[A description of red cell shape and haemolysis published in Pavia in eighteenth century (author's transl)].
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The effect of limited platelet activation, in the absence of aggregation, on the subsequent ability of rabbit platelets to adhere to collagen was studied in vitro. ADP at concentrations that initiate shape change ( greater than 0.01 micro M) reduce platelet adhesion. Shape change per se however, was not responsible since the time-dependence of the effect of ADP on shape change and adhesion is different and ADP induces reduced adhesion even when shape change is prevented with PGE or fixatives. Platelets shape-changed without ADP addition, e.g. by chilling or by low ethanol concentrations, display normal adhesion to collagen. It appears likely that upon binding to the platelet ADP induces a time-dependent alteration in the membrane, akin to refractoriness, that influences binding sites for collagen. The effect of ADP can be blocked by prior addition of AMP but not if the additions are reversed. The implications of the present finding for platelet adhesion studies are discussed.
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Shapes of dendritic spines are changed by various physiological or pathological states. The high degree of spine shape heterogeneity suggests that they would be the morphological basis for synaptic plasticity. An increasing number of proteins and signal transduction pathways have recently been shown to be associated with structural modifications of spines. Here, we review the possible functional roles of spine shapes in cerebellar Purkinje neurons. Several studies have suggested that spine shapes in Purkinje cells are regulated by both intrinsic and environmental factors, and different spine shapes could have significantly different consequences for brain function. Clearly constricted necks observed in thin, mushroom-shaped, and branched spines serve for compartmentalization of calcium and other second messenger molecules, influencing different signaling mechanisms and synaptic plasticity. Mushroom-shaped spines frequently have perforated postsynaptic density and the area of the spine head is much larger than simple spines, implying that membrane dynamics and receptor turnover are occurring. Branched spines might form additional synapses with afferent inputs resulting in the modification of neuronal circuits. Taken together, all these studies suggest that each spine shape is likely to have a distinct role in Purkinje cell function.
The cytoskeleton (CSK) of eukaryotic cells is composed of a complex interconnected network of filaments which is important in a wide variety of cellular functions including changes in cell shape, cell motility, mitosis, anchorage-dependent growth, and the localization of cellular organelles such as mitochondria, polyribosomes, and secretory granules. The various proteins comprising the cytoskeleton include actin in microfilaments, tubulin in microtubules, and the heterogeneous group of intermediate filament proteins that are associated with different cell types (keratin in epithelial cells, vimentin in fibroblasts, desmin in muscle cells, glial filament protein in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins in glial cells, and the neurofilament protein subunits in neural tissue). Many other proteins are closely associated with the cytoskeleton and influence its organization. In neoplastic cells, the expression of these different CSK proteins, especially the intermediate filament proteins, reflects their morphologic and functional differentiation. The carcinomas contain keratin; identification of individual keratin components may allow further sub-classification of carcinomas which is consistent with their tissue of origin. The sarcomas of muscle origin contain desmin. Vimentin is found primarily with cells of mesenchymal origin, but may coexist with other intermediate filament proteins in other tumors. One example is the coexistence of keratin and vimentin in tumors, such as mesotheliomas, which are derived from epithelial cells of embryonic origin. Glial fibrillary acidic protein is the most specific marker for glial tumors. Tumors of neural origin are characterized by the presence of neurofilament subunits. Therefore, analysis of CSK composition would be useful in diagnosis of clinical specimens and aid in studies of lineage relationships of neoplasms. Although no consistent differences in cytoskeletal structure between neoplastic and normal cells have been identified so far, the presence of more subtle biochemical alterations in the cytoskeletal structure of neoplastic cells that contributes to malignant behavior has not been ruled out. Since the cytoskeletal network plays an important role in cell shape and cell locomotion, which in turn are thought to be involved in growth control, invasion, and metastasis, further work is directed at identifying the various alterations in cytoskeletal architecture that may influence the malignant behavior of neoplastic cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Twenty-four-hour-old aggregates of human diploid skin fibroblasts are allowed to attach to a glass or plastic substratum. As a result of this attachment the cells in the aggregate demonstrate rapid and generalized changes in cell shape, cell surface and cytoplasm ultrastructure and in their ability to incorporate [3H]thymidine. Within 24 h they grow out on the substratum to attain the regular monolayer configuration. During the process of leaving the aggregate for the substratum a great number of different morphogenetic properties are displayed by the cells, resembling the properties of embryonic or epithelial cells. The simultaneous occurrence of this great variety of cell shape and cell surface changes, many of them unusual for fibroblasts, as well as the concurrent formation of organized cytoplasmic structures - microfilaments, microtubules - at localized areas of the cells, makes this system a potentially useful tool in the study of cell behaviour.
A study is made of the influence on hemagglutination of various physicochemical parameters, such as: cell shape, cell distance, extracellular colloid-osmotic pressure, degree of hydration of the cell surface, and cell zeta-potential. To a varying extent these are changed by: the addition of divers soluble polymers, the action of enzymes, the presence of various salt ions, centrifugation, agglomeration at low ionic strength, complex coacervation with cationic polymers, and the interaction with different kinds of antibodies. Among the more important parameters are cell distance and cell shape (particularly when the latter tends to spiculation), while the influence of zeta-potential appears to be of fairly minor consequence. The action of dissolved polymers is mediated through polymer bridging, increase in extracellular colloid-osmotic pressure, decrease of cell surface hydration, and change in cell shape. A peculiarity of dextran is that in addition to all of the above, it causes pronounced erythrocytic spiculation.
We studied the effects of dilazep, K-7259 (a novel derivative of dilazep) and d-propranolol on the change in cell shape and accumulation of nonesterified fatty acids (NEFA) induced by hydrogen peroxide (H2O2) in isolated rat cardiac myocytes. Myocytes were incubated in a Krebs-Ringer bicarbonate buffer containing 2 mM diethyltriamine pentaacetic acid (DETAPAC) and 2mM FeSO4 for 10 min, and then treated with 2mM H2O2 for 50 min. Before the treatment with H2O2, the percentage of the number of rod-shaped cells to that of total cells was 66 +/- 2%, and decreased to 35 +/- 3%, 25 +/- 4% and 14 +/- 2%, after 30, 40 and 50 min of the H2O2 treatment, respectively. The levels of NEFA (lauric, myristic, palmitoleic, arachidonic, linoleic, palmitic, oleic and stearic acids) increased after the treatment with H2O2. In the absence of FeSO4 and DETAPAC, however, H2O2 did not have these effects, and therefore all the experiments with drugs were performed in the presence of Fe2SO4 and DETAPAC. K-7259 (30 microM) and d-propranolol (50 microM) attenuated both the changes in cell shape and accumulation of NEFA induced by H2O2, whereas dilazep (30 or 50 microM) did not. N-(2-mercaptopropionyl)glycine (2 mM), an .OH scavenger, inhibited the H2O2-induced changes completely. These results suggest that K-7259 and d-propranolol attenuate the H2O2-induced changes in cell shape and accumulation of NEFA, probably because of their .OH-scavenging effect.
Morphological modifications, i.e., cell shape, cell surface sugar residues, cytoskeleton, and apoptosis of Hep G2 cells during 24 h exposure to 6 mT static magnetic field (static MF) were studied by means of light and electron microscopy and cytochemistry. Progressive modifications of cell shape and surface were observed during the entire period of exposure to static MF. Control cells were polyhedric with short microvilli covering the cell surface, while those exposed to static MF, were elongated with many irregular microvilli randomly distributed on the cell surface. At the end of the exposure period, the cells had a less flat shape due to partial detachment from the culture dishes. However, throughout the period of exposure under investigation, the morphology of the organelles remained unmodified and cell proliferation was only partially affected. In parallel with cell shape changes, the microfilaments and microtubules, as well as the quantity and distribution of surface ConA-FITC and Ricinus communnis-FITC labeling sites, were modified in a time dependent manner. Apoptosis, which was almost negligible at the beginning of experiment, increased to about 20% after 24 h of continuous exposure. The induction of apoptosis was likely due to the increment of [Ca2+]i during exposure. In conclusion, the data reported in the present work indicates that 6 mT static MF exposure exerts time dependent biological effects on Hep G2 cells.
Adhesion to extracellular matrix mediates cell cycle progression in mid-late G1; this effect involves an integrin-dependent organization of the cytoskeleton and a consequent change in cell shape. In an effort to identify potential signal-transducing agents that are associated with integrin-dependent shape changes, we looked for kinase activities that were stimulated by long-term adhesion of G0-synchronized NIH-3T3 cells to fibronectin-coated dishes. Several kinase activities were stimulated by this procedure, two of which migrated at 42 and 44 kDa and phosphorylated myelin basic protein in vitro. Blotting with anti-phosphotyrosine and anti-mitogen-activated protein (MAP) kinase antibodies identified these enzymes as ERK 1 and ERK 2. In contrast to the rapid and transient activation of these MAP kinases by platelet-derived growth factor, stimulation of MAP kinase activity by fibronectin was gradual, persistent, and associated with cell spreading rather than cell attachment itself. Cytochalasin D blocked the activation of MAP kinase activity that was induced by the binding of cells to fibronectin. Moreover, MAP kinase was also activated by adhesion of cells to vitronectin and type IV collagen; these effects were also associated with cell spreading. These results distinguish the regulation of G1 phase MAP kinase activity by soluble mitogens and extracellular matrix. They also implicate MAP kinase in shape-dependent cell cycle progression.
Ileocystoplasty was performed in rats and the morphological and cell-kinetic changes occurring in the ileal grafts were determined at intervals up to 18 months postoperatively. The intestinal mucosa underwent no progressive changes but included villous and avillous regions associated with crypts of various sizes at all time intervals. Newly appearing and densely packed epithelial cells, shaped like petals, were always present in the lower parts of the villi associated with crypts showing no elongation, but seldom present in those with elongated crypts in the villous mucosa. Bromodeoxyuridine studies showed that the petal-shaped cells interfered with cell migration. No petal-shaped cells were observed in avillous mucosa in which the rate of cell turnover depended on crypt size. Fine-structural changes in absorptive epithelial cells in both types of mucosa included features of prematurity or hypermaturity in the cytoplasm and close adherence to the basal portions of adjacent cells and to the basal lamina. These changes may possibly contribute to the prevention of reabsorption of urine. However, some of the mechanisms responsible for adherence of the basal parts might incidentally interfere with the normal cell kinetics of the intestinal epithelium, resulting in dense packing of cells and the formation of multiple types of mucosa in ileal grafts.
Reviewed are studies on alterations of the plasma membrane of neoplastic epithelial cells. Changes in the plasma membrane are probably of unique importance in the major clinical manifestations of cancer. Discussed are sequences in cell membrane changes in vivo and in vitro in both human tumors and chemical-induced animal models of carcinogenesis. Emphasis is placed on alterations in specializations of the plasma membrane, including cell junctions, antigenic and enzyme markers, intramembranous components, ion regulation, and the cytoskeleton. In general, the plasma membrane of neoplastic cells is less specialized than the cell of origin. In mammalian bladder, pleomorphis microvilli may occur concomitant with neoplastic transformation. Cell junctions in tumor cells may be reduced in number of functional characteristics compared to normal cells, which may affect cell-cell communication. Such alterations may be related to tumor cell invasion and metastasis. Normal membrane antigens may be lost or new ones gained in neoplasia. Thus, ABO blood group antigens may be lost in the case of human bronchus and bladder, while carcinoembryonic antigen occurs de novo in tumors of the colon and lung. Similarly, several marker enzymes may be reduced in activity, or appear de novo. Alterations in the number and pattern of distribution of intramembranous particles have been observed in bladder tumors, possibly related to changes in membrane function. Shifts in ion ratios (Na+/K+/Ca++) within neoplastic cells may result in abnormalities in cell shape, cell movement, and cell-cell communication. Many of these changes may reflect defects in function of the Golgi apparatus, which synthesizes components of the plasma membrane. Alterations in one or more components of the cytoskeleton may adversely affect cell shape, mobility of membrane proteins, cell-cell adhesion, etc., and play a major role in malignant cell behavior.
PURPOSE: To assess whether the size of the cells obtained by conjunctival impression cytology can be quantitatively assessed by measurement of the longest dimension of the cells. METHODS: Under topical benoxinate anaesthesia, cells were removed from the normally exposed nasal bulbar conjunctival surface using a 0.4 micron pore diameter filter (Biopore filter; type Millcell-CM). The filters were stained with haematoxylin after ethanol denaturation, photographed at 40 x magnification, and 35 mm slides prepared. An optical overlay method was used to outline the borders of sets of 30-35 contiguous cells on each image. The cell area, longest and shortest dimensions were measured by planimetry to an accuracy of +/- 3%. RESULTS: Analyses of 20 sets of samples, from individuals aged 21 to 48 years and without clinically significant ocular surface disease, revealed a median cell area of 133 micron 2 (n = 621, range 46-1602 micron 2; average 212 micron 2), a median longest dimension of 13.9 microns (range 6.6-68.8 microns; average 16.9 microns) and a shorter dimension of 10.0 microns (range 4.7-43.0 microns; average 11.9 microns); the distributions of values indicated bimodality. Most cells had a long:short ratio (L:S ratio) value between 1.00 and 1.80, but 11.9 +/- 6.1% of the cells had L:S ratios between 1.80 and 4.60. The overall relationship between the longest dimension and the area of the cells was nonlinear, with cells having larger L:S ratios having disproportionately smaller areas. CONCLUSIONS: The superficial conjunctival cells are small, and their longest dimensions are systematically related to area. Analyses of cell shape indicate further possible ways of identifying different cells on the bulbar conjunctiva. Compared to literature values, there is a substantial overlap in longest dimensions of the conjunctival cells with those of cells that can be collected off the corneal surface. This means that superficial conjunctival and corneal cells cannot be distinguished simply on the basis of measurements of the long dimension.