Macrophage migration inhibitory factor production by Leydig cells: evidence for a role in the regulation of testicular function

Macrophage migration inhibitory factor (MIF), described originally as a product of activated T lymphocytes, recently has been found to be released by monocytes/macrophages and the anterior pituitary gland. Immunohistochemical studies of the adult rat testis using an affinity-purified polyclonal antimurine MIF antibody demonstrated strong staining for MIF in Leydig cells and their putative precursors. Peritubular myoid cells and the seminiferous epithelium were negative for MIF staining; however, a weak reaction around the heads of elongated spermatids also was observed. The expression of MIF messenger RNA and protein in whole rat testis was demonstrated by Northern blot and Western blot analyses, respectively. Both MIF messenger RNA and protein immunoreactivity in Leydig cells was observed in testes obtained from long term hypophysectomized rats. Significant concentrations of intracellular MIF were detected in lysates of the TM3 Leydig cell line (7.23 +/- 2.6 pg/microgram protein), and testicular interstitial fluid contained 14.7 +/- 1.6 ng/ml MIF protein, as measured by MIF-specific enzyme-linked immunosorbent assay. To gain insight into the possible biological role of MIF in the testis, cultures of adult rat seminiferous tubules and purified Leydig cells were incubated together with recombinant murine MIF (rMIF). Neither rMIF (50 ng/ml) nor a neutralizing anti-MIF antiserum was found to affect basal or LH-stimulated Leydig cell steroidogenesis in vitro. However, a dose-dependent decrease in the secretion of inhibin by the seminiferous tubules was observed at rMIF concentrations ranging from 10-100 ng/ml. Taken together, these data indicate that Leydig cells produce MIF in vivo and suggest an important regulatory role for this newly discovered mediator of testicular function.     

Iatrogenic posterior tibial nerve division during ankle arthroscopy

AIM: To evaluate the validity of cumulative rim/disc area (RA/DA) curve analysis as a clinical tool for the identification of glaucoma induced optic disc pathology. METHODS: 71 normal and 83 glaucomatous eyes were evaluated from a series of 154 subjects recruited for this study. For each eye, the cumulative distribution of RA/DA was calculated from 36 equally spaced rim sectors of each optic disc obtained by the automatic evaluation of simultaneous videographics (Image-net X Rev.3/51b). To increase the sensitivity of this analysis in early glaucoma and in normal eyes, these cumulative curves were subsequently divided into two equal segments and the slopes of their respective regression lines compared. RESULTS: The median RA/DA value obtained from the 36 sectors was significantly different in glaucomatous eyes compared with normals (p < 0.001). Nevertheless, the curves (5th-95th percentile of the cumulative curves distribution) of early glaucomatous eyes fell within the normal range. When the cumulative curve of these marginal cases was then divided into two equal segments, the comparison of the slopes of the regression lines showed a significant difference (p < 0.05) in 100% of early glaucomatous eyes. Furthermore, normal eyes were shown to be true negatives in 93% of the cases in which no significant difference between the two slopes was observed. CONCLUSION: Analysis of the RA/DA cumulative curve from 36 sectors of the optic disc was a valid method for the identification of glaucomatous disc pathology; however, a further calculation of the slopes of the two RA/DA regression lines was needed to identify early glaucomatous damage.     

Molecular organization of the cholesteryl ester droplets in the fatty streaks of human aorta

X-ray diffraction patterns from human arterial specimens containing atherosclerotic fatty streak lesions exhibited a single sharp reflection, corresponding to a structural spacing of about 35 A. Specimens without lesions did not. When specimens with fatty streaks were heated, an order-to-disorder phase transition was revealed by the disappearance of the sharp reflection. The transition was thermally reversible and its temperature varied from aorta to aorta over a range from 28 degrees to 42 degrees C. Since cholesteryl ester droplets are a major component of fatty streaks, comparison studies were made of the diffraction behavior from pure cholesteryl esters. We found that the diffraction patterns of the fatty streak material could be accounted for by the organization of the cholesteryl esters into a liquid-crystalline smectic phase that melts from the smectic to a less ordered phase upon heating. When combined with the conclusions of others from polarized light microscopy, our study shows that a droplet in the smectic phase has well-defined concentric layers of lipid molecules. In each layer, the long axes of the molecules have a net radial orientation with respect to the droplet, but the side-to-side organization is disordered. We suggest that the accessibility of portions of the lipids for specific binding to enzymes or transport proteins may be restricted when they are in the smectic state, and that exchange of lipids with surrounding membranes or other potential binding sites may likewise be inhibited. The restriction in the smectic phase should be greater than in the less ordered phases that exist at higher temperatures.