The mutation of p53 tumor suppressor gene is the most common genetic variation of primary malignant tumors. The occurrence, progression and reaction for medical management of cancers can be different according to the characteristics of p53 gene, even if they are same kinds of malignant tumors. In this study, the property of p53 gene in 4 kinds of squamous cell carcinoma cell lines were investigated by using immunocytochemistry, PCR-SSCP, sequencing and Western blot methods. As a result, p53 mutation detected in 3 kinds of squamous cell carcinoma cell lines. Namely, it is found that T in codon 176 changed to A, and G in codon 281 changed to A in KUMA3 cell lines; CC in codon 241 changed to TT in KUMA4 cell lines; G in codon 266 changed to T in KUMA6 cell lines. In single nucleotide polymorphism of codon 72 of p53 gene, the genetic variations are Arg/Pro heterozygote in KUMA3 and KUMA4 cell lines; Arg/Arg homozygote in KUMA5 cell lines; Pro/Pro homozygote in KUMA6 cell lines. These results will provide useful data for p53 gene researches of various squamous cell carcinomas.
Blotting, Western ; Carcinoma, Squamous Cell* ; Cell Line* ; Codon ; Genes, p53* ; Genes, Tumor Suppressor ; Genetic Variation ; Heterozygote ; Homozygote ; Immunohistochemistry ; Polymorphism, Single Nucleotide

Heterotrimeric GTP-binding proteins (G protein) are known to participate in the transduction of signals from ligand activated receptors to effector molecules to elicit cellular responses. Sustained activation of cAMP-G protein signaling system by agonist results in desensitization of the pathway at receptor levels, however it is not clear whether such receptor responses induce other changes in post-receptor signaling path that are associated with maintenance of AMP levels, i.e. cAMP-forming adenylate cyclase (AC), cAMP-degrading cyclic nucleotide phosphodiesterase (PDE) and cAMP-dependent protein kinase (PKA). Experiments were performed to determine the expression of AC, PDE, and PKA isoforms in SH-SY5Y neuroblastoma cells, in which cAMP system was activated by expressing a constitutively activated mutant of stimulatory G protein (Q227L Gsalpha). Expression of ACI mRNA was increased, but levels of ACVIII and ACIX mRNA were decreased. All of the 4 expressed isoforms of PDE (PDE1C, PDE2, PDE 4A, and PDE4B) were increased in mRNA expression; the levels of PKA RIalpha, RIbeta, and RIIbeta were increased moderately, however, those of RIIalpha and Calpha were increased remarkably. The activities of AC, PDE and PKA were also increased in the SH-SY5Y cells expressing Q227L Gsalpha. The similar changes in expression and activity of AC, PDE and PKA were observed in the SH-SY5Y cells treated with dbcAMP for 6 days. Consequently, it is concluded that the cAMP system adapts at the post-receptor level to a sustained activation of the system by differential expression of the isoforms of AC, PDE, and PKA in SH-SY5Y neuroblastoma. We also showed that an increase in cellular cAMP concentration might mediate the observed changes in the cAMP system.
3',5'-Cyclic-Nucleotide Phosphodiesterase/genetics/metabolism ; Adenylate Cyclase/genetics/metabolism ; Cyclic AMP/*metabolism ; Cyclic AMP-Dependent Protein Kinases/genetics/metabolism ; G-Protein, Stimulatory Gs/genetics/metabolism ; Heterotrimeric GTP-Binding Proteins/genetics/*metabolism ; Human ; Isoenzymes ; Isoproterenol/pharmacology ; Mutation ; Neuroblastoma/*metabolism ; *Signal Transduction ; Support, Non-U.S. Gov't ; Tumor Cells, Cultured

To investigate the interaction of stimulatory GTP binding protein (G(s)) pathways with others, we overexpressed wild type alpha subunit of G(s) (G(s) alpha), constitutively activated R201E G(s) alpha, and dominant negative G226A G(s) alpha in COS-1 cells by transfection with DEAE-dextran, respectively, The expression of various G proteins in the transfected cells was analyzed after 72 h by quantitative Western blots, and cAMP production by stimulation with isoproterenol and forskolin was quantitated using cAMP binding proteins, The expression of Gs alpha increased about 5-fold in the transfected cells, with concomitant increase in the small forms. However, there was no significant alteration the in the level of the alpha subunit of inhibitory G protein (G(i)) and G(q), and the beta subunits of G proteins. The cAMP level without stimulation increased in the cells transfected with G(s) alpha regardless to the type of mutation, Treatment with either isoproterenol or forskolin resulted in comparable increase of the cAMP level in all the transfected cells, though the ratio to its respective basal level was smaller in the G(s) alpha-transfected cells, From this experiment, we found that the expression of the other G proteins and the signaling pathway producing cAMP did not change significantly by transiently expressing wild type, constitutively activated type, and dominant negative type of G(s) alpha. Analysis of the effects of long-term expression of Gs alpha would contribute to better understanding on how the G(s) alpha signaling system interacts with other signaling pathways and how it adapts to the changed environments.
Animals ; Blotting, Western ; Carrier Proteins ; Colforsin ; COS Cells* ; Cyclic AMP ; DEAE-Dextran ; GTP-Binding Proteins* ; Isoproterenol ; Protein Engineering ; Recombinant Proteins ; Transfection

OBJECTIVES: Protein-calorie malnutrition has been shown to be prevalent among patients on chronic dialysis, And assessment of nutritional status of continuous ambulatory peritoneal dialysis(CAPD) patients has assumed greater importance because of the association of protein-calorie malnutrition with increasing morbidity and mortality. So we observed the incidence and clinical effect of protein-calorie malnutrition, and we compared the indices of nutrition with dialysis adequacy utilizing urea kinetic modeling and cretinine clearance in CAPD patients. METHODS: We performed a cross-sectional study in which eight parameters, based on anthropometry, blood chemistry and subjective symptoms, were scored according to the degree of abnormalities in 82CAPD patients. A malnutrition index was derived from these scores. We also performed comparative analysis to identify significant correlations of the indices of urea kinetic modeling and creatinine clearance with the other parameters of nutritional status. RESULTS: The malnutrition index classified 47(57%) patients as normal, 30(37%) intermediately malnourished, and 5(6%) as severely malnourished. Malnutrition index showed a significant correlation with the body mass index(BMI), triceps skinfold thickness(TSF), mid-arm circumference(MAC), mid-arm muscle area (MAMA), duration of CAPD, subjective symptoms, serum albumin, transferrin, cholesterol, and triglyceride. The malnutrition index also showed a significant correlation with residual renal function(RRF), and standardized creatinine clearance(SCCr). The TWR-Kt/V(total Kt/Vurea per week with consideration of residual renal urea clearance) was significantly lower in the severely malnourished group than in the normal group. Serum alkaline phosphatase and BUN levels were higher in the severely malnourished group than in the normal and inter-mediate groups. CONCLUSION: In assessing the nutrition status of CAPD patients, body weight, TSF, MAC, MAMA, subjective symptoms, serum albumin, transferrin, cholesterol, triglyceride, urea nitrogen, and alkaline phosphatase were considered useful parameters. There was a trend of increased BUN and decreased TWR-Kt/V in severely malnourished patients, and the value of SCCr was significantly lower in malnourished patients. However, no meaningful relationships between TW-Kt/V and malnutrition index or between NPCR(normalized protein catabolic rate) and malnutrition index were found m this cross-sectional study. As the number of patients with longer duration of CAPD or negligible RRF has increased in the malnourished patients, regular monitoring of these parameters, especially TWR-Kt/V and SCCr, may be helpful to assess dialysis adequacy to keep good nutritional status of each CAPD patient.
Alkaline Phosphatase ; Anthropometry ; Body Weight ; Chemistry ; Cholesterol ; Creatinine* ; Cross-Sectional Studies ; Dialysis ; Humans ; Incidence ; Malnutrition ; Mortality ; Nitrogen ; Nutritional Status ; Peritoneal Dialysis, Continuous Ambulatory* ; Protein-Energy Malnutrition ; Serum Albumin ; Transferrin ; Triglycerides ; Urea*

Trisomy 9 syndrome was first reported by Retheore in 1970 and has been rarely reported. This syndrome consists of partial and complete trisomy 9. It is characterized by growth and mental retardation, craniofacial abnormalities including microcephaly, hypertelorism, prominent nose, deep-set ears and down-slanting palpebral fissures. Congenital heart diseases and congenital dislocations of knee are also common in trisomy 9 syndrome. Here, we report a very rare case of partial trisomy 9 due to maternal balanced translocation t(9;21). He showed craniofacial abnormalities, brain malformation, cardiac defect, hydronephrosis and congenital dislocations of hip and knee joints.
Brain ; Chromosomes, Human, Pair 9 ; Craniofacial Abnormalities ; Dislocations ; Ear ; Heart Diseases ; Hip ; Hydronephrosis ; Hypertelorism ; Intellectual Disability ; Knee ; Knee Joint ; Microcephaly ; Nose ; Trisomy

Trisomy 9 syndrome was first reported by Retheore in 1970 and has been rarely reported. This syndrome consists of partial and complete trisomy 9. It is characterized by growth and mental retardation, craniofacial abnormalities including microcephaly, hypertelorism, prominent nose, deep-set ears and down-slanting palpebral fissures. Congenital heart diseases and congenital dislocations of knee are also common in trisomy 9 syndrome. Here, we report a very rare case of partial trisomy 9 due to maternal balanced translocation t(9;21). He showed craniofacial abnormalities, brain malformation, cardiac defect, hydronephrosis and congenital dislocations of hip and knee joints.
Brain ; Chromosomes, Human, Pair 9 ; Craniofacial Abnormalities ; Dislocations ; Ear ; Heart Diseases ; Hip ; Hydronephrosis ; Hypertelorism ; Intellectual Disability ; Knee ; Knee Joint ; Microcephaly ; Nose ; Trisomy

Heart disease is one of the major cause of death in diabetic patients, but the thogenesis of diabetic cardio-myopathy remains unclear. In this experiment, to sess the significance of G protein signaling pathways in the pathogenesis of abetic cardiomyopathy, we analyzed the expression of G proteins and the tivities of second messenger dependent protein kinases: cAMP-dependent protein nase (PKA), DAG-mediated protein kinase C (PKC), and calmodulin dependent otein kinase II (CaM kinase II) in the streptozotocin induced diabetic rat art. The expression of Galphaq was increased by slightly over 10% (P<0.05) in abetic rat heart, while Galphas, Galphai, and Gbeta remained unchanged. The A activity in the heart did not change significantly but increased by 27%<0.01) in the liver. Insulin treatment did not restore the increased activity the liver. Total PKC activity in the heart was increased by 56% (P<0.01), and sulin treatment did not restore such increase. The CaM kinase II activity in e heart remained at the same level but was slightly increased in the liver 4% increase, P<0.05). These findings of increased expression of Galphaq in the reptozotocin-diabetic rat heart that are reflected by the increased level of C activity and insensitivity to insulin demonstrate that alteration of Galphaq y underlie, at least partly, the cardiac dysfunction that is associated with abetes. Copyright 2000 Academic Press.
Animal ; Ca(2+)-Calmodulin Dependent Protein Kinase/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Diabetes Mellitus, Experimental/metabolism* ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/chemically induced ; GTP-Binding Proteins/metabolism* ; Insulin/pharmacology ; Liver/metabolism ; Liver/drug effects ; Male ; Myocardium/metabolism* ; Protein Kinase C/metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Streptozocin

This study evaluated the methodological quality of CPGs using the Korean AGREE II scoring guide and a web-based appraisal system and was conducted by qualified appraisers. A total of 27 Korean CPGs were assessed under 6 domains and 23 items on the AGREE II instrument using the Korean scoring guide. The domain scores of the 27 guidelines were as following: the mean domain score was 82.7% (median 84.7%, ranging from 55.6% to 97.2%) for domain 1 (scope and purpose); 53.4% (median 56.9%, ranging from 11.1% to 95.8%) for domain 2 (stakeholder involvement); 63.0% (median 71.4%, ranging from 13.5% to 90.6%) for domain 3 (rigor of development); 88.9% (median 91.7%, ranging from 58.3% to 100.0%) for domain 4 (clarity of presentation); 30.1% (median 27.1%, ranging from 3.1% to 67.7%) for domain 5 (applicability); and 50.2% (median 58.3%, ranging from 0.0% to 93.8%) for domain 6 (editorial independence). Three domains including scope and purpose, rigor of development, and clarity of presentation were rated at more than 60% of the scaled domain score. Three domains including stakeholder involvement, applicability, and editorial independence were rated at less than 60% of the scaled domain score. Finally, of the 27 guidelines, 18 (66.7%) were rated at more than 60% of the scaled domain score for rigor of development and were categorized as high-quality guidelines.
Humans ; Internet ; *Practice Guidelines as Topic ; *Program Evaluation ; Quality Assurance, Health Care ; Republic of Korea

BACKGROUND: Patients with end-stage renal disease have farther excess rate of coronary artery disease (CAD) than nonuremic population. There is a possibility that atherosclerosis may aggravate renal insufficiency, but it is not certain. Pulse pressure was also significantly increased in patients with chronic renal disease (CRD), and had been implicated in the development of atherosclerosis. The purpose of this study is to identify the association of atherosclerotic CAD and pulse pressure with renal disease progression in patients with mild CRD METHODS: The patients with mild CRD who had been followed up more than 3 years in Asan medical center, Seoul, Korea, were included. We evaluated their CAD via coronary angiography, and followed up their serum creatinine levels and other parameters assumed to be associated with progression of CRD. All clinical and laboratory parameters were analyzed by multivariate logistic method. And we examined the association between pulse pressure and progression of CRD with related factors via multivariate logistic analysis. RESULTS: Total 87 patients (54 were men and 33 were women) were included in this study. 45 patients had coronary heart disease and 42 had not. Comparison of CRD progression between the patients who had CAD (n=45) and those who had not (n=42) showed a significant difference (76% vs 52%, p< 0.05). Mean arterial pressure, pulse pressure, presence of diabetic nephropathy, 24hour urine protein, total cholesterol were the parameters associated with the progression of CRD. Among of them, proteinuria and mean arterial pressure were independent risk factors for renal disease progression. There was a significant association between CAD and pulse pressure. CONCLUSION: Atherosclerotic CAD and increased pulse pressure were associated with renal disease progression in the patients with mild renal insufficiency.
Arterial Pressure ; Atherosclerosis ; Blood Pressure* ; Cholesterol ; Chungcheongnam-do ; Coronary Angiography ; Coronary Artery Disease* ; Coronary Disease ; Coronary Vessels* ; Creatinine ; Diabetic Nephropathies ; Disease Progression ; Humans ; Kidney Failure, Chronic ; Korea ; Male ; Proteinuria ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Risk Factors ; Seoul

BACKGROUND: Atherosclerotic vascular disease is the major cause of morbidity and mortality in dialysis patients. C-reactive protein (CRP) appears to be clinically useful in prediction of coronary heart disease. Elevated pulse pressure has been associated with an increased risk of cardiovascular disease among apparently healthy adults. Therefore, we evaluated the association between a persistent elevation of C-reactive protein level, pulse pressure and the presence of ischemic heart disease in patients with continuous ambulatory peritoneal dialysis (CAPD). METHODS: A total of 71 CAPD patients (42 males, 29 females) who underwent thallium SPECT and followed up more than 6 months were included. We collected the data about age, sex, smoking, diabetes, hypertension, pulse pressure and body mass index. Blood levels of albumin, total cholesterol, fibrinogen, lipoprotein (a) and C-reactive protein were measured. RESULTS: The values of C-reactive protein, pulse pressure, smoking and fibrinogen were significantly higher in thallium SPECT positive group (p<0.05). A 0.01 mg/dL increase in C-reactive protein was associated with a 1.014 increase in the odds of having an elevated risk of coronary artery disease (95% confidence interval 1.008-1.019) and a 1 mmHg increase in pulse pressure was associated with a 1.017 increase in the odds of having an elevated risk of coronary artery disease (95% confidence interval 1.011-1.023). By multivariate logistic regression analysis, C-reactive protein and pulse pressure were independent risk factors for ischemic heart disease. Log CRP level was positively correlated with pulse pressure level (p<0.01). CONCLUSION: The baseline level of CRP and pulse pressure independently predicts the risk of coronary heart disease in CAPD patients. For patients who have a persistent elevation of CRP and pulse pressure without an apparent cause, we recommend a workup for ischemic heart disease.
Adult ; Blood Pressure* ; Body Mass Index ; C-Reactive Protein* ; Cardiovascular Diseases ; Cholesterol ; Coronary Artery Disease ; Coronary Disease ; Dialysis ; Fibrinogen ; Humans ; Hypertension ; Lipoprotein(a) ; Logistic Models ; Male ; Mortality ; Myocardial Ischemia* ; Peritoneal Dialysis, Continuous Ambulatory* ; Risk Factors ; Smoke ; Smoking ; Thallium ; Tomography, Emission-Computed, Single-Photon ; Vascular Diseases