BACKGROUND: The purposes of this study were (1) to investigate the abilities of word definition in patients with Alzheimer's disease (AD) according to the severity, and (2) to examine the error patterns in patients with Alzheimer's disease. METHODS: Eight individuals with MCI (CDR=0.5) and 16 patients with AD (eight for probable AD mild group of CDR=1 and eight for probable AD moderate group of CDR=2) participated in the study. Eight normal age-, gender-, and education-matched elderly adults served as a control group for the MCI and AD groups. As stimuli for the word definition, eleven semantic categories were used, and two concrete words were selected from each category, resulting in a total of 22 items. Prior to the task, four definition categories were provided: 1) functional, 2) relational, 3) perceptual, and 4) categorical. Statistical analyses were performed using Kruskal-Wallis test, and Bonferroni analyses were used as a post-hoc comparison for any significant results. RESULTS: There were significant differences in word definition scores among four groups. The probable AD moderate group showed the lower definition score than the probable AD mild group. And the probable AD moderate group showed the lower definition score than MCI group. Each group defined words in different ways. While the control group employed four definition different categories equally, the probable AD moderate group used a functional definition category mainly. However, relational and categorical definition categories were rarely observed in the probable AD moderate group. The analysis of error pattern showed that inadequate definition was frequently observed in all groups. CONCLUSIONS: The results from this study suggest that word definition task could be a sensitive indicator of the impairment of semantic knowledge in patients with AD.
Adult ; Aged ; Alzheimer Disease* ; Humans ; Mild Cognitive Impairment ; Semantics

Here we have investigated how lactosylceramide (LacCer) modulates gene expression of adhesion molecules in TNF-alpha and IFNgamma (CM)-stimulated astrocytes. We have observed that stimulation of astrocytes with CM increased the gene expression of ICAM-1 and VCAM-1. D-Threo-1-phenyl- 2-decanoylamino-3-morpholino-1-propanol (PDMP) and N-butyldeoxynojirimycin (NBDNJ), inhibitors of glucosylceramide synthase (GLS) and LacCer synthase (galactosyltransferase, GalT-2), inhibited the gene expression of ICAM-1 and VCAM-1 and activation of their gene promoter induced by CM, which were reversed by exogenously supplied LacCer. Silencing of GalT-2 gene using its antisense oligonucleotides also attenuated CM-induced ICAM-1 and VCAM-1 expression, which were reversed by LacCer. PDMP treatment and silencing of GalT-2 gene significantly reduced CM-induced luciferase activities in NF-KB, AP-1, GAS, and STAT-3 luciferase vectors-transfected cells. In addition, LacCer reversed the inhibition of NF-KB and STAT-1 luciferase activities by PDMP. Taken together, our results suggest that LacCer may play a crucial role in the expression of ICAM-1 and VCAM-1 via modulating transcription factors, such as NF-KB, AP-1, STAT-1, and STAT-3 in CM-stimulated astrocytes.
1-Deoxynojirimycin ; Antigens, CD ; Astrocytes ; Galactosyltransferases ; Gene Expression ; Glucosyltransferases ; Intercellular Adhesion Molecule-1 ; Lactosylceramides ; Luciferases ; Morpholines ; NF-kappa B ; Oligonucleotides, Antisense ; Transcription Factor AP-1 ; Transcription Factors ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1

PURPOSE: To explore the role of cell cycle and apoptosis regulators during hepatocarcinogenesis, the expression of cell cycle-related proteins (cyclin D1 and p27kip1) and apoptosis-related proteins (p53, survivin, caspase 3). METHODS: Sprague-Dawley rats were given 120 ppm diethylnitrosamine (DEN) as a carcinogen and sequentially sacrificed. The expression of cell cycle and apoptotic related proteins were examined by light microscopy and immunohistochemistry. RESULTS: During the DEN-induced hepatocarcinogenesis, sequential histologic changes from preneoplastic lesions (altered hepatic cellular foci, hyperplastic nodules, and hepatocellular adenomas) and ultimately overt hepatocellular carcinomas and metastatic lesions were noted. The cyclin D1 were progressively increased from preneoplastic lesions to hepatocellular carcinomas. However, the p27kip1 and the survivine proteins did not show any other difference with the increasing degree of carcinogenesis. The p53 and caspase 3 proteins were more significantly increased in hepatocellular carcinomas than preneoplastic lesions. The cyclin D1 protein expression did not show any correlation with the expression of p27Kip1 protein, but the p53 expression was related to the expression of survivin and caspase 3. CONCLUSION: From the above results, over-expression of cyclin D1 plays a role in the early and late stages of hepatocarcinogenesis. In addition p53 and caspase 3 might be useful markers for evaluating the risk of malignant transformation.
Animals ; Apoptosis ; Carcinoma, Hepatocellular ; Caspase 3 ; Cell Cycle ; Cyclin D1 ; Cyclin-Dependent Kinase Inhibitor p27 ; Diethylnitrosamine ; Light ; Microscopy ; Proteins ; Rats ; Rats, Sprague-Dawley

Tracheobronchial rupture associated with esophageal rupture due to blunt chest trauma is very rare. However, increasing number of thoracic inj uries have been reported during the recent years; This trend could be attributed to an increase in high-speed traffic accidents, and also to the better care for patients suffering from trauma. We report two cases of long tracheal disruption associated with esophageal rupture as a result of a nonpenetrating thoracic trauma. One patient who was transferred from another hospital after failed tracheoesophageal reconstruction received secondary reconstructive surgery but expired, and the other patient survived without any serious complications with reconstructive surgery.
Accidents, Traffic ; Humans ; Reconstructive Surgical Procedures ; Rupture* ; Thorax

PURPOSE: In general, tumor growth is dependent on angiogenesis. COX, known as modulator of angiogenesis, consists of two at least isozymes constitutive COX-1 and stress- induced COX-2. The latter is known in case of gastric cancer to be overexpressed in neoplastic tissue but not in adjacent normal tissue. To clarify the effect of COX-2 inhibitors on tumor growth and angiogenesis, we investigated the effects of Meloxicam (a selective COX-2 inhibitor) on gastric cancer xenograft in nude mise that overexpress COX-2. METHODS: MKN45 gastric cancer cell lines that overexpress COX-2 were inoculated subcutaneously into athymic mice. The mean tumor volume, apoptotic index, proliferative index, microvessel count and angiogenic factors (VEGF and bFGF) were measured in the control group (12 cases) and the meloxicam treated group (23 cases). RESULTS: There was no significant difference of COX-2 expression between the control and meloxicam treated groups in mRNA level as measured by RT-PCR, nor in protein level by Western blotting. However, in the meloxicam treated group, apoptosis was increased to a statistically significant degree (P<0.01) while the proliferation index as measured by Ki-67, the mean tumor volume and angiogenesis were all significantly decreased, as compared with the control group (P<0.01). CONCLUSION: The possible suppression of angiogenesis and tumor growth in gastric cancer xenograft by meloxicam suggests potentially. Novel and promising applications of COX-2 inhibitors in the adjuvant treatment of gastric cancer. However, further clinical study will be needed to determine its efficacy in such treatment modalities.
Angiogenesis Inducing Agents ; Animals ; Apoptosis ; Blotting, Western ; Cell Line* ; Cyclooxygenase 2 Inhibitors ; Heterografts* ; Humans* ; Isoenzymes ; Mice ; Mice, Nude* ; Microvessels ; RNA, Messenger ; Stomach Neoplasms ; Tumor Burden

PURPOSE: Tumor invasion and metastasis are known to be extremely important factors in the prognosis of cancer patients. Although recent studies have demonstrated that cyclooxygenase-2 (COX-2) is overexpressed in various cancers including gastric cancer, the mechanisms underlying the contribution of COX-2 to tumorigenesis and tumor promotion remain unclear. METHODS: In order to determine the role of COX-2 in tumor growth and metastasis, we investigated COX-2 expression, apoptosis and the expression of E-cadherin, CD44v6, MMP-2 and TIMP-2 in gastric cancer xenografts treated with meloxicam (a selective COX-2 inhibitor). RESULTS: Cells from the MKN45 gastric cancer cell line that overexpress COX-2 were inoculated subcutaneously into athymic mice. Oral administration with meloxicam reduced the tumor volume (P<0.01), induced apoptosis of cancer cells (P<0.01), suppressed the proliferation rates (P<0.01), increased the expression of E-cadhrin (P<0.05) and reduced the expression of MMP-2 and TIMP-2. CONCLUSION: The above data showed that COX-2 inhibitors can inhibit tumor growth and suppress metastatic potential by expression of adhesion molecules and suppression of metalloproteinases, suggesting that this inhibitor can be used as an additive anti-cancer drug in cases of stomach cancer with radical resection, although further evaluation is required.
Administration, Oral ; Animals ; Apoptosis ; Cadherins ; Carcinogenesis ; Cell Line ; Cyclooxygenase 2 ; Cyclooxygenase 2 Inhibitors ; Heterografts* ; Humans ; Metalloproteases ; Mice ; Mice, Nude ; Neoplasm Metastasis* ; Prognosis ; Stomach Neoplasms* ; Tissue Inhibitor of Metalloproteinase-2 ; Tumor Burden

Visnagin (4-methoxy-7-methyl-5H-furo[3,2-g][1]-benzopyran-5-one), which is an active principle extracted from the fruits of Ammi visnaga, has been used as a treatment for low blood-pressure and blocked blood vessel contraction by inhibition of calcium influx into blood cells. However, the neuroprotective effect of visnagin was not clearly known until now. Thus, we investigated whether visnagin has a neuroprotective effect against kainic acid (KA)-induced neuronal cell death. In the cresyl violet staining, pre-treatment or post-treatment visnagin (100 mg/kg, p.o. or i.p.) showed a neuroprotective effect on KA (0.1 microgram) toxicity. KA-induced gliosis and proinflammatory marker (IL-1beta, TNF-alpha, IL-6, and COX-2) inductions were also suppressed by visnagin administration. These results suggest that visnagin has a neuroprotective effect in terms of suppressing KA-induced pathogenesis in the brain, and that these neuroprotective effects are associated with its anti-inflammatory effects.
Ammi ; Animals ; Benzoxazines ; Blood Cells ; Blood Vessels ; Brain ; Calcium ; Cell Death ; Contracts ; Cytokines ; Fruit ; Gliosis ; Glycosaminoglycans ; Hippocampus ; Interleukin-6 ; Kainic Acid ; Khellin ; Mice ; Neurons ; Neuroprotective Agents ; Tumor Necrosis Factor-alpha ; Viola

The present study demonstrates the effect of fibrates, agonists of PPARalpha on cytokines-induced proliferation in primary cultured astrocytes. Alone or combination treatment with cytokines, such as IL-1beta (10 ng/ml), IFNgamma (10 ng/ml), and TNF-alpha (10 ng/ml) cause a significant increase of cell proliferation in a time-dependent manner. Treatment of astrocytes with bezafibrate and fenofibrate (0, 5, and 10 micrometer) reduced the IFNgamma and IL-1beta-induced cell proliferation in a dose-dependent manner. To address the involvement of IL-6 on the IFNgamma and IL-1beta-induced cell proliferation, released IL-6 level was measured. IFNgamma and IL-1beta cause an increase of released IL-6 protein level in a time-dependent manner. Furthermore, pretreatment with IL-6 antibody (0, 0.1, 1, 2.5, and 5 ng/ml) dose-dependently inhibited the IFNgamma and IL-1beta-induced cell proliferation. However, bezafibrate and fenofibrate did not affect increased mRNA and protein levels of IL-6 in IFNgamma and IL-1beta-stimulated astrocytes. Taken together, these results clearly suggest that activation of PPARalpha attenuates the IFNgamma and IL-1beta-induced cell proliferation through IL-6 independent pathway.
Astrocytes ; Bezafibrate ; Cell Proliferation ; Cytokines ; Fenofibrate ; Fibric Acids ; Interleukin-6 ; PPAR alpha ; RNA, Messenger ; Tumor Necrosis Factor-alpha

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 microg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.
Animals ; Blood Glucose* ; Brain ; Corticosterone ; Glipizide ; Glyburide ; Immobilization* ; Insulin ; Mice ; Mice, Inbred ICR ; Plasma ; Tolazamide

BACKGROUND: Thoracoscopic bullectomy (VATS-B) is now the preferred treatment for spontaneous pneumothorax despite of higher recurrence rate than open thoracotomy. Several methods have been used to prevent this problem. The effectiveness of staple line reinforcement (SLR) in VATA-B using endostaplers was assessed by clinical and experimental study. MATERIAL AND METHOD: In experimental study, canine lungs were harvested immediately (group I, N=5) and 48 hours (group II, N=5) after stapling. The pressures at which initial air leaks occurred were measured. In clinical study from February 1997 to March 1999, 106 procedures in 104 patients undergoing VATS-B for spontaneous pneumothorax were classified into two groups according to the presence of SLR and were compared. RESULT: The average pressure of the initial air leakage was significantly higher in SLR than that of staples alone (18+/-1.6 vs 48+/-3 mm Hg in group I; 23.8+/-1.9 vs 54+/-4.6 mm Hg in group II, p<0.001). In the clinical data, there were significant differences seen in the duration of drainage, the total length of endostaplers used, and the duration of the postoperative hospital stay between patients with staple alone and patients with SLR (4.4+/-1.4 vs 3.1+/-1.1 days in duration of drainage, 92.3+/-28.1 vs 71.1+/-30.6 mm in total length of endostaplers used, 5.9+/-1.9 vs 4.6+/-1.7 days in postoperative hospital stays, p<0.001). CONCLUSION: SLR was effective for preventing prolonged air leakage and responsible for shorter hospital stays after VATS-B for the treatment of spontaneous pneumothorax.
Drainage ; Humans ; Length of Stay ; Lung ; Models, Theoretical ; Pneumothorax* ; Polytetrafluoroethylene* ; Recurrence ; Surgical Staplers ; Thoracoscopy ; Thoracotomy