Biomedical subjects

D Feng

Publications and source records attributed to D Feng.

At least 37 records · Page 2Linked to original sources

PubMed2000

Optimal image sampling schedule for both image-derived input and output functions in PET cardiac studies.

Optimal sampling schedule (OSS) design for both image-derived input and output functions in tracer kinetic modeling with positron emission tomography (PET) is investigated. This problem is very important in noninvasive PET dynamic cardiac studies where both the input function, i.e., the plasma time-activity curve (PTAC), and the output function, i.e., the tissue time-activity curve (TTAC), are obtained simultaneously from the same sequence of PET images. The integral PET measurement is used in this study. The spillover correction for the cross contaminations in cardiac studies is incorporated into the OSS design procedure. A new target function based on the D-optimal criterion involving both the input and output sensitivity functions is proposed. The fluorodeoxyglucose (FDG) model and a six-parameter PTAC model are used to illustrate the simultaneous OSS design for both the PTAC and TTAC. An OSS design consisting of six different scanning intervals is derived. Computer simulations are performed based on the estimated parameters from real studies to evaluate the effectiveness of the OSS. The double modeling approach is used in parameter estimation to simultaneously estimate the parameters involved. The results have shown that, for a wide range of parameter variations, the OSS is as effective as a conventional sampling schedule (CSS) and comparable parameter estimates can be obtained. Compared with the use of the CSS, the use of the OSS leads to an approximately 70% reduction in the storage space and data processing time.

Computer Simulation↗

PubMed2000

Factor VII gene polymorphism, factor VII levels, and prevalent cardiovascular disease: the Framingham Heart Study.

Elevated factor VII levels have been associated with increased cardiovascular risk in some studies. The arginine/glutamine (Arg/Gln) polymorphism of the factor VII gene has been previously shown to modify factor VII levels. However, the presence of a gene/environment interaction on factor VII levels or a link with cardiovascular disease (CVD) remains uncertain. We studied subjects from the Framingham Heart Study to determine (1) the extent to which this genetic polymorphism affects factor VII levels; (2) whether interactions exist between this polymorphism and environmental factors on factor VII levels; and (3) the association between the polymorphism and CVD. Genotype data and factor VII antigen levels were available in 1816 subjects. Factor VII levels differed significantly among genotypes in an additive fashion: Gln homozygous, 82.7+/-2.5%; heterozygous, 92.2+/-0.7%; and Arg homozygous, 100. 5+/-0.4% (P<0.0001). The polymorphism was the strongest, single predictor of factor VII levels, explaining 7.7% of the total variance of factor VII levels, whereas other traditional risk factors combined explained an additional 11.5% of the variance. There was an interaction (P=0.02) between the genotype and total cholesterol on factor VII levels, such that the correlation coefficient and slope (factor VII level/total cholesterol) were greatest in Gln/Gln subjects. Among 3204 subjects characterized for genotype and CVD, there was no significant relationship between the genotype and CVD (P=0.12). In the Framingham Heart Study, the Arg/Gln polymorphism was significantly associated with factor VII antigen levels. The strength of the association suggests that genetic variation plays an important role in determining factor VII levels. However, despite being associated with factor VII levels, the Arg/Gln polymorphism was not associated with prevalent CVD.

Amino Acid Sequence↗

PubMed2000

Ultrastructural localization of the vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) receptor-2 (FLK-1, KDR) in normal mouse kidney and in the hyperpermeable vessels induced by VPF/VEGF-expressing tumors and adenoviral vectors.

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) interacts with two high-affinity tyrosine kinase receptors, VEGFR-1 and VEGFR-2, to increase microvascular permeability and induce angiogenesis. Both receptors are selectively expressed by vascular endothelial cells and are strikingly increased in tumor vessels. We used a specific antibody to localize VEGFR-2 (FLK-1, KDR) in microvascular endothelium of normal mouse kidneys and in the microvessels induced by the TA3/St mammary tumor or by infection with an adenoviral vector engineered to express VPF/VEGF. A pre-embedding method was employed at the light and electron microscopic levels using either nanogold or peroxidase as reporters. Equivalent staining was observed on both the luminal and abluminal surfaces of tumor- and adenovirus-induced vascular endothelium, but plasma membranes at interendothelial junctions were spared except at sites connected to vesiculovacuolar organelles (VVOs). VEGFR-2 was also localized to the membranes and stomatal diaphragms of some VVOs. This staining distribution is consistent with a model in which VPF/VEGF increases microvascular permeability by opening VVOs to allow the transendothelial cell passage of plasma and plasma proteins.

Adenoviridae↗

PubMed2000

von Willebrand factor and retinal circulation in early-stage retinopathy of type 1 diabetes.

OBJECTIVE: Although retinopathy is a common microvascular complication of type 1 diabetes, the mechanism for this complication is still unknown. Changes in retinal circulation have been noted before the development of overt retinal pathology. Because von Willebrand factor (vWF) is a marker for endothelial dysfunction and mediates platelet adhesion, we determined if there was an association between vWF and retinal circulation in the early stages of diabetic retinopathy. RESEARCH DESIGN AND METHODS: Twenty subjects (aged 32.4 +/- 7.8 years) with type 1 diabetes and minimal or no retinopathy were studied. The mean duration of diabetes was 4.7 +/- 2.6 years. Data were collected at baseline and after 4 months of 1,800 IU vitamin E therapy or placebo. Retinal circulation was evaluated by video fluorescein angiography. Plasma vWF antigen levels were measured by enzyme-linked immunosorbent assay and fibrinogen by the Clauss method. RESULTS: Retinal blood flow was negatively correlated with vWF levels (r = -0.44, P = 0.008), whereas retinal circulation time was positively correlated with vWF levels (r = 0.33, P = 0.048). Fibrinogen levels were not significantly associated with either retinal index. However, fibrinogen levels were positively associated with HbA1c levels (r = 0.34, P = 0.01), indicating an association between poor glycemic control and higher fibrinogen levels. CONCLUSIONS: Increased vWF was associated with a prolonged retinal circulation time and reduced retinal blood flow in early-stage retinopathy of type 1 diabetes. Reduced blood flow associated with increased vWF levels may promote stasis in the retinal circulation and lead to local hypoxemia. These changes might contribute to the microvascular complications of diabetes. Whether the vWF levels predict retinal complications deserves further investigation.

Adult↗

PubMed2000

[Detection of K-ras gene mutations in DNA extracted from the plasma of patients with pancreatic cancer].

OBJECTIVES: To detect mutations of the K-ras codon 12 in DNA extracted from the plasma of patients with pancreatic cancer, and to explore the possibility of using this method in early diagnosis of pancreatic cancer. METHODS: Plasma DNA was isolated from the blood of 22 patients with pancreatic cancer and from 20 normal controls. K-ras codon 12 mutations were detected by mutant enriched polymerase chain reaction-restriction fragment length polymorphism technique and subsequent product sequencing. The relation of K-ras mutations in plasma to clinical features in pancreatic cancer patients was analyzed. RESULTS: Seventeen (77.3%) of 22 patients with pancreatic cancer had a codon 12 K-ras mutation in their plasma DNA. In two patients, the PCR products were sequenced and the mutations were confirmed. The occurrence of K-ras mutations in the plasma DNA was not related to tumor location, tumor size, and TNM stage. No K-ras mutation was detected in the plasma specimen of any of the normal controls. CONCLUSIONS: K-ras mutations are frequently found in the plasma DNA of patients with pancreatic cancer. Analysis of K-ras mutation in the plasma DNA may be useful in the early detection of pancreatic cancer.

Adult↗

PubMed1999

Characterization of unstable ion-exchange chromatographic separation of proteins.

Very fine separation of proteins by stepwise elution ion-exchange chromatography is very often a unstable process. To characterize the unstability of such processes the elution volume variations were examined by the model equation which contained the ion-exchange capacity and the number of adsorption sites. The data needed for the model calculation were obtained from gradient elution experiments. As a model separation system stepwise elution of a model protein (beta-lactoglobulin) near the isoelectric point on a weak cation-exchange chromatography column was chosen. The elution volume varied significantly with a small change in the ion-exchange capacity. It was found that the ionic strength of the elution buffer must be adjusted in order to compensate a change in the elution volume due to the ion-exchange capacity variations. The ionic strength and the pH of the elution buffer were also found to be important variables affecting the elution volume. In this model separation system, it was indicated that the pH should be within +/-0.1 unit and the ionic strength within +/-0.002 mol/l in order to meet the criteria (+/-5% elution volume variation). It is recommended that gradient elution data be obtained for predicting elution volume variations in stepwise elution. By using the gradient elution data the process diagnosis can be performed, and the important information on the process stability can be obtained.

Chromatography, Ion Exchange↗

PubMed1999

Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis.

This Chapter has reviewed the literature concerning VPF/VEGF as a potent vascular permeabilizing cytokine. In accord with this important role, microvessels have been found to be hyperpermeable to plasma proteins and other circulating macromolecules at sites where VPF/VEGF and its receptors are overexpressed, i.e., in tumors, healing wounds, retinopathies, many important inflammatory conditions and in certain physiological processes, such as ovulation and corpus luteum formation. Moreover, microvascular hyperpermeability to plasma proteins was shown to have an important consequence: the laying down of a fibrin-rich extracellular matrix. This provisional matrix, in turn, favors and supports the ingrowth of fibroblasts and endothelial cells which, together, transform the provisional matrix into the mature stroma characteristic of tumors and healed wounds. Finally, we have considered the pathways by which these and other circulating macromolecules cross the endothelium of normal and VPF/VEGF-permeabilized microvessels. These pathways include VVOs and trans-endothelial openings that have been variously interpreted as inter-endothelial cell gaps or trans-endothelial cell pores. At least some trans-endothelial cell pores may arise from VVOs. In conclusion, these data provide new insights into the mechanisms of angiogenesis and stroma formation, insights which are potentially applicable to a wide variety of disease states and which may lead to identification of new targets for therapeutic intervention.

Animals↗

PubMed1999

Rapid algorithms for the construction of cerebral blood flow and oxygen utilization images with oxygen-15 and dynamic positron emission tomography.

Two rapid estimation algorithms for construction of cerebral blood flow (CBF) and oxygen utilization (CMRO) images with dynamic positron emission tomography (PET) are presented. These algorithms are based on the linear least squares (LLS) and generalized linear least squares (GLLS) methodologies. Using the conventional two-compartmental model and multiple tracer studies, we derived a linear relationship for brain tissue activity to arterial blood activity, time-integrated arterial blood activity and time-integrated brain tissue activity. The LLS technique is computationally efficient as no regression analysis is required, while GLLS is used to refine the estimates obtained from LLS. A comparative study using non-linear least squares regression (NLS) revealed excellent correlation between the new algorithms for various noise levels expected in clinical applications. A sensitivity analysis was performed to examine reliability and identifiability of the parameter estimates. In view of the results, LLS and GLLS provide rapid and reliable estimates of CBF and CMRO when applied to dynamic PET data. These algorithms are particularly suitable for pixel-by-pixel construction of high resolution and highly accurate PET functional images.

Algorithms↗

PubMed1999

GLLS for optimally sampled continuous dynamic system modeling: theory and algorithm.

The original generalized linear least squares (GLLS) algorithm was developed for non-uniformly sampled biomedical system parameter estimation using finely sampled instantaneous measurements (D. Feng, S.C. Huang, Z. Wang, D. Ho, An unbiased parametric imaging algorithm for non-uniformly sampled biomedical system parameter estimation, IEEE Trans. Med. Imag. 15 (1996) 512-518). This algorithm is particularly useful for image-wide generation of parametric images with positron emission tomography (PET), as it is computationally efficient and statistically reliable (D. Feng, D. Ho, Chen, K., L.C. Wu, J.K. Wang, R.S. Liu, S.H. Yeh, An evaluation of the algorithms for determining local cerebral metabolic rates of glucose using positron emission tomography dynamic data, IEEE Trans. Med. Imag. 14 (1995) 697-710). However, when dynamic PET image data are sampled according to the optimal image sampling schedule (OISS) to reduce memory and storage space (X. Li, D. Feng, K. Chen, Optimal image sampling schedule: A new effective way to reduce dynamic image storage space and functional image processing time, IEEE Trans. Med. Imag. 15 (1996) 710-718), only a few temporal image frames are recorded (e.g. only four images are recorded for the four parameter fluoro-deoxy-glucose (FDG) model). These image frames are recorded in terms of accumulated radio-activity counts and as a result, the direct application of GLLS is not reliable as instantaneous measurement samples can no longer be approximated by averaging of accumulated measurements over the sampling intervals. In this paper, we extend GLLS to OISS-GLLS which deals with the fewer accumulated measurement samples obtained from OISS dynamic systems. The theory and algorithm of this new technique are formulated and studied extensively. To investigate statistical reliability and computational efficiency of OISS-GLLS, a simulation study using dynamic PET data was performed. OISS-GLLS using 4-measurement samples was compared to the non-linear least squares (NLS) method using 22-measurement samples, GLLS using 22-measurement samples and OISS-NLS using 4-measurement samples. Results demonstrated that OISS-GLLS was able to achieve parameter estimates of equivalent accuracy and reliability in comparison to NLS or GLLS using finely sampled measurements (22-measurement samples), or OISS-NLS using optimally sampled measurements (4-measurement samples). Further more, as fewer measurement samples are used in OISS-GLLS, this algorithm is computationally faster than NLS or GLLS. Therefore, OISS-GLLS is well-suited for image-wide parameter estimation when PET image data are recorded according to the optimal image sampling schedule.

Algorithms↗

PubMed1999

Information technology applications in biomedical functional imaging.

In parallel with rapid advances in computer technology, biomedical functional imaging is having an ever-increasing impact on healthcare. Functional imaging allows us to see dynamic processes quantitatively in the living human body. However, as we need to deal with four-dimensional time-varying images, space requirements and computational complexity are extremely high. This makes information management, processing, and communication difficult. Using the minimum amount of data to represent the required information, developing fast algorithms to process the data, organizing the data in such a way as to facilitate information management, and extracting the maximum amount of useful information from the recorded data have become important research tasks in biomedical information technology. For the last ten years, the Biomedical and Multimedia Information Technology (BMIT) Group and, recently, the Center for Multimedia Signal Processing have conducted systematic studies on these topics. Some of the results relating to functional imaging data acquisition, compression, storage, management, processing, modeling, and simulation are briefly reported in this paper.

Algorithms↗

PubMed1999

Increased platelet aggregability associated with platelet GPIIIa PlA2 polymorphism: the Framingham Offspring Study.

The platelet glycoprotein IIb/IIIa (GP IIb/IIIa) plays a pivotal role in platelet aggregation. Recent data suggest that the PlA2 polymorphism of GPIIIa may be associated with an increased risk for cardiovascular disease. However, it is unknown if there is any association between this polymorphism and platelet reactivity. We determined GP IIIa genotype and platelet reactivity phenotype data in 1422 subjects from the Framingham Offspring Study. Genotyping was performed using PCR-based restriction fragment length polymorphism analysis. Platelet aggregability was evaluated by the Born method. The threshold concentrations of epinephrine and ADP were determined. Allele frequencies of PlA1 and PlA2 were 0.84 and 0.16, respectively. The presence of 1 or 2 PlA2 alleles was associated with increased platelet aggregability as indicated by incrementally lower threshold concentrations for epinephrine and ADP. For epinephrine, the mean concentrations were 0.9 micromol/L (0.9 to 1.0) for homozygous PlA1, 0.7 mmol/L (0.7 to 0.9) for the heterozygous PlA1/PlA2, and 0.6 micromol/L (0.4 to 1.0) for homozygous PlA2 individuals, P=0.009. The increase in aggregability induced by epinephrine remained highly significant (P=0.007) after adjustment for covariates. For ADP-induced aggregation, the respective mean concentrations were 3.1 micromol/L (3.0 to 3.2), 3.0 micromol/L (2.9 to 3.2), and 2.8 micromol/L (2.4 to 3.3); P=0.19 after adjustment for covariates. Our findings indicate that molecular variants of the gene encoding GP IIIa play a role in platelet reactivity in vitro. Our observations are compatible with and provide an explanation for the reported association of the PlA2 allotype with increased risk for cardiovascular disease.

Adenosine Diphosphate↗

PubMed1999

Pathways of macromolecular extravasation across microvascular endothelium in response to VPF/VEGF and other vasoactive mediators.

OBJECTIVE: The goal of these studies was to define the anatomic pathways by which circulating macromolecules extravasate from the hyperpermeable microvessels that supply tumors and from normal venules that have been rendered hyperpermeable by vasoactive mediators. METHODS: Extravasation pathways of circulating macromolecular tracers were followed by several morphological techniques: light and fluorescence microscopy, transmission electron microscopy of routine as well as ultrathin and serial sections, computer-assisted three-dimensional reconstructions, and morphometry. RESULTS AND DISCUSSION: Macromolecules extravasated across tumor microvessels or across normal venules rendered hyperpermeable by VPF/VEGF, histamine, or serotonin by three primary pathways: 1) Vesiculo-vacuolar organelles (VVOs), clusters of cytoplasmic vesicles and vacuoles that span endothelial cytoplasm from lumen to ablumen; 2) trans-endothelial cell (EC), pores, and 3) fenestrae. We also present data concerning the structure and function of VVOs as well as evidence that VVOs form as the result of linking together and fusion of caveolae-sized unit vesicles. Under suitable conditions VVOs also afforded a pathway for macromolecular transport in the reverse direction, i.e., from vascular ablumen to lumen. Finally, in addition to opening VVOs to the passage of macromolecules, mediators such as VPF/VEGF may also induce structural rearrangements of VVOs, transforming them into trans-EC pores or fenestrae.

Animals↗

PubMed1999

[Clinical applications of the anterolateral skin flap and the fascial flap in the lower leg].

OBJECTIVE: To introduce the applied anatomy, operative method and clinical application of the anterolateral skin flap and fascial flap of the lower leg. METHODS: Anatomic dissection was performed on 14 adult cadavers' legs and one amputated lower limb. The origin, course and distribution of cutaneous branches of the superficial peroneal vessels were traced. Four types of anterolateral flaps were designed in the lower leg including the island skin flap, the island fascial flap, the rectangular flap, and the cross-leg flap. Since 1988, twenty-six cases of leg defects(21 patients), chronic osteomyelitis of the tibia(3 cases) and defects on the back of the opposite heel and ankle(2 cases) were treated with the operative methods. RESULTS: All the flaps survived. Primary healing occurred in 23 and secondary in 3 cases. Twenty cases were followed-up for 4 months to 5 years. The flaps were growing well, the tibia fracture healed 3 months after the treatment and the chronic osteomyelitis of tibia had no recurrence. CONCLUSION: This flap is a useful method for repairing various defects in the leg and adjacent regions. It is simple, safe and reliable in manipulation and has minimal influence to the donor site.

Adolescent↗

PubMed1999

[Association of polymorphisms of apolipoprotein B gene with cholesterol gallstone disease].

OBJECTIVE: To investigate the association between the apolipoprotein B (apoB) gene polymorphic sites Ins/Del and Xbal, and cholesterol gallstone disease. METHODS: The two polymorphic sites of apoB gene were examed in 101 cholesterol gallstone patients and 50 controls by polymerase chain reaction and restriction fragment length polymorphism methods. RESULTS: For Xbal polymorphic site, the frequency of the rare allele X+ and the distribution of X+X- genotype were significantly higher in the patient group than in the control group (P < 0.05). For Ins/Del polymorphic site, no significant difference was found in allele frequency and genotype distribution between the patient group and the control group. CONCLUSIONS: Xba1 polymorphism of apoB gene may be associated with cholesterol gallstone disease. The association, however, is not present for Ins/De1 polymorphism of apoB gene with cholesterol gallstone disease.

Adult↗

PubMed1999

[Changes on positive rate and distribution of Helicobacter pylori during progression of gastric cancer].

We observed changes on the positive rate and the distribution of helicobacter pylori (HP) in 7 case during early stage of gastric cancer and in 42 cases during middle-late stage of gastric cancer. The results showed that 1. the positive rate during early stage of gastric cancer was 57.1%, the positive rate during middle-rate stage of gastric cancer was 23.8%, 2. HP was not found within the gastric cancer lesions, 3. for HP positive cases, HP distribution during early stage of gastric cancer was more sparse than during middle-late stage of gastric cancer. These results suggested that HP can hardly live within the gastric cancer tissue, so the progression of gastric cancer is probably independent of HP. It may be a question that HP eradication can prevent later development of gastric cancer.

Adenocarcinoma↗

PubMed1999

[Regulation of p53 and bcl-2 proteins to apoptosis and cell proliferation in liver cirrhosis and hepatocellular carcinoma].

In situ apoptosis labelling was used for detecting apoptotic cells, and immunohistochemistry for p53, bcl-2 proteins and proliferation cell nuclear antigen(PCNA) in hepatocellular carcinoma(HCC) and liver cirrhosis tissues. The results were that in HCC, the number of apoptotic cells was higher, the density of proliferation cells lower, and expressions of p53 and bcl-2 protein were stronger than that in liver cirrhosis, and they were related to differentiation degree of HCC. The data indicate that overexpression of bcl-2 and mutant p53 proteins, which causes imbalance between cell proliferation and apoptosis, may bring about genesis and development of HCC by selecting proliferation of cells.

Adult↗

PubMed1999

[Observation of apoptosis and proliferation in nasopharyngeal carcinoma].

In order to observe the apoptosis and proliferation of cells in nasopharyngeal carcinoma(NPC) and pericarcinomatous tissue(PCT), 49 cases of NPC and partly PCT were detected by in situ end-labelling (ISEL) technique and proliferating cell nuclear antigen(PCNA) immunohistochemical staining. The results showed that: 1. Massive distribution of ISEL positive cells was frequently exhibited in vesicular nucleus cell carcinoma(VNCC) of NPC, in which no apoptotic pattern character was found. 2. The positive rate and the staining intensity index(SII) of ISEL signals in NPC were higher than that in PCT(P < 0.05); the positive correlation between ISEL SII and PCNA SII was found in NPC(r = 0.341, P < 0.05), whereas the positive rate and the SII of ISEL signals were significantly lower than that of PCNA (P < 0.01). 3. The ISEL SII and the PCNA SII in VNCC were obviously higher than that in poorly differentiated squamous cell carcinoma(PDSCC) (P < 0.01, P < 0.05). Patients with VNCC had a high five-year survival rate. The results suggest that there is a relationship between cellular proliferation and cellular apoptosis in NPC.

Apoptosis↗

PubMed1999

[Apoptosis of CD4(+) T cells during experimental autoimmune neuritis in Wistar rats].

The present study describes apoptosis of T cells in the sciatic nerve in Wistar rats with experimental autoimmune neuritis(EAN). Morphological characterizations of apoptosis were found at the 18th day from onset, peaked at the 22nd day by immunocytochemical analysis. In situ end labeling(ISEL) techniques confirmed the presence of DNA fragmentation in CD4(+) T cells. It is suggested that apoptosis is an important clearance mechanism of infiltrated T cells in the peripheral nervous system(PNS) in EAN.

Animals↗