Familial breast/ovarian cancer and BRCA1/2 genetic screening: the role of immunohistochemistry as an additional method in the selection of patients.

Only 20-25% of families screened for BRCA1/2 mutations are found positive. Because only a positive result is informative, we studied the role of BRCA1/2 immunohistochemistry as an additional method for patient selection. From 53 high-risk-affected probands, 18 (34%) had available paraffin blocks of their tumors and were selected for this study. Mutation screening was done by conformation-sensitive gel electrophoresis and multiplex ligation-dependent probe amplification. For immunohistochemistry, 21 neoplastic specimens (15 breast carcinomas, 5 ovary neoplasms, and 1 rectal adenocarcinoma) were analyzed with BRCA1 (monoclonal antibody, Ab-1, oncogene) and BRCA2 (polyclonal antibody, Ab-2, oncogene) antibodies. Absence of the BRCA1 protein was confirmed in negative tumors by Western blotting. Seven patients were positive for BRCA1/2 mutations: 5 for BRCA1 and 2 for BRCA2. Four out of five positive patients had tumors negative for BRCA1 immunostaining, and the remaining 13 BRCA1-negative patients had positive BRCA1 immunostaining in all tumor samples. Sensitivity to predict for BRCA1 mutation carriers was 80%, and specificity was 100%, with a positive predictive value of 100% and a negative predictive value of 93%. This correlation was statistically significant (p=0.001). No correlation was observed for BRCA2. If larger studies confirm these results, high-risk patients with BRCA1-negative tumors should be screened first for this gene.     

Glutamic acid decarboxylase of embryonic avian retina cells in culture: Regulation byγ-aminobutyric acid (GABA)

1. Retina-cell aggregate cultures expressed glutamate decarboxylase activity (L-glutamate 1-carboxylase; EC 4.1.1.15) as a function of culture differentiation. 2. Glutamic acid decarboxylase (GAD) activity was low in the initial phases of culture and increased eight-fold until culture day 7, remaining high up to day 13 (last stage studied). 3. The addition of GABA to the culture medium 24 h after cell seeding almost totally prevented the expression of GAD activity. 4. In association with decreased enzyme activity, aggregates exposed to GABA did not display immunoreactivity for GAD, suggesting that GAD molecules were either lost from GABAergic neurons or significantly altered with GABA treatment. 5. Control, untreated aggregates showed intense GAD immunoreactivity in neurons. Positive cell bodies were characterized by a thin rim of labeled cytoplasm with thickest labeling at the emergence of the main neurite. 6. Heavily labeled patches were also observed throughout the aggregates, possibly reflecting regions enriched in neurites. 7. The GABA-mediated reduction of GAD immunoreactivity was a reversible phenomenon and could be prevented by picrotoxin.     

Linkage disequilibrium analysis in Machado-Joseph disease patients of different ethnic origins

Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar degeneration originally described in families of Portuguese-Azorean ancestry. The hypothesis that its present world distribution could result from the spread of an original founder mutation has been raised. To test this possibility we have conducted a linkage disequilibrium study of markers segregating with the MJD1 locus in a total of 64 unrelated families of different geographical origins. Significant association was detected between the MJD1 locus and marker alleles at loci D14S280, D14S1050 and D14S81. All affected individuals, except one Chinese family, had allele 3 (237 bp) at D14S280. This finding is consistent with a founder effect in our MJD population. However, distinct haplotypes were observed in patients originating from the two Azorean islands showing the highest disease prevalence; therefore, the possible existence of more than one founder mutation can not be excluded with the markers currently available. Received: 27 February 1996 / Revised: 4 June 1996     

Anti-inflammatory effect of l-cysteine (a semi-essential amino acid) on 5-FU-induced oral mucositis in hamsters

Oral mucositis is an inflammation of the oral mucosa mainly resulting from the cytotoxic effect of 5-fluorouracil (5-FU). The literature shows anti-inflammatory action of l-cysteine (l-cys) involving hydrogen sulfide (H₂S). In view of these properties, we investigate the effect of l-cys in oral mucositis induced by 5-FU in hamsters. The animals were divided into the following groups: saline 0.9%, mechanical trauma, 5-FU 60–40 mg/kg, l-cys 10/40 mg and NaHS 27 µg/kg. 5-FU was administered on days 1st to 2nd; 4th day excoriations were made on the mucosa; 5th–6th received l-cys and NaHS. For data analysis, histological analyses, mast cell count, inflammatory and antioxidants markers, and immunohistochemistry (cyclooxygenase-2(COX-2)/inducible nitric oxide synthase (iNOs)/H₂S) were performed. Results showed that l-cys decreased levels of inflammatory markers, mast cells, levels of COX-2, iNOS and increased levels of antioxidants markers and H₂S when compared to the group 5-FU (p < 0.005). It is suggested that l-cys increases the H₂S production with anti-inflammatory action in the 5-FU lesion.

     

Cultivable fungi present in deep-sea sediments of Antarctica: taxonomy,diversity, and bioprospecting of bioactive compounds

Extremophiles - We accessed the culturable mycobiota present in marine sediments at different depths in Antarctica Ocean. Acremonium fusidioides, Penicillium allii-sativi, Penicillium chrysogenum,...     

Black capuchin monkeys dynamically adjust group spread throughout the day

Variation in group spread can affect communication between individuals, synchrony of activity and collective decision-making. Most studies have measured this variation in large time scales, but the variables that influence group spread change as the social unit ranges over different areas throughout the day. Thus, our aim was to analyze the diurnal variation in group spread of a group of black capuchin monkeys (Sapajus nigritus) inhabiting an area within the southeastern Brazilian Atlantic Forest, the Carlos Botelho State Park. We measured group spread as the distance between the coordinates of the location of the two most distant group members every 5 min during entire days. Using time series analysis, we found that the group spread varied within short periods of time (15 min) throughout the day, revolving around the average group spread distance of 36 m. Group members tended to decrease the interindividual distance over time when they were more than 36 m apart, and to increase the distance when they were at a distance of less than 36 m. In addition, group spread was higher when monkeys were eating fruit than during other activities. We conclude that the variation in group spread may reflect competition for discrete food resources and that increasing cohesion several times throughout the day can be a way of resuming social contact between individuals.

     

Reproductive biology of the white marlin (Kajikia albida) in the southwestern and equatorial Atlantic Ocean

The present work describes the reproductive biology of the white marlin (Kajikia albida) caught in the southwestern and equatorial Atlantic Ocean. The gonads of 924 fish were collected by observers on board Brazilian tuna longliners, between November 2004 and December 2006. The spawning season was assessed by the monthly frequency distribution of distinct stages of maturity and monthly mean female gonadosomatic index GSI. Sixty-one percent (n = 656) of the fish examined were female, with a Lower Jaw Fork Length (LJFL) between 83 and 236 cm (mean = 155.5 ± 16.63). The 268 males had a LJFL between 90 and 220 cm (mean = 152.3 ± 34.62). Although the northeastern region of Brazil does not appear to be a significant spawning area for the species, the results suggest a higher reproductive activity in the third quarter of the year. Using a Bayesian logistic model approach, length at 50% maturity was estimated at 145.04 cm (credibility interval of 95%, 143.94–146.09 cm), for females, and at 140.03 cm (credibility interval of 95%, 137.28–142.52 cm), for males.     

Gamma-Decanolactone Alters the Expression of GluN2B,A1 Receptors,and COX-2 and Reduces DNA Damage in the PTZ-Induced Seizure Model After Subchronic Treatment in Mice

Neurochemical Research - Gamma-decanolactone (GD) has been shown to reduce epileptic behavior in different models, inflammatory decreasing, oxidative stress, and genotoxic parameters. This study...