bluuebunny/crossref_metadata_2025_split huggingface dataset:
ISOLATION OF A FRAGMENT (C3a) OF THE THIRD COMPONENT OF HUMAN COMPLEMENT CONTAINING ANAPHYLATOXIN AND CHEMOTACTIC ACTIVITY AND DESCRIPTION OF AN ANAPHYLATOXIN INACTIVATOR OF HUMAN SERUM
Authors: Bokisch Viktor A. , Müller-Eberhard Hans J. , Cochrane Charles G. 
Published: June 2004

A small fragment of C3, called C3a, which has smooth muscle contracting activity, was isolated by three different methods. At pH 8.6, C3a behaved as cation, and using the Archibald method, its mol wt was determined to be 7000. A specific antiserum to C3a showed the fragment to be antigenically distinct from the rest of the C3 molecule, i.e., the C3b portion. The same antiserum and an anti-whole C3 were able to inhibit the biologic activity of C3a. In addition to anaphylatoxin activity, leukocyte chemotactic activity was shown to reside in C3a. Treatment with trypsin caused the cationic fragment to become anionic and abolished the anaphylatoxin but not the chemotactic activity.
C3a fragments with identical biologic activity and comparable cationic properties, as determined by acid disc electrophoresis, were obtained by treatment of C3 with C3 convertase, C3 inactivator complex, trypsin, and plasmin. Thrombin produced a similar C3 fragment which was inactive. It was concluded that C3a corresponds to an unusually basic portion of C3 which may be liberated by attack of a variety of enzymes on a highly susceptible region of the native C3 molecule.
C3b was cleaved by trypsin and less efficiently by thrombin or plasmin into two antigenically distinct pieces: the larger C3c fragment corresponding to ß1A and the smaller C3d fragment to α2D of aged serum. The c- and the d-fragments were separated and characterized.
Isolated C3a rapidly lost its anaphylatoxin activity when treated with small amounts of a partially purified, thermolabile 10S α-pseudoglobulin of human serum. The conditions of inactivation suggested an enzymatic reaction. The anaphylatoxin inactivator also destroyed the activity of C5-derived anaphylatoxin and of lysyl bradykinin.
THE REQUIREMENT OF MORE THAN ONE ANTIGENIC DETERMINANT FOR IMMUNOGENICITY
Authors: Rajewsky K. , Schirrmacher V. , Nase S. , Jerne N. K. 
Published: June 2004

Rabbits primarily stimulated with a BSA (bovine serum albumin)-sulfanilic acid complex will produce a good secondary response to the sulfanilic acid hapten if the carrier used in the secondary stimulus is again BSA, and not if the secondary carrier is HGG (human gamma globulin). In the latter situation, a good secondary response is obtained, however, if the rabbits are pretreated a few weeks earlier with free HGG. We conclude that the immune stimulus involves the recognition of carrier determinants unrelated to the hapten.
As the receptors for recognition of unrelated determinants are probably situated on different cells, we suggest that the immune stimulus leading to antibody formation requires the interaction of two antigen-bridged cells.
COMPARISON OF REACTIONS OF ANTIBODIES TO RAT COLLAGEN AND TO RAT KIDNEY IN THE BASEMENT MEMBRANES OF RAT RENAL GLOMERULI
Authors: Rothbard Sidney , Watson Robert F. 
Published: June 2004

By in vivo and in vitro methods of immunofluorescence, antibody to rat collagen and to rat kidney show the same regular, linear fluorescence following the outlines of the renal glomerular capillaries. Absorption of each antiserum with its homologous antigen completely removed the antibody for immunofluorescence, while absorption with the heterologous antigen had no effect. The nephrotoxicity persisted in the anti-kidney serum absorbed with collagen.
By pretreatment of frozen normal rat kidney sections with various enzymes followed by immunofluorescence, it was shown that trypsin and hyaluronidase had no effect on the subsequent fluorescence of either antibody; papain reduced the fluorescence; and pepsin and Pronase acted on both antigens so that no fluorescence was present. One preparation of neuraminidase, derived from V. cholerae, reduced fluorescence of both antibodies in some preparations, but the same enzyme derived from influenza virus or C. perfringens had no effect on either. Collagenase completely prevented fluorescence of the antibody to collagen and had no effect on that to rat kidney.
The findings in this study show that the antibody to collagen is directed to collagen in rat renal glomerular basement membranes and that the antibody to rat kidney reacts with some antigen other than collagen in these membranes.
HUMAN IMMUNITY TO THE MENINGOCOCCUS
Authors: Gotschlich Emil C. , Goldschneider Irving , Artenstein Malcolm S. 
Published: June 2004

High molecular weight group A and group C meningococcal polysaccharides had no significant toxicity for mice or guinea pigs. Furthermore, these polysaccharide preparations contained negligible amounts of biologically active endotoxin.
The high molecular weight group A and group C meningococcal polysaccharides were excellent immunogens in six human volunteers. Antibodies belonging to the immunoglobulin classes IgG, IgM, and IgA were produced.
These antibodies were highly meningococcocidal in the presence of complement.
THE ROLE OF MYCOBACTERIA AND THE EFFECT OF PROTEOLYTIC DEGRADATION OF THYROGLOBULIN ON THE PRODUCTION OF AUTOIMMUNE THYROIDITIS
Authors: Weigle W. O. , High Gloria J. , Nakamura R. M. 
Published: June 2004

Data are presented which suggest that the initial event involved in experimental autoimmune thyroiditis following injection of rabbits with homologous thyroglobulin in complete Freund's adjuvant is alteration of the thyroglobulin. Alteration of the thyroglobulin does not occur during incorporation into the adjuvant or in vitro storage in the adjuvant, and the mycobacteria in the adjuvant have no direct effect on the thyroglobulin. Most likely, the alteration results from an increase in hydrogen ion concentration within cells or local areas in the granuloma and the subsequent action of proteolytic enzymes. These conditions are probably established in the granuloma as the result of neutrophilic response to the mycobacteria in the adjuvant.
Rabbits injected with aqueous preparations of homologous thyroglobulin partially degraded in vitro with pepsin at acid pH produced antibody to native thyroglobulin and developed thyroiditis. Most of these rabbits responded to a subsequent injection of native thyroglobulin given 1 month later.
IMMUNE RESPONSES IN VITRO
Authors: Pierce Carl W. 
Published: June 2004

A cell suspension culture system combined with a procedure which separates most macrophages from lymphoid cells was used to investigate some of the cellular requirements for direct and indirect plaque-forming cell responses by nonprimed and primed mouse spleen cells in vitro.
The plaque-forming cell response to heterologous erythrocytes in cultures of nonprimed spleen cells required both macrophages and lymphoid cells for its development. A significant indirect plaque-forming cell response did not develop in cultures of nonprimed spleen cells.
In contrast, cultures of separated or macrophage-poor lymphoid cells from primed mice exhibited increasing responses relative to the response of unseparated spleen cells as the interval after priming increased. The cultures of separated lymphoid cells were not entirely free of phagocytic cells. Despite some evidence which suggests that these phagocytic cells had little function in the response, one cannot ascertain whether the lymphoid cells were responding directly to a second contact with antigen or whether the few contaminating phagocytic cells were performing a function essential to the response by the lymphoid cells. Physiologically different populations of cells appear to develop after priming and are able to respond in vitro in a macrophage-poor culture. Some of the properties of these populations suggest that they are "memory cell" pools containing precursors of direct and indirect plaque-forming cells highly susceptible to a second antigenic stimulus.
THE NATURE OF THE ANTIGENIC DETERMINANT IN A GENETIC CONTROL OF THE ANTIBODY RESPONSE
Authors: Mozes Edna , McDevitt Hugh O. , Jaton Jean-Claude , Sela Michael 
Published: June 2004

The response of inbred mouse strains to two polypeptides derived from multichain polyprolines, (T,G)-Pro--L and (Phe,G)-Pro--L, is different from the response of the same mouse strains to a similar series of polymers built on multi-poly-D,L-alanyl--poly-L-lysine, although the same short sequences of amino acids are attached to the side chains of the polypeptides in the two series. These results indicate that a portion of the side chain (e.g. polyalanine or polyproline) participates in the antigenic determinant. This was confirmed by studying the response of different mouse strains to two kinds of polypeptides: (T,G)-Pro-A--L 717 and 718 and (T,G)-A-Pro--L 719 and 721.
Antibody assay of antisera to (Phe,G)-Pro--L with the cross-reacting antigens (T,G)-Pro--L and (Phe,G)-A-L indicates that different inbred mouse strains make antibodies specific for different parts of the same polypeptide. Thus, antibody from DBA/1 mice reacts almost exclusively with the (Phe,G) sequence, while SJL antisera bind only (T,G)-Pro--L and fail to bind (Phe,G)-A-L.
The immune responses to the same amino acids on two different polypeptides (i.e. A--L and Pro--L) appear to be under separate genetic control.
C3 LEUKOTACTIC FACTORS PRODUCED BY A TISSUE PROTEASE
Authors: Hill Jeffrey H. , Ward Peter A. 
Published: June 2004

When various rat tissues are incubated in homologous serum, a factor chemotactic in vitro for neutrophils is generated. The amount of chemotactic activity is a function of duration of incubation and the quantity of heart tissue or serum employed. Addition of trypsin inhibitor or antibody to the third component of complement (C3) precludes generation of chemotactic activity. In addition, antibody to C3 ablates chemotactic activity even after its formation.
Purified human C3 (ß1C-globulin) effectively substitutes for serum in the generation of chemotactic activity by heart tissue. The active product, as determined by gel filtration or by ultracentrifugal analysis in a sucrose density gradient, appears to be a cleavage product of C3 with a molecular weight of approximately 14,000. In addition, a larger C3 fragmentation product varying in molecular weight, depending upon experimental conditions, is also found.
The protease in rat heart tissue capable of cleaving C3 into chemotactic fragments is a serine esterase with trypsin-like properties and can be inhibited by organophophorous compounds or trypsin inhibitors. The use of amino acid esters in the manner of competitive substrate inhibition confirms the trypsin-like nature of the protease.
The presence of a protease in heart, and presumably in other normal tissues, capable of fragmenting C3 into factors with chemotactic activities may explain the development of the acute inflammatory response when tissues are non-specifically injured. If true, this would reinforce the role of the complement system in the mediation of nonimmunologically induced inflammation.
LACTOFERRIN, AN IRON-BINBING PROTEIN NI NEUTROPHILIC LEUKOCYTES
Authors: Masson P. L. , Heremans J. F. , Schonne E. 
Published: June 2004

Lactoferrin, an iron-binding protein previously shown to occur in many external secretions, is identified as one of the major proteins present in human and guinea pig neutrophilic polymorphonuclear leukocytes.
The identification of this protein in leukocyte extracts was based upon a comparison of its electrophoretic, antigenic, and iron-combining properties with the corresponding properties of the same protein isolated from human and guinea pig milk. Immunochemical quantitations showed that lactoferrin occurs in human neutrophilic leukocytes at the concentration of 3 µg per 106 cells. Tissue cultures from guinea pig bone marrow and spleen actively synthesized the protein, as shown both by net production of lactoferrin and incorporation of labeled amino acids into the protein. Immunohistochemical data indicate that lactoferrin first appears in myeloid cells at the stage of the promyelocyte.
SMALL INTESTINAL MUCOSAL CELL PROLIFERATION AND BACTERIAL FLORA IN THE CONVENTIONALIZATION OF THE GERMFREE MOUSE
Authors: Khoury Kenneth A. , Floch Martin H. , Hersh Theodore 
Published: June 2004

The relationship between intestinal colonization and the small bowel mucosal cellular proliferation rate during conventionalization of the germfree mouse was examined. 16 mice were maintained under standard germfree conditions, and 54 others were conventionalized. Migration of the small bowel epithelial cells was followed by radioautography with administration of tritiated thymidine. Colonization was followed by qualitative and quantitative bacteriological fecal analyses. The percentages of the villi labeled (as determined by cell count) 24, 48, and 72 hr following thymidine administration showed immediate progression in the conventionalized animals from the germfree villus migration time (4 days) toward the conventional villus migration time (2 days). The epithelial migration rate of animals conventionalized for 8 days was comparable to that of conventional animals.
After conventionalization, aerobic and anaerobic organisms undergo a period of extensive multiplication; however, 72 hr later the number of these microorganisms cultured in the stool decrease and are similar to those recovered from normal animals. Coliforms and streptococci are recovered in large numbers only in the first days after conventionalization, while the Bacteroides are first recovered in significant numbers on the fifth day of conventionalization. Except for smaller numbers of Bacteroides, the bacterial populations in the stools of the conventionalized animals are qualitatively and quantitatively similar by the eighth day of conventionalization to those of true conventional mice.
Adaptive balance between cell proliferation and sloughing, and thus migration rate, begins immediately after conventionalization of germfree animals as bacterial populations establish themselves throughout the gastrointestinal tract, and results in a doubling of the mucosal cell turnover after 8 days. At this time both the small intestinal epithelial cell migration rate and the intestinal microflora are similar to those of conventional animals.
PHYSICAL, CHEMICAL, AND ULTRASTRUCTURAL STUDIES OF WATER-SOLUBLE HUMAN AMYLOID FIBRILS
Authors: Pras Mordechai , Zucker-Franklin Dorothea , Rimon Abraham , Franklin Edward C. 
Published: June 2004

Amyloid fibrils were isolated from the tissues of nine patients with amyloidosis in a state of high purity by homogenization of the tissue followed by extraction with distilled water. Physical, chemical, and ultrastructural studies suggest that amyloid fibrils from different individuals resemble each other, but are not identical. In tissue sections as well as by negative staining of isolated fibrils, morphologic variations were observed. Among the isolated fibrils at least three types were noted. The majority resembled those described previously. However, one subject had two types of fibrils which differed in size and appearance.
Most of the preparations sedimented as a single component with a sedimentation coefficient of 45–50S or as a larger polymer. However, two of the preparations had sedimentation coefficients of 8–9S, and a third one had a major 95S component and a minor 9S fraction.
While the preparations of amyloid were not sufficiently pure for amino acid analyses, peptide maps demonstrated differences among amyloid preparations from different subjects.
The amyloid fibrils in their native state proved to be remarkably resistant to digestion by a number of proteolytic enzymes. Several chemical methods were tried to produce smaller subunits. Of these, the most successful one was the use of 0.1 M NaOH which yielded a smaller, soluble fraction with sedimentation coefficients ranging from 1.1 to 2.8S. Accompanying this degradation, there was little loss of peptides or carbohydrates. Based on the results of the chemical analyses, it is estimated that the subunit produced by sodium hydroxide had a molecular weight of approximately 35,000–40,000.
QUANTITATIVE INVESTIGATIONS OF IDIOTYPIC ANTIBODIES
Authors: Daugharty Harry , Hopper John E. , MacDonald A. Bruce , Nisonoff Alfred 
Published: June 2004

Specifically purified anti-p-azobenzoate antibodies of the IgG class from individual rabbits were used to elicit anti-idiotypic antibodies in recipient rabbits. Allotypes of each donor and recipient were matched. When polymerized antibodies were used for immunization, more than 80% of the recipients responded with the formation of antibodies that precipitated the monomeric donor antibody. Percentages of precipitable molecules in the donor antibody population (D) varied from 4 to 56. As little as 4% was readily detectable by the Ouchterlony method or precipitin test. Specificity of the reaction was tested by double diffusion in agar gel against a panel of purified antibenzoate antibodies from 14 heterologous rabbits and, quantitatively, in three systems by measurement of the extent of coprecipitation of heterologous, radiolabeled antibenzoate antibodies. No cross-reactions were observed. Reactions were shown to be attributable to antibenzoate antibodies in the donor serum, and contributions of allotypic reactions were excluded. In three systems investigated quantitatively, and in one studied qualitatively, two recipients of the same donor antibody produced anti-antibody that reacted with essentially the same subfraction of the donor antibody population. The findings that only a portion of the D population is immunogenic, and that the same subfraction is frequently immunogenic in different recipients, suggest that the immunogenic population comprises a limited number of homogeneous groups of antibody molecules. This is supported by the small number of bands usually observed by the Ouchterlony technique.
Quantitative methods of analysis should provide an approach to the study of cell populations producing antibodies of a particular idiotype.
BINDING BETWEEN COMPONENTS OF THE TUBERCLE BACILLUS AND HUMORAL ANTIBODIES
Authors: Minden Percy , Farr Richard S. 
Published: June 2004

Studies were undertaken to find a substance or substances for use in primary binding types of tests to detect humoral antibodies in rabbits and monkeys exposed to the tubercle bacillus that would distinguish between strains of mycobacteria. The antigen employed was a component of the 5159 strain of Mycobacterium tuberculosis that was obtained following sonification, ultracentrifugation, electrophoresis, and elution from a preparative polyacrylamide column. When the antigen was labeled with 131I, specific binding was observed in sera from immunized rabbits and BCG-protected rhesus monkeys by the radio-gel electrophoresis and ammonium sulfate tests.
This component was partially characterized, and its major antigenic determinants were associated with anionic mucopolysaccharides. Electrophoretically at pH 8.3 it migrated anodally to albumin, its molecular weight was between 9,000 and 12,000, and it was soluble in 50% saturated ammonium sulfate. Binding to antibody was destroyed after treatment with Pronase, but not after DNase or RNase.
Inhibition of the reaction, as measured by the ammonium sulfate test, between the 131I-labeled component and antisera from rabbits that had been immunized with sonicated 5159 organisms, was studied. These experiments demonstrated a capacity to define subtle similarities and differences among different mycobacteria and mycobacterial components. Some microorganisms not clearly related to mycobacteria also partially inhibited this reaction, suggesting that they shared antigenic groups with the component derived from 5159 organisms. The studies described suggested the advisability of using direct primary tests and purified components of mycobacteria to differentiate further the antigenic groups between individual pathogenic mycobacteria and between pathogenic and nonpathogenic organisms.
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Lee Chi-Jen , Dubos Rene 
Published: June 2004

Physicochemical and immunological techniques have been used in an attempt to characterize a filterable agent, separated from the intestines of mice raised under ordinary conditions of husbandry, which produces a lasting depression of weight in specific pathogen-free (SPF) mice when administered to them orally shortly after birth. Although this agent has not yet been identified, it will be tentatively designated here as enterovirus.
The mouse enterovirus can be readily sedimented by ultracentrifugation and by precipitation at pH 4.3; it does not pass through cellophane membranes. Its infective power is completely destroyed by ultraviolet radiation, but is resistant to heating at 56°C, exposure to ether, treatment with trypsin, ribonuclease, and deoxyribonuclease.
Dialysis and treatment with ether and nucleases greatly increase the infective activity of the intestinal filtrates containing the enterovirus, a finding which suggests that these procedures eliminate or destroy some inhibitory substance(s).
The mouse enterovirus causes hemagglutination of mouse red blood cells. When injected into rabbits, it elicits in them an immune response that renders their serum capable of neutralizing its weight-depressing activity. As measured by inhibition of hemagglutination or complement fixation, the sera of infected mice do not exhibit any significant activity against usual mouse viruses.
Centrifugation of the mouse enterovirus in 50%–20% sucrose gradient gave almost complete recovery of the infectivity and of hemagglutinating activity in the same fraction. In contrast, the protein content of the material was distributed through the various fractions. Consequently, this procedure resulted in a marked increase of specific activity.
GENETIC INFLUENCE ON THE DEVELOPMENT OF RENOPRIVAL HYPERTENSION IN PARABIOTIC RATS
Authors: Knudsen K. D. , Iwai J. , Heine M. , Leitl G. , Dahl L. K. 
Published: June 2004

Rats from two strains with opposite constitutional predisposition to hypertension were joined in parabiosis and one partner was nephrectomized. The influence of genetic factors and of diet on the blood pressures of the two classes of parabionts, operated and intact, indicated that renoprival hypertension occurred with equal frequency in rats from both strains; that the development of renoprival hypertension depended on the influence from an intact S partner, or on a high salt intake, or on both.
A nephrectomized S rat developing renoprival hypertension did not induce high blood pressure in its intact R partner. In this respect renoprival hypertension differs from salt and renal hypertension.
The findings are interpreted to mean that the hypertensinogenic agent specific for S rats is produced by S kidneys.
IMMUNOLOGICAL EFFECTS OF THERMAL INJURY
Authors: Rapaport Felix T. , Sampath Angus , Kano Kyiochi , McCluskey Robert T. , Milgrom Felix 
Published: June 2004

Unilateral thermal injury to guinea pig testes has elicited the formation of organ- and species-specific antibodies against a testicular antigen. The antibodies were of an IgG1 nature, and reacted with autologous as well as homologous testicular extracts.
A significant number of burned animals showed pathological changes in the contralateral testis, which were similar to those observed after the induction of experimental allergic orchitis by active immunization with testicular tissue.
These results indicate that thermal injury may be associated with autoimmunization of the host by the injured organ.