Plasma membrane receptors for the cancer-regulating progesterone metabolites, 5alpha-pregnane-3,20-dione and 3alpha-hydroxy-4-pregnen-20-one in MCF-7 breast cancer cells.

Recent observations indicate that the progesterone metabolite, 5alpha-pregnane-3,20-dione (5alphaP), which is produced at higher levels in tumorous breast tissue, promotes cell proliferation and detachment, whereas 3alpha-hydroxy-4-pregnen-20-one (3alphaHP), which is produced at higher levels in nontumorous breast tissue, suppresses proliferation and detachment of MCF-7 breast cancer cells. The objective of the current study was to determine the presence and characteristics of binding sites for these endogenous putative cancer-regulating steroid hormones. Radiolabeled 5alphaP and 3alphaHP were used in radioligand binding assays on MCF-7 cell (membrane, cytosolic, and nuclear) fractions. Binding of [(3)H]5alphaP and [(3)H]3alphaHP was observed only in the plasma membrane fraction, whereas estradiol binding sites were confirmed in the cytosolic and nuclear fractions. The respective membrane binding sites exhibited specificity for the 5alphaP and 3alphaHP ligands with no appreciable displacement at 200- to 500-fold excess by other steroids. The association rate constants were calculated as 0. 107/min and 0.0089/min and the dissociation rate constants were 0. 049 9 and 0.011 for 5alphaP and 3alphaHP, respectively. Saturation analyses indicated single classes of molecules with dissociation constants of 4.5 and 4.87 nM and receptor densities of 486 and 629 fmol/mg protein, respectively, for 5alphaP and 3alphaHP. Exposure of MCF-7 cells to estradiol for 1, 24, 48, and 72 h resulted in 2.3, 4. 2-, 2.99-, and 1.7-fold increases, respectively, in 5alphaP receptor density. 3alphaHP resulted in partial suppression of the estradiol-mediated increase in 5alphaP receptor density. This is the first report of receptors for the progesterone metabolites, 5alphaP and 3alphaHP, of their occurrence in breast cancer cell membranes, and of the induction of 5alphaP receptors by estradiol. The results provide further support for the potential importance of progesterone metabolites in breast cancer.

Kinematics of the distal radioulnar joint in rheumatoid arthritis: an in vivo study using centrode analysis.

The kinematics of the distal radioulnar joint were examined using the method of centrode analysis in vivo. A group of normal subjects was studied along with a group of rheumatoid arthritis patients who had distal radioulnar joint involvement. Serial computed tomographic scans were obtained through the distal radioulnar joint of nine subjects (10 wrists) in varying degrees of pronation and supination. For normal subjects, the movement that occurs in a stable distal radioulnar joint is not erratic and the center of rotation lies within a well-defined area. When subjects with rheumatoid arthritis were analyzed, it was determined that early in the disease process bone erosions may occur in the sigmoid notch of the distal radius. When the joint contour in this region is maintained, the kinematics are not markedly altered. Erosion involving the dorsal border of the sigmoid notch of the radius is associated with subluxation of the distal radioulnar joint. The ulna becomes dorsally positioned relative to the radius, and significant alteration in the kinematics of the distal radioulnar joint occurs.

Numerical [corrected] analysis of the load capacity of the human spine fitted with L-rod instrumentation.

L-rod procedures with sublaminar wiring have become widespread in orthopaedic practice, and serious mechanical problems involving fatigue failure, creep, and fixation have been reported. To address these problems, numerical [corrected] analysis was developed to provide estimates for the maximum bending stresses, approximately equal to maximum tensile stresses, in L-rods subject to various axial loads and postoperative Cobb angles. The superior load capacity of L-rods made from MP35N multiphase alloy compared with 316L stainless steel was demonstrated. Bending stresses in excess of the fatigue limit were predicted for eight patients with broken rods, suggesting that such failures might be prevented by prior analysis. This analytic approach provides a foundation for future studies of custom-designed L-rods and perhaps the successful use of L-rods without arthrodesis.

Analysis of sagittal plane instability of the lumbar spine in vivo.

Segmental instability secondary to degenerative disc disease may result in chronic low-back pain. In the sagittal plane, segmental instability can be characterized during lumbar motion from full extension to full flexion. The authors studied this movement using a translational method for the kinematic analysis, implementing a new concept known as the instability factor. Both translational and angular components of motion are evaluated. By computing the incremental motion parameters at different stages of spinal bending, the total amount of translation and angulation is obtained and combined in a ratio termed the instability factor. This factor increases with linear instability and decreases with rotational instability. The authors reviewed 12 control subjects and 36 patients with chronic low-back pain. The diagnoses of patients were categorized into three groups: idiopathic low-back pain, lumbar disc prolapse, and degenerative disc disease. Lateral radiographs of each subject's spine at the L4-5 level were obtained using low dose radiography and were performed serially as the subjects moved from full extension to full flexion. It was found that the group of patients with degenerative disc disease had an average age-corrected instability factor of 37.3 (mm/radian), which was significantly larger than that of normal subjects 25.5 (mm/radian), (P = 0.0065). No significant difference was seen in the instability factor of patients with idiopathic low-back pain or lumbar disc prolapse.

Listeria monocytogenes--an unusual cause of late infection in a prosthetic hip joint.

As the scope of patients having arthroplasty with compromised immune systems expands, the incidence of late prosthetic infections will increase and the variety of infecting organisms will broaden. The role of prophylactic antibiotics for such patients undergoing procedures known to cause a transient bacteremia is currently unknown. Their use is not universal and many patients undergo procedures frequently without any form of protection. The following case report outlines an unusual organism causing late hip arthroplasty infection in an immunocompromised host and examines the role of prophylactic antibiotics in preventing such complications.

An experimental study of the buckling behavior of L-rod implants used in the surgical treatment of scoliosis.

A test facility was developed to study the buckling behavior of the scoliotic spine fitted with L-rod implants. The facility included a model, constructed from polymeric materials, that was similar in geometric detail and flexural stiffness to the ligamentous thoracolumbar spine with a severe scoliotic curvature. Nondestructive tests were performed in which the transverse deflection was recorded at various axial load levels. Southwell regression was used on the data to estimate the buckling loads. Attaching L-rods of 3.2-mm diameter did not increase the buckling load significantly, compared to the uninstrumented spine and thus were judged to be ineffective in halting the progression of a scoliotic curve. However, L-rods of 4.8-mm diameter increased the buckling load about four times and L-rods of 6.4 mm increased the buckling load about eight times.