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M W Chase

Publications and source records attributed to M W Chase.

52 records · Page 3Linked to original sources
PubMed1972

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↗
PubMed1971

The Kveim test.

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Antigens↗
PubMed1969

Studies on the sensitization of animals with simple chemical compounds. XII. The influence of excision of allergenic depots on onset of delayed hypersensitivity and tolerance.

In light of knowledge of the rate and route of dispersal of allergenic chemicals from ear sites (0.25 microg of picryl chloride, or 2:4 dinitrochlorobenzene in 0.25 microg and 5.0 microg amounts), dispersal was interrupted at selected times by ear excision. The animals exposed in this manner to different, tiny amounts of allergen were tested for development of contact type hypersensitivity. Both of these allergenic chemicals left the local ear site in about three phases of successively lengthening "half-lives." In the first phase, the escape rate was high. The principal pathway of escape was not via the lymphatics but via the blood vessels. Ear excisions made at 24 hr after injection of 0.25 microg of picryl chloride (PCl) or at 12 hr after injection of 5.0 microg of dinitrochlorobenzene (DNCB) essentially blocked onset of delayed type hypersensitivity, hence the first fraction to escape (80% of PCl, 98% of DNCB) was not used for sensitization. This large fraction serves rather to set up a state of specific tolerance, for these individuals showed extensive deficits in their ability to respond to a later sensitizing course. Also the ability to form hapten-specific antibody appeared nearly completely suppressed. Injections of allergen into the blood stream or directly in auricular nodes, in an amount approximating that which escaped early from the ear, also led to the same degrees of unresponsiveness-sometimes full, sometimes partial tolerance. The same types of specific tolerance were secured also by injecting subsensitizing doses into the ear, without excision, or into the flank and by contact tests applied to the flank. The allergen remaining in the ear after the early outflow, particularly between 12-24 hr and 3-4 days, appeared to constitute the sensitizing depot. The longer this depot was available to the animals the greater the immunological "information" for sensitization was picked up until the depot had served its full function around the 4th day. "Peripheral sensitization" was clearly demonstrable. The eventual degree of sensitivity attained by the animals was a resultant of two immunologic processes which occurred independently-tolerogenic effects of escaped chemical on the one hand and on the other the sensitizing effect of the local sensitizing depot of allergen bound in the ear tissue.

Allergens↗
PubMed1969

Studies on the sensitization of animals with simple chemical compounds. XI. The fate of labeled picryl chloride and dinitrochlorobenzene after sensitizing injections.

The fate of (14)C-labeled allergens injected intradermally into guinea pigs, namely picryl chloride (PCl*) and 2:4 dinitrochlorobenzene (DNCB*), was followed during the induction period of delayed hypersensitivity. Both chemicals were applied in a single injection into one ear in amounts that approached their minimal sensitizing doses (PCl, 0.25 microg; DNCB, 5.0 microg). Radioactivity in the various tissues was determined by liquid scintillation counting after combustion of tissues to CO(2) and H(2)O. The injected allergens seemed to leave the injection site in three phases. A large proportion of allergen escaped rapidly from the ear, about 50% within 3 hr in the case of PCl, within 15 min for DNCB, the difference probably reflecting their unequal reaction constants. Initially there was a "half-life" escape in 2.5 hr with injected dosage of 0.25 microg PCl and in 18 hr for 5.0 microg DNCB. This escape occurred via the regional veins and not via the lymphatics. Radioactive decomposition products of the allergens were already present in the urine within 3-4 hr. After 6-8 hr, the half-life time of escape lengthened to approximately 28 hr for both allergens used in their respective initial dosages, holding up to 2 days after which there occurred still further slowing; between 2 and 4 days the time was about 43 hr for PCl, much longer (72-88 hr?) for DNCB, apparently reflecting different physicochemical properties of this second fraction. Sensitization seemed to be connected with the portion that was present between 12 hr and 4 days of the induction period. It is not known how far the escape of radioactivity during this period may represent gradual hydrolysis of attached picryl and dinitrophenyl groupings, respectively, to form picric acid and dinitrophenol. Gradual accumulation of the second fraction in the regional lymph nodes could definitely be excluded. It was noted that no hypersensitivity arose and essentially no depot of radioactivity existed between 12 hr and 4 days when DNCB was injected in a dose of 0.25 microg, owing to its ready escape from the ear; but 20 times as much DNCB caused sensitization and provided about the same fixed depot as 0.25 microg of picryl chloride. After delayed hypersensitivity had been established, traces of radioactivity were still measurable at the site. This third fraction, probably representing a different coupling product, escaped at a very low rate and was traceable up through several weeks. No demonstrable radioactivity could be detected in thymus, spleen, and mesenteric nodes when examined at short intervals between (1/2) min and 17 days. In analogy with findings on transplantation "immunity" and with studies reported in the following paper, the induction of delayed hypersensitivity can be explained by encounters between lymphoid cells and the hapten complex which is found present in the local site for 4 days, in agreement with Medawar's concept of peripheral sensitization.

Allergens↗