ULCERATIVE TYPES AS DETERMINED BY INHERITANCE AND AS RELATED TO NATURAL RESISTANCE AGAINST TUBERCULOSIS: AN EXPERIMENTAL STUDY ON INBRED GUINEA PIGS.
Five families of strictly inbred guinea pig whose general resistance to experimental tuberculosis had previously been determined by Wright and Lewis have now been studied with reference to the characteristics of the local lesion produced by intracutaneous inoculation with the tubercle bacillus. It is found that there are clearly recognizable familial types based on the size and quality of the nodular lesion, the ulcerative lesion consecutive to this and the general effectiveness of the healing process when in evidence. Family 39 which has the lowest general resistance forms an initial papule which does not differ appreciably from that formed by Family 35 which is the most resistant. In the ulcerative stage Family 39 shows an indolent excoriating process which exhibits none of the qualities which would be expected to make for healing. Family 35 exhibits a firm primary papule and nodule followed by an active healthy type of ulceration which is definitely restrained in comparison with that of the low resistance Family 13. Family 35 also presents the largest number of completely healed lesions in the later observation periods. Family 13 shows a larger, softer, primary papule and nodule than any of the others. The ulcer when formed is less restrained; that is, it is larger in proportion to the total size of the lesion. It is also more generally destructive. This family also shows a singular tendency to the formation of secondary ulcers along the lymphatic channels leading toward the adjacent lymph nodes. The adjacent lymph nodes are likewise more severely affected and frequently ulcerate through the skin giving rise to residual discharging sinuses. Families 2 and 32 are less definitely characterized. They are of the same order as 35 and 13 in that the ulcerations are active and healthy. Such similarities as are recognizable place Family 2 more nearly with 13 and Family 32 more nearly with 35. In general the qualities of lesion exhibited are such as to agree with the general resistance as previously determined and it is believed that the qualities underlying the tissue reaction may be safely considered to be among the influential factors in the make-up of the natural resistance against tuberculosis. The differences in reaction are in part manifested against agents causing simple inflammation also, and hence must be designated as non-specific with reference to the tubercle bacillus. There are definite indications of other "constitutional" differences in the character of the tissues and the general make-up of these families. The accumulated evidence from the study of the separate families and intercrosses between them is to the effect that the differences in question are transmitted by the blending type of inheritance and are therefore controlled by multiple unit characters. It is also suggested by the observations that certain of the significant characters are recessive in nature. It is of considerable interest that the observations agree very well with the older conception of an inherited, predisposing, constitutional diathesis as a significant factor in the incidence of tuberculosis.
Henry Phipps Institute of the University of Pennsylvania, Philadelphia, and the Department of Animal Pathology of The Rockefeller Institute for Medical Research, Princeton, N. J.
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Lewis
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Loomis