Activation of macrophage cytostatic effector mechanisms during acute graft-versus-host disease: release of intracellular iron and nitric oxide-mediated cytostasis.

During acute graft-versus-host disease (GVHD) the activation of macrophages (Mphi) is mediated by 2 signals, interferon (IFN)-gamma and bacteria-derived lipopolysaccharide (LPS). A cascade of inflammatory responses that includes the release of mediators of tissue injury follows Mphi activation. Among the tissues characteristically targeted during acute GVHD are epithelial tissues of the skin and gastrointestinal tract that normally undergo continuous proliferation and are therefore sensitive to cytostatic processes. We have investigated whether Mphi can mediate cytostatic mechanisms capable of interrupting cell proliferation during acute GVHD. GVHD was induced in nonirradiated C57BL/6XAF(1) (B6AF(1)) mice by the injection of 60 x 10(6) (acute GVHD) or 30 x 10(6) (nonlethal GVHD) C57BL/6 (B6) lymphoid cells. Mphi from animals undergoing acute GVHD could be triggered by normally insignificant quantities of LPS to mediate a cytostatic effect on target cells, resulting in the complete shutdown of cellular proliferation. The same amounts of LPS had no effect on Mphi from normal or syngeneically transplanted animals. Mphi mediated the release of significant quantities of intracellular iron from target cells undergoing cytostasis. Reversal of cytostasis occurred following inhibition of nitric oxide (NO) production by N(G)-monomethyl-L-arginine (NMMA). Production of NO by LPS-triggered Mphi reflected the severity of GVHD. NO release increased significantly during acute GVHD but was only transiently increased during nonlethal GVHD. The results provide evidence that, as a result of activation during acute GVHD, Mphi produce NO and induce the release of iron from target cells, resulting in a potent cytostatic effect that inhibits cellular proliferation. (Blood. 2000;96:1836-1843)

Adolescent idiopathic scoliosis. Correction of vertebral rotation with use of Wisconsin segmental spinal instrumentation.

We retrospectively reviewed the results of use of Wisconsin segmental spinal instrumentation in twenty-four patients who had adolescent idiopathic scoliosis. Our purpose was to determine whether there had been any correction of the rotational component. The mean age at the time of the operation was thirteen years and eight months (range, eleven to seventeen years). Computerized tomography was used to measure the degree of vertebral rotation relative to the midline of the body and relative to the mid-sagittal plane in thirty curves that had been treated with instrumentation and in fifteen that had not. According to the criteria of King et al., five patients had a type-I curve; fourteen, a type-II curve; four, a type-III curve; and one, a type-V curve. The mean correction in the coronal plane was 23 degrees (43 per cent; range, 20 to 69 per cent) for the curves that had been treated with instrumentation and 15 degrees (35 per cent; range, 11 to 77 per cent) for those that had not. The mean derotation of the apical vertebra, in relation to the midline of the body, in twenty-two curves that had been treated with instrumentation and that had had a mean initial rotation of 26 degrees (range, 8 to 53 degrees) was 6 degrees (range, 1 to 29 degrees). For seven curves, with a mean initial rotation of 25 degrees (range, 21 to 35 degrees), rotation increased a mean of 3 degrees (range, 1 to 7 degrees) after instrumentation. The rotation of the apical vertebra did not change in one curve treated with instrumentation. Derotation was seen in twelve of the fifteen curves that had not been treated with instrumentation.