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Biomedical subjects

J Prothero

Publications and source records attributed to J Prothero.

At least 19 recordsLinked to original sources

Bone and fat as a function of body weight in adult mammals.

Three independent data sets, for both bone and fat weight, in adult mammals, expressed as a function of body weight, were submitted to linear regression analysis of the log-log transformed data. For land mammals generally, weighing up to 6.6 metric tons, the slope of the best-fit regression line for skeletal weight is 1.073 +/- 0.021. This regression line underestimates skeletal weight in the elephant by about 40%. For cetaceans, varying in body weight from about 0.1 to over 100 metric tons, the slope of the best-fit regression line for skeletal weight is 1.133 +/- 0.044. Since the slopes for these two groups of mammals are not statistically different, and since cetaceans are normally shielded from gravity, due to buoyancy, it is suggested that the slope (1.073) in land mammals may not be an adaption to gravity. After pooling the data from the three data sets for fat, the resultant regression has a slope of 1.146 +/- 0.026. It is argued, on theoretical grounds, that slopes greater than 1.2-1.3 will not be found for the log-log regression of any major tissue on body weight, taken over the whole mammalian weight range.

Adipose Tissue

A resource guide to VR in medicine.

This guide provides a bibliography of many of the most noteworthy contributions to the emerging literature about virtual reality in medicine, along with listings of the most relevant conferences and resources for researchers. This is an abridged version of a continuously updated comprehensive document which is available on-line to the research community.

Computer Graphics

Determination of relative fiber orientation in heart muscle: methodological problems.

Knowledge of the muscle pattern in the heart is important to understanding cardiac contraction and propagation of the electrical stimulus. Most work on this pattern has been carried out by blunt gross dissection, whereby fiber bundles are easily visible on the peeled heart wall. However, it has never been shown, to our knowledge, that the orientation of macroscopic fiber bundles seen in a peeled heart corresponds to that of the constituent myofibers (muscle cells). For this purpose, one needs to carry out a three-dimensional microscopic reconstruction within a documented macroscopic reference frame. To draw valid conclusions in such a coordinated macroscopic and microscopic study, one must estimate the (slice) angle between the long axis of a muscle cell and the plane of section. Otherwise any alleged differences between the macroscopic and microscopic orientations may be just an artifact of sectioning. In this study we have shown that, provided the images of the myofibers meet simple criteria, one can be reasonably confident that the potential error incurred by sectioning is small. On this basis, we demonstrated that while there is a general correspondence between the macroscopic fiber and the microscopic myofiber orientations, there are significant differences in detail.

Animals

Scaling of bodily proportions in adult terrestrial mammals.

To model body shape, a data base was constructed for body, forelimb, and hindlimb length, surface area, and girth, each as a function of body weight, in a diversity of mammals. These data were submitted to linear least-squares regression analysis. In addition, data on the partitioning of weight and surface area among the body segments (head-trunk, forelimbs, and hindlimbs) were collected. These data imply a relatively constant partitioning of body weight and surface area among the body segments. The regression parameters and the body segment data were used to build and test a model of bodily proportions. The model consists of three classes of cylinders, each specified by a length and a diameter, representing the three classes of body segments. The parameters of the model were constrained to enforce geometric similarity (constant shape). The model was found to agree reasonably well with an independent subset of the data. It is concluded that adult land mammals do exhibit geometric similarity over a substantial weight range.

Animals

Myofiber orientation in the weanling mouse heart.

This study provides a quantitative description at the cellular level of myofiber orientation throughout the ventricles of the mouse heart. We employed computer-based methods of three-dimensional reconstruction from 3 microns plastic-embedded serial sections. Registration marks were introduced by drilling minute holes into each plastic block. Subfields of selected sections were photographed at 20 x magnification, using a computer-controlled microscope. The 35-mm film frames were projected onto a digitizer tablet and the epi- and endocardial boundaries were digitized manually. The "heads" and "tails" of linear segments of a representative myofiber sample present in each projected image were digitized in point mode. The many x-, y-, z-coordinate tables generated by digitization were reassembled automatically, giving a numerical description of the myofiber pattern. This pattern was studied interactively on a high-performance graphics workstation. We find that the heart wall is, to a first approximation, a "sandwich," in which the myofibers in the middle layer run mainly circumferentially, whereas those in the inner and outer layers run parallel or oblique to the apical-basal axis, a variant of the classical model of the myofiber pattern. We observed a "sleeve" in the interventricular septum, formed by longitudinal and oblique myofibers, a feature which apparently has not been described previously. Myofibers not running parallel to the transverse or longitudinal planes were not resolved in this study. We conclude that three-dimensional reconstruction of the cardiac myofiber pattern at the light-microscopic level, while laborious, is technically feasible and scientifically worthwhile.

Animals

Lifetime energy budgets in mammals and birds.

1. Two data sets for standard energy metabolism (351 and 320 species, respectively) and one for maximal lifespan (494 species) in mammals have been assembled from the literature. 2. In addition smaller data sets of active (field) energy metabolism in mammals (36 species) and in birds (25 species) have been drawn on. 3. The products of the respective regression parameters as well as the products of energy metabolism and maximal lifespan in individual species have been computed in order to estimate lifetime energy metabolism in mammals generally and in various mammalian orders. 4. It is found that lifetime energy budgets in mammals generally, whether standard or active, very systematically with body mass with slopes between 0.87 and 0.93, significantly different from unity (P less than 0.001 or P less than 0.01). 5. In birds, lifetime energy budgets, whether standard or active, vary with slopes of 0.94 +/- 0.05 and 0.88 +/- 0.09, which are not significantly different from unity (P greater than 0.1). 6. In carnivores, artiodactyls, primates and bats the slopes for lifetime standard as well as lifetime active energy budgets are not significantly different from one in any of the investigated data sets. 7. In rodents the lifetime standard energy budgets have slope significantly different from one; in marsupials one data set for lifetime standard and the one for lifetime active energy budget lead to slopes significantly different from one. 8. It is concluded from this analysis that current data do not support the hypothesis that lifetime energy budgets, whether standard or active, vary as the first power of body mass in mammals generally.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Three-dimensional reconstruction of the myofiber pattern in the fetal and neonatal mouse heart.

A methodology for three-dimensional reconstruction from serial sections and interactive computer graphics is described briefly. This methodology was applied to study the morphogenesis of the cardiac myofiber pattern in the fetal and neonatal mouse heart (ventricles). Few organized in-plane myofibers were found in the myocardial wall before 12 days postconception, but many fibers were observed in the very numerous trabeculae at all times up to birth. However, beginning at about 12 days, the number of fibers in the myocardial wall increases rapidly: these are seen predominantly in the transverse plane. The neonatal mouse heart, especially the left ventricle, resembles a small adult muscular artery. But the global myofiber pattern in the mouse heart at these stages appears to be more complex than might be inferred from earlier studies of the local myofiber pattern at a few sites in the ventricles of a few species of adult mammals. In particular, the pattern in and adjacent to the interventricular septum appears quite complex.

Animals

Cell enlargement: one possible mechanism underlying cellular senescence.

We previously demonstrated an inverse relationship between the G1 volume of human diploid fibroblast-like (HDFL) cells obtained from foreskin tissue and clonal replicative potential. On the basis of these results, we suggested that one process underlying in vitro senescence is a progressive increase in the mean cell volume of successive progeny within clonal lineages. We now report that the size of HDFL cells, as well as of chick embryo fibroblasts, can be increased in the virtual absence of cell division by culturing at low density and at low serum concentration (0.1-1.0%). Consequent to an increase in cell size, the replicative potential of the cells is reduced to the level of later-passage cells of similar size. By clonal analysis, the populations of enlarged cells contain up to three times as many nondividing cells as do controls. In the enlarged populations, the proportion of cells producing attenuated clones (four or fewer progeny) increases by about 30%, whereas the proportion of cells yielding greater than 32 cells declines by a similar percentage. These observations lead us to propose that replicative potential may be limited by cell size, which in turn may be regulated by a kinetic relationship between cellular growth and cell division cycles.

Animals

Independent evidence for a commitment model of clonal attenuation.

We previously reported a model of clonal attenuation which assumes three classes of cells: small highly replicative cells; intermediate size cells of limited replicative potential and large non-diving cells. Computer simulations carried out with the model lead to predictions of how the relative proportion of each cell type varies throughout the in vitro replicative life span of a mass population. These predictions appear to be broadly confirmed by independent data recently reported by another laboratory.

Clone Cells

Coordinated three-dimensional reconstruction from serial sections at macroscopic and microscopic levels of resolution: the human heart.

This report describes procedures we have developed for obtaining correlated quantitative structural information at two very different levels of resolution. Accurate reconstructions of entire organs and samples of tissue within organs were produced in correct scalar and topographical relationship using computer-assisted techniques. A specially designed sectioning apparatus, a macrovibratome, was used to section serially the ventricles of the human heart macroscopically. Photographs were taken of every slice. A tissue block excised from a slice at a specified locus in the left ventricular wall was embedded in plastic; serial-3 micron sections were cut in each of two orthogonal orientations. Photomicrographs were taken by semi-automated microscopy. Images of both macroscopic and microscopic sections were projected onto a bitpad and manually digitized. The resulting tables of x-, y-, and z-coordinates were reassembled on a VAX 11/750 computer, then transferred to a high-performance graphics workstation and displayed as three-dimensional images. Microscopic images were shown in the correct reference frame with respect to the macroscopic (parent) structure.

Heart

Proliferative potential of human fibroblasts: an inverse dependence on cell size.

Human foreskin fibroblast-like cells were separated on the basis of DNA content and cell size by fluorescence-activated cell sorting. Subpopulations of "large" or "small" cells with the same (G1) DNA content were clonally expanded and found to contain predominantly nondividing or highly proliferative cells, respectively. From the rate of clonal growth, we deduce that small cells divide faster than large cells. Intermediate-sized cells were found to yield primarily smaller ("attenuated") clones. The clonal data can be incorporated into a previously reported kinetic model of clonal attenuation. This version of the model postulates that small "stem" cells yield larger daughters which have only a limited proliferative potential. We also postulate that a progressive increase in cell size can account for the decreasing concentration of DNA polymerase alpha, which has been reported in older cultures.

Cell Division

Scaling of maximal lifespan in bats.

1. Values for maximal lifespan in heterothermic and homeothermic bats as a function of body weight, brain weight and lifetime basal energy consumption were submitted to linear (log-log) and multiple regression analysis. 2. The results of the regression analyses of maximal lifespan in bats were compared with those reported for non-flying mammals based on both narrow and wide weight ranges. 3. It was found that the regression lines (linear or multiple) for maximal lifespan in bats (heterothermic or homeothermic) lie well above the regression lines for non-flying mammals. 4. Predictions of maximal lifespan in heterothermic bats based on estimated lifetime basal energy consumption and body weight are in reasonable agreement with observed values when torpor and hibernation behaviour are taken into account. 5. But observed values of maximal lifespan in homeothermic bats were found to lie substantially above the regression lines derived for non-flying mammals. 6. It was concluded that existing hypotheses do not account for the long lifespan observed in bats generally.

Animals

Methodological aspects of scaling in biology.

Interest in the scaling approach to problems of biological design has increased dramatically in the past few years. But thus far no systematic attempt has been made to review the possible pitfalls attendant upon this approach. As a beginning, the problems which can arise from rounding exponents, or taking standard errors at face value, or expressing dependent variables in ratio form are discussed. There follows a discussion of fitting specific functions to scaling data, of the special needs for documentation and of the potential value to be derived from suitable computer programs in scaling studies. Finally, the possible difficulties of demonstrating global optimization in biological systems, the risks of dimensional analysis and the value and nature of scaling models are discussed.

Animals

Scaling of energy metabolism in unicellular organisms: a re-analysis.

The database used by Hemmingsen (1960) to compute energy metabolism in unicellular organisms was reassembled and submitted to linear (log-log) analysis. As Hemmingsen noted, this data set includes marine zygotes, which are not unicellular organisms. If no temperature correction factors are applied to the data the best-fit regression line has a slope of 0.698 +/- 0.024. Application of the temperature correction factors assumed to have been used by Hemmingsen gave a slope of 0.756 +/- 0.021, identical to the value he reported. The correlation coefficient is 0.97. The mean scatter about the regression line exceeds 100%. A revised set of temperature correction factors gave a slope of 0.730 +/- 0.021, suggesting that the value of almost exactly three-quarters obtained by Hemmingsen was probably fortuitous. The slope of the best-fit regression line is very sensitive to the inclusion of bacteria and flagellates. When the data points for these organisms are omitted from the calculation the slope decreases to 0.645 +/- 0.045. When the data points for bacteria, flagellates and marine zygotes are omitted, the slope drops to 0.608 +/- 0.025. The correlation coefficient (0.97), compared to the best-fit line reported by Hemmingsen, is unaffected; the mean deviation about the regression line drops to 40% and the points are evenly distributed about the regression line. Because of the small number of species for which measurements have been made, the existing database relating energy metabolism to cell size is not representative of unicellular organisms generally. It is concluded that the case for a three-quarters power rule expressing energy metabolism as a function of size in unicellular organisms generally is not at all persuasive.

Animals

Scaling of standard energy metabolism in mammals: I. Neglect of circadian rhythms.

The original data employed to derive the three-quarters power rule relating standard or basal energy metabolism in mammals to adult body weight are examined. It is shown that the data may contain a systematic bias due to an (apparent) neglect of circadian rhythms. Correction for this bias would tend to decrease the slope of the regression line, bringing it into better conformity with the value of about two-thirds obtained in a recent study of a larger sample by Bartels (1982).

Animals

Organ scaling in mammals: the kidneys.

Values of kidney weight in adult male and female mammals, both terrestrial and aquatic, as well as values for renal blood flow and glomerular number and diameter, were submitted to linear (log-log) regression analysis. The slope of the regression line for kidney weight in 63 species of adult terrestrial mammals was 0.85 %/- 0.01. No statistically significant difference was found between the slopes of the regression lines for male and female terrestrial mammals. The slope of regression line for kidney weight in eight species of adult aquatic mammals was 0.92 +/- 0.01. Again, no statistically significant difference was found between the slopes for males and females. However, the slope (0.92) of the regression line for aquatic mammals was significantly different from the slope (0.85) for terrestrial mammals (P much less than 0.001). The slope of the regression of renal blood flow on body weight was 0.82 +/- 0.01. This value is consistent with the hypothesis that renal blood flow represents a constant fraction of cardiac output (over about 3.4 orders of magnitude in body weight). The slopes of the regression lines for glomerular number (per kidney) and mean glomerular diameter were 0.59 +/- 0.02 and 0.11 +/- 0.01, respectively. A schematic model representing the scaling of energy-partitioning in mammals is introduced.

Animals