bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Indomethacin on Cyclic Nucleotide Levels and Histamine Release from Rat Serosal Mast Cells
Authors: Lewis Robert A. , Holgate Stephen T. , Jackson Roberts L. , Maguire James F. , Oates John A. , Frank Austen K. 
Published: December 2022

Abstract
Previous studies in homogeneous and mixed cell systems on the changes in cyclic nucleotide levels that accompany the immunologic activation of mast cells for histamine release have not considered the extent to which these changes occur secondarily to the generation of the oxidative products of arachidonate. The recognition that mast cells themselves generate oxidative products of arachidonate upon immunologic activation and that exogenous prostaglandins can modulate cellular levels of 3′,5′-cyclic adenosine monophosphate (cyclic AMP) prompted the assessment of the effects of endogenous oxidation of arachidonate on changes in cyclic nucleotide levels accompanying immunologic activation. Thus, immunologic activation of purified rat serosal mast cells was carried out in the presence of a concentration of indomethacin that completely suppressed the oxidative conversion of arachidonate to the prostaglandins D2 (PGD2) and F2a (PGF2a) without having any effect on the time course and magnitude of histamine release. The immunologic activation of rat mast cells gave an early and a late monophasic rise of both cyclic AMP and 3′,5′-cyclic guanosine monophosphate (cyclic GMP). The inhibition of cyclo-oxygenase by 10 µM indomethacin abolished both monophasic rises in cyclic GMP and the second monophasic rise in cyclic AMP, but had no significant effect on the early peak of cyclic AMP that followed immunologic activation. Thus, those changes in cyclic nucleotide levels that are suppressed by indomethacin are not part of the primary activation-secretion event of mast cells and may be secondary to the generation of oxidative products of arachidonate. In contrast, the indomethacin-resistant elevations in cyclic AMP observed in the homogeneous rat mast cell system 5 to 15 sec after activation may represent an early event in the coupled activation-secretion response.
Effects of Arachidonic Acid and Its Metabolites on Antigen-Induced Histamine Release from Human Basophils in Vitro
Authors: Marone Gianni , Kagey-Sobotka Anne , Lichtenstein Lawrence M. 
Published: December 2022

Abstract
We have studied the role of arachidonic acid (AA) metabolism in immediate hypersensitivity reactions. The AA analog, eicosa-5,8,11,14-tetraynoic acid (ETYA), which inhibits both the cyclo-oxygenase and lipoxygenase pathways of AA metabolism, was found to cause a dose-dependent inhibition of antigen-induced histamine release from human basophils; complete inhibition occurred at 10-4 M. In contrast, nonsteroidal anti-inflammatory drugs (NSAID) including indomethacin (10-9 to 10-6 M), meclofenamic acid (10-6 to 10-4 M), and aspirin (10-5 to 10-3 M), which block the cyclo-oxygenase pathway of AA metabolism, enhanced mediator release. AA (10-7 to 10-5 M) also enhanced basophil mediator release, an effect that was not affected by preincubation with indomethacin. Other fatty acids including linoleic, linolenic, and stearic acids were without effect. Indomethacin (and the other NSAID studied) reversed the inhibition caused by the AA metabolite, prostaglandin (PG) E2, in a dose-dependent fashion. This reversal of inhibition was not unique to PG, but was observed with all inhibitors of histamine release studied that act via activation of adenylate cyclase including isoproterenol and the H2 agonist, dimaprit. NSAID, however, did not reverse the inhibition caused by drugs that do not act on adenylate cyclase, i.e., dibutyryl cAMP, isobutylmethylxanthine, and 2-deoxyglucose. In the leukocyte preparations studied, the NSAID did not block the increase in the intracellular cAMP levels caused by agonists that act via adenylate cyclase. It appears that a product(s) of AA metabolism, generated via the lipoxygenase pathway, is involved in IgE-mediated histamine release and that the same or a different product(s) modulates the control mechanisms that are linked to adenylate cyclase.
Characterization of Isolated Guinea Pig Kupffer Cells: Accessory Cell Function in Mitogen-Induced T Lymphocyte Activation
Authors: Rogoff Thomas M. , Lipsky Peter E. 
Published: December 2022

Abstract
Techniques were developed to isolate and purify guinea pig Kupffer cells (KC) so that their potential to interact with immunocompetent lymphocytes could be assessed. KC were prepared from guinea pig liver by sequential enzymatic digestion with collagenase and trypsin, followed by differential centrifugation, overnight culture, and glass adherence. Peritoneal exudate macrophages (PEM), induced with mineral oil but treated in otherwise identical fashion, were used for comparison in all experiments. More than 95% of the cells in KC preparations had the morphologic features of mononuclear phagocytes (Mø) and possessed peroxidase and nonspecific esterase activity. KC also exhibited many of the physiologic characteristics of Mø, including glass adherence, fluid phase pinocytosis, and phagocytosis of both nonspecific and opsonized particles. The capacity of KC to function as accessory cells necessary for the induction of mitogen-stimulated T lymphocyte proliferation was examined. Lymph node lymphocytes (LNL) depleted of adherent cells by passage over nylon wool columns were used as the responding T cell population. LNL when cultured alone were unable to undergo proliferative responses to optimal concentrations of phytomitogens. The addition of either KC or PEM to these cultures restored mitogen responsiveness to LNL. Furthermore, modification of both KC and PEM by treatment with neuraminidase and galactose oxidase generated mitogenic moieties capable of inducing blastogenesis in adherent cell-depleted LNL populations. These results provide evidence that KC are capable of functioning as accessory cells for the activation of T lymphocytes.
Human Macrophage and Lymphocyte Responses to Mitogen Stimulation after Exposure to Influenza Virus, Ascorbic Acid, and Hyperthermia
Authors: Manzella John P. , Roberts Norbert J. 
Published: December 2022

Abstract
Ascorbic acid supplementation, in several clinical cold-like viral illness studies, produced a modest reduction in severity and duration of symptoms. The current studies examined effects of ascorbic acid and hyperthermia (38.5°C) on PHA-stimulated transformation responsiveness of normal and influenza A virus-exposed human mononuclear leukocytes.
PHA responsiveness was significantly depressed by exposure to influenza virus (p &lt;0.02), but enhanced by ascorbic acid (p &lt;0.02) or hyperthermia (p &lt;0.001). Neither ascorbic acid nor hyperthermia stimulated the mononuclear leukocytes in the absence of PHA. The adverse effect on PHA responsiveness caused by exposure to influenza virus was counteracted by ascorbic acid (p &lt;0.005), hyperthermia (p &lt;0.02), or both ascorbic acid and hyperthermia (p &lt;0.001). Highly purified normal macrophages and lymphocytes were exposed independently to ascorbic acid or hyperthermia and tested for PHA responsiveness singly and together. Ascorbic acid, and probably hyperthermia, appeared to enhance macrophage function primarily. The data demonstrated that ascorbic acid and hyperthermia affected PHA-induced transformation responses of normal human mononuclear leukocytes, and counteracted the depression of PHA transformation responsiveness caused by exposure of the mononuclear leukocytes to influenza A virus.
Maturation of Bursal Stem Cells within Allogeneic or Syngeneic Bursal Microenvironment: Acquisition of Postbursal Maturity
Authors: Vainio Olli , Toivanen Auli 
Published: December 2022

Abstract
Differentiation of bursal stem cells in an allogeneic or syngeneic bursal microenvironment was compared. Bursal stem cells were transplanted into CY-treated 4-day-old recipients and permitted to differentiate in these hosts for 6 weeks. Their maturity degree was thereafter assessed by transplanting them into secondary recipients by using morphologic and functional criteria. As the secondary recipients 4-day-old CY-treated or CY-treated and surgically bursectomized chicks were used. The results obtained demonstrate that bursal stem cells develop to mature postbursal cells also within an allogeneic bursa. They also indicate that although the interaction of different lymphoid cells requires histocompatibility, the interaction between stromal cells in the bursa and lymphoid progenitors is not genetically restricted.
C9 Hemolytic Activity of the Soluble C5b-9 Complex of Guinea Pig Complement, Analogous to Human SC5b-9
Authors: Kinoshita Taroh , Hong Kyongsu , Inoue Kozo 
Published: December 2022

Abstract
When guinea pig serum was treated with zymosan, hemolytic activity of C9 appeared in a macromolecular complex with a m.w. of about 1,000,000 as well as free C9. The complex was isolated by sequential gel filtrations and sucrose density gradient centrifugation. On immunodiffusion analysis the C5 and C9 incorporated into the complex showed loss of some antigenic determinants of the respective precursor proteins. Immunoelectrophoretic analysis revealed that the complex moved faster than free C9. Preliminary estimation of the subunit composition of the complex by sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis showed that it contained similar proteins to those found in the human SC5b-9 complex. The complex seemed to contain one molecule each of C5b, C6, C7, C8, and protein corresponding to human S protein and three molecules of C9.
The C9 hemolytic activity of the complex was found to be very similar to that of free C9, both dose dependently and kinetically. It was neutralized with antibody to free C9 in a first order fashion, but the antibody to C5 did not neutralize the hemolytic activity in spite of its ability to precipitate the complex. The complex showed C9 hemolytic activity and also slight C7 activity. However, no other hemolytic activity was found when assayed with all the intermediate cells along the classical pathway or when assayed as any other of the components of complement. On the other hand, the human counterpart, SC5b-9, showed no C9 hemolytic activity but competitively inhibited the hemolytic activity of free C9, as reported previously by Kolb and Müller-Eberhard.
Lymphocyte Adherence to High Endothelial Venules: Characterization of a Modified in Vitro Assay, and Examination of the Binding of Syngeneic and Allogeneic Lymphocyte Populations
Authors: Butcher Eugene C. , Scollay Roland G. , Weissman Irving L. 
Published: December 2022

Abstract
Mouse lymphocytes incubated on fresh frozen sections of mesenteric lymph nodes adhere specifically to the endothelium of high endothelial venules (HEV), specialized vessels through which lymphocytes normally enter lymph nodes from the blood. An assay of the specific binding of lymphocytes to HEV in frozen sections is characterized and is used to compare the capacity of various syngeneic and allogeneic lymphocyte populations to adhere to HEV in mouse mesenteric lymph nodes. The relative adherence of lymphocyte populations to HEV in this in vitro system correlates highly with their localization in HEV a) during single-pass perfusion through the lymph node at 37°C, or b) in vivo 15 min after i.v. injection. With this assay we have shown that the binding of mesenteric node lymphocytes (MNL) to syngeneic mesenteric node HEV is constant: no significant variation was observed between individual mice, between sexes, between mice of various ages (3 weeks to 9 months), or after treatment of the lymphocyte donor with hydrocortisone acetate. B lymphocytes adhered as well as T lymphocytes and exhibited no preference for HEV bordering on B areas in the lymph node section. In general, other syngeneic cell populations bind in proportion to their content of mature lymphocytes. MNL exhibited no preferential adherence to syngeneic as opposed to allogeneic HEV, but A/J and BALB/c MNL demonstrated greater binding than C57BL/6J and AKR/Cum MNL, regardless of the HEV donor strain.
T Lymphocyte-Mediated Suppression of Myeloma Function in Vitro
Authors: Abbas Abul K. 
Published: December 2022

Abstract
Alloreactive cells generated by in vitro stimulation of C57BL/6 (H-2b) spleen lymphocytes with irradiated MOPC 315 or MOPC 104E (H-2d) cells were shown to lyse 51Cr-labeled myeloma targets at high effector:target ratios under conditions of maximal cell contact. After coculture at low effector:target ratios under conditions of inefficient cell contact, the alloreactive cells cause variable and frequently minimal lysis of myeloma targets but markedly suppress antibody secretion even by viable myeloma cells. The suppressor cells are radioresistant T cells lacking I-J subregion-encoded surface determinants; their precursors are insensitive to cyclophosphamide; suppression is H-2 specific and not mediated by secreted factors; and the suppression is blocked by Cytochalasin B, a known inhibitor of T cell-mediated cytolysis. These properties are typical of cytolytic T lymphocytes (CTL) and not of defined suppressor T cells, suggesting that inhibition of myeloma function probably represents a pre-lytic effect of the alloreactive CTL, although a CTL-like suppressor cell effect cannot be definitively excluded. These results are discussed with reference to the possible relationships between suppressor and cytolytic T lymphocytes.
Studies on the Induction and Expression of T Cell-Mediated Immunity
Authors: Grimm Elizabeth A. , Bonavida Benjamin 
Published: December 2022

Abstract
Secondary cytotoxic thymus-derived lymphocytes (CTL) with specificity for the priming alloantigen are shown to be generated by in vitro stimulation of allosensitized memory splenocytes with NAGO-oxidized syngeneic, allogeneic, or xenogeneic cells. The cell surface aldehyde resulting from NAGO modification of stimulator cells is required for triggering both lymphocyte proliferation and secondary (2°) CTL activation, since treatment with the reducing agent, KBH4, completely inhibited these responses. Compared to alloantigen stimulation, NAGO-oxidized stimulator cells induced an earlier peak of proliferation (2 to 3 vs 4 to 5 days), whereas the peak of the cytotoxic activity was identical (days 3 to 4).
Syngeneic splenocytes, peripheral T cells, plastic and nylon nonadherent cells, and the P388D1 macrophagelike cell line were all efficient stimulators after NAGO modification. Stimulation by syngeneic cells was shown to be mitomycin C resistant, U.V. irradiation sensitive, and ineffective when heat killed cells are used. Therefore, NAGO stimulation is distinct from antigen specific activation whereby U.V. treated cells, heated cells and nonviable membrane fragments have been shown to differentiate memory cells into 2° CTL. In addition, neither NAGO-treated sheep red blood cells nor syngeneic thymocytes were found to be effective stimulators. The addition of specific anti-Ia serum to the culture fluid inhibited both the proliferative and cytotoxic response, suggesting a role for an Ia signal during NAGO stimulation. These results show that the signal(s) required for the activation of 2° CTL from memory populations can be provided by certain subpopulations of NAGO-modified cells and is also dependent on the presence of Ia or an Ia-like molecule.
Activation to IgG Secretion by Lipopolysaccharide Requires Several Proliferation Cycles
Authors: Gronowicz Eva Severinson , Doss Carol , Schröder Jim 
Published: December 2022

Abstract
We have investigated the relationship between IgG secretion and cell proliferation after polyclonal activation of murine spleen cells with lipopolysaccharide (LPS). It was found that IgG secretion was optimal when cells proliferated extensively. Under those conditions, DNA synthesis commenced 8 to 12 hr after exposure to LPS. Increased proliferative activity was observed up to day 3, when the majority of the lymphoblasts were mitotically active. Two inhibitors of DNA synthesis, thymidine (TdR) and hydroxyurea (HU) caused a reduction in both the IgM and the IgG response, but the latter was more severely reduced. The inhibition was strongest when TdR and HU were added to cultures early after exposure to LPS, indicating that the cells developing to Ig secretion were continuously proliferating. 5-bromo-2′-deoxyuridine (BrdU) caused a general inhibition of IgM and IgG secretion at high concentrations, and a selective inhibition at low concentrations. The selective inhibition of IgG secretion, when measured on day 4, was also observed after a pulse of BrdU on days 1 and 2. The data suggest that development to IgG secretion is a complex process, which requires several proliferation cycles.
Functional Differentiation of T Cell Precursors
Authors: Cohn Marjorie L. , Scott David W. 
Published: December 2022

Abstract
Irradiated mice reconstituted with bone marrow from sheep γ-globulin- (SGG) tolerant syngeneic donors display reduced IgG responsiveness to challenge with trinitrophenylated (TNP)-SGG compared with recipients of normal marrow. This effect is SGG-specific and is due neither to suppressor T cells nor to antigen carryover. “Helper T cell precursor tolerance” can be induced with as little as 40 µg tolerogen (SGG). Unlike mature helper T cells, these precursors show both a rapid induction and rapid waning patterns, suggesting a high rate of turnover. Our results imply that marrow helper T cell precursors bear antigen-specific receptors and that the T cell repertoire must be at least partially generated before residence in the thymus.
Structural Evidence for Recombination at the Igh (H Chain) Complex Locus in BAB 14 Mice
Authors: Claflin J. Latham , Wolfe Jacqueline , Ruppert Valerie J. 
Published: December 2022

Abstract
Anti-PC antibodies from the recombinant mouse BAB 14 were evaluated by analytical isoelectric focusing in an attempt to gain information on the crucial question of whether the recombinational event in this strain occurred in V region structural genes or in allotype-linked regulatory genes. Immune sera from BAB 14, C57BL/6 and its congenic partner CB20 (both Ighb), BALB/c and its congenic partner BC8 (both Igha) were isofocused. Antibodies bearing two distinct idiotypes, T15 Id and M511 Id, were detected by an in situ localization procedure with radiolabeled anti-T15 and anti-M511 idiotypic antibodies. The IEF spectrotypic pattern of IgG antibodies of each strain revealed separate populations of T15 Id-positive (IEF-T15) and M511 Id-positive (IEF-M511) antibodies. The IEF-T15 and IEF-M511 spectrotypes in BAB 14 most closely resembled those of C57BL/6 due to the dominant charge effect of the CH region. However, the entire set of IEF-T15 bands and a portion of the IEF-M511 bands in BAB 14 show a slight but clearly evident anodal shift in its pI relative to C57BL/6. This finding of a shift, regardless of IgG subclass, demonstrates that the difference between BAB 14 and C57BL/6 resides in the VH region and not the CH region. Thus, there is direct evidence from structural data that H chains of BAB 14 are composed of a CH segment (allotype marker) commonly expressed by C57BL/Ka (Ighb) mice and VH segment commonly expressed by BALB/c (Igha) mice. These findings are discussed in terms of recombination in structural versus regulatory genes.
Emergence of Suppressor Cells of Immunoglobulin Synthesis During Acute Epstein-Barr Virus-Induced Infectious Mononucleosis
Authors: Haynes Barton F. , Schooley Robert T. , Payling-Wright Charles R. , Grouse Jan E. , Dolin Raphael , Fauci Anthony S. 
Published: December 2022

Abstract
In vitro polyclonal immunoglobulin (Ig) production and immunoregulation were studied in peripheral blood lymphocytes (PBL) from 17 acute (&lt;2 weeks after onset of symptoms) and 14 convalescent (2 to 5 weeks after onset of symptoms) Epstein-Barr virus (EBV)-induced infectious mononucleosis (IM) patients. PBL from both groups developed fewer anti-sheep red blood cell (SRBC) plaque-forming cells (PFC) (p &lt; 0.001) and fewer intracytoplasmic (ICP) Ig-positive cells (p &lt; 0.01) than normal PBL after in vitro stimulation with pokeweed mitogen (PWM). However, there was a significant trend toward increased PWM-induced anti-SRBC PFC with increasing time after onset of IM symptoms (R = 0.389, p &lt; 0.025). PBL from acute but not convalescent IM patients significantly suppressed the PWM-induced anti-SRBC PFC response (15 ± 8% of expected, p &lt; 0.001) and the ICP Ig response (21 ± 8% of expected, p &lt; 0.001) of normal PBL in allogeneic co-cultures. The suppressor cell activity in PBL of acute IM patients was removed by treatment with anti-T cell antiserum and complement as well as by the addition of 10-5 M hydrocortisone to the cell cultures.
In addition, acute IM cells in the presence of normal T cell help were able to respond normally in vitro to PWM to generate both anti-SRBC PFC and ICP Ig. Thus, PBL from both acute and convalescent IM patients manifest decreased Ig production after in vitro polyclonal stimulation. These decreased responses were associated with the emergence of corticosteroid sensitive suppressor T cells that were demonstrable in PBL of acute IM patients, and were no longer demonstrable in PBL of convalescent IM patients. The transient presence of peripheral blood suppressor T cells in these acute IM patients was associated with an uneventful clinical course and may represent in vivo immunoregulatory cell activation in response to EBV-induced polyclonal B cell activation.
Specific 125I-Iodination of Cell Surface Lipids: Plasma Membrane Alterations Induced During Humoral Immune Attack
Authors: Schlager Seymour I. 
Published: December 2022

Abstract
A method whereby lactoperoxidase-catalyzed 125I-iodination of plasma membrane lipids can be achieved is described. The reaction results in a uniform and stable labeling of neutral lipids, phospholipids, lysophosphatides, free fatty acids, and triacylglycerides. By the use of this method, the action of antibody plus complement (C) on the specific release of lipid from the plasma membrane of line-10 tumor cells was studied. Within 15 min after the addition of C to antibody-sensitized cells, the enhanced release of specific lipid classes from the cell surface was observed; these lipids included sphingomyelin, phosphatidylserine, and phosphatidylcholine. The release of phosphatidylethanolamine and, in some instances, triglycerides, was reduced after antibody-C attack. Neither the specificity of the antibody used to sensitize the cells nor the ability of the antibody plus C to be cytotoxic to the cells appeared to affect the identity or amounts of lipids released from the cells.
Deficient Production of the Lymphokine Eosinophil Stimulation Promoter in Chemically Induced and Mutation Diabetes Mellitus in Mice
Authors: Kazura James W. , Gandola Carl , Rodman Harvey R. , Mahmoud Adel A. F. 
Published: December 2022

Abstract
The cellular defects possibly responsible for diminished in vivo granuloma formation in diabetic Schistosoma mansoni-infected mice were investigated. Diabetic and control animals develop a similar degree of eosinophilia. Eosinophils obtained from diabetic mice also respond normally to the lymphokine eosinophil stimulation promoter (ESP). Lymphoid cells of chemically induced (streptozotocin) and mutation diabetic (db/db) mice, however, have a decreased capacity to produce/secrete ESP in response to soluble egg antigens of S. mansoni. Administration of insulin to diabetic mice is associated with a partial reversal of the decreased ability of their lymphoid cells to generate ESP. These findings show that defective cellular immunity in diabetic animals may be partially explained by the failure of their lymphocytes to produce the soluble mediators involved in recruitment of target cells.