Biomedical subjects

D Feng

Publications and source records attributed to D Feng.

At least 37 records · Page 2Linked to original sources

PubMed2000

The effect of vitamin C supplementation on coagulability and lipid levels in healthy male subjects.

Although dietary intake and plasma levels of vitamin C have been inversely associated with cardiovascular disease, the mechanism through which it may exert its effect has not been fully explained. Since thrombosis plays an important role in the onset of cardiovascular disease, we investigated the effect of vitamin C on measures of hemostasis that have been associated with cardiovascular risk. The effect of vitamin C on lipid levels was also evaluated. In a randomized, placebo-controlled, crossover study, we determined the effect of 2 g daily of vitamin C supplementation on platelet adhesion and aggregation, levels of tissue plasminogen activator antigen, plasminogen activator inhibitor, fibrinogen, plasma viscosity, von Willebrand factor, and lipid levels in 18 healthy male volunteers with low normal vitamin C levels. No striking effects of vitamin C on the hemostatic measures were observed, although tissue plasminogen activator antigen levels were inversely related to Vitamin C levels. Von Willebrand factor levels were slightly higher with vitamin C, although within the normal range. Total cholesterol levels were 10% lower when subjects were receiving vitamin C compared to placebo (167+/-7 mg/dL vs. 184+/-7 mg/dL), P=0. 007), although the total cholesterol/HDL ratio was not significantly different. Higher levels of tissue plasminogen activator antigen, which in the present study were associated with lower vitamin C levels, have been shown in prospective studies to convey an increased risk of cardiovascular events. Further studies of the effect of vitamin C on hemostatic measures are required in higher risk populations or those with known cardiovascular disease.

Adult↗

PubMed2000

Identification of a PDZ-domain-containing protein that interacts with the scavenger receptor class B type I.

The scavenger receptor class B type I (SR-BI) mediates the selective uptake of cholesteryl esters from high-density lipoprotein (HDL) and cholesterol secretion into bile in the liver. In this study, we identified an SR-BI-associated protein from rat liver membrane extracts by using an affinity chromatography technique. This protein of 523 amino acids contains four PDZ domains and associates with the C terminus of SR-BI by using its N-terminal first PDZ domain. Therefore, we denoted this protein as CLAMP (C-terminal linking and modulating protein). CLAMP was located mostly in the sinusoidal membranes, whereas SR-BI was detected in both sinusoidal and canalicular membranes. After the solubilization of the liver membranes with Triton X-100, SR-BI was immunoprecipitated with anti-CLAMP monoclonal antibody, suggesting the association of these proteins in vivo. By coexpressing SR-BI with CLAMP in Chinese hamster ovary cells, we observed (i) the increase in the expression level of SR-BI, (ii) the reduction in the deacylation rate of the cholesteryl esters taken up from HDL, and (iii) the change in the intracellular distribution of fluorescent lipid 1,1'-dioctadecyl-3,3, 3',3'-tetramethylindocarbocyanine percholate taken up from HDL. Taken together, these data suggest that CLAMP, a four-PDZ-domain-containing protein, is associated with SR-BI in the liver sinusoidal plasma membranes and may modulate the intracellular transport and metabolism of cholesteryl esters taken up from HDL.

Amino Acid Sequence↗

PubMed2000

Different pathways of macromolecule extravasation from hyperpermeable tumor vessels.

Tumor microvessels are hyperpermeable to plasma proteins, a consequence of tumor cell-secreted vascular permeability factor/vascular endothelial growth factor (VPF/VEGF). However, the pathways by which macromolecules extravasate from tumor vessels have been little investigated. To characterize tumor vessels more precisely and to elucidate the pathways by which macromolecules extravasated from them, we studied two well-defined, VPF/VEGF-secreting murine carcinomas, MOT and TA3/St. Whether grown in ascites or solid form, MOT tumors induced large, pericyte-poor "mother" vessels whose lining endothelium developed fenestrae that involved 1.8-5.6% of the surface. Fenestrae developed in parallel with markedly reduced endothelial cell vesiculo-vacuolar organelles (VVOs). TA3/St tumors, which secreted more VPF/VEGF than MOT tumors, elicited mother vessels with unchanged VVOs and without fenestrae. In both tumors, a plasma protein tracer, ferritin, extravasated through VVOs and in MOT tumors ferritin also extravasated through fenestrae. Endothelial gaps were not observed in either tumor. Thus, not all VPF/VEGF-secreting tumors induce fenestrated endothelium. Also, VVOs provide an internal store of membrane that can be transferred to the endothelial cell surface to provide the substantial increase in plasma membrane necessary for mother vessel formation in MOT tumors. Such transfer was apparently unnecessary in TA3/St tumors in which extensive early endothelial cell division provided the increased plasma membrane necessary for forming mother vessels.

Animals↗

PubMed2000

Effect of short-term aspirin use on C-reactive protein.

Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, have been shown to be predictive of cardiovascular disease. In the Physicians Health Study, the magnitude of reduction in the risk of myocardial infarction with aspirin therapy was related to baseline CRP levels, raising the possibility that the protective effect of aspirin may be due to antiinflammatory properties in addition to its antiplatelet effect. We therefore investigated whether aspirin therapy lowers CRP levels. Because heavy physical exertion is a well-known trigger of myocardial infarction, we also investigated the effect of aspirin on CRP levels before and after strenuous exercise. Thirty-two healthy men, aged 29 +/- 6 years, were enrolled in a randomized, double-blind, parallel study. Blood samples were obtained immediately before and after maximal treadmill exercise at baseline and following 7 days of aspirin therapy (81 or 325 mg). The levels of CRP, as measured by ELISA, increased by 13% following exercise (P < 0.0001). However, aspirin did not significantly alter CRP levels, either at rest (0.81 +/- 0.13 mg/L before aspirin vs. 0.78 +/- 0.13 mg/L on aspirin) or following exercise (0.92 +/- 0.13 mg/L before aspirin vs. 0.86 +/- 0. 13 mg/L on aspirin), P = 0.73. When the resting and postexercise data were combined, the levels were 0.87 +/- 0.13 mg/L before aspirin and 0.82 +/- 0.13 mg/L on aspirin (a nonsignificant 6% reduction, P = 0.20). In conclusion, in healthy male subjects CRP levels were not significantly reduced by short-term aspirin therapy. Our data, taking together with other reports, suggest that aspirin may not affect the levels of inflammatory markers. However, further studies are needed with a longer duration of therapy, among subjects with coronary heart disease, and using additional markers of inflammation besides CRP to determine the long-term effects of aspirin use.

Acute-Phase Proteins↗

PubMed2000

Heterogeneity of the angiogenic response induced in different normal adult tissues by vascular permeability factor/vascular endothelial growth factor.

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) is an angiogenic cytokine with potential for the treatment of tissue ischemia. To investigate the properties of the new blood vessels induced by VPF/VEGF, we injected an adenoviral vector engineered to express murine VPF/VEGF164 into several normal tissues of adult nude mice or rats. A dose-dependent angiogenic response was induced in all tissues studied but was more intense and persisted longer (months) in skin and fat than in heart or skeletal muscle (< or =3 weeks). The initial response (within 18 hours) was identical in all tissues studied and was characterized by microvascular hyperpermeability, edema, deposition of an extravascular fibrin gel, and the formation of enlarged, thin-walled pericyte-poor vessels ("mother" vessels). Mother vessels developed from preexisting microvessels after pericyte detachment and basement membrane degradation. Mother vessels were transient structures that evolved variably in different tissues into smaller daughter vessels, disorganized vessel tangles (glomeruloid bodies), and medium-sized muscular arteries and veins. Vascular structures closely resembling mother vessels and each mother vessel derivative have been observed in benign and malignant tumors, in other examples of pathological and physiological angiogenesis, and in vascular malformations. Together these data suggest that VPF/VEGF has a role in the pathogenesis of these entities. They also indicate that the angiogenic response induced by VPF/VEGF is heterogeneous and tissue specific. Finally, the muscular vessels that developed from mother vessels in skin and perimuscle fat have the structure of collaterals and could be useful clinically in the relief of tissue ischemia.

Animals↗

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↗

PubMed2000

[Spectrofluorometric trace determination of cerium(III) with ethylenediamintetraksi (methylphosphonic acid)].

Fluorescence of Ce(III) was greatly enhanced when Ce(III) forming 1:1 complex with ethylenediaminetetrakis (methylphosphonic acid)(EDTP) in solution of pH 7-8. The use of EDTP in the spectrofluorometric determination of trace amounts of cerium(III) ions is described. The apparent excitation and fluorescence wavelength are 313 and 397 nm, respectively. The fluorescence varies linearly with the concentration of cerium(III) in the range of 1 x 10(-8)-1 x 10(-4) mol.L-1, which is closed to the known best method. The quenching effects of some inorganic ions and other lanthanides are also investigated, which indicated that the method is superior to others in climinating the interfere of other ions, especially for Pr3+ and PO4(3-) ions.

Cerium↗

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↗