bluuebunny/crossref_metadata_2025 huggingface dataset:
THE IN VITRO DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES
Authors: Cohn Zanvil A. , Benson Belinda
Published: June 2004

The influence of selected inhibitors of protein synthesis on the in vitro differentiation of mouse mononuclear phagocytes has been investigated. DL-p-Fluorophenylalanine at concentrations of 250 µg/ml inhibits the formation of three lysosomal hydrolases, cytochemically demonstrable acid phosphatase and osmiophilic, phase-dense granules. These effects occur in the absence of cell death and are reversed by L-phenylalanine. Puromycin at concentrations of 0.2 to 0.4 µg/ml has a similar effect on both the morphology and biochemistry of cell maturation.

Colchicine at a concentration of 0.05 µg/ml inhibits the growth in cell diameter and has less of an effect on enzyme production.

Cells exposed to leucine-H3 for 2 to 3 minutes exhibit the localization of grains in the perinuclear-dense granule region. After an exposure of 60 minutes a similar localization is evident but with a correspondingly greater number of grains. A similar localization of grains occurs when choline-methyl-H3 is employed as a tracer. The data suggest the storage of newly formed protein and possibly phospholipid in the centrosphere region.
THE CATABOLISM OF HOMOLOGOUS AND HETEROLOGOUS 7S GAMMA GLOBULIN FRAGMENTS
Authors: Spiegelberg Hans L. , Weigle William O.
Published: June 2004

The catabolism of homologous and heterologous 7S gamma globulin fragments obtained by pepsin and papain digestion was studied in rabbits, guinea pigs, and mice. The elimination from the circulation of I* labeled gamma globulin fragments was followed and the urinary excretion of the total and protein-bound I* activity determined.

Evidence is presented that the molecular structure responsible for the catabolism of 7S gamma globulin is located in papain fragment III. The elimination of papain fragment III was slow and closely related to the intact gamma globulin, whereas the pepsin fragment and papain fragments I and II were rapidly eliminated and catabolized in all species examined.

Prolonged incubation with cysteine altered papain fragment III as shown by a rapid catabolism of a large portion of incubated fragment III within 24 hours after injection.

Small amounts of intact RGG and RGG papain fragment III were excreted as protein-bound I* activity in the urine. On the other hand, large amounts of the pepsin fragment and papain fragments I and II of RGG were excreted as protein-bound I* activity in the urine. The possibility of a molecular structure present in papain fragment III, which may be responsible for tubular reabsorption in the kidney, is discussed. The rate of urinary excretion of fragments obtained from RGG was different from that of fragments obtained from gamma globulin of several other species. In general, small amounts of the pepsin fragment and papain fragment III obtained from gamma globulin other than RGG were excreted as protein-bound I* activity. The amounts of fragment I* excreted as protein-bound I* activity depended on the species in which it was injected, as well as the source of the gamma globulin.

The rapid catabolism of the pepsin fragment and papain fragments I or II which bear antibody-combining sites suggest that their use for the prophylactic treatment of tetanus and diphtheria in man is limited.
THE RELATION OF INFLAMMATION TO THE MOLECULAR STRUCTURE OF CARBON COMPOUNDS SOLUBLE IN THE FLUIDS OF THE BODY
Authors: Opie Eugene L.
Published: June 2004

The peritoneal, like the pleural cavity, gives opportunity to measure with adequate accuracy the activity of inflammatory reactions defined by movement of fluid within the cavity, by migration of leucocytes into it, and by exudation of proteins from the plasma.

The activity of inflammatory reactions caused by saccharides or by alcohols that were tested varied in accord with their molecular weight, the osmotic pressure maintained by solutions of corresponding concentration, their boiling point, or by other colligative properties.

Blood serum or globulin in the concentration with which it occurs in blood serum injected into the peritoneal cavity caused changes which differed little from those caused by physiological salt solution.

Protein with molecular weight as low as that of cytochrome C (12,000) or ovalbumin (45,000) when in dilute solution (1 per cent) were rapidly absorbed, whereas trypsin and chymotrypsin under the same conditions caused very active inflammatory reactions because they set free amino acids and perhaps polypeptides with amino acids in short chains.

The activity of inflammatory reactions caused by carbon compounds soluble in body fluids varied in accord with their colligative properties.
PROPERTIES OF VARIOUS ANTI-γ-GLOBULIN FACTORS IN HUMAN SERA
Authors: Harboe Morten , Rau Barbara , Aho Kimmo
Published: June 2004

The serological and physicochemical properties of the following three forms of human anti-γ-globulin factors were compared: (a) rheumatoid factors; (b) Milgrom type anti-γ-globulin factors; and (c) factors directed against an antigen in human γG-globulin that is hidden in the intact molecule and revealed by enzymatic digestion at low pH. The property common to these factors is ability to interact with human γG-globulin; they are distinguishable because they react with different antigenic groups on this molecule.

In all of five sera, the Milgrom type anti-γ-globulin factors were γM-globulins. They reacted with various human γG-globulin antibodies but failed to interact with γM-globulin type antibodies in agglutination and absorption experiments. When isolated from other anti-γ-globulin factors, they agglutinated red cells coated with intact anti-Rh antibodies, but failed to react with cells cells coated with pepsin-digested anti-Rh antibody. These observations indicate that the agglutinator reacts with the crystallizable, inert fragment of γG-globulin.

Anti-γ-globulin activity directed against an antigen in human γG-globulin revealed by pepsin digestion was demonstrated in γG-, γA-, and γM-globulins. This anti-γ-globulin factor could be absorbed by antigen-antibody precipitates containing human antibody, which shows that the hidden antigen in human γG-globulin is revealed not only by enzymatic digestion at low pH, but also when γG-globulin is present as antibody in an antigen-antibody precipitate. Rheumatoid factors and Milgrom type anti-γ-globulin factors were also absorbed by antigen-antibody precipitates containing human antibody.

The results indicate that the three distinct forms of antiγ-globulin factors may all be produced as a result of antigenic stimulation by autologous antigen-antibody complexes.
INDUCED UNRESPONSIVENESS TO SIMPLE ALLERGENIC CHEMICALS
Authors: Battisto Jack R. , Chase Merrill W.
Published: June 2004

Normal guinea pigs fed chemical haptens develop a specific state of unresponsiveness, inhibiting subsequent development of dermal sensitization with the same hapten and modifying profoundly the synthesis of anaphylactic antibody in response to hapten conjugated to guinea pig proteins.

The degree of unresponsiveness has been tested by exposing hapten-fed animals to intense haptenic stimulation. Animals of groups that were demonstrably unresponsive to picryl chloride could be made to form hapten-specific antibody by injecting picrylated bovine gamma globulin. Specific anaphylactic-type antibodies, presumably 7S γ1, were synthesized, and in animals given PBGG adsorbed to alumina there arose a measurable concentration of precipitating antibody, presumably 7S γ2, perhaps slightly earlier than in similarly treated control animals.

Attempts to impose contact-type reactivity on such unresponsive animals met with limited success. Injection of picrylated guinea pig erythrocyte stromata in a complete Freund's adjuvant, with subsequent applications of picryl chloride to the dermis, led to definite contact sensitivity to 0.3 per cent picryl chloride, whereas parallel treatment of normal control animals induced sensitivity to 0.006 or 0.002 per cent. By this double method of stimulation, hapten-fed animals did not advance in sensitivity by reason of the secondary dermal applications of the simple chemical, whereas control animals developed increasingly higher sensitivity by these contacts in what appeared to be a stepwise manner.

Picryl chloride-fed guinea pigs injected intradermally with picryl chloride either after or before forming picryl-specific circulating antibody still remained unable to develop picryl-specific contact hypersensitivity.

Control animals synthesizing picryl-specific antibody subsequently responded to intradermal injection of picryl chloride with contact-type sensitivity.

Interpretations of these results are discussed and the view is presented that delayed-type hypersensitivity and circulating antibodies of the varieties measured here are formed independently of each other.
THE PRODUCTION OF ERYTHROCYTE AUTOANTIBODIES IN CHIMPANZEES
Authors: Zmijewski Chester M.
Published: June 2004

Young adult chimpanzees immunized with human blood products produced circulating antibodies which reacted with human red cells of a certain proportion of chimpanzees. In addition, agglutinins were formed which reacted with the animals' own erythrocytes. That these agglutinins were true autoantibodies was demonstrated by: (a) their ability to sensitize the animals' own erythrocytes at 37°C both in vivo and in intro; (b) the iso-specificity which they displayed toward other chimpanzee red cells; and (c) the fact that they belonged to the γG-class of immunoglobulins. Complement appeared to be bound to the in vivo sensitized cells but no evidence of increased cell destruction was observed. It seemed most likely that these autoagglutinins were produced as a result of active immunization with closely related antigens.
EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Unanue Emil R. , Dixon Frank J.
Published: June 2004

Nephrotoxic serum nephritis was studied in rats receiving variable amounts of kidney-fixing antibody and active or passive immunization to the heterologous gamma globulin of the species supplying the nephrotoxic antibody. Rats injected with a moderate to a large amount of kidney-fixing antibody (180 to 380 µg) and immunized to the heterologous gamma globulin developed a more severe nephritis than rats receiving similar amounts of antibody without further immunization. Rats injected with minimal amounts of kidney-fixing antibody (2 to 45 µg) and immunized to the heterologous gamma globulin developed a moderate nephritis in contrast to rats receiving similar amounts of antibody without further immunizations which showed no evidence of renal injury. In the rats receiving small doses of kidney-fixing antibody and immunization to the heterologous gamma globulin a lag period existed between the appearance of circulating antibody and kidney-fixed host antibodies and the appearance of renal injury. This delay apparently reflects the need for a continuing antigen-antibody reaction for some time in order to produce detectable injury with the small amounts of reactants involved. From these data it appears that, in the presence of excess circulating antibody, antigens occupying at most a few per cent of the glomerular capillary surface can provide an antigen-antibody interaction which will over a period of time cause detectable morphological and functional alterations of the glomerulus.
MORPHOLOGICAL AND BIOLOGICAL STUDIES ON A VIRUS IN CULTURED LYMPHOBLASTS FROM BURKITT'S LYMPHOMA
Authors: Epstein M. A. , Henle G. , Achong B. G. , Barr Y. M.
Published: June 2004

Lymphoblasts of two tissue culture strains (EB1 and EB2) from different biopsy specimens of Burkitt's lymphoma have been examined in thin sections by electron microscopy, and have each been found to carry a morphologically identical virus.

The virus was observed in samples taken over many months, being present in about 1 to 2 per cent of the cells in two forms: Immature particles about 75 mµ in diameter which were seen in both the nucleus and cytoplasm; and larger mature particles with a diameter of 110 to 115 mµ, which were either within membrane-bounded cytoplasmic spaces or at the cell surface. There was some indication that the particles matured by budding through the cytoplasmic membranes.

Both types of particle occurred in dead degenerating cells or, less frequently, in intact altered cells. The characteristic alterations of the latter included margination of the chromatin, fragmentation of the nuclear envelope, beaded opaque material in the mitochondria, and, with one of the cell strains (EB1), sheaves of altered spindle tubules.

All attempts to isolate and identify the virus carried by the two strains of lymphoblasts failed. No pathological effects were caused in 8-day chick embryos inoculated either with whole lymphoblasts or extracts of disrupted lymphoblasts, using the intraallantoic, amniotic, and chorioallantoic routes, and the extraembryonic fluids of such chicks were without haemagglutinating activity for human, chicken, guinea pig, or monkey erythrocytes. Whole lymphoblasts or lymphoblast extracts were likewise without effect when inoculated intraperitoneally into newborn hamsters or two strains of newborn mice. Similar lymphoblast inocula did not cause detectable changes in 9 different test tissue culture systems even after 8 blind passages.

The nature of the unknown, unidentified virus in the cultured lymphoblasts from Burkitt's lymphomas is considered and its possible relationship to the cells discussed.
THE DETERMINATION OF ANTIBODY TO GROUP A STREPTOCOCCAL POLYSACCHARIDE IN HUMAN SERA BY HEMAGGLUTINATION
Authors: Schmidt Willard C. , Moore Dorothy J.
Published: June 2004

A hemagglutination method employing tanned human O erythrocytes sensitized with purified Group A streptococcal polysaccharide has been developed to measure A polysaccharide antibody in antistreptococcal rabbit and human sera.

The reaction of sensitized RBC with known Group A streptococcal rabbit antisera, inhibition of hemagglutination with A polysaccharide, and abolition of hemagglutination and hemagglutination-inhibition by exposure of polysaccharide antigen to A enzyme, which destroys the specific immunologic determinant of A carbohydrate, were utilized to demonstrate the specificity of this hemagglutinating system.

The results of A polysaccharide antibody determinations on sera from normal persons, patients convalescent from streptococcal infection, and patients with non-suppurative streptococcal sequelae are presented.
IMMUNOFLUORESCENT EXAMINATION OF THE HUMAN CHORIONIC VILLUS FOR BLOOD GROUP A AND B SUBSTANCE
Authors: Thiede H. A. , Choate J. W. , Gardner H. H. , Santay H.
Published: June 2004

The chorionic villi of term placentas were examined for A and B blood group substance using the IF technique with heterologous and homologous antisera. No specific fluorescence was found in either the villous trophoblast or vessels of the chorionic villi. The implications of these findings in relation to the question of trophoblastic antigenicity are discussed.
A GENETIC STUDY OF SUSCEPTIBILITY TO EXPERIMENTAL TUBERCULOSIS IN MICE INFECTED WITH MAMMALIAN TUBERCLE BACILLI
Authors: Lynch Clara J. , Pierce-Chase Cynthia H. , Dubos Rene
Published: June 2004

A study has been made of the genetic aspects of the difference between two inbred strains of mice (C57B1/6 and Swiss) in response to experimental infection with mammalian tubercle bacilli. Males and females, 4 to 6 weeks of age were inoculated intravenously with 0.2 ml of a 1/50 culture dilution of Mycobacterium tuberculosis var. bovis (Vallée strain) grown in tween albumin medium. Mean survival time for C57B1 animals was 28.1 ± 0.6 days and for Swiss, 55.3 ± 0.6 days postinfection. The characteristic survival time of the two strains was reversed in mice receiving a smaller infective dose. The age of mice at the time of inoculation also affected the results of infection: both C57B1 and Swiss, inoculated at 12 months of age, died at the same rate, but when inoculated at older ages, C57B1 survived slightly longer.

Bacteriologic studies demonstrated that there was no significant difference between the two mouse strains with regard to the numbers of viable units of tubercle bacilli recovered from various organs during the 2 week period following infection with a 10–3 culture dilution of Vallée. Moreover, the standard infective inoculum (1/50 culture dilution) did not activate corynebacterial pseudotuberculosis in C57B1 mice, a strain known to be latently infected with Corynebacterium kutscheri, rapid multiplication of tubercle bacilli occurred, but no corynebacteria were recovered.

When C57B1 and Swiss strains were crossed, survival tests after infection with the standard inoculum demonstrated that mice of the F1 generation were more resistant than either parent. Whether the overdominance was due to a new combination of parental genes for resistance or to heterosis was not determined. The increased litter size of the F1 mice, an evidence of increased vigor, supports the view that heterosis was involved. In backcrosses to the resistant strain (Swiss), survival time gradually became stabilized at approximately the parental level. In the 1st backcross to the susceptible strain (C57B1), survival times fell into two classes indicating segregation of genes, with perhaps dominance of genes from the Swiss. After repeated backcrosses to C57B1, mice of the 4th backcross generation had a survival time essentially the same as that of the original parental strain.

On the basis of having obtained progeny characterized by the original parental susceptibilities after genetic tendencies had been intermingled by crossbreeding, it was concluded that hereditary factors influenced the response of mice to experimental infection with M. tuberculosis. The number of genes was not determined.
METABOLISM AND FUNCTION OF GAMMA GLOBULIN IN ALEUTIAN DISEASE OF MINK
Authors: Porter David D. , Dixon Frank J. , Larsen Austin E.
Published: June 2004

Aleutian disease-affected mink, which are markedly hypergammaglobulinemic, show a decreased half-life of the serum gamma globulin indicating that the hyperglobulinemia is due to increased production. No evidence that the gamma globulin was antibody to the infectious agent, to autologous or isologous tissues, or to antigens the animal was responding to prior to development of the disease was obtained. The increased gamma globulin was found to be of the 6.4S variety, and gamma globulin containing protein-protein complexes of 9S to 17S and 22S to 25S classes were observed in serums of affected mink. The findings are most consistent with the Aleutian disease virus acting as a direct and somewhat selective stimulus to plasma cell proliferation. There is no evidence that the arterial and glomerular lesions of Aleutian disease have an immunologic pathogenesis. It seems possible that these vascular changes may be directly caused by the viral agent, or may be the result of the increased gamma globulin levels.
THE DYNAMICS OF RETICULOENDOTHELIAL BLOCKADE
Authors: Koenig M. Glenn , Heyssel Robert M. , Melly M. Ann , Rogers David E.
Published: June 2004

The dynamics of "reticuloendothelial blockade" were studied in living rabbits and isolated, perfused rabbit livers utilizing gelatin as a blockading agent and Au198 stabilized in gelatin as a tracer.

Employing the above experimental model, the following observations were made. (a) RES blockade was specific and dependent on the surface properties of the particle under study. (b) RES blockade was not caused by saturation of hepatic removal mechanisms. (c) RES blockade was not caused by depletion of demonstrable serum opsonins. (d) RES blockade appeared to correlate with high circulating levels of the blockading agent, per se.

Thus, under the conditions employed, the term "reticuloendothelial blockade" was a misnomer. Although specificity of liver macrophage-particle interaction was evident and deserves further study, the data suggest that blockade as usually studied is a laboratory phenomenon induced by the continuing circulation of the blockading agent.
THE IMMUNOGLOBULINS OF MICE
Authors: Fahey John L. , Sell Stewart
Published: June 2004

The metabolic properties of immunoglobulin were investigated by comparing five classes of mouse immunoglobulin. Three forms of 7S immunoglobulin had different rates of catabolism. The fractional rates of catabolism were found to be about 13 per cent per day for 7S γ2a-globulin; 25 per cent for 7S γ2b-globulin; and 17 per cent for 7S γ1-globulin. Catabolism of the three classes of 7S γ-globulin (γ2a, γ2b, and γ1) were prolonged at low serum 7S γ-globulin levels and accelerated at high serum 7S γ-globulin levels. Each of the 7S γ-globulin components was influenced by the serum level of the other mouse 7S γ-globulin components and by exogenously administered human 7S γ-globulin. They were not appreciably altered, however, by the serum level of IgA (γ1A-, ß2A-globulin).

The progressively changing (longer) half-times observed in turnover studies of normal IgG (7S γ-globulin) may be caused by catabolic heterogeneity of normal 7S immunoglobulins which are immunochemically and catabolically related to γ2a-, γ2b-, and 7S γ1-myeloma proteins.

These studies indicate that the 7S γ2a-, 7S γ2b-, and 7S γ1-globulins share a common catabolic control mechanism. This mechanism is influenced by the serum level of each of these components, but is independent of the serum level of IgA (γ1A-globulin) and probably is independent of IgM (γ1M-globulin).

Catabolism of IgA (γ1A-, ß2A-globulin) and IgM (γ1M-globulin) was much more rapid than the catabolism of the 7S γ-globulins. The halftimes of the IgA and IgM were approximately 1.2 and 0.5 days respectively. The fractional rate of catabolism of IgA and IgM seemed to be independent of their serum concentration.

The rate of catabolism, as well as the rate of synthesis, was shown to play a major role in determining the serum level of each class of immunoglobulin.
INDIGENOUS, NORMAL, AND AUTOCHTHONOUS FLORA OF THE GASTROINTESTINAL TRACT
Authors: Dubos René , Schaedler Russell W. , Costello Richard , Hoet Philippe
Published: June 2004

The bacterial flora of the gastrointestinal tract differs qualitatively and quantitatively from one colony of mice to another. Certain components of this flora, however, are always present in large and approximately constant numbers in healthy adult mice, irrespective of the colony from which the animals are derived.

Lactobacilli and anaerobic streptococci are extremely numerous in the stomach, the small intestine, and the large intestine. In contrast, organisms of the bacteroides group proliferate only in the large intestine. These three bacterial species persist at approximately constant levels in their characteristic localization throughout the life span of healthy animals. They are closely associated with the walls of the digestive organs, and are probably concentrated in the mucous layer.

A few experiments carried out with rats and young swine indicate that lactobacilli are also present in large numbers in the stomach of these animal species.

It is suggested that some of the components of the gastrointestinal flora have become symbiotic with their hosts in the course of evolutionary development and thus constitute a true autochthonous flora. The other components of the indigenous flora are acquired early in life either through accidental contact or because they are ubiquitous in the environment. The "normal" flora is that which is always present in the environment of the animal colony under consideration.
DETECTION OF STREPTOCOCCAL GROUP-SPECIFIC ANTIBODIES IN HUMAN SERA
Authors: Karakawa Walter W. , Osterland C. Kirk , Krause Richard
Published: June 2004

Two serologically distinct antibodies directed against different antigenic sites on the Group A carbohydrate were detected in human sera by agglutination techniques. Agglutinins with A-variant specificity were demonstrable by the direct agglutination of purified A-variant cell walls, whereas indirect Coombs-type agglutinins with Group A specificity were demonstrable with Group A cell walls. Selective adsorption with homologous cell walls as well as inhibition studies with the soluble carbohydrates confirmed the specificity of the two types of agglutinins.

There was an obvious correlation between the magnitude of the antistreptolysin O titer, and the direct Group A-variant and the indirect Group titers. These data suggest that indirect anti-Group A agglutinins and direct anti-Group A-variant agglutinins are produced following a Group A streptococcal infection.
STUDIES ON TUBERCULIN FEVER
Authors: Atkins Elisha , Heijn Cornelis
Published: June 2004

In a search for the source of the circulating endogenous pyrogen (EP) that mediates tuberculin-induced fever, tuberculin was incubated in vitro with various tissues of rabbits sensitized by intravenous infection with BCG.

Evidence was obtained that tuberculin specifically stimulates cells in the blood of sensitized rabbits to generate pyrogen in vitro, whereas both lymph node and spleen cells from the same donors were inactive.

Since normal blood cells, incubated in plasma of sensitized donors, were similarly activated, it is postulated that circulating antibodies play a role in sensitizing cells (presumably granulocytes) to release pyrogen on contact with tuberculin) both in vitro and in vivo.

Release of endogenous pyrogen in vitro may be a sensitive means of detecting immunologic reactions between antigen and specifically sensitized blood cells-in other allergic states accompanied by fever.
EFFECT OF 6-MERCAPTOPURINE (6-MP) ON DIFFERENT CLASSES OF ANTIBODY
Authors: Borel Yves , Fauconnet Marthe , Miescher Peter A.
Published: June 2004

In the primary response of mice and rabbits immunized with foreign red cells, 6-MP administration prolonged the formation of 19S antibody. 7S antibody formation was delayed and reduced in these animals.

Animals treated with 6-MP during primary response exhibited a preferential 19S response when challenged in the anamnestic response.

Animals immunized with small doses of antigen and treated with 6-MP only during the secondary response, reversed the usual antibody pattern and responded with preferential 19S antibody formation.
ISOLATION OF ß1F-GLOBULIN FROM HUMAN SERUM AND ITS CHARACTERIZATION AS THE FIFTH COMPONENT OF COMPLEMENT
Authors: Nilsson Ulf R. , Müller-Eberhard Hans J.
Published: June 2004

At least 3 complement factors were found necessary for the conversion of the thermolabile intermediate complex EAC'1a,4,2a to a thermostable state. One of these factors is the earlier described ß1C-globulin. The second, a heretofore unrecorded serum protein, ß1F-globulin. The third factor has not yet been defined as a discrete serum protein entity. Kinetic experiments indicated that ß1C reacted prior to ß1F, which in turn seemed to precede the third factor in the reaction sequence. Therefore, the 3 components were tentatively designated the third (C'3), the fifth (C'5), and the sixth (C'6) components of complement, respectively. A procedure was developed allowing the isolation of highly purified ß1C-(C'3) and ß1F-globulin (C'5) and of partially purified C'6.

With respect to its function in immune hemolysis, ß1F-globulin or C'5 was found to be closely dependent on the simultaneous presence of C'6. The hypothesis that C'5 and C'6 form a functional unit was supported by the finding that both components interact with each other in solution resulting in the formation of a complex. A similar complex was also found in fresh human serum.
THE ISOLATION AND BIOLOGICAL ACTIVITIES OF RABBIT γM- AND γG-ANTI-SALMONELLA TYPHIMURIUM ANTIBODIES
Authors: Robbins John B. , Kenny Kathryn , Suter Emanuel
Published: June 2004

Rabbit γM- and γG-anti-S. typhimurium antibodies were isolated by combined immune specific and physical methods and some of their properties in immunological systems were measured. γM-Antibody was detectable at lower concentrations and revealed a higher specific activity than the γG-globulins. Indirect studies indicated that the γG-globulin was the more "avid" immunoglobulin. Treatment of the γM-globulin with the reducing agent 2-ME decreased but did not destroy the immune activity of the subunits. The results confirm the necessity of analysis of purified immunoglobulin antibodies to evaluate the significance of their biological properties secondary to their interaction with antigens.
FURTHER STUDIES ON SPECIFIC TRANSPLANTATION ANTIGENS IN ROUS SARCOMA OF MICE
Authors: Jonsson Nils , Sjögren Hans O.
Published: June 2004

Mice allografted with different sarcomas, induced by the Schmidt-Ruppin variant of Rous sarcoma virus (RSV-SR), showed a resistance against subsequent isografting of 9 different Rous sarcomas. Transplantation resistance could also be induced by Rous mouse tumor cells x-irradiated with 8000 r or with cell-free tumor extracts, containing no demonstrable virus. No transplantation resistance could be demonstrated after allograft pretreatment with various polyoma tumors or non-viral tumors. Allograft pretreatment with Rous tumors induced no demonstrable resistance against isografting of polyoma tumors. Inoculation of RSV-SR or Rous chicken sarcoma suspension into adult mice gave no clear cut resistance against isografting of mouse sarcomas. Neither after allografting of Rous tumors nor after virus or chicken sarcoma inoculation into adult mice could virus-neutralizing activity be demonstrated in the sera.

The results demonstrate the presence of common, specific transplantation antigen(s) in different Rous sarcomas in mice and speak against an identity between the transplantation antigen(s) and viral antigen(s).
IMMUNOLOGIC RELATIONS AMONG VARIOUS ANIMAL COLLAGENS
Authors: Rothbard Sidney , Watson Robert F.
Published: June 2004

By the use of complement fixation and in vivo immunofluorescence with cross-absorption studies it was shown that acid soluble collagens prepared from rat, mouse, guinea pig, chicken, carp, and man exhibit species specificity. Rat and mouse collagens were found to be indistinguishable and to cross-react with guinea pig collagen. Cross-reactions also occurred between the collagens of rat and man and chicken and man. Tissue specificity, or an antigen common to all of the collagens, was not demonstrated. There was complete agreement in the results of the two immunologic methods. The findings in this study support the conclusion that collagen in some form is present in the renal glomerular basement membranes.
IMMUNOCHEMICAL STUDY OF ANTIGENIC SPECIFICITY IN DELAYED HYPERSENSITIVITY
Authors: Jones Valerie E. , Leskowitz Sidney
Published: June 2004

Injections of various conjugates of arsanilic acid into newborn guinea pigs produced a specific tolerance in respect to subsequent development of hapten-specific delayed hypersensitivity. In general, larger polyvalent conjugates produced longer lasting and more profound suppression of delayed sensitivity than did the smaller ones. Carrier injections alone were ineffective. At lower doses of conjugate, breakthrough of tolerance occurred first with animals immunized with the heterologous carrier conjugate.

The duration of tolerance produced by injection of monovalent conjugates into neonates is in contrast to the transient inhibition produced by the same conjugates in previously sensitized animals, suggesting that different target cells may be involved in these two phenomena.
EFFECTS OF CHRONIC EXCESS SALT INGESTION
Authors: Dahl Lewis K. , Heine Martha , Tassinari Lorraine
Published: June 2004

Two strains of selectively inbred rats were demonstrated previously to have opposite genetic predisposition to develop hypertension from NaCl ingestion (1, 2), DOCA-NaCl (3), and unilateral renal artery compression without NaCl (3).

Using these same strains, similar disparate responses were elicited with two other models for inducing experimental hypertension, namely cortisone and adrenal regeneration.

On the basis of these experiences, it is proposed that the genetic substrate will be found to modify significantly the influence of all non-genetic factors considered to play a primary role in the etiology of experimental hypertension. Furthermore, it is suggested that similar genetic and non-genetic factors interact to produce hypertension in man. An hypothesis has been elaborated that is compatible with the experimental data and there is some clinical evidence to support this hypothesis.
PHYLOGENETIC ORIGINS OF ANTIBODY STRUCTURE
Authors: Marchalonis J. , Edelman G. M.
Published: June 2004

The elasmobranch Mustelus canis has been shown to produce antibodies to Limulus hemocyanin. The serum of both normal and immunized M. canis contains immunoglobulins having sedimentation coefficients of approximately 7S and 17S. Antibody activity was found in the 17S immunoglobulin which may be dissociated to 7S components with concomitant loss of activity. Both 17S and 7S serum, immunoglobulins were antigenically identical. They consisted of light and heavy chains present in amounts comparable to those of higher vertebrates. Peptide maps indicated that the light chains had an entirely different primary structure than the heavy chains, but that the corresponding chains of 7S and 17S dogfish serum immunoglobulins were similar in primary structure. The heavy chains appeared to resemble the n chains of immunoglobulins of higher vertebrates in their starch gel electrophoretic behavior. It is suggested that the elasmobranch M. canis may have only one major class of immunoglobulins resembling that of macroglobulins (γM-immunoglobulins) seen in higher vertebrates.

The results indicate that the multichain structure of antibodies is an ancient evolutionary development.
FURTHER STUDIES OF THE STIMULATION OF DNA SYNTHESIS IN CULTURES OF SPLEEN CELL SUSPENSIONS BY HOMOLOGOUS CELLS IN INBRED STRAINS OF MICE AND RATS
Authors: Dutton Richard W.
Published: June 2004

The early proliferative response previously demonstrated in rabbits has now been shown to follow the mixing of spleen cell suspensions from 2 inbred strains of mice or rats. The size of the response is comparable to that seen in cells from hyperimmune animals exposed to antigen in vitro. Autoradiographs of cells from stimulated cultures showed 1 to 4 per cent of the total population had incorporated thymidine. Modifications in the conditions necessary for the culture of mice and rat spleen cell suspensions and the measurement of thymidine incorporation are described.

No responses were observed in isologous mixes. The responses obtained on mixing individual pairs of spleens from different strains showed relatively little variation. Responses were obtained in all of the 21 possible combinations between 7 inbred strains of mice. Responses were obtained when parental cells were mixed with their F1 hybrids. Analysis of these responses showed that, in every case, parental-F1 hybrid responses were less intense than those between the 2 parents. It was shown that there was no inherent defect in the ability of the hybrid cells to respond when mixed with an unrelated strain. The results suggested that the hybrid cells made no response to the parent cells although this was not conclusively established. This has been taken as circumstantial evidence that the response is immunological in nature.

The significance of the vigor of the response and the large fraction of the immunologically competent cells that take part is discussed.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Gell P. G. H. , Sell Stewart
Published: June 2004

Specific antisera directed against all six of the well characterised allotypic determinants of rabbit IgG (As1, 2, 3, 4, 5, and 6) are capable of inducing blast transformation and DNA synthesis when added to lymphocyte cultures obtained from donor rabbits having the appropriate IgG allotype. Mixtures of antisera directed against two different allotypic determinants induce a "summation" of transformation and DNA synthesis over and above the effect of mixtures of two antisera directed against the same allotypic determinant. This summation effect is observed regardless of whether the antisera which have been mixed are directed against allotypic determinants controlled by the same locus or by different loci. The finding that summation occurs with mixtures of two antisera directed against both the allotypic determinants of a double homozygote rabbit (As1, 6) suggests that lymphocytes from the peripheral blood may be primed to produce only one or the other of the two polypeptide chains of IgG, but not both.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Sell Stewart , Rowe David S. , Gell P. G. H.
Published: June 2004

In vitro cultures of the peripheral blood lymphocytes of rabbits may be stimulated with phytohaemagglutinin, staphylococcal filtrate, antiallotype serum, or sheep anti-rabbit whole serum to synthesize protein, RNA and DNA as indicated by the incorporation of radiolabelled precursor substances into these products. A sequence of events found in all stimulated cultures characteristically shows protein synthesis followed by RNA synthesis, histologic blast transformation, DNA synthesis, and mitosis, with the complete sequence requiring 48 hours. All four stimulants induce essentially identical metabolic changes. Characterization of the proteins synthesized by lymphocytes in vitro has failed to demonstrate immunoglobulin synthesis by stimulated or non-stimulated cultures. It is concluded that the majority of proteins produced by peripheral lymphocytes stimulated in vitro are most likely cellular proteins related to the metabolic alterations necessary for mitosis.

Absorption of sheep antisera to whole rabbit serum with rabbit IgG does not always remove the transforming capacity of the sheep antisera. Thus, it is likely that antibodies to proteins other than IgG present in the small lymphocyte may also be able to stimulate transformation. A possible common mechanism for the induction of lymphoblast transformation may be the ability of both specific and non-specific stimulants to react with protein constituents of the lymphocyte which may also be present in serum.
THE INFLUENCE OF ENDOTOXIN ADMINISTRATION ON THE NUTRITIONAL REQUIREMENTS OF MICE
Authors: Dubos René , Costello Richard , Schaedler Russell W.
Published: June 2004

Albino mice lose weight within 24 hours following administration of bacterial endotoxin. The initial weight loss is proportional to the dose of endotoxin injected only when this dose is very small. The loss during the 1st day reaches a maximum with 10 to 30 µg of endotoxin; larger doses increase the duration of the overall effect.

The rate at which mice regain weight after administration of endotoxin is markedly influenced by the composition of the diet. Recovery was rapid and complete within a few days when the animals were fed commercial pellets or a semisynthetic diet containing casein. In contrast, recovery was slow and incomplete when wheat gluten was used instead of casein in the diet. The deleterious effect of the gluten diet was less marked in older than in younger animals, probably because the latter have less exacting nutritional requirements.

It was postulated that the failure of endotoxin-treated mice to regain weight when fed the gluten diet was due to the fact that this protein is low in certain amino acids. In fact, rapid and complete recovery from the weight loss uniformly occurred when the gluten diet was supplemented with proper amounts of lysine and threonine.

The composition of the diet did not influence the extent of the initial loss of weight caused by endotoxin, nor did it prevent the animals from developing tolerance to this substance.
CELLULAR LOCALIZATION OF IMMUNOGLOBULINS WITH DIFFERENT ALLOTYPIC SPECIFICITIES IN RABBIT LYMPHOID TISSUES
Authors: Pernis Benvenuto , Chiappino Gerolamo , Kelus Andrew S. , Gell Philip G. H.
Published: June 2004

The cellular localization of allotypes in rabbit lymphoid tissues has been studied by immunofluorescence. In heterozygous animals the double staining for two allotypes controlled by allelic genes (A1 and A2; A4 and A5; A4 and A6) has shown the existence of two populations of plasma cells, one containing one allotype and the other the alternative one. The localization in different cells of immunoglobulins marked by allelic allotypic specificities has been confirmed by microspectrography of single cells. An exception to this rule was given by the presence in the germinal centers of lymphoid follicles of apparently uniform mixtures of products of the two allelic genes.

Double staining for two allotypes controlled by genes at different loci showed, instead, the presence of many cells containing both allotypes; the number of these cells was highest in doubly homozygotes, in the other it was consistent with random association of non-allelic specificities.

In addition double staining for one allotype and gamma G globulins in the lymphoid tissues of rabbits homozygous at the a or at the b locus, has shown the presence of cells containing immunoglobulins that lack one allotype.
INCREASED VASCULAR PERMEABILITY INDUCED BY HUMAN PLASMIN
Authors: Ratnoff Oscar D.
Published: June 2004

Preparations of plasminogen, soluble in aqueous media, increased vascular permeability in guinea pig skin when activated by streptokinase or urokinase. The permeability-enhancing effect was inhibited by soybean trypsin inhibitor but not by triprolidine. Permeability-enhancing activity evolved when plasmin was incubated with fractions of plasma rich in prokinin. The experiments described suggest that plasmin exerts its permeability-increasing effect through the elaboration of kinins.
STUDIES ON THE MECHANISM OF ACTION OF RILEY VIRUS
Authors: Mahy B. W. J. , Rowson K. E. K. , Parr C. W. , Salaman M. H.
Published: June 2004

Plasma LDH levels were determined in normal and Riley virus-infected mice following treatment with various drugs known to alter the activity of the RES. The rise in plasma LDH level after Riley virus infection was considerably enhanced by previous treatment with thorotrast (to produce blockade of the RES), and decreased by previous treatment with stilboestrol (to stimulate the RES).

A dose of 2000 r whole-body x-irradiation, lethal within 3 to 4 days, did not alter the phagocytic activity of the RES, and was without effect on plasma LDH activity in normal mice, or on the rise in plasma LDH level following infection with Riley virus.

Blockade of the RES with cholesterol oleate, thorotrast, or zymosan, resulted in a 2- to 3-fold rise in plasma LDH level within a few hours. The level returned to normal by 1 to 3 days. Stimulation of the RES with stilboestrol resulted in a decrease in plasma LDH level by 1 to 2 days in both normal and infected mice, with a return to normal by about a week.

Blockade of the RES in uninfected mice with thorotrast or cholesterol oleate, besides increasing the plasma LDH level caused a rise in plasma phosphoglucose isomerase level, but no significant alterations in plasma aldolase or alanine transaminase levels, studied up to 10 days. Riley virus causes a similar pattern of enzyme elevation. It is suggested that the increased levels of certain plasma enzymes in Riley virus-infected mice may be due to competitive inhibition by virus particles of plasma enzyme clearance by the RES.
STUDY OF PENICILLIN ANTIBODIES BY FLUORESCENCE POLARIZATION AND IMMUNODIFFUSION
Authors: Dandliker W. B. , Halbert S. P. , Florin M. C. , Alonso R. , Schapiro H. C.
Published: June 2004

1. Antibodies prepared in the rabbit to penicilloyl-rabbit serum albumin or to penicilloyl-bovine serum albumin were demonstrated by immunodiffusion and absorption methods to be apparently directed exclusively against the penicilloyl moiety. The antibodies could precipitate heavily substituted penicilloyl polylysine, as well as each other, with "reactions of identity". All could mutually deplete detectable antibodies by cross-absorption.

2. Small haptens containing both fluorescein and the penicilloyl group were synthesized. They were also capable of completely absorbing the antipenicilloyl antibodies from rabbit antiserum, as evidenced by immunodiffusion tests. The haptens were used in fluorescence polarization tests with gamma globulin from normal and immunized rabbits, and from normal and allergic humans. The rabbit antipenicilloyl gamma globulins in concentrations as low as 5 to 10 µg of protein/ml could significantly increase the polarization of the haptens. Normal gamma globulin had no effect at the highest concentrations tested, 1200 µg/ml. In all tests, rabbit and human antibody reacted similarly.

3. Fluorescence polarization titration curves for both human and rabbit antipenicilloyl gamma globulins were analyzed by computer and the antibody concentrations, avidities, and heterogeneity constants were determined. For the human antibody, the latter two values were 3.0 x 107 M–1 and 0.78, while for the rabbit, they were 8.7 x 106 M–1 and 0.71. The data were employed to estimate the limit of sensitivity of fluorescence polarization for detecting antipenicilloyl antibodies. Under the conditions employed, this value was roughly 0.4 µg antibody/ml.

4. When the whole rabbit sera were tested for penicilloyl antibodies by fluorescence polarization, both normal (preimmune) and immune sera revealed striking and equivalent increases in polarization with the penicilloyl haptens. This non-specific binding was shown to be due at least in part to serum albumin. Indications were obtained that it might be significantly reduced by increasing the pH or the salt concentration of the medium, or by addition of certain anions.
THE PRODUCTION OF THYROIDITIS AND ANTIBODY FOLLOWING INJECTION OF UNALTERED THYROGLOBULIN WITHOUT ADJUVANT INTO RABBITS PREVIOUSLY STIMULATED WITH ALTERED THYROGLOBULIN
Authors: Weigle William O.
Published: June 2004

Injection of rabbits with arsanil-sulfanil-thyroglobulin without adjuvant resulted in the production of hemagglutinating and precipitating antibody to native thyroglobulin and thyroiditis. Following a latent period of 1 month, these same rabbits responded to an injection of native thyroglobulin with an increase in both circulating antibody to native thyroglobulin and severity and frequency of thyroid lesions. Some rabbits initially immunized with arsanil-sulfanil-thyroglobulin also responded to a second and third monthly injection of native thyroglobulin, but the response to the third injection was usually not as good as the response to the first injection. A few of the rabbits showed a transient production of 19S antibody after the injection of native thyroglobulin was initiated. Neither circulating antibody nor thyroiditis were ever observed in rabbits injected with only native thyroglobulin without adjuvant. The correlation of the thyroiditis with the presence or absence of circulating antibody was discussed. Following a latent period after injections of aqueous arsanil-sulfanil-thyroglobulin some rabbits made a response to their own thyroglobulin released from an autotransplant of thyroid tissue.
THE IMMUNOLOGICAL DEVELOPMENT OF THE HUMAN FETUS
Authors: van Furth R. , Schuit Henrica R. E. , Hijmans W.
Published: June 2004

The immunogenesis of the human fetus has been investigated by means of the formation of immunoglobulins in vitro, immunofluorescence, morphological studies, and analysis of the immunoglobulins in the serum. Twenty fetuses which were born alive but died soon after delivery, were studied; their ages ranged from 13 to 31 weeks.

The results of the spleen cultures demonstrated the synthesis of IgG and IgM, which starts at about the twentieth week of gestation. In the serum, IgM could be detected at about the same period. The immunofluorescent staining of the spleen tissue showed that medium sized and large lymphoid cells as well as plasma cells, even with Russell bodies, were positive for either IgG or IgM. The peripheral blood was also found to contain a small number of medium sized IgG and IgM-positive cells. Both the spleen and the peripheral blood showed a considerable number of fluorescent small lymphocytes which exclusively contained IgM. The relatively high ratio of IgM to IgG production prenatally as compared to the postnatal situation, agrees with a predominantly primary antibody response in fetal life.

In general, the fetal thymus did not synthesize immunoglobulins. No indications for the synthesis of IgA and IgD during fetal life were found.