Biomedical subjects

Y N Sun

Publications and source records attributed to Y N Sun.

At least 19 recordsLinked to original sources

PubMed2000

Novel image analysis of corpus cavernous tissue in impotent men.

OBJECTIVES: To objectively evaluate the contents of corpus cavernous tissue in impotent men using an automated novel image analysis system. METHODS: Thirty-three impotent men and 2 normal potent men (controls) underwent corpus cavernous biopsies. The procedures were performed using a Biopty gun under local anesthesia. The obtained specimens were stained with Masson's trichome technique, and the collagen fiber contents were evaluated by a computerized morphometric analysis method. In addition, we estimated the intraobserver and interobserver reliability of this automated image analysis system. RESULTS: No major complication was noted during or after the biopsies. Of the 33 impotent patients, 3 were diagnosed as having psychogenic, 11 as having arteriogenic, 13 as having venogenic, 1 as having neurogenic, and 5 as having idiopathic impotence. The collagen fiber percentages in the 35 men were as follows: normal potent: 48.2% +/- 1.4%, psychogenic 55.2% +/- 11.6%, arteriogenic 73.2% +/- 4.4%, venogenic 66.5% +/- 4.2%, neurogenic 76.9%, and idiopathic 77.4% +/- 4.2%. Significant differences were found between the normal potent and arteriogenic groups (P <0.05) and between the normal potent and idiopathic groups (P <0.05). Patients older than 60 years had a higher collagen fiber content (70.4% +/- 3.7%) than those younger than 50 years old (58.6% +/- 5.2%). The interobserver and intraobserver variances were both negligible for this automated image analysis system. This method significantly reduced the amount of variation introduced by the intra-rater reliability of a technician compared with the manual method. CONCLUSIONS: The present automated image analysis system is believed to be a reliable, accurate quantitative measurement tool for studies of penile tissue. Cavernous biopsy is a rapid, safe, and representative modality to study penile disease. An increase in cavernous collagen fibers (or corporal fibrosis) is considered an important factor in impaired erectile function.

Adult↗

PubMed1999

Role of baseline parameters in determining indirect pharmacodynamic responses.

Indirect Response Models account for the pharmacodynamics of numerous drugs which inhibit or stimulate the production (k(in)) or loss (k(out)) of the response variable (R). The dose and pharmacokinetics, capacity (S(max), I(max)), and potency (SC(50), IC(50)) factors of the Hill function incorporated in these models are the primary determinants of overall responsiveness. However, the initial or baseline value for the response (R(0) = k(in)/k(out)) should also be considered as an important factor for the net response. Using Indirect Response Model III (stimulation of input) as an example, the net area under the effect curve (AUEC(NET)) can be proportional to the R(0) values. Such a feature is demonstrated in this report by computer simulations, by examination of the integral of the simulated response vs time profiles, and with examples from the literature. Also shown is an adjustment of R(0) when the therapeutic agent is an endogenous substance. These analyses show that the role of R(0) and k(in) should not be overlooked as determinants of indirect responses and source of variation among subjects or patient groups.

Algorithms↗

PubMed1999

Interactive 3-D virtual colonoscopy system.

We describe a low-cost three-dimensional (3-D) virtual colonoscopy system that is a noninvasive technique for examining the entire colon and can assist physicians in detecting polyps inside the colon. Using the helical CT data and proposed techniques, we can three-dimensionally reconstruct and visualize the inner surface of the colon. We generate high resolution of video views of the colon interior structures as if the viewer's eyes were inside the colon. The physicians can virtually navigate inside the colon in two different modes: interactive and automatic navigation, respectively. For automatic navigation, the flythrough path is determined a priori using the 3-D thinning and two-pass tracking schemes. The whole colon is spatially subdivided into several cells, and only potentially visible cells are taken into account during rendering. To further improve rendering efficiency, potentially visible cells are rendered at different levels of detail. Additionally, a chain of bounding volume in each cell is used to avoid penetrating through the colon during navigation. In comparison with previous work, the proposed system can efficiently accomplish required preprocessing tasks and afford adequate rendering speeds on a low-cost PC system.

Automation↗

PubMed1999

Three-dimensional facial model reconstruction and plastic surgery simulation.

Facial model reconstruction and surgical simulation are essential to plastic surgery in today's medicine. Both can help surgeons to design appropriate repair plans and procedures prior to actual surgery. In this paper, we exploit a metamorphosis technique in our new design. First, using metamorphosis and vision techniques, we can establish three-dimensional facial models from a given photo. Second, we design several morphing operators, including augmentation, cutting, and lacerating. Experiments show that the proposed algorithms can successfully create acceptable facial models and generate realistically visual effects of surgical simulation.

Computer Simulation↗

PubMed1999

A pharmacokinetic/pharmacodynamic model for recombinant human growth hormone effects on induction of insulin-like growth factor I in monkeys.

The pharmacokinetics of recombinant human growth hormone (rhGH) and its effects on the induction of insulin-like growth factor I (IGF-I) were studied in juvenile rhesus monkeys. Disposition profiles of rhGH from two short-term i.v. infusion studies were described by a two-compartment model yielding a clearance of 16.1 ml/min and T1/2 of 2.0 h. Four rhGH treatment groups were included in this study: group A, ProLease rhGH (24 mg), a sustained-release microsphere formulation; group B, a single s.c. injection plus an implanted osmotic pump (24.4 mg); group C, a single s.c. injection (25.9 mg); group D, daily 0.86-mg s.c. injection for 28 days. Their rhGH input profiles were analyzed by a numerical deconvolution method. ProLease and osmotic pump provided zero-order inputs of rhGH and maintained the serum rhGH concentrations around 9 to 13 ng/ml for 16 (group A) and 30 days (group B). For s.c. injections, rhGH underwent first-order absorption. An indirect response model was applied based on use of a Hill function for stimulation of IGF-I production. Parameter values obtained included Smax = 2.2, SC50 = 6.5 ng/ml, and gamma (slope coefficient) = 6.8, which were applicable to all treatments. The area under effect curve showed group B to be most effective for IGF-I induction, whereas group A produced the highest peak level in 16 days. Group C had the lowest induction among the four groups, despite being given the highest dose. Group D had modest IGF-I induction, but the pulsatile rhGH input is less effective than continuous input provided by ProLease. Our pharmacokinetic/pharmacodynamic model demonstrates that ProLease and osmotic pump delivery were best able to maintain rhGH level above the s.c.50 value, which provided more effective IGF-I induction compared with the single or daily subcutaneous injections in solution.

Animals↗

PubMed1999

Pharmacokinetic/Pharmacodynamic models for corticosteroid receptor down-regulation and glutamine synthetase induction in rat skeletal muscle by a Receptor/Gene-mediated mechanism.

Muscle wasting and excessive fat deposition are side effects attendant to chronic corticosteroid treatment. Corticosteroid immunosuppression is necessary in circumstances such as transplantation. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was used to help elucidate the relationships between the events in the molecular cascade that result in muscle wasting and fat deposition by corticosteroids. Specifically, the relationships for receptor/gene-mediated effects that result in increased glutamine synthetase (GS) activity in skeletal muscle were quantitatively analyzed after an i.v. bolus dose of 50 mg/kg methylprednisolone in male adrenalectomized Wistar rats. Profiles of methylprednisolone pharmacokinetics, glucocorticoid receptor density, and its mRNA, GS mRNA, and GS activity in gastrocnemius muscles were determined. The results were used to develop PK/PD models using differential equations in the ADAPT II program. Two indirect response models were tested for the dynamics of glucocorticoid receptor mRNA regulation by activated steroid/receptor complex. Both reduction in message synthesis and message destabilization may be involved but with some tissue specificity. The recovery of active receptor after down-regulation is biphasic. The initial recovery may involve receptor recycling from the nucleus, whereas the later phase may involve de novo synthesis of new receptor protein. The nuclear events and GS mRNA/GS induction in rat skeletal muscle show sequential relationships for each component for corticosteroid actions. The PK/PD models provide mechanism-based methods of quantifying complex processes in receptor/gene-mediated enzyme induction featuring the characteristics of time delay and possible nonlinearity in intact tissues.

Animals↗

PubMed1998

Transit compartments versus gamma distribution function to model signal transduction processes in pharmacodynamics.

Delayed effects for pharmacodynamic responses can be observed for many signal transduction processes. Three approaches are summarized in this report to describe such effects caused by cascading steps: stochastic process model, gamma distribution function, and transit compartment model. The gamma distribution function, a probability density function of the waiting time for the final step in a stochastic process model, is a function of time with two variables: number of compartments N, and the expected number of compartments occurring per unit time k. The parameter k is equal to 1/tau, where tau is the mean transit time in the stochastic process model. Effects of N and k on the gamma distribution function were examined. The transit compartment model can link the pharmacokinetic profile of the tested compound, receptor occupancy, and cascade steps for the signal transduction process. Time delays are described by numbers of steps, the mean transit time tau, and the amplification or suppression of the process as characterized by a power coefficient gamma. The effects of N, tau, and gamma on signal transduction profiles are shown. The gamma distribution function can be utilized to estimate N and k values when the final response profile is available, but it is less flexible than transit compartments when dose-response relationships, receptor dynamics, and efficiency of the transduction process are of concern. The transit compartment model is useful in pharmacokinetic/pharmacodynamic modeling to describe precursor/product relationships in signal transduction process.

Animals↗

PubMed1998

Dose-dependence and repeated-dose studies for receptor/gene-mediated pharmacodynamics of methylprednisolone on glucocorticoid receptor down-regulation and tyrosine aminotransferase induction in rat liver.

Dose-dependent and repeated-dose effects of methylprednisolone (MPL) on down-regulation of glucocorticoid receptor messenger RNA (GR mRNA) and GR density, as well as tyrosine aminotransferase (TAT) mRNA and TAT induction by receptor/gene-mediated mechanisms in rat liver were examined. A previously developed pharmacokinetic/pharmacodynamic (PK/PD) model was used to design these studies which sought to challenge the model. Three groups of male adrenalectomized Wistar rats received MPL by i.v. injection: low-dose (10 mg/kg at Time 0), high-dose (50 mg/kg at Time 0), and dual-dose (50 mg/kg at Time 0 and 24 hr). Plasma concentrations of MPL, and hepatic content of free GR, GR mRNA, TAT mRNA, and TAT activity were determined. The P-Pharm program was applied for population analysis of MPL PK revealing low interindividual variation in CL and Vc values (3-14%). Two indirect response models were applied to test two competing hypotheses for GR mRNA dynamics. Indirect Pharmacodynamic Response Model I (Model A) where the complex in the nucleus decreases the transcription rate of GR mRNA better described GR mRNA/GR down-regulation. Levels of TAT mRNA began to increase at 1-2 hr, reached a maximum at 5-6 hr, and declined to the baseline at 12-14 hr after MPL dosing. The induction of TAT activity followed a similar pattern with a delay of about 1-2 hr. The low-dose group had 50-60% of the TAT mRNA and TAT induction compared to the high-dose group. Since the GR density returned to about 70% of the baseline level before the second 50 mg/kg dose at 24 hr, tolerance was found for TAT mRNA/TAT induction where only 50-60% of the initial responses were produced. Our fourth-generation model describes the dose dependence and tolerance effects of TAT mRNA/TAT induction by MPL involving multiple-step signal transduction controlled by the steroid regimen, free GR density, and GR occupancy. This model may provide the foundation for studying other induced proteins or enzymes mediated by the similar receptor/nuclear events.

Animals↗

PubMed1998

Fourth-generation model for corticosteroid pharmacodynamics: a model for methylprednisolone effects on receptor/gene-mediated glucocorticoid receptor down-regulation and tyrosine aminotransferase induction in rat liver.

A fourth-generation pharmacokinetic/pharmacodynamic (PK/PD) model for receptor/genemediated effects of corticosteroids was developed. Male adrenalectomized Wistar rats received a 50 mg/kg i.v. bolus dose of methylprednisolone (MPL). Plasma concentrations of MPL, hepatic glucocorticoid receptor (GR) messenger RNA (mRNA) and GR density, tyrosine amino-transferase (TAT) mRNA, and TAT activity in liver were determined at various time points up to 72 hr after MPL dosing. Down-regulation of GR mRNA and GR density were observed: GR mRNA level declined to 45-50% of the baseline in 8-10 hr, and slowly returned to predose level in about 3 days; GR density fell to 0 soon after dosing and returned to the baseline in two phases. The first phase, occurring in the first 10 hr, entailed recovery from 0 to 30%. The second phase was parallel to the GR mRNA recovery phase. Two indirect response models were applied for GR mRNA dynamics regulated by activated steroid-receptor complex. A full PK/PD model for GR mRNA/GR down-regulation was proposed, including GR recycling theory. TAT mRNA began to increase at about 1.5 hr, reached the maximum at about 5.5 hr, and declined to the baseline at about 14 hr after MPL dosing. TAT induction followed a similar pattern with a delay of about 1-2 hr. A transcription compartment was applied as one of the cascade events leading to TAT mRNA and TAT induction. Pharmacodynamic parameters were obtained by fitting seven differential equations piecewise using the maximum likelihood method in the ADAPT II program. This model can describe GR down-regulation and the precursor/product relationship between TAT mRNA and TAT in receptor/gene-mediated corticosteroid effects.

Animals↗

PubMed1998

Expression of fibroblast growth factor-1 and fibroblast growth factor-2 in normal liver and hepatocellular carcinoma.

This study was performed to examine the immunohistochemical expression of fibroblast growth factor-1 and fibroblast growth factor-2 in normal liver and a total of 31 cases of hepatocellular carcinoma (HCC). Reactivity for both types of angiogenic factor did not exist in any cellular component of normal liver. For HCC, variable amounts of fibroblast growth factor-1 were detected in 6 of 31 cases (19.4%). There was no apparent relationship between the expression pattern and clinicopathologic factors (P > 0.1, respectively), except a positive correlation with histologic grading (P = 0.04). No tumor showed reactivity for fibroblast growth factor-2 in their cancer cells. However, both types of peptide could be demonstrated in the pericellular stroma of HCC. With a mean follow-up at 60 months, fibroblast growth factor-1 expression did not correlate with patients' outcome (P > 0.1). Our study suggested that fibroblast growth factor-1 appears to play a certain role in hepatocarcinogenesis.

Adolescent↗

PubMed1998

Computer morphometry for quantitative measurement of liver fibrosis: comparison with Knodell's score, colorimetry and conventional description reports.

Liver fibrosis is currently described quite subjectively or, at best, semiquantitatively by scoring systems. In order to measure the severity of liver fibrosis quantitatively and to compare this with established methods, such as Knodell's scoring system, the colorimetric method and conventional description reports, we undertook the present study. A personal computer with an image grabber card and a microscope equipped with a computer-controlled slide-driver was used for computer morphometry. The principle behind morphometry is based on the different colours of hepatocytes and fibres following staining with Masson's trichrome stain. There were 31 patients (25 male, six female) recruited into the present study with a mean +/- SD age of 41.6 +/- 15 years (range 24-66 years). Of these patients, 16 had chronic hepatitis B, 12 had chronic hepatitis C and three were alcoholics. Colorimetric methods and Knodell's fibrosis score were performed according to established protocols. Conventional description reports were obtained from reviews of patient charts. The results from computer morphometry were highly correlated with results from the colorimetric method, with a correlation coefficiency gamma = 0.85 (P<0.0001). The results from computer morphometry also correlated with both Knodell's scoring system (gamma = 0.69; P<0.001) and conventional description reports (gamma = 0.46; P<0.01). Results from Knodell's scoring system were significantly correlated with computer morphometry, as follows: score 0, 2.7 +/- 1.4; score 1, 5.7 +/- 1.2; score 2, 7.7 +/- 2.3; score 3, 10.7 +/- 3.2; score 4, 21.8 +/- 14.1. The trend was statistically significant by the Wilcoxon rank sum test. In conclusion, our computerized morphometry system is a reliable tool for the evaluation of the severity of liver fibrosis and can be used as a tool for the objective quantification of liver fibrosis.

Adult↗

PubMed1997

Corticosteroid effects in skeletal muscle: gene induction/receptor autoregulation.

Common side effects of corticosteroid therapy include muscle weakness and atrophy, which are in part mediated by the induction of the enzyme glutamine synthetase. In addition, corticosteroids autoregulate their own receptor, thereby modulating tissue sensitivity to the hormone. The data in this report demonstrate that these gene-mediated effects are evident in muscle after short-term administration. Determination of molecular response dynamics could be useful in the design of future treatment regimens.

Animals↗

PubMed1997

Multiresolution registration of coronary artery image sequences.

Registration of coronary arterial images taken at different times is very important for obtaining better visibility of differences between sequential images. A typical image registration algorithm often employs a similarity measure to detect the differences generated from the relative motion or gray level changes between these images. Although a number of image registration approaches have been proposed to resolve the registration problem of digital angiography, they are either computationally expensive or not very robust in the application to practical images. This paper presents a feature-based sum of absolute values of difference (SAVD) using a coarse-to-fine strategy. The proposed algorithm was demonstrated to be capable to automatically registering the arterial structures in the areas of interest selected from a pair of sequential images as well as providing fractional pixel precision in registration. Compared to other existing methods, the algorithm improves the speed and the reliability of registration when a pair of coronary arterial images are acquired at the same or almost the same phase of cardiac motion.

Algorithms↗

PubMed1996

Mapping of HPV-11 E1 binding site and determination of other important cis elements for replication of the origin.

The viral proteins E1 and E2 are essential for the replication of the HPV-11 origin. We have now mapped the E1 binding site (E1BS) and show by mutation analysis that the E1BS and an adjoining poly(A)-rich region are necessary for efficient replication of the origin. We have also shown, using suboptimal levels of E1 protein, that enhancement of E1 binding by E2 partially protects the E1BS. Finally, we show that E1 can enhance the binding of E2 even in the absence of the E1BS.

Base Sequence↗

PubMed1995

Third-generation model for corticosteroid pharmacodynamics: roles of glucocorticoid receptor mRNA and tyrosine aminotransferase mRNA in rat liver.

A third-generation pharmacokinetic/pharmacodynamic model was proposed for receptor/gene-mediated corticosteroid effects. The roles of the messenger RNA (mRNA) for the glucocorticoid receptor (GR) in hepatic GR down-regulation and the mRNA for hepatic tyrosine aminotransferase (TAT) induction by methylprednisolone (MPL) were examined. Male adrenalectomized Wistar rats received 50 mg/kg MPL iv. Blood and liver samples were collected at various time points for a period of 18 hr. Plasma concentrations of MPL, free hepatic cytosolic GR densities, GR mRNA, TAT mRNA, and TAT activities in liver were determined. Plasma MPL profile was biexponential with a terminal t1/2 of 0.57 hr. Free hepatic GR density rapidly disappeared from cytoplasm after the MPL dose and then slowly returned to about 60% of starting level after 16 hr. Meanwhile, GR mRNA level fell to 45% of baseline within 2 hr postdosing, and remained at that level for at least 18 hr. The GR down-regulation of GR mRNA and protein turnover rate were modeled. The TAT mRNA began to increase at about 2 hr, reached a maximum at about 5 hr, and declined to baseline by 14 hr. TAT induction followed a similar pattern, except the induction was delayed about 0.5 hr. Pharmacodynamic parameters were obtained by fitting seven differential equations in a piecewise fashion. The cascade of corticosteroid steps were modeled by a series of inductions for steroid-receptor-DNA complex, two intermediate transit compartments, TAT mRNA, and TAT activity. Results indicate that GR mRNA and TAT mRNA are major controlling factors for the receptor/gene-mediated effects of corticosteroids.

Adrenal Cortex Hormones↗

PubMed1995

A fully automated identification of coronary borders from the tree structure of coronary angiograms.

The accurate assessment of variations in coronary arterial dimensions plays an important role in the evaluation of ischemic heart disease and the effectiveness of treatment. Although there exist a variety of edge detection algorithms in the literature, most of them are human interactive and may provide a poor estimate on coronary lesion. In this paper, we present a new method for automatic identification of arterial borders. The proposed algorithm makes use of mathematical morphology to segment blood vessels which follow a tree structure, based on a priori knowledge of coronary anatomy. Finally, an adaptive tracking strategy is applied to automatically identify 2-D arterial borders along both sides of the vessels. This is accomplished by using an edge detection model at a branching point, matched filters, and the tree structure of the coronary artery. Experimental results show that our approach not only is insensitive to the intensity variations of background and noise, but also can extract the boundary of the coronary artery accurately.

Algorithms↗

PubMed1995

Three-dimensional reconstruction of biliary tract from biplane projections.

Over the past few years, very little has been done in the area of 3-D reconstruction of the bile duct. Since the system in use for 3-D visualization of the biliary tree is built by surgical or autopsy materials, it generally cannot be applied to clinical diagnosis. In this paper, an algorithm for three-dimensional reconstruction of the biliary tree from two mutually orthogonal is presented to provide accurate and reproducible 3-D information of the biliary tree structure. It has been proven to be useful in diagnosis prior to operation or non-surgical treatment, particularly, obstructive stones can be visualized by using a transparency technique. As experiments demonstrated, the proposed method can be used as a useful tool for the visualization of 3-D structure of biliary tree in clinical applications.

Algorithms↗

PubMed1995

Three-dimensional reconstruction of the biliary tract from two-dimensional biliary images.

To make conventional two-dimensional cholangiography easier and more precise to read, we used techniques in computer vision to reconstruct the images in three dimensions. A 72-year-old man and a 70-year-old woman suffering from acute cholangitis were treated using endoscopic nasobiliary drainage. Their cholangiograms, from two orthogonal views, were used for three-dimensional reconstruction. We used video image-grabber and film scanner methods to digitize the original conventional biliary radiographs, and applied two different image processing methods to show the biliary structure. Both methods of three-dimensional reconstruction of the biliary tract were highly useful in evaluating the biliary tracts in these two patients, especially when a semitranslucence overlapping display technique was applied in the second patient. With this technique, the biliary tree itself and the stones inside the common bile duct can be clearly delineated. The technique of three-dimensional reconstruction of biliary images can make the conventional cholangiographs more lifelike and has great potential in surgical simulation in the near future.

Aged↗