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Biomedical subjects

C W Chen

Publications and source records attributed to C W Chen.

At least 37 records · Page 2Linked to original sources

Two-dimensional phase unwrapping with use of statistical models for cost functions in nonlinear optimization.

Interferometric radar techniques often necessitate two-dimensional (2-D) phase unwrapping, defined here as the estimation of unambiguous phase data from a 2-D array known only modulo 2pi rad. We develop a maximum a posteriori probability (MAP) estimation approach for this problem, and we derive an algorithm that approximately maximizes the conditional probability of its phase-unwrapped solution given observable quantities such as wrapped phase, image intensity, and interferogram coherence. Examining topographic and differential interferometry separately, we derive simple, working models for the joint statistics of the estimated and the observed signals. We use generalized, nonlinear cost functions to reflect these probability relationships, and we employ nonlinear network-flow techniques to approximate MAP solutions. We apply our algorithm both to a topographic interferogram exhibiting rough terrain and layover and to a differential interferogram measuring the deformation from a large earthquake. The MAP solutions are complete and are more accurate than those of other tested algorithms.

Journal Article↗

Adult Wilms' tumor associated with polycythemia--a case report.

Both Wilms' tumor (nephroblastoma) in adults and polycythemia in Wilms' tumor are rare. Herein we report an extremely rare case of adult Wilms' tumor associated with polycythemia. A 41-year-old female was incidentally found to have right renal mass by abdominal sonography in a routine health examination. Laboratory examination revealed polycythemia (hemoglobin 20.2 g/dL). Although physical examination was unremarkable, CT scan revealed an homogeneous mass at the middle pole of right kidney, and chest x-ray revealed no metastatic lesions. Right radical nephrectomy was performed smoothly. Grossly, the tumor of 5 x 4.5 x 4.5 cm in size was well circumscribed, and had no vascular structure or collecting system involvement. Microscopic features were consistent with adult nephroblastoma. The post-operative course was uneventful. At follow-up, the patient was well, showed no evidence of recurrence and her hemoglobin level had returned to normal (hemoglobin 14.5 g/dl). We suggest that the relationship between polycythemia and Wilms' tumor should be carefully evaluated before surgical treatment.

Adult↗

Assessment of endocrine disruptors: approaches, issues, and uncertainties.

This paper focuses on the quantitative risk assessment of environmental endocrine-disrupting chemicals (EDCs) to human health. An EDC can be defined as an exogenous agent that interferes with the normal endocrine signaling and communication mechanisms. The normal feedback control system of natural hormones is responsible for regulatory mechanisms that maintain homeostasis. Hormones deliver their message to target cells by interacting with receptors, initiating signal transduction, gene transcription, and mRNA translation, and ultimately leading to cellular response. Because effects of EDCs include diverse disease endpoints such as cancer, reproductive toxicity, developmental toxicity, immune system effects, acute toxicity, and neurotoxicity, risk assessment of EDCs is necessarily endpoint-specific. From the quantitative viewpoint, it is best to model the normal endocrinology and then extend the model to include impacts attributable to a particular exogenous agent. A practical approach to such a complex process is to break the spectrum of biochemical and biological events into modular components: e.g., pharmacokinetics, biochemical/molecular (including cellular signaling), and cellular response/dynamics. A flexible mathematical procedure that is capable of modeling each of these components is suggested. However, a real biologically based model is not yet feasible because of a lack of necessary biological information. A challenge to risk assessors is how to develop a hybrid risk assessment approach that can use the limited biological information available for a specific agent and avoid relying on a default approach that incorporates no biological information. The USEPA's default approach is to derive benchmark dose (BMD) or benchmark concentration (BMC) on the basis of a predetermined empirical dose-response model. BMD (or BMC) is the highest dose (or concentration and duration) of exposure that is considered unlikely to cause adverse effects in a human population, including sensitive subgroups. Data from two studies are used to stimulate discussion of issues and the needs for new quantitative approaches and data for assessing endocrine disruptors. Statistical concepts about threshold effect and the U-shaped dose-response relationship are also discussed. This report is a condensed version of the one to be published in the monograph of the NATO Advanced Research Workshop, Endocrine Disrupters and Carcinogenesis Risk Assessment" held May 8-12, 2001, in Bialystok, Poland.

Endocrine System↗

Y-chromosome microdeletion and its effect on reproductive decisions in taiwanese patients presenting with nonobstructive azoospermia.

OBJECTIVES: To investigate the position, extent, and frequency of Y chromosome microdeletions in Taiwanese patients presenting with nonobstructive azoospermia, and to investigate the effect of microdeletions on reproductive decisions. METHODS: We studied 176 consecutive men with azoospermia in our urology clinic. Polymerase chain reaction tests were performed in 94 patients with nonobstructive azoospermia, and a series of 27 sequence-tagged sites (STSs) mapped within intervals 5 and 6 of Yq11 was selected for analysis. Clinical genetics counseling was provided to couples with microdeletions, and these couples made their own choices about further treatment modalities. RESULTS: Among 94 patients screened for microdeletion, 11 (11.7%) showed microdeletions of one or more STSs. One had a deletion confined to the azoospermia factor b (AZFb) region (encompassing the RBM gene). Two were found to have deletions of both the AZFb and AZFc regions. Eight patients had deletions in the AZFc region (encompassing the DAZ gene). Five had deletions distal to the DAZ gene family. One had multiple, noncontiguous deletions. In 8 patients with testicular histology available, a lack of genotype/phenotype correlation was noted. Of the 11 couples with deletions, 3 thought microdeletion was a serious defect and opted for an artificial insemination of donor or adoption, 5 chose intracytoplasmic sperm injection, and the other 3 decided to undergo treatment with Chinese medicinal herbs. CONCLUSIONS: The most commonly deleted region in the Taiwanese population is AZFc. The genes implicated in Taiwanese spermatogenesis defects are the DAZ and RBM gene families. Twenty-seven percent of couples with microdeletions deferred assisted reproductive technologies because of concern about their underlying genetic defects.

Adoption↗

Empirical Bayes approach to estimating the number of HIV-infected individuals in hidden and elusive populations.

In this paper we estimate the numbers of intravenous drug users (IVDUs) and commercial sex workers (CSWs) in Thailand infected with human immunodeficiency virus (HIV) who have not developed acquired immunodeficiency syndrome (AIDS) directly from the semi-annual HIV serosurveillance data of Thailand from June 1993 to June 1995. We propose a 'generalized removal model for open populations' for estimating HIV-infected population size within a hidden, elusive, and perhaps high-risk population group, for all sampling time when capture probabilities vary with time. We apply empirical Bayes methodology to the generalized removal model for open populations by using the Gibbs sampler, a Markov chain Monte Carlo method. No assumption on the size of the hidden population in question is needed to implement this procedure. The statistical method proposed here requires very little computing and only a minimum of two sets of serosurvey data to obtain an estimate, thereby providing a simple and viable option in epidemiological studies when either powerful computing facilities or abundant sampling data are lacking.

Bayes Theorem↗

Dynamic expression of lunatic fringe during feather morphogenesis: a switch from medial-lateral to anterior-posterior asymmetry.

Expression of Lunatic fringe mRNA was studied during feather morphogenesis and showed three stages of dynamic expression pattern. (1) Lunatic fringe was first expressed in the epithelium as a ring bordering the feather primordium when it was initially induced. (2) Shortly after, it showed a polarized pattern, first toward the lateral side of the feather primordium and then made a 90 degrees C switch toward the posterior side of the short bud. It then becomes weakly expressed in the long bud stage. (3) Finally, it is expressed in the marginal plate epithelia of feather filaments. In contrast, Radical fringe is weakly expressed in the feather bud, but is also present in the marginal plate epithelia of feather filaments.

Animals↗

In vivo fMRI demonstration of hypothalamic function following intraperitoneal glucose administration in a rat model.

The hypothalamic functional MRI (fMRI) response in an animal model was studied following energy intake. Six fasted (12 h) Sprague-Dawley (SD) rats were administered an intraperitoneal injection of glucose (0.72 grams/kg body weight), while a mid-sagittal slice through the hypothalamus was continuously imaged for 60 min using a conventional T2*-weighted gradient-echo sequence. All rats demonstrated a significant acute transient decrease in the fMRI signal intensity (mean: 3.4%) in the hypothalamic region within 12-16 min after intraperitoneal glucose injection. The SD rat may be a suitable model for future fMRI studies of the hypothalamus involving the administration of exogenous nutrients and medications.

Animals↗

Vestibular neuritis: three-dimensional videonystagmography and vestibular evoked myogenic potential results.

Eight patients diagnosed with vestibular neuritis received the newly developed three-dimensional videonystagmography (3D VNG) and vestibular evoked myogenic potential (VEMP) examination in order to localize the lesion site. Two (25%) of the 8 patients exhibited spontaneous nystagmus with 3 components, indicating that both the horizontal semicircular canal (HSCC) and anterior semicircular canal (ASCC) were affected. The remaining 6 patients (75%) displayed only horizontal nystagmus, meaning that only the HSCC was involved. Seven (88%) of the 8 patients had bilateral normal VEMPs, revealing sparing of the posterior semicircular canal (PSCC). In a comparative study, another seven patients with vestibular neuritis 1 year post-treatment also received the caloric test, 3D VNG and VEMP examination. Only one patient exhibited spontaneous nystagmus. An absent caloric response of the lesioned side persisted in 5 (71%) of the 7 patients. However, all patients showed normal VEMPs bilaterally. 3D VNG and VEMP examination indicates that vestibular neuritis mainly affects the superior division of the vestibular nerve, which innervates the HSCC and ASCC. Meanwhile, the function of the PSCC and saccule, innervated by the inferior vestibular nerve, is preserved.

Adolescent↗

Mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation.

The mechanism of adenosine-induced vasodilation in rat diaphragm microcirculation was investigated using laser Doppler flowmetry. Adenosine (10(-5), 3.2 x 10(-5), and 10(-4) M), the nonselective adenosine agonist 5'-N-ethylcarboxamido-adenosine (NECA) (10(-8)-10(-7) M), the specific A(2A) agonist 2-p-(2-carboxyethyl)phenyl-amino-5'-N-ethyl carboxamidoadenosine (CGS-21680) (10(-8)-10(-7) M), and the adenosine agonist with higher A(1)-receptor affinity, R-N(6)-phenylisopropyladenosine (R-PIA) (10(-7), 3.2 x 10(-7), and 10(-6) M) elicited a similar degree of incremental increase of microcirculatory flow in a dose-dependent manner. The ATP-dependent potassium (K(ATP)) channel blocker glibenclamide (3.2 x 10(-6) M) significantly attenuated the vasodilation effects of these agonists. Adenosine-induced vasodilation could be significantly attenuated by the nonselective adenosine antagonist 8-(p-sulfophenyl)-theophylline (3 x 10(-5) M) or the selective A(2A) antagonist 4-(2-[7-amino-2-(2-furyl)[1,2, 4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl) phenol (ZM-241385, 10(-6) M), but not by the selective A(1) antagonist 8-cyclopentyl-1, 3-dipropylxanthine (5 x 10(-8) M). Adenylate cyclase inhibitor N-(cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride (MDL-12330A, 10(-5)M) effectively suppressed the vasodilator response of adenosine and forskolin. These results suggest that adenosine-induced vasodilation in rat diaphragm microcirculation is mediated through the stimulation of A(2A) receptors, which are coupled to adenylate cyclase activation and opening of the K(ATP) channel.

Adenosine↗

Biologically based dose-response model for liver tumors induced by trichloroethylene.

The existing extensive laboratory data on trichloroethylene (TCE) and its two metabolites, dichloroacetic (DCA) and trichloroacetic (TCA), are used to explore the relationship among these three compounds. Under the hypothesis that these compounds induce liver tumors in mice through promotion of preexisting initiated cells, it is demonstrated that DCA alone could be responsible for all the response of carcinomas in liver of B6CF(1) mice. The focus of this paper is on how a plausible biological assumption could impact on low-dose risk estimates, rather than on the risk estimate per se. The findings suggest that low-dose risk estimates to humans would be overestimated unless the different background rates between mice and humans are properly accounted for.

Animals↗

Network approaches to two-dimensional phase unwrapping: intractability and two new algorithms.

Two-dimensional (2-D) phase unwrapping, that is, deducing unambiguous phase values from a 2-D array of values known only modulo 2pi, is a key step in interpreting data acquired with synthetic aperture radar interferometry. Noting the recent network formulation of the phase unwrapping problem, we apply here some well-established ideas of network theory to formalize the problem, analyze its complexity, and derive algorithms for its solution. It has been suggested that the objective of phase unwrapping should be to minimize the total number of places where unwrapped and wrapped phase gradients differ. Here we use network constructions to show that this so-called minimum L0-norm problem is NP-hard, or one that complexity theory suggests is impossible for efficient algorithms to solve exactly. Therefore we must instead find approximate solutions; we present two new algorithms for doing so. The first uses the network ideas of shortest paths and spanning trees to improve on the Goldstein et al. residue-cut algorithm [Radio Sci. 23, 713 (1988)]. Our improved algorithm is very fast, provides complete coverage, and allows user-defined weights. With our second algorithm, we extend the ideas of linear network flow problems to the nonlinear L0 case. This algorithm yields excellent approximations to the minimum L0 norm. Using interferometric data, we demonstrate that our algorithms are highly competitive with other existing algorithms in speed and accuracy, outperforming them in the cases presented here.

Algorithms↗

Avian integument provides multiple possibilities to analyse different phases of skin appendage morphogenesis.

To analyse the morphogenic events during skin appendage formation, it is important to have an animal model that offers distinct patterns at various stages of development and is accessible to analysis using state of the art technology. The avian integument is such a model. Combining experimental embryologic approaches, organ cultures, and gene transduction technology, we are now able to begin to address the molecular basis of pattern formation, primordium initiation, anterior-posterior axis formation, proximo-distal axis formation, phenotypic determination, and others. Parallel mechanisms are usually found in feathers and hairs, and the avian integument model has matured to be a major source of new findings in the study of skin appendage morphogenesis. More information on the avian integument model can be found at website http://www.hsc.usc.educmchuong.

Animals↗

Toxic effects of mitomycin-C on cultured corneal keratocytes and endothelial cells.

Improper use of mitomycin-C in ocular medication may result in damage to corneal cells. In this study, the toxic effects of mitomycin-C on cultured porcine keratocytes and endothelial cells were estimated by MTT, 3H-thymidine uptake and cellular counting assay methods. It was found that mitomycin-C caused a dose-dependent toxic effect to keratocytes and endothelial cells. Both cells were treated with mitomycin-C at the concentration ranging from 100, 10, 1, 0.1 to 0.01 microg/ml for 3 min, 5 min or 100 min. The 50% inhibitory dose (ID50) of mitomycin-C to keratocytes and endothelial cells as measured by MTT assay was 0.40, 0.18, 0.16 mg/ml and 0.27, 0.15, 0.14 mg/ml, respectively, after 3, 5 and 100 minutes drug treatment. The ID50 for keratocytes and endothelial cells as measured by 3H-thymidine uptake immediately, 1 day and 7 days after 100 minutes mitomycin-C treatment was 0.3, 0.0002, 143.2 microg/ml and 45.1, 101.1, 450.2 microg/ml, respectively. The ID50 for keratocytes and endothelial cells as measured by cellular counting 1 day and 7 days after mitomycin-C treatment was 232.5, 109.7 microg/ml and 239.9, 367.5 microg/ml, respectively. It is concluded that mitomycin-C is more toxic to cellular proliferation in cultured corneal keratocytes than in endothelial cells.

Animals↗

Effects of N(omega)-nitro-L-arginine (L-NOARG) on blood flow and vasomotion in rat diaphragm microcirculation during hemorrhagic hypotension.

The role of N(omega)-nitro-L-arginine (L-NOARG), a nitric oxide (NO) synthase inhibitor, in the control of blood flow and vasomotion in rat diaphragm microcirculation during hemorrhagic hypotension was investigated by means of laser Doppler flowmetry (LDF). Fifty-six Sprague-Dawley rats were divided into seven groups. Ten minutes after one-stage hemorrhage to 40-60% of initial blood pressure, the rats received 15 min topical superfusion of saline (group 1, time control), 0.1 mM L-NOARG (group 2), 10 mM L-arginine (group 3), or vehicle (0.1% DMSO and 0.9 mN NaOH, group 4). For groups 5 and 6, L-NOARG or its vehicle was superfused for 15 min without hemorrhage. In group 7, the vasodilator responses to the endothelium-dependent vasorelaxant acetylcholine (ACH) and the endothelium-independent vasorelaxant sodium nitroprusside (SNP) were assessed at rest and after 25 min of hemorrhagic hypotension. The results showed no significant differences in blood flow, fundamental frequency, or relative amplitude of the rat diaphragm microcirculation before or after administration of the test agents among the first four groups during hemorrhagic hypotension or in groups 5 and 6 during sham operation without hypoperfusion. Hemorrhagic hypotension significantly decreased the vasodilator response to ACH (p = 0.003), but not to SNP. We conclude that NO did not play an important role in the regulation of blood flow or vasomotion in rat diaphragm microcirculation during acute hemorrhagic hypotension.

Animals↗

Time course of pharmacological modulation of peak eosinophilic airway inflammation after mite challenge in guinea pigs: a therapeutic approach.

BACKGROUND: It is well known that eosinophilic airway inflammation develops after allergen challenge in sensitized humans and animals. However, the detailed time course of suppression of early eosinophilic airway inflammation by pharmacological agents given just after challenge has not been discussed. Therefore, we aimed to evaluate the time course relationship of the suppression of peak eosinophilia by anti-cytokines and pharmacological agents given several hours after the aerosol challenge by a therapeutic approach. METHODS: We used crude mite extract as an allergen to create a sensitization and inhalation challenge, and performed bronchoalveolar lavages (BAL) after the inhalation challenge to observe the degree of eosinophilic airway inflammation in guinea pigs. Various anti-cytokines (anti-IL-3 and anti-IL-5) and pharmacological agents (dexamethasone, theophylline, and roxithromycin) were given within several hours after the acute aeorosol challenge to evaluate the suppressive effect on peak eosinophilia in BAL fluid, which occurred 24 h after the challenge. RESULTS: Our results show that anti-IL-5 and dexamethasone, given within 4 and 8 h after the inhalation challenge, respectively, inhibit the acute allergen-induced peak eosinophilia in BAL fluid. However, anti-IL-3, theophylline, and roxithromycin had no effect on peak eosinophilic airway inflammation after challenge. CONCLUSION: These observations suggest that several hours are needed to complete the process of cytokine-induced recruitment of eosinophils from the blood to the airways after acute allergen challenge. This may be the optimal time to administer anti-cytokines and dexamethasone to attenuate the subsequent eosinophilic airway inflammation after acute allergen-induced asthmatic attacks.

Aerosols↗

Lack of effect of dietary alpha-tocopherol on chemically induced hepatocarcinogenesis in rats.

We investigated the effects of alpha-tocopherol on diethylnitrosamine (DEN) initiation-phenobarbital (PB) promotion of hepatic foci in female Sprague-Dawley rats. Groups of eight rats were initiated with DEN (15 mg/kg) at 24 hours of age. After weaning, they received diets containing 500 ppm PB and various concentrations of alpha-tocopherol, deficient (0 ppm), adequate (100 ppm), and supplemented (5,000 ppm), for 24 weeks. Rats fed alpha-tocopherol-supplemented diets had significantly greater hepatic alpha-tocopherol levels than those fed alpha-tocopherol-deficient or -adequate diets (p < 0.05). Liver lipid peroxidation (measured as thiobarbituric acid-reactive substances) was significantly greater in rats fed alpha-tocopherol-deficient diets than in those fed alpha-tocopherol-adequate or -supplemented diets (p < 0.05). The dietary alpha-tocopherol level had no significant effect on the ratios of reduced glutathione (GSH) to oxidized GSH or reduced GSH to total GSH in the liver or on the plasma prostaglandin E2 concentration or on the activities of hepatic cytosolic and particulate protein kinase C. Rats fed alpha-tocopherol-adequate or -supplemented diets had significantly greater hepatic glutathione S-transferase, GSH reductase, and GSH peroxidase activities than those fed alpha-tocopherol-deficient diets (p < 0.05). The dietary alpha-tocopherol level did not significantly affect the formation of hepatic gamma-glutamyl transpeptidase- and placental glutathione S-transferase-positive foci. These results suggest that alpha-tocopherol does not influence hepatic foci formation and that reactive oxygen species may not be the underlying mechanism of hepatic foci formation in this DEN initiation-PB promotion model of hepatocarcinogenesis.

Animals↗

Wnt-7a in feather morphogenesis: involvement of anterior-posterior asymmetry and proximal-distal elongation demonstrated with an in vitro reconstitution model.

How do vertebrate epithelial appendages form from the flat epithelia? Following the formation of feather placodes, the previously radially symmetrical primordia become anterior-posterior (A-P) asymmetrical and develop a proximo-distal (P-D) axis. Analysis of the molecular heterogeneity revealed a surprising parallel of molecular profiles in the A-P feather buds and the ventral-dorsal (V-D) Drosophila appendage imaginal discs. The functional significance was tested with an in vitro feather reconstitution model. Wnt-7a expression initiated all over the feather tract epithelium, intensifying as it became restricted first to the primordia domain, then to an accentuated ring pattern within the primordia border, and finally to the posterior bud. In contrast, sonic hedgehog expression was induced later as a dot within the primordia. RCAS was used to overexpress Wnt-7a in reconstituted feather explants derived from stage 29 dorsal skin to further test its function in feather formation. Control skin formed normal elongated, slender buds with A-P orientation, but Wnt-7a overexpression led to plateau-like skin appendages lacking an A-P axis. Feathers in the Wnt-7a overexpressing skin also had inhibited elongation of the P-D axes. This was not due to a lack of cell proliferation, which actually was increased although randomly distributed. While morphogenesis was perturbed, differentiation proceeded as indicated by the formation of barb ridges. Wnt-7a buds have reduced expression of anterior (Tenascin) bud markers. Middle (Notch-1) and posterior bud markers including Delta-1 and Serrate-1 were diffusely expressed. The results showed that ectopic Wnt-7a expression enhanced properties characteristic of the middle and posterior feather buds and suggest that P-D elongation of vertebrate skin appendages requires balanced interactions between the anterior and posterior buds.

Animals↗