Selection of rifampicin-resistant Staphylococcus aureus during tuberculosis therapy: concurrent bacterial eradication and acquisition of resistance.

J Antimicrob Chemother. 2005 Dec;56(6):1172-5

Authors: Liu Y, Cui J, Wang R, Wang X, Drlica K, Zhao X

Acquired antimicrobial resistance is commonly attributed to regimens that expose bacteria to subinhibitory concentrations; consequently, eradication of susceptible cells is advocated. The mutant selection window hypothesis predicts that resistance can be acquired even when inhibitory concentrations are exceeded and susceptible bacteria are eradicated. The objective was to test that prediction clinically.

PMID: 16207765 [PubMed - indexed for MEDLINE]

Estimation of diabetes risk in Brazilian population by typing for polymorphisms in HLA-DR-DQ, INS and CTLA-4 genes.

Dis Markers. 2005;21(3):139-45

Authors: Hauache OM, Reis AF, Oliveira CS, Vieira JG, Sjöroos M, Ilonen J

The study aimed to further characterise HLA encoded risk factors of type 1 diabetes (T1D) in Brazilian population and test the capability of a low resolution full-house DR-DQ typing method to find subjects at diabetes risk. Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401, *0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301, (DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes were significantly decreased among patients. Genotypes with two risk haplotypes or a combination of a susceptibility associated and a neutral haplotype were found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control subjects (P < 0.0001). Insulin gene -2221 C/T polymorphism was also associated with diabetes risk: CC genotype was found among 83.1% of patients compared to 69.3% of healthy controls (P=0.0369, OR 1.98) but CTLA-4 gene +49 A/G polymorphism did not significantly differ between patients and controls. Despite the diversity of the Brazilian population the screening sensitivity and specificity of the used method for T1D risk was similar to that obtained in Europe.

PMID: 16276008 [PubMed - indexed for MEDLINE]

Characterization of a new NIH-registered variant human embryonic stem cell line, BG01V: a tool for human embryonic stem cell research.

Stem Cells. 2006 Mar;24(3):531-46

Authors: Plaia TW, Josephson R, Liu Y, Zeng X, Ording C, Toumadje A, Brimble SN, Sherrer ES, Uhl EW, Freed WJ, Schulz TC, Maitra A, Rao MS, Auerbach JM

Human embryonic stem cells (hESCs) offer a renewable source of a wide range of cell types for use in research and cell-based therapies. Characterizing these cells provides important information about their current state and affords relevant details for subsequent manipulations. For example, identifying genes expressed during culture, as well as their temporal expression order after passaging and conditions influencing the formation of all three germ layers may be helpful for the production of functional beta islet cells used in treating type I diabetes. Although several hESC lines have demonstrated karyotypic instability during extended time in culture, select variant lines exhibit characteristics similar to their normal parental lines. Such variant lines may be excellent tools and abundant sources of cells for pilot studies and in vitro differentiation research in which chromosome number is not a concern, similar to the role currently played by embryonal carcinoma cell lines. It is crucial that the cells be surveyed at a genetic and proteomic level during extensive propagation, expansion, and manipulation in vitro. Here we describe a comprehensive characterization of the variant hESC line BG01V, which was derived from the karyotypically normal, parental hESC line BG01. Our characterization process employs cytogenetic analysis, short tandem repeat and HLA typing, mitochondrial DNA sequencing, gene expression analysis using quantitative reverse transcription-polymerase chain reaction and microarray, assessment of telomerase activity, methylation analysis, and immunophenotyping and teratoma formation, in addition to screening for bacterial, fungal, mycoplasma, and human pathogen contamination.

PMID: 16293579 [PubMed - indexed for MEDLINE]

D6S265*15 marks a DRB1*15, DQB1*0602 haplotype associated with attenuated protection from type 1 diabetes mellitus.

Diabetologia. 2005 Dec;48(12):2540-3

Authors: Valdes AM, Thomson G, Graham J, Zarghami M, McNeney B, Kockum I, Smith A, Lathrop M, Steenkiste AR, Dorman JS, Noble JA, Hansen JA, Pugliese A, Lernmark A, , ,

The HLA class II DQB1*0602 allele confers strong dominant protection against type 1 diabetes but protection is not absolute. The aim of this study was to identify markers within the HLA region that differentiate DQB1*0602 haplotypes and show different associations with disease risk.

PMID: 16320082 [PubMed - indexed for MEDLINE]