Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation.

Splenic marginal zone lymphoma (SMZL) is a B-cell neoplasm whose molecular pathogenesis remains fundamentally unexplained, requiring more precise diagnostic markers. Previous molecular studies have revealed 7q loss and mutations of nuclear factor κB (NF-κB), B-cell receptor (BCR) and Notch signalling genes. We performed whole-exome sequencing in a series of SMZL cases. Results confirmed that SMZL is an entity distinct from other low-grade B-cell lymphomas, and identified mutations in multiple genes involved in marginal zone development, and others involved in NF-κB, BCR, chromatin remodelling and the cytoskeleton.

Polymorphisms and haplotypes across the osteoprotegerin gene associated with bone mineral density and osteoporotic fractures.

UNLABELLED: Osteoprotegerin plays a key role in bone remodelling. We studied the association between 24 polymorphisms and haplotypes on the OPG gene and bone mineral density and fractures. After multiple-testing correction, one SNP and two block-haplotypes were significantly associated with FN BMD. Two other block-haplotypes were associated with fracture. INTRODUCTION AND HYPOTHESIS: Osteoprotegerin (OPG) plays a key role in bone remodelling. Here we studied the association between polymorphisms and haplotypes on the OPG gene and bone mineral density (BMD) and fractures. METHODS: Twenty-four single nucleotide polymorphisms (SNPs) were selected to cover six haplotypic blocks and were genotyped in 964 postmenopausal Spanish women. Haplotypes were established with HaploStats. Association was analysed by GLM (for BMD) and logistic regression (for fractures) both at single SNP and haplotype levels. RESULTS: Upon adjustment for multiple testing (p < 0.0073), one of the SNPs (SNP #17, rs1032129) remained significantly associated with FN BMD (p = 0.001). Four block-haplotypes stood multiple-testing correction. Two remained associated with FN BMD and two with fracture. The association of block-4 haplotype "AC" (of SNPs #18 and #17) with FN BMD (p = 0.0002) was stronger than that of SNP#17 alone and was the best result overall. A global assessment of the results indicated that all the alleles and haplotypes with a protective effect, at p < 0.05, belonged to a frequent long-range haplotype. CONCLUSIONS: In conclusion, these results provide a detailed picture of the involvement of common variants and haplotypes of the OPG gene in bone phenotypes.

Polymorphisms in the interleukin-6 receptor gene are associated with bone mineral density and body mass index in Spanish postmenopausal women.

OBJECTIVE: Osteoporosis and obesity are complex diseases with a strong genetic component. Bone mineral density (BMD) and body mass index (BMI) linkage studies identified a locus at 1q21-23, where the interleukin-6 receptor (IL6R) gene is located. The IL6R and the gp130 receptors are the mediators of IL6 action. Serum levels of IL6 and sIL6R (the soluble form of IL6R) are higher in several diseases such as osteoporosis or obesity. Variants at IL6R have been associated with BMI and obesity. However, IL6R is an as-yet-unexplored osteoporosis candidate gene. DESIGN: In the present study we analysed two polymorphisms in the IL6R promoter, -1435 C/T (rs3887104) and -208 G/A (rs4845617), and the Asp358Ala polymorphism (rs8192284), in relation to both BMD and BMI in a cohort of 559 postmenopausal Spanish women. RESULTS: The promoter polymorphisms, -1435 C/T and -208 G/A were associated with femoral neck (FN) BMD (P=0.011 and P=0.025 respectively). The C-A and T-G promoter haplotypes were also associated with FN BMD. Additionally, the Asp358Ala variant was associated with lumbar spine BMD (P=0.038). Finally, the -208 G/A polymorphism and the C-G and C-A haplotypes were associated with BMI and obesity, where GG was the risk genotype (P=0.033 for BMI; P=0.010 for obesity). CONCLUSION: These data suggest that variants in the IL6R gene are not only involved in the determination of BMI but also relevant for the determination of BMD. The IL6R gene may belong to the growing list of genes known to be involved in both phenotypes.

Empoderamento e recursos para a participação em conselhos gestores / Empowerment and resources for participation in management councils

A criação de conselhos gestores a partir de 1988 suscitou diversas experiências participativas, embora ainda predominem práticas autoritárias que inviabilizam a participação e o empoderamento. O objetivo deste estudo foi mapear recursos para o empoderamento/participação, em quatro conselhos municipais gestores de Itajaí/SC: Saúde, Assistência social, Segurança alimentar e Nutricional e do Idoso. Foram colhidas informações junto aos conselhos e aplicados 53 questionários aos participantes. A maioria está na idade adulta, são mulheres, possuem alto grau de escolaridade e foi indicada para o conselho sem eleição; metade recebe entre 1-5 salários mínimos e outra, entre 6-10 ou mais; um terço refere algum tipo de formação para atuar. O alto grau de escolaridade é recurso positivo, porém, pode indicar que as entidades valorizam apenas a participação de pessoas preparadas, excluindo as camadas menos favorecidas. Isto associado ao fato de que a maioria não foi eleita sugere que os representantes podem ser pouco legítimos e representativos. Os achados nos fazem considerar que existem alguns recursos positivos, porém outros nem tanto e há questões que devem ser aprofundadas para buscar maior compreensão em relação à possibilidade de influírem na participação.

Empoderamento e recursos para a participação em conselhos gestores / Empowerment and resources for participation in management councils

A criação de conselhos gestores a partir de 1988 suscitou diversas experiências participativas, embora ainda predominem práticas autoritárias que inviabilizam a participação e o empoderamento. O objetivo deste estudo foi mapear recursos para o empoderamento/participação, em quatro conselhos municipais gestores de Itajaí/SC: Saúde, Assistência social, Segurança alimentar e Nutricional e do Idoso. Foram colhidas informações junto aos conselhos e aplicados 53 questionários aos participantes. A maioria está na idade adulta, são mulheres, possuem alto grau de escolaridade e foi indicada para o conselho sem eleição; metade recebe entre 1-5 salários mínimos e outra, entre 6-10 ou mais; um terço refere algum tipo de formação para atuar. O alto grau de escolaridade é recurso positivo, porém, pode indicar que as entidades valorizam apenas a participação de pessoas preparadas, excluindo as camadas menos favorecidas. Isto associado ao fato de que a maioria não foi eleita sugere que os representantes podem ser pouco legítimos e representativos. Os achados nos fazem considerar que existem alguns recursos positivos, porém outros nem tanto e há questões que devem ser aprofundadas para buscar maior compreensão em relação à possibilidade de influírem na participação. (AU)

[Evaluation of the Spiral method to determine the MIC of various antibiotics]. / Evaluation de la méthode spiral pour déterminer la CMI de divers antibiotiques.

The determination of minimal inhibitory concentrations (MICs), which is sometimes necessary in routine, is cumbersome. We tried to compare the Spiral gradient endpoint method, using the Spiral plater in order to prepare continual antibiotic gradient plates, vs. the reference agar dilution MIC determination. In an attempt to evaluate this method, 6 different antibiotics and 10 to 20 various strains with each antibiotic were used: imipenem and P. cepacia, imipenem, amikacin, ciprofloxacin and P. aeruginosa, vancomycin, teicoplanin and Streptococcus sp., Enterococcus sp., penicillin G and S. pneumoniae. The MICs obtained with the Spiral method were shown by regression analysis to be similar to the MICs obtained with the reference agar dilution method. Rates of agreement (+/- 1 dilution) between the two methods were > or = 90 p. cent for all six antibiotics tested and minor discrepancies between the categories S, I, R were only found for imipenem and penicillin. The Spiral gradient endpoint method for MIC determination seems to be interesting in routine because it is a reproducible and sensitive method, which reduces materials and personnel time.

[Determination of factors promoting, in vitro, the expression of adhesion of Pseudomonas aeruginosa to buccal cells]. / Détermination des facteurs favorisant, in vitro, l'expression de l'adhésion de Pseudomonas aeruginosa aux cellules buccales.

The composition of the bacterial flora in the upper respiratory tract is closely correlated with the type of pathogens recovered from the respiratory tract in patients. In intensive care patients, colonization of the oral cavity with Gram-negative organisms increases the risk of Gram-negative respiratory tract infection; the ability of bacterial cells to attach to buccal cells seems to play a central role in this correlation. Similar findings have been reported in chronic respiratory tract infections, including bronchiectasis and cystic fibrosis, with Pseudomonas aeruginosa colonization. This study was undertaken to determine the conditions best suited to in vitro detection of adhesion of P. aeruginosa to buccal cells. Use of brain-heart-infusion medium, incubation at 35 degrees C for 2 hours, and a bacterial concentration of 2 x 10(9) cells/ml were the factors correlated with improved detection of adhesion to buccal cells. Furthermore, attachment of bacteria to buccal cells was not found to vary across donors or over time in a given donor. Adhesion was independent of cell viability.

Adherence and hemagglutination of Corynebacterium group D2.

Sixty-one strains of Corynebacterium group D2 were examined for their ability to adhere to human uroepithelial cells and to agglutinate human and guinea-pig erythrocytes. Strains were isolated from samples of two origins: urine of bacteriuric patients and healthy skin of patients without urinary infection. In addition, the isolates were examined by scanning and transmission electron microscopy. Heavy adherence to the uroepithelial cells but weak hemagglutination were noted. No statistical association was demonstrated between the adherence and the origin of the strains (65.2% of urinary isolates and 80% of healthy skin isolates were adherent). On transmission electron microscopy, a close association was observed between adherent bacteria and cells on thin sections and only few strains were piliated with negative staining. These results do not support a role of adherence as a predictor of pathogenicity of Corynebacterium group D2 which seems to act as an opportunistic pathogen in urinary tract infections.

[In vitro bactericidal activity of tobramycin and amikacin alone or in combination against Pseudomonas aeruginosa isolated from patients with cystic fibrosis]. / Activité bactéricide in vitro de tobramycine et amikacine seuls et en association vis-à-vis de Pseudomonas aeruginosa isolés de patients atteints de mucoviscidose.

The bactericidal kinetic of 60 P. aeruginosa isolates (40 from cystic fibrosis sputum and 20 from various origins) was studied. Liquid medium micromethod was performed. Bacteria were incubated with tobramycin and amikacin alone at several concentrations and combined with piperacillin, cefsulodin, ceftazidim, imipenem, and ciprofloxacin at concentrations obtained in vivo. When used alone, tobramycin showed the most rapid bactericidal activity, whatever the concentration used. The bactericidal activity (greater than or equal to 99.99% killing of the inoculum) was obtained in 5 hours, with 1 or 2 x MIC of the majority of the strains, with the 2 aminoglycosides. No difference was found between tobramycin and amikacin, when combinated with an antibiotic which provides a notable increase of the rapidity of the bactericidal activity. The combination of amikacin plus imipenem was more rapidly bactericidal: 48% of strains; 26% were synergistically inhibited by amikacin plus ciprofloxacin. When correlated with the susceptibility patterns of studied micro-organisms, the results were rather unpredictive.

Effects of five antibiotics on adhesion and haemagglutinating properties of Pseudomonas aeruginosa isolated from cystic fibrosis patients.

The aim of this study was to evaluate the in vitro effect of five antibiotics at sub-inhibitory concentrations on the adhesive and haemagglutinating properties of Pseudomonas aeruginosa isolated from cystic fibrosis sputa. Eleven isolates (mucoid and non-mucoid) from cystic fibrosis, and four isolates (mucoid and non-mucoid) from other chronic respiratory infections were tested. The adhesion test was performed on human lymphoblastoid cell-lines; the haemagglutination test used human O+ and guinea-pig erythrocytes. The antibiotics were tested at six sub-inhibitory concentrations, from MIC/2 to MIC/64. Among the five antibiotics, cefsulodin and pefloxacin were the most active in decreasing the adhesive properties: this effect was statistically significant at MIC/2 and MIC/4 for cefsulodin and at all sub-inhibitory concentrations for pefloxacin. No differences appeared between mucoid and non-mucoid strains, and no correlation was noted with their clinical origins. The three other antibiotics (ceftazidime, latamoxef and imipenem) had no significant effect on the adhesion of all the strains tested, but their effect was rather strain-dependent. This fact and the heterogeneity found in adherence and haemagglutinating activity of each strain suggest that the adhesins and the haemagglutinins of P. aeruginosa are very complex structures.

[In vitro study of the effects of oxolinic acid at sub-inhibitory concentrations on the activity of hemagglutinins and adhesion to uroepithelial cells by Escherichia coli isolated from urine]. / Etude in vitro des effets de l'acide oxolinique à concentrations sub-inhibitrices sur l'activité des hémagglutinines et de l'adhésion aux cellules uro-épithéliales des Escherichia coli isolés des urines.

The aim of the present study was to investigate the effects of sub-MIC doses of oxolinic acid (quinolone), widely used in the treatment of urinary tract infections, on both haemagglutinating activity and adhesion capacity of 13 Escherichia coli strains isolated from urine during acute cystitis or pyelonephritis. All these strains adhered to uroepithelial cells and showed mannose-sensitive and/or mannose-resistant haemagglutinating activity. Sub-MIC doses of oxolinic acid induced filaments in most of the bacterial cultures; however, inhibition of haemagglutination and adhesion was variable in vitro. When inhibition did take place in any one strain, both haemagglutination and adhesion were affected. These results confirm those of other authors and indicate that the effect of sub-MIC doses of a given antibiotic is strain-specific; they also indirectly show the heterogeneity of E. coli strains isolated from urine. It thus seems unlikely that, in clinical conditions, a single antibiotic is capable of reducing adhesion, given the diversity of the adhesins found in pathogenic E. coli strains.