bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immature and advanced patterns of T cell receptor gene rearrangement among lymphocytes in splenic culture.
Authors: Hurwitz J L , Samaridis J , Pelkonen J 
Published: December 2022

Abstract
Bulk populations and 39 hybridomas from splenic Con A cultures were analyzed for rearrangements among TCR genes: alpha, beta, gamma, and delta. Patterns were categorized to reveal general rules governing gene rearrangement within the activated adult peripheral population. Many patterns of gene rearrangement were consistent with previous studies of T cell lines. Additional points of interest were the following: 1) A large proportion of Con A-stimulated splenic cells bore no TCR gene rearrangements. 2) One splenic hybridoma exhibited an unusual gene pattern, with rearrangements, at alpha and beta, but not J gamma 1 or J gamma 2 loci. 3) Multiple gamma rearrangements were noted other than V1.2-J2 and V2-J1. 4) One hybridoma exhibited TCR gene rearrangements typical of day 14 to 15 fetal thymocytes, as well as rearrangements at immunoglobulin gene loci. 5) Among hybridomas with J alpha rearrangements, homologous chromosomes exhibited rearrangements at similar positions along the J alpha locus.
Inhibition of acute passive transfer experimental autoimmune myasthenia gravis with Fab antibody to complement C6.
Authors: Biesecker G , Gomez C M 
Published: December 2022

Abstract
The role of the lytic complement C5b-9 membrane attack complex (MAC) in acute passive transfer experimental autoimmune myasthenia gravis (EAMG) produced in rats was investigated by in vivo inhibition of MAC formation with anti-C6 Fab. Anti-C6 Fab totally inhibited in vitro serum hemolytic activity, but did not consume or inhibit early complement pathways. Injection of rats with 0.12 mg/ml anti-C6 Fab reduced serum C6 to 8% and inhibited the muscle weakness, electrophysiologic abnormalities and loss of acetylcholine receptor (AChR) associated with acute EAMG. This level of C6 inhibition reduced the total serum complement hemolytic activity to 29% of normal but did not reduce the serum levels of complement components C3, C5, or C7. Treatment of rats with lower amounts of anti-C6 Fab (0.08 mg/ml) also inhibited clinical and electrophysiologic signs of EAMG, however, the lower amount of anti-C6 did not prevent the loss of muscle AChR. Both the higher and the lower amount of anti-C6 Fab inhibited the accumulation of macrophages at muscle motor end-plates. The inhibition by anti-C6 indicates that muscle weakness and electrophysiologic abnormalities associated with EAMG are dependent on the complement MAC, and that muscle weakness results from tissue injury in addition to loss of muscle membrane and AChR.
A circulating suppressive factor of platelet cytotoxic functions after rush immunotherapy in Hymenoptera venom hypersensitivity.
Authors: Tsicopoulos A , Tonnel A B , Wallaert B , Joseph M , Ramon P , Capron A 
Published: December 2022

Abstract
A receptor for the Fc fragment of IgE has been described on human blood platelets. This receptor mediated the IgE-dependent stimulation of platelets by the specific allergen in Hymenoptera venom (HV) hypersensitivity. This platelet reactivity was abolished after rush desensitization. To understand the mechanism of such a down-regulation, we studied the effects of sera recovered from patients treated by HV rush desensitization on platelets of untreated HV sensitive patients. The present data describe the presence of a circulating factor able to suppress, in a dose-dependent manner, platelet stimulation by the specific allergen. This circulating factor was not allergen specific, not depleted by IgE or IgG antibody immunoadsorption, and was found at higher concentrations in the sera of patients receiving monthly high dosages of HV (200 micrograms maintenance dose). The physicochemical characterization showed that this circulating factor had a m.w. of 20,000 to 25,000, an isoelectric point of 4.2, was heat and acid stable, and sensitive to trypsin, but not to neuraminidase. These characteristics were similar to a newly described lymphokine, platelet activity suppressive lymphokine, suggesting the intervention of such a lymphokine in HV rush desensitization.
Specific binding of human C-reactive protein to human monocytes in vitro.
Authors: Ballou S P , Buniel J , Macintyre S S 
Published: December 2022

Abstract
The precise biologic function of C-reactive protein (CRP), a major acute phase protein in man, is unknown. The abilities of CRP to bind biologic substrates and to activate the C pathway, and its localization at sites of inflammation argue for an opsonic role for this protein. Such a role has been supported by recent reports of specific binding of CRP to neutrophils. Using highly purified radioiodinated human CRP, we have observed specific binding of this protein to human monocytes in vitro. The binding was reversible and rapid, with a t1/2 for the dissociation reaction of approximately 3 min. Binding was saturable at a CRP concentration of approximately 0.2 microM, with an estimated K from Scatchard analysis of 1.1 x 10(-7) M. Specific binding was calcium-dependent, with optimal binding occurring at calcium concentrations of more than 1.0 mM. No specific binding could be demonstrated to a non-adherent population of mononuclear cells (more than 80% lymphocytes). In other experiments, a 100-fold excess of human IgG failed to inhibit binding, although rabbit CRP produced competitive inhibition of binding which was quantitatively similar to human CRP. The binding was maximal at pH 7.4 and was sensitive to prior trypsin treatment of cells. These studies provide direct evidence for specific binding of soluble human CRP to human monocytes in vitro and thus provide further support for an important functional interaction of this acute phase protein with phagocytic cells in man.
Human erythrocytes inhibit complement-mediated solubilization of immune complexes.
Authors: Dorval B L , Cosio F G , Birmingham D J , Hebert L A 
Published: December 2022

Abstract
Incubation of precipitable immune complexes (IC) with fresh human serum or guinea pig serum resulted in solubilization of IC. When packed human E were added to human serum or guinea pig serum, binding of IC to the E occurred and IC solubilization was significantly inhibited. By contrast, SRBC did not bind IC nor inhibit IC solubilization. Because IC binding to human E is mediated by CR type 1 (CR1) we evaluated whether CR1 was responsible for the inhibition of IC solubilization. Human E were treated with trypsin or anti-CR1 mAb. Both treatments abrogated IC binding to human E but did not affect the ability of the human E to inhibit IC solubilization. Human E inhibited C activation by IC. Thus, incubation of IC in human serum caused significant activation of C3 and C5, but not C4. However, when IC were incubated in whole blood or with isolated human E and serum, C3 activation by IC was inhibited significantly. In addition, we demonstrated that the C3b generated during C activation by IC deposited on both IC and human E. Thus, human E may compete for nascent C3 generated during C activation by IC. In conclusion, human E inhibit both complement-mediated solubilization of IC and C activation by IC.
Targeting of complement to tumor cells by heteroconjugates composed of antibodies and of the complement component C3b.
Authors: Reiter Y , Fishelson Z 
Published: December 2022

Abstract
Tumor cells have adapted several strategies which permit them to grow in an immunologically hostile environment. The C system can potentially destroy these cells; however, its action needs to be specifically potentiated on the surface of the tumor cells. To this end, a heteroconjugate composed of a mouse mAb and of the human C3b C component has been generated by using the heterobifunctional reagent N-succinimidyl-3-(2-pyridyldithio)propionate. The two mAb which were used in this study are V1-10 and TIB219 which bind to the human and mouse transferrin receptors, respectively. The mAb-C3b conjugates were purified by gel filtration and were each composed of one mAb and one C3b. They bound to the human K562 and HL60 or mouse ALB1 cell lines and amplified the killing of these cells by C from 10 to 15% to 70 to 100%. Fresh normal human or mouse sera were used as a source of C. The mAb-C3b conjugates activated primarily the alternative pathway of C since only C3 and factor B but not C4 were cleaved in the sera. After disulfide-linking to the mAb, the C3b became highly resistant to inactivation by factors H and I, probably due to its reduced factor H binding capacity. On the other hand, the conjugated C3b bound factor B better than free C3b and produced more C3 convertases which expressed increased stability. These results suggest that mAb-C3b conjugates may serve as an effective tool for the specific activation of the cytolytic C system on selected cells. As such, they may be used in vitro or in vivo to target the autologous C to tumor cells or to lymphocytes and may promote tumor immunotherapy.
Preferential binding of the neutrophil cytoplasmic granule-derived bactericidal/permeability increasing protein to target bacteria. Implications and use as a means of purification.
Authors: Mannion B A , Kalatzis E S , Weiss J , Elsbach P 
Published: December 2022

Abstract
The specificity of the basic bactericidal/permeability increasing protein (BPI) of polymorphonuclear leukocytes (PMN) for gram-negative bacteria is attributable to its strong attraction for the negatively charged envelope LPS. The antibacterial activity of PMN homogenates or extracts toward Escherichia coli corresponds to their BPI content and is blocked by anti-BPI IgG, suggesting that BPI action is unaffected by the presence of other PMN proteins. To test if BPI is preferentially bound to E. coli when other antibacterial proteins are present, we have measured binding in buffered (pH 7.5) balanced salts solution of [125I] human BPI to E. coli J5 in the presence and absence of other human PMN granule proteins. BPI binding is saturable with an apparent K = 23 nM and 2.2 million binding sites/cell. While binding of [125I] human BPI is competitively inhibited by human or rabbit BPI, it is only weakly inhibited by myeloperoxidase, lysozyme, or cathepsin G. In contrast, myeloperoxidase binding to E. coli is strongly inhibited by BPI. Moreover, incubation of E. coli with crude extracts of PMN or CML spleen results in near quantitative binding of BPI, identified by silver staining and immunoblotting after SDS-PAGE of the washed E. coli pellet, without recognizable binding of other leukocyte proteins (greater than 98% of added total protein is recovered in supernatant). After addition of 200 mM MgCl2, approximately 80% of bound BPI is released as fully active and pure protein (as judged by SDS-PAGE and HPLC). Thus the selective and reversible binding of BPI in crude PMN extracts to target bacteria provides a one-step "affinity" purification procedure.
Immunogenic Gal alpha 1----3Gal carbohydrate epitopes are present on pathogenic American Trypanosoma and Leishmania.
Authors: Avila J L , Rojas M , Galili U 
Published: December 2022

Abstract
Anti-Gal is a natural antibody present in unusually high concentrations in human sera. It constitutes as much as 1% of circulating IgG and displays a distinct specificity for the Gal alpha 1----3Gal carbohydrate epitope. In the present study, we have found in the sera of patients with Chagas' disease and Leishmania infection anti-Gal titers 10- and 16-fold higher than that of healthy or bacteria-infected individuals. This increase in anti-Gal titer seemed to be the result of a specific immune response toward parasitic Gal alpha 1----3Gal epitopes. Binding studies of affinity chromatography-purified anti-Gal antibodies to Trypanosoma cruzi and American Leishmania parasites indeed demonstrated the presence of Gal alpha 1----3Gal epitopes on these parasites. This finding was supported by the observed binding to the parasites of two additional Gal alpha 1----3Gal recognizing molecules: the mAb Gal-13, and the lectin, Bandeiraea simplicifolia I B4. Furthermore, the binding of both anti-Gal antibody and of the B. simplicifolia I B4 lectin could be inhibited by galactose, and not glucose. In addition, removal of the terminal alpha-galactosyl residues from the parasites by pretreatment with alpha-galactosidase, or the oxidation of the binding epitopes by periodate prevented the subsequent binding of both the antibody and the lectin. A crude leishmanial lipid extract readily bound these three reagents, suggesting that at least part of these epitopes are of a glycolipid nature. These Gal alpha 1----3Gal epitopes may thus serve as an antigenic source for the excess production of anti-Gal. In view of the naturally high level of anti-Gal in humans and its binding to T. cruzi and Leishmania, it is argued that these antibodies may contribute to the natural defense against the invasion of such parasites.
A beta-adrenergic agonist modulates DR alpha gene transcription via enhanced cAMP levels in a glioblastoma multiforme line.
Authors: Basta P V , Moore T L , Yokota S , Ting J P 
Published: December 2022

Abstract
In this study we have examined the ability of the beta-adrenergic agonist isoproterenol (ISO) to alter the expression of the human MHC class II Ag, DR, on a glioblastoma multiforme cell line. We have determined that ISO induces an increase in both DR alpha-specific RNA and protein. This induction is most likely due to the increase in cAMP levels elicited by the agonist, based on the direct measurements of cAMP levels and the ability of DBcAMP and the adenylate cyclase activator, forskolin to mimic the effects of isoproterenol. Blocking of the induction was achieved with the beta-antagonist, propranolol, but not with the alpha-antagonist phentolamine, indicating that this is a beta-adrenergic receptor-mediated phenomenon. Finally this induction is transcriptionally regulated as determined by nuclear run-on experiments. Future studies will center on identifying DNA regions of the DR alpha-chain gene which are important in this regulation.
Dissociation between murine spleen cell mitogenic activity of enterotoxin contaminants and anti-tumor activity of staphylococcal protein A.
Authors: Das C , Langone J J 
Published: December 2022

Abstract
Soluble staphylococcal protein A (SpA) in the form of high m.w. complexes with IgG has been shown to significantly inhibit the growth of Meth A fibrosarcomas in BALB/c mice. Although SpA reportedly is a potent T cell mitogen that can induce immune cell proliferation and production of humoral factors with anti-tumor activity, it has been suggested that mitogenic enterotoxin contaminants might be responsible for these effects. The purpose of the present study was to investigate the nature of SpA-induced cell proliferation and the relationship between mitogenicity and the anti-tumor effect that we observed in our mouse model. SpA stimulated the proliferation of a mixed population of splenic B and T cells from BALB/c mice, but activity did not require the presence of IgG in the culture medium. Furthermore, mitogenic activity could be inhibited completely by anti-SEA plus anti-SEB, but was unaffected by anti-SpA. HPLC-purified SpA was inactive while the mitogenic factor(s) had the same retention time as authentic enterotoxin and its activity was inhibited by anti-SEA and anti-SEB, but not by anti-SpA. Enterotoxin-free rSpA produced in Escherichia coli had the same IgG binding capacity as the staphylococcal product but was not mitogenic. These data indicate that SEA and SEB completely account for mitogenicity in SpA preparations. In contrast, we found that optimal concentrations of rSpA as well as crude and HPLC purified staphylococcal SpA were equally effective in inhibiting the growth of established Meth A fibrosarcomas demonstrating that SpA is responsible for antitumor activity without any apparent role for enterotoxins.
In vivo effects in mice of an anti-T cell immunotoxin.
Authors: Marcucci F , Lappi D A , Ghislieri M , Martineau D , Formosa A , Siena S , Bregni M , Soria M , Gianni A M 
Published: December 2022

Abstract
We have evaluated both the proliferative response as well as the Thy-1 Ag expression of lymphocytes from mice treated in vivo with an anti-Thy-1 immunotoxin (IT). The IT was a rat IgG2c mAb recognizing the Thy-1 Ag, disulfide-linked to a ribosome-inactivating protein isolated from the seeds of the plant Saponaria officinalis (soapwort). Toxicity studies showed that a single i.v. injection of doses up to 20 micrograms IT/mouse was well tolerated and allowed indefinite survival. The Con A-induced proliferative response of spleen cells from mice killed 1 day after treatment with sublethal doses of IT was inhibited in a dose-dependent manner, with complete inhibition observed at doses of greater than or equal to 5 micrograms IT/mouse. Control experiments showed that the inhibition was due to the IT and not to its single components. Moreover, the IT effect was abolished by a large (100-fold) excess of anti-Thy-1 mAb alone given concurrently, but not by an unrelated, isotype-matched rat mAb. At all IT doses, the proliferative response to a B cell mitogen (LPS) was normal. Kinetic studies showed a time- and dose-dependent reconstitution of Con A responsiveness. In limiting dilution cultures of spleen cells from mice treated with 5 micrograms IT 1 or 4 days before death, a 97% depletion of T lymphocytes capable of proliferation was observed. Limiting dilution cultures showed that also the thymus of IT-treated mice was depleted by more than 90% of growth-competent T lymphocytes. Cytofluorographic studies of Thy-1+ cells from the spleens of IT-treated mice gave results which did not correlate with those obtained in functional assays. Thus, a dose-dependent reduction, followed by a time-dependent reconstitution of Thy-1+ cells was observed in this case too, but the depletion occurred at later time points and was less complete than that observed in functional assays. Moreover, the mean fluorescence intensity of the residual Thy-1+ cells decreased below normal levels.
Cytotoxic T lymphocyte recognition of secreted HLA class I molecules.
Authors: Kahn-Perles B , Barra C , Jehan J , Fourel D , Barad M , Maryanski J L , Lemonnier F A 
Published: December 2022

Abstract
The cytolytic responses of DBA/2 mice against syngeneic transfected P815 mastocytoma cells expressing either membrane-associated (HLA-Cw3) or -secreted hybrid (HLA-Cw3 x H-2 Q10b) molecules were compared. In spite of the absence of serologically detectable hybrid molecules on their plasma membrane, cells secreting these molecules elicited a CTL response similar to that of cells expressing the membrane associated HLA-Cw3 molecules, in terms of both MHC-restriction and peptide specificity. Together with the observation that syngeneic mice were capable of rejecting the injected secreting cells, these results imply that secreted HLA class I molecules can function as minor histocompatibility Ag and suggest that processing of both the membrane-bound and the -secreted forms of a protein may follow common or overlapping pathways.
Modulation of antibody-mediated glomerular injury in vivo by bacterial lipopolysaccharide, tumor necrosis factor, and IL-1.
Authors: Tomosugi N I , Cashman S J , Hay H , Pusey C D , Evans D J , Shaw A , Rees A J 
Published: December 2022

Abstract
We have investigated the effects of LPS, human rTNF (hrTNF) and human rIL-1 beta (hrIL-1 beta) pretreatment on the intensity of antibody-mediated injury in vivo by using a passive model of anti-glomerular basement membrane (GBM) antibody-mediated nephritis in rats. The experiments show that all three pretreatments exacerbate injury in this model whether judged by albuminuria or the prevalence of glomerular capillary thrombi. The effect on albuminuria was dose dependent with all three treatments. The lowest effective dose of LPS was 0.025 microgram while those for hrTNF and hrIL-1 beta were 0.4 microgram and 0.5 microgram, respectively. All three pretreatments also increased the prevalence of glomerular capillary thrombi which were rare in rats injected with anti-GBM antibodies without pretreatment. LPS pretreatment appeared to be more effective in causing glomerular capillary thrombi than hrTNF or hrIL-1 beta and this was reflected in the correlations between albuminuria and the proportion of glomeruli with capillary thrombi. This relation was linear for all three pretreatments but the slope was appreciably greater for rats pretreated with LPS (0.37) when compared with results from rats given either hrTNF (0.22) or hrIL-1 beta (0.29). Pretreatment of nephritic rats with both cytokines increased the slope to 0.42 demonstrating a synergistic effect. The synergism of hrTNF with hrIL-1 beta was also demonstrated by the effective doses needed to induce albuminuria which was evident in rats treated with 0.05 microgram of IL-1 beta and 0.4 microgram of TNF. Neither the cytokines nor LPS caused clinical, morphologic, or biochemical evidence of renal toxicity when given alone in the dose used here but they did cause a transient increase in the number of neutrophils marginated in glomerular capillaries. Pretreatment of rats with LPS or cytokines increased the glomerular neutrophil influx after anti-GBM antibodies by roughly sixfold. Our experiments show that TNF and IL-1 can increase the severity of glomerular injury in nephritis; they may be important in modulating glomerular injury clinically.
IgE-dependent regulation of human basophil adherence to vascular endothelium.
Authors: Bochner B S , MacGlashan D W , Marcotte G V , Schleimer R P 
Published: December 2022

Abstract
Mechanisms favoring the recruitment of circulating human basophils to extravascular sites of allergic inflammation are unknown. The basophil secretagogues anti-IgE, and pollen allergens rye grass I and ragweed Ag E (Lol p I and Amb a I) were tested for their ability to promote basophil adherence to umbilical vein endothelial cells. Co-incubation of endothelial cells and basophils with anti-IgE resulted in time and dose-dependent increases in basophil adhesion. These effects were due to activation of the basophil, required both magnesium and calcium, occurred before or in the absence of histamine release, and were seen at concentrations of stimulus below the usual range of secretagogue activity. In contrast, anti-IgE or Ag stimulation of neutrophils, or basophils from donors non-responsive to anti-IgE or Ag with respect to histamine release, had no effect on cell adherence. mAb 60.3, recognizing the CD18 leukocyte adhesion molecule, inhibited anti-IgE-induced enhancement of basophil-endothelial cell binding. Exposure of basophils to low concentrations of Ag in vivo may selectively initiate basophil infiltration into tissue sites of allergic inflammation by enhancing their adherence to endothelium.