Gene expression patterns of insulin-like growth factor 1, insulin-like growth factor 2 and insulin-like growth factor binding protein 3 in human placenta from pregnancies with intrauterine growth restriction.

INTRODUCTION: In this study, we compared insulin-like growth factor (IGF)-gene expression patterns and characteristics of glucose and insulin metabolism in human placenta from pregnancies with or without intrauterine growth restriction (IUGR). MATERIALS AND METHODS: We compared 101 human placentas from intrauterine growth restriction pregnancies to those of 140 normal pregnancies treated at our department in a one-year period. We have also assessed the serum glucose and insulin levels of the IUGR and control groups. Several possible predicting factors of IUGR were also investigated. RESULTS: Risk for IUGR was suggested by gestational weight gain and gestational increase in maternal body mass index (BMI) as well as maternal birthweight. In pregnancies without IUGR, umbilical cord glucose and insulin levels were significantly higher than in pregnancies with IUGR. In placentas from pregnancies with IUGR an overexpression of the IGF-2 and the insulin-like growth factor binding protein (IGFBP)-3 genes was found. In placentas from pregnancies with male fetal gender we found a significant overexpression of the IGF-2 gene. DISCUSSION: Gestational weight gain and BMI increase seem to predict the development of IUGR. Insulin and carbohydrate metabolism are also impaired in IUGR fetuses. In the placentas from pregnancies with IUGR, IGF-2 is overexpressed reflecting its physiological role in optimizing energy distribution in a low-energy environment.

[Clinical-genetic care of BRCA-mutation carrier women: prevention, diagnosis and therapy]. / A BRCA-génmutációt hordozó nok klinikogenetikai ellátása: szurés, diagnosztika, terápia.

Predictive genetics opens a considerable perspective in the diagnostics as well as the treatment of breast and ovarian cancer. Current recommendations and guidelines for the management of BRCA 1 and BRCA 2 mutation carriers are not based on controlled randomized trials, but on expert opinions. The existing options of prevention, early diagnosis and treatment must be clearly interpreted to the patient. In the context of a dedicated genetic counseling the participation of all involved professionals (geneticist, oncologist, surgeon, gynecologist) is required. The decision-making process concerning the possibilities of prevention, diagnosis and treatment is always deeply influenced by the patient's own experience with the cancer occurred in the family, as well as by her values and expectations of life. The focused multidisciplinary approach, with the application of results from prospective studies in cohorts of BRCA mutation carriers allow the concerned individuals to benefit from this kind of approach of medical treatment.

[Risk assessment in familial breast cancer]. / Az ismétlodési kockázat becslése családi halmozódást mutató emlorák esetén.

Women with a history of breast cancer are common at centers for cancer genetic risk all over Europe. Given limited health care resources, managing this demand, while achieving good value for money coming from health services, is generally a major challenge. This paper recapitulates and summarizes the available methods of the risk assessment of familial breast cancer. After a systematic review of the literature Gail-model, Claus-model and BOADICEA-model were selected, as well as softwares (LINKAGE software; MENDEL v3.3 software) available in the application of these algorhythms are also summarized. Comparisons were made between the models concerning their advantages and disadvantages. The really reliable methods of risk estimation of familial breast cancer are always based on the analysis of the pedigree structure and allow the estimation of the patient's probability of carrying a susceptibility gene under a particular genetic model, given her family history. For this method the knowledge of BRCA mutation status is absolutely indispensable. The methods of BRCA mutation analysis as well as the main characteristics of the occurrence of BRCA mutation carrier condition are discussed in details.

Current concepts in the genetic diagnostics of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic, chronic and inflammatory disease of unknown etiology. HLA-DRB1 and PTPN22 1858T gene variants are risk factors of RA, clinical manifestations and rate of progression of joint destruction in this autoimmune disease. Currently, several immunopathogenetic models of other genes (CTLA4, MIF, PADI4 and SLC22A4) are under debate. The clinical influence of some of the gene polymorphisms associated with RA and the principles of pharmacogenetics applied to different therapies, such as classical disease-modifying anti-rheumatic drugs and new biological agents. Pharmacogenetics is a rapidly advancing area of research that holds the promise that therapies will soon be tailored to an individual patient's genetic profile.

Gene expression profiling in Paget's disease of bone: upregulation of interferon signaling pathways in pagetic monocytes and lymphocytes.

UNLABELLED: We examined the gene expression profile of genes involved in bone metabolism in 23 patients with PD compared with 23 healthy controls. We found a significant overexpression of the genes of the IFN pathway along with a downregulation of tnf-alpha. Our result suggest that IFN-mediated signaling may play important roles in aberrant osteoclastogenesis of PD. INTRODUCTION: Paget's disease of bone (PD) is characterized by focal regions of highly exaggerated bone remodeling and aberrant osteoclastogenesis. Under physiological conditions, circulating monocytes may serve as early progenitors of osteoclasts and along with peripheral blood lymphocytes produce a wide variety of factors important in bone metabolism. Nevertheless, little is known about the roles of circulating monocytes and lymphocytes in relation to the pathological bone turnover in PD. MATERIALS AND METHODS: In this study, we aimed at investigating the gene expression pattern of PD using quantitative real-time PCR in monocytes and lymphocytes isolated from peripheral blood mononuclear cells (PBMCs). Fifteen genes known to be involved in osteoclastogenesis were studied in cells from 23 patients with PD and in cells from 23 healthy controls. Eight human genes including ifn-alpha (3.48-fold, p < 0.001), ifn-beta (2.68-fold, p < 0.001), ifn-gamma (1.98-fold, p = 0.002), p38 beta2 mapk (2.47-fold, p = 0.002), ifn-gammar1 (2.03-fold, p = 0.01), ifn-gammar2 (1.81-fold, p = 0.02), stat1 (1.57-fold, p = 0.037), and tnf-alpha (-2.34, p < 0.001) were found to be significantly altered in pagetic monocytes compared with monocytes of healthy controls. RESULTS: In pagetic lymphocytes, significant changes in the expression of ifn-alpha (2.17-fold, p < 0.001), ifn-beta (2.13-fold, p = 0.005), ifn-gamma (1.89-fold, p < 0.001), ifn-gammar1 (1.02-fold, p = 0.04), ifn-gammar2 (1.01-fold, p = 0.031), stat2 (1.79-fold, p < 0.001), and tnf-alpha (-1.49, p < 0.001) were found compared with lymphocytes of healthy controls. Furthermore, IFN-gamma protein was significantly elevated in the sera of PD patients (18.7 +/- 6.69 pg/ml) compared with healthy controls (3.87 +/- 6.48 pg/ml, p = 0.042). CONCLUSIONS: In conclusion, our data suggest that novel pathways mainly related to the IFN-mediated signaling may play important roles in the aberrant osteoclastogenesis of PD.