25 results on '"Berney SM"'
Search Results
2. Safety profile and clinical activity of sifalimumab, a fully human anti-interferon [alpha] monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study.
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Merrill JT, Wallace DJ, Petri M, Kirou KA, Yao Y, White WI, Robbie G, Levin R, Berney SM, Chindalore V, Olsen N, Richman L, Le C, Jallal B, White B, and Lupus Interferon Skin Activity (LISA) Study Investigators
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- 2011
- Full Text
- View/download PDF
3. Risk of development of lung cancer is increase in patients with rheumatoid arthritis: a large case control study in US veterans.
- Author
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Khurana R, Wolf R, Berney S, Caldito G, Hayat S, and Berney SM
- Published
- 2008
4. Case studies. A swollen painful knee in an elderly man with recently diagnosed acute myelogenous leukemia.
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Solanki SK, Latif S, Veillon DM, Nordberg ML, Saccaro SJ, Cotelingam JD, and Berney SM
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- 2003
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5. Spontaneous ulcerations of the breast.
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Matlock SM, Rush JL, Afzal W, Fulton EH, Berney SM, and Wong HK
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- Angiomatosis drug therapy, Breast Diseases drug therapy, Female, Humans, Middle Aged, Obesity complications, Pentoxifylline therapeutic use, Phosphodiesterase Inhibitors therapeutic use, Skin Diseases, Vascular drug therapy, Angiomatosis pathology, Breast pathology, Breast Diseases pathology, Skin Diseases, Vascular pathology
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- 2020
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6. Safety profile and clinical activity of sifalimumab, a fully human anti-interferon α monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study.
- Author
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Merrill JT, Wallace DJ, Petri M, Kirou KA, Yao Y, White WI, Robbie G, Levin R, Berney SM, Chindalore V, Olsen N, Richman L, Le C, Jallal B, and White B
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- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal blood, Antibodies, Monoclonal therapeutic use, Antibodies, Monoclonal, Humanized, Dose-Response Relationship, Drug, Double-Blind Method, Female, Gene Expression Regulation drug effects, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents blood, Immunosuppressive Agents therapeutic use, Injections, Intravenous, Interferon Type I biosynthesis, Interferon Type I genetics, Interferon-alpha immunology, Lupus Erythematosus, Systemic blood, Lupus Erythematosus, Systemic immunology, Male, Middle Aged, RNA, Messenger genetics, Severity of Illness Index, Treatment Outcome, Young Adult, Antibodies, Monoclonal adverse effects, Immunosuppressive Agents adverse effects, Interferon-alpha antagonists & inhibitors, Lupus Erythematosus, Systemic drug therapy
- Abstract
Background: Type I interferons (IFNs) appear to play a central role in disease pathogenesis in systemic lupus erythematosus (SLE), making them potential therapeutic targets., Methods: Safety profile, pharmacokinetics, immunogenicity, pharmacodynamics and clinical activity of sifalimumab, an anti-IFNα monoclonal antibody, were assessed in a phase I, multicentre, randomised, double-blind, dose-escalation study with an open-label extension in adults with moderately active SLE., Subjects: received one intravenous dose of sifalimumab (n=33 blinded phase, 0.3, 1, 3, 10 or 30 mg/kg; n=17 open-label, 1, 3, 10 or 30 mg/kg) or placebo (n=17). Each phase lasted 84 days., Results: Adverse events (AEs) were similar between groups; about 97% of AEs were grade 1 or 2. All grade 3 and 4 AEs and all serious AEs (2 placebo, 1 sifalimumab) were deemed unrelated to the study drug. No increase in viral infections or reactivation was observed. Sifalimumab caused dose-dependent inhibition of type I IFN-induced mRNAs (type I IFN signature) in whole blood and corresponding changes in related proteins in affected skin. Exploratory analyses showed consistent trends toward improvement in disease activity in sifalimumab-treated versus placebo-treated subjects. A lower proportion of sifalimumab-treated subjects required new or increased immunosuppressive treatments (12% vs 41%; p=0.03) and had fewer Systemic Lupus Erythematosus Disease Activity Index flares (3% vs 29%; p=0.014)., Conclusions: Sifalimumab had a safety profile that supports further clinical development. This trial demonstrated that overexpression of type I IFN signature in SLE is at least partly driven by IFNα, and exploratory analyses suggest that IFNα inhibition may be associated with clinical benefit in SLE. Trial registration number NCT00299819.
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- 2011
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7. Pulmonary hypertension in a patient with adult-onset Stills disease.
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Mubashir E, Ahmed MM, Hayat S, Heldmann M, and Berney SM
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- Adult, Fatal Outcome, Female, Humans, Hypertension, Pulmonary etiology, Still's Disease, Adult-Onset complications
- Abstract
Pulmonary manifestations of adult-onset Still's disease (AOSD) include aseptic pneumonitis, pleural effusions, rarely acute respiratory distress syndrome, and restrictive lung disease. Pulmonary arterial hypertension (PAH) occurs with several rheumatologic diseases, however, has only been reported once in AOSD. We describe a 29-year-old woman with a 9-year history of AOSD, who developed PAH without any other obvious cause. Therefore, we conclude that this is likely a result of pulmonary vascular changes related to AOSD.
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- 2007
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8. Treatment of refractory temporal arteritis with adalimumab.
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Ahmed MM, Mubashir E, Hayat S, Fowler M, and Berney SM
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- Adalimumab, Adrenal Cortex Hormones adverse effects, Adrenal Cortex Hormones pharmacology, Aged, Antibodies, Monoclonal, Humanized, Drug Resistance, Female, Humans, Antibodies, Monoclonal therapeutic use, Giant Cell Arteritis drug therapy, Immunologic Factors therapeutic use
- Abstract
High-dose corticosteroids (CS) are the mainstay of treatment for temporal (giant cell) arteritis (TA). A usually required long-term treatment with CS, ranging from 1 to 5 years or more, frequently leads to serious side effects in about 60% of patients. There is no conclusive evidence about the role of immunosuppressive agents like methotrexate and azathioprine in the treatment of TA. There are few reports of treatment of refractory or steroid-dependent TA with tumor necrosis factor alpha (TNF-alpha) inhibitors including infliximab and etanercept. TA is characterized by infiltration of the vessel wall by macrophages, giant cells, and T lymphocytes, with production of several cytokines responsible for the acute phase response. TNF-alpha has been demonstrated in up to 60% of the cells in all areas of inflamed arteries by immunohistochemical techniques; hence, it could play a pivotal role in the pathogenesis of TA. We report the first case of resistant TA, which was treated successfully with adalimumab, a fully human recombinant IgG1, anti-TNF-alpha monoclonal antibody. The efficacy of TNF-alpha inhibitors in resistant TA should be studied in larger, controlled studies.
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- 2007
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9. Impact of treatment with infliximab on anticyclic citrullinated peptide antibody and rheumatoid factor in patients with rheumatoid arthritis.
- Author
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Ahmed MM, Mubashir E, Wolf RE, Hayat S, Hall V, Shi R, and Berney SM
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- Adult, Aged, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid immunology, Female, Humans, Immunoglobulin A immunology, Immunoglobulin M immunology, Infliximab, Male, Middle Aged, Peptides, Cyclic immunology, Antibodies, Monoclonal therapeutic use, Antirheumatic Agents therapeutic use, Arthritis, Rheumatoid blood, Arthritis, Rheumatoid drug therapy, Peptides, Cyclic blood, Rheumatoid Factor blood
- Abstract
Objective: To investigate the impact of infliximab treatment on anticyclic citrullinated peptide (anti-CCP) antibody and rheumatoid factor (RF) levels in patients with rheumatoid arthritis (RA)., Methods: Sera from 33 RA patients receiving infliximab and disease modifying antirheumatic drugs were tested for anti-CCP antibody, IgA-, IgG- and IgM-RF using a commercially available semiquantitative ELISA at baseline, 30 and 54 weeks after treatment., Results: The serum levels of anti-CCP antibody and IgA-RF decreased significantly after 30 weeks (P = 0.002 and 0.024); however, the decrease was not significant at week 54 (P = 0.147 and 0.207). The decrease in IgG-RF level was not significant at 30 and 54 weeks (P = 0.059 and 0.097). IgM-RF levels, however decreased significantly at 30 and 54 weeks (P = 0.002 and 0.004). A strong correlation between anti-CCP and IgA-, IgG- and IgM-RF was observed at baseline (r(s) = 0.48, 0.43, 0.65, P = < 0.05) and after infliximab treatment at 30 (r(s) = 0.45, 0.46, 0.62, P = < 0.05) and 54 (r(s) = 0.49, 0.45, 0.60, P = < 0.05) weeks., Conclusion: Treatment with infliximab results in decreased anti-CCP antibody and IgA-RF early in the course of therapy that is not sustained. IgM-RF declines and remains decreased for at least 54 weeks. Investigations in larger cohorts of RA patients (especially early RA) with longer follow-up are needed to assess the impact of specific therapeutic interventions on anti-CCP antibody and RF levels and the relationship of their levels to disease activity.
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- 2006
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10. Wegener granulomatosis: a case report and update.
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Mubashir E, Ahmed MM, Hayat S, Latif S, Heldmann M, and Berney SM
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- Cyclophosphamide therapeutic use, Drug Administration Schedule, Female, Granulomatosis with Polyangiitis complications, Humans, Kidney Failure, Chronic etiology, Kidney Failure, Chronic therapy, Male, Middle Aged, Plasmapheresis, Prednisone therapeutic use, Pregnancy, Pregnancy Complications, Recurrence, Tumor Necrosis Factor-alpha antagonists & inhibitors, Antibodies, Antineutrophil Cytoplasmic blood, Glucocorticoids therapeutic use, Granulomatosis with Polyangiitis diagnosis, Granulomatosis with Polyangiitis therapy, Immunosuppressive Agents therapeutic use
- Abstract
Wegener granulomatosis (WG) is a systemic disease of unknown etiology characterized by necrotizing granulomatous inflammation, tissue necrosis, and variable degrees of vasculitis in small and medium-sized blood vessels. The classic clinical pattern is a triad involving the upper airways, lungs and kidneys. Ninety percent of patients present with symptoms involving the upper and/or lower airways, and 80% will eventually develop renal disease. WG should be suspected in any patient with progressive or unresponsive sinus disease, glomerulonephritis, pulmonary hemorrhage, mononeuritis multiplex or unexplained multisystem disease. Before the routine use of glucocorticoids and cyclophosphamide, the one year mortality was 82%. However in 1973, Fauci and Wolf discovered that daily prednisone and cyclophosphamide induced complete remission in 75% of patients. The continued use of prednisone and cyclophosphamide for 1 year past remission leads to marked improvement in more than 90% of patients; however, is also associated with serious toxicities. Depending on the disease severity, current treatments employ induction with short-term cyclophosphamide followed by less toxic agents such as methotrexate to maintain disease remission. Although it is a rare disorder, it is pertinent to internists because it is a multisystem disease that presents in a variety of ways. We describe a 63-year-old white male with WG who presented with progressively worsening headaches, bilateral eye redness, epistaxis, hemoptysis and an unintentional 20 pound weight loss, and review the current treatment recommendations.
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- 2006
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11. Prevalence of active hepatitis C virus infection in patients with systemic lupus erythematosus.
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Ahmed MM, Berney SM, Wolf RE, Hearth-Holmes M, Hayat S, Mubashir E, Vanderheyde H, Chang WL, and King JW
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- Adult, Autoantibodies blood, Blood Donors, Female, Hepacivirus genetics, Hepacivirus immunology, Hepatitis C complications, Hepatitis C diagnosis, Hepatitis C Antibodies blood, Humans, Louisiana epidemiology, Lupus Erythematosus, Systemic immunology, Male, Prevalence, RNA, Viral blood, Viral Load, Hepatitis C epidemiology, Lupus Erythematosus, Systemic complications
- Abstract
Objective: Hepatitis C virus (HCV) infection is associated with various autoimmune disorders and can mimic systemic lupus erythematosus (SLE) clinically and serologically. There are few reports of prevalence of HCV infection in patients with SLE. The aim of this study was to determine the prevalence of HCV viremia by polymerase chain reaction (PCR) in patients with SLE., Methods: We tested sera from 40 consecutive patients with SLE collected from 1993 to 2000. All of the patients had HCV viral load measured by PCR. The results were compared with the prevalence of HCV viremia in a control group of blood donors in our geographic area as well as in United States general population., Results: HCV was detected in 4 of 40 patients (10%). The prevalence of HCV in our area blood donors is 130 cases per 100,000 persons (0.13%; P<0.0001). The prevalence of HCV infection in the United States general population, screened by PCR, is 1330 cases per 100,000 people (1.33%; P=0.002). The prevalence of HCV infection was significantly higher in our SLE patients than in our area blood donors. The frequency of HCV infection was also higher than that of the United States general population., Conclusion: Our observations support those of other investigators who have reported an increased prevalence of HCV infection in SLE patients. Further detailed investigation of this association may help in understanding the pathogenesis of SLE. HCV infection should be tested when the diagnosis of SLE is considered.
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- 2006
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12. Clinical aspects of rheumatoid arthritis.
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Khurana R and Berney SM
- Abstract
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown etiology affecting both articular tissues and extraarticular organs. The disease is often progressive and results in pain, stiffness, and swelling of joints culminating in significant morbidity and increased mortality. This chapter discusses the epidemiology, possible etiology, clinical manifestations, diagnostic approach and treatment options of RA.
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- 2005
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13. Cutaneous vasculitis.
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Hayat S and Berney SM
- Subjects
- Diagnosis, Differential, Humans, Skin blood supply, Vasculitis diagnosis, Vasculitis therapy
- Abstract
Vasculitis is defined as inflammation of blood vessels and can affect multiple organs. Several classification systems exist to categorize vasculitis such as vessel size, presence of anti-neutrophil cytoplasmic antibody, pathogenesis of the inflammation, and type of inflammatory cell infiltrate. Cutaneous vasculitis occurs as a manifestation of many diseases including rheumatologic diseases, hypersensitivity syndromes, infections, and malignancies. The diagnosis of the cutaneous vasculitis and the underlying cause requires a complete history and physical exam and usually a biopsy or angiogram. The treatment depends on the etiology of the inflammation and includes immunosuppression, withdrawal of the offending agent, antibacterial/antiviral agents, and chemotherapies. A clear understanding and approach to this condition will improve the physician's ability to provide optimal patient care.
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- 2005
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14. Pathology case of the month. 39-year-old woman with abdominal pain and weight loss. Takayasu's arteritis (TA).
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Desai KA, Cotter NM, Doucet L, Veillon DM, Cotelingam JD, Herrera GA, Heldmann M, and Berney SM
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- Abdominal Pain, Adult, Angiography, Aorta, Abdominal pathology, Female, Humans, Takayasu Arteritis diagnostic imaging, Takayasu Arteritis drug therapy, Weight Loss, Takayasu Arteritis pathology
- Abstract
A 39-year-old white woman presented with a history of aortoiliac occlusive disease diagnosed in 1992 attributed to oral contraceptive use. Shortly thereafter, aortoiliac replacement was performed. Mild hyperlipidemia was diagnosed in 2001. At the current clinic visit, she presented to her primary care physician with a 3-month history of postprandial midepigastric abdominal pain relieved by vomiting and a 30-pound weight loss. Her evaluation included an esophagogastroduodenoscopy, a colonoscopy, and an abdominal ultrasound, all of which were within normal limits. Because of her medical history, the patient underwent an arteriogram, which revealed brachiocephalic stenosis (Figure 1), occlusion of the left subclavian artery (Figures 2a and 2b), and narrowing of the superior and inferior mesenteric arteries (not shown). Since she had discontinued her oral contraceptives in 1992 and her hyperlipidemia was mild, the rheumatology service was consulted to evaluate this patient. On physical examination, she had decreased left brachial and radial pulses and a right carotid bruit. Laboratory evaluation revealed a normal complete blood count, comprehensive metabolic panel, erythrocyte sedimentation rate, and C - reactive protein. Subsequent testing included a prothrombin time, activated partial thromboplastin time, protein S, protein C, reptilase time, antithrombin III, anticardiolipin antibody, antiphospholipid antibody, lupus anticoagulant, homocysteine, RPR, and a lipid profile. All test results were within normal limits. Due to the severity of her abdominal pain, the patient underwent superior mesenteric artery (SMA) bypass surgery. Sections from the aorta resected in 1992 are shown in Figures 3 and 4.
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- 2004
15. Inhibition of platelet adherence to brain microvasculature protects against severe Plasmodium berghei malaria.
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Sun G, Chang WL, Li J, Berney SM, Kimpel D, and van der Heyde HC
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- Animals, Antibodies, Monoclonal therapeutic use, Cell Communication, Endothelial Cells physiology, Female, Intercellular Adhesion Molecule-1 physiology, Mice, Mice, Inbred C57BL, Microcirculation, P-Selectin physiology, Platelet Membrane Glycoprotein IIb physiology, Brain blood supply, Malaria, Cerebral prevention & control, Plasmodium berghei, Platelet Adhesiveness
- Abstract
Some patients with Plasmodium falciparum infections develop cerebral malaria, acute respiratory distress, and shock and ultimately die even though drug therapy has eliminated the parasite from the blood, suggesting that a systemic inflammatory response contributes to malarial pathogenesis. Plasmodium berghei-infected mice are a well-recognized model of severe malaria (experimental severe malaria [ESM]), and infected mice exhibit a systemic inflammatory response. Because platelets are proposed to contribute to ESM and other systemic inflammatory responses, we determined whether platelet adherence contributes to experimental malarial pathogenesis. Indeed, a significant (P < 0.005) increase in the number of rolling and adherent platelets was observed by intravital microscopy in brain venules of P. berghei-infected mice compared with the number in uninfected controls. P-selectin- or ICAM-1-deficient mice exhibit increased survival after P. berghei infection. We observed a significant (P < 0.0001) reduction in the morbidity of mice injected with anti-CD41 (alpha(IIb) or gpIIb) monoclonal antibody on day 1 of P. berghei infection compared with the morbidity of infected controls injected with rat immunoglobulin G. Additionally, platelet rolling and adhesion in brain venules were reduced in P. berghei mice lacking either P-selectin or ICAM-1 or when the platelets were coated with anti-CD41 monoclonal antibody. Unlike other inflammatory conditions, we did not detect platelet-leukocyte interactions during P. berghei malaria. Because (i). leukocyte adhesion is not markedly altered in the absence of P-selectin or ICAM-1 and (ii). CD41 is not an adhesion molecule for parasitized erythrocytes, these findings support the hypothesis that inhibition of platelet adhesion to the brain microvasculature protects against development of malarial pathogenesis.
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- 2003
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16. Intercellular adhesion molecule 1 is important for the development of severe experimental malaria but is not required for leukocyte adhesion in the brain.
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Li J, Chang WL, Sun G, Chen HL, Specian RD, Berney SM, Kimpel D, Granger DN, and van der Heyde HC
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- Animals, Capillary Permeability, Cell Adhesion, Endothelium, Vascular pathology, Endothelium, Vascular physiopathology, Female, Intercellular Adhesion Molecule-1 genetics, Leukocytes physiology, Malaria, Cerebral pathology, Malaria, Cerebral physiopathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Pia Mater blood supply, Plasmodium berghei, Intercellular Adhesion Molecule-1 physiology, Malaria, Cerebral etiology
- Abstract
Plasmodium berghei-infected mice, a well-recognized model of experimental cerebral malaria (ECM), exhibit a systemic inflammatory response. Most investigators hypothesize that leukocytes bind to endothelial cells via intercellular adhesion molecule 1 (ICAM-1), which causes endothelial damage, increased microvascular permeability, and, ultimately, death. ICAM-1-deficient mice on an ECM-susceptible C57BL/6 background were significantly (p = .04) protected from P. berghei mortality compared with ICAM-1 intact controls. ICAM-1 expression assessed by the dual radiolabeled monoclonal antibody technique was increased in the brain and lung in C57BL/6 mice on day 6 of P. berghei infection compared with uninfected controls (5.3-fold, p = .0003 for brain and 1.8-fold, p = .04 for lung). The increase in ICAM-1 expression coincided with significant (p < .05) increases in microvascular permeability in the brain and lung. In contrast to the hypothesized role for ICAM-1, in vivo analysis by intravital microscopy of leukocyte rolling and adhesion in brain microvasculature of mice revealed markedly increased levels of leukocyte rolling and adhesion in ICAM-1-deficient mice on day 6 of P. berghei infection compared with uninfected controls. In addition, ICAM-1 expression and microvascular permeability were increased in infected ECM-resistant BALB/c mice compared with uninfected BALB/c controls. These results collectively indicate that although ICAM-1 contributes to the mortality of experimental malaria, it is not sufficient for the development of severe experimental malaria. In addition, ICAM-1 expressed on the endothelium or on leukocytes is not required for leukocyte rolling or adhesion to the brain microvasculature of mice during P. berghei malaria. Leukocyte rolling and adhesion in the brain vasculature during P. berghei malaria use different ligands than observed during inflammation in other vascular beds.
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- 2003
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17. P-selectin contributes to severe experimental malaria but is not required for leukocyte adhesion to brain microvasculature.
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Chang WL, Li J, Sun G, Chen HL, Specian RD, Berney SM, Granger DN, and van der Heyde HC
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- Animals, Brain parasitology, Cell Adhesion, Disease Models, Animal, Endothelium, Vascular metabolism, Humans, Malaria, Cerebral parasitology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Microcirculation, Brain blood supply, Leukocytes physiology, Malaria, Cerebral physiopathology, P-Selectin metabolism, Plasmodium berghei pathogenicity
- Abstract
Plasmodium berghei-infected mice, a well-recognized model of experimental cerebral malaria (ECM), exhibit many of the hallmarks of a systemic inflammatory response, with organ damage in brain, lung, and kidneys. Identification of the molecules mediating pathogenesis of the inflammatory response, such as leukocyte adhesion, may lead to new therapies. Indeed, mice lacking the cell adhesion molecule P-selectin were significantly (P = 0.005) protected from death due to P. berghei malaria compared with C57BL/6 controls despite similar parasitemia (P = 0.6) being found in both groups of mice. P-selectin levels assessed by the quantitative dual radiolabeled monoclonal antibody technique increased significantly (P < 0.05) in several organs in C57BL/6 mice infected with P. berghei, supporting the concept of a systemic inflammatory response mediating malarial pathogenesis. Intravital microscopic analysis of the brain microvasculature demonstrated significant (P < 0.001) leukocyte rolling and adhesion in brain venules of P. berghei-infected mice compared with those found in uninfected controls. The maximum leukocyte adhesion occurred on day 6 of P. berghei infection, when the mice become moribund and exhibit marked vascular leakage into the brain, lung, and heart. However, P-selectin levels were significantly (P < 0.005) increased in brain, lung, and kidneys during P. berghei malaria in ECM-resistant BALB/c mice compared with those found in uninfected BALB/c controls, indicating that increased P-selectin alone is not sufficient to mediate malarial pathogenesis. Leukocyte adhesion to brain microvessels of P-selectin-deficient mice with P. berghei malaria was similar to that observed in control mice. Collectively, these results indicate that P-selectin is important for the development of malarial pathogenesis but is not required for leukocyte adhesion in brain.
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- 2003
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18. CD5 (OKT1) augments CD3-mediated intracellular signaling events in human T lymphocytes.
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Berney SM, Schaan T, Wolf RE, Kimpel DL, van der Heyde H, and Atkinson TP
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- Adolescent, Adult, Aged, Antibodies, Monoclonal pharmacology, Antigens, CD biosynthesis, Antigens, Differentiation, T-Lymphocyte biosynthesis, CD3 Complex immunology, CD5 Antigens immunology, Humans, Hydrolysis, Lectins, C-Type, Middle Aged, Phosphatidylinositols metabolism, T-Lymphocytes metabolism, CD3 Complex physiology, CD5 Antigens physiology, Signal Transduction drug effects, T-Lymphocytes immunology
- Abstract
CD5 is expressed on thymocytes, all mature T cells, and a subset of mature B cells, and probably contributes to T-cell-B-cell adhesion. We assessed whether CD5-crosslinking by mAb augments T-cell stimulation. Plate-bound anti-CD5 or anti-CD3 mAb alone had no effect on any of the assessed activation parameters of resting T cells. However, concomitant signaling through both CD5 and CD3 by plate-bound antibodies resulted in marked increases in T-cell surface CD69 expression and T-cell metabolism, as assessed by the T cell's ability to reduce 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium (MTS) to formazen. In addition, simultaneous cross-linking of CD5 and CD3 caused a significant (p < 0.001) increase in phosphatidylinositol hydrolysis in resting T cells compared to stimulation with anti-CD3 mAb alone or anti-CD3 mAb plus anti-CD5 isotype control antibody. These results indicate that CD5 augments signaling through CD3 and consequently functions as a costimulatory molecule for resting T cells.
- Published
- 2001
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19. CD2 (OKT11) augments CD3-mediated intracellular signaling events in human T lymphocytes.
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Berney SM, Schaan T, Wolf RE, van der Heyde H, and Atkinson TP
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- Animals, Antibodies, Monoclonal, Antigens, CD metabolism, Antigens, Differentiation, T-Lymphocyte metabolism, Humans, Lectins, C-Type, Lymphocyte Activation, Mice, Phosphatidylinositols metabolism, Signal Transduction, T-Lymphocytes metabolism, CD2 Antigens metabolism, CD3 Complex metabolism, T-Lymphocytes immunology
- Abstract
CD2 (LFA-2) is expressed on thymocytes, natural killer cells, and virtually all peripheral T cells. CD2 binds to its primary ligand CD58 (LFA-3) on antigen presenting cells (APC) and stabilizes the T cell-APC interaction; this stable interaction then optimizes Ag-specific T-cell activation. We assessed whether CD2-cross-linking by mAb augments the process of T-cell stimulation through the TCR/CD3 complex. Plate-bound anti-CD2 or anti-CD3 mAb alone had no measurable effect on any of the assessed activation parameters of resting T cells. However, concomitant signaling through both CD2 and CD3 by plate-bound antibodies resulted in marked increases in CD69 expression on the T-cell surface and T-cell-cellular metabolism, as assessed by the ability of the cell to reduce 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxylmethoxyphenyl)-2-( 4-sulphophenyl)- 2H-tetrazolium (MTS) to formazen. In addition, simultaneous cross-linking of CD2 and CD3 caused a significant (P < 0.001) increase in phosphatidylinositol hydrolysis in resting T cells compared to stimulation with anti-CD3 mAb alone and anti-CD3 mAb plus anti-CD2 isotype control antibody. These results indicate that CD2 augments signaling through CD3, and consequently functions as a costimulatory molecule for resting T cells in the initial activation step.
- Published
- 2000
20. Measurement of phosphatidylinositol (PI) hydrolysis in activated T lymphocytes.
- Author
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Berney SM and Atkinson TP
- Subjects
- Cell Separation methods, Humans, Hydrolysis, In Vitro Techniques, Inositol metabolism, Radioisotope Dilution Technique, T-Lymphocytes cytology, T-Lymphocytes immunology, Tritium, Lymphocyte Activation, Phosphatidylinositols metabolism, T-Lymphocytes physiology
- Published
- 2000
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21. ICAM-3 (CD50) cross-linking augments signaling in CD3-activated peripheral human T lymphocytes.
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Berney SM, Schaan T, Alexander JS, Peterman G, Hoffman PA, Wolf RE, van der Heyde H, and Atkinson TP
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- Cross-Linking Reagents pharmacology, Humans, Hydrolysis, Lymphocyte Activation immunology, Membrane Potentials, Phosphatidylinositols metabolism, Phosphorylation, Signal Transduction drug effects, T-Lymphocytes physiology, Type C Phospholipases metabolism, Antigens, CD, Antigens, Differentiation, CD3 Complex immunology, Cell Adhesion Molecules metabolism, Cross-Linking Reagents metabolism, T-Lymphocytes immunology
- Abstract
ICAM-3 is a pan-hematopoietic, constitutive adhesion molecule. ICAM-3 binds to LFA-1 on antigen-presenting cells (APC) stabilizing the T cell-APC interaction, facilitating signaling through the CD3/TCR complex. However, recent evidence using cultured and transformed T cells suggests ICAM-3 may also function in signaling. Because ICAM-3 is constitutively expressed on resting T cells, we postulated that signaling through ICAM-3 in resting T cells represents an important costimulatory mechanism in these cells. In purified resting human T cells, cross-linking both ICAM-3 and CD3 with plate-bound antibodies resulted in a marked increase in cell size (consistent with blastogenesis), synergistically increased surface expression of CD25 and CD69, and increased T cell metabolism. Similarly, concomitant ICAM-3 and CD3 stimulation significantly (P < 0.001) increased resting human T cell phosphatidylinositol hydrolysis and phospholipase C-gamma1 phosphorylation. These results indicate that ICAM-3 augments signaling through CD3, functioning as a costimulatory molecule for resting T cells in the initial activation step.
- Published
- 1999
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22. Activated T-lymphocytes express occludin, a component of tight junctions.
- Author
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Alexander JS, Dayton T, Davis C, Hill S, Jackson TH, Blaschuk O, Symonds M, Okayama N, Kevil CG, Laroux FS, Berney SM, and Kimpel D
- Subjects
- Animals, Occludin, Rats, T-Lymphocytes immunology, T-Lymphocytes ultrastructure, Tight Junctions metabolism, Lymphocyte Activation, Membrane Proteins biosynthesis, T-Lymphocytes metabolism
- Abstract
T-lymphocytes routinely traffic from the lymphoid and vascular compartments to the tissues during immune surveillance and inflammatory responses. This egress occurs without compromising endothelial barrier, which is maintained by tight junctions (zonula occludens). We report that T-lymphocytes up-regulate the expression of occludin, a major component of the tight junction in response to stimulation with phorbol ester (PMA) + calcium ionophore, CD3 antibody or T-cell receptor (TCR) antibody. Only activated T-lymphocytes express occludin; this adhesion molecule is nearly absent in resting T-lymphocytes. By immunofluorescence, occludin is seen in lymphocyte aggregates, but does not appear to mediate aggregation since only 50% of the cells in these clusters express occludin. Occludin is expressed between 8 and 24 h following stimulation, and persists for at least 48 h. These data indicate that activated T cells produce occludin which may regulate lymphocyte adhesion and trafficking.
- Published
- 1998
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23. Myosin-reactive autoantibodies in rheumatic carditis and normal fetus.
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Wu X, Liu B, Van der Merwe PL, Kalis NN, Berney SM, and Young DC
- Subjects
- Adult, Aged, Animals, Antigens, Bacterial immunology, Autoantibodies blood, B-Lymphocytes immunology, Cells, Cultured, Cross Reactions, Fetal Blood immunology, Humans, Myocarditis blood, Rats, Rheumatic Heart Disease blood, Spleen cytology, Spleen immunology, Streptococcus pyogenes immunology, Autoantibodies immunology, Fetus immunology, Myocarditis immunology, Myosins immunology, Rheumatic Heart Disease immunology
- Abstract
EBV-transformed B cells from a 20-week human fetal spleen and from blood of patients with poststreptococcal rheumatic carditis were studied. Most antibodies from nine fetal and six patient myosin-reactive B cell clones were multireactive (reacting with cardiac myosin, Streptococcus pyogenes, and rat cardiac myocytes) which supports a role for molecular mimicry in stimulation of these autoantibodies. Sequence analysis revealed that fetal and patient anti-myosin repertoires were composed of unrelated clones with diverse V gene usages. Fetal and patient antibodies had reduced VH CDR3 length on average and reduced light chain N region addition with a low rate of somatic mutation in the variable region genes, characteristics generally associated with fetal B cells but also with some adult B cells. Five of six myosin-reactive patient clones used VH3, whereas only two of nine fetal clones used VH3, suggesting skewing from the average 50-60% VH3 gene usage found in randomly selected adult and fetal antibodies.
- Published
- 1998
- Full Text
- View/download PDF
24. Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, -A1 haplotypes.
- Author
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Schroeder HW Jr, Zhu ZB, March RE, Campbell RD, Berney SM, Nedospasov SA, Turetskaya RL, Atkinson TP, Go RC, Cooper MD, and Volanakis JE
- Subjects
- Adult, Disease Susceptibility, Female, Genetic Markers, Haplotypes genetics, Humans, Infant, Male, Pedigree, Common Variable Immunodeficiency genetics, HLA-A1 Antigen genetics, HLA-B8 Antigen genetics, HLA-DR3 Antigen genetics, IgA Deficiency genetics
- Abstract
Background: A common genetic basis for IgA deficiency (IgAD) and common variable immunodeficiency (CVID) is suggested by their occurrence in members of the same family and the similarity of the underlying B cell differentiation defects. An association between IgAD/CVID and HLA alleles DR3, B8, and A1 has also been documented. In a search for the gene(s) in the major histocompatibility complex (MHC) that predispose to IgAD/CVID, we analyzed the extended MHC haplotypes present in a large family with 8 affected members., Materials and Methods: We examined the CVID proband, 72 immediate relatives, and 21 spouses, and determined their serum immunoglobulin concentrations. The MHC haplotype analysis of individual family members employed 21 allelic DNA and protein markers, including seven newly available microsatellite markers., Results: Forty-one (56%) of the 73 relatives by common descent were heterozygous and nine (12%) were homozygous for a fragment or the entire extended MHC haplotype designated haplotype 1 that included HLA- DR3, -C4A-0, -B8, and -A1. The remarkable prevalence of haplotype 1 was due in part to marital introduction into the family of 11 different copies of the haplotype, eight sharing 20 identical genotype markers between HLA-DR3 and HLA-B8, and three that contained fragments of haplotype 1., Conclusion: Crossover events within the MHC indicated a susceptibility locus for IgAD/CVID between the class III markers D821/D823 and HLA-B8, a region populated by 21 genes that include tumor necrosis factor alpha and lymphotoxins alpha and beta. Inheritance of at least this fragment of haplotype 1 appears to be necessary for the development of IgAD/CVID in this family.
- Published
- 1998
25. Phosphatidylinositol hydrolysis in freshly isolated human T lymphocytes.
- Author
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Berney SM and Atkinson TP
- Subjects
- Cell Separation, Cells, Cultured, Flow Cytometry, Humans, Lymphocyte Activation, Signal Transduction, CD28 Antigens physiology, CD3 Complex physiology, Phosphatidylinositols metabolism, Receptors, Immunologic physiology, T-Lymphocytes metabolism
- Abstract
Antigen receptor-mediated activation of T and B lymphocytes results in activation of phospholipase C-gamma isozymes with subsequent hydrolysis of membrane inositol phospholipids. As a method of screening autoimmune or immunodeficient patients for early receptor signaling defects, we have developed a rapid technique for studying phosphatidylinositol (PI) hydrolysis in cultured cells and fresh clinical specimens resulting from surface receptor crosslinking. Using staphylococcal alpha-toxin, we permeabilized freshly isolated, purified human T lymphocytes to facilitate incorporation of [3H]myoinositol into membrane phospholipids. Aggregation of surface antigen receptors (TCR-CD3 complex and CD28 on T cells) with specific antibodies produced extensive ATP and Mg(2+)-dependent hydrolysis of the membrane inositol phospholipids as measured by release of water soluble inositol phosphates. Anti-human CD3 antibody produced 18.5 +/- 1.6 net % PI hydrolysis and anti-human CD28 antibody produced 4.6 +/- 0.2 net % PI hydrolysis. Simultaneous anti CD3/CD28 crosslinking produced 30.8 +/- 1.2 net % PI hydrolysis, an increase over either stimulus alone (p = 0.0013 two tailed t test). Isotype matched control antibodies produced 11.6 +/- 0.4% PI hydrolysis. The tyrosine phosphatase inhibitor orthovanadate (Na3VO4) was used as a positive control because it induces maximal protein tyrosine kinase-dependent PI hydrolysis in permeabilized cells. Na3VO4 consistently induced hydrolysis of > 50% of the membrane inositol phospholipid pool. These data indicate that costimulation of T cells with antibodies to CD3 and CD28 is synergistic and reinforces the importance of CD28 as an accessory T cell stimulus. This easy technique allows quick evaluation of the integrity of the early signaling cascade in lymphocytes as a screen for autoimmune and immunodeficiency diseases.
- Published
- 1995
- Full Text
- View/download PDF
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