bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDIES ON STREPTOCOCCUS PYOGENES
Authors: Slade Hutton D. , Kimura Yoshitami
Published: June 2004

Heat-killed cells of Group A streptococci caused death of the adrenalectomized rat. While the adrenalectomized rat readily succumbed to intraperitoneal infection with living cells, death was due primarily to toxicity. The normal rat was highly resistant under either condition.

For studies on the toxic materials, the cells of numerous serological types of group A streptococci, and of a Group B and a Group D streptococcus, were extracted with 0.1 N HCl at 100°C. or by sonic oscillation. The extracts, containing macromolecular components, were subjected to chemical fractionation and purification.

C substance and M protein of Group A streptococci released from the cell by sonic oscillation were toxic to the adrenalectomized rat in quantities of 1 mg./100 gm. rat. Death usually occurred within 2 hours. On the other hand, C substance and M protein released from the cell with HCl at 100°C. were relatively non-toxic to the adrenalectomized rat. The sonic-extracted C substance of streptococcal Groups B, C, and D was also toxic.

The toxic property of the C and M preparations was neutralized in vitro in each case by group and type-specific rabbit antiserum. Heterologous antiserum was without effect. Adrenalectomized rats which received homologous antiserum 18 hours before challenge were also resistant to the toxicity of the C and M preparations.

Trypsin destroyed the toxic effect of the M protein preparations and was without effect on the toxicity of the C substance.

The R antigen and a nucleoprotein component of Group A streptococci, preparations of protein from Groups B and D streptococci, and coagulase from Staphylococcus aureus were all found to be essentially non-toxicic for the adrenalectomized rat. Large quantities of peptone, crystalline albumin, and rabbit serum were also without effect.
EFFECT OF HUMAN BLOOD SERUM ON TISSUE CULTURES
Authors: Fedoroff S. , Cook B.
Published: June 2004

When NCTC clone 929 (strain L) cells were grown either continuously or at intervals in toxic human serum, they became resistant to the toxic substance or substances.

The resistance developed to toxic human serum was passed from one cell generation to another; i.e., it was heritable.

The resistance to toxic human serum, developed in strain L cells, was associated with a decrease in their ability to adsorb toxic substances from the serum. This suggests that there is a decrease in the number of loci in the resistant cells where toxic substances can be bound.

The resistant cells differed from the sensitive cells in their morphological appearance, the increased frequency of minute chromosomes, and the increased adhesion to glass surfaces.

The cells which developed a resistance to a particular toxic serum also resisted the toxic effects of some other sera, but not of all.
STUDIES OF THE HEMOLYSIS OF RED BLOOD CELLS BY MUMPS VIRUS
Authors: Soule David W. , Marinetti Guido V. , Morgan Herbert R.
Published: June 2004

Hemolysis of chicken red blood cells by mumps virus is associated with the release of sphingomyelin from the stromal lipoprotein and the destruction of 65 per cent of the sphingomyelin of the red cell stroma. However, the virus had no effect on isolated phosphatides extracted from the erythrocytes. The hemolytic action of the virus and changes in sphingomyelin content of the erythrocytes fail to occur at a pH of 6.0. The viral hemolysis of human erythrocytes is not associated with similar alterations in their content of sphingomyelin. The absence of lecithin from sheep erythrocytes, which are also lysed by mumps virus, is additional evidence that a viral lecithinase is not associated with the hemolytic property of mumps virus.

Mumps virus concentrated from the amniotic fluid of viral infected chick embryos contains about 7 per cent phosphatide, 60 per cent of which is sphingomyelin.
CHROMATOGRAPHIC STUDIES OF THE RHEUMATOID FACTOR
Authors: Lospalluto J. , Ziff M.
Published: June 2004

Serum and serum fractions from patients with rheumatoid arthritis have been subjected to anion exchange chromatography on diethylaminoethyl cellulose. The rheumatoid factor activity was clearly separated from the bulk of the gamma globulin by virtue of the anomalous behavior of macroglobulins on this column.

Purification of rheumatoid factor by precipitation with fraction II, resolution in 4 M urea, and two successive fractionations on an anion exchanger yielded a highly active preparation consisting of approximately 95 per cent 19S gamma globulin with no detectable amount of 7S contaminant.

Evidence was obtained for the existence of two factors by cation exchange chromatography (carboxymethyl cellulose) of rheumatoid serum and of macroglobulin previously separated by anion exchange chromatography. One factor (factor I) agglutinated sensitized sheep cells and latex particles and also precipitated with human fraction II. The second (factor II) agglutinated latex partides and precipitated with fraction II but did not agglutinate sensitized sheep cells.

A substance with the properties of factor II was demonstrated in two of four normal sera by cation exchange chromatography. It was suggested that the agglutination of latex particles and precipitation with human fraction II, observed in the case of certain abnormal sera, may be due to elevated concentrations of factor II.
THE STREPTOKINASE-PLASMINOGEN SYSTEM
Authors: Krasner Robert I. , Young Genevieve
Published: June 2004

Human plasminogen, plasma, or serum increased the pathogenicity of six streptokinase-positive streptococcal strains for mice. Combinations of commercial streptokinase and plasminogen or streptokinase and plasma did not usually increase mouse mortality to a greater degree than did plasminogen or plasma alone, suggesting that the maximal effective amount of streptokinase was produced by the organisms.

The pathogenicity of Salmonella paratyphi (fibrinolysin variable) and a Group D streptococcus (streptokinase-negative) was not increased by plasminogen, plasma, or streptokinase, whereas a combination of streptokinase and plasminogen, or streptokinase and plasma did significantly increase mouse mortality resulting from these organisms.

Combinations of certain concentrations of streptokinase and plasminogen increased the pathogenicity of a fibrinolysin-negative staphylococcal strain for mice to a greater extent than did either substance alone.

The observed results provide evidence that streptokinase, by an interaction with plasminogen, contributes to the pathogenicity of streptokinase-positive streptococci.
INVESTIGATIONS CONCERNING THE CHANGES IN SERUM PROTEINS DURING IMMUNIZATION
Authors: Bjørneboe M. , Schwartz Michael
Published: June 2004

On hyperimmunization of rabbits with pneumococcal vaccine, increase in the content of gamma globulin and fall of albumin in the serum are produced. In such hyperimmunized rabbits, investigations of the plasma volume, albumin degradation, and the distribution of the albumin intra- and extravascularly were undertaken by Sterling's method employing rabbit albumin labelled with I131.

The investigations do not suggest any significant alteration in the albumin degradation nor in the distribution between the intra- and extravascular albumin. It was demonstrated that the plasma volume increases simultaneously with increase in the gamma globulin and fall in albumin.

It is concluded that the fall in serum albumin observed is due to a regulative mechanism which attempts to maintain the colloid-osmotic pressure by increasing the plasma volume.
THE IN VIVO STABILITY OF ANTIBODY
Authors: Garvey Justine S. , Campbell Dan H.
Published: June 2004

When rabbits were fed S35-labelled amino acids and simultaneously injected with antigen at the peak of antibody production, the circulating antibody became rapidly labelled within a few hours with the isotope. The specific radioactivity of antibody was measured as antibody was allowed to decline in the absence of antigenic stimulation. At various times, in different animals, antigen was reinjected and circulating antibody was measured for specific radioactivity. The initial antibody which appeared after the antigenic stimulus always had a higher specific activity than antibody circulating just prior to the reinjection. The appearance of antibody of higher specific activity was demonstrated to be a specific response to the antigen which was reinjected. It was concluded that there is a reservoir of antibody which is stabilized in tissue and which is not in equilibrium with that in circulation. A mechanism for this stabilization is suggested and discussed from previous investigations demonstrating the long retention of antigen in liver tissue.
INTERACTIONS BETWEEN RABBIT POLYMORPHONUCLEAR LEUCOCYTES AND STAPHYLOCOCCI
Authors: Cohn Zanvil A. , Morse Stephen I.
Published: June 2004

A method has been described for the study in vitro of leucocyte-bacteria interactions which permits the simultaneous evaluation of both phagocytosis and intracellular bacterial inactivation. Employing this technique, the fate and localization of staphylococci in homogeneous suspensions of rabbit polymorphonuclear leucocytes have been studied.

Coagulase-positive strains of S. aureus were not efficiently ingested in the presence of normal rabbit serum. In contrast, coagulase-negative strains of S. albus were rapidly engulfed and inactivated.

Immune sera prepared against a coagulase-positive strain enhanced the the ingestion of the homologous organism as well as of three heterologous strains of S. aureus. Following phagocytosis, prompt intracellular killing of S. aureus occurred. The thermostable opsonins in immune sera reacted only with strains of S. aureus.

A comparison between polymorphonuclear leucocytes obtained from normal and immune animals revealed no differences in their ability either to ingest or kill coagulase-positive staphylococci.

Studies with other bacterial species are presented to illustrate: (a) phagocytosis followed by intracellular inactivation; (b) phagocytosis followed by intracellular survival; and (c) the absence of phagocytosis.
STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES
Authors: Henle Werner , Henle Gertrude , Deinhardt Friedrich , Bergs Victor V.
Published: June 2004

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.
ELECTRON MICROSCOPE STUDY OF THE DEVELOPMENT OF THE PAPILLOMA VIRUS IN THE SKIN OF THE RABBIT
Authors: Stone Robert S. , Shope Richard E. , Moore Dan H.
Published: June 2004

Rabbit papilloma virus seems uniquely to begin its proliferation in the nucleolus of infected cells. In cells near the germinal layer of the stratum Malpighii spherical viral bodies seem to develop within a reticulum which forms out of the fine granular matrix of the nucleolus. The virus may later fill the nucleus and spread into the whole cell. The age of the cell, determined by its position in the Malpighian layer and by the extent of keratinization, can be correlated with the viral development.
STUDIES ON THE PATHOGENICITY OF GROUP A STREPTOCOCCI
Authors: Foley Marie Judith , Smith Mary Ruth , Wood W. Barry
Published: June 2004

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.
EFFECT OF ANTIBODY AND COMPLEMENT ON PERMEABILITY CONTROL IN ASCITES TUMOR CELLS AND ERYTHROCYTES
Authors: Green H. , Barrow P. , Goldberg B.
Published: June 2004

Rabbit antibody + complement alters the permeability properties of mouse Krebs ascites tumor cells and erythrocytes. When antibody + C' acts on ascites tumor cells in a low protein medium, intracellular K+ is lost from the cells at a rate far greater than the normal leak rate. At the same time the cells lose amino acids and ribonucleotides and become fully permeable to the Na+ of the medium. When antibody + C' acts in a low protein medium, the cells swell extensively and lose most of their macromolecules to the medium (hemoglobin from erythrocytes, protein and RNA from the ascites tumor cells). If the antibody + C' acts in a medium containing protein in sufficient concentration to balance the colloid osmotic pressure of the cells, the swelling is prevented; no macromolecules are then lost from the cells, but the loss of K+ and entrance of Na+ are not altered, and the loss of amino acids and ribonucleotides is only slightly affected.

It therefore appears that the action of antibody + C' is to produce functional "holes" in the animal cell membrane which permit the equilibration of cations and small molecules between cell and medium. This leads to an increase in the osmotic pressure of the cell and a rapid influx of water. The cell membrane and its "holes" are thereby stretched, permitting macromolecules to escape from the cell.
INACTIVATION OF ENDOTOXIN BY A HUMORAL COMPONENT
Authors: Landy Maurice , Trapani Robert-John , Shear Murray J.
Published: June 2004

The immunological properties of typhoid endotoxin were investigated after incubating it with serum under conditions in which EDC (endotoxin-detoxifying component) was operative. Brief interaction of endotoxin in vitro with this system in serum (human, rabbit, mouse) abolished its antigenicity for rabbits. Suitable modification of the host permitted separate elicitation of toxic and antigenic responses to typhoid endotoxin. Endotoxin altered by EDC was still capable of precipitating specific antibody; moreover, it did so in a manner which resembled that of the haptenic polysaccharide.
SEQUENTIAL CELLULAR CHANGES PRODUCED BY TYPES 5 AND 7 ADENOVIRUSES IN HELA CELLS AND IN HUMAN AMNIOTIC CELLS
Authors: Boyer Georgiana S. , Denny Floyd W. , Ginsberg Harold S.
Published: June 2004

The sequential cytological changes which develop in tissue culture cells infected with adenovirus types 5 and 7 are described and compared with those produced by adenovirus types 1, 2, 3, and 4. The evidence that is presented indicates that types 1, 2, and 5 belong to one major subdivision of the adenovirus group and types 3, 4, and 7 to another. That the host cell nucleus is the principal site of adenovirus synthesis has been confirmed by fluorescent antibody studies. They have demonstrated the occurrence of type-specific adenovirus antigen in the characteristic intranuclear inclusions and other virus-induced structures reported to contain virus-like particles or shown by electronmicroscopy.
THE DEVELOPMENT OF THE ACUTE INFLAMMATORY RESPONSE TO EXPERIMENTAL CUTANEOUS MUCORMYCOSIS IN NORMAL AND DIABETIC RABBITS
Authors: Sheldon Walter H. , Bauer Heinz
Published: June 2004

The histologic changes associated with the development of the acute inflammatory response to experimental cutaneous mucormycosis were studied at various times from 5 minutes to 24 hours after inoculation into normal rabbits and in rabbits with acute alloxan diabetes and acidosis. In normal animals the response by polymorphonuclear leukocytes began within a few minutes after inoculation, increased rapidly in extent and intensity and reached its peak within 6 to 12 hours. By that time there was also early proliferation of fibroblasts and of large mononuclear cells and these cellular reactions, together with the accumulated granulocytes, began to produce a demarcation of the lesions. Beginning 4 to 6 hours after inoculation the fungus showed some growth but this remained confined to the necrotic center of the lesions. In the diabetic rabbits the onset of the response by polymorphonuclear leukocytes was delayed by several hours, reduced in intensity and was apparently less effective. There was no proliferation of fibroblasts and the lesions were spreading rather than circumscribed. Fungus growth in the tissues began shortly after inoculation, was marked, progressed rapidly, and soon extended beyond the site of inoculation. The large mononuclear cells, however, appeared at about the same time and in equal number in the lesions of both diabetic and non-diabetic animals and showed no morphologic changes.

It is concluded that a significant delay and impaired effectiveness of the response by polymorphonuclear leukocytes, a lack of fibroblastic proliferation and an enhanced growth of the fungus lower host resistance to infection with it and are directly consequent on severe alterations in host metabolism.
EVALUATION OF THE "LONG CHAIN REACTION" AS A MEANS FOR DETECTING TYPE-SPECIFIC ANTIBODY TO GROUP A STREPTOCOCCI IN HUMAN SERA
Authors: Stollerman Gene H. , Siegel Alan C. , Johnson Eloise E.
Published: June 2004

Certain strains of Group A streptococci showed striking increase in chain length when grown in liquid media to which was added human sera that contained antibody to M protein of homologous type. This "long chain reaction" was shown to be a highly specific and sensitive biological test for human type-specific antibody and correlated closely with the classical bactericidal test.

Patients infected with Type 12 or Type 3 Group A streptococci showed the appearance of anti-M antibody in their sera by both methods at similar intervals during convalescence. Of 217 sera studied in these patients the two tests showed agreement in all but 11 specimens. Of 99 patients who were bled serially following Type 12 or Type 3 infections, and whose sera were tested by both methods, there was close agreement, the bactericidal test being only slightly more sensitive.

The advantages and limitations of this new biological test for human type-specific immunity are discussed.
STUDIES ON THE ANTIGENIC PROPERTIES OF COMPLEMENT
Authors: Klein Paul G. , Burkholder Peter M.
Published: June 2004

Sheep erythrocytes sensitized with amboceptor and persensitized thereafter with guinea pig complement are agglutinated by rabbit anti-guinea pig globulin and by immune sera obtained by injection of rabbits with fixed complement. In this agglutination neither C'1 nor C'2 takes part. Fixed C'4 acts as an agglutinogen. An additional agglutinogen, distinct from C'4, was found on persensitized cells. This additional agglutinogen appears to be distinct from hemolytically active C'3.
TRANSFER OF ALLERGIC ENCEPHALOMYELITIS IN RATS BY MEANS OF LYMPH NODE CELLS
Authors: Paterson Philip Y.
Published: June 2004

Transfer of allergic encephalomyelitis has been accomplished by injection of lymph node cells, obtained from donor rats sensitized to spinal cord, into recipient rats pretreated neonatally with normal rat spleen cells. Transfer of the disease may be achieved most frequently when the recipients are pretreated with spleen cells of the prospective lymph node cell donors. These transfers are attributed to the use of recipients which have acquired immunological tolerance to donor lymph node cells, as a result of the spleen cell pretreatment, and in which, therefore, the donor cells can survive and function longer after transfer.
THE IMMUNOLOGICAL SPECIFICITY OF TYPE II PNEUMOCOCCUS AND ITS SEPARATION INTO PARTIAL SPECIFICITIES. II
Authors: Heidelberger Michael
Published: June 2004

Quantitative data are given on the cross reactions in Type II antipneumococcal horse sera of plant gums and hemicelluloses containing multiple terminal groupings of glucuronic acid and/or 4-O-methylglucuronic acid.

Great variability is shown both in the reactivities of the polysaccharides and in the antibodies in the sera of different animals immunized with the same antigen.

The 4-O-methyl substituent on the glucuronic acid residues in a gum often appears to diminish cross-precipitation with antibodies to S II.
THE BINDING OF MYOGLOBIN BY PLASMA PROTEIN
Authors: Lathem Willoughby
Published: June 2004

When added to dog plasma in vitro and in vivo, myoglobin was bound to plasma protein in a concentration which, maximally, averaged 21 ± 6 mg. per cent. Electrophoretically, bound myoglobin was separated from free myoglobin and migrated between alpha-2 and beta globulin. The electrophoretic characteristics of protein-bound myoglobin were similar to, although not identical with, those of protein-bound hemoglobin. The maximal binding capacity of plasma for myoglobin was less than for hemoglobin, which averaged 123 mg. per cent. At concentrations below the maximal binding capacity, from 15 to 50 per cent of the myoglobin was in the free, unbound state, differing from hemoglobin which was completely bound at all concentrations below the binding capacity.

When myoglobin and hemoglobin were added together to plasma, hemoglobin appeared to interfere with the binding of myoglobin or to replace it at the binding sites. Myoglobin, however, did not appear to interfere with the binding of hemoglobin. These observations suggested that myoglobin and hemoglobin were bound at least in part by the same protein.

When myoglobin was given intravenously, free myoglobin was excreted in the urine, whereas protein-bound myoglobin was not excreted. This suggests that protein-binding contributes to or determines the apparent renal threshold to myoglobin.
A VIRUS-INDUCED EPIZOOTIC HEMORRHAGIC DISEASE OF THE VIRGINIA WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS)
Authors: Shope Richard E. , MacNamara Lester G. , Mangold Robert
Published: June 2004

A circumscribed natural outbreak of a highly fatal disease of deer, which we have designated epizootic hemorrhagic disease (EHD), has been studied. The disease has proven readily transmissible in deer but not in other experimental or domestic animals tested, nor in embryonating eggs or deer kidney cell cultures. The causative agent is a virus which is readily filterable and is capable of storage, either frozen or in glycerol, for relatively long periods of time. It produces a solid immunity in the few animals that survive and the blood sera of such convalescent animals contain virus-neutralizing antibodies. The disease is one in which large and small hemorrhages occur in both the viscera and skeletal structures of the body, as well as in the subcutaneous tissues. It is probably the same as one known popularly in the southeastern United States as "black tongue" of deer. It is unrelated to epidemic hemorrhagic fever of man or to the disease caused in horses by the equine arteritis virus. At least two serologically different types of EHD virus exist. The New Jersey strain is of greater lethality for experimental deer than the serologically different one obtained from an outbreak that occurred in South Dakota a year after the New Jersey epizootic.
THE PATHOLOGIC EFFECTS OF INTRAVENOUSLY ADMINISTERED SOLUBLE ANTIGEN-ANTIBODY COMPLEXES
Authors: Benacerraf Baruj , Potter Jacobus L. , McCluskey Robert T. , Miller Frederick
Published: June 2004

The intravenous administration to rats of soluble antigen-antibody complexes in antigen excess resulted in acute glomerulonephritis. This occurred with both rabbit antiovalbumin and rabbit anti-BSA systems.

The rats so treated regularly showed proteinuria and elevation of blood urea nitrogen.

These findings are compared with those reported in rats injected with anti-kidney serum.
ISOLATION AND CHARACTERIZATION OF TWO ß1-GLYCOPROTEINS OF HUMAN SERUM
Authors: Müller-Eberhard H. J. , Nilsson U. , Aronsson T.
Published: June 2004

Two immunoelectrophoretically defined, heretofore unidentified ß1-globulins of human serum, provisionally designated ß1C- and ß1A-globulin, were isolated by means of preparative electrophoresis and chromatography on anion exchange cellulose.

The sedimentation coefficient S020, w of ß1C-globulin was shown to be 9.5 S, and that of ß1A-globulin, 6.9 S. Both proteins were found to contain similar amounts of carbohydrate, to be devoid of lipids, and to possess the solubility characteristics of euglobulins. In the Ouchterlony double diffusion test they gave the reaction of partial identity, which revealed ß1A-globulin to be anti-genically deficient as compared to ß1C-globulin.

ß1A-globulin could not be detected in fresh sera and ß1C-globulin was absent from aged sera. Highly purified ß1C-globulin stored at 1°C. was converted to ß1A-globulin within 4 to 6 weeks, and at 37°C. was converted within 6 days. The likelihood of a dimer-monomer relationship between these two proteins was discussed.
HOST-PARASITE FACTORS IN GROUP A STREPTOCOCCAL INFECTIONS
Authors: Watson Dennis W.
Published: June 2004

The factors present in streptococcal lesion extracts (SLE) which enhanced the lethal and tissue-damaging properties of Gram-negative bacterial endotoxins and streptolysin O were identified with the scarlet fever group of toxins.

Toxic manifestations attributed to this group of toxins included lethality, cardiotoxic and other tissue damage, enhancement of toxicity, and pyrogenicity. Of these, the measurement of febrile response in American Dutch rabbits was the most useful parameter of toxicity.

In rabbits, repeated daily intravenous injections of 0.125 Lf of a purified erythrogenic toxin immunizes specifically against the pyrogenic activity; this technique was used to type the toxins and to distinguish them from exogenous and endogenous pyrogens; non-specific pyrogens, such as streptococcal endotoxin, were not found in SLE.

All types of the Lancefield Group A streptococci tested produced one or or more immunologically distinct toxins in vivo in contrast to Groups B and C which did not produce them; toxins A and B, previously distinguished by neutralization of rash-inducing activity in the skin, were produced in vivo. The A toxin was the most common, as indicated by its presence in extracts prepared with Types 28, 12, 17, and 10 (NY-5); B toxin was found in 10 (NY-5) and 19. A new toxin, designated C, was obtained from a Type 18.

In American Dutch rabbits, purified toxin at a concentration of 15 Lf (900,000 STD) neither gave a Dick test nor prepared the skin for the local Shwartzman reaction; by this route, however, in contrast to classical endotoxins, they enhance the lethal and tissue-damaging properties of sublethal doses of these and other toxins.

These properties of the immunologic distinct exotoxins as demonstrated in American Dutch rabbits suggest by analogy their importance in the pathogenesis of streptococcal disease in man. Evidence that might implicate them in sequelae, in addition to scarlet fever, is discussed.
FURTHER STUDIES ON PREPARATION AND PROPERTIES OF PHAGOCYTIN
Authors: Hirsch James G.
Published: June 2004

Phagocytin and histone differ significantly in the following regards: (a) the bactericidal action of histone is rapidly lost on peptic digestion, while that of phagocytin is but little affected; (b) the lethal effect of phagocytin on coliform bacteria is much more resistant than that of histone to antagonism by spermine or by increasing ionic strength of the medium; (c) phagocytin can be extracted from disrupted granulocytes with dilute citric acid whereas effective extraction of histone requires stronger mineral acid or strong salt solution; (d) phagocytin is limited in distribution to polymorphonuclear leucocytes while histone is demonstrable in many tissues.

A new technique has been devised which permits extraction of phagocytin essentially free of lysozyme and histones. Phagocytin thus prepared kills certain Gram-positive bacteria as well as Gram-negative bacilli under appropriate in vitro test conditions. Among susceptible Gram-positive microbes are Group A streptococci and staphylococci.

Phagocytin is demonstrable in citric acid extracts of granulocytes obtained from rabbit, man, horse, and guinea pig, the only species thus far investigated. Circulating blood leucocytes as well as exudate cells contain this bactericidal substance.

The lethal effects of phagocytin on bacteria may be influenced, depending on the particular microorganism, by either pH or ionic strength of the medium.

The bactericidal action of phagocytin is only slightly reduced following digestion with trypsin, chymotrypsin or papain. The active ingredient is, however, non-dialyzable and apparently precipitated by trichloracetic acid. Data available at present are insufficient to define the chemical nature of phagocytin.
HEREDITARY PREMATURE SENESCENCE OF THE RABBIT
Authors: Pearce Louise , Brown Wade H.
Published: June 2004

The acute form of hereditary premature senescence in 79 rabbits, among which the 20th generation of the condition was represented, has been described. The manifestations did not differ in kind from those previously described in connection with the chronic form (1) of the complex but their degree and, in particular, the severity and the rate of progression of systemic degeneration were much greater. The rabbits either did not survive to 2 years 6 months, of age or their physical condition had become critical by this time. A senile appearance, largely due to deteriorative changes of the coat, was frequently observed.

The essential nature of the senescence condition was obviously a degeneration and one in which vital mechanisms essential to the maintenance of health were involved.
STUDIES OF MOUSE POLYOMA VIRUS INFECTION
Authors: Law Lloyd W. , Rowe Wallace P. , Hartley Janet W.
Published: June 2004

The relationship of polyoma (parotid tumor) virus infection to spontaneous and x-ray induced lymphocytic neoplasms (leukemia) in mice has been studied in two sublines of the high leukemic AKR strain, in the high leukemic C58 strain and in the x-ray responsive C3Hf/Bi strain. There was found to be no correlation of hemagglutination-inhibiting (HI) antibody with leukemia appearing at various times throughout life, and there was no evidence of increased risk of developing leukemia in mice with prior antibody to polyoma virus. Virus isolation experiments accomplished with AKR leukemic mice showed that HI antibody status of these mice had the same significance with regard to presence or absence of detectable virus as was previously observed for non-leukemic mice from infected colonies.

The results of this study were interpreted as supporting the concept that the repeated association of polyoma virus and experimental transmission of leukemia is fortuitous.
THE DEVELOPMENT OF ANTIBODIES TO PENICILLIN IN RABBITS
Authors: Josephson Alan S.
Published: June 2004

A method for the production of antibodies specifically directed against penicillin is described.

The inability of this antibody to significantly reduce the antibiotic activity of penicillin is noted.

Evidence to show the variability of specificities of various sera, some directed for the most part against the side chain, others against the nucleus is presented.

Studies on serum fractions separated electrophorectically indicate that the antibody migrates in the fast γ-globulin and ß-globulin fractions and requires dextran or albumin to effect agglutination.

The inability of penicilloic acid, an hydrolysis product of penicillin to provoke antibody formation despite its ability to inhibit the antibody is shown and the implications of this observations are discussed.
THE ROLE OF THE RETICULOENDOTHELIAL SYSTEM IN MOUSE ANAPHYLAXIS AS TESTED WITH HOMOLOGOUS ANTIBODY-ANTIGEN COMPLEXES
Authors: Wistar Richard , Treadwell Perry E. , Rasmussen A. F.
Published: June 2004

Blockade of the RES was accomplished by the intravenous injection of carbon particles, thorotrast, zymosan, or a suspension of Bordetella pertussis. The blockade resulted in a decrease in sensitivity to anaphylaxis produced by the intravenous injection of soluble antigen-antibody complexes consisting of an optimal shocking mixture of bovine plasma albumin and mouse antibody to this antigen. The decrease in sensitivity to anaphylaxis was dependent on the dose of blockading agent and on the time between blockade and challenge with complex. The loss of sensitivity to anaphylaxis could not be restored by the administration of fresh serum from normal mice nor by guinea pig complement. Antigen-antibody complexes were rapidly removed from the blood with an average half-time of 11.9 minutes in normal mice. Complexes were cleared at significantly more rapid rates in mice previously sensitized to antigen.

Although not all the results can be explained on the basis of blockade the facts indicate that the RES does play an important but as yet undefined role in passive homologous anaphylaxis in the mouse.
FUNCTIONAL AND METABOLIC PROPERTIES OF POLYMORPHONUCLEAR LEUCOCYTES
Authors: Cohn Zanvil A. , Morse Stephen I.
Published: June 2004

The phagocytosis and intracellular destruction of bacteria by rabbit polymorphonuclear leucocytes has been studied in vitro under defined conditions.

The efficient and continuing ingestion of bacteria was dependent upon (a) opsonic factors present in fresh rabbit serum as well as upon, (b) the availability of an adequate supply of glucose in the medium.

The effects of selected enzymatic inhibitors on the metabolic and functional activities of the leucocytes was investigated. Cyanide which inhibited oxygen consumption had no effect on the ingestion or inactivation of bacteria, Iodoacetate and arsenite which blocked glycolysis produced a marked inhibition in particle ingestion. 2,4-Dinitrophenol which stimulated both oxygen consumption and glycolysis, depressed phagocytosis after a 1 hour latent period. It was concluded that phagocytosis was an energy-requiring process in which glycolysis served as the most important source of energy.

Leucocytes which were ingesting heat-killed bacteria exhibited increases in oxygen consumption, glucose utilization, and lactic acid synthesis. The effect of particle ingestion on glycogen metabolism was characterized by an initial period of glycogenolysis followed by an enhanced rate of glycogen synthesis.

Leucocytes which had previously ingested heat-killed bacteria also demonstrated increased rates of phagocytosis.
COMPARISON OF THE EFFECTS OF PAPAIN AND VITAMIN A ON CARTILAGE
Authors: Thomas Lewis , McCluskey Robert T. , Potter Jacobus L. , Weissmann Gerald
Published: June 2004

The administration of large amounts of vitamin A to rabbits has been shown to result in depletion of cartilage matrix. The normal basophilic, metachromatic, and Alcian blue staining properties of the matrix are lost, especially in articular and epiphyseal cartilage. The cartilage cells remain intact, but are reduced in size.

These changes sometimes appeared as early as 48 hours after the initiation of daily injection of 1 million units of vitamin A, and were usually well established by 5 days. Some rabbits failed to show changes in cartilage, even after 5 daily injections.

Increased amounts of material presumed to be chondroitin sulfate were present in the sera of vitamin A-treated rabbits, usually by 72 hours after the first injection. This was demonstrated by a turbidimetric procedure using hexamminecobaltic chloride.

In rabbits given sulfur-35 (Na2S35O4) 5 days before the initiation of vitamin A treatment, it was shown that sulfur-35 was lost from articular and epiphyseal cartilage. This was associated with an increase in the non-dialyzable sulfur-35 in both serum and in the cobalt-precipitable material. These rabbits also excreted more sulfur-35 than rabbits not given vitamin A. There was a reduction in sulfur-35 activity in chondromucoprotein extracted from the ear cartilage of vitamin A-treated rabbits.

The changes are interpreted as indicating that the administration of large amounts of vitamin A to rabbits results in removal of chondroitin sulfate from cartilage matrix.

The administration of small amounts of crude papain causes histologic changes in cartilage that are remarkably similar to those seen in vitamin A-treated rabbits.

The possibility is suggested that the changes in cartilage produced by administration of vitamin A to rabbits may be the result of activation of a proteolytic enzyme or enzymes, with properties similar to those of papain.
COMPARISON OF THE EFFECTS OF PAPAIN AND VITAMIN A ON CARTILAGE
Authors: Fell Honor B. , Thomas Lewis
Published: June 2004

The effects of papain protease and of vitamin A on explanted limb bone rudiments from 7- and 13-day chick embryos and fetal mice have been studied and compared.

The incubation of cartilaginous rudiments from 7-day chick embryos in a solution containing papain and cysteine resulted in complete loss of the metachromasia of the cartilage matrix within 1 hour; explants treated in this fashion recovered normal metachromatic staining properties when grown in normal medium for 4 days.

The incubation of 7-day chick cartilage rudiments in a solution containing papain without cysteine resulted in partial loss of metachromasia from cartilage within 1 hour; the addition of vitamin A to the solution did not enhance the effect of papain during this period.

The addition of papain to the culture medium in which 7-day chick embryo cartilage rudiments were grown resulted in uniform loss of the metachromasia of the cartilage matrix; similar explants grown in the presence of excess vitamin A also showed loss of the metachromasia of cartilage, but certain regions of the cartilage were affected earlier and more severely than others. Changes in cartilage cells, including loss of glycogen, occurred when the rudiment was grown in medium containing excess vitamin A, but not when it was grown in the presence of papain.

Bone rudiments from 13-day chick embryos showed changes in cartilage similar to those seen in 7-day chick embryo rudiments when grown in the presence of papain or of excess vitamin A; the existing bone was not affected under these conditions. When grown in the presence of papain or excess vitamin A, the cartilage of late fetal mouse bone underwent changes similar to those already described in chick embryo rudiments.

In contrast to the chick embryo rudiments, those from the fetal mouse showed rapid resorption of bone when grown in the presence of excess vitamin A. Papain had no effect on bone from either source.

The changes seen in cartilage of explants grown in the presence of vitamin A and papain together were greater than those seen with either agent alone. The changes seen in fetal mouse bone grown in the presence of vitamin A were not enhanced by the additional presence of papain.

On the basis of these observations, it is suggested that the changes in cartilage seen in experimental hypervitaminosis A may be the result of activation of a proteolytic enzyme or enzymes with properties similar to papain.
HEREDITARY DISTAL FORELEG CURVATURE IN THE RABBIT
Authors: Pearce Louise
Published: June 2004

An inwardly directed curvature of the distal segment of both forelegs of the rabbit has been described. The condition was detected at 2 to 3 weeks of age, developed rapidly, and reached its final and permanent stage at 2 to 3 months of age. Only the distal epiphysis of the ulna was primarily affected and this in the form of a massive chondrodystrophic lesion accompanied by a progressive curvature of the shaft. The curvature of the growing radius was a secondary effect due to the firm, immovable, anatomical connection of the ulna and radius. The positional changes of the wrist and paw were likewise effects secondary to the changed form of the ulna and radius.

The bowing abnormality occurred only in certain families of pure bred Beveren, Belgian, French Silver, and Dutch rabbits and was found to be inherited. The mode of inheritance was on the basis of a single recessive unit factor (5).
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Rafter Gale W. , Collins Robert D. , Wood W. Barry
Published: June 2004

Study of the chemical properties of the pyrogenic component of rabbit polymorphonuclear leucocytes reveals it to contain an essential, non-dialyzable protein which: (a) is precipitated by perchloric acid, (b) is removed by extraction with phenol, (c) is soluble in 50 per cent methanol and 33 per cent saturated ammonium sulfate, and (d) is destroyed by the proteolytic action of both trypsin and pepsin.

By combined chemical and chromatographic techniques the leucocytic pyrogen has been purified approximately 50-fold. The partially purified material contains less than 1 per cent carbohydrate, is resistant to periodate oxidation, is unaffected by extraction with butanol and contains at least two immunologically active components when tested by the Ouchterlony gel-diffusion technique. Its chemical properties distinguish it from other known pyrogenic substances which have been implicated in the pathogenesis of fever.
THE EFFECTS OF X-RAYS AND BETA RAYS (TRITIUM) ON THE GROWTH OF RICKETTSIA MOOSERI AND RICKETTSIA AKARI IN EMBRYONATE EGGS
Authors: Greiff Donald , Powers E. L. , Kisieleski Walter E. , Pinkerton Henry
Published: June 2004

The growth of Rickettsia mooseri was accelerated and quantitatively increased in embryonate eggs containing tritium oxide at levels of 180, 90, and 45 mc./egg during the growth period. The eggs of a group containing 22.5 mc./egg showed only a slight increase in the rate of growth of organisms; the infections in the eggs of a group given 11.2 mc./egg did not differ significantly from those of the control group. On the other hand, growth of R. akari was inhibited in embryonate eggs containing tritium oxide at levels of 180, 90, and 45 mc./egg, and partially inhibited in groups containing 22.5 and 11.2 mc./egg. The patterns of growth of R. mooseri and of R. akari exposed to tritium oxide for 6 hours prior to inoculation into embryonate eggs did not differ significantly from that of the control group.

Single and divided doses of x-rays to the host resulted in partial inhibition of the growth of R. akari.
COMPARATIVE BACTERICIDAL ACTIVITIES OF BLOOD SERUM AND PLASMA SERUM
Authors: Hirsch James G.
Published: June 2004

Rabbit and human plasma can be prepared without resort to anticoagulants by employing low temperatures and non-wetting surfaces. Serum formed after clotting of rabbit plasma devoid of cells and platelets manifests essentially no bactericidal activity on Bacillus subtilis, Bacillus megaterium, and a strain of Staphylococcus aureus. In contrast, rabbit blood serum exhibits this activity to a high degree.

Rabbit plasma rich in platelets gives rise to a serum with capacity to kill these Gram-positive microbes equal to that of serum prepared from whole blood. This heat-stable antibacterial agent is efficiently formed or released when platelets are present during the coagulation of plasma, but not on incubation of platelets in heparinized or citrated plasma or in saline. Leucocytes and red cells appear to play no significant role in its production.

Rabbit blood serum and plasma serum have similar heat-labile lethal effects on enteric bacilli.

Human serum, whether from blood or plasma, manifests much less bactericidal activity on Bacillus subtilis than does rabbit blood serum.

These findings serve to emphasize the fact that substances formed or released during coagulation of whole blood may impart to the serum activities not present in circulating plasma.
EXPERIMENTAL IMMUNOLOGIC ADRENAL INJURY
Authors: Steiner Jan W. , Langer B. , Schatz D. L. , Volpe R.
Published: June 2004

Twenty-three unilaterally adrenalectomized guinea pigs were injected with autologous and homologous adrenal tissue homogenates respectively, in Freund's adjuvant. Widespread adrenal lesions were found in 10 of 12 animals receiving auto-antigen and to a lesser extent in 6 of 11 animals injected with homologous pooled antigen. Widespread systemic lesions were present in both these and in control animals receiving Freund's adjuvant alone. These latter animals showed no adrenal involvement.

The early changes within the adrenal consisted of perisinusoidal cellular proliferations in the deeper layers of the cortex. Focal granulomata developing at a later stage tended to become confluent and to displace cortical cells. Some loss of these cells was attributable to ischemic injury.

The localization in the deep fasciculata and reticularis was thought to depend (a) on the varying antigenicity of adrenal cortical components, (b) the possible inhibitory effect of antiphlogistic adrenal cortical hormones on the development of lesions in the outer cortex, and (c) the presence of littoral cells in the deep cortex. These cells are thought to be involved in the mediation of the stimulus initiating differentiation of primitive mesenchymal cells in response to a circulating auto-antigen. The medullary lesions may be related to the presence of ectopic reticularis cells in this location.

It was suggested that the cellular response in the target organ to injections of adrenal homogenates may denote a specific "organ-self" recognition mechanism involving an immune (i.e. defensive) reaction. It was postulated that this may be an accentuation of the physiological function of immunologically competent cells. Their proliferation, under normal circumstances, would prevent by means of production of "binding" globulins, the escape and dissemination of endogenous freed adrenal antigens into the circulation. Although the experimental stimulus arose from without the gland, by virtue of the presence of a circulating adjuvant-bound antigen, the adrenal reaction followed the same pattern as would obtain if the antigen was liberated within the suprarenal cortex.