimal diagnostic value of serum CA199 for pancreatic cancer was 93 U/mL, with a sensitivity of 73.7% and specificity of 91.4%. The positive likelihood ratio of CA199 was 8.57, and the negative likelihood ratio was 0.29. The optimal diagnostic value of serum CA242 was 25 U/mL, with a sensitivity of 71.1% and specificity of 93.5%. The positive likelihood ratio of CA242 was 10.94, and the negative likelihood ratio was 0.31. The sensitivity of fecal k-ras gene mutation for diagnosis of pancreatic cancer was 77.4%, and the specificity was 81.2%. The positive and negative likelihood ratios of fecal k-ras gene mutation were 4.12 and 0.28, respectively. The sensitivity and specificity of fecal p53 gene mutation were 25.8% and 95.3%, respectively, and its positive and negative likelihood ratios were 5.49 and 0.78. The rate of fecal k-ras mutation was higher in patients with benign pancreatic diseases (57.14%) than that of controls with non-pancreatic disorders. The values of serum tumor markers and fecal k-ras and p53 gene mutation rates were not significantly different in subgroups according to site or stage of pancreatic cancer. The sensitivity and specificity of the parallel test of serum CA199 and fecal k-ras gene mutation were 94.06% and 74.22%, respectively, while the sensitivity and specificity of the parallel test of serum CA242 and fecal k-ras were 93.47% and 75.92%, respectively. CONCLUSIONS: Serum CA199 and CA242 are valuable diagnostic tools for pancreatic cancer. The diagnostic value is further improved when they are combined with fecal k-ras gene mutation measurement.

Aged↗

PubMed2006

The use of bacterial minicells to transfer plasmid DNA to eukaryotic cells.

The delivery of DNA to mammalian cells is of critical importance to the development of genetic vaccines, gene replacement therapies and gene silencing. For these applications, targeting, effective DNA transfer and vector safety are the major roadblocks in furthering development. In this report, we present a novel DNA delivery vehicle that makes use of protoplasted, achromosomal bacterial minicells. Transfer of plasmid DNA as measured by green fluorescent protein expression was found to occur in as high as 25% of cultured Cos-7 cells when a novel chimeric protein containing the D2-D5 region of invasin was expressed and displayed on the surface of protoplasted minicells. Based on endoplasmic reticulum stress and other responses, protoplasted minicells were non-toxic to recipient eukaryotic cells as a consequence of the transfection process. Taken together, these results suggest that bacterial minicells may represent a novel and promising gene delivery vehicle.

Adhesins, Bacterial↗

PubMed2006

Optimization of a flat-panel based real time dual-energy system for cardiac imaging.

A simulation study was conducted to evaluate the effects of high-energy beam filtration, dual-gain operation and noise reduction on dual-energy images using a digital flat-panel detector. High-energy beam filtration increases image contrast through greater beam separation and tends to reduce total radiation exposure and dose per image pair. It is also possible to reduce dual-energy image noise by acquiring low and high-energy images at two different detector gains. In addition, dual-energy noise reduction algorithms can further reduce image noise. The cumulative effect of these techniques applied in series was investigated in this study. The contrast from a small thickness of calcium was simulated over a step phantom of tissue equivalent material with a CsI phosphor as the image detector. The dual-energy contrast-to-noise ratio was calculated using values of energy absorption and energy variance. A figure-of-merit (FOM) was calculated from dual-energy contrast-to-noise ratio (CNR) and patient effective dose estimated from values of entrance exposure. Filter atomic numbers in the range of 1-100 were considered with thicknesses ranging from 0-2500 mg/cm2. The simulation examined combinations of the above techniques which maximized the FOM. The application of a filter increased image contrast by as much as 45%. Near maximal increases were seen for filter atomic numbers in the range of 40-60 and 85-100 with masses above 750 mg/cm2. Increasing filter thickness beyond 1000 mg/cm2 increased tube loading without further significant contrast enhancement. No additional FOM improvements were seen with dual gain before or after the application of any noise reduction algorithm. Narrow beam experiments were carried out to verify predictions. The measured FOM increased by more than a factor of 3.5 for a silver filter thickness of 800 microm, equal energy weighting and application of a noise clipping algorithm. The main limitation of dynamic high-energy filtration is increased tube loading. The results of this study can be used to help develop an optimal dual-energy imaging system.

Algorithms↗

PubMed2006

Feasibility of real time dual-energy imaging based on a flat panel detector for coronary artery calcium quantification.

The feasibility of a real-time dual-energy imaging technique with dynamic filtration using a flat panel detector for quantifying coronary arterial calcium was evaluated. In this technique, the x-ray beam was switched at 15 Hz between 60 kVp and 120 kVp with the 120 kVp beam having an additional 0.8 mm silver filter. The performance of the dynamic filtration technique was compared with a static filtration technique (4 mm Al+0.2 mm Cu for both beams). The ability to quantify calcium mass was evaluated using calcified arterial vessel phantoms with 20-230 mg of hydroxylapatite. The vessel phantoms were imaged over a Lucite phantom and then an anthropomorphic chest phantom. The total thickness of Lucite phantom ranges from 13.5-26.5 cm to simulate patient thickness of 16-32 cm. The calcium mass was measured using a densitometric technique. The effective dose to patient was estimated from the measured entrance exposure. The effects of patient thickness on contrast-to-noise ratio (CNR), effective dose, and the precision of calcium mass quantification (i.e., the frame to frame variability) were studied. The effects of misregistration artifacts were also measured by shifting the vessel phantoms manually between low- and high-energy images. The results show that, with the same detector signal level, the dynamic filtration technique produced 70% higher calcium contrast-to-noise ratio with only 4% increase in patient dose as compared to the static filtration technique. At the same time, x-ray tube loading increased by 30% with dynamic filtration. The minimum detectability of calcium with anatomical background was measured to be 34 mg of hydroxyapatite. The precision in calcium mass measurement, determined from 16 repeated dual-energy images, ranges from 13 mg to 41 mg when the patient thickness increased from 16 to 32 cm. The CNR was found to decrease with the patient thickness linearly at a rate of (-7%/cm). The anatomic background produced measurement root-mean-square (RMS) errors of 13 mg and 18 mg when the vessel phantoms were imaged over a uniform (over the rib) and nonuniform (across the edge of rib) bone background, respectively. Misregistration artifacts due to motions of up to 1.0 mm between the low- and high-energy images introduce RMS error of less than 4.3 mg, which is much smaller than the frame to frame variability and the measurement error due to anatomic background. The effective dose ranged from 1.1 to 6.6 microSv for each dual-energy image, depending on patient thickness. The study shows that real-time dual-energy imaging can potentially be used as a low dose technique for quantifying coronary arterial calcium.

Artifacts↗

PubMed2006

Real-time tumor tracking using implanted positron emission markers: concept and simulation study.

The delivery accuracy of radiation therapy for pulmonary and abdominal tumors suffers from tumor motion due to respiration. Respiratory gating should be applied to avoid the use of a large target volume margin that results in a substantial dose to the surrounding normal tissue. Precise respiratory gating requires the exact spatial position of the tumor to be determined in real time during treatment. Usually, fiducial markers are implanted inside or next to the tumor to provide both accurate patient setup and real-time tumor tracking. However, current tumor tracking systems require either substantial x-ray exposure to the patient or large fiducial markers that limit the value of their application for pulmonary tumors. We propose a real-time tumor tracking system using implanted positron emission markers (PeTrack). Each marker will be labeled with low activity positron emitting isotopes, such as 124I, 74As, or 84Rb. These isotopes have half-lives comparable to the duration of radiation therapy (from a few days to a few weeks). The size of the proposed PeTrack marker will be 0.5-0.8 mm, which is approximately one-half the size of markers currently employed in other techniques. By detecting annihilation gammas using position-sensitive detectors, multiple positron emission markers can be tracked in real time. A multimarker localization algorithm was developed using an Expectation-Maximization clustering technique. A Monte Carlo simulation model was developed for the PeTrack system. Patient dose, detector sensitivity, and scatter fraction were evaluated. Depending on the isotope, the lifetime dose from a 3.7 MBq PeTrack marker was determined to be 0.7-5.0 Gy at 10 mm from the marker. At the center of the field of view (FOV), the sensitivity of the PeTrack system was 240-320 counts/s per 1 MBq marker activity within a 30 cm thick patient. The sensitivity was reduced by 45% when the marker was near the edge of the FOV. The scatter fraction ranged from 12% (124I, 74As) to 16% (84Rb). In addition, four markers (labeled with 124I) inside a 30 cm diameter water phantom were simulated to evaluate the feasibility of the multimarker localization algorithm. Localization was considered successful if a marker was localized to within 2 mm from its true location. The success rate of marker localization was found to depend on the number of annihilation events used and the error in the initial estimate of the marker position. By detecting 250 positron annihilation events from 4 markers (average of 62 events per marker), the marker success rates for initial errors of +/-5, +/-10, and +/-15 mm were 99.9%, 99.6%, and 92.4%, respectively. Moreover, the average localization error was 0.55 (+/-0.27) mm, which was independent of initial error. The computing time for localizing four markers was less than 20 ms (Pentium 4, 2.8 GHz processor, 512 MB memory). In conclusion, preliminary results demonstrate that the PeTrack technique can potentially provide real-time tumor tracking with low doses associated with the marker's activity. Furthermore, the small size of PeTrack markers is expected to facilitate implantation and reduce patient risk.

Algorithms↗

PubMed2005

Trichoderma biodiversity in China: evidence for a North to South distribution of species in East Asia.

Towards assessing the biodiversity and biogeography of Trichoderma, we have analyzed the occurrence of Trichoderma species in soil and litter from four areas in China: North (Hebei province), South-East (Zhejiang province), West (Himalayan, Tibet) and South-West (Yunnan province). One hundred and thirty five isolates were grouped according to tentative morphological identification. A representative 64 isolates were verified at the species level by the oligonucleotide barcode program TrichO Key v.1.0 and the custom BLAST server TrichoBLAST, using sequences of the ITS1 and 2 region of the rRNA cluster and from the longest intron of the tef1 (translation elongation factor 1-alpha) gene. Eleven known species (Trichoderma asperellum, T. koningii, T. atroviride, T. viride, T. velutinum, T. cerinum, T. virens, T. harzianum, T. sinensis, T. citrinoviride, T. longibrachiatum) and two putative new species (T. sp. C1, and T. sp. C2), distinguished from known species both by morphological characters and phylogenetic analysis, were identified. A significant difference in the occurrence of these species was found between the North (Hebei) and South-West (Yunnan) areas, which correlates with previously reported species distributions in Siberia and South-East Asia, respectively. As in previous studies, T. harzianum accounted for almost half of the biodiversity; although, in this study, it was exclusively found in the North, and was predominantly represented by an ITS1 and 2 haplotype, which has so far been rarely found elsewhere. This study therefore reveals a North-South gradient in species distribution in East Asia, and identifies Northern China as a potential center of origin of a unique haplotype of T. harzianum.

China↗

PubMed2005

Role of cytokines in promoting immune escape of FasL-expressing human colon cancer cells.

AIM: To investigate the potential role of cytokines in promoting Fas ligand (FasL)-expressing colon cancer cells. METHODS: Immunohistochemical SABC method was used to observe the expression of Fas receptor and ligand in SW620 colon cancer cell line and Jurkat T cells in order to provide the morphological evidence for the functions of Fas receptor and ligand. To examine the cytotoxicity of effector cells, CytoTox96(r) non-radioactive cytotoxicity assay was adopted to measure the lactate dehydrogenase-releasing value after SW620 cells were co-cultured with Jurkat T lymphocytes. RESULTS: The FasL of colon cancer SW620 cells was positive. The positive substances were distributed in the cell membrane and cytoplasm. The Fas receptor of colon cancer SW620 cells was negative. The Fas receptor and ligand of Jurkat T lymphocytes turned out to be positive. The positive substances were distributed in the cell membrane. After phytohemagglutinin (PHA)-stimulated Jurkat T lymp-hocytes were co-cultured with phorbol 12-myristate 13-acetate (PMA)-plus-ionomycin-stimulated (for 48 h) SW620 cells or tumor necrosis factor-alpha (TNF-alpha)-stimulated (for 48 h) SW620 cells or unstimulated SW620 cells for 4 h, the cytotoxicity of SW620 cells to PHA-stimulated Jurkat cells at effector-to-target ratios of 10:1, 5:1, 2.5:1, and 1.25:1 was 74.6%, 40.8%, 32.4%, and 10.9% (F = 8.19, P<0.05); or 54.9%, 35.3%, 22.0%, and 10.3% (F = 11.12, P<0.05); or 14.9%, 10.5%, 6.9%, and 5.8% (F = 3.45, P<0.05). After PHA-stimulated Jurkat T lymphocytes were co-cultured with unstimulated SW620 cells for 8 h, the cytotoxicity of SW620 cells to PHA-stimulated Jurkat cells at effector-to-target ratios of 5:1, 2.5:1, and 1.25:1 from the experiment was 83.9%, 74.1%, and 28.5% (F = 137.04, P<0.05) respectively. Non-radioactive cytotoxicity assay showed that the apoptotic rate of Jurkat cells remarkably increased with the increase of planting concentration of SW620 cells and co-culture time after the SW620 cells were co-cultured with the Jurkat T lymphocytes. The cytotoxicity was significantly enhanced by PMA+ionomycin or TNF-alpha. CONCLUSION: The FasL expressed in human colon cancer cells may be regulated by endogenous factors in the microenvironment of the host and facilitate the escape of tumor cells from the host immune system.

Cell Communication↗

PubMed2005

Memory T cells have gene expression patterns intermediate between naive and effector.

The biological basis underlying differentiation of naive (NAI) T cells into effector (EFFE) and memory (MEM) cells is incompletely understood. Furthermore, whether NAI T cells serially differentiate into EFFE and then MEM cells (linear differentiation) or whether they concurrently differentiate into either EFFE or MEM cells (parallel differentiation) remains unresolved. We isolated NAI, EFFE, and MEM CD8(+) T cell subsets from human peripheral blood and analyzed their gene expression by using microarrays. We identified 156 genes that strongly differentiate NAI, EFFE, and MEM CD8(+) T cells; these genes provide previously unrecognized markers to help identify each cell type. Using several statistical approaches to analyze and group the data (standard heat-map and hierarchical clustering, a unique circular representation, multivariate analyses based on principal components, and a clustering method based on phylogenetic parsimony analysis), we assessed the lineage relationships between these subsets and showed that MEM cells have gene expression patterns intermediate between NAI and EFFE T cells. Our analysis suggests a common differentiation pathway to an intermediate state followed by a split into EFFE or MEM cells, hence supporting the parallel differentiation model. As such, conditions under which NAI T cells are activated may determine the magnitude of both EFFE and MEM cells, which arise subsequently. A better understanding of these conditions may be very useful in the design of future vaccine strategies to maximize MEM cell generation.

CD8-Positive T-Lymphocytes↗

PubMed2005

Photon counting computed tomography: concept and initial results.

A concept of a photon counting cone beam CT is proposed. The system uses a new Multi Slit Multi Slice (MSMS) cone beam acquisition geometry utilizing a linear array photon counting detectors. The MSMS cone beam acquisition is a direct analogy of the scanning multislit acquisition used in projection x-ray imaging. This geometry provides a CT imaging with dose efficient scatter rejection and allows for using available photon counting detectors. The microchannel plate (MCP) detector is proposed as a linear array photon counting detector for MSMS cone beam CT system. Initial testing of the MCP detector for CT application was performed. The field of view of the prototype MCP detector is 60 mm. A delay line position encoding electronics was used. The electronics has a single channel input for evaluation of events from the entire detector field of view. This limits the system count rate at 2 x 10(5) count/s. The spatial resolution of this detector is 80 microm FWHM at 40 kVp and 200 microm FWHM at 90 kVp tube voltages. The detector noise in CT projections is less than 1 count/pixel for the 80 microm pixel size. The CT projections contain quantum-limited and scatter free signal. Images of a contrast phantom and a small animal were acquired at 50 kVp and 80 kVp tube voltages. The CT numbers for different contrast elements were calculated for a given x-ray spectrum and compared with experimental values. The quantum efficiency of the current detector is 56% at 90 kVp, which is suboptimal because of the large channel diameter (25 microm) of these MCPs. The MCPs with smaller channels and higher efficiencies are being tested. The quantum efficiency was measured to be 70% for a new MCP with 5 microm channel diameter. Design parameters of a clinically applicable photon counting MSMS cone beam CT for breast imaging was evaluated. System uses 20 cm field of view MCP detectors based on 5 microm channel MCPs and high count rate ASIC electronics. It was concluded that the MSMS cone beam CT with a photon counting MCP detector is feasible for volume breast imaging.

Breast Neoplasms↗

PubMed2005

[The diagnostic value of serum carcinoma markers, fecal K-ras and p53 gene mutation in pancreatic cancers].

OBJECTIVE: To evaluate the diagnostic value of serum carcinoma markers CA19-9, CA242, CA50 and carcinoembryonic antigens (CEA), fecal K-ras and p53 gene mutation in pancreatic cancer. METHODS: We collected 136 new cases of pancreatic cancer and 240 patients with benign digestive diseases including 49 patients with benign pancreatic diseases diagnosed in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Tumor Hospital and Shenyang PLA General Hospital from February 2002 to March 2004. Blood samples were collected and serum carcinoma markers CA19-9, CA242, CA50 and CEA were measured. Fecal K-ras and p53 gene mutation were also measured. We decided the optimal cut-off points with receiver operating characteristic curves and calculated the areas under the curve (AUC). RESULTS: The AUC of serum CA19-9 and CA242 were 0.855 +/- 0.031 (95% CI 0.794 - 0.916) and 0.859 +/- 0.031 (95% CI 0.799 - 0.920) respectively. The optimal cut-off point for serum CA19-9 was 68 U/ml, with the sensitivity of 84.4% (98/116) and the specificity of 84.3% (145/172) for the diagnosis of pancreatic cancer. The optimal cut-off point for serum CA242 was 25 U/ml, with the sensitivity of 88.4% (84/95) and the specificity of 79.1% (144/182). The sensitivity of fecal K-ras mutation was 77.8%, and the specificity was 82.2%. The sensitivity and specificity of fecal p53 gene mutation were 27.8% and 95.2% respectively. The diagnostic scale of pancreatic cancer was calculated by four variables: serum CA19-9, CA242, fecal K-ras and p53, of which each variable deserved one point if measured positive. The optimal cut-off point for the scale was 2, and the AUC of the diagnostic scale was 0.946 +/- 0.017 (95% CI 0.912 - 0.980). CONCLUSIONS: Serum CA19-9 and CA242 are valuable diagnostic tools for pancreatic cancer. The diagnostic value will be further improved when they are combined with the measurement of fecal K-ras and p53 gene mutation.

Adolescent↗

PubMed2004

Effect of area x-ray beam equalization on image quality and dose in digital mammography.

In mammography, thick or dense breast regions persistently suffer from reduced contrast-to-noise ratio (CNR) because of degraded contrast from large scatter intensities and relatively high noise. Area x-ray beam equalization can improve image quality by increasing the x-ray exposure to under-penetrated regions without increasing the exposure to other breast regions. Optimal equalization parameters with respect to image quality and patient dose were determined through computer simulations and validated with experimental observations on a step phantom and an anthropomorphic breast phantom. Three parameters important in equalization digital mammography were considered: attenuator material (Z = 13-92), beam energy (22-34 kVp) and equalization level. A Mo/Mo digital mammography system was used for image acquisition. A prototype 16 x 16 piston driven equalization system was used for preparing patient-specific equalization masks. Simulation studies showed that a molybdenum attenuator and an equalization level of 20 were optimal for improving contrast, CNR and figure of merit (FOM = CNR2/dose). Experimental measurements using these parameters showed significant improvements in contrast, CNR and FOM. Moreover, equalized images of a breast phantom showed improved image quality. These results indicate that area beam equalization can improve image quality in digital mammography.

Artifacts↗

PubMed2004

Microarray analysis reveals differences in gene expression of circulating CD8(+) T cells in melanoma patients and healthy donors.

Circulating T cells from many cancer patients are known to be dysfunctional and undergo spontaneous apoptosis. We used microarray technology to determine whether gene expression differences exist in T cells from melanoma patients versus healthy subjects, which may underlie these abnormalities. To maximize the resolution of our data, we sort purified CD8(+) subsets and amplified the extracted RNA for microarray analysis. These analyses show subtle but statistically significant expression differences for 10 genes in T cells from melanoma patients versus healthy controls, which were additionally confirmed by quantitative real-time PCR analysis. Whereas none of these genes are members of the classical apoptosis pathways, several may be linked to apoptosis. To additionally investigate the significance of these 10 genes, we combined them into a classifier and found that they provide a much better discrimination between melanoma and healthy T cells as compared with a classifier built uniquely with classical apoptosis-related genes. These results suggest the possible engagement of an alternative apoptosis pathway in circulating T cells from cancer patients.

Cluster Analysis↗

PubMed2004

Enhancing rice resistance to fungal pathogens by transformation with cell wall degrading enzyme genes from Trichoderma atroviride.

Three genes encoding for fungal cell wall degrading enzymes (CWDEs), ech42, nag70 and gluc78 from the biocontrol fungus Trichoderma atroviride were inserted into the binary vector pCAMBIA1305.2 singly and in all possible combinations and transformed to rice plants. More than 1800 independently regenerated plantlets in seven different populations (for each of the three genes and each of the four gene combinations) were obtained. The ech42 gene encoding for an endochitinase increased resistance to sheath blight caused by Rhizoctonia solani, while the exochitinase-encoding gene, nag70, had lesser effect. The expression level of endochitinase but exochitinase was correlated with disease resistance. Nevertheless, exochitinase enhanced the effect of endochitinase on disease resistance when the two genes co-expressed in transgenics. Resistance to Magnaporthe grisea was found in all kinds of regenerated plants including that with single gluc78. A few lines expressing either ech42 or nag70 gene were immune to the disease. Transgenic plants are being tested to further evaluate disease resistance at field level. This is the first report of multiple of expression of genes encoding CWDEs from Trichoderma atroviride that result in resistance to blast and sheath blight in rice.

Cell Membrane↗