Tissue inhibitor of matrix metalloproteinase-2 regulates matrix metalloproteinase-2 activation by modulation of membrane-type 1 matrix metalloproteinase activity in high and low invasive melanoma cell lines.

Activation of pro-matrix metalloproteinase (MMP)-2 on the surface of malignant cells by membrane-bound MT1-MMP is believed to play a critical role during tumor progression and metastasis. In this study we present evidence that MT1-MMP plays a key role for the in vitro invasiveness of malignant melanoma. Melanoma cell lines secreted latent MMP-2 when cultured on plastic. However, when cells were grown in floating type I collagen lattices, only high invasive melanoma cells activated proMMP-2. Activation could be inhibited by antibodies against MT1-MMP, by addition of recombinant tissue inhibitor of metalloproteinases (TIMP)-2 and by inhibition of MT1-MMP cleavage. MT1-MMP protein was detected as an inactive protein in all cell lines cultured as monolayers, whereas in collagen gels, active MT1-MMP protein was detected in the membranes of both high and low invasive melanoma cells. Production of TIMP-2 was about 10-fold higher in low invasive cells as compared with high invasive melanoma cells and was further increased in the low invasive cells upon contact to collagen. Thus, in melanoma cells TIMP-2 expression levels might regulate MT1-MMP-mediated activation of proMMP-2. High invasive melanoma cells displayed increased in vitro invasiveness, which was inhibited by TIMP-2. These data indicate the importance of these enzymes for the invasion processes and support a role for MT1-MMP as an activator of proMMP-2 in malignant melanoma.

Thermography as a diagnostic aid in sciatica.

Thermography has been proposed as a diagnostic aid in patients with sciatica. Supporters of thermography state that: (a) normal patients have normal thermograms of their lower extremities, and (b) abnormal patients (with disk ruptures causing sciatica) have abnormal thermograms. To test these two hypotheses, 56 patients with clinically documented acute sciatica, with a supporting diagnostic study [computed tomography (CT), CT/myelography, and/or magnetic resonance imaging] showing a ruptured disk, had presurgical thermograms. One year after surgical intervention, they had to have had a documented success to surgical treatment intervention to stay in the study. These 56 patients were then matched with 56 control (normal) patients who had electronic thermograms. The 112 thermograms were then interpreted blindly by two thermographers. The sensitivity and specificity of thermography as a diagnostic aid in sciatica were statistically analyzed. The sensitivity of thermography (its ability to be positive when sciatica was clinically obvious) was 60% and 50% for the two thermographic readers. The specificity of thermography (its ability to be negative in asymptomatic patients) was 45% and 48% for the two thermographers. Our conclusions are no different than those published in 1985: thermography is not useful as a diagnostic aid in sciatica.

A technique for quantitative assessment of three-dimensional motion with applications to human joints.

A technique is developed for quantitative measurement of general three-dimensional motion, and this technique is applied to the kinematics of anatomical joints. The spatial locations of three orthogonal points representing coordinate frames on each member of the joint are measured during motion of the joint by photo encoders of a three-dimensional mechanical pointer. Kinematic calculations are used to derive, from the experimentally collected data, the six orthogonal components of the motion of one member relative to the other. The accuracy of this technique is presented. Applications to the knee and ankle are discussed.

Patellectomy: a clinical study and biomechanical evaluation.

This study presents a long-term follow-up and evaluation of a single technique of patellectomy involving a cruciform repair of the extensor mechanism. The techniques of evaluation, namely: clinical observation, instant center analysis and an acoustical method of cartilage evaluation provide a more thorough and objective basis for clinical study than previously reported. Cruciform repair produced results comparable to conventional methods of surgical repairs. Patellectomized knees function well in people with patellofemoral disease but not in those with panarticular disease. Patellectomy substantially alters normal joint mechanics as evidenced by persistent changes in instant center analysis. Degenerative changes caused by the patellectomy are progressive. In view of newer concepts of the function of the patella in normal joint mechanics and improved designs of total knee arthroplasty, the indications for patellectomy are now more questionable than ever before in the history of orthopedics.