bluuebunny/crossref_metadata_2025_split huggingface dataset:
PHYLOGENY OF IMMUNOGLOBULIN STRUCTURE AND FUNCTION
Authors: Clem L. W. , Small P. A. 
Published: June 2004

Lemon sharks immunized with bovine serum albumin produced two molecular forms of antibodies detectable by passive hemagglutination of antigen-coated, tanned sheep erythrocytes. Throughout the course of immunization 2-ME-sensitive antibody was associated with a 19S immunoglobulin fraction (4–5 mg/ml serum) while late in the course of immunization antibody was found also associated with a 7S immunoglobulin fraction (7–8 mg/ml serum). No evidence for any anamnestic response was found in these animals. Naturally occurring hemagglutinins for sheep erythrocytes were found to be 2-ME-sensitive and present in the 19S immunoglobulin fraction.
These immunoglobulin fractions were readily purified by DEAE-cellulose chromatography and Sephadex G-200 gel filtration. Both immunoglobulin molecules yielded equimolar amounts of H and L polypeptide chains when subjected to extensive reduction and alkylation followed by gel filtration in 5 M guanidine-HCl. Antigenically reactive H and L chains were obtained by partial reduction and alkylation followed by gel filtration in 1 M propionic acid. The 7S and 19S immunoglobulin H chains were indistinguishable by fingerprints of tryptic digests, disc electrophoretic patterns, antigenic properties, and mass (molecular weight ∼70,000), thus suggesting these two molecules to belong to the same immunoglobulin class. The shark 19S and 7S immunoglobulin L chains were indistinguishable from each other by similar criteria and were different from the H chains. These L chains exhibited the electrophoretic heterogeneity of their mammalian counterparts.
The 7S (shark immunoglobulin) molecule was shown to have a molecular weight of ∼160,000 and to consist of 2H and 2L polypeptide chains (total mass ≅180,000). The 19S molecule was shown to have a molecular weight of 800,000–900,000; therefore, there were probably five 7S subunits per 19S molecule, comparable to mammalian γM. Other reasons for considering the 7S and the 19S lemon shark molecules to belong to a class of immunoglobulins comparable to the γM class of mammals are that they both have high carbohydrate contents, and H chains of mass similar to µ chains.
The lemon shark serum proteins with electrophoretic mobilities comparable to gamma G of mammals were not related to the immunoglobulins of this species. These proteins had no antibody activity and had no antigenic or chemical similarity to either the H chains, the L chains, or the intact immunoglobulin molecules from the lemon shark.
THE REGULATION OF PINOCYTOSIS IN MOUSE MACROPHAGES
Authors: Cohn Zanvil A. , Parks Eileen 
Published: June 2004

Bovine sera contain factors which are capable of agglutinating mouse erythrocytes and stimulating the pinocytic activity of cultivated mouse macrophages. The hemagglutinating and vesicle-inducing activities of sera increase with the age of the animal and are absent in fetal calf serum.
The majority of this material is recovered in globulin fractions prepared with Na2SO4-(NH4)2SO4 and is absent in bovine fraction II. It behaves as a macroglobulin in studies employing zone electrophoresis, Sephadex G-200 filtration, sucrose density gradient centrifugation, and in its sensitivity to 2-mercaptoethanol and heat.
Absorption of bovine sera with either mouse erythrocytes or spleen cells removes the hemagglutinating and pinosome-inducing properties of the sera.
The addition of small quantities of bovine macroglobulin to mouse macrophages results in a stimulation of pinocytic activity, phase-dense granule formation and the cellular content of three acid hydrolases.
In the presence of heat-labile factors, the macroglobulin initiates the hemolysis of mouse erythrocytes and the cytolysis of mouse macrophages.
This material is thought to represent an interspecies γM-type antibody directed against common antigenic determinants on the mouse erythrocyte and macrophage surface.
PRIMARY IMMUNE RESPONSE IN GRAFTED CELLS
Authors: Nisbet Norman W. , Simonsen Morten 
Published: June 2004

The primary immune response elicited by host antigens in a grafted population of immunologically competent cells has been compared in conditions where the same dose of parental cells were grafted simultaneously to F1 hybrid embryos of 13 or 17 days of age. The enlarged chimeric spleens harvested 4 days later were analyzed for donor cell proliferation by using the sex chromosomes as karyological markers, and for proliferation of immunological activity by means of transfer to secondary hosts of the same genotype.
Whereas the total number of dividing donor cells were on the average 16 times higher in 17-day than in 13-day hosts, the recovery of immunological reactivity showed a 6- to 7-fold difference in the opposite direction.
The experiments cast doubt on the proposition that cellular proliferation is necessary for development of a primary immune response. They suggest that there exists an alternative way in which a primary immune response may unfold from involving a few to involving a much larger number of cells.
A PLASMIN-SPLIT FRAGMENT OF C'3 AS A NEW CHEMOTACTIC FACTOR
Authors: Ward Peter A. 
Published: June 2004

When streptokinase and highly purified human plasminogen are added to human serum or to partly purified or highly purified preparations containing the third component of complement (C'3), either rabbit or human, a chemotactic factor is generated. This chemotactic factor is a split product of C'3 and is dialyzable, fast moving electrophoretically, slowly sedimenting in sucrose density gradient ultracentrifugation, and has an approximate molecular weight of 6000. It is calculated that this fragment accounts for approximately 4% of the intact molecule.
The C'3 fragment has the following biologic properties: It is chemotactic for rabbit PMN's in vitro, it causes accumulation of PMN's in vivo, and it increases vascular permeability in rat skin.
In addition to generating a chemotactic factor, plasmin destroys the complement-associated chemotactic factor that is a trimolecular complex consisting of the fifth (C'5), sixth (C'6), and seventh (C'7) components of complement. This has been shown by a loss of chemotactic activity, as well as a dissociation of the C'5, C'6, C'7 complex and a destruction of C'6 hemolytic activity.
The biologic significance of the plasmin-generated chemotactic factor is discussed in relation to other recently discovered biologically active fragments of C'3.
THE EFFECT OF MALNUTRITION ON THE INFLAMMATORY RESPONSE
Authors: Taylor Patricia E. , Tejada Carlos , Sánchez Margarita 
Published: June 2004

In the present experiments, Selye's granuloma pouch technique was applied to the study of the effect of host nutritional state on inflammation and the local tissue response. The normal response of well-nourished laboratory rats fed a diet containing 28% protein to the injection of 1% croton oil into a preformed subcutaneous air sac involved the accumulation of hemorrhagic exudate in the pouch lumen and the progressive thickening of the pouch wall, with the proliferation and maturation of fibroblasts and the eventual laying-down of collagen. In malnourished animals, fed a diet containing only 3–4% protein but adequate in all other nutrients, the above reactions were inhibited. This inhibitory effect was encountered after a relatively short period of deficiency and became more marked as the deficiency progressed. No consistent, clear-cut difference was seen in the leukocytic or neutrophilic response between the two dietary groups after the injection of 1% croton oil.
A significantly higher proportion of accidental bacterial infections was found in the pouches of malnourished animals than in those of well-nourished animals. This was considered to be a possible consequence of the depressed inflammatory response in malnourished rats.
The advantages of the granuloma pouch as an experimental procedure for the study of local reactions to different noxae, and the influence of malnutrition on these reactions have been discussed and suggestions for future studies presented.
THE IMMUNE RESPONSE TO A HYBRID PROTEIN MOLECULE
Authors: Rajewsky K. , Rottländer Elke , Peltre G. , Müller Brigitte 
Published: June 2004

Upon immunization with LDH-III (subunit composition AABB) rabbits produce anti-A and anti-B antibodies in comparable amounts. These antibodies fit equally well to the hybrid enzyme and to LDH-V (AAAA) or LDH-I (BBBB) respectively, as tested by passive hemagglutination inhibition. No antibodies reacting with both LDH-I and LDH-V were detected. A minority of hybrid-specific antibodies was, however, present in the sera.
Animals primed with LDH-III respond regularly to a boosting injection of LDH-V with the production of large amounts of anti-A (but not anti-B) antibodies. A similar injection of LDH-I stimulates (if it has any effect at all) the production of anti-B antibodies only. Stimulation with one of the pure types does not impair a subsequent response to the other.
The majority of the animals primed with LDH-III responded not at all or weakly to a boosting injection of LDH-I, though antibodies to LDH-I were present in the sera at the time of stimulation. This effect can hardly be explained on the basis of serological sepcificity.
Hyporesponsiveness to LDH-III can be induced by injection of LDH-V into the newborn. Both anti-A and anti-B titers are equally depressed. Within the dose range tested, LDH-I does not exert any tolerogenic action with respect to LDH-III.
The carrier property of subunit A is evident in the induction of both immunity and tolerance to LDH-III. The early phase of the immune response to the hybrid enzyme may be carrier-specific, and receptors for the haptenic subunit B may not exist at that stage.
QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS
Authors: Wilson Darcy B. , Silvers Willys K. , Nowell Peter C. 
Published: June 2004

The influence of the immunologic status of the cell donors on the proliferative behavior of rat lymphocytes in the mixed lymphocyte interaction has been studied.
Mixed cultures of cells from various parental and F1 combinations having morphologically distinguishable sex chromosomes exhibited unidirectional proliferative reactivity. The mitotic figures were predominately of parental origin.
Lymphocytes from donors made tolerant at birth to homologous transplantation isoantigens were specifically unreactive against cells bearing antigens of the tolerance inducing strain, but not to indifferent third party homologous lymphocytes.
Cells from animals that had been surgically thymectomized at birth exhibited a markedly and sometimes totally diminished reactivity against homologous lymphocytes.
Presensitization of the cell donors resulted in a curtailment of proliferative reactivity in cultures with cells bearing the immunizing antigens. This may reflect the destructive properties that lymphocytes from sensitized animals are known to possess.
The results of these experiments show that the proliferative activity of lymphocytes in the mixed lymphocyte interaction accurately reflects the immunologic status of the cell donors, and these findings provide further support for the premise that the mixed lymphocyte interaction represents a primary immunologic response by cells in culture against homologous cells bearing histocompatibility antigens.
FACTORS INFLUENCING HEMATOPOIETIC SPLEEN COLONY FORMATION IN IRRADIATED MICE
Authors: Boggs Dane R. , Marsh John C. , Chervenick Paul A. , Cartwright George E. , Wintrobe Maxwell M. 
Published: June 2004

Mice were irradiated repetitively at 6 wk intervals. The proliferative capacity of the hematopoietic stem cell compartment was studied after each irradiation and compared to that of age-matched controls which had been irradiated only once. Hematopoietic proliferation capacity was measured by determining the number of spleen colonies, splenic iron uptake, spleen weight, and volume of packed red cells 10 days after irradiation.
6 wk after the first irradiation, the hematopoietic compartment was apparently supranormal in size for, when such mice were again irradiated, their postirradiation hematopoiesis was in excess of that of the controls. Thereafter, there was a steady decline in regenerative capacity with each sequential irradiation. After the sixth irradiation, the number of spleen colonies and iron uptake were reduced to one-fifth of that of singly irradiated controls. A decline in body weight and an increase in irradiation mortality accompanied the decline in postirradiation hematopoiesis.
The degree of measured decline in hematopoietic proliferative ability was less than that observed by other investigators who studied the effect of serial transplantation of cells upon their ability to proliferate. Furthermore, even after the sixth irradiation, a marked stimulation of postirradiation hematopoiesis was induced by bleeding the animals before irradiation.
THE UPTAKE AND DIGESTION OF IODINATED HUMAN SERUM ALBUMIN BY MACROPHAGES IN VITRO
Authors: Ehrenreich Barbara A. , Cohn Zanvil A. 
Published: June 2004

Mouse peritoneal macrophages take up I*-HSA from their medium during in vitro cultivation. Conditions which promote I*-HSA uptake are the same as those which stimulate formation of pinocytic vesicles. Autoradiography of cells pulsed with 125I-HSA showed that intracellular isotope is localized in perinuclear granules, or secondary lysosomes.
Following a pulse of 125I-HSA, intracellular radioactivity decreases and the amount of TCA-soluble isotope in the medium increases correspondingly. About 50% of the intracellular isotope is lost in 5 hr. The release of isotope from pulsed cells is not inhibited by parafluorophenylalanine, 2,4-dinitrophenol or by a reduction of the serum concentration of the medium. However, the processing of ingested 125I-HSA is reversibly inhibited by reduced temperature.
The TCA-soluble radioactive material excreted by pulsed macrophages was identified as monoiodotyrosine.
ANTIGENS IN IMMUNITY
Authors: Nossal G. J. V. , Abbot A. , Mitchell Judith , Lummus Z. 
Published: June 2004

This paper describes the trapping of antigen in lymphoid follicles of rat popliteal lymph nodes as revealed by electron microscopic radioautographs following injection of 125I-labeled Salmonella adelaide flagella and other materials.
The antigen was taken up vigorously, and to an approximately equal extent, by both primary and secondary follicles. The rate of uptake was faster in preimmunized than in virgin adult rats. The bulk of the antigen in follicles was extracellular, and persisted in this location for at least 3 wk. Label was most frequently found at or near the surface of fine cell processes. Many of these were branches of dendritic follicular reticular cells. Such processes interdigitated with equally fine processes of lymphocytes, creating an elaborate meshwork. In some cases, antigen was found between lymphocytes which appeared to be in close apposition. Occasionally, a few grains appeared over lymphocyte nuclei and study of serial sections suggested that this probably represented true entry of small amounts of antigen into lymphocytes.
The characteristic "tingible body" macrophages (TBM) of germinal centers appeared to play only a secondary role in follicular antigen retention. They showed degrees of labeling over their phagocytic inclusions varying from negligible to moderately heavy. Moreover, follicles lacking or poor in TBM retained antigen just as effectively as those containing numerous TBM. The hypothesis is advanced that TBM may be derived from monocytes that migrate down from the circular sinus.
Follicular localization of three other materials was also studied, though not in such detail. These were 125I-HSA complexed to anti-HSA: 125I-labeled autologous IgG; and 125I-monomeric flagellin. All of these showed the basic features of intercellular, membrane-associated deposition noted with 125I-flagella.
The role of follicular antigen depots in immune induction is discussed. The tentative conclusion is reached that follicular antigen in a primary follicle encounters natural antibody on the surface of certain antigen-reactive lymphocytes. The resultant reaction causes blast cell transformation and eventually the genesis of a germinal center.
THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION
Authors: Byers Vera S. , Sercarz Eli E. 
Published: June 2004

A set of conditions has been described under which primed rabbit lymph nodes produce a secondary antibody response upon in vivo stimulation with a large dose of antigen, but are subsequently "exhausted;" that is, lymph node cultures prepared at intervals following the booster injection cannot be re-stimulated to display tertiary responses. Rabbits given 100-fold less antigen in the booster inoculum were able to give a tertiary response upon in vitro challenge. The system used permits neither induction nor continuation of a primary response to BSA in vitro. Since it could be demonstrated that no memory cells were generated by the booster injection within the intervals between in vivo injection and culture, the tertiary response in nonexhausted nodes must have been due to residual memory cells which remained untriggered by the in vivo booster injection.
The unresponsive state was not caused by antibody feedback.
These results are interpreted to mean that a population of memory cells can be exhausted by a supraoptimal dose of antigen, rendering the node temporarily incapable of further response. This implies that long-lived memory is not due to asymmetric division of memory cells. The source and fate of memory cells is discussed with regard to this evidence.
STUDIES ON THE PATHOGENESIS OF FEVER
Authors: Kozak Marilyn Sue , Hahn Helmut H. , Lennarz William J. , Wood W. Barry 
Published: June 2004

Small quantities of highly purified granulocytic pyrogen have been separated from contaminating proteins by disc electrophoresis in polyacrylamide gel. The biologically active material thus isolated was shown to be electrophoretically homogeneous at pH 9 and pH 3.8.
Earlier work on the chemical properties of the pyrogen molecule has been extended to include: (a) estimation of its molecular weight by gel filtration; (b) demonstration of free sulfhydryl groups essential for its biological activity; and (c) evidence that it is not inactivated by exhaustive extraction with ethanolether or n-heptane.
AN INTESTINAL THREADWORM AS A RESERVOIR AND INTERMEDIATE HOST FOR SWINE INFLUENZA VIRUS
Authors: Shotts Emmett B. , Foster John W. , Brugh Max , Jordan Helen E. , McQueen James L. 
Published: June 2004

A laboratory model exemplifying Shope's concept of virus carriage by helminths was developed using Strongyloides ratti (Sandground, 1925), swine influenza virus, and caesarean-originated, barrier-sustained (COBS) mice and rats.
It was shown that S. ratti can act as a carrier of swine influenza virus and infect mice, despite the fact that the nematode has undergone a complete life cycle after exposure to virus in infected rats.
COBS rats were inoculated with the virus via the intranasal route and subsequently infected with S. ratti. The larvae and eggs found in the feces collected from these rats were allowed to develop in vitro. These second generation filariform larvae were then inoculated subcutaneously into COBS mice. At necropsy, 5–8 days postinoculation, swine influenza virus was isolated from 15% of the mouse lungs. In control studies, swine influenza virus was not isolated from the feces of the COBS rats which served as a source of both unexposed and exposed S. ratti. Swine influenza virus was recovered in vitro from S. ratti homogenates. It is suggested that this laboratory model be used to study more closely the various aspects of the ecology of virus-helminth relationships in vertebrate hosts.
THE DERIVATION OF TWO DISTINCT ANAPHYLATOXIN ACTIVITIES FROM THE THIRD AND FIFTH COMPONENTS OF HUMAN COMPLEMENT
Authors: Cochrane C. G. , Müller-Eberhard H. J. 
Published: June 2004

Anaphylatoxin activity was derived from both human C'5 and C'3 molecules. This was achieved in the case of C'5 by interaction with trypsin or with EAC'4, oxy2a, 3. The smooth muscle-contracting material obtained from the treated C'5 was found to be a fragment of approximately 9,000–11,000 molecular weight. Its action was inhibited with antihistamine. The trypsinized C'5 also increased vascular permeability in guinea pig skin.
When human C'3 was incubated with C'3 inactivator complex, which consists of a cobra venom protein and a ß-globulin of human serum, anaphylatoxin activity was observed. The activity was associated with a fragment cleaved from the C'3 molecule, having a molecular weight of between 6,000 and 15,000 as determined by gel filtration techniques. Similar activity was derived from C'3 by the C'3-converting enzyme in free or in cell-bound form.
The C'5 anaphylatoxin failed to cross-desensitize guinea pig ileum to the contracting capacities of C'3 and guinea pig anaphylatoxin and vice versa. Anaphylatoxin prepared from C'3 by all methods mentioned above caused cross-desensitization to the other C'3 derivatives, but failed to desensitize to guinea pig anaphylatoxin.
STUDIES ON HUMAN ANTIBODIES
Authors: Yount William J. , Dorner Marianne M. , Kunkel Henry G. , Kabat Elvin A. 
Published: June 2004

The composition of various isolated antibodies was determined by quantitative analyses for heavy chain subgroups and light chain types. Certain antibodies such as anti-tetanus toxoid and anti-A isoagglutinins were predominantly of the major γG1-type. However, a high preponderance of molecules of the minor γG2-subgroup was found for antibodies to dextran, levan, and teichoic acid. These findings explain some unusual features previously noted for anti-dextrans such as weak PCA reactions and lack of Gm antigens.
Studies of several isolated antibodies from single heterozygous individuals showed a selective absence of genetic markers in certain antibodies and their presence in others. The "allelic exclusion" principle was clearly evident in the isolated antibodies of two different individuals.
Large differences in the ratio of kappa to lambda light chains were observed for the same type of antibody from different individuals. Subfractionation of dextran antibodies by affinity for specific glycosidic linkage or combining site size produced marked changes in the ratios. The isomaltohexaose eluates of the dextran antibodies from two subjects were primarily kappa and the isomaltotriose eluates were predominantly lambda.
The one anti-levan antibody studied was uniquely homogeneous, consisting exclusively of γG2-heavy chains and kappa light chains. By these criteria as well as others, it closely resembled myeloma proteins.
INTRAPHAGOCYTIC ß-N-ACETYLGLUCOSAMINIDASE
Authors: Ayoub Elia M. , McCarty Maclyn 
Published: June 2004

The ß-N-acetylglucosaminidases of rabbit and human polymorphonuclear leukocytes and of rabbit alveolar macrophages have been studied in comparison with the ß-N-acetylglucosaminidase derived from a soil bacillus which had previously been shown to hydrolyze the group-specific polysaccharide of Group A streptococci. The phagocytic enzymes are lysosome associated and have an acid pH optimum. In contrast, the soil bacillus enzyme is an extracellular product, has a higher pH optimum, and is probaby of smaller molecular size.
When tested on p-nitrophenyl-ßN-acetylglucosaminide as substrate, the Km of the phagocytic enzymes is slightly higher than that of the soil bacillus. However, there were extreme differences in their effect on the Group A streptococcal polysaccharide. Thus, 5 x 106 units of the alveolar macrophage enzyme were required to hydrolyze the available N-acetylglucosamine of 1 mg of polysaccharide in 18 hr, while 100 units of the soil bacillus enzyme were sufficient to achieve this hydrolysis. In both cases, the serological reactivity of the polysaccharide is altered with loss of Group A specificity and acquisition of a new specificity characteristic of A-variant streptococci. Possible explanations for differences in the activity of the enzymes are considered, and the role of the phagocytic enzymes in intracellular degradation of Group A streptococci is discussed.