Mg Of BSA Research Articles

Enhanced bone regeneration using Antheraea mylitta silk fibroin and chitosan based scaffold: in-vivo and in-vitro study

In this study, highly interconnected porous scaffolds from Antheraea mylitta silk fibroin (SF) and chitosan (CH) were fabricated using the freeze-drying method. The weight ratios of SF to CH were varied from 90:10 (SF90/CH10) to 50:50 (SF50/CH50) to prepare the scaffolds from the aqueous suspension of the protein-polysaccharide mix. From the initial optimization of scaffold composition with respect to their microstructure, porosity, and mechanical properties, the SF80/CH20 scaffold exhibited the most suitable properties for bone tissue engineering application as compared to others compositions. Hence in-vitro hemocompatibility, protein adsorption, and MG-63 cell culture studies were carried out for SF80/CH20 scaffold. The fabricated SF80/CH20 scaffold showed a more controlled swelling percentage of 42.8%, with high BSA protein adsorption of 0.39 mg of BSA per gm of the scaffold at 24 h incubation period. Furthermore, in-vitro MG-63 cell culture study onto the fabricated SF80/CH20 scaffold elicited excellent MG-63 cell attachment with better biocompatibility and cell viability with increased F-action production from day 3 to day 7 of the cell culture period. In vivo bone defect healing in a rabbit tibia model revealed excellent bone healing capacity in SF80/CH20 scaffold implanted specimens compared to control ones, as evident from histology and fluorochrome labeling analysis.

Carrier-bound and carrier-free immobilization of type A feruloyl esterase from Aspergillus niger: Searching for an operationally stable heterogeneous biocatalyst for the synthesis of butyl hydroxycinnamates

Feruloyl esterases synthesize butyl hydroxycinnamates, molecules possessing interesting biological properties, nonetheless, they exhibit a low stability under synthesis conditions in organic solvents, restricting its use. To enhance its operational stability in synthesis, we immobilized type A feruloyl esterase from Aspergillus niger (AnFAEA) using several carrier-bound and carrier-free strategies. The most active biocatalysts were: 1) AnFAEA immobilized on epoxy-activated carriers (protein load of 0.6 mgenzyme x mg−1carrier) that recovered 91 % of the initial hydrolytic activity, and 2) AnFAEA aggregated and cross-linked in the presence of 5 mg of BSA and 15 mM of glutaraldehyde (AnFAEA-amino-CLEAs), which exhibited 385 % of its initial hydrolytic activity; both using 4-nitrophenyl butyrate as substrate. The AnFAEA-amino-CLEAs were 12.7 times more thermostable at 60 °C than the AnFAEA immobilized on epoxy-activated carrier, thus AnFAEA-amino-CLEAs were selected for further characterization. Interestingly, during methyl sinapate hydrolysis (pH 7.2 and 30 °C), AnFAEA-amino-CLEAs KM was 15 % higher, while during butyl sinapate synthesis the KM was reduced in 63 %, both compared with the soluble enzyme. The direct esterification of butyl sinapate at solvent free conditions using sinapic acid 50 mM, reached 95 % conversion after 24 h employing AnFAEA-amino-CLEAs, which could be used for 10 cycles without significant activity losses, demonstrating their outstanding operational stability.

Different sources of dietary zinc for broilers submitted to immunological, nutritional, and environmental challenge

SUMMARY A total of 1,248 one-day-old male Cobb chicks were used to evaluate the effect of different sources and levels of dietary zinc on the humoral immune response, zinc concentration in the tibia and carcass, footpad integrity, and performance. The birds were exposed to immunological (infectious bronchitis vaccine in the hatchery), nutritional (250 ppm of Cu in the diet) and environmental (reused litter sprayed daily with water; 1 to 21 d) challenges. The diets consisted of different levels of zinc from an organic source (10, 20, or 40 ppm of chelate Zn-HMTBa/ Mintrex Zn; Novus International Inc.), an inorganic source (10, 20, 40, or 100 ppm of zinc sulfate), and a negative control without zinc (0 ppm of Zn). The birds were immunized with 0.2 mg of BSA at 28 d and blood was collected at 41 d to measure antigen-specific antibody titer. Antibody titer, Zn concentration in the carcass, and performance (feed intake, BW gain, and feed conversion) were not affected by levels or sources of Zn. The absence of supplementary zinc in the diets significantly decreased its concentration in the tibia ash. Using 10 or 20 ppm of Zn from an organic source decreased the incidence of footpad lesions compared with the same levels of the inorganic source. It was concluded that both sources of Zn may be supplemented individually in broiler chicken diets, even in levels below 100 ppm, with no effect in carcass Zn concentration, performance, and humoral immunity, under the conditions tested. However, to keep footpad integrity, an organic source of Zn seems to be more efficient.

Induction of immunological tolerance in chickens inoculated with xenogeneic antigens at a late stage of embryonic development

To induce immunotolerance, chicken embryos were inoculated with BSA on embryonic incubation day (EID) 20. All hatched chickens were challenged with BSA four times at 10-day intervals, beginning at 3 weeks of age. Serum anti-BSA antibodies were analyzed and our results show that immunotolerance was obtained in the group micro-injected with 1 mg of BSA. We administered BSA labeled with 2,4-dinitrophenyl (DNP) into blood vessels on EID 20 and detected the distribution of BSA by immunohistochemistry. Our results show that DNP-BSA was located in the bursal cortex, thymus and spleen. PBMCs were separated on the seventh day after the fourth immunization to determine the effect of treatments on lymphocytes and the percentage of CD4(+) T cells among the CD3(+) T cell population. Results from these experiments show that there was an influence on T lymphocyte proliferation, with the number of CD4(+) T cells in the tolerance group significantly increased. To determine whether tolerance was induced in B cells, 2,4,6-trinitrophenyl coupled to BSA (TNP-BSA) was inoculated into birds, followed by detection of anti-TNP antibodies in the serum. Immunological tolerance in B cells was not observed following these experiments. The results from our study demonstrate that immunological tolerance was induced in T cells when 1 mg of BSA was micro-injected on EID 20.

항원의 투여방법 및 사육환경 변화에 따른 넙치의 특이항체 반응

The specific antibody response of olive flounder, Paralichthys olivaceus to change in rearing-environmental conditions post immunization with antigen (bovine serum albumin, BSA) and different routes of antigen administration were investigated by enzyme-linked immunosorbent assay (ELISA). To test the effect of routes of antigen administration, flounder were injected intraperioneally or intramuscularlly with 1 mg of BSA. In addition, to test the effect of change in environmental condition post immunization, flounder were injected intraperioneally with 1 mg of antigen, and then were exposed to acute thermal change (the water temperature (WT) was decreased from 21 ℃ to 15℃ within 30 min and maintained at 15℃ for 3 h), handling (fish were caught and subsequently held out of water for 1 min) or heavy oil (76 g/ 200 L for 2 days). Consequently, there was no significant difference between intraperioneal (IP) and intramuscular (IM) injections except at 10 days post-immunization. With these results, it suggests that both IM and IP injections may be used as route of vaccination. Futhermore, no significant difference was observed in the antibody response among the groups exposed to heavy oil, handling, sudden drop of WT and positive control except at 10 days post-immunization. From these results, it was confirmed that specific antibody response was not affected by the above mentioned rearing-environmental conditions, suggesting that vaccination can be employed at changing rearing-environmental conditions.

Identification of squalamine in the plasma membrane of white blood cells in the sea lamprey, Petromyzon marinus

It is well established that innate mechanisms play an important role in the immunity of fish. Antimicrobial peptides have been isolated and characterized from several species of teleosts. Here, we report the isolation of an antimicrobial compound from the blood of bacterially challenged sea lamprey, Petromyzon marinus. An acetic acid extract from the blood cells of challenged fish was subjected to solid-phase extraction, cation-exchange chromatography, gel-filtration chromatography, and reverse-phase high-performance liquid chromatography, with the purified fractions assayed for antimicrobial activity. Surprisingly, antimicrobial activity in these fractions originated from squalamine, an aminosterol previously identified in the dogfish shark, Squalus acanthias. Further chromatographic and mass spectrometric analyses confirmed the identity of squalamine, an antimicrobial and antiangiogenic agent, in the active fraction from the sea lamprey blood cells. Immunocytochemical analysis localized squalamine to the plasma membrane of white blood cells. Therefore, we postulate that squalamine has an important role in the innate immunity that defends the lamprey against microbial invasion. The full biochemical and immunological roles of squalamine in the white blood cell membrane remain to be investigated.

Biotin Sensing in Saccharomyces cerevisiae Is Mediated by a Conserved DNA Element and Requires the Activity of Biotin-Protein Ligase

Biotin is a water-soluble vitamin that functions as a prosthetic group in carboxylation reactions. In addition to its role as a cofactor, biotin has multiple roles in gene regulation. We analyzed biotin effects on gene expression in the yeast Saccharomyces cerevisiae and demonstrated by microarray, Northern, and Western analyses that all yeast genes encoding proteins involved in biotin metabolism are up-regulated following biotin depletion. Many of these genes contain a palindromic promoter element that is necessary and sufficient for mediating the biotin response and functions as an upstream-activating sequence. Mutants lacking the plasma membrane biotin transporter Vht1p display constitutively high expression levels of biotin-responsive genes. However, they react normally to biotin precursors that do not require Vht1p for uptake. The biotin-like effect of precursors with regard to gene expression requires their intracellular conversion to biotin. This demonstrates that Vht1p does not act as a sensor for biotin and that intracellular biotin is crucial for gene expression. Mutants with defects in biotin-protein ligase, similar to vht1delta mutants, also display aberrantly high expression of biotin-responsive genes. Like vht1delta cells, they have reduced levels of protein biotinylation, but unlike vht1delta mutants, they possess normal levels of free intracellular biotin. This indicates that free intracellular biotin is irrelevant for gene regulation and identifies biotin-protein ligase as an important element of the biotin-sensing pathway in yeast.

Maternal dietary ratio of linoleic acid to alpha-linolenic acid affects the passive immunity of hatching chicks

The objective of the current study was to examine the effect of dietary ratio of linoleic acid (LA) to alpha-linolenic acid (LNA) on the humoral immune response in laying hens and further on the passive immunity of their progeny. Thirty-two Single Comb White Leghorn laying hens, 24 wk of age, were randomly assigned to 1 of 4 diets that had LA-to-LNA ratios of 0.8, 5.4, 12.5, and 27.7, respectively, by changing the proportions of sunflower and linseed oils. After 5 wk on the experimental diets, hens were immunized intramuscularly with 1 mg of BSA, followed by 2 boosters 2 and 6 wk later. Serum and egg yolk were obtained weekly from 0 to 6 wk following the first injection of BSA. One week after the second booster, fertile eggs were collected and incubated. The sera of 11-d-old embryos and hatchlings were collected. All serum samples were stored at -20 degrees C before analysis. The results showed that dietary LA-to-LNA ratio had no effect on the total IgG and BSA-specific antibody IgG concentrations in the serum or egg yolk of laying hens. Hatchlings from hens fed the diet containing the LA-to-LNA ratio of 12.4 showed lower (P < 0.05) BSA-specific IgG titer in the serum than those from hens given the diet containing LA-to-LNA ratio of 0.8. A lower (P < 0.05) total IgG concentration was observed in hatchlings from hens fed the diet containing LA-to-LNA ratio of 12.4 compared with those from hens fed diets containing 0.8 and 5.4 of LA-to-LNA ratios. It is suggested that the dietary ratio of LA to LNA has no effect on laying hen humoral response but affects the passive immunity of hatching chicks.

Exogenous TGF-beta1 promotes stromal development in the heifer mammary gland.

The objectives of this study were to determine the local effects of transforming growth factor-beta1 (TGF-beta1) on mammary epithelial and stromal cell proliferation and expression of the TGF-beta1 responsive genes c-myc and fibronectin. A single slow-release plastic pellet containing 5 microg of TGF-beta1 and 20 mg of BSA was implanted in the parenchyma of the right rear quarter of the mammary gland of 9-mo-old prepubertal heifers. A control pellet containing 20 mg of BSA was implanted in the left rear quarter of each heifer. All heifers were treated with bromodeoxyuridine (BrdU) at 4, 12.5, and 22 h after the pellets were implanted to label proliferating cells. Two hours after the last BrdU injection, the animals were euthanatized, and their mammary glands were recovered. Proliferation of mammary stromal cells was significantly higher in TGF-beta1-treated quarters than in BSA-treated, control quarters (3.5 vs. 1.8% BrdU-positive cells). This result coincided with a lack of significant effect of TGF-beta1 on proliferation of mammary epithelial cells and apoptosis. By quantitative reverse transcriptase-polymerase chain reaction, we found that c-myc gene expression was unchanged after TGF-beta1 treatment, but fibronectin gene expression was increased 3-fold in TGF-beta1-treated quarters compared with BSA-treated, control quarters. Thus, we concluded that TGF-beta1 selectively acts on the stromal compartment of the bovine mammary gland by increasing cell proliferation and gene expression of the extracellular matrix protein fibronectin.

Treatment with Recombinant Bovine Interferon-τ In Utero Attenuates Secretion of Prostaglandin F from Cultured Endometrial Epithelial Cells

Endometrial oxytocin receptors and total production of PGF by endometrial epithelial cells were measured in 10 cyclic cows after intrauterine injections of recombinant bovine interferon-τ plus BSA or BSA alone. Cows received twice daily injections (via intrauterine catheters) of 200μg of recombinant bovine interferon-τ plus 1.3mg of BSA (n = 5) or 1.5mg of BSA (n = 5) from d 14 to 17 after estrus. On d 17, the reproductive tracts of each cow was removed at slaughter, and endometrial epithelial cells were cultured with 0, 2, or 50ng/ml of recombinant bovine interferon-τ. After 24h, oxytocin (2×10−7M) was added to one-half of the culture wells, and the medium was sampled at 0, 30, and 90min for analysis of total PGF (PGF plus 13,14-dihydro-15-keto-PGF2α). In vivo treatment with recombinant bovine interferon-τ + BSA reduced total secretion of PGF in culture (1.49±0.06 vs. 2.80±0.07 ng/μg of DNA), but did not block the oxytocin-induced stimulation in total secretion of PGF. In vitro treatment of cells with recombinant-bovine interferon-τ did not decrease basal secretion of total PGF. Oxytocin receptor binding at d 17 was low in both treatments but slightly attenuated in the group treated with recombinant bovine interferon-τ.

Extension of Corpus Luteum Lifespan and Reduction of Uterine Secretion of Prostaglandin F2α of Cows in Response to Recombinant Interferon-τ

Two experiments tested the effect of recombinant ovine and bovine interferon-τ on corpus luteum lifespan, interestrous interval, and oxytocin-induced uterine secretion of prostaglandin F2α. Cows received intrauterine injections of 100μg of recombinant ovine interferon-τ plus 1.4mg of BSA or of 1.5mg of BSA alone in Experiment 1 and 200μg of recombinant bovine interferon-τ plus 1.3mg of BSA or 1.5mg of BSA alone in Experiment 2. Twice daily injections (0700 and 1900h) were split evenly between the uterine horns from d 14 to 24 of the experimental estrous cycle via an AI pipette in Experiment 1 and via intrauterine catheters in Experiment 2. On d 17, cows were injected with 100 IU of oxytocin, and plasma was collected for analysis of 13,14-dihydro-15-keto-prostaglandinF2α. Recombinant ovine interferon-τ extended the lifespan of the corpus luteum (27.5 vs. 19.2 d) and interestrous interval (30.5 vs. 20.6 d) and abolished the oxytocin-induced increase in 13,14-dihydro-15-keto-prostaglandinF2α, which peaked at 30min for the BSA control group (210.8 pg/ml). Recombinant bovine interferon-τ also extended the lifespan of the corpus luteum (29.0 vs. 21.4 d) and interestrous interval (31.5 vs. 22.6 d) and abolished the oxytocin-induced increase in 13,14-dihydro-15-keto-prostaglandin F2α, which peaked at 30min for the BSA control group (205.6 pg/ml). In conclusion, recombinant ovine interferon-τ and recombinant bovine interferon-τ were effective antiluteolytic agents in cattle.

Kinetic studies of human and rat neutrophil lysoPAF acetyltransferase using lysoPAF and dansyllysoPAF as substrates

Enzyme kinetic studies of lysoPAF acetyltransferase from microsomal preparations of human and rat neutrophils were carried out using lysoPAF or dansyllysoPAF as substrate. With the human enzyme, incomplete conversion of the substrate into the product was observed at 37 degrees C with both substrates. The acetyltransferase was inactivated at 37 degrees C in the absence of substrate with a half-life of 7.5 min. However, the initial rate of product formation under the assay conditions was linear up to 10 min. Both enzymes were optimally active at 40 microM concentration with either substrate, but enzyme activity was inhibited at higher substrate levels. At a constant substrate concentration (40 microM), the Km (microM) and Vmax (nmol product/min/mg protein) values for the human acetyltransferase, with respect to acetyl-CoA were 132 and 23.1, respectively, with lysoPAF as substrate, and 105 and 26.7, respectively, when dansyllysoPAF was used. The Km and Vmax values for the rat enzyme were 105 and 6.5, respectively, with lysoPAF as substrate, and 120 and 5.4, respectively, when dansyllysoPAF was used. Under our standard conditions, lysoPAF required 1 mg of BSA per mL in the assay, whereas full activity of both enzymes was seen with dansyllysoPAF even in the absence of BSA. The results show that dansyllysoPAF can replace lysoPAF in the assay without any significant changes in kinetic parameters.

On-line deproteinization of serum sample for HPLC analysis of hydrophilic compounds and its application to gentamicin

The binding of serum proteins with Butyl Toyopearl (BT) 650-M has been investigated and applied to on-line deproteinization for the HPLC determination of gentamicin components, c1, c1a, c2, in serum. It was found that in 0.4% perchloric acid medium about 36mg of BSA was adsorbed on 1ml of wet gel. Under this condition hydrophilic components such as gentamicin passed through the pre-column packed with BT 650-M, while serum proteins and hydrophobic components were trapped in the pre-column. The ion pair between gentamicin components and pantanesulfonate anion was effectively trapped in a reversed-phase analytical column. It was then eluted and fluorometrically determined by post-column derivatization with o-phthalaldehyde. The recovery was quantitative with good reproducibility at therapeutic concentrations in sera. Several clinical samples were analyzed by the method.

The role of platelets on the development and progression of BSA nephritis in rabbits

The role of platelets on the progression of immune complex induced nephritis (BSA nephritis) was examined in the albino rabbits, and the effect of dipyridamole was tested.All animals were sensitized with 3mg of BSA with adjuvant followed by 2 shots of BSA (250mg and 500mg) on the 3rd day and the 10th day after the initial BSA injection, respectively.All animals were examined for urinary protein contents, platelet number, platelet volume, platelet aggregability induced by ADP and collagen, fibrinolytic activity and blood coagulation. Animals were killed for the histological examination of the kidney on the 16th day after the initial administration of BSA.The control group (9 cases) developed lesions which revealed glomerular endothelial-mesangial cell proliferation, and animals which received low dose of dipyridamole (2.5mg/day, i. v., 9 cases) developed more severe glomerular endothelial-mesangial cell proliferation and interstitial cell infiltration than non-treated groug, however, the group which received moderate dose of dipyridamole (10mg/day, i. v., 5 cases) showed mild glomerular changes.The level of proteinuria was 1.0-308mg/day (mean±SE; 56.0±27.5mg/day) in the control group; 51-340mg/day (268±115.6mg/day) in the low dose therapy group. The level in the moderate dose group is in study.The platelet volume decreased in the control group, and the platelet number increased in the low dose therapy group. The disaggregation induced by ADP was prominent in the control and the low dose therapy group. These data suggest that the large size of platelets may be consumed by BSA injection in the control group.All three groups revealed hyperfibrinogenemia, high level of serum fibrinogen/fibrin degradation products, and low plasminogen activator activity after BSA treatment, and there were no differences between these groups. These results indicate that the hypercoagulability and the comparative lower fibrinolytic activity occurred in non-treated and treated group, and these states seem to influence the progression of this nephritis. Judging from the results of histlogical study, adequate dose of dipyridamole may have beneficial effect, but low dose of dipyridamole may have adverse effect on this nephritis.

ANTIBODY RESPONSE TO HAPTEN‐PROTEIN CONJUGATES IN CARRIER PRIMED MICE

Priming mice with a protein (bovine serum albumin or ovalbumin) prepared them for a markedly enhanced anti‐hapten response to the conjugate of a hapten NIP (4‐hydroxy‐3‐iodo‐5‐nitrophenacetyl) and the protein. The enhancing effect of this preimmunization was carrier‐specific and dependent on the priming dose of the carrier. Thus, on day 6, anti‐NIP titers were 6 to 240 times (p&lt;0.01‐&lt;0.001) higher in groups primed with 0.01 to 10 mg of BSA and challenged with NIP‐BSA than in groups not primed with the carrier. The optimum dose (0.1 to 1 mg) of BSA for an enhanced anti‐NIP response also resulted in the highest secondary anti‐BSA titers. The enhancing effect of the carrier priming was observed only at the beginning of the anti‐NIP response. Corresponding findings were obtained when ovalbumin was used for preimmunization and as the carrier in the challenge. This dose‐response relationship in mice was different from that found earlier in chickens. Small doses of carrier induced optimal priming in chickens. Priming with higher doses which induced high titers of anti‐carrier antibody had a suppressive effect on the anti‐hapten response in these birds.

Ultrastructural Alterations of the Glomeruli after Prolonged Immunization Correlation with Urinary Excretion of Kidney Specific Antigens in the Rat

Kidney specimens of rats injected every 3rd day with 20 mg of BSA for 9–15 months were examined. Immunohistologically, deposition of rat gammaglobulin and avidity for heterologous complement were demonstrated in a mesangial pattern. Mesangial increase was found by light microscopy. Electronmicroscopically, matrix increase and electron dense deposits were noted in the mesangium in a segmental distribution. Subendothelial accumulations of loose coarsely granular material were also observed. Kidney specific antigens were more often detected in the urine during the early phase than in the late phase. Chronic glomerulonephritis did not develop despite prolonged administration of antigen and the renal findings are indicative of sequelae of a glomerulonephritic process. The pathogenesis and significance of these findings are discussed. Es wurden Nierenschnitte von Ratten untersucht, welche während 9–15 Monaten jeden 3. Tag 20 mg BSA erhalten hatten. Immunhistologisch konnten Ablagerungen von Ratten-Gammaglobulin und Avidität für heterologes Komplement mesangial demonstriert werden. Eine mesangiale Verbreiterung wurde lichtmikroskopisch gefunden. Elektronenmikroskopisch konnten eine Vermehrung der Matrix sowie elektronendichte Ablagerungen im Mesangium in segmentaler Verteilung beobachtet werden. Daneben bestanden subendotheliale Ansammlungen von lockerem grobgranulärem Material. Nierenspezifische Antigene konnten im Urin nachgewiesen werden, häufiger in der Frühphase als in den Spätphasen. Eine chronische Glomerulonephritis hat sich nicht entwickelt trotz prolongierter Verabreichung des Antigens und die morphologischen Veränderungen deuten auf Seguolen eines abgelaufenen glomerulonephritischen Prozeß. Die Pathogenese und die Bedeutung dieser Befunde werden diskutiert.

Immunogenicity of bovine serum albumin in adult rabbits of various strains.

Adult rabbits of 3 different strains were immunized by an intravenous injection of 7 mg BSA, followed 18 days later by a booster injection of 7 mg BSA and endotoxin. ‘Gris’ rabbits responded the best (86% responders) and ‘fauve de Bourgogne’ the worst (25%), whereas ‘albinos’ were intermediate between the other 2 strains (48%). After 100 mg of BSA, the poor response of ‘fauve de Bourgogne’ was slightly increased. These animals responded also poorly to HSA.

Immunologic Tolerance Induced in the Adult Rabbit with Modified BSA

Summary Previous experiments have shown that bovine serum albumin, cleared of its larger phagocytizable particles, is much less immunogenic than regular BSA and can sometimes induce tolerance. These findings are confirmed in the present paper. It was also shown that 1 mg of BSA was the dose most likely to induce tolerance in the rabbit; a smaller proportion of tolerant animals was obtained with 7 mg, whereas no tolerance was obtained with 25 mg of the antigen. The 0.1-mg dose induced slightly less tolerance than 1 mg, but the difference was not significant. In most experiments the antigen was screened by injection into a filter animal before injection into experimental animals. In some experiments this biologic filtration was replaced by gel filtration, which also allowed the separation of a “tolerigen” fraction from an immunogenic one. The immunogenic role of the larger component is probably related to its function of adjuvant, since screened BSA injected together with endotoxin is immunogenic and can no longer induce tolerance. The specificity of this kind of tolerance was established by showing a normal immune response to HSA in rabbits tolerant to BSA. This state of tolerance may persist for several months—one animal has now been tolerant for more than 2 years.

The immune response of rabbits tolerant to bovine serum albumin to the injection of other heterologous serum albumins.

Immunological tolerance produced in rabbits by neonatal injections of BSA can be terminated by a series of injections of certain heterologous serum albumins which cross-react with BSA. Injections of albumins distantly related to BSA were more effective in terminating the tolerant state than injections of albumins closely related to BSA. It was concluded from results obtained with several heterologous albumins that immunological tolerance to BSA is directed to both the over-all antigenic or physical-chemical composition of the protein and the individual determinant groups present on the protein. Several possible mechanisms were given to explain the ability of cross-reacting albumins to terminate the tolerant state of BSA-tolerant rabbits. A possible relationship between the termination of tolerance in BSA-tolerant rabbits injected with cross-reacting albumins and autoimmunily was discussed. It was also suggested that the relative ease with which tolerance could be established to heterologous serum proteins in comparison to bacterial antigens is the result of the close serological and physical-chemical relationship of the heterologous serum proteins to the serum proteins of the rabbit. Rabbits injected with 500 mg of BSA during the first 5 days of life failed to form antibody capable of either eliciting an immune elimination of an injection of I* BSA given 3 to 4 months later or complexing with the circulating I* BSA.