[Subjective illness in non-malignant chronic pain--working patients are feeling better than sick-listed patients].
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
M Hansson
Publications and source records attributed to M Hansson.
Diverse effect of cytokine treatment of tumor cells on specific versus non-specific cytotoxicity.
The effect of IFN-gamma and TNF-alpha treatment of an ovarian carcinoma line on the sensitivity to lysis by specific CTL clones and non-specific Tumor Associated Lymphocytes (TAL), isolated from the ascites fluid, was analyzed. The in vitro established TAL line displayed a non-specific lytic activity against the autologous tumor as well as against several allogeneic tumor lines. Pretreatment with IFN-gamma alone, or in combination with TNF-alpha, rendered the carcinoma line less susceptible to lysis by the autologous TAL line. Conversely, susceptibility to lysis by tumor specific T cell clones, isolated from the TAL line, was increased as a result of cytokine pretreatment. Several TCR-alpha/beta+, CD8+ T-cell clones showing a more specific pattern of lysis against the autologous tumor were isolated. Lysis of the autologous tumor by these clones involved the TCR-alpha/beta via a MHC-class I restricted mechanism dependent on the adhesion molecules ICAM-1 and LFA-3, as inferred from antibody blocking studies. The enhanced sensitivity to specific CTL clones seen after cytokine treatment may be related to the enhanced expression of ICAM-1 molecules on the ovarian carcinoma. These results have implications for cytokine based immunotherapy, where IFN-gamma may enhance the effects of tumor associated specific CTL while decreasing that of non-specific effector cells.
Ascitic Fluid↗
OKT3-induced cytokine mRNA expression in human peripheral blood mononuclear cells measured by polymerase chain reaction.
The kinetic profile of cytokine gene expression in normal human peripheral mononuclear cells (MNC) activated by an anti-CD3 monoclonal antibody was studied. The presence or absence of 10 different cytokine mRNA were measured in a polymerase chain reaction (PCR) assisted mRNA amplification assay. After 2 h of stimulation the mRNA for interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), interleukin-3 (IL-3), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were detectable and remained present during the whole time period studied (22 h). Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were detected after 4 h, while interleukin-10 (IL-10) mRNA did not appear until after 7 h; they all remained expressed at 22 h. A transient expression of interleukin-4 (IL-4) mRNA was observed between 4 and 7 h of stimulation. No gene expression of granulocyte colony stimulating factor (G-CSF) was detected at any time. These results show that anti-CD3 stimulation of MNC leads to a rapid sequential induction of different cytokine mRNA, some with a very transient expression.
Base Sequence↗
Murine thymocytes with ability to inhibit Il-2 production: I. Genetic differences between mouse strains and characterization of the model system.
An experimental system has been established to understand the poor interleukin-2 (Il-2) production by activated thymocytes. This model system is further characterized here and studies were done on the possible mechanism(s) involved. Thymocytes activated by Concanavalin-A (Con-A), or through the CD3 complex of the T-cell receptor (TCR), inhibit 95-99% of the Il-2 production by spleen cells, while thymocytes stimulated by rIl-2 or lipopolysaccharides (LPS) do not. The mechanism of inhibition is not due to production of soluble factors, consumption of available interleukin-1 (Il-1) or Il-2, but is dependent on cell-to-cell contact. Although cellular contact is needed, cytotoxicity is not involved. Prostaglandin production is not required for the generation or exertion of the inhibitory activity. Protein and DNA synthesis are necessary for exertion of the suppressive effect. We also demonstrate a genetic difference between different mouse strains in the ability to generate the inhibitory thymocytes. Activated Balb/c thymocytes inhibit spleen cells' Il-2 production in a non-MHC-restricted manner. Our studies demonstrate a regulatory capacity of activated thymocytes in vitro. This ability of the postnatal cells could be of relevance for understanding the latter events in T-cell education in the thymus and the role of Il-2 during this process.
Animals↗
Expression of recombinant proteins on the surface of the coagulase-negative bacterium Staphylococcus xylosus.
An expression system to allow targeting of heterologous proteins to the cell surface of Staphylococcus xylosus, a coagulase-negative gram-positive bacterium, is described. The expression of recombinant gene fragments, fused between gene fragments encoding the signal peptide and the cell surface-binding regions of staphylococcal protein A, targets the resulting fusion proteins to the outer bacterial cell surface via the membrane-anchoring region and the highly charged cell wall-spanning region of staphylococcal protein A. The expression system was used to secrete fusion proteins containing sequences from a malaria blood-stage antigen and a streptococcal albumin-binding receptor to the cell surface of S. xylosus. Analysis of the recombinant cells by immunogold staining and immunofluorescence revealed that both the receptor and the malaria peptide were properly processed and exposed on the surface of the host cells. However, only approximately 40 to 50% of the recombinant cells were strongly stained with antiserum reactive with the albumin-binding receptor, while approximately 10 to 15% of the cells were stained with antiserum reactive with the malaria peptide. The incomplete staining of some of the cells suggests steric effects that make the recombinant fusion proteins inaccessible to the reactive antibodies because of variable cell wall structures. However, the results demonstrate for the first time that recombinant techniques can be used to express heterologous receptors and immunogens on the surface of gram-positive cells.
Amino Acid Sequence↗
Cloning and characterization of the Bacillus subtilis hemEHY gene cluster, which encodes protoheme IX biosynthetic enzymes.
Mutations that cause a block in a late step of the protoheme IX biosynthetic pathway, i.e., in a step after uroporphyrinogen III, map at 94 degrees on the Bacillus subtilis chromosomal genetic map. We have cloned and sequenced the hem genes at this location. The sequenced region contains six open reading frames: ponA, hemE, hemH, hemY, ORFA, and ORFB. The ponA gene product shows over 30% sequence identity to penicillin-binding proteins 1A of Escherichia coli, Streptococcus pneumoniae, and Streptococcus oralis and probably has a role in cell wall metabolism. The hemE gene was identified from amino acid sequence comparisons as encoding uroporphyrinogen III decarboxylase. The hemH gene was identified by enzyme activity analysis of the HemH protein expressed in E. coli. It encodes a water-soluble ferrochelatase which catalyzes the final step in protoheme IX synthesis, the insertion of ferrous iron into protoporphyrin IX. The function of the hemY gene product was not elucidated, but mutation analysis shows that it is required for a late step in protoheme IX synthesis. The hemY gene probably encodes an enzyme with coproporphyrinogen III oxidase or protoporphyrinogen IX oxidase activity or both of these activities. Inactivation of the ORFA and ORFB genes did not block protoheme IX synthesis. Preliminary evidence for a hemEHY mRNA was obtained, and a promoter region located in front of hemE was identified. From these combined results we conclude that the hemEHY gene cluster encodes enzymes for the synthesis of protoheme IX from uroporphyrinogen III and probably constitutes an operon.
Amino Acid Sequence↗
Natural killer (NK) cell activity in human long-term bone marrow cultures (LTBMC): effects of interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on the progenitor cells.
Human bone marrow-derived progenitor cells were studied in a long-term bone marrow culture system (LTBMC) dependent on an autologous stroma cell layer. The establishment of the stromal cell layer was facilitated by using marrow obtained from small pieces of sternum, which was cultured for 4 weeks without addition of exogenous growth factors. After this period, the response of LTBMC to two different cytokines [recombinant human interleukin-2 (rhIL-2) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF)] was investigated. Our results show proliferation in response to both cytokines and induction of differentiation of cells able to bind IL-2 and/or GM-CSF again. The two cytokines also generate cells responding to rhGM-CSF by colony formation. However, a difference with respect to morphology, phenotype and cytotoxic function of cells in the LTBMC, was noted between the two cytokines. Cells with large granular lymphocyte (LGL) morphology and cytotoxic activity against K562 and Daudi were generated only in the rhIL-2-supplemented LTBMC. This was compatible with a higher frequency of cells expressing the CD56+ phenotype in the IL-2-stimulated LTBMC as compared to the GM-CSF supplemented LTBMC. Our results also demonstrate the existence of a population of myeloid progenitor cells (CD33+) with ability to bind IL-2 in fresh bone marrow (BM).
Antigens, CD↗
Hypercytokinemia in familial hemophagocytic lymphohistiocytosis.
Familial hemophagocytic lymphohistiocytosis (FHL) is a frequently missed and almost uniformly fatal childhood disorder. It is characterized by fever, hepatosplenomegaly, cytopenia, coagulopathy, and hypertriglyceridemia. The pathogenesis of FHL is not known but the above clinical and laboratory findings are compatible with reported in vitro and in vivo effects of several inflammatory cytokines. We measured circulating interferon-gamma (IFN-gamma), tumor necrosis factor/cachectin (TNF), and interleukin-6 (IL-6) in nine children with FHL. During active disease, elevated IFN-gamma was detected in seven of seven children, TNF in six of six, and IL-6 in two of six children studied. Thus, important inflammatory cytokines are augmented in active FHL and may contribute to the pathogenesis of the disease. Soluble CD8 was also increased in seven of seven children, which suggests a pathophysiologic importance of cytotoxic T lymphocytes. Because FHL appears to be associated with a systemic hypercytokinemia, our results also indicate that studies of FHL may contribute to the understanding of cytokine effects in vivo. Moreover, FHL is a hereditary disorder, suggesting that the hypercytokinemia is caused by a genetic defect in cytokine regulation.
CD8 Antigens↗
Increased susceptibility of IFN-gamma-treated neuroblastoma cells to lysis by lymphokine-activated killer cells: participation of ICAM-1 induction on target cells.
We have investigated the effect of interferon-gamma (IFN-gamma) treatment of neuroblastoma cells on the susceptibility to lysis by lymphokine-activated killer (LAK) cells and examined the participation of cell-adhesion molecules on the target cells in LAK cell lysis. Untreated neuroblastoma cells expressed lymphocyte-function-associated antigen 3 (LFA-3) and neural-cell-adhesion molecule (NCAM), but did not express MHC-class-I, MHC-class-II, or intercellular-adhesion molecule I (ICAM-I). IFN-gamma treatment of neuroblastoma cells induced the expression of MHC-class-I and ICAM-I antigens, but did not affect the expression of MHC-class-II, LFA-3, and NCAM. This was accompanied by an increased susceptibility to lysis by LAK cells. Anti-ICAM-I antibody inhibited partially the increased sensitivity of IFN-gamma-treated neuroblastoma cells to LAK cell lysis, and blocked completely the increase in binding of LAK cells observed after IFN-gamma treatment of the target cells. These results suggest that the increased LAK sensitivity of IFN-gamma-treated neuroblastoma cells is partially attributable to the induction of ICAM-I on neuroblastoma cells and indicate that post-binding events also play a role in the increased sensitivity to LAK cell lysis observed after IFN-gamma treatment.
Cell Adhesion Molecules↗
Exposure to dioxins and dibenzofurans through the consumption of fish.
BACKGROUND: In some regions, including the Baltic Sea, fatty fish such as salmon and herring contain high levels of polychlorinated dibenzodioxins and dibenzofurans. We investigated human exposure to these potentially toxic substances in relation to the consumption of fish from the Baltic Sea. METHODS: Plasma levels of 10 different dibenzofurans and 7 dioxins were analyzed in three groups of Swedish men: one group with a high intake of fish (fish eaten almost daily; n = 11), one with a moderate intake of fish (about once per week; n = 9), and one with no consumption of fish (usually because of allergy; n = 9). RESULTS: Plasma levels of several of the compounds we measured were higher in the men with a high intake of fish than in those who consumed moderate amounts, and the levels were higher in those who ate moderate amounts of fish than in those who ate none. The median amounts of the most toxic dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin) were 8.0 pg per gram of plasma lipid (range, 2.0 to 13) in the high-intake group, 2.6 pg per gram (range, 1.2 to 4.2) in the moderate-intake group, and 1.8 pg per gram (range, 1.0 to 2.5) in the nonconsumers (P = 0.001 and 0.02, respectively). There were consistent and statistically significant associations between the reported amount of fish eaten and the plasma levels of several of the dibenzofurans and dioxins. CONCLUSIONS: Contaminated fish such as those from the Baltic Sea are an important source of exposure to polychlorinated dibenzofurans and dibenzodioxins in persons who eat fish regularly. However, the clinical consequences of such exposure remain uncertain.
Adult↗
Multiple interactions at the natural killer workshop.
The cell surface receptors and their ligands that control natural killer (NK) cell adhesion, homing, cytokine secretion and target cell recognition are beginning to yield their secrets, as 'NKologists' adopt the same 'multiple interaction strategy' as the cells themselves. This report from the recent NK workshop updates progress on these receptors and on the origin, regulation and physiology of the cells.
Animals↗
High antibody responses in rabbits immunized with influenza virus ISCOMs containing a repeated sequence of the Plasmodium falciparum antigen Pf155/RESA.
Immunostimulating complexes (ISCOMs) are spherical structures where immunogens are presented as multimers in a matrix of the adjuvant Quil A. ISCOMs have been shown to enhance the immunogenicity of several antigens important to both human and veterinary vaccine development. We have coupled a fusion protein, designated ZZ-M2, comprising eight copies of the C-terminal repeat subunit EENV of the Plasmodium falciparum blood-stage antigen Pf155/RESA and two IgG-binding domains of staphylococcal protein A (SpA), to preformed influenza virus envelope protein ISCOMs. Rabbits immunized with the conjugated ISCOMs produced high titres of antibodies even after the first injection. These antibodies reacted with the EENV repeat sequence in ELISA and with Pf155/RESA in immunofluorescence on infected erythrocytes. The antibody response, which was sustained for more than 20 weeks, was efficiently boosted and superior or equal to that obtained after immunization with ZZ-M2 in Freund's complete adjuvant. In contrast, the antibody response induced in rabbits immunized with ZZ-M2 in Syntex Adjuvant Formulation-MF (SAF-MF) was weak and of short duration. The antibodies produced after immunization with ZZ-M2 coupled to influenza virus ISCOMs mainly recognized epitopes formed by two or more EENV subunits and were highly specific for Pf155/RESA. Furthermore, the antibodies efficiently inhibited merozoite reinvasion of erythrocytes in vitro, indicating that they recognized epitopes exposed on the native antigen. In addition, the ZZ-M2-conjugated ISCOMs also induced high titres of antibodies reacting with SpA or the influenza virus envelope protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Adjuvants, Immunologic↗
A monoclonal IgM antibody to a methylcholanthrene-induced tumour. I. Specificity for alpha-N-acetylgalactosamine but with no cross-reactivity to the human blood group A determinant.
A monoclonal IgM antibody, H17, has been obtained from rats immunized with mouse fibrosarcoma cells from an in vitro established methylcholanthrene (MCA)-induced tumour. H17 shows specific and very selective binding to alpha-N-acetylgalactosamine (GalNAc alpha) when tested for reactivity to a panel of glycolipids. It cross-reacts with GalNAc alpha on the Forssman antigen extracted from dog small intestine, but not from the human blood group A determinant, a finding not commonly observed among antibodies with this specificity. Despite its specificity, H17 does not react with TA3-Ha, a mouse mammary adenocarcinoma, known to express the Tn antigen (GalNAc alpha-O-Ser/Thr). The uniqueness of H17 probably relates to the fact that it has been generated against an MCA-induced tumour rather than against the pure saccharide itself. Minimum energy conformation structures of different GalNAc alpha containing saccharide molecules were computer modelled to allow a plausible interpretation of the accessible site of GalNAc alpha for successful interaction with the H17 paratope as compared to other GalNAc alpha binding antibodies.
ABO Blood-Group System↗
The Bacillus subtilis hemAXCDBL gene cluster, which encodes enzymes of the biosynthetic pathway from glutamate to uroporphyrinogen III.
We have recently reported (M. Petricek, L. Rutberg, I. Schröder, and L. Hederstedt, J. Bacteriol. 172: 2250-2258, 1990) the cloning and sequence of a Bacillus subtilis chromosomal DNA fragment containing hemA proposed to encode the NAD(P)H-dependent glutamyl-tRNA reductase of the C5 pathway for 5-aminolevulinic acid (ALA) synthesis, hemX encoding a hydrophobic protein of unknown function, and hemC encoding hydroxymethylbilane synthase. In the present communication, we report the sequences and identities of three additional hem genes located immediately downstreatm of hemC, namely, hemD encoding uroporphyrinogen III synthase, hemB encoding porphobilinogen synthase, and hemL encoding glutamate-1-semialdehyde 2,1-aminotransferase. The six genes are proposed to constitute a hem operon encoding enzymes required for the synthesis of uroporphyrinogen III from glutamyl-tRNA. hemA, hemB, hemC, and hemD have all been shown to be essential for heme synthesis. However, deletion of an internal 427-bp fragment of hemL did not create a growth requirement for ALA or heme, indicating that formation of ALA from glutamate-1-semialdehyde can occur spontaneously in vivo or that this reaction may also be catalyzed by other enzymes. An analysis of B. subtilis carrying integrated plasmids or deletions-substitutions in or downstream of hemL indicates that no further genes in heme synthesis are part of the proposed hem operon.
Amino Acid Sequence↗
Chloracne caused by ingestion of olive oil contaminated with PCDDs and PCDFs.
1. All members of a Spanish family (father, mother and six children) developed chloracne. 2. The causative agent was found to be the family's stock of olive oil, which had become contaminated with polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), pentachlorophenol, and hexachlorobenzene. 3. The more highly chlorinated PCDDs, in particular octachlorodibenzo-p-dioxin, were the predominant congeners in the oil. 4. Three members of the family exhibited either an overt or a sub-clinical disturbance of kidney function. The father also had a chronic respiratory problem. These changes could not be unequivocally attributed to the PCDDs. 5. Experimental toxicity of the oil was limited to the development of an hepatic porphyria in mice. 6. A serum sample, taken 5 years after consumption of the oil ceased, contained high levels of the PCDDs and PCDFs. Extrapolation back to ingested dose was used to validate dosage estimates. 7. The use of toxicity equivalence factors (TEFs) provided estimates of cumulative dosage to produce chloracne as 0.13-0.31 micrograms 2378-TCDD kg-1 (using EPA TEFs) or 6.7-16 micrograms 2378-TCDD kg-1 (using Nordic/NATO TEFs). 8. This is the first incident in which human toxicity is related primarily to ingestion of PCDDs and for which estimates of dosage can be made.
Acne Vulgaris↗
A monoclonal IgM antibody to a methylcholanthrene-induced tumor. 2. A biologically relevant glycoprotein antigen with a molecular weight of 40-43 kilodaltons.
We have recently described a monoclonal IgM antibody, H17, to a mouse methylcholanthrene-induced tumor with specificity for a common saccharide, namely alpha-N-acetylgalactosamine. Although recognizing a glycosidic determinant most likely to be part of many cell surface glycoproteins, H17 was highly specific for the immunizing tumor. This discriminatory ability was investigated by testing the antibody binding to a panel of normal and transformed mouse and human cells. Cross-linking studies showed that H17 reacts with a glycoprotein with a molecular weight of 40-43 kD, which through blockage during the process of immunization has an impact in vivo on tumor growth. Moreover, the uncommon sensitivity to complement-mediated lysis by this methylcholanthrene-induced tumor was blocked by the H17 monoclonal antibody.
Animals↗
A general strategy for polymerization, assembly and expression of epitope-carrying peptides applied to the Plasmodium falciparum antigen Pf155/RESA.
Polymerization of DNA fragments in a head-to-tail arrangement provides a convenient way to obtain multimeric expression of a specific gene product, e.g., epitope-carrying peptides for immunological studies. A novel technique for the polymerization and assembly of peptides has been developed, involving the use of the class-IIS restriction enzyme BspMI which enables unidirectional insertion of the DNA fragments to be polymerized [Kim and Szybalski, Gene 71 (1988) 1-8]. One or several DNA fragments are polymerized in subsequent steps, using in vitro DNA polymerization, and the obtained gene constructs containing several repeats are screened and sequenced using polymerase chain reaction techniques. Using a two-step polymerization strategy a peptide, comprising two repetitive sequences from the Plasmodium falciparum malaria blood-stage antigen Pf155/RESA, was assembled and subsequently synthesized in Escherichia coli. Two different fusion proteins suitable for affinity purification were produced using a dual affinity system. Rabbits were immunized with one of the fusion proteins and the antibody response was analyzed by the enzyme-linked immunosorbent assay and immunofluorescence using the second fusion protein.
Amino Acid Sequence↗
Comparison and functional characterization of C-CAM, glycoprotein IIb/IIIa and integrin beta 1 in rat platelets.
Three adhesion-related proteins in rat platelets were compared, namely C-CAM, gpIIb/IIIa, and integrin beta 1. These three proteins behaved as distinct components as judged by both biochemical and immunological analyses. GpIIb/IIIa bound to a GRGDSPC-peptide, but neither beta 1-containing integrins nor C-CAM had any affinity either for this peptide or for a large cell-binding fragment of fibronectin. C-CAM and integrin beta 1 behaved differently when platelets were labeled with 125I, solubilized by detergent, and immunoprecipitated. Significant amounts of labeled C-CAM was precipitated when the platelets were first solubilized with detergent and then 125I-labeled. Almost no labeled C-CAM could be precipitated when intact platelets, that were unactivated or activated by ADP, were labeled. In contrast, labeled integrin beta 1 was immunoprecipitated when unactivated platelets were surface-labeled. However, when platelets that were activated by ADP and calcium ions were labeled almost no labeled integrin beta 1 could be immunoprecipitated. These data indicate 1) that C-CAM in intact platelets is inaccessible to surface-labeling and 2) that beta 1 integrin is less accessible to surface-labeling after platelet activation in the presence of calcium ions.
Adenosine Triphosphatases↗