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1

Gachet, C., A. Astier, H. de la Salle, C. de la Salle, WH Fridman, JP Cazenave, D. Hanau, and JL Teillaud. "Release of Fc gamma RIIa2 by activated platelets and inhibition of anti- CD9-mediated platelet aggregation by recombinant Fc gamma RIIa2." Blood 85, no. 3 (February 1, 1995): 698–704. http://dx.doi.org/10.1182/blood.v85.3.698.bloodjournal853698.

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Thrombin-activated human platelets and megakaryocyte cell lines release soluble Fc gamma RII (Fc gamma RIIa2) containing the extracellular and intracellular regions of Fc gamma RIIa1, but lacking the transmembrane domain. Use of polyclonal antibodies directed either against the entire intracytoplasmic tail, or against a peptide located near the C-terminal part of the intracellular region of Fc gamma RIIa2, showed the presence of both a complete form of Fc gamma RIIa2 and a C-terminal truncated form in supernatants of platelets after release of their alpha granule contents and in culture supernatants of megakaryocyte cell lines. Furthermore, recombinant Fc gamma RIIa2 inhibited in a dose-dependent manner Fc-dependent anti-CD9 antibody-induced platelet aggregation. Thus, release of Fc gamma RIIa2 by activated platelets could play an important role in the regulation of platelet activation by immune complexes.
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2

Indik, ZK, JG Park, S. Hunter, and AD Schreiber. "The molecular dissection of Fc gamma receptor mediated phagocytosis." Blood 86, no. 12 (December 15, 1995): 4389–99. http://dx.doi.org/10.1182/blood.v86.12.4389.bloodjournal86124389.

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Because hematopoietic cells express multiple Fc gamma receptor isoforms, the role of the individual Fc gamma receptors in phagocytosis has been difficult to define. Transfection of Fc gamma receptors into COS-1 cells, which lack endogeneous Fc gamma receptors but have phagocytic potential, has proved valuable for the study of individual Fc gamma receptor function. Using this model system, we have established that a single class of human Fc gamma receptor mediates phagocytosis in the absence of other Fc receptors and that isoforms from each Fc gamma receptor class mediate phagocytosis, although the requirements for phagocytosis differ. In investigating the relationship between structure and function for Fc gamma receptor mediated phagocytosis, the importance of the cytoplasmic tyrosines of the receptor or its associated gamma chain has been established. For example, two cytoplasmic YXXL sequences, in a configuration similar to the conserved tyrosine-containing motif found in Ig gene family receptors, are important for phagocytosis by the human Fc gamma receptor, Fc gamma RIIA. Fc gamma RI and Fc gamma RIIIA do not possess cytoplasmic tyrosines but transmit a phagocytic signal through interaction with an associated gamma subunit that contains two YXXL sequences in a conserved motif required for phagocytosis. The human Fc gamma RII isoforms Fc gamma RIIB1 and Fc gamma RIIB2 do not induce phagocytosis and have only a single YXXL sequence. Cross-linking the phagocytic Fc gamma receptors induces tyrosine phosphorylation of either Fc gamma RIIA or the gamma chain, and treatment with tyrosine kinase inhibitors reduces both phagocytosis and phosphorylation of the receptor tyrosine residues. Activation of protein tyrosine kinases follows Fc gamma receptor engagement of IgG-coated cells. The data indicate that coexpression of the protein tyrosine kinase Syk, which is associated with the gamma chain in monocytes/macrophages, is important for phagocytosis mediated by Fc gamma RI and Fc gamma RIIIA. Furthermore, phosphatidylinositol-3 kinase is required for phagocytosis mediated by Fc gamma RIIA as well as for phagocytosis mediated by Fc gamma RI/gamma and Rc gamma RIIIA/gamma.
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3

Weng, Wen-Kai, Jeffrey Stavenhagen, Scott Koenig, and Ronald Levy. "Rituximab Variants with Re-Engineered Fc with Higher Affinity to Activating Fcγ R Eliminate the Functional Difference between Fcγ R Genotypes." Blood 106, no. 11 (November 16, 2005): 347. http://dx.doi.org/10.1182/blood.v106.11.347.347.

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Abstract We and others have found that IgG Fc receptor, Fcγ RIIIa Valine/Valine (V/V) and Fcγ RIIa Histidine/Histidine (H/H) genotypes predicted the response to rituximab in follicular lymphoma patients probably due to their higher affinity to the constant region (Fc) of rituximab during antibody-dependent cellular cytotoxicity (ADCC). Patients with low affinity Fcγ RIIIa Phenylalanine (F) carrier (V/F and F/F) and Fcγ RIIa Arginine (R) carrier (H/R and R/R) have much lower chance to respond to rituximab and have a brief remission when they responded. This observation implicates the interaction between the Fc of rituximab and Fcγ R on effectors (NK cells and macrophages) as a determinant for clinical response. Therefore, it may be possible to re-engineer the Fc of rituximab to increase its affinity to Fcγ R and thereby to enhance the antibody’s ability to mediate ADCC and to improve its clinical efficacy. Rituximab variants with re-engineered Fc were generated by MacroGenics. Single amino acid substitutions with increased affinity to different Fcγ R alleles were identified by screening a yeast library containing randomly mutated Fc. Further re-engineering was accomplished by combining multiple amino acid substitutions within both the Fcγ R-binding CH2 and the conformational CH3 domains of the Fc to further improve their affinity. We have tested 12 such variants for their ability to mediate ADCC against primary follicular lymphoma targets. Three variants (4, 10, 12) showed significant enhancement in ADCC compared to rituximab, using effector cells of V/V genotype. We then tested whether the enhancement of ADCC applies to effectors of different Fcγ RIIIa genotypes. In one experiment, at a 30:1 effector/target ratio, specific ADCC lysis for rituximab, Variant 6 (a modest enhancer) and Variant 10 (a strong enhancer) were 37%, 50% and 66%, respectively, with V/V effectors and 23%, 36% and 65%, respectively, with F/F effectors. Thus, enhancement of ADCC by these variants applied to effectors of both high (V/V) and low (F/F) affinity Fcγ Rs. In one case, Variant 10, enhancement of ADCC with effctors of low affinity Fcγ R, brought its activity up to that of effectors with the high affinity Fcγ R. We further examined the ability of these variants to engage and internalize the Fcγ R on NK cells as a measure of primary engagement of Fcγ R. Rituximab-coated tumor cells reduced the surface Fcγ RIIIa on NK cells of V/V genotype by 78% determined by flow cytometric analysis. By comparison, Variant 6 down-regulated surface Fcγ RIIIa by 84% and Variant 10 by 88%. For NK cells of F/F genotype, rituximab down-regulated surface Fcγ RIIIa by 32%, Variant 6 by 64% and Variant 10 by 68%. This result confirmed that two rituximab variants were more effective in interacting with effectors of both high and low affinity Fcγ Rs. This study has demonstrated that several rituximab variants with re-engineered Fc showed increased interaction with Fcγ R on effectors and mediated ADCC more effectively than rituximab even with effectors of low affinity Fcγ R genotypes. These rituximab variants may prove to be more effective therapeutic anti-CD20 antibodies than rituximab, especially for patients with low affinity Fcγ Rs. Figure Figure
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4

Meisel, P., LE Carlsson, H. Sawaf, J. Fanghaenel, A. Greinacher, and T. Kocher. "Polymorphisms of Fcγ-receptors RIIa, RIIIa, and RIIIb in patients with adult periodontal diseases." Genes & Immunity 2, no. 5 (August 2001): 258–62. http://dx.doi.org/10.1038/sj.gene.6363777.

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5

Riis, Erling, Lars-Ulrik Andersen, Nis Bjerre, Ove Poulsen, Siu-Au Lee, and John L. Hall. "Riiset al.Reply." Physical Review Letters 62, no. 7 (February 13, 1989): 842. http://dx.doi.org/10.1103/physrevlett.62.842.

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6

Ahlgrimm, Manfred, Evi Regitz, Klaus-Dieter Preuss, Sandra Grass, Viola Poeschel, Markus Kreuz, and Michael Pfreundschuh. "Single Nucleotide Polymorphisms (SNPs) of FCγRIIA and FCγRIIIA in Patients with Diffuse Large B-Cell Lymphoma Have No Impact On Treatment Outcome of Elderly Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with CHOP with and without Rituximab: Results From the RICOVER-60 Trial of the German High-Grade Non-Hodgkin Lymhoma Study Group (DSHNHL)." Blood 114, no. 22 (November 20, 2009): 3956. http://dx.doi.org/10.1182/blood.v114.22.3956.3956.

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Abstract Abstract 3956 Poster Board III-892 BACKGROUND During the last decade the outcome of patients with diffuse large B-cell lymphoma (DLBCL) has significantly improved by the addition of rituximab (R) to the standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Despite this improvement in response rates, event- progression and overall survival, about one third of the patients with DLBCL will eventually fail. The main therapeutic efficacy of rituximab is not fully elucidated. One major effector mechanism is by antibody dependent cellular cytotoxicity (ADCC) mediated by cell-bound rituximab via its FCg part that activates effector cells by binding to their Fcg receptor (FCγR). Three classes and eight subclasses of FCγR have been described. SNPs have been detected for FcgRIIA at amino acid position (AA) 131 where histidin is substituted by arginin (131 R/H) and for FCγRIIIA at position 158, where phenylalanine is substituted by valine (158 V/F). These SNPs have an increased affinity to Fcg and induce a stronger ADCC which explains better responses to rituximab treatment in follicular lymphoma. The aim of this study was to determine the impact of FCγRIIA and FCγRIIIA SNPs on the outcome R-CHOP chemotherapy in elderly patients with newly diagnosed DLBCL. PATIENTS AND METHODS In the RICOVER-60 therapy study 1222 elderly patients (aged 61-80 years) were randomly assigned to 6 or 8 cycles of CHOP, both with or without rituximab (Pfreundschuh et al., Lancet Oncology 2008). The control group (n=100) consisted of anonymous healthy blood donors of Saarland University Institute of Transfusion Medicine. Available for this study were peripheral blood samples from 570 patients who were representative for the entire RICOVER-60 population. The 2 FCgR SNPs FCγ-RIIa AA 131 R/H and FCγ-RIIIa 158 V/F were determined and univariate and multivariate analyses adjusting for the IPI-relevant risk factors (LDH, ECOG performance status, advanced stage and >1 extranodal involvement) were performed for the entire study population and separately for patients receiving or not receiving rituximab. RESULTS Frequencies of FCγ-RIIa and FCγ-RIIIa polymorphisms were not different in healthy controls compared to DLBCL patients. In our statistical analyses finaly 512 patients were included. The characteristic for the groups were for group 1 (6x CHOP-14) 127 patients (24.8%), for group 2 (8x CHOP-14) 122 patients (23.83%), for group 3 (6x CHOP-14+8x rituximab) 124 patients (24.22%) and for group 4 (8x CHOP-14 + 8x rituximab) 139 patients (27.15%) [fisher test (included vs excluded): p=0.4691]. The median age at admission was the same for included and excluded patients. The gender characteristics for the included patients were well balanced [fisher test (included vs excluded): p=1.0000]. The median observation time for the included vs. excluded patients was 40.25 months vs. 34.50 months. This verification shows that the collective of included patients represents the whole RICOVER-60 population. Statistical analyses of overall survival, 3 year event-free survival and 3 year overall-survival were done for the complete RICOVER-60 population. 3-year event-free survival was 47.2% after six cycles of CHOP-14 (95% CI 41.2-53.3), 53.0% (47.0-59.1) after eight cycles of CHOP-14, 66.5% (60.9-72.0) after six cycles of R-CHOP-14, and 63.1% (57.4-68.8) after eight cycles of R-CHOP-14. 3-year overall survival was 67.7% (62.0-73.5) for six cycles of CHOP-14, 66.0% (60.1-71.9) for eight cycles of CHOP-14, 78.1% (73.2-83.0) for six cycles of R-CHOP-14, and 72.5% (67.1-77.9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by -1.7% (-10.0-6.6) after eight cycles of CHOP-14, 10.4% (2.8-18.0) after six cycles of R-CHOP-14, and 4.8% (-3.1-12.7) after eight cycles of R-CHOP-14. In summary, event-free, progression free, overall survival and complete remission rates were not different among patients with FCγ-RIIa (AA 131R/H) and FCγ-RIIIa (AA 158 V/F) SNPs, irrespective of whether the entire RICOVER-60 population was analysed or when patients treated with and without rituximab were analysed separately. CONCLUSIONS FCγ-RIIa and FCγ-RIIIa SNPs have no influence on the outcome of patients treated with CHOP-14 with or without rituximab. Therefore, modifications of schedule and dose of rituximab according to the underlying FCγ-R SNPs are not justified. Supported by a HOMFOR grant of Saarland University Medical School, Homburg, Germany Disclosures: Pfreundschuh: Roche MabThera Advisory Board: Consultancy, Honoraria.
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7

Matsuda, M., J. G. Park, D. C. Wang, S. Hunter, P. Chien, and A. D. Schreiber. "Abrogation of the Fc gamma receptor IIA-mediated phagocytic signal by stem-loop Syk antisense oligonucleotides." Molecular Biology of the Cell 7, no. 7 (July 1996): 1095–106. http://dx.doi.org/10.1091/mbc.7.7.1095.

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The role of Syk kinase in Fc gamma receptor (Fc gamma R) IIA-mediated phagocytosis was examined with two forms of antisense oligodeoxynucleotides (ODNs) designed to hybridize to human Syk mRNA. Monocytes were incubated with linear and stem-loop antisense ODNs targeted to Syk mRNA. When complexed with cationic liposomes, stem-loop Syk antisense ODN with phosphorothioate modification exhibited stability in fetal bovine and human serum. The stem-loop Syk antisense ODN at a concentration of 0.2 microM inhibited Fc gamma RIIA-mediated phagocytosis by 90% and completely eliminated Syk mRNA and protein in monocytes, whereas scrambled-control ODNs had no effect. The Syk antisense ODNs did not change beta-actin mRNA levels and Fc gamma RII cell-surface expression. In addition, stem-loop Syk antisense ODN inhibited Fc gamma RI and Fc gamma RIIIA-mediated phagocytosis. These data indicate the efficacy of stem-loop Syk antisense ODN for targeting and degrading Syk mRNA and protein and the importance of Syk kinase in Fc gamma receptor-mediated phagocytosis. Immunoblotting assay demonstrated that Fc gamma RII tyrosine phosphorylation after Fc gamma RII cross-linking did not change in the absence of Syk protein. These results indicate that Syk kinase is required for Fc gamma RIIA-mediated phagocytic signaling and that Fc gamma RII cross-linking leads to tyrosine phosphorylation of Fc gamma RII independent of Syk kinase.
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8

Edberg, J. C., and R. P. Kimberly. "Cell type-specific glycoforms of Fc gamma RIIIa (CD16): differential ligand binding." Journal of Immunology 159, no. 8 (October 15, 1997): 3849–57. http://dx.doi.org/10.4049/jimmunol.159.8.3849.

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Abstract Fc gamma RIIIa, considered an intermediate affinity receptor, can variably bind monomeric IgG and appears to have a higher affinity for IgG than the lower affinity Fc gamma Rs, Fc gamma RII and Fc gamma RIIIb. We explored this property for both NK cell and monocyte Fc gamma RIIIa and found higher affinity ligand binding by Fc gamma RIIIa expressed on NK cells compared with Fc gamma RIIIa on monocytes. In normal whole blood or plasma (containing 8-11 mg/ml IgG), NK cell Fc gamma RIIIa was fully blocked, but in monocytes Fc gamma RIIIa showed approximately 60% blockade of the binding of mAb 3G8, which binds in or near the ligand binding site. The ligand binding site of NK cell Fc gamma RIIIa was blocked with as little as 2 mg/ml of human IgG, while monocyte Fc gamma RIIIa was only partially (30%) blocked by 2 mg/ml of human IgG. In contrast, plasma containing approximately 26 mg/ml of IgG (obtained from patients receiving therapeutic gamma-globulin) showed complete saturation of monocyte Fc gamma RIIIa with blockade of mAb 3G8 binding. These binding differences are not due to allelic polymorphisms or primary sequence differences between donors. Although NK cell and monocyte Fc gamma RIIIa have identical protein cores, they each undergo differential cell type-specific glycosylation. NK cell Fc gamma RIIIa is glycosylated with high mannose- and complex-type oligosaccharides, while monocyte Fc gamma RIIIa has no high mannose-type oligosaccharides. These results indicate that natural glycoforms of Fc gamma RIIIa (cell type-specific glycosylation variants) bind ligand differently, conferring a lower affinity on monocyte/macrophage Fc gamma RIIIa, which makes the receptor ideal for initial immune complex capture and sensitive to moderate changes in serum IgG levels.
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9

de Haas, M., H. R. Koene, M. Kleijer, E. de Vries, S. Simsek, M. J. van Tol, D. Roos, and A. E. von dem Borne. "A triallelic Fc gamma receptor type IIIA polymorphism influences the binding of human IgG by NK cell Fc gamma RIIIa." Journal of Immunology 156, no. 8 (April 15, 1996): 2948–55. http://dx.doi.org/10.4049/jimmunol.156.8.2948.

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Abstract A donor-dependent difference in electrophoretic mobility of deglycosylated released Fc gamma RIIIa derived from NK cells and macrophages was observed. We investigated whether this was based on a polymorphism of the Fc gamma RIIIA gene. Cloning and sequencing of Fc gamma RIIIa-encoding cDNA derived from an apparently heterozygous donor showed one single nucleotide substitution at position 230 (T-->G), which was responsible for a leucine (L)-->arginine (R) substitution at position 48 in the first extracellular Ig-like domain (EC1) of Fc-gamma RIIIa and caused a higher electrophoretic mobility of Fc gamma RIIIa. An allele-specific primer annealing PCR assay was developed to amplify specifically an Fc gamma RIIIA gene-derived fragment, which was digested with AciI (recognizing G230) or MnlI (recognizing T230). MnlI restriction analysis revealed the presence of a third Fc gamma RIIIa allele with a T230-->A substitution, which predicts a change of 48-leucine into 48-histidine (H). A gene frequency of 86% for the T230 (48-L) allele, 6% for G230 (48-R), and 8% for A230 (48-H) was found. A significantly different genotype distribution was found among 12 unrelated Caucasian Fc gamma RIIIB gene-deficient donors. Fc gamma RIIIa-48R and Fc gamma RIIIa-48H showed a higher binding capacity of human (h)IgG1, hIgG3, and hIgG4 compared with Fc gamma RIIIa-48L. Finally, the CD16 mAbs 1D3 and MEM154 bound more strongly and Leu11c (B73.1) bound less to the newly identified Fc gamma RIIIa isoforms.
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10

Chen, Tiffany F., Stephen L. Sazinsky, Damian Houde, David J. DiLillo, Julie Bird, Kevin K. Li, George T. Cheng, et al. "Engineering Aglycosylated IgG Variants with Wild-Type or Improved Binding Affinity to Human Fc Gamma RIIA and Fc Gamma RIIIAs." Journal of Molecular Biology 429, no. 16 (August 2017): 2528–41. http://dx.doi.org/10.1016/j.jmb.2017.07.001.

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11

Hernandez, A., E. Bandres, J. Rodriguez, N. Bitarte, N. Ramirez, R. Zarate, A. Abajo, A. Chopitea, A. Viudez, and J. Garcia-Foncillas. "Pharmacogenomic analysis of the triplet combination of gemcitabine, oxaliplatin, and cetuximab as salvage therapy for metastatic colorectal cancer (mCRC) patients." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e14531-e14531. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e14531.

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e14531 Background: We have previously reported that biweekly gemcitabine-based therapy was active in pretreated mCRC pts (De la Cruz et al, ASCO GI 2008, abstr 377). We aimed to investigate whether germ line polymorphisms may be predictors of clinical outcome in mCRC pts treated with this combination. Methods: We evaluated SNPs of genes involved in gemcitabine metabolism (CDA, dCDK, RRM1, DCTD, SLC28A1), DNA repair (XRCC1, XRCC 3, ERCC1, XPD) and two IgG Fcγ R polymorphisms (Fcγ RIIa- H131R and Fcγ RIIIa-V158F), reported to be predictive of cetuximab-based therapy, even in K-ras mutated pts. Whole blood was collected and DNA extracted from peripheral lymphocytes using a DNA isolation Kit (Qiagen, CA). Polymorphisms were detected using the TaqMan genotyping assays (Applied Biosystems, CA). Clinical response was evaluated according to RECIST criteria. Univariate analysis (Fisher´s exact test for response; log-rank test for TTP and OS) was performed to examine associations between polymorphisms and clinical outcome. Results: Blood samples of 35 out of 39 enrolled pts were tested for genomic analysis. Patient‘s characteristics are as follows; M/F: 26/13, median age: 59 years, median number of prior chemotherapy lines: 2 (1–4), Köhne risk groups; low: 8 pts, intermediate: 18 pts, high: 13 pts. After a median follow-up of 20 months, median progression-free survival (PFS) is 6.7 months (95% CI; 5.2–8.3) and median overall survival 15.4 m (95% CI; 14.7–16.1). Overall response rate (ORR) was 53.8%. RRM1 R284R SNPs (p=0.06), T741T (p=0.02) and RRM1–524CT (p=0.04) were linked to clinical responsiveness. All pts possessing 2 or 3 favourable RRM1 SNPs responded. ORR was 53.3% for pts with no favourable SNPs versus 85% for pts with any favourable SNP (p=0.04). ORR was also significantly higher in pts with any histidine allele in the Fcγ RIIa polymorphism (93% vs. 60%, p=0.034). Median PFS was adversely affected in pts harbouring no favourable RRM1 SNPs (4.2m versus 6.7 months, p=0.019) and in those pts with homozygous Fcγ RIIa-131R allele (4.4 vs. 7.5 months, p=0.007). Conclusions: Polymorphic variants of RRM1 and Fcγ RIIa may play a key role in the efficacy of gemcitabine and cetuximab-based therapy for mCRC pts. No significant financial relationships to disclose.
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Boettcher, Sebastian, Matthias Ritgen, Christiane Pott, Andreas Humpe, and Michael Kneba. "Development and Evaluation of a Novel Flow Cytometric Assay for Determination of Fcγ Receptor IIIa-158 V/F Dimorphism." Blood 104, no. 11 (November 16, 2004): 1366. http://dx.doi.org/10.1182/blood.v104.11.1366.1366.

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Abstract A recently described dimorphism at position 559 of FCGR3A gene results in two allotypes of Fcγ receptor IIIa (Fcγ RIIIa) with phenylalanine (F) or valine (V) at amino acid position 158. It has been shown that Fcγ RIIIa-VV homozygous patients with follicular lymphoma respond better to Rituximab as a single agent than F carriers. However, there is evidence that this disadvantage in F carriers can be overcome by higher Rituximab concentrations or by the use of defucosylated therapeutic antibodies. Therefore rapid, widely applicable, and cost-effective methods for the determination of this Fcγ RIIIa dimorphism are necessary. Currently available methods to determine this dimorphism are based on PCR techniques. To simplify the determination of Fcγ RIIIa-V/F dimorphism we developed a novel flow cytometric approach using known differences in epitope recognition of monoclonal antibodies (moabs) to Fcγ RIIIa. The moab MEM-154 recognizes Fcγ RIIIa-V only, whereas moab 3G8 recognizes Fcγ RIIIa irrespective of the dimorphism. We determined the expression level of epitopes recognized by 3G8 and MEM-154 in NK cells of 35 healthy donors (FF 14; V/F 17; VV 4) by three color flow cytometry and secondary immunofluorescence. Results were compared to genotypes determined by a TaqMan assay using allele specific fluorochrome labelled probes. Donors genotyped as Fcγ RIIIa FF, V/F, and VV demonstrated overlapping immunofluorescence levels detected by both 3G8 and MEM-154. However, the ratio of fluorescence measured using MEM-154 divided by the immunofluorescence measured using 3G8 was 100% accurate for predicting genotypes. Ratios below 0.05 were measured in Fcγ RIIIa FF individuals, ratios between 0.1 and 0.5 were measured in heterozygotes, whereas ratios higher than 0.6 were found in Fcγ RIIIa VV individuals only. Quantitative flow cytometry demonstrated a great variation in Fcγ RIIIa expression on NK cells between individuals with identical Fcγ R IIIa genotype explaining the failure to predict the genotype by a single Fcγ R IIIa moab only. This novel flow cytometric assay is cost-efficient, easy to implement, reliable and uses standard flow cytometric techniques. Compared to known methods to determine the dimorphism it is faster and applicable in laboratories without sophisticated PCR technology.
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de Haas, M., M. Kleijer, R. M. Minchinton, D. Roos, and A. E. von dem Borne. "Soluble Fc gamma RIIIa is present in plasma and is derived from natural killer cells." Journal of Immunology 152, no. 2 (January 15, 1994): 900–907. http://dx.doi.org/10.4049/jimmunol.152.2.900.

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Abstract Fc gamma RIII (CD16), a receptor for complexed IgG, is encoded by two very homologous genes: Fc gamma RIIIA and Fc gamma RIIIB. NK cells and macrophages express Fc gamma RIIIa, whereas only neutrophils constitutively express Fc gamma RIIIb. In a previous study we found that soluble (s)Fc gamma RIII in plasma seemed to originate only from neutrophils. However, CD16 mAb, directed against different epitopes of Fc gamma RIII, precipitated a glycoprotein from plasma of homozygous Fc gamma RIIIB gene-deficient donors. This glycoprotein migrated in a similar way as did released Fc gamma RIIIa derived from NK cells, whereas Fc gamma RIIIa released by cultured monocytes migrated differently and appeared to be more heavily glycosylated on SDS-PAGE. After deglycosylation, the M(r) of the plasma sFc gamma RIIIa was similar to that of released Fc gamma RIIIa. Moreover, V8-protease maps were identical. Therefore, we conclude that sFc gamma RIIIa is also present in plasma and is derived from NK cells. Because sFc gamma RIII levels are hardly detectable in the plasma of most homozygous Fc gamma RIIIB gene-deficient donors, we suspect that the sFc gamma RIIIa level is negligible compared with the level of sFc gamma RIIIb in plasma of healthy donors. Two patients with an NK cell lymphocytosis had a high plasma level of sFc gamma RIIIaNK. Furthermore, high levels of sFc gamma RIIIaNK were found in plasma of two patients with rheumatoid arthritis. Thus, the level of sFc gamma RIIIaNK might reflect either an increase in circulating NK cells or an enhanced release of Fc gamma RIIIaNK in certain diseases. This study shows that an assay that discriminates between sFc gamma RIIIa and sFc gamma RIIIb is necessary for the interpretation of sFc gamma RIII levels in patients.
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Indik, ZK, JG Park, XQ Pan, and AD Schreiber. "Induction of phagocytosis by a protein tyrosine kinase." Blood 85, no. 5 (March 1, 1995): 1175–80. http://dx.doi.org/10.1182/blood.v85.5.1175.bloodjournal8551175.

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The transmission of extracellular signals to cellular targets by many noncatalytic surface receptors is dependent on interaction between cytoplasmic protein tyrosine kinases (PTKs) and tyrosine-containing sequences in the cytoplasmic domain of the receptor or an associated subunit. Isoforms of each of the three classes of the noncatalytic Fc gamma receptors, Fc gamma RI, Fc gamma RII, and Fc gamma RIII, are able to transmit a phagocytic signal in transfected COS-1 cells. Both Fc gamma RI and Fc gamma RIIIA require the gamma subunit for this signaling event. The protein tyrosine kinase Syk dramatically enhances phagocytosis mediated by both these receptors and increases the number of cells able to mediate phagocytosis. Two gamma chain cytoplasmic YXXL sequences are required for this effect. The action of Syk is less pronounced on the phagocytic Fc gamma RII receptor, Fc gamma RIIA, which does not require the gamma chain for phagocytosis. However, Syk allows phagocytosis by the nonphagocytic Fc gamma RII receptor Fc gamma RIIB2, which contains only a single YXXL sequence, when an additional tyrosine-containing sequence, YMTL, is introduced. These studies indicate that the efficiency of phagocytosis is markedly enhanced by the presence of a specific protein tyrosine kinase.
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15

Matikainen, Johanna. "Suvaitsevaisuuskasvatuksen haasteita." Aikuiskasvatus 16, no. 4 (December 1, 1996): 315–16. http://dx.doi.org/10.33336/aik.92419.

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16

Ojeda, Dario I., Max John, Robert L. Hammond, Riitta Savolainen, Kari Vepsäläinen, and Torstein Kvamme. "Phylogeny of the Formicoxenus genus-group (Hymenoptera: Formicidae) reveals isolated lineages of Leptothorax acervorum in the Iberian Peninsula predating the Last Glacial Maximum." Biodiversity Journal 14, no. 4 (2023): 547–70. http://dx.doi.org/10.31396/biodiv.jour.2023.14.4.547.570.

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17

Li, Xiaodi, A. Vinodkumar, and T. Senthilkumar. "Exponential Stability Results on Random and Fixed Time Impulsive Differential Systems with Infinite Delay." Mathematics 7, no. 9 (September 12, 2019): 843. http://dx.doi.org/10.3390/math7090843.

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In this paper, we investigated the stability criteria like an exponential and weakly exponential stable for random impulsive infinite delay differential systems (RIIDDS). Furthermore, we proved some extended exponential and weakly exponential stability results for RIIDDS by using the Lyapunov function and Razumikhin technique. Unlike other studies, we show that the stability behavior of the random time impulses is faster than the fixed time impulses. Finally, two examples were studied for comparative results of fixed and random time impulses it shows by simulation.
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Toivola, Heikki. "Aikuiskasvatus arvojen mosaiikissa – mikä on jatkuvuuden voima?" Aikuiskasvatus 15, no. 2 (February 1, 1995): 138–40. http://dx.doi.org/10.33336/aik.92324.

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19

Salcedo, T. W., T. Kurosaki, P. Kanakaraj, J. V. Ravetch, and B. Perussia. "Physical and functional association of p56lck with Fc gamma RIIIA (CD16) in natural killer cells." Journal of Experimental Medicine 177, no. 5 (May 1, 1993): 1475–80. http://dx.doi.org/10.1084/jem.177.5.1475.

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The transmembrane receptor for immunoglobulin G immune complexes on natural killer (NK) cells and macrophages, Fc gamma RIIIA (CD16), mediates cellular activation through a tyrosine kinase-dependent pathway. We show that Fc gamma RIII crosslinking results in activation of the src-related kinase p56lck in NK cells and demonstrate a physical association of p56lck with Fc gamma RIIIA in immunoprecipitates from NK cells obtained using anti-Fc gamma RIII antibodies or immune complexes. Our studies show that the zeta chain, the signal transducing subunit of Fc gamma RIIIA and of T cell receptor, associates with p56lck and, in NK cells, is a substrate for this kinase. Such direct association of p56lck with the zeta subunit as confirmed by demonstrating the interaction in heterologous cells transfected with cDNA expressing p56lck and zeta. Our findings demonstrate both functional and physical association of p56lck with Fc gamma RIIIA, through direct interaction of the kinase with the zeta and/or the gamma signal transducer subunits of the receptor. These data suggest a possible mechanism by which activation via Fc gamma RIIIA occurs.
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Azzoni, L., M. Kamoun, T. W. Salcedo, P. Kanakaraj, and B. Perussia. "Stimulation of Fc gamma RIIIA results in phospholipase C-gamma 1 tyrosine phosphorylation and p56lck activation." Journal of Experimental Medicine 176, no. 6 (December 1, 1992): 1745–50. http://dx.doi.org/10.1084/jem.176.6.1745.

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Binding of ligand to the alpha subunit of Fc gamma RIIIA(CD16), expressed at the natural killer (NK) cell membrane in association with homo or heterodimers of proteins of the zeta family, results in phosphorylation of several proteins on tyrosine residues. We have analyzed the role of protein tyrosine phosphorylation in the regulation of molecular events induced upon stimulation of Fc gamma RIIIA in NK cells and in T cells expressing the Fc gamma RIII alpha chain in association with endogenous zeta 2 homodimers and devoid of other (CD3, CD2) transducing molecules. Our data indicate that treatment of these cells with protein tyrosine kinase inhibitors prevents not only Fc gamma RIIIA-induced protein tyrosine phosphorylation but also phosphatidylinositol 4,5 diphosphate hydrolysis and increased intracellular Ca2+ concentration, indicating a primary role of tyrosine kinase(s) in the induction of these early activation events. Occupancy of Fc gamma RIIIA by ligand results in phospholipase C (PLC)-gamma 1 tyrosine phosphorylation in NK cells and in Fc gamma RIIIA-transfected CD3-/CD2- T cells, and induces functional activation of p56lck in Fc gamma RIIIA alpha/zeta 2-transfected T cells, suggesting the possibility that the receptor-induced PLC-gamma 1 activation occurs upon phosphorylation of its tyrosine residues mediated by this kinase and is, at least in part, responsible for the signal transduction mediated via CD16 upon ligand binding.
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Garcia-Foncillas, Jesus, Javier Rodriguez, Valentina Boni, Iosu Sola, Beatriz Honorato, Ruth Zarate, and Eva Bandres. "Role of polymorphic fc gamma receptor II/III in the efficacy of cetuximab in KRAS-NRAS-BRAF-PI3K mutated." Journal of Clinical Oncology 30, no. 4_suppl (February 1, 2012): 477. http://dx.doi.org/10.1200/jco.2012.30.4_suppl.477.

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477 Background: The immunoglobulin G1 (IgG1) monoclonal antibody (MoAb) cetuximab is active in metastatic colorectal cancer (mCRC) as first or subsequent lines of therapy. Efficacy seems restricted to KRAS wild-type tumors. IgG1 may also induce antibody dependent cell mediated citotoxicity (ADCC) by recruitment of immune effector cells. ADCC is influenced by FcγR polymorphisms. We investigated the association of FcγR polymorphisms and disease control rate (DCR) in mCRC patients treated with chemotherapy plus cetuximab. Methods: Tumor tissues from 106 patients were screened for KRAS codon 12 and 13 mutations using a sensitive multiplex assay (DxS, Manchester. UK). NRAS (codons: 12, 13 and 61), PI3K (exon 20) and BRAF (exon 15) were analysed by direct sequencing. Fcγ RIIa and Fcγ RIIIa polymorphisms were genotyped by TaqMan assays. Results: DCR was significantly higher in KRAS wild-type tumors (61% vs 39%, p=0.049). In EGFR downstream-mutated mCRC patients, those harbouring a FcγRIIa H/H genotype had a higher DCR than alternative genotypes (67% vs 33%, p=0.017). By multivariate analysis, FcγRIIa-131H/H remained significantly correlated with DCR (p=0.008). Conclusions: FcγR polymorphisms may play a role in the clinical efficacy of cetuximab in EGFR downstream mutated mCRC patients. Further research into cetuximab immune-based mechanisms in KRAS-mutated patients seems warranted.
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Kupiainen, Reijo. "Aikuisten mediatajuun kuuluu myös omaa kokemusta laajempi horisontti." Aikuiskasvatus 26, no. 3 (September 15, 2006): 262–63. http://dx.doi.org/10.33336/aik.93712.

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23

Masuda, M., A. J. Verhoeven, and D. Roos. "Tyrosine phosphorylation of a gamma-chain homodimer associated with Fc gamma RIII (CD16) in cultured human monocytes." Journal of Immunology 151, no. 11 (December 1, 1993): 6382–88. http://dx.doi.org/10.4049/jimmunol.151.11.6382.

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Abstract The efficient expression of transmembrane-anchored Fc gamma RIIIa requires the presence of other peptides, such as the gamma-chain of the IgE receptor I or the zeta-chain of the TCR. We found that Fc gamma RIIIa in cultured human monocytes is specifically associated with the gamma-chain homodimer, and that the gamma-chains in this complex are phosphorylated on tyrosine residues. Anti-Fc gamma RIII immunoprecipitates, which were prepared from 1% digitonin lysates of cultured human monocytes, incorporated phosphate into a homodimer consisting of two 14-kDa polypeptides when incubated with [gamma-32P]ATP. Identity of this co-associated structure of Fc gamma RIIIa as the gamma-chain dimer was confirmed by elution of the protein from the anti-Fc gamma RIII immunoabsorbent with 1% Nonidet P-40 detergent and reimmunoprecipitation with anti-gamma-chain antibody. Phosphoamino acid analysis showed that the gamma-chain exclusively contained phosphotyrosine. The gamma-chain was also phosphorylated when electropermeabilized cells were activated by cross-linking Fc gamma RIIIa. The gamma-chain may play an important role in signal transduction via Fc gamma RIIIa in human macrophages.
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Ciaś, Kinga. "Being reborn into the new family." Folia Scandinavica Posnaniensia 28, no. 1 (June 1, 2020): 17–26. http://dx.doi.org/10.2478/fsp-2020-0002.

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Abstract Every child brought up outside the biological family suffered a loss, some of them were lucky to be “born again’’ for another family who accepted them with love. The experiences of children in this situation often remain secretive and emotions suppressed. In this case, literature can become a way of therapy, both for the author and the reader who perceive through the novel their emotions that were not previously named. After many years, two Finnish writers Anu Mylläri and Riitta Jalonen decided to reveal their stories. Anu Mylläri, born in Bangladesh, was adopted by a family of Finnish farmers, while Riitta Jalonen included in her novel autobiographical plots related to the admission of a new child to her family. I will present the image of the “second birth” and the associated emotions from the perspective of the child on the basis of the autobiography of Anu Mylläri Adoptoitu (Adopted, 2006) and the autobiographical novel Kuka sinut omistaa (Who Owns You, 2013) by Riitta Jalonen. The aim of the article is thus to present these perspectives with relation to the bibliotherapeutic values of the mentioned literary works.
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Nerdrum, Monica. "Den finländska byn." Budkavlen 80 (June 13, 2023): 89–91. http://dx.doi.org/10.37447/bk.130781.

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Darby, C., R. L. Geahlen, and A. D. Schreiber. "Stimulation of macrophage Fc gamma RIIIA activates the receptor-associated protein tyrosine kinase Syk and induces phosphorylation of multiple proteins including p95Vav and p62/GAP-associated protein." Journal of Immunology 152, no. 11 (June 1, 1994): 5429–37. http://dx.doi.org/10.4049/jimmunol.152.11.5429.

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Abstract The role of tyrosine phosphorylation during signal transduction by the phagocytic macrophage (Mphi) FcR Fc gamma RIIIA was investigated. Cross-linking Fc gamma RIIIA on pulmonary Mphi or cultured monocytes used as in vitro model for differentiated Mphi induced rapid and transient phosphorylation of multiple protein substrates. The lymphocyte/mast cell 72-kDa protein tyrosine kinase (PTK) designated PTK72 or Syk, whose expression in Mphi was previously unknown, was identified as a major substrate by immunoprecipitation and phosphopeptide mapping. Activation of Fc gamma RIIIA stimulated a fourfold increase in Syk kinase activity assessed by autophosphorylation. Under mild lysis conditions several specific proteins were co-precipitated with the gamma subunit of Fc gamma RIIIA. Tyrosine kinase activity was also co-precipitated with gamma, as shown by in vitro phosphorylation of gamma. One of these kinases was identified as Syk by phosphopeptide mapping, suggesting a physical association between this PTK and the receptor. Two additional phosphoproteins induced by Fc gamma RIIIA cross-linking were identified: the hematopoietic proto-oncogene product p95Vav, previously implicated in B lymphocyte and mast cell signaling; and p62, a protein associated with p21Ras-GAP. Our results also establish that there are important functional similarities in signal transduction between a phagocytic Mphi FcR and other multi-subunit Ig gene family receptors in diverse cell lineages.
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Weinberg, Adriana, and Miranda L. Walker. "Evaluation of Three Immunoassay Kits for Rapid Detection of Influenza Virus A and B." Clinical Diagnostic Laboratory Immunology 12, no. 3 (March 2005): 367–70. http://dx.doi.org/10.1128/cdli.12.3.367-370.2005.

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ABSTRACT Influenza causes high morbidity and mortality in very young and elderly individuals, which can be controlled with antivirals and/or vaccines. The success of therapeutic measures is predicated on the rapid and precise diagnosis of the infection. We compared three rapid influenza immunoassay (RIIA) kits for the diagnosis of influenza virus A and B using 178 respiratory specimens submitted for routine testing. BD Directigen Flu A+B (Directigen), Directigen EZ Flu A+B (EZ), and NOW Flu A NOW Flu B (NOW; Binax) tests had comparable combined influenza virus A and B specificities, varying from 94 to 98%. In contrast, the sensitivity of EZ was significantly lower (39%) than that of NOW (76%) and marginally lower than that of Directigen (56%). The differences in sensitivity were most evident in patients who were >9 years old (Directigen, 53%; EZ, 32%; and NOW, 69%). Among specimens, bronchoalveolar lavage fluids yielded the most discrepant results, with sensitivities varying from 0 (EZ) to 100% (NOW), followed by nasopharyngeal swabs (sensitivities of 27 to 100%) and nasal washes (50 to 81%). The Directigen kit format allowed for faster completion but more cumbersome performance and more difficult interpretation compared with the other two kits. Overall, NOW provided the most accurate diagnoses and had user-friendly technical characteristics. However, the low overall sensitivity of the RIIAs indicates that these can be used as screening tools only.
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Vehviläinen, Sanna. "Mitä mielessä mielen tutkimuksessa?" Aikuiskasvatus 35, no. 4 (December 1, 2015): 310–11. http://dx.doi.org/10.33336/aik.94161.

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29

Liao, F., H. S. Shin, and S. G. Rhee. "Cross-linking of Fc gamma RIIIA on natural killer cells results in tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2." Journal of Immunology 150, no. 7 (April 1, 1993): 2668–74. http://dx.doi.org/10.4049/jimmunol.150.7.2668.

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Abstract The Fc gamma RIIIA, which is composed of a transmembrane IgG-binding glycoprotein and either a disulfide-linked homodimer (zeta zeta, gamma gamma) or heterodimer (zeta gamma), mediates the antibody-dependent cellular cytotoxicity in NK cells. The role of phospholipase C (PLC) isozymes in Fc gamma RIIIA-mediated signal transduction was investigated. The NK cell line NK3.3 was found to contain PLC-gamma 1 and an especially high concentration of PLC-gamma 2, but PLC-beta 1 and PLC-delta 1 were not detected. Cross-linking of Fc gamma RIIIA on NK3.3 cells induced a rapid phosphorylation of PLC-gamma 1 and PLC-gamma 2 on tyrosine residues. Pretreatment of NK3.3 cells with a tyrosine kinase inhibitor, herbimycin A, prevented the tyrosine phosphorylation of both PLC-gamma 1 and PLC-gamma 2. These results indicate that activation of Fc gamma RIIIA on NK3.3 cells is coupled either directly or indirectly to a nonreceptor tyrosine kinase, which phosphorylates, and thereby activates PLC-gamma 1 and PLC-gamma 2.
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30

Lillbroända-Annala, Sanna. "Materiell kultur." Budkavlen 88 (June 1, 2023): 110–11. http://dx.doi.org/10.37447/bk.130183.

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Recension av: Touching Things. Ethnological Aspects of Modern Material Culture. 2008 Red. Pirjo Korkiakangas, Tiina-Riitta Lappi & Heli Niskanen. (Studia Fennica Ethnologica 11.) Helsinki: SKS, 277 s.
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31

Kanakaraj, P., B. Duckworth, L. Azzoni, M. Kamoun, L. C. Cantley, and B. Perussia. "Phosphatidylinositol-3 kinase activation induced upon Fc gamma RIIIA-ligand interaction." Journal of Experimental Medicine 179, no. 2 (February 1, 1994): 551–58. http://dx.doi.org/10.1084/jem.179.2.551.

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Induced activation of protein tyrosine kinase(s) is a central event in signal transduction mediated via the low affinity receptor for IgG (Fc gamma RIIIA, CD16) in natural killer (NK) cells. Tyrosine phosphorylation may affect the function of several protein directly, or indirectly by inducing their association with other tyrosine phosphorylated proteins. Here, we report that Fc gamma RIII stimulation induces activation of phosphatidylinositol (PI)-3 kinase in NK cells. Phosphotyrosine immunoprecipitates from Fc gamma RIII-stimulated NK cells contain PI-kinase activity and PI-3 kinase can be directly precipitated from them. Conversely, a series of tyrosine-phosphorylated proteins is coprecipitated with PI-3 kinase from the stimulated, but not from control cells. Analogous results obtained using Jurkat T cells expressing transfected Fc gamma RIIIA alpha ligand binding chain in association with gamma 2 or zeta 2 homodimers indicate that both complexes transduce this effect, although the Fc gamma RIIIA-zeta 2 complexes do so with greater efficiency. Accumulation of phosphoinositide D3 phosphorylated products in stimulated cells confirms PI-3 kinase activation, indicating the participation of this enzyme in Fc gamma RIIIA-mediated signal transduction.
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32

Boettcher, Sebastian, Christiane Pott, Matthias Ritgen, Wolfgang Hiddemann, Michael Unterhalt, and Michael Kneba. "Evidence for Fcγ Receptor IIIA-Independent Rituximab Effector Mechanisms in Patients with Follicular Lymphoma Treated with Combined Immuno-Chemotherapy." Blood 104, no. 11 (November 16, 2004): 590. http://dx.doi.org/10.1182/blood.v104.11.590.590.

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Abstract The response to the anti-CD20 antibody Rituximab used as a single agent in follicular lymphoma (FL) patients can be predicted by the valine/phenylalanine (V/F) dimorphism of amino acid 158 of Fcγ Receptor IIIA (Fcγ RIIIA) (Cartron et al., Blood99: 754, 2002; Weng and Levy, JCO21: 3940, 2003). This suggested important contributions for Fcγ RIIIA mediated mechanisms like antibody dependent cellular cytotoxicity to the efficacy of the antibody. Recently, the German Low Grade Lymphoma Study Group (GLSG) demonstrated a significant shorter time to treatment failure (TTF) in patients who received standard CHOP (cyclophosphamide d1, doxorubicin d1, vincristin d1, prednisone d1-5) chemotherapy only compared to patients who received Rituximab (d1) plus CHOP (R-CHOP). Estimated median TTF was 2.6 years in FL patients treated with CHOP and was not reached after 3 years observation time in R-CHOP treated FL patients (p<0.0007) (Blood 102, Abstract # 352, 2003). We examined the Fcγ RIIIA dimorphism in 75 FL patients from this GLSG trial who were treated with 6 to 8 cycles R-CHOP followed by interferon maintenance or high dose chemo-radiotherapy and autologous stem cell transplantation. Using a TaqMan assay with allele specific fluorochrome labelled probes we detected a V/V genotype in 8 patients (10.7%), a V/F genotype in 38 patients (50.6%), and an F/F genotype in 29 patients (38.7%). Patients with different Fcγ RIIIA status responded similarly to R-CHOP (CR rate: V/V 37.5%, V/F 36.8%, F/F 24.1%; overall response rate: V/V 100.0 %, V/F 97.4%, F/F 96.6%; ns). Moreover, TTF was not significantly different between the groups with V/V, V/F, and F/F Fcγ RIIIA(log rank p = 0.48) after a median observation time of 24 months. A correlation between the Fcγ RIIIA status and the efficacy of R-CHOP could not be demonstrated in this large patient cohort. On the other hand it is evident that R-CHOP treated patients significantly benefited from the addition of Rituximab to CHOP chemotherapy in comparison to the standard arm of this randomized trial. This observation supports the hypothesis that the anti-lymphoma effects of Rituximab when used in combination with chemotherapy might be mediated by Fcγ RIIIA-independent mechanisms such as complement dependent cytotoxicity or direct apoptosis induction.
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33

Pennanen, Eveliina. "Sairaalatyöyhteisön hallinnollisessa vuorovaikutuksessa rakennetaan työn resursseja ja työn yhteisyyttä." Prologi 14, no. 1 (December 15, 2018): 78–83. http://dx.doi.org/10.33352/prlg.95933.

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Lectio praecursoria viestinnän väitöskirjaksi tarkoitetun tutkimuksen Hallinnollinen vuorovaikutus sairaalatyöyhteisössä tarkastustilaisuudessa Jyväskylän yliopistossa 6.4.2018. Vastaväittäjänä toimi yliopistonlehtori, dosentti Tuula-Riitta Välikoski (Tampereen yliopisto) ja kustoksena yliopistonlehtori, FT Leena Mikkola (Jyväskylän yliopisto).
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34

Laki, Ildikó. "Az önkéntesség mint társadalmi és közösségi befogadás az időskorúaknál : Egy finn vizsgálat tanulságai." Önkéntes Szemle 2, no. 4 (2022): 130–34. http://dx.doi.org/10.53585/onkszem.2022.4.130-134.

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Utta Tiittanen – Riitta Turjamaa (2022): Social inclusion and communality of volunteering: A focus group study of older people’s experiences. Int. J.Environ. Res. Public Health, 19(9). 5141. pp. 1-10.
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35

Rouhiainen-Neunhäuserer, Maijastiina. "Johtamisen viestintähaasteet tietoperustaisessa työssä." Prologi 5, no. 1 (December 15, 2009): 90–95. http://dx.doi.org/10.33352/prlg.95809.

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Lectio praecursoria puheviestinnän väitöskirjaksi tarkoitetun tutkimuksen Johtajan vuorovaikutusosaaminen ja sen kehittyminen. Johtamisen viestintähaasteet tietoperustaisessa organisaatiossa tarkastustilaisuudessa Jyväskylän yliopistossa 20.11.2009. Vastaväittäjänä toimi professori Riitta Viitala (Vaasan yliopisto) ja kustoksena professori Tarja Valkonen.
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36

Mitrovic, Z., I. Aurer, I. Radman, R. Ajdukovic, J. Sertic, and B. Labar. "FC RIIIA and FC RIIA polymorphisms are not associated with response to rituximab and CHOP in patients with diffuse large B-cell lymphoma." Haematologica 92, no. 7 (July 1, 2007): 998–99. http://dx.doi.org/10.3324/haematol.10327.

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37

Carlotti, E., G. A. Palumbo, E. Oldani, D. Tibullo, S. Salmoiraghi, A. Rossi, J. Golay, A. Pulsoni, R. Foa, and A. Rambaldi. "Fc RIIIA and Fc RIIA polymorphisms do not predict clinical outcome of follicular non-Hodgkin's lymphoma patients treated with sequential CHOP and rituximab." Haematologica 92, no. 8 (August 1, 2007): 1127–30. http://dx.doi.org/10.3324/haematol.11288.

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38

Paatsi, Vello. "Kui Liivimaa ajakirjandust tsenseeriti Riias." Keel ja Kirjandus 57, no. 4 (April 2014): 284–90. http://dx.doi.org/10.54013/kk677a3.

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39

Kurosaki, T., I. Gander, U. Wirthmueller, and J. V. Ravetch. "The beta subunit of the Fc epsilon RI is associated with the Fc gamma RIII on mast cells." Journal of Experimental Medicine 175, no. 2 (February 1, 1992): 447–51. http://dx.doi.org/10.1084/jem.175.2.447.

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Fc epsilon RI is a tetrameric receptor, composed of a ligand recognition subunit, alpha, a beta chain, and dimeric gamma chains. Previous studies have indicated that the dimeric gamma chain is associated with Fc gamma RIIIA (CD16) on natural killer cells and macrophages as well as the clonotypic T cell receptor. Here we show that in mast cells, in addition to the dimeric gamma chains, the beta subunit is associated not only with Fc epsilon RI, but also with Fc gamma RIIIA. Functional reconstitution studies with a mastocytoma cell line indicate that Fc gamma RIIIA composed of alpha, beta, and gamma subunits has the capacity for signal transduction. These studies suggest that through the association of alternative ligand recognition subunits (alpha epsilon, alpha gamma), a common signal transduction complex (beta gamma 2) mediates similar biochemical and effector functions in response to immunoglobulin G (IgG) and IgE.
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Wirthmueller, U., T. Kurosaki, M. S. Murakami, and J. V. Ravetch. "Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain." Journal of Experimental Medicine 175, no. 5 (May 1, 1992): 1381–90. http://dx.doi.org/10.1084/jem.175.5.1381.

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To determine the functional role of the two isoforms of Fc gamma RIII (CD16) (IIIA, IIIB), the signal transduction capabilities of wild-type and mutant forms of these receptors were analyzed in transfected lymphoid, myeloid, and fibroblastic cell lines. Functional reconstitution of receptor signalling was observed in hematopoietic T and mast cells, and was absent in nonhematopoietic (CHO) cells. Fc gamma RIIIA, a hetero-oligomeric receptor composed of a ligand-binding subunit alpha and dimeric gamma chains, generated both proximal and distal responses in Jurkat and P815 cells, typical of what is seen in natural killer cells and macrophages upon receptor activation. In contrast, Fc gamma RIIIB, which is normally attached to the cell surface via a glycosyl-phosphatidylinositol anchor, was incapable of transducing signals. After crosslinking, Fc gamma RIIIA signalling was dependent only upon the gamma chain. Fc gamma RIIIA chimeras in which the alpha subunit transmembrane and cytoplasmic domains were substituted with the corresponding gamma chain sequences functioned as well as wild-type hetero-oligomeric receptors. These data indicate that the ability of the Fc gamma RIIIA complex to activate the appropriate pathways for cell activation is cell-type restricted and independent of the transmembrane and cytoplasmic domains of the alpha subunit. The presence of the gamma chain is responsible for the assembly of, as well as the signal transduction by, the functional cell surface complex.
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41

Daegelen, P., and E. Brody. "The rIIA gene of bacteriophage T4. I. Its DNA sequence and discovery of a new open reading frame between genes 60 and rIIA." Genetics 125, no. 2 (June 1, 1990): 237–48. http://dx.doi.org/10.1093/genetics/125.2.237.

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Abstract We have determined the DNA sequence of the rIIA gene and have discovered a small open reading frame, rIIA.1, between genes 60 and rIIA. The predicted molecular weights of these proteins are 82,840 for rIIA and 8,124 for rIIA.1. The rIIA protein has a repeated motif which suggests that the gene has evolved by duplication. It also has a motif which suggests that it belongs to a group of ompR-like proteins that control regulation of gene expression in response to changes in the external environment. We have sequenced three different missense mutants whose mutations lie in the Ala segment of the rIIA genetic map. All three changes are found within the first 35 bp of the rIIA coding sequence. The region of control of protein synthesis is identical in the rIIA gene and in gene 44 of T4. We relate this finding to the high sensitivity of both RNAs to translational repression by the T4 regA gene product.
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42

Rodrigues, Louis J. "Review of “Translating for Children” by Riitta Oittinen." Babel. Revue internationale de la traduction / International Journal of Translation 47, no. 4 (December 31, 2001): 382–84. http://dx.doi.org/10.1075/babel.47.4.17rod.

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43

Seow, Cherng Jye, and Abel Weiliang Chen. "Abstract #829 Macroprolactinoma Complicated by Riight Hemispheric Syndrome." Endocrine Practice 24 (April 2018): 187–88. http://dx.doi.org/10.1016/s1530-891x(20)47316-1.

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44

Graziano, Francesco, Annamaria Ruzzo, Fotios Loupakis, Emanuele Canestrari, Daniele Santini, Vincenzo Catalano, Renato Bisonni, et al. "Pharmacogenetic Profiling for Cetuximab Plus Irinotecan Therapy in Patients With Refractory Advanced Colorectal Cancer." Journal of Clinical Oncology 26, no. 9 (March 20, 2008): 1427–34. http://dx.doi.org/10.1200/jco.2007.12.4602.

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PurposeRegulation of epidermal growth factor receptor (EGFR) signaling pathways may play a relevant role in determining the activity of cetuximab therapy in patients with metastatic colorectal cancer (MCRC). We investigated possible associations between genetic variants and clinical outcomes of MCRC patients treated with cetuximab-irinotecan salvage therapy.Patients and MethodsPatients who underwent cetuximab-irinotecan salvage therapy after disease progression during or after first-line bolus/infusional fluorouracil, leucovorin, and oxaliplatin chemotherapy and a second-line irinotecan-based regimen were considered eligible for analysis of polymorphisms with putative influence on cetuximab-related pathways. Epidermal growth factor (EGF) 61A>G, EGF receptor (EGFR) 216G>T, EGFR 497G>A, EGFR intron-1 (CA)ndinucleotide short (S)/long (L) variant, cyclin-D1 870A>G, immunoglobulin-G fragment-C receptors RIIIa 158G>T, and RIIa 131G>A were studied for a possible association with overall survival (OS) as the primary end point. Additional analyses were addressed at possible associations among polymorphisms and EGFR expression, toxicity, and response.ResultsIn 110 assessable patients, significant association with favorable OS was observed for EGFR intron-1 S/S and EGF 61 G/G genotypes. In the multivariate model, EGFR intron-1 S/S and EGF 61 G/G genotypes showed a hazard ratio of 0.41 (95% CI, 0.21 to 0.78; P = .006) and 0.44 (95% CI, 0.23 to 0.84; P = .01), respectively. EGFR intron-1 S/S carriers showed more frequent G2-G3 skin toxicity (χ2test = 12.7; P = .001) and treatment response (χ2test = 9.45; P = .008) than EGFR intron-1 L/L carriers.ConclusionAlthough additional studies are required for confirmation, our findings could optimize the use of cetuximab in MCRC patients.
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Strandén, Sofie. "Metodologiska frågor i oral history -forskning." Budkavlen 86 (June 6, 2023): 89–90. http://dx.doi.org/10.37447/bk.130269.

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46

Alkio, Olavi. "Elinikäisen oppimisen komitea – uusien leilien uudet etiketit." Aikuiskasvatus 18, no. 2 (May 15, 1998): 155–57. http://dx.doi.org/10.33336/aik.92502.

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Elinikäisen oppimisen hyvät käytännöt : intohimo oppia / Markku Markkula & Riitta Suurla & Elinikäisen oppimisen komitea. (Komiteanmietintö ; 1997:14 liite) Helsinki, 1997. – Oppimisen ilo : kansallinen elinikäisen oppimisen strategia / Jorma Ahola & Elinikäisen oppimisen komitea. Helsinki : Kansanvalistusseura, 1997. – Näkökulmia elinikäiseen oppimiseen : elinikäisen oppimisen komitean mietinnön (1997:14) liite / Elinikäisen oppimisen komitea. Helsinki : Opetusministeriö, 1997.
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47

Marander-Eklund, Lena. "Affekter och känslor." Budkavlen 99 (November 10, 2020): 186–88. http://dx.doi.org/10.37447/bk.99544.

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48

Hull, Judith. "Review: Erik Bryggman 1891-1955 Arkkitehti by Riitta Nikula." Journal of the Society of Architectural Historians 54, no. 2 (June 1, 1995): 246–48. http://dx.doi.org/10.2307/990977.

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49

MARQUES DA SILVA, OTÁVIO LUIS, and INÊS CORDEIRO. "A new record of Euphorbia riinae (Euphorbiaceae) for Brazil." Phytotaxa 560, no. 2 (September 1, 2022): 259–62. http://dx.doi.org/10.11646/phytotaxa.560.2.10.

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50

Yanaga, F., A. Poole, J. Asselin, R. Blake, G. L. Schieven, E. A. Clark, C. L. Law, and S. P. Watson. "Syk interacts with tyrosine-phosphorylated proteins in human platelets activated by collagen and cross-linking of the Fc γ-IIA receptor." Biochemical Journal 311, no. 2 (October 15, 1995): 471–78. http://dx.doi.org/10.1042/bj3110471.

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Activation of human platelets by cross-linking of the platelet low-affinity IgG receptor, the Fc gamma receptor IIA (Fc gamma-RIIA), or by collagen is associated with rapid phosphorylation on tyrosine of the non-receptor tyrosine kinase syk. Phosphorylation is still observed, albeit sometimes reduced, in the presence of a combination of a protein kinase C inhibitor, Ro 31-8220, and the intracellular calcium chelator, BAPTA-AM, demonstrating independence from phosphoinositide-specific phospholipase C (PLC) activity. In contrast, the combination of Ro 31-8220 and BAPTA-AM completely inhibits phosphorylation of syk in thrombin-stimulated platelets. Phosphorylation of syk increases its autophosphorylation activity measured in a kinase assay performed on syk immunoprecipitates. Fc gamma-RIIA also undergoes phosphorylation in syk immunoprecipitates from platelets activated by cross-linking of Fc gamma-RIIA but not by collagen, suggesting that it associates with the kinase. Consistent with this, tyrosine-phosphorylated Fc gamma-RIIA is precipitated by a glutathione S-transferase (GST) fusion protein containing the tandem src homology (SH2) domains of syk from Fc gamma-RIIA- but not collagen-activated cells. Two uncharacterized tyrosine-phosphorylated proteins of 40 and 65 kDa are uniquely precipitated by a GST fusion protein containing the tandem syk-SH2 domains in collagen-stimulated platelets. A peptide based on the antigen recognition activation motif (ARAM) of Fc gamma-RIIA, and phosphorylated on the two tyrosine residues found within this region, selectively binds syk from lysates of resting platelets; this interaction is not seen with a non-phosphorylated peptide. Kinase assays on Fc gamma-RIIA immunoprecipitates reveal the constitutive association of an unidentified kinase activity in resting cells which phosphorylates a 67 kDa protein. Syk is not detected in Fc gamma-RIIA immunoprecipitates from resting cells but associates with the receptor following activation and, together with Fc gamma-RIIA, is phosphorylated in the kinase assay in vitro. These results demonstrate that syk is activated by Fc gamma-RIIA cross-linking and collagen, independent of PLC, suggesting that it may have an important role in the early events associated with platelet activation. The association of syk with Fc gamma-RIIA appears to be mediated through the tandem SH2 domains in syk and the ARAM motif of Fc gamma-RIIA. A similar interaction may underlie the response to collagen, suggesting that its signalling receptor contains an ARAM motif.
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