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• An explanation of chronic thyroiditis in man was sought in observations made on rabbits, dogs, guinea pigs, and human subjects. The rabbits received injections of saline extracts of rabbit thyroid glands. The tests for circulating autoantibodies utilized the phenomena of precipitation, complement fixation, and tanned-cell hemagglutination. The third of these, based upon the principle of altering the surface of the red blood cells by dilute tannic acid so that they absorb proteins, was particularly sensitive. The three tests were applied to serums from 35 rabbits injected with rabbit thyroid extract, and thyroid autoantibodies were found in 32. Structural damage was found in the thyroid roughly in proportion to the autoantibody titer in the serum. Similar studies were carried out in dogs and guinea pigs with canine and guinea pig thyroid extracts respectively. The three tests were then applied to serums from patients with chronic thyroiditis. Twelve such patients were found whose serums contained circulating antibodies specifically directed against extracts of human thyroid glands. Three typical case histories are given, with histological findings on thyroid tissue removed during surgery. Six other patients with chronic thyroiditis, proved histologically, were not found to have autoantibodies in their serums at the time of study. These findings lead to the hypotheses that some types of chronic thyroiditis are related to an autoimmunization process within the patient against his own thyroid tissue, and that thyroid autoantibodies are at once indicators and links in the chain of pathological processes.

Actinomycin D, puromycin, 6-mercaptopurine, and cytosine arabinoside were shown to decrease the number of plaque-forming units upon in vitroincubation with suspensions of spleen cells taken from sheep-cell immunized mice. Under similar conditions, 5-iodo-2′-deoxyuridine, 5-bromo-2′-deoxyuridine, azauridine, and chloramphenicol had no effect. Administered in vivo, 6-mercaptopurine, cytosine arabinoside, and chloramphenicol all suppressed plaque production. In the case of the latter two antimetabolites, serum antibody titers remained unaffected by the dosages given.

Use of either incomplete Freund, alhydrogel, or pertussis vaccine as adjuvants together with rat thyroid extract (RATE) elicited neither antibodies nor thyroiditis when injected into Lewis rats. A complete Freund adjuvant emulsion with RATE gave inconsistent results. Multiple, spaced injections of such an emulsion elicited a severe thyroid reaction. Combination of pertussis vaccine with either incomplete Freund adjuvant or alhydrogel elicited moderate thyroiditis. The most marked thyroiditis was obtained using a combination of CFA and RATE emulsion and a separate injection of pertussis vaccine.The authors thank Mr. Steven Buck for his expert technical assistance. The pertussis vaccine was donated by Dr. H. B. Devlin of Parke, Davis & Co., Detroit, Mich. The alhydrogel was donated by Dr. Niels Neergaard, Superfos Export Co., Copenhagen, Denmark.

Spontaneous, 3-methylcholanthrene-induced, and immunologically induced thyroiditis have been investigated in the Buffalo strain of inbred rat. Circulating autoantibodies to thyroid antigen are present in each form of the disease. Antibodies to other organs, or mononuclear cell infiltrations in them were not found. The major stimulus appears to be thyroglobulin. The evidence indicates that these 3 different forms of disease have an autoimmune basis.

Administration of bovine tetanus antitoxin to a patient who was sensitive to horse serum was followed by serum disease. Immunological studies revealed a preexisting hemagglutinating antibody titer of 2,000 against horse serum, but none to bovine serum. After the onset of symptoms, both titers rose. The reaction against bovine serum reached a titer of 100,000. A transitory skin-sensitizing antibody against bovine serum was also produced. An alpha globulin component of bovine serum was found to be the precipitating antigen. Thus, this patient probably reacted to a serum fraction other than the active antitoxin. The results suggest an antigenic cross relationship between horse and beef sera, limiting the usefulness of bovine antitoxin. Greater use of toxoid could help eliminate the problem of serum reactions. Certainly, horse-serum sensitivity should make active immunization mandatory.

Gottlieb, S. F. (Linde Division, Union Carbide Corporation, Tonawanda, N.Y.), Noel R. Rose, Jerome Maurizi, and Edward H. Lanphier. Oxygen inhibition of growth of Mycobacterium tuberculosis. J. Bacteriol. 87:838–843. 1964.—Continuous or intermittent exposure to 3 atm of oxygen in the presence or absence of 40 mm of Hg CO2resulted in marked delay or inhibition of growth of Mycobacterium tuberculosis. This inhibition was more pronounced with newly inoculated cultures, as compared to young, actively growing cultures. Oxygen inhibition of growth was observed on both Lowenstein-Jensen and blood agar media. Bacteriostatic effects of oxygen are a direct function of exposure time. A more marked effect of oxygen was observed in the presence of isoniazid, streptomycin, or p-aminosalicyclic acid.

Injections of mouse thymus cells from fetal, neonatal, 4-week- and 1-year-old syngeneic donors were compared for their ability to potentiate the production of serum antibody to sheep red blood cells in thymectomized, irradiated recipients previously injected with syngeneic bone marrow. Five million fetal thymus cells afforded no restoration of the immunologic response and one-year-old thymus cells gave marginal improvement. The apparent deficiency of the fetal thymus cell inoculum was quantitative since 20 million of these cells proved to be as active as five million neonatal thymus cells. Neonatal and 4-week-old thymus cells induced significant and virtually equal immunologic reactivity in terms of serum antibody titers. Immunologic restoration estimated by the number of spleen direct PFC was insignificant in all the groups given thymus cells. There was no increase in the number of indirect PFC observed in the experimental groups except for the one treated with 4-week-old thymus cells and here the restoration was significant but incomplete. These findings are discussed with reference to the cellular changes in the thymus in the perinatal period.

A relative quantitative estimation of cathodal esterase in normal and malignant tissues has been performed. The highest concentration of esterase was found in the kidney. A comparison shows that human hepatomas have a distinctly increased level of the esterase over normal liver.