Strong tolerance mediated by allografting in the rat is due to donor liver leukocytes.
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Animals↗
Biomedical subjects
S Jung
Publications and source records attributed to S Jung.
Proliferating cell nuclear antigen (PCNA) and nucleolar organizer regions (NORs) in benign, atypical and malignant meningiomas.
Expression of proliferating cell nuclear antigen (PCNA) and numbers of nucleolar organizer regions (NORs) were studied by immunohistochemistry and the silver staining technique in 99 meningiomas and related to histopathologic grading, recurrence and their predictive value for recurrence. The results indicated that there was a significant correlation between PCNA or AgNORs and histopathologic grading of meningiomas. Slightly higher expression of PCNA in atypical meningiomas was correlated with the increased recurrence rate; however, expression of PCNA and numbers of AgNORs in meningiomas are not reliable criteria to predict tumor recurrence.
Humans↗
Crystallization and X-ray crystallographic analysis of recombinant chicken poly(ADP-ribose) polymerase catalytic domain produced in Sf9 insect cells.
Poly (ADP-ribose) polymerase (PARP) participates in the immediate response in mammalian cells exposed to DNA-damaging agents. Recombinant baculovirus harboring the cDNA of the chicken PARP catalytic domain (40 kDa) have been used to infect Spodoptera frugiperda (Sf9) insect cells. The recombinant polypeptide (30 mg per 1 x 10(9) cells) was purified to homogeneity by 3-aminobenzamide affinity chromatography. The enzymatic properties of the recombinant domain were similar to those of the native fragment. Crystals of the purified recombinant catalytic domain were grown by vapor diffusion. The crystals belong to space group P2(1)2(1)2(1) with unit cell dimensions of a = 59.2 A, b = 65.0 A, c = 96.9 A. They are suitable for X-ray analysis and diffract to 2.0 A.
Animals↗
Frequency of immunoglobulin E class switching is autonomously determined and independent of prior switching to other classes.
Both, in humans and in mice, a major fraction of immunoglobulin E (IgE)-expressing B lymphocytes develops by sequential Ig class switching from IgM via IgG to IgE. This sequential class switch might have functional implications for the frequency and repertoire of IgE+ cells. Here we show that in mutant mice, in which sequential switching to IgE via IgG1 is blocked, the frequency of cells switching to IgE is not affected. Thus, sequential class switching to IgE merely reflects the simultaneous accessibility of two acceptor switch regions for switch recombination, induced by one cytokine, but with markedly distinct efficiency. Analysis of switch recombination on both IgH alleles of switched cells shows that the low frequency of switching to IgE is an inherent feature of the S epsilon switch region and its control elements.
Animals↗
The Saccharomyces cerevisiae gene PPH3 encodes a protein phosphatase with properties different from PPX, PP1 and PP2A.
A clone encoding the catalytic subunit of a protein phosphatase from Saccharomyces cerevisiae was isolated. Except for replacement of IIe-245 by Met the structure of the phosphatase was identical to that encoded by PPH3 (Ronne, H., Carlberg, M., Hu, G. Z. and Nehlin, J. O. (1991). Mol. Cell. Biochem. 11, 4876-4884) and exhibited 63% sequence identity to PPX cloned from a rabbit liver cDNA library (Brewis, N.D., Street, A.J., Prescott, A.R. and Cohen, P.T.W. (1993). EMBO J. 12, 987-996). Expression of active enzyme was achieved in Escherichia coli mutants which were generated by a genetic selection based on functional complementation of bacterial phosphoserine phosphatase. Though some of the properties of PPH3 resembled those of protein phosphatase 2A and PPX, others were different. PPH3 exhibited lower sensitivity against inhibition by okadaic acid, showed different substrate specificity and required a divalent cation (Mn2+ was preferred before Mg2+ and Ca2+) for activity when assayed with phospho-histone as a substrate. However, 25% of maximum activity was observed in the absence of divalent cations when the peptide LRRAS(P)LG was used as substrate. The PPH3-protein was also identified by chromatography of extracts from S. cerevisiae on DEAE-cellulose. Protein immunoreactive with an antiserum raised against the non-conserved N-terminal 53 amino acids of PPH3 was coeluted with a single peak of LRRAS(P)LG dephosphorylating activity.
Amino Acid Sequence↗
Impact of 15-deoxyspergualin on effector cells in experimental autoimmune diseases of the nervous system in the Lewis rat.
The influence of the immunosuppressive antibiotic agent 15-deoxyspergualin (DSG) on macrophages and autoreactive T helper lymphocytes from Lewis rats was analysed in vitro and in vivo. DSG did not inhibit antigen- or mitogen-induced proliferation of encephalitogenic or neuritogenic T helper cell lines in vitro. However, the presence of DSG during in vitro activation of the T cells strongly suppressed or completely abrogated their capacity to induce encephalitis (EAE) or neuritis (EAN) after adoptive transfer to naive rats, although expression of activation markers or adhesion molecules on the T line blasts was not down-regulated by DSG. Like activation-induced T cell proliferation, IL-2-dependent growth of CD4+ T line cells was not affected by DSG. Preincubation of CD4+ T line cells in DSG during IL-2-driven proliferation for 48 h, however, inhibited the subsequent antigen- but not mitogen-induced activation of these T cells, although neither density of T cell receptors nor other surface molecules involved in antigen recognition were lowered on the cells exposed to DSG. Similar to its effect in vitro, in vivo administration of DSG for 10 days even at a concentration with cumulative toxicity did not suppress in vitro proliferation of spleen cells induced by mitogen or a mitogenic combination of anti-CD2 antibodies. Furthermore, spleen cell and peripheral blood lymphocyte (PBL) surface antigens, particularly MHC molecules, were not altered by long-term treatment with DSG for 30 days. While there was a slight reduction in the number of polymorphonuclear cells in both populations, the proportion of the different leucocyte subpopulations remained unchanged. In contrast to the strong functional impact of DSG on autoreactive T helper cells, the drug did not inhibit the oxidative burst of macrophages or their MHC antigen expression. This study demonstrates a clear inhibitory effect of DSG on CD4+ T lymphocytes, but not macrophages. It provides an explanation for recent observations of a strong immunosuppressive in vivo effect of DSG on transplantation rejection and experimental autoimmune diseases, despite a normal mitogen response of T cells exposed to DSG in vivo and in vitro.
Animals↗
Therapeutic effect of transforming growth factor-beta 2 on actively induced EAN but not adoptive transfer EAN.
A possible effect of transforming growth factor type-beta 2 (TGF-beta 2) on autoimmune inflammation of the peripheral nervous system (PNS) was evaluated in experimental autoimmune neuritis (EAN) in Lewis rats, a disease model of the human Guillain-Barré syndrome. First, EAN was actively induced by immunization with a neuritogenic peptide corresponding to amino acids 53-78 of the bovine P2 protein. Intraperitoneal (i.p.) administration of 5 micrograms TGF-beta 2 per day after onset of clinical disease shortened the duration and ameliorated the severity of EAN compared to sham-injected control animals. Inflammatory infiltration and demyelination was significantly reduced in sciatic nerves of TGF-beta-treated animals, although expression of major histocompatibility complex (MHC) class II antigens was not down-regulated. Second, EAN was induced by adoptive transfer (AT) of activated P2-specific T-line cells (AT-EAN). Daily injections of 5 micrograms TGF-beta 2 i.p., beginning on the day of first clinical signs, failed to modify the clinical course of AT-EAN, although the antigen-induced activation of the neuritogenic T-line cells used for induction of disease was found to be partially sensitive to the inhibitory effect of TGF-beta in vitro. The experiments indicate that TGF-beta 2 holds promise as a therapeutic agent to combat autoimmunity in the PNS. They also suggest that the therapeutic efficacy of TGF-beta on rapidly developing disease such as AT-EAN is limited, as with other non-specific immunosuppressive drugs.
Animals↗
[Comparative study of lipids, apoproteins and lipoproteins in patients with coronary disease and in a control population].
We carried out a comparative study of various lipid parameters (apo AI and B, LpAI, Lp(a) and LpBCIII) in coronary heart disease patients (19 males and 4 females, mean age 61 +/- 11 years) and in controls (18 males and 14 females, mean age 55 +/- 3 years) selected so that cholesterol and triglycerides levels be beneath 6 and 2.3 mmol/l in both populations. Apo AI and B were analysed by immunonephelometry and lipoparticles by electroimmunodiffusion. Nonparametric statistics tests were performed on account of the small numbers in both groups. Our study confirms the protective effect of Lp AI but did not show an obvious superiority of Lp AI quantification compared to apo AI. It highlights the interest of Lp(a) as an independent and additional risk factor for atherogenesis: no obvious correlation with any other lipidic parameter was demonstrated. An increase in Lp(a) beyond 0.30 g/l increases atherogenic risk 2.5 fold. We did not show any benefit of LpBCIII quantification in 'normolipemic' coronary patients. In conclusion, a discriminant analysis including the apo B/apo AI and apo B/LpAI ratios and Lp(a) allows an accurate classification of 67% of the patients.
Apolipoproteins A↗
Structures and stereochemistry of the very long alpha, omega-bifunctional alkyl species in the membrane of Sarcina ventriculi indicate that they are formed by tail-to-tail coupling of normal fatty acids.
In a previous study, we demonstrated that Sarcina ventriculi is capable of adjusting to alterations in environmental conditions (such as increase in temperature, lowering of pH, or addition of exogenous organic solvents) by the synthesis of a family of alpha, omega-dicarboxylic acids ranging from 28 to 36 carbons long (Jung, S., et al. 1993. J. Biol. Chem. 268: 2828-2835). The chain lengths and relative abundance of the very long dicarboxylic acids found in S. ventriculi suggest that they may be formed after the perturbation by the (enzymatic) tail-to-tail combinations of existing regular monofunctional fatty acids and not completely de novo by direct 2-carbon addition of acetyl coenzyme A (CoA). If this were true, knowing the structures of the regular fatty acids, we can predict those of the very long chain bifunctional acids. In this work we present definitive chemical results that strongly support this mechanism. This was done by analyzing the structures and stereochemistry of the very long bifunctional species in the light of those of the regular monofunctional species. The exact structures of membrane fatty acid methyl ester derivatives components were determined by various spectroscopic and chemical methods including gas chromatographic (GC) analysis, gas chromatography-mass spectrometry (GC-MS), 1H and 13C nuclear magnetic resonance (NMR) spectroscopy, Fourier transform infrared (FTIR) spectroscopy, polarimetry, and reductive ozonolysis. This yielded precise structural and stereochemical information on the position of substitution of the acyl chain by methyl groups, position and configuration of double bonds, and optical activity. These results, coupled with the absence of intermediate length acyl species, indicated that the very long alkyl species (without exception) can be formed by tail-to-tail joining of existing fatty acids. The ideas of a dynamically regulated catalytic system is proposed.
Cell Membrane↗
Modulation of EAE by vaccination with T cell receptor peptides: V beta 8 T cell receptor peptide-specific CD4+ lack direct immunoregulatory activity.
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Amino Acid Sequence↗
A new family of very long chain alpha,omega-dicarboxylic acids is a major structural fatty acyl component of the membrane lipids of Thermoanaerobacter ethanolicus 39E.
A new family of alpha,omega-dicarboxylic, very long chain fatty acids was isolated and characterized from the lipids of thermophilic anaerobic eubacterium, Thermoanaerobacter ethanolicus 39E. After the isolation of the membrane, the fatty acyl components were converted to methyl esters by acid-catalyzed methanolysis. The esterified fatty acyl components were purified by a variety of chromatographic techniques and analyzed by gas chromatography (GC) and GC-mass spectrometry (MS). One of the isolated, esterified alpha,omega-dicarboxylic, very long chain fatty acids was characterized by mass spectrometry, 1H and 13C NMR spectroscopy and Fourier transform infrared spectroscopy. NMR experiments used included double quantum filtered correlated spectroscopy (DQF-COSY) to establish spin connectivities and polarization transfer (DEPT) to measure the multiplicity of carbon signals split by protons. Based on these results, the structures of the other components could be deduced from their mass spectra. The new family of very long chain fatty acid methyl esters are alpha,omega-13,16-dimethylheptacosanedioate dimethyl ester (C29), alpha,omega-13,16-dimethyloctacosanedioate dimethyl ester (C30), alpha,omega-13,16-dimethylnonacosanedioate dimethyl ester (C31), and alpha,omega-13,16-dimethyltriacotanedioate dimethyl ester (C32). This family of fatty acids make up about 40% of fatty acyl components of the membrane of Thermoanaerobacter ethanolicus 39E. Almost all (> 90%) of the very long chain, alpha,omega-dicarboxylic fatty acid was alpha,omega-13,16-dimethyloctacosanedioic acid. A careful analysis of the structures of the alpha,omega-dicarboxylic acid strongly implies that the synthetic mechanism for formation is by tail-to-tail (omega)coupling of regular iso-branched fatty acids across opposite sides of the membrane.
Bacteria, Anaerobic↗
Inhibition of experimental autoimmune neuritis by an antibody to the lymphocyte function-associated antigen-1.
BACKGROUND: Experimental autoimmune neuritis (EAN) is an animal model of Guillain-Barré syndrome. The mechanisms underlying cellular trafficking and homing of autoreactive immune cells to the peripheral nervous system during EAN and Guillain-Barré syndrome are unknown. We investigated the role of the adhesion molecule lymphocyte function-associated antigen-1 in the pathogenesis of EAN. EXPERIMENTAL DESIGN: EAN was induced in Lewis rats either by immunization with bovine spinal root myelin or by adoptive transfer of P2-specific T cells. Animals were treated intraperitoneally with a monoclonal antibody to lymphocyte function-associated antigen-1 (WT-1) or phosphate-buffered saline and scored for clinical signs. Histology was performed on sciatic nerve and cauda equina and assessed for infiltration and demyelination. Severity of EAN and the corresponding histologic alterations were compared in the different treatment groups. The in vitro effect of WT-1 on T cell proliferation was evaluated. RESULTS: Treatment with WT-1 prevented or efficiently suppressed myelin-induced EAN. In contrast, sham treatment of animals failed to alter the clinical course of EAN. Histologic examination of the peripheral nervous system showed a marked reduction of inflammatory infiltration and perivascular demyelination in animals treated with WT-1. Adoptive transfer EAN was not affected by the administration of WT-1. The differential action in the two models suggests that WT-1 appears to act primarily on the induction phase of the immune response but has no significant impact on the effector phase. In vitro studies with WT-1 revealed that the antibody inhibits the concanavalin A-dependent proliferation of neuritogenic P2-specific T cells. CONCLUSIONS: Our data indicate that lymphocyte function-associated antigen-1 is critically involved in the pathogenesis of EAN. Further analysis of this model may provide insight into the process of immune cell recruitment from the circulation into the peripheral nervous system in immune-mediated neuropathies.
Animals↗
Shutdown of class switch recombination by deletion of a switch region control element.
Upon activation, B lymphocytes can change the class of the antibody they express by immunoglobulin class switch recombination. Cytokines can direct this recombination to distinct classes by the specific activation of repetitive recombinogenic DNA sequences, the switch regions. Recombination to a particular switch region (s gamma 1) was abolished in mice that were altered to lack sequences that are 5' to the s gamma 1 region. This result directly implicates the functional importance of 5' switch region flanking sequences in the control of class switch recombination. Mutant mice exhibit a selective agammaglobulinemia and may be useful in the assessment of the biological importance of immunoglobulin G1.
Animals↗
Sarcina ventriculi synthesizes very long chain dicarboxylic acids in response to different forms of environmental stress.
Changes in the composition of membrane lipids in a strictly anaerobic, facultative acidophilic eubacterium, Sarcina ventriculi, were studied in response to various forms of environmental stress. Changes in lipid composition and structure occurred in response to changes in environmental pH. At neutral pH, the predominant membrane fatty acids ranged in chain length from C14 to C18. However, when cells were grown at pH 3.0, a family of unique very long chain fatty acids containing 32-36 carbon atoms was synthesized and accounted for 50% of the total membrane fatty acids. These acids were identified as very long chain alpha,omega-dicarboxylic acids ranging in length from 28 to 36 carbons by electron impact mass spectrometry of methyl and (perdeuterio) methyl ester derivatives. These methyl esters all bore a vicinal dimethyl group toward the center of the chain. The assignment of the structures was confirmed by isolating one of the very long chain unusual fatty acids as the ester form after methanolysis and performing further analyses including 1H and 13C NMR spectroscopy and Fourier transform infrared spectroscopy. Coupling this information with the data from gas chromatography/mass spectrometry analysis, the exact structure was confirmed as alpha,omega-15,16-dimethyltricotanedioate dimethyl ester. Addition of alcohols, either metabolic (0.25 M ethanol) or nonmetabolic (0.05 M butanol) to cells grown at pH 7.0, or thermal stress (growth temperature at pH 7.0 was raised from 37 to 45 or 55 degrees C) also resulted in the synthesis of these very long chain fatty acids. Synthesis of these very long chain alpha,omega-dicarboxylic acids was reversed by reducing the temperature back to 37 degrees C. S. ventriculi is also unusual in that the membrane components are not the usual phospholipid components but appear to be predominantly glycolipids.
Cell Membrane↗
Shared T-cell receptor gene usage in experimental allergic neuritis and encephalomyelitis.
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Animals↗
Inhibition of experimental autoimmune encephalomyelitis by an antibody to the intercellular adhesion molecule ICAM-1.
Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats by active immunization with myelin from guinea pig spinal cord by the encephalitogenic myelin basic protein or by adoptive transfer using myelin basic protein-specific CD4-positive T cells. Treatment with purified monoclonal antibody (1A-29) to the intercellular adhesion molecule-1 and its F(ab')2 fragments efficiently suppressed active EAE. Control treatment with an irrelevant antibody or saline did not alter the course of the disease. Histological sections of the central nervous system showed a pronounced reduction of inflammatory infiltrates during treatment with antibody to intercellular adhesion molecule-1. In the adoptive transfer model of EAE, 1A-29 had only a minor effect. Proliferation assays on lymph node cells ex vivo from 1A-29- and saline-treated animals were performed. Administration of 1A-29 suppressed antigen-specific T-cell proliferation. The differential effects in EAE versus adoptive transfer EAE suggest that 1A-29 acts predominantly on the induction phase of the immune response and, to a lesser extent, on the transendothelial migration of T cells. We conclude that intercellular adhesion molecule-1-dependent pathways are critically involved in the pathogenesis of EAE and that antibodies to leukocyte adhesion molecules could be a novel therapeutic approach to autoimmune disease of the central nervous system.
Animals↗
The influence of intravenous anaesthetics on polymorphonuclear leukocyte function.
Polymorphonuclear leukocytes (PMNL) play a vital role in the defence against invading bacteria. It is known that some anaesthetics inhibit PMNL function and, thus, possibly enhance perioperative infection. We investigated the effect of methohexitone, flunitrazepam, and droperidol on three bactericidal PMNL functions, i.e., superoxide anion production, hydrogen peroxide generation, and activity of released myeloperoxidase, in vitro. Approved photometrical assays were used. Superoxide anion was measured by the reduction of cytochrome C, hydrogen peroxide by the horse radish peroxidase catalysed oxidation of phenol red, and myeloperoxidase by the turnover of 2,2'-azino-di(3-ethylbenzthiazoline) sulfonic acid. Methohexitone (P < or = 0.001) and flunitrazepam (P < or = 0.01) inhibited superoxide anion production, and methohexitone (P < or = 0.01) reduced hydrogen peroxide generation but only at concentrations beyond clinical relevance. Droperidol did not cause any alteration of the PMNL functions tested. Consequently, it seems unlikely that the usual doses of methohexitone, flunitrazepam, or droperidol promote bacterial infections in vivo by impairing the activity of myeloperoxidase or by inhibiting the generation of superoxide anion or hydrogen peroxide.
Adult↗
Selective elimination of macrophages by dichlormethylene diphosphonate-containing liposomes suppresses experimental autoimmune neuritis.
The injection of liposome-encapsulated dichlormethylene diphosphonate (Cl2MDP) constitutes an effective method to selectively eliminate phagocytic cells from spleen, liver and the circulation. We evaluated the effect of Cl2MDP-liposomes on the course of actively induced and adoptively transferred experimental autoimmune neuritis (EAN), both animal models of the human Guillain-Barré syndrome. Injection of Cl2MDP-liposomes 11 and 13 days postimmunization (p.i.) of Lewis rats with bovine peripheral nerve myelin efficiently prevented clinical signs of EAN up to day 15 p.i., when all control animals were affected. Thereafter, EAN gradually also developed in Cl2MDP-liposome-treated rats, but until day 19 disease was significantly milder than in control rats injected with buffer-filled liposomes. Adoptive transfer EAN (AT-EAN) induced by injection of activated P2-specific T cells could be suppressed even more markedly by application of Cl2MDP-liposomes 1, 3, and 6 days after cell transfer. Efficient suppression of AT-EAN by Cl2MDP-liposomes rules out the possibility that EAN is prevented due to interference with the induction phase of this experimental disease and confirms that macrophages are important effector cells during EAN. Selective suppression of phagocytic cell function by drug-containing liposomes may hold promise as a novel treatment of demyelinating autoimmune diseases of the nervous system.
Animals↗