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  1. Article: Rationale for interleukin-6 blockade in systemic lupus erythematosus.

    Tackey, E / Lipsky, P E / Illei, G G

    Lupus

    2004  Volume 13, Issue 5, Page(s) 339–343

    Abstract: Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities that plays an important role in immune regulation and inflammation. Among other actions, it induces terminal differentiation of B lymphocytes into antibody-forming ... ...

    Abstract Interleukin-6 (IL-6) is a pleiotropic cytokine with a wide range of biological activities that plays an important role in immune regulation and inflammation. Among other actions, it induces terminal differentiation of B lymphocytes into antibody-forming cells and the differentiation of T cells into effector cells. IL-6 also has multiple potent proinflammatory effects. An association between IL-6 and lupus was demonstrated in murine models of SLE and blocking IL-6 improved lupus in all models tested. Data from several studies suggest that IL-6 plays a critical role in the B cell hyperactivity and immunopathology of human SLE, and may have a direct role in mediating tissue damage. Based on these data, we propose that blocking the effect of IL-6 in humans may improve lupus by interacting with the autoinflammatory process both systemically and locally.
    MeSH term(s) Animals ; Disease Models, Animal ; Humans ; Interleukin-6/antagonists & inhibitors ; Interleukin-6/immunology ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/therapy ; Receptors, Interleukin-6/immunology
    Chemical Substances Interleukin-6 ; Receptors, Interleukin-6
    Language English
    Publishing date 2004-06-22
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1154407-7
    ISSN 0961-2033
    ISSN 0961-2033
    DOI 10.1191/0961203304lu1023oa
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Biomarkers in systemic lupus erythematosus. I. General overview of biomarkers and their applicability.

    Illei, Gabor G / Tackey, Edward / Lapteva, Larissa / Lipsky, Peter E

    Arthritis and rheumatism

    2004  Volume 50, Issue 6, Page(s) 1709–1720

    MeSH term(s) Biomarkers ; Genetic Markers ; Humans ; Lupus Erythematosus, Systemic/diagnosis ; Lupus Erythematosus, Systemic/epidemiology ; Lupus Erythematosus, Systemic/genetics ; Risk Factors
    Chemical Substances Biomarkers ; Genetic Markers
    Language English
    Publishing date 2004-06
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 127294-9
    ISSN 1529-0131 ; 0004-3591 ; 2326-5191
    ISSN (online) 1529-0131
    ISSN 0004-3591 ; 2326-5191
    DOI 10.1002/art.20344
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Biomarkers in systemic lupus erythematosus: II. Markers of disease activity.

    Illei, Gabor G / Tackey, Edward / Lapteva, Larissa / Lipsky, Peter E

    Arthritis and rheumatism

    2004  Volume 50, Issue 7, Page(s) 2048–2065

    MeSH term(s) Antigen-Antibody Complex/metabolism ; B-Lymphocytes/immunology ; Biomarkers/analysis ; Biomarkers/urine ; Complement Activation ; Cytokines/metabolism ; Humans ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/metabolism ; Lupus Erythematosus, Systemic/physiopathology ; T-Lymphocytes/immunology
    Chemical Substances Antigen-Antibody Complex ; Biomarkers ; Cytokines
    Language English
    Publishing date 2004-07
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 127294-9
    ISSN 1529-0131 ; 0004-3591 ; 2326-5191
    ISSN (online) 1529-0131
    ISSN 0004-3591 ; 2326-5191
    DOI 10.1002/art.20345
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Bystander T cells participate in specific response to cockroach antigen (CR) in vitro.

    Walters, C S / Tackey, R N / Reece, E / Paluvoi, S

    Immunological investigations

    2003  Volume 32, Issue 1-2, Page(s) 105–118

    Abstract: Allergic reactions due to whole body, body parts and fecal products of cockroach (CR) are characterized by inflammatory reaction that may lead to symptoms of rhinitis or asthma in atopic individuals. Although the majority of T cells at the site of CR ... ...

    Abstract Allergic reactions due to whole body, body parts and fecal products of cockroach (CR) are characterized by inflammatory reaction that may lead to symptoms of rhinitis or asthma in atopic individuals. Although the majority of T cells at the site of CR hypersensitivity are not antigen specific, the cellular subset and cytokine receptors that participate and control the outcome of the reaction have not been fully studied. In this study, we have used fluorescent activated cell sorter (FACS) analysis to characterize the activation marker and cytokine profile of antigen specific and bystander T cells after in vitro stimulation of peripheral blood lymphocytes with whole body extract of CR antigen. There was significant enhancement of CD69 on blast and bystander T cells in all atopic subjects compared to non-atopics. Both antigen specific and bystander T cells showed increased expression of HLA-DR, CD25 and CD71 in 9 of 11 atopic patients compared to control. There was also an increase in CD45RA+ and a decrease in CD45RO+ cells following antigen stimulation. These results correlated with the increase in the early apoptotic cells observed in patients as measured by Annexin V stain. Our data revealed that there was no difference in the expression of CD95 in both stimulated and bystander T cells. However, there was enhancement of FasL by CR antigen, suggesting that the increased apoptosis that was observed was probably due to the Fas/FasL interaction. Positive intracellular IL2, IL-4 and IFN-gamma in T cells were observed in only the antigen specific blast cells in 83% of patients studied. These results suggest interplay of memory T cell response, apoptosis, and activated bystander T cells activities in maintaining cellular homeostasis during allergic reaction in cockroach sensitive atopic subjects.
    MeSH term(s) Adolescent ; Adult ; Allergens/immunology ; Animals ; Antigens, CD/immunology ; Antigens, Differentiation, B-Lymphocyte/immunology ; Antigens, Differentiation, T-Lymphocyte/immunology ; Apoptosis/immunology ; Child ; Cockroaches/immunology ; Cytokines/biosynthesis ; Cytokines/immunology ; Fas Ligand Protein ; Female ; Flow Cytometry ; Humans ; Hypersensitivity, Immediate/immunology ; Hypersensitivity, Immediate/pathology ; Lectins, C-Type ; Lymphocyte Activation/immunology ; Male ; Membrane Glycoproteins/immunology ; Middle Aged ; Receptors, Transferrin ; T-Lymphocytes/immunology ; T-Lymphocytes/pathology ; fas Receptor/immunology
    Chemical Substances Allergens ; Antigens, CD ; Antigens, Differentiation, B-Lymphocyte ; Antigens, Differentiation, T-Lymphocyte ; CD69 antigen ; CD71 antigen ; Cytokines ; FASLG protein, human ; Fas Ligand Protein ; Lectins, C-Type ; Membrane Glycoproteins ; Receptors, Transferrin ; fas Receptor
    Language English
    Publishing date 2003-04-08
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 632565-8
    ISSN 1532-4311 ; 0882-0139
    ISSN (online) 1532-4311
    ISSN 0882-0139
    DOI 10.1081/imm-120019212
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Tocilizumab in systemic lupus erythematosus: data on safety, preliminary efficacy, and impact on circulating plasma cells from an open-label phase I dosage-escalation study.

    Illei, Gabor G / Shirota, Yuko / Yarboro, Cheryl H / Daruwalla, Jimmy / Tackey, Edward / Takada, Kazuki / Fleisher, Thomas / Balow, James E / Lipsky, Peter E

    Arthritis and rheumatism

    2010  Volume 62, Issue 2, Page(s) 542–552

    Abstract: Objective: To assess the safety of interleukin-6 receptor inhibition and to collect preliminary data on the clinical and immunologic efficacy of tocilizumab in patients with systemic lupus erythematosus (SLE).: Methods: In an open-label phase I ... ...

    Abstract Objective: To assess the safety of interleukin-6 receptor inhibition and to collect preliminary data on the clinical and immunologic efficacy of tocilizumab in patients with systemic lupus erythematosus (SLE).
    Methods: In an open-label phase I dosage-escalation study, 16 patients with mild-to-moderate disease activity were assigned to receive 1 of 3 doses of tocilizumab given intravenously every other week for 12 weeks (total of 7 infusions): 2 mg/kg in 4 patients, 4 mg/kg in 6 patients, or 8 mg/kg in 6 patients. Patients were then monitored for an additional 8 weeks.
    Results: The infusions were well tolerated. Tocilizumab treatment led to dosage-related decreases in the absolute neutrophil count, with a median decrease of 38% in the 4 mg/kg dosage group and 56% in the 8 mg/kg dosage group. Neutrophil counts returned to normal after cessation of treatment. One patient was withdrawn from the study because of neutropenia. Infections occurred in 11 patients; none was associated with neutropenia. Disease activity showed significant improvement, with a decrease of > or =4 points in the modified Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index score in 8 of the 15 evaluable patients. Arthritis improved in all 7 patients who had arthritis at baseline and resolved in 4 of them. Levels of anti-double-stranded DNA antibodies decreased by a median of 47% in patients in the 4 mg/kg and 8 mg/kg dosage groups, with a 7.8% decrease in their IgG levels. These changes, together with a significant decrease in the frequency of circulating plasma cells, suggest a specific effect of tocilizumab on autoantibody-producing cells.
    Conclusion: Although neutropenia may limit the maximum dosage of tocilizumab in patients with SLE, the observed clinical and serologic responses are promising and warrant further studies to establish the optimal dosing regimen and efficacy.
    MeSH term(s) Adult ; Antibodies, Antinuclear/blood ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal, Humanized ; Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/adverse effects ; Biomarkers/blood ; DNA/immunology ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Glucocorticoids/administration & dosage ; Humans ; Infusions, Intravenous ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/immunology ; Male ; Middle Aged ; Plasma Cells/drug effects ; Plasma Cells/immunology ; Prednisone/administration & dosage ; Receptors, Interleukin-6/antagonists & inhibitors ; Treatment Outcome ; Young Adult
    Chemical Substances Antibodies, Antinuclear ; Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antirheumatic Agents ; Biomarkers ; Glucocorticoids ; Receptors, Interleukin-6 ; DNA (9007-49-2) ; tocilizumab (I031V2H011) ; Prednisone (VB0R961HZT)
    Language English
    Publishing date 2010-01-29
    Publishing country United States
    Document type Clinical Trial, Phase I ; Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 127294-9
    ISSN 1529-0131 ; 0004-3591 ; 2326-5191
    ISSN (online) 1529-0131
    ISSN 0004-3591 ; 2326-5191
    DOI 10.1002/art.27221
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Helicobacter pylori inhibits gastric cell cycle progression.

    Ahmed, A / Smoot, D / Littleton, G / Tackey, R / Walters, C S / Kashanchi, F / Allen, C R / Ashktorab, H

    Microbes and infection

    2000  Volume 2, Issue 10, Page(s) 1159–1169

    Abstract: ... determined by flow cytometry using propidium iodide (PI), and by analysis of cyclin E, p21, and p53 protein ... The expression of cyclin E was downregulated in AGS cells following exposure of AGS cells to H. pylori for 24 h ... pylori and its involvement in changing the regulatory proteins, p53, p21, and cyclin E in the cell cycle. ...

    Abstract Helicobacter pylori infection of the gastric mucosa is associated with changes in gastric epithelial cell proliferation. In vitro studies have shown that exposure to H. pylori inhibits proliferation of gastric cells. This study sought to investigate the cell cycle progression of gastric epithelial cell lines in the presence and absence of H. pylori. Unsynchronized and synchronized gastric epithelial cell lines AGS and KatoIII were exposed to H. pylori over a 24-h period. Cell cycle progression was determined by flow cytometry using propidium iodide (PI), and by analysis of cyclin E, p21, and p53 protein expression using Western blots. In the absence of H. pylori 40, 45, and 15% of unsynchronized AGS cells were in G(0)-G(1), S, and G(2)-M phases, respectively, by flow cytometry analysis. When AGS cells were cultured in the presence of H. pylori, the S phase decreased 10% and the G(0)-G(1) phase increased 17% after 24 h compared with the controls. KatoIII cells, which have a deleted p53 gene, showed little or no response to H. pylori. When G1/S synchronized AGS cells were incubated with media containing H. pylori, the G(1) phase increased significantly (25%, P < 0.05) compared with controls after 24 h. In contrast, the control cells were able to pass through S phase. The inhibitory effects of H. pylori on the cell cycle of AGS cells were associated with a significant increase in p53 and p21 expression after 24 h. The expression of cyclin E was downregulated in AGS cells following exposure of AGS cells to H. pylori for 24 h. This study shows that H. pylori-induced growth inhibition in vitro is predominantly at the G(0)-G(1) checkpoint. Our results suggest that p53 may be important in H. pylori-induced cell cycle arrest. These results support a role for cyclin-dependent kinase inhibitors in the G(1) cell cycle arrest exerted by H. pylori and its involvement in changing the regulatory proteins, p53, p21, and cyclin E in the cell cycle.
    MeSH term(s) Antigens, Bacterial ; Bacterial Proteins/metabolism ; Cell Cycle ; Cell Cycle Proteins/metabolism ; Cells, Cultured ; Coloring Agents ; Cyclin E/metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins/metabolism ; Epithelial Cells/microbiology ; Epithelial Cells/pathology ; Flow Cytometry ; Gastric Mucosa/microbiology ; Gastric Mucosa/pathology ; Helicobacter pylori/metabolism ; Immunoblotting ; Propidium ; Tumor Suppressor Protein p53/metabolism
    Chemical Substances Antigens, Bacterial ; Bacterial Proteins ; Cell Cycle Proteins ; Coloring Agents ; Cyclin E ; Cyclin-Dependent Kinase Inhibitor p21 ; Cyclins ; Tumor Suppressor Protein p53 ; cagA protein, Helicobacter pylori ; Propidium (36015-30-2)
    Language English
    Publishing date 2000-08
    Publishing country France
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1465093-9
    ISSN 1769-714X ; 1286-4579
    ISSN (online) 1769-714X
    ISSN 1286-4579
    DOI 10.1016/s1286-4579(00)01270-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Comparison of human eosinophil and neutrophil adhesion to endothelial cells under nonstatic conditions. Role of L-selectin.

    Knol, E F / Tackey, F / Tedder, T F / Klunk, D A / Bickel, C A / Sterbinsky, S A / Bochner, B S

    Journal of immunology (Baltimore, Md. : 1950)

    1994  Volume 153, Issue 5, Page(s) 2161–2167

    Abstract: ... neutrophils (e.g., LAM1-3: 43 +/- 14% vs 63 +/- 3% inhibition; LAM1-6: 73 +/- 5% vs 36 +/- 6% inhibition ...

    Abstract To simulate adhesion that occurs under conditions of flow, we investigated the attachment of eosinophils to endothelium under rotational conditions. Tissue-culture plates containing monolayers of HUVEC were placed on a horizontal rotator (80 revolutions per minute (rpm)), and equal numbers of purified human eosinophils or neutrophils were added to separate wells at 4 degrees C. Binding of eosinophils and neutrophils to unstimulated endothelial cells was 15 +/- 3 and 31 +/- 11 cells/four high power fields (HPF), respectively. After preincubation of HUVEC with IL-1 beta (1 ng/ml, 4 h, 37 degrees C), adhesion increased to 56 +/- 4 and 290 +/- 26 cells/four HPF, respectively (p < 0.0002 for both, n = 8-14). Eosinophils with reduced levels of L-selectin (blood eosinophils activated in vitro or eosinophils obtained from bronchoalveolar lavage (BAL) performed after segmental lung allergen challenge of allergic subjects) demonstrated reduced binding under rotating conditions. Several L-selectin Abs inhibited adhesion of eosinophils and neutrophils (e.g., LAM1-3: 43 +/- 14% vs 63 +/- 3% inhibition; LAM1-6: 73 +/- 5% vs 36 +/- 6% inhibition, respectively, n > or = 6). Interestingly, one additional L-selectin Ab, LAM1-11, inhibited eosinophil but not neutrophil adhesion (51 +/- 2% vs 1 +/- 7% inhibition, respectively, n > or = 5). We conclude that eosinophils, like neutrophils, use L-selectin to bind to activated endothelial cells under conditions of flow, although mAb LAM1-11 can selectively inhibit eosinophil attachment to stimulated endothelial cells in vitro, suggesting different functional epitopes on L-selectin among eosinophils and neutrophils.
    MeSH term(s) Cell Adhesion ; Cell Adhesion Molecules/physiology ; Endothelium, Vascular/cytology ; Eosinophils/cytology ; Humans ; In Vitro Techniques ; L-Selectin ; Macrophage-1 Antigen/metabolism ; Neutrophils/cytology
    Chemical Substances Cell Adhesion Molecules ; Macrophage-1 Antigen ; L-Selectin (126880-86-2)
    Language English
    Publishing date 1994-09-01
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    Database MEDical Literature Analysis and Retrieval System OnLINE

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