Clozapine-induced cardiac failure.

A 73-year-old woman with dementia was given clozapine for treatment-resistant psychotic symptoms. Subsequently, she developed cardiac failure. Caution should be exercised when using clozapine, especially in the elderly.

Enhancement of differentiation of human lens epithelium in tissue culture by changes in cell-substrate adhesion.

Differentiation of human lens epithelial (HLE) cells cultured in vitro was drastically accelerated when the cells were cultured on cell-substrate adhesion-free surfaces. Spontaneous differentiation of the lens epithelial cells in monolayer cultures could be recognized with the appearance of lentoid bodies after 40-50 days if maintained without further passage. Although dissociated HLE cells reconstituted into monolayers consistently on the haptotactic substrates (either gold-coated biopore membrane or regular plastic dishes), the cells from the same batches exclusively formed cell aggregates when cultured on either biopore membrane or agarose-coated plastic dishes (nonhaptotactic). The cells on nonadhesion substrate first aggregate, then synchronously develop into lentoids by the 10th day of culture. The differentiation of HLE cells into lentoid structures with lens-fiber characteristics was documented by both ultrastructural and biochemical markers, such as loss of cytoplasmic organelles, formation of gap junctions, and the expression of gamma-crystallin and MP26. The system, in which differentiation of epithelial cells can be induced predictably in a short period of time, provides an excellent model for the study of differentiation and gene expression in human lens cells cultured in vitro.

Effect of inhibition of the glutathione redox cycle on the ultrastructure of peroxide-treated rabbit epithelial cells.

Our previous studies have shown that exposure of cultured rabbit lenses to physiological levels of hydrogen peroxide, following inhibition of the glutathione redox cycle, leads to the formation of distinct vacuoles in the anterior region of the lens at the germinative zone between the epithelium and lens fibers. In the present study the ultrastructure of H2O2-induced membrane damage in the intact lens and in cultured lens epithelial cells was examined by scanning and transmission electron microscopy (SEM and TEM), following the inhibition of glutathione reductase with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Lenses treated with BCNU/H2O2 exhibited swollen epithelial cells which were observed only above the peroxide-induced vacuoles. The apical surface of the swollen cells had membrane blebs which protruded into the underlying vacuolar space. The appearance of the blebs coincided with a change in the organization of the layer of microfilaments which is normally associated with the apical surface of the cell. Cultured lens epithelial cells treated with BCNU/H2O2 showed membrane blebs which increased in size and number with the duration of exposure. Initially, the blebs were seen only on certain regions of the cell surface with other regions appearing normal. TEM revealed a disorganization of microfilaments in the BCNU/H2O2 treated cells. Neither BCNU nor H2O2 alone affected the morphology of intact lenses or of cultured lens epithelial cells. In culture, isolated lens epithelial cells exposed to BCNU/H2O2 were more susceptible to damage than contiguous cells. While the exact mechanism by which H2O2-induced damage leads to bleb formation on the cell surface is not known, the inability of the cells to detoxify H2O2 due to the inhibition of glutathione reductase results in the disturbance of membrane cytoskeleton and a focal weakening of the cell surface. These results indicate a correlation between the active glutathione redox cycle in lens epithelium and maintenance of normal cytoskeletal protein organization.

Bovine non-pigmented and pigmented ciliary epithelial cells in culture: comparison of catalase, superoxide dismutase and glutathione peroxidase activities.

Non-pigmented epithelial (NPE) cells and pigmented epithelial (PE) cells were dissociated from bovine ciliary processes by brief digestion with pronase and grown in a culture medium containing high fetal bovine serum for at least 25 generations. Both types of cells grown to confluence showed the presence of intermediate junctions with associated tonofilaments. PE cells were distinguished from NPE cells by pigmentation during the early passages. Gamma-glutamyl transpeptidase activity was associated almost exclusively with NPE cells and proved to be a useful enzymatic marker to distinguish NPE from PE. A comparison was made between NPE and PE cells as to the levels of enzymes involved in the detoxification of active oxygen species. Catalase, Se-dependent glutathione peroxidase and superoxide dismutase activities were significantly higher in NPE than in PE cells. The results suggest that NPE cells play the major role in detoxification of active oxygen species during aqueous humor formation.

Calcium-containing opacities in the human lens.

Cooperative Cataract Research Group (CCRG) photographic procedures developed by Chylack have made it possible to localize and analyze specific lens opacities for their ultrastructural and chemical characteristics. One group of human lens opacities has been shown to have a high phosphorus/sulfur ratio (as compared to normal lens fiber cells) and an accumulation of unit membranes. The present paper describes another variety of human lens opacity with the following characteristics: (1) high calcium, low sulfur, undetectable phosphorus, as determined by Energy Dispersive X-ray Analysis (EDXA) of bulk specimens in the scanning electron microscope (SEM), or "thick" sections with the transmission mode of the SEM; (2) spheroidal shape; (3) up to approximately 300 microns in size; and (4) birefringence. Microchemical analysis of these opacities shows that the calcium is in the form of calcium oxalate. These calcium-containing opacities, which have been detected in 14 out of 406 human cataractous lenses, have a characteristic morphology, as seen in the CCRG stereo photographs. Therefore, the presence of these calcium opacities, if not obscured by other kinds of opacities, can be detected with a high degree of accuracy in the fresh lens from the CCRG photographs alone.

A newly described organ associated with the eye and lateral line system in the marine teleost, Stenotomus chrysops.

A hitherto undescribed type of organ, possibly sensory, is reported. It is in the form of small cylindrical projections primarily concentrated on the surface in the area of the reticular lateral-line complex and around the eye of the scup (Stenotomus chrysops). The projection is composed of a central core cell surrounded by an epithelium. Enveloped within the epithelium and parallel to the core cell are six to eight symmetrically arranged 'bulbs' with cytoplasmic stems extending to cell bodies within the epidermis proper. A circle of 'collar' cells at the base of the cylinder facilitates the observed bending of the projection. Detection of the direction of water movement is hypothesized.

Comparative study on drug sensitivity of the TA3/Ha and TA3/St tumor sublines.

TA3/Ha and TA3/St sublines differ from each other in some characteristics, like malignancy, survival time and drug sensitivity. TA3/St exhibited a peculiar response to the Vinca derivatives examined.

The nuclear envelope in the crystalline lens fiber cell.

Rabbit lenses which have been fixed, dehydrated, and dried by a critical-point drying method, can be fractured through the cytoplasm of the differentiating lens fibers, exposing the cell nuclei. The fracture, under these conditions, causes a complete separation of the two membranes of the nuclear envelope from one another, thus exposing entire membrane surfaces (those which line the perinuclear space). These surfaces are not seen in their entirety in typical freeze-fracture or freeze-etch preparations, and consequently have not been described previously. The exposed membrane surfaces which line the perinuclear space have numerous convex structures of approximately 1,000 A, and some larger more irregularly shaped structures. These appear to be fragments of the nuclear pore complexes. Differences in these structures between young fibers and those nearing completion of differentiation is suggested.