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Biomedical subjects

Q Xue

Publications and source records attributed to Q Xue.

At least 55 records · Page 3Linked to original sources

Cutting edge: bacterial DNA and LPS act in synergy in inducing nitric oxide production in RAW 264.7 macrophages.

LPS is well recognized for its potent capacity to activate mouse macrophages to produce NO, an important inflammatory mediator in innate host defense. We demonstrate here that, although inducing little NO alone, DNA from both Gram-negative and Gram-positive bacteria synergizes with subthreshold concentrations of LPS (0.3 ng/ml) to induce NO in cultures of RAW 264.7 macrophages. The effects of the DNA are mimicked by synthetic CpG-containing oligodeoxynucleotides but not by non-CpG-containing oligodeoxynucleotides. This synergistic activity is not inhibited by neutralizing Abs against IFN. Preincubation of macrophages with DNA for 8-24 h suppresses subsequent synergistic macrophage responses to DNA/LPS, whereas prolonged pretreatment with LPS enhances synergy. RT-PCR analysis indicates that the mRNA levels of the inducible NO synthase gene are also coordinately suppressed or induced. These findings indicate that temporally controlled, synergistic interactions exist between microbial DNA and LPS in the induction of macrophage NO via enhanced inducible NO synthase gene expression.

Animals↗

A multiplasmid approach to preparing large libraries of polyketides.

A three-plasmid system for heterologous expression of 6-deoxyerythronolide B synthase (DEBS) has been developed to facilitate combinatorial biosynthesis of polyketides made by type I modular polyketide synthases (PKSs). The eryA PKS genes encoding the three DEBS subunits were individually cloned into three compatible Streptomyces vectors carrying mutually selectable antibiotic resistance markers. A strain of Streptomyces lividans transformed with all three plasmids produced 6-deoxyerythronolide B at a level similar to that of a strain transformed with a single plasmid containing all three genes. The utility of this system in combinatorial biosynthesis was demonstrated through production of a library of modified polyketide macrolactones by using versions of each plasmid constructed to contain defined mutations. Combinations of these vector sets were introduced into S. lividans, resulting in strains producing a wide range of 6-deoxyerythronolide B analogs. This method can be extended to any modular PKS and has the potential to produce thousands of novel natural products, including ones derived from further modification of the PKS products by tailoring enzymes.

Anti-Bacterial Agents↗

Invasion and metastasis of liver cancer: expression of intercellular adhesion molecule 1.

PURPOSE: To study the relationship between intercellular adhesion molecule 1 (ICAM-1) and liver cancer metastasis and to find predicting factors that could indicate the growth and metastasis of liver cancer. METHODS: ICAM-1 expression in fresh tissue of normal liver and hepatocellular cancer (HCC) was examined by immunoperoxidase staining. Serum soluble intercellular adhesion molecule 1 (sICAM-1) from patients with a benign HCC tumor, and the expression of ICAM-1 in the orthotopically transplanted LCI-D20 tumor of a nude mouse liver cancer metastasis model, and in human hepatoma, the tumor surrounding tissue and normal liver, was analyzed semiquantitatively by the immuno-dot blot method. Tissue ICAM-1 expression (mRNA level) was detected by Northern blotting. RESULTS: ICAM-1 expression in LD1-20 D metastatic liver cancer had a positive correlation with tumor size and the time after implantation. It increased suddenly as metastasis occurred being 3.03+/-0.51 before metastasis and 8.24+/-0.95 after metastasis, P < 0.01, then remained high, appending on the number of sites involved (monosite metastasis 5.48+/-0.49, multisite metastasis 10.05+/-1.17, P < 0.05). All six cases of normal liver samples were negative in anti-ICAM-1 immunohistochemical staining, 80.0% (36/45) of the HCC showed some ICAM-1 expression. The rate of positive cells was a little higher in large tumors, tumors with an intact capsule and tumors with metastasis, but there was no significant difference. It was noticed that two cancer emboli also had high ICAM-1 expression. The ICAM-1 concentration in HCC (13.43+/-0.09) was higher than that in tumor surrounding the liver (5.89+/-0.17, P < 0.01) and that in normal liver (4.27+/-0.21, P < 0.01). sICAM-1, like tissue ICAM-1, was higher in HCC patients than in patients (with benign liver tumor and normal controls. Both tissue ICAM-1 and sICAM-1 were higher in the metastasis group than in the group without metastasis (tissue ICAM-1 20.24+/-0.30 vs 10.23+/-0.12 P < 0.05; sICAM-1 12.18+/-0.25 vs 9.77+/-0.54 P < 0.05). Northern blot analysis revealed that ICAM-1 expression, as indicated by mRNA level, was also higher in HCC and in cancer emboli than in tumor surrounding liver and normal liver. CONCLUSIONS: Tissue ICAM-1 and serum sICAM-1 could indicate the stage of HCC, and the potential of hepatoma cells for invasion and metastasis. They may play an important role in the metastasis cascade.

Animals↗

Review of methods to predict and detect atrial fibrillation in post-cardiac surgery patients.

Atrial fibrillation (AF) is the most common sustained arrhythmia after cardiac surgery. Postoperative AF is known to substantially lengthen hospital stay and affect patient recovery. Identification of those at risk of developing AF after surgery and early detection of AF during recovery would be extremely helpful in effective management of these patients, including targeting prophylactic therapy to prevent AF in high-risk patients. In this communication, diagnostic methods to identify those at risk of developing AF after surgery and early identification of AF before, during, and after surgery have been reviewed. Signal-averaged P wave analysis, done before surgery, identifies patients who are likely to develop AF during recovery. When combined with low ejection fraction, signal-averaged P wave can discriminate those who develop AF from those who do not. During recovery, AF can be detected early either from a detailed analysis of atrial activity in a 10-second electrocardiogram or an analysis of R-to-R intervals from an extended rhythm strip (1 minute or longer). Analysis of the 10-second electrocardiogram includes median QRST subtraction from rhythm data and detection and analysis of atrial signals in the resulting residual. AF is detected from extended rhythm strips by using a statistical model to identify the presence of characteristic irregular patterns of R-to-R intervals.

Atrial Fibrillation↗

Injured primary sensory neurons switch phenotype for brain-derived neurotrophic factor in the rat.

Peripheral nerve injury results in plastic changes in the dorsal root ganglia and spinal cord, and is often complicated with neuropathic pain. The mechanisms underlying these changes are not known. We have now investigated the expression of brain-derived neurotrophic factor in the dorsal root ganglia with histochemical and biochemical methods following sciatic nerve lesion in the rat. The percentage of neurons immunoreactive for brain-derived neurotrophic factor in the ipsilateral dorsal root ganglia was significantly increased as early as 24 h after the nerve lesion and the increase lasted for at least two weeks. The level of brain-derived neurotrophic factor messenger RNA was also significantly increased in the ipsibut not contralateral dorsal root ganglia. Both neurons and satellite cells in the lesioned dorsal root ganglia synthesized brain-derived neurotrophic factor messenger RNA after the nerve lesion. There was a dramatic shift in size distribution of positive neurons towards large sizes seven days after sciatic nerve lesion. Morphometric analysis and retrograde tracing studies showed that no injured neurons smaller than 600 microm2 were immunoreactive for brain-derived neurotrophic factor, whereas the majority of large injured neurons were immunoreactive in the ipsilateral dorsal root ganglia seven days postlesion. The brain-derived neurotrophic factor-immunoreactive nerve terminals in the ipsilateral spinal cord were reduced in the central region of lamina II, but increased in more medial regions or deeper into laminae III/IV. These studies indicate that sciatic nerve injury results in a differential regulation of brain-derived neurotrophic factor in different subpopulations of sensory neurons in the dorsal root ganglia. Small neurons switched off their normal synthesis of brain-derived neurotrophic factor, whereas larger ones switched to a brain-derived neurotrophic factor phenotype. The phenotypic switch may have functional implications in neuronal plasticity and generation of neuropathic pain after nerve injury.

Animals↗

New human hepatocellular carcinoma (HCC) cell line with highly metastatic potential (MHCC97) and its expressions of the factors associated with metastasis.

A new human hepatocellular carcinoma (HCC) cell line with a highly metastatic potential was established from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) by means of alternating cell culture in vitro and growth in nude mice. The line, designated MHCC97, has been cultivated for 18 months and subcultured for more than 90 passages. The line was showed to be of human origin by karyotype analysis. The cells were either grown as compact colonies (in clusters) or as a monolayered sheet with about 31 h of population-doubling time, exhibited typical malignant epithelial in morphology and were positive for alpha-fetoprotein (AFP). Flow cytometric analysis of the cell DNA content showed an aneuploid pattern, and its index was 1.5 as compared to that of normal human peripheral blood lymphocytes. Karyotypic analyses of G- and C-banding techniques revealed that all cells presented chromosome abnormalities in number and structure. The number of cell line MHCC97 chromosome ranged from 59 to 65 with a modal number of 60 and 61. At least two common chromosome markers, i(1q) and der(4)t(4;?)(4pter-->q35::?), were present in all cells, and deletion of Y chromosome also occurred in all cells. The subcutaneous and intrahepatic xenografts were formed and metastatic lesions in lungs were found after the cells were inoculated into nude mice. The rate of metastasis to lungs was 100% using orthotopic inoculation. Reverse transcription polymerase chain reaction products revealed positive expressions of integrin alpha5 and beta1, urokinase type plasminogen activator receptor (uPAR), vascular endothelial growth factor and nm23-H1 mRNAs of cell line MHCC97. Immunostaining of c-Met, uPAR showed strongly positive in both subcutaneous xenografts and lung metastatic lesions; while positive in xenografts and negative in metastatic lesions for integrin alpha5, beta1. E-cadherin and P53 was not expressed either in xenograft or in the metastatic lesions. PCR products of HBsAg and HBxAg were both positive. The cell line MHCC97 still retained some characteristic features of original tumour. Establishment of cell line MHCC97 should be beneficial to the studies of HCC metastatic mechanisms.

Adult↗

Satellite-cell-derived nerve growth factor and neurotrophin-3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat.

Injury to a peripheral nerve induces in the dorsal root ganglia (DRG) sprouting of sympathetic and peptidergic terminals around large-diameter sensory neurons that project in the damaged nerve. This pathological change may be implicated in the chronic pain syndromes seen in some patients with peripheral nerve injury. The mechanisms underlying the sprouting are not known. Using in situ hybridization and immunohistochemical techniques, we have now found that nerve growth factor (NGF) and neurotrophin-3 (NT3) synthesis is upregulated in satellite cells surrounding neurons in lesioned DRG as early as 48 h after nerve injury. This response lasts for at least 2 months. Quantitative analysis showed that the levels of mRNAs for NT3 and NGF increased in ipsilateral but not contralateral DRG after nerve injury. Noradrenergic sprouting around the axotomized neurons was associated with p75-immunoreactive satellite cells. Further, antibodies specific to NGF or NT3, delivered by an osmotic mini-pump to the DRG via the lesioned L5 spinal nerve, significantly reduced noradrenergic sprouting. These results implicate satellite cell-derived neurotrophins in the induction of sympathetic sprouting following peripheral nerve injury.

Animals↗

[Expressions of the metastasis-associated factors of a new human hepatocellular carcinoma cell line with highly metastatic potential].

OBJECTIVE: To explore the expressions of some metastasis-related factors in a new human hepatocellular carcinoma cell line with a highly metastatic potential by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. METHODS: A human hepatocellular carcinoma (HCC) cell line (MHCC97) was established derived from subcutaneous xenograft of a metastatic model of human HCC in nude mice (LCI-D20) by means of alternating cell culture in vitro and grown in nude mice. RT-PCR and immunohistochemistry were performed on this line and its intrahepatic xenografts and metastatic lesions to explore the expressions of metastasis-related factors. RESULTS: The tumorigenicity and metastatic rate to lungs of MHCC97 cell line was 100% by orthotopic inoculation. RT-PCR products for integrin alpha 5 and beta 1, uPAR, VEGF and nm23-H1 mRNA from MHCC97 cell line were positive. Immunostaining showed strongly positive for c-Met, uPAR in both of xenografts and lung metastatic lesions, and also positive in xenografts, but negative in lung metastatic lesions for integrin alpha 5 and beta 1. E-cadherin was not expressed either in xenografts or in the metastatic lesions. The PCR productions for HBsAg and HBxAg were positive, and negative for HBcAg. CONCLUSIONS: MHCC97 cell line has a ability to express some metastasis-associated factors. DNA for virus hepatitis B may be integrated into the genome of MHCC97 cells.

Animals↗

The late-expressed region of the temperate coliphage 186 genome.

The late-lytic region of the genome of bacteriophage 186 encodes the phage proteins that synthesize the complex viral particle and lyse the bacterial host. We report the completion of the DNA sequence of the late region and the assignment of 18 previously identified genes to open reading frames in the sequence. The 186 late region is similar to the late region of phage P2, sharing 26 genes of known function: the single gene for activation of late gene transcription, 6 genes for construction of DNA-containing heads, 16 for tail morphogenesis, and 3 for cell lysis. We identified two 186 late genes with unknown function; one is homologous to previously unrecognised genes in P2, HP1, and phiCTX, and the other may modulate DNA packaging. The 186 late region, like the rest of the genome, lacks the lysogenic conversion genes that are carried by P2, allowing the 186 late region to be transcribed from only three late promoters rather than four. The relative absence of lysogenic conversion genes in 186 suggests that the two phages have evolved to use the lytic and lysogenic reproductive modes to different extents.

Amino Acid Sequence↗

Algorithms for computerized QT analysis.

Several methods for measurement of the offset, peak, and morphology of the T wave in multilead ECGs are reviewed and compared. The T wave offset is the most important and also the most difficult measurement for analysis of QT interval dispersion. Measurement methods compared here include (1) the point at which the T wave intersects the isoelectric line plus a threshold; (2) the point at which the derivative of T wave intersects the isoelectric line plus a threshold; (3) the intersection of the maximum slope of the T wave and the isoelectric line; (4) the intersection of a line fitted by least squares to the maximum slope of the T wave and an isoelectric line (LSI); and (5) the point at which the T wave area reaches 90% of the entire T wave area (TA). The reproducibility tests show that the LSI method has the best reproducibility of all the algorithms examined. Although the T wave peak is better defined than the T wave offset, it is not simple to find the right peak when there are multiple T wave peaks and when the T wave is flat and/or noisy. Methods to find T wave patterns with multiple peaks and to locate the point at which the T wave is flat and noisy are therefore reviewed here. Finally, the principal component analysis-based T wave complexity measurement and its relation to other QT interval dispersion measurements are discussed.

Algorithms↗

Dynamic stability of glenohumeral joint during scapular plane elevation.

OBJECTIVE: To investigate the muscle-controlled dynamic stability of the glenohumeral joint through X-ray fluoroscopy in active and passive shoulder elevation in scapular plane. METHODS: Sixty healthy volunteers were collected in this study, including 23 men and 37 women, with an average age of 28.4 years. Passive and active shoulder elevation in scapular plane were observed under X-ray imaging. In 18 subjects, X-ray films were taken when the shoulder elevated in scapular plane from 0 degree to 150 degrees with a 30 degrees interval at each stage in both active and passive movements. The angles between the pivot of the humerus and the glenoid surface (GHA) during the active and passive motion were calculated and analyzed. Manual examination was also applied in the same manner. RESULTS: The pivot of the humerus had a tendency to be vertically closer to the glenoid surface in the active elevation than in the passive elevation. The differences of GHA between the active and passive motion at 0 degree, 30 degrees, 60 degrees, 90 degrees, 120 degrees and 150 degrees elevation were 4.55 degrees +/- 0.37 degree, 5.44 degrees +/- 1.16 degrees, 6.50 degrees +/- 1.50 degrees, 4.94 degrees +/- 0.82 degree, 4.50 degrees +/- 0.40 degree and 1.44 degrees +/- 0.68 degree, respectively. Manual examination found the angle between the scapula and the humerus tended to be larger in the active motion than in the passive motion. CONCLUSION: The active coordination of the muscles around the shoulder is beneficial to the dynamic stability of the glenohumeral joint.

Adolescent↗

[Changes of PAI-1 and biological behaviour of human hepatocellular carcinoma in metastatic model of nude mice].

OBJECTIVE: To study the relationship between plasminogen activator inhibitor type-1 (PAI-1) and biological behaviour of hepatocellular carcinoma (HCC). METHOD: 40 nude mice with LCI-D20 metastatic modes of human HCC (MMHCC) were established. The change of PAI-1 was determined by PAI-1 kit and immunohistochemistry with monoclonal antibody against PAI-1 in MMHCC progression. RESULT: Following MMHCC progression from early to advanced stage, PAI-1 increased from 6.2 +/- 1.8 Au/ml to 15.4 +/- 0.7 Au/ml in plasma (P < 0.05), from 0.4 +/- 0.1 Au/mg to 0.8 +/- 0.3 Au/mg in extract (P < 0.05). The correlation between PAI-1 and tumor size and AFP level was strong (r = 0.9648 and r = 0.9544, P < 0.05 and P < 0.05). CONCLUSION: PAI-1 was increased gradually following tumor progression in MMHCC. PAI-1 correlated with tumor size and AFP level. PAI-1 related well with the invasiveness and prognosis of HCC.

Animals↗

Multichannel microchip electrospray mass spectrometry.

Microfabricated multiple-channel glass chips were successfully interfaced to an electrospray ionization mass spectrometer (ESI-MS). The microchip device was fabricated by standard photolithographic, wet chemical etching, and thermal bonding procedures. A high voltage was applied individually from each buffer reservoir for spraying sample sequentially from each channel. With the sampling orifice of the MS grounded, it was found that a liquid flow of 100-200 nL/min was necessary to maintain a stable electrospray. The detection limit of the microchip MS experiment for myoglobin was found to be lower than 6 x 10(-8) M. Samples in 75% methanol were successfully analyzed with good sensitivity, as were aqueous samples. The parallel mutliple-channel microchip system allowed ESI-MS analysis of different samples of standard peptides and proteins in one chip.

Mass Spectrometry↗

Integrated multichannel microchip electrospray ionization mass spectrometry: analysis of peptides from on-chip tryptic digestion of melittin.

In continuation of our work to develop an integrated multichannel microchip interfaced to electrospray mass spectrometry (ESI-MS), this paper demonstrates one of several applications of this approach in monitoring tryptic digestion products. The multichannel microchip allowed integration of sample preparation onto the microchip to facilitate the analysis process. Melittin was selected as a model oligopeptide because it possesses a cluster of four adjacent basic residues which enable probing the site specificity of trypsin as a function of digest times. Reactions were performed on-chip in different wells for specific time periods and then analyzed by infusion from the microchip by ESI-MS, using leucine enkephalin as internal standard. The rate of formation and disappearance of the molecular ion and individual fragments was followed for a melittin to trypsin concentration ratio of 300:1. The results indicate the potential of integrating enzymatic reactions with multichannel microchip ESI-MS for automated optimization of reaction condition while consuming only small amounts of sample.

Amino Acid Sequence↗

Inhibitory effect of the angiogenesis inhibitor TNP-470 on tumor growth and metastasis in nude mice bearing human hepatocellular carcinoma.

The antitumor and anti-metastatic effects of a potent angiogenesis inhibitor, O-(chloroacetyl-carbamoyl)fumagillol (TNP-470), was investigated in a highly metastatic model of human hepatocellular carcinoma-LCI-D20. Small pieces of LCI-D20 tumor tissue were implanted subcutaneously into the right axillary region of 24 nude mice; the mice were then randomized into two groups. To one group, TNP-470 30 mg/kg was given as a subcutaneous injection every other day from day 1 to day 15 and the mice were sacrificed on day 26. An antitumor effect of TNP-470 was clearly demonstrated by tumor weight (0.97 +/- 0.34 g compared to 2.04 +/- 0.34 g, P < 0.001) and alpha-Fetoprotein value (93 +/- 59 micrograms/L compared to 769 +/- 282 micrograms/L, P < 0.001). There was also an anti-metastatic effect of TNP-470. Lung metastases developed in only 1 of 12 mice in the treated group, while they developed in 6 of mice of the control group. No severe side-effect of TNP-470 was found in this study. In vitro study revealed that the purified hepatoma cells were insensitive to TNP-470 (the 50% inhibitory concentration was 43 micrograms/ml). These results suggest that the angiogenesis inhibitor TNP-470 has both strong antitumor and anti-metastatic effects on a human hepatocellular carcinoma model in nude mice.

Animals↗

Late potential recognition by artificial neural networks.

Ventricular late potentials (LP's) are high-frequency low-amplitude signals obtained from signal-averaged electrocardiograms (ECG's) [SAECG's]. LP's are useful in identifying patients prone to ventricular tachycardia (VT), spontaneous or inducible during electrophysiology testing. A combination of self-organizing and supervised artificial neural network (ANN) models was developed to identify patients with a positive electrophysiology (PEP) test for inducible ventricular tachycardia from patients with a negative electrophysiology (NEP) test using LP's. We have added morphology information of vector magnitude waveform to original set of three time-domain features of LP's, which are total QRS duration (TQRSD), high-frequency low-amplitude signal duration (HFLAD), and root-mean-square voltage (RMSV). Pattern recognition results from an ANN model with this combination feature set are superior to the results from Bayesian classification model based on conventional three time-domain features of SAECG. In order to increase the robustness of the recognition, a filtered QRS offset point is randomly shifted +/- 8 ms to form a fuzzy training set, which was to simulate the possible error in detecting QRS offset point of filtered SAECG. We also found that nonlinear transformation through the hidden layer of developed ANN model could increase Euclidean distance between PEP and NEP patterns.

Algorithms↗

[Impingement syndrome of the subacromial area: analysis of 42 cases].

To create a new classification of subacromial impingement phenomena according to different etiology, we treated 42 cases of impingement syndrome. They were 29 male, and 23 females, with an average age of 45 years. 29 patients had typical subacromial pain are signs. Positive impingement test was found in 30 patients. Roentgenographic findings showed that the high density of the great tuberosity (GT) in 27 cases, 8 cases got the cystic changes around the CT, and exostosis formed on the G. T. in 3 cases. The abnormal acromion with sloped or over hanging form was found in 6 cases. 11 cases had an irregular inferior surface of the acromion in two cases with the spur formed at inferior surface of acromion. Four patients combined with calcium deposit at subacromial space. Space narrowing of the AH interval was in noted 12 cases. According to the X-ray findings, 35 cases were classified into the abnormal anatomy structure group. The other 7 patients were in dynamic impingement group. 13 cases of impingement syndrome combined with the complication of rotator cuff tear were treated by the Mclaughlin's procedure for repairing the rotator cuff with the acromion plasty. 11 patients were followed up for more than 6 months after operation. 7 cases had excellent results and 4 cases good results. This classification includes two kinds of impingement syndromes: anatomical of structural and dynamic or dysfunction.

Adult↗

A biomechanical study of fast throwing movements of the shoulder in baseball pitching.

OBJECTIVE: To define the biomechanic function of the shoulder in fast throwing movements in baseball pitching. METHODS: Using NAC high-speed video and PIAS LA-555 computer system, overhand pitching movements carried out by 12 healthy Japanese professional baseball pitchers were analyzed in three dimensions. The pitching motion was displayed as stick to sick figures dynamically. RESULTS: Pitching motion was a combination of translational and rotational movements. Acceleration and deceleration, being two typical motion patterns, worked sequentially through the anatomic link system from the pivot leg to the pitching hand. During the acceleration phase, the shoulder joint acted as a junction point and a fulcrum, supporting the rotational acceleration motion, shoulder forward flexion and elbow extension. According to the changing glenohumeral angles of the pitching shoulder, shearing force turned into tension force which worked on the anterior shoulder structures and then shifted to the posterior part of the joint. CONCLUSIONS: In fast throwing motion, the shoulder functions as an important fulcrum to support the pitching arm during the acceleration phase. Avoiding excessive stress and shearing force on the joint components and enhancing coordination of muscle action are important to a successful throwing motion and the prevention of shoulder injury.

Athletic Injuries↗