To examine the protection of retinal cell death by glutamate antagonists in vivo, this study was carried out in pressure-induced ischemia model. Firstly, we observed that ischemia resulted in the similar retinaldamage to the injuries caused by NMAD and Kainate toxicity. Secondly, the retinal cell death caused by ischemia was prevented by MK801 and CNQX, glutamate antagonists for NMDA and Kainate excitotoxicity, respectively at 24hr after ischemia. MK801 was shown to prevent the cell death in ganglion cell layer and CNQX in inner unclear layer. In addition, the combination of CNQX and MK801 protected the retina neuronal cell from ischemic injury better than when they were applied separately. The partial protection of retinal cell death by glutamate antagonists in ischemia model indicates that glutamate eoxicity as well as other cell death mechanism such as apoptosis mediates ischemia induced retinal cell death. Thus, cell death by other mechanism must be also blocked in order to prevent retinal cell death, completely.
6-Cyano-7-nitroquinoxaline-2,3-dione* ; Apoptosis ; Cell Death ; Dizocilpine Maleate* ; Excitatory Amino Acid Antagonists ; Ganglion Cysts ; Glutamic Acid ; Ischemia* ; Kainic Acid* ; N-Methylaspartate* ; Neurons ; Retina ; Retinaldehyde*

This study was conducted to compare degeneration of retinal neurons in retina ischemia induced by sudden elevation of intraocular pressure(IOP)(Group A) with that by steady elevation of IOP(Group B). Adult male Sprague Dawley rats were used and IOP of 160-180mmHg was maintained for 90 min. Entraocular pressure of 160-180mmHg was achived in a second for Group A, while in one minutes for Group B. The neuronal damage in retina was ascertained by light microscopy and transmission electron microscopy at various time points after ischemic insult. In Group A, retinal neurons were destroyed severely in ganglion cell layer(GCL) and inner nuclear layer(INL) at 24hrs and the number of cells in ganglion cell layer(GCL) was decreased markedly. And some cells in GCL and INL were spread out in inner plexiform layer(IPL) by the 3rd day after ischemia. At each time point, both vecrosis and apoptosis were observed mainly by trasmission electron microscope. In group B, the retinal cell death was observed mainly in ganglion cell layer(GCL) at 24hrs and mainly in inner nuclear layer(INL) of 3 days after ischemia. The characteristics of the retinal injury after 3 days in Group B was similar to that after 24hrs in Group A. Therefore, cell death pattern was delayed in Group B compared with in Group A. With these results It was found that apoptosis as aell as necrosis of the retinal neurons were observed in retina ischemia induced by elevation of IOP cause faster neronal damage than slow elevation of IOP.
Adult ; Apoptosis ; Cell Death* ; Ganglion Cysts ; Humans ; Intraocular Pressure* ; Ischemia* ; Male ; Microscopy ; Microscopy, Electron, Transmission ; Necrosis ; Neurons* ; Rats, Sprague-Dawley ; Retina ; Retinal Neurons ; Retinaldehyde

In order to elucidate the mechanism of neuronal cell death induced by retina ischemia and reperfusion, we investigated expression of p53, Bcl-2, and ICE(interleukin converting enzyme) in retinal neuronal cell death. Adult male Spague-Dawley rats were used and their intraocular pressures were maintained between 160 and 180mmHg for 90 min to induce retina ischemia. Retinal cell death was observed by light microscopy from 4 hours and peaked at 24 hours after retinal ischemia. By the 3rd day after retinal ischemia, the number of cells in GCL was decreased markedly and some cells in GCL and INL were spread out in inner plexiform layer(IPL). Finally, the boundary between GCL and INL became obscure and a few alive cells were found in GCL and INL on 7 days after retinal ischemia. The thickness of the retina was also decreased in a time-dependent manner. IN the study of gene expression in retinal ischemil, p53 expression was increased prominently at 24 hours and 3 days and decreased at 7 days, while Bcl02 expression was increased slightly at 24 hours by RT-PCR and in situ hybridization. ICE expression was not changed in this model. The expression of p53 was also observed at 24 hours after retinal ischemia by immunohistochemistry. With these results it was found that cell death was increased from 4 hours to 3 days after retina ischemia and the thickness of retina decreased markedly during the same period. Delayed neuronal cell death in retina seemed to be correlated with the expression of p53 in the retina ischemia model.
Adult ; Animals ; Cell Death* ; Gene Expression ; Humans ; Ice ; Immunohistochemistry ; In Situ Hybridization ; Intraocular Pressure ; Ischemia* ; Male ; Microscopy ; Neurons* ; Rats ; Reperfusion* ; Retina* ; Retinal Neurons ; Retinaldehyde

PURPOSE: The mitotic index (MI) and Ki-67 labeling index have been used as cell proliferative markers in the various tumors. Topoisomerase II alpha (Topo II alpha) is also expressed in proliferating cells. The aim of this study was to evaluate the correlations between the MI, Ki-67, and Topo II alpha expression as proliferative markers of breast cancer. METHODS: The cell proliferative activity of 181 breast cancers was measured using MI, Ki-67 labeling index and Topo II alpha expression. The correlation between the measured markers was also analyzed. RESULTS: The MI, Ki-67, and Topo II alpha were significantly correlated with each other(p < 0.000). The MI and Ki-67 labeling index were associated with high histological grade, and absence of hormone receptor (p < 0.000). Topo II alpha expression was correlated with high histological grade (p < 0.000), absence of hormone receptor and HER-2/neu overexpression (p < 0.043). The MI, Ki-67, and Topo II alpha were not associated with any other clinical variables, such as age, tumor size, and lymph node status. CONCLUSION: The three proliferative indices were significantly associated with aggressive features of breast cancer, and significantly correlated with each other.
Breast Neoplasms* ; Breast* ; DNA Topoisomerases, Type II ; Lymph Nodes ; Mitotic Index

PURPOSE: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and are immunohistochemically defined as c-KIT (CD117) positive tumors. This study investigated the behaviors of GISTs of the gastrointestinal tract and determined the prognostic factors associated with GISTs. METHOD: The clinical records of 22 patients, who were diagnosed and underwent surgery for a GIST of the GI tract at Inje university Sanggye Paik hospital from 1998 to 2004, were retrospectively analyzed. The relationship between the disease-free survival rate of the GISTs and several factors including age, gender, mitotic count, tumor site, tumor size, tumor necrosis & hemorrhage, and Ki-67 index was examined. RESULTS: The study group comprised of 13 men and 9 women. The mean age was 57.1 years (31~77 years) at the time of diagnosis. The median follow-up period was 24 months (3~45 months). A complete resection of the tumor was performed in 19 patients. There were lymph node metastases in 1 case. Five out of the 19 patients who had undergone a complete tumor resection showed recurrence (27%). The sites of recurrence were the back (1), liver (1), and abdominal cavity (3). Univariate analysis revealed, the following to be prognostic factors for the disease-free survival of patients with GISTs: high power field mitotic counts of the tumor (<5/50 vs. > or =5/50; P=0.013), the tumor size (<5 cm vs. > or =5 cm; P=0.047) and the Ki-67 index (<5% vs. > or =5%; P=0.001). CONCLUSION: The prognostic factors for disease-free survival rate of GISTs were high power field mitotic counts of the tumor, the tumor size and the Ki-67 index. It is recommended that more careful and frequent postoperative follow-up examinations be performed for patients showing the poor prognostic factors.
Abdominal Cavity ; Diagnosis ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gastrointestinal Stromal Tumors* ; Gastrointestinal Tract ; Hemorrhage ; Humans ; Liver ; Lymph Nodes ; Male ; Necrosis ; Neoplasm Metastasis ; Prognosis ; Recurrence ; Retrospective Studies