Hepatocyte growth factor ameliorates dermal sclerosis in the tight-skin mouse model of scleroderma

The tight-skin (TSK/+) mouse, a genetic model of systemic sclerosis (SSc), develops cutaneous fibrosis and defects in pulmonary architecture. Because hepatocyte growth factor (HGF) is an important mitogen and morphogen that contributes to the repair process after tissue injury, we investigated the role of HGF in cutaneous fibrosis and pulmonary architecture defects in SSc using TSK/+ mice. TSK/+ mice were injected in the gluteal muscle with either hemagglutinating virus of Japan (HVJ) liposomes containing 8 μg of a human HGF expression vector (HGF-HVJ liposomes) or a mock vector (untreated control). Gene transfer was repeated once weekly for 8 weeks. The effects of HGF gene transfection on the histopathology and expression of tumor growth factor (TGF)-β and IL-4 mRNA in TSK/+ mice were examined. The effect of recombinant HGF on IL-4 production by TSK/+ CD4(+ )T cells stimulated by allogeneic dendritic cells (DCs) in vitro was also examined. Histologic analysis revealed that HGF gene transfection in TSK/+ mice resulted in a marked reduction of hypodermal thickness, including the subcutaneous connective tissue layer. The hypodermal thickness of HGF-treated TSK/+ mice was decreased two-fold to three-fold compared with untreated TSK/+ mice. However, TSK/+ associated defects in pulmonary architecture were unaffected by HGF gene transfection. HGF gene transfection significantly inhibited the expression of IL-4 and TGF-β1 mRNA in the spleen and skin but not in the lung. We also performed a mixed lymphocyte culture and examined the effect of recombinant HGF on the generation of IL-4. Recombinant HGF significantly inhibited IL-4 production in TSK/+ CD4(+ )T cells stimulated by allogeneic DCs. HGF gene transfection inhibited IL-4 and TGF-β mRNA expression, which has been postulated to have a major role in fibrinogenesis and reduced hypodermal thickness, including the subcutaneous connective tissue layer of TSK/+ mice. HGF might represent a novel strategy for the treatment of SSc

Demonstration of local expansion toward large-scale entangled webs

We demonstrate an optical gate that increases the size of polarization-based W states by accessing only one of the qubits. Using this gate, we have generated three-photon and four-photon W states with fidelities $0.836\pm 0.042$ and $0.784\pm 0.028$, respectively. We also confirmed existence of pairwise entanglement in every pair of the qubits including the one that was left untouched by the gate. The gate is applicable to any size of W states and hence is a universal tool for expanding entanglement.Comment: 5 pages, 4 figure

Pseudotachylytes from Langhovde and Skarvsnes in the Lützow-Holm Complex, East Antarctica, and their conditions of formation

The Tenth Symposium on Polar Science/Ordinary sessions: [OG] Polar Geosciences, Wed. 4 Dec. / Entrance Hall (1st floor), National Institute of Polar Researc

Geological field survey in the regions of L*tzow-Holm Bay, Prince Olav Coast and Enderby Land, 2018-2019 (JARE-60)

The Tenth Symposium on Polar Science/Ordinary sessions: [OG] Polar Geosciences, Wed. 4 Dec. / 3F Seminar room, National Institute of Polar Researc

Convenient Estimation for Counterion Dissociation of Cationic Micelles Using Chloride-Sensitive Fluorescence Probe

Chloride-sensitive fluorescence probe provides a new approach to studying the degree of micellar counterion dissociation (α). The fluorescence of N-ethoxycarbonylmethyl-6-methoxyquinolinium bromide (MQAE) is quenched by chloride ion with linear Stern–Volmer plots. Thus the fluorescence intensity can be used to monitor the concentration of free chloride ion in micellar solutions. The Stern–Volmer plot gave a distinct break at critical micelle concentration (CMC) due to the counterion binding to micelles. The estimated α and CMCs of cationic surfactants including fluorocarbon ones were in fair agreement with the reported experimental values. The MQAE has greater sensitivity to bromide ion of CTAB than chloride ion of CTAC. The α of 0.16 for CTAB micelles was almost constant up to 0.2 M CTAB at 35°C. The α values of CTAB micelles decreased with increasing the concentrations of CTAB and NaBr along with micellar growth

Molecular targeting of hepatocyte growth factor by an antagonist, NK4, in the treatment of rheumatoid arthritis

INTRODUCTION: Hepatocyte growth factor (HGF) is a potent proangiogenic molecule that induces neovascularization. The HGF antagonist, NK4, competitively antagonizes HGF binding to its receptor. In the present study, we determined the inhibitory effect of NK4 in a rheumatoid arthritis (RA) model using SKG mice. METHODS: Arthritis was induced in SKG mice by a single intraperitoneal injection of β-glucan. Recombinant adenovirus containing NK4 cDNA (AdCMV.NK4) was also injected intravenously at the time of or 1 month after β-glucan injection. Ankle bone destruction was examined radiographically. The histopathologic features of joints were examined using hematoxylin and eosin and immunohistochemical staining. Enzyme-linked immunosorbent assays were used to determine the serum levels of HGF, interferon γ (IFN-γ, interleukin 4 (IL-4) and IL-17 production by CD4(+ )T cells stimulated with allogeneic spleen cells. RESULTS: The intravenous injection of AdCMV.NK4 into SKG mice suppressed the progression of β-glucan-induced arthritis. Bone destruction was also inhibited by NK4 treatment. The histopathologic findings of the ankles revealed that angiogenesis, inflammatory cytokines and RANKL expression in synovial tissues were significantly inhibited by NK4 treatment. Recombinant NK4 (rNK4) proteins inhibited IFN-γ, IL-4 and IL-17 production by CD4(+ )T cells stimulated with allogeneic spleen cells. CONCLUSIONS: These results indicate that NK4 inhibits arthritis by inhibition of angiogenesis and inflammatory cytokine production by CD4(+ )T cells. Therefore, molecular targeting of angiogenic inducers by NK4 can potentially be used as a novel therapeutic approach for the treatment of RA

Tight junctions in Schwann cells of peripheral myelinated axons: a lesson from claudin-19–deficient mice

Tight junction (TJ)–like structures have been reported in Schwann cells, but their molecular composition and physiological function remain elusive. We found that claudin-19, a novel member of the claudin family (TJ adhesion molecules in epithelia), constituted these structures. Claudin-19–deficient mice were generated, and they exhibited behavioral abnormalities that could be attributed to peripheral nervous system deficits. Electrophysiological analyses showed that the claudin-19 deficiency affected the nerve conduction of peripheral myelinated fibers. Interestingly, the overall morphology of Schwann cells lacking claudin-19 expression appeared to be normal not only in the internodal region but also at the node of Ranvier, except that TJs completely disappeared, at least from the outer/inner mesaxons. These findings have indicated that, similar to epithelial cells, Schwann cells also bear claudin-based TJs, and they have also suggested that these TJs are not involved in the polarized morphogenesis but are involved in the electrophysiological “sealing” function of Schwann cells

Immunohistochemical Features of Primary Pure Squamous Cell Carcinoma in the Thyroid: An Autopsy Case

Primary squamous cell carcinoma (SCC) in the thyroid is extremely rare and has been reported in < 1% of all thyroid cancer cases. Primary SCC in the thyroid was thought to be a transitional form derived from adenocarcinomas; therefore, the majority of reported cases have focused on the conjunction with other histological adenocarcinomas. A 73-year-old male presented to our hospital with bilateral vocal fold palsy and an anterior neck mass. Ultrasound sonography revealed a bulky tumor in the thyroid and bilateral cervical lymphadenopathy. We performed fine-needle aspiration cytology from the thyroid tumor, which revealed SCC. Positron emission tomography/computed tomography showed distant metastases in the lungs, mediastinal lymph nodes, and vertebra. We diagnosed the patient as having stage IVC SCC in the thyroid and administered weekly paclitaxel. Four and a half months after treatment initiation, the tumor progression resulted in aspiration pneumonia, which proved fatal. We performed an autopsy in accordance with the patient’s wishes. Pathological findings revealed that all carcinomas in the thyroid, cervical lymph nodes, and lungs were pure SCCs. Immunohistochemical examinations for PAX8, thyroglobulin, and TTF-1 were all negative. Differentiated thyroid carcinomas have 3 major positive markers – PAX8, thyroglobulin, and TTF-1 –, and PAX8 is also sometimes positive for SCC in the thyroid. PAX8 positivity of SCC in the thyroid might, however, be associated with conjunction with other histological adenocarcinomas such as papillary or follicular thyroid carcinoma; therefore, pure SCC in the thyroid might be negative for PAX8