Enucleation combined with orbital implants for malignant melanoma of the uvea

Advanced malignant melanomas of the uvea unsuited for an eye salvaging approach require enucleation of the tumor containing eye. A series of 68 patients is reported who underwent enucleation combined with insertion of a spherical dura-encased implant after 30 Gray pre-irridiation therapy of the orbit. Postoperative results with special attention to cosmetic outcome and motility of the prosthesis suggest that the insertion of an orbital implant should be preferred to the enucleation with no implant.     

Zinc, calcium, and magnesium metabolism: effects on plasmacytomas in Balb/c mice

The effects of different amounts of dietary zinc on the Zn absorption rate and on Zn, calcium and magnesium concentrations in tissues of MOPC 104E tumor-bearing Balb/c mice were determined. The Zn absorption rate was inversely related to the amounts of Zn in their diets and was lower than that of nontumor-bearing control mice fed a laboratory mice chow. Zn concentrations of tumor-bearing mice were also low compared with control mice but tumor Zn concentrations, regardless of the concentrations of Zn in the diets, were higher than those of normal tissues of the host other than the pancreas. Ca concentrations in tumor and tissues of tumor-bearing mice were higher than in control animals but Mg concentrations in tissues of tumor-bearing mice appeared to be similar to those of control mice. Results suggest that tumor-bearing mice have a lower intestinal Zn absorption capacity and a higher Zn uptake rate causing other tissues to become hypozincemic and hypercalcemic.     

4-Aminopyridine affects synaptosomal protein phosphorylation in rat hippocampal slices

Rat brain hippocampal slices were incubated with or without the convulsant 4-aminopyridine (4-AP). From these slices a crude mitochondrial/synaptosomal membrane fraction was prepared and analyzed for endogenous protein phosphorylation. 4-AP (10(-5) M) stimulated the phosphorylation of a 50 kDa protein by 86%. The phosphorylation of this 50 kDa protein is Ca2+/calmodulin-dependent and we suggest that this protein is the lower molecular weight subunit of Ca2+/calmodulin-dependent protein kinase II (CaMK II).     

Angiotensin-converting enzyme in sarcoid and chalazion granulomas of the conjunctiva

Angiotensin-converting enzyme (ACE) was studied immunohistochemically in conjunctival biopsies from 6 patients with systemic sarcoidosis, 4 patients with posterior non-sarcoid uveitis and in specimens from 4 patients with chalazion of the eyelid. Specimens with sarcoid granulomas showed intense ACE-positive immunoreactivity in epitheloid cells of the granuloma, whereas chalazion granulomas did not contain ACE-immunoreactivity. There was no difference in staining patterns between specimens without granulomas. Thus immunohistochemical staining for ACE may be of help in differentiating conjunctival granulomatous tissue of a chalazion from sarcoid granuloma.     

Association between human IgM autoantibodies and kappa chain allotypes

The relationship between the immunoglobulin kappa light chain allotypes and autoantibodies was studied in a series of seven human monoclonal kappa-bearing IgM antibodies with Rheumatoid Factor (RF) activity, two IgM anti-low density lipoprotein (LDL) antibodies, and one IgM anti-intermediate filament (IF) antibody. Residues at amino acid positions 153 and 191 related to the Km allotypes in human kappa chains were determined by an HPLC tryptic fingerprint and corroborated by amino acid sequence analysis. All the autoantibodies shared similar variable regions derived from the V kappa IIIb gene(s). The seven RF and the anti-IF were associated with the Km(3) constant region allotype whereas the two anti-LDL were associated with the Km(1,2) allotype. Thus, monoclonal autoantibodies showed the same Km allotypic distribution as the normal population. However, although the number of samples is small, it seems likely that a preferential association may exist between particular V kappa genes and Km alleles in the generation of autoantibodies with different specificities.     

CD44 ligation induces apoptosis via caspase- and serine protease-dependent pathways in acute promyelocytic leukemia cells.

We have recently reported that ligation of the CD44 cell surface antigen with A3D8 monoclonal antibody (mAb) triggers incomplete differentiation and apoptosis of the acute promyelocytic leukemia (APL)-derived NB4 cells. The present study characterizes the mechanisms underlying the apoptotic effect of A3D8 in NB4 cells. We show that A3D8 induces activation of both initiator caspase-8 and -9 and effector caspase-3 and -7 but only inhibition of caspase-3/7 and caspase-8 reduces A3D8-induced apoptosis. Moreover, A3D8 induces mitochondrial alterations (decrease in mitochondrial membrane potential DeltaPsi m and cytochrome c release), which are reduced by caspase-8 inhibitor, suggesting that caspase-8 is primarily involved in A3D8-induced apoptosis of NB4 cells. However, the apoptotic process is independent of TNF-family death receptor signalling. Interestingly, the general serine protease inhibitor 4-(2-aminoethyl)-benzenesulfonyl fluoride (AEBSF) decreases A3D8-induced apoptosis and when combined with general caspase inhibitor displays an additive effect resulting in complete prevention of apoptosis. These results suggest that both caspase-dependent and serine protease-dependent pathways contribute to A3D8-induced apoptosis. Finally, A3D8 induces apoptosis in all-trans-retinoic acid-resistant NB4-derived cells and in APL primary blasts, characterizing the A3D8 anti-CD44 mAb as a novel class of apoptosis-inducing agent in APL.