Ewald R. Weibel

Bio: Ewald R. Weibel is an academic researcher from University of Bern. The author has contributed to research in topics: Lung & Diffusing capacity. The author has an hindex of 85, co-authored 235 publications receiving 34005 citations. Previous affiliations of Ewald R. Weibel include Universidad Iberoamericana (UNIBE) & Rockefeller Institute of Government.

Stereological principles for morphometry in electron microscopic cytology.

Abstract: Publisher Summary This chapter focuses on the stereological principles for morphometry in electron microscopic cytology. Morphometry of the cell serves the purpose of furnishing quantitative information on cellular fine structure with the aim of allowing quantitative correlation of biochemical or physiological data with morphological data obtained on structurally intact cells. the morphometric approach to cytology is not a purpose in itself, although admirable dimensional equilibria can be revealed which satisfy the esthetic needs. It is a means that serves the aim of structure-function correlation and derives its justification from the recognition that all orderly function must have an organized structural basis of a size that is adequate but not excessive. The chapter emphasizes on the possibilities of applying morphometric methods to correlative cell biology.

Practical stereological methods for morphometric cytology.

Abstract: Stereological principles provide efficient and reliable tools for the determination of quantitative parameters of tissue structure on sections. Some principles which allow the estimation of volumetric ratios, surface areas, surface-to-volume ratios, thicknesses of tissue or cell sheets, and the number of structures are reviewed and presented in general form; means for their practical application in electron microscopy are outlined. The systematic and statistical errors involved in such measurements are discussed.

Practical methods for biological morphometry

Abstract: This is the first textbook dealing with stereological methods that puts the emphasis on practical versus theoretical stereology, on its use in biology versus in materials sciences and on sampling efficiency versus measuring precision. As such, the book reflects the transition of stereology from the ‘It can be done!’ phase to the ‘How to do it the best way?’ phase. Being one of the principal engineers of this transition, the author needs no further presentation neither in stereological nor in biological quarters (nor among readers of this Journal !) The book is the first of two volumes, of which the second will deal explicitly with the theoretical foundations of stereology. In round figures, there are 350 pages, only few of which are not written in the lucid and very easily comprehensive Weibel-style. The book contains 175 illustrations, among which, especially the more than 100 drawings, is a rich combination of artistical dexterity and pedagogicai clarity. The list of 300-odd references is too short to be exhaustive (nor is it claimed to be so) but it is also rather too long to be an easily accessible guide for newcomers in the field. A short list with suggestions for further reading might have been useful. The 25-page appendix showing variants of three basic designs of test-grids is rather superfluous considering the large number of examples of the same designs given throughout the text. Addressed to ‘biologists of varied denominations’ who want to ‘do good stereology’ the book provides a wealth of information and discussions of the great number of more or less specific practical problems encountered in biological stereology. T o name a few, the multiple stage sampling imposed on biologists by the hierachical organization of organisms when studied at 100,000-fold varying magnification is very clearly explained and exemplified several times in the text. The multitude of biases involved in, for example, the transmission microscopy of thick sections (overprojection), the use of fixatives and osmotic active solutes (shrinkage! swelling), etc., etc., are frequently mentioned and some of them are discussed to a certain depth, including working corrections if available. Throughout the text there is a cleverly kept balance between always keeping the reader well aware of these biases-albeit, unfortunately, almost always under the name of ‘errors’-without ever allowing the unavoidable ones to be hindrances for obtaining biologically significant structural information. To summarize the treatment of the biological and practical problems : Here speaks a vastly experienced biologist and microscopist, he is not only careful and cautious but also brave and I think he succeeds in actually encouraging his readers into ‘doing good stereology’. The theoretical parts of the book are more uneven. The introduction to geometric probability starts at a very elementary level, explains the essential geometric operations involved and then proceeds in a straightforward manner through the principles of stereology to the desired formulae. The statistical nature of these relationships is thereby clearly revealed without scaring away anybody by the use of n-dimensional space integrals. On the other hand, the almost exhaustive treatment of the (unavoidable) computational nitty-gritty involved in NV estimation does not offer much help to the more practically oriented reader in selecting the method appropriate for his biological problem. SI T and LV estimation in general is derived only for isotropic

CORRELATED MORPHOMETRIC AND BIOCHEMICAL STUDIES ON THE LIVER CELL I. Morphometric Model, Stereologic Methods, and Normal Morphometric Data for Rat Liver

Abstract: The basic morphological properties of liver cells are defined in the form of a morphometric model to permit integrated quantitative characterization of functionally important parameters. Stereologic methods which allow efficient and reliable quantitative evaluation of sectioned liver tissue are presented. Material, obtained by a rigorous three-stage sampling procedure from five normal rat livers, is systematically subjected to this analysis at four levels of magnification. This yields quantitative data which are expressed as "densities," i.e. content per 1 ml of tissue, as "specific dimensions" related to 100 g body weight, and as absolute dimensions per average "mononuclear" hepatocyte. Base line data relating to the normal rat liver are presented for the entire spectrum of parameters. As examples, 1 ml of liver tissue contains 169 x 106 hepatocyte nuclei, some 90 x 106 nuclei of other cells, and 280 x 109 mitochondria. Hepatocyte cytoplasm accounts for 77% of liver volume, and the mitochondria for 18%. The surface area of endoplasmic reticulum membranes in 1 ml of liver tissue measures 11 m2 of which are ⅔ of the rough form carrying some 2 x 1013 ribosomes. The surface area of mitochondrial cristae in the unit volume is estimated at 6 m2. The validity and applicability of the method are discussed, and the data are compared with available information from other studies.

Culture of Human Endothelial Cells Derived from Umbilical Veins. IDENTIFICATION BY MORPHOLOGIC AND IMMUNOLOGIC CRITERIA

Abstract: Endothelial cells were isolated from freshly obtained human umbilical cords by collagenase digestion of the interior of the umbilical vein. The cells were grown in tissue culture as a homogeneous population for periods up to 5 mo and some lines were subcultured for 10 serial passages. During the logarithmic phase of cell growth, cell-doubling time was 92 h. Light, phase contrast, and scanning electron microscopy demonstrated that cultured human endothelial cells grew as monolayers of closely opposed, polygonal large cells whereas both cultured human fibroblasts and human smooth muscle cells grew as overlapping layers of parallel arrays of slender, spindle-shaped cells. By transmission electron microscopy, cultured endothelial cells were seen to contain cytoplasmic inclusions (Weibel-Palade bodies) characteristic of in situ endothelial cells. These inclusions were also found in endothelial cells lining umbilical veins but were not seen in smooth muscle cells or fibroblasts in culture or in situ. Cultured endothelial cells contained abundant quantities of smooth muscle actomyosin. Cultured endothelial cells also contained ABH antigens appropriate to the tissue donor's blood type; these antigens were not detectable on cultured smooth muscle cells or fibroblasts. These studies demonstrate that it is possible to culture morphologically and immunologically identifiable human endothelial cells for periods up to 5 mo.

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure flux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation, it is imperative to target by gene knockout or RNA interference more than one autophagy-related protein. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways implying that not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular assays, we hope to encourage technical innovation in the field.

The acute respiratory distress syndrome

Abstract: The acute respiratory distress syndrome is a common, devastating clinical syndrome of acute lung injury that affects both medical and surgical patients. Since the last review of this syndrome appeared in the Journal, 1 more uniform definitions have been devised and important advances have occurred in the understanding of the epidemiology, natural history, and pathogenesis of the disease, leading to the design and testing of new treatment strategies. This article provides an overview of the definitions, clinical features, and epidemiology of the acute respiratory distress syndrome and discusses advances in the areas of pathogenesis, resolution, and treatment. Historical Perspective and Definitions . . .

Guidelines for the use and interpretation of assays for monitoring autophagy

Abstract: In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.

A general model for the origin of allometric scaling laws in biology

Abstract: Allometric scaling relations, including the 3/4 power law for metabolic rates, are characteristic of all organisms and are here derived from a general model that describes how essential materials are transported through space-filling fractal networks of branching tubes. The model assumes that the energy dissipated is minimized and that the terminal tubes do not vary with body size. It provides a complete analysis of scaling relations for mammalian circulatory systems that are in agreement with data. More generally, the model predicts structural and functional properties of vertebrate cardiovascular and respiratory systems, plant vascular systems, insect tracheal tubes, and other distribution networks.