Manganese superoxide dismutase (MnSOD) genetic polymorphisms, dietary antioxidants, and risk of breast cancer

Oxidative stress, resulting from the imbalance between prooxidant and antioxidant states, damages DNA, proteins, cell membranes, and mitochondria and seems to play a role in human breast carcinogenesis. Dietary sources of antioxidants (chemical) and endogenous antioxidants (enzymatic), including the polymorphic manganese superoxide dismutase (MnSOD), can act to reduce the load of oxidative stress. We hypothesized that the valine-to-alanine substitution that seems to alter transport of the enzyme into the mitochondrion, changing its efficacy in fighting oxidative stress, was associated with breast cancer risk and that a diet rich in sources of antioxidants could ameliorate the effects on risk. Data were collected in a case-control study of diet and breast cancer in western New York from 1986 to 1991. Caucasian women with incident, primary, histologically confirmed breast cancer were frequency-matched on age and county of residence to community controls. Blood specimens were collected and processed from a subset of participants in the study (266 cases and 295 controls). Using a RFLP that distinguishes a valine (V) to alanine (A) change in the -9 position in the signal sequence of the protein for MnSOD, we characterized MnSOD genotypes in relation to breast cancer risk. We also evaluated the effect of the polymorphism on risk among low and high consumers of fruits and vegetables. Premenopausal women who were homozygous for the A allele had a 4-fold increase in breast cancer risk in comparison to those with 1 or 2 V alleles (odds ratio, 4.3; 95% confidence interval, 1.7-10.8). Risk was most pronounced among women below the median consumption of fruits and vegetables and of dietary ascorbic acid and alpha-tocopherol, with little increased risk for those with diets rich in these foods. Relationships were weaker among postmenopausal women, although the MnSOD AA genotype was associated with an almost 2-fold increase in risk (odds ratio, 1.8; confidence interval, 0.9-3.6). No appreciable modification of risk by diet was detected for these older women. These data support the hypothesis that MnSOD and oxidative stress play a significant role in breast cancer risk, particularly in premenopausal women. The finding that risk was greatest among women who consumed lower amounts of dietary antioxidants and was minimal among high consumers indicates that a diet rich in sources of antioxidants may minimize the deleterious effects of the MnSOD polymorphism, thereby supporting public health recommendations for the consumption of diets rich in fruits and vegetables as a preventive measure against cancer.     

Characterization of a negative cis-acting DNA element regulating the transcription of CYP2B1/B2 gene in rat liver

Polymeric films were deposited from hydroxyethylmethacrylate (HEMA) plasma on non-woven poly(butyleneterephtalate) (PBT) filter materials. To test the effect of deposition conditions on surface properties, film were deposited using a constant monomer flow rate and a discharge power ranging from 40-100 W. Surface composition and surface energetics were evaluated by Electron Spectroscopy for Chemical Analysis (ESCA) and contact angle measurement, respectively. Albumin (Alb) and fibrinogen (Fg) adsorption from single protein solutions to the plasma-coated filters was measured. Results illustrate the marked effects of the deposition condition on the surface composition, the surface field of forces, and the protein adsorption behavior. The latter is modeled by the application of the Good-van Oss-Chaudhury theory of Lewis acid-base contribution to interfacial energetics. Materials endowed with widely different properties are obtained from the same monomer and different deposition conditions, a result that must be taken into account both in the production step, to assure constant quality, and in the development of specifically tailored materials.     

Laminar distribution of nicotinic receptor subtypes in human cerebral cortex as determined by [3H](-)nicotine, [3H]cytisine and [3H]epibatidine in vitro autoradiography

We have used gene disruption to isolate two talin (-/-) ES cell mutants that contain no intact talin. The undifferentiated cells (a) were unable to spread on gelatin or laminin and grew as rounded colonies, although they were able to spread on fibronectin (b) showed reduced adhesion to laminin, but not fibronectin (c) expressed much reduced levels of beta1 integrin, although levels of alpha5 and alphaV were wild-type (d) were less polarized with increased membrane protrusions compared with a vinculin (-/-) ES cell mutant (e) were unable to assemble vinculin or paxillin-containing focal adhesions or actin stress fibers on fibronectin, whereas vinculin (-/-) ES cells were able to assemble talin-containing focal adhesions. Both talin (-/-) ES cell mutants formed embryoid bodies, but differentiation was restricted to two morphologically distinct cell types. Interestingly, these differentiated talin (-/-) ES cells were able to spread and form focal adhesion-like structures containing vinculin and paxillin on fibronectin. Moreover, the levels of the beta1 integrin subunit were comparable to those in wild-type ES cells. We conclude that talin is essential for beta1 integrin expression and focal adhesion assembly in undifferentiated ES cells, but that a subset of differentiated cells are talin independent for both characteristics.     

Recent advances in capillary zone electrophoresis of DNA

The present minireview summarizes recent developments in the field of DNA separations by capillary zone electrophoresis (CZE), as developed by our group. Separation of antisense oligonucleotides in sieving liquid polymers in isoelectric buffers is discussed first. It is shown that the use of isoelectric buffers permits very high voltage gradients (up to 1000 V cm-1) with much reduced transit times and increased resolution of all truncated and failed sequences. Oligonucleotides can also be analysed by zone electrophoresis against a stationary pH gradient (typically a pH 6.5-10 range): if injected at the alkaline end, the sample components experience stacking and zone sharpening due to modulation of charge as the oligonucleotides move along the pH gradient. Oligonucleotides having the same length, but differing by one single nucleotide in the chain, can be separated in free solution (i.e. in the absence of a sieving matrix) at strongly acidic pH values (pH 3.0-3.3) where charge differences due to base protonation are maximized. By working in free solution, it has also been possible to measure accurately the free mobility of DNAs, shown to reach a constant value of 3.75 +/- 0.04 10(-4) cm2 V-1 s-1 at 25 degrees C and in Tris-acetate-EDTA buffer, pH 8.3, above a critical length of ca. 400 base pairs. Finally, detection of point mutations in human genomic DNA is proven to be feasible in nonisocratic CZE, by running temperature-programmed CZE. The temperature gradient is activated within the capillary lumen by voltage ramps during the run, by exploiting joule effects. This technique has been proven to work for all point mutants, from low-, to intermediate-, to high-melters and has been applied to a number of point mutants in cystic fibrosis and thalassemia.     

Color Doppler echography in the study of pseudo-occlusion of the internal carotid

The differentiation of pseudo-occlusion from complete internal carotid artery occlusion may have important clinical consequences for patients with the former tend not to benefit from reconstructive surgery. The Authors report a case in which color-Doppler duplex-scanner revealed a persisting string-like lumen that was not demonstrated by angiography. The Authors believe that ultrasonography may in future permit the reliable differentiation of pseudo-from complete carotid occlusion, thereby reducing the need for angiography.     

Neurotoxicity of the drug Ecstasy. Functional consequences of serotonergic hypoactivity

Ingestion of the increasingly popular designer drug, ecstasy, results in an acute increase in the brain's monoamines: serotonin, dopamine, and noradrenaline. Animal research involving ecstasy has shown lasting damage to serotonergic axons and terminals, leading to reduced serotonin transmission in the CNS. Moreover, several studies suggest that the ingestion of ecstasy may be toxic to the human serotonin system. In animals repeated ecstasy administration has not shown persistent behavioural changes. In humans long lasting alterations in sleep pattern, mental state, personality, and cognition have been reported after repeated ecstasy use. However, these results have not been replicated, and most of them originate from uncontrolled studies of rather small populations.