The time-resolved and extreme conditions XAS (TEXAS) facility at the European Synchrotron Radiation Facility: the general-purpose EXAFS bending-magnet beamline BM23.

BM23 is the general-purpose EXAFS bending-magnet beamline at the ESRF, replacing the former BM29 beamline in the framework of the ESRF upgrade. Its mission is to serve the whole XAS user community by providing access to a basic service in addition to the many specialized instruments available at the ESRF. BM23 offers high signal-to-noise ratio EXAFS in a large energy range (5-75 keV), continuous energy scanning for quick-EXAFS on the second timescale and a micro-XAS station delivering a spot size of 4 µm × 4 µm FWHM. It is a user-friendly facility featuring a high degree of automation, online EXAFS data reduction and a flexible sample environment.

Therapeutic strategy for lower limb lymphedema and lymphatic fistula after resection of a malignant tumor in the hip joint region: a case report.

Lymphatic fistula complicating lymphedema is thought to occur due to communication between lymph vessels and the skin, which has yet to be shown objectively. The objective of this case report is to show the pathology and treatment using simultaneous lymphatic fistula resection and lymphatico-venous anastomosis (LVA). A 40-year-old woman underwent extended resection and total hip arthroplasty for primitive neuroectodermal tumor in the right proximal femur 23 years ago. Right lower limb lymphedema developed immediately after surgery and lymphatic fistula appeared in the posterior thigh. On ICG lymphography, lymph reflux toward the distal side dispersing in a fan-shape reticular pattern from the lymphatic fistula region was noted after intracutaneous injection of ICG into the foot. We performed simultaneous lymphatic fistula resection and of LVA. Pathological examination showed that the epidermis and stratum corneum of the healthy skin were lost in the lymphatic fistula region. Dilated lymph vessels were open in this region. The examinations provide the first objective evidence that the cause of lymphatic fistula may be lymph reflux from lymphatic stems to precollectors through lymphatic perforators.

Increased circulating Th17 frequencies and serum IL-22 levels in patients with acute generalized exanthematous pustulosis.

BACKGROUND/OBJECTIVE: Acute generalized exanthematous pustulosis (AGEP) is a diffuse pustular disorder that usually begins in intertriginous folds with widespread erythema. The causes in the majority of the cases are drugs. T cells and interleukin (IL)-8 play roles in the development of AGEP, but the mechanism remains to be elucidated. We investigated the involvement of Th17 cells and their cytokine IL-22 in the pathogenesis. METHODS: Three patients with AGEP were enrolled in this study. The percentages of IL-17(+) Th17 cells, interferon γ(+) T cells and IL-4(+) T cells were measured in the patients' peripheral blood lymphocytes by intracellular cytokine staining and flow cytometry. The concentration of IL-22 in the sera was measured by enzyme-linked immunosorbent assay. RESULTS: The percentages of Th17 cells were markedly higher in all three patients than healthy control individuals. The frequencies of interferon γ(+) T cells were slightly high in the patients compared with the control, and there was no definite tendency in IL-4(+) T-cell frequencies. The concentration of IL-22 was remarkably high in all patients when compared with normal subjects with levels under detection. CONCLUSION: Th17 cells and their produced cytokine IL-22 were elevated in the peripheral blood of patients with AGEP. As IL-17 and IL-22 cooperatively stimulate keratinocytes to produce IL-8, IL-8 may contribute to the accumulation of neutrophils in the lesional epidermis of AGEP.

Inhibition of T helper 2 chemokine production by narrowband ultraviolet B in cultured keratinocytes.

BACKGROUND: Narrowband ultraviolet B (NB-UVB) has recently been used for the treatment of various skin disorders. Its effects on the production of cytokines and chemokines by keratinocytes are unknown. OBJECTIVES: To investigate the effect of NB-UVB on production of chemokines and proinflammatory cytokines by keratinocytes in comparison with broadband (BB)-UVB. METHODS: Normal human epidermal keratinocytes (or the human keratinocyte cell line HaCaT in some experiments) at semiconfluency were irradiated with NB-UVB at 10, 100, 500 or 1000 mJ cm(-2) or BB-UVB at 10 or 100 mJ cm(-2). The cultures were maintained in the presence or absence of interferon (IFN)-gamma at 200 U mL(-1). The 72-h culture supernatants were analysed by enzyme-linked immunosorbent assay to quantify T helper (Th)1 chemokines (IFN-inducible protein 10 and monokine induced by IFN-gamma), Th2 chemokines [macrophage-derived chemokine (MDC) and thymus and activation-regulated chemokine (TARC)] and proinflammatory cytokines [interleukin (IL)-1alpha and tumour necrosis factor (TNF)-alpha]. The expression of mRNA for these molecules was simultaneously assessed by reverse transcriptase-polymerase chain reaction. The culture supernatants were also tested for their chemotactic activity for Th1 and Th2 cells. The two UVB sources were compared on the basis of their minimal erythemal doses and clinically used doses. RESULTS: Although both NB-UVB and BB-UVB increased the production of IL-1alpha and TNF-alpha, the augmentative effect of NB-UVB was less than that of BB-UVB. Both wavelength ranges of UVB enhanced or had no effect on Th1 chemokine production, but suppressed the production of Th2 chemokines MDC and TARC. This was confirmed by chemotactic assay, which showed decreased chemotactic activity for Th2 cells by the culture supernatants from NB-UVB-irradiated keratinocytes. CONCLUSIONS: NB-UVB reduces the production of Th2 chemokines without excess production of proinflammatory cytokines, suggesting its therapeutic effectiveness on Th2-mediated skin disorders as well as its relative safety in clinical usage.

Evidence for polyclonal infection of Epstein-Barr virus in a patient with primary cutaneous anaplastic large cell lymphoma.

We report a case of CD30 + primary cutaneous anaplastic large cell lymphoma. The lymphoma cells were shown to express the Epstein-Barr virus (EBV)-encoded small RNAs by in situ hybridization and to have EBV genomes by PCR, whereas no monoclonal band was detected by Southern blot analysis using the EBV terminal repeat probe. These data suggested polyclonal infection by EBV, which provides evidence that EBV plays little part in the pathogenesis of this tumour even in the infected cases.

Cloning and characterization of FGF23 as a causative factor of tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) is one of the paraneoplastic diseases characterized by hypophosphatemia caused by renal phosphate wasting. Because removal of responsible tumors normalizes phosphate metabolism, an unidentified humoral phosphaturic factor is believed to be responsible for this syndrome. To identify the causative factor of TIO, we obtained cDNA clones that were abundantly expressed only in a tumor causing TIO and constructed tumor-specific cDNA contigs. Based on the sequence of one major contig, we cloned 2,270-bp cDNA, which turned out to encode fibroblast growth factor 23 (FGF23). Administration of recombinant FGF23 decreased serum phosphate in mice within 12 h. When Chinese hamster ovary cells stably expressing FGF23 were s.c. implanted into nude mice, hypophosphatemia with increased renal phosphate clearance was observed. In addition, a high level of serum alkaline phosphatase, low 1,25-dihydroxyvitamin D, deformity of bone, and impairment of body weight gain became evident. Histological examination showed marked increase of osteoid and widening of growth plate. Thus, continuous production of FGF23 reproduced clinical, biochemical, and histological features of TIO in vivo. Analyses for recombinant FGF23 products produced by Chinese hamster ovary cells indicated proteolytic cleavage of FGF23 at the RXXR motif. Recent genetic study indicates that missense mutations in this RXXR motif of FGF23 are responsible for autosomal dominant hypophosphatemic rickets, another hypophosphatemic disease with similar features to TIO. We conclude that overproduction of FGF23 causes TIO, whereas mutations in the FGF23 gene result in autosomal dominant hypophosphatemic rickets possibly by preventing proteolytic cleavage and enhancing biological activity of FGF23.

[Successful treatment of refractory idiopathic thrombocytopenic purpura by eradication of Helicobacter pylori].

A 53-year-old woman was diagnosed as having idiopathic thrombocytopenic purpura (ITP) in 1990, and treated with prednisolone and splenectomy, which did not result in remission. In November 2000, gastrointestinal endoscopy showed superficial gastritis, and Helicobacter pylori infection was revealed by the rapid urease test and histologic examination. After eradication of Helicobacter pylori by amoxicillin, clarithromycin and lansoprazole, the patient's platelet count was increased from 24 x 10(9)/l to 134 x 10(9)/l and platelet-associated IgG (PAIgG) was decreased from 695 ng/10(7) cells to 33 ng/10(7) cells. This case suggests that eradication of Helicobacter pylori may be useful for treating some patients with refractory ITP.

[Multiple myeloma with massive ascites fluid--immunophenotypic analysis of myeloma cell and its IL-6-dependent growth].

A 75-year-old female was diagnosed as having multiple myeloma (IgG.lambda type. Stage IIA) with plasmacytoma of the head and back in October, 1989. She obtained partial remission by MCNU and MP therapy, but relapsed with massive ascites in January, 1991. VAD therapy was not effective and she died of multiple organ failure on February 23. Her ascites contained a large number of myeloma cells, and the phenotypic analysis and the response to interleukin-6 (IL-6) of these myeloma cells were examined. The myeloma cells were positive for CD33, CD45, CD45RA, CD63, CD71, plasma cell associated antigens such as CD38, PCA-1, BL3, and various kinds of adhesion molecules: CD11a/CD18 (LFA-1), CD29 (VLA-beta 1), CD44 (H-CAM), CD49d (VLA-4), CD54 (ICAM-1), CD56 (N-CAM), CD58 (LFA-3). IL-6 level in the ascites was increased at 91.0pg/ml. The myeloma cells showed an IL-6 dependent growth, which was inhibited by anti-IL-6 antibody (Ab) and anti-IL-6 receptor Ab in vitro. Myeloma cells appearing in ascites have rarely been reported. Our case suggested that IL-6 was a potent growth factor of myeloma cells through an autocrine mechanism in the ascites, and resulted in an aggressive myeloma.

The site of action of the histamine releaser compound 45/80 in causing mast cell degranulation.

A primary amine analog of compound 48/80 (nor-48/80) was purified and attached to Sepharose beads through an albumin link. Suspensions of rat peritoneal cells were passed over the beads in an affinity chromatography column, and the proportion of the mast cells that was retained by the beads was determined. Sixty-seven percent of the mast cells were found to be retained by the column, indicating the existence of a binding site for nor-48/80 on the exterior of mast cells. The beads were larger than the cells, and hence precluded the entry of the nor-48/80 into the cells. Neither the Sepharose beads nor the albumin link was responsible for this amount of binding because control beads without nor-48-80 retained only 22% of the mast cells. Mast cells incubated with large quantities of the beads in a batch procedure released up to 53% of the mast cell histamine, whereas control beads without the polymer released only 18%. This release could not be attributable to soluble nor-48/80 because only trace amounts of radioactive nor-48/80 were released from beads soaked overnight, and these supernatants released insignificant amounts of histamine when incubated with mast cells. These studies indicate the presence of a receptor for 48/80 on the mast cell membrane which can trigger histamine release.