Interleukin-1 beta and interferon-gamma induce proliferation and apoptosis in cultured Schwann cells

This study reports that in Schwann cell tissue culture the administration of the two pro-inflammatory cytokines, interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma), at different dosages, singly or in combination, can induce apoptosis and/or mitosis.Schwann cell apoptosis was maximal within 24 h of stimulation with 50 U/ml of IFN-gamma, while proliferation was at its peak within 24 h with 10 U/ml IL-1 beta, and both processes decreased progressively by 48 and 72 h. Moreover, the combination of the two cytokines did not show any synergistic effect. These data can be interpreted as a possible involvement of pro-inflammatory cytokines not only in myelin disruption but also in promoting remyelination.     

Arteriovenous brain malformations: is functional MR imaging reliable for studying language reorganization in patients? Initial observations

PURPOSE: To determine whether the blood flow abnormalities frequently associated with arteriovenous malformations (AVMs) can alter functional magnetic resonance (MR) imaging evaluation of language lateralization and whether reorganization of language function occurs in patients with brain AVMs. MATERIALS AND METHODS: Eleven patients with left-hemisphere brain AVMs and 10 age-matched control subjects were examined with 1.5-T blood oxygen level-dependent (BOLD) functional MR imaging. Verbal fluency, sentence repetition, and story listening tasks were performed. The functional MR imaging laterality index in the frontal and temporal lobes was defined as the (L - R)/(L + R) ratio, where L and R are the numbers of activated pixels in the left and right hemispheres, respectively. Statistical analyses were performed with Wilcoxon signed rank, Fisher exact, and Kruskal-Wallis tests. RESULTS: Control subjects had left-sided language dominance, although symmetric pixel counts were observed in the frontal lobes in two subjects and in the temporal lobes in one subject. Six patients had left-sided language dominance similar to that observed in control subjects. Five of these patients had AVMs outside frontal or temporal language areas, without flow abnormalities. Five patients had abnormally right-sided asymmetric indexes (below mean control subject value - 2 SDs), which suggested language reorganization (P <.05). Results of Wada examination and/or postembolization functional MR imaging performed in two of these patients showed that the abnormal laterality indexes were at least partly due to severe flow abnormalities that impaired detection of BOLD MR imaging signal intensity. CONCLUSION: These data suggest that flow abnormalities may interfere with language lateralization assessment with functional MR imaging.     

Insulin-like growth factor II and colorectal cancer risk in women.

Recently, a number of prospective studies showed evidence that the growth hormone/insulin-like growth factor I (IGF-I) axis may be important in the development of colorectal cancer. However, only a few studies have reported on the possible relationship of colorectal cancer risk with circulating levels of IGF-II, which are not growth hormone dependent and which do not vary with alterations in energy balance. In a case-control study of 102 cases and 200 matched controls nested within a cohort of 14,275 women in New York, we examined the relationship between colorectal cancer risk and prediagnostic serum levels of IGF-II. Conditional logistic regression analysis showed an odds ratio (OR) for colorectal cancer of 2.02 (95% confidence interval (CI): 0.83-4.93), comparing the upper to lower quintile of IGF-II. This association was slightly attenuated after excluding IGF-II measurements in serum samples taken within 1 year before case diagnosis (OR of 1.81; 95% CI: 0.71-4.64) and moderately attenuated after excluding IGF-II measurements in serum samples taken within 2 years before case diagnosis (OR of 1.47; 95% CI: 0.56-3.91). Adjustment for IGF-1, IGF binding protein (BP)-1, IGFBP-3, smoking, or body mass index did not substantially alter the association, whereas adjustment for IGFBP-2 moderately attenuated the relationship. Our results confirm those of three recent case-control studies, and collectively these results suggest a possible increase in colorectal cancer risk among subjects with comparatively elevated serum IGF-II. Mechanisms that might cause the increase in IGF-II levels are unknown but may include loss of parental imprinting of the IGF-II gene.     

C-peptide, IGF-I, sex-steroid hormones and adiposity: a cross-sectional study in healthy women within the European Prospective Investigation into Cancer and Nutrition (EPIC)

Objectives: The risk of some cancers is positively associated with body weight, which may influence circulating levels of sex-steroid hormones, insulin and IGF-I. Interrelationships between these hormones and the associations with adiposity were evaluated in healthy women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).Methods: A cross-sectional analysis was performed on anthropometric and hormonal data from 743 pre- and 1217 postmenopausal women. Body mass index (BMI) and waist circumference were used as indicators of adiposity. C-peptide, Insulin Growth Factor (IGF)-I, Insulin Growth Factor binding protein (IGFBP)-3, androgens, estrogens and sex hormone binding globulin (SHBG) were measured by immunoassays; free sex steroid concentrations were calculated.Results: BMI and waist circumference were positively correlated with estrogens in postmenopausal women and with C-peptide, free testosterone and inversely with SHBG in all women. C-peptide and IGF-I were inversely correlated with SHBG, and positively with free sex steroids in postmenopausal women. IGF-I was positively associated with postmenopausal estrogens and androgen concentrations in all women.Conclusions: Sex-steroid concentrations appear to be regulated along several axes. Adiposity correlated directly with estrogens in postmenopausal women and with insulin, resulting in lower SHBG and increased levels of free sex steroids. Independent of adiposity and insulin, IGF-I was associated with decreased SHBG levels, and increased concentrations of androgens and postmenopausal estrogens.     

A network of investigator networks in human genome epidemiology

The task of identifying genetic determinants for complex, multigenetic diseases is hampered by small studies, publication and reporting biases, and lack of common standards worldwide. The authors propose the creation of a network of networks that include groups of investigators collecting data for human genome epidemiology research. Twenty-three networks of investigators addressing specific diseases or research topics and representing several hundreds of teams have already joined this initiative. For each field, the authors are currently creating a core registry of teams already participating in the respective network. A wider international registry will include all other teams also working in the same field. Independent investigators are invited to join the registries and existing networks and to join forces in creating additional ones as needed. The network of networks aims to register these networks, teams, and investigators; be a resource for information about or connections to the many networks; offer methodological support; promote sound design and standardization of analytical practices; generate inclusive overviews of fields at large; facilitate rapid confirmation of findings; and avoid duplication of effort.     

Age at menarche in relation to adult height: the EPIC study

In the last two centuries, age at menarche has decreased in several European populations, whereas adult height has increased. It is unclear whether these trends have ceased in recent years or how age at menarche and height are related in individuals. In this study, the authors first investigated trends in age at menarche and adult height among 286,205 women from nine European countries by computing the mean age at menarche and height in 5-year birth cohorts, adjusted for differences in socioeconomic status. Second, the relation between age at menarche and height was estimated by linear regression models, adjusted for age at enrollment between 1992 and 1998 and socioeconomic status. Mean age at menarche decreased by 44 days per 5-year birth cohort (beta = -0.12, standard error = 0.002), varying from 18 days in the United Kingdom to 58 days in Spain and Germany. Women grew 0.29 cm taller per 5-year birth cohort (standard error = 0.007), varying from 0.42 cm in Italy to 0.98 cm in Denmark. Furthermore, women grew approximately 0.31 cm taller when menarche occurred 1 year later (range by country: 0.13-0.50 cm). Based on time trends, more recent birth cohorts have their menarche earlier and grow taller. However, women with earlier menarche reach a shorter adult height compared with women who have menarche at a later age.     

Homocysteinemia is inversely correlated with platelet count and directly correlated with sE- and sP-selectin levels in females homozygous for C677T methylenetetrahydrofolate reductase

Plasma homocysteine levels depend in part on the molecular nature of the methylenetetrahydrofolate reductase (MTHFR) and on blood folate intake. Little has been reported on platelet counts in the presence of hyperhomocysteinemia and MTHFR polymorphisms, with the exception of delayed platelet recovery in homozygous MTHFR C677T subjects after treatment with methotrexate for ovarian cancer. The aim of this investigation was to evaluate the possibility of a link between the platelet count and plasma homocysteine levels in different MTHFR variants in 165 female patients. Determinations of plasma homocysteine levels were by ELISA and of MTHFR polymorphisms (A1298C and C677T) were by inverse hybridization. Serum P- and E-selectin concentrations were obtained by ELISA. An inverse correlation (R=-0.88, P<0.001) was observed between blood platelet counts and plasma homocysteine levels in the women homozygous for MTHFR C677T. This correlation did not depend on pregnancy or other variables reported. Serum concentrations of sE- and sP-selectin, markers of endothelial and platelet activation, were significantly and positively correlated with homocysteine levels. These findings suggest that homocysteine affects platelet numbers in women with MTHFR C677T possibly consequent to endothelial and platelet activation.