Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic systemic inflammation causing progressive joint damage that can lead to lifelong disability. The pathogenesis of RA involves a complex network of various cytokines and cells that trigger synovial cell proliferation and cause damage to both cartilage and bone. Involvement of the cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6 is central to the pathogenesis of RA, but recent research has revealed that other cytokines such as IL-7, IL-17, IL-21, IL-23, granulocyte macrophage colony-stimulating factor (GM-CSF), IL-1β, IL-18, IL-33, and IL-2 also play a role. Clarification of RA pathology has led to the development of therapeutic agents such as biological disease-modifying anti-rheumatic drugs (DMARDs) and Janus kinase (JAK) inhibitors, and further details of the immunological background to RA are emerging. This review covers existing knowledge regarding the roles of cytokines, related immune cells and the immune system in RA, manipulation of which may offer the potential for even safer and more effective treatments in the future.

The effect of basic fibroblast growth factor (bFGF) on the healing of partial anterior cruciate ligament (ACL) lacerations was investigated in 17 adult mongrel canines. The defect was created in the midsubstance of both ACLs using a biopsy punch. In the bFGF group, a bFGF-impregnated pellet was sutured to the infrapatellar fat pad close to the defect. In the control group, the same pellet without bFGF was used. The healing process was evaluated macroscopically and histologically at 1, 3, 6, and 24 weeks postoperatively. In the bFGF group, a pannus-like tissue which contained abundant blood vessels extended into the defect from the adjacent synovial tissue in the early postoperative phase. Histological examination of the tissue which filled the defect revealed initial remodeling processes with a decreased number of cells and better orientation of the collagen fibers at 6-24 weeks. On the other hand, in the control group, poor healing processes were observed at each examination period. This study demonstrated that the application of a bFGF-impregnated pellet may enhance the healing potential of a partially injured ACL. Enhanced neovascularization and the formation of granulation tissue induced by bFGF early in the healing process accounted for the increased healing response.

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Nitric oxide (NO) relaxes the internal anal sphincter (IAS), but its enzymatic source(s) remains unknown; neuronal (nNOS) and endothelial (eNOS) NO synthase (NOS) isoforms could be involved. Also, interstitial cells of Cajal (ICC) may be involved in IAS relaxation. We studied the relative roles of nNOS, eNOS, and c-Kit-expressing ICC for IAS relaxation using genetic murine models. The basal IAS tone and the rectoanal inhibitory reflex (RAIR) were assessed in vivo by a purpose-built solid-state manometric probe and by using wild-type, nNOS-deficient (nNOS-/-), eNOS-deficient (eNOS-/-), and W/W(v) mice (lacking certain c-Kit-expressing ICC) with or without L-arginine or N(omega)-nitro-L-arginine methyl ester (L-NAME) treatment. Moreover, the basal tone and response to electrical field stimulation (EFS) were studied in organ bath using wild-type and mutant IAS. In vivo, the basal tone of eNOS-/- was higher and W/W(v) was lower than wild-type and nNOS-/- mice. L-arginine administered rectally, but not intravenously, decreased the basal tone in wild-type, nNOS-/-, and W/W(v) mice. However, neither L-arginine nor L-NAME affected basal tone in eNOS-/- mice. In vitro, L-arginine decreased basal tone in wild-type and nNOS-/- IAS but not in eNOS-/- or wild-type IAS without mucosa. The in vivo RAIR was intact in wild-type, eNOS-/-, and W/W(v) mice but absent in all nNOS-/- mice. EFS-induced IAS relaxation was also reduced in nNOS-/- IAS. Thus the basal IAS tone is largely controlled by eNOS in the mucosa, whereas the RAIR is controlled by nNOS. c-Kit-expressing ICC may not be essential for the RAIR.

We retrospectively reviewed 16 patients who presented to hospitals with orthopaedic complaints. Twelve patients experienced initial symptoms in the extremities and four patients had back pain. The leukocyte count was elevated in one patient, decreased in two patients, and normal in 13 patients. On radiographic examination, osteopenia was observed in 10 patients, osteolytic lesions were observed in five, and pathologic fractures were observed in five. Because the initial presentation of patients with leukemia often involves the musculoskeletal system, orthopaedists need to recognize the symptoms of this disease to avoid misdiagnosis and to expedite the initiation of appropriate potentially lifesaving treatment.