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Biomedical subjects

F Yuan

Publications and source records attributed to F Yuan.

82 records · Page 5Linked to original sources
PubMed1992

[Effects of calcium blockers on the performance of left and right ventricles during acute hypoxia].

In anesthetized and thoracotomized 20 adult dogs under artificial respiration, the effects of calcium blockers (nifedipine, diltiazem and verapamil) on the mechanics of the left and right cardiac pumps under acute hypoxia were observed. The left and right ventricular pressure (LVP and RVP) and their dp/dt (+/- dp/dtmax), aortic flow (Fa), pulmonary pressure (Ppa) and heart rate (HR) were recorded. After treatment with calcium blockers, LVP and L +/- dp/dtmax decreased, and Fa increased, while RVP, R +/- dp/dtmax and Ppa all tended to increase. These results showed that the effects of calcium blockers on the performance of the left and right ventricles were different, suggesting that the dependence of left and right myocardium on calcium was different in degree. The mechanics of the left and right ventricles responded differently to calcium blockers under acute hypoxia. After treatment with calcium blockers, pressor responses on LVP by acute hypoxia disappeared. There was a great increase in Fa. Decrease in pressor response of RVP and Ppa was also observed in acute hypoxic dogs receiving verapamil and diltiazem. Comparing the effects of nifedipine, diltiazem and verapamil on the mechanics of the left and right cardiac pumps under acute hypoxia, it appears that diltiazem exerts beneficial effect on the performance of cardiac pump under acute hypoxia.

Animals↗
PubMed1991

Pharmacokinetic analysis of two-step approaches using bifunctional and enzyme-conjugated antibodies.

Bifunctional antibodies (BFA) and enzyme-conjugated antibodies (ECA) can be used to preferentially deliver a hapten or drug to tumor sites for diagnosis and therapy. We present here a simple pharmacokinetic model for the above two systems by considering only two compartments, the plasma and tumor. The models predict that the longer the time delay between the BFA and hapten or between the ECA and prodrug injections, the higher the tumor:plasma concentration ratio of the hapten or drug. In addition, multiple injections of the hapten or prodrug is predicted to give a more uniform concentration of the hapten or drug in both the tumor and plasma than bolus injection. We suggest that, initially, the most effective dose of BFA should be selected and then the hapten concentration chosen accordingly. The decrease of the ECA injection dose would increase the tumor:plasma concentration ratio of the drug and yet decrease the tumor concentration of the drug. In clinical application of the ECA system, consideration of ECA dose should be balanced between the tumor concentration and the tumor:plasma concentration ratio of the drug. The dose of the prodrug injection is suggested to be equal to the required toxic concentration of the drug in the tumor. There are several ways to improve the tumor:plasma concentration ratio of the hapten or drug, such as changing the binding kinetics of the antibody to tumor or the hapten to BFA and removing the antibody from the plasma before the injection of the hapten or prodrug. One notable difference between the BFA and ECA approaches is that there is an upper limit for maximum hapten concentration in the former, and hence, from the point of drug delivery alone the latter approach is presumably superior. The limitations of the models and therapeutic implications are also discussed.

Antibodies, Monoclonal↗
PubMed1991

A mathematical model for the receptor mediated cellular regulation of the low density lipoprotein metabolism.

A prototype mathematical model for Brown and Goldstein's pioneering studies on the LDL receptor mediated pathway for the regulation of the cellular content of cholesterol has been developed in this paper. In order to analyze the essential features of this complex system quantitatively and still reflect the framework of the total system, six important processes are considered in the model. They are: (1A, B) the hydrolysis and synthesis of the LDL receptor; (2) the binding of LDL to its receptors; (3) the hydrolysis of LDL; (4) the storage of cholesteryl esters; (5) the regulation of de novo synthesis of cholesterol; and (6) the efflux of free cholesterol to the external medium. All these processes form a system to let the cells take up enough cholesterol from the external medium for their utilization and yet avoid the excessive accumulation of the lipid within the cells. The validity of the model is tested by showing that it can predict many of experimental curves obtained for human fibroblasts in tissue culture studies. The main purpose of the model is to determine how the free cholesterol level in the cell is related to the external LDL concentration and the regulatory capacity of the cells to adapt to a changing LDL environment. In addition, the model reveals an important behavior of SMC, i.e., for a slowly increasing LDL concentration in the extracellular medium, the rate of intracellular degradation of LDL will first increase and then become saturated. It is proposed based on these results that the saturation of LDL degradation by SMCs and the subsequent increase in subendothelial LDL levels in regions of high macromolecular permeability might play a vital role in the formation of the early foam cell lesion.

Cells, Cultured↗
PubMed1991

A new view of convective-diffusive transport processes in the arterial intima.

In this paper a new theoretical framework is presented for analyzing the filtration and macromolecular convective-diffusive transport processes in the intimal region of an artery wall with widely dispersed macromolecular cellular leakage sites, as proposed in the leaky junction-cell turnover hypothesis of Weinbaum et al. In contrast to existing convection-diffusive models, which assume that the transport is either 1-D, or convection is primarily in a direction normal to the endothelial surface, the present model considers for the first time the nonuniform subendothelial pressure field that arises from the different hydraulic resistances of normal and leaky endothelial clefts and the special role of the internal elastic lamina (IEL) in modulating the horizontal transport of macromolecules after they have passed through the leaky clefts of cells that are either in mitosis or demonstrate IgG labeling. The new theory is able to quantitatively explain the growing body of recent experiments in which an unexpectedly rapid early-time growth of the leakage spot has been observed and the longer time asymptotic behavior in which the leakage spot appears to approach an equilibrium diameter. The new theory also predicts the observed doubling in macromolecular permeability between EBA labeled blue and white areas when the frequency of leakage sites is doubled. This frequency for doubling of permeability, however, is an order of magnitude smaller than predicted by the author's previous model, Tzeghai et al., in which only convection normal to the endothelial surface was considered and the pressure was uniform in the intima. The longer time model predictions are used to explain the time scale for the formation of liposomes in subendothelial tissue matrix in animal feeding experiments where it has been observed that the extracellular lipid concentration rises sharply prior to the entry of monocytes into the intima.

Arteries↗
PubMed1990

[Changes in systolic and diastolic function of reperfused myocardium after short coronary occlusions in conscious dogs].

Mongrel dogs were chronically implanted with sonomicrometer crystals and a high fidelity tip micromanometer to measure ventricular wall thickness (WT) and left ventricular pressure (LVP), respectively. Two weeks after surgical operation, the left circumflex coronary artery was occluded with a hydraulic occluder for 3 minutes in conscious condition. During reperfusion, the hemodynamic parameters and systolic wall thickening recovered to the normal level quickly, while an abnormal thickening phase during early relaxation (extra phase) appeared in the dWT/dt-WT loop (X-axis = WT, Y-axis = dWT/dt) with its pattern different from that during control and ischemic conditions. This kind of pattern of the loop could be observed during hypoxia and during rapid overfilling of coronary artery. It is supposed that some substances, which may be produced in the ischemic myocardium, induced an extra dilation of coronary artery during reperfusion and a rapid overperfusion in the early relaxation phase of the cardiac cycle, leading to the abnormal pattern in the loop.

Animals↗
PubMedDate not supplied

Effects of cell damage and glycosaminoglycan degradation on available extravascular space of different dextrans in a rat fibrosarcoma.

Drug delivery to solid tumors may be enhanced through increasing the available volume fraction (K(AV)) of drugs. Therefore, two approaches were investigated that may increase K(AV) of dextrans in a rat fibrosarcoma: (a) damaging cells in tumours via ex vivo incubation of tumour tissues, and (b) degrading tumour glycosaminoglycans (GAGs) with exogenous hyaluronidase. The molecular weights of dextrans used in this study were approximately 10,000 (D10), 70,000 (D70) and 2,000,000 (D2000), respectively. It was found that GAG degradation had minimal effects on K(AV) of dextrans. Ex vivo incubation at 37 degrees C for up to 3 h caused only minor cell damage and had minimal effects on K(AV) of D10 and D70. However, the ex vivo incubation reduced K(AV) of D2000 (p < 0.05). When the incubation at 37 degrees C was maintained for 20 h, the amount of viable cells in tumours was reduced by 56% and K(AV) of all dextrans were significantly increased (p < 0.05). Ex vivo incubation at 41 degrees C for 3 h caused similar cell damage to that at 37 degrees C for 20 h, but only K(AV) of D10 and D70 were increased significantly (p < 0.05). There was no significant change in K(AV) of D2000, although it was higher than that in tumours incubated at 37 degrees C for 3 h (p < 0.05). These data suggest that cell damage is a more effective approach than GAG degradation for increasing K(AV) of macromolecules and that the amount of increase depends on the degree of cell damage and the size of molecules.

Animals↗
PubMedDate not supplied

Effect of basic fibroblast growth factor on angiogenesis and growth of isografted bone: quantitative in vitro-in vivo analysis in mice.

Basic fibroblast growth factor (bFGF), a constituent of bone and cartilage matrix, has been shown to be a potent mitogen for osteoblasts and chondrocytes and yet an inhibitor of chondrocyte terminal differentiation in cell culture. To characterize the effect of bFGF on bone formation, whole neonatal murine femora were cultured in the presence or absence of bFGF and a neutralizing antibody against bFGF. In vitro, femoral elongation was provided by cartilage growth only; the calcified diaphyseal zone stained by oxytetracycline did not increase. When bFGF was added to the culture medium, longitudinal growth of the proximal and distal cartilage was inhibited in a dose-dependent manner (p < 0.05), and the number of hypertrophic chondrocytes in the growth plate was reduced. This phenomenon was absent in the presence of a neutralizing antibody, which when given alone significantly promoted femoral elongation. In contrast, in vivo after transplantation into adult mice bearing dorsal skin fold chambers, femora rapidly calcified after revascularization. This observation supports the notion that bone formation largely depends on angiogenesis-mediated events. To verify this hypothesis, angiogenesis and bone formation were quantified using bFGF known to be a stimulator of angiogenesis. Calcification of grafted femora was accelerated by bFGF given intraperitoneally. The neutralizing antibody slightly suppressed angiogenesis and femoral elongation (not statistically significant), whereas intravenous injections of both substances did not reveal a significant modulatory effect. In vivo the effect of systemically administered bFGF was inhomogeneous, but there was a strong correlation between angiogenesis and endochondral calcification (p < 0.001). These results suggest that exogenous bFGF modulates bone formation in vitro by inhibition of terminal differentiation of chondrocytes in the growth plate, and angiogenesis and concomitant in vivo events are pivotal in the promotion of rapid bone formation.

Animals↗
PubMedDate not supplied

Anti-estrogenic activities of indole-3-carbinol in cervical cells: implication for prevention of cervical cancer.

BACKGROUND: Cervical cancer constitutes the second most common cancer in women. Estrogen promotes development of cervical cancer in cells infected with high risk human papillomaviruses (HPVs). We asked whether the phytochemical indole-3-carbinol (I3C) has anti-estrogenic activities in cervical cells with the goal of preventing cancer in HPV infected cells. MATERIALS AND METHODS: Using the cervical cancer cell line CaSki, we evaluated expression of HPV and cytochrome p450 (CYP) enzymes by Northern, RNase protection or quantitative RT-PCR. I3C binding to estrogen receptor was measured by competition with estradiol. Estrogen metabolites were measured by gas chromarography-mass spectrometry (GC-MS). RESULTS: Estradiol increased expression of HPV oncogenes whereas I3C and the estrogen metabolite 2-hydroxyestrone (2-OHE) abrogated the estrogen-increased expression of HPV oncogenes. Both I3C and 2-OHE competed with estradiol for estrogen receptor binding. I3C enhanced gene expression of CYP enzymes responsible for 2-hydroxylation of estrogen, and induced the formation of 2-OHE. CONCLUSION: I3C has anti-estrogenic activities which should prevent cancer in cervical cells.

Anticarcinogenic Agents↗
PubMedDate not supplied

Inspection for gastric occult blood at regular intervals is the optimum program for the screening of esophageal-gastric cancer.

Gastric occult blood screening has been performed for 242296 persons from 1986 to 1993. 30227 persons had positive reactions to the occult blood reagent. Among them, 17915 persons were asked to accept gastroscopy exam, and 638 esophageal-gastric cancers were found. The cancer detection rates were 3.56%. 4774 persons were asked to accept screening twice and 203 persons were asked to accept screening three times. After follow-up, the cancer detection rates were 2.11% for occult blood positive group if the screening was conducted once a year. The missing case was 0.77% for negative group and it was 0.05% in the same group if the screening was performed twice. Lastly, the missing case would be decreased to 0% when the patients undergone the exam, for three times in continuity. Two thirds of patients still belonged to the early-middle stage of cancer. The 5-year survival rates were 95.2%. The missing case of cancer would be reduced to 0% if the screening was conducted for three years in continuity. The death rates were deducted as well. It is certified that this method is the most effective and reliable way for reducing the death rate of cancer and screening of the upper digestive tract cancer.

Adolescent↗