Low-grade fibromyxoid sarcoma arising in the big toe

Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor. Reported herein is a case of LGFMS arising in the big toe. The patient was a 58-year-old man who underwent excision of the tumor. The tumor was well-demarcated. Histologically, there were proliferating spindle-shaped tumor cells arranged in a whorled growth pattern, and the stroma showed hyalinized collagen bundles and a myxoid matrix. Nuclear mitotic figures were conspicuous in part. A large rosette-like structure with hyalinized stroma was found, which is characteristic of LGFMS. The differential diagnosis included tumor occurrence in adults; tending to arise in distal extremities; and having bland fibromyxoid histological features, such as fibroma of tendon sheath, low-grade myxofibrosarcoma and acral myxoinflammatory fibroblastic sarcoma. It was not possible to detect the FUS/CREB3L2 and FUS/CREB3L1 fusion genes from the formalin-fixed and paraffin-embedded tissue, although the histological features of the present case were typical of LGFMS. LGFMS may become more common with time, and unique cases may accumulate.     

Angiogenic endothelium-specific nestin expression is enhanced by the first intron of the nestin gene

Nestin is a member of intermediate filaments abundantly expressed in neural stem cells and glioblastomas. The nestin gene has four exons and three introns, and neural cell-specific expression is regulated by the second intron. We previously reported that nestin was invariably detected in the tumor endothelium in gliomas even though tumor cells were negative for nestin. In the present study, we further confirmed nestin immunostaining in tumor endothelium of a variety of common cancers, including lung, stomach, colon, and cervical carcinomas. We examined an endothelium-specific regulator using human umbilical vein endothelial cells (HUVECs) and human glioblastoma-derived U251 cells. In a luciferase reporter assay, the first intron plus 5' upstream promoter (5'UP) gave the highest activity, followed by 5'UP, and the second intron plus 5'UP. However, the assay values were much lower by HUVEC extracts than by U251 cell extracts. Although green fluorescent protein expression was positive over all U251 cells under either the first intron, second intron, or ubiquitously active CAG promoter, the fluorescence in HUVECs was limited to a few cells even under the first intron. This difference came from the growth feature of HUVECs which exhibit growth arrest by contact inhibition. We found that the nestin expression was specific to proliferative endothelium, by using proliferation markers in hemangioblastomas and in situ hybridization. Using an endothelial tube formation assay, tyrosine kinase domain-deleted VEGF receptor KDR effectively abolished the tube formation under the first intron. We suggest that the nestin expression in tumor endothelium is enhanced by the first intron.     

Changes in the somatosensory N250 and P300 by the variation of reaction time

We investigated the relationship between somatosensory event-related potentials (ERP) and the variation of reaction time (RT). For this purpose, we recorded the ERPs (N250 and P300) in fast- and slow-reaction trials during a somatosensory discrimination task. Strong, standard, and weak target electrical stimuli were randomly delivered to the left median nerve at the wrist with a random interstimulus interval (900–1,100 ms). All the subjects were instructed to respond by pressing a button with their right thumb as fast as possible whenever a target stimulus was presented. We divided all the trials into fast- and slow-RT trials and averaged the data. N250 latency tended to be delayed when the RT was slow, but not significantly. P300 latency was delayed significantly when the RT was slow, but to a much lesser extent than the RT delay, so we concluded that the change of RT was not fully determined by the processes reflected by the somatosensory N250 or P300. Furthermore, the larger and earlier P300 in the fast-RT trials implied that when larger amounts of attentional resources were allocated to a given task, the speed of stimulus evaluation somewhat increased and RT was shortened to a great extent. N250 amplitude did not significantly vary in the two RT clusters. In conclusion, the somatosensory N250 reflects active target detection, which is relatively independent of the modulation of the response speed, whereas the somatosensory P300 could change without manipulation of either the stimulus or the response processing demand. Electronic Publication     

Copolymerization of N-carboxy-γ-benzyl-L-glutamate anhydride and alkylene oxides by organometallic compounds

Copolymerization of N-carboxy-γ-benzyl-L -glutamate anhydride and ethylene oxide or DL-propylene oxide was carried out in the presence of triethylaluminum or diethylzine as catalyst with (or without) dioxane as solvent. From the data obtained by nuclear magnetic resonance spectroscopy, optical rotatory dispersion measurements, infrared absorption spectroscopy and turbidimetry, it was concluded that the copolymer obtained by the triethylaluminum catalyst consisted of two parts, peptide-block part and random or alternate part, while diethylzinc catalyst resulted in the formation of a less random copolymer only. In dioxane, formation of peptide-block part by triethylaluminum was suppressed to some extent.     

Identification and characterization of intestinal Peyer's patch interferon-alpha producing (plasmacytoid) dendritic cells

Recently, a subset of murine dendritic cells (DC) has been identified that resembles human plasmacytoid (pDC) the principal interferon-alpha (IFN-alpha) producing cells in blood. In this study, C57BL/10 (B10;H2b) mice were treated with fms-like tyrosine 3 kinase Ligand (Flt3L; 10 microg/d; i.p.; 10 days) that expands DC selectively in vivo. Putative pDC (CD11c+B220+) were identified in the subepithelial dome and in interfollicular regions of intestinal Peyer's patches (PP) from both normal and Flt3L-treated animals. Freshly-isolated, immunobead-purified CD11c+ DC from PP were flow-sorted to obtain lineage- (CD11b-CD19-) CD11c+ B220+ DC (purity>96%). Flow cytometric analysis revealed that these sorted PPpDC were negative for surface markers associated with myeloid DC (CD11b) and expressed only low levels of the "lymphoid-related" DC marker CD8alphaalpha+. They expressed low levels of costimulatory molecules and moderate MHC class II. They proved weak stimulators of na?ve allogeneic (C3H; H2k) T-cell proliferation. Cytospin preparations of sorted CD11c+B220+ cells revealed plasmacytoid morphology similar to that of human pDC. Immunocytochemistry and enzyme immunoassay revealed that, within 24-hour culture with Herpes simplex virus (10 p.f.u./cell), a subpopulation of stimulated (but not unstimulated) CD11c+B220+ DC produced and secreted IFN-alpha. This novel DC subset may play important roles in innate and adaptive immune responses of the gut and in the regulation of mucosal immune reactions.     

Genetic and phenotypic characteristics of enterovirus 71 isolates from patients with encephalitis and with hand,foot and mouth disease

Summary Biological and biochemical characters of seven enterovirus 71 (E71) isolates were compared. Four isolates (two from patients with hand, foot and mouth disease [HFMD] and two from patients with encephalitis) grew in cynomolgus monkey kidney cells both at 39.5 and 35° C. However, the remaining three strains (from patients with HFMD) grew at 35° C, but not at 39.5° C. Three temperature-resistant and two temperature-sensitive strains were tested for neurovirulence in monkeys. Temperature-resistant strains were shown to be neurovirulent, whereas temperature-sensitive strains were less neurovirulent. The results suggest correlation between temperature-sensitive growth and neurovirulence in monkeys of E71. Variation in the electrophoretic mobility of the viral polypeptides was detected in three out of seven strains. The fingerprinting of oligonucleotides generated from the viral genome showed similar patterns in two isolates from patients with HFMD and one from patient with encephalitis and variable patterns in each genomic map of remaining four strains. These variations of polypeptide patterns and of oligonucleotide maps could not be correlated with pathogenicity (encephalitis or HFMD), temperature-sensitive growth and neurovirulence in monkeys.With 4 Figures     

Chitosan hydrogel as a drug delivery carrier to control angiogenesis

An aqueous solution of photocrosslinkable chitosan containing azide groups and lactose moieties (Az-CH-LA) incorporating paclitaxel formed an insoluble hydrogel within 30 s of ultraviolet light (UV) irradiation. The chitosan hydrogel showed strong potential for use as a new tissue adhesive in surgical applications and wound dressing. The fibroblast growth factor (FGF)-2 molecules retained in the chitosan hydrogel and in an injectable chitosan/IO₄-heparin hydrogel remain biologically active, and were gradually released from the hydrogels as they biodegraded in vivo. The controlled release of biologically active FGF-2 molecules from the hydrogels caused induction of angiogenesis and collateral circulation occurred in healing-impaired diabetic (db/db) mice and in the ischemic limbs of rats. Paclitaxel, which is an antitumor reagent, was also retained in the chitosan hydrogel and remained biologically active as it was released on degradation of the hydrogel in vivo. The chitosan hydrogels incorporating paclitaxel effectively inhibited tumor growth and angiogenesis in mice. The purpose of this review is to describe the effectiveness of chitosan hydrogel as a local drug delivery carrier for agents (e.g., FGF-2 and paclitaxel) to control angiogenesis. It is thus proposed that chitosan hydrogel may be a promising new local carrier for drugs such as FGF-2 and paclitaxel to control vascularization.     

Increased circulating CD11b+CD11c+ dendritic cells (DC) in aged BWF1 mice which can be matured by TNF-alpha into BLC/CXCL13-producing DC

Dendritic cells (DC) play a pivotal role in regulating immune responses. We previously reported aberrant high production of B lymphocyte chemoattractant (BLC/CXCL13) by DC in aged BWF1 mice, amurine model for systemic lupus erythematosus (SLE). We describe here that CD11b+CD11c+ cells were markedly increased in the peripheral blood (PBL-DC) in aged BWF1, but not in similarly aged NZB or NZW mice. Part of PBL-DC showed a typical dendritic morphology and expressed MHC class II molecules, and had a weak, but significant antigen-presenting ability in mixed lymphocytereaction. PBL-DC were chemoattracted to several chemokines in vitro including secondary lymphoid tissue chemokine (SLC), liver and activation-regulated chemokine (LARC), RANTES, macrophage inflammatory protein-1alpha, whereas splenic mature DC from aged BWF1 mice were preferentially chemoattracted towards SLC. BLC production was induced when PBL-DC were cultured in the presence of TNF-alpha for 3 days. BLC expression was also induced in bone marrow-derived DC when they were differentiated into mature DC in the presence of TNF-alpha and IL-1beta, while both IFN-alpha and IFN-gamma failed to induce BLC expression in bone marrow-derived DC. Since TNF-alpha expression is increased in aged BWF1 mice, DC recruitment in the circulation and maturation into BLC-producing DC by TNF-alpha may play a pivotal role in the development of systemic autoimmune diseases.