A model for slow axonal transport and its application to neurofilamentous neuropathies.

A model for slow axonal transport is developed in which the essential features are reversible binding of cytoskeletal elements and of soluble cytosolic proteins to each other and to motile elements such as actin microfilaments. Computer simulation of the equations of the model demonstrate that the model can account for many of the features of the SCa and SCb waves observed in pulse experiments. The model also provides a unified explanation for the increase and decrease of neurofilament transport rates observed in various toxicant-induced neuropathies.

Expression of cytoskeleton components in various Epstein-Barr virus infected cell lines.

It has been shown that viruses can induce alterations in the content and distribution of cytoskeleton structures, particularly actin microfilaments and microtubules. An immunomorphologic study of the cytoskeleton components of various EBV-infected cell lines with expression of different functions of EBV genome has been performed using antibodies to each of its three major components. Intermediate filaments and microtubules were similarly represented in all examined lymphoblastoid cell lines. The distribution of actin microfilaments, on the contrary, differed significantly from cell line to cell line. It is concluded that the morphologic expression of actin might depend on the expression of EBV genome. Furthermore, some of these cell lines might represent a useful substrate for the identification of anticytoskeleton antibodies, mainly anti-actin antibodies, in human sera.

Adhesive properties of metastasizing tumour cells.

Cancer metastasis depends on a functional property which enables tumour cells to depart from the primary site of growth, to disseminate to distant organs and to establish secondary growth. The acquisition of a metastatic phenotype by neoplastic cells most probably involves alterations in their adhesive properties as the migrating cells continuously break and establish cellular contacts throughout the process. In vitro, normal cells of either mesenchymal or epithelial origin usually depend on adhesion to and spreading on a solid substratum (anchoring) for cell division. Neoplastic cells, however, are free of dependence on the support of solid substrata for cell proliferation (anchorage independent). The search for the characteristic alterations in cell adhesion, spreading and morphology which may accompany neoplastic transformation in general and cancer metastasis in particular has engendered a wide range of research activities. These studies have led to the identification of various membrane receptors that mediate cell-cell and cell-extracellular matrix recognition and adhesion on normal and tumour cells. Central to this is the effect of cell adhesion on cell shape and cytoskeleton organization in relation to metastasis. The use of specific antibodies, ligands, drugs and culture conditions permits exploration and identification of some of the macromolecules involved in tumour cell adhesion in vitro and metastasis in vivo. Nevertheless the specificity of the interactions which might determine organ-specific metastasis remains to be elucidated. This paper discusses the interrelation between cell adhesion, cell shape, cytoskeleton and metastasis.

The pathophysiology of proximal neurofilamentous giant axonal swellings: implications for the pathogenesis of amyotrophic lateral sclerosis.

Neurofilamentous giant axonal swellings are observed in a number of human disorders, although they can manifest at different locations (i.e. proximal or distal) along the axon. Recent advances in understanding the pathogenesis of these changes has resulted from correlations of ultrastructural changes with abnormalities in the axonal transport of neurofilament proteins in experimental models produced by toxic chemicals. Using single, high doses of either acrylamide or 2,5-hexanedione, a reduction in neurofilament transport has been shown in the rat sciatic nerve. In contrast to the distal axonal swellings observed upon repeated exposures to these agents, modest proximal axonal swellings containing increased neurofilament content are found following high dose exposures. Thus, regardless of the location of swelling production, a defect in slow transport appears to underlie swelling formation. beta,beta'-Iminodipropionitrile (IDPN) produces proximal neurofilamentous giant axonal swellings which are indistinguishable from those observed in some patients with amyotrophic lateral sclerosis (ALS). Although not a model for ALS, IDPN provides a means to study the functional consequences of proximal giant axonal swellings. Intracellular recordings from IDPN-intoxicated cats reveal a number of abnormalities which may have electrophysiological counterparts in ALS, suggesting that the swellings may be important in the expression of the disease. Although axonal degeneration is rarely observed in the cat, perikaryal recordings reveal a number of alterations which are strikingly similar to those obtained from chromatolytic motor neurons following nerve transection. A perturbation of "trophic" signals from the periphery may be involved in the generation of axotomy-like changes in IDPN-intoxicated cats.

Actin filament alterations in glomerular epithelial cells of adriamycin-induced nephrotic rats.

The alterations of actin filaments in the glomerular epithelial cells of adriamycin-induced nephrotic rats were studied by electron microscopy and immunohistochemistry using both of the peroxidase-antiperoxidase and avidin-biotin methods. After the administration of adriamycin, the glomerular epithelial cells showed cell swelling, deformation of cell shape, vacuole formations, retraction or fusion of foot processes, detachment of the plasma membrane from the glomerular besement membrane (GBM), and an increase of cellular organelles. In parallel with these alterations, abnormal distribution of intracytoplasmic microfilaments of 5-6 nm in diameter was observed, which formed clusters, particularly gathering densely along the plasma membrane of the fused foot processes that abutted the GBM. Immnohistochemically, actin was demonstrated on the site of the above described filaments. The above results suggest that actin filaments may closely relate to the morphological maintenance of the glomerular epithelial cells and to their function as well.