• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.362-368
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• 2008

Background: LKB1(STK11) is a serine/threonine kinase that functions as a tumor growth suppressor. The functions of LKB1 in lung cancer are not completely understood. This study evaluated the relationship between LKB1 protein expression and the clinicopathological features in lung cancer tissues. Methods: The expression of LKB1 was studied in paraffin-embedded tumor blocks, which were obtained from 77 patients who had undergone surgery at Wonkwang University Hospital. The expression of the LKB1 protein was considered positive if the staining intensity in the tumor tissue adjacent to the normal airway epithelium was >30%. Results: The LKB1 expression was positive in 31 (40%) of samples. Loss of LKB1 expression was significantly associated with being male, smoking history, and squamous cell carcinoma. In the peripheral sites, the loss of LKB1 expression was strongly associated with a smoking history. A loss of LKB1 expression was more frequently associated with progression according to TNM staging, particularly more than T2, N progression. Conclusion: There was a significant relationship between the loss of the LKB1 protein and gender, smoking history, and histological type in primary lung cancer. Although LKB1 expression was not found to be a significant prognostic factor, further studies with a larger cohort of patient's lung cancer tissue samples will be needed to confirm this.

• Ultrasonography
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• v.32 no.2
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• pp.132-142
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• 2013

Purpose: The purpose of this study is to investigate the correlations of various kinetic parameters derived from the time intensity curve in a xenograft mouse model injected with a prostate cancer model (PC-3 and LNCaP) using an ultrasound contrast agent with histopathologic parameters. Materials and Methods: Twenty nude mice were injected with human prostate cancer cells (15 PC-3 and five LNCaP) on their hind limbs. A bolus of $500{\mu}L$ ($1{\times}10^8$ microbubbles) of second-generation US contrast agent (SonoVue) was injected into the retroorbital vein. The region of interest was drawn over the entire tumor. The time intensity curve was acquired and then fitted to a gamma variate function. The maximal intensity (A), time to peak (Tp), maximal wash-in rate (washin), washout rate (washout), area under the curve up to 50 sec ($AUC_{50}$), area under the ascending slope ($AUC_{in}$), and area under the descending slope ($AUC_{out}$) were derived from the parameters of the gamma variate fit. Immunohistochemical staining for VEGF and CD31 was performed. Tumor volume, the area percentage of VEGF stained in a field, and the count of CD31 (microvessel density, MVD) positive vessels showed correlation with the parameters from the time intensity curve. Results: No significant differences were observed between the kinetic and histopathological parameters from each group. MVD showed positive correlation with A (r=0.625, p=0.003), washin (r=0.462, p=0.040), $AUC_{50}$ (r=0.604, p=0.005), and $AUC_{out}$ (r=0.587, p=0.007). Positive correlations were also observed between tumor volume and $AUC_{50}$ (r=0.481, p=0.032), washin (r=0.662, p=0.001), and $AUC_{out}$ (r=0.547, p=0.012). Washout showed negative correlations with MVD (r=-0.454, p=0.044) and tumor volume (r=-0.464, p=0.039). The area percentage of VEGF did not show any correlation with calculated data from the curve. Conclusion: MVD showed correlations with several of the kinetic parameters. CEUS has the potential for prediction of tumor vascularity in a prostate cancer animal model.

• Journal of Yeungnam Medical Science
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• v.15 no.1
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• pp.75-96
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• 1998

The local arrangement of sensory nerve cell bodies and nerve fibers in the brain stem, spinal ganglia and nodose ganglia were observed following injection of cholera toxin B subunit(CTB) and wheat germ agglutinin-horseradish peroxidase(WGA-HRP) into the rat intestine. The tracers were injected in the stomach(anterior and posterior portion), duodenum, jejunum, ileum, cecum, ascending colon or descending colon. After survival times of 48-96 hours, the rats were perfused and their brain, spinal and nodose ganglia were frozen sectioned ($40{\mu}m$). These sectiones were stained by CTB immunohistochemical and HRP histochemical staining methods and observed by dark and light microscopy. The results were as follows: 1. WGA-HRP labeled afferent terminal fields in the brain stem were seen in the stomach and cecum, and CTB labeled afferent terminal fields in the brain stem were seen in all parts of the intestine. 2. Afferent terminal fields innervating the intestine were heavily labeled bilaterally gelalinous part of nucleus of tractus solitarius(gelNTS), dorsomedial part of gelNTS, commissural part of NTS(comNTS), medial part of NTS(medNTS), wall of the fourth ventricle, ventral border of area postrema and comNTS in midline dorsal to the central canal. 3. WGA-HRP labeled sensory neurons were observed bilaterally within the spinal ganglia, and labeled sensory neurons innervating the stomach were observed in spinal ganglia $T_2-L_1$ and the most numerous in spinal ganglia $T_{8-9}$. 4. Labeled sensory neurons innervating the duodenum were observed in spinal ganglia $T_6-L_2$ and labeled cell number were fewer than the other parts of the intestines. 5. Labeled sensory neurons innervating the jejunum were observed in spinal ganglia $T_6-L_2$ and the most numerous area in the spinal ganglia were $T_{12}$ in left and $T_{13}$ in right. 6. Labeled sensory neurons innervating the ileum were observed in spinal ganglia $T_6-L_2$ and the most numerous area in the spinal ganglia were $T_{11}$ in left and $L_1$ in right. 7. Labeled sensory neurons innervating the cecum were observed in spinal ganglia $T_7-L_2$ and the most numerous area in the spinal ganglia were $T_{11}$ in left and $T_{11-12}$ in right. 8. Labeled sensory neurons innervating the ascending colon were observed in spinal ganglia $T_7-L_2$ in left, and $T_9-L_4$ in right. The most numerous area in the spinal ganglia were $T_9$ in left and $T_{11}$ in right. 9. Labeled sensory neurons innervating the descending colon were observed in spinal ganglia $T_9-L_2$ in left, and $T_6-L_2$ in right. The most numerous area in the spinal ganglia were $T_{13}$ in left and $L_1$ in right. 10. WGA-HRP labeled sensory neurons were observed bilaterally within the nodose ganglia, and the most numerous labeled sensory neurons innervating the abdominal organs were observed in the stomach. 11. The number of labeled sensory neurons within the nodose ganglia innervating small and large intestines were fewer than that of labeled sensory neurons innervating stomach These results indicated that area of sensory neurons innervated all parts of intestines were bilaterally gelatinous part of nucleus tractus solitarius(gelNTS), dorsomedial part of gelNTS, commissural part of NTS (comNTS), medial part of NTS, wall of the fourth ventricle, ventral border of area postrema and com NTS in midline dorsal to the central canal within brain stem, spinal ganglia $T_2-L_4$ and nodose ganglia. Labeled sensory neurons innervating the intestines except the stomach were observed in spinal ganglia $T_6-L_4$. The most labeled sensory neurons from the small intestine to large intestine came from middle thoracic spinal ganglia to upper lumbar spinal ganglia.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.846-860
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• 1998

Background: Endotoxin (LPS : lipopolysaccharide), a potent activator of immune system, can induce acute and chronic inflammation through the production of cytokines by a variety of cells, such as monocytes, endothelial cells, lymphocytes, eosinophils, neutrophils and fibroblasts. LPS stimulate the mononucelar cells by two different pathway, the CD14 dependent and independent way, of which the former has been well documented, but not the latter. LPS binds to the LPS-binding protein (LBP), in serum, to make the LPS-LBP complex which interacts with CD14 molecules on the mononuclear cell surface in peripheral blood or is transported to the tissues. In case of high concentration of LPS, LPS can stimulate directly the macrophages without LBP. We investigated to detect the generation of proinflammatory cytokines such as interleukin 1 (IL-1), IL-6 and TNF-$\alpha$ and fibrogenic cytokine, TGF-$\beta$, by peripheral blood mononuclear cells (PBMC) after LPS stimulation under serum-free conditions, which lacks LBPs. Methods : PBMC were obtained by centrifugation on Ficoll Hypaque solution of peripheral venous bloods from healthy normal subjects, then stimulated in the presence of LPS (0.1 ${\mu}g/mL$ to 100 ${\mu}g/mL$ ). The activities of IL-1, IL-6, TNF, and TGF-$\beta$ were measured by bioassaies using cytokines - dependent proliferating or inhibiting cell lines. The cellular sources producing the cytokines was investigated by immunohistochemical stains and in situ hybridization. Results : PBMC started to produce IL-6, TNF-$\alpha$ and TGF-$\beta$ in 1 hr, 4 hrs and 8hrs, respectively, after LPS stimulation. The production of IL-6, TNF-$\alpha$ and TGF-$\beta$ continuously increased 96 hrs after stimulation of LPS. The amount of production was 19.8 ng/ml of IL-6 by $10^5$ PBMC, 4.1 ng/mL of TNF by $10^6$ PBMC and 34.4 pg/mL of TGF-$\beta$ by $2{\times}10^6$ PBMC. The immunoreactivity to IL-6, TNF-$\alpha$ and TGF-$\beta$ were detected on monocytes in LPS-stimulated PBMC. Some of lymphocytes showed positive immunoreactivity to TGF-$\beta$. Double immunohistochemical stain showed that IL-1$\beta$, IL-6, TNF-$\alpha$ expression was not associated with CD14 postivity on monocytes. IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$mRNA expression were same as observed in immunoreactivity for each cytokines. Conclusion: When monocytes are stimulated with LPS under serum-free conditions, IL-6 and TNF-$\alpha$ are secreted in early stage of inflammation. In contrast, the secretion of TGF-$\beta$ arise in the late stages and that is maintained after 96 hrs. The main cells releasing IL-1$\beta$, IL-6, TNF-$\alpha$ and TGF-$\beta$ are monocytes, but also lymphocytes can secret TGF-$\beta$.