STUDIES ON BLOOD FACTORS RhA, RhB, AND RhCUnger, Lester J.; Wiener, Alexander S.; Katz, L.
doi: 10.1084/jem.110.4.495pmid: 13840401
Observations are described of the incidence among Caucasians and Negroes of the blood factors Rh A , Rh B and Rh C which occur associated with the Rh 0 factor in typical Rh-positive blood. The antiserums used for the tests were derived from Rh-positive patients who had had hemolytic transfusion reactions or erythroblastotic babies. Among a large series of individuals, it was found that only rarely is any of the blood factors Rh A , Rh B , or Rh C lacking from "standard" Rh 0 -positive blood. On the other hand, about half of the specimens of Rh 0 variant blood lack one or more of the factors Rh A , Rh B , and Rh C , which, when present in such blood, are also almost always variants. Judging from the incidence of specimens lacking one or more of these factors, Rh A , Rh B , and Rh B appear to be relatively independent of one another despite their association with blood factor Rh 0 . Tests for factors Rh A , Rh B , and Rh C distinguish new rare varieties of Rh and ℜh agglutinogens, each genetically determined by corresponding allelic genes. There is no doubt that more clinical cases will be found in which sensitized Rh-positive individuals have antibodies resembling anti- Rh 0 in specificity. Four such cases have already been studied by the present authors, and in each case the antibodies were shown to be different from anti- Rh 0 in specificity. Since they were also different from one another, they have been assigned the symbols anti- Rh A , anti- Rh B , anti- Rh C , and anti- Rh D , respectively, the first three being the antiserums used in the present study. Obviously, in order to avoid confusion of nomenclature, the specificity of antiserums from other similar cases will have to be compared with anti- Rh A , anti- Rh B , anti- Rh C , and anti- Rh D and shown to be different from all four, as well as anti- Rh 0 , before a distinctive symbol is assigned to them.
STUDIES ON THE RUNTING SYNDROME IN NEWBORN MICESiskind, Gregory W.; Thomas, Lewis
doi: 10.1084/jem.110.4.511pmid: 14447223
Runting was produced by homologous spleen or lymph node cell suspensions, but not by isologous spleen or homologous liver or kidney cell suspensions. The incidence of runting ( a ) varied with the particular strain combination employed, ( b ) increased with increased dose of foreign cells, and ( c ) decreased as the time interval between birth and inoculation with foreign cells was increased. A focal, coagulative necrotic, liver lesion was described in runted mice. It was found that viable cells were required to produce the runting syndrome. Frozen-thawed cells, homogenized cells, and the cell-free supernatant of ground spleen suspensions failed to produce runting. Runted mice were found to have an anemia of variable degree, and white blood cell counts ranging from marked leukopenia to severe leucocytosis. Mice receiving isologous spleen or homologous liver or kidney showed normal red and white blood cell counts. Isologous spleen cells, given to newborn mice within 30 minutes following injection of homologous spleen cells, conferred significant protection against the runting syndrome. Isologous spleen injected 1 day after the injection of homologous spleen failed to protect. Newborn mice which had received homologous spleen cells were protected from becoming runted by treatment with "anti-cell donor strain" serum. The offspring of mothers which had been immunized against the spleen cell donor's strain failed to become runted when treated with homologous spleen cells. The data are regarded as compatible with the concept, presented by previous workers, that runting is the result of an immunological reaction of foreign cells against a tolerant host. Footnotes Submitted: 9 June 1959
STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURESHenle, Werner; Henle, Gertrude; Deinhardt, Friedrich; Bergs, Victor V.
doi: 10.1084/jem.110.4.525pmid: 14401038
In previous reports of this series, it was shown that persistent infection of MCN cultures with certain myxoviruses rendered the cells insusceptible to superinfection by several cytopathogenic viruses. It was thought that production of an interferon might be the cause of this resistance and efforts to confirm this suggestion have been presented. Addition of ultraviolet-inactivated myxoviruses (mumps, Newcastle disease, influenza A, and Sendai) to MCN cultures for periods of 2 to 3 hours, followed by washing and refeeding of the cells, led to the subsequent release into the media of a substance which induced in fresh MCN cells a transitory resistance to infection by vesicular stomatitis virus, and prevented incomplete reproductive cycles of influenza A and Sendai viruses. Media containing this substance were free of detectable hemagglutinating activity and viral complement-fixing antigens. The substance was not neutralized by specific antiviral sera; it was not sedimentable by high speed centrifugation; it was not adsorbed onto red cells; but it was inactivated by trypsin. Thus, its properties matched those of the interferon described by Isaacs and his associates. A comparison of the extent of resistance induced in MCN cells by decreasing doses of ultraviolet-inactivated myxoviruses (interference test) and the protection afforded by the media removed from the cultures prior to challenge and transferred to fresh MCN tubes (interferon test) revealed that wherever interference became detectable in the cells, the media of the corresponding cultures contained some interferon. Interferon was obtained by inactivated myxoviruses also from primary cell cultures by the same techniques, but not from HeLa cells. Interferons derived from one type of culture may protect others equally well or show a certain degree of host specificity in that resistance in homologous cells may be somewhat more pronounced than in heterologous cultures. No resistance could be induced in HeLa cells by the interferon preparations employed. Interferon was detected also in MCN cultures, persistently infected with mumps virus. Its concentration was apparently too small in carrier cultures maintained as routine to be measurable. However, when the cells were grown in heavy sheets in roller bottles, and especially when the volume of medium was reduced for several days prior to harvest, interferon became readily detectable. These results strengthen the suggestion that interferon may play a decisive role in the establishment and maintenance of persistent infections in the system under study. Its nature, source, mode of action, and exact role in persistent infection remains to be elucidated. Footnotes Submitted: 24 June 1959
THE ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN HEMORRHAGIC SHOCKFine, J.; Rutenburg, S.; Schweinburg, F. B.
doi: 10.1084/jem.110.4.547pmid: 13822851
"Blockade" of the RES by thorotrast so lowered the tolerance of hemorrhagic shock in rabbits and dogs that a reversible degree of hemorrhagic shock became irreversible. This was true not only in normal rabbits, but in rabbits made resistant to hemorrhagic shock by producing resistance to endotoxins. Rabbits which had been pretreated with thorotrast and then subjected to hemorrhagic shock displayed at death the hemorrhagic lesions and the renal cortical necrosis characteristic of the Shwartzman reaction, in addition to the intramural hemorrhages in the gut which are characteristic of animals dying of hemorrhagic or of endotoxic shock. Elimination of the Shwartzman reaction by the prior administration of nitrogen mustard did not prevent the endotoxemia or the death in shock. Rabbits made more resistant to thorotrast than normal rabbits by prior repeated administration of this substance were also more resistant than normal rabbits to endotoxin, and survived an ordinarily lethal exposure to hemorrhagic shock. During the first few hours after its administration thorotrast induced excessive vulnerability not only to endotoxin and to hemorrhagic shock, but also to an additional small dose of thorotrast. Moreover, a non-absorbable antibiotic given by gavage shortly after thorotrast produced the same lesions as these other agents; i.e . endotoxic shock, the Shwartzman reaction, and death. These data indicate that the lesions induced by thorotrast are produced by endotoxins which the injured or blockaded RES cannot inactivate. The presence of endotoxins in the blood of these rabbits was indicated by the lethal effect of this blood in test recipients. The foregoing observations did not apply to rabbits with an intestinal flora free of coliform bacteria. Over 80 per cent of such rabbits were resistant to an ordinarily lethal exposure to hemorrhagic shock, and they escaped the damage caused by the usual doses of thorotrast. They did, however, develop endotoxic shock and die if given a large dose of thorotrast. These data were taken to indicate that coliform-free rabbits are not entirely free of endotoxins. (In the ordinary environment animals cannot avoid swallowing endotoxin and coliform bacteria.) The absence of the Shwartzman reaction in the coliform-free rabbits is taken to signify that this reaction requires the participation of the endotoxins derived from the intraintestinal bacteria. The absence of endotoxic shock in the coliform-free rabbits is taken to signify that the endotoxins of the coliform bacteria are involved in the shock and death of the coliform-bearing rabbits. Finally the prevention by dibenamine of both the Shwartzman reaction and endotoxic shock and death in rabbits with a normal flora demonstrates that adrenergic activity plays an indispensable role in both phenomena. The foregoing data provide strong support for the thesis that when the RES is severely disabled by any agent, endotoxins which normally and continuously enter the circulation from the gut will produce endotoxic shock and death. Footnotes Submitted: 17 June 1959
SIMULTANEOUS PRODUCTION OF TWO CAPSULAR POLYSACCHARIDES BY PNEUMOCOCCUSAustrian, Robert; Bernheimer, Harriet P.; Smith, Evelyn E. B.; Mills, George T.
doi: 10.1084/jem.110.4.585pmid: 13795197
Study of the capsular genome of pneumococcus has shown that it controls a multiplicity of biochemical reactions essential to the synthesis of capsular polysaccharide. Mutation affecting any one of several biochemical reactions concerned with capsular synthesis may result in loss of capsulation without alteration of other biochemical functions similarly concerned. Mutations affecting the synthesis of uronic acids are an important cause of loss of capsulation and of virulence by strains of pneumococcus Type I and Type III. The capsular genome appears to have a specific location in the total genome of the cell, this locus being occupied by the capsular genome of whatever capsular type is expressed by the cell. Transformation of capsulated or of non-capsulated pneumococci to heterologous capsular type results probably from a genetic exchange followed by the development of a new biosynthetic pathway in the transformed cell. The new capsular genome is transferred to the transformed cell as a single particle of DNA. Binary capsulation results from the simultaneous presence within the pneumococcal cell of two capsular genomes, one mutated, the other normal. Interaction between the biochemical pathways controlled by the two capsular genomes leads to augmentation of the phenotypic expression of the product controlled by one and to partial suppression of the product determined by the other. Knowledge of the biochemical basis of binary capsulation can be used to indicate the presence of uronic acid in the capsular polysaccharide of a pneurnococcal type the composition of the capsule of which is unknown. Footnotes Submitted: 4 June 1959
STUDIES ON THE PATHOGENICITY OF GROUP A STREPTOCOCCIFoley, Marie Judith; Smith, Mary Ruth; Wood, W. Barry
doi: 10.1084/jem.110.4.603pmid: 13823727
Four strains of Group A streptococci, possessing different degrees of virulence for both mice and rats, were tested for susceptibility to phagocytosis on glass slides, in glass roller tubes, and on the surfaces of freshly excised tissues and moistened filter paper. All of the tests were performed in the absence of serum to exclude the possible presence of opsonins. Only under conditions which allowed surface phagocytosis to take place was there a correlation between virulence and susceptibility to phagocytosis. A similar relationship between virulence and surface phagocytosis was also demonstrable in vivo during the early stages of experimental streptococcal peritonitis. Systematic study of the evolution of the peritonitis revealed that its outcome was determined by the phagocytic reaction which occurred in the first few hours of the infection. Footnotes Submitted: 29 June 1959
STUDIES ON THE PATHOGENICITY OF GROUP A STREPTOCOCCIFoley, Marie Judith; Wood, W. Barry
doi: 10.1084/jem.110.4.617pmid: 13823728
A quantitative study of the combined antiphagocytic effects of the M protein and the hyaluronic acid capsules of four strains of Group A streptococci revealed the following facts relating to their intraperitoneal virulence in mice and rats: 1. The most virulent strain, S23M (matt), produced both a large hyaluronic acid capsule and a full complement of M protein, the combined effects of which rendered the organism highly resistant to surface phagocytosis. 2. The slightly less virulent strain, T14/46 (matt virulent) was somewhat more susceptible to surface phagocytosis owing to the fact that its smaller capsule was less antiphagocytic than that of the S23M organism. 3. The glossy variant of the S23 strain (S23G), which ranked third in virulence, was still more susceptible to surface phagocytosis because of its lack of detectable M substance. Its large hyaluronic acid capsule, however, was capable of protecting it against phagocytosis on glass. 4. The least virulent strain, T14 (matt avirulent), was the most susceptible of all to phagocytosis. Though it possessed both M substance and capsule, which together prevented its phagocytosis on glass, each of them was shown to be quantitatively and functionally deficient as compared to Strain S23M. The differences in phagocytability, which appear to be directly related to the pathogenicity of the organisms, could be adequately demonstrated in vitro only by phagocytic tests designed to measure surface phagocytosis in the absence of opsonins. This fact is in keeping with the observation, previously reported, that surface phagocytosis plays a critical role in the defense of the host, particularly during the earliest stages of experimental streptococcal infections. Its possible relation to suppuration during the later stages of infection is also discussed. Footnotes Submitted: 29 June 1959
DIFFERENTIATION OF CLOSELY RELATED CELLS BY A VARIANT OF POLIOVIRUS, TYPE 2, MEF1 STRAINMurphy, William H.; Armstrong, Raymond
doi: 10.1084/jem.110.4.629pmid: 14425416
By application of a variant of poliovirus, Type 2, MEF 1 strain, as a selective agent it was possible to distinguish among stable parent strains of epithelial cells and their clonal derivatives by their differential morphologic response to infection. The variant of poliovirus grew in a number of cell strains without induction of observable cytopathogenic changes. Other strains of cells reacted to viral infection by manifesting partial or complete degeneration. Parent HeLa cells and virus underwent simultaneous serial propagation in the absence of homotypic antiserum to virus. The stability of the virus-cell relationship was established by results from replicate experiments conducted over a period of years. Some cell strains of common origin maintained in different laboratories did not react similarly to the cytopathogenic effect of virus. Representative experiments revealed that the morphologic response of HeLa cells to MEF virus infection was not influenced by the presence or absence of pleuropneumonia-like organisms. The differential morphologic response of cells to infection was confirmed by efficiency-of-plating experiments which revealed differences in the capacity of MEF virus to form plaques in the test cell strains. Serial passages of MEF virus in cell strains demonstrated differences in their selection for cytopathogenic "mutants" of virus. Footnotes Submitted: 27 June 1959