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.     

Ophthalmic manifestations of vertebral artery dissection. Patients seen at the Mayo Clinic from 1976 to 1992

PURPOSE: To determine the ophthalmic manifestations of vertebral artery dissections. METHODS: Fifty-one separate episodes of vertebral artery dissections evaluated at the Mayo Clinic from 1976 through 1992 were studied. In all cases, the diagnosis had been documented with angiography. RESULTS: There were 28 men and 19 women (mean and median age, 39 and 40 years, respectively; range, 8-61 years). There were ophthalmic findings in 86% of the episodes. Visual symptoms, in decreasing order of frequency, were diplopia (45% of the episodes), blurred vision (14%), transient visual dimming (8%), oscillopsia (4%), photophobia (4%), upside-down vision (2%), positional transient visual obscuration (2%), and unilateral dry eye (2%). Ophthalmic signs in decreasing order of frequency were nystagmus (37% of the episodes), ocular misalignment (cranial nerve palsy or skew) (33%), Horner syndrome (27%), decreased corneal sensation (22%), ptosis (16%), visual field defect (10%), abnormal pursuits and saccades (6%), ocular bobbing (4%), internuclear ophthalmoplegia (4%), anisocoria (4%), and pinpoint pupils (2%). CONCLUSION: Vertebral artery dissections occur in a relatively young population. Most of the patients in our study had ophthalmic manifestations at the time of diagnosis. Heightened awareness of this entity should enable the consulting ophthalmologist to have a role in the diagnosis and treatment of vertebral artery dissection.     

No detectable bioeffects following acute exposure to high peak power ultra-wide band electromagnetic radiation in rats

A wide range assessment of the possible bioeffects of an acute exposure to high peak power ultra-wide band (UWB) electromagnetic radiation was performed in rats. The UWB-exposure consisted of 2 min of pulsed (frequency: 60 Hz, pulse width: 5-10 ns) UWB (bandwidth: 0.25-2.50 GHz) electromagnetic radiation. Rats were examined using one of the following: 1) a functional observational battery (FOB); 2) a swimming performance test; 3) a complete panel of blood chemistries; or 4) determination of the expression of the c-fos protein in immunohistologically-stained sections of the brain. No significant differences were found between UWB- or sham-exposed rats on any of the measured parameters.     

V beta-specific immunotoxin selectively kills acetylcholine receptor-reactive T lymphocytes from mice with experimental autoimmune myasthenia gravis

Immunization of C57BL/6 mice with purified acetylcholine receptor (AChR) is known to induce a T cell-dependent antibody response that results in experimental autoimmune myasthenia gravis (EAMG). Since past observations link V beta 6+ T cells with a prominent AChR epitope specificity, a V beta 6-specific immunotoxin (VIT6) was tested in vitro for its ability to selectively kill monoclonal and polyclonal T cells that demonstrate reactivity against AChR. Results described below clearly demonstrate the ability to selectively kill AChR-reactive T cells based on their expression of a particular V beta-associated antigen receptor.