Citations

ABSTRACT We present a case of tenosynovitis caused by a novel, slowly growing, nonchromogenic, nontuberculous mycobacterium (NTM). Originally misidentified as Mycobacterium tuberculosis complex, the NTM cross-reacts with the M. tuberculosis complex nucleic acid hybridization probe, a M. tuberculosis gamma interferon release assay, and is closely related to M. tuberculosis by 16S rRNA gene sequencing.

Linking data from a case–control study of Alzheimer’s disease with data from a Minnesota Multiphasic Personality Inventory (MMPI) outpatient study, we identified 13 Alzheimer's disease cases and 16 controls for case–control comparison. The mean time between personality testing and onset of Alzheimer's disease (or corresponding age for controls) was 13 years in cases and 14 years in controls. Alzheimer's disease cases, but not the controls, had scores significantly greater than the normative reference on MMPI scales measuring Social Introversion (p = 0.05), and Pessimism (p = 0.01). When compared to controls, Alzheimer's disease cases had significantly greater scores on the Social Introversion scale (p = 0.03). Despite the small sample size and some design limitations of this exploratory study, our findings may suggest that subjects who score higher on these personality scales have a greater risk of Alzheimer's disease.

Objective IBS shows genetic predisposition, but adequately powered gene-hunting efforts have been scarce so far. We sought to identify true IBS genetic risk factors by means of genome-wide association (GWA) and independent replication studies. Design We conducted a GWA study (GWAS) of IBS in a general population sample of 11 326 Swedish twins. IBS cases (N=534) and asymptomatic controls (N=4932) were identified based on questionnaire data. Suggestive association signals were followed-up in 3511 individuals from six case-control cohorts. We sought genotype-gene expression correlations through single nucleotide polymorphism (SNP)-expression quantitative trait loci interactions testing, and performed in silico prediction of gene function. We compared candidate gene expression by real-time qPCR in rectal mucosal biopsies of patients with IBS and controls. Results One locus at 7p22.1, which includes the genes KDELR2 (KDEL endoplasmic reticulum protein retention receptor 2) and GRID2IP (glutamate receptor, ionotropic, delta 2 (Grid2) interacting protein), showed consistent IBS risk effects in the index GWAS and all replication cohorts and reached p=9.31×10 −6 in a meta-analysis of all datasets. Several SNPs in this region are associated with cis effects on KDELR2 expression, and a trend for increased mucosal KDLER2 mRNA expression was observed in IBS cases compared with controls. Conclusions Our results demonstrate that general population-based studies combined with analyses of patient cohorts provide good opportunities for gene discovery in IBS. The 7p22.1 and other risk signals detected in this study constitute a good starting platform for hypothesis testing in future functional investigations.

Abstract Tumor metastasis refers to spread of a tumor from site of its origin to distant organs and causes majority of cancer deaths. Although >30 metastasis suppressor genes (MSGs) that negatively regulate metastasis have been identified so far, two issues are poorly understood: first, which MSGs oppose metastasis in a tumor type, and second, which molecular function of MSG controls metastasis. Herein, integrative analyses of tumor-transcriptomes (n = 382), survival data (n = 530) and lymph node metastases (n = 100) in lung cancer patients identified non-metastatic 2 (NME2) as a key MSG from a pool of >30 metastasis suppressors. Subsequently, we generated a promoter-wide binding map for NME2 using chromatin immunoprecipitation with promoter microarrays (ChIP-chip), and transcriptome profiling. We discovered novel targets of NME2 which are involved in focal adhesion signaling. Importantly, we detected binding of NME2 in promoter of focal adhesion factor, vinculin. Reduced expression of NME2 led to enhanced transcription of vinculin. In comparison, NME1, a close homolog of NME2, did not bind to vinculin promoter nor regulate its expression. In line, enhanced metastasis of NME2-depleted lung cancer cells was found in zebrafish and nude mice tumor models. The metastatic potential of NME2-depleted cells was remarkably diminished upon selective RNA-i-mediated silencing of vinculin. Together, we demonstrate that reduced NME2 levels lead to transcriptional de-repression of vinculin and regulate lung cancer metastasis.

Background: Ankle arthrodesis is considered to be a well-accepted technique for end-stage ankle arthritis. Our purpose was to evaluate outcomes of patients with bilateral ankle arthrodeses with attention to radiographic and functional outcomes. Methods: Medical records of 31 patients were reviewed from 1977 through 2007. All patients had 1 year of clinical follow-up after their contralateral ankle arthrodesis, with an average follow-up of 11.2 years following the initial arthrodesis. Pertinent patient demographics and information pertaining to the operative procedure, complications, and subsequent adjacent joint fusions was collected. Radiographs were reviewed for time to fusion and adjacent joint arthritis. Functional outcomes were measured using the Foot and Ankle Ability Measure (FAAM) and the American Orthopaedic Foot and Ankle Society (AOFAS) Ankle and Hindfoot scale. Results: Ten females and 21 males underwent bilateral ankle fusions at an average age of 57 years at the time of the initial fusion. The contralateral fusion occurred on average 3.1 years following the initial fusion. Radiographic fusion occurred 12 weeks following the initial fusion and 14 weeks following the contralateral fusion. There was a significant increase ( P = .0001) in the average AOFAS score postoperatively in both ankles. The average FAAM score at last follow-up was 70. Adjacent joint arthritis developed in the majority of patients; however, most of the patients were free from adjacent fusions and reported their function as “normal” or “nearly normal” at last follow-up. Conclusion: Bilateral ankle arthrodesis was an acceptable treatment option for patients with bilateral, end-stage ankle arthritis. Level of Evidence: Level IV, retrospective case series.