Common CCR 5 polymorphism in stroke: the CCR 5 delta32 polymorphism differentiates cardioembolism from other aetiologies of ischaemic cerebrovascular diseases.

Inflammation is involved in the development of atherosclerosis. The CC chemokine receptor 5 (CCR5) initiates chemotaxis and modulates the inflammation secondary to atherosclerosis and related vascular diseases. The CCR5 Delta32 polymorphism influences the expression of CCR5 on the cell surface. The purpose of this study was to examine the effect of the Delta32 polymorphism in ischaemic cerebrovascular disease (ICVD). The CCR5 Delta32 polymorphism was genotyped in 1462 individuals: 562 ischaemic stroke (IS), 97 transient ischaemic attack (TIA) and in 803 healthy controls. All 659 ICVD patients were categorized according to the Trial of Org 10172 in Acute Stroke Treatment aetiological classification. The investigated subtypes were large artery atherosclerosis (LAA), cardioembolism (CE), small artery occlusion (SAO) and cryptogenic disease (CRYPT). Genotyping was performed with the TaqMan polymerase chain reaction. The Delta32 allele was less frequent in CE patients compared with LAA (OR, 0.4; 95% CI, 0.24-0.79; P = 0.008), SAO (OR, 0.5; 95% CI, 0.29-0.84; P = 0.01), CRYPT (OR, 0.5; 95% CI, 0.28-0.82; P = 0.008) and controls (OR, 0.5; 95% CI, 0.36-0.82; P = 0.002). Multiple logistic regression analysis showed that the Delta32 allele is associated with a lower risk for cardioembolic ICVD (OR 0.5; 95% CI, 0.28-0.75; P = 0.002) when compared with ICVD of other causes. The Delta32 polymorphism of CCR5 may differentiate cardioembolism from the remaining causes of ICVD.

Co-expression of trypsin and tumour-associated trypsin inhibitor (TATI) in colorectal adenocarcinomas.

Trypsin and its specific inhibitor, TATI (tumour-associated trypsin inhibitor), are expressed in normal human pancreas and in a variety of tumours. The aim of the present study was to assess the parallel expression of trypsin and TATI in colorectal cancer, in comparison with their expression in normal epithelial tissue, since proteases and their inhibitors are thought to be co-expressed in malignant neoplasms. We also assessed the possible significance of their expression as a means of differentiation between normal and malignant tissue. We examined qualitatively and semi-quantitatively the immunohistochemical expression of trypsin and TATI on paraffin-embedded serial tissue sections from 91 colorectal adenocarcinomas. The reverse-transcriptase-polymerase-chain reaction (RT-PCR) was also performed on fresh malignant tissue from 55 of the above adenocarcinomas. Normal and non-malignant tissues adjacent to the tumours were also evaluated. Cytoplasmic expression of trypsin (more than 25% of the cancer cells positive) was found in 67 (73.6%) adenocarcinomas, whereas TATI was expressed in the cytoplasm of 59 (64.8%) cases studied. Statistical analysis using Spearman's test has demonstrated a significant correlation between trypsin and TATI immunohistochemical expression (p<0.01). RT-PCR showed co-expression of trypsin and TATI mRNA in all carcinomas studied. Distinct patterns of trypsin and TATI immunohistochemical expression were observed in adjacent, non-malignant tissues, where both trypsin and TATI mRNA were also detected. Normal tissues were negative by immunohistochemistry. Our results indicate co-expression of trypsin and TATI in colorectal tumours both at the mRNA and protein level. We conclude that in colorectal neoplasms, high levels of trypsin and TATI may be important for malignant tumour formation and/or metastatic process.

The influence of dietary patterns on the development of thyroid cancer.

To elucidate the role of diet in the development of thyroid cancer, we conducted a case-control study of 113 persons with histologically-verified thyroid cancer and 138 controls, matched by age, gender and health unit. Socio-economic data, known risk factors and food consumption of more than 100 items were recorded by interviewer-administered prestructured questionnaire. Factor analysis was used to identify possible dietary patterns and logistic regression analysis was used to explore the effect of food items or dietary patterns on thyroid cancer. After adjustment for age, gender, body mass index (BMI), and total energy intake, significant positive associations were observed for pork consumption, while negative ones were observed for tomatoes, lemons and pasta. Dietary patterns of fruits, raw vegetables and mixed raw vegetables and fruits, led to a reduced risk (corresponding odds ratios (ORs) 0.68, 0.71, 0.73) for all thyroid cancers and similar figures were obtained for papillary thyroid cancers. A dietary pattern of fish and cooked vegetables led to an increased risk (OR 2.79) of follicular cancer.

Dietary fat and carbohydrates are independently associated with circulating insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 concentrations in healthy adults.

PURPOSE: To evaluate and quantify the association between consumption of specific food groups/macronutrients and concentrations of serum insulin-like growth factor 1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3). SUBJECTS AND METHODS: Data from a comprehensive food-frequency questionnaire administered to 115 healthy subjects were used to study cross-sectionally the relationship between nutritional factors and circulating IGF-1 and IGFBP-3 concentrations. Adjustment for the effect of total energy intake and a series of epidemiologic parameters (age, sex, height, body mass index, smoking, alcohol consumption, and coffee drinking) was implemented through multivariate linear regression. RESULTS: We observed that serum levels of IGF-1 are positively associated with consumption of red meats, fats, and oils. In addition, serum levels of IGF-1 are independently and positively associated with energy intake from lipids and negatively associated with energy intake from carbohydrates. Finally, serum levels of IGFBP-3 are independently and negatively associated with energy intake from saturated fat. CONCLUSION: Serum IGF-1 and/or IGFBP-3 concentrations are associated with red meat, carbohydrate intake, and fat intake and, thus, may mediate the effect of these dietary factors on the pathogenesis of several disease states. Additional studies are needed to further quantify these associations and elucidate the underlying mechanisms.

Age, sex, and smoking are predictors of circulating insulin-like growth factor 1 and insulin-like growth factor-binding protein 3.

PURPOSE: Insulin-like growth factor (IGF-1) and its major binding protein (IGF-BP3) have recently been implicated in the pathogenesis of several malignancies. However, anthropometric and lifestyle predictors of these hormones have not been elucidated. Here we report the results of a cross-sectional study. SUBJECTS AND METHODS: This cross-sectional study examines the relationship of a series of epidemiologic parameters (age, sex, height, body mass index, smoking, alcohol consumption, and coffee drinking) with IGF-1 and IGF-BP3 in a sample of 130 healthy adults. RESULTS: We observed that serum levels of IGF-1 are higher, whereas levels of IGF-BP3 are lower, in men than in women. In addition, serum levels of IGF-1 are independently and negatively associated with age and positively associated with pack-year history of smoking. Finally, serum levels of IGF-BP3 are independently and negatively associated with the number of cigarettes smoked per day or pack-year history of smoking. CONCLUSION: Age, sex, and smoking are independent predictors of IGF-1 and/or IGF-BP3. The influence of these epidemiologic variables on the pathogenesis of disease states associated with IGF-1 and IGF-BP3 warrants further exploration.