Expression profiling of metalloproteinases and inhibitors in cartilage

Objective   To profile the expression of all known members of the matrix metalloproteinase ( MMP ), a disintegrin and metalloproteinase with thrombospondin motifs ( ADAMTS ), and tissue inhibitor of metalloproteinases ( TIMP s) gene families in normal cartilage and that from patients with osteoarthritis (OA).
Methods   Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur. Total RNA was purified and expression of genes assayed using quantitative real-time PCR.
Results   Several members of the above gene families were regulated in OA. Genes increasing in expression in OA were: at P  < 0.001, MMP-13 , MMP-28 , ADAMTS-16 ; at P  < 0.01, MMP-9 , MMP-16 , ADAMTS-2 , ADAMTS-14 and at P  < 0.05, MMP-2 , TIMP-3 , ADAMTS-12 . Genes decreasing in expression in OA were: at P  < 0.001, MMP-1 , MMP-3 , ADAMTS-1 ; at P  < 0.01, MMP-10 , TIMP-1 , ADAMTS-9 and at P  < 0.05, TIMP-4 , ADAMTS-5 , ADAMTS-15 . Correlation analysis revealed that groups of genes across the gene families are co-expressed in cartilage.
Conclusion   This is the first comprehensive expression profile of all known MMP , ADAMTS and TIMP genes in cartilage. Patterns of expression provide a foundation on which to understand mechanisms of gene regulation in OA and potentially for refining the specificity of anti-proteolytic therapies.     

Treatment of an infected total hip replacement with the PROSTALAC system: Part 1: Infection resolution

INTRODUCTION: Infection after total hip replacement (THR) is a serious medical complication with significant negative ramifications for both the patient and the health care system. The prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) was designed to treat the joint infection while maintaining functional movement in the hip. METHODS: We identified 28 patients treated for infected THR with the PROSTALAC system, by retrospective chart review. Preoperative and intraoperative cultures were taken to identify the causative organism. After PROSTALAC insertion, patients underwent at least 6 weeks of intravenous (IV) antibiotics. Prior to undergoing posttreatment cultures, patients were required to be antibiotic-free for a minimum of 6 weeks, with normal laboratory values. We defined resolution infection as retention of a joint prosthesis for a minimum of 2 years. RESULTS: Infection was identified in 28 patients in either the joint aspirate or intraoperative cultures. Of these patients, 2 failed to clear infection, requiring repeat PROSTALAC insertion. Two additional patients had positive 48-hour cultures post-second stage, treated with additional IV antibiotics. Retention of the post-PROSTALAC prosthesis is 100% at 2 years. CONCLUSION: PROSTALAC has acceptable infection resolution outcomes and appears effective for treating infected THR.     

Construction and validation of a Parkinson's disease mutation genotyping array for the Parkin gene.

Parkin mutations account for the majority of familial and sporadic early onset Parkinson's disease (EOPD) cases with a known genetic association. More than 100 mutations have been described in the Parkin gene that includes homozygous, compound heterozygous, and single heterozygous mutations. We have designed a Parkin mutation genotyping array (gene chip) that includes published Parkin sequence variants and allows their simultaneous detection. The chip was validated by screening 85 PD cases and 47 controls previously tested for Parkin mutations. Similar genotyping microarrays have been developed for other genetically heterogeneous diseases including age-related macular degeneration. Here, we show the utility of a genotyping array for Parkinson's disease by analysis of 60 subjects from the Genetic Epidemiology of Parkinson Disease (GEPD) study that includes 15 early-onset PD case probands and 45 relatives.     

Predictors of punding in Parkinson's disease: results from a questionnaire survey.

Dopamine replacement therapy (DRT) for Parkinson's disease (PD) has recently been linked to the development of a number of nonmotor behavioral control problems. Punding, one of these nonmotor problems, is a term used to describe complex, purposeless stereotyped behaviors such as the repetitive handling or sorting of objects. A self-report questionnaire was adapted to assess punding in the context of dysfunctional hobby-related activities. We report the results of a survey of PD outpatients from a PD research clinic (n = 141) and non-PD controls (n = 103); conducted to identify clinical and psychological factors predictive of punding behaviors. The PD group reported hobbies and activities, which scored significantly higher on the Punding Scale than controls. Higher impulsivity, poorer disease-related quality of life, younger age of disease onset, and concomitant daily medication dosage from dopamine receptor agonists were independently predictive of higher Punding Scale scores in the PD group. These findings are similar to those seen in dopamine dysregulation syndrome, and provide further evidence for the role of impulsivity and age at disease onset in DRT-related nonmotor behavioral problems in PD.