Citations

ABSTRACT Rifampin monotherapy was compared to the combination of linezolid or vancomycin with rifampin in an experimental rat model of methicillin-resistant Staphylococcus aureus (MRSA) chronic foreign body osteomyelitis. MRSA was inoculated into the proximal tibia, and a titanium wire was implanted. Four weeks after infection, rats were treated intraperitoneally for 21 days with rifampin alone ( n = 16), linezolid plus rifampin ( n = 14), or vancomycin plus rifampin ( n = 13). Thirteen animals received no treatment. At completion of treatment, qualitative cultures of the wire and quantitative cultures of the bone (reported as median values) were performed. Quantitative cultures from the control, rifampin monotherapy, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups revealed 4.54, 0.71, 0.10, and 0.50 log 10 CFU/gram of bone, respectively. The bacterial load was significantly reduced in all treatment groups compared to that in the control group. Rifampin resistance was detected in isolates from 10, 2, and 1 animal in the rifampin, linezolid-plus-rifampin, and vancomycin-plus-rifampin groups, respectively. Cultures of the removed wire revealed bacterial growth in 1 and 2 animals in the rifampin and linezolid-plus-rifampin groups, respectively, with no growth in the vancomycin-plus-rifampin group and growth from all wires in the untreated group. In conclusion, we demonstrated that combination treatment with linezolid plus rifampin or vancomycin plus rifampin is effective in an animal model of MRSA foreign body osteomyelitis in the context of retention of the infected foreign body.

Abstract The Task Force on Nomenclature was commissioned in 2007 by the Association for Applied Psychophysiology and Biofeedback, the Biofeedback Certification Institute of America, and the International Society for Neurofeedback and Research to develop an updated official definition of biofeedback. The article describes the task force participants and the process and publishes the task force's definition of biofeedback, which was approved by the three participating professional organizations.

Abstract Prior genome-wide association (GWA) studies have identified 10 susceptibility loci for risk of chronic lymphocytic leukemia (CLL). To identify additional loci, we performed a GWA study in 407 CLL cases (of which 102 had a family history of CLL) and 296 controls. Moreover, given the strong familial risk of CLL, we further subset our GWA analysis to the CLL cases with a family history of CLL to identify loci specific to these familial CLL cases. Our top hits from these analyses were evaluated in an additional sample of 252 familial CLL cases and 965 controls. Using all available data, we identified and confirmed an independent association of 4 single-nucleotide polymorphisms (SNPs) that met genome-wide statistical significance within the IRF8 (interferon regulatory factor 8) gene (combined P values ≤ 3.37 × 10−8), located in the previously identified 16q24.1 locus. Subsetting to familial CLL cases, we identified and confirmed a new locus on chromosome 6p21.3 (combined P value = 6.92 × 10−9). This novel region harbors the HLA-DQA1 and HLA-DRB5 genes. Finally, we evaluated the 10 previously reported SNPs in the overall sample and replicated 8 of them. Our findings support the hypothesis that familial CLL cases have additional genetic variants not seen in sporadic CLL. Additional loci among familial CLL cases may be identified through larger studies.

Abstract Background: The t(14;18)(q32;q21) translocation is the most commonly observed chromosomal translocation in non–Hodgkin's lymphoma (NHL), resulting in constitutive Bcl-2 expression and apoptosis inhibition. In addition, germline variation in both BCL2L11 (BIM) and CASP9, known regulators of apoptosis, has recently been linked to NHL risk. We conducted a comprehensive evaluation of 36 apoptosis pathway genes with risk of NHL. Methods: We genotyped 226 single-nucleotide polymorphisms (SNP) from 36 candidate genes in a clinic-based study of 441 newly diagnosed NHL cases and 475 frequency-matched controls. We used principal components analysis to assess gene-level associations, and logistic regression to assess SNP-level associations. MACH was used for imputation of SNPs in BCL2L11 and CASP9. Results: In gene-level analyses, BCL2L11 (P = 0.0019), BCLAF1 (P = 0.0097), BAG5 (P = 0.026), and CASP9 (P = 0.0022) were associated with NHL risk after accounting for multiple testing (tail strength, 0.38; 95% confidence interval, 0.05-0.70). Two of the five BCL2L11 tagSNPs (rs6746608 and rs12613243), both genotyped BCLAF1 tagSNPs (rs797558 and rs703193), the single genotyped BAG5 tagSNP (rs7693), and three of the seven genotyped CASP9 tagSNPs (rs6685648, rs2020902, and rs2042370) were significant at P < 0.05. We successfully imputed BCL2L11 and CASP9 SNPs previously linked to NHL, and replicated all four BCL2L11 and two of three CASP9 SNPs. Conclusion: We replicated the association of BCL2L11 and CASP9 with NHL risk at the gene and SNP level, and identified novel associations with BCLAF1 and BAG5. Impact: Closer evaluation of germline variation of genes in the apoptosis pathway with risk of NHL and its subtypes is warranted. Cancer Epidemiol Biomarkers Prev; 19(11); 2847–58. ©2010 AACR.

Abstract Background Previous epidemiologic findings suggest an association between exposure to trichloroethylene (TCE), a chlorinated solvent primarily used for vapor degreasing of metal parts, and non-Hodgkin lymphoma (NHL). Objectives We investigated the association between occupational TCE exposure and NHL within a population-based case–control study using detailed exposure assessment methods. Methods Cases (n = 1,189; 76% participation rate) and controls (n = 982; 52% participation rate) provided information on their occupational histories and, for selected occupations, on possible workplace exposure to TCE using job-specific interview modules. An industrial hygienist assessed potential TCE exposure based on this information and a review of the TCE industrial hygiene literature. We computed odds ratios (ORs) and 95% confidence intervals (CIs) relating NHL and different metrics of estimated TCE exposure, categorized using tertiles among exposed controls, with unexposed subjects as the reference group. Results We observed associations with NHL for the highest tertiles of estimated average weekly exposure (23 exposed cases; OR = 2.5; 95% CI, 1.1–6.1) and cumulative exposure (24 exposed cases; OR = 2.3; 95% CI, 1.0–5.0) to TCE. Tests for trend with these metrics surpassed or approached statistical significance (p-value for trend = 0.02 and 0.08, respectively); however, we did not observe dose–response relationships across the exposure levels. Overall, neither duration nor intensity of exposure was associated with NHL, although we observed an association with the lowest tertile of exposure duration (OR = 2.1; 95% CI, 1.0–4.7). Conclusions Our findings offer additional support for an association between high levels of exposure to TCE and increased risk of NHL. However, we cannot rule out the possibility of confounding from other chlorinated solvents used for vapor degreasing and note that our exposure assessment methods have not been validated.

Abstract The genetics of peripheral T-cell lymphomas are poorly understood. The most well-characterized abnormalities are translocations involving ALK, occurring in approximately half of anaplastic large cell lymphomas (ALCLs). To gain insight into the genetics of ALCLs lacking ALK translocations, we combined mate-pair DNA library construction, massively parallel (“Next Generation”) sequencing, and a novel bioinformatic algorithm. We identified a balanced translocation disrupting the DUSP22 phosphatase gene on 6p25.3 and adjoining the FRA7H fragile site on 7q32.3 in a systemic ALK-negative ALCL. Using fluorescence in situ hybridization, we demonstrated that the t(6;7)(p25.3;q32.3) was recurrent in ALK-negative ALCLs. Furthermore, t(6;7)(p25.3;q32.3) was associated with down-regulation of DUSP22 and up-regulation of MIR29 microRNAs on 7q32.3. These findings represent the first recurrent translocation reported in ALK-negative ALCL and highlight the utility of massively parallel genomic sequencing to discover novel translocations in lymphoma and other cancers.

Abstract Although the importance of RGS-GAIP–interacting protein (GIPC) in the biology of malignant cells is well known, the molecular mechanism of GIPC in the inhibition of tumor progression has not been identified. This study focused on elucidating the molecular role of GIPC in breast cancer progression. By using a human breast tumor specimen, an in vivo mouse model, and breast cancer cell lines, we showed for the first time that GIPC is involved in breast cancer progression through regulation of breast cancer cell proliferation, survival, and invasion. Furthermore, we found that the Akt/Mdm2/p53 axis, insulin-like growth factor-1 receptor, matrix metalloproteinase-9, and Cdc42 were downstream of GIPC signaling in breast cancer cells. Moreover, we showed that wild-type p53 reduced GIPC-induced breast cancer cell survival, whereas mutant p53 inhibited GIPC-induced cell invasion. Finally, we demonstrated that an N-myristoylated GIPC peptide (CR1023, N-myristoyl-PSQSSSEA) capable of blocking the PDZ domain of GIPC successfully inhibited MDA-MB-231 cell proliferation, survival, and further in vivo tumor growth. Taken together, these findings demonstrate the importance of GIPC in breast tumor progression, which has a potentially significant impact on the development of therapies against many common cancers expressing GIPC, including breast and renal cancer. Mol Cancer Res; 8(12); 1591–600. ©2010 AACR.

Background— Health status is a key outcome for comparing treatments, particularly when mortality does not differ significantly. Methods and Results— Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized 2368 patients with type 2 diabetes mellitus and stable ischemic heart disease to (1) prompt revascularization versus medical therapy and (2) insulin sensitization versus insulin provision. Randomization was stratified by the intended method of revascularization, coronary artery bypass graft surgery or percutaneous coronary intervention. The Duke Activity Status Index and RAND Energy, Health Distress, and Self-Rated Health scales were assessed at study entry and annually thereafter; linear mixed models were used to evaluate the effect of randomized treatment on these measures. Health status improved significantly from baseline to 1 year ( P <0.001) in each randomized treatment group. Compared with medical therapy, prompt revascularization was associated with significantly greater improvements in Duke Activity Status Index (1.32 points; P <0.001), Energy (1.36 points; P =0.02), and Self-rated Health (1.77 points; P =0.007) but not Health Distress (−0.47; P =0.46). These treatment effects were largely maintained over 4 years of follow-up. The effect of revascularization on the Duke Activity Status Index was significantly larger in the subgroup of patients intended for coronary artery bypass graft surgery compared with the subgroup intended for percutaneous coronary intervention. Health status did not differ significantly on any of the 4 measures between the insulin provision and insulin sensitization strategies. Conclusions— Prompt coronary revascularization was associated with small yet statistically significant improvements in health status compared with initial medical therapy among patients with diabetes mellitus and stable ischemic heart disease. Clinical Trial Registration— http://www.clinicaltrials.gov . Unique identifier: NCT00006305.