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Biomedical subjects

M W Chase

Publications and source records attributed to M W Chase.

At least 19 recordsLinked to original sources

Carnivorous plants: phylogeny and structural evolution.

The carnivorous habit in flowering plants represents a grade of structural organization. Different morphological features associated with the attraction, trapping, and digestion of prey characterize a diversity of specialized forms, including the familiar pitcher and flypaper traps. Phylogenetic analysis of nucleotide sequence data from the plastic rbcL gene indicates that both carnivory and stereotyped trap forms have arisen independently in different lineages of angiosperms. Furthermore, these results demonstrate that flypaper traps share close common ancestry with all other trap forms. Recognition of these patterns of diversification may provide ideal, naturally occurring systems for studies of developmental processes underlying macromorphological evolution in angiosperms.

Base Sequence

The induction of tolerance to allergenic chemicals.

The first recognition of tolerance and partial tolerance to attempted sensitization with simple allergenic chemicals is described. A proper designation would be the Frei-Sulzbeger-Chase phenomenon. Coupling with self occurs in these experiments; there is not only resistance to developing contactant-type sensitivity but also to synthesis of immunoglobulins toward hapten-self complexes. The onset of tolerance is initiated by small doses of haptens. Various facets of these investigations speak strongly against a concept of clonal deletion as an explanation. The concept of the relative numbers of suppressor and effector cells also argues against clonal deletion. Evidence exists that tolerance can be transferred to syngeneic animals by cells during parabiosis (Polak, this volume). Contact sensitivity can be imposed on a tolerized guinea pig through a transfer of cells from outbred sensitized donors, but the tolerance remains after the transferred cells have been rejected. Tolerance could not be overcome in inbred guinea pigs by infusing normal or functionally "labeled" cell populations from close relatives before attempting sensitization, a fact that supports the existence of overwhelmingly large numbers of suppressor cells. Various routes of application have been explored to find a way to establish the tolerant state. The most successful are (1) feeding of small doses and (2) two intravenous injections of massive doses of DNP- or TNP-benzene sulfonates. Several other methods will effect tolerance in about half the animals, but experimental sensitization is the only method that will locate the tolerized animals.

Allergens

Control of antibody heterogeneity in strain 2 guinea pigs.

When Wright's strain 2 guinea pigs are immunized with 2,4-dinitrophenyl conjugates in complete Freund's adjuvant, the antibody response varies with the choice of carrier. Immunization with 2,4-dinitrophenyl-guinea pig albumin elicits a response that requires approximately 21 days to detect. The antibody produced is, according to isoelectric focusing, relatively homogeneous IgG2 having a neutral isoelectric point. On small amounts of IgG are produced. Stimulation of animals with 2,4-dinitrophenyl-keyhole Limpet hemocyanin produces a response by 14 days is similar to the peak response inititated by 2,4-dinitrophenyl-guinea pig albumin. With time, however, basic IgG2 populations are added to the response. By days 28-35, when the anti-hapten response has reached a plateau, the major subpopulation of antibody is neutral IgG2, but there exists several times as much basic IgG2 as IgG1. These data suggest that antigen-responsive cells may be ordered into groups having different thresholds of activation. Regardless of the strength of the antigenic stimulus, there is a set sequence of activation. The same cells always play the primary role, contributing most of the antibody regardless of whether secondary clones of cells are activated.

Animals

Developments in delayed-type hypersensitivities: 1950-1975.

Significant developments during the last 25 years are discussed and interpreted. The following areas of delayed hypersensitivity are included: the mode of active sensitization to simple allergenic chemicals; evidence for anamnestic responses; cell types and cell-cell interactions via lymphokines; function of skin and lymphatics, and the role of the carrier in initial sensitization to allergenic chemicals; acquired tolerance; transfer factor. Some prognostications for the future are attempted.

Amino Acids

Multiple mycobacterial antigens in diagnostic tuberculins.

Guinea-pig antisera containing IgG1 antibodies have been prepared either with killed mycobacterial in paraffin oil or living BCG or intradermal injections of fractions of unheated culture filtrate. Sera, found to contain antibodies specific for different mycobacterial antigens are used in passive cutaneous anaphylaxis (PCA) in 12 times the dilution-to-extinction titer. Animals prepared with sera respond in all sites when unheated culture filtrate, strain H37Rv, is injected intravenously (i.v.) at 17-20 hours. Injection of diagnostic tuberculins i.v. into parallel recipients, in selected amounts, reveals, through reacting sites, the presence of the corresponding antigens and some information on relative amounts. Tuberculins of PPD type are precipitated from heated culture filtrate by ammonium sulfate or trichloroacetic acid (TCA) or benzoic acid. Old Tuberculins are made classically by long heating and evaporation. In all products heat-labile antigens are absent or present in small amount; yet, PPD-S was found to possess five antigens. In all PPD products, there was one dominant antigen, absent from Old Tuberculins. The dominant antigen of OT's was excluded from the TCA-PPD's but was present in most ammonium sulfate-type PPD's. It can be concluded that diagnostic testing made with OT detects a particular delayed-type sensitivity that is different in specificity from that which reacts to TCA-PPD's. Many but not all of the ammonium sulfate PPD's test for both specificities. Several different delayed-type sensitivities are acquired during infection. Supported by Grant AI 01258 of the National Institute of Health.

Animals

Studies on the sensitization of animals with simple chemical compounds. 13. Sensitization of guinea pigs with picric acid.

A method of establishing regular and intense sensitivity to picric acid is described, based upon an initial sensitization by a "split-adjuvant" technique in which the intradermal injection of mycobacteria in paraffin oil precedes or follows the administration of allergen to the same sites. When subsequent contact applications of picric acid are later made, the degree of sensitivity rises in steps such that reactivity occurs in tests made with low concentrations of picric acid, in the range of 0.06-0.006% but varying somewhat from one experiment to another. This heightening of picric acid reactivity represents an anamnestic response in the area of delayed hypersensitivity. The characteristics of contact reactions to the weak allergen, picric acid, differ from those encountered with covalently binding haptens, PCI and DNCB. A slow evolution from an initial micropapular reaction to full reaction requires about 3 days, leading often to a micaceous scale, with histological evidence of vesiculation even while the reaction is still feeble, and to an infiltrate containing a significant number of polymorphonuclear leukocytes. Substitution of an emulsion of picric acid in complete Freund's adjuvant as a priming experience proved to be much less efficient. The split-adjuvant technique offers a general plan for sensitizing with weak allergens. Indeed, technically, sensitization can be acquired even when, for priming, the allergen is applied topically over intradermal depots of mycobacteria in paraffin oil. Compatibility between sensitizer and adjuvant is not required.

Allergens

The Kveim test.

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Antigens