The Journal of Experimental Medicine

Follis, Richard H.; Wintrobe, Maxwell M.

doi: 10.1084/jem.81.6.539pmid: 19871474

1. When pigs were fed diets deficient in pyridoxine or pantothenic acid, ataxia developed and lesions were found in the sensory neuron. 2. The morphological pattern of the lesions differed in the early stages of the two deficient states. Degeneration of the peripheral process of the sensory neuron was the initial and most prominent feature in pyridoxine deficiency. Chromatolysis was the first evidence of damage to the afferent neuron in pantothenic acid-deficient animals. 3. The possible significance of this evidence of damage to different portions of the sensory neuron is discussed. Footnotes Submitted: 1 March 1945

Friedman, Nathan B.

doi: 10.1084/jem.81.6.553pmid: 19871475

Although irradiation of the duodenum of rats inhibits mitosis in the crypts and halts the normal passage of cells up the villi, the maturation of goblet cells is not affected. The ripening of mucous elements while arrested in the crypts, where they form, instead of during their migration along the villi, results in the so called mucous change, which has hitherto been considered a form of degeneration. During the phase of recovery, the reestablishment of normal migration and desquamation is marked by the appearance of strata of fully formed goblet cells at successive levels out along the villi. It is suggested that some gastrointestinal disturbances known to occur in spontaneous and experimental vitamin deficiency might be explained in terms of aberrations in the cellular replacement of the intestinal mucosa. Footnotes Submitted: 19 March 1945

Wiener, Alexander S.; Zepeda, J. Preciado; Sonn, Eve B.; Polivka, H. R.

doi: 10.1084/jem.81.6.559pmid: 19871476

98 Mexican Indians were tested for the blood properties A-B-O, A 1 -A 2 , M-N, P, Rh'-Rh''-Rh 0 -rh, and Hr. Of the 98 Indians, 90.8 per cent belonged to group 0, 6.1 per cent belonged to A 1 , and 3.1 per cent to group B. There were 61.2 per cent of type M, 3.1 per cent of type N, and 35.7 per cent of type MN. Of the 95 Mexican Indians tested with anti-P serum, 21.1 per cent were found to lack the P agglutinogen. In tests for the Rh blood types, 48.0 per cent of the Indians were found to belong to type Rh 1 , 9.2 per cent to type Rh 2 , 41.8 per cent to type Rh 1 Rh 2 , and 1 per cent to type Rh 0 . There were no bloods giving intermediate reactions. Of the 95 Indians tested for the Hr factor 44.2 per cent were found to lack this property. The reactions for the Rh blood types and Hr factor were correlated with each other and the results supported the conclusion of Race et al . that in addition to the six standard allelic genes and the so called intermediate genes, there is one or possibly two genes having the property of determining agglutinogens which react with anti-Rh' and anti-Rh'' sera, but not with anti-Hr serum. This gene (or genes) appears to be relatively common among Mexican Indians (approximately 3.3 per cent) in contrast to its rareness in white individuals. Footnotes Submitted: 30 March 1945

Elliott, Stuart D.

doi: 10.1084/jem.81.6.573pmid: 19871477

1. Group A streptococci sometimes produce in broth culture an extracellular proteolytic enzyme. 2. Under suitable cultural conditions the enzyme has been demonstrated in representative cultures of most of the Griffith types. Its production by a given strain may be suppressed by serial passage through mice and the variant so produced has been found to maintain this change in character on subculture in artificial media. 3. Under certain conditions, the enzyme attacks the type-specific M antigens of all the group A streptococci so far tested, with the exception of that of type 28. The enzyme exhibits its maximal activity at 37°C.: Extracts made from enzyme-producing cultures which have been grown at this temperature lack the M antigen; enzyme-producing strains may sometimes be induced to yield M substance in extracts by culturing the streptococci at 22° C. Cultures which, when grown at 37° C. yield M substance in extracts, do not produce the enzyme. 4. Human and rabbit fibrin are attacked and streptococcal fibrinolysin is also inactivated by the enzyme. Other susceptible substrates include casein, milk, gelatin, and benzoyl- l -arginineamide but not l -leucylglycylglycine. 5. The general properties of the enzyme resemble those of papain and some of the cathepsins: It is active under the reducing conditions produced in broth cultures by the presence of living bacteria; it is also activated by substances which reduce disulfide to sulfhydryl groups, e.g. potassium cyanide, cysteine, glutathione, and thioglycollic acid, but it is not activated by ascorbic acid. The enzyme is inactivated by iodoacetic acid and also by normal rabbit or mouse serum. Footnotes Submitted: 28 March 1945

Wilson, Armine T.

doi: 10.1084/jem.81.6.593pmid: 19871478

In the course of rapid passages through mice a strain of group A type 27 hemolytic streptococcus was found to have lost its group carbohydrate without the loss of type-specific precipitinogens, agglutinogens, or its capacity to induce protective antibodies in rabbits, and without the acquisition of the carbohydrate of another group. The loss of group carbohydrate was shown to be complete, within the limits of the methods for its detection. Extracts of the anomalous strain did not react with group A antisera; and antisera prepared with organisms of this anomalous strain did not contain demonstrable antibodies for the group carbohydrate. Bacterial suspension of the anomalous strain failed to absorb any appreciable amount of group-specific antibody. The fact that the anomalous strain lacking group-specific carbohydrate, C, was derived from the original was established by the demonstration of persistence of its other characteristics, in particular the precipitinogens, agglutinogens, and antigens responsible for protective antibodies of type 27. Footnotes Submitted: 6 April 1945

Rous, Peyton; Smith, William E.

doi: 10.1084/jem.81.6.597pmid: 19871479

A method has been devised whereby the transplanted epidermis of mouse embryos can be selectively exposed to the action of a chemical carcinogen. Scharlach R was dissolved in olive oil with the aim of stimulating and attracting the epidermal cells, methylcholanthrene was added to the solution, and numerous fine globules of it were injected into the thigh muscles of adult mice together with fragments of embryo skin. Much of the oil underwent primary inclusion in the resulting cysts, and the proliferating epidermis, while forming them, extended to not a few of the outlying droplets with result that they too were added to the cyst contents. During these activities the methylcholanthrene came into direct contact with many of the epithelial cells, and later on the layer lining the cyst was continually exposed to the influence of the carcinogen. The epidermis underwent neoplastic changes with great rapidity; often in less than 4 weeks papillomas and carcinomas had arisen like those deriving from adult epidermis. The growths were punctate in origin and usually multiple. Many were transplanted to adults of the same homologous breed of mice that furnished the embryo material (mice of C strain). The grafts did not uniformly succeed as was the case with those of normal skin of embryos of the same stock,—which regularly grew at first in the new hosts and remained alive long after. The benign papillomas failed to live or barely survived, and the apparently malignant papillomas, though rapidly forming nodules of considerable size, usually regressed later. Some of the carcinomas also regressed or wholly failed, while others gave rise to progressively enlarging tumors. The best results were obtained with grafts in which several neoplasms were intermingled, these flourishing together in the new hosts. Methylcholanthrene in olive oil exerts an influence on epidermal cells like that of Scharlach R, stimulating them to multiply, attracting them, and causing them to mimic carcinomatous elements. Footnotes Submitted: 6 April 1945

Smith, William E.; Rous, Peyton

doi: 10.1084/jem.81.6.621pmid: 19871480

Experiments were carried out to learn whether the widely differing liabilities to induced epidermal tumors of individual mice and rabbits are due to a previous localization out of the blood of an agent capable of undergoing change when the skin is exposed to carcinogenic influences, and of producing tumors in consequence. On the assumption that such an agent would localize in increased quantity where cutaneous inflammation exists, like various inert substances of large molecule and the epidermotrophic viruses when circulating, skin areas on adult and new-born animals were for some weeks kept inflamed, and months later, when the areas appeared normal, methylcholanthrene was applied to them and to control areas on the same or other individuals. No differences were observable in tumor incidence. These results led to attempts to test whether embryo epidermis is capable of undergoing neoplastic change, and the work of Paper I was done which showed that epidermal tumors arise with great rapidity and regularity from embryo skin transplanted to adults of homologous strain (C strain) together with methylcholanthrene. Webster-Swiss mice proved unsuited to experiments of the sort owing to heterogeneity of the breed, the transplanted embryo skin dying in most instances before the methylcholanthrene introduced with it could have been carcinogenic. The skin of C3H embryos also did badly, as if from incompatibility in some instances but mostly because its epidermal cells proliferated less vigorously than those of C embryos and did not tolerate methylcholanthrene nearly so well. Despite these difficulties, epidermal tumors were occasionally induced, as also in the transplanted skin of Webster-Swiss embryos, and the growths appeared quite soon, all things considered. The effect of methylcholanthrene on the skin of sucklings, their mothers, and young adult mice of the C strain was studied in order to find out whether the rapid rate of neoplastic change in the transplanted epidermis of embryos is indicative of some liability connected with its period of development. The skin of new-born animals proved very refractory to the carcinogen, hair coming in at the same rate as on control litters and no perceptible inflammation occurring for about 2 weeks, although within this period the mothers of the treated animals and the young adults became hairless where the methylcholanthrene had been put and their skin was much inflamed. Later on, as the applications were kept up, similar changes took place in the sucklings, but none of these developed tumors during some 6 weeks of observation whereas growths appeared within 3 weeks on more than half of the mother mice and on some of the young adults. The failure to produce tumors in the sucklings seems to have been due to cutaneous conditions preventing the necessary exposure of the deeper epidermal cells to methylcholanthrene. In any projected correlation of age differences with the response of cells to carcinogens allowance must be made for such factors. The present findings give no ground for the supposition that embryo skin has any special liability to neoplastic change. The results of transferring the tumors derived from embryo epidermis to new hosts have made plain that the neoplastic state not infrequently entails disabilities which are crucial, the tumor cells failing to succeed unless aided. This holds true of some carcinomas as well as of papillomas. By transplanting pieces of the organs of C embryos together with methylcholanthrene tumors of many sorts besides the epidermal have been obtained. As yet only those of the stomach have been worked with extensively. They can be elicited as quickly and regularly as those of the epidermis and can be as easily transplanted. The findings as a whole render it impossible to suppose that the neoplastic potentialities possessed by transplanted embryo tissues are due to the lodgement in them of tumor-producing viruses as specialized in their effects as those now known, or of precursor agents conferring neoplastic liabilities specialized to the same degree. Some other possibilities are mentioned. The rarity of neoplasms at birth is due to the circumstances of intrauterine life and to its brevity, not to any lack of capacity of the cells of the embryo to undergo neoplastic change. Footnotes Submitted: 6 April 1945

Wright, George G.

doi: 10.1084/jem.81.6.647pmid: 19871481

The specific rate of inactivation of antitoxin in urea solutions, as measured by the Römer neutralization test with toxin, has been shown to be independent of the concentration of protein under the conditions studied. The amount of precipitate obtained in the quantitative precipitation test with toxin, however, increases greatly with increasing protein concentration during denaturation. The time during which the protein concentration is important in this respect has been shown to be the interval in which the urea is being dialyzed from the solutions. The meaning of the results is discussed. Footnotes Submitted: 2 April 1945