There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.

Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …

I and i

다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

Human mesenchymal stem cells are thought to be multipotent cells, which are present in adult marrow, that can replicate as undifferentiated cells and that have the potential to differentiate to lineages of mesenchymal tissues, including bone, cartilage, fat, tendon, muscle, and marrow stroma. Cells that have the characteristics of human mesenchymal stem cells were isolated from marrow aspirates of volunteer donors. These cells displayed a stable phenotype and remained as a monolayer in vitro. These adult stem cells could be induced to differentiate exclusively into the adipocytic, chondrocytic, or osteocytic lineages. Individual stem cells were identified that, when expanded to colonies, retained their multilineage potential.

http://science.sciencemag.org/content/sci/284/5411/143.full.pdf

Multilineage Potential of Adult Human Mesenchymal Stem Cells

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

The Aging Lungs:Mechanisms and Clinical Sequelae

Current views of rheumatoid arthritis (RA) pathogenesis emphasize an autoimmune etiology marshalling components of the innate and adaptive immune responses (1). As a consequence of rheumatoid inflammation, joint synovium develops into the erosive granulation tissue known as pannus, which is a pathologic hallmark of RA (2). Within pannus tissue, there is an enormous increase in the number of fibroblast-like synoviocytes, persistent inflammatory foci, lymphoid germinal centers, and angiogenesis. In vitro studies have established that fibroblasts isolated from the synovia of patients with RA exhibit an activated phenotype with enhanced proliferation, invasive properties, and increased secretion of growth-promoting cytokines and matrix-degrading enzymes. Rheumatoid synovial fibroblasts proliferate in an anchorage-independent manner, escape contact inhibition, and invade cartilage implants (2–5). Remarkably, this aggressive phenotype endures after multiple cell passages and prolonged culture, suggesting that synovial fibroblasts are persistently, if not irreversibly, altered in the rheumatoid joint. The precise manner in which synovial fibroblasts maintain this activated state after removal from the inflammatory articular milieu is unknown, but such maintenance may result from a selfperpetuating or reentrant stimulatory pathway involving autocrine mediators and sustained intracellular signaling. There is evidence in rheumatoid synovial fibroblasts for protooncogene activation and for the functional (and perhaps mutational) inactivation of the tumor suppressor gene p53, which regulates cell cycle progression (6). Although the notion of a mutational origin for pannus tissue has been largely discounted (and does not account for multicentric rheumatoid synovitis), longterm epigenetic changes may explain the activated phenotype of rheumatoid synovial fibroblasts. Beyond exhibiting an invasive phenotype, the hyperplastic synovium also supports leukocyte recruitment and may be directly activating to the immune system (7,8). Why pannus develops in RA but not in other arthritides also is unknown, but pannus development is central to the progression of joint destruction. Another important clinical question is whether the currently available therapies are effective for treating rheumatoid pannus or whether, as in systemic sclerosis, activated connective tissue is intrinsically resistant to immunosuppression and should be targeted pharmacologically in order to achieve effective disease control. In this issue of Arthritis & Rheumatism, Galligan and Fish present experimental evidence for the participation of circulating fibrocytes in the pathogenesis of inflammatory synovitis (9). The fibrocyte is a monocytederived cell that expresses features of both a macrophage and a connective tissue cell. First identified in the 1990s by their coexpression of hematopoietic progenitor markers together with extracellular matrix proteins, fibrocytes are among the earliest responding cells in the innate response to injury or tissue invasion (10). Fibrocytes normally comprise a minor population of circulating leukocytes, but they are mobilized from the bone marrow and circulate in increased numbers during the systemic inflammatory response, in the setting of ongoing fibrogenesis, or as a consequence of aging (11). Galligan and Fish approached their investigation Richard Bucala, MD, PhD: Yale University School of Medicine, New Haven, Connecticut. Dr. Bucala has received honoraria for service on the Scientific Advisory Board of Promedior (less than $10,000) and owns stock or stock options in the company. Promedior is developing recombinant pentraxin to inhibit fibrocytes. Address correspondence to Richard Bucala, MD, PhD, Department of Medicine, Section of Rheumatology, The Anlyan Center, S521, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06520. E-mail: Richard.Bucala@Yale.edu. Submitted for publication June 3, 2012; accepted in revised form June 12, 2012. Arthritis & Rheumatism

https://www.onlinelibrary.wiley.com/doi/pdf/10.1002/art.34585

Fibrocytes in rheumatoid pannus: seed and soil?

One year ago, we discussed the continued importance of reporting randomized controlled clinical trials in Arthritis & Rheumatology (A&R) (1). The journal encouraged submissions through a fast-track option and consultation with a senior clinical trialist (Dr. Michael Weinblatt) to help facilitate submissions and reviews. The process appears to be working. In 2016, A&R published results of 14 randomized clinical trials (RCTs), whereas during 2014–2015 the number was 7. Perhaps more important, of the RCTs published during the past year, 8 were accepted for fast-track review, and the mean turnaround time for fast-track review was 17 days. The current issue of A&R reports 2 important parallel phase IIb RCTs of the same selective JAK-1 inhibitor, ABT-494 (2,3). These 2 trials evaluated this new JAK-1 inhibitor in 2 populations of patients with rheumatoid arthritis (RA). The study by Genovese et al (2) focuses on patients with moderate-to-severe RA and an inadequate response to methotrexate (MTX), and the study by Kremer et al (3) examines a similar population of patients who have had an inadequate response to a tumor necrosis factor antagonist. These are both highly clinically relevant populations to study for this agent. The investigators tested ABT494 using a range of dosages, and after 12 weeks of treatment, both studies demonstrated positive outcomes for both the primary end point, i.e., the proportion of patients who met the American College of Rheumatology 20% improvement criteria (achieved an ACR20 response) (4), and the secondary end points, i.e., the proportions of patients achieving ACR50 and ACR70 responses and the proportion of patients achieving a score of #3.2 or ,2.6 on the 28-joint Disease Activity Score using the C-reactive protein level (5). As phase IIb studies, there are several aspects of both trials that are worth discussing. Phase II trials are intended to test the effectiveness of treatments in patients with the targeted clinical condition, typically after phase I trials have demonstrated an acceptable safety profile. Different dosages of a drug are often tested against placebo, and trials are often brief but allow for planning of more definitive phase III trials. The 2 trials reported in this issue have led to an active phase III trials program that will likely be reported in the ensuing few years. The emphasis on RCTs by the journal speaks to several issues. First, RCTs provide a very high level of evidence for clinical practice. Determining the value of any new treatment in medicine requires adequately powered and well-conducted RCTs. While an intervention’s safety often can be best determined from phase IV postmarketing surveillance, RCTs provide information to determine the most efficacious treatments that clinicians can offer to patients. Second, our focus on RCTs flows from the journal’s interest in serving its readers, many of whom are practicing rheumatologists looking to offer the best therapies to their patients. Increasingly, patients come to the clinic with information from journals and other sources for providers to consider. Publishing high-quality evidence through RCTs ensures that provider–patient discussions are informed and timely. Finally, RCTs play a vital role in establishing standards of care and defining the future therapeutic armamentarium for rheumatology. Advances in immunology Daniel H. Solomon, MD, MPH (Deputy Editor, A&R): Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts; Richard J. Bucala, MD, PhD (Editor in Chief, A&R): Yale University School of Medicine, New Haven, Connecticut. Address correspondence to Daniel H. Solomon, MD, Division of Rheumatology, Immunology, and Allergy, Brigham and Women’s Hospital, 75 Francis Street, PBB-B3, Boston, MA 02120. E-mail: dhsolomon@partners.org. Submitted for publication August 12, 2016; accepted August 16, 2016.

Richard Bucala

Papers

The Aging Lungs:Mechanisms and Clinical Sequelae

Fibrocytes in rheumatoid pannus: seed and soil?

Editorial: The Enduring Value of Reporting Randomized Controlled Clinical Trials in Arthritis & Rheumatology: 2016 and Beyond.

Deletion of macrophage migration inhibitory factor reduces severity of osteoarthritis in mice

Pathway Induced by CD74 Regulate Mature B Cell Survival in a Growth Factor/Scatter Factor c-Met and Its Ligand Hepatocyte