bluuebunny/crossref_metadata_2025 huggingface dataset:
THE AKR THYMIC ANTIGEN AND ITS DISTRIBUTION IN LEUKEMIAS AND NERVOUS TISSUES
Authors: Reif Arnold E. , Allen Joan M. V.
Published: June 2004

A clear-cut serological differentiation between AKR lymphocytes of thymic and non-thymic origin is reported: these two cell types are antigenically distinct.

In newborn mice, the AKR thymic antigen was found at a high concentration only in thymus. In adult mice, the antigen was present at a high level in thymus, all nervous tissues tested, and some leukemias. It was present at much lower levels in lymph node lymphocytes, splenic lymphocytes, appendix, lung, and certain other leukemias, which appeared to be of non-thymic origin. The AKR thymic antigen was present at a high level in thymus and nervous tissues of RF mice, but was absent from thymocytes of sixteen other mouse strains.

These sixteen strains possessed the C3HeB/Fe thymic antigen. The distribution of this antigen in neonatal and adult tissues of the strains tested was similar to that of the AKR thymic antigen in AKR mice. No exceptions were found.

These results were obtained by use of immune cytolysis, and of a new method for the quantitative treatment of data from absorption experiments.
THE ANTICOAGULANT AND ANTILYMPHOMA PROPERTIES OF ARSENIC AZOPROTEINS
Authors: Broome J. D. , Kidd John G.
Published: June 2004

Experiments given in this paper have shown that 4-arsonophenylazoproteins possess marked anticoagulant activity both in vivo and in vitro. Mice and rabbits given moderate amounts of the arsenic azoprotein, for example, often bled to death from injuries that proved trivial in control animals, and their blood remained liquid during many hours' postmortem even when left in contact with transected tissues, fibrinolysis having no part in the outcome. So, too, the addition of minute amounts of 4-arsonophenylazoprotein to plasma procured from citrated rabbit or human blood greatly prolonged the time required for clotting after recalcification.

Other arsenic-containing compounds,—for example, those in which arsenic

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was joined to amino acids or peptides through the azo linkage, or to proteins through couplings other than the azo linkage,—were largely devoid of anticoagulant and antilymphoma effects. The findings as a whole show clearly that the structural requirements for anticoagulant and antilymphoma effects are: (a) possession of negatively charged arsonic or arsinoso groups, (b) large molecular size (protein), and (c) linkage of arsenic-containing groups to protein through the azo bond.

Two acidic azoproteins that were devoid of arsenic,—namely 4-carboxyphenylazoprotein and 4-sulfonophenylazoprotein,—were also found to have marked anticoagulant effects in vitro, but they had no inhibitory action against cells of Lymphoma 6C3HED in vivo, even when they were given to mice in maximum tolerated amounts. The essential part played by arsenic in the antilymphoma activity of arsenic azoproteins was further emphasized by the action of dimercaprol (BAL) in preventing the antilymphoma effects of 4-arsonophenylazoprotein on Lymphoma 6C3HED cells in vivo.

In an associated paper the anticoagulant and antilymphoma effects of 4-arsonophenylazoproteins are studied further, and consideration is given to the ways in which these effects may be brought about.
ELECTRON MICROSCOPE STUDIES ON THE DEGRANULATION OF RABBIT PERITONEAL LEUKOCYTES DURING PHAGOCYTOSIS
Authors: Zucker-Franklin Dorothea , Hirsch James G.
Published: June 2004

Electron microscopic observations have established the mechanisms underlying degranulation of neutrophils and eosinophils during phagocytosis. The content of the granules is released into the phagocytic vacuole when their membranes fuse with the membrane lining the vacuole. The discharge mechanism appears to be applicable to the various morphological types of granules seen in rabbit polymorphs.

It has been proposed that the release of material to the outside of the cell or the discharge of material into intracellular vacuoles, events involving membrane fusion, be termed "exoplasmosis."
STUDIES ON THE MECHANISM OF EXPERIMENTAL PROTEINURIA INDUCED BY RENIN
Authors: Deodhar Sharad D. , Cuppage Francis E. , Gableman E.
Published: June 2004

Renin-induced proteinuria in the rat was investigated, with special emphasis on the relationship between the enzymatic activity and the proteinuric effect of renin. The dependence of the proteinuric effect on the enzymatic activity was shown by using (a) renin preparations of widely varying purity and (b) chemically modified "active" and "inactive" renin derivatives.

Angiotensin II, the pressor product of the enzymatic action of renin, also produced significant proteinuria.

Adrenalectomy abolished the proteinuria induced by renin. Proteinuria, however, occurred as a result of pretreatment with DOCA, or aldosterone, or without treatment, 7 to 8 weeks after adrenalectomy.

Electron microscopic studies of the kidney at the time of maximal proteinuria showed focal flattening and fusion of epithelial foot processes, as well as swelling and vesicle formation in endothelial and epithelial cells of the glomeruli. Studies with intravenously injected saccharated iron oxide showed increased permeability of the glomerular capillary basement membrane to these particles. These changes were transient and were not seen 24 hours after renin injection. Adrenalectomy prevented these changes.

It is concluded that renin, acting through angiotensin, causes glomerular capillary damage with increased permeability of these structures to protein and resultant proteinuria. The adrenal glands participate in a permissive role in this phenomenon.
CROSS-REACTIONS OF PNEUMOCOCCAL TYPES
Authors: Heidelberger Michael , Tyler Jean M.
Published: June 2004

Data are given on the amounts of antibody nitrogen precipitated in the crossreactions, often reciprocal, of the specific capsular polysaccharides of the pneumococcal type pairs II and XX, II and XIX, VII and XIV, VII and XVIII, VII and XIX, VIII and XVIII, VIII and XIX, X and XIV, and X and XX. Since little is known of the fine structures of the polysaccharides of Types VII, X, XIX, and XX, rigorous correlations between chemical structure and specificity can not be made, but several tentative conclusions are drawn.
THE DIFFERING SURVIVAL OF NORMAL AND SENSITIZED SPLEEN CELLS TRANSFERRED TO ALLOGENEIC HOSTS
Authors: Hattler Brack G. , Schlesinger Michael , Amos D. Bernard
Published: June 2004

Normal and isoimmune C3H and C57BL spleen cells were transferred intravenously into normal and irradiated allogeneic recipients and the fate of the donor cells determined by differential cytotoxicity and radioautographic techniques. It was found that spleen cells sensitized against their prospective recipients could be identified in the host's spleen for 1 day, whereas normal donor cells survived 2 to 3 days. Spleen cells presensitized with an indifferent antigen had survival times similar to normal donor cells. Irradiation of the recipients prior to cell transfer eliminated any difference in survival times between normal and presensitized donor cells in allogeneic hosts. It is concluded that the host plays an important role in the rapid destruction of spleen cells presensitized against host antigens.

Experiments in which sensitized and normal C57BL spleen cells were mixed and transferred into normal C3H mice indicated that as little as 5 to 10 per cent of the donor cell population need be sensitized for the entire mixture to behave as if it were obtained from a sensitized animal, as shown by its elimination in the 1-day interval.
VIRUS PARTICLES IN THE THYMUS OF CONVENTIONAL AND GERM-FREE MICE
Authors: de Harven Etienne
Published: June 2004

Electron microscope study of thymuses of both conventional and germ-free mice has revealed the presence of typical virus particles associated with the thymic lymphocytes or with the thymic epithelial cells. The particles resemble those associated with several murine leukemias and their viral nature seems convincingly substantiated by morphological observation. Germ-free mice are therefore not virus-free. The biological significance of these particles is still unknown and we can only speculate as to the possible relationship of these particles to the incidence of "spontaneous" leukemia, to the lymphocytosis stimulating factor of Metcalf, and to the numerous latent viral infections of laboratory mice.
STUDIES ON THE MODE OF ACTION OF DIPHTHERIA TOXIN
Authors: Collier R. J. , Pappenheimer A. M.
Published: June 2004

It has been demonstrated that low concentrations of highly purified diphtheria toxin specifically inhibit incorporation of labeled amino acids into polypeptides in extracts from HeLa cells and from rabbit reticulocytes. No inhibition of incorporation occurs in the absence of a specific cofactor. This cofactor has been identified as nicotinamide adenine dinucleotide (NAD). It has been shown that it is one of the steps involving transfer of amino acids from soluble ribonucleic acid to the growing polypeptide chain that is affected by the toxin in the presence of NAD.
INCREASED SUSCEPTIBILITY OF MICE INFECTED WITH MOUSE ADENOVIRUS TO ESCHERICHIA COLI-INDUCED PYELONEPHRITIS
Authors: Ginder David R.
Published: June 2004

Mouse adenovirus causes a persistent infection in the mouse kidney that produces extensive mononuclear cell infiltrates in cortex and medulla. Tubular necrosis, dilatation, and occasional collapse occur but no glomerular changes or periglomerular fibrosis have been observed. Acute and chronic adenovirus infection of the kidney predispose the kidney to develop acute pyelonephritis when the mouse is challenged by the intravenous or retrograde route with Escherichia coli.
ON THE RELATIONSHIPS BETWEEN THE γ-GLOBULIN GENES OF THE GM SYSTEM
Authors: Mårtensson Lars
Published: June 2004

Gm types of sera from Caucasians and Negroes, of myeloma globulins, and of specific antibodies were investigated. In particular the relationship between the recently identified gene Gmf and other Gm genes was analyzed.

1. Caucasians were, with rare exceptions, either Gm(b+f+) or Gm(b-f-).

2. In Negroes, on the other band, type Gm(b+f-) was found to be common.

3. No myeloma globulins appeared to contain the product of more than 1 of the 3 genes Gma, Gmb, and Gmf, even though the large majority of normal individuals, as well as myeloma patients, possess 2 or all 3 of these genes.

4. The types Gm(a+b-f-) and Gm(a-b-f+) represented the 2 major groups among the γ2-myeloma globulins; each comprised roughly 40 per cent. The types Gm(a- b+f-) and Gm(a-b-f-) are minor groups.

5. All Gm(x+) myeloma globulins were also Gm(a+). Approximately half of the Gm(a+) myeloma globulins were Gm(x+).

6. In the majority, but not in all, of Gm(a+) sera the anti-Rh antibodies were clearly Gm(a+). Similarly, the anti-Rh antibodies of Gm(f+) sera were most often, but not always, also Gm(f+). In contrast, only a minor proportion of Gm(b+) anti-Rh sera sensitized red cells to anti-Gm(b).
CHARACTERISTICS OF AN IMMUNE SYSTEM COMMON TO CERTAIN EXTERNAL SECRETIONS
Authors: Tomasi Thomas B. , Tan Eng M. , Solomon Alan , Prendergast Robert A.
Published: June 2004

The γ1A present in saliva and colostrum exists largely in the form of higher polymers, the major component of which has a sedimentation coefficient of 11S. The 11S γ1A in these fluids differs from the polymers found in normal and myeloma sera both immunologically and by the fact that their sedimentation coefficients are unaffected by disulfide bond reduction in the absence of urea. However, like other γ-globulins the 11S γ1A molecules consist of multiple polypeptide chains linked by disulfide bonds.

Local synthesis of γ1A in the salivary gland has been shown by fluorescent and autoradiographic studies, although the fraction of the total salivary γ1A which is derived from local production is uncertain. No evidence of transport of intravenously administered I131-labeled 7S γ1A from serum to saliva was obtained.

Immunological specificity has been demonstrated in the salivary and colostral γ1A. Whether that portion of the γ1A which is immunologically specific is a piece incorporated during the local synthesis of γ1A in the gland or is added by the epithelial cell in the process of transport remains to be determined.

Antibody activity (isohemagglutinins) have been demonstrated in saliva and colostrum and have been shown to be of the γ1A-type. In both of these fluids activity is associated primarily with γ1A-polymers of 11S and 18S sizes. There appears to be an immunological system which is characteristic of certain external secretions. Its properties including the local production of a distinctive type of antibody separate it from the "systemic" system responsible for the production of circulating antibody. This system may play a significant role in the body's defense mechanisms against allergens and microorganisms.
ISOLATION, CHARACTERIZATION, AND DISTRIBUTION OF ACID MUCOPOLYSACCHARIDES IN RABBIT LEUCOCYTES
Authors: Fedorko Martha E. , Morse Stephen I.
Published: June 2004

Acid mucopolysaccharides have been extracted from whole rabbit polymorphonuclear leucocytes and from the cytoplasmic granules of these cells.

The leucocyte acid mucopolysaccharides can be separated into two fractions by the solubility of their CPC complexes in solutions of differing salt concentration. One of these fractions appears to be identical with hyaluronic acid; the other appears to be an atypical chondroitin sulfate.

On both a dry weight and total protein basis the polymorphonuclear leucocyte granule contains approximately 2.6 times as much acid mucopolysaccharide as does the whole cell. Hyaluronic acid is concentrated in the granules in particular; its function is unknown.

These results do not indicate that all lysosomes contain abundant acid mucopolysaccharides, for no detectable carbohydrate of this class could be extracted from lysosome-rich alveolar macrophages.
ENHANCEMENT OF ANTIBIOTIC ACTIVITY OF COLICINE K AND ALTERATION OF SEROLOGICAL PROPERTIES OF COLICINE K AND ENDOTOXINS
Authors: van Vunakis Helen , Ruffilli Anna , Levine Lawrence
Published: June 2004

Hemoglobin, its chains, and myoglobin enhance the antibiotic activity of colicine K. These proteins also interact with colicine K and other O antigens to alter their serological activity. The hemoglobin proteins did not alter the serological activities of three Pneumococcus polysaccharides or T4 bacteriophage DNA antigens but did alter the antigenic activity of fetuin.

Interaction of hemoglobin and colicine K resulted in a retardation of colicine K antibiotic moiety as measured by gel filtration but did not affect the gel filtration properties of the lipopolysaccharide moiety.
ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS)
Authors: Maurer Paul H.
Published: June 2004

It has been demonstrated that polymers consisting solely of D-α-amino acids are not immunogenic in rabbits, guinea pigs, man, and mouse, whereas the same polymers of L-α-amino acids are very effective antigens. This has been attributed to the importance of metabolizability of a polymer in contributing to its immunogenicity. In the glu-lys-ala series of polymers, the immunogenicity of a polymer of 2 L-amino acids and a D-amino acid appears to be governed by the immunogenicity of the 2 L-amino acids. However, some of the specificity may be directed towards configurations containing the D-amino acid. It has been noted that injections of rabbits with polymers of D-amino acids has resulted in a reduced response against the isomeric L polymer.
PHYSICAL AND IMMUNOLOGICAL DIFFERENCES AMONG STREPTOKINASES
Authors: Dillon Hugh C. , Wannamaker Lewis W.
Published: June 2004

Two strains of Group A streptococci have been shown to produce streptokinases with different physical and immunologic characteristics. These streptokinases have been designated SK-A and SK-B. Examination of additional strains of Group A streptococci has indicated that SK-A is the more commonly encountered streptokinase.

Studies comparing the two Group A streptokinases with streptokinase of Group C origin have indicated that the latter streptokinase is intermediate between SK-A and SK-B in regard to its electrophoretic mobility. Immunological data suggest that the Group C streptokinase differs from SK-B but is closely related to SK-A.
THE BRAIN LESION OF GOLDTHIOGLUCOSE OBESITY
Authors: Brecher G. , Laqueur G. L. , Cronkite E. P. , Edelman P. M. , Schwartz I. L.
Published: June 2004

The development of hypothalamic lesions due to goldthioglucose are described. The initial extensive necrotic lesion occurs in close to 100 per cent of animals injected with LD50. Within 2 weeks the necrotic material has been removed and a narrow scar results. After a lapse of several months, the scar is often difficult to visualize, especially in animals that have not developed obesity. The ventromedial nucleus is not the center of the lesion. The nucleus is preserved in some instances, and partially or completely destroyed in others, depending on the extent of the lesion. The more prominent scar in the obese animals correlates with the larger initial lesion necessary for the complete bilateral destruction of the ventromedial nucleus which is known to be a prerequisite for the development of hypothalamic obesity.

Thus, contrary to earlier suggestions, goldthioglucose does not localize specifically in the cells of the ventromedial nucleus.
LYSOSOMAL ENZYMES IN CELLS INFECTED WITH CYTOPATHIC AND NON-CYTOPATHIC VIRUSES
Authors: Mallucci L. , Allison A. C.
Published: June 2004

In chick embryo cells infected with fowl plague virus, an avian strain of influenza A which produces cytopathic effects, lysosomal enzymes were released from the particulate to the supernatant fraction of homogenates within 6 hours of infection. This change occurred in the presence of high concentrations of parafluorophenylalanine, suggesting that the changes were due to redistribution of preformed enzymes rather than to de novo protein synthesis. No such changes were observed when the Melbourne strain of influenza A virus multiplied in the same cell system without cytopathic effects. The possible role of lysosomal enzymes in virus uncoating and in the genesis of cytopathic effects is discussed.
THE EFFECT OF ANTISERUM, ALONE AND WITH HYDROCORTISONE, ON FOETAL MOUSE BONES IN CULTURE
Authors: Fell Honor B. , Weiss L.
Published: June 2004

1. The effects of normal rabbit serum and of rabbit antiserum to whole foetal mouse tissues, on the isolated limb bones of late foetal mice were studied in organ culture, and the influence of hydrocortisone on these effects was investigated.

2. Unheated normal serum caused slight loss of metachromatic material from the cartilage matrix, and some resorption of both cartilage and bone.

3. In unheated antiserum to foetal mouse tissues, the terminal cartilage was smaller and less metachromatic than in paired controls in normal serum, while osteoclasis was so intense that in many explants the bone had almost disappeared. The amount of necrosis varied with different batches of antiserum.

4. The changes produced by normal serum and antiserum could be largely prevented by heating the sera to 57°C for 45 minutes.

5. The effects could also be inhibited by the addition of hydrocortisone to the unheated sera; as little as 0.1 µg hydrocortisone per ml of medium had a well marked protective action.

6. It is suggested that (a) unheated antiserum causes a release of lysosomal enzymes with consequent breakdown of intercellular material, (b) this release is due to an indirect action on the lysosome via an increased permeability of the cell membrane, (c) hydrocortisone does not affect the antigen-antibody reaction, but inhibits the autolytic changes that normally follow this reaction, possibly by stabilising both the lysosomal and cell membranes.
FIBRINOGEN PRECIPITATION BY STREPTOCOCCAL M PROTEIN
Authors: Kantor Fred S.
Published: June 2004

Evidence confirming the identity of fibrinogen-precipitating factor and streptococcal M protein is provided by the demonstration of bactericidal, mouse protective, and long chain-producing antibodies in the sera of rabbits immunized with washed M-fibrinogen precipitates. Two precipitin lines were observed in immunoelectrophoresis of human plasma vs. rabbit anti-M-fibrinogen antiserum; no precipitin reactions were observed between human serum and rabbit anti-M-fibrinogen antiserum. The reaction between M protein and fibrinogen was stoichiometric; a constant equimolar ratio of reactants was observed in precipitates formed with a wide range of M protein concentrations.
LEUKOCYTES AND INTERFERON IN THE HOST RESPONSE TO VIRAL INFECTIONS
Authors: Glasgow Lowell A.
Published: June 2004

1. Investigation of the role of leukocytes in vaccinia virus infection is reported in an in vitro model, in the absence of an immune response.

2. Mouse leukocytes were shown to be capable of inhibiting the progression of vaccinia virus infection in primary mouse embryo fibroblast cultures. The degree of protection varied from slowing of spread of infection to complete control of the infection with eventual elimination of detectable virus and recovery of the culture.

3. Interferon production by leukocytes is thought to be an important factor in the observed protective effect.
THE PRESENCE OF ENDOGENOUS PYROGEN IN NORMAL RABBIT TISSUES
Authors: Snell E. S. , Atkins Elisha
Published: June 2004

Saline extracts of homogenized, uninfected, rabbit tissues produced febrile responses when injected intravenously into rabbits. Extracts of muscle, lung, and heart evoked fevers that were similar to those induced by leucocyte pyrogen; extracts of spleen, liver, and kidney caused more sustained fevers. The minimal pyrogenic dose appeared to be between 1.5 and 3 gm wet weight of tissue.

Evidence is presented that neither Gram-negative bacterial endotoxin nor polymorphonuclear leucocytes (circulating or sequestered in the tissues) can be implicated as the source of pyrogen in tissue extracts. It seems likely, therefore, that a pyrogenic material of truly endogenous origin is widely distributed in tissues.

Tissue pyrogen appears to be a large molecule which is relatively resistant to treatment with acid but not with alkali. Possible pathological roles for this endogenous agent (or agents) are briefly indicated.
EXPERIMENTAL INFECTION WITH MYCOPLASMA PNEUMONIAE (EATON'S AGENT)
Authors: Dajani Adnan S. , Clyde Wallace A. , Denny Floyd W.
Published: June 2004

The pathogenesis of Mycoplasma pneumoniae infection was studied in the Syrian hamster with qualitative and quantitative culture methods and special histopathologic techniques. The animals were readily infected with the mycoplasma, which multiplied throughout the respiratory tract. Sensitivity of this experimental host to infection was indicated by the 50 per cent infective dose, which was 10 colony-forming units of the organism. Inoculation consistently resulted in the production of peribronchial pneumonitis which was induced by the mycoplasma. The organisms were visualized in a superficial location in the mucosa of involved bronchi, by means of indirect fluorescent antibody staining and by a modification of the Brown and Brenn technique. The data indicate applicability of the hamster to the study of problems concerned with M. pneumoniae disease which are impractical or impossible to resolve in the human host.
STUDIES ON DELAYED HYPERSENSITIVITY
Authors: Levine Bernard B.
Published: June 2004

Experiments carried out with several well defined antigenic systems (hapten conjugates of poly-L-lysine and guinea pig serum albumin) in guinea pigs demonstrated that:

1. Arthus reactions also manifest carrier specificity, although to a smaller extent than do delayed hypersensitivity reactions.

2. Desensitization by injection of minute doses of antigen results in moderate specific desensitization of delayed hypersensitivity without desensitization of Arthus reactivity to the same antigenic determinant.

3. Insoluble antigen-antibody complexes prepared from high affinity guinea pig antibodies can elicit specific delayed skin reactions in sensitized guinea pigs.

4. Homologous conjugates of structurally similar haptens show considerably less cross-reactivity in delayed reactions than in immediate hypersensitivity reactions to the same antigenic determinant.

These experimental results are interpreted as indicating that delayed hypersensitivity reactions in the guinea pig are mediated by "antibodies" of comparatively high binding affinities. High binding affinities are achieved for these antibodies more likely by closer structural adaptation between antigen and antibody than by a larger area of specific contact.
THE ORIGIN OF THE CELLS IN THE EFFERENT LYMPH FROM A SINGLE LYMPH NODE
Authors: Hall J. G. , Morris Bede
Published: June 2004

The popliteal nodes of sheep were perfused continuously for over 100 hours with a solution containing 3H-thymidine. The labelling pattern of the lymphocytes in the efferent lymph from the perfused nodes showed that under normal conditions not more than 4 per cent of these lymphocytes were actually produced in the node. The transitional cells, large lymphocytes and cells of the plasma cell series which appeared in the lymph following antigenic stimulation of the node were all produced in the node.
DIFFERENTIAL EFFECTS OF INHIBITORS ON THE STEPS LEADING TO THE FORMATION OF SV40 TUMOR AND VIRUS ANTIGENS
Authors: Rapp F. , Butel J. S. , Feldman L. A. , Kitahara T. , Melnick J. L.
Published: June 2004

The effect of DNA antagonists and various antibiotics on steps in the synthesis of SV40 virus in green monkey kidney cells was investigated. Both the early forming tumor (T) antigen, as well as the later synthesized virus (V) antigen, were synthesized in the presence of fluorouracil and iododeoxyuridine. Cytosine arabinoside (and fluorodeoxyuridine in starved cells) prevented synthesis of V antigen but not T antigen. The synthesis of T antigen therefore does not require synthesis of virus DNA. Virus particles formed only in the presence of the iododeoxyuridine and they were non-infectious.

Actinomycin D inhibited synthesis of both tumor and virus antigens, suggesting that the synthesis of these antigens involves DNA-dependent RNA. Puromycin allowed synthesis of the T antigen which remained localized at the nucleolar membrane. This finding with puromycin suggests that the T antigen is a protein of low molecular weight. Virus antigen forming in the presence of mitomycin C, p-fluorophenylalanine, iododeoxyuridine, or fluorouracil was distributed atypically. These inhibitors caused the V antigen to be diffusely spread throughout the nucleus, or to be concentrated at the nuclear membrane.
A ROLE OF POLYMORPHONUCLEAR LEUKOCYTES AND COMPLEMENT IN NEPHROTOXIC NEPHRITIS
Authors: Cochrane Charles G. , Unanue Emil R. , Dixon Frank J.
Published: June 2004

In acute nephrotoxic nephritis, polymorphonuclear leukocytes (polymorphs) accumulated in large numbers in the glomeruli in the first 12 hours. The endothelial cells were dislodged by the polymorphs which then came to lie immediately adjacent to the glomerular basement membranes. Ultrastructural changes in neither polymorphs nor basement membranes were observed.

Depletion of polymorphs in both rats and rabbits prevented the development of proteinuria. This occurred when doses of nephrotoxic globulin were employed that produced proteinurias of as much as 1800 mg/kg/24 hours in intact rabbits, or enough to yield near maximal immediate proteinuria in intact rats. In addition, measurable glomerular damage was frequently averted until the onset of the secondary stage of NTN. Controls indicated that the polymorph depleted animals exhibited minimal non-specific changes in the blood, that the ability of their vascular beds to react to stimuli was not affected, and that deposition of nephrotoxic antibody and C' in the glomeruli was not inhibited. Elimination of polymorphs from the circulation was only partially effective in preventing glomerular damage when large doses of nephrotoxic globulin were used. This indicated that under these circumstances, a polymorph independent glomerular injury may also take place in first stage nephrotoxic nephritis.

An indirect role of C', i.e., the accumulation of polymorphs, in bringing about glomerular injury in first stage nephrotoxic nephritis was apparent. When rabbit nephrotoxic globulin was injected into rats depleted of C', or when duck nephrotoxic globulin that fixed C' poorly was injected into normal rats, C' failed to bind with the antibody along glomerular basement membranes and polymorphs did not accumulate.
SPECIFIC CARCINOEMBRYONIC ANTIGENS OF THE HUMAN DIGESTIVE SYSTEM
Authors: Gold Phil , Freedman Samuel O.
Published: June 2004

A wide variety of human adult and fetal tissues were studied by immune-diffusion techniques in agar gel to determine whether they contained the tumor-specific antigen(s) previously found in coionic cancers. In the adult tissues it was demonstrated that identical antigens were present in all tested specimens of malignant tumors of the entodermally derived epithelium of the gastrointestinal tract and pancreas, but were absent from all other tested adult tissues. The common antigenic constituents, therefore, represent system-specific cancer antigens of the human digestive system. System-specific cancer antigens have not previously been demonstrated in humans.

Experiments with fetal tissues demonstrated that identical antigens were also present in fetal gut, liver, and pancreas between 2 and 6 months of gestation. These components were named "carcinoembryonic" antigens of the human digestive system. On the basis of the present findings and the recent work regarding control of the expression of genetic potentialities in various types of cells, it was concluded that the carcinoembryonic antigens represent cellular constituents which are repressed during the course of differentiation of the normal digestive system epithelium and reappear in the corresponding malignant cells by a process of derepressive-dedifferentiation.
EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Unanue Emil R. , Lee Sun , Dixon Frank J. , Feldman Joseph D.
Published: June 2004

Rats with nephrotoxic serum nephritis were studied for the presence of a possible autoimmune response to renal antigens formed and/or liberated during the immunologic reactions taking place in the glomeruli. The experiments consisted of transplantation of a normal isologous kidney to a nephritic rat and parabiosis of a normal rat to a nephritic rat. Neither functional nor morphologic abnormalities were noted in the normal kidneys in either situation. Transfer of the rabbit nephrotoxic antibody to the normal kidneys was noted in both experiments, indicating a continual dissociation and reassociation of nephrotoxic antibody with the tissue antigens of the host. Some of the nephritic rats showed a decrease in proteinuria and a slowing in the progression of the nephritis during the period in which the normal kidney was transplanted or a normal rat was united in parabiosis.
ANTIGENICITY OF POLYPEPTIDES (POLY ALPHA AMINO ACIDS)
Authors: Pinchuck Paul , Maurer Paul H.
Published: June 2004

The response of mice to synthetic linear polypeptides of known composition but random sequence has been studied. Neither Swiss mice nor a number of inbred strains could respond to copolymers of only 2 amino acids (G60L40, G60A40, G90T10). Upon introduction of as little as 4 mole per cent of a third amino acid, good immune responses were obtained, regardless of the nature of the third amino acid. The level of the immune response to a series of glu-lys-ala polymers increased with increasing alanine content of the polymer.
HOMOLOGOUS DISEASE IN THE ADULT RAT, A MODEL FOR AUTOIMMUNE DISEASE
Authors: Stastny Peter , Stembridge Vernie A. , Vischer Thomas , Ziff Morris
Published: June 2004

Polyarthritis and cardiac lesions have been observed in the adult rat with homologous disease. Changes in the lymphoid tissue and kidney have also been noted.

A migratory polyarthritis occurred in over half of the affected animals, and cardiac involvement of varying intensity was present in all. Histologically, the arthritis was characterized by a mononuclear synovial inflammatory reaction. In the heart, the valves and myocardium demonstrated a similar type of response. Cultures of involved joints and hearts for pyogens and pleuropneumonia-like organisms were negative.

The lymphoid tissues showed progressive changes in three stages: (a) disappearance of follicles; (b) increase in plasma-like cells and histiocytes; and (c) fibrosis. The second stage tended to coincide with the development of the polyarthritis. The kidney showed mild interstitial mononuclear infiltration.

The pathologic changes described appear to be a consequence of reaction between foreign immunologically competent cells and host antigens, but the possibility that these lesions represent a response to antigens derived from unknown infectious agents is, however, not ruled out.
FUNCTION OF THE RETICULOENDOTHELIAL SYSTEM
Authors: Normann Sigurd J. , Benditt Earl P.
Published: June 2004

Reticuloendothelial clearance of carbon particles is inhibited by injection of heat-aggregated albumin. The possibility that this inhibition might involve a serum component has been explored. Evidence that such a serum factor does participate in carbon clearance inhibition by heat-aggregated albumin derives from the fact that prior treatment of the carbon with homologous serum eliminates the blockade; and also, if serum previously absorbed with carbon is mixed with the carbon particles no restoration of "blockade" by albumin occurs. A method for extracting the component from serum using barium sulfate adsorption is described which allows concentration of the factor and sensitive assay for its presence. It is concluded that while large or multiple carbon injections may bring about a saturation of the phagocytic cell, this saturation masks an underlying factor which protects against acute inhibition of carbon phagocytosis by denatured albumin when subsaturating carbon doses are used.
GENETIC CONTROL OF COMBINING SITES OF INSULIN ANTIBODIES PRODUCED BY GUINEA PIGS
Authors: Arquilla Edward R. , Finn Jack
Published: June 2004

1. Genetic factors control the configuration of combining sites of guinea pig insulin antibodies.

2. It is possible that the configuration of the combining sites of guinea pig insulin antibodies is controlled by more than one gene and not by multiple alleles at a given gene locus.
PREFERENTIAL RECOMBINATION OF ANTIBODY CHAINS TO FORM EFFECTIVE BINDING SITES
Authors: Roholt O. A. , Radzimski G. , Pressman D.
Published: June 2004

The recovery of hapten-binding activity by a mixture of H and L polypeptide chains of the whole γG-immunoglobulin fraction from rabbit anti-p-azobenzenearsonate (Rp) serum is almost as great as that by a mixture of H and L chains from specifically purified Rp antibody. Random combination among the H and L chains from the anti-Rp antibodies and the normal γG-immunoglobulin present would result in little recovery of hapten-binding activity. This suggests a preferential recombination of H and L chains from antibody. Mixtures of H or L chains from anti-p-azobenzoate (Xp) antibody and the complementary chains from antibody-depleted γG-immunoglobulin show little hapten-binding. When anti-Xp antibody H chains are added to mixtures of one equivalent of anti-Xp L chain and increasing amounts of non-specific L chain, the hapten-binding by the mixtures decreases, but not as much as if the H chains combined with the L chains randomly. Hapten was not present during these recombination procedures. These data indicate that in the cases of anti-Xp and of anti-Rp antibodies, there is a selective combination between those H and L chains which give effective hapten binding regions.
ELECTRON MICROSCOPIC OBSERVATIONS ON ANTIBODY-PRODUCING LYMPH NODE CELLS
Authors: Harris T. N. , Hummeler Klaus , Harris Susanna
Published: June 2004

Lymph node cells of rabbits injected with sheep erythrocytes, identified as antibody-producing by their ability to produce plaques of hemolysis in erythrocyte-containing agar layers, have been examined by electron microscopy, by the use of a procedure devised for subjecting single cells to such examination.

The antibody-producing cells thus examined were found to fall into two classes, according to the current terminology: some were in the category of lymphocytes, and others, in the category of plasma cells. Within each class, cells were found to vary in certain characteristics, especially in the degree of development of such organelles as the nucleolus, Golgi apparatus, and the endoplasmic reticulum. In the case of the endoplasmic reticulum especially, it could be seen that a series of these plaque-producing cells, ranked in order of increasing size and development of the endoplasmic reticulum, would extend over a considerable range from those lymphocytes with the least developed organelles to the mature plasma cells with the greatest development of these structures.
ISOLATION OF RABBIT IGA ANTIHAPTEN ANTIBODY AND DEMONSTRATION OF SKIN-SENSITIZING ACTIVITY IN HOMOLOGOUS SKIN
Authors: Onoue Kaoru , Yagi Yasuo , Pressman David
Published: June 2004

Multiple antibody components of rabbit antisera against p-azobenzenearsonate (Rp) were studied with respect to their globulin nature and skin-sensitizing activity. IgA antibody was characterized by isolating two IgA-rich fractions from a specifically purified antibody preparation. Examination of these fractions showed that IgA antibodies existed in two molecular forms, one with a sedimentation constant of 7S and the other 9S. Skin-sensitizing activity was examined by a P-K type test and a PCA test with Rp-rabbit serum albumin in homologous (rabbit) species. Only the 7S but not 9S IgA antibody sensitized rabbit skin. IgM antibody showed no activity and IgG antibody showed very low activity. In contrast, only IgG antibody was active in the P-K type test to sensitize a heterologous species (guinea pig). None of the antibodies of other classes showed sensitizing activity in heterologous skin.

The 7S IgA antibody lost its sensitizing activity upon reduction and alkylation, although no change in its molecular size could be observed. The loss of sensitizing activity was not due to the destruction of antigen-binding activity since the treated 7S IgA antibody retained this activity as shown by radioimmunoelectrophoresis and by binding to the specific immunoadsorbent. The 9S IgA antibody was more resistant to these treatments than the IgM antibody and showed no indication of dissociation. The treated 9S IgA also retained antigen-binding activity.

Both the P-K type and PCA reactions were considerably stronger when the interval between injections of antibody and antigen was 24 hr rather than 4 to 5 hr.
SPECIFIC TRANSPLANTATION IMMUNITY IN RELATION TO ROUS SARCOMA VIRUS TUMORIGENESIS IN MICE
Authors: Jonsson Nils , Sjögren Hans Olof
Published: June 2004

Tests for transplantation immunity and for the occurrence of virus-neutralizing serum antibodies were performed on mice, inoculated when newborn with the Schmidt-Ruppin strain of Rous sarcoma virus (RSV-SR). Mice developing no palpable primary sarcomas showed a clear-cut resistance against the isografting of established specifically antigenic Rous tumors. Transplantation tests performed on primary tumor hosts after extirpation of the tumors revealed neither any clear-cut immunity nor tolerance to the specific transplantation antigen(s). Serial pretreatment of operated primary tumor animals with irradiated autologous or syngeneic tumor cells resulted in a clear-cut transplantation immunity. Virus-neutralizing activity was only found in a few sera from newborn infected mice, and in these cases there was no positive correlation with the transplantation immunity.

It seems probable that a successful immunization against the RSV-SR specific transplantation antigen(s) prevents the development of primary tumors. There is no indication of any tolerance to this antigen in connection with the induction of primary tumors.
COLIFORM BACTERIA IN THE INTESTINE OF MICE
Authors: Mushin Rose , Dubos René
Published: June 2004

Mice of the NCS and NCS-D colonies, bred at the Rockefeller University, harbored in their intestine an endemic strain of slow lactose-fermenting Escherichia coli 081±: :H21 serotype. In addition, NCS mice have recently acquired E. coli 0109±:K48:H14. Both strains persisted during the period of observation, whereas they were not encountered in the feces of mice from two other colonies. Other coliform strains encountered were more transient in their occurrence.

Since strains of E. coli 081±: :H21 and 0109±:K48:H14 are extremely uncommon in human beings, it seems probable that they possess specificity for the mouse host.
THE IN VITRO DIFFERENTIATION OF MONONUCLEAR PHAGOCYTES
Authors: Cohn Zanvil A. , Hirsch James G. , Fedorko Martha E.
Published: June 2004

The structure of unstimulated mouse peritoneal phagocytes has been examined by electron microscopy and compared to cells obtained from the inflamed peritoneum and from cultures maintained in vitro.

The unstimulated cell resembles the blood monocyte and contains a moderate amount of rough surfaced endoplasmic reticulum, a small but well defined Golgi apparatus and a few, small, electron-opaque granules in the cytoplasm.

During in vitro cultivation there are marked changes in cell ultrastructure. Most prominent is the formation of large electron-opaque granules, some of which have a complex matrix containing both electron-opaque and lucent vesicles. In addition, there is an increase in size of the Golgi apparatus with the appearance of new lamellae and tiny, smooth surfaced vesicles. With continued cultivation, large lipid droplets are found in apposition to the rough endoplasmic reticulum. The formation and size of electron-opaque granules as well as the enlargement of the Golgi region is stimulated by high concentrations of serum in the medium.

Cells obtained from the peritoneal cavity of lipopolysaccharide stimulated animals demonstrated changes in ultrastructure similar to those seen in cells cultured in vitro.
SPECIFICITY IN THE COMBINATION OF FD FRAGMENTS WITH L CHAINS TO FORM HAPTEN-BINDING SITES
Authors: Roholt O. A. , Radzimski G. , Pressman D.
Published: June 2004

In the work reported here we have shown that light chains and Fd fragments can be separated completely in propionic acid and then recombined to form Fab fragments with antibody activity. This experiment indicates that in the recombination a correct alignment of the Fd fragments and the L chains occurs to give a competent antibody site, just as occurs with the recombination of separated heavy and light chains of the antibody; thus the Fc fragment is not required for correct alignment.

Fd fragments of antibody alone show very low binding activity toward the specific hapten.

As is the case for the combination of heavy and light chains, the combination of Fd fragments and light chains also requires that both components come from antibody from the same rabbit in order to give binding sites. When they are derived from different rabbits producing antibody against the same antigen, they still give Fab fragments as shown by immunoelectrophoresis but do not have competent binding sites.

An important observation is that the subunits of the papain digest fractions, FabI and FabII, have the capacity to cross-combine to form active Fab fragments with competent binding sites. FdI from FabI combines with LII chains from FabII to give the composite (FdI-LII) with good binding activity. Likewise, the composite (FdII-LI) has good binding activity. The composites from the two types of antibody molecules yielding different Fab fragments have antibody activity although heretofore these molecules have appeared to be different on the bases of chromatography and amino acid analysis.

There is also a preferential combination of the Fd fragments to combine with the correct L fragments to give binding sites since this combination takes preference over the combination of Fd fragments of antibody with light chains of normal globulin (or of light chains of antibody with Fd fragments of normal globulin).
γA-BLOOD GROUP ANTIBODIES
Authors: Adinolfi M. , Mollison P. L. , Polley Margaret J. , Rose Jane M.
Published: June 2004

The serological characteristics of γA-anti-A and anti-B were studied using, as a source, either colostrum, or fractions relatively rich in γA obtained from selected potent antisera. γA-anti-A and anti-B were never hemolytic nor did they sensitize red cells to agglutination by anticomplement globulin sera.

γA-anti-A, like γG-anti-A and unlike γM-anti-A was unaffected by heating at 56°C for 3 hr. On the other hand in the following three characteristics the behavior of γA fell between that of γG- or γM-anti-A: sensitivity to inactivation by 2-mercaptoethanol, ease of neutralization by A substance and degree of enhancement of agglutination in a medium of serum rather than saline. The agglutination produced by γA-anti-A was regularly enhanced by addition of anti-γA-globulin serum.

In searching for γA-blood group antibodies of other specificities the following sera were tested: anti-D (32 examples); anti-c (2 examples); anti-Lea or -Leb (3 examples); anti-K (3 examples); anti-Fya (3 examples), and anti-Jka (3 examples). Only 3 sera, all containing anti-D, sensitized red cells to agglutination by anti-γA. There were no discrepancies between results obtained with four different anti-γA-globulin sera. Approximately half the sera were fractionated on DEAE-cellulose, and the fractions rich in γA tested for their ability to sensitize red cells to agglutination by anti-γA; no additional examples of γA-antibodies were detected.

One of the three examples of γA-anti-D appeared in the serum of a woman during the course of deliberate reimmunization. γA-anti-D appeared only after three intravenous injections of red cells although the γG-anti-D titer rose considerably after a single injection. 3 yr after a fourth injection of Rh-positive cells γA-anti-D, as well as γG-anti-D, was still present in the serum.