The extract from Nandina domestica THUNBERG inhibits histamine- and serotonin-induced contraction in isolated guinea pig trachea

Although the fruit of Nandina domestica THUNBERG (ND) has been used to treat respiratory disorders such as coughing and breathing difficulty in Japan for many years, very little is known about mechanisms underlying its action. In the present study, we investigated effects of the crude extract from ND (NDE) and one of its constituents, nantenine, on contractile responses in isolated guinea pig tracheal ring preparations. In normal experimental condition, guinea pig trachea remained tonically contracted during the resting state, and addition of NDE (1 mg/ml) caused a relaxation of tracheal smooth muscles, but had little effect on the responsiveness of trachea to acetylcholine. The basal, tonic contraction was abolished by the presence of atropine and indomethacin. In this condition, NDE at 0.1-1 mg/ml inhibited histamine-induced contraction in both competitive and non-competitive manners. NDE at 0.01-1 mg/ml inhibited serotonin-induced contraction in a competitive manner. Nantenine (2-20 microM) did not affect histamine-induced contraction, and slightly inhibited serotonin-induced contraction. These results suggest that NDE has inhibitory effects on tracheal smooth muscle contraction, and nantenine cannot account solely for this effect of NDE.     

Association between passive smoking and salivary markers related to periodontitis

OBJECTIVES: The mechanism of passive smoking in terms of development of periodontitis has not been investigated. This study examined the effect of passive smoking on salivary markers related to periodontitis. METHODS: Periodontal status was evaluated on the basis of probing pocket depth and clinical attachment level in 273 workers. Salivary marker levels were determined by enzyme assay including enzyme-linked immunosorbent assay. Six periodontal pathogens in saliva were assessed using real-time PCR methodology. Non-, passive and active smokers were defined as subjects exhibiting salivary cotinine levels of 0 (53 subjects), 1-7 (118) and > or = 8 ng/ml (102). RESULTS: Levels of salivary markers, including IL-1beta, lactoferrin, albumin and aspartate aminotransferase (AST), were elevated significantly in passive smokers relative to non-smokers. Additionally, these marker levels, with the exception of IL-1beta, decreased significantly in active smokers in comparison with passive smokers. However, no meaningful differences in percentages of periodontal pathogens were observed between non- and passive smokers. Multiple linear regression analyses were performed for each marker utilizing age, gender, cotinine level and periodontal status as independent variables. IL-1beta, albumin and AST were independently associated with cotinine level. CONCLUSION: Passive smoke exposure leads to elevation of IL-1beta, albumin and AST levels in saliva.     

Mechanisms of mucin production by rhinovirus infection in cultured human airway epithelial cells

Mucus hypersecretion relates to exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD) caused by rhinovirus (RV) infection. We examined the mechanisms of RV infection-induced mucin production in human tracheal surface epithelial cells and submucosal gland cells. RV14 up-regulated the mRNA expression of MUC2, MUC3, MUC5AC, MUC5B and MUC6, and increased MUC5AC and total mucin concentration in supernatants and lysates of the surface cells. An inhibitor of the nuclear factor kappaB caffeic acid phenylethyl ester, inhibitors of selective p44/42 mitogen-activated protein kinase-kinase PD98059 and U0126, and a selective Src inhibitor PP1 attenuated MUC5AC mRNA expression, and secretion and production of MUC5AC and total mucin glycoprotein in the surface cells. In the gland cells, RV14 also increased mRNA expression of MUC2, MUC5AC, MUC5B and MUC7, and the inhibitors attenuated the secretion of total mucin glycoprotein. Src-related p44/42 mitogen-activated protein kinase pathway may be associated with RV-induced mucin hypersecretion in human airways.     

Statins,inhibitors of 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase,function as inhibitors of cellular and molecular components involved in type I interferon production

Objective

Statins, which are used as cholesterol‐lowering agents, have pleiotropic immunomodulatory properties. Although beneficial effects of statins have been reported in autoimmune diseases, the mechanisms of these immunomodulatory effects are still poorly understood. Type I interferons (IFNs) and plasmacytoid dendritic cells (PDCs) represent key molecular and cellular pathogenic components in autoimmune diseases such as systemic lupus erythematosus (SLE). Therefore, PDCs may be a specific target of statins in therapeutic strategies against SLE. This study was undertaken to investigate the immunomodulatory mechanisms of statins that target the IFN response in PDCs.

Methods

We isolated human blood PDCs by flow cytometry and examined the effects of simvastatin and pitavastatin on PDC activation, IFNα production, and intracellular signaling.

Results

Statins inhibited IFNα production profoundly and tumor necrosis factor α production modestly in human PDCs in response to Toll‐like receptor ligands. The inhibitory effect on IFNα production was reversed by geranylgeranyl pyrophosphate and was mimicked by either geranylgeranyl transferase inhibitor or Rho kinase inhibitor, suggesting that statins exert their inhibitory actions through geranylgeranylated Rho inactivation. Statins inhibited the expression of phosphorylated p38 MAPK and Akt, and the inhibitory effect on the IFN response was through the prevention of nuclear translocation of IFN regulatory factor 7. In addition, statins had an inhibitory effect on both IFNα production by PDCs from SLE patients and SLE serum–induced IFNα production.

Conclusion

Our findings suggest a specific role of statins in controlling type I IFN production and a therapeutic potential in IFN‐related autoimmune diseases such as SLE.

     

Worsened long-term outcomes and postoperative complications in octogenarians with lung cancer following mediastinal lymph-node dissection

We evaluated the effects of mediastinal lymph-node dissection on outcomes in octogenarians with primary lung cancer. Outcomes and postoperative complications were retrospectively investigated in 48 octogenarians with anatomically resected lung cancer, of whom 23 underwent a mediastinal lymph-node dissection (ND2 group) and 25 a limited lymphadenectomy (ND0-1 group). Forty-three patients underwent a lobectomy, two a pneumonectomy, and three a segmentectomy. The five-year survival rate for all was 35%, while that for those in pathological stage I was 43.3% and for those in stage II+III was 21.2%. As for lymph node dissection, the five-year survival rate for the ND0-1 group (54.3%) was superior to that for the ND2 group (21.7%) (P=0.022). For patients in pathological stage I, those rated ND0-1 had a better five-year survival than those rated ND2 (61.9% vs. 28.6%) (P=0.041). In addition, mediastinal lymph-node dissection increased the incidence of postoperative cardiac complications (P=0.004). Our results indicate that major pulmonary resection with mediastinal lymph-node dissection is associated with a higher rate of mortality in octogenarians with lung cancer.     

Preferential expansion of human umbilical cord blood-derived CD34-positive cells on major histocompatibility complex-matched amnion-derived mesenchymal stem cells

Background

We previously found in a murine hematopoietic system that hematopoietic stem cells show high differentiation and proliferation capacity on bone marrow-derived mesenchymal stem cells/stromal cells (microenvironment) with “self” major histocompatibility complex (MHC).

Design and Methods

We examined whether amnion-derived adherent cells have the characteristics of mesenchymal stem cells, and whether these adherent cells can support the proliferation of umbilical cord blood-derived lineage-negative and CD34-positive cells (Lin^–CD34⁺ cells) obtained from the same fetus to a greater extent than those derived from other fetuses.

Results

Culture-expanded amnion-derived adherent cells expressed mesenchymal stem cell markers and HLA-ABC molecules and could differentiate into osteoblasts, adipocytes and chondrocyte-like cells, indicating that the cells have the characteristics of mesenchymal stem cells. The Lin^–CD34⁺ cells purified from the frozen umbilical cord blood were strongly positive for HLA-ABC, and contained a large number of hematopoietic stem cells. When the Lin^–CD34⁺ cells were cultured on the autologous (MHC-matched) or MHC-mismatched amnion-derived adherent cells in short-term assays (hematopoietic stem cell-proliferation) and long-term culture-initiating cell assays, greater expansion of the Lin^–CD34⁺ cells was observed in the MHC-matched combination than in MHC-mismatched combinations. The concentration of granulocyte-macrophage colony-stimulating factor in the culture supernatants of the long-term culture-initiating cell assays was significantly higher in the MHC-matched combination than in MHC-mismatched combinations.

Conclusions

It is likely that a MHC restriction exists between hematopoietic stem cells and mesenchymal stem cells/stromal cells in the human hematopoietic system and that granulocute-macropage colony-stimulating factor contributes to some extent to the preferential hematopoiesis-supporting ability of the MHC-matched amnion-derived adherent cells.     

A case of superficial angiomyxoma

We report a case of a 19-year-old man who showed a brownish, elastic-soft, multilocular, pedunculated, solid tumor (10 × 6 × 6 cm), with scale crust and erosion, on the medial side of the right thigh. The histopathology of a specimen removed completely revealed a tumor that was located between the middle layer of the dermis and the subcutaneous fatty tissue, was filled with a mucoid material, and was surrounded by a fibrous tissue. The tumor consisted of small thin-walled blood vessels and spindle-shaped or stellate tumor cells without cytological atypia in addition to the mucoid material. Immunohistochemistory revealed that the tumor cells express the vimentin stain. Based on these clinical and histologic findings, we diagnosed the skin condition as superficial angiomyxoma.     

Ultrasonic tissue characterization of photodamaged skin by scanning acoustic microscopy

The aim of this study was to ultrasonically characterize photodamaged skin of the elderly at the microscopic level using scanning acoustic microscopy which showed two-dimentional distribution of sound speed in the skin section. We confirmed that the expression level of the elastin gene was increased in the preauricular skin (photodamaged area), compared with postauricular skin (photo-protected area). The expression level of the procollagen gene was also increased in the preauricular skin compared with postauricular skin. The preauricular skin showed higher sound speed in the papillary dermis (Grenz zone). The site of progressive solar elastosis showed a somewhat sound speed velocity than that of the Grenz zone. Immunohistochemical staining showed conserved deposition of collagen in the Grenz zone even in the more photodamaged preauricular skin. These results suggest that fibrosis in the Grenz zone compensates tissue strength with the progress of solar elastosis. The sound speed analysis of skin will provide important information on heterogeneous mechanical changes in the skin during the process of photoaging.     

Cardiac functional analysis with multi-detector row CT and segmental reconstruction algorithm: comparison with echocardiography, SPECT, and MR imaging

PURPOSE: To evaluate accuracy of cardiac functional analysis with multi-detector row computed tomography (CT) and segmental reconstruction algorithm over a range of heart rates. MATERIALS AND METHODS: Institutional review board approval was obtained. Informed consent was not required. Multi-detector row CT (500-msec rotation time, 8 x 1-mm detector collimation) and magnetic resonance (MR) imaging were performed in 50 patients (28 men, 22 women; age range, 46-84 years; mean age, 67 years). Two-dimensional echocardiography was performed in 41 patients, and electrocardiographically (ECG)-gated single photon emission computed tomography (SPECT) was performed in 27. End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), and left ventricular (LV) mass were estimated with multi-detector row CT and compared with values estimated with MR imaging, which served as the reference standard. Additionally, EF values estimated with multi-detector row CT, echocardiography, and SPECT were compared with those estimated with MR imaging. Systemic error and degree of agreement of global functional parameters measured with MR imaging and other modalities were assessed. In a second analysis, linear regression analysis was added. RESULTS: EF estimated with multi-detector row CT agreed and correlated well with EF estimated with MR imaging (bias +/- standard deviation, -1.2% +/- 4.6; r = 0.96). Agreement and correlation were similar for EDV (-0.35 mL +/- 15.2; r = 0.97), ESV (1.1 mL +/- 8.6; r = 0.99), and LV mass (2.5 mL +/- 15.0; r = 0.96). Standard deviation of EF difference between multi-detector row CT and MR imaging was significantly less than that between echocardiography and MR imaging (P < .001) or that between SPECT and MR imaging (P < .001). CONCLUSION: Various LV functional parameters were measured with multi-detector row CT with a segmental approach, and measurements correlated and agreed with those obtained with MR imaging. Moreover, functional analysis with multi-detector row CT was more accurate than that with two-dimensional echocardiography or ECG-gated SPECT.