Safety and Efficacy of ECT in Depressed Patients with Dementia: A Review of Clinical Experience

The authors review the results of electroconvulsive therpay (ECT) in 135 cases of depression occurring in conjunction with organic dementia, subcortical leukoencephalopathy without dementia, and depressive dementia (22 cases). Overall, 86% had a positive therapeutic response to ECT, whereas 21% experienced significant cognitive or memory side effects, virtually all of which were transient and reversible. Forty-nine percent of the patients with organic or depressive dementias experienced improvement in cognitive or memory function consequent to ECT.     

Comparative genomic hybridization of 49 primary retinoblastoma tumors identifies chromosomal regions associated with histopathology,progression, and patient outcome

Forty-nine primary retinoblastoma (Rb) tumors were analyzed by the use of comparative genomic hybridization (CGH), and clinical/histological correlations were performed. Adverse histological factors were present in 13 patients. Chromosomal imbalance was a frequent phenomenon, seen in 96% of the tumors. Gain of 6p represented the most frequent event (69% of the tumors), whereas +1q was observed in 57%, confirming that these abnormalities are key secondary events in retinoblastoma tumor progression. Loss of 13q and 16 was significantly associated with tumors displaying adverse histo-prognostic factors, whereas -16q was significantly associated with tumors without adverse features. In three patients who developed an extra-ocular relapse, the tumors showed -13q and 2/3 had -5q, suggesting that these abnormalities may be associated with metastasis. Children >or= 36 months of age at enucleation tended to have more CGH abnormalities per tumor than children < 12 months (median numbers 11 vs. 3). In addition, +1q, +13q, -16, and -16q were more frequent in children with an older age at enucleation. Identical CGH changes were found in both tumors from one patient with bilateral tumors, suggesting a common origin. It is possible that tumors displaying loss of 13q and 5q indicate those patients who may suffer an adverse outcome and who would require alternative or more intensive therapy. CGH analysis on larger cohorts and in prospective clinical trials will be invaluable in determining whether a genetic classification of retinoblastoma represents a reliable measure of prognosis.     

Susceptibility to multiple sclerosis mediated by HLA-DRB1 is influenced by a second gene telomeric of the TNF cluster

Susceptibility to multiple sclerosis (MS) is clearly associated with human leukocyte antigen (HLA)-DRB1*1501, but some studies show associations with HLA-B7 and -B18. These are often co-expressed with DRB1*1501 in the ancestral haplotypes (AH) denoted 7.1 (HLA-A3, B7, tumor necrosis factor [TNF]a11b4, DRB1*1501) and 18.1 (HLA-A25, B18, TNFa10b4, DRB1*1501). Here we present a systematic study of 218 patients and 274 controls typed at all standard class II and TNF microsatellite loci, and a novel non-synonymous polymorphism in the central major histocompatibility complex gene, inhibitor of κ B-like protein (IKBL). The C allele at IKBL+738 is only found on the 7.1 haplotype. HLA-DRB1*1501 was associated with disease, as expected. When subjects expressing DRB1*1501 were analyzed separately, TNFa11b4 and IKBL+738C were less common in the patients and, hence, mark an allele that mediates resistance which lies telomeric of IKBL.

TNFa10b4 and TNFa1b5 were more common in DRB1*1501 patients than in controls. These alleles have been associated with the 18.1 and 18.2 AH, respectively. Since no component of these haplotypes was an independent risk factor in this study, it appears likely that a gene linked to TNFa10b4 and TNFa1b5 modifies the effect of the susceptibility locus marked by HLA-DRB1*1501. Potential candidate genes telomeric of the TNF cluster are discussed.     

Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells

PMC42-LA cells display an epithelial phenotype: the cells congregate into pavement epithelial sheets in which E-cadherin and beta-catenin are localized at cell-cell borders. They abundantly express cytokeratins, although 5% to 10% of the cells also express the mesenchymal marker vimentin. Stimulation of PMC42-LA cells with epidermal growth factor (EGF) leads to epithelio-mesenchymal transition-like changes including up-regulation of vimentin and down-regulation of E-cadherin. Vimentin expression is seen in virtually all cells, and this increase is abrogated by treatment of cells with an EGF receptor antagonist. The expression of the mesenchyme-associated extracellular matrix molecules fibronectin and chondroitin sulfate proteoglycan also increase in the presence of EGF. PMC42-LA cells adhere rapidly to collagen I, collagen IV, and laminin-1 substrates and markedly more slowly to fibronectin and vitronectin. EGF increases the speed of cell adhesion to most of these extracellular matrix molecules without altering the order of adhesive preference. EGF also caused a time-dependent increase in the motility of PMC42-LA cells, commensurate with the degree of vimentin staining. The increase in motility was at least partly chemokinetic, because it was evident both with and without chemoattractive stimuli. Although E-cadherin staining at cell-cell junctions disappeared in response to EGF, beta-catenin persisted at the cell periphery. Further analysis revealed that N-cadherin was present at the cell-cell junctions of untreated cells and that expression was increased after EGF treatment. N- and E-cadherin are not usually coexpressed in human carcinoma cell lines but can be coexpressed in embryonic tissues, and this may signify an epithelial cell population prone to epithelio-mesenchymal-like responses.     

Busulfan and chloramphenicol induced T cell lymphoma: cell surface characteristics and functional properties.

We report the immunological studies on three transplantable lymphoma lines that developed when CAF1 mice were injected with busulfan and chloramphenicol. The lymphoma cells displayed Thy-1.2, brain associated antigen, and H-2d alloantigen. They were negative for surface IgM and Ia antigens. Expression of T cell differentiation antigens differed among the three lines. The 508 tumour line displayed only Thy-1.2: 408 tumour line displayed Thy-1.2, Lyt-2.2 and TL; and 808 tumour line was positive for Thy-1.2, Lyt-1.2, Lyt-2.2 and TL antigens. We established in vitro culture lines from 508 and 808 lymphoma cells. The lymphoma cells did not respond to mitogens and antigens. The splenic cells from mice bearing 508 or 808 had decreased phytohaemagglutinin (PHA), concanavalin A (Con A) and mixed leucocyte responses (MLR). When mitomycin-C treated lymphoma cells from the tumour bearing mice were cocultured with normal splenic mononuclear cells, the 808 lymphoma cells suppressed the mitogenic responses of the normal cells more profoundly than 508 lymphoma cells. Adherent cells from both tumours suppressed the Con A responses of normal spleen cells. Cells from in vitro 508 or 808 cell lines had no effect on mitogenic responses of normal cells. Plasma from tumour bearing mice, but not the supernatants taken from cultures of these lymphoma cells, suppressed the mitogenic responses of normal lymphocytes. Spleen cells from normal CAF1 mice responded in mixed leucocyte tumour reactions (MLTR) when cocultured with lymphoma cells. Mice immunized with mitomycin-C treated tumour cells had greater response. Responder cells taken from mice with established 508 or 808 tumors had suppressed MLTR responses. Although prior immunization with tumor antigen increased the MLTR response, injection of live tumour cells into immunized mice resulted in a more rapid tumour growth and suppression of MLTR response.