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The preoperative diagnosis of infection during joint arthroplasty is important for clinical management. However, the evaluation of polymorphonuclear leukocytes (PMNs) during frozen section analysis is sometimes difficult due to frozen artifacts. In the present study, we sought to investigate the utility of intraoperative fresh frozen section (FFS) examination for diagnosis of infection and to evaluate whether the neutrophil-specific surface marker CD66b helps to improve the diagnostic accuracy of infection. A consecutive series of 65 original frozen sections at the time of resection arthroplasty was retrospectively reviewed compared with corresponding permanent sections. The presence of PMNs was determined using intraoperative FFS and permanent sections. Furthermore, CD66b staining was performed to identify PMNs clearly. The ratio of male to female patients was 21:42. The mean age was 70 years. Postoperatively, 25 of 65 cases were histologically diagnosed with infection (25/65; 39%). The sensitivity and specificity of intraoperative FFS relative to permanent section histology were 100% (25/25) and 95% (38/40), respectively. Among 40 patients without infection, two showed false-positive results during intraoperative FFS diagnosis (2/40, 5%). In addition, on CD66b staining, six cases (9%) experienced changes in results, which altered the sensitivity and specificity of intraoperative FFS compared with permanent histology only to 87% and 87%, respectively. In conclusion, the diagnostic performance of intraoperative FFS is high and comparable to yields of permanent section histology. Therefore, intraoperative FFS is highly suitable diagnostic method for detection of infection during joint arthroplasty. And CD66b immunostaining facilitates delicate identification of PMNs, especially in equivocal cases.

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Magnetostrictive materials transduce magnetic and mechanical energies and when combined with piezoelectric elements, evoke magnetoelectric transduction for high-sensitivity magnetic field sensors and energy-efficient beyond-CMOS technologies. The dearth of ductile, rare-earth-free materials with high magnetostrictive coefficients motivates the discovery of superior materials. Fe1-xGax alloys are amongst the highest performing rare-earth-free magnetostrictive materials; however, magnetostriction becomes sharply suppressed beyond x = 19% due to the formation of a parasitic ordered intermetallic phase. Here, we harness epitaxy to extend the stability of the BCC Fe1-xGax alloy to gallium compositions as high as x = 30% and in so doing dramatically boost the magnetostriction by as much as 10x relative to the bulk and 2x larger than canonical rare-earth based magnetostrictors. A Fe1-xGax - [Pb(Mg1/3Nb2/3)O3]0.7-[PbTiO3]0.3 (PMN-PT) composite magnetoelectric shows robust 90° electrical switching of magnetic anisotropy and a converse magnetoelectric coefficient of 2.0 × 10-5 s m-1. When optimally scaled, this high coefficient implies stable switching at ~80 aJ per bit.

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In a previous study, we established a collection of appropriate porcine placental extracts using PBS at 80°C (PE-PBS80) as a food supplement to increase immune activities in a mice model. In this study, piglets were treated with 0.1%, 0.3%, and 0.5% PE-PBS80 for 3 wk after weaning. Experiments were performed at 2 separate farms using 2 different pig varieties. Composition of white blood cells, lymphocyte activation, and cytokine concentrations were analyzed to assess the immune modulation effect. In Exp. 1, the number of white blood cells increased significantly in the PE-PBS80 treatment and T- and B-cell activation increased as well (P < 0.01). Interestingly, piglets in all treatments in Exp. 2 were naturally infected by a rotavirus at the third day of the experiment but recovered after d 10. Increased lymphocyte activation was observed in the PE-PBS80 treatment (P < 0.01) regardless of viral infection. Additionally, unlike in Exp. 1, the percentage of granulocytes and concentrations of interferon-γ, IL-1ß, and IgG increased in the PE-PBS80 treatment (P < 0.01) and were more active in the 0.3% PE-PBS80 treatment compared with the control and the other treatment. In conclusion, 0.3% PE-PBS80 treatment modulated immune activities in antigen-infected piglets. Therefore, the PE-PBS80 pig placental extract, particularly the 0.3% supplement to the normal diet, could be useful as an alternative feed supplement to modulate immune activity during the early piglet period.

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Central aortic systolic blood pressure (SBP-C) can be estimated from a cuff oscillometric waveform derived during the pulse volume plethysmography (PVP) by applying a device-specific aortic pressure-to-PVP waveform-generalized transfer function (A2P(GTF)). The present study compared the performance of an aortic-to-brachial pressure waveforms generalized transfer function (A2B(GTF)), which is independent of any PVP devices, with an A2P(GTF). Generalized transfer function of aortic-to-brachial (A2B(GTF)) and aortic-to-PVP (A2P(GTF)) were generated from the simultaneously obtained central aortic and brachial pressure waveforms recorded by a high-fidelity dual pressure sensor catheter, and the PVP waveform recorded by a customized noninvasive blood pressure monitor during cardiac catheterization in 40 patients, and were then applied in another 100 patients with simultaneously recorded invasive aortic pressure and noninvasively calibrated (using cuff SBP and diastolic blood pressures) PVP waveforms. The mean difference±s.d. between the noninvasively estimated and invasively recorded SBP-C was -2.1±7.7 mm Hg for A2B(GTF), which was not greater than that of -3.0±7.7 mm Hg for A2P(GTF) (P<0.01). In conclusion, SBP-C can be measured reliably using a noninvasive blood pressure monitor by applying either an A2P(GTF) or A2B(GTF) to a noninvasively calibrated PVP waveform. The performance of an A2B(GTF) is not inferior to that of an A2P(GTF).

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OBJECTIVES: Keratinocyte stem/progenitor cells (KSCs) are known to regenerate epidermal tissue which they perform through to their great regenerative capacity. MATERIALS AND METHODS: Because stimulation of resident KSCs may regenerate epidermal tissue, we devised a strategy to find an appropriate KSC activator from natural products and to develop it as a skin-rejuvenating agent. RESULTS: Ent-16α, 17-dihydroxy-kauran-19-oic acid (DHK) isolated from Siegesbeckia pubescens exhibited a KSC-stimulating effect during screening of natural products. DHK increased proliferation and migration of KSCs using the Akt/ERK pathway. We further examined the mechanism of KSC stimulation and found that phosphorylation of Y1068 epithelial growth factor receptor (EGFR) was significantly increased. Functional inhibition of EGFR using neutralizing antibody and a chemical inhibitor, AG1478, attenuated DHK-induced KSC stimulation. In a 3D culture model of KSCs, DHK treatment significantly induced establishment of fully stratified epidermis and increased numbers of p63-positive cells. Likewise, DHK treatment significantly accelerated healing of epidermal wounds created by laser and dermatome, and increased p63-positive cells, in animal models. CONCLUSION: Collectively, these results indicate that DHK regenerates epidermal tissue mainly through EGFR phosphorylation. As DHK has diverse advantages over recombinant growth factors for commercialization (that is long-term stability and skin permeability), DHK might be applied to wound-healing agents and to a basic materials used in cosmetics.

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The effects of pressure wave reflection have been incompletely described by the central augmentation index (cAI) and augmented pressure (Pa). We therefore investigated the determinants of amplitude of the reflected wave (Pb), which is independent of the reflected wave transit time (RWTT) and has been shown to predict cardiovascular mortality in the general population. A total of 180 (117 men, mean age 68 years old) patients were recruited. Carotid pressure waveforms derived by tonometry at baseline and 3 min after administration of sublingual nitroglycerin (NTG) were calibrated and then decomposed into the forward and backward waves to yield Pb. The ratio of pre-ejection period/ejection time (PEP/ET) was measured. By stepwise multivariate analysis, independent determinants of Pb included brachial mean blood pressure (ß=0.56, P<0.001), heart rate (ß=-0.29, P<0.001), age (ß=0.20, P<0.001), PEP/ET (ß=-0.16, P=0.004) and height (ß=-0.13, P=0.018). RWTT, body mass index and sex were significant independent determinants of Pa and cAI but did not contribute to Pb. Change of Pb but not Pa or cAI significantly predicted the changes of carotid systolic (r=0.550, P<0.001) and pulse pressure (r=0.618, P<0.001) after NTG. In conclusion, determinants of Pb differ from those of cAI and Pa. Pb is independent of sex and RWTT.

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BACKGROUND AND PURPOSE: We conducted a genome wide gene expression analysis to explore the biological aspects of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis and tried to confirm the suitability of 15-MPA as a therapeutic candidate for CNS injuries focusing on microglia. EXPERIMENTAL APPROACH: Murine microglial BV2 cells were treated with 15-MPA, and their transcriptome was analysed by using oligonucleotide microarrays. Genes differentially expressed upon 15-MPA treatment were selected for RT-PCR (reverse transcription-polymerase chain reaction) analysis to confirm the gene expression. Inhibition of cell proliferation and induction of apoptosis by 15-MPA were examined by bromodeoxyuridine assay, Western blot analysis of poly-ADP-ribose polymerase and flow cytometry. KEY RESULTS: A total of 514 genes were differentially expressed by 15-MPA treatment. Biological pathway analysis revealed that 15-MPA induced significant changes in expression of genes in the cell cycle pathway. Genes involved in growth arrest and DNA damage [gadd45alpha, gadd45gamma and ddit3 (DNA damage-inducible transcript 3)] and cyclin-dependent kinase inhibitor (cdkn2b) were up-regulated, whereas genes involved in cell cycle progression (ccnd1, ccnd3 and ccne1), DNA replication (mcm4, orc1l and cdc6) and cell proliferation (fos and jun) were down-regulated. RT-PCR analysis for representative genes confirmed the expression levels. 15-MPA significantly reduced bromodeoxyuridine incorporation, increased poly-ADP-ribose polymerase cleavage and the number of apoptotic cells, indicating that 15-MPA induces apoptosis in BV2 cells. CONCLUSION AND IMPLICATIONS: 15-MPA induced apoptosis in murine microglial cells, presumably via inhibition of the cell cycle progression. As microglial activation is detrimental in CNS injuries, these data suggest a strong therapeutic potential of 15-MPA.

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BACKGROUND AND PURPOSE: Traditionally, the stem and root bark of Ulmus davidiana var. japonica (Ulmaceae) have been known to be anti-inflammatory in Korea. Anti-inflammatory effects of torilin, isolated from this plant and the underlying mechanisms were examined by using lipopolysaccharide (LPS)-stimulated microglial BV2 cells. EXPERIMENTAL APPROACH: The cells were treated with torilin prior to LPS exposure and the effects on pro-inflammatory enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and a pro-inflammatory cytokine, interleukin-1beta (IL-1beta) were analysed by RT-PCR, Western blot or elisa. To reveal the mechanism of action of torilin we investigated the involvement of mitogen-activated protein kinase (MAPK) cascades and their downstream transcription factors, nuclear factor-kappaB (NF-kappaB) and cyclic AMP-responsive element (CRE)-binding protein (CREB). KEY RESULTS: Torilin significantly reduced the LPS-induced expression of iNOS, COX-2 and IL-1beta, and the subsequent release of NO, prostaglandin E(2) and IL-1beta into culture medium. LPS stimulation of extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 MAPK was inhibited by torilin. In addition, the inhibitory effect of torilin on NF-kappaB and CREB was shown by torilin-mediated recovery of LPS-induced degradation of inhibitor kappaB-alpha and suppression of LPS-induced phosphorylation of CREB respectively. CONCLUSION AND IMPLICATIONS: This study indicates that torilin inhibited LPS-induced iNOS, COX-2 and IL-1beta via down-regulation of ERK1/2, p38 MAPK, NF-kappaB and CREB and suggests that torilin has a potential as an anti-inflammatory drug candidate.

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PURPOSE: Effective suppression of Kupffer cell function is believed to contribute to the prevention of preservation/reperfusion injury. In this study, effect of gadolinium, a synthetic Kupffer cell suppressant, on the reperfusion injury was examined using a canine partial liver transplantation model. METHODS: About a 70% partial liver segment was harvested and reimplanted in a mongrel recipient dog weighing 20 to 25 kg. Gadolinium chloride (10 mg/kg) was infused via the cephalic vein 24 hours before harvest of the partial liver (gadolinium group, n = 5). Serum aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and morphologic grading of graft were compared with those of a control group (n = 5). Statistical analysis was done with an independent t-test. RESULTS: Average total ischemic time was 4 hours and 27 minutes. At 1 hour after reperfusion, there were no significant differences in AST, ALP, or LDH levels, or pathologic scores. At 48 hours after reperfusion, AST (P = .03) and LDH (P = .05) levels were significantly lower in the gadolinium group. CONCLUSION: Kupffer cell blockade using gadolinium chloride may be effective to reduce ischemia reperfusion injury, but the effect is not evident at an early stage of reperfusion.

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The balance between nitric oxide (NO) and endothelin-1 (ET-1) production is essential to the vascular function that controls organ perfusion. Elevated ET-1 levels in the peritubular capillary network following renal transplantation may be associated with renal allograft rejection. Administration of a nitric oxide donor during the preischemic period has been shown to protect kidney against ischemia-reperfusion injury, but the mechanism underlying this therapeutic benefit remains incompletely understood. We hypothesized that early administration of the NO donor sodium nitroprusside (SNP) may suppress ET-1, thereby improving renal function in an ischemia/reperfusion injury. Sprague-Dawley rats were subjected to 60 minutes of renal warm ischemia and contralateral nephrectomy. Renal biopsies were performed prior to ischemia and reperfusion, and at 1 hour and 48 hours after reperfusion. The animals were divided into four groups: sham group without warm ischemia; early SNP group (SNP given before ischemia); late SNP group (SNP given before reperfusion); and ischemic control. ET-1 expression was assessed by semiquantitative analysis with immunohistochemical stain using ET-1 monoclonal antibody and hematoxylin-eosin staining. Serum creatinine was measured at 48 hours after reperfusion. There were significant improvements in all parameters of the early compared with the late SNP group and the ischemic control, but there was no difference between the late SNP group and the ischemic control. These data suggest that early administration of SNP in renal ischemia-reperfusion improves renal function by suppressing ET-1 expression.

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An aggressive variant of adenosarcoma, mullerian adenosarcoma with sarcomatous overgrowth (MASO) in the cervix is extremely rare. This variant contains obvious, high-grade sarcoma in addition to a low-grade form. In this report, we describe a case of MASO of the uterine cervix and review the clinical and pathological features of these tumors. The patient was a 37-year-old woman with a cervical polypoid mass, which was morphologically considered as a benign endocervical polyp. Microscopically, polypoid cervical mass showed diffuse and dense malignant spindle cell proliferation around the benign endocervical glands and also an area of markedly anaplastic and pleomorphic spindle cell proliferation, so called, sarcomatous overgrowth. Total abdominal hysterectomy and bilateral salpingo-oophorectomy with pelvic lymph node dissection were performed. The patient has been followed-up and neither chemotherapy nor other adjuvant therapies have been administered. At present, she has been clinically free of disease for 9 months since she received surgery. It is extremely rare that MASO of the uterine cervix is presented in premenopausal woman. Gynecologists and pathologists should be aware of the difficulties associated with a delay in the diagnosis of MASO when the tumor is present as a benign looking cervical polyp.

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The availability of a reliable heart failure model in large animals is important. We report upon our efforts to develop a chronic heart failure model in seven goats using sequential ligation of the left anterior descending (LAD) coronary artery and its diagonal branch. After anesthesia and left thoracotomy, the LAD artery was ligated, and the diagonal vessel at the same level was ligated one hour later. Cardiac measurements were performed with a thermodilution catheter and by ultrasonography. Two months after the operation, the same measurements were made and animals were sacrificed for postmortem examinations of their hearts. Hemodynamic measurements, except cardiac output, showed no significant changes immediately after the coronary artery ligation. Echocardiographic measurements showed significant changes in the ejection fraction and fractional shortening without changes in left ventricular dimensions. Wall motion analyses demonstrated variable degrees of anteroseptal dyskinesia and akinesia in all animals immediately after coronary artery ligation. Five animals have undergone hemodynamic and ultrasonographic studies 2 months after coronary artery ligation. The results obtained from these animals showed significant increases in central venous pressure, right ventricular pressure, pulmonary artery pressure, and pulmonary artery capillary wedge pressure, and a significant decrease in cardiac output. Increases in left ventricular dimensions and decreases in ejection fraction with fractional shortening in ultrasonographic studies were also observed. Pathologically, well-demarcated thin-walled anteroseptal infarcts, with chamber enlargement, were clearly seen with dilatation of the heart chambers in all specimens. Based on this study, we conclude that goats, like sheep, can provide a reliable model of chronic heart failure by coronary artery ligation and in view of the many advantages offered by goats, we believe that this animal model will be useful for cardiac experimentation.

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Although peripheral blood eosinophilia is observed in patients with active inflammatory rheumatoid arthritis (RA), RA is not a recognised cause of pulmonary eosinophilia. We describe a 55-year-old woman affected by chronic eosinophilic pneumonia (CEP) concomitantly with an initiation of RA. Both diseases responded rapidly and completely to high-dose corticosteroid therapy. In this patient, the initiation of RA and CEP was directly related, implying a common pathogenetic link between the two diseases.

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Three new tetrahydrofuran-type sesquilignans, called saucerneol A, saucerneol B and saucerneol C were isolated from the underground parts of Saururus chinensis (Saururaceae), together with known lignans, di-O-methyltetrahydrofuriguaiacin B, machilin D and machilin D 4-methyl ether. Their structures were established from several spectral data.

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Four lignan xylosides and two neolignan glycosides were isolated from the stem and root barks of Ulmus davidiana var. japonica. Their structures were identified as lyoniside, nudiposide, 5'-methoxyisolariciresinol-9'-O-beta-D-xylopyranoside, isolariciresinol-9'-O-1-D-xylopyranoside, rel-trans-dihydrodehydroconiferyl alcohol 4'-O-alpha-L-rhamnopyranoside and icariside E3 by comparison of their spectral data with those reported in the literatures, respectively.

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Solitary schwannoma is a benign neoplasm of Schwann cell origin, most frequently occurring in the extremities and the trunk and head regions. The breast is a very unusual site for this tumor. We report a case of benign schwannoma of the breast in a 76-year-old woman. The palpable mass was localized in the lower outer quadrant of the right breast. This intramammary schwannoma appeared sonographically as a well-circumscribed, hypoechoic, slightly inhomogeneous solid mass. Microscopically, it had a pattern similar to that of schwannoma at other sites.

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Acetylcholinesterase (AChE) inhibitory activity-guided fractionation of Angelica gigas led to isolation and identification of a new coumarin, peucedanone (12), and isolation of 11 known coumarins. Among them, decursinol (1) represented the highest inhibitory activity toward AChE in vitro. The correlation of the inhibitory activities of the coumarins toward AChE with their chemical structures was studied.

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Starvation potentiates the hepatotoxicity of a variety of small molecules, including chlorinated hydrocarbons and nitrosamines, through the induction of CYP2E1. A change in CYP2E1 expression during starvation may also alter the pharmacokinetic profiles of xenobiotics. Northern blot and Western blot analyses revealed that hepatic CYP2E1 was not induced during starvation in rats placed in metabolic or wire-bottom cages in contrast to the induction of CYP2E1 in animals housed in solid-bottom cages. We studied the effect of coprophagy on the expression of hepatic CYP2E1 during starvation. The extent of coprophagy was 24% in fed rats. Fecal matter of starving rats was reduced to 14% of control and starving rats re-ingested ~1.6 g of feces per day. The effect of fecal matter on CYP2E1 expression (i.e., 1.6 g/kg/day for 3 days) was assessed in fed or starving rats. Starving rats gavaged with fecal matter for 3 days resulted in a 3.5-fold increase in the level of CYP2E1 mRNA, while fed rats gavaged with feces failed to show an increase in the mRNA. The increase in the CYP2E1 mRNA level accompanied the induction of CYP2E1. Starving rats gavaged with methanol extract of feces (500 mg/kg/day for 3 days) showed a 3.3-fold increase in CYP2E1 mRNA level in the liver. These results provide evidence that CYP2E1 is not induced by starvation without coprophagy, raising the contention that the mechanistic basis for CYP2E1 induction by starvation should be reevaluated.

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