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Biomedical subjects

H W Chung

Publications and source records attributed to H W Chung.

At least 37 records · Page 2Linked to original sources

T2-Weighted fast MR imaging with true FISP versus HASTE: comparative efficacy in the evaluation of normal fetal brain maturation.

OBJECTIVE: This study compares the relative efficacy of two fast T2-weighted MR imaging techniques-fast imaging with steady-state free precession (true FISP) and half-Fourier acquisition single-shot turbo spin-echo (HASTE)-in the evaluation of the normal fetal brain maturation during the second and third trimesters of gestation. SUBJECTS AND METHODS: The brain maturation of 10 normal nonsedated fetuses (5 during the second trimester and 6 during the third trimester of gestation [1 fetus underwent 2 examinations]) was examined by both techniques using a Vision+ 1.5-T MR system. We specifically looked for developing events, including white matter myelination, neuronal migration, and cortical sulcation. Image quality was graded according to the presence or absence of undesirable blurring. RESULTS: The specific absorption rate was lower for true FISP than for HASTE by a factor of 3 at equivalent imaging conditions. HASTE and true FISP provide comparable image quality in the second trimester when myelination of the cerebrum has not begun. Neuronal migration could be recognized as hypodense bands on both sequences during the second trimester. Myelination beginning at the third trimester was better delineated with true FISP than with HASTE because of point spread function-related blurring effects inherent in HASTE that hampered visualization of short-T2 structures. Cortical sulcation was well delineated by both sequences. CONCLUSION: With relatively superior image quality and significantly lower radiofrequency absorption than HASTE, true FISP is a safer and more effective alternative in the prenatal evaluation of normal fetal brain.

Basal Ganglia↗

Frame-shift mutation in hormone binding domain of human androgen receptor gene causes complete androgen insensitivity.

Mutation of the human androgen receptor gene impairs normal sexual differentiation and development in karyotypic males, resulting in a spectrum of external genital phenotypes ranging from complete female to nearly complete male. The androgen insensitivity syndrome (AIS) is an X-linked disorder in which genetic males fail to undergo normal fetal masculinization or pubertal virilization. PCR amplification of AR exons followed by SSCP analysis was performed with the genomic DNA of a patient having complete AIS. Mutation was observed at the exon E, where a single nucleotide deletion of T at the nucleotide 3286 was observed by cyclic sequencing. A single base deletion in Exon E in the hormone binding domain causes a frame-shift mutation, which leads to changes in the open reading frame, and causes the early termination of AR synthesis. The structural change of the hormone binding domain and AR might cause an insensitivity to the androgen thus leading to AIS.

Adult↗

Genetic integrity of transforming growth factor beta (TGF-beta) receptors in cervical carcinoma cell lines: loss of growth sensitivity but conserved transcriptional response to TGF-beta.

Transforming growth factor beta (TGF-beta) exerts an inhibitory effect on the growth of most epithelial cell types, and the loss of responsiveness to this growth inhibition has been implicated in the development of a variety of human cancers. The genetic alteration of TGF-beta receptors is known to play a critical role in this escape from growth regulation. We asked whether there is a correlation between TGF-beta sensitivity and the genetic status of TGF-beta type I and type II receptors (RI and RII, respectively) in human cervical carcinoma cell lines. Among 8 cell lines examined, 3 (ME-180, C-33A and HeLaS3) showed resistance to TGF-beta and 3 (SiHa, CaSki and HeLa229) showed minimal response to the growth inhibitory effect of TGF-beta; the other cell lines (HeLa and HT-3) were sensitive. Northern blot analysis revealed that the RII mRNA was not expressed in 2 TGF-beta-resistant cell lines (ME-180 and C-33A) but was expressed in the other cell lines. Southern blot analysis of RI and RII revealed a homozygous deletion of the entire TGF-beta RII gene in the cell line ME-180. We then asked whether the other TGF-beta-resistant or refractory cell lines had microsatellite instability and/or poly-adenine tract mutations of RII. We also checked for point mutations in the individual exons of the entire RII using polymerase chain reaction-single-strand conformational polymorphism (PCR-SSCP). Although C-33A exhibited poly-adenine microsatellite instability, its RII gene showed no signs of mutation. The molecular integrity of the TGF-beta, receptors in all cell lines, except ME-180 and C-33A, could be confirmed by examining the distinct transcriptional induction of plasminogen activator inhibitor-1 (PAI-1), p21(WAF1/CIP1) and, in some cases, the accompanying downregulation of c-myc in response to TGF-beta. Our observations, taken together, indicate that inactivation of the RII contributes to the resistance to TGF-beta of some cervical carcinoma cell lines. Loss of or attenuated sensitivity to TGF-beta growth inhibition in other cells may be attributed to the disruption of distal components in the TGF-beta signal pathway, but not to the receptor system.

Blotting, Southern↗

A novel ets-related transcription factor, ERT/ESX/ESE-1, regulates expression of the transforming growth factor-beta type II receptor.

A 2.5-kilobase cDNA clone that encodes a 371-amino acid novel transcription factor was isolated from a human placenta cDNA library using a yeast one-hybrid system. The novel ets-related transcription factor (ERT) showed a homology with the ETS DNA-binding domain. Using constructs of the transforming growth factor-beta (TGF-beta) type II receptor (RII) promoter linked to the luciferase gene, we have demonstrated that ERT activates transcription of the TGF-beta RII gene through the 5'-TTTCCTGTTTCC-3' response element spanning nucleotides +13 to +24 and multiple additional ETS binding sites between -1816 and -82 of the TGF-beta RII promoter. A specific interaction between ERT and the ETS binding sites was also demonstrated using an electrophoretic mobility shift assay. Deletion mapping of ERT protein suggests that the transactivation domain resides in the amino terminus while the DNA-binding domain is localized to the carboxyl-terminal region. Our results suggest that ERT might be a major transcription factor involved in the transcriptional regulation of the TGF-beta RII gene.

Cloning, Molecular↗

Chromosome aberrations in workers of nuclear-power plants.

The frequencies of chromosome aberrations in 135 workers from nuclear- power plants were compared with those in 135 age-matched controls. A total of 135,000 cells was scored. The frequencies of dicentric chromosome were 1.67 x 10(-3) in the exposed group and 0.49 x 10(-3) in the control group and those of chromosome-type deletion were 3.33 x 10(-3) and 1.10 x 10(-3), respectively. The frequencies of all types of chromosome aberrations in the exposed subjects were higher than those in the control group, but no significant trend of dose-dependent increase was observed when only the exposed group were considered. Poisson regression analysis, with both exposed and control included, showed that there was a significant association of chromosome aberration with radiation dose and the duration of work, but not with age, smoking habit and alcohol intake. It was also found that recent exposure to radiation, within the last 5 years, had contributed more to the observed chromosome aberration than earlier exposure.

Adult↗

Quantitative analysis of trabecular microstructure by 400 MHz nuclear magnetic resonance imaging.

A new approach for the quantitative analysis of trabecular microstructure, based on high-field proton nuclear magnetic resonance (NMR) imaging, is presented. NMR is ideal because it provides high contrast between the marrow proton signal and the bone, which appears with background intensity. Images from 1 cm3 defatted specimens of trabecular bone, suspended in water doped with 1 mM Gd(DTPA) to shorten T1 to about 300 ms, can be obtained at a resolution on the order of 30-50 microns and slice thickness of 150 microns, in 10 minutes at 400 MHz proton frequency. Digital image processing algorithms were designed and evaluated for the measurement of bone area fraction, perimeter length, mean trabecular thickness, and separation. Bone area fraction derived from the NMR images was found to be in excellent agreement with bone volume fraction measured independently (slope = 0.96, r2 = 0.924, p < 0.0001). Errors in the mean trabecular thickness and separation were < 6%. The effects of finite imaging slice thickness and signal-to-noise ratio (SNR) were also evaluated. The data suggest a resolution of 50 x 50 x 200 microns 3 and an SNR on the order of 10 to provide safe margins for precise and accurate structural analysis by means of the algorithms presented in this paper. The method allows simultaneous measurement at multiple locations within the specimen volume without the need for physical sectioning.

Algorithms↗

Three-dimensional nuclear magnetic resonance microimaging of trabecular bone.

The conventional approach to measuring structural parameters in trabecular bone rests on stereology from optical images, derived from sections of embedded bone. In order to provide data that are statistically representative of a sufficiently large volume, multiple sections need to be analyzed in each of the three orthogonal planes. In this work, an alternative technique is presented which is based on three-dimensional (3D) volumetric proton nuclear magnetic resonance (NMR) microimaging. The method presented provides from 9 x 9 x 4 mm3 volumes of defatted bone specimens in 15-20 minutes scan time at isotropic resolution corresponding to (78 microm)3 voxel size. Surface-rendered images of bovine and human trabecular bone are shown and an algorithm was developed and implemented for determining the orientation and magnitude of the principle axes of the mean intercept length tensor.

Adult↗

A Bayesian approach to subvoxel tissue classification in NMR microscopic images of trabecular bone.

NMR microscopy is currently being used as an investigational tool for the evaluation of micromorphometric parameters of trabecular bone as a possible means to assess its strength. Since, typically, the image voxel size is not significantly smaller than individual trabecular elements, partial volume blurring can be a major complication for accurate tissue classification. In this paper, a Bayesian segmentation technique is reported that achieves improved subvoxel tissue classification. Each voxel is subdivided either into eight subvoxels twice the original resolution, or up to four subvoxels along the transaxial direction and the subvoxels optimally classified as volume blurring, the likelihood for the number of marrow subvoxels in each voxel can be computed on the basis of its measured signal. To resolve the ambiguity of the location of the marrow subvoxels, a Gibbs distribution is introduced to model the interaction between the subvoxels. Neighboring subvoxel pairs with the same tissue label are encouraged, and pairs with distinct labels are penalized. The segmentation is achieved by maximizing the a posteriori probability of the label image using the block ICM (iterative conditional mode) algorithm. The potential of the proposed technique is demonstrated in real and synthetic NMR microscopic images.

Algorithms↗

On the fractal nature of trabecular structure.

Fractal analysis has recently been suggested [Med. Phys. 20, 1611-1619 (1993)] as a means to characterize the structure of cancellous bone by measuring the fractal dimension using a box counting algorithm. This work re-examines the possible fractal nature of such structures on nuclear magnetic resonance (NMR) images of cancellous bone by estimating the trabecular boundary length as a function of box size under various experimental conditions. On high-resolution images (pixel sizes on the order of 50 microns) and signal-to-noise ratios of 30, the trabecular boundary turns out to be a smooth surface relative to the achievable resolution and is thus nonfractal. The fractal dimension of the trabecular structure is undefined and can vary significantly as a function of image signal-to-noise ratio. The present work further indicates the "apparent" fractal dimension obtained by box counting to be a reflection of marrow pore size. In conclusion, the results indicate that, at the currently achievable resolution, the box counting algorithm is not suitable for fractal analysis on images of cancellous bone and that the fractal appearance of the trabecular network reported previously is artifactual.

Algorithms↗

Magnetic field distribution in models of trabecular bone.

A magnetostatic model consisting of a tetragonal lattice of struts of diamagnetic material, mimicking vertebral trabecular bone, was developed. The model allows estimation of the magnetic field histogram within the lattice's unit cell as a function of geometric parameters. The field was computed analytically from the induced magnetic surface charge density on the faces of the struts. The contribution from the induced magnetic field to the effective transverse relaxation rate, R2', was obtained as the mean decay rate of the Fourier transformed histograms, for both fixed and randomly oriented lattices. The model predicts the field distribution to increase with both strut thickness and density, paralleling material density. Finally, significant changes in R2' are predicted at constant material density, in that the field distribution widens with simultaneously increasing strut number density and decreasing strut thickness.

Algorithms↗

Potential role of nuclear magnetic resonance for the evaluation of trabecular bone quality.

This paper discusses two novel applications of nuclear magnetic resonance (NMR) as an investigational tool for the assessment of cancellous bone microarchitecture. It further outlines extensions of the method for in vivo clinical evaluation of bone strength in patients with skeletal disorders such as osteoporosis. The first method relies on the hypothesis that the presence of two phases of different magnetic permeability, i.e., bone and bone marrow, causes a spatial nonuniformity of the magnetic field across the measurement volume. The resulting spread in resonance frequency shortens the decay time constant (T2*) of the time domain proton signal in bone marrow or its substitute (water). Increased trabecular spacing, such as it occurs in osteoporosis, reduces the spatial field inhomogeneity and thus prolongs T2*, which has been shown both in vitro and in vivo. Subjects with osteoporosis, characterized by either low bone mineral density and/or spine compression fractures, have T2* values that are significantly prolonged. The second method focuses on a direct measurement of micromorphometric parameters of cancellous bone, using the principles of proton NMR microscopy in conjunction with computer processing of the resulting digital images. Image contrast between the trabeculae and the intertrabecular space is based on the marrow protons providing a signal, as opposed to bone, which appears with background intensity. Once tissues have been classified (into bone and marrow), for example, by means of a histogram-based segmentation algorithm, bone area fraction, mean trabecular plate density (MTPD), and mean trabecular plate thickness (MTPT) can be computed without the need for further operator intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A survival study of surgically treated lung cancer in Korea. Lung Cancer Surgical Study Group.

Survival rate over a 5-year period were studied in a series of 658 proven primary lung cancer patients treated by thoracic surgeons at 8 institutes during the period from 1976 to 1987 in Korea. The study was designed as a multi-center cooperative work for the statistical analysis of the followup result. Clinical data of age, sex, morbidity, and staging of the tumor were assessed in 540 patients to evaluate their 5-year survival rates. Eventually, 405 resectable patients were analyzed by stage, cell type, surgical procedure, and TNM status. The 5-year actuarial survival rates by stage in the resectable group were: stage I 39.7%, II 30.6% III A 16.3%, III B 6.7%, and IV 0%. The 5-year survival rates by cell type were: squamous cell 31.9%, adenocarcinoma 21.2%, large cell 11%, and small cell 6%. The survival rates by surgical procedures were: lobectomy 30.7% and pneumonectomy 25.7%. The survival rates by TNM status in the operable group were: T1 34.7%, T2 26.8%, T3 7.5%, T4 5%; N1 23%, N2 10%, N3 3%; MO 21%, and M1 0%, respectively. The overall actuarial 5-year survival rate in the group of 405 resectable patients was 25.9%.

Adult↗

Modulation of restriction enzyme-induced damage by chemicals that interfere with cellular responses to DNA damage: a cytogenetic and pulsed-field gel analysis.

The electroporation of restriction enzymes into mammalian cells results in DNA double-strand breaks that can lead to chromosome aberrations. Four chemicals known to interfere with cellular responses to DNA damage were investigated for their effects on chromosome aberrations induced by AluI and Sau3AI; in addition, the number of DNA double-strand breaks at various times after enzyme treatment was determined by pulsed-field gel electrophoresis (PFGE). The poly(ADP-ribose) polymerase inhibitor 3-aminobenzamide (3AB) dramatically increased the yield of exchanges and deletions and caused a small but transitory increase in the yield of double-strand breaks induced by the enzymes. 1-beta-D-Arabinofuranosylcytosine, which can inhibit DNA repair either by direct action on DNA polymerases alpha and delta or by incorporation into DNA, potentiated aberration induction but to a lesser extent than 3AB and did not affect the amount of DNA double-strand breakage. Aphidicolin, which inhibits polymerases alpha and delta, had no effect on AluI-induced aberrations but did increase the aberration yield induced by Sau3AI. The postreplication repair inhibitor caffeine had no effect on aberration yields induced by either enzyme. Neither aphidicolin nor caffeine modulated the amount of DNA double-strand breakage as measured by PFGE. These data implicate poly(ADP-ribosyl)ation and polymerases alpha and delta as important components of the cellular processes required for the normal repair of DNA double-strand breaks with blunt or cohesive ends. Comparison of these data with the effect of inhibitors on the frequency of X-ray-induced aberrations leads us to the conclusion that X-ray-induced aberrations can result from the misjoining or nonrejoining of double-strand breaks, particularly breaks with cohesive ends, but that this process accounts for only a portion of the induced aberrations.

Animals↗

Restriction endonucleases do not induce sister-chromatid exchanges in Chinese hamster ovary cells.

Bacterial restriction enzymes offer the unique opportunity to determine the biological and cytogenetic consequences of DNA double-strand breakage. To examine the role of various types of breaks in sister-chromatid exchange (SCE) formation, we used restriction enzymes with different recognition sequences and different cutting frequencies to generate DNA double-strand breaks in Chinese hamster ovary (CHO) cells. The restriction enzymes were introduced by electroporation into exponentially growing cells during the second replication cycle in bromodeoxyuridine, and SCEs were analyzed at mitosis. Contrary to results reported by others, we found no increase in SCE frequency in cells exposed to restriction enzymes despite the presence of numerous cells with chromatid aberrations. These data suggest that DNA double-strand breaks do not lead to SCE formation.

Animals↗

Malignant melanoma of the sinonasal cavity: explanation of magnetic resonance signal intensities with histopathologic characteristics.

PURPOSE: To evaluate the magnetic resonance (MR) findings of malignant melanoma of the sinonasal cavity and compare these findings with those of the histopathological examination. MATERIALS AND METHODS: The MR images of 11 patients with malignant melanoma of the sinonasal cavity were retrospectively reviewed. Ten patients had primary malignant melanoma of the sinonasal cavity and one had a local recurrence. The imaging findings were evaluated with special attention given to the signal intensity of the tumor, internal characteristics, and growth pattern on MR. Signal intensity and enhancement patterns of the tumors were compared with the histopathological findings. RESULTS: On T1-weighted image, 6 tumors were hyperintense (5 melanotic and one amelanotic melanoma), and 5 tumors were isointense or hypointense (4 amelanotic and one melanotic). On T2-weighted images, 2 amelanotic tumors showed hyperintensity, and 5 melanotic tumors showed hypointensity. Four tumors (one melanotic and 3 amelanotic) were isointense. Four of the 7 tumors with hyperintensity on T1-weighted images showed patchy, higher-signal intensity areas. In 3 of them, patchy areas of a higher degree of pigmentation were found on histopathological examination. There were multiple linear dark signal intensities on T2-weighted images and/or linear-enhancing areas on enhanced T1-weighted images within the masses in 5 of the 11 patients. These findings could be explained as intratumoral vessels in 4 tumors and fibrous septa in one tumor on histopathological examinations. CONCLUSION: Malignant melanoma of the sinonasal cavity shows characteristic MR signal intensity, which is mainly attributable to the degree and distribution of melanin pigmentation, and partly attributable to hemorrhage within the mass. The linear, low-signal intensity on T2-weighted images or enhanced lines are intratumoral vessels or fibrous septa.

Adult↗