No abstract available.
Animals, Laboratory

PURPOSE: It has been recognized that interaction of the Fas : Fas ligand plays an important role in radiation-induced apoptosis. The purpose of this study was to investigate the role of Fas mutation in radiation-induced apoptosis in vivo. MATERIALS AND METHODS: Mice with mutations in Fas, MRL/Mpj-Fas(lpr), and its normal control, MRL/Mpj, were used in this study. Eight-week old male mice were given whole body radiation. After irradiation, the mice were killed and their spleens were collected at different time intervals. Tissue samples were stained with hematoxylin-eosin and the numbers of apoptotic cells were scored. Regulating molecules of apoptosis including p53, Bcl-2, Bax, Bcl-XL, and Bcl-XS were also analyzed by Western blotting. RESULTS: At 25 Gy irradiation, the level of apoptosis reached the peak value at 8 hr after radiation and recovered to the normal value at 24 hr after radiation in MRL/Mpj mice. In contrast, the peak apoptosis level appeared at 4 hr after radiation in MRL/Mpj-Fas(lpr) mice. At 8 hr after radiation, the levels of apoptosis in MRL/Mpj mice and MRL/Mpj-Fas(lpr) mice were 52.3+/-7.8% and 8.0+/-8.6%, respectively (p<0.05). The expression of apoptosis regulating molecules, p53, Bcl-XL and Bcl-XS, increased in MRL/Mpj mice in response to radiation; p53 with a peak level of 3-fold at 8 h, Bcl-XL with a peak level of 3.3-fold at 12 h, and Bcl-XS with a peak level of 3-fold at 12 h after 25 Gy radiation. Bcl-2 and Bax did not show significant change in MRL/Mpj mice. However in MRL/Mpj-Fas(lpr) mice, the expression levels of p53, Bcl-2, Bax, Bcl-XL and Bcl-XS showed no significant change. CONCLUSION: The level of radiation-induced apoptosis was lower in Fas mutated mice, lpr, than in control mice. This seemed to be related to the lack of radiation-induced p53 activation in the lpr mice. This result suggests that Fas plays an important role in radiation-induced apoptosis in vivo.
Animals ; Apoptosis* ; Blotting, Western ; Fas Ligand Protein ; Humans ; Male ; Mice ; Radiation Dosage ; Reference Values ; Spleen ; Whole-Body Irradiation

BACKGROUND: The goal of successful resuscitation is not only to stop the process of ischemia as soon as possible but also to overcome the secondary injury process after resuscitation, which involves a complex interplay of mechanisms. Brain damage accompanying cardiac arrest and resuscitation is frequent and devastating. Cells die by one of two mechanisms: necrosis or delayed neuronal death. Delayed neuronal death may require protein synthesis. Neurons in the CA1 subfield of the hippocampus are selectively vulnerable to death after injury by ischemia and reperfusion. Death of these neurons occurs after an interval of 1 or 2 days. We assessed the effects of a protein synthesis inhibitor, cycloheximide(CHX), on hippocampal neuronal death of rats by using the ventricular fibrillation cardiac arrest(VFCA) model. METHODS: The effect of CHX(3mg/kg, s.c.) on hippocampal neuronal death was studied in two groups of 18 rats each, one group being subjected to a 2-min VFCA and the other to a 3-min VFCA. Each group was divided into three subgroups: control(group I,II) without subcutaneous injection of CHX, 'exp-12' of group I/II treated with CHX 12 hours after return of spontaneous circulation (ROSC), and 'exp-24' of group I/II treated with CHX 24 hours after ROSC. The coronal sections of the hippocampus levels were stained with hematoxylin-eosin after 72 hours of survival. The histologic damage score(HDS) was used to assign a score to the total number of damaged neurons counted in each of the hippocampal CA1 subfields. RESULTS: 1. There were not significan differences in heart rates, blood pressures, blood sugar, and blood gas in group I & II during the pre-arrest steady state or at 5 min and 30 min after ROSC. 2. In group I & II, the HDS, were significantly reduced in rats(I exp-12, 1.1+/-0.6; I exp-24, 1.3+/-0.5; II exp-12, 1.4+/-0.7; and II exp-24, 1.8+/-0.8) treated with CHX 12 hours or 24 hours after ROSC than control rats(I, 2.5+/-0.9, II, 2.9+/-0.8)(p<0.05). CONCLUSION: These results suggest that delayed hippocampal neuronal death from ischemic insult after ventricular fibrillation cardiac arrest followed by resuscitation can be prevented by a protein synthesis inhibitor, CHX. Further experimental studies of the action mechanism of protein synthesis inhibitors to delayed neuronal death and clinical applications are required.
Animals ; Blood Glucose ; Brain ; Heart Arrest* ; Heart Rate ; Hippocampus ; Injections, Subcutaneous ; Ischemia ; Necrosis ; Neurons* ; Protein Synthesis Inhibitors ; Rats* ; Reperfusion ; Resuscitation ; Ventricular Fibrillation*

PURPOSE: Although adjuvant chemotherapy reduces the risk of disease recurrence in stage III colon cancer patients, published guidelines do not specify when it should be initiated. This study aimed to assess the effect of adjuvant chemotherapy initiation time on disease recurrence and survival in stage III colon cancer patients undergoing curative surgical resection. METHODS: The medical records of stage III colon cancer patients undergoing curative resection between February 2004 and December 2009 were reviewed. RESULTS: Of the 133 enrolled patients, 27 (20.3%) began adjuvant chemotherapy within 3 weeks of surgery, whereas 106 (79.7%) did after 3 weeks following surgery. Patients receiving chemotherapy within 3 weeks of surgery were less likely to experience recurrences than those beginning treatment later (11.1% vs. 33%, P = 0.018). The mean disease-free survival of patients receiving adjuvant therapy earlier was 54.6 months, whereas that of patients with later treatment was 43.5 months (P = 0.014). However, no significant differences in overall survival were observed between the 2 groups. CONCLUSION: Adjuvant chemotherapy should be initiated as soon as a patient's clinical condition allows. Patients with stage III colon cancer may benefit from adjuvant chemotherapy initiated within 3 weeks of surgery.
Chemotherapy, Adjuvant* ; Colon* ; Colonic Neoplasms* ; Disease-Free Survival ; Drug Therapy ; Humans ; Medical Records ; Prognosis ; Recurrence

OBJECTIVE: In acute spinal cord injury, biomechanical and pathological changes in the cord may worsen after injury. To explain these phenomena, the concept of the secondary injury has evolved and numerous pathophysiological mechanisms have postulated. These, however, have mainly focused only on the cell necrosis. The aim of present study is to verify whether apoptosis plays a role in the animal model of secondary injury of spinal cord. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were laminectomized and spinal cord injury was induced using NYU spinal impactor at T9 segment. The animals were sacrificed periodically and tissue specimen was obtained at the injury segment, adjacent segments, and remote segments to observe the secondary injury ultimately for the observation of the spatial and temporal distribution and the related cells for the appearance of apoptosis, if present. RESULTS: In the spatial distribution of apoptosis, the apoptotic cells were located at gray matter of spinal cord and the number of apoptotic cells were significantly higher in adjacent segments than in the injured segment. In the temporal distribution of apoptosis, the number of apoptotic cells were maximal at 4 hours after injury and decreased subsequently. No apoptotic cells were found at remote segments which implies that there were no influence of apoptosis on transneuronal degeneration. CONCLUSION: These results suggest that the lesioned area of spinal cord expanded over time in acute spinal cord injury and apoptosis contributed to the spinal cord neuronal and glial cell loss. In conclusion, apoptosis is thought to have an important role in secondary injury of acute spinal cord injury.
Adult ; Animals ; Apoptosis ; Cell Death* ; Humans ; Male ; Models, Animal ; Necrosis ; Neuroglia ; Neurons ; Rats, Sprague-Dawley ; Spinal Cord Injuries* ; Spinal Cord*

BACKGROUND: Vascular lesions are the major cause of morbidity and mortality in hypertensive patients. However, the pathologic characteristics of gradually evolving, chronic hypertension have not been adequately studied and the mechanism by which hypertension accelerates atherosclerosis is still uncertain. This study was undertaken to invertigate the ultrastructural changes of the aorta and the effect of high cholesterol diet in spontaneously hypertensive rats(SHR). METHODS: Spontaneously hypertensive rats (n=80, male, 5 weeks old) and Wistar rats (n=40, male, 5 week old) were used. Forty SHR were fed with 2% cholestrol diete, while the remainder with control diet. Systolic blood pressure was measured weekly until 16 weeks after birth, and then biweekly until 40 weeks after birth. Transmission and scanning electron microscopy were used to evaluate ultrastrucural changes of the aorta. RESULTS: 1) The blood pressure of SHR rose stedily and progressively from the 5 weeks after birth and reached nearly 190mmHG at the 16 weeks after birth. 2) In SHR, the subendothelial component contained finely granular substances, abundant fibrillar collagen and elastin. Infiltration of the mononuclear blood leukocytes into the intima was frequently seen. 3) Endothelium from cholestrol-fed SHR did exhibit numerous pinocytotic vesicles and contained many cytoplasmic filaments. There were a number of large mononuclear lipid-filled cells in the intimal lesions. Blistering of the endothelial plasma membrane was also observed in high cholesterol diet-fed SHR. Later on, adhesion of platelets, febrin, and white blood cells as well as damage of intima shown as multiple small holes were more marked. 4) There was no significant difference in systoloic blood pressure between high cholesterol diet-fed and control diet-fed SHR. CONCLUSION: In the aorta of SHR, the most prominent change was an expansion of the subendothelial space and infiltration of the mononuclear leukocytes into the intima. The present study showed that the SHR was indeed a reliable model for the essential hypertension. In some SHR, high cholesterol diet could induce more pronounced vascular lesions, which were enhanced by hypertension.
Aorta* ; Atherosclerosis ; Blister ; Blood Pressure ; Cell Membrane ; Cholesterol* ; Cytoskeleton ; Diet* ; Elastin ; Endothelium ; Fibrillar Collagens ; Humans ; Hypertension ; Leukocytes ; Leukocytes, Mononuclear ; Male ; Microscopy, Electron ; Microscopy, Electron, Scanning ; Mortality ; Parturition ; Rats, Inbred SHR* ; Rats, Wistar

The X-ray synchrotron is quite different from conventional radiation sources. This technique may expand the capabilities of conventional radiology and be applied in novel manners for special cases. To evaluate the usefulness of X-ray synchrotron radiation systems for real time observations, mouse fetal skeleton development was monitored with a high resolution X-ray synchrotron. A non-monochromatized X-ray synchrotron (white beam, 5C1 beamline) was employed to observe the skeleton of mice under anesthesia at embryonic day (E)12, E14, E15, and E18. At the same time, conventional radiography and mammography were used to compare with X-ray synchrotron. After synchrotron radiation, each mouse was sacrificed and stained with Alizarin red S and Alcian blue to observe bony structures. Synchrotron radiation enabled us to view the mouse fetal skeleton beginning at gestation. Synchrotron radiation systems facilitate real time observations of the fetal skeleton with greater accuracy and magnification compared to mammography and conventional radiography. Our results show that X-ray synchrotron systems can be used to observe the fine structures of internal organs at high magnification.
Animals ; Bone and Bones/*anatomy & histology/radiography ; Female ; Fetus/*anatomy & histology/radiography ; Histocytochemistry ; Mice ; Mice, Inbred ICR ; Pregnancy ; Synchrotrons ; X-Rays

No abstract available.
Caroli Disease*

PURPOSE: To evaluate the parameters of optic nerve head (ONH) and retinal nerve fiber layer (RNFL) in patients with large cup/disc ratio (CDR) and normal neuroretinal rim configuration who have normal perimetry (physiologic large cups, LC) and to compare these parameters with those of the normal and early glaucoma patients. METHODS: Using Heidelberg retinal tomography (HRT) and optical coherence tomography (OCT), 30 patients with LC, 29 normal subjects, and 31 early glaucoma patients were examined. One eye from each subject was randomly selected. RESULTS: Significant differences between LC and glaucomatous eyes (GE) were found in parameters indicating loss of nerve fibers, such as rim area, rim volume, and mean RNFL thickness. However, there was no difference between LC and normal eyes (NE) in RNFL thickness, rim area, and rim volume. LC was able to be defined as a normal central excavation with a large disc and large CDR with a normal rim area. CONCLUSIONS: HRT ONH parameters and RNFL thickness obtained with OCT may be useful for differentiating between glaucoma and LC eyes.
Retina/*pathology ; Optic Disk/*pathology ; Nerve Fibers/*pathology ; Middle Aged ; Humans ; Glaucoma/*pathology ; Adult ; Adolescent

Type 1 diabetes is a common metabolic disorder accompanied by increased blood glucose levels along with glucocorticoid and cognitive deficits. The disease is also thought to be associated with environmental changes in brain and constantly induces oxidative stress in patients. Therefore, glucocorticoid-mediated negative feedback mechanisms involving the glucocorticoid receptor (GR) binding site are very important to understand the development of this disease. Many researchers have used streptozotocin (STZ)-treated diabetic animals to study changes in GR expression in the brain. However, few scientists have evaluated the hyperglycemic period following STZ exposure. In the present study, we found GR expression in the hippocampus varied based on the period after STZ administration for up to 4 weeks. We performed immunohistochemistry and Western blotting to validate the sequential alterations of GR expression in the hippocampus of STZ-treated type 1 diabetic rats. GR protein expression increased significantly until week 3 but decreased at week 4 following STZ administration. GR expression after 70 mg/kg STZ administration was highest at 3 weeks post-treatment and decreased thereafter. Although STZ-induced increase in GR expression in diabetic animals has been described, our data indicate that researchers should consider the sequential GR expression changes during the hyperglycemic period following STZ exposure.
Animals ; Diabetes Mellitus, Experimental/chemically induced/*metabolism/*physiopathology ; Disease Models, Animal ; *Gene Expression Regulation ; Hippocampus/metabolism/*physiopathology ; Humans ; Male ; Rats ; Rats, Wistar ; Receptors, Glucocorticoid/*genetics/*metabolism ; Time Factors