The Journal of Experimental Medicine

Smith, Mary Ruth; Wood, W. Barry

doi: 10.1084/jem.107.1.1pmid: 13481251

Experiments recently reported (18) have been interpreted to indicate that surface phagocytosis plays no significant part in natural antipneumococcal defense. A repetition of these experiments has revealed: ( a ) that the cellular content of the leucocytic suspensions used in the phagocytic tests was of a different order of magnitude from that of the exudates which usually exist in infected tissues, ( b ) that the suspensions were too dilute to allow surface phagocytosis of pneumococci to occur, and ( c ) that the ratio of bacteria to leucocytes. was such that, when a sufficiently concentrated exudate was employed, the pneumococci injured the leucocytes and thus prevented phagocytosis from taking place. When conditions of the tests were suitably controlled, and conventional quantitative methods were employed to measure the end results of the phagocytic reaction, the essential observations relating to surface phagocytosis were fully confirmed. The significance of this non-antibody mechanism of defense in pneumococcal infections was thus further substantiated. Footnotes Submitted: 29 June 1957

Huggins, Charles; Pollice, Lucio

doi: 10.1084/jem.107.1.13pmid: 13481252

The repeated administration of 3-methylcholanthrene to adolescent rats resulted in ( a ) a profound, incomplete, and selective depression of certain hypophyseal functions; ( b ) decreased growth of transplanted mammary tumors; and ( c ) a retardation of body growth. Only the last mentioned effect was reversed by forced feeding. The retarded rate of body growth induced by 3-methylcholanthrene was prevented by the concurrent administration of dihydrotestosterone or progesterone, or by ovariectomy; rats so treated became overweight despite the injection of 3-methylcholanthrene. Phenolic estrogens intensified the retardation of body growth induced by 3-methylcholanthrene and emaciation resulted. The administration of 3-methylcholanthrene resulted in decreased gonadotrophin production by the pituitary and the ovaries were more drastically affected by the depression of pituitary activity than the adrenals were. The compound exerted differential effects on the pituitary glands of males and females respectively. Hormonal functions of both ovary and testis were decreased in rats treated with 3-methylcholanthrene but, whilst ovarian weight was much reduced, the size of the testis was not decreased and the germinal epithelium of the male was little affected by the treatment in most instances. There was a considerable reduction of the content of alkaline phosphatase in the breast of intact rats treated with 3-methylcholanthrene but atrophy of the mammary epithelium did not occur and hyperplasia of the mammary tree was often observed. The administration of 3-methylcholanthrene considerably slowed the growth of transplanted mammary tumors characterized by high dependence on hormones and the concurrent administration of gonadotrophin restored the growth rate of the tumors. The administration of 3-methylcholanthrene or androstan-17ß-ol-3-one was only moderately effective in controlling the growth of transplanted mammary tumors characterized by low hormonal dependence; the combined administration of these compounds was highly efficacious in retarding the growth of these refractory tumors. 3-Methylcholanthrene partially retarded the growth of mammary fibroadenomas in hypophysectomized rats. Footnotes Submitted: 22 July 1957

Patnode, Robert A.; Hudgins, Paul C.; Janicki, Bernard W.

doi: 10.1084/jem.107.1.33pmid: 13481253

Guinea pigs given three subcutaneous injections of triton WR-1339, 300 mg./kg., at 3 day intervals develop an intense lipemia as evidenced by marked increases in serum phospholipide, free cholesterol, ester cholesterol, neutral fat, and total fatty acids. The total fatty acid content of the lung, liver, and spleen, however, remains unchanged. No qualitative change in the fatty acids of the lung and liver from treated animals could be detected by the methods used. The injection of triton was found to diminish slightly the cholesterol content of the adrenal glands. The implications of these findings are discussed in relation to an understanding of the mechanism involved in the therapeutic action of triton in experimental tuberculosis. Footnotes Submitted: 5 August 1957

Hudgins, Paul C.; Patnode, Robert A.

doi: 10.1084/jem.107.1.43pmid: 13481254

Guinea pig red cells exposed to triton WR-1339 either in vitro or in vivo demonstrate an increased sensitivity to hemolysis by thermal shock. Although the sensitivity of guinea pig leucocytes to thermal shock remains unchanged after a single injection of triton, their resistance to disruption by acetone and by sonic vibration is increased significantly. Resistance to sonic vibration appears to be maximum within a few hours after injection and then it gradually wanes. Paraffin oil-induced peritoneal exudate cells (monocytes) and leucocytes from whole blood are rendered more resistant to disruption by sonic vibration when exposed to triton in vitro . These findings are discussed briefly in relation to the therapeutic effect of triton in experimental tuberculosis. Footnotes Submitted: 5 August 1957

Patnode, Robert A.; Hudgins, Paul C.

doi: 10.1084/jem.107.1.55pmid: 13481255

The administration of triton WR-1339 (300 mg./kg. subcutaneously) to tuberculin-sensitive guinea pigs 2 hours before the intradermal injection of PPD depresses slightly their skin sensitivity to tuberculin and essentially obliterates the lytic effect of tuberculin on their circulating leucocytes. When leucocytes from tuberculin-sensitive guinea pigs are exposed to triton in vitro at a concentration level attainable in vivo the cells are partially protected against lysis by PPD. Footnotes Submitted: 5 August 1957

Rous, Peyton; Allen, Raymond A.

doi: 10.1084/jem.107.1.63pmid: 13481256

Six out of eight epidermal papillomas, induced with tar in mice of homogeneous strain, have grown after transfer to the subcutaneous tissue of sucklings and weanlings. Five of them have been thus maintained for nearly or quite a year and a half, and in seven to nine successive groups of mice. The tumor studied longest has been kept going in five parallel lines since its primary implantation. The papillomas have all grown progressively in most instances, and proved fatal. None has altered except through the occurrence of derivative cancers, but these have arisen so often as only to be excluded on transfer by a rigorous selection of grafts. Histologically the papillomas have been of a single, completely unaggressive kind, yet transfer has disclosed great differences in their abilities. The tumors they form are of unique sorts. The cells of some are able-bodied (Type A), capable of spreading along bare connective tissue and keratinizing like normal, reparative epidermis. They line graft pockets, differentiate into the free space these provide, and form cysts densely packed with keratin. The papilloma is thus turned outside in. The cysts become huge as keratin accumulates in them, and eventually they rupture with result either in subcutaneous dissecting cysts or keratinizing surface growths that are often prodigious in size and fantastic in shape, but sometimes are completely like the cutaneous papillomas ordinarily induced by carcinogens, and tend, when small, to regress or come away as these frequently do. One growth of Type A was placed in the peritoneal cavity or in the liver, spleen or lung, and at all these situations it formed introverted cysts resembling the subcutaneous. The cells of other papillomas are more or less crippled (Type C). In extreme instances they are unable to spread laterally, and produce relatively little keratin. They fail to line graft pockets, but their keratin inflames the exposed connective tissue, extravasation ensues, and a continually enlarging, fluid-filled cyst forms, with walls that are bare except where a stalked or cauliflower papilloma exists, projecting inwards. At last the cyst ruptures and a second dissecting cyst forms, also devoid of papilloma tissue; or else the overlying skin undergoes pressure necrosis, the cyst fluid escapes through a rent, and fatal infection ensues. All gradations exist between Type A and Type C. The cancers derivative from both exhibit a marked disability,—though invasive they are almost or quite unable to extend along bare connective tissue. The papillomas that are possessed of this faculty spread beyond them along the cyst wall, and kill the host through their unceasing activity. In collateral work a papilloma was transplanted that was found protruding from the external auditory canal of a mouse which had received an intramuscular injection of methylcholanthrene many months previously. The tumor is now in its 5th generation, after 15 months. The growths it forms are of Type A. All of the papillomas are functioning tumors, with their own cells as the functioning product. Their papilliferous shape, when on the skin, is due solely to inability of their cells to gain space in other ways. Intrinsically they are keratomas. The papillomas do well after transfer to deep situations because the growth of their cells is indirectly promoted , through favoring local conditions. No direct promotion takes place like that when the cells of prostatic and mammary tumors are stimulated to multiply by hormones. Doubtless many agents act in both ways, that is to say by dual promotion . Footnotes Submitted: 6 August 1957

Moberly, Merle L.; Marinetti, Guido V.; Witter, Robert F.; Morgan, Herbert R.

doi: 10.1084/jem.107.1.87pmid: 13481257

Evidence from microscopic studies indicates that hemolysis caused by the mumps virus hemolysin is a chemical type of hemolysis. Chromatographic analyses of the reaction mixture of erythrocytes and mumps virus following hemolysis indicate that hemolysis is not due to the action of a lecithinase A and that lysolecithin does not play a part in this process. The alteration of a component of the erythrocyte similar to sphingomyelin suggests that some of the phosphatides other than lecithin may be either directly or indirectly affected in the process of hemolysis of red blood cells by the mumps virus. Footnotes Submitted: 9 August 1957

Katsh, Seymour

doi: 10.1084/jem.107.1.95pmid: 13481258

Female guinea pigs were injected with the following materials: homogenates of guinea pig testis in saline or in adjuvant; suspensions of washed guinea pig sperm in saline or in adjuvant; homogenates of rabbit testis in adjuvant; guinea pig sperm and rabbit sperm in adjuvant. Control animals were not injected or were injected with adjuvant alone. At various times between 15 and 39 days after injection, the animals were sacrificed. Their ilea and uterine horns were removed and tested in vitro for reaction to washed epididymal sperm of the guinea pig, rabbit, or bull. It was found that the animals which were injected with homologous testis or sperm in adjuvant possessed organs which responded strongly to the challenge with homologous sperm. The response was a contracture which began 10 to 30 seconds after the sperm were injected into the bath and lasted for 5 minutes to 4 hours, the longest period of observation. Responses which lasted for periods of 5 minutes to 30 minutes were obtained with the uteri of the animals injected with guinea pig testis in saline or with guinea pig sperm in saline. Animals which were injected with rabbit testis and adjuvant responded to rabbit sperm, and animals injected with guinea pig sperm and rabbit sperm in adjuvant reacted to both gametes. A large proportion of the control animals possessed organs which reacted weakly to the challenge with homologous sperm. Retesting the organ which had contracted following exposure to sperm indicated that desensitization had occurred. Testing with heterologous sperm indicated a species selectivity. The evidence is interpreted to mean that injections of sperm or testis induce a hypersensitivity which is similar in some respects but differs from true anaphylaxis. The findings are discussed from the point of view of the nature of the response and the implications regarding natural immunity to sperm. Footnotes Submitted: 17 September 1957

Salvin, S. B.

doi: 10.1084/jem.107.1.109pmid: 13481259

Guinea pigs were injected in the footpads with either purified diphtheria toxoid or recrystallized egg albumin in Freund adjuvant without mycobacteria. Each guinea pig was then skin-tested only once with the specific antigen and bled for antibody determination. After injection of the sensitizing antigen, a latent period occurred during which neither sensitivity nor circulating antibody could be detected. A period of delayed sensitivity followed wherein circulating antibody could not be discerned and which could be transferred by lymph node cells. Ultimately, the Arthus type sensitivity developed, accompanied by circulating antibody. The duration and severity of reactions to homologous antigens during the last 2 phases varied with the antigen and with the dose. An increase in the sensitizing dose decreased the duration of the delayed type of allergy, a decrease in the dose prolonged the delayed type. Inclusion of mycobacterium in the sensitizing inoculum tended to introduce delayed sensitivity earlier and delay the onset of Arthus type sensitivity. When specific precipitate in antibody excess was included with the toxoid in the sensitizing dose, the onset of the Arthus phase was hastened. When lymph nodes from a large number of sensitized donors were removed during the latter part of the latent period, recipients of the cells showed a delayed type sensitivity. Footnotes Submitted: 30 July 1957

Maurer, Paul H.

doi: 10.1084/jem.107.1.125pmid: 13481260

The effects of physical and enzymatic treatments of gelatin on the gelatin-antigelatin reaction have been presented. The data obtained indicate that the gelatin-antigelatin reaction is indeed a specific one. It appears that a definite limiting molecular size and specific molecular pattern of this molecular unit are necessary for reaction with antibody. Footnotes Submitted: 5 August 1957