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Biomedical subjects

Chang Hyun Lee

Publications and source records attributed to Chang Hyun Lee.

8 recordsLinked to original sources

Identification of gene expression signatures for molecular classification in human leukemia cells.

Although the methods by which leukemia is classified have been improved for effective therapies, leukemia patients occasionally exhibit diverse, sometimes unpredictable, responses to treatment. Consequently, these patients also evidence individually different clinical courses when administered with anti-leukemia drugs. In order to find new, more precise molecular markers for leukemia classification, we have analyzed the gene expression profiles from 65 diagnostic bone marrow specimens of adult patients with AML, ALL, CML or CLL by using high-throughput DNA microarrays harboring approximately 8,300 unique human genes or expression sequence tags. In the present study, we identified a group of leukemia-specific genes, which manifest gene expression profiles distinctly representative of normal bone marrow samples, as determined by a significance analysis of microarray (SAM) and GeneSpring 6.1 programs. We also determined the minimal number of genes showing a difference between acute and chronic leukemia patient groups. Furthermore, the unsupervised cluster analysis revealed a gene subset which can be used to distinguish between AML, ALL, CML and CLL patient groups, based on expression signatures. The expression levels of differentially regulated genes were verified via the principle component analysis (PCA). Our results may provide a novel set of molecular criteria for the classification of leukemia patients, and may also facilitate effects to discovery new targets, allowing for more effective treatment of leukemia patients.

Adolescent↗

Laser welding of rat's facial nerve.

The aim of this study is to compare regeneration of the severed nerves that were repaired by laser welding with those repaired by microsurgical suturing and evaluate the value in use of laser nerve welding in the head and neck area. In 12 rats the buccal branches of the facial nerves on the both sides were transected, and CO2 laser welding of the epineurium was performed on the right side and microsurgical suture technique was applied on the left side. In six rats Cholera Toxin B Subunit (CTb) was injected in the epineurium distal to the nerve anastomosis site at postoperative week 4. Another six rats were treated exactly in the same way in postoperative week 8. Six normal rats were used as controls. Intact facial nerve was observed after injection of CTb as well. Neurons of facial nuclei labeled positively by CTb were detected immunohistochemically, and the numbers were counted. CTb-positive neurons in the control group were 1311 +/- 258 (n = 6). CTb-positive neurons in the group (n = 6) with laser nerve welding were 1174 +/- 122 in postoperative week 4 and 1562 +/- 565 in postoperative week 8. CTb-positive neurons in the group (n = 6) with microsurgical suture were 1066 +/- 89 in postoperative week 4 and 1443 +/- 531 in postoperative week 8. CTb-positive neurons were seen significantly more in the group with laser welding than in the group with microsurgical suture in postoperative week (P = 0.028), but there was not much difference in postoperative week 8 (P = 0.463). None of 12 rats showed dehiscence at the nerve anastomosis done by laser welding. This study shows that nerve regeneration is more apparent in the nerve repaired by laser welding than in that repaired by microsurgical suture.

Animals↗

Enhanced oral bioavailability of paclitaxel by coadministration of the P-glycoprotein inhibitor KR30031.

PURPOSE: In an attempt to improve the oral bioavailability of paclitaxel, a novel P-glycoprotein inhibitor, KR30031, which is verapamil analog with fewer cardiovascular effects, was coadministered with paclitaxel, and to elucidate other possible causes of the low oral bioavailability of paclitaxel, an inhibitor of hepatic metabolism, ketoconazole, was also coadministered with paclitaxel. METHODS: In vivo oral absorption was tested in rats, and an in vitro study was also performed with a Caco-2 cell monolayer to identify the extent of P-glycoprotein inhibition. RESULTS: After coadministration of paclitaxel with ketoconazole, KR-30031, or KR-30031 and ketoconazole, bioavailability was increased about 1.6-, 7.5-, or 8.9-fold as compared with control, respectively. These results show that P-glycoprotein plays a major role in the oral bioavailability of paclitaxel. The effect of ketoconazole on oral bioavailability of paclitaxel was limited relative to the P-glycoprotein inhibition effect of KR-30031. In vitro study of Caco-2 cell transport showed that paclitaxel permeation was significantly higher when the drug was given from the basolateral side as compared to the permeation from the apical side, indicating the involvement of an enzyme reaction in the active efflux mechanism. Apical-to-basolateral transport of paclitaxel was increased in the presence of KR-30031. The ability of KR-30031 to reduce this efflux transport is equal to that of verapamil, a well-known P-glycoprotein inhibitor. CONCLUSIONS: Our findings suggest that about 54% of a paclitaxel oral dose is extruded to the gut lumen by P-glycoprotein. Thus, the bioavailability of paclitaxel could be enhanced by coadministration of a P-glycoprotein inhibitor, KR-30031.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Inhibitory effect of Carthamus tinctorius L. seed extracts on bone resorption mediated by tyrosine kinase, COX-2 (cyclooxygenase) and PG (prostaglandin) E2.

Anti-bone resorption properties of the Korean herbal formulation, Honghwain (HHI; Carthamus tinctorius L. seed) was biochemically investigated. On processing bone metabolism, PGE2 accelerated production of IL-1beta in fetal mouse osteoblast and stimulated physiological activation substance, IL-1beta. The novel class of Src tyrosine kinase inhibitors, Herbimycin A (HERB) and HHI reduced COX-2 mRNA levels as well as PGE2 production induced by IL-1beta, TNF-alpha and IL-6. HHI inhibited in vitro and in vivo bone resorption by inhibition of phosphorylation of peptide substrates. HHI dose-dependently reduced the hypercalcemia induced in mice by IL-1beta and partly prevented bone loss and microarchitectural changes in young ovariectomized rats, showing that the protective effect on bone was exerted via the inhibition of bone resorption. These results indicate that the synergy between IL-beta, TNF-alpha, IL-6 on PGE2 production is due to an enhanced gene expression of COX-2 and that tyrosine kinase (s) are involved in the signal transduction of COX-2 in mouse calvarial osteoblasts. Thus, HHI as a possible Src family kinase inhibitor may be useful for the treatment of diseases associated with elevated bone loss.

Animals↗

The value of computed tomography for predicting empyema-associated malignancy.

OBJECTIVE: To determine the value of computed tomography (CT) scanning in detecting associated malignancy in patients with chronic empyema. METHODS: Two radiologists retrospectively reviewed CT scans of 112 consecutive patients with chronic empyema and arrived at a consensus about the findings. Among these patients, 6 were confirmed by pathology evaluation to have empyema-associated malignancy (EAM), including 4 lymphomas. The CT scans were evaluated for the presence of the following findings: a mass in the empyema sac; mass involvement of the extrapleural fat, chest wall, rib, and lung; bulging of the empyema sac; nodular pleural thickening; empyema involvement of the mediastinal pleura; presence of lung nodules (>1 cm); and mediastinal lymph node enlargement. The association between the CT findings and the EAM was analyzed with the Fisher exact test. A multiple logistic regression analysis was used to determine the predictive variables for EAM. Sensitivity, specificity, and positive predictive value were calculated for each finding. RESULTS: All CT findings, except rib involvement and bulging of empyema sac, were significantly associated with EAM (P<0.05). The finding of the presence of a mass, extrapleural fat, and mediastinal involvement showed relatively high sensitivity (100%, 67%, 67%, respectively) and specificity (81%, 87%, 91%, respectively). A bulging of the empyema sac and nodular pleural thickening showed 100% sensitivity, but low specificity (39% and 44%, respectively). Findings from the multiple logistic regression analysis revealed that the presence of a mass and empyema of the mediastinal pleura were significant variables associated with EAM (P<0.05). CONCLUSIONS: Although many CT findings are associated with EAM, most showed either low positive predictive value or low sensitivity. A variety of CT findings should be considered when evaluating CT image-based detection of EAM.

Adolescent↗

Fatigue stress fractures of the pubic ramus in the army: imaging features with radiographic, scintigraphic and MR imaging findings.

Although fatigue fractures are not unusual in athletes and military personnel those of the pubic ramus are rare. We report three cases of fatigue fractures of the inferior pubic rami in two male recruits and one female military cadet. On the initial radiograph, most of the lesions were subtle and easy to overlook. However, bone scintigraphy provided more distinct images that allowed easy and early detection of lesions, and MR imaging presented more diagnostic information, which allowed a precise diagnosis.

Adult↗

CT findings of atypical adenomatous hyperplasia in the lung.

OBJECTIVE: The aim of this study was to analyze the computed tomographic (CT) findings of atypical adenomatous hyperplasia (AAH) in the lung. MATERIALS AND METHODS: The CT findings of AAHs in eight patients were retrospectively reviewed. The CT findings of each AAH lesion were evaluated for multiplicity, location, shape, size and internal density of the lesion, the interface between the normal lung and the lesion, the internal features within the lesion and any change of the lesion on the follow-up CT scans (range: 33 to 540 days; average: 145.3 days). RESULTS: The eight patients consisted of three men and five women (age range: 43-71 years). Six of eight patients were asymptomatic. Four of them (50%) had synchronous malignancies in the lung: adenocarcinoma of the lung (n = 3), and metastatic squamous cell carcinoma from the uterus (n = 1). We could identify and evaluate eleven AAH nodules in seven patients on the CT scans. Three patients had multiple AAHs. Seven of the 11 lesions (64%) were located in the upper lobe. All the AAHs showed a well-defined oval or round shape and pure ground-glass opacity (GGO) without any solid component (size: 3.9x3 mm to 19x17 mm; internal attenuation: -467 to -785 HU). All the AAHs showed no change of their size and internal density on the follow-up CT scans. CONCLUSION: Atypical adenomatous hyperplasia is often associated with malignancy. This tumor is shown on CT as persistent well-defined oval or round nodular GGOs without solid components, and it does not change on the follow-up CT.

Adenocarcinoma↗

CT analysis of the anterior mediastinum in idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia.

OBJECTIVE: We wanted to determine whether the amount and shape of the anterior mediastinal fat in the patients suffering with usual interstitial pneumonia (UIP) or nonspecific interstitial pneumonia (NSIP) was different from those of the normal control group. MATERIALS AND METHODS: We selected patients who suffered with UIP (n = 26) and NSIP (n = 26) who had undergone CT scans. Twenty-six controls were selected from individuals with normal CT findings and normal pulmonary function tests. All three groups (n = 78) were individually matched for age and gender. The amounts of anterior mediastinal fat, and the retrosternal anteroposterior (AP) and transverse dimensions of the anterior mediastinal fat were compared by one-way analysis of variance and Bonferroni's test. The shapes of the anterior mediastinum were compared using the Chi-square test. Exact logistic regression analysis and polychotomous logistic regression analysis were employed to assess whether the patients with NSIP or UIP had a tendency to show a convex shape of their anterior mediastinal fat. RESULTS: The amount of anterior mediastinal fat was not different among the three groups (p = 0.175). For the UIP patients, the retrosternal AP dimension of the anterior mediastinal fat was shorter (p = 0.037) and the transverse dimension of the anterior mediastinal fat was longer (p = 0.001) than those of the normal control group. For the NSIP patients, only the transverse dimension was significantly longer than those of the normal control group (p < 0.001). The convex shape of the anterior mediastinum was predictive of NSIP (OR = 19.7, CI 3.32-infinity, p < 0.001) and UIP (OR = 24.42, CI 4.06-infinity, p < 0.001). CONCLUSION: For UIP patients, the retrosternal AP and transverse dimensions are different from those of normal individuals, whereas the amounts of anterior mediastinal fat are similar. UIP and NSIP patients have a tendency to have a convex shape of their anterior mediastinal fat.

Adipose Tissue↗