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Biomedical subjects

J T Bonner

Publications and source records attributed to J T Bonner.

At least 37 records · Page 2Linked to original sources

Proteases in cellular slime mold development: evidence for their involvement.

Protein degradation appears to be essential for normal differentiation in the cellular slime mold Dictyostelium discoideum. Several protease inhibitors block normal differentiation, and in most cases this inhibition can be reversed by addition of amino acids. For example, chloroquine, which inhibits slime mold cathepsin B activity, interferred with development by blocking sorocarp formation, and this inhibition was reversed by the addition of amino acids. Tosyllysyl chloromethyl ketone also blocked development, and this inhibition was reversed by simultaneous additions of amino acids and glutathione. Moreover, the addition of antipain and leupeptin delayed sorocarp formation. These results, together with the finding reported earlier that cathepsin B activity is differentially localized in the prestalk-prespore zones of the migrating slugs, suggest that proteolysis might play a regulatory role in cellular slime mold differentiation.

Amino Acids↗

The prestalk-prespore pattern in cellular slime molds.

In cellular slime molds the slugs become divided into two regions with different properties, and anterior prestalk-zone and a posterior prespore zone. Although the cells in these zones are normally destined to form the stalk cells and spores of the fruiting body, respectively, they are not irreversibly committed to one sort of differentiation or the other during the slug stage. The volume ratio of the two zones remains almost constant over a wide range of slug sizes. If the prestalk-prespore pattern is distrubed by removing tissue from the slug, conversion of tissue from prestalk to prespore or vice versa occurs as necessary to restore a normal pattern with normal proportions. Conversions also occur in both directions during normal development. The initial formation of the prestalk-prespore pattern may well involve sorting-out, but other mechanisms must be invoked to account for regulation. We describe three different models of the generation of the prestalk-prespore pattern, the'cell-contact model' of McMahon, in which pattern is created by interactions of cells with their immediate neighbors, the 'positional-information model' of various authors, in which pattern formation involves an overall gradient and a gradient-reading mechanism, and the 'activator-inhibitor model' of Gierer and Meinhardt, in which the prestalk-prespore pattern is formed by a system of diffusible substances that affect one another's production. The activator-inhibitor model is the most successful of the models at describing the known features of the prestalk-prespore pattern. The various models lead to a number of distinctive predictions. According to the cell-contact model, small transplants may cause gross changes in the prestalk-prespore pattern, and mutants may exist which severely disrupt pattern formation even if diluted with a large excess of wild-type cells. Positional-information models predict the existence of 'gradient-reading mutants'; slugs that are a mixture of such mutants and wild-type cells would show two prestalk-prespore boundaries, one at the mutant and one at the normal position. Both the activator-inhibitor model and some versions of the positional-information model predict that small transplants will sometimes induce accessory prestalk or prespore zones; the quantitative characteristics of these effects may allow one to make a case in favor of one or other of the two models. Finally, the activator-inhibitor model leads one to expect that mutants may be isolated which normally show accessory prestalk or prespore zones. A search for these phenomena may help determine whether the activator-inhibitor model will continue to enjoy its present preeminent position.

Cell Adhesion↗

Factors influencing intraoperative gastric regurgitation: a prospective random study of nasogastric tube drainage.

A prospective study was conducted to determine the incidence of "silent" gastric regurgitation and aspiration during general anesthesia in 146 patients randomized with respect to presence of a nasogastric tube. A bland dye was instilled in the stomach to serve as the determinant marker. The overall incidence of regugitation was 8.9% and of aspiration, 2.1% in spite of the uniform use of an endotracheal tube. The incidence of regurgitation was twice as high when anesthesia was given by an inexperienced anesthetist (11% vs 5.6%) and in patients without nasogastric tubes (12% vs 6%), although such differences were not statistically significant. The primary agent used, difficulty of endotracheal intubation, location of surgical incision, and duration of anesthesia did not alter the incidence of regurgitation or aspiration. No correlation was found between the detection of subclinical aspiration and the development of postoperative pulmonary complications.

Adolescent↗

Cell differentiation in Dictyostelium under submerged conditions.

Hitherto it has not been possible to obtain spore and stalk cell differentiation of the cellular slime molds in submerged cultures. It is shown here that cells, when placed in roller tubes under an atmosphere of oxygen, will form clumps and differentiate in 48-72 hr into mature spores and stalk cells. Although differentiation occurs without the normal morphogenetic movements, there is the appearance of an anteroposterior polarity of the cells in the clump. In addition to oxygen we examined a number of other factors that affect differentiation.

Cell Differentiation↗

Negative chemotaxis in cellular slime molds.

This study confirms the suggestion of earlier workers that the vegetative amoebae of Dictyostelium repel each other while those of Polysphondylium violaceum do not. When Dictyostelium amoebae were placed in drops on thin and thick agar, the cells moved out faster on the thin agar, presumably because the repellent was more concentrated. This did not occur with Polysphondylium amoebae. Also, if 2 drops of cells were placed side by side, or a single drop was placed near an edge, in Dictyostelium there were fewer cells emerging between the drops (or near an edge) than on the far side. Polysphondylium showed no such difference. However, Polysphondylium amoebae were repelled by Dictyostelium cells (but not vice versa) when drops of each were placed beside one another. Finally, if Dictyostelium discoideum cells were placed in drops over thick and thin agar, but separated from the agar by a dialysis membrane, the cells again spread farther on the thin agar, indicating that the repellent is a dialyzable molecule.

Chemotaxis↗

Preliminary characterization of the acrasin of the cellular slime mold Polysphondylium violaceum.

Some species of cellular slime mold do not respond to cyclic AMP as an acrasin, or chemoattractant. In one such species, Polysphondylium violaceum, we have isolated and purified its acrasin and determined some of its chemical properties, which lead us to believe it is a small molecule of less than 1500 daltons. One possibility is that it might be a peptide. The acrasin specifically attracts the amoebae of P. violaceum and P. pallidum and fails to do so for six species of Dictyostelium tested. We also have evidence for a specific acrasinase that inactivates the Polysphondylium acrasin.

Amines↗

Determination of the active portion of the folic acid molecule in cellular slime mold chemotaxis.

From earlier work it is known that folic acid attracts the amoebae of various species of cellular slime molds (11). Here we have tested a wide variety of pteridines, pyrimidines, and pyrazines to determine what part of the folic acid molecule is chemotactically active. It was shown that the activity lies in the pteridine ring itself. Furthermore, the cell-free supernatants of slime mold amoebae contain an enzyme that renders pterin and folic acid chemotactically inactive, which apparently increases the chemotactic sensitivity of the amoebae to those compounds. Despite the fact that slime mold amoebae secrete small amounts of folic acid-related compounds, there is no evidence that folates are acrasins; rather it is postulated that attraction to folates may be a food-seeking device for the amoebae which prey on folate-secreting bacteria in the soil.

Agar↗

Immunofluorescence evidence for the distribution of cyclic AMP in cells and cell masses of the cellular slime molds.

With immunofluorescent techniques it has been possible to show that bound cyclic AMP is uniformly distributed in the nucleus and cytoplasm of a number of species of cellular slime molds. One species (which does not respond to cyclic AMP as an acrasin) is an exception and has its cyclic AMP concentrated in the nucleus during the feeding and aggregation stage. In cell masses of Dictyostelium discoideum that show early signs of differentiation the anterior, prestalk cells contain more cyclic AMP than the posterior, prespore cells.

Animals↗