The Journal of Experimental Medicine

Atkins, Elisha; Wood, W. Barry

doi: 10.1084/jem.102.5.499pmid: 13271667

Further studies have been made of a pyrogenic substance which appears in the circulation of rabbits during the course of experimental fever induced by injection of typhoid vaccine. With the use of a passive transfer method and pyrogen-tolerant recipients, the biological properties of this substance have been differentiated from those of the uncleared vaccine in the circulation. The newly identified factor resembles leucocytic pyrogen in the rapidity with which it produces fever and in its failure to exhibit cross-tolerance with bacterial pyrogen. This striking similarity of properties suggests that the circulating factor is of endogenous origin and may arise from cell injury. A close correlation between its presence in the circulation and the existence of fever has been demonstrated. The possible relationship of these findings to the pathogenesis of fever is evident. Footnotes Submitted: 7 July 1955

Dumbell, Keith; Rous, Peyton

doi: 10.1084/jem.102.5.517pmid: 13271668

Three spontaneous pulmonary adenomas of C mice, morphologically resembling those induced by methylcholanthrene or urethane, were propagated in host after host under conditions such that the neoplastic cells were directly exposed, while proliferating, to one or the other of these agents. The successive periods of test lasted for more than a year in some instances, the total exposure to the carcinogens far exceeding that required to change normal pulmonary cells into adenoma cells. One of the adenomas remained unaltered, and the others underwent cancerous changes; but these took place with equal frequency in the control growths, and their occurrence was neither hastened nor delayed by the carcinogens. Two polymorphous mammary carcinomas of "milk-factor" type, with the characteristic tendency to form acini and tubules, were exposed to methylcholanthrene in the same way as the pulmonary adenomas and for periods quite as long. Their cells continued to differentiate, and in other respects underwent no significant change. Urethane had no influence on the rate of growth of the adenomas exposed to it; methylcholanthrene, on the other hand, markedly retarded the enlargement both of them and of the mammary tumors. Its inhibitory influence was not passed on from cell to cell however; when freed of the carcinogen by further transplantation, the retarded tumors grew as fast as the controls. Furthermore the retardation caused no evident delay in the occurrence of cancerous changes in the adenomas. One of the adenomas was maintained in twelve parallel lines while under test and new tumors arose in nine of them, the earliest appearing more than fifteen months after initial transfer of the growth. Always it was an adenoma solidum, this appearing almost concurrently in eight of the nine lines. In six of them it was soon followed by carcinomas, the sequence of events and the morphological findings both indicating that they had derived from it. Individually the cancers were widely various, but they were similar on the whole from line to line. Carcinomas of a wholly different aspect arose from the other adenoma undergoing cancerous change, and they were not preceded by adenoma solidum. In both instances the character of the superimposed neoplastic alterations seemed to have been determined by some inherent trait of the adenoma concerned. Footnotes Submitted: 23 June 1955

Ackermann, W. Wilbur; Ishida, Nakao; Maassab, H. F.

doi: 10.1084/jem.102.5.545pmid: 13271669

Under certain conditions, influenza virus may bind to chorioallantoic membrane and the infectious property is retained upon prolonged incubation of the complex. Apparently the bound active virus is not functioning in the initiation of viral increase. The bound infectious virus may be partially removed by extensive washing. The characteristics of the washing are suggestive of a reversible equilibrium type of binding. Binding will also occur when the tissue has been pretreated with RDE or in the presence of AMPS. However, under these conditions the binding is of a lesser degree. When the tissue has been treated with RDE and AMPS is present, no stable binding occurs. In the presence of AMPS, the initiating activity is bound but cannot function in promoting viral increase. It is proposed that active virus is held by two types of binding at the same site; one type of binding is sensitive to the action of RDE; the second type is sensitive to the blocking effect of AMPS. Virus can be held to the receptor site by either type of binding or both. It is further suggested that the bound infectious virus is a result of an abortive attempt at initiating infection. The nature of the binding of infectious virus is of significance for understanding the binding of initiating activity. Footnotes Submitted: 9 July 1955

Ackermann, W. Wilbur; Kurtz, Hilda

doi: 10.1084/jem.102.5.555pmid: 13271670

A culture of HeLa cells has been subjected to prolonged observation with the finding that periodically Type III poliomyelitis virus could be isolated from it. A requirement of the culture for survival was the presence in it of serum of certain individuals who had had previous experience with poliomyelitis virus. In the presence of serum containing no antibodies to poliomyelitis virus, the culture demonstrated spontaneous cytopathology. From certain series of passages virus could be isolated while attempts were unsuccessful from others also showing cellular disintegration. The conclusion is reached that the virus does not persist in the culture always in a state exhibiting the infectious property, rather what persists is the potentiality of the culture to give rise to fully active virus. The immune serum could inhibit the cytopathogenic effect of the virus without eliminating the infection. Footnotes Submitted: 14 July 1955

Shope, Richard E.

doi: 10.1084/jem.102.5.567pmid: 13271671

Twenty-five swine, infested with lungworms infected with masked swine influenza virus, were exposed to adverse weather conditions on one or more occasions. Of these, 4 came down with apparent swine influenza, while 6 others developed serological evidence of infection with swine influenza virus. The remaining 15 prepared swine, as well as 8 lungworm-free control swine, failed to show evidence of swine influenza virus infection, despite repeated exposures to adverse weather. The data presented indicate that, in the 10 swine in which swine influenza virus infections were elicited, some feature of the weather to which the animals were exposed was responsible for provoking masked influenza virus to infectivity. The exact constituent of the meteorological complex comprising "weather", responsible for the provocation, cannot be determined from the data obtained. Footnotes Submitted: 22 July 1955

Piel, Carolyn F.; Dong, Luther; Modern, F.W.S.; Goodman, Joseph R.; Moore, Roger

doi: 10.1084/jem.102.5.573pmid: 13271672

Nephrotoxic serum disease in rats has been studied by light and electron microscopy from 1 hour to 10 weeks after production of the disease. By light microscopy leucocytic infiltration of the glomerular capillary was observed between the 3rd and 6th hour. At 6 hours an increase in colloidal iron-positive material was observed coating the extraluminal surface of the capillaries. Also at this time swelling of the endothelial cells becomes prominent. By 72 hours, thickening of the basement membrane was observed. Glomerular capillary thrombi were observed in approximately half the tissue examined in the first 2 weeks of disease. 50 per cent of the animals showed severe chronic lesions, exudation into the capsular space, crescent formation, and obliteration of glomeruli. At 1 hour electron microscopic pictures showed that osmophilic material may line the foot processes of the epithelial cells and obliterate all but narrow channels of the space between the feet. By 6 hours thickening of the basement membrane was prominent. This change persisted throughout 10 weeks of observation. The tissue from animals which had severe chronic alterations by light microscopy revealed changes which could not be interpreted at this time. Footnotes Submitted: 3 August 1955

Nelson, John B.

doi: 10.1084/jem.102.5.581pmid: 13271673

Observations on the behavior of MHV (Pr) in the cerebral tissue of Princeton and Swiss weanling mice indicated a limited neurotropism. The virus migrated to the brain on intraperitoneal injection and was established there by cranial passage, though with difficulty in Swiss mice. Intracerebral multiplication was rarely followed by outward signs of nervous disorder. A slight pathologic reaction occurred in the brains of intracerebrally injected Princeton mice, but it was negligible compared with that of the ensuing hepatitis. In Swiss mice, injected intracerebrally with a mixture of MHV (Pr) and Eperythrozoon coccoides , a related virus with restricted pathogenicity and host range, possibly a mutant, was isolated from the liver and brain. MHV (C), an actively hepatotropic virus recovered from leukemic Balb C mice, was much more neurotropic than MHV (Pr). Intracerebral injection of Balb C and Swiss weanling mice was attended by marked leptomeningeal and encephalitic lesions. Paralysis of the extremities occurred in some of the animals. The virus was essentially inactive in Princeton mice. During the intracerebral passage of MHV (C) in Swiss mice a pleuropneumonia-like organism was isolated from the brain. In conjunction with the virus this organism produced a vigorous leukocytic reaction. Footnotes Submitted: 27 June 1955

Eagle, Harry

doi: 10.1084/jem.102.5.595pmid: 13271674

Seven vitamins have to date proved essential for the survival and multiplication of a mouse fibroblast (strain L) and a human carcinoma cell (strain HeLa) in tissue culture: choline, folic acid, nicotinamide, pantothenic acid, pyridoxal, riboflavin, and thiamin. It was necessary to cultivate the cells for 5 to 15 days in a medium lacking the specific vitamin before the deficiency became apparent in the cessation of multiplication and the development of specific cytopathogenic effects. In their early stages these changes could be reversed by the addition of the missing vitamin, an in vitro , "cure" of a vitamin deficiency. The maximally effective concentrations were in the range 10 7 to 10 8 gm. per ml. The probability that additional vitamins not demonstrably essential under the conditions of the present experiments are nevertheless required for survival and growth is discussed in the text. Footnotes Submitted: 7 June 1955

Jordan, Janet; Mirick, George S.

doi: 10.1084/jem.102.5.601pmid: 13271675

Serial intraperitoneal passage in mice of a saline extract of the pooled livers, spleens, and kidneys of such animals has led to the demonstration after three or more passages of a transmissible agent causing hepatitis. The mice developed an illness after 3 to 4 weeks characterized by hepatosplenomegaly, and serous ascites. Spontaneous diuresis and recovery usually occurred during the subsequent 2 to 4 weeks. Histological studies of the livers showed diffuse mononuclear infiltrations, focal accumulations of mononuclear cells, perivascular mononuclear cuffing, dilated sinusoids, and occasionally focal areas of necrosis. Mice which have recovered from the disease showed no noteworthy resistance to it, and their sera failed to protect against the infectious agent. Attempts to infect rabbits, guinea pigs, monkeys, and embryonated hens' eggs yielded negative results, but young hamsters developed the disease in mild form. Footnotes Submitted: 3 August 1955

Jordan, Janet; Mirick, George S.

doi: 10.1084/jem.102.5.617pmid: 13271676

A transmissible agent (AHA) causing ascites and hepatitis in mice has been described. No known pathogenic bacteria, fungi, protozoa, leptospira, rickettsia, or viruses have been demonstrated in the infected mice. AHA does not pass through a Seitz filter and differs in most respects from the agents previously described which produce hepatitis in mice. Footnotes Submitted: 3 August 1955