Gyung Hyuck Ko

Preventing collapse in early osteonecrosis of the femoral head. A randomised clinical trial of core decompression

We performed a randomised trial on 37 hips (33 patients) with early-stage osteonecrosis (ON). After the initial clinical evaluation, including plain radiography and MRI, 18 hips were randomly assigned to a core-decompression group and 19 to a conservatively-treated group. All the patients were regularly followed up by clinical evaluation, plain radiography and MRI at intervals of three months. Hip pain was relieved in nine out of ten initially symptomatic hips in the core-decompression group but persisted in three out of four initially painful hips in the conservatively-treated group at the second assessment (p < 0.05). At a minimum follow-up of 24 months, 14 of the 18 core-decompressed hips (78%) and 15 of the 19 non-operated hips (79%) developed collapse of the femoral head. By survival analysis, there was no significant difference in the time to collapse between the two groups (log-rank test p = 0.79). Core decompression may be effective tin symptomatic relief, but is of no greater value than conservative management in preventing collapse in early osteonecrosis of the femoral head.

Monoclonal Antibodies against Helicobacter pylori Cross‐React with Human Tissue

H. pylori is a causative agent of chronic gastritis. However, the pathogenic mechanism by which H. pylori induces chronic inflammation and epithelial injuries in the gastric and duodenal mucosa is not well known. Investigators have recently reported that some monoclonal antibodies against H. pylori cross‐react with the gastric epithelial cells. So, there exists the possibility that the autoimmune mechanism may be involved in the pathogenesis of chronic gastritis caused by H. pylori. The purpose of his study is to investigate whether the antibodies against H. pylori react with human tissues or not, using a large panel of monoclonal antibodies.

Langerhans Cell Sarcoma Arising from Langerhans Cell Histiocytosis : A Case Report

Langerhans cell sarcoma (LCS) is a neoplastic proliferation of Langerhans cells that have overtly malignant cytologic features. It is a very rare disease and theoretically, it can present de novo or progress from an antecedent Langerhans cell histiocytosis (LCH). However, to our knowledge, LCS arising from an antecedent LCH has not been reported on. We present here a case of LCS arising from a pulmonary LCH. A 34 yr-old man who was a smoker, had a fever and a chronic cough. Computed tomographic (CT) scan revealed multiple tiny nodules in both lungs. The thoracoscopic lung biopsy revealed LCH. The patient quit smoking, but he received no other specific treatment. One year later, the follow up chest CT scan showed a 4 cm-sized mass in the left lower lobe of the lung. A lobectomy was then performed. Microscopic examination of the mass revealed an infiltrative proliferation of large cells that had malignant cytologic features. Immunohistochemical stains showed a strong reactivity for S-100 and CD68, and a focal reactivity for CD1a. We think this is the first case of LCS arising from LCH.

Invasiveness of Helicobacter pylori into Human Gastric Mucosa

Background. Helicobacter pylori has generally been observed only in the gastric mucous layer or in the spaces between gastric mucus‐secreting cells and not in the gastric epithelial cells or in the lamina propria. The purpose of this study is to determine whether H. pylori invades the gastric mucosa, using an immunoelectron microscopical examination of human gastric mucosa infected with H. pylori.

Rebamipide abolishes Helicobacter pylori CagA-induced phospholipase D1 expression via inhibition of NFκB and suppresses invasion of gastric cancer cells

Infection with cagA-positive Helicobacter pylori is a risk factor for the development of severe gastritis and gastric cancer (GC). CagA protein is injected into gastric epithelial cells and deregulates a variety of cellular signaling molecules. Phospholipase D (PLD) is elevated in many different types of human cancers and has been implicated as a critical factor in inflammation and carcinogenesis. In this study, we show that infection with cagA-positive H. pylori in GC cells significantly induces PLD1 expression via CagA-dependent activation of nuclear factor κB (NFκB). Interestingly, the level of PLD1 protein and IκBα phosphorylation is aberrantly upregulated in H. pylori-infected human GC tissues. Infection with cagA-positive H. pylori and expression of CagA enhanced the binding of NFκB to the PLD1 promoter, and two functional NFκB-binding sites were identified within the PLD1 promoter. Rebamipide, a mucosal-protective antiulcer agent, abolished H. pylori cagA-induced PLD1 expression via inhibition of binding of NFκB to the PLD1 promoter, and also inhibited PLD activity. Moreover, rebamipide suppressed H. pylori-induced matrix metalloproteinase-9, interleukin-8 and activation-induced cytidine deaminase expression as well as invasion of GC cells through downregulation of PLD1. Our data suggest that H. pylori cagA targets PLD1 for invasion of GC cells, and rebamipide might contribute to the antitumorigenic effect of GC cells via inhibition of the H. pylori cagA-NFκB-PLD1 signaling pathway.

Compound C independent of AMPK inhibits ICAM-1 and VCAM-1 expression in inflammatory stimulants-activated endothelial cells in vitro and in vivo

Activation of the NF-κB and mitogen activated protein (MAP) kinases plays an important role in the expression of inflammatory genes such as adhesion molecules. Although compound C is known as an AMPK inhibitor, AMPK-independent action of it has been recognized. Effects on the expression of ICAM-1 and VCAM-1 by compound C were investigated in TNF-α-activated human umbilical vein endothelial cells (HUVECs) in vitro and in thoracic aorta of rats treated with lipopolysaccharide (LPS) in vivo. Compound C inhibited ICAM-1 and VCAM-1 expression at the transcriptional as well as translational level in TNF-α-activated HUVECs. In both DN-AMPK- and AMPKα(1)-siRNA-transfected HUVECs, compound C still inhibited TNF-α-induced VCAM-1 and ICAM-1 expression, indicating that this is AMPK-independent action. Interestingly, compound C significantly inhibited NF-κB activity and translocation of p65 to nucleus in HUVECs when activated with TNF-α. Importantly, administration of compound C (0.2 mg/kg) significantly reduced expression of both ICAM-1 and VCAM-1 in LPS-treated rat thoracic aortas. In addition, compound C significantly inhibited iNOS and production of NO in both TNF-α- and LPS-activated RAW 264.7 cells. Finally, compound C significantly inhibited phosphorylation of Akt and p-38MAPK but not protein kinase c or ERK1/2 in HUVECs. Taken together, we conclude that adhesion molecules (ICAM-1, VCAM-1) are to be the novel targets of compound C in preventing inflammatory insult to endothelial cells independent of AMPK inhibition via inhibition of NF-κB activity along with inhibition of phosphorylation of PI3K and P38 MAPK.

Angiography, Scintigraphy, Intraosseous Pressure, and Histologic Findings in High-Risk Osteonecrotic Femoral Heads With Negative Magnetic Resonance Images

One hundred twenty-six hips of 68 patients who were suspected of having osteonecrosis or being at risk for osteonecrosis were studied with magnetic resonance (MR) imaging. Abnormal patterns on MR imaging characteristic of osteonecrosis were observed in 98 hips. The remaining 28 hips (22 patients) with negative MR images underwent superselective angiography of the medial femoral circumflex artery. Angiography showed interruption of the superior retinacular arteries in 13 hips (12 patients), including 6 of 7 symptomatic hips. Bone scans were performed on 8 of 13 hips angiographically positive for osteonecrosis. Decrease of radionuclide uptake (cold lesions) was observed in all 8 of these femoral heads. Thirteen femoral heads with interruption of superior retinacular arteries underwent intraosseous pressure measurement and core biopsy. Intraosseous pressure was elevated in 11 hips. The results of histologic study showed evidence of early necrosis in 10 femoral heads. This study indicates that there are a considerable number of femoral heads at high risk, even when they have negative MR images. They do, however, show positive findings on angiography, scintigraphy (cold lesions), intraosseous pressure measurement, and histologic study.

Peroxiredoxin IV Protects Cells From Radiation-Induced Apoptosis in Head-and-Neck Squamous Cell Carcinoma

PURPOSE Human peroxiredoxins (Prxs) are known as a family of thiol-specific antioxidant enzymes, among which Prx-I and -II play an important role in protecting cells from irradiation-induced cell death. It is not known whether Prx-IV also protects cells from ionizing radiation (IR). METHODS AND MATERIALS To evaluate the protective role of Prx-IV in IR, we transfected full-length Prx-IV cDNA into AMC-HN3 cells, which weakly express endogenous Prx-IV, and knocked down the expression of Prx-IV with siRNA methods using AMC-HN7 cells, which express high levels of endogenous Prx-IV. Radiosensitivity profiles in these cells were evaluated using clonogenic assay, FACS analysis, cell viability, and TUNEL assay. RESULTS Three Prx-IV expressing clones were isolated. Prx-IV regulated intracellular reactive oxygen species (ROS) levels and made cells more resistant to IR-induced apoptosis. Furthermore, the knockdown of Prx-IV with siRNA made cells more sensitive to IR-induced apoptosis. CONCLUSION The results of these studies suggest that Prx-IV may play an important role in protecting cells from IR-induced apoptosis in head-and-neck squamous cell carcinoma.

Benign Schwannoma of the Liver: A Case Report

A primary benign schwannoma of the liver is extremely rare. Only nine cases have been reported in the medical literature worldwide and no case has been reported in Korea previously. A 36-yr-old woman was admitted to our hospital with vague epigastric pain. The ultrasound and computed tomography scan revealed a multi-septated cystic mass in the right lobe of the liver. The mass was resected; it was found to be a 5 × 4 × 2 cm mass filled with reddish yellow fluid. The histological examination confirmed the diagnosis of a benign schwannoma, proven by positive immunoreaction with the neurogenic marker S-100 protein and a negative response to CD34, CD117 and smooth muscle actin. This is the first report of a benign schwannoma of the liver parenchyma in a Korean patient.

CD44 Variant 9 Serves as a Poor Prognostic Marker in Early Gastric Cancer, But Not in Advanced Gastric Cancer

Purpose The present study is to investigate the significance of CD44 variant 9 (CD44v9) expression as a biomarker in primary gastric cancer. Materials and Methods With various gastric tissues, we performed immunohistochemical staining for CD44v9. Results The positive expression rates for CD44v9 in tumor, including adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were higher than those in non-tumor tissues (p=0.003). In addition, the higher expression for CD44v9 was observed as the tissue becomes malignant. In the analysis of 333 gastric cancer tissues, we found that positive expression rates for CD44v9 were higher in the intestinal type or well differentiated gastric cancer than in the diffuse type or poorly differentiated gastric cancer. Interestingly, the positive expression indicated poor prognosis in EGC (5-year survival rate [5-YSR] in stage I, 81.7% vs. 95.2%; p=0.013), but not in AGC (5-YSR in stage II, 66.9% vs. 62.2%; p=0.821; 5-YSR in stage III, 34.5% vs. 32.0%; p=0.929). Moreover, strong positive expression (3+) showed a trend suggesting worse prognosis only in EGC, and it appeared to be associated with lymph node metastasis. Conclusion This study suggests that CD44v9 may be a good biomarker for prognosis prediction and for chemoprevention or biomarker-driven therapies only for EGC.