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Biomedical subjects

Y H Chang

Publications and source records attributed to Y H Chang.

At least 73 records · Page 4Linked to original sources

Feature selection for computerized mass detection in digitized mammograms by using a genetic algorithm.

RATIONALE AND OBJECTIVES: To investigate optimization of feature selection for computerized mass detection in digitized mammograms, and to compare the effectiveness of a genetic algorithm (GA) in such optimization with that of an "exhaustive" search of all feature permutations. MATERIALS AND METHODS: A Bayesian belief network (BBN) was used to classify positive and negative regions for masses depicted in digitized mammograms; 20 features were computed for each of 592 positive and 3,790 negative regions in two databases. Conditional probabilities for the BBN were computed by using a "training" database of 288 positive and 2,204 negative regions. Performance was measured by the area under the receiver operating characteristic curve (A) by using the remainder database (304 positive and 1,586 negative regions). The optimal set was first found by using an "exhaustive" (complete permutation) searching method. A GA-based search for the optimal set then was applied, and the results of the two approaches were compared. RESULTS: As the number of features in the classifier increased, the A value increased until it reached a maximum performance for 11 features of 0.876 +/- 0.008. The A value then decreased monotonically as the number of features increased from 11 to 20. Using 100 random chromosomes (seeds) in the first generation, the GA identified the same optimal set of features but reduced the total computation time by a factor of 65. CONCLUSION: A GA-based search might be an efficient and effective approach to selecting an optimal feature set.

Algorithms↗

Computer-assisted diagnosis of breast cancer using a data-driven Bayesian belief network.

This study investigates a simple Bayesian belief network for the diagnosis of breast cancer, and specifically addresses the question of whether integrating image and non-image based features into a single network can yield better performance than hybrid combinations of independent networks. From a dataset of 419 cases, including 92 malignancies, 13 features relating to mammographic findings, physical examinations and patients' clinical histories, were extracted to build three Bayesian belief networks. The scenarios tested included a network incorporating all features and two hybrids which combined the outputs of sub-networks corresponding to the image or non-image features. Average areas (Az) under the corresponding ROC curves were used as measures of performance. The network incorporating only image based features performed better (Az =0.81) than that using nonimage features (Az = 0.71). Both hybrid classifiers yielded better performance (Az =0.85 for averaging and Az = 0.87 for logistic regression), but neither hybrid was as accurate as the network incorporating all features (Az = 0.89). This preliminary study suggests that, like human observers who concurrently consider different types of information, a single classifier that simultaneously evaluates both image and non-image information can achieve better diagnostic performance than the hybrid combinations considered here.

Adult↗

A model of ventilation distribution in the human lung.

A thorough analysis of aerosol particle deposition in the human lung requires the knowledge of the distribution of inspired air at respiration. In this paper, a mathematical model of ventilation distribution has been developed using a five-lobe airway model. The model accounts for the nonlinear effects of compliance and resistance on airway dynamics. Ventilation distributions were determined under different gravitational force conditions. A larger gravity leads to a greater nonuniformity of ventilation between the upper and lower lobes of the lung. Ventilation distributions in different lobes of the lung at various inspiratory flow rates were also calculated. At slow inspiratory flow rates, ventilation was found to be nonuniform with more air entering the lower lobes. As the flow rate increases, this nonuniformity became smaller. The calculated results compare favorably with existing experimental data. When a different gas is inspired instead of air, a preferential distribution of ventilation to the upper lobes was found if the density of the inspired gas is greater than that of the air.

Aerosols↗

Computerized localization of breast lesions from two views. An experimental comparison of two methods.

RATIONALE AND OBJECTIVES: The authors compared two computerized methods, the arc and cartesian straight-line, for the localization of breast lesions in two mammographic views. METHODS: A total of 571 craniocaudal and 571 mediolateral oblique matched mammographic image pairs (or 1142 individual images) depicting 290 pathology-verified masses on both views were selected from our image database. Using a previously developed computer-aided detection scheme, all 290 masses and 3992 suspicious but negative regions were identified. After pairing all identified regions from both views, all masses (true-positive-true-positive matched pairs) and a total of 10330 false-positive pairs (including false-positive-false-positive, true-positive-false-positive, and false-positive-true positive pairs) were assessed as to their position in relation to the nipple using both the arc and the cartesian straight-line methods. Receiver operating characteristic methodology was used to evaluate the performance levels for each method in determining, based solely on location, whether a pair of suspicious regions represented a true mass or a false-positive combination. RESULTS: The areas under the receiver operating characteristic curves (Az) were 0.79 and 0.78 for the arc and cartesian straight-line methods, respectively. The difference between the two techniques (as measured by Az) was not statistically significant (P > 0.99). CONCLUSIONS: These preliminary results demonstrated that the two methods are comparable in identifying true masses from triangulated observations on two views. However, the arc method is somewhat favorable because only the nipple location is required for localization.

Biopsy↗

Therapeutic effects of moxibustion on experimental tumor.

This work investigated the therapeutic effects of the improved form of moxibustion (MT) on experimental tumor. Sarcoma 180 cells (1 x 10(7)) were transplanted into the subcutaneous tissue in the breast area of female ICR mice. Mice bearing a tumor were divided into one control and four experimental groups. The experimental groups were treated with MT for 1, 2, 3 and 4 times (abbreviated as MT1, MT2, MT3, MT4, respectively). This study showed that the experimental group treated with MT3 displayed the optimal therapeutic response. The longest mean survival time (87.8 days) within 120 days after treatment of MT3 significantly differed from the control group (60.2 days). In addition, uptake of 86Rb-radioactive tracer significantly decreased in tumors treated with MT3. The improved form of moxibustion used in this study is a reliable model of localized hyperthermia in tumor therapy.

Animals↗

Effects of acupuncture at pai-hui on the deficit of memory storage in rats.

In this study, we investigated the effects of Pai-Hui by acupuncture on cycloheximide (CXM)-induced impairment of the passive avoidance response in rats. Acupuncture at Pai-Hui (Go-20) treated 15 min before or immediately after training trial for 15 min significantly attenuated CXM-induced impairment of passive avoidance response in rats, but did not have the same effect 30 and 60 min before or 30 min after the training trial or before the retention trial. Acupuncture at Pai-Hui 15 min before the training trial for 15, 30 and 60 min significantly attenuated CXM-induced impairment of passive avoidance response in rats, and its efficacy paralleled the acupuncture duration. Furthermore, acupuncture at Pai-Hui did not attenuate scopolamine (SCOP)-induced impairment of passive avoidance response, but was slightly inhibited by SCOP at 0.3 mg/kg. Second, acupuncture at Pai-Hui attenuated p-chloroamphetamine (PCA)-induced impairment of passive avoidance response and was significantly antagonized by PCA at 1 mg/kg. These results suggest that acupuncture at Pai-Hui mainly affects the memory storage process and has preventive and immediate therapeutic effects on CXM-induced impairment of passive avoidance response. Its efficacy paralleled the acupuncture duration. The preventive effect of acupuncture at Pai-Hui on CXM-induced impairment is significantly reduced by serotonergic 5-HT releaser, and slightly by cholinergic manipulations.

Acupuncture Points↗

Metabolic cost of generating horizontal forces during human running.

Previous studies have suggested that generating vertical force on the ground to support body weight (BWt) is the major determinant of the metabolic cost of running. Because horizontal forces exerted on the ground are often an order of magnitude smaller than vertical forces, some have reasoned that they have negligible cost. Using applied horizontal forces (AHF; negative is impeding, positive is aiding) equal to -6, -3, 0, +3, +6, +9, +12, and +15% of BWt, we estimated the cost of generating horizontal forces while subjects were running at 3.3 m/s. We measured rates of oxygen consumption (VO2) for eight subjects. We then used a force-measuring treadmill to measure ground reaction forces from another eight subjects. With an AHF of -6% BWt, VO2 increased 30% compared with normal running, presumably because of the extra work involved. With an AHF of +15% BWt, the subjects exerted approximately 70% less propulsive impulse and exhibited a 33% reduction in VO2. Our data suggest that generating horizontal propulsive forces constitutes more than one-third of the total metabolic cost of normal running.

Adult↗

Cholesterol oxidation products induce vascular foam cell lesion formation in hypercholesterolemic New Zealand white rabbits.

Circulating cholesterol oxidation products (ChOx) have long been implicated in the etiology of early atherosclerosis; however, direct in vivo evidence elucidating their role in atherogenesis is only recently becoming available. This study investigated ChOx effects on vascular lesion formation in New Zealand White rabbits under controlled hypercholesterolemic conditions. By closely monitoring plasma cholesterol levels and adjusting dietary cholesterol intake during a 78-day period, total plasma cholesterol exposures (cumulative plasma cholesterol levels over time) were controlled between 27 000 and 34 000 mg/dLxday (final plasma cholesterol concentration, 467+/-77 mg/mL), representing a threshold range for sudanophilic lesion formation in the aorta. Twenty injections of a ChOx mixture (70 mg per injection) were made bearing an oxysterol composition similar to that found in circulating oxidatively modified low density lipoprotein. At sacrifice, the ChOx-injected rabbits (n=5) had (1) significantly higher plasma ChOx levels, (2) significantly increased cholesterol content in the aortas, mainly as esterified cholesterol, and (3) significantly greater sudanophilic lesion size and frequency in the aortas compared with vehicle-injected control rabbits (n=5). The aortic cholesterol content and extent of sudanophilic lesion area were correlated significantly with total plasma ChOx exposure (P<0.003 and P<0.0001, respectively) but not with total cholesterol exposure. The results indicate that for moderate experimental hypercholesterolemia, a situation more relevant to physiological hypercholesterolemia in humans, circulating ChOx may play an important role in inducing formation of early atherosclerotic lesions. Because ChOx are often present in cholesterol-containing diets, foam cell lesion formation induced by ChOx rather than cholesterol cannot be overlooked.

Animals↗

A point-mass model of gibbon locomotion.

In brachiation, an animal uses alternating bimanual support to move beneath an overhead support. Past brachiation models have been based on the oscillations of a simple pendulum over half of a full cycle of oscillation. These models have been unsatisfying because the natural behavior of gibbons and siamangs appears to be far less restricted than so predicted. Cursorial mammals use an inverted pendulum-like energy exchange in walking, but switch to a spring-based energy exchange in running as velocity increases. Brachiating apes do not possess the anatomical springs characteristic of the limbs of terrestrial runners and do not appear to be using a spring-based gait. How do these animals move so easily within the branches of the forest canopy? Are there fundamental mechanical factors responsible for the transition from a continuous-contact gait where at least one hand is on a hand hold at a time, to a ricochetal gait where the animal vaults between hand holds? We present a simple model of ricochetal locomotion based on a combination of parabolic free flight and simple circular pendulum motion of a single point mass on a massless arm. In this simple brachiation model, energy losses due to inelastic collisions of the animal with the support are avoided, either because the collisions occur at zero velocity (continuous-contact brachiation) or by a smooth matching of the circular and parabolic trajectories at the point of contact (ricochetal brachiation). This model predicts that brachiation is possible over a large range of speeds, handhold spacings and gait frequencies with (theoretically) no mechanical energy cost. We then add the further assumption that a brachiator minimizes either its total energy or, equivalently, its peak arm tension, or a peak tension-related measure of muscle contraction metabolic cost. However, near the optimum the model is still rather unrestrictive. We present some comparisons with gibbon brachiation showing that the simple dynamic model presented has predictive value. However, natural gibbon motion is even smoother than the smoothest motions predicted by this primitive model.

Animals↗

Observations after orchiectomy in clinical stage I nonseminomatous germ cell tumors of the testis.

BACKGROUND: The optimal management of clinical stage I nonseminomatous germ cell tumor (NSGCT) of the testis remains controversial. For years, retroperitoneal lymph node dissection in combination with orchiectomy, has been the standard treatment in patients with clinical stage I NSGCT. Recently, with advancement of effective cisplatin-based chemotherapy and clinical staging procedures, a new approach of observation after orchiectomy is being evaluated. We reviewed cases of orchiectomy and observation for clinical stage I NSGCT of the testis in order to evaluate the treatment outcome. METHODS: We retrospectively reviewed the records of 13 patients with clinical stage I NSGCT of the testis treated at our hospital from February, 1981 to August, 1996. The patient age at diagnosis ranged from 0.6 to 44 years. Nine patients had yolk sac tumors, and four had mixed germ cell tumors. Median follow-up was 42 months (range, 20-132 months). RESULTS: Prior to orchiectomy, serum beta-human chorionic gonadotropin and alpha-fetoprotein (AFP) were raised to abnormal concentrations in four and in 13 patients, respectively. With a median follow-up of 42 months, three of 13 patients relapsed at a median of three months after orchiectomy. Two patients showed elevated AFP and radiographically identifiable tumors simultaneously, and one patient showed elevated AFP as the only evidence of relapse. Following treatment with cisplatin-based chemotherapy, the three patients who relapsed responded successfully and the elevated AFP returned to normal. The patients are currently alive and disease free. CONCLUSIONS: Observation after orchiectomy is a reasonable approach for patients with clinical stage I NSGCT of the testis.

Adolescent↗

A new technique for generating a computer-aided design and computer-integrated machining crown: case report.

A new technique for producing a Computer-Aided Design and Computer-Integrated Machining Ceramic Reconstruction crown is presented. After completion of the tooth preparation, an "optical" impression of the tooth was made with a charged couple device camera, and the electronic image was transferred to a computer screen. The "proposed" crown was electronically designed on the screen by the operator, and a proper prefabricated ceramic block was selected and used as milling material. A miniature milling machine then fabricated the crown from the ceramic block. The marginal adaptation and the contour of the crown were verified, and an external shading technique was utilized to improve the esthetics. The prepared tooth and crown were acid-etched, and the crown was cemented with a dual-curing composite luting agent. Once bonded in place, the occlusion was adjusted and the crown polished and finished. The advantage of this technique is that it eliminates the traditional laboratory casting procedure and corresponding laboratory fee while utilizing materials with superior physical properties for maximum strength and esthetics.

Adult↗

Astrocyte-conditioned saline supports embryonic rat hippocampal neuron differentiation in short-term cultures.

Embryonic rat hippocampal neurons were cultured for 1-2 days in serum-free, HEPES-buffered Tyrode's solution. The effects of cortical astrocytes and astrocyte-conditioned saline on neuron survival, membrane surface area and the expression of functional amino acid neurotransmitter receptors were studied. Neurons grown in Tyrode's solution alone survived well for 1 day but deteriorated thereafter both in terms of percent neurons surviving and the amplitudes and densities of GABA-, glycine-, kainate-and NMDA-induced currents. Neurons grown in Tyrode's previously conditioned by astrocytes for 24 h had significantly larger apparent plasma membrane surface area, as indexed by whole-cell membrane capacitance, and larger amplitudes and densities of the amino acid-induced currents after both 1 and 2 days. The survival rate and neurite outgrowth were also greater in the astrocyte-conditioned saline group after 2 days in culture. Similarly, neurons cultured on glass cover-slips facing a confluent monolayer of astrocyte were larger in apparent plasma membrane area and amino acid-induced currents than neurons cultured in Tyrode's alone. Neurons cultured in saline conditioned by astrocytes provide a strategy to study the physiological basis of astrocyte-directed neuronal differentiation in the absence of ambiguities arising from the inclusion of sera and other additives often used in vitro.

Animals↗

Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2.

Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer and other human diseases. Fumagillin and ovalicin compose a class of structurally related natural products that potently inhibit angiogenesis by blocking endothelial cell proliferation. A synthetic analog of fumagillin, TNP-470, is currently undergoing clinical trials for treatment of a variety of cancers. A common target for fumagillin and ovalicin recently was identified as the type 2 methionine aminopeptidase (MetAP2). These natural products bind MetAP2 covalently, inhibiting its enzymatic activity. The specificity of this binding is underscored by the lack of inhibition of the closely related type 1 enzyme, MetAP1. The molecular basis of the high affinity and specificity of these inhibitors for MetAP2 has remained undiscovered. To determine the structural elements of these inhibitors and MetAP2 that are involved in this interaction, we synthesized fumagillin analogs in which each of the potentially reactive epoxide groups was removed either individually or in combination. We found that the ring epoxide in fumagillin is involved in the covalent modification of MetAP2, whereas the side chain epoxide group is dispensable. By using a fumagillin analog tagged with fluorescein, His-231 in MetAP2 was identified as the residue that is covalently modified by fumagillin. Site-directed mutagenesis of His-231 demonstrated its importance for the catalytic activity of MetAP2 and confirmed that the same residue is covalently modified by fumagillin. These results, in agreement with a recent structural study, suggest that fumagillin and ovalicin inhibit MetAP2 by irreversible blockage of the active site.

Amino Acid Sequence↗

Amyloid beta-protein impairs astrocyte-mediated differentiation of hippocampal neurons.

Embryonic rat hippocampal neurons were cultured on poly-D-lysine (PDL) or on cortical astrocytes, some of which had been pretreated for 24 h with amyloid beta-protein (beta-AP). Amino acid-induced currents were quantified. Membrane capacitance (Cm), as well as the amplitude and density of amino acid-evoked currents recorded in neurons cultured on untreated astrocytes were all statistically greater than those recorded in neurons grown on PDL. However, compared to untreated astrocytes, those treated with beta-AP led to significantly lower values in neurons for Cm and GABA, kainate- and NMDA-induced currents, while glycine-activated current values were not significantly different. Furthermore, beta-AP treatment abolished spontaneous Cac2+ fluctuations in astrocytes, which may account for their impaired ability to promote the expression of functional transmitter receptors in neurons.

Amyloid beta-Peptides↗

Influence of SCH23390 and spiperone on the expression of conditioned place preference induced by d-amphetamine or cocaine in the rat.

The present study investigated the effects of selective dopamine D1 and D2 receptor antagonists, SCH23390 and spiperone, on the expression of conditioned place preference (CPP) induced by either d-amphetamine or cocaine. The CPP protocol consisted of three phases: pre-conditioning exploration, conditioning, and a post-conditioning test. The data indicated that CPP was significantly induced by intraperitoneal injection of either d-amphetamine (2 mg/kg) or cocaine (10 mg/kg). The expression of d-amphetamine CPP was significantly inhibited by SCH23390 (0.08, 0.16 mg/kg) and spiperone (0.15 mg/kg) when given alone before the post-conditioning test session. In contrast, such pretreatment to produce antagonistic effects was not observed for cocaine CPP. However, the expression of cocaine CPP was significantly attenuated by a combination of SCH23390 and spiperone administered prior to the test session. These data indicate that the rewarding properties of d-amphetamine and cocaine as expressed under the CPP task may depend upon different neural substrates. The degrees of D1 and D2 receptors involved in mediating the expression of CPP induced by d-amphetamine and cocaine are different.

Animals↗

Decreased drug accumulation without increased drug efflux in a novel MRP-overexpressing multidrug-resistant cell line.

KB/7D cells represent a multidrug-resistant subclone of human nasopharyngeal carcinoma KB cells generated by continuous exposure to the topoisomerase II inhibitor VP-16 (etoposide). KB/7D cells also show cross-resistance to doxorubicin and vincristine. Phenotypic traits of the cell line include a 2-fold decrease in topoisomerase II levels and a decrease in the uptake of VP-16 without an increase in the rate of drug efflux or expression of P-glycoprotein, suggesting a novel mechanism associated with the uptake of anticancer drugs. This study demonstrated that the multidrug-resistance associated protein (MRP) is overexpressed in KB/7D cells, and that the loss of resistance in revertant cells correlates with the loss of MRP. The resistance to VP-16 and doxorubicin could be overcome, partially, and resistance to vincristine could be overcome completely, by the L-enantiomer of verapamil, but not by the D-enantiomer or by BIBW 22 (4-[N-(2-hydroxy-2-methyl-propyl)-ethanolamino]-2,7-bis[cis-2,6-++ +dimethylmorpholino)-6-phenylpteridin), an inhibitor of MDR-1. L-Verapamil was shown to be significantly more potent than D-verapamil in modulating the accumulation defect in KB/7D cells towards doxorubicin, as measured by flow cytometry and confocal microscopy, and towards VP-16, as measured by increases in protein-linked DNA strand breaks. This suggests that KB/7D cells are multidrug resistant due to decreases in topoisomerase II levels and the overexpression of MRP, that MRP leads to a decrease in drug accumulation, and that L-verapamil can modulate the MRP-associated accumulation defect and drug-resistance phenotype. This contrasts with previous studies that suggest that MRP causes multidrug resistance by exporting cytotoxic drugs out of the cell and that did not show modulation of MRP by verapamil.

ATP-Binding Cassette Transporters↗

Basic FGF-responsive telencephalic precursor cells express functional GABA(A) receptor/Cl-channels in vitro.

We have previously described the expression of specific gamma-aminobutyric acid (GABA)A receptor subunits and their transcripts in the cortical neuroepithelium (Ma and Barker, 1995, 1998). However, it is not clear whether neural precursor cells exposed to basic fibroblast growth factor (bFGF) in vitro reproduce the biological properties of neuroepithelial cells in vivo within the embryonic ventricular zone. In the present study, neural precursor cells were isolated from the telencephalic neuroepithelium of embryonic day 13-13.5 rats and exposed to bFGF in serum-free medium. Basic FGF-responsive cells were capable of dividing and differentiating into neurons and astrocytes. The rapidly dividing cells formed multicellular spheres and then a rosette-like formation in which a majority of cells expressed GABA(A) receptor alpha4, beta1, or gamma1 subunit proteins. We found in perforated patch-clamp recordings that GABA depolarized bromodeoxyundine (BrdU)+ precursor cells, and under voltage-clamp induced a bicuculline-sensitive current that reversed at the Cl- equilibrium potential. GABA also increased cytoplasmic Ca2+ in a significant number of BrdU+ cells that was blocked by bicuculline. The bicuculline sensitivity of these pharmacological effects implicates GABA(A) receptor/Cl- channels, since bicuculline is a competitive GABA(A) antagonist at these channels in well-differentiated cells. It is possible that the three GABA(A) receptor subunits (alpha4, beta1, and gamma1) found in precursor cells form the Cl- channels detected electrophysiologically. The functional GABA(A) receptor/Cl- channels and associated regulation of their cytoplasmic Ca2+ levels via bicuculline-sensitive mechanisms may play significant roles in the regulation of neural cell proliferation in this model neuroepithelium.

Animals↗