A comparison of vascular inflammation in psoriasis, rheumatoid arthritis, and healthy subjects by FDG-PET/CT: a pilot study.

Objective: Psoriasis (PSO) and rheumatoid arthritis (RA) increase cardiovascular diseases (CVD) beyond traditional risk factors. Vascular inflammation has previously been demonstrated to be present in PSO and RA using [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging. However, vascular inflammation has not been compared in these two disorders relative to a healthy reference population.

Monogenic autoinflammatory diseases: disorders of amplified danger sensing and cytokine dysregulation.

The pathogenesis of monogenic autoinflammatory diseases converges on the presence of exaggerated immune responses that are triggered through activation of altered pattern recognition receptor (PRR) pathways and result in cytokine/chemokine amplification loops and the inflammatory clinical phenotype seen in autoinflammatory patients. The PRR response can be triggered by accumulation of metabolites, by mutations in sensors leading to their constitutive overactivation, or by mutations in mediator cytokine pathways that lead to amplification and/or inability to downregulate an inflammatory response in hematopoietic and/or nonhematopoietic cells. The study of the pathogenesis of sterile inflammation in patients with autoinflammatory syndromes continues to uncover novel inflammatory pathways.

Lighting the fires within: the cell biology of autoinflammatory diseases.

Autoinflammatory diseases are characterized by seemingly unprovoked pathological activation of the innate immune system in the absence of autoantibodies or autoreactive T cells. Discovery of the causative mutations underlying several monogenic autoinflammatory diseases has identified key regulators of innate immune responses. Recent studies have highlighted the role of misfolding, oligomerization and abnormal trafficking of pathogenic mutant proteins in triggering autoinflammation, and suggest that more common rheumatic diseases may have an autoinflammatory component.

Bubblegrams reveal the inner body of bacteriophage φKZ.

Dense packing of macromolecules in cellular compartments and higher-order assemblies makes it difficult to pick out even quite large components in electron micrographs, despite nominally high resolution. Immunogold labeling and histochemical procedures offer ways to map certain components but are limited in their applicability. Here, we present a differential mapping procedure, based on the physical principle of protein's greater sensitivity to radiation damage compared with that of nucleic acid.

Basophils and the T helper 2 environment can promote the development of lupus nephritis.

In systemic lupus erythematosus (SLE), self-reactive antibodies can target the kidney (lupus nephritis), leading to functional failure and possible mortality. We report that activation of basophils by autoreactive IgE causes their homing to lymph nodes, promoting T helper type 2 (T(H)2) cell differentiation and enhancing the production of self-reactive antibodies that cause lupus-like nephritis in mice lacking the Src family protein tyrosine kinase Lyn (Lyn(-/-) mice). Individuals with SLE also have elevated serum IgE, self-reactive IgEs and activated basophils that express CD62 ligand (CD62L) and the major histocompatibility complex (MHC) class II molecule human leukocyte antigen-DR (HLA-DR), parameters that are associated with increased disease activity and active lupus nephritis.

Comparison of the construct validity and sensitivity to change of the visual analog scale and a modified rating scale as measures of patient global assessment in rheumatoid arthritis.

Objective: Patient global assessment (PGA) is commonly measured using a visual analog scale (VAS). The VAS asks patients to integrate many dimensions of rheumatoid arthritis (RA) activity, yet its scope is poorly defined and its endpoints are vague. We investigated whether a modified Rating Scale that used marker states and more defined endpoints would provide a more valid measure of PGA.

Stepwise differentiation of CD4 memory T cells defined by expression of CCR7 and CD27.

To study the steps in the differentiation of human memory CD4 T cells, we characterized the functional and lineage relationships of three distinct memory CD4 subpopulations distinguished by their expression of the cysteine chemokine receptor CCR7 and the TNFR family member CD27. Using the combination of these phenotypic markers, three populations were defined: the CCR7+CD27+, the CCR7-CD27+, and the CCR7-CD27- population. In vitro stimulation led to a stepwise differentiation from naive to CCR7+CD27+ to CCR7-CD27+ to CCR7-CD27-.

Severity of illness in patients with systemic lupus erythematosus hospitalized at academic medical centers.

Objective: To compare the severity of illness of patients with systemic lupus erythematosus (SLE) between those hospitalized at academic medical centers and those hospitalized at community hospitals.

Methods: In this population based cross-sectional survey, data on all hospitalizations of patients with SLE in California, New York, and Pennsylvania in 2000 were obtained from discharge abstracts submitted by acute care hospitals to state health planning agencies. Patients hospitalized at one of 36 academic medical centers in these states (N = 2072) were compared to patients hospitalized at community hospitals (N = 9373).

Macromolecular protein signaling complexes and mast cell responses: a view of the organization of IgE-dependent mast cell signaling.

The generation of signals following engagement of cell surface receptors is an ordered process that requires tight regulation as spurious signals could result in unwanted, and possibly deleterious, cellular responses. Like other cell surface receptors, stimulation of a mast cell via the high affinity IgE receptor (FcepsilonRI) causes multiple biochemical events that ultimately result in cell activation and effector responses. Recently, our knowledge of how these events are ordered has increased.

Evidence for the involvement of a hematopoietic progenitor cell in systemic mastocytosis from single-cell analysis of mutations in the c-kit gene.

Mast cells are derived from multipotential hematopoietic progenitors and are clonally increased in systemic mastocytosis, a disease associated with point mutations of codon 816 (most commonly Asp816Val) of c-kit. To study the lineage relationship and the extent of expansion of cells derived from the mutated clone, we examined the occurrence of the Asp816Val c-kit mutation in genomic DNA of individual sorted peripheral blood T cells, B cells, and monocytes in patients with indolent systemic mastocytosis. The mutation was detected in varying frequencies in the genomic DNA of individual B cells and monocytes and bone marrow mast cells in patients with extensive disease.

Epidemiology of osteoporosis.

Osteoporosis is a "disease characterized by low bone mass and microar-chitectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk" (Consensus Development Conference. Diagnosis, prophylaxis, and treatment of osteoporosis. Am J Med 1993;94:646-650).

Low prevalences of chronic widespread pain and shoulder disorders among the Pima Indians.

Objective: To establish the prevalence of shoulder disease and chronic widespread pain in Pima Indians.

Methods: Cross sectional analyses of data from 4230 subjects for shoulder disease and 105 subjects for chronic widespread pain participating in population surveys

Results: The prevalence of shoulder disease was 4.4% (95% CI, 3.

Outpatient monthly oral bolus cyclophosphamide therapy in systemic lupus erythematosus.

Objective: An open label study to determine the feasibility and acute toxicity of a 6 month course of outpatient intermittent bolus high dose oral cyclophosphamide in patients with active systemic lupus erythematosus (SLE).

Methods: Oral cyclophosphamide in a single dose of 0.5 to 1.

Hypothalamic-pituitary-adrenal axis perturbations in patients with fibromyalgia.

Objective: To examine basal and stimulated hypothalamic-pituitary-adrenal (HPA) axis and related hormone levels, including adrenocorticotropin (ACTH), cortisol, arginine vasopressin (AVP), and neuropeptide Y (NPY), in patients with fibromyalgia (FM).

Methods: Basal and ovine corticotropin-releasing hormone (oCRH)-stimulated HPA axis function were assessed in 12 patients with FM and in age- and sex-matched normal subjects. Basal plasma AVP levels and AVP release after postural change were assessed, and plasma NPY levels were measured in the same samples.

A pilot study of anti-CD5 ricin A chain immunoconjugate in systemic lupus erythematosus.

Objective: To determine the safety and clinical and biological effects of a murine monoclonal anti-CD5 ricin A chain immunoconjugate (CD5 Plus) in patients with systemic lupus erythematosus (SLE).

Methods: An open label phase I study of CD5 Plus. A dose of 0.