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  • 1
    Electronic Resource
    Electronic Resource
    Morphometric Approaches for Evaluating Pulmonary Toxicity in Mammals: Implications for Risk Assessment (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Risk analysis 14 (1994), S. 0 
    Details
    ISSN: 1539-6924
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Recent advances in quantitative morphology provide all the tools necessary to obtain structural information in the lung that can be quantified and interpreted in the three-dimensional world of toxicology. Structural hierarchies of conducting airways and parenchyma of the lung provide: (1) numbers of cells per airway, lobe, or lung; (2) surface areas of cells, airways, and alveoli; (3) length of airways and vessels; and (4) volumes of cells, alveoli, airways, vessels, and individual lobes or the entire lung. Unbiased sampling of these subcompartments of the lung requires fractionation of lobes or individual airways. Individual airways of proximal and distal generations are obtained by airway microdissection along one axial pathway and comparisons made between airway generations. Vertical sections of selected airways are used to sample epithelium and interstitium. Using this unbiased approach of quantitative morphology, we have shown that inhalation of low ambient concentrations of ozone ([O3]0.15 ppm) near or at the United States National Ambient Air Quality Standard (NAAQS) (0.12 ppm O3) induces significant alterations in bronchiolar epithelium and interstitium in nonhuman primates but not rats. The alterations do not appear to be concentration- or time-dependent, thereby bringing into question the current NAAQS that may be at or above the threshold for distal airway injury in primates. Unbiased morphometric methods are critical in a quantitative evaluation of toxicological injury of mammalian tracheobronchial airways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1539-6924.1994.tb00244.x
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  • 2
    Electronic Resource
    Electronic Resource
    STEREOLOGY AND ITS USES IN CELL BIOLOGY (1982)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 383 (1982), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1982.tb23158.x
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  • 3
    Electronic Resource
    Electronic Resource
    Surface area ratios II. A stereological method for estimating changes in average cell volume and frequency (1979)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 195 (1979), S. 257-264 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The study describes a stereological method for detecting relative changes in cells-with respect to their average volumes and to their frequencies within one cm3 of exocrine cells. The method is based on surface area ratios (Bolender, '1979) and can detect changes comparable to those obtained with the numerical density approaches (Loud, '68; Weibel et al., '69; Bolender, '74; Williams, '77). The new method requires only intersection counts- the same ones that are used for surface density estimates- and, as a result, avoids the difficult and often problematic procedures of the numerical densities. In analyzing the cellular changes in vitro, the choice of either a zero or timed control was found to exert a major influence on the results. Timed controls were required to “isolate” the experimentally induced changes from those Produced by the incubation medium.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091950202
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  • 4
    Electronic Resource
    Electronic Resource
    Surface area ratios. III. A stereological method for estimating relative changes in average hepatocytes (1980)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 196 (1980), S. 323-331 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Stereological information seems to be most interpretable, with respect to experimental changes, when related to an average cell. Current methods for obtaining an average cell volume essentially consist of dividing an aggregate volume of cells by the number of nuclei therein, assuming one nucleus per cell (Loud, ′68). Hepatocytes represent a somewhat special case, however, in that some are binucleated. Since the number of hepatocytes in one cm3 of tissue is less than the number of hepatocyte nuclei in the same cm3, dividing the hepatocytic volume by the number of nuclei gives only an average “mononuclear” hepatocyte. Such an estimate creates two interpretation difficulties: (1) the volume of an average mononuclear hepatocyte is less than that of an average hepatocyte; and (2) changes in the proportion of binucleated cells may compromise the “relative comparisons” for which the method was originally intended. The purpose of this study is to describe a new approach that can avoid these difficulties altogether, and then to assess the errors associated with the average mononuclear hepatocyte estimates. This was accomplished by combining a surface area ratio method, which can detect average cell changes without being influenced by binucleated cells, with the method of Loud (′68), which is affected as described above. The experimental model was the rat liver (n = 20) recovering for 3 days from 5 daily injections of sodium phenobarbital (100 mg/kg). The results indicate that changes in the average cell volumes for the two methods have similar slopes, but by not accounting for binucleated cells, the average mononuclear hepatocyte reference overestimates average hepatocytic volume changes by 63.1%. Similarly, the mononuclear hepatocyte reference overestimates changes in the surface areas of the ER by 32.1% (range = 26.1% to 39.1%), the SER by 21.6% (range = 14.3 to 30.1%), and the RER by 65.1% (range = 54.6% to 76.4%).
    Additional Material: 7 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091960308
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  • 5
    Electronic Resource
    Electronic Resource
    Method for decreasing the statistical variance of stereological estimates (1983)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 207 (1983), S. 89-106 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Three methods are described for decreasing the statistical variance of stereological estimates. Methods 1 uses profile boundaries and surface densities of nuclear membranes, measured in thin sections, to estimate the mean diameter, surface area, and numerical density of spherical and nonspherical nuclei. For the guinea pig pancreas (number(m) = 4), the standard deviations (s.d.) as a percent of the mean for the estimates of the diameters of the exocrine, duct, and endothelial cell nuclei were 1.5%, 3.3% and 1.4%. The estimate for the mean diameter of exocrine nuclei (6.4 ± 0.1 μm) was based on a spherical model, whereas the estimates for the diameters of the nonspherical (and nonconvex) nuclei of the duct (6.4 ± 0.2 μm) and endothelial (6.7 ± 0.1 μm) cells were calculated from the numerical density of the exocrine cells and the relative frequenceis of the three cell types (determined from serial reconstructions). In an average cubic centimeter, there were 6.17 × 108 ± 0.32 × 108 (s.d. 5.1% of mean) exocrine cells, 1.64 × 108 ± 0.18 × 108 (10.9%) duct cells, and 0.803 × 108 ± 0.13 × 108 (16.6%) endothelial cells. In contrast to method 1, conventional stereological approaches were found to have standard deviations two-to eightfold larger. Method 2 uses a mean nuclear surface area and a ratio of surface densities to estimate the surface area of a membrane compartment in an average cell. A s.d. equal to 6.5% of the mean was found for the surface are of the outer mitochondrial membrane in an average exocrine cell (672 ± 43.6 μm2), which represented an almost fourfold reduction in the s.d. compared with an earlier estimate (Bolender, 1974). Method 3 relates the surface area of a membrane compartment to a standard number of cells. Referenced to 106 cells, for example, the surface area of the inner nuclear membrane of endothelial cells had a s.d. equal to 2.9% of the mean, whereas the surface density of the same membrane compartment - referenced to a cm3 to cells - had a s.d. at 19.1% of the mean. In this case, method 3 produced almost a sevenfold reduction in the standard deviation. Similar results were found for exocrine and duct cells.The results of the study indicate that the standard deviation of a stereological estimate can be reduced to a miniumum by using a mean nuclear profile boundary to generate an estimate for a nuclear numerical density, which, in turn, can be combined with a surface density to obtain average cell information.
    Additional Material: 6 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1092070110
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  • 6
    Electronic Resource
    Electronic Resource
    Surface area ratios. I. A stereological method for estimating average cell changes in membrane surface areas (1979)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 194 (1979), S. 511-522 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The study (i) describes a method for estimating relative changes in membrane surface areas as they occur in stereological “average cells,” and (ii) considers the effect of the controls on these estimates. The results indicate that changes in five membrane compartments of pancreatic exocrine cells-produced by a secretagogue (carbomylcholine chloride)-were detected similarly when related to either an average cell surface (surface area ratio method) or to an average cell volume (method of Loud, '68). Changes, however, detected with surface densities, which relate these membrane compartments to 1 cm3 of exocrine cell cytoplasm or pancreas, were notably different from the first two estimates. This inconsistency could be explained by the fact that the surface densities were influenced not only by membrane changes within the exocrine cells, but also by changes in the number of these cells filling the cm3 of reference volume. Relating the data to an average cell reference-instead of 1 cm3-improved the accuracy of the estimates for changes in membrane surface areas by as much as several fold; the choice of controls had a similar several-fold effect on the results.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091940405
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  • 7
    Electronic Resource
    Electronic Resource
    Quantitative morphology for biologists and computer scientists: I. Computer-aided tutorial for biological stereology (version 1.0) (1992)
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 21 (1992), S. 338-346 
    Details
    ISSN: 1059-910X
    Keywords: Tutorial ; Electron microscopy ; Light microscopy ; Software ; Quantitative morphology ; Stereology ; Morphometry ; Simulations ; Terminology ; Data types ; Sampling ; Hierarchies ; Interpretation of data ; Bio-Matrix Project ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: This paper describes a computer-aided tutorial for biological stereology. Stereology, a type of quantitative morphology, includes a collection of statistical methods that quantify the structural compartments that can be viewed in sections with light and electron microscopy. These methods provide volume, surface, length, shape, and number data, and help define the quantitative relationships among the structural compartments of biological hierarchies. Hierarchies, which connect structural data ranging in size from molecules to organs, serve as a central core to which the data of biological databases can be linked. The tutorial focuses on two objectives. It provides the user primarily interested in using quantitative morphology databases with background information, and offers a set of state-of-the-art tools to researchers wishing to use these methods in the laboratory. The main topics of the tutorial include: introduction to quantitative morphology, symbols/terms, data types, sampling, hierarchies, data interpretation, and utilities. The tutorial runs under the MS-DOS operating system and requires at least an IBM PC AT (or compatible), a color monitor (EGA, VGA), 540 KB of RAM, and 3 MB of hard disk space. © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jemt.1070210409
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  • 8
    Electronic Resource
    Electronic Resource
    Computer assisted data collection for stereology: Rationale and description of point counting stereology (PCS) software (1992)
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 21 (1992), S. 347-354 
    Details
    ISSN: 1059-910X
    Keywords: Quantitative morphology ; Morphometry ; Light microscopy ; Electron microscopy ; PCS System III ; MS-DOS ; UNIX ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: The paper describes microcomputer software for point counting stereology. Stereology includes a collection of statistical methods that quantify the images of light and transmission electron microscopy. The methods use test grids placed over images to collect raw data, which includes counts of points, intersections, transections, and profiles. In turn, the counts are included in stereological equations that give estimates of compartmental volumes, surfaces, lengths, or numbers. These parameters describe the composition of a structure in three-dimensional space. The PCS (point counting stereology) System Software III serves as a data collection, storage, and management tool. Users set up point counting protocols without programming, enter data by pressing predefined function (MS-DOS) or alphabetic keys (UNIX), store data in files, select files for analysis, and calculate results as stereological densities. The latest version of the PCS software includes a new user interface and is designed as a research “front end” that can feed data either into the calculation tools of a stereology tutorial (Bolender, 1992, this issue) or into the analysis routines of quantitative morphology databases (Bolender and Bluhm, 1992). © 1992 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jemt.1070210410
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  • 9
    Electronic Resource
    Electronic Resource
    Software for quantitative immunogold and in situ hybridization (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 25 (1993), S. 304-313 
    Details
    ISSN: 1059-910X
    Keywords: Quantitative morphology ; Stereology ; Morphometry ; Software ; Tutorials ; Toolkits ; Simulators ; Immunogold ; In situ hybridization ; Gene expression ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: A well-deserved criticism of stereology is that it is often too difficult to understand and use. Nevertheless, it is rapidly becoming one of the most effective ways of collecting and interpreting structural data in experimental biology. Recent breakthroughs in theory have produced a remarkable set of tools that can be used to engineer new methods. The dilemma remains, however, in that some of these new methods continue to be too difficult to understand and use. One solution to this growing problem of technology transfer might be to simplify the methods with computer software. To test this idea, programs were written for quantitative immunogold and in situ hybridization. Simulators were used to develop and test new experimental designs, which, in turn, were translated into step-by-step laboratory toolkits. This paper shows how these toolkits can turn two-dimensional section data into estimates for the number of labeled molecules in three-dimensional organelles, cells, tissues, and organs. The results indicate that software can identify the key data of an experiment and reduce the computational requirements of a new stereological method to entering constants and variables into data entry forms. © 1993 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jemt.1070250407
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  • 10
    Electronic Resource
    Electronic Resource
    Biological stereology: History, present state, future directions (1992)
    New York, NY [u.a.] : Wiley-Blackwell
    Microscopy Research and Technique 21 (1992), S. 255-261 
    Details
    ISSN: 1059-910X
    Keywords: Sterology ; Morphometry ; Quantitative morphology ; Computers ; Software ; Tutorials ; Simulations ; Databases ; Bio-Matrix Project ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Natural Sciences in General
    Notes: The development of a quantitative structural platform for experimental biology - extending across a hierarchy of sizes ranging from molecules to organisms - has been punctuated by a series of major achievements over the last 30 years. Stereology, a form of quantitative morphology, has contributed handsomely to this success. A personal view is presented highlighting key events in the development of biological stereology. We also examine stereology with a view toward future developments in biology and speculate how stereology might contribute to the new biological infrastructure currently being built with computers. © 1992 Wiley-Liss, Inc.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/jemt.1070210402
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