Synergy between the genes for butyrylcholinesterase K variant and apolipoprotein E4 in late-onset confirmed Alzheimer's disease

The allelic frequency of the gene for the K variant of butyrylcholinesterase (BCHE-K) was 0.17 in 74 subjects with late-onset (age > 65 years) histopathologically diagnosed Alzheimer's disease (AD), which was higher than the frequencies in 104 elderly control subjects (0.09), in 14 early-onset cases of confirmed AD (0.07) and in 29 confirmed cases of other dementia (0.10). The association of BCHE-K with late-onset AD was limited to carriers of the epsilon 4 allele of the apolipoprotein E gene (APOE), among whom the presence of BCHE-K gave an odds ratio of confirmed late-onset AD of 6.9 (95% C.I. 1.65-29) in subjects > 65 years and of 12.8 (1.9-86) in subjects > 75 years. In APOE epsilon 4 carriers over 75 years, only 1/22 controls, compared with 10/24 confirmed late-onset AD cases, had BCHE-K. We suggest that BCHE-K, or a nearby gene on chromosome 3, acts in synergy with APOE epsilon 4 as a susceptibility gene for late-onset AD.      

The salivary microbiota as a diagnostic indicator of oral cancer: A descriptive,non-randomized study of cancer-free and oral squamous cell carcinoma subjects

Background  

The purpose of the present investigation was to determine if the salivary counts of 40 common oral bacteria in subjects with an oral squamous cell carcinoma (OSCC) lesion would differ from those found in cancer-free (OSCC-free) controls.     

Development-dependent inheritance of 5-azacytidine-induced epimutations in triticale: analysis of rDNA expression patterns

Genomic imprinting of rye origin rDNA sequences in triticale is modulated by DNA methylation responsible for ontogenic expression patterns of those sequences. Considering the dynamic nature of these phenomena, we evaluated the influence of plant development on the inheritance of modified rye rDNA expression patterns. DNA hypomethylation was induced in triticale by 5-azacytidine (5AC) treatments at distinct developmental stages of M₁ plants, and expression patterns were analysed in M₂. The activity of rye origin rRNA genes in progeny of untreated and 5AC-treated plants was evaluated by silver staining in meristematic root tip cells and in meiocytes at diplotene. In the progeny of 5AC-treated plants, a significant increase in rye rDNA expression was observed, contrasting with the residual activity in untreated plants. Significant differential effects of 5AC treatments were observed in M₂ plants and correlated with the M₁ plant developmental stage in which DNA hypomethylation was induced. Hypotheses to explain the origin of those differences are discussed here.This revised version was published online in November 2005 with corrections to the Cover Date.     

What Are the Maternal Factors that Potentially Intervenes in the Nutritional Composition of Human Milk?

Background: To evaluate the potential factors associated with the nutritional composition of human milk of puerperal women. Methods: cross-sectional study, conducted between March 2016 and August 2017, with 107 women, selected in a Tertiary Health Care Tertiary Health Facility of the Unified Health System (SUS) in the Municipality of Rio de Janeiro. Data were collected two months after delivery. The dependent variable of the study was the nutritional composition of human milk. We divided the independent variables into hierarchical levels: distal (age, schooling, parity and pregestational nutritional status), intermediate (number of prenatal visits and gestational weight gain) and proximal (alcohol consumption, smoking, diabetes mellitus and hypertension). For data analysis, we applied the multiple linear regression, centered on the hierarchical model. Only the variables associated with the nutritional composition of breast milk remained in the final model at a 5% level of significance. Results: The nutritional composition of human milk yielded by women with pregestational overweight, smokers and hypertensive had higher amounts of lipids and energy. Conversely, women with gestational weight gain below the recommended had lower amounts of these components. Conclusion: The evaluation of factors associated with the nutritional composition of human milk is extremely important to assist post-partum care practices. In this study, we observed that lipid and energy contents were associated to pregestational nutritional status, gestational weight gain, smoking and hypertension.     

X-radiation induces 8-hydroxy-2'-deoxyguanosine formation in vivo in rat mammary gland DNA

Ionizing radiation is a carcinogen that induces oxidative DNA damage. 8- Hydroxy-2'-deoxyguanosine (8-OHdG) is a relatively abundant, mutagenic lesion that is widely regarded as a reliable index of oxidative DNA damage. The purpose of this study was to examine the effects of X- radiation on levels of 8-OHdG in the context of an experimental model for breast cancer in which chronic radiation exposure has been shown to be carcinogenic in Sprague-Dawley rats. A secondary objective of this study was to determine if the use of phenol during DNA isolation affected the concentration of 8-OHdG subsequently measured. Our results indicate that a profoundly carcinogenic dose of radiation induced a small but significant increase in 8-OHdG concentration in mammary gland DNA, and that the use of a phenol-based versus a salt-based method of DNA isolation had no significant impact on the levels of 8-OHdG detected in either control or irradiated tissue.      

Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and cancer susceptibility. Mutations within the FA complementation group C (FAC) gene account for approximately 14% of diagnosed FA cases. Two mutations, one in exon 1 (delG322) and one in exon 4 (IVS4 + 4 A to T), account for 90% of known FAC mutations. The delG322 mutation results in a mild FA phenotype, while the IVS4 + 4 A to T mutation results in severe FA phenotype. To determine the molecular basis for this clinical variability, we analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the delG322 mutation expressed a 50-kD FAC polypeptides, FRP-50 (FAC-related protein), shown to be an amino terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 + 4 A to T mutation lacked FRP-50. Overexpression of a cDNA encoding FRP-50 in an FA(C) cell line resulted in partial correction of mitomycin C sensitivity. In conclusion, expression of an amino terminal truncated FAC protein accounts, at least in part, for the clinical heterogeneity among FA(C) patients.