Biochemical and Neuropathological Findings in a Creutzfeldt-Jakob Disease Patient with the Rare Val180Ile-129Val Haplotype in the Prion Protein Gene.

Genetic Creutzfeldt-Jakob disease (gCJD) associated with the V180I mutation in the prion protein (PrP) gene (PRNP) in phase with residue 129M is the most frequent cause of gCJD in East Asia, whereas it is quite uncommon in Caucasians. We report on a gCJD patient with the rare V180I-129V haplotype, showing an unusually long duration of the disease and a characteristic pathological PrP (PrPSc) glycotype. Family members carrying the mutation were fully asymptomatic, as commonly observed with this mutation. Neuropathological examination showed a lesion pattern corresponding to that commonly reported in Japanese V180I cases with vacuolization and gliosis of the cerebral cortexes, olfactory areas, hippocampus and amygdala. PrP was deposited with a punctate, synaptic-like pattern in the cerebral cortex, amygdala and olfactory tract. Western blot analyses of proteinase-K-resistant PrP showed the characteristic two-banding pattern of V180I gCJD, composed of mono- and un-glycosylated isoforms. In line with reports on other V180I cases in the literature, Real-Time Quaking Induced Conversion (RT-QuIC) analyses did not demonstrate the presence of seeding activity in the cerebrospinal fluid and olfactory mucosa, suggesting that this haplotype also may result in a reduced seeding efficiency of the pathological PrP. Further studies are required to understand the origin, penetrance, disease phenotype and transmissibility of 180I-129V haplotype in Caucasians.

[LIFE CONDITIONS: NON-SPECIFIC STRESS INDICATORS AND DENTOALVEOLAR PATHOLOGIES]. / LE CONDIZIONI DI VITA: INDICATORI DI STRESS ASPECIFICI E AFFEZIONI DENTO-ALVEOLARI.

Trauma, diseases, diet, daily work and environmental factors shape bodies. From birth to death, these processes leave on the skeleton markers that can be recognized and studied, thus providing an overview of the health conditions of past populations. The present work analyzes data collected in seven necropolises. During our study, we exploited nonspecific stress and dental pathologies as key indicators of health conditions. In particula; we analyzed the three most common indicators of stress: porotic hyperostosis; enamel hypoplasia; and Harris lines on shins. Additionally, we examined the most important dental alveolar pathologies, including carious lesions, periodontal diseases, antemortem tooth loss, abscesses, and calculi. The data we analyzed suggest that, despite the different urban and suburban origins, all the samples belong to a middle-range or low social class, whose living conditions were modest. The only necropolis which stands out is Casal Bertone Mausoleo, where the samples present the lowest frequencies with respect to both the stress indicators and the oral pathologies, suggesting better living conditions.

GSTT1 and GSTM1 gene polymorphisms in European and African populations.

Glutathione S-transferases (GSTs) are a superfamily of detoxificant enzymes. Pharmacogenomic studies have revealed interethnic differences in GST allelic frequencies. This study is focused on GSTT1 (gene deletion, rs17850155, rs2234953, and rs11550605) and GSTM1 (gene deletion) gene frequency distributions in two population samples of Europe origin (Italy, n = 120; Spain, n = 94) and two population samples of Africa origin (Cameroon, n = 126; Ethiopia, n = 153). Detection of GSTT1 and GSTM1 null genotypes was performed by multiplex PCR analysis, while the other GSTT1 gene polymorphisms were detected using allele specific PCR and sequencing. GSTT1 and GSTM1 null frequencies in the samples analyzed fit with the variability range observed in European and African populations, respectively. The SNP analysis in GSTT1 gene did not highlight any nucleotide substitution in 493 individuals analyzed. The comparisons among GSTM1 and GSTT1 null phenotype frequencies in worldwide populations show different patterns between Asians, Africans, and Europeans. Important insights into the effects of GSTM1 and GSTT1 gene deletions on the pathogenesis of human diseases have been hypothesized. Detailed studies on the geography of GST variants could therefore increase knowledge about the relationship between ethnicity and the prevalence of certain diseases.

Serum proteins and work habits in a group of farm-workers exposed to EBDCs.

BACKGROUND: Study of the association between genetic variability and individual susceptibility can help to characterize occupational or environmental risks due to xenobiotics. AIM: This study evaluates the influence of genetic components and environmental factors in relation to pesticide exposure. SUBJECTS AND METHODS: The study population consisted of 37 non-occupationally exposed workers and 74 farm-workers exposed to pesticide. Exposure was assessed through the measurement of urine concentration of ethylenethiourea (ETU). Genetic differences in drug metabolism were detected by a qualitative variability in serum proteins. The environmental factors were recorded by using a questionnaire. RESULTS: The results show a difference between ETU levels in farm-workers and in non-occupationally exposed workers. In the non-exposed group a relationship between ETU urinary concentration and lifestyle habits is present. In farm-workers ETU urinary concentration is less correlated with lifestyle habits, but is associated, rather, with their work. In the exposed individuals the serum protein analyses show a possible link between ETU urinary concentration and the polymorphism of group-specific component (Gc). CONCLUSIONS: The association between Gc polymorphism and ETU urinary concentration of subjects exposed to EBDCs could be due to the immunological function of Gc and the effects on the immune system of EBDCs.

Glutathione S-transferase ω class (GSTO) polymorphisms in a sample from Rome (Central Italy).

Glutathione S-transferases are a superfamily of enzymes that are involved in biotransformation of drugs, xenobiotics and play a fundamental role in the protection of cells from oxidative stress. In humans, the recently described GST Omega class contains two expressed genes GSTO1 and GSTO2, located on chromosome 10 (10q24.3). Four polymorphisms in GSTO genes have been identified in ethnic groups: GSTO1*A140D (rs4925), GSTO1*E155del (rs56204475), GSTO1*E208K (rs11509438) and GSTO2*N142D (rs156697). This study provides the allele frequencies of GSTO polymorphism in a sample consisting of 116 apparently healthy individuals of both sexes from Rome (Central Italy). Detection of GSTO1*A140D and GSTO2*N142D alleles was performed by PCR-RFLP analysis, while GSTO1*E155del and GSTO1*E208K alleles were detected using the Confronting Two-Pair Primers analysis (PCR-CTPP) and allele specific PCR, respectively. The GSTO allele frequencies found in the Italian sample were included in the variability range observed in European populations. Comparison between the data presented in this study and data in previous studies showed different patterns among European, Asian and African populations.

Modulation of the GSTT1 activity by the GSTM1 phenotype in a sample of Italian farm-workers.

Glutathione S-transferase (GST) isozymes catalyze nucleophilic attack by reduced Glutathione (GSH) on a variety of electrophilic compounds and play a central role in biotransformation of xenobiotics (Hayes et al., Annu Rev Pharmacol Toxicol 45:51-88, 2005). We performed a case-control study to evaluate the GSTM1 and GSTT1 polymorphisms and to investigate if exposure to pesticides conditions the GSTT1 activity level in 115 healthy controls and 90 farm-workers exposed to pesticides. Polymorphisms were investigated using a GSTM1 or a GSTT1-specific PCR. Enzyme activity was measured by means of DCM as co-substrate, as described by Bruhn et al. (Biochem Pharmacol 56:1189-1193, 1998). There was no significant difference between the farm-workers and the healthy controls regarding the distribution of various alleles of the GSTM1 and GSTT1 genes and the GSTT1 enzyme activity. In farm-workers, the GSTM1 null genotype was associated with a significant increase of GSTT1 activity, suggesting a regulative mechanism common to GSTM1 and GSTT1 enzymes after exposure to xenobiotics.