bluuebunny/crossref_metadata_2025_split huggingface dataset:
HAPTEN-SPECIFIC IgE ANTIBODY RESPONSES IN MICE
Authors: Hamaoka Toshiyuki , Katz David H. , Benacerraf Baruj 
Published: June 2004

The present studies have established conditions for the demonstration of cooperative interactions between specific T and B lymphocyte populations in the development of IgE antibody responses in vivo in mice. This has been accomplished by utilizing a system which permits the successful adoptive transfer to irradiated recipients of DNP-specific secondary IgE responses with spleen cells from suitably primed syngeneic donor mice. Thus, adoptively transferred DNP-KLH or DNP-ASC-primed spleen cells produced high levels of anti-DNP antibodies of both IgE and IgG antibody classes in response to challenge with the appropriate homologous priming conjugate but failed to develop more than meager responses to the reciprocal heterologous conjugate. However, when spleen cells from donors primed to the second carrier were concomitantly transferred with hapten-primed lymphocytes, secondary IgE ant-DNP responses were consistently obtained upon challenge with the heterologous conjugate. Moreover, we have been able to elicit augmented primary IgE anti-DNP antibody responses to either DNP-ASC or DNP-KLH after adoptive transfer of spleen cells from donors primed only to the carrier, ASC or KLH, respectively.
This adoptive transfer system has enabled us to provide direct proof for the participation of θ-bearing T lymphocytes in antibody responses of the IgE class. Thus, the capacity of ASC-primed spleen cells to effectively cooperate with the DNP-KLH-primed lymphocytes in the adoptive secondary response to DNP-ASC could be abolished by in vitro treatment of such cells with anti-θ serum plus complement. This was true not only for the anti-DNP response of the IgG antibody class, but for the IgE antibody class as well.
These studies have, furthermore, demonstrated the capacity to stimulate secondary anti-DNP antibody production in vivo by the concomitant administration of the DNP and relevant carrier determinants on separate molecules. This was more readily seen in the IgE than in the IgG antibody class. Thus, DNP-ASC-primed cells developed significant IgE, but more variable IgG, anti-DNP responses upon challenge with DNP-KLH plus unconjugated ASC. Antibody responses of both classes elicited in this manner were appreciably improved by the transfer of additional carrier (ASC)-primed cells. These and other results presented herein suggest that IgE B lymphocyte precursors may be inherently more sensitive than IgG B cells to at least certain of the functions of T lymphocytes concerned with regulatory mechanisms involved in antibody production.
CHARACTERIZATION OF SPLENIC LYMPHOID CELLS IN FETAL AND NEWBORN MICE
Authors: Spear Patricia G. , Wang Ai-Lan , Rutishauser Urs , Edelman Gerald M. 
Published: June 2004

In order to clarify the cellular events that precede the onset of immunological competence in the mouse, we have characterized and quantitated the lymphoid cells of the spleen as a function of age. Our results show that T cells and B cells both appeared in the spleens of Swiss-L mice as early as the 15th-16th day of gestation. Antigen-binding cells specific for each of three different antigens were also first detected during this same 24 h interval. The B cells and three varieties of antigen-binding cells increased in number rapidly and in parallel until about 1 wk after birth. The T cells, which were more numerous than B cells at first, increased in number somewhat more slowly.
Coincident with the onset of response to antigen, there was a further increase in B cell numbers and a decrease in the T cell to B cell ratio. The capacity to respond to antigen by cellular proliferation and synthesis of antibody did not arise until about 2 wk after birth although there were no quantitative changes in the total numbers of T cells, B cells, and antigen-binding cells between 1 and 2 wk of age. Some qualitative change, such as the functional maturation of an antigen-reactive cell, may be required during this interval for the onset of this immunological response. Although the numbers of antigen-binding cells present in fetuses and young animals were smaller than in adults, we have as yet been unable to detect any restriction in the variety of specificities that can be expressed in fetuses, either in the kinds of antigens bound or in the range of avidities with which a single antigen is bound.
SELF-REGULATION OF GROWTH IN THREE DIMENSIONS
Authors: Folkman Judah , Hochberg Mark 
Published: June 2004

Multi-cell spheroids were grown in soft agar. When each spheroid was cultured in a large volume of medium, frequently renewed, all spheroids eventually reached a dormant phase at a diameter of approximately 3–4 mm and a population of approximately 106 cells. In the dormant spheroid, newly generated cells at the periphery balanced those lost by necrosis in the center. We propose that this dormant phase is due to a gradual reduction in the ratio of surface area to volume: a size is achieved beyond which there is insufficient surface area for the spheroid to eliminate catabolites and absorb nutrients. Thus, in the face of unlimited space and of new medium, three-dimensional cell populations become self-regulating. This phenomenon contrasts with standard tissue culture in which cell populations, living on a flat plane in two dimensions, will not stop growing in the face of unlimited space and new medium because the ratio of surface area to volume remains constant.
These experiments provide a mechanism for our observations in vivo: before vascularization, solid tumors live by simple diffusion as three-dimensional spheroids or ellipsoids. They become dormant at a diameter of only a few millimeters; once vascularized, they are released from this dormant phase and begin exponential growth. Thus, tumor dormancy resulting from absence of angiogenesis in vivo, may operate by the same mechanism responsible for dormancy of spheroids in vitro.
STUDIES IN PORPHYRIA
Authors: Bradlow H. Leon , Gillette Peter N. , Gallagher T. F. , Kappas Attallah 
Published: June 2004

Patients with the genetic liver disease, acute intermittent porphyria (AIP), have a defect in the reductive transformation of steroid hormones that is manifest by the disproportionate generation of 5ß-steroid metabolites from precursor hormones. 5ß-steroid metabolites were earlier shown to be potent inducers experimentally of δ-aminolevulinate synthetase (ALAS), the mitochondrial enzyme that is rate-limiting in porphyrin synthesis, and that is found at high levels of activity in the livers of AIP patients.
In this report, the basis for the defective steroid metabolism in AIP has been shown, through studies with the 14C-labeled adrenal hormone 11ß-hydroxy-Δ4-androstenedione, to reside in a substantial deficiency of hepatic steroid Δ4-5α-reductase activity. This enzymic deficiency was found in all seven AIP patients studied, and ranged from 34% to as much as 70% below the mean enzyme activity characterizing normal subjects.
The functional consequence of the low levels of 5α-reductase activity in AIP is to divert the reductive transformation of certain natural hormones from the 5α- to the 5ß-pathway; the latter is the metabolic route through which endogenous steroids having the potential for inducing hepatic ALAS are generated. It is not presently known whether the 5α-reductase deficiency in AIP is acquired in some fashion or whether it has partial genetic determinants. It seems probable, however, that this enzymatic abnormality, coupled with the dramatic increase in hormone synthesis that occurs at puberty, may be of major importance in determining clinical expression of the latent gene defect for AIP in many individuals. The 5α-reductases for steroid hormones are known to be localized in the endoplasmic reticulum of hepatic cells and the present findings in AIP thus represent the first demonstration that an enzymic component of these membranous structures is functionally abnormal in this hereditary liver disease.
IMMUNOCHEMICAL ANALYSIS OF THE IDIOTYPES OF MOUSE MYELOMA PROTEINS WITH SPECIFICITY FOR LEVAN OR DEXTRAN
Authors: Weigert Martin , Raschke William C. , Carson Dennis , Cohn Melvin 
Published: June 2004

This paper deals solely with idiotypic determinants, the configurations of which are modified when the antibody bearing them interacts with its ligand. This phenomenon is measured as an inhibition of the reaction between anti-idiotype and idiotype.
Two points are made: (a) The assay for ligand-modifiable determinants can be used to determine the "size" of the combining site. This is illustrated here with the anti-α(1 → 6) dextran mouse myeloma immunoglobulin W3129. Whether the interaction between a homologous series of α(1 → 6) oligosaccharide ligands and the combining site of W3129 is measured by inhibition of precipitation with α(1 → 6) dextran (4) or of binding of W3129 to anti-W3129 idiotype, the finding is the same. The order of inhibition is isomaltohexaose = isomaltopentaose &gt;&gt; isomaltotetraose &gt; isomaltotriose &gt;&gt;&gt; isomaltose. The combining site is optimally complementary to isomaltopentaose.
(b) Cross-idiotypic specificity is closely correlated with cross-combining specificity; the converse is not true. This is illustrated here with three groups of mouse myeloma immunoglobulin, each specific for α(1 → 3) dextran, α(1 →6) dextran, ß(2 → 1) or ß(2 → 6) levan. If a given anti-idiotypic serum cross-reacted with several myeloma proteins, they always had similar combining specificity. Thus the three proteins, J558, MOPC 104E, and UPC 102, which cross-react with anti-J558 have combining specificity for α(1 → 3) dextran; cross-reacting W3082, UPC 61, and Y5476 have specificity for levan; and cross-reacting W3129 and W3434 have specificity for α(1 → 6) dextran. This extends previous studies with proteins specific for phosphorylcholine (7) or γ-globulin (8). As expected, the converse is not true, for proteins may have combining specificity for α(1 → 6) dextran e.g. QUPC 52, or levan e.g. J606, UPC 10 and yet not carry the above-mentioned reference idiotypes.
The correlation between cross-idiotypic and combining specificity breaks down when idiotypic determinants which are not modifiable by ligand are studied. The implications of this are pointed out since most investigations deal with ligand-nonmodifiable determinants.
MECHANISM OF THYMUS-INDEPENDENT IMMUNOCYTE TRIGGERING
Authors: Coutinho Antonio , Gronowicz Eva , Bullock Wesley W. , Möller Göran 
Published: June 2004

The present experiments were performed in order to analyze the mechanism by which thymus-independent antigens (nonspecific B-cell mitogens) can induce specific immune responses to antigenic determinants present on the same molecule. The hapten NNP was coupled to the B-cell mitogen, lipopolysaccharide (LPS). The conjugate retained full mitogenic activity and bound specifically to NNP-reactive cells. NNP-LPS activated polyclonal as well as specific anti-NNP antibody synthesis, but the optimal concentrations for induction of specific anti-NNP cells were several orders of magnitude lower than the concentrations required for polyclonal activation. These low concentrations failed to activate nonspecific cells, but they induced specific thymus-independent responses of high-avidity NNP-specific cells with the typical kinetics of antigenic responses in vitro. Furthermore, hapten-specific cells were paralyzed by NNP-LPS concentrations that were optimal for induction of polyclonal activation. Specific activation and paralysis could be abolished by free hapten indicating that selective binding of NNP-LPS to hapten-specific cells was responsible for the specificity of the response. However, the triggering signal lacked specificity, since high-avidity specific anti-NNP cells could still be activated by stimulating concentrations of NNP-LPS in the presence of free hapten, even though the Ig receptor combining sites were presumably occupied by NNP.
The findings show that B cells with specific Ig receptors for the antigenic determinants on mitogen molecules preferentially bind these molecules and become activated at concentrations still unsufficient to trigger other B cells that lack specific receptors. It is suggested that activation for primary IgM responses in B cells is the result of "one nonspecific signal." This nonspecific signal is provided by the mitogenic properties of some antigens (highly thymus independent or, alternatively, by nonspecific T-cell factors (for highly T cell-dependent antigens), or both, and the surface structures responsible for triggering are not the Ig receptors. The specific Ig receptors only act as passive focusing devices for nonspecific stimuli, entitling the cell to be selectively activated, even though both the signal and the receptors for the triggering are nonspecific.
PERSISTENCE OF HAPTEN-ANTIBODY COMPLEXES IN THE CIRCULATION OF IMMUNIZED ANIMALS AFTER A SINGLE INTRAVENOUS INJECTION OF HAPTEN
Authors: Schmidt Donald H. , Kaufman Bette M. , Butler Vincent P. 
Published: June 2004

To study the fate of a low molecular weight antigen (hapten) in the circulation of animals whose sera contain antibodies specific for that low molecular weight antigen, a single injection of digoxin-3H (0.4 mg/kg) was administered intravenously to 18 rabbits. Thirteen animals (nine nonimmunized and four immunized with bovine serum albumin) served as control animals. In five rabbits which had been immunized with a digoxin-bovine serum albumin conjugate and whose sera contained digoxin-specific antibodies, the mean 12-h serum digoxin concentration was 8,300 ng/ml (control: 92 ng/ml) and the mean serum concentration 12 mo after the single injection of digoxin-3H was 85 ng/ml. In digoxin-immunized rabbits, less than 10% of the digoxin-3H was excreted in the first 10 days (control: 77% recovered in urine and feces) and the mean biological half-life of digoxin, as calculated from serum digoxin-3H disappearance curves, was 72 days (control: 3.4 days). In sera of digoxin-immunized rabbits, more than 90% of the circulating digoxin-3H was immunoglobulin bound, as determined by the double-antibody and dextran-coated charcoal methods.
The serum disappearance rate of 125I-antidigoxin antibodies was similar in nonimmunized and in immunized animals and in the presence or absence of digoxin.
It is concluded that the biological half-life of a hapten may be markedly prolonged when the hapten is bound to specific antibody. The persistence of antibody-hapten complexes in the circulation suggests that these complexes may not be deposited in tissues and raises the possibility that low molecular weight determinants may be capable of preventing or reversing the deposition of immune complexes, containing macromolecular antigens, in the tissues of experimental animals and man.
CHARACTERIZATION OF A HUMAN ACUTE PHASE PROTEIN FOUND IN ASSOCIATION WITH RUBELLA VIRUS INFECTION
Authors: Cappel Roger , Schluederberg Ann , Gifford Robert H. , Horstmann Dorothy M. 
Published: June 2004

A precipitating antigen, rho, was first detected in the blood of persons with rubella and in rubella virus-infected cell culture fluids (1). Partially purified antigens from both sources were examined and shown to have similar properties, although antigen from serum sedimented more heterogeneously, with estimated coefficients from 15 to 21 S, while that from culture fluids sedimented in the 11–14 S region. In each case, antigen was located in the ß-1 zone after electrophoresis in agarose, and at a density of 1.305 g/ml after centrifugation in CsCl. Stability characteristics were typical of protein antigens.
Immunofluorescent microscopy revealed that rubella virus induced the appearance of rho antigen scattered throughout the cytoplasm of infected cells. When cells containing antigen were exposed for 24 h to 5 µg/ml actinomycin D rho was no longer detectable, indicating the probable cellular origin of the antigen. Also, titers in medium of infected cultures showed a reduction after actinomycin treatment, but levels of the virus-specified antigen, iota, were relatively unaffected.
Rho appears to be a protein common to man and many animals. In vitro, it was induced by rubella virus and by adenovirus. In vivo, rho titers were shown to be elevated after rubella virus infection and, to a lesser extent, after infection with certain other viruses. High titers were also demonstrated in women late in pregnancy and in patients with rheumatoid arthritis. In man and the chimpanzee, the appearance and decline of rho in the blood after rubella virus infection were temporally similar to the patterns of CRP, although rho seemed to be a more sensitive indicator of infection.
The data presented indicate that rho is a newly recognized acute phase protein inducible by certain virus infections and by other unidentified stimuli present prominently in pregnancy and rheumatoid arthritis.
ALLOANTISERUM-INDUCED INHIBITION OF IMMUNE RESPONSE GENE PRODUCT FUNCTION
Authors: Shevach Ethan M. , Paul William E. , Green Ira 
Published: June 2004

It has been previously shown that alloantisera prepared by reciprocal immunization of strain 2 and strain 13 guinea pigs specifically block the activation of T lymphocytes from immune guinea pigs by antigens, the response to which is controlled by Ir genes. In this report we have examined the effect of absorption of the 13 anti-2 serum with different populations of lymphoid cells. It is unlikely that the inhibitory activity of the anti-2 serum on the proliferation of (2 x 13)F1 lymphocytes to a DNP derivative of a copolymer of L-glutamic and L-lysine (DNP-GL) is due to the presence of antibodies specific for the unique antigenic determinants (idiotypes) of clonally distributed T-lymphocyte receptors. Thus, cells obtained from a normal animal and a DNP-GL immune animal were equivalent in their absorptive capacity. Populations of T lymphocytes were ineffective in absorbing either the cytotoxic or inhibitory activity of the anti-2 serum, while L2C leukemia cells, a malignant B-cell population, were most efficient in absorbing both activities. Thus, the antigen(s) against which the cytotoxic and inhibitory activities are directed are present to a greater extent on B lymphocytes than on T lymphocytes. However, these results do not allow us to definitively determine whether the inhibitory activity of the alloantisera is due to antibodies specific for Ir gene products or antibodies specific for linked antigens in the MHC.
We also examined the effect of a number of anti-immunoglobulin reagents which had specificity for the heavy and/or light chains of guinea pig immunoglobulin on the in vitro lymphocyte proliferative response to antigen. Under conditions in which we were able to completely and specifically suppress the response of (2 x 13)F1 lymphocytes to DNP-GL with anti-2 serum, the anti-immunoglobulin reagents were devoid of inhibitory effect on the response of these same F1 cells to DNP-GL, a copolymer of L-glutamic and L-tyrosine (GT), or purified protein derivative of tuberculin (PPD). These results strongly suggest that conventional serum-type immunoglobulin is not important in antigen recognition by the T cells involved in the DNA synthetic response.
SECRETION OF PLASMINOGEN ACTIVATOR BY STIMULATED MACROPHAGES
Authors: Unkeless Jay C. , Gordon Saimon , Reich E. 
Published: June 2004

Cultured thioglycollate-stimulated peritoneal macrophages synthesize, accumulate, and continuously release high levels of plasminogen activators for at least 4 days whereas cultures of unstimulated macrophages do not; the higher specific catalytic activity of released vs. cell-associated enzyme suggests that the plasminogen activators are actively secreted. The major macrophage plasminogen activator is a serine protease of mol wt 48,000, and thus resembles the comparable enzyme released by virally transformed fibroblasts. Macrophages release a second plasminogen activator of mol wt 28,000 that is also a serine enzyme.
The secretion products released by stimulated and unstimulated macrophages have been compared by SDS-polyacrylamide gel electrophoresis after chemical labeling with 3H-DFP or biosynthetic labeling with 14C-amino acids. These procedures show that some proteins are formed in both cultures, whereas others are uniquely secreted by each type of macrophage. The serine enzymes released by the two kinds of macrophages differ in specificity and electrophoretic mobility.
CELL SURFACE IMMUNOGLOBULIN
Authors: Vitetta Ellen S. , Grundke-Iqbal Inge , Holmes Kathryn V. , Uhr Jonathan W. 
Published: June 2004

Lymphoid cells from the spleen, lymph nodes, and thoracic duct of axenic and control mice were incubated with [3H]tyrosine and synthesis and secretion of protein and Ig studied. It was found that only IgM was synthesized by cells from axenic mice whereas cells from control mice also synthesized IgG. Splenocytes from both axenic and control mice had 8S IgM on their surface. Radiolabeled splenocytes from axenic mice were incubated to determine the kinetics of release of 125I-labeled cell surface IgM and [3H]tyrosine-labeled IgM. Cell surface IgM was shed as 8S with an initial half-life of release of 5–8 h whereas [3H]tyrosine-labeled Ig was secreted as 19S with an initial half-life of 2–3 h. These findings suggest that two independent pathways are involved. It is suggested that small lymphocytes shed 8S IgM and plasma cells secrete 19S IgM.
It was observed that lymphoid cells from axenic mice synthesize a higher proportion of IgM relative to total protein. Electron microscopic examination of splenocytes from such mice revealed a markedly higher proportion of plasma cells and a paucity of lymphoblasts compared to controls. It was suggested, therefore, that axenic mice lack a population of stimulated T cells which can induce a switch from IgM to IgG synthesis and which is capable of suppressing IgM synthesis. Lymphoid cells from axenic mice synthesize and secrete less protein that coprecipitates with antigen-antibody complexes.
EFFECT OF B-CELL MITOGENS ON LYMPHOCYTE SUBPOPULATIONS POSSESSING C'3 AND Fc RECEPTORS
Authors: Möller Göran 
Published: June 2004

By the use of a rosette method allowing the detection at the cellular level of lymphocytes simultaneously binding Fc- and C'3-sensitized red cells it was found that about 70% of the rosette-forming cells from spleens of nude and normal mice possessed receptors for both Fc and C'3, whereas 30% only had Fc receptors. Very few, if any, lymphocytes possessed only C'3 receptors.
The B-cell mitogens, purified-protein derivative of tuberculin (PPD), lipopolysaccharide from Escherichia coli (LPS), and pneumococcal polysaccharide type SIII (SIII), induced marked changes of these receptor-bearing lymphocytes. PPD caused a rapid loss of cells capable of binding C'3 and a concomitant increase of only Fc-binding cells, which was detected after only 24 h. LPS and SIII induced analogous changes, but they were not detected until 48 h and were not complete until after 72 h. It is suggested that immature lymphocytes possess both Fc and C'3 receptors and lose the latter receptor upon differentiation induced by B-cell mitogens PPD. and LPS would affect different populations of B cells, PPD-activating cells that have already reached a higher differentiation stage, whereas LPS and SIII would activate more immature B cells.
UPTAKE AND REDUCTION OF OXIDIZED AND REDUCED ASCORBATE BY HUMAN LEUKOCYTES
Authors: Bigley Robert H. , Stankova Libuse 
Published: June 2004

Incubation of human leukocytes with dehydroascorbate (DHA) results in an increase in their reduced ascorbate (AA) content and hexose monophosphate shunt (HMS) activity, independent of oxygen supply. Incubation with AA induces these changes only in the presence of oxygen. The increase in HMS activity observed as cell AA increases by 1 µmol is the same during incubation with either DHA or AA.
We propose that human leukocytes take up ascorbate as DHA (AA after oxidation to DHA) and reduce it promptly to AA, and that HMS stimulation upon incubation with either AA or DHA is a result of DHA reduction.