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1.  The progression from obesity to type 2 diabetes in Alström syndrome 
Pediatric Diabetes  2011;13(1):59-67.
Background
Alström syndrome (ALMS) is a rare autosomal recessive monogenic disease associated with obesity, hyperinsulinemia and alterations of glucose metabolism that often lead to the development of type 2 diabetes in a young age.
Objective
Relationship between weight and metabolism has been studied in a group of ALMS patients and matched controls.
Research design and methods
Fifteen ALMS patients (8 M, 7 F, aged 3-51 yrs) were compared in a cross-sectional study with an age- and weight-matched control population. Anthropometric parameters, fat mass, glucose and insulin secretion in basal and dynamic (OGTT) conditions were measured. Further anthropometric and body composition data were obtained from an International group of 27 ALMS patients (13 M, 14 F, age range: 4-29 yrs).
Results
In ALMS we observed an inverse correlation between age and SDS for height, weight and BMI. The OGTT glycemic curves of ALMS subjects were similar to those of age-matched controls, while insulin response was clearly greater. In ALMS individuals the insulin response showed a reduction with age. We documented pathologic values of the derived indices HOMA-IR, ISI, HOMA%β cell and Insulinogenic Index in ALMS, but unlike the insulin-resistance indices, the beta-cell function indices showed a significant reduction with age.
Conclusions
In ALMS the progression from the early onset obesity towards the impaired fasting glucose or IGT and overt diabetes is mostly due to a progressive failure of β-cell insulin secretion without any further worsening of insulin resistance with age, even in the presence of weight reduction.
doi:10.1111/j.1399-5448.2011.00789.x
PMCID: PMC3345208  PMID: 21722283
Alström syndrome; ALMS1; obesity; diabetes; insulin resistance
2.  Comparative diffusion assay to assess efficacy of topical antimicrobial agents against Pseudomonas aeruginosa in burns care 
Background
Severely burned patients may develop life-threatening nosocomial infections due to Pseudomonas aeruginosa, which can exhibit a high-level of resistance to antimicrobial drugs and has a propensity to cause nosocomial outbreaks. Antiseptic and topical antimicrobial compounds constitute major resources for burns care but in vitro testing of their activity is not performed in practice.
Results
In our burn unit, a P. aeruginosa clone multiresistant to antibiotics colonized or infected 26 patients over a 2-year period. This resident clone was characterized by PCR based on ERIC sequences. We investigated the susceptibility of the resident clone to silver sulphadiazine and to the main topical antimicrobial agents currently used in the burn unit. We proposed an optimized diffusion assay used for comparative analysis of P. aeruginosa strains. The resident clone displayed lower susceptibility to silver sulphadiazine and cerium silver sulphadiazine than strains unrelated to the resident clone in the unit or unrelated to the burn unit.
Conclusions
The diffusion assay developed herein detects differences in behaviour against antimicrobials between tested strains and a reference population. The method could be proposed for use in semi-routine practice of medical microbiology.
doi:10.1186/1476-0711-10-27
PMCID: PMC3146812  PMID: 21702921
Pseudomonas aeruginosa; burns; silver sulphadiazine; antiseptics; ERIC-PCR; diffusion assay
3.  ALMS1-Deficient Fibroblasts Over-Express Extra-Cellular Matrix Components, Display Cell Cycle Delay and Are Resistant to Apoptosis 
PLoS ONE  2011;6(4):e19081.
Alström Syndrome (ALMS) is a rare genetic disorder (483 living cases), characterized by many clinical manifestations, including blindness, obesity, type 2 diabetes and cardiomyopathy. ALMS is caused by mutations in the ALMS1 gene, encoding for a large protein with implicated roles in ciliary function, cellular quiescence and intracellular transport. Patients with ALMS have extensive fibrosis in nearly all tissues resulting in a progressive organ failure which is often the ultimate cause of death. To focus on the role of ALMS1 mutations in the generation and maintenance of this pathological fibrosis, we performed gene expression analysis, ultrastructural characterization and functional assays in 4 dermal fibroblast cultures from ALMS patients. Using a genome-wide gene expression analysis we found alterations in genes belonging to specific categories (cell cycle, extracellular matrix (ECM) and fibrosis, cellular architecture/motility and apoptosis). ALMS fibroblasts display cytoskeleton abnormalities and migration impairment, up-regulate the expression and production of collagens and despite the increase in the cell cycle length are more resistant to apoptosis. Therefore ALMS1-deficient fibroblasts showed a constitutively activated myofibroblast phenotype even if they do not derive from a fibrotic lesion. Our results support a genetic basis for the fibrosis observed in ALMS and show that both an excessive ECM production and a failure to eliminate myofibroblasts are key mechanisms. Furthermore, our findings suggest new roles for ALMS1 in both intra- and extra-cellular events which are essential not only for the normal cellular function but also for cell-cell and ECM-cell interactions.
doi:10.1371/journal.pone.0019081
PMCID: PMC3082548  PMID: 21541333
4.  Multilocus sequence typing supports the hypothesis that Ochrobactrum anthropi displays a human-associated subpopulation 
BMC Microbiology  2009;9:267.
Background
Ochrobactrum anthropi is a versatile bacterial species with strains living in very diverse habitats. It is increasingly recognized as opportunistic pathogen in hospitalized patients. The population biology of the species particularly with regard to the characteristics of the human isolates is being investigated. To address this issue, we proposed a polyphasic approach consisting in Multi-Locus Sequence Typing (MLST), multi-locus phylogeny, genomic-based fingerprinting by pulsed-field gel electrophoresis (PFGE) and antibiotyping.
Results
We tested a population of 70 O. anthropi clinical (n = 43) and environmental (n = 24) isolates as well as the type strain O. anthropi ATCC49188T and 2 strains of Ochrobactrum lupini and Ochrobactrum cytisi isolated from plant nodules. A Multi-Locus Sequence Typing (MLST) scheme for O. anthropi is proposed here for the first time. It was based on 7 genes (3490 nucleotides) evolving mostly by neutral mutations. The MLST approach suggested an epidemic population structure. A major clonal complex corresponded to a human-associated lineage since it exclusively contained clinical isolates. Genomic fingerprinting separated isolates displaying the same sequence type but it did not detect a population structure that could be related to the origin of the strains. None of the molecular method allowed the definition of particular lineages associated to the host-bacteria relationship (carriage, colonisation or infection). Antibiotyping was the least discriminative method.
Conclusion
The results reveal a human-associated subpopulation in our collection of strains. The emergence of this clonal complex was probably not driven by the antibiotic selective pressure. Therefore, we hypothesise that the versatile species O. anthropi could be considered as a human-specialized opportunistic pathogen.
doi:10.1186/1471-2180-9-267
PMCID: PMC2810298  PMID: 20021660

Results 1-4 (4)