1,720,964 research outputs found
Swelling of hepatocytes injured by oxidative stress suggests pathological changes related to macromolecular crowding
No full textA fundamental property of living matter is the ability to establish and maintain order. Mild changes in cell volume have a role in metabolic control. Furthermore, cellular swelling is a way of living cells to react to a variety of stressors. Data from experimental pathology, biochemistry and biophysics and theoretical arguments from biology, biochemical evolution, cytology and biophysics are considered to attempt an integration of several current concepts on different subjects (intracellular compartmentation, cellular swelling, macromolecular crowding, perturbing and non-perturbing solutes). The purpose is to provide a framework for conceptualizing in modern terms the question whether cellular swelling induced by oxidative stress should be considered merely a cell adaptation balanced by antioxidant defenses and by other biochemical devices apt to preserve the intracellular environment and normal cell functioning, or whether swelling of high amplitude should be regarded as a true pathological change. The basic question dated 1982: "how crowded is the cytoplasm?" is a matter for discussion as far as swollen cells are concerned. This paper examines the liver for cellular swelling of high amplitude (about + 30%) caused by iron or by thyroid hormone + iron (histological picture of "cloudy swelling") or the steatogenic poison CCl4, also known as a source of oxyradicals, which causes an even more pronounced cellular swelling. In CCl4-toxic fatty liver the strong increase of tissue water is substantially masked by the parallel increase of tissue dry solids due to fat accumulation. This example of a "tissue dilution artefact" is discussed in connection with the increase of tissue water also in toxic fatty liver induced by white phosphorus and ethanol. In CCl4-toxic fatty liver the normal K+/Na+ ratio (about 3) is substantially maintained, whereas the concentrations of the two cations ("perturbing osmolytes") in tissue water are noticeably decreased, a finding which was not further studied at the time the observations were made because biochemistry was not yet advanced enough to allow an explanation. Today, a logic hypothesis is that an increase of non-perturbing solutes such as taurine and betaine, maintains the physiological intracellular osmotic pressure and that the harmful effects of CCl4 are limited because of the protective effects of these molecules and of molecular chaperones against damage by oxyradicals. However, as a consequence of cellular swelling, intracellular changes in ionic strength and macromolecular crowding should occur thus affecting enzyme activities. Models and techniques apt to investigate this problem experimentally are suggested. (copyright) 2004 Elsevier Ltd. All rights reserved
Focusing experimentally on polyploidy in physiology and pathology of mammals
No full textThis paper, aimed at focusing on polyploidy in mammalian cells with attention to pathology, consists of two parts. The experimental part shows the results of a retrospective morphometric analysis carried out on histological, specimens of toxic fatty livers saved together with the inherent records of year 1959. Some polyploid anaphases detected merely by chance and suitable to be quantitated have been analysed by computer-assisted microscopy. The results of this analysis prove that genome amplification may occur even in 16n hepatocytes infiltrated by lipid droplets and, presumably, heavily swollen. This information is relevant to re-interpret correctly pathophysiology of toxic fatty liver. In addition, this paper traces the outline of present knowledge on genome amplification in normal and pathological mammalian cell types, Morphometric data and recent progress of molecular cell biology and genetics are indicative of the importance of ploidy values in connection (i) with differentiation, growth and aging of the normal organism, (ii) with the so-called final differentiation of some cell types, and (iii) with some processes closely linked together, namely, inflammation and repair. Evidence suggests that in the life history of the organism mammal polyploidy is controlled, in the various organs, tissues and cell lines, and/or at different times, by different genetic programs
Does the cell number 10(9) still really fit one gram of tumor tissue?
No full textA tumor reaching the size of 1 cm(3) (approximately 1 g wet weight) is commonly assumed to contain 1 x 10(9) cells. This paper comments on the probable origin of this "magic" number and on some possible reasons why it has remained in use until now. However, mostly in epithelial tumors (85% of all human tumors) a cell number one order of magnitude smaller would be more realistic
Drop of connexin 43 in replicative senescence of human fibroblasts HEL-299 as a possible biomarker of senescence
No full textThe expression of connexin 43 (cx43) and cell-cell communication were studied in replicative senescence of cultured HEL-299 fibroblasts. A progressive decrease in fluorescent dye transfer was detected by a scrape-loading technique in aging fibroblasts. This change was accounted for by a marked decrease in the amount of cx43 in aging cells, as detected by western blot analysis (cell extracts) and indirect fluorescence (cells in culture). However, semiquantitative RT-PCR assays of cx43 mRNA did not reveal appreciable changes, which suggests several possible explanations for the mechanism(s) underlying the decrease of cx43 in aging cells. These findings support the idea that the reduced expression of cx43 might be a biomarker of cell senescence
From Kepler’s conjecture and fcc lattice to modelling of crowding in living matter
Full text linkUp to now, sphere packing has been investigated without any reference to living matter. This study focuses on the void space (VS) of sphere packing to mimic the extracellular spaces of living tissues. It was inspired by the importance of the extracellular matrix, the vehicle of micro and macromolecules involved in cell metabolism, intercellular communication and drug delivery.
The analysis of sphere packing evidenced that in uniform random packing VS is about 1.9 times greater than in the face centered cubic (fcc) lattice (thus being very close to the 1.9 volume ratio of the cube to the sphere). This datum is a good reference for cell packing in vivo.
The disproportionate increase of VS per sphere in loose packing in vitro is analyzed having in mind the variability in volume and composition of the interstitial spaces in vivo and cell trafficking.
Arrangements of lymphocytes mimicking a two-dimensional hexagonal pattern and
dense packing of disks generated by numerical procedures, are described in 7 μm-thick haematoxylin and eosin-stained histological slices from a human lymph node. In narrow tubes simulating roundish cells arranged in limited compartments of the interstice, sphere packing is characterized by noticeable increases of VS. The VS of this packing in vitro is compatible with variability in volume and composition of the interstitial spaces and with cell trafficking in vivo. This
paper stresses that in mammalian tissues and organs cells can be packed quite more densely than spheres in the fcc lattice. As to pathology, attention is focused: (i) on overcrowding of cell
organelles in some diseases, (ii) on shrinking or swelling of high amplitude, whose opposite effects are to concentrate or dilute intracellular structures and crowding of macromolecules, and (iii) on neoplastic tissues
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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