bluuebunny/crossref_metadata_2025 huggingface dataset:
DEMONSTRATION OF TUMOR-SPECIFIC ANTIGENS IN HUMAN COLONIC CARCINOMATA BY IMMUNOLOGICAL TOLERANCE AND ABSORPTION TECHNIQUES
Authors: Gold Phil , Freedman Samuel O.
Published: June 2004

Two methods were used to demonstrate the presence of tumor-specific antigens in adenocarcinomata of the human colon: (a) rabbits were immunized with extracts of pooled colonic carcinomata, and the antitumor antisera thus produced were absorbed with a pooled extract of normal human colon and with human blood components; (b) newborn rabbits were made immunologically tolerant to normal colonic tissue at birth, and were then immunized with pooled tumor material in adult life. Normal and tumor tissues were obtained from the same human donors in order to avoid misinterpretation of results due to individual-specific antigenic differences.

The antisera prepared by both methods were tested against normal and tumor antigens by the techniques of agar gel diffusion, immunoelectrophoresis, hemagglutination, PCA, and immunofluorescence. Distinct antibody activity directed against at least two qualitatively tumor-specific antigens, or antigenic determinants, was detected in the antisera prepared by both methods and at least two additional tumor antigens were detected exclusively in antisera prepared by the tolerance technique. Whether these additional antigens were qualitatively different from normal tissue antigens, or merely present in tumor tissue in higher concentrations than in normal tissue has not as yet been determined. Furthermore, it was shown that the tumor-specific antibodies were not directed against bacterial contaminants or against the unusually high concentrations of fibrin found in many neoplastic tissues.

It was concluded from these results that the pooled tumor extracts contained tumor-specific antigens not present in normal colonic tissue. Identical tumor-specific antigens were also demonstrated in a number of individual colonic carcinomata obtained from different human donors.
CELLULAR SITES OF SYNTHESIS OF RABBIT IMMUNOGLOBULINS DURING PRIMARY RESPONSE TO DIPHTHERIA TOXOID-FREUND'S ADJUVANT
Authors: Schoenberg M. D. , Stavitsky A. B. , Moore R. D. , Freeman M. J.
Published: June 2004

The present studies are based on previous observations that the intravenous injection of diphtheria toxoid and complete Freund's adjuvant into rabbits resulted in an increased proliferation of cells associated with antibody synthesis; an accelerated, enhanced, and prolonged synthesis of antibody; and a lengthened interval between the appearance of γM- and γG-hemagglutinating antibodies in the circulation. The molecular species of antibodies that were synthesized by fragments of the spleens were determined by the incorporation of labeled amino acid into antibody and by binding of radioactive antigen by antibody. These studies were paralleled by determination of the presence and type of antibody within the cell by immunofluorescence. Evidence was obtained that non-phagocytic mononuclear cells in the walls of the sinusoids of the red pulp of the spleen are a major source of 19S γM-antibody and plasma cells in the non-follicular white pulp are a major source of γG-antibody. The data did not exclude the synthesis of γG-antibodies by the mononuclear cells, the synthesis of γM-antibodies by the plasma cells, or the synthesis of both antibodies by an occasional cell of either morphology. It was hypothesized that the 19S and 7S antibody responses evolved independently with the development of at least two different cell types, a mononuclear cell with capacity for 19S immunoglobulin synthesis and a plasma cell with capacity for 7S immunoglobulin synthesis.
STUDIES ON IMMUNOLOGIC RECONSTITUTION OF THYMECTOMIZED MICE
Authors: Yunis Edmond J. , Hilgard Henry R. , Martinez Carlos , Good Robert A.
Published: June 2004

1. Immunologic function, growth, and longevity of neonatally thymectomized mice was restored by intraperitoneal administration of 100 to 400 million syngeneic, hemiallogeneic, or ailogeneic thymus cells from newborn or adult donors. Assays of the graft versus host capabilities of spleen cells from the animals restored with allogeneic cells showed that their immunologically competent cells are of donor histocompatibility characteristics. Such animals accepted skin grafts from mice of the cell donor strain, but rejected skin from a third strain.

2. Similar results were obtained when the neonatally thymectomized animals were treated with 10 to 100 million syngeneic, hemiallogeneic, or allogeneic cells from adult spleen.

3. In one strain combination, C3H recipients and A donors, injected thymus or spleen cells apparently attacked host tissues, since the animals died very early of wasting disease. When this combination was reversed, A strain recipients treated with C3H cells were reconstituted immunologically and physiologically.

4. Syngeneic or allogeneic adult spleen, grafted in the newborn period, reconstituted neonatally thymectomized mice, but all experiments involving grafting of newborn spleen failed. Immunogenetic analysis of the host spleen cells from two allogeneic spleen-grafted animals previously thymectomized showed that the reconstitution was entirely of donor histocompatibility characteristics.

5. Postthymectomy wasting disease was reversed by administration of 200 million adult syngeneic spleen or thymus cells. Immunologic recovery was confirmed by graft versus host assays of the spleens of the recovered animals and by application of allogeneic skin grafts. Some of the animals have been under observation for 42 weeks and appear to be normal.

6. The wasting syndrome in neonatally thymectomized mice was also reversed by injection of 200 million hemiallogeneic or allogeneic spleen cells.

7. Thymus grafts did not reverse wasting disease, whether the donors were adult or newborn, of the same strain or a different one.

8. Spleen, lymph node, and Peyer's patches from representative animals of the reconstituted groups were examined and compared with the tissues of untreated neonatally thymectomized mice and intact animals of the same strain. Tissues of normal cellularity and follicular organization were found in some of the reconstituted animals and also in mice with reversed wasting disease. Extreme deficit of the lymphoid tissues was rare in either group.
MODIFICATION OF HOST RESPONSES TO BACTERIAL ENDOTOXINS
Authors: Kim Yoon Berm , Watson Dennis W.
Published: June 2004

Serum from rabbits rendered tolerant or immune to 100 MPD-3/kg of endotoxin when passively transferred to normal rabbits gave partial tolerance to the standard dose of endotoxin. The same serum was fractionated by DEAE chromatography into 4 major fractions. Immunoelectrophoretic analysis indicated that the 7S γ2-and the 19S γ1-immunoglobulins were separated into two distinct fractions. Of the four fractions tested, only fraction IV containing 19S γ1-immunoglobulm conferred complete pyrogenic tolerance to 100 MPD-3/kg of endotoxin.

Additional fractionation of DEAE fraction IV by exclusion chromatography on sephadex G-200 gave 3 fractions. Of these only the first, containing 19S γ1-immunoglobulin conferred complete pyrogenic and lethal tolerance to normal rabbits. There was no correlation between the quantity of O-specific antibodies and the ability to transfer tolerance.

It is concluded that endotoxin tolerance involves a classical immune mechanism which includes both 19S γ1-immunoglobulin specific for toxophore groups common to many endotoxins and a normally functioning RES.

To avoid confusion with immunologic tolerance, it is suggested that the term endotoxin immunity be substituted for endotoxin tolerance.
THE LYSIS OF CELL WALLS OF GROUP A STREPTOCOCCI BY STREPTOMYCES ALBUS ENZYME TREATED WITH DIISOPROPYL FLUOROPHOSPHATE
Authors: Schmidt Willard C.
Published: June 2004

Diisopropyl fluorophosphate (DFP) effectively inhibited proteolytic activity in preparations of partially purified Streptomyces albus enzyme used to lyse cell walls of Group A streptococci.

Lysis of non-trypsinized Group A cell walls with DFP-treated S. albus enzyme released a soluble protein fraction containing antigenic type-specific M protein, a carbohydrate fraction consisting of Group A and a small amount of A-variant polysaccharides, and a dialyzable fraction. The similarities of the products of DFP-treated S. albus enzyme lysis of streptococcal cell walls to those released by phage muralytic enzyme furnish additional evidence of the close relationship of these wall lysins.

In view of small differences in electrophoretic mobility, immunodiffusion, and chemical composition, it is suggested that Group A streptococcal cell wall polysaccharide dissolved by DFP-S. albus enzyme consists of a spectrum of molecules having the same immunological determinants but differing in content of conjugated mucopeptide.
PATHOGENESIS OF INFLAMMATION
Authors: Graham Richard C. , Ebert Robert H. , Ratnoff Oscar D. , Moses John M.
Published: June 2004

Activated Hageman factor, when injected into the rabbit ear chamber, produces a delayed and prolonged inflammatory response characterized by prominent sticking and emigration of leucocytes. In contrast, preformed bradykinin evokes an immediate and more transient response in which leucocytic emigration occurs less frequently. It is concluded that either Hageman factor produces its inflammatory effects by mechanisms other than kinin release, or bradykinin released endogenously has effects quite different from those resulting from a single injection of the exogenous material.
THE IN VITRO DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES
Authors: Cohn Zanvil A. , Benson Belinda
Published: June 2004

The concentration of newborn calf serum in the medium has marked effects on the morphological and biochemical properties of mouse mononuclear phagocytes. At a low serum concentration, the cells developed small numbers of tiny cytoplasmic granules and little or no increase in acid phosphatase, cathepsin, and ß-glucuronidase. As the serum concentration was raised, granules were formed at a more rapid rate and were larger in size. The rate of production and total amount of three hydrolytic enzymes was increased at higher levels of serum.

Observations on living cells indicated that the phase-dense granules which accumulated in the perinuclear region were derived from pinocytic vesicles. These clear vesicles fused and migrated to the centrosphere where they underwent a gradual increase in phase density and reacted positively for acid phosphatase.

A microscopic technique was described for the evaluation of the pinocytic process. When this method was employed, the rate of pinocytosis increased curvilinearly with elevations in the calf serum concentration of the medium.

The comparative influence of bovine, horse, and rabbit serum on mouse cells was evaluated.

It is suggested that pinocytosis is a major regulator of granule formation and hydrolytic enzyme production by the mouse macrophage.
FIBRINOGEN PRECIPITATION BY STREPTOCOCCAL M PROTEIN
Authors: Kantor Fred S.
Published: June 2004

Intravenous injection of Type 1 streptococcal M protein into mice and rats produced lesions confined to renal glomeruli. Thrombi of eosinophilic amorphous material, seen to occlude glomerular capillaries, were shown to contain M protein and fibrinogen. Gradual regression of the morphological lesions was observed during the 3 weeks following injection. Initial abnormal proteinuria and azotemia returned to control levels by the end of the 1st week; a second rise in urinary protein excretion and urea retention was demonstrated in some rats coincident with appearance of anti-M antibodies. The mechanism of renal localization of streptococcal M protein by means of a complex with fibrinogen was suggested, which may comprise an initial phase in the pathogenesis of acute poststreptococcal glomerulonephritis.
A STUDY OF THE ANTIGENS INVOLVED IN ADENOVIRUS 12 TUMORIGENESIS BY IMMUNODIFFUSION TECHNIQUES
Authors: Berman Leonard D. , Rowe Wallace P.
Published: June 2004

The use of the agar gel diffusion technique has established the presence of three distinct antigenic reactions in the sera of Ad. 12 tumor-bearing hamsters. Only one of these antigens is directly demonstrable in the tumor. This "tumor" antigen is also formed during early stages of the infectious cycle in tissue culture cells. Other antigens present in the tumor, but only demonstrable indirectly with the use of antibody-containing serum of tumored hamsters, are the classical type-specific C antigen, and a new antigen, termed D.

Of ninety-eight Ad. 12 tumored hamster sera, six reacted in gel diffusion with virus and tumor preparations, and thirty-one with tumor only.

Sera which reacted in gel diffusion with viral antigen uniformly bad neutralizing antibody and high titers of CF antibody against viral and tumor antigens; however, many sera with comparable antibody titers did not react with the virus in gel diffusion. Sera which reacted in gel diffusion only with tumor antigen also had high CF antibody titers, but there was no correlation with neutralizing antibody.
EFFECTS OF ANTICELLULAR SERUM ON PHAGOCYTOSIS AND THE UPTAKE OF TRITIATED THYMIDINE AND URIDINE BY HELA CELLS
Authors: Carey Francis J. , Kuhn Nobuko O. , Harford Carl G.
Published: June 2004

Anticellular serum inhibited phagocytosis of colloidal gold and staphylococci by HeLa cells. This inhibition of phagocytosis was reversed by conditions which allowed the antibody to elute from the cell. Concentrations of antiserum that inhibited phagocytosis did not interfere with the transport of tritiated thymidine and uridine across the cell membrane, and their incorporation into cell nucleic acids was unaltered as evaluated by autoradiography. These results indicate that thymidine and uridine were taken into cells independently of phagocytosis.

Morphologic changes induced in the cells by antibody suggest that the antibody agglutinates adjacent portions of the cell membrane. This agglutination of the cell membrane by antibody would be expected to interfere with the continuous evagination and invagination of the cell membrane associated with phagocytosis.

The inhibition of virus infection by anticellular antibody may be a result of the effect of the antiserum upon phagocytosis.
THE ENHANCEMENT OF 19S ANTIBODY PRODUCTION BY PARTICULATE ANTIGEN
Authors: Torrigiani G. , Roitt I. M.
Published: June 2004

Injection of human thyroglobulin solution into rabbits gave rise to a transient 19S antibody response which could however be maintained by repeated administration of antigen. When the antigen was coated onto acrylic resin particles, the titre of 19S antibodies was increased nearly 20-fold whereas 7S antibody levels were unchanged. This selective enhancement of 19S antibody synthesis by particulate antigen was also seen using human γ-globulin. "Intermediate" sedimenting and 7S γ1-antibodies were also increased in animals given particulate antigen. These phenomena may be due to prolonged persistence of the antigen in appropriate macrophages or perhaps to an increased uptake into these cells. The results are discussed in terms of the relationship between 19S and 7S globulin-producing cells.
THE DEVELOPMENT OF THE BACTERIAL FLORA IN THE GASTROINTESTINAL TRACT OF MICE
Authors: Schaedler Russell W. , Dubos René , Costello Richard
Published: June 2004

Selective culture media, and equipment for anaerobic incubation of large numbers of specimens, have been developed to facilitate the quantitative enumeration of the various aerobic and anaerobic bacterial species present in the gastrointestinal tract.

The evolution of this flora has been followed in young mice from several colonies by cultivating homogenates of the different parts of the gastrointestinal tract at daily intervals from the time of birth to the time of weaning.

It has been found that the lactobacilli and anaerobic streptococci become established immediately after birth and persist in large numbers, not only in the large intestine but also in the stomach and in the small intestine. In contrast, the anaerobic bacilli of the bacteroides group become established only after the 16th day; they multiply only in the large intestine but persist in this organ in very large numbers. Other bacterial species become established at different periods of time after birth, exhibit characteristic anatomic localizations, and greatly fluctuate in numbers. In general, the populations of enterobacilli and enterococci decrease precipitously after having reached a maximum level shortly after the beginning of colonization.
ASSOCIATION OF GERMFREE MICE WITH BACTERIA ISOLATED FROM NORMAL MICE
Authors: Schaedler Russell W. , Dubos René , Costello Richard
Published: June 2004

Germfree mice were given food contaminated with pure cultures of various bacterial species isolated from ordinary healthy mice. The cultures were given singly, or in association, or consecutively at weekly intervals.

Whatever the technique of administration, the lactobacilli and anaerobic streptococci immediately established themselves throughout the gastrointestinal tract, and became closely associated with the walls of the organs. In contrast, the organisms of the bacteroides group were found in large numbers only in the large intestine.

Within a week after exposure, the populations of these three bacterial species reached levels similar to those found in ordinary mice. They remained at these characteristic levels throughout the period of observation (several months). Their presence resulted in a progressive decrease in the size of the cecum which eventually became normal in gross appearance.

Coliform bacilli multiplied extensively and persisted at high levels in all parts of the gastrointestinal tract of germfree mice, even after these had become colonized with lactobacilli, anaerobic streptococci and bacteroides. However, the coliform population fell precipitously within a few days after the animals were fed the intestinal contents of healthy pathogen-free mice.
THE CELL WALLS OF GROUP D STREPTOCOCCI
Authors: Bleiweis Arnold S. , Krause Richard M.
Published: June 2004

Group D Types 1 and 26 cell walls and the corresponding type-specific carbohydrates, extracted from the walls by various means, contain rhamnose, glucose, galactose, N-acetylglucosamine, and N-acetylgalactosamine. Mucopeptide elements are also present in the walls and in enzymatically-extracted carbohydrates. Types 1 and 26 carbohydrates extracted by formamide contain no mucopeptide, but the serologic reactivity of Type 1 antigen is destroyed by this procedure. The Type 1 antigen was successfully extracted, however, by a new technique involving autolysis of cell walls at pH 6.2. The type carbohydrate prepared by this procedure has chemical and serological similarities to the antigens prepared by the S. albus enzyme and the lysozyme methods.

Quantitative precipitin inhibition studies with Type 1 antigen and antibody indicate that D-glucose and N-acetylglucosamine may be components of the antigenic determinant. The terminal residue is probably bound by an ß-glycosidic bond to the subterminal sugar.

Similar studies with the Type 26 carbohydrate have not revealed any of the chemical features of the antigenic determinant.
STUDIES ON HUMAN ANTIBODIES
Authors: Bassett Emmett W. , Tanenbaum Stuart W. , Pryzwansky Katherine , Beiser Sam M. , Kabat Elvin A.
Published: June 2004

Antilevan, antidextran, antiteichoic acid, anti-"A" and normal γG, all isolated from a single human, as well as pooled γG and γM, were analyzed for amino acid content. Differences ranging from 7 to 32 residues were found among these antibodies in glycine, valine, leucine, tyrosine, arginine, lysine, and threonine content. These conspicuous differences in amino acid composition were not correlated with the Gm type of these antibodies.

Hydroxylysine was found in two of the four antibodies, antidextran and antiteichoic acid, and in γM- immunoglobulin. No hydroxylysine was found in γG- globulins. These findings probably account for discrepancies in the literature concerning the occurrence of this residue in antibody protein.
PROLIFERATIVE RESPONSE OF THE SPLEEN AND LIVER TO HEMOLYSIS
Authors: Jandl James H. , Files Nancye M. , Barnett Susan Bell , MacDonald Richard A.
Published: June 2004

Combined chemical and autoradiographic studies in rats injected with tritiated thymidine indicate that acute red cell sequestration stimulates reticuloendothelial (RE) proliferation. In the spleen DNA synthesis is most markedly stimulated in the marginal zone which is also the initial site of red cell sequestration. This proliferative response involves several division steps and eventuates in a colonization of the red pulp with increased numbers of all cell lines native to the spleen. In both spleen and liver there occurs also a generalized stimulation of division in the macrophages and littoral cells which involves only 1 or 2 division steps.

Chronic compensated hemolytic anemia achieved in rats by injections of phenylhydrazine caused functional overactivity of the RE system, including increased sequestering function and hypergammaglobulinemia. This splenic hyperplasia did not entirely regress after cessation of the injections. In man the splenomegaly of a chronic non-immunological hemolytic anemia, hereditary spherocytosis, was found to involve a marked (average: 8-fold) hyperplasia of all spleen cellular elements.

Neither the acute nor chronic proliferative reaction appears to arise from immunological or "toxic" stimuli and the findings support the view that the size of the RE system is a function of its particulate "work load." It is suggested that the cytoproliferative aspects of immune responses may depend upon non-specific, usually particulate stimulation. After prolonged stimulation, hyperplasia of the RES may become partly irreversible.
THE ROLE OF LYMPHOCYTES IN THE SENSITIZATION OF RATS TO RENAL HOMOGRAFTS
Authors: Strober S. , Gowans J. L.
Published: June 2004

In order to study the role of blood-borne small lymphocytes in the sensitization of rats to renal homografts 2 techniques for the perfusion of isolated rat kidneys were employed: (a) the in vitro perfusion of kidneys with thoracic duct cells suspended in either an artificial medium or in blood; the perfusates were then injected into rats syngeneic with the lymphocyte donors; (b) the in vivo perfusion of kidneys with blood issuing from the femoral artery and returning to the femoral vein of living rats. The degree of sensitization conferred on the recipients by the perfusates was assessed by applying a skin homograft from the kidney donor and scoring the epithelial necrosis at 6 days. The in vitro experiments indicated that parental strain thoracic duct cells, which had passed through an F1 hybrid kidney could confer upon a parental rat sensitivity to an F1 skin graft. Several perfusions with radioactively labelled lymphocytes showed that the injected cells migrated to the lymph nodes and spleen of the recipients Labelled large pyroninophilic cells were occasionally seen in the spleen and lymph nodes of recipients, and it was suggested that these had arisen from the injected cells. Although the in vitro perfusions with blood indicated that renal homografts might sensitize their hosts within 1 hour, the in vivo perfusions suggested that about 5 to 12 hours were required. The more rapid sensitization in vitro was possibly due to the more frequent opportunity for contact between lymphocytes and kidney vascular endothelium which was afforded by the conditions in vitro.
STUDIES ON RABBIT LYMPHOCYTES IN VITRO
Authors: Sell Stewart , Gell P. G. H.
Published: June 2004

Rabbit lymphocytes may be stimulated in vitro with specific antiallotype sera to transform into "blast" cells and to synthesize DNA. This transformation only occurs when the donor cells are obtained from a rabbit having a given γ-globulin allotype (As4) and these cells are cultured in the presence of an antiserum prepared against the given allotype (As4). Heterologous (sheep, goat, and guinea pig) anti-rabbit γ-globulin sera also induce significant blast transformation and DNA synthesis in rabbit lymphocytes. Allotypic transformation and DNA synthesis are due to 7S antiallotype antibodies and do not require complement. The degree of transformation and rate of DNA synthesis is related to the concentration of antibody. Incubation of the appropriate cells with the antiallotype antibody for as short a time as 15 minutes results in a significant degree of "blast" transformation, indicating that the recognition of the antiallotype specificity in the cells and stimulation of the cellular changes leading to eventual transformation is rapid. The activity of the antiallotype sera as measured by transforming or haemagglutinating capacity, may be absorbed by lymphocytes of the appropriate allotype, but is not absorbed by lymphocytes from a donor rabbit not having the allotype to which the antiserum is directed. Transformation does not occur with mixtures of lymphocytes from different rabbits even if 1 donor is immunized against an allotype present in the other donor.

Peripheral rabbit lymphocytes can also be induced to undergo "blast transformation" in vitro by phytohaemagglutinin and staphylococcal filtrate. The lack of demonstrable leucoagglutinins in staphylococcal filtrate and antiallotype serum indicates that agglutination is not a necessary prerequisite to the induction of blast transformation.
A NEW ACUTE PHASE PROTEIN ELICITED IN MICE BY STREPTOLYSIN O AND OTHER TOXIC OR INFECTIOUS AGENTS
Authors: Rowen Robert , Wiest Myrtle A.
Published: June 2004

A new acute phase plasma component has been found in mice exposed to certain toxic materials and pathogenic bacteria. The abnormal component, detected by immunodiffusion employing absorbed antiserum, was chiefly studied in plasma of streptolysin O-treated mice where it appears within 24 hours after intravenous administration of a sublethal dose of the toxin. The new factor is a protein having the electrophoretic mobility of a slow α2-globulin. It is devoid of lipid and separate from the streptolysin O inhibitory lipoprotein that is also induced by administration of the streptococcal toxin. The factor, moreover, appears clearly distinct from haptoglobin or C-reactive protein and seems to be a unique type of acute phase protein. Its partial purification by starch block electrophoresis is described.

A number of toxic materials other than streptolysin O, i.e. saponin, Cl. welchii phospholipase C (α-toxin), and endotoxins, were found to elicit the abnormal protein in mice. Phospholipase A (Crotalus adamanteus venom) and staphylococcal α-toxin failed to cause its appearance. Plasma samples of mice acutely infected with Group A streptococci, Staphylococcus aureus or pneumococcus uniformly contained the abnormal component.

The significance of this acute phase protein has been considered in relation to the streptolysin O inhibitor and to the acute phase proteins of other animal species. It has been suggested that production of the new component and of the streptolysin O inhibitor may be manifestations of a single process constituting a physiological response to a variety of deleterious agents.
SOME PROPERTIES OF THE LACTIC DEHYDROGENASE AGENT OF MICE
Authors: du Buy Herman G. , Johnson Martin L.
Published: June 2004

The lactic dehydrogenase agent was obtained in quantities sufficient for purification studies by growing the virus in Ehrlich ascites tumor-bearing mice.

A rapid method of titration of the agent is described.

Subsequent to the standard procedure of concentration of virus by treatment with hyaluronidase and centrifugation, lipids were removed by extraction with PE, without major loss of infectivity.

Electron microscopic sections of purified preparations contained particles consisting of a dense inner ring of about 25 mµ and a less dense ring extending to about 50 mµ.

The particles occur frequently in single-membraned vesicles of varying size, and occasionally in large double-membraned bodies.

The purified LDH agent did not stimulate the formation of neutralizing antibodies in rabbits and guinea pigs.

The crude LDH agent was found to be a low interferon producer.

Increased interferon, produced by secondary inoculation with Newcastle disease virus temporarily decreased the titer of the LDH agent.

The results of others regarding the nature and the size of the LDH agent are interpreted in regard to the findings presented, and the role of interferon in permanently LDH agent infected mice is discussed.
SPECIFICITY OF RECOMBINATION OF H AND L CHAINS FROM HUMAN γG-MYELOMA PROTEINS
Authors: Grey Howard M. , Mannik Mart
Published: June 2004

Dissociated H and L chains of human γG-myeloma proteins were recombined by removal of conditions interrupting non-covalent interactions. In the process of recombination 7S molecules were formed. It was demonstrated that the H chains from individual γG-myeloma proteins recombine with their own L chains but also with L chains derived from other myeloma proteins. In some instances, however, the L chains from other myeloma proteins did not recombine as avidly with the H chains as the autologous L chains.

The specificity of the non-covalent interactions of H and L chains was particularly well brought out by competitive recombination experiments where an individual H chain had a choice of recombining with its own L chain or with the L chain obtained from another myeloma protein. In this manner a spectrum of affinities between individual H chains and several L chains was demonstrated. In the vast majority of recombinations there was a clearcut preference for recombination to take place between the H and L chains derived from the same protein. It is postulated that this specificity is related to differences in the primary structure, which cause differences in configuration of these homogeneous H and L chains and that these configurations then dictate on thermodynamic grounds the pairing of H chains with particular L chains.
THE EFFECT OF SKIN HOMOGRAFT REJECTION ON RECIPIENT AND DONOR MIXED LEUKOCYTE CULTURES
Authors: Oppenheim Joost J. , Whang Jacqueline , Frei Emil
Published: June 2004

The lymphocyte proliferation in repeatedly studied mixed leukocyte cultures of peripheral white blood cells from a skin graft donor and 2 recipients was significantly increased at the time of graft rejection. This was determined from the increased proportions of mononuclear cells labeling with tritiated thymidine, increased mitotic indices, and the appearance of increased numbers of transformed lymphocytes after rejection of 1st and 2nd skin grafts. The temporarily enhanced response occurred sooner and was of shorter duration after the second than after the first graft, but was quantitatively similar each time. The cell proliferation in the mixed leukocyte cultures of the two recipients was similarly affected by the homograft rejections. The cultures containing three cell populations usually manifested a greater lymphocyte response than corresponding cultures of leukocytes from only two unrelated subjects.

An increase in the ratio of female recipient to male graft donor metaphases in the cultures at the time of enhanced lymphocyte transformation indicated that proliferation of the graft recipient lymphocytes was responsible for the above findings. Unmixed, unstimulated control cultures grown in autologous, the other subjects plasma, or heterologous calf serum failed to support significant lymphocyte transformation. The role of humoral factors and relationship of the in vitro cellular responses to the in vivo homograft reaction are discussed.
THE BACTERIAL INDUCTION OF HOMOGRAFT SENSITIVITY
Authors: Chase Randolph M. , Rapaport Felix T.
Published: June 2004

Heat-killed Group A hemolytic streptococci can induce in guinea pigs a state of altered reactivity to skin homografts which is indistinguishable from that which results from sensitization with homologous tissues. Challenge of suitably prepared recipients with first-set skin homografts obtained from unrelated randomly selected donors elicits white graft reactions or accelerated rejection of such grafts. The gross and histologic appearance of these grafts is identical with that observed in similar reactions obtained in guinea pigs sensitized with homologous tissues. The ability of Group A hemolytic streptococci to induce homograft sensitivity in the guinea pig is a property shared by Types 4, 5, 6, 11, 12, 14, and 49 of Group A streptococci.
THE BACTERIAL INDUCTION OF HOMOGRAFT SENSITIVITY
Authors: Rapaport Felix T. , Chase Randolph M.
Published: June 2004

Heat-killed strains of Staphylococcus aureus and Staphylococcus albus can induce in guinea pigs a state of altered reactivity to skin homografts which is indistinguishable from that which results from sensitization with homologous tissues or Group A streptococci. Challenge of suitably prepared recipients with first-set skin homografts obtained from unrelated randomly selected donors elicits white graft reactions or accelerated rejection of such grafts.

Other bacteria tested included Lancefield streptococcal groups B, C, D, E, G, H, L, and O, pneumococcus Types II, III, XIV and a rough strain, Corynebacterium xerosis, Bacillus subtilis, Escherichia coli, Aerobacter aerogenes, Salmonella typhimurium, Proteus vulgaris, Neisseria catarrhalis, Haemophilus influenzae, and two human virulent strains of Mycobacterium tuberculosis. None of these microorganisms was active in the induction of homograft sensitivity in the guinea pig. Pretreatment of recipients with Gram-negative bacterial suspensions was associated with a slight increase in the mean survival time of first-set skin homografts.

Results of this study suggest the presence in staphylococci, as well as in Group A streptococci, of antigens related in their biologic effects to tissue transplantation antigens.
MEDIATORS OF INFLAMMATION IN LEUKOCYTE LYSOSOMES
Authors: Janoff Aaron , Schaefer Sonja , Scherer Joan , Bean Michael A.
Published: June 2004

The vascular permeability-increasing action of rabbit PMNL lysosomes has been studied in skin and cremaster muscle of the rat.

Both an extract of frozen-thawed granules and a cathepsin-free cationic protein fraction of the granules (which had previously been demonstrated to cause leukocyte adhesion and emigration in vivo) induce increased vascular permeability in skin and muscle which resembles that produced by histamine or histamine-liberators with respect to the timing of the response and the predominant type of microvessel affected.

Extracts of frozen-thawed lysosomes and the inflammatory lysosomal cationic protein both cause disruption of rat mesenteric mast cells in vitro, whereas a granule-free cytoplasmic fraction of PMN leukocytes and a non-inflammatory cationic protein fraction of the granules do not do so under identical test conditions. The mastocytolytic action of lysosomal materials in vitro is not inhibited in the presence of 10 kallikrein-inhibiting units of trasylol per ml. The mast cell rupturing fraction of PMNL granules (cationic protein) possesses no detectable peroxidase activity or acid-mucopolysaccharase activity. When compared with compound 48/80 on the basis of estimated molecular weight, the lysosomal cationic protein appears to be at least as active as the latter compound with respect to in vitro mastocytolytic potency.

Chronic pretreatment of rats with an agent known to reduce tissue mast cell numbers causes marked suppression of the vascular permeability change normally induced in skin and muscle by lysosomal extracts and cationic protein. Similar results are obtained if lysosomal materials are tested in rats pretreated with an antihistaminic.

These observations are discussed with respect to the mode of action of PMNL lysosomes in the early and late phases of local tissue-injury reactions.
PATHOGENESIS OF THYMIC CHANGES IN NZB MICE WITH HEMOLYTIC ANEMIA
Authors: Siegler Richard
Published: June 2004

Lymphoid follicles evolve in the perivascular connective tissue of many organs, including the thymuses, in NZB/Bl mice with hemolytic anemia. In previously published studies, these thymic follicles have been held to be causal in the autoimmune genesis of the hemolytic anemia. The present study contradicts this interpretation by demonstrating: (a) lymphoid follicles develop in the perivascular connective tissue of many organs in NZB mice, and are not restricted to the thymuses; and (b) thymic lymphoid follicles develop in aged Swiss mice without hemolytic anemia.

Contrary to previous reports, the thymuses of NZB mice contain normal numbers of Hassall's corpuscles, which develop from preexisting thymic epithelial cells, and not from blood vessels.
STUDIES OF ADENOVIRUS SV40 HYBRID VIRUSES
Authors: Rowe Wallace P. , Baum Stephen G. , Pugh Wendell E. , Hoggan M. David
Published: June 2004

The titers of adenovirus and SV40 genetic carriers in hybrid preparations (E46+) can be quantitated by determining the percentage of cells showing neoantigens stainable with fluorescent antibody (FA) at 21 to 24 hours; both titers can be obtained with a single coverslip. The adenovirus and SV40 antigen-inducing titers so obtained are of the same order of magnitude in stock preparations of E46+ grown in either African green monkey kidney (AGMK) or human embryonic kidney tissue culture (HEK), and are generally within one log of the infectivity titer.

Quantitative studies of 50°C heat inactivation, ultracentrifugation, and equilibrium density gradient centrifugation of E46+ gave no indication that SV40 neoantigen induction could be dissociated from adenovirus, whereas adenovirus and SV40 virus grown as a mixed infection were readily dissociated by these procedures.

Pretreatment of HEK cells with a medium containing 5-fluorouracil desoxyriboside (FUDR) did not affect induction of either adenovirus or SV40 neoantigen or development of cytopathic effects after infection with E46+, but did prevent formation of Ad. 7 viral antigen.
STUDIES ON THE MECHANISM OF ACTION OF RILEY VIRUS
Authors: Evans R. , Salaman M. H.
Published: June 2004

A study was made of the replication of Riley virus in various tissue cultures. It was observed that Riley virus replicated in primary mouse embryo cultures for 8 to 12 days. As they aged primary cultures became less susceptible to Riley virus infection, and subcultured cells were not susceptible. Suspensions of virus, in the absence of cells, were inactivated at 36.5°C. Serial passage by transfer of supernatant fluids to fresh embryo cultures was not successful. Replication of the virus was more active in mouse embryo liver cultures than in the cultures of the embryo minus the livers.

In cultures of mouse macrophages, the supernatants remained infective throughout the life of the cultures (21 days). The virus was passed 23 times through fresh macrophage cultures over a period of 80 days, during which the original inoculum (106.0ID50/ml) was theoretically diluted to 10–14.

The possibility that the cells of the RES are involved in Riley virus replication is discussed.
SUPPRESSION OF DELAYED HYPERSENSITIVITY IN VITRO BY INHIBITION OF PROTEIN SYNTHESIS
Authors: David John R.
Published: June 2004

Peritoneal cells from guinea pigs exhibiting delayed hypersensitivity are inhibited from migrating in vitro by specific antigen. This inhibition is prevented by the addition of puromycin to the culture medium. The amount of puromycin necessary to prevent the inhibition by antigen also suppressed the incorporation of C14-leucine into peritoneal cell protein. Additional evidence that the action of puromycin is due to its inhibition of protein synthesis has been obtained with analogues of puromycin; those that inhibit protein synthesis also prevent the action of antigen on the cells, while those analogues that do not inhibit protein synthesis have no effect. Actinomycin also prevents the inhibition of sensitive cells by antigen while chloramphenicol has no effect. The data indicate that the inhibition of sensitive cell migration by antigen requires active protein synthesis. The possible mechanisms by which inhibition of protein synthesis may influence the in vitro reactions of delayed hypersensitivity are discussed.
IN VITRO DEMONSTRATION OF CELLULAR SENSITIVITY IN ALLERGIC ENCEPHALOMYELITIS
Authors: David John R. , Paterson Philip Y.
Published: June 2004

Peritoneal cells obtained from animals exhibiting delayed hypersensitivity are inhibited from migrating in vitro by specific sensitizing antigen. This test for the detection of delayed hypersensitivity was applied to the problem of cellular sensitivity in allergic encephalomyelitis (AE). The migration of peritoneal cells obtained from guinea pigs with AE was inhibited specifically by nervous tissue antigens. The specificity of this reaction was further studied. Neonatal rat nervous tissue, which was shown to lack the encephalitogenic antigen, i.e. did not produce AE when injected with complete adjuvant into guinea pigs and rats, did not inhibit the migration of cells from animals with AE. Adult rat nervous tissue, which readily produces AE, and thus contains the encephalitogenic antigen did inhibit the migration of such cells. The finding that cells from animals with AE display hypersensitivity which appears to be directed specifically to the encephalitogenic antigen strongly supports the view that such cells could play an important role in the pathogenesis of this disease.
EFFECTS OF INSULIN ON THE WEIGHT OF THE RABBIT'S SUPRARENAL GLANDS
Authors: Thatcher Harvey S.
Published: June 2004

There is no gross hypertrophy of the adrenals in rabbits after long continued, daily doses of insulin.
THE IMMUNITY PRODUCED BY THE GROWTH OF TETANUS BACILLI IN THE DIGESTIVE TRACT
Authors: Tenbroeck Carl , Bauer Johannes H.
Published: June 2004

1. A method for the production of tetanus by the injection of a fixed number of spores is described together with the tests made in selecting animals for experimental work.

2. Guinea pigs fed a single serological type of tetanus bacilli will, after 6 months, show considerable amounts of antitoxin in their sera and will manifest immunity to the type fed. To other types they are just as susceptible as are controls.

3. Animals fed several types are immunized to each of these types. It is pointed out in the discussion that the digestive tract of man may carry several types and that he probably reacts in a manner resembling the guinea pig carriers.

4. Guinea pigs that carry tetanus bacilli and have antitoxin in their sera show little if any resistance to tetanus toxin.

5. As there is no relation between the amount of antitoxin in the blood and immunity to tetanus we believe that other bodies, specific for type, must occur and make for the immunity observed.
STUDIES ON THE BIOLOGY OF STREPTOCOCCUS
Authors: Stevens Franklin A. , Dochez A. R.
Published: June 2004

1. Strains of hemolytic streptococci isolated from cases of erysipelas agglutinate in a high percentage of instances with erysipelas immune sera. When agglutination occurs with one serum, the strain usually agglutinates with all other erysipelas sera.

2. Erysipelas immune sera agglutinate strains from erysipelas in a higher percentage of instances than they agglutinate scarlatinal strains.

3. Strains from miscellaneous pyogenic infections may agglutinate in these sera, but the percentage of positive reactions is low and a strain usually agglutinates in but one or two of several sera.

4. Erysipelas strains which agglutinate in immune sera are not necessarily identical, although identical strains may occur. Similarly, identical strains may occur among scarlatinal strains agglutinated by scarlatinal immune sera.

5. Erysipelas strains form a closely related group of hemolytic streptococci. Scarlatinal strains form an equally compact group. The two groups are related antigenically but less closely related than the strains within the groups. These groups are related to pyogenic strains, but less closely than they are related to each other.

6. Erysipelas, scarlatinal, or pyogenic strains which agglutinate in erysipelas or scarlatinal sera are capable of absorbing the agglutinin for all other strains except the homologous strain and strains identical with it. Strains identical with the homologous strain absorb the agglutinin completely.

7. Erysipelas or scarlatinal strains may absorb the common group agglutinin from their respective sera, when they are incapable of agglutination in these sera.

8. The agglutinogen is probably of complex or composite nature, with characteristic variations in the scarlet fever and erysipelas groups.
ON THE FREQUENCY OF SPONTANEOUS TUMORS IN THE DOMESTIC FOWL
Authors: Schneider Margaret
Published: June 2004

1. Analysis of records from the Storrs Contest, the Harper Adams Trials, and a farm flock indicate an increase of tumors in the second half of the pullet year (May through October) over the first half (November through April).

2. Some evidence seems to indicate that heavy antecedent egg production is associated with a rise in tumor rate.

3. The normal annual tumor rate for fowls between the ages of 6 and 18 months is about 2 or 3 per cent.

4. The appearance of tumors in "epidemic" form probably indicates that the neoplasms found differ in etiology from those upon which the normal rate is based.
THE TRANSFORMATION OF MONOCYTES INTO FIBROBLASTS THROUGH THE ACTION OF ROUS VIRUS
Authors: Carrel Alexis , Ebeling Albert H.
Published: June 2004

In normal cultures, the transformation of monocytes into fibroblasts generally occurred when cells became packed together through some mechanical factors that prevented their free migration and determined their accumulation. Various modifications of the medium, the addition of dead tissue, and of trypsin or the products of trypsin digestion, failed to bring about the transformation. The inoculation af cultures of monocytes with filtered extract of Rous sarcoma frequently determined the appearance of fibroblasts. The first change undergone by the monocytes cultivated in vitro was a large increase in their size. Later, the giant monocytes became transformed into cells that did not differ essentially from those that grow from a fragment of adult connective tissue.
THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES
Authors: Drury Douglas R. , Rous Peyton
Published: June 2004

The present paper is the first of two dealing with experiments which were planned to disclose the meaning of the colors assumed by mammalian tissues when vitally stained with some phthalein indicators. Derivatives of the tissues themselves were employed after tests had shown, in agreement with certain facts in the literature, that inferences from model experiments, so called, would be misleading.

Organs were perfused with water, or salt, or lymph of the same creature and extracted with small quantities of the fluid. The turbid extracts were colored with phthalein, the reaction determined colorimetrically with the aid of an arc light, and the findings were compared with potentiometer readings upon the material. The results of the two methods were in close agreement.

The significance of the data will be discussed in our second paper.
THE RELATIVE REACTION WITHIN LIVING MAMMALIAN TISSUES
Authors: Drury Douglas R. , Rous Peyton
Published: June 2004

The influence of lymph-insoluble tissue materials upon the colors manifested by phthalein indicators has been tested by comparing the hue of sections of various organs, stained by immersion in colored lymph, with the hue of the surrounding fluid. The reaction has been brought to approximate that of life by a greater or less saturation of the material with carbon dioxide. No evidence has been obtained of indicator errors referable to the association of the phthaleins with tissue substances.

The inferences to be derived from the experiments, and from others detailed in a preceding paper, are discussed. The results of them all are in essential agreement. They demonstrate that the observed hues in tissues vitally stained with phenol red, brom cresol purple, and chlor phenol red cannot be laid to indicator errors resulting from an association of the phthalein with tissue materials. The fact is of special note in connection with organs which exhibit, when stained, the colors indicative of an outspoken acidity.

The findings constitute a control upon the influence of the tissue materials on the colors manifested by the phthalein indicators when used as vital stains; but they leave untouched the problem of the influence of tissue activities upon the coloration.