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Biomedical subjects

Chang Hun Lee

Publications and source records attributed to Chang Hun Lee.

17 recordsLinked to original sources
PubMed2006

Proapoptotic activity of NAG-1 is cell type specific and not related to COX-2 expression.

Non-steroidal anti-inflammatory drugs (NSAIDs) activated gene (NAG-1) is a newly identified member of the transforming growth factor-beta (TGF-beta) superfamily. Members of the TGF-beta family are multifunctional growth factors, and the nature of their effects depends on the cellular context and cell type. NAG-1 has antitumorigenic and proapoptotic activities in colon and gastric cancer cells lacking endogenous cyclooxgenase-2 (COX-2) expression. In contrast, COX-2 overexpression is related to antiapoptotic activity. The purpose of this study is to evaluate the proapoptotic activity of NAG-1 according to COX-2 expression and cell type. NAG-1 cDNA was transfected in SNU668 cells with endogenous COX-2 expression, SNU601 cells with forced COX-2 expression and Hep3B hepatocellular carcinoma cells. SNU668 cells with ectopic expression of NAG-1 showed markedly elevated subG1 population, induced death receptor-4 (DR-4) and DR-5, and revealed smaller active fragments of caspase-3. Forced COX-2 expression in SNU601 cells did not inhibit apoptosis caused by NAG-1 expression. Sulindac sulfide caused apoptosis, and induced expression of DR-5 and NAG-1 in Hep3B cells. However, Hep3B cells ectopically expressing NAG-1 did not cause apoptosis, and smaller active fragments of caspase-3 and an 85 kDa band of poly ADP-ribose polymerase (PARP) did not appear in the transfected cells, either. This study suggests that proapoptotic activity of NAG-1 is cell type specific and not related to COX-2 expression.

Antineoplastic Agents↗
PubMed2006

Gene expression in mixed type liposarcoma.

AIMS: Mixed type liposarcomas are rare. Here, we analysed the characteristics of an unusual case of mixed type liposarcoma, which consisted of a well-differentiated liposarcoma (WDL) and a pleomorphic liposarcoma (PL), with a special emphasis on molecular alterations. METHODS: Microscopic and immunohistochemical approaches were used to investigate this case of mixed type liposarcoma, and to identify molecular alterations in this tumour, gene expression was examined in PL, WDL, and normal adipose tissue (NA) samples using a 17,000 cDNA microarray. RESULTS: The tumour mass, 9 x 5 x 5 cm, was located in the left upper arm of a 76-year-old man. Grossly, the proximal portion of the tumour was composed of a yellowish fatty lesion, whereas the distal portion of the tumour was whitish and necrotic in nature. Histologically, the tumour was composed of two distinct components. The proximal component of the tumour was a WDL and the distal component was a PL. Immunohistochemically, S100 protein immunoreactivity highlighted lipoblasts in both tumour portions. The Ki-67 proliferation index was <1% in the WDL and 20% in the PL. MDM2 was positive in the WDL, but negative in the PL. p53 was negative in both areas. Numerous differentially expressed genes were found, which included genes coding for signal transduction, transcription, cell cycle, enzyme, structural protein, immune system and others. CONCLUSIONS: Our data demonstrate that multiple genes are differentially expressed in mixed type liposarcoma and suggest that these genes are associated with the differences in the morphological characteristics and pathogenesis of mixed type liposarcoma.

Adipose Tissue↗
PubMed2006

Electrospun PLGA nanofiber scaffolds for articular cartilage reconstruction: mechanical stability, degradation and cellular responses under mechanical stimulation in vitro.

We investigated the potential of a nanofiber-based poly(DL-lactide-co-glycolide) (PLGA) scaffold to be used for cartilage reconstruction. The mechanical properties of the nanofiber scaffold, degradation of the scaffold and cellular responses to the scaffold under mechanical stimulation were studied. Three different types of scaffold (lactic acid/glycolic acid content ratio = 75 : 25, 50 : 50, or a blend of 75 : 25 and 50 : 50) were tested. The tensile modulus, ultimate tensile stress and corresponding strain of the scaffolds were similar to those of skin and were slightly lower than those of human cartilage. This suggested that the nanofiber scaffold was sufficiently mechanically stable to withstand implantation and to support regenerated cartilage. The 50 : 50 PLGA scaffold was degraded faster than 75 : 25 PLGA, probably due to the higher hydrophilic glycolic acid content in the former. The nanofiber scaffold was degraded faster than a block-type scaffold that had a similar molecular weight. Therefore, degradation of the scaffold depended on the lactic acid/glycolic acid content ratio and might be controlled by mixing ratio of blend PLGA. Cellular responses were evaluated by examining toxicity, cell proliferation and extracellular matrix (ECM) formation using freshly isolated chondrocytes from porcine articular cartilage. The scaffolds were non-toxic, and cell proliferation and ECM formation in nanofiber scaffolds were superior to those in membrane-type scaffolds. Intermittent hydrostatic pressure applied to cell-seeded nanofiber scaffolds increased chondrocyte proliferation and ECM formation. In conclusion, our nanofiber-based PLGA scaffold has the potential to be used for cartilage reconstruction.

Animals↗
PubMed2005

An in vitro animal study of the biomechanical responses of anulus fibrosus with aging.

STUDY DESIGN: In vitro biomechanical tests were performed on aged (group A) and young (group B) porcine intervertebral discs. OBJECTIVES: The in vitro biomechanical responses of aged and young porcine intervertebral discs were measured under designated axial compressive loads and analyzed. SUMMARY OF BACKGROUND DATA: From the biomechanical point of view, the major biomechanical functions of intervertebral discs are to absorb and distribute external loadings. Although the histological observation of intervertebral discs on the effect of aging and related degeneration has been extensively studied and described, the changes in those biomechanical functions attributable to aging are still left to be studied. METHODS: Two groups were set for mechanical tests. Group A consisted of 24 motion segments obtained from female porcine lumbar (44.0 +/- 2.8-months old). The group B consisted of 30 motion segments from female porcine lumbar (6.2 +/- 1.3 months old). The specimens were chosen randomly from all levels. For the measurements of biomechanical responses, a pressure transducer was placed on anterior and posterolateral locations of anulus fibrosus. Morphological and histological observations were carried out to confirm any age-related changes in both groups. Intradiscal pressures and relaxation times were measured and calculated at points in the anulus fibrosus under designated axial compressive loads. RESULTS: Morphological and histological difference between group A and group B were confirmed with H&E staining and other measurements. Group A showed a lower ratio of nucleus pulposus area to total disc area than did group B. There was no significant difference in the intradiscal pressure between groups as measured in the anterior zone, except at an axial load of 740 N. However, a significant pressure difference was found in the posterolateral zone when the axial load was 542 N or greater (P < 0.05). At 740 N, the average relaxation time for group A was significantly longer than that for group B (P < 0.05). CONCLUSIONS: Differences in biomechanical responses between groups were confirmed. Group A was less flexible and slower at energy relaxation under axial loading. A larger proportion of the external load was taken by the posterolateral part of the degenerative discs. These results were consistent with clinical experiences: 1) most hernias are observed more often at the posterolateral side than other sides, and 2) the degeneration attributable to age reduces the function of absorbing and distribution of external loadings.

Aging↗
PubMed2005

Biomechanical comparisons of three different tibial tunnel directions in posterior cruciate ligament reconstruction.

PURPOSE: To investigate the effects of 3 different tunnel directions on the outcomes of posterior cruciate ligament (PCL) reconstruction surgery based on the forces exerted on the replacement ligament from a biomechanical point of view. The 3 tunnel directions in the proximal tibia are medial, central, and lateral. TYPE OF STUDY: Biomechanical study. METHODS: The forces exerted on the replaced PCL were calculated using finite element analyses as well as measurements from 6 cadavers. The results of the 3 surgical approaches were then compared. In the finite element analyses, the replaced ligament was assumed to have nonlinear elastic as well as viscoelastic properties. To simulate the overload in exercise, the femur was forced to move in the anterior direction abruptly while the tibia was held. From numerical analyses, the resultant forces, von Mises stresses, and maximum shear stresses on the replacement PCLs were calculated and compared. In the cadaveric study, a pressure-sensitive thin film was inserted between the replacement PCL and the killer turn area of the tibia. The color changes in films were evaluated using digital image processing in each case. RESULTS: The medial approach showed remarkably higher stresses and forces on the interface between the replaced PCL and the killer turn in both the numerical and cadaveric study. In contrast, the lateral approach showed the lowest stresses. CONCLUSIONS: The numerical and cadaveric studies indicate that the lateral approach is highly promising compared with the other approaches. CLINICAL RELEVANCE: The lateral approach has been shown to minimize stress concentration around the killer turn during in vitro experiments and a computer simulation of PCL reconstruction for long-term stability. The lateral approach technique appears to provide a promising clinical outcome in patients undergoing PCL reconstruction.

Arthroscopy↗
PubMed2005

Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast.

The effects of fiber alignment and direction of mechanical stimuli on the ECM generation of human ligament fibroblast (HLF) were assessed. The nanofiber matrix was fabricated using electrospinning technique. To align the nanofibers, a rotating target was used. The HLFs on the aligned nanofibers were spindle-shaped and oriented in the direction of the nanofibers. The degree of ECM production was evaluated by comparing the amount of collagen on aligned and randomly oriented structures. Significantly more collagen was synthesized on aligned nanofiber sheets, although the proliferation did not differ significantly. This suggests that the spindle-shape observable in intact ligaments is preferable in producing ECM. To evaluate the effect of strain direction on the ECM production, HLFs were seeded on parallel aligned, vertically aligned to the strain direction, and randomly oriented nanofiber sheets attached to Flexcell plates. After a 48-h culture, 5% uniaxial strain was applied for 24h at a frequency of 12 cycles/min. The amounts of collagen produced were measured 2 days after halting the strain application. The HLFs were more sensitive to strain in the longitudinal direction. In conclusion, the aligned nanofiber scaffold used in this study constitutes a promising base material for tissue-engineered ligament in that it provides more preferable biomimetic structure, along with proper mechanical environment.

Anterior Cruciate Ligament↗
PubMed2005

Recommendations for the management of cystic thyroid nodules.

BACKGROUND: The management of cystic thyroid nodules has not been standardized with respect to an initial fine-needle aspiration cytology (FNAC) cystic change result, which is defined as fluid aspiration and a smear with numerous macrophages but scant or no follicular cells. In the present study the physical characteristics of cystic thyroid nodules predictive of the pathology were investigated, and recommendations made on their management. METHODS: The aspiration results of 1436 thyroid nodules managed between 1998 and 2000 were investigated. A total of 157 patients who had a subsequent operation or follow-up data with reaspiration were the subjects of the present study. Age, sex, nodule characteristics and others were examined as possible predictors of cancer risk. RESULTS: The malignancy rate was 8.9%. Ten cases (71%) of malignancy were not cytologically diagnosed. Male sex and a nodule size of > or = 4 cm were found to be statistically significant predictors of malignancy. The malignancy rate was highest (100%) when a cystic lesion had malignant cytology on reaspiration and local invasion on radiology. CONCLUSIONS: When a cystic change is observed by initial FNAC of thyroid nodules, nodules of > or = 4 cm must be reaspirated and a firm cytologic diagnosis made to rule out malignancy. Nodules should be considered for surgery having taken into account other characteristics, in particular male sex and radiologic findings of local invasion.

Adult↗
PubMed2005

Emodin suppresses hyaluronic acid-induced MMP-9 secretion and invasion of glioma cells.

Emodin, an inhibitor of protein tyrosine kinase, possesses antiviral, immunosuppressive, anti-inflammatory and anticancer effects. In the present study, we investigated the effect of emodin on the hyaluronic acid (HA)-induced invasion of human glioma cells. Emodin significantly inhibited the HA-induced invasion through a Matrigel coated chamber, secretion of matrix metalloproteinase (MMP)-2, and HA-induced secretion of MMP-9 in glioma cells. To investigate the possible mechanisms involved in these events, we performed Western blot analysis using phospho-specific antibodies, and found that emodin inhibited phosphorylation of focal adhesion kinase (FAK), extracellular regulated protein kinase (ERK) 1/2 and Akt/PKB; emodin also suppressed the transcriptional activity of two transcription factors, activator protein-1 (AP-1) and nuclear factor-kappaB (NF-kappaB), in glioma cells. In addition, oral administration of emodin suppressed in vivo MMP secretion by glioma tumors in nude mice. Taken together, our results indicate that emodin can effectively inhibit HA-induced MMP secretion and invasion of glioma through inhibition of FAK, ERK1/2 and Akt/PKB activation and partial inhibition of AP-1 and NF-kappaB transcriptional activities. Consequently, these results provide important insights into emodin as an anti-invasive agent for the therapy of human glioma.

Animals↗
PubMed2004

Intrapulmonary cystic lymphangioma in a 2-month-old infant.

Lymphangioma is an abnormal collection of lymphatics that are developmentally isolated from the normal lymphatic system. Lymphangioma rarely presents as a solitary pulmonary lesion. We report a rare case of intrapulmonary cystic lymphangioma involving the upper lobe of the right lung, which presented with dyspnea in a 2-month-old infant. High-resolution computed tomography (HRCT) of the chest demonstrated a well-circumscribed, multiseptate, cystic lesion in the upper lobe of the right lung, mimicking the feature of type I congenital cystic adenomatoid mal-formation. The tumor was removed by bilobectomy of the upper and middle lobes of the right lung, and its pathologic examination confirmed the diagnosis of an intra-pulmonary cystic lymphangioma.

Female↗
PubMed2003

Magnetic resonance imaging and histologic findings of experimental cerebral fat embolism.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine whether cerebral fat embolism demonstrated reversible or irreversible findings in magnetic resonance (MR) imaging over time and to compare the features in MR images with histologic findings in a cat model. MATERIALS AND METHODS: MR images were obtained serially at 2 hours, 1 and 4 days, and 1, 2, and 3 weeks after embolization with 0.05 mL of triolein into the internal carotid artery in 19 cats. Any abnormal signal intensity and change in the signal intensity were evaluated on T2-weighted images, T1-weighted images, diffusion-weighted images (DWIs; including apparent diffusion coefficient [ADC] maps), and gadolinium-enhanced T1-weighted images (Gd-T1WI) over time. After MR imaging at 3 weeks, brain tissue was obtained and evaluated for light microscopic (LM) examination using hematoxylin-eosin and Luxol fast blue staining. For electron microscopic examination, the specimens were obtained at the cortex. The histologic and MR findings were compared. RESULTS: The embolization lesions showed hyperintensity on T2-weighted images, hyperintensity, or isointensity on DWIs, hypointensity, or isointensity on ADC maps and contrast enhancement on Gd-T1WIs at 2 hours. The T2-weighted hyperintensity extended to the white matter at day 1 and decreased thereafter. Contrast enhancement decreased continuously from day 1, and hyperintensity on DWI decreased after day 4. Hypointensity on ADC maps became less prominent after day 4. By week 3, most lesions had reverted to a normal appearance on MR images and were correlated with LM findings. However, small focal lesions remained in the gray matter of 8 cats and in the white matter of 3 cats on MR images, and this correlated with the cystic changes on LM findings. Electron microscopic examination of the cortical lesions that reverted to normal at week 3 in MR images showed that most of these lesions appeared normal but showed sporadic intracapillary fat vacuoles and disruption of the endothelial walls. CONCLUSIONS: The embolized lesions of the hyperacute stage were of 2 types: type 1 lesions, showing hyperintensity on DWIs and hypointensity on ADC maps, have irreversible sequelae, such as cystic changes; whereas type 2 lesions, showing isointensity or mild hyperintensity on DWIs and ADC maps, reverted to a normal appearance in the subacute stage.

Animals↗
PubMed2003

Differential expression of hypoxia inducible factor-1 alpha and tumor cell proliferation between squamous cell carcinomas and adenocarcinomas among operable non-small cell lung carcinomas.

This study aimed to evaluate whether the elevated level of hypoxia-inducible factor-1alpha (HIF-1alpha) correlated with histologic types, angiogenesis, tumor cell proliferation, and clinical parameters in common non-small cell lung carcinomas (NSCLCs). We performed immunohistochemical stains using paraffin-embedded tissue blocks from 84 cases of operable NSCLC [No. of squamous cell carcinoma (SCC), 45; No. of adenocarcinoma (AC), 39]. HIF-1alpha expression was related with histologic types (66.7% in SCCs vs 20.5% in ACs, p<0.001), but not with lymph node status, tumor stage, vascular endothelial growth factor expression, microvessel density (MVD), and proliferating cell nuclear antigen (PCNA) index (p>0.05, respectively). As for the histologic types, MVD and PCNA index were significantly higher in SCCs than in ACs (p=0.009 and p=0.016, respectively). Among HIF-1alpha positive carcinomas, MVD was significantly higher in HIF-1alpha positive SCCs than in HIF-1alpha positive ACs (p=0.023). The overall survival curves were not associated with HIF-1alpha expression or any other histologic parameters (p>0.05). These findings suggest that HIF-1alpha expression in NSCLCs may play a differential role according to histologic types, but its prognostic significance is indeterminate.

Adenocarcinoma↗
PubMed2003

Expression and localization of the transforming growth factor-beta type I receptor and Smads in preneoplastic lesions during chemical hepatocarcinogenesis in rats.

Little is known about the involvement of Smad-related molecules in the regulation of the Transforming Growth Factor (TGF)-beta signaling pathway during hepatocarcinogenesis, particularly with respect to preneoplastic lesions of a rat liver. The aims of this study were to investigate the localizations and temporal expressions of TGF-beta Receptor Type 1 (TGR1) and Smads during the promotion stage of chemical hepatocarcinogenesis in rats. We investigated expressions and localizations of TGR1, Smad2, Smad4, and Smad7 by using semi-quantitative RT-PCR and immunohistochemistry in preneoplastic lesions during rat chemical hepatocarcinogenesis induced by Solt and Farber's method. The down-regulation of TGR1, Smad2, and Smad4 was evident during the later steps of the promotion stage of chemical hepatocarcinogenesis. In contrast with other Smads, increased Smad7 expression was evident during the later steps of the promotion stage. Also immunohistochemistry revealed that the main site of TGR1, Smad2, Smad4, and Smad7 expression was mainly in hepatocytes of the preneoplastic lesions of a rat liver. Dysregulation of the downstream effectors of TGF-beta such as TGR1, Smad2, Smad4 and, Smad7 might contribute to the progression of preneoplastic lesions during chemical hepatocarcinogenesis in a rat.

Activin Receptors, Type I↗
PubMed2003

Pleuropulmonary blastoma in a young adult presenting as a ruptured cystic teratoma in radiology.

Pleuropulmonary blastoma (PPB) is a rare malignant dysontogenetic neoplasm primarily affecting children and is characterized histologically by a variably mixed blastematous and sarcomatous patterns. We herein report a very exceptional adult case of PPB. A 21-yr-old male patient presented with a left chest pain of two weeks' duration. A computed tomography scan revealed a large, multicystic tumor occupying the left lower hemithorax, leading to the impression of a ruptured mediastinal cystic teratoma. A thoracotomy for resection of the tumor was performed. On histologic examination, the tumor consisted of cystic walls and associated solid lesions which showed undifferentiated blastemal tissues with focal fibrosarcomatous and rhabdoid features. Immunohistochemically the tumor cells only showed diffuse strong positivity for vimentin. The histologic findings corresponded to a type II PPB. The authors suggest that PPB, especially of type I or II, should be included in the radiologic differential diagnosis of mediastinal cystic neoplasms in a young adult.

Adult↗
PubMed2003

Comparison of polymerase chain reaction with histopathologic features for diagnosis of tuberculosis in formalin-fixed, paraffin-embedded histologic specimens.

Objective.-To investigate the relationship between various histopathologic features and the results of the tuberculosis (TB)-polymerase chain reaction (PCR) method in routinely submitted histologic specimens for the histopathologic diagnosis of TB. Design.-We used 95 formalin-fixed, paraffin-embedded tissue blocks from 81 patients who were clinically suspected of having TB. We assessed the presence of histopathologic features including well-formed granuloma, poorly formed granuloma, caseous necrosis, and Langhans-type giant cells. We performed nested PCR for IS6110 and Ziehl-Neelsen staining for acid-fast bacilli (AFB). Results.-Of the 81 patients studied, 53 patients had chronic granulomatous inflammation, whereas 28 patients had only chronic inflammation without definite granulomatous inflammation. Of the 53 cases with chronic granulomatous inflammation, 17 (32%) were AFB positive and 36 (68%) were TB-PCR positive. Among cases with chronic granulomatous inflammation, the percentage that were positive and negative by TB-PCR differed significantly with the presence of various histopathologic features. All of the 13 cases with well-formed granuloma, caseous necrosis, and Langhans-type giant cells were TB-PCR positive; however, 10 (36%) of the 28 cases with chronic inflammation without granulomatous lesions were also TB-PCR positive. Conclusions.-TB-PCR is a rapid, sensitive method for the diagnosis of TB in routinely processed formalin-fixed, paraffin-embedded histologic specimens and is readily available in histopathology laboratories. We recommend use of TB-PCR when TB is suspected clinically, especially in cases of chronic inflammation without definite evidence of granulomatous inflammation.

Chronic Disease↗
PubMed2002

Experimental cerebral fat embolism: embolic effects of triolein and oleic acid depicted by MR imaging and electron microscopy.

BACKGROUND AND PURPOSE: In fat embolism, free fatty acid is more toxic than neutral fat in terms of tissue damage. We evaluated the hyperacute embolic effects of triolein and oleic acid in cat brains by using MR imaging and electron microscopy. METHODS: T2-weighted imaging, diffusion-weighted imaging, and contrast-enhanced T1-weighted imaging were performed in cat brains after the injection of triolein (group 1, n = 8) or oleic acid (group 2, n = 10) into the internal carotid artery. MR images were quantitatively assessed by comparing the signal intensity ratios of the lesions with their counterparts on T2-weighted images, apparent diffusion coefficient (ADC) maps, and contrast-enhanced T1-weighted images. Electron microscopic findings in group 1 were compared with those in group 2. RESULTS: Qualitatively, MR images revealed two types of lesions. Type 1 lesions were hyperintense on diffusion-weighted images and hypointense on ADC maps. Type 2 lesions were isointense or mildly hyperintense on diffusion-weighted images and isointense on ADC maps. Quantitatively, the signal intensity ratios of type 1 lesions in group 2 specimens were significantly higher on T2-weighted images (P =.013)/(P =.027) and lower on ADC maps compared with those of group 1. Electron microscopy of type 1 lesions in both groups revealed more prominent widening of the perivascular space and swelling of the neural cells in group 2, in contrast to notable endothelial defects in group 1. CONCLUSION: MR and electron microscopic data on cerebral fat embolism induced by either triolein or oleic acid revealed characteristics suggestive of both vasogenic and cytotoxic edema in the hyperacute stage. Tissue damage appeared more severe in the oleic acid group than in the triolein group.

Animals↗
PubMed2002

[A case of idiopathic hypereosinophilic syndrome with hepatic involvement in a 5-year-old boy].

Idiopathic hypereosinophilic syndrome is defined as the presence of prolonged eosinophilia without an identifiable underlying cause and with evidence of end-organ dysfunction. The organs involved are the heart, bone marrow, nervous system, lungs, liver, skin, and gastrointestinal tract. Hepatic involvement is found in about 30% of patients of idiopathic hypereosinophilic syndrome. It occurs rarely in infants and children. In this report, we experienced one case of idiopathic hypereosinophilic syndrome with hepatic involvement in a 5-year-old boy who complained of intermittent fever and right upper quadrant abdominal pain. An abdominal ultrasound examination revealed an ill-defined low-echoic lesion in the liver. Pathologic findings of a biopsy specimen clearly showed the infiltration of eosinophils in the liver. Laboratory data disclosed absolute eosinophilia. There was no evidence of allergic disease or parasitic infestation.

Child, Preschool↗