Substrate specificity and inducibility of TACE (tumour necrosis factor alpha-converting enzyme) revisited: the Ala-Val preference, and induced intrinsic activity.

Tumour necrosis factor alpha (TNF alpha)-converting enzyme (TACE/ADAM-17, where ADAM stands for a disintegrin and metalloproteinase) releases from the cell surface the extracellular domains of TNF and several other proteins. Previous studies have found that, while purified TACE preferentially cleaves peptides representing the processing sites in TNF and transforming growth factor alpha, the cellular enzyme nonetheless also sheds proteins with divergent cleavage sites very efficiently. More recent work, identifying the cleavage site in the p75 TNF receptor, quantifying the susceptibility of additional peptides to cleavage by TACE and identifying additional protein substrates, underlines the complexity of TACE-substrate interactions. In addition to substrate specificity, the mechanism underlying the increased rate of shedding caused by agents that activate cells remains poorly understood. Recent work in this area, utilizing a peptide substrate as a probe for cellular TACE activity, indicates that the intrinsic activity of the enzyme is somehow increased.

An implantable strain measurement system designed to detect spine fusion: preliminary results from a biomechanical in vivo study.

STUDY DESIGN: The strain distribution on the thoracic vertebrae during anteroposterior bending and torsion was examined for use with an implantable strain gauge system and miniature radio transmitter, which also were evaluated. OBJECTIVES: To identify strain gauge placement sites by testing cadaver spines in vivo, and to evaluate an implantable gauge bonding technique and subminiature radio transmitter for accurate strain monitoring. SUMMARY OF BACKGROUND DATA: Fusion is determined currently through the use of radiographic techniques. Discrepancies exist between radiographic evidence and more direct measurements of fusion such as operative exploration4,5,12 and biomechanical or histologic measurements.12,15 To facilitate the return of patients to full unrestricted activity, it would be useful to develop a technique for accurate in vivo determination of fusion. METHODS: Three cadaver spines were tested during anteroposterior bending and torsional loading in the control, instrumented, and instrumented plus polymethylmethacrylate states. The spines were instrumented with an ISOLA(R) (Acromed Corporation, Cleveland, Ohio) construct, and a simulated fusion was achieved through the application of polymethylmethacrylate. Strain gauges were attached in uniaxial, biaxial, and rosette configurations. The principal strains were calculated. Calcium phosphate ceramic-coated gauges were implanted in patients and recovered after up to 15 months in vivo. A radio transmitter was developed and tested for use in patients. RESULTS: The largest and most consistent strain changes after simulated fusion were recorded during torsional loading on the laminae of a vertebra directly underneath a hook. Calcium phosphate ceramic-coated strain gauges showed excellent bone bonding to the lamina when fusion occurred. Radio telemetry accurately tracked strain magnitudes and strain rates expected in patients. CONCLUSIONS: The consistency obtained in torsional loading indicates that this type of loading will provide the most useful data from patients in vivo. Excellent bonebonding and accurate strain transmission using a long-term strain measurement system and miniature radio transmitter indicate that strains collected from patients with this system will be accurate.