The E-cadherin, alpha-catenin, and beta-catenin expressions were immunohistochemically investigated in paraffin-embedded materials of 80 cases of colorectal adenocarcinomas. The staining similar to normal colorectal mucosa with preserved strong membranous staining pattern was considered normal or preserved expression. The X2 test was used to analyse the statistical correlation of cadherin/catenin expression with clinicopathologic parameters and the Breslow test for the correlation with survival length. Normal colorectal mucosa showed strong membranous expression of cadherin/catenin complex. The reduced E-cadherin, alpha-catenin, and beta-catenin expression were found in 53/80 (66.3%), 46/80 (57.5%), and 44/80 (55.5%) cases of colorectal cancers examined, respectively. There were significant correlations between E- cadherin and alpha -catenin (p=0.035), and between alpha-catenin and beta-catenin (p=0.013). The reduced E-cadherin expression was associated with histologic dedifferentiation, tumor depth, lymph node metastasis, clinical stage (p<0.05), poor clinical outcome in stage II (p=0.016) and the reduced alpha-catenin expression with lymph node metastasis and clinical stage (p<0.05). Reduced expression of two or more proteins was correlated with lymph node matastasis, histologic dedifferentiation, clinical stage, and survival (p<0.05). The present study demonstrates a significant down-regulation of E-cadherin and alpha-catenin expression in colorectal cancer is associated with tumor invasiveness, histologic dedifferentiation, lymph node metastasis, and clinical stage. These results suggest that E-cadherin and alpha-catenin may be useful markers of invasiveness, lymph node metastatic potential, and clinical stage and of value as prognostic markers in the earlier stage. Further studies are needed to confirm the prognostic value of these cadherin/catenin complex.
Adenocarcinoma* ; alpha Catenin* ; beta Catenin* ; Cadherins* ; Colorectal Neoplasms ; Down-Regulation ; Lymph Nodes ; Mucous Membrane ; Neoplasm Metastasis

An experimental studies were carried out to observe the protective effects of malotilate, a new antihepatotoxic agent, on the chronic hepatic injury induced by CCl4 with or without ethanol. The rats used weighed about 200g were divided into 2 groups, 4 weeks & 8 weeks. Each group was given by orally with malotilate, 100 mg/kg, once a day, and was injected by subcutaneously with CCl4 1.5 mg/kg in a mixture with olive oil twice a week. Aqueous ethanol (20%) was administered in drinking water daily. The serochemical and histopathological studies were carried out in each experimental group. The results were as follows: 1. The chronic liver injuries induced by CCl4 with or without ethanol were significantly ameliorated by normalize serum values GOT, GPT. Alkaline phosphatase, Cholesterol, HDL-Cholesterol, and gamma glutamyl transpeptidase. 2. In Group of 4 weeks, malotilate manifested protective effects by significant inhibition of fatty changes, spotty necrosis and fibrosis in CCl4-intoxicated liver with or without additional ethanol. 3. In group of 8 weeks, malotilate significantly imoproved fatty changes, fibrogenic activity in the group administered with CCl4, followed by ethanol.
Rats ; Animals

From July 1989 to February 1993, twelve patients were analysed for infected bone loss which treated with radically debriding all infected dead bone and closed suction-irrigation system with antibiotics and internal lengthening by using the external fixator. The results are summarized as follows. 1, The average time for application of external fixation was 30.7 weeks in tibia, 27 weeks in femur and average time for bone union was 31.5 weeks in femur, 34.2 weeks in tibia. 2. Soft tissue defects were treated with split thickness skin graft in 6 cases, secondary closure in 4 cases, gastrocnemius rotational flap in 2 cases. 3. The length of bone defects after infected bone excision ranged from 2cm to 9.3cm, averaging 4.5cm. The bone defect was treated by internal lengthening after corticotomy with the Ilizarov apparatus in 4 cases, the Orthofix external fixator in 8 cases. 4. Four cases in this series were complicated; one pin tract infection, one angulation deformity, one checkrein deformity, one flexion contracture of knee joint. 5. Infection was managed with radical debriding infected dead bone and closed suction-irrigation system with antibiotics in all cases. 6. We recommend that the infected bone loss can be effectively managed with radically debriding dead bone and closed suction-irrigation system with antibiotics and lengthening with Ilizarov apparatus or Orthofix external fixator.
Anti-Bacterial Agents ; Congenital Abnormalities ; Contracture ; External Fixators ; Femur ; Humans ; Knee Joint ; Skin ; Tibia ; Transplants

N,N-Diethylnitrosamine (DEN) has been proved to have carcinogenic potential in the initiation or promotion stage and the transformed cells proliferate to form preneoplastic nodules which are positive for placental form of glutathione S-transferase (GST-P). E-Cadherin, a member of the cadherin family, is expressed in epithelial cells. To evaluate the role of adhesion molecules (E-Cadherin, alpha-catenin, and beta-catenin), which have not been well understood in carcinogenesis, we investigated the changes of E-cadherin, alpha-Catenin and beta-Catenins by immunohistochemistry and immunoblotting in DEN-induced hepatocarcinogenesis of rat liver. In addition, the sequential analysis of histopathology and the expression of GST-P were also examined. Immunoreactive areas for GST-P were gradually increased from early period of carcinogenesis and strong GST-P positive foci were noted in various lesions, especially in the clear cell and eosinophilic cell nodules. Immunohistochemically, the E-Cadherin expression was increased in DEN-treated preneoplastic nodules in 4 and 10 weeks and hepatocellular carcinomas displayed relatively reduced expression compared with the hyperplastic nodules. But alpha- and beta-catenin expression was increased in hyperplastic nodules and hepatocellular carcinomas. Immunoblotting studies revealed that the level of alpha-catenin (cytosol and membranous fraction) was overexpressed in hyperplastic nodules as well as hepatocellular carcinomas, which showed markedly increased expression. The membranous fraction of beta-catenin was markedly increased in 10 weeks of DEN treatment and slightly reduced in hepatocellular carcinomas. These findings suggest that during DEN-induced hepatocarcinogenesis, the clear cell and eosinophilic cell nodules expressing GST-P in their cytoplasm are early transformed cell nodules. The altered expression of E-Cadherin and catenins is closely related with tumor propagation. Loss or reduced expression of E-cadherin may play a role in the progression of late hyperplastic nodule to hepatocellular carcinoma in DEN-induced rat hepato carcinogenesis.
alpha Catenin ; Animals ; beta Catenin ; Cadherins* ; Carcinogenesis ; Carcinoma, Hepatocellular ; Catenins* ; Cytoplasm ; Eosinophils ; Epithelial Cells ; Glutathione Transferase* ; Glutathione* ; Humans ; Immunoblotting ; Immunohistochemistry ; Liver* ; Rats*

PURPOSE: MDM-2 is an oncoprotein that inhibits p53 tumor-suppressor protein. These abnor malities have a role in tumorigenesis through inactivation of p53 function. To determine the clini copathological and prognostic value of MDM2 abnormalities in gastric adendegrees Carcinoma, MDM-2& p53 protein expression were analysed in surgically resected materials of gastric adendegrees Carcinoma. MATERIALS AND METHODS: Fifty cases which had got follow-up after surgical resection were immunohistdegrees Chemically studied with p53 and MDM-2 antibodies. We defined variable clinico pathologic factors for expression of p53 and MDM-2 protein and analysed their relationships. RESULTS: Immunohistdegrees Chemical stain revealed expression of MDM-2 protein as a 52.0% (26/50) and p53 protein 20.0% (10/50), respectively. But their expressions were not assdegrees Ciated with clinicopathological factors such as T-factor, N-factor, stage, histology and differentiation. Overall, p53-negative patients seemed to have a better prognosis regardless of MDM-2 protein status (P= 0.057). MDM-2 protein status was considered to have no play as a prognostic factor. CONCLUSION: In the gastric adendegrees Carcinoma, p53 protein expression seemed to have a inverse relationship with clinical outcomes but MDM-2 protein expression, which was observed more frequently than those of p53, seemed not to be prognostic indicator.
Antibodies ; Carcinogenesis ; Follow-Up Studies ; Humans ; Prognosis ; Proto-Oncogene Proteins c-mdm2 ; Stomach Neoplasms

Proximal cerebrospinal fluid shuntmalfunction due to ventricular catheter occlusion remains the most common sourceof the shunt problem. The position of the hole-bearing segment of the catheter affects the long term patency of the ventricular catheter of a cerebrospinalfluid shunt.Placementof thissegmentnear thechoroidplexus or injured ependyma increases the probability of obstruction. Accurate locationof ventriculoperitoneal(V-P)shunt tip inrelation to foramen Monro canbe well establishedby plain radiographyregardless of agesor sizes and shapes of head dueto the fact that foramen Monro tothe spatial matrix of the skull is constant. Of 147patients who underwentV-P shunt operations, 49(33.3%)patients had more thanone operations. Radiologicgradingof theventricularcatheterposition is compared betweensingle operatedgroup andreoperated group.Single operated group showed excellentin 33.6%, good41.8%, poor 24.4%of accuracy rateof catheter tip position. Incases ofreoperation, placement ofcatheter tipresulted in excellent 12.5%, good21.8%, and poor 65.6%.These results indicatethat accurate location of ventricular catheter tip affects favorably to the patency of V-P shunt.
Catheters ; Cerebrospinal Fluid ; Ependyma ; Head ; Skull ; Ventriculoperitoneal Shunt*

BACKGROUND: Aberrations of cell cycle-related genes have been reported to contribute to the formation and development of various human tumors. To investigate the gastric carcinogenesis, the expression of cell cycle-related genes (p53, p21wafl/cipl, cyclin D1 and Rb protein) compared to the morphological changes of gastric epithelial lesions were studied. METHODS: The expression of p53, p21wafl/cipl, cyclin D1 and Rb protein was immunohistochemically studied in a series of surgical specimens including the 36 normal/regenerating lesions and the 127 gastric epithelial proliferative lesions (GEPLs). The gastric epithelial proliferative lesions consisted of 25 regenerating epithelia with atypias (REAs), 27 low grade gastric dysplasias (LGDs), 17 high grade dysplasias (HGDs), 24 early gastrc carcinomas (EGCs), and 34 advanced gastric carcinomas (AGCs). RESULTS:The frequency of p53 protein overexpression was significantly associated with histologic grades of GEPLs (p=0.031); occurring in 4% of REAs, in 14.8% of LGDs, in 23.5% of HGDs, in 41.7% of EGCs and 58.9% of AGCs. The p21 wafl/cipl immunohistochemical reaction showed superficial eccentric positivity, representing an inverse correlation with histologic grades of GEPLs (p=0.04); occurring in 83.4% of normal/regenerating lesions, in 80% of REAs, in 74.1% of LGDs, in 29.4% of HGDs, 20.8% of EGCs and 8.8% of AGCs. Although Cyclin D1 and Rb proteins were expressed highly in the GEPLs, the frequency of both proteins were insignificantly associated with histologic grades of GEPLs (p=0.092). However, cases with both the Rb and cyclin D1 positivity were increased with statistical significance along histologic grades of GEPLs (p=0.044). CONCLUSIONS: The altered expression of p53, p21, Rb, and cyclin D1 was considered to be related to dysplastic progression and advancement of malignancy in GEPLs. Therefore, immunohistochemical studies of cell cycle related proteins and a combined analysis may be useful for estimating and following up cases of GEPLs.
Carcinogenesis ; Cell Cycle ; Cyclin D1* ; Cyclins* ; Humans ; Retinoblastoma Protein

In order to understand the effect of retinoic acid (RA) on the craniofacial pattern formation during embryogenesis, we injected RA intraperitoneally into the pregnant female rat on day 11 post coitum (p.c.) and then embryos of day 13 to day 17 p.c. were isolated consequently. The overall morphology and the differential gene expression patterns were analyzed by the microscopic and (DD) RT-PCR methods, respectively. For the morphological study, the retardation of craniofacial region, the shortage of crown rump length and limbs were analyzed in the RA-treated embryos. In the RA-treated embryos of day 17, it was observed that the palatogenesis was completely finished just like in the normal embryos. However, the cleft plate was observed in 36 out of 52 total samples with the distance of cleft palate being 0.80+/-0.36 mm in average. The temporal expression pattern of Hox genes through RT-PCR revealed that the expression of Hoxa7 reached its peak on day 13 then slowly declined in the normal embryos. Whereas in the RA-treated embryos, the expression peak was observed on day 15, then declined subsequently. With the Hoxc8 gene, its expression was low in all stages until the day 16 of normal embryogenesis. On the other hand, Hoxc8 gene expression was detected slightly early on day 15 in the RA-treated embryos. In the study of Bcl-2 family genes, uniformly strong expression of anti-apoptotic and pro-apoptotic genes was observed from day 13 to day 17 of normal embryos, whereas anti-apoptotic gene expressions were decreased after day 16 in the RAtreated embryos. Additionally, a dramatic decline of pro-apoptotic gene expression was observed from day 13 to day 15 of the RA-treated embryos. Therefore, we believe that RA is a potential factor that is actively involved in the cleft palate formation. Moreover, it is profoundly linked with the regulation of Hox and Bcl-2 family gene expression pattern that leads to the embryonic malformation.
Animals ; Cleft Palate ; Crown-Rump Length ; Embryonic Development* ; Embryonic Structures ; Extremities ; Female ; Gene Expression ; Genes, Homeobox ; Hand ; Humans ; Palate* ; Pregnancy ; Rats* ; Tretinoin*

Cytochrome P450 2E1 (CYP2E1) is a member of the cytochrome P450 superfamily, and it is a key enzyme responsible for the metabolic activation of many smallmolecular-weight compounds such as alcohol, which is classified as a human carcinogen. In this study, we identified 19 single nucleotide polymorphisms (SNPs) in CYP2E1 in Korean population. In these SNPs, we examined possible genetic association of CYP2E1 polymorphisms with HBV clearance and the risk of hepatocellular carcinoma (HCC). Five common polymorphic sites were selected, CYP2E1 polymorphisms at rs381-3867, rs3813870, rs2070673, rs2515641 and rs2480257 , considering their allele frequencies, haplotype-tagging status and LDs for genotyping in larger-scale subjects (n=1,092). Statistical analysis demonstrated that CYP2E1 polymorphisms and haplotypes show no significant association with HBV clearance, HCC occurrence and onset age of HCC (p>0.05). Previous studies, however, have shown contradictory findings on associations of CYP2E1 polymorphisms with CYP2E1 activities and HCC risk. Comparing the contrasting results of previous researches suggest that CYP2E1 polymorphism is associated with CYP2E1 activity induced by ethanol, but is not directly associated with HCC risk. CYP2E1 variation/haploype information identified in this study will provide valuable information for future studies on CYP2E1.
Age of Onset ; Biotransformation ; Carcinoma, Hepatocellular ; Cytochrome P-450 CYP2E1 ; Cytochrome P-450 Enzyme System ; Ethanol ; Gene Frequency ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide

Interleukin 10 (IL10) is a powerful TH2-cell cytokine that inhibits lymphocyte replication and secretion of inflammatory cytokines. The genetic associations of polymorphisms in IL10 with clinical manifestations of tuberculosis (TB) were examined in a large number of patients with clinical TB infection (n=459) and normal controls (n=871). One common promoter SNP (IL10 -592 A>C) was found to be significantly associated with decreased risk of TB manifestation. The frequency of the "C"-bearing genotype was higher in normal controls than in patients with clinical TB infection (P=0.005, OR=0.69). A summary of the genetic effect of IL10 -1082 A>G, the other nearby promoter SNP, in other ethnic groups is also presented.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Genetic Predisposition to Disease ; Genotype ; Humans ; Interleukin-10/*genetics ; Korea ; Middle Aged ; Polymorphism, Single Nucleotide ; Research Support, Non-U.S. Gov't ; Risk ; Tuberculosis, Pulmonary/*genetics