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Biomedical subjects

D Feng

Publications and source records attributed to D Feng.

At least 73 records · Page 4Linked to original sources

[Polymorphism at the LDL receptor gene locus in patients with cholesterol gallstone disease].

OBJECTIVE: To investigate the association between the dinucleotide repeat polymorphism at the 3' end of the LDL receptor gene and cholesterol gallstone disease. METHODS: Polymorphism of the (dTA)n was amplified by using polymerase chain reaction, and the alleles identification was performed with denaturing polyacrylamide gel electrophoresis and silver stain technique. RESULTS: Analysis of allele frequencies in 131 unrelated Chinese gallstone patients and 79 controls indicated that the C allele was more frequent in the patients with cholesterol gallstones than that in the controls (0.40 vs 0.27, P < 0.01), and the frequency of the BB genotype of the LDL receptor gene was markedly lower (P < 0.005), while the CC and BC genotypes were significantly higher in the patients with cholesterol gallstones than in the controls respectively (P < 0.05, P < 0.05). CONCLUSION: The present study suggests that the LDL receptor gene polymorphism may be associated with cholesterol gallstone disease.

Adolescent↗

[The effect of HCV NS3 protein on expression of p53 gene protein in hepatocarcinogenesis].

OBJECTIVE: To investigate hepatocarcinogenesis by detecting the effect of HCV NS3 protein on expression of P53 protein in hepatocellular carcinoma (HCC) and pericarcinomatous liver tissue. METHODS: The expression of HCV NS3 and P53 protein was detected by immuno-histochemical technique (SP method) in specimens of HCC and their surrounding liver tissues from 47 patients with negative HBV. RESULTS: The positive rate of HCV NS3 protein was lower in HCC(62%) than in pericarcinomatous liver tissue(83%) (P < 0.025). The expressive strength of HCV NS3 protein in HCC was related to the degree of carcinomatous cell differentiation(P < 0.025). The positive rate of P53 protein in carcinomatous tissue(81%) was higher than in pericarcinomatous liver tissue (47%)(P < 0.025). The worse differentiation of cancer cells, the stronger expression of P53 protein (P < 0.05). The expression of P53 protein was not correlated with the expression of HCV NS3 protein in carcinomatous tissiue (P > 0.5), whereas their expression was closely related in pericarcinomatous liver tissue(P < 0.01), and the expressive rate of P53 protein in the cases of positive HCV NS3 protein was higher than that in the cases of negative HCV NS3 protein. CONCLUSION: HCV NS3 protein may exert its hepatocarcinogenic effect in early stage on host cells by endogenous pathway which may bring about mutation of p53 gene and transformation of hepatocytes.

Carcinoma, Hepatocellular↗

Reinterpretation of endothelial cell gaps induced by vasoactive mediators in guinea-pig, mouse and rat: many are transcellular pores.

1. In response to vascular permeabilizing agents, particulates circulating in the blood extravasate from venules through endothelial cell openings. These openings have been thought to be intercellular gaps though recently this view has been challenged. 2. To define the precise location of endothelial cell gaps, serial section electron microscopy and three-dimensional reconstructions were performed in skin and cremaster muscle of guinea-pigs, mice and rats injected locally with agents that enhance microvascular permeability: vascular permeability factor, histamine or serotonin. Ferritin and colloidal carbon were injected intravenously as soluble and particulate macromolecular tracers, respectively. 3. Both tracers extravasated from venules in response to all three permeability enhancing agents. The soluble plasma protein ferritin extravasated primarily by way of vesiculo-vacuolar organelles (VVOs), interconnected clusters of vesicles and vacuoles that traverse venular endothelium. In contrast, exogenous particulates (colloidal carbon) and endogenous particulates (erythrocytes, platelets) extravasated from plasma through transendothelial openings. 4. Serial electron microscopic sections and three-dimensional reconstructions demonstrated that eighty-nine of ninety-two openings were transendothelial pores, not intercellular gaps. Pore frequency increased 3- to 33-fold when carbon was used as tracer. 5. The results demonstrate that soluble and particulate tracers extravasate from venules by apparently different transcellular pathways in response to vasoactive mediators. However, some pores may derive from rearrangements of VVOs.

Animals↗

Effect of aspirin dosage and enteric coating on platelet reactivity.

Although aspirin is effective in the prevention and treatment of cardiovascular diseases, the optimal dose remains uncertain. The purpose of this study was to compare the platelet inhibitory and prostacyclin-sparing effects of 2 doses (81 and 325 mg) and forms (enteric-coated and regular) of aspirin. Since platelet reactivity has been reported to increase after strenuous exercise, a known trigger of myocardial infarction, subjects were studied following maximal treadmill exercise as well as at rest. Forty male healthy subjects were evaluated using a randomized, double-blind, parallel study design. Blood samples were obtained before and after maximal treadmill exercise at baseline and after 7 days on aspirin therapy. Both enteric and regular aspirin in 81- and 325-mg dosages markedly inhibited adenosine diphosphate and epinephrine-induced aggregation at rest and after exercise. Aspirin also inhibited the platelet response to collagen as assessed by a longer lag time to aggregation. The prolongation of lag time was greater for 325 mg than for 81 mg (100 +/- 7 vs 91 +/- 7; p = 0.04, after exercise). There were no significant dose-related differences in plasma 6-keto-prostaglandin F1alpha level; however, enteric-coated aspirin inhibited the exercise-induced increase in 6-keto-prostaglandin F1alpha to a lesser extent than regular aspirin. Although both doses (81 and 325 mg) and types (regular and enteric-coated) of aspirin inhibited adenosine diphosphate and epinephrine-induced aggregation equally, the 325-mg dose inhibited collagen-induced aggregation to a greater extent than 81 mg. The greater platelet inhibition observed with 325 mg may be clinically relevant in acute coronary syndromes characterized by plaque rupture with extensive collagen exposure and platelet activation.

6-Ketoprostaglandin F1 alpha↗

Vascular permeability factor/vascular endothelial growth factor: a multifunctional angiogenic cytokine.

VPF/VEGF is a multifunctional cytokine that contributes to angiogenesis by both direct and indirect mechanisms. On the one hand, VPF/VEGF stimulates the endothelial cells lining nearby microvessels to proliferate, to migrate and to alter their pattern of gene expression. On the other hand, VPF/VEGF renders these same microvascular endothelial cells hyperpermeable so that they spill plasma proteins into the extravascular space, leading to profound alterations in the extracellular matrix that favor angiogenesis. These same principles apply in tumors, in several examples of non-neoplastic pathology, and in physiological processes that involve angiogenesis and new stroma generation. In all of these examples, microvascular hyperpermeability and the introduction of a provisional, plasma-derived matrix precede and accompany the onset of endothelial cell division and new blood vessel formation. It would seem, therefore, that tumors have made use of fundamental pathways that developed in multicellular organisms for purposes of tissue defense, renewal and repair. VPF/VEGF, therefore, has taught us something new about angiogenesis; namely, that vascular hyperpermeability and consequent plasma protein extravasation are important--perhaps essential--elements in its generation. However, this finding raises a paradox. While VPF/VEGF induces vascular hyperpermeability, other potent angiogenic factors apparently do not, at least in sub-toxic concentrations that are more than sufficient to induce angiogenesis (Connolly et al., 1989a). Nonetheless, wherever angiogenesis has been studied, the newly generated vessels have been found to be hyperpermeable. How, therefore, do angiogenic factors other than VPF/VEGF lead to the formation of new and leaky blood vessels? We do not as yet have a complete answer to this question. One possibility is that at least some angiogenic factors mediate their effect by inducing or stimulating VPF/VEGF expression. In fact, there are already clear example of this. A number of putative angiogenic factors including small molecules (e.g. prostaglandins, adenosine) as well as many cytokines (e.g. TGF-alpha, bFGF, TGF-beta, TNF-alpha, KGF, PDGF) have all been shown to upregulate VPF/VEGF expression. Further studies that elucidate the crosstalk among various angiogenic factors are likely to contribute significantly to a better understanding of the mechanisms by which new blood vessels are formed in health and in disease.

Adult↗

Towards the reduction of dynamic image data in position emission tomography studies.

In this study, we propose a method and investigate the reduction of dynamic image data with positron emission tomography (PET). The method is based upon the use of sampling schedules with a reduced number of scanning intervals and the use of an integral model in the cost function of nonlinear regression. The application of this method is illustrated by the problem of estimating the metabolic rate of glucose with the [18F]2-fluoro-2-deoxyglucose (FDG) model. Computer simulations were performed using various sampling schedules with scanning intervals of different lengths. The results were compared in terms of the accuracy and precision of the estimated parameters. It has been found that the use of sampling schedules with a reduced number of scanning intervals in conjunction with the integral model is very effective. The number of images in dynamic PET FDG studies can be reduced by a factor of 4.5 without losing the accuracy and precision of the parameter estimates.

Computer Simulation↗

Dynamic image data compression in spatial and temporal domains: theory and algorithm.

Advanced medical imaging requires storage of large quantities of digitized clinical data. These data must be stored in such a way that their retrieval does not impair the clinician's ability to make a diagnosis. In this paper, we propose the theory and algorithm for near (or diagnostically) lossless dynamic image data compression. Taking advantage of domain-specific knowledge related to medical imaging, the medical practice and the dynamic imaging modality, a compression ratio greater than 80:1 is achieved. The high compression ratios are achieved by the proposed compression algorithm through three stages: 1) addressing temporal redundancies in the data through application of image optimal sampling, 2) addressing spatial redundancies in the data through cluster analysis, and 3) efficient coding of image data using standard still-image compression techniques. To illustrate the practicality of the proposed compression algorithm, a simulated positron emission tomography (PET) study using the fluoro-deoxy-glucose (FDG) tracer is presented. Realistic dynamic image data are generated by "virtual scanning" of a simulated brain phantom as a real PET scanner. These data are processed using the conventional [8] and proposed algorithms as well as the techniques for storage and analysis. The resulting parametric images obtained from the conventional and proposed approaches are subsequently compared to evaluate the proposed compression algorithm. As a result of this study, storage space for dynamic image data is able to be reduced by more than 95%, without loss in diagnostic quality. Therefore, the proposed theory and algorithm are expected to be very useful in medical image database management and telecommunication.

Algorithms↗

A technique for extracting physiological parameters and the required input function simultaneously from PET image measurements: theory and simulation study.

Positron emission tomography (PET) is an important tool for enabling quantification of human brain function. However, quantitative studies using tracer kinetic modeling require the measurement of the tracer time-activity curve in plasma (PTAC) as the model input function. It is widely believed that the insertion of arterial lines and the subsequent collection and processing of the biomedical signal sampled from the arterial blood are not compatible with the practice of clinical PET, as it is invasive and exposes personnel to the risks associated with the handling of patient blood and radiation dose. Therefore, it is of interest to develop practical noninvasive measurement techniques for tracer kinetic modeling with PET. In this paper, a technique is proposed to extract the input function together with the physiological parameters from the brain dynamic images alone. The identifiability of this method is tested rigorously by using Monte Carlo simulation. The results show that the proposed method is able to quantify all the required parameters by using the information obtained from two or more regions of interest (ROI's) with very different dynamics in the PET dynamic images. There is no significant improvement in parameter estimation for the local cerebral metabolic rate of glucose (LCMRGlc) if the number of ROI's are more than three. The proposed method can provide very reliable estimation of LCMRGlc, which is our primary interest in this study.

Brain↗

Study on enzyme electrode biosensor of choline.

Choline oxidase was immobilized at a hydrogen peroxide electrode and the enzyme electrode was used for the amperometric determination of choline. The linear range is 0-200 mg/L with a response time of 40 seconds and a 25-microliter sample injection. The relative standard deviation (RSD) is less than 1.5% in 20 assays. The enzyme membrane can be used continuously at 25 degrees C for 60 days. The recovery rate of this method is 100.3-102.3%.

Alcohol Oxidoreductases↗

[Dumbbell-shaped double-leaf flap for the repair of penetrating wound of palm with tissue defect].

The penetrating wound of palm with the defect of tissues was usually caused by blunt crushing of gun-shot injury. It was difficult to treat clinically. In order to repair the skin defect of palm and dorsum in one operation, 2 kinds of dumbbell-shaped double-leaf flap were desigened. From February 1993 to March 1996, 5 cases with penetrating wound of palm were treated by this method in which the interosseous posterior artery flap in 4, and the superficial epigastric flap in 1. There were 4 males and 1 female with the ages ranging from 15 to 47 years old. The results were as follows: total survival of the flap in 4 cases and partial necrosis of skin margin of the distal leaf in 1 case. The appearance and function of the flap were satisfactory after a follow-up from 4 months to 3 years. It was concluded that the interosseous posterior artery flap had a long vascular pedicle with its constant anatomical distribution, and the 2nd stage of division of the pedicle of the flap was not necessary. It was a perfect flap in repairing the penetrating wound of the palm with small skin defect. The superficial epigastric flap was cumbersome in appearance and was necessary to divide the pedicle of the flap in 2nd staged operation. It was suitable in repairing the penetrating wound with large skin defect. Regarding the operative technique, a meticulous debridement and the appropriate flap area were required, and the blood vessel of the flap should not be compressed by the surrounding tissues. The advantages of this operation provided a simple method to handle, high rate of survival, and one-staged operation.

Adolescent↗

[Comparative study of expression of p21 and c-myc protein in hepatocellular carcinoma with pericarcinomatous liver tissue].

Expression of p21 and c-myc protein in hepatocellular carcinomas and their surrounding liver tissue was detected on serial sections by immunohistochemical method. The results showed that the positive rates of p21 expression were 53.3% (16/30) and 96.7% (29/30) in hepatocellular carcinomas and pericarcinomatous liver tissue, and 40% (12/30) and 86.7% (26/30) and 86.7% (26/30) for c-myc protein expression respectively. Their incidences in pericarcinomatous liver tissue were higher than that in cancer tissue (P < 0.01). The patterns of p21 and c-myc protein in cells were cytoplasm, membrane and/or nuclear types. Their expression was more intensive in pericarcinomatous hepatocytes, especially in liver cirrhosis nodes. The results indicate that abnormal activiation and expression of oncogene ras and c-myc may be related to hepatocellular carcinogenesis.

Adult↗

Isolation and characterization of a disulfide-linked human stem cell factor dimer. Biochemical, biophysical, and biological comparison to the noncovalently held dimer.

Distinct from the noncovalently linked recombinant human stem call factor (rhSCF) dimer, we report here the isolation and identification of an SDS-nondissociable dimer produced during folding/oxidation of rhSCF. Experimental evidence using various cleavage strategies and analyses shows that the isolated dimer is composed of two rhSCF monomers covalently linked by four disulfide bonds. The cysteines are paired as in the noncovalently associated dimer except that all pairings are intermolecular rather than intramolecular. Other structural models, involving intertwining of intramolecular disulfide loops, are ruled out. The molecule behaves similarly to the noncovalently associated dimer during ion-exchange or gel permeation chromatography. However, the disulfide-linked dimer exhibits increased hydrophobicity in reverse-phase columns and in the native state does not undergo spontaneous dimer dissociation-association as seen for the noncovalent dimer. Spectroscopic analyses indicate that the disulfide-linked and noncovalently associated rhSCF dimers have grossly similar secondary and tertiary structures. In vitro, the disulfide-linked dimer exhibits approximately 3-fold higher biological activity in supporting growth of a hematopoietic cell line and stimulating hematopoietic cell colony formation from enriched human CD34+ cells. The molecule binds to the rhSCF receptor, Kit, with an efficiency only half that of the noncovalently associated dimer. Formation of intermolecular disulfides in the disulfide-linked dimer with retention of biological activity has implications for the three-dimensional structure of noncovalently held dimer and disulfide-linked dimer.

Amino Acid Sequence↗

Vesiculo-vacuolar organelles and the regulation of venule permeability to macromolecules by vascular permeability factor, histamine, and serotonin.

In contrast to normal microvessels, those that supply tumors are strikingly hyperpermeable to circulating macromolecules such as plasma proteins. This leakiness is largely attributable to a tumor-secreted cytokine, vascular permeability factor (VPF). Tracer studies have shown that macromolecules cross tumor vascular endothelium by way of a recently described cytoplasmic organelle, the vesiculo-vacuolar organelle or VVO (VVOs are grapelike clusters of interconnected, uncoated vesicles and vacuoles). However, equivalent VVOs are also present in the cytoplasm of normal venules that do not leak substantial amounts of plasma protein. To explain these findings, we hypothesized that VPF increased the permeability of tumor blood vessels by increasing VVO function and that the VVOs of normal venules were relatively impermeable in the absence of VPF stimulation. To test this hypothesis, VPF was injected intradermally in normal animals after intravenous injection of a soluble macromolecular tracer, ferritin, whose extravasation could be followed by electron microscopy. VPF caused normal venules to leak ferritin, and, as predicted by our hypothesis, ferritin extravasated by way of VVOs, just as in hyperpermeable tumor microvessels. Ultrathin (14-nm) serial electron microscopic sections and computer-aided three-dimensional reconstructions better defined VVO structure. VVOs occupied 16-18% of endothelial cytoplasm in normal venules. Individual VVOs were clusters of numerous (median, 124) interconnected vesicles and vacuoles that formed complex pathways across venular endothelium with multiple openings to both luminal and abluminal surfaces. Like VPF, histamine and serotonin also stimulated ferritin extravasation across venules by way of VVOs. Together, these data establish VVOs as the major pathway by which soluble plasma proteins exit venules in response to several mediators that increase venular hyperpermeability. These same mediators also increased the extravasation of colloidal carbon, but this large particulate nonphysiological tracer exited venules primarily through endothelial gaps.

Animals↗

A new double modeling approach for dynamic cardiac PET studies using noise and spillover contaminated LV measurements.

A new double modeling approach for dynamic cardiac studies with positron emission tomography (PET) to estimate physiological parameters is proposed. This approach is exemplified by tracer fluorodeoxyglucose (FDG) studies and estimation of myocardial metabolic rate of glucose (MMRGlc). A separate input function model characterising the tracer kinetics in plasma is used to account for the measurement noise and spillover problems of the input curve obtained from the left ventricular region on the PET images. Measured left ventricle (LV) plasma time-activity and tissue time-activity curves are fitted simultaneously with cross contaminations by this input function model and the FDG model. The results indicate that the MMRGlc can be estimated much more accurately and reliably by this new approach. Compared with the traditional method, an improvement of about 20% in the estimated MMRGlc was achieved when the bidirectional spillover fractions are 20% at different noise levels studied. This new double modeling approach using two models fitting both the input and the output functions simultaneously is expected to be generally applicable to a broad range of system modeling.

Artifacts↗

Optimized sampling and parameter estimation for quantification in whole body PET.

Whole-body positron emission tomography (PET) has recently emerged as an important imaging tool for cancer detection and staging. Initial applications of the technique have been primarily qualitative. One of the major reasons is the limits imposed by kinetically undersampled data over the whole body, as opposed to the standard method of continuous dynamic sampling in one body location. In this paper, a new estimation method using weighted nonlinear least squares (WNLS) for the first bed position and Bayesian regression (BR) for subsequent positions is proposed. A general criterion for designing optimal sampling schedules which maximizes the measurement information with multiple bed positions is developed. The overall approach is illustrated with the problem of estimating the metabolic rate of glucose (MRGLu) in tumors at different axial positions (image bed positions) in the body by using computer simulations and patient data. The results show that estimates of MRGLu using sparse data and the optimized Bayesian approach are comparable with those obtained by standard methods and fully sampled data. This study demonstrates the potential of the technique described for quantification where several bed positions have to be used to image all the regions of interest (ROI).

Abdominal Muscles↗