James T. Rosenbaum

Bio: James T. Rosenbaum is an academic researcher from Oregon Health & Science University. The author has contributed to research in topics: Uveitis & Scleritis. The author has an hindex of 77, co-authored 509 publications receiving 23701 citations. Previous affiliations of James T. Rosenbaum include Johns Hopkins University & Stanford University.

Endotoxin-induced uveitis in rats as a model for human disease.

Abstract: Acute anterior uveitis is a relatively common disease of uncertain aetiology. Its association with a wide variety of systemic disorders including ankylosing spondylitis, Reiter's syndrome, Behcet's disease, juvenile rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease and sarcoidosis and the prevalence of the HLA antigen B27 (ref. 1) in cases without associated disease have been noted but not explained. In general, animal models for uveitis have not clarified the mechanism of human disease. Most require direct intravitreal injection2 or repeated immunizations with retinal or uveal antigens3. Uveitis does occur in adjuvant arthritis, a syndrome that can be produced in rats by the systemic injection of pepti-doglycan from the cell wall of a variety of Gram-positive bacteria4. The disease, which was initially described following the injection of mycobacteria in mineral oil, has many similarities to Reiter's syndrome5, including the development of eye pathology in as many as 40% of the animals6. As Reiter's syndrome is associated with enteric Gram-negative infections such as Shigella, Salmonella and Yersinia, we sought to produce an arthritis in rats by injecting killed Gram-negative bacteria. Although we have not observed clinical arthritis in these animals, careful histological study has shown the near-universal appearance of uveitis. The studies described below indicate that the eye disease is due to a portion of the bacterial cell wall known as endotoxin or lipopolysaccharide (LPS).

American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.

Abstract: Objective To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). Methods A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946–2014), PubMed (1966–2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. Results In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. Conclusion These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.

The Design and Analysis of Experiments

Abstract: THE DESIGN AND ANALYSIS OF EXPERIMENTS. By Oscar Kempthorne. New York, John Wiley and Sons, Inc., 1952. 631 pp. $8.50. This book by a teacher of statistics (as well as a consultant for \"experimenters\") is a comprehensive study of the philosophical background for the statistical design of experiment. It is necessary to have some facility with algebraic notation and manipulation to be able to use the volume intelligently. The problems are presented from the theoretical point of view, without such practical examples as would be helpful for those not acquainted with mathematics. The mathematical justification for the techniques is given. As a somewhat advanced treatment of the design and analysis of experiments, this volume will be interesting and helpful for many who approach statistics theoretically as well as practically. With emphasis on the \"why,\" and with description given broadly, the author relates the subject matter to the general theory of statistics and to the general problem of experimental inference. MARGARET J. ROBERTSON

Interleukin-10 and the interleukin-10 receptor.

Abstract: Interleukin-10 (IL-10), first recognized for its ability to inhibit activation and effector function of T cells, monocytes, and macrophages, is a multifunctional cytokine with diverse effects on most hemopoietic cell types. The principal routine function of IL-10 appears to be to limit and ultimately terminate inflammatory responses. In addition to these activities, IL-10 regulates growth and/or differentiation of B cells, NK cells, cytotoxic and helper T cells, mast cells, granulocytes, dendritic cells, keratinocytes, and endothelial cells. IL-10 plays a key role in differentiation and function of a newly appreciated type of T cell, the T regulatory cell, which may figure prominently in control of immune responses and tolerance in vivo. Uniquely among hemopoietic cytokines, IL-10 has closely related homologs in several virus genomes, which testify to its crucial role in regulating immune and inflammatory responses. This review highlights findings that have advanced our understanding of IL-10 and its receptor, as well as its in vivo function in health and disease.

Metagenomic biomarker discovery and explanation

Abstract: This study describes and validates a new method for metagenomic biomarker discovery by way of class comparison, tests of biological consistency and effect size estimation. This addresses the challenge of finding organisms, genes, or pathways that consistently explain the differences between two or more microbial communities, which is a central problem to the study of metagenomics. We extensively validate our method on several microbiomes and a convenient online interface for the method is provided at http://huttenhower.sph.harvard.edu/lefse/.

Intestinal mucosal barrier function in health and disease.

Abstract: Mucosal surfaces are lined by epithelial cells. These cells establish a barrier between sometimes hostile external environments and the internal milieu. However, mucosae are also responsible for nutrient absorption and waste secretion, which require a selectively permeable barrier. These functions place the mucosal epithelium at the centre of interactions between the mucosal immune system and luminal contents, including dietary antigens and microbial products. Recent advances have uncovered mechanisms by which the intestinal mucosal barrier is regulated in response to physiological and immunological stimuli. Here I discuss these discoveries along with evidence that this regulation shapes mucosal immune responses in the gut and, when dysfunctional, may contribute to disease.