bluuebunny/crossref_metadata_2025_split huggingface dataset:
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Lee Chi-Jen , Dubos René 
Published: June 2004

The metabolism of adenosine 3',5'-monophosphate (cyclic AMP) was studied in specific pathogen-free mice exposed to neonatal infection with mouse enterovirus or to malnutrition during early life. Metabolic activity was determined by measuring the turnover of cyclic AMP-8-14C to respiratory 14CO2, its incorporation into various organs and plasma, and the binding activity of synaptosome for cyclic AMP.
Early malnutrition increased the catabolism of cyclic AMP as measured by expiration in respiratory CO2. The level of cyclic AMP was lower in plasma and its incorporation into various tissues was decreased in infected and malnourished animals. Metabolic products of cyclic AMP were isolated from plasma by ion exchange chromatography. Cyclic AMP-8-14C had completely disappeared 9 hr after injection. Fewer metabolites of cyclic AMP were detected in infected or malnourished groups than in controls and the metabolic reaction from 5'-AMP to adenosine seemed to be slow in these animals. The ability to incorporate cyclic AMP to synaptosome was also impaired in the experimental groups.
The concentrations of brain cyclic AMP were lower in infected or malnourished animals than in controls. Depression of accumulation of cyclic AMP probably resulted from excessive activity of phosphodiesterase, rather than from impairment of adenyl cyclase. Intraperitoneal administration of theophylline brought the activity level of phosphodiesterase to normal in infected or malnourished mice; this fact probably accounted for enhanced accumulation of brain cyclic AMP.
THE PATHOGENESIS OF CHRONIC INFLAMMATION IN EXPERIMENTAL ANTIGEN-INDUCED ARTHRITIS
Authors: Cooke T. Derek , Hurd Eric R. , Ziff Morris , Jasin Hugo E. 
Published: June 2004

In an experimental arthritis induced by injection of bovine serum albumin or egg albumin into the joints of previously immunized animals, it has been demonstrated that the major portion of the radioactively labeled antigens injected was localized to avascular collagenous tissues in the joint, i.e., articular cartilage, menisci, and intra-articular ligaments. The antigens were partially eluted from the tissues with 5 M guanidine solution, but not with acid buffers or by 3 M magnesium chloride. The radioactive material eluted with guanidine was at least 80% precipitable by specific antisera.
The radioactively labeled-inducing antigen was identified on the surface of articular collagenous tissues from arthritic joints by radioautography and immunofluorescence. Rabbit immunoglobulin and C3 were demonstrated in the same sites by immunofluorescence. The presence of specific antibody in collagenous tissues was demonstrated by the selective in vitro binding of 125I-labeled-inducing antigen to menisci from arthritic joints of immunized animals.
The evidence obtained indicates that in this model of chronic arthritis, the inducing antigen persists for long periods of time in the form of immune complexes in the surface layers of the intra-articular collagenous tissue. The antigen retained in this form may be responsible for the chronicity of the synovitis by serving as a direct stimulus for the maintenance of prolonged antibody synthesis in the synovium and by providing a source of complement-fixing antigen-antibody complexes for the mediation of joint inflammation.
STUDIES ON THYMUS FUNCTION
Authors: Stutman Osias , Yunis Edmond J. , Good Robert A. 
Published: June 2004

The immune functions of neonatally thymectomized C3Hf mice exposed only temporarily to thymus function show a progressive decay with time in the absence of the thymus. The immune responses studied at different ages in the range of 100–600 days were: first-set rejection of H-2-compatible and incompatible skin allografts, second-set rejection of skin allografts, capacity of spleen cells to produce graft-versus-host reactions in F1 hybrids, resistance to infection with mouse hepatitis virus, and response of spleen cells to phytohemagglutinin in vitro. These long-term studies had the purpose of determining the duration of the restoration induced by thymus function when the mice were exposed only temporarily to it. Different models were used but the two basic ones were: (a) mice grafted intraperitoneally at 15 days of age with a syngeneic thymus that was removed surgically at 10, 20, or 30 days after grafting, and (b) mice grafted at 15 days of age with allogeneic strain A thymoma or C57BL thymus, these representing situations in which there is spontaneous rejection of the restoring graft. In all the experimental models used, the animals were restored when tested at 100 days of age, but progressively became immunologically incapacitated at 200–300 days of age. From the more controlled experiments in which the restoring thymus graft was removed surgically, the following conclusions can be drawn. (a) A short exposure to a thymus graft can produce restoration of immune functions in neonatally thymectomized mice, but this restoration is not self-sustaining in the absence of the thymus and declines progressively with age. The decline usually starts at 200–300 days of age. (b) This was especially clear in experiments in which the same animal was tested twice in its lifetime for capacity to produce graft-versus-host reactions; these animals were competent at 100 days and became incompetent at 400 days of age. (c) The shortest period of thymic exposure studied was 10 days; if vascularization of the graft is taken into account, 2–3 days of thymic function are sufficient to produce restoration. (d) The immune decay observed in the thymectomized animals exposed temporarily to thymus was more profound than the physiological decay of immunity observed in control animals of similar age. (e) Of all the tests studied, the response of spleen cells to phytohemagglutinin was to be preserved the longest in animals exposed only temporarily to thymic function.
The present results were interpreted in accordance with our previous findings indicating that a population of postthymic cells can be developed by temporary exposure of neonatally thymectomized animals to thymic function, but that this population is not self-sustaining in the absence of thymus and progressively decays by physiological attrition.
THE RELATIONSHIP OF THE CHEMOTACTIC BEHAVIOR OF THE COMPLEMENT-DERIVED FACTORS, C3a, C5a, AND C567, AND A BACTERIAL CHEMOTACTIC FACTOR TO THEIR ABILITY TO ACTIVATE THE PROESTERASE 1 OF RABBIT POLYMORPHONUCLEAR LEUKOCYTES
Authors: Becker Elmer L. 
Published: June 2004

The inhibition profiles obtained when a series of p-nitrophenyl ethyl alkylphosphonates and of p-nitrophenyl ethyl chloroalkylphosphonates were used to interfere with the chemotactic activity of polymorphonuclear leukocytes stimulated by C3a, C5a, and bacterial factor were the same as found previously when C567 was the chemotactic agent. This indicates that as in the chemotactic activity induced by C567, an obligatory step in the chemotaxis caused by C3a, C5a, and bacterial factor is the activation of proesterase 1 of the rabbit polymorphonuclear leukocyte.
C5a and C3a activate proesterase 1 of peripheral blood polymophonuclear leukocytes as measured by the increase of acetyl DL-phenylalanine ß-naphthyl esterase activity. Attempts to detect in a like manner the proesterase 1 of the same leukocytes using bacterial factor under varying circumstances have consistently failed. It is concluded that bacterial factor, for unknown reasons, is unable to activate proesterase 1 to the same extent as the complement-derived chemotactic factors.
The hypothesis of there being a quantitative difference in the ability of bacterial factor to activate proesterase 1 compared with the complement-derived factors explains the previous observations that bacterial factor can not deactivate to itself or to the complement-derived factors, although these latter factors can deactivate to themselves, to each other, and to the bacterial factor.
The quantitative difference in the ability of bacterial factor to activate proesterase 1 compared to the complement-derived factors is also associated with and explains the finding that the maximal chemotactic activity attainable when bacterial factor is the chemotactic agent is distinctly less than that obtained using either C3a, C5a, or C567.
These results indicate that the activation of proesterase 1 is a general requirement for the chemotactic activity of rabbit polymorphonuclear leukocytes with known macromolecular chemotactic agents and suggest that under several different circumstances the level of chemotactic activity attained is related to the degree of such activation.
SYNERGY AMONG LYMPHOID CELLS MEDIATING THE GRAFT-VERSUS-HOST RESPONSE
Authors: Tigelaar Robert E. , Asofsky Richard 
Published: June 2004

A mortality assay was used to quantitate graft-versus-host (GVH) reactions in sublethally irradiated (400 R) neonatal (C57BL/6 x BALB/c)F1 recipients of BALB/c lymphoid cells from various tissues. The probit of the 35 day cumulative per cent of mortality was a linear function of the logarithm of the cell inoculum for any tissue; reactivities of different tissues fell on a series of parallel lines. Peripheral blood leukocytes (PBL), the most active cells, were about 30 times as active as thymocytes, the least active cells studied; femoral lymph node cells and spleen cells were about 23 and 8 times as reactive as thymocytes, respectively. The average survival time of recipients of thymocytes who eventually died was nearly a week longer than that of recipients of comparably lethal numbers of PBL, lymph node, or spleen cells.
Mixtures of PBL and thymocytes gave levels of 35 day mortality significantly greater than those expected if the reactivities of the mixture had been merely the sum of the reactivities of the components measured separately, thereby confirming in any assay independent of host splenomegaly the synergistic interaction of thymocytes and PBL in the GVH reaction. Both populations of cells in the mixture had to be allogeneic to the host in order to observe this synergy.
The kinetics of cumulative mortality observed for mixtures of PBL and thymocytes were indistinguishable from those seen with thymocytes alone, indicating activation of the latter cell type. Finally, comparison of the relative abilities of different cell populations to cause splenomegaly on the one hand and lethal runting on the other has raised the possibility that expression of different effector functions of cell-mediated immune reactions may in fact be initiated by distinct cells.
STUDIES ON THE MECHANISM OF FEVER ACCOMPANYING DELAYED HYPERSENSITIVITY
Authors: Atkins Elisha , Feldman Joseph D. , Francis Lorraine , Hursh Ellen 
Published: June 2004

Experiments have been carried out to investigate the possible role of the sensitized lymphocyte in mediating the fevers of delayed hypersensitivity. Rabbits were made delayed hypersensitive to one of several heterologous proteins (bovine gamma globulin, bovine serum albumin, or human serum albumin) by footpad injection of antigen or antigen conjugated with dinitrophenol and incorporated in complete Freund's adjuvant. At intervals after sensitization, various tissues were removed, and single cell suspensions were incubated overnight with either carrier protein or conjugate in vitro. Release of an endogenous pyrogen (EP) was assayed by intravenous injection of the supernatant fluid into unsensitized rabbits. Of the tissues tested only those containing both lymphocytes and pyrogen-producing cells, blood, spleen, and draining lymph nodes, released detectable amounts of EP when incubated with antigen in vitro. Incubation of normal blood cells with specifically sensitized lymphocytes and antigen also resulted in significant release of pyrogen. Similarly, blood leukocytes released EP in vitro after mixture with supernates derived from incubation of sensitized lymphocytes and antigen. Cells and supernatant fluids from draining lymph nodes were usually effective in activating normal blood leukocytes earlier after sensitization than were those from mesenteric lymph nodes, suggesting that such cells, or antigen, had migrated from the original site of sensitization.
The activator was soluble, nonpyrogenic in the dosages tested, and required incubation of viable cells with specific antigen for its production. These properties suggest that it may belong to the class of "lymphokines," biologically active agents released from lymphocytes that have been activated by immunologic or certain nonimmunologic stimuli.
FURTHER EVIDENCE CONCERNING THE AUTOANTIGENIC STATUS OF THE TROPHOBLAST
Authors: Beer Alan E. , Billingham R. E. , Yang S. L. 
Published: June 2004

Heterologous antisera were raised by inoculation of rabbits with fairly pure suspensions of trophoblast, lymphoid, fetal (excluding placental components), epidermal, decidual, and renal cells from Fischer rats. After absorption of hemagglutinins, these antisera were assayed for abortifacient activity by intramuscular inoculation into time-mated Fischer females.
The anti-trophoblast serum aborted all the recipients, but had some nonspecific activity in that it caused the deaths of 12% of them. Anti-lymphocyte serum was more toxic and less potent as an abortifacient. None of the other sera harmed either the mothers or their fetuses. However, the anti-kidney cell serum caused kidney lesions.
Absorption of the anti-trophoblast serum with lymphoid cells completely removed its toxicity for the pregnant females without perceptible impairment of its abortifacient activity. However, the latter could be removed by absorption with trophoblast cells.
(a) The lymphocyte-absorbed anti-trophoblast serum was equally effective in aborting rats over the range 7–18 days postconception; (b) a single injection of 1 ml was sufficient in most cases, and (c) it was equally efficacious in terminating gestation in rats irrespective of their genetic constitution, and (d) its effect was highly species-specific.
These findings support the premise that a unique antigen (or antigens), of possible clinical significance, is associated with trophoblast cells.
IMMUNE STATUS OF MICE TOLERANT OF LIVING CELLS
Authors: Voisin G. A. , Kinsky R. G. , Duc H. T. 
Published: June 2004

CBA mice were rendered highly tolerant to A/Jax cells by neonatal intravenous injections of (CBA x A)F1 spleen cells. The high degree of tolerance was ascertained by the absence of circulating antibodies detected in the sera by the usual tests and by the perfect state of A skin grafts during all the experiments. Tolerant sera (sera from tolerant animals) were studied at three periods of tolerance: before skin test grafting, from 2 to 11 wk after grafting, and at time of sacrifice at almost 6 months of age.
The tolerant sera were shown to have specific facilitation-enhancing properties promoting the take and growth of A/Jax sarcoma (SaI and /Sa 15091a grafted on normal CBA mice. These properties were present throughout the duration of the experiments, showing that they were not the result of a beginning interruption of tolerance. The tolerant sera, although lacking the usual serological properties (hemagglutination, hemolysis, cytotoxicity, passive cutaneous anaphylaxis) had, however, specific synergistic hemagglutinating properties (increasing the hemagglutinating titer of a reference immune serum). Antibodies giving direct specific hemagglutination could be extracted from spleens of 20% of highly tolerant mice. The tolerant sera were also found to contain more IgG1 and more IgA than normal sera while they contained normal quantities of the complement-fixing immunoglobulins IgG2 and IgM.
Fractionation of tolerant sera on DEAE chromatography column confirmed the data concerning immunoglobulin classes and demonstrated direct specific serological activities undetected in unfractionated sera: a weak hemolysis in the most cationic fractions and a weak hemagglutination in the middle fractions. Synergistic hemagglutination, detected in unfractionated serum, was localized in fast anionic fractions containing high IgA concentration, along with facilitation-enhancing activity, thus confirming a link suggested previously between these three properties.
The relation between immunological tolerance and facilitating antibodies was discussed in the light of the fact that antibodies, possibly of a particular class continuously present at low dose in the sera of highly tolerant animals, are able to transfer (at least partly) this state of tolerance provided a sensitive test system is utilized.
ANTIGEN RECOGNITION AND THE IMMUNE RESPONSE
Authors: Alkan Sefik S. , Williams E. Brady , Nitecki Danute E. , Goodman Joel W. 
Published: June 2004

L-Tyrosine azobenzene-p-arsonate (RAT) induced cellular immunity without antibody production in guinea pigs. Bifunctional antigens were prepared consisting of one RAT carrier moiety linked either directly to a dinitrophenyl (DNP) haptenic determinant or through one or more 6-amino-caproyl (SAC) spacers. Each SAC unit has an extended span of 8 A. Guinea pigs immunized with these conjugates developed cellular immunity directed against the RAT determinant and antibody specific for the DNP determinant. The anti-DNP response was the same with one or three SAC spacers, but was significantly weaker when the two determinants were joined without a spacer. Animals immunized with either DNP-SAC-TYR or DNP-TYR developed neither cellular nor humoral immunity. Prior immunization with RAT potentiated the secondary anti-hapten response to DNP-SAC-RAT.
Modification of RAT at either the arsonate or tyrosine positions showed that other charged groups (sulfonate and trimethylammonium) could substitute for arsonate without loss of immunogenicity. Removal of either the amino or carboxyl group from the side chain of tyrosine did not abolish immunogenicity, but immunogenicity was lost upon removal of both.
Immunization with symmetrical bifunctional RAT-(SAC)n-RAT and cyclo-(L-RAT-D-RAT) antigens led to cellular immunity but no anti-arsonate antibody, suggesting a barrier to "self-help." These compounds were also ineffective in inducing a secondary anti-arsonate response in animals primed with arsonate-BSA conjugates and RAT.
GENETIC CONTROL OF THE IMMUNE RESPONSE
Authors: McDevitt Hugh O. , Deak Beverly D. , Shreffler Donald C. , Klein Jan , Stimpfling Jack H. , Snell George D. 
Published: June 2004

Eleven strains of mice bearing recombinant H-2 chromosomes derived from known crossover events between known H-2 types were immunized with a series of branched, multichain, synthetic polypeptide antigens [(T,G)-A--L, (H,G)-A--L, and (Phe,G)-A--L]. Results with nine of the eleven H-2 recombinants indicated that the gene(s) controlling immune response to these synthetic polypeptides (Ir-1) is on the centromeric or H-2K part of the recombinant H-2 chromosome. Results with two of the eleven recombinant H-2 chromosomes indicated that Ir-1 was on the telomeric or H-2D part of the recombinant H-2 chromosome. Both of these recombinants were derived from crossovers between the H-2K locus and the Ss-Slp locus near the center of the H-2 region. One of these recombinants, H-2y, was derived from a known single crossover event. These results indicate that Ir-1 lies near the center of the H-2 region between the H-2K locus and the Ss-Slp locus.
The results of a four-point linkage test were consistent with these results. In 484 offspring of a cross designed to detect recombinants between H-2 and Ir-1, only two putative recombinants were detected. Both of these recombinants were confirmed by progeny testing. Extensive analysis of one of them has shown that the crossover event occurred within the H-2 region. (Testing of the second recombinant is currently under way.) Thus, in the linkage test, recombinants between H-2 and Ir-1 are in fact intra-H-2 crossovers. These results permit assignment of Ir-1 to a position between the H-2K locus and the Ss-Slp locus.
IMMUNOSUPPRESSION OF MICE INJECTED WITH HETEROLOGOUS ANTI-IMMUNOGLOBULIN HEAVY CHAIN ANTISERA
Authors: Manning Dean D. , Jutila John W. 
Published: June 2004

Neonatal injection of mice with rabbit anti-µ antiserum has been shown to produce complete loss of direct and indirect plaque-forming responses to sheep erythrocytes as well as loss of serum IgM and severe depressions of all other serum immunoglobulins. Similar injection of anti-γ1γ2 or anti-γ1 antibodies effects a loss of the indirect response but induces relatively minor alterations in serum Ig levels. Delaying initiation of anti-µ treatment until young adulthood results in a somewhat diminished effect on plaque-forming responses and serum Ig levels but triggers the release of high serum levels of an aberrant µ-bearing protein.
Anti-µ suppression of genetically thymusless mice indicates that at least part of the target cells for suppression are bone marrow derived. A working hypothesis for the maturation of humoral antibody-producing cell lines as it relates to these data is discussed.
THE HOST CELL RESPONSE IN THE LOCAL GRAFT-VERSUS-HOST REACTION INDUCED IN THE KIDNEYS OF F1 RATS BY PARENTAL THORACIC DUCT LYMPHOCYTES
Authors: Volkman Alvin 
Published: June 2004

Radioautographs of infiltrative cells in the kidneys of (Lewis x BN)F1 rats labeled with tritiated thymidine (TdR3H) before the subcapsular injection of parental (Lewis) thoracic duct lymphocytes (TDL) showed a predominantly host-proliferative response by 4 days after grafting. The immediate renal incorporation of TdR3H was used to measure the local graft-vs.-host (GVH) reactions. Substantial reactions could still be induced in the face of the considerable degree of leukopenia after 400 R whole body γ-irradiation. These results suggest that radioresistant cells are capable of carrying on the appropriate host activities and that the weakness of GVH reactions induced after higher doses of irradiation may be due to impairment of the mitotic mechanism of host cells. The importance of circulating leukocytes as a source of immunogenic stimulation was nevertheless substantiated by inducing local GVH reactions with Lew TDL in chimeric parental-type rats that had been repopulated with F1 bone marrow. This result also emphasizes the nonspecific nature of tissue destruction in the renal GVH reaction in confirmation of Elkins. In this and other situations in which B cells were the predominant F1 type elements available for interaction with parental-type TDL the reactions were nearly equivalent or equivalent to those in the appropriate controls.
Typical local GVH reactions could be induced in heavily irradiated hosts by an inoculum of combined parental and F1-type TDL in the apparent absence of mononuclear phagocytes.
The possible relationship between the activation of host lymphocytes, the involvement of B cells, and the nonspecific nature of tissue damage in the renal GVH is discussed.
COMPLEMENT-DEPENDENT PLATELET INJURY BY STAPHYLOCOCCAL PROTEIN A
Authors: Hawiger Jacek , Marney Samuel R. , Colley Daniel G. , Des Prez Roger M. 
Published: June 2004

A new example of complement-mediated platelet injury has been described. Staphylococcal protein A (SPA) causes rabbit platelet injury as manifested by release of platelet 5-hydroxytryptamine (5HT). This reaction is complement-dependent and occurs over a very small range of SPA concentration, larger amounts being inhibitory. Complement fixation by SPA demonstrates the same narrow SPA concentration requirement whereas precipitation of IgG by SPA is roughly proportional to SPA concentration over a wide concentration range. The reaction can be separated into a sensitization step which requires SPA and plasma but not complement, and a release step which does require complement.
Complement-mediated platelet damage induced by SPA is a new biologic property of this common component of the cell wall of pathogenic staphylococci which may contribute to the development of inflammatory and thromboembolic reactions complicating intravascular staphylococcal infection.