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Biomedical subjects

J C Fu

Publications and source records attributed to J C Fu.

At least 19 recordsLinked to original sources

Myocardial border detection by branch-and-bound dynamic programming in magnetic resonance images.

Dynamic programming (DP) is a mathematical technique for making optimal decisions on the sequencing of interrelated problems. It has been used widely to detect borders in magnetic resonance images (MRI). MRI is noninvasive and generates clear images; however, it is impractical for manual measurement of the huge number of images generated by dynamic organs such as those of the cardiovascular system. A fast and effective algorithm is essential for on-line implementation of MRI-based computer aided measurement and diagnosis. In this paper, a branch-and-bound dynamic programming technique is applied to detect the endocardial borders of the left ventricular. The proposed branch-and-bound method drastically reduces the computational time required in conventional exhaustive search methods. Statistical tests are conducted to verify the CPU time performance of the branch-and-bound technique in comparison to the conventional exhaustive search method.

Computers↗

Image segmentation feature selection and pattern classification for mammographic microcalcifications.

Since microcalcifications in X-ray mammograms are the primary indicator of breast cancer, detection of microcalcifications is central to the development of an effective diagnostic system. This paper proposes a two-stage detection procedure. In the first stage, a data driven, closed form mathematical model is used to calculate the location and shape of suspected microcalcifications. When tested on the Nijmegen University Hospital (Netherlands) database, data analysis shows that the proposed model can effectively detect the occurrence of microcalcifications. The proposed mathematical model not only eliminates the need for system training, but also provides information on the borders of suspected microcalcifications for further feature extraction. In the second stage, 61 features are extracted for each suspected microcalcification, representing texture, the spatial domain and the spectral domain. From these features, a sequential forward search (SFS) algorithm selects the classification input vector, which consists of features sensitive only to microcalcifications. Two types of classifiers-a general regression neural network (GRNN) and a support vector machine (SVM)--are applied, and their classification performance is compared using the Az value of the Receiver Operating Characteristic curve. For all 61 features used as input vectors, the test data set yielded Az values of 97.01% for the SVM and 96.00% for the GRNN. With input features selected by SFS, the corresponding Az values were 98.00% for the SVM and 97.80% for the GRNN. The SVM outperformed the GRNN, whether or not the input vectors first underwent SFS feature selection. In both cases, feature selection dramatically reduced the dimension of the input vectors (82% for the SVM and 59% for the GRNN). Moreover, SFS feature selection improved the classification performance, increasing the Az value from 97.01 to 98.00% for the SVM and from 96.00 to 97.80% for the GRNN.

Breast Neoplasms↗

A neuroinformatics database system for disease-oriented neuroimaging research.

Clinical databases are continually growing and accruing more patient information. One of the challenges for managing this wealth of data is efficient retrieval and analysis of a broad range of image and non-image patient data from diverse data sources. This article describes the design and implementation of a new class of research data warehouse, neuroinformatics database system (NIDS), which will alleviate these problems for clinicians and researchers studying and treating patients with intractable temporal lobe epilepsy. The NIDS is a secured, multi-tier system that enables the user to gather, proofread, analyze, and store data from multiple underlying sources. In addition to data management, the NIDS provides several key functions including image analysis and processing, free text search of patient reports, construction of general queries, and on-line statistical analysis. The establishment of this integrated research database will serve as a foundation for future hypothesis-driven experiments, which could uncover previously unsuspected correlations and perhaps help to identify new and accurate predictors for image diagnosis.

Biomedical Research↗

A web-based federated neuroinformatics model for surgical planning and clinical research applications in epilepsy.

There is an increasing need to efficiently share diverse clinical and image data among different clinics, labs, and departments of a medical center enterprise to facilitate better quality care and more effective clinical research. In this paper, we describe a web-based, federated information model as a viable technical solution with applications in medical refractory epilepsy and other neurological disorders. We describe four such online applications developed in a federated system prototype: surgical planning, image analysis, statistical data analysis, and dynamic extraction, transforming, and loading (ETL) of data from a heterogeneous collection of data sources into an epilepsy multimedia data warehouse (EMDW). The federated information system adopts a three-tiered architecture, consisting of a user-interface layer, an application logic layer, and a data service layer. We implemented two complementary federated information technologies, i.e., XML (eXtensible Markup Language) and CORBA (Common Object Request Broker Architecture), in the prototype to enable multimedia data exchange and brain images transmission. The preliminary results show that the federated prototype system provides a uniform interface, heterogeneous information integration and efficient data sharing for users in our institution who are concerned with the care of patients with epilepsy and who pursue research in this area.

Animals↗

De-noising of left ventricular myocardial borders in magnetic resonance images.

In short axis left ventricular MR images, endocardial borders are the major parameters in evaluation of cardiovascular functions such as end diastolic volume, end systolic volume, and ejection fraction. Functional analysis captures the dynamic behavior of the cardiovascular system as revealed by the movement of the endocardial borders over time. Because of the huge number of MR images, an effective computerized tool is required for real time applications. One of the widely used automatic border detection algorithm-dynamic programming-generates zigzag borderlines, which lead to measurement errors. This paper surveys the performance of the wavelet adaptive filter, the snake, and the medial filter in smoothing over the zigzag borders generated by dynamic programming. Statistical analysis of two hundred and sixty four images from sixteen subjects show that all three algorithms can reduce the border line errors in terms of Hausdorff distance and border area error; however, only the wavelet adaptive filter is effective in providing the physiological measurements such as ejection fraction, end systolic volume and end diastolic volume.

Algorithms↗

Wavelet-based enhancement for detection of left ventricular myocardial boundaries in magnetic resonance images.

MRI is noninvasive and generates clear images, giving it great potential as a diagnostic instrument. However, current methods of image analysis are too time-consuming for dynamic systems such as the cardiovascular system. Since dynamic imagery generate a huge number of images, a computer aided machine vision diagnostic tool is essential for implementing MRI-based measurement. In this paper, a wavelet-based image technique is applied to enhance left ventricular endocardial and epicardial profiles as the preprocessor for a dynamic programming-based automatic border detection algorithm. Statistical tests are conducted to verify the performance of the enhancement technique by comparing borders manually drawn with 1. borders generated from the enhanced images, and 2. borders generated for the original images.

Algorithms↗

A new gene involved in stationary-phase survival located at 59 minutes on the Escherichia coli chromosome.

We determined the DNA sequence of a 2,232-bp region immediately upstream of the pcm gene at 59 min on the Escherichia coli chromosome that encodes an L-isoaspartyl protein methyltransferase with an important role in stationary-phase survival. Two open reading frames of 477 and 1,524 bp were found oriented in the same direction as that of the pcm gene. The latter open reading frame overlapped the 5' end of the pcm gene by 4 bp. Coupled in vitro transcription-translation analysis of DNA containing the 1,524-bp open reading frame directly demonstrated the production of a 37,000-Da polypeptide corresponding to a RNA species generated from a promoter within the open reading frame. The deduced amino acid sequence showed no similarity to known protein sequences. To test the function of this gene product, we constructed a mutant strain in which a kanamycin resistance element was inserted at a BstEII site in the middle of its coding region in an orientation that does not result in reduction of Pcm methyltransferase activity. These cells were found to survive poorly in stationary phase, at elevated temperatures, and in high-salt media compared with parent cells containing the intact gene, and we thus designate this gene surE (survival). surE appears to be the first gene of a bicistronic operon also containing the pcm gene. The phenotypes of mutations in either gene are very similar and indicate that both gene products are important for the viability of E. coli cells under stressful conditions.

Acid Phosphatase↗

Purification, gene cloning, and sequence analysis of an L-isoaspartyl protein carboxyl methyltransferase from Escherichia coli.

Mammalian tissues contain protein carboxyl methyltransferases that catalyze the transfer of methyl groups from S-adenosylmethionine to the free carboxyl groups of D-aspartyl or L-isoaspartyl residues (EC 2.1.1.77). These enzymes have been postulated to play a role in the repair and/or degradation of spontaneously damaged proteins. We have now characterized a similar activity from Escherichia coli that recognizes L-isoaspartyl-containing peptides as well as protein substrates such as ovalbumin. The enzyme was purified by DEAE-cellulose, hydroxylapatite, Sephadex G-100, polyaspartate, and reversed-phase chromatography and was shown to consist of a single 24-kDa polypeptide chain. The sequence determined for the N-terminal 39 residues was used to design an oligonucleotide probe that allowed the precise localization of its structural gene (pcm) on the physical map of the E. coli chromosome at 59 min. Transformation of E. coli cells with a plasmid containing DNA from this region results in a 3-4-fold overproduction of enzyme activity. The nucleotide sequence determined for the pcm gene and its flanking regions was used to deduce a mature amino acid sequence of 207 residues with a calculated molecular weight of 23,128. This sequence shows 30.8% sequence identity with the human L-isoaspartyl/D-aspartyl methyltransferase and suggests that this enzyme catalyzes a fundamental reaction in both procaryotic and eucaryotic cells.

Amino Acid Sequence↗

Inhibition of collagen fibril formation in vitro and subsequent cross-linking by glucose.

Glucose inhibits collagen fibril formation in vitro. A linear dose response was observed, with half-maximum inhibition of fibril formation occurring at 50 mM glucose. Nonfibrillar collagen cannot be cross-linked by lysyl oxidase, an enzyme that catalyzes the initial cross-linking reaction. The degree of decreased fibril formation correlated with the loss of ability of the collagen to serve as a substrate for lysyl oxidase. Collagen that is not cross-linked is unstable and more susceptible to collagenolytic attack. Interference with collagen cross-linking and more rapid degradation may explain the decreased amounts of interstitial collagen and the poor healing of wounds associated with diabetes mellitus.

Animals↗

Marfan syndrome: abnormal alpha 2 chain in type I collagen.

Cells in culture from a woman with a variety of the Marfan syndrome produce two species of the alpha 2 chains of type I collagen. One alpha 2 chain appears normal; the abnormal chain has a higher apparent molecular weight than normal and migrates more slowly during electrophoresis in sodium dodecyl sulfate/polyacrylamide gels. A similar change in electrophoretic behavior is seen in the prepro alpha 2 chain and the pN alpha 2 chain (which contains the amino-terminal extension). Asymmetric cleavage of the pepsin-treated procollagens with a fibroblast collagenase locates the abnormal segment amino terminal to the cleavage site, and analysis of cyanogen bromide peptides of collagenase cleavage peptides and of whole collagens indicates that the abnormal segment is in either the alpha 2CB3 peptide or the short segment of alpha 2CB5 amino terminal to the collagenase site of the altered alpha 2 chain. The higher apparent molecular weight is consistent with the insertion of a small peptide fragment of approximately 20 amino acids. This alteration in chain size has marked effects on crosslinking because collagen from the patient's skin was 5-10 times more extractable in nondenaturing solvents than that from control skins. Although the abnormal chain was not found in several other individuals with the Marfan syndrome, these findings suggest that the phenotype may be the expression of a variety of primary structure alterations in the chains of type I collagen that interfere with normal crosslink formation.

Adult↗

Aortic aneurysm in Marfan's syndrome: changes in the ultrastructure and composition of collagen.

Aneurysmal aortic tissue and the mitral valve of a patient with Marfan's syndrome were examined. Biochemical analysis of the tissue showed a qualitative and quantitative defect in alpha 2 chain production of Type I collagen. On polyacrylamide gel electrophoresis of the aortic extract, two separate bands in the alpha 2 region and an increase of the alpha 1 to alpha 2 ratio were found. Examination by electron microscopy revealed elastic fibre degeneration, helical collagen fibres, and metabolically active modified smooth muscle cells. The formation of helical collagen fibres is attributed to a defect in the development of chains and cross-links of collagen precursors produced by the hypertrophic smooth muscle cells. Elastic fibre disintegration is believed to be due to a lack of support by Type I collagen fibres, which have decreased tensile strength. A scheme for the pathogenesis of aortic aneurysm and other connective tissue abnormalities in Marfan's syndrome is proposed as follows. Type I collagen fibres have decreased tensile strength because of a defect in the alpha 2 chain biosynthesis and decreased cross-linking. Over many years the wall of the ascending aorta is subjected to cyclic stresses and it dilates. Elastic fibres disintegrate. The attempt at repair by metabolically activated modified smooth muscle cells is abortive, and rupture is likely to occur.

Adult↗

Effect of comonomer ratio on hydrocortisone diffusion from sustained-release composite capsules.

The daily in vitro release of hydrocortisone from composite polymer capsules is reported here for over 120 days. Increase in vinyl acetate comonomer content of the ethylene-vinyl acetate copolymer matrix brought about an increase in the diffusion rate. Variation in the initial drug content of the capsules from 40 mg to 20 mg affects the daily drug release less significantly than the variation in copolymer ratio. The correlation between vinyl acetate comonomer content and the percent crystallinity of the copolymer matrix is suggested as one of the possible major factors in controlling diffusion rate from this drug-polymer system. The diffusion constant (D) calculated was 0.212 X 10(10) cm2/sec when the copolymer carrier has 30% vinyl acetate content and 0.430 X 10(11) cm2/sec when the copolymer carrier has 20% vinyl acetate content for capsules with 20 mg initial drug content, and 0.118 X 10(-11) cm2/sec and 0.226 X 10(-11) cm2/sec, respectively, for capsules with 40 mg initial drug content.

Capsules↗

Response of lymphoid leukemia L1210 in mice to implantable sustained release cytosine arabinoside capsules.

The lifespan of BDF mice with ascitic L1210 leukemia is more than doubled when they are treated with a single subcutaneously or intraperitoneally implanted sustained release cytosine arabinoside capsule. These capsules are drug-polymer composites, with dimensions of 1.0 cm in diameter and 0.15 cm in thickness, and a drug content of 17 +/- 3 mg each. Blank silicone rubber discs implanted intraperitoneally or subcutaneously in the leukemic mice produced no beneficial effects. Control healthy mice receiving the ARA-C releasing capsules continued to live with no obvious signs of drug toxicity. In vitro release of ARA-C from the discs was measured. Drug release was maintained above 20 micrograms per day for more than 35 days. ARA-C extracted from discs recovered from implant studies showed that less than 16% of the total drug content was released in vivo.

Animals↗

Response of intramuscular Walker 256 rat tumor to sustained-release cyclophosphamide and ARA-C capsules.

Randomly bred Sprague-Dawley rats with the intramuscular form of Walker 256 tumor growing in the right thigh region were treated with sustained-release cyclophosphamide capsules as well as with cytosine arabinoside capsules. A disk-shaped caps-le was implanted subcutaneously adjacent to the tumor mass. Tumor regression, weight gain, and prolongation of lifespan were observed in animals treated with cyclophosphamide capsules of 10 mg or 20 mg total drug content each. However, the walker 256 intramuscular tumor did not respond to ARA-C capsules implanted, and the animals died at the same rate as the controls, with large ulcerated tumor masses and some metastasis. The in vitro diffusion data of ARA-C capsules is shown. Gross and histological changes associated with cyclophosphamide administered in this manner are reported.

Animals↗

Effects of subcutaneously implanted sustained-release cyclophosphamide capsules on Walker 256 solid rat tumor.

Complete regression of Walker 256 solid rat tumor was brought about by the subcutaneous implantation of a single sustained-release cyclophosphamide capsule adjacent to the tumor mass. Untreated control animals died within 3 weeks after receiving the tumor with large necrotic masses. Rats with sustained-release capsules experienced complete tumor regression within 28 days. Upon examination, the tissues around the previous tumor mass has regenerated, and no viable tumor cells could be found in the area where the previous tumor mass was. Around the implanted sustained-release cyclophosphamide capsule a fibrous sheath has developed over the 3 weeks it was in situ. This study suggests an alternate means of cytoxic drug administration in the treatment of solid tumors in experimental animals.

Animals↗

Collagen cross-linking. Purification and substrate specificity of lysyl oxidase.

Lysyl oxidase is a specific amine oxidase that catalyzes the formation of aldehyde cross-link intermediates in collagen and elastin. In this study, lysyl oxidase from embryonic chick cartilage was purified to constant specific activity and a single protein band on sodium dodecyl sulfate acrylamide gel electrophoresis. This band had an apparent molecular weight of 62,000. The eluted protein cross-reacted with inhibiting antisera developed against highly purified lysyl oxidase. The highly purified enzyme was active with both insoluble elastin and embryonic chick skin or bone collagen precipitated as reconstituted, native fibrils. There was low activity with nonhydroxylated collagen, collagen monomers, or native fibrils isolated from lathyritic calvaria. The maximum number of aldehyde intermediates formed per molecule of collagen that became insoluble was two. These results indicate that lysyl oxidase has maximum activity on ordered aggregates of collagen molecules that may be overlapping associations of only a few collagen molecules across. Formation of aldehyde intermediates and cross-links during fibril formation may facilitate the biosynthesis of stable collagen fibrils and contribute to increased fibril tensile strength in vivo.

Amino Acid Oxidoreductases↗