bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIGH-DOSE DELAY OF THE IMMUNE RESPONSE
Authors: Iványi J. , Maler M. , Wudl L. , Sercarz E. 
Published: June 2004

The continuation of the primary and secondary antibody response to human serum albumin (HSA), induced in vivo, was followed in explanted chicken spleen fragments. The effect of actinomycin D (AMD) on the in vitro response was studied in spleens from chickens injected with various doses of HSA and removed at differing intervals after injection.
The antibody response of "early spleen" cultures was AMD-sensitive, while cultures of spleens removed later were AMD-resistant. It was suggested that this shift represented the development of cells with in vivo preformed RNA involved in specific immunoglobulin synthesis.
With increasing doses of HSA, the AMD-sensitive phase was prolonged, suggesting the delay of mRNA formation or some other AMD-inhibitable process in vivo. With large doses of HSA, the immune response in vitro was decreased, starting after a 1–2 day delay and not occurring in the presence of AMD. Massive doses of HSA completely inhibited the continuation of the response in vitro by spleen fragments removed between the 2nd and 5th day after injection.
The results point to the controlling role of antigen dose in determining the onset of macromolecular synthesis during immunocyte maturation.
GENETIC CONTROL OF THE ANTIBODY RESPONSE IN INBRED MICE
Authors: McDevitt Hugh O. , Tyan Marvin L. 
Published: June 2004

The transfer of spleen cells from (C3H x C57Bl/6) F1 mice, capable of responding to (T,G)-A--L, into irradiated C3H parental recipients, normally incapable of responding to (T,G)-A--L, transfers the ability to make either a primary or secondary immune response to this synthetic polypeptide antigen. This localizes the genetic control of the ability to respond to the spleen cell population and indicates that the genetic control is exerted upon a process directly related to antibody formation. Studies with congenic strains of mice and linkage studies in segregating backcross populations show that the ability to respond to (T,G)-A--L and (H,G)-A--L is linked to the H-2 locus and can thus be localized to the IXth mouse linkage group.
Note Added in Proof: Of the three possible recombinant animals noted in Tables IV and V, two were infertile. The third animal was not a recombinant, since progeny testing and reimmunization showed that this animal was an H-22/H-2k heterozygote capable of responding well to (T,G)-A--L.
RELATIONSHIP OF GERMINAL CENTERS IN LYMPHOID TISSUE TO IMMUNOLOGICAL MEMORY
Authors: Wakefield J. D. , Thorbecke G. J. 
Published: June 2004

The fate, proliferation, and developmental potentialities of cell suspensions made from white pulp containing large germinal centers have been studied in the mouse by transfer of cells labeled with thymidine-3H to lethally irradiated, syngeneic recipients. Radioautographic analyses were made using both smears and sections of a variety of tissues. Thymidine-3H-labeling patterns of white pulp showed that, initially, labeling occurred in a majority of blast and "intermediate cells" but in very few or no small lymphocytes. After intravenous transfer, most of the labeled cells localized in the lymphoid tissues of spleen, lymph nodes, and Peyer's patches. Few cells migrated to the thymus, lung, liver, and intestinal mucosa.
Both after intravenous and after intraperitoneal transfer there was a rapid increase in the incidence of labeled small lymphocytes and a decrease of labeled blasts and intermediate cells. This was accompanied by an increase in the grain count of the small lymphocytes and a progressive decrease in the grain counts of the blast cells. Exposure of nonlabeled donor cells to thymidine-3H at various time intervals after transfer indicated that dividing cells were present early after transfer but that their incidence progressively decreased. Between 24 and 48 hr, very little cell division was detectable.
RELATIONSHIP OF GERMINAL CENTERS IN LYMPHOID TISSUE TO IMMUNOLOGICAL MEMORY
Authors: Wakefield J. D. , Thorbecke G. J. 
Published: June 2004

White-pulp cells and whole spleen from donor mice immunized with sheep erythrocytes were transferred intravenously to heavily irradiated mice. The numbers of plaque-forming cells and the amount of hemagglutinating antibody produced after reexposure to antigen were measured.
When reexposure to sheep erythrocytes was delayed, a much greater response occurred in the transferred cells. Peak responsiveness was reached at 24 hr after transfer. This "lag effect" was greatly reduced by repeated injections of 5-bromodeoxyuridine into the recipient mice prior to challenge with antigen. It was therefore concluded that much of the increase in responsiveness was due to a proliferation of "primed" cells after cell transfer. The fact that a significant response was given by the transferred cells in spite of 5-bromodeoxyuridine treatment suggested that some of the primed cells were nondividing.
White pulp was a much richer source of responsive cells than was whole spleen.
STUDIES ON THE INDUCTION OF TOLERANCE OF THE H-Y ANTIGEN IN MICE WITH NEONATAL SKIN GRAFTS
Authors: Silvers Willys K. 
Published: June 2004

In contrast to the uniform rejection of adult male skin isografts by C57BL/6 females, neonatal male skin isografts are frequently accepted. Moreover, 50% of all females which accept a neonatal male skin graft for 50 days accept a subsequent adult male skin graft as well.
This ability of neonatal skin to produce tolerance has been investigated under a variety of experimental conditions. The results indicate: (a) Even when a newborn male skin graft is transplanted concomitantly with an adult graft, it can produce tolerance of the latter although it is less effective in this regard than when transplanted beforehand. (b) The continued exposure of the host to the newborn graft is vitally important in maintaining the unresponsive state; and most females deprived of these grafts for 50 days manifest an immune response when challenged with adult male skin. (c) Newborn male skin isografts raised on adult females are not as antigenic as normal male skin grafts. (d) Occasionally, even a presensitized female can be rendered tolerant by grafting with neonatal male skin. (e) Neonatal male skin grafts are not accepted when transplanted to the spleens of adult females although they may occasionally induce tolerance of a subsequent orthotopic adult male skin graft. The failure of these intrasplenic grafts to survive can be attributed at least partly to their small size since orthotopic grafts of comparable size usually do not survive. (f) Females bearing neonatal male skin grafts are not perceptible cellular chimeras.
Because the unresponsive condition induced with neonatal skin is similar to that which results from multiparity, this latter condition has also received attention. In this regard it has been established that unlike the removal of a neonatal male skin isograft, the delayed grafting of isolated females with a previous history of multiparity does not result in many of them manifesting what may be considered an immune response. However, this delay in grafting does seem to impair the tolerance multiparity produces.
The results are discussed in relation to other methods of producing tolerance in adult animals.
ALTERATIONS IN THE MOUSE CECUM AND ITS FLORA PRODUCED BY ANTIBACTERIAL DRUGS
Authors: Savage Dwayne C. , Dubos René 
Published: June 2004

Addition of penicillin, Terramycin, or kanamycin to the drinking water of adult mice rapidly induced in them an enlargement of the cecum. In all animals, this occurred within 12 hr after the beginning of drug administration—the effect being most pronounced with penicillin. The cecums remained enlarged and generally continued to increase in size as long as the antibacterial drugs were administered.
The increase in wet weight of the cecums was due primarily to an accumulation of water in the lumens during the first 24–48 hr of drug administration. At that time, there were no detectable histological changes in any case, but the bacteriological picture differed from drug to drug. The cecums were free of bacteria in animals receiving penicillin, fusiform-shaped bacteria and bacteroides were present in those receiving Terramycin, and lactobacilli and bacteroides in those receiving kanamycin. After the initial 48 hr, an abundant and complex secondary microflora developed in all treated animals, its composition being characteristic for each type of antibacterial drug.
When penicillin was administered for 2 wk, the cecal weights and microbial populations did not return to normal levels for over 14 days after discontinuance of the drug. This recovery period could be shortened to 10 days by giving the mice food contaminated with cecal homogenates prepared from normal animals. A period of 7 or 8 days was required for the cecal weights and microflora to reach normal levels when the administration of penicillin lasted only 24 hr; this period could not be shortened by giving the animals contaminated food.
The effects of drugs on the size and bacterial contents of the cecum have been discussed in the light of earlier findings concerning the characteristics of the huge cecums uniformly found in germfree mice. Taken together, these observations support the hypothesis that certain elements of the intestinal microflora—not yet completely identified—play an essential role in maintaining the integrity of the water-transport mechanism in the intestinal epithelium.
CELLULAR DIFFERENTIATION OF THE IMMUNE SYSTEM OF MICE
Authors: Shearer G. M. , Cudkowicz G. , Connell Mary St. James , Priore R. L. 
Published: June 2004

Spleen cell suspensions of unprimed donor mice containing precursors of immunocytes have been transplanted into X-irradiated recipient mice. In the presence of antigen (sheep erythrocytes) these precursors, called antigen-sensitive units, gave rise to progeny cells secreting specific antibody. We studied quantitatively the production of cells releasing IgM hemolysins (direct plaque-forming cells), IgG hemolysins (indirect plaque-forming cells), and hemagglutinins (cluster-forming cells). We found that each of these immunocyte populations was distinct, i.e., that cells releasing agglutinins did not, as a rule, release hemolysins, and vice versa. We also found that cell populations secreting IgM hemolysins did not shift, under certain experimental conditions, to the production of IgG hemolysins during the primary immune response.
By transplanting graded numbers of spleen cells, we succeeded in limiting to one or a few the number of antigen-sensitive units that reached the recipient spleen. We estimated thereby the frequency of antigen-sensitive units in donor cell suspensions and tested their potential for production of immunocytes of more than one type. Our results indicated that antigen-sensitive units were unipotent for they displayed in the spleens of unprimed donors the same restrictions of function and heterogeneity (antibody-specificity differentiation, antibody-class differentiation) found among antibody-forming cells. Furthermore, antigen-sensitive precursors for direct plaque-forming cells, indirect plaque-forming cells, and cluster-forming cells were detected in the spleens of unprimed mice in different frequencies, i.e., 1 in ∼ 106, 1 in ∼ 7 x 106, and 1 in ∼ 19 x 106 spleen cells, respectively.
We concluded that relatively advanced differentiation of potentially competent cells occurs before sheep erythrocyte administration. The relevance of this finding for the broad spectrum of immunologic reactivities and for the heterogeneity of antibody responses to given antigens was discussed.
EFFECT OF REMOVAL OF CHOLESTEROL DIET UPON SERUM SICKNESS-CHOLESTEROL-INDUCED ATHEROSCLEROSIS
Authors: Van Winkle M. , Levy L. 
Published: June 2004

In this report, the role of vascular allergy (i.e., hypersensitivity) in the potentiation of atherogenesis has been studied. In order to accomplish this, bovine serum albumin (BSA) was administered to rabbits in quantities sufficient to cause the occurrence of serum sickness (a type of hypersensitivity known to cause injury to the endothelial linings of certain blood vessels). This was immediately followed by the feeding of a special cholesterol-supplemented diet, which is known to be capable of initiating a high incidence of atheromatous disease in rabbits after prolonged feeding. Results indicated that those animals which received the combined treatment developed an incidence of pathology after only 2 wk of special diet which was not equaled in the diet-only control groups until they had been treated for 4 wk. This indicated that vascular allergy could potentiate lipemia-induced atherogenesis in the rabbit, and was in confirmation of an earlier study of a similar nature. Indeed, because of the relatively mild vascular injury caused by a single injection of BSA, it would seem as though vascular hypersensitivity was extremely effective in the potentiation of atherogenesis.
In addition, these results may have given some indication of the degree of vascular injury necessary for the induction of irreversible atheromatous disease. While the incidence of lesions in serum sickness controls was seen to decrease with passage of time after BSA challenge, it appeared to increase after cessation of treatment in those animals which received the combined treatment of BSA plus 2 wk of cholesterol-supplemented diet. It would therefore appear that the atheromatous lesions seen as early as 2 wk after initiation of the experiment may already have been irreversible in terms of the resolution of established pathology.
SYNTHESIS OF THE FIRST COMPONENT OF HUMAN COMPLEMENT IN VITRO
Authors: Colten Harvey R. , Gordon James M. , Borsos Tibor , Rapp Herbert J. 
Published: June 2004

Isolated segments of human colon and to a lesser extent ileum were capable of synthesizing hemolytically active C'1. This conclusion was based on the following evidence:
After elimination of C'1 from tissue with EDTA, we found that segments of the intestinal tract in short-term organ culture showed a 50–1000-fold increase in C'1 activity. The rate of production of C'1 in human intestine was highly temperature dependent; C'1 production was reversibly inhibited by puromycin and actinomycin D. Furthermore, 14C-labeled amino acids were incorporated into molecules which behaved like C'1. No significant C'1hu synthesis was observed in isolated segments of jejunum, stomach, liver, kidney, lung, spleen, lymph node, and thymus.
ISOLATION AND CHARACTERIZATION OF PERMEABILITY FACTORS FROM RABBIT NEUTROPHILS
Authors: Ranadive N. S. , Cochrane C. G. 
Published: June 2004

Four basic proteins that increase vascular permeability have been isolated in purified form from rabbit neutrophilic granules. These proteins are termed band 1, 2, 3, and 4 protein according to their electrophoretic migration in acrylamide gel. Molecular weights of band 1 and 2 protein derived from amino acid composition were 4800 and 5300, respectively. These values are in good agreement with those obtained for these proteins by gel diffusion techniques. The molecular weight of band 3 protein was also in the range of 5000 by the latter technique. The molecular weight of band 4 protein determined by ultracentrifugal analysis and amino acid composition was 12,000.
Although all four proteins had the capacity to induce immediate increase in vascular permeability, only band 2 protein was found to release histamine from isolated rat peritoneal mast cells. Furthermore, it has been shown that the permeability-inducing activity of band 2 protein can be inhibited by pretreating rabbits with antihistamine. Band 2 protein did not release histamine from rabbit platelets and depletion of rabbit platelets from the circulation had no influence on the permeability-inducing activity of this protein.
Band 1, 3, and 4 proteins did not release histamine from isolated rat peritoneal mast cells and their capacity to increase vascular permeability remained unaffected by treatment of rabbits with antihistamine.
These investigations suggest that the histamine-releasing activity of band 2 protein is a specific phenomenon and is associated with particular amino acid grouping or spacial configuration of the molecules. By the same token, the increase in vascular permeability induced by the nonhistamine-releasing band 1, 3, and 4 proteins represents a specific phenomenon (or phenomena) not particularly related to the over-all charge of these molecules.
LASTING BIOLOGICAL EFFECTS OF EARLY ENVIRONMENTAL INFLUENCES
Authors: Lee Chi-Jen , Dubos René 
Published: June 2004

A lasting depression of body weight was consistently produced in SPF mice by infecting them orally 2 days after birth with a nonlethal, bacteria-free filtrate, prepared from the intestine of young SPF mice previously infected with an unidentified agent.
Neonatal infection caused a decrease of muscle DNA and of muscle and brain protein in the adults. No other effect was detected in the chemical composition of various organs.
Incorporation of 14C-amino acid into the acid precipitable fractions of liver, kidney, muscle, and brain was lower in infected than in control animals. No difference in incorporation was recognized in the thymus and spleen.
The free amino acid pool of adults, measured as blood levels of free amino nitrogen, was decreased by neonatal infection.
Surprisingly, the food intake of young animals infected neonatally was higher than that of the controls, measured on the basis of body weight. Their fecal excretion of nitrogen was also higher.
The comparative responses of infected and control adults to a stressful situation was measured by giving them intravenously the antituberculous vaccine BCG. Under these conditions, the mice infected neonatally excreted some 20% more nitrogen in their urine and 40% more in their feces than did the controls.
The mechanisms through which neonatal infection caused a lasting weight depression are discussed in the light of these metabolic findings.
FURTHER STUDIES ON THE γG-HEAVY CHAIN GENE COMPLEXES, WITH PARTICULAR REFERENCE TO THE GENETIC MARKERS Gm(g) AND Gm(n)
Authors: Natvig J. B. , Kunkel H. G. , Yount W. J. , Nielsen J. C. 
Published: June 2004

The recently described Gm (g) and Gm (n) genetic markers of the γG3- and γG2-subgroups of γ-globulin were characterized in detail primarily through studies of myeloma proteins, their polypeptide chains and fragments. Antisera derived from rabbits, non-human primates and rheumatoid arthritis patients gave identical results. This contrasted with the Gm (b) system where the rabbit antisera react with a different genetic determinant (b0) than the sera from rheumatoid arthritis patients (b). The Gm (g) and Gm (n) antigens were detected both by precipitin analysis and by hemagglutination inhibition. The Gm (g) antigen was not associated with any of the other genetic antigens of the γG3-proteins which all belonged in the Gm (b) class. The genes for the latter were always allelic to the gene coding for Gm (g), with that for Gm (b0) constantly present when that for Gm (g) was absent.
The Gm (g) and Gm (n) markers were of particular value in tracing the various gene complexes made up of the closely linked subgroup genes. Further support was gained for the concept that the different gene complexes of various population groups arose primarily through crossing-over. The Gmg and Gmb genes for the γG3-subgroup were extremely closely linked to those for the γG1-subgroup. However the Gm (n) marker indicated that the γG2-subgroup genes were probably further separated on the chromosome. Additional evidence was obtained for the γG2-γG3-γG1-order of the subgroup cistrons.
Among the wide range of gene complexes a new type (γG2,—,γ/G1) was described. This complex appeared to have a deletion of the γG3-cistron. Lower levels of γG3-globulin were found in the sera of the individuals with this gene in the heterozygous state. The possibility that this unusual complex arose through an unequal nonhomologous crossing-over is discussed.
THE SUBCELLULAR DISTRIBUTION OF ANTIGEN IN MACROPHAGES
Authors: Kölsch E. , Mitchison N. A. 
Published: June 2004

The intracellular fate of phagocytosed antigens in cells from peritoneal exudate in CBA mice has been studied by using 126I and 131I labeled antigens. After uptake of labeled antigen, cells were homogenized and the subcellular fractions were analyzed by isopycnic centrifugation in a sucrose gradient.
The uptake of heat-denatured BSA (c BSA) by these cells in vivo is 3.5 µg/mg c BSA injected/108 cells. The uptake by cells in animals which were exposed 2 days earlier to 900 r whole body irradiation is slightly lower but does not differ significantly. 90% of the phagocytosed material is degraded within 2–3 hr, the residual 10% is retained at least over an 8 hr periods. Using a pulse and chase technique, with 125I and 131I c BSA in vitro and in vivo it was shown that newly phagocytosed antigen is found mainly in a lysosomal turnover compartment of a density 1.19 g cm–3. Antigen which has been in the cells for longer was found in a denser fraction (1.26 g cm–3). In a comparison of nhrmal and X-irradiated cells it can be shown that after irradiation with 900 r less c BSA is found in this storage compartment.
Binding of the antigen to the subcellular fractions, and its behavior towards several detergents has been studied. Subcellular fractions do not have the increased immunogenic capacity of antigen enclosed in living macrophages.
Two synthetic polypeptide antigens, poly(D-Tyr, D-Glu, D-Ala) and poly-(L-Tyr, L-Glu) have a different subcellular distribution from c BSA, BSA, or bovine gamma globulin. Apart from also being found in the 1.26 storage compartment the polypeptide antigens are mainly located in a 1.15 compartment and only to a small extent in the 1.19 compartment. The half-life of these antigens in the cells is much longer than the half-life of the protein antigens studied.
The finding of several subcellular compartments is discussed in connection with the functions possibly performed by macrophages.