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1.
J Immunol ; 188(7): 3009-18, 2012 Apr 01.
Article in English | MEDLINE | ID: mdl-22351938

ABSTRACT

Calcium-modulating cyclophilin ligand (CAML) is a ubiquitously expressed protein that is important during thymopoiesis. However, whether it serves a function in mature lymphocytes is unknown. In this article, we show that CAML is essential for survival of peripheral follicular (Fo) B cells. Conditional deletion of CAML in CD19-Cre transgenic mice caused a significant reduction in Fo cell numbers and increased rates of homeostatic proliferation. CAML-deficient Fo cells showed increased cellular turnover and normal proliferative ability. Although CAML-deficient Fo cells responded to AgR stimulation and to B cell activating factor, they displayed decreased survival and increased apoptosis following stimulation with LPS and IL-4 in vitro. Failure to survive was not due to aberrant B cell development in the absence of CAML, because induced deletion of the gene in mature cells resulted in a similar phenotype. These data establish an essential and ongoing role for CAML in the long-term survival of mature B cells.


Subject(s)
Adaptor Proteins, Signal Transducing/physiology , B-Lymphocyte Subsets/immunology , Adaptor Proteins, Signal Transducing/deficiency , Adaptor Proteins, Signal Transducing/genetics , Adoptive Transfer , Animals , Apoptosis/drug effects , B-Cell Activating Factor/pharmacology , Cell Survival , Homeostasis , Interleukin-4/pharmacology , Lipopolysaccharides/pharmacology , Lymph Nodes/immunology , Lymph Nodes/ultrastructure , Mice , Mice, Inbred NOD , Mice, Knockout , Mice, SCID , Receptors, Antigen, B-Cell/immunology , Specific Pathogen-Free Organisms , Spleen/cytology , Spleen/immunology
2.
Cardiovasc Pathol ; 21(6): 470-5, 2012.
Article in English | MEDLINE | ID: mdl-22406174

ABSTRACT

BACKGROUND: IgG4-related aortitis is a newly recognized form of noninfectious aortitis that occurs as part of the spectrum of a systemic disease referred to as IgG4-related disease. IgG4-related aortitis is distinguished from giant cell aortitis and Takayasu aortitis in part by the presence of increased numbers of IgG4-expressing plasma cells. Chronic infectious aortitis can also display lymphoplasmacytic infiltrates, but the degree of IgG4 expression in these cases has not been specifically evaluated. METHODS: Two cases of chronic active infectious abdominal aortitis were prospectively identified. Both were due to gram-positive bacteria, and at least one of the cases was due to chronic active Staphylococcus aureus infection. The degree of IgG4 plasma cell infiltration was assessed by immunohistochemistry. RESULTS: Both cases of chronic infectious aortitis focally displayed high levels of IgG4-expressing plasma cells, greater than 50% of the IgG-expressing plasma cells, and greater than 50 IgG4-expressing plasma cells per high-power field. CONCLUSIONS: Focal dense IgG4 plasma cell infiltrates can be seen in association with chronic infectious aortitis due to gram-positive bacteria, including Staphylococcus aureus. This observation supports the proposal that chronic Staphylococcus aureus infection may stimulate a Th2-mediated elevation in IgG4. The pathologic diagnosis of IgG4-related aortitis should not be based solely on the presence of increased IgG4 plasma cell counts from immunohistochemistry, but requires consideration of the overall pathology, including careful exclusion of infectious aortitis.


Subject(s)
Aortitis/diagnosis , Bacterial Infections/diagnosis , Immune System Diseases/diagnosis , Immunoglobulin G/metabolism , Plasma Cells/pathology , Aged , Aged, 80 and over , Aorta, Abdominal/immunology , Aorta, Abdominal/microbiology , Aorta, Abdominal/pathology , Aortitis/immunology , Aortitis/microbiology , Bacterial Infections/immunology , Chronic Disease , Fatal Outcome , Female , Gram-Positive Bacteria/isolation & purification , Humans , Immune System Diseases/immunology , Immune System Diseases/microbiology , Lymphocyte Count , Male , Plasma Cells/immunology , Prospective Studies
3.
Chest ; 137(6): 1382-90, 2010 Jun.
Article in English | MEDLINE | ID: mdl-20081101

ABSTRACT

BACKGROUND: Acute pulmonary embolism (PE) may be rapidly fatal if not diagnosed and treated. IV heparin reduces mortality and recurrence of PE, but the relationship between survival and timing of anticoagulation has not been extensively studied. METHODS: We studied 400 consecutive patients in the ED diagnosed with acute PE by CT scan angiography and treated in the hospital with IV unfractionated heparin from 2002 to 2005. Patients received heparin either in the ED or after admission. Time from ED arrival to therapeutic activated partial thromboplastin time (aPTT) was calculated. Outcomes included in-hospital and 30-day mortality, hospital and ICU lengths of stay, hemorrhagic events on heparin, and recurrent venous thromboembolism within 90 days. RESULTS: In-hospital and 30-day mortality rates were 3.0% and 7.7%, respectively. Patients who received heparin in the ED had lower in-hospital (1.4% vs 6.7%; P = .009) and 30-day (4.4% vs 15.3%; P < .001) mortality rates as compared with patients given heparin after admission. Patients who achieved a therapeutic aPTT within 24 h had lower in-hospital (1.5% vs 5.6%; P = .093) and 30-day (5.6% vs 14.8%; P = .037) mortality rates as compared with patients who achieved a therapeutic aPTT after 24 h. In multiple logistic regression models, receiving heparin in the ED remained predictive of reduced mortality, and ICU admission remained predictive of increased mortality. CONCLUSIONS: We report an association between early anticoagulation and reduced mortality for patients with acute PE. We advocate further study with regard to comorbidities to assess the usefulness of modifications to hospital protocols.


Subject(s)
Anticoagulants/administration & dosage , Heparin/administration & dosage , Pulmonary Embolism/drug therapy , Pulmonary Embolism/mortality , Acute Disease , Aged , Chi-Square Distribution , Emergency Service, Hospital , Female , Hospital Mortality , Humans , Length of Stay/statistics & numerical data , Logistic Models , Male , Partial Thromboplastin Time , Pulmonary Embolism/diagnostic imaging , Recurrence , Retrospective Studies , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
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