Abstract-Recent findings suggest that inflammation plays a role in atherosclerosis and its acute complications. Cellular response in infections with Gram-negative bacteria is mediated by bacterial lipopolysaccharide (LPS), which activates monocytes to expression of cytokines, growth factors, and procoagulatory factors via LPS receptor CD14. Endothelial cells and smooth muscle cells are stimulated by a complex of LPS and soluble CD14. In this study, LPS receptor CD14 was analyzed to find genetic variants and check them for an association with coronary artery disease or myocardial infarction (MI). When screening the CD14 gene by single-strand conformation polymorphism analysis, a promoter polymorphism was detected and confirmed as a T-to-C exchange at position Ϫ159. We determined the genotypes of 2228 men who had undergone coronary angiography for diagnostic purposes. Within the total study group there was no significant association of either genotype with MI or coronary artery disease. However, in a subgroup with low coronary risk (normotensive nonsmokers), a relative risk for MI in probands homozygous for the T allele could be evaluated (OR, 1.6; 95% CI, 1.0 to 2.4; PϽ0.05). The association was even stronger in low-risk patients older than 62 years (OR, 3.8; 95% CI, 1.6 to 9.0; PϽ0.01). In conclusion, we describe a new CD14 promoter polymorphism that is associated with MI, especially in older patients with a low atherosclerotic risk profile. (Arterioscler Thromb Vasc Biol. 1999;19:932-938.)Key Words: CD14 Ⅲ genetics Ⅲ coronary disease Ⅲ myocardial infarction Ⅲ risk factors C D14 is a leucine-rich 55-kDa glycoprotein that is expressed in considerable amounts by mature monocytes, macrophages, and activated neutrophil granulocytes. 1 In these cells CD14 is known as a surface marker, being glycosylphosphatidylinositol anchored in the cell membrane (mCD14). 2 In addition, soluble CD14 (sCD14) can be found in serum where 2 major isoforms coexist, differing in molecular weight. 3 CD14 serves as receptor for bacterial lipopolysaccharide (LPS, endotoxin) and mediates cell activation by LPS. 4 The receptor-ligand interaction depends on a serum protein, LPS-binding protein, which complexes LPS and facilitates binding to mCD14 or sCD14. 5 Endothelial cells 6 and smooth muscle cells 7 are activated via sCD14, lacking their own membranous protein and CD14 mRNA. 7 In addition, they are activated indirectly by cytokines from LPSstimulated monocytes. 8 Endotoxin-activated monocytes produce proinflammatory cytokines such as tumor necrosis factor-␣, interleukin-1 and interleukin-6, and growth factors. 9 In stimulated endothelial cells, expression of endothelial leukocyte adhesion molecule-1, 10 intercellular adhesion molecule-1, 11 and vascular cell adhesion molecule-1 12 is induced, accompanying cell adhesion to endothelium. 12 LPS increases the levels of LDL and VLDL and supports the oxidation of LDL; HDL levels are decreased. 13 It stimulates smooth muscle cell proliferation and migration by release of platelet-derived growth f...

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These organ culture models demonstrate the effects of insulin and PDGF on intimal hyperplasia in IMA and SV representing models for arteriosclerosis and bypass graft stenosis and stressing the role of insulin and growth factors for neointima development.

Tumor markers were used for disease monitoring in small-cell lung cancer patients. The aim of this study was to improve diagnostic efficiency in the detection of tumor progression in small-cell lung cancer patients by using fuzzy logic modeling in combination with a tumor marker panel (NSE, ProGRP, Tumor M2-PK, CYFRA 21-1, and CEA). Thirty-three consecutive small-cell lung cancer patients were included in a prospective study. The changes in blood levels of tumor markers and their analysis by fuzzy logic modeling were compared with the clinical evaluation of response versus non-response to therapy. Clinical monitoring was performed according to the standard criteria of the WHO. Tumor M2-PK was measured in plasma with an ELISA, all other markers were measured in sera. At 90% specificity, clinically detected tumor progression was found by the best single marker, NSE, in 32% of all cases. A fuzzy logic rule-based system employing a tumor marker panel increased the sensitivity significantly (P>0.0001) in small-cell carcinomas to 67% with the threemarker combination NSE/ProGRP/Tumor M2-PK and to 56% with the best two-marker combination ProGRP/Tumor M2-PK, respectively. An improvement of sensitivity was also observed using the two-marker combination of ProGRP/NSE (sensitivity 49%) or NSE/Tumor M2-PK (sensitivity 52%). The fuzzy classifier was able to detect a higher rate of progression in small-cell lung cancer patients compared with the multiple logistic regression analysis using the marker combination NSE/ProGRP/Tumor M2-PK (sensitivity 44%; AUC=0.76). With the fuzzy logic method and different tumor marker panels (NSE, ProGRP and Tumor M2-PK), a new diagnostic tool for the detection of progression in patients with small-cell lung cancer is available.

The present study extends previous observations by the finding that carriers of the N5,N10-methylenetetrahydrofolate reductase C677T TT genotype with various coronary high risk profiles had clearly higher coronary heart disease scores than individuals with at least one C677T C allele.

Ataxia-telangiectasia is an autosomal recessive disease characterized by neurological and immunological symptoms, radiosensitivity and cancer predisposition. Heterozygous carriers of an ataxia-telangiectasia gene mutation are predisposed to epithelial cancers. We initiated a study to elucidate the frequency and clinical relevance of ATM gene mutations in former uranium miners exposed to high levels of radiation from radon and its decay products. Former uranium miners with Schneeberg lung cancer (n=48), former uranium miners suffering from silicosis (n=60) and uranium miners without occupational lung disorders (n=102) were investigated for nine mutations in the ATM gene. One gastric and one prostate cancer occurred in the group of miners without occupational lung diseases. Mutation analyses for S707P,