Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: evidence of small-study bias

BACKGROUND: Inappropriate activation of the renin-angiotensin system may play a part in the development of preeclampsia. An insertion/deletion polymorphism within the angiotensin-I converting enzyme gene (ACE-I/D) has shown to be reliably associated with differences in angiotensin-converting enzyme (ACE) activity. However, previous studies of the ACE-I/D variant and preeclampsia have been individually underpowered to detect plausible genotypic risks. METHODS AND FINDINGS: A prospective case-control study was conducted in 1,711 unrelated young pregnant women (665 preeclamptic and 1,046 healthy pregnant controls) recruited from five Colombian cities. Maternal blood was obtained to genotype for the ACE-I/D polymorphism. Crude and adjusted odds ratio (OR) and 95% confidence interval (CI) using logistic regression models were obtained to evaluate the strength of the association between ACE-I/D variant and preeclampsia risk. A meta-analysis was then undertaken of all published studies to February 2006 evaluating the ACE-I/D variant in preeclampsia. An additive model (per-D-allele) revealed a null association between the ACE-I/D variant and preeclampsia risk (crude OR = 0.95 [95% CI, 0.81-1.10]) in the new case-control study. Similar results were obtained after adjusting for confounders (adjusted per-allele OR = 0.90 [95% CI, 0.77-1.06]) and using other genetic models of inheritance. A meta-analysis (2,596 cases and 3,828 controls from 22 studies) showed a per-allele OR of 1.26 (95% CI, 1.07-1.49). An analysis stratified by study size showed an attenuated OR toward the null as study size increased. CONCLUSIONS: It is highly likely that the observed small nominal increase in risk of preeclampsia associated with the ACE D-allele is due to small-study bias, similar to that observed in cardiovascular disease. Reliable assessment of the origins of preeclampsia using a genetic approach may require the establishment of a collaborating consortium to generate a dataset of adequate size

Serum Tumor Necrosis Factor-alpha and Interleukin-2 Concentrations in Newly Diagnosed ERBB2 (HER2/neu) Positive Breast Cancer Patients

Aim Cytokines have been associated with symptoms and adverse outcomes in breast cancer. Overexpression of ERBB2 (c-erb-b2; formerly HER2/neu), which is a member of the epidermal growth receptor family, is associated with involvement of lymph nodes, large tumor size, high grade, steroid receptor negativity, aneuploidy, high proliferation rate, and low overall survival in breast cancer. The aim of the study was to examine whether ERBB2 amplification has any effect on circulating levels of tumor necrosis factor-alpha (TNF-α) and interleukin-2 (IL-2) in breast cancer patients. Material and methods Fifty patients with primary breast carcinoma, classified as either ERBB2 (+) or (-) by the fluorescence in situ hybridization (FISH) technique, were included in the study. Cytokines were studied by ELISA according to the procedure described in the commercial kit. Results IL-2 levels were found significantly higher in ERBB2+ patients than in controls (p&lt;0.05). A significant negative correlation existed between ERBB2 positivity and estrogen receptor status (p=0.004). Plasma TNF-α and IL-2 levels were positively correlated in ERBB2+ breast cancer patients (p&lt;0.01). Conclusion The increase in IL-2 concentrations observed in our study suggests an activation of T cells by ERBB2 peptides. </jats:sec

Serum tumor necrosis factor-alpha and interleukin-2 concentrations in newly diagnosed ERBB2 (HER2/neu) positive breast cancer patients

Aim: Cytokines have been associated with symptoms and adverse outcomes in breast cancer. Overexpression of ERBB2 (c-erb-b2; formerly HER2/neu), which is a member of the epidermal growth receptor family, is associated with involvement of lymph nodes, large tumor size, high grade, steroid receptor negativity, aneuploidy, high proliferation rate, and low overall survival in breast cancer. The aim of the study was to examine whether ERBB2 amplification has any effect on circulating levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) in breast cancer patients

GAMMA-GLUTAMYL-TRANSFERASE ACTIVITY IN HUMAN PLATELETS - QUANTIFICATION OF ACTIVITY, ISOENZYME CHARACTERIZATION AND POTENTIAL CLINICAL RELEVANCE

Gamma-glutamyltransferase (GGT) activity in human platelet sonicates was 13.6 u/g of protein (range: 7.9-25.0) in 13 healthy, non-smoking, female volunteers; corresponding values in 16 males were: 20.3 (10.1-26.0), These values differed significantly (p = 0.034). Platelet and serum GGT activity correlated significantly (p < 0.04). Platelets seem to contain only the isoenzyme GGT 4, Part of this enzyme activity is in the form of aggregates or linked with membranes/proteins. This activity is released by Triton X-100 and trypsin and migrates as GGT 4, Serum GGT activity, a measurement in routine use, could be influenced by GGT released by platelets, It is therefore of interest that serum GGT activity can be increased in clinical conditions (e,g, myocardial infarction, diabetes, peripheral vascular disease) associated with platelet hyperactivity, Platelet GGT may influence intracellular S-nitrosoglutathione (a putative nitric oxide donor) levels, Potential associations between serum GGT activity and platelet function indices deserve investigation