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Murine lupus in MRL mice has been strongly attributed to alphabeta T cell-dependent mechanisms. Non-alphabeta T cell-dependent mechanisms, such as gammadelta T cells, have been shown to drive antibody and autoantibody production, but they have not been considered capable of inducing end-organ disease. Here, we have expanded upon the findings of such previous work by examining the mechanism and extent of end-organ disease attainable via gammadelta T cells and/or non-alphabeta T cell-dependent mechanisms, assessing two prototypical lupus lesions, renal and skin disease, in TCR alpha -/- MRL mice that possessed either functional or defective Fas antigen (Fas + or lpr). Observed to 1 year of age, TCR alpha -/- MRL mice developed disease characterized by increased mortality, overt renal disease and skin lesions. While delayed in onset and/or reduced in severity compared with TCR alpha +/+ MRL/lpr animals, renal and skin lesions in alphabeta T cell-deficient animals were clearly increased in severity compared with age-matched control non-autoimmune mice. In contrast to TCR alpha +/+ MRL mice, whose disease reflected pan-isotype immune complex deposition with significant complement fixation, renal disease in TCR alpha -/- MRL animals reflected predominantly IgG1 immune complex deposition, with poor complement fixation. Thus, this study demonstrates conclusively that non-alphabeta T cell-dependent mechanisms can induce renal and skin injury in murine lupus, but at least in the kidney, only via humoral autoimmunity of a relatively non-pathological isotype which results in the delayed onset of end-organ damage.

Study Design: Lumbosacral spondylolisthesis was simulated using four embalmed human spines, and the path of the L5 nerve was studied., Objectives: To quantify the change in length of the L5 nerve root associated with reduction of spondylolisthesis, correction of slip angle, and changing disc height., Summary of Background Data: Stretch injury to the lumbar nerves remains a complication of spondylolisthesis reduction. To date, no anatomic studies have been performed to quantify this effect of reduction on the lumbar nerves., Methods: The L5 vertebral body and the sacrum of four embalmed human spines were constrained in an adjustable jig, and the length of a simulated nerve was determined for various position variables--sagittal translation (0-100% slip), slip angle (-40 degrees to +20 degrees), and disc height (5 or 10 mm). Two standard points of reference were chosen to represent fixed points along the path of the L5 nerve. An inelastic cord was used to measure the path length between these points as L5 was reduced from 100% to 0% slip. Testing was performed using a 5-mm and a 10-mm disc height. The effect of varying slip angle alone was also studied., Results: The effect of spondylolisthesis reduction and slip angle correction on nerve length varied depending on the location of L5 with respect to the sacrum. There was an increasing effect of partial reduction on nerve length as L5 approached full reduction. Initially, little strain was produced in the L5 nerve as L5 was reduced in higher grade slips. However, as L5 approached full reduction, the strain per increment of reduction increased rapidly. On average, the mean nerve strain was 4.0% for the first 50% of reduction and 10.0% for the second half of reduction. Increasing lordosis relaxed the nerve in high-grade slips and stretched the nerve in fully reduced slips. At 100% slip, the mean nerve excursion decreased 5.1 mm (nerve slackening) when L5 was rotated from +20 degrees to -40 degrees. At 0% slip, the mean nerve excursion increased 3.1 mm (nerve stretch). Increasing disc height directly stretched the L5 nerve. However, given a larger disc height, the strain on the nerve per increment of reduction was less than for the smaller height., Conclusion: The findings suggest that the risk of stretch injury to the L5 nerve with reduction of a high-grade spondylolisthesis is not linear; with 71% of the total L5 nerve strain occurring during the second half of reduction, partial reduction may be a significantly safer treatment approach for high-grade spondylolisthesis than complete reduction. Correction of lumbosacral kyphosis in high-grade spondylolisthesis may be protective of the L5 nerve.

The hazardous chemical waste disposal issue is a widespread problem. Large quantities of chemical wastes have been produced by the chemical industries in the past forty years. Estimates now number disposal sites in the United States at least 30,000. The public and scientists have grown increasingly concerned about the effects of these waste disposal sites not only on the environment, but also on the human body. In this article, we review the number of hazardous chemical waste disposal sites (HCWDS), their construction, difficulties in defining their contents, and the establishment of the Superfund Act. We then discuss various studies in the literature that have attempted to define adverse health effects of HCWDS, particularly those examining Love Canal and sites in New Jersey. In our conclusions, we note the difficulties in establishing direct causal links between HCWDS and dangerous health effects. We suggest that more epidemiological studies are needed, with improved methodology for gathering complete data and studying large samples. Both positive and negative findings of epidemiological studies are important. Positive results will substantiate an association of health effects with HCWDS. Negative results may reduce the concerns of people living near HCWDS. Future investigators need sufficient information about HCWDS materials, possible routes of exposure, and measurements of exposure, as well as sufficient statistical power to detect even modest associations of health effects with HCWDS exposure.