An autopsy case of hypertrophic pachymeningitis and multiple cranial neuropathies is reported. A 53-year-old woman with paraplegia and various neurological signs which developed over a 2 year period was diagnosed as having an epidural mass with thickened dura mater extending from the lower cervical to the thoracic spinal cord. In addition, bilateral episcleritis, blephaloptosis, and blindness of the right eye with various cranial nerve deficits were found to be caused by the mass lesions involving the paranasal sinuses, orbit, and the cavernous sinus. Perinuclear antineutrophil cytoplasmic antibody (p-ANCA) was positive, but cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA) was negative by enzyme-linked immunosorbent assay. The partially removed epidural mass with hypertrophied dura mater and biopsy of the paranasal lesions showed chronic granulomatous inflammation with vasculitis. The remaining lesions resolved with steroid therapy with remarkable neurological improvement. The positive p-ANCA test, paranasal involvement, the report of a similar histopathological case and a review of the literature on granulomatous pachymeningitis suggest the presence of p-ANCA-positive Wegener's granulomatosis with central nervous system involvement characterized by hypertrophic pachymeningitis and/or multiple cranial neuropathies.

Macrophages act to protect the body against inflammation and infection by engaging in chemotaxis and phagocytosis. In chemotaxis, macrophages use an actin-based membrane structure, the podosome, to migrate to inflamed tissues. In phagocytosis, macrophages form another type of actin-based membrane structure, the phagocytic cup, to ingest foreign materials such as bacteria. The formation of these membrane structures is severely affected in macrophages from patients with WiskottAldrich syndrome (WAS), an X chromosome-linked immunodeficiency disorder. WAS patients lack WAS protein (WASP), suggesting that WASP is required for the formation of podosomes and phagocytic cups. Here we have demonstrated that formin-binding protein 17 (FBP17) recruits WASP, WASP-interacting protein (WIP), and dynamin-2 to the plasma membrane and that this recruitment is necessary for the formation of podosomes and phagocytic cups. The N-terminal EFC (extended FER-CIP4 homology)/F-BAR (FER-CIP4 homology and Bin-amphiphysin-Rvs) domain of FBP17 was previously shown to have membrane binding and deformation activities. Our results suggest that FBP17 facilitates membrane deformation and actin polymerization to occur simultaneously at the same membrane sites, which mediates a common molecular step in the formation of podosomes and phagocytic cups. These results provide a potential mechanism underlying the recurrent infections in WAS patients.Podosomes (see Fig. 1A) are micron-scale, dynamic, actinbased protrusions observed in motile cells such as macrophages, dendritic cells, osteoclasts, certain transformed fibroblasts, and carcinoma cells (1). Podosomes play an important role in macrophage chemotactic migration, which is critical for recruitment of leukocytes to inflamed tissues. Podosomes are both adhesion structures and the sites of extracellular matrix degradation (2). Adhesion to and degradation of the extracellular matrix are essential processes for the successful migration of macrophages in tissues. Podosomes occur in most macrophages and can be observed by differentiating human primary monocytes into macrophages with macrophage-colony stimulating factor-1 (M-CSF-1) 2 and staining the F-actin using phalloidin (3, 4). Podosomes labeled in this way appear as F-actinrich dots (see Fig. 1C). Podosome formation has recently been directly observed in vitro and in vivo in leukocyte migration through the endothelium, diapedesis (5).Phagocytosis of bacterial pathogens is one of the most important primary host defense mechanisms against infections. The phagocytic cup (see Fig. 1B) is an actin-based membrane structure formed at the plasma membrane of phagocytes, including macrophages, upon stimulation with foreign materials such as bacteria. The phagocytic cup captures and ingests foreign materials, and its formation is an essential first step in phagocytosis leading to the digestion of foreign materials (6, 7). When macrophages are stimulated by foreign materials, podosomes disappear, and phagocytic cups, which are also rich in F-actin, are formed...

No abstract

No abstract

Aim: Atherosclerosis can be evaluated by carotid intima media thickness (IMT), the aortic calcification index (ACI), and pulse wave velocity (PWV). We investigated which test was most closely related to cerebro-and cardiovascular disorders (CCVD) in hemodialysis patients. Methods: Maximum IMT (max-IMT), ACI, and PWV were examined in 110 hemodialysis patients, using carotid ultrasonography, abdominal CT and a blood pressure pulse wave instrument, respectively. Blood hemoglobin A1c (HbA1c), serum total cholesterol, high density lipoprotein cholesterol, triglyceride, total protein, albumin, high sensitivity C reactive protein (hs-CRP), and tumor necrosis factor a were measured. The patients were divided into two groups; with and without CCVD and the degree of atherosclerosis was evaluated in each group. Results: Compared to the CCVD (-) group, the CCVD (+) group showed significantly higher percentages of males and diabetic patients, higher levels of HbA1c (5.14 vs 4.83%) and hs-CRP (0.320 vs 0.167 mg/dL), an older age group (64.5 vs 57.5 years), a greater max-IMT (2.05 vs 1.19 mm), and a higher ACI (71.8 vs 41.0%); and significantly lower diastolic blood pressure (82.8 vs 89.2 mmHg). Multiple logistic regression analysis showed that the factors influencing the development of CCVD were age (odds ratio: 1.092), ACI (odds ratio: 1.025), and max-IMT (odds ratio: 2.006). However, PWV did not significantly relate to CCVD. Conclusions: In hemodialysis patients, the ACI and max-IMT were significantly associated with CCVD, but the association of PWV was weak. A prospective cohort study is warranted to determine the risk factors for CCVD in hemodialysis patients.