Increased stromal cell production of M-CSF, an event caused by enhanced phosphorylation of the nuclear protein Egr-1, is central to the mechanism by which estrogen (E2) deficiency upregulates osteoclast (OC) formation. However, the contribution of enhanced M-CSF production to the bone loss induced by E2 deficiency remains to be determined. We found that treatment with an Ab that neutralizes M-CSF in vivo completely prevents the rise in OC number, the increase in bone resorption, and the resulting bone loss induced by ovariectomy (ovx). We also found that adult, intact Egr-1–deficient mice, a strain characterized by maximally stimulated stromal cell production of M-CSF, exhibit increased bone resorption and decreased bone mass. In these mice, treatment with anti–M-CSF Ab restored normal levels of bone resorption, thus confirming that increased M-CSF production accounts for the remodeling abnormalities of Egr-1–deficient mice. Consistent with the failure of ovx to further increase M-CSF production in Egr-1–deficient mice, ovx neither increased bone resorption further, nor caused bone loss in these animals. In summary, the data demonstrate that E2 deficiency induces M-CSF production via an Egr-1-dependent mechanism that is central to the pathogenesis of ovx-induced bone loss. Thus, Egr-1 and M-CSF are critical mediators of the bone sparing effects of E2 in vivo.

Aim: To assess the sensitivity of biparametric magnetic resonance imaging (bpMRI) with non-endorectal coil in the detection and localization of index (dominant) and non-index lesions in patients suspected of having prostate cancer. Patients and Methods: We carried-out a retrospective analysis of multiparametric MRI (mpMRI) of 41 patients who underwent radical prostatectomy. Results of MRI for detection and localization of index and non-index lesions were correlated with those of histology. Results: No statistically significant difference in size was seen between tumor lesion at histology and index lesion at MRI. In 41 patients, a total of 131 tumors were identified at histology, while bpMRI (T2-weighted and diffusion-weighted MRI) approach detected 181 lesions. bpMRI gave 27.6% false-positives and 3.3% false-negatives. Sensitivity in lesion detection by bpMRI increased with lesion size assuming high values for lesions ≥10 mm. For bpMRI and mpMRI, the sensitivity for detecting index lesions was the same and equal: 100% in the peripheral zone 97.6% and 94.7% in the entire prostate and transitional zone, respectively. Conclusion: bpMRI can be used alternatively to mpMRI to detect and localize index prostate cancer.

We studied the cellular and subcellular distribution of S-100b protein in normal, crushed, and transected rat sciatic nerves by an immunocytochemical procedure. In uninjured nerves, S-100b protein was restricted to the cytoplasm and membranes of Schwann cells, with no reaction product present in the nucleus or in axons. Similar images were seen from the first to the thirtieth day after the crush in activated Schwann cells during the degeneration period, i.e., up to the seventh post-lesion day, and in normal Schwann cells reappearing during the regeneration period, i.e., after the seventh post-lesion day, in the zone of the crush and proximal and distal to it. By the technique employed, there seemed to be no differences in the intensity of the immune reaction product in normal and activated Schwann cells. Also, similar images were seen in the proximal stump of transected nerves. Only a slight S-100b protein immune reaction product could be observed in the rare activated Schwann cells present in the distal stump around the seventh post-lesion day, the majority of cell types being represented by fibroblasts and elongated cells at this stage and thereafter. By immunochemical assays, similar results as those presented here have been reported and interpreted as indicative of the presence of S-100 protein in axons or, alternatively, of axonal control over expression of S-100 protein in Schwann cells. Our immunocytochemical data clearly show that the strong reduction in the S-100 protein content of the distal stump of transected nerves is owing to the paucity of Schwann cells and to the decrease in the S-100 protein content of these cells, rather than to degeneration of axons.