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Total electron content (TEC) and L‐band scintillations measured by several networks of GPS and GNSS receivers that operate in South and Central America and the Caribbean region are used to observe the morphology of the equatorial ionization anomaly (EIA), examine the evolution of plasma bubbles, and investigate the enhancement of L‐band scintillations that occurred on February 12 and 13, 2016. A few weak and short magnetic storms developed these days, and a minor sudden stratospheric warming (SSW) event was initiated a few days before. During these unusual conditions, TEC maps reported a split of the otherwise continuous crests of the EIA and the formation of a large‐scale (thousands of kilometers) almost‐circular structure. The western part of the southern crest faded, and a north‐south aligned segment developed near the center of the South American continent, joining the north and south crests of the EIA, forming an anomaly that resembled a closed loop on the eastern side of the continent. Concurrently with the anomaly events, several GPS stations reported increases in the L‐band scintillation index from 0.4 to values greater than 1. We analyzed TEC values from receivers between ±6° from the magnetic equator to identify and follow TEC depletions associated with plasma bubbles when they reach different stations. Although the magnetic activity was moderate (Kp = 3°), we believe that the anomaly redistribution and the scintillation enhancements are not related to a prompt penetration electric field but to enhancing the semidiurnal lunar tide propitiated by the onset of the minor SSW event. We found that depending on the lunar tide phase cycle, the neutral wind's meridional component can augment sub‐km scale irregularities and enhance L‐band scintillations through the wind gradient instability when U·∇ $\nabla $n < 0 or the action of wind gradients (∇ $\nabla $U) within the bubbles. Our observations imply that the SSW event enables prominent changes in the thermosphere wind system at F‐region altitudes. Plain Language Summary: GPS receivers can measure the total electron content (TEC) between the satellite and the ground receivers. We have used TEC data collected with several networks of GPS receivers in South America to construct maps of TEC over the continent. These maps are used to examine the variability of the low latitude ionosphere during a special event that originates in the northern polar stratosphere called sudden stratospheric warming (SSW), consisting of an increase in the local temperature. In February 2016, a minor SSW produced prominent changes in the equatorial ionization anomaly. The anomaly consists of a pattern of two regions of enhanced densities on both sides of the magnetic equator that develops during the daytime and early evening. A few days after the initiation of the SSW event, the low‐latitude ionosphere dynamics changed, forming a large‐scale structure resembling a closed loop on the continent's eastern side. Concurrently with the anomaly events, several GPS stations reported increases in the level of fadings of the GPS signal‐to‐noise ratio, a process called scintillation. It is indicated that the neutral wind meridional component developed shears and a reversal increasing the level of plasma irregularities at km and sub‐km‐scale lengths, originating a scintillation enhancement. Key Points: Sudden increases in L‐band scintillations coincide with changes in the geometry of the equatorial ionization anomalyThese events occurred on February 12 and 13, 2016, a few days after a minor sudden stratospheric warming eventThe analysis suggests that a meridional neutral wind associated with an increased lunar tide is responsible for anomaly variability [ABSTRACT FROM AUTHOR]

This paper presents updated methods for locating the Poleward and Equatorward Auroral Luminosity Boundaries (PALB and EALB) directly from IMAGE Far UltraViolet (FUV) images of the Northern Hemisphere auroral oval. Separate boundaries are determined from images measured at different FUV wavelengths. In addition, new methods for indirectly estimating the Open‐Closed magnetic field line Boundary (OCB) and the Equatorward Precipitation Boundary (EPB) locations are presented; these new boundaries are derived from a combination of the auroral luminosity boundary estimates with statistical latitudinal offsets derived from comparisons with low‐altitude spacecraft Particle Precipitation Boundaries (PPBs). Subsequently, we derive new circle model fits for all these boundary data sets, as well as new quality control criteria for these model fits. The suitability of circle fits for each of the data sets is discussed, and the OCB and PALB circle fits are validated against the Convection Reversal Boundary (CRB), as measured by low‐altitude in situ spacecraft. All the new boundary data sets, covering the epoch May 2000 to October 2002, are freely available online. Plain Language Summary: The ability to measure and model near‐Earth space, its response to driving forces in the interplanetary solar wind, and the impact of these forces on the Earth's upper atmosphere is the basis for the understanding and forecasting of space weather. Because there is a strong physical connection between the Earth's magnetosphere (the region of near‐Earth space dominated by the Earth's magnetic field) and ionosphere (the ionized region of the upper atmosphere) near the poles, observations of the ionosphere provide information about the magnetospheric state. Dynamic processes within the magnetosphere accelerate electrons and ions within the space environment giving them the energy to precipitate in the upper atmosphere. These high‐energy charged particles excite atmospheric atoms and molecules, creating aurora. The light from the aurora can be observed at ultraviolet wavelengths by space‐based imagers. In this study we identify the higher and lower latitude edges of the aurora and determine their relationship to important particle boundaries. Circles are then fitted to the spatial boundary variations to make sure they are defined across all longitudes. These data sets can be used to identify and track the spatial extent and dynamics of magnetospheric regions and boundaries. Key Points: Improved poleward and equatorward auroral luminosity boundaries are determined from IMAGE FUV measurementsNew Open‐Closed magnetic field line Boundary (OCB) and Equatorward Precipitation Boundary (EPB) data sets are derived from these observationsNew circle model fits are derived for all the boundary data sets [ABSTRACT FROM AUTHOR]

Simultaneous measurements of F‐region neutral winds near 250 km and topside field‐aligned interhemispheric plasma flow near 600 km, made by the ionospheric connections satellite, allow the connection between these parameters to be observationally established for the first time. The largest variations in the topside plasma flows are seen as a function of season and are shown to depend on trans‐equatorial neutral winds near the F peak in a manner that is essentially the same during the daytime and the nighttime for the solar minimum conditions that prevail in 2020. This finding is consistent with established principles of a servo model of the ionosphere for which both production and loss rates in the topside are specified by the O/N2 ratio at the F‐peak height. The intermediate relationships, describing how the neutral wind influences the F‐peak height and how the O+ plasma pressure gradient across the equator influences the interhemispheric plasma flow are also investigated and found to be consistent with expectations. Plain Language Summary: Neutral winds in the upper atmosphere apply collisional forces to the charged particles that produce motions parallel and perpendicular to the magnetic field. Motions parallel to the magnetic field influence the distribution of charged particle pressure and thus change the plasma motion everywhere along the magnetic field. Simultaneous measurements of the neutral winds and the plasma motions at remote locations connected by the magnetic field allow the relationships between these quantities to be observationally established for the first time. These relationships show the direct relationships between the meridional winds near 250 km, the peak height of the ionospheric density and the field‐aligned interhemispheric plasma transport velocity at the apex of the magnetic field near 600 km. Key Points: Meridional winds near the F‐peak directly drive F‐peak height and topside field‐aligned interhemispheric plasma flowsMeridional wind across the magnetic equator at 250 km is linearly related to field‐aligned plasma flow across the magnetic equator at 600 kmIonospheric Connections satellite provides the first simultaneous observations of F‐region winds and topside field‐aligned interhemispheric plasma flows [ABSTRACT FROM AUTHOR]

Background: Microbial dysbiosis has been implicated in the development of atopic dermatitis (AD). The risk of development of AD following early‐life infections remains unclear. Objective: To investigate the impact of early‐life infections on AD development. Methods: This population‐based nested case–control study was conducted using the Taiwan's National Health Insurance Research Database. A total of 5454 AD patients and 16 362 control subjects without AD were identified, for the period 1997 to 2013. Demographic characteristics, comorbidities and maternal factors were compared. Adjusted odds ratio (aOR) was calculated to examine the associations between early‐life infections and subsequent AD by conditional stepwise logistic regression analysis. Results: Mean age was 2.6 ± 2.9 years in both groups. Overall infections (41.8% vs. 28.9%) before the diagnosis of AD were more common in AD patients than in control subjects (P < 0.001). Infectious diseases [aOR, 1.40; 95% confidence interval (CI), 1.29–1.51], skin infections (aOR, 1.55; 95% CI, 1.40–1.71) and systemic antibiotic exposure (aOR 1.67, 95% CI 1.55–1.79) before AD diagnosis were independently associated with AD development on multivariate analyses. These results were consistent across observation periods (0–1, 1–2 and >2 years after birth) and sensitivity analyses after redefining the index date as 3 or 6 months before the date of AD diagnosis. Other independent risk factors included asthma, allergic rhinitis, intussusception and neonatal hyperbilirubinemia. No association with subsequent AD was found for maternal age at delivery, Caesarean delivery or prenatal antibiotic exposure. Conclusion: Infections in early life are associated with AD development in infancy and early childhood. [ABSTRACT FROM AUTHOR]

Abstract: It has been reported that the susceptibility of insect herbivores to entomoviruses is affected by phytochemicals ingested during the acquisition of viral inoculum on the foliage of host plants. However, the relationship between this susceptibility and phytochemicals is poorly understood. To test this hypothesis of plant‐mediated effects on this susceptibility, we measured the effects of foliage from three plants, soybeans (Glycine max), collards (Brassica oleracea) and water convolvuluses (Ipomoea aquatica), on the susceptibility of larval beet armyworm (Spodoptera exigua) to nucleopolyhedrovirus (NPV), and analysed six foliar chemicals (total phenolics, peroxidase [POD], catalase [CAT], superoxide dismutase [SOD], endochitinase and exochitinase) in the three plants, respectively. The results of exponential modelling indicated that the LD50s (median lethal dose) of NPV to larvae increased with the increase in both phenolics and POD but declined with the increase in four other foliar chemicals, while the opposite trend was found between median lethal time (LT50) of NPV and the six foliar chemicals. This study reveals that phenolics and POD decrease host susceptibility to the entomoviruses and that CAT, SOD, endochitinase and exochitinase increase this susceptibility. [ABSTRACT FROM AUTHOR]

The self‐consistent COREDIV code has been used to simulate the Experimental Advanced Superconducting Tokamak (EAST) L‐mode discharges of upper and lower single null configurations operated with tungsten and carbon divertors, respectively. In the simulations, a uniform lithium injection (and, in addition, a C injection for W divertor) from the wall is assumed, and calculations are performed for different diffusion coefficients in the Scrape‐Off Layer (SOL) region. Simulations demonstrate that, in the case with C target, higher lithium flux leads to lower sputtered carbon flux because of the lower particle flux to divertor due to the plasma dilution by lithium. For the case of tungsten target, lithium has almost no influence on plasma parameters. Carbon seeding first leads to higher W concentrations and then to saturated W afterwards. The effect of a prompt re‐deposition process is moderate due to the self‐regulated increase of plasma temperature at the target through tungsten radiation in the core plasma. The simulations can well reproduce the experimental measurements such as plasma density and temperature profiles in the core region, Zeff, total radiation loss and radiation profiles, and electron density and temperature profiles along divertor target. [ABSTRACT FROM AUTHOR]

Contents: Amniotic fluid is a rich source of multipotent mesenchymal stem cells (MSCs). Amniotic fluid stem cells (AFSCs) have become a new source of stem cells; they have low immunogenicity and are easily harvested. For this reason, they may be useful in clinical tissue engineering. Moreover, AFSCs have anti‐inflammatory properties and can repair tissues. This study evaluated the utility of AFSC injection to treat bilateral ovarian dystrophy in Holstein‐Friesian cows. Bovine AFSCs (BAFSCs) were collected at slaughter from Holstein‐Friesian cows during the third or fourth month of pregnancy and cultured in vitro. The BAFSCs began to show a fibroblast‐like morphology. They were positive for β‐integrin, CD44, CD73, CD106 and Oct4 and negative for CD34 and CD45. After induction, the cells differentiated into mesodermal lineages. Bilateral ovarian dystrophy was confirmed by ultrasonography in 16 lactating cows. The subsequent experiment lasted 15 weeks. Serum was collected weekly to analyse progesterone concentrations, and weekly ultrasonography recorded ovarian changes. Each cow was equipped with an automatic heat detection system to facilitate oestrus observation and breeding records. The progesterone concentration of two cows in the treatment group (25%) significantly increased during weeks 10–15. On ultrasonography, the treatment group demonstrated mature follicles after BAFSCs injection, and foetuses were visualized approximately 40 days after artificial insemination (AI). Oestrus rates in the control and treatment groups were 0% (0/8) and 50% (4/8), respectively; pregnancy rates were 0% (0/8) and 25% (2/8), respectively. Calves were successfully delivered in both cases of pregnancy. These results show that BAFSCs can alleviate bovine ovarian dystrophy and restore fertility. [ABSTRACT FROM AUTHOR]

Efficient intersection queries are important for ray tracing. However, building and maintaining the acceleration structures is demanding, especially for fully dynamic scenes. In this paper, we propose a quantized intersection framework based on compact voxels to quantize the intersection as an approximation. With high-resolution voxels, the scene geometry can be well represented, which enables more accurate simulation of global illumination, such as detailed glossy reflections. In terms of memory usage in our graphics processing unit implementation, voxels are binarized and compactly encoded in a few 2D textures. We evaluate the rendering quality at various voxel resolutions. Empirically, high-fidelity rendering can be achieved at the voxel resolution of 1 K3 or above, which produces images very similar to those of ray tracing. Moreover, we demonstrate the feasibility of our framework for various illumination effects with several applications, including first-bounce indirect illumination, glossy refraction, path tracing, direct illumination, and ambient occlusion. [ABSTRACT FROM AUTHOR]

Aim Atrial fibrosis plays a pivotal role in the pathophysiology of heart failure ( HF). The left atrium ( LA) experiences greater fibrosis than the right atrium ( RA) during HF. It is not clear whether LA cardiac fibroblasts contain distinctive activities that predispose LA to fibrosis. Methods LA and RA fibrosis were evaluated in healthy and isoproterenol-induced HF Sprague Dawley rats. Rat LA and RA primary isolated fibroblasts were subjected to proliferation assay, oxidative stress assay, cell migration analysis, collagen measurement, cytokine array and Western blot. Results Healthy rat LA and RA had a similar extent of collagen deposition. HF significantly increased fibrosis to a greater severity in LA than in RA. Compared to isolated RA fibroblasts, the in vitro experiments showed that isolated LA fibroblasts had higher oxidative stress and exhibited higher collagen, transforming growth factor- β1, connective tissue growth factor production and less vascular endothelial growth factor ( VEGF) production, but had similar migration, myofibroblast differentiation and proliferation activities. VEGF significantly increased the collagen production ability of LA fibroblasts, but not RA fibroblasts. LA fibroblasts had more phosphorylated ERK1/2 and P38 expression. ERK inhibitor ( PD98059, 50 μmol L−1) significantly attenuated collagen production and increased VEGF production in RA fibroblasts but not in LA fibroblasts. P38 inhibitor ( SB203580, 30 μmol L−1) significantly attenuated collagen production in LA fibroblasts but not in RA fibroblasts. P38 inhibitor also significantly increased VEGF production in RA and LA fibroblasts. Conclusions Differences in profibrotic activity between LA and RA fibroblasts may be caused by different responses to mitogen-activated protein kinase signalling. [ABSTRACT FROM AUTHOR]

The carmine spider mite Tetranychus cinnabarinus (Boisduval) is a serious pest affecting various glasshouse vegetables, fruits and crops and causes significant damage to crop yields and quality by piercing and sucking foliar tissues. The control of this mite primarily involves the application of synthetic chemical pesticides. In this study, a Solanum nigrum L. extract was evaluated for its potential acaricidal activity against adult female T. cinnabarinus in laboratory conditions, and the S. nigrum extract showed marked efficacy in controlling the carmine spider mite both in vitro and in potted seedlings. Furthermore, the active compound, a phytostanol ester (β-sitosterol-3- O-heptadeca-8 Z, 11 Z-dienoate), was isolated from the petroleum ether-soluble fraction of S. nigrum extract via repeated column chromatography and identified based on its physiochemical properties and spectral data. At 7 days after treatment in a potted seedling experiment, the LC50 values of the S. nigrum extract and active compound were found to be 4.70 and 1.85 g/l, respectively. All of these results demonstrated that the S. nigrum extract and its active component exhibit the potential for use as new natural acaricides for controlling carmine spider mites. [ABSTRACT FROM AUTHOR]

Objective To evaluate the utility of a proposed cell transfer technique for constructing cytological smear microarrays and its potential applications in multiplex immunocytochemical ( ICC) staining. Methods Ninety-six cytology smears, including two pericardial effusions, 22 ascites and 72 pleural effusions, were transferred to a 33-plex cytological microarray. Paired staining of thyroid transcription factor-1 ( TTF-1) and calretinin ICC was performed in duplicate slides. Results Most of the smeared cells selected for transfer could be removed from the original slides with a minimal loss of cells and with no change in morphological features or immunoreactivity. Comparison of the staining results with immunohistochemical staining results, clinical history and histopathological reports available for each patient revealed that TTF-1 was positive in 32/33 metastatic pulmonary adenocarcinomas ( PACs), 1/15 non-pulmonary adenocarcinomas and 0/45 benign effusions. The ICC results for TTF-1 on a transferred cytological microarray revealed high (97%) sensitivity and high (96.7%) specificity for the detection of metastatic PAC. Conclusion Cytology microarrays can be constructed by transferring cells from serous fluid cytological smears, and cells transferred to the microarray retain their morphological integrity and immunoreactivity. Researchers can use the technique for simultaneous immunostaining of multiple specimens in studies of neoplastic or non-neoplastic diseases when available tissue samples are limited. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to "Acute hearing loss in the only hearing ear of 21 patients" by Chen, Y.-J., Tseng, C.-c. & Young, Y.-H. on 6th January 2015 issue.

Background Lichen planus ( LP) is a chronic inflammatory disorder with unknown aetiology. The association between LP and various autoimmune diseases has been reported, but nationwide study of the relationship of LP with associated diseases is quite limited. Objective Our study aims to clarify the association between LP and a variety of autoimmune diseases in Taiwanese. Methods Data were obtained from the National Health Insurance Research Database ( NHIRD) of Taiwan from 1997 to 2011. In total, 12 427 patients with LP and 49 708 age- and gender-matched controls were enrolled. Results Among patients with LP, there were significant associations with systemic lupus erythematosus ( SLE) (multivariate odds ratio [ mOR]: 2.87; 95% CI: 1.97-4.17), Sjögren's syndrome ( mOR: 3.75; 95% CI: 2.66-5.28), dermatomyositis ( mOR: 6.34; 95% CI: 1.82-22.16), vitiligo ( mOR: 2.09; 95% CI: 1.31-3.32) and alopecia areata ( mOR: 2.82; 95% CI: 2.20-3.62). On gender-stratified analyses, SLE and alopecia areata were significantly associated with LP in both genders. The association with Sjögren's syndrome was significant only in female patients. The associations with dermatomyositis and vitiligo became insignificant in both genders. Conclusion Lichen planus is associated with various autoimmune diseases. Further study is required to elucidate the possible underlying mechanisms and roles of autoimmunity in the aetiology of LP. [ABSTRACT FROM AUTHOR]

Ubiquitously distributed in different plant species, plant lectins are highly diverse carbohydrate-binding proteins of non-immune origin. They have interesting pharmacological activities and currently are of great interest to thousands of people working on biomedical research in cancer-related problems. It has been widely accepted that plant lectins affect both apoptosis and autophagy by modulating representative signalling pathways involved in Bcl-2 family, caspase family, p53, PI3K/Akt, ERK, BNIP3, Ras-Raf and ATG families, in cancer. Plant lectins may have a role as potential new anti-tumour agents in cancer drug discovery. Thus, here we summarize these findings on pathway- involved plant lectins, to provide a comprehensive perspective for further elucidating their potential role as novel anti-cancer drugs, with respect to both apoptosis and autophagy in cancer pathogenesis, and future therapy. [ABSTRACT FROM AUTHOR]

Background Some patients with a phenotypic appearance of eosinophilic oesophagitis (EoE) respond histologically to PPI, and are described as having PPI-responsive oesophageal eosinophilia ( PPI- REE). It is unclear if PPI- REE is a GERD-related phenomenon, a subtype of EoE, or a completely unique entity. Aim To compare demographic, clinical and histological features of EoE and PPI- REE. Methods Two databases were reviewed from the Walter Reed and Swiss EoE databases. Patients were stratified into two groups, EoE and PPI- REE, based on recent EoE consensus guidelines. Response to PPI was defined as achieving less than 15 eos/hpf and a 50% decrease from baseline following at least a 6-week course of treatment. Results One hundred and three patients were identified (63 EoE and 40 PPI- REE; mean age 40.2 years, 75% male and 89% Caucasian). The two cohorts had similar dysphagia (97% vs. 100%, P = 0.520), food impaction (43% vs. 35%, P = 0.536), and heartburn (33% vs. 32%, P = 1.000) and a similar duration of symptoms (6.0 years vs. 5.8 years, P = 0.850). Endoscopic features were also similar between EoE and PPI- REE; rings (68% vs. 68%, P = 1.000), furrows (70% vs. 70%, P = 1.000), plaques (19% vs. 10%, P = 0.272), strictures (49% vs. 30%, P = 0.066). EoE and PPI- REE were similar in the number of proximal (39 eos/hpf vs. 38 eos/hpf, P = 0.919) and distal eosinophils (50 vs. 43 eos/hpf, P = 0.285). Conclusions EoE and PPI-responsive oesophageal eosinophilia are similar in clinical, histological and endoscopic features and therefore are indistinguishable without a PPI trial. Further studies are needed to determine why a subset of patients with oesophageal eosinophilia respond to PPI. [ABSTRACT FROM AUTHOR]

Background and Objective Mechanical stretching modulates extracellular matrix ( ECM) protein synthesis by periodontal ligament ( PDL) cells. However, the mechanoregulation of lysyl oxidase ( LOX), a key enzyme for collagen cross-linking, is not fully understood. In the present study, we hypothesized that low-level and high-level mechanical stretching differentially regulates collagen deposition and the expression of LOX and the enzymes responsible for ECM degradation, such as MMP-2 in PDL cells. Material and Methods Human PDL cells were cultured on flexible-bottom culture plates and subjected to cyclic mechanical stretching (3% and 10% elongation at 0.1 Hz) for 24 and 48 h in a Flexercell FX-4000 strain unit. The levels of expression of type I collagen alpha 1 ( COL1A1), type III collagen alpha 1 ( COL3A1), lysyl oxidase ( LOX), MMP2 and TIMP2 mRNAs were analyzed using an RT-PCR technique. The cell layer and the culture medium were separately collected and processed for detection of the following ECM-related molecules: (i) total collagen content using a Sircol dye-binding method; (ii) LOX protein expression by western blotting; (iii) LOX activity using a fluorometric assay; and (iv) MMP-2 enzyme activity by gelatin zymography. Results Low-level (3%) mechanical stretching of PDL cells upregulated the expression of COL1A1, COL3A1 and LOX mRNAs, enhanced the production of collagen and increased the LOX activity but did not change the level of expression of MMP2 or TIMP2 mRNA. The collagen content and LOX activity showed obvious elevation in the medium, but not in the cell layer. High-level (10%) mechanical stretching downregulated COL1A1 mRNA but upregulated COL3A1 mRNA; however, the effect on COL3A1 was smaller, and occurred earlier, compared with the effect on the COL1A1 gene. High-level mechanical stretching upregulated the expression of MMP2 and TIMP2 mRNAs but did not change collagen production or LOX activity. Moreover, high-level mechanical stretching increased the level of pro-MMP-2, especially in the cell layer. Conclusions This study substantiates the mechanoregulation of the expression of ECM-related molecules in PDL cells. High-level mechanical stretching upregulated the expression of MMP2 and TIMP2 mRNAs, but did not affect collagen production or LOX activity. In addition to increasing the transcription of COL1A1, COL3A1 and LOX genes, low-level mechanical stretching enhanced total collagen production and LOX activity, which should favor ECM stabilization. As an effective regulator of ECM remodeling, mechanical stretching can be exploited in periodontal regeneration and ligament tissue engineering via application of appropriate mechanical stimulation. [ABSTRACT FROM AUTHOR]

Background Combined with 24-h pH monitoring, the use of impedance is the most sensitive method available for detecting oesophageal reflux. Normal values for impedance have been previously established in healthy controls studied on and off proton pump inhibitors (PPI). Aims To determine the effects of PPIs on the total number of reflux episodes in the distal oesophagus measured by impedance in patients with and without gastro-oesophageal reflux disease ( GERD). Methods In this prospective randomised double-blinded placebo controlled crossover study, all patients underwent two 24-h pH with impedance studies at least 2 weeks apart. Based on a randomisation scheme, patients received either 40 mg of esomeprazole twice daily for 1 week or identical capsule placebo for 1 week, then all patients were crossed over to the other treatment arm. GERD was defined by the validated Johnson-DeMeester score. Reflux by impedance was defined as a 50% decrease from baseline in retrograde movement of liquid between two impedance sites. Results Sixty-three patients were enrolled and 41 patients completed the study [mean age 52 ± 12 years, 42% (17/41) men, 56% (23/41) Caucasian and 34% (14/41) African American]. Overall, there was no significant decrease in the total number of distal impedance episodes with esomeprazole compared with placebo (mean change 6.1 ± 22, P = 0.100). When analysed separately by GERD status, among GERD-positive patients, there was a significant decrease in distal impedance episodes while on esomeprazole compared with placebo (mean change −16 ± 22, P = 0.023), but not in GERD-negative patients (mean change −0.35 ± 20, P = 0.872). Conclusion Esomeprazole decreases significantly the number of reflux episodes detected by impedance, but only in patients with GERD. [ABSTRACT FROM AUTHOR]

Background and Purpose The KCa3.1 channel is a potential target for therapy of immune disease. We identified a compound from a new chemical class of KCa3.1 inhibitors and assessed in vitro and in vivo inhibition of immune responses. Experimental Approach We characterized the benzothiazinone NS6180 (4-[[3-(trifluoromethyl)phenyl]methyl]-2 H-1,4-benzothiazin-3(4 H)-one) with respect to potency and molecular site of action on KCa3.1 channels, selectivity towards other targets, effects on T-cell activation as well as pharmacokinetics and inflammation control in colitis induced by 2,4-dinitrobenzene sulfonic acid, a rat model of inflammatory bowel disease ( IBD). Key Results NS6180 inhibited cloned human KCa3.1 channels ( IC50 = 9 n M) via T250 and V275, the same amino acid residues conferring sensitivity to triarylmethanes such as like TRAM-34. NS6180 inhibited endogenously expressed KCa3.1 channels in human, mouse and rat erythrocytes, with similar potencies (15-20 n M). NS6180 suppressed rat and mouse splenocyte proliferation at submicrolar concentrations and potently inhibited IL-2 and IFN-γ production, while exerting smaller effects on IL-4 and TNF-α and no effect on IL-17 production. Antibody staining showed KCa3.1 channels in healthy colon and strong up-regulation in association with infiltrating immune cells after induction of colitis. Despite poor plasma exposure, NS6180 (3 and 10 mg·kg−1 b.i.d.) dampened colon inflammation and improved body weight gain as effectively as the standard IBD drug sulfasalazine (300 mg·kg−1 q.d.). Conclusions and Implications NS6180 represents a novel class of KCa3.1 channel inhibitors which inhibited experimental colitis, suggesting KCa3.1 channels as targets for pharmacological control of intestinal inflammation. [ABSTRACT FROM AUTHOR]

Oral Diseases (2012) 18, 809-815 Objective: The infection of human papilloma virus (HPV) has been reported in head and neck cancer; however, the clinical significance of HPV infection on the pathogenesis of oral cavity squamous cell carcinoma (OSCC) is still uncertain. Materials and Methods: The study recruited 103 patients with pathological early-stage OSCC between March 1997 and December 2003 from Chang Gung Memorial Hospital, Taiwan. Tumor specimens were HPV-genotyped by the EasychipVR HPV Blot method. Clinical association study was performed by using chi-square, Kaplan-Meier, and logrank tests. Results: Thirty-one patients (30.1%) were positive for HPV infection. The most frequent HPV types were types 16 (16 patients, 51.6%) and 18 (seven patients, 22.6%). HPV infection was not associated with tumor aggressiveness (pathological tumor stage or differentiation status), risk exposure (alcohol, cigarette, or areca quid chewing habit), or the treatment outcome (disease-free survival or overall survival). However, infection with HPV-18 was associated with the occurrence of a second primary cancers ( P = 0.033), indicating the infection of HPV in OSCC enhances the susceptibility of developing secondary malignancy. Conclusions: There are 30% of the patients with OSCC infected with HPV, with most high-risk types. HPV-18 infection may enhance the susceptibility of second primary tumors. Large scale of validation study will be needed to confirm this result. [ABSTRACT FROM AUTHOR]

Mehl, M. L., Tell, L., Kyles, A. E., Chen, Y.-J., Craigmill, A., Gregory, C. R. Pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide in domestic cats. J. vet. Pharmacol. Therap. 35, 139-146. The pharmacokinetics and pharmacodynamics of A77 1726 and leflunomide after intravenous (i.v.) and oral (p.o.) administration were evaluated in adult cats. Three treatments were administered: a single i.v. dose of A77 1726 (4 mg/kg), a single oral dose of leflunomide (4 mg/kg), and multiple oral doses of leflunomide (2 mg/kg). Mean pharmacokinetic parameter values after a single i.v. dose of A77 1726 were distribution (A) and elimination (B) intercepts (15.2 μg/mL and 34.5 μg/mL, respectively), distribution and elimination half-lives (1.5 and 71.8 h, respectively), area under the curve (AUC0→∞; 3723 μg*h/mL), mean residence time (MRT; 93 h), clearance (Clobs; 1.1 mL/kg/h), and volume of distribution at steady state (Vdss; 97 mL/kg). Mean pharmacokinetic parameter values after a single oral dose of leflunomide were absorption and elimination rate constants (0.3 1/h and 0.01 1/h, respectively), absorption and elimination half-lives (2.3 and 59.1 h, respectively), AUC0→∞ (3966 μg*h/mL), and maximum observed plasma concentration ( Cmax; 38 μg/mL). The bioavailability after a single oral dose of leflunomide was 100%. The mean ± SD A77 1726 concentration that inhibited 50% lymphocytes (EC50) was 16 ± 13.5 μg/mL. The mean ± SD maximum A77 1726 concentration (ECmax) was 61.0 ± 23.9 μg/mL. [ABSTRACT FROM AUTHOR]

Inflammatory responses to microbial products are amplified by a pathway mediated by triggering a receptor expressed on the myeloid cells (TREM)-1. Relatively a few studies have been performed to investigate the role of TREM-1 in macrophage activation in response to parasitic infection. In this study, we delineate the role of the innate immunoreceptor TREM-1 in the parasite Schistosoma mansoni infection model from early to late (chronic) phases of infection. Flow cytometry analysis revealed gradual increase in the production of TREM-1 protein on CD11b myeloid cells, with maximum production at 5 weeks p.i. Similar results in the pattern of TREM-1 mRNA expressions in splenic CD11b cells from infected mice were obtained by real-time PCR. However, unlike in spleen, the TREM-1 mRNA expression in liver tissue showed no significant increase throughout the infection, including periods of maximum production of parasite eggs. Administration of schistosoma egg homogenate antigen to stimulate J774A.1 cells inhibited TREM-1 expression on the surface, indicating that some substances of the Schistosma eggs may inhibit the expression of TREM-1 on macrophages, lowering the macrophage-mediated inflammatory response of infected hosts. [ABSTRACT FROM AUTHOR]

Chien W-H, Gau SS-F, Wu Y-Y, Huang Y-S, Fang J-S, Chen Y-J, Soong W-T, Chiu Y-N, Chen C-H. Identification and molecular characterization of two novel chromosomal deletions associated with autism. Autism is a childhood-onset neurodevelopmental disorder with a strong genetic basis in its etiology. Conventional karyotype analysis has revealed that chromosomal structural aberrations such as translocation, inversion, deletion, and duplication play a role in causing autism spectrum disorders (ASD). In addition, recent array-based comparative genomic hybridization (array CGH) studies discovered that submicroscopic deletion and duplication of DNA segments also contributed significantly to the genetic etiology of ASD. Together, these studies indicate that genomic rearrangement is an important genetic mechanism of ASD. Using karyotyping analysis and array CGH technology, we identified a subtelomeric deletion of approximately 6.8 Mb at 4q35.1-35.2 and a terminal deletion of approximately 2.4 Mb at 8p23.2-pter in two autistic boys, respectively. These two deletions were further validated using fluorescent in situ hybridization and real-time quantitative polymerase chain reaction, and their breakpoints were delineated using high-resolution array CGH. The 4q deletion is a rare de novo mutation, while the transmission of 8p deletion is unknown, because the father of the patient was unavailable for study. These two deletions are rare mutations and were not found in the additional 282 patients with ASD and in the 300 control subjects in our population. The identification of these two chromosomal deletions contribute to our understanding of the genetic basis of ASD, and the haploinsufficiency of several genes located at the deleted regions of chromosome 8p and 4q may contribute to the clinical phenotypes of autism. [ABSTRACT FROM AUTHOR]

Chang MC, Chen YJ, Lee MY, Lin LD, Wang TM, Chan CP, Tsai YL, Wang CY, Lin BR, Jeng JH. Prostaglandin F2α stimulates MEK-ERK signalling but decreases the expression of alkaline phosphatase in dental pulp cells. International Endodontic Journal, 43, 461–468, 2010. Aim To study prostaglandin F2α (PGF2α) receptor expression and downstream signalling in cultured human dental pulp cells and the effect of PGF2α on the alkaline phosphatase (ALP) activity of dental pulp cells. Methodology Human dental pulp cells were cultured and exposed to PGF2α. The expression of PGF2α (FP) receptors was analysed by reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting. The activation of extracellular regulated kinase (ERK) and cAMP responsive element binding protein/activating transcription factor-1 (CREB/ATF-1) signalling was determined by Western blotting. The expression of ALP in pulp cells after exposure to PGF2α was evaluated by ALP staining and PCR. Results Dental pulp cells expressed FP receptor mRNA and protein. Exposure to PGF2α revealed little cytotoxicity to pulp cells. PGF2α induced both ERK and CREB/ATF-1 phosphorylation in pulp cells. Exposure to PGF2α (>1 μmol L−1) further decreased the ALP activity and mRNA expression. However, U0126 (an inhibitor of MEK1) showed little preventive effect on the decline of ALP activity in dental pulp cells by PGF2α. Conclusion PGF2α may potentially activate FP receptors leading to ERK/CREB-ATF-1 activation during its production in inflamed dental pulp. PGF2α attenuated the ALP activity of pulp cells possibly via pathways not solely by MEK/ERK activation. PGF2α is a contributing factor of pulpal inflammation by regulating the activities of pulp cells. [ABSTRACT FROM AUTHOR]

Chang MC, Lin LD, Chen YJ, Tsai YL, Cheng YA, Kuo CS, Chang HH, Tai TF, Lin HJ, Jeng JH. Comparative cytotoxicity of five root canal sealers on cultured human periodontal ligament fibroblasts. International Endodontic Journal, 43, 251–257, 2010. Aim To evaluate the cytotoxicity of current root canal sealers to periodontal ligament (PDL) fibroblasts. Methodology Five root canal sealers (Canals, Canals-N, Topseal, Sealapex, Tubliseal) were prepared and placed into transwells. After initial setting for 1 h, the transwells with sealers were placed into cultured PDL fibroblasts. They were cultured for further 3 or 18 h. Morphological changes were observed. Cell viability was estimated by 3-(4,5-dimethyl-thiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) assay. Results Marked retraction and death of PDL fibroblasts were observed after exposure to Canals or Topseal for 3 h. A 3-h exposure of PDL fibroblasts to Tubliseal stimulated MTT reduction. Canals-N showed little cytotoxicity even after an exposure of 18 h. Conclusion Canals was the most toxic sealer, followed by Topseal. Sealapex and Tubliseal had comparable and moderate cytotoxicity to PDL fibroblasts, whereas Canals-N showed little cytotoxicity. Exposure to Tubliseal may modulate MTT reduction in PDL fibroblasts. Canals-N had good biocompatibility. [ABSTRACT FROM AUTHOR]

HOXD gene cluster maps to chromosome 2q31 and plays a key role in embryonic limb morphogenesis. Mutations of the HOXD13 and HOXD10 genes have been found to be associated with digital and limb malformations. In addition, dysregulation of HOXD gene cluster has been proposed to account for the limb abnormalities in patients with chromosome 2q rearrangements. In this report, we investigated a three-generation family presenting clinical phenotypes of duplication of great toes, tapering fingers, and clinodactyly of the fifth finger in both hands, which were transmitted in a dominant fashion in this family. We identified and validated an interstitial microdeletion of ∼3.4 Mb at chromosome 2q31.1-31.2 by array-based comparative genomic hybridization, fluorescence in situ hybridization, and real-time quantitative polymerase chain reaction that cosegregates with the clinical phenotypes in this family. The microdeletion removes 30 labeled genes including the entire HOXD gene cluster, suggesting that the digital abnormalities of this family may be attributed to the haploinsufficiency of the HOXD gene cluster. The delineation of the microdeletion region may contribute to the genotype–phenotype correlation study in patients with genomic rearrangements of the long arm of chromosome 2 and helps to understand the pathogenesis of haploinsufficiency of the HOXD gene cluster. [ABSTRACT FROM AUTHOR]

Background Peroxisome proliferator-activated receptors (PPAR) mediate inflammatory processes and alter cardiac function. However, it is not clear whether inflammatory cytokines or PPAR ligands regulate PPARs in the cardiomyocytes to modulate cardiac functions. We investigated the effects of tumour necrosis factor-alpha (TNF-α) and PPAR ligands on the expression of PPARs in HL-1 cardiomyocytes. Materials and methods HL-1 cardiomyocytes were incubated with and without TNF-α (1, 10, 25 and 50 ng mL−1) or PPAR ligands (rosiglitazone, pioglitazone and fenofibrate) at concentrations of 0·1, 1 and 10 µm for 24 h. The cells also received SN-50 (NF-κB inhibitor, 50 µg mL−1), ascorbic acid (100 µm) and coenzyme Q10 (10 µm) alone or combined with TNF-α. Results Using reverse transcriptase–polymerase chain reaction and Western blot, we found that incubation of TNF-α (50 ng mL−1) for 24 h decreased PPAR-α, but increased PPAR-γ without altering PPAR-δ. These effects were not changed by co-administration of SN-50. However, co-administration of ascorbic acid prevented the effect of TNF-α both on PPAR-α and PPAR-γ. Coenzyme Q10 partially attenuated the effect of TNF-α on PPAR-γ but did not alter its effect on PPAR-α. The administration of rosiglitazone (10 µm) and pioglitazone (10 µm) for 24 h increased PPAR-γ mRNA, but did not alter PPAR-α or PPAR-δ. Moreover, fenofibrate (0·1, 1 and 10 µm) increased PPAR-γ without any effects on PPAR-α or PPAR-δ. Conclusions Oxidative stress causes the regulations of PPAR-α and PPAR-γ in the TNF-α-treated cardiomyocytes. The up-regulation of PPAR-γ by PPAR ligands may contribute to their anti-inflammation effects. [ABSTRACT FROM AUTHOR]

Background and Purpose: Pulmonary veins are the most important focus for the generation of atrial fibrillation. Abnormal calcium homeostasis with ryanodine receptor dysfunction may underlie the arrhythmogenic activity in pulmonary veins. The preferential ryanodine receptor stabilizer (K201) possesses antiarrhythmic effects through calcium regulation. The purpose of this study was to investigate the effects of K201 on the arrhythmogenic activity and calcium regulation of pulmonary vein cardiomyocytes.Experimental Approach: The ionic currents and intracellular calcium were studied in isolated single cardiomyocytes from rabbit pulmonary vein before and after the administration of K201, by the whole-cell patch clamp and indo-1 fluorimetric ratio techniques.Key Results: K201 (0.1, 0.3, 1 microM) reduced the firing rates in pulmonary vein cardiomyocytes, decreased the amplitudes of the delayed afterdepolarizations and prolonged the action potential duration. K201 decreased the L-type calcium currents, Na(+)/Ca(2+) exchanger currents, transient inward currents and calcium transients. K201 (1 microM, but not 0.1 microM or 0.3 microM) also reduced the sarcoplasmic reticulum calcium content. Moreover, both the pretreatment and administration of K201 (0.3 microM) decreased the isoprenaline (10 nM)-induced arrhythmogenesis in pulmonary veins.Conclusions and Implications: K201 reduced the arrhythmogenic activity of pulmonary vein cardiomyocytes and attenuated the arrhythmogenicity induced by isoprenaline. These findings may reveal the anti-arrhythmic potential of K201. [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the effect of pre-exercise low and high glycaemic index (GI) carbohydrate meals on running performance. Eight endurance-trained male runners (mean age 33 years, sx=1.7; [image omitted] 63 ml · kg-1 · min-1, sx=1.8) completed two trials separated by at least 7 days in a counterbalanced design. Two hours before they were to run and after an overnight fast, each participant consumed an isocaloric meal containing either low (gi=37) or high (gi=77) GI carbohydrate foods (2.4 MJ; 65% carbohydrate; 15% protein; 20% fat) that provided 1.5 g carbohydrate per kilogram of body mass in random order. Each trial consisted of a 21-km performance run on a level treadmill. The participants were required to run at 70% [image omitted] during the first 5 km of the run. They subsequently completed the remaining 16 km in as short a time as possible. All participants achieved a faster performance time after the consumption of the low GI meal (low vs. high GI: 98.7 min, sx=2 vs. 101.5 min, sx=2; P<0.01). Blood glucose and serum free fatty acids concentrations were higher throughout the performance run in the low GI trial. Serum insulin concentrations were higher in the high GI trial during the postpandial resting period. However, there were no differences between trials in serum insulin or blood lactate concentrations throughout exercise. Compared with the high GI trial, carbohydrate oxidation was 9.5% lower and fat oxidation was 17.9% higher during exercise in the low GI trial. In conclusion, our results indicate that compared with an isocaloric high GI meal, the consumption of a low GI meal 2 h before a 21-km performance run is a more effective means of improving performance time. [ABSTRACT FROM AUTHOR]

Background Pulmonary veins (PVs) contain cardiomyocytes with a high arrhythmogenicity for inducing atrial fibrillation. The swelling-activated outwardly rectifying Cl− currents (ICl,swell) are important in the electrical activity of cardiomyocytes. This study was to investigate whether ICl,swell play a role in the PV electrophysiological characteristics. Materials and methods A whole-cell patch clamp was used to investigate the action potentials and ICl,swell in isolated rabbit single PV and atrial cardiomyocytes during immersion in isotonic (290–300 mosm L−1) and hypotonic (220–230 mosm L−1) solutions. The cell length and cell width were measured using confocal microscopy. Results Hypotonic solution induced larger ICl,swell in the PV cardiomyocytes with pacemaker activity than those in the PV cardiomyocytes without pacemaker activity or atrial cardiomyocytes. Hypotonic solution shortened the action potential duration and increased the cell width to a greater extent in the PV cardiomyocytes than in the atrial cardiomyocytes. Moreover, hypotonic solution decreased the PV firing with a decrease in the transient inward currents and delayed after depolarizations. Conclusions These findings suggest that the ICl,swell plays an important role in the electrical activity of the PV cardiomyocytes. [ABSTRACT FROM AUTHOR]

Background and purpose:Platelet hyperactivity is important in the pathogenesis of cardiovascular diseases. Betel leaf (PBL) is consumed by 200-600 million betel quid chewers in the world. Hydroxychavicol (HC), a betel leaf component, was tested for its antiplatelet effect.Experimental approach:We tested the effect of HC on platelet aggregation, thromboxane B2 (TXB2) and reactive oxygen species (ROS) production, cyclooxygenase (COX) activity, ex vivo platelet aggregation and mouse bleeding time and platelet plug formation in vivo. The pharmacokinetics of HC in rats was also assessed.Key results:HC inhibited arachidonic acid (AA) and collagen-induced platelet aggregation and TXB2 production. HC inhibited the thrombin-induced TXB2 production, but not platelet aggregation. SQ29548, suppressed collagen- and thrombin-induced TXB2 production, but not thrombin-induced platelet aggregation. HC also suppressed COX-1/COX-2 enzyme activity and the AA-induced ROS production and Ca2+ mobilization. HC further inhibited the ex vivo platelet aggregation of platelet-rich plasma (>100 nmole/mouse) and prolonged platelet plug formation (>300 nmole/mouse) in mesenteric microvessels, but showed little effect on bleeding time in mouse tail. Moreover, pharmacokinetics analysis found that more than 99% of HC was metabolized within 3 min of administration in Sprague-Dawley rats in vivo.Conclusions and implications:HC is a potent COX-1/COX-2 inhibitor, ROS scavenger and inhibits platelet calcium signaling, TXB2 production and aggregation. HC could be a potential therapeutic agent for prevention and treatment of atherosclerosis and other cardiovascular diseases through its anti-inflammatory and antiplatelet effects, without effects on haemostatic functions.British Journal of Pharmacology (2007) 152, 73–82; doi:10.1038/sj.bjp.0707367; published online 16 July 2007 [ABSTRACT FROM AUTHOR]

Human B7-H3, a novel member of B7 family, has two isoforms (2IgB7-H3 and 4IgB7-H3). As costimulatory functions of both isoforms are not clarified, there has been much discussion on their expression patterns, T-cell responses, etc. This study generated two specific mouse anti-human 2IgB7-H3 monoclonal antibodies (mAbs) (7D7 and 10F1), whose specificities are quite different from those of the available B7-H3 mAb (21D4) by competition assay. The use of antibodies indicated that B7-H3 was found to have different expression patterns on monocyte-derived dendritic cells, that is the isoform 2IgB7-H3 is tended to express on immature dendritic cells (iDCs), whereas 4IgB7-H3 could be detected in the whole process of maturation of dendritic cells. The isoform 4IgB7-H3 was shown in the immunohistochemistry assay to be more widely expressed than 2IgB7-H3 in human benign and malignant hepatic tissues. Furthermore, flow cytometry and reverse transcription–polymerase chain reaction indicated that 4IgB7-H3 rather than 2IgB7-H3 was the major isoform on many human tumor cell lines. In addition, both 2IgB7-H3- and 4IgB7-H3-transfected cells could promote T-cell proliferation, which could be blocked by 7D7 mAb. These two novel antibodies may shed light on the function of the two B7-H3 isoforms. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the use of transvaginal Doppler ultrasound analysis of urethral clear cell carcinoma.

Objective: Plasminogen activators and their inhibitors are thought to be key participants in the balance of proteolytic and antiproteolytic activities that regulate extracellular matrix (ECM) turnover. However, little is known about the expression of plasminogen/plasmin system at the site of oral submucous fibrosis (OSF). Methods: We compared the activities of tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) between fibroblasts derived from normal buccal mucosa and OSF by using an enzyme-linked immunosorbent assay. Furthermore, arecoline, a major areca nut alkaloid, was challenged with normal buccal mucosal fibroblasts (BMFs) to elucidate whether the activities of t-PA and PAI-1 could be affected by arecoline. Results: Both t-PA and PAI-1 were found to be increased in OSF than in BMFs ( P < 0.01). In addition, there was a statistically significant difference in PAI-1/t-PA ratio between OSF and BMF ( P < 0.01). The addition of arecoline upregulated not only PAI-1, but also t-PA in BMFs ( P < 0.05). In addition, the ratio between PAI-1 and t-PA was found to be significantly increased by a linear regression assay ( P < 0.01). Conclusion: These results suggest that OSF caused by areca quid chewing may be the result of an imbalance in the plasminogen/plasmin system, the net result of which is increased deposition of ECM. [ABSTRACT FROM AUTHOR]

B and T lymphocyte attenuator (BTLA) has been recently identified as a new inhibitory receptor of the CD28 superfamily, with similarities to cytotoxic T lymphocyte activation antigen (CTLA)-4 and programmed death (PD)-1. Engagement of BTLA on T lymphocytes can profoundly reduce the T cell receptor (TCR)-mediated activation. In this study, we generated four monoclonal antibodies (mAbs) against human BTLA. Using the produced mAb 8H9, the BTLA molecule was found to distinctly express on many subgroups of immunocytes and show a regulatory expression, which was in accordance with its unique ligand herpes virus entry mediator (HVEM) in the process of T cell activation. In addition, the expression of BTLA was increased in the CD4+ and CD8+ T cells of pleural fluid in lung cancer patients. Furthermore, we showed that the BTLA-induced negative signals could be triggered by mAb 7D7. Cross-linking of BTLA with mAb 7D7 suppressed T lymphocyte proliferation, downregulated the expression of T cell activation marker CD25, and inhibited the production of interferon (IFN)-γ, interleukin (IL)-2, IL-4, and IL-10. [ABSTRACT FROM AUTHOR]

The aim of the study was to determine pharmacokinetic and pharmacodynamic profiles of FTY720 in cats and identify any toxic side effects. Six adult cats were used for the experimental study. Single oral dosages were tested at 0.05, 0.3 and 1.0 mg/kg. Whole blood drug concentration, total white blood cell and differential counts were monitored. Flow cytometry evaluated the effects on lymphocyte subsets. A toxicity study consisted of cats receiving a dose of 0.15 mg/kg daily for 30 days. Daily observation, physical examination and bloodwork were evaluated to assess for toxicity. All single doses resulted in ≥80% reduction in circulating lymphocytes within 12 h after administration, with the duration of lymphopenia being dose dependent. CD4+ and CD5+ T cells were specifically depleted. Peripheral neutrophils declined by approximately 70% at all dosages tested. No other toxic side effects were observed. Results of this study suggest that FTY720 is effective at inducing a peripheral lymphopenia in cats without any toxic side effects. Currently, cats appear to be the only species in which FTY720 induces a neutropenia. This study provides the foundation for future clinical transplantation trials using FTY720 in cats. By using combination therapy of FTY720 and low dose cyclosporine, the incidence of serious side effects may be reduced while still preventing allograft rejection. [ABSTRACT FROM AUTHOR]

Aim To determine whether (i) proinflammatory cytokines stimulate prostaglandin E2 (PGE2) production and cyclooxygenase (COX) gene expression in dental pulp cells, and (ii) pulp cells that express different prostaglandin E2 receptor (EP) isoforms and their activation by PGE2 leads to downstream Ca2+ signalling. Methodology Cultured human dental pulp cells were exposed to interleukin (IL)-1 β and tumour necrotic factor-alpha (TNF- α). The expression of COX-1 and COX-2 was measured with reverse transcriptase-polymerase chain reaction (RT-PCR). The production of PGE2 was measured using an enzyme-linked immunosorbent assay. Expression of prostaglandin EP receptor isoforms was studied by RT-PCR, whereas fura-2 fluorescence was used to measure calcium mobilization. The Kruskal–Wallis test and Wilcoxon sum rank test with Bonferroni correction were used for statistical analysis. Results Interleukin-1 β and TNF- α stimulate PGE2 production of human dental pulp cells ( P < 0.05). IL-1 β stimulated the COX-2 but not COX-1 mRNA expression. Pulp cells express mainly EP2, EP3 and EP1 receptors as analysed by RT-PCR. PGE2 (0.25–2 μmol L−1) stimulated the Ca2+ mobilization as indicated by increase in fura-2 fluorescence. Conclusions Interleukin-1 β and TNF- α may stimulate PGE2 production in dental pulp cells. Activation of prostaglandin EP receptors in dental pulp cells by PGE2 may induce Ca2+ signalling to regulate cellular biological activity during inflammation. [ABSTRACT FROM AUTHOR]

Background and Objectives The ABO blood group system is the most important blood group system in transfusion medicine. In addition to the major A, B and O alleles, many rare alleles have been defined. Polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and analysis by PCR sequence specific primers (SSP) are commonly conducted for genotyping but have the limitation of being unable to detect unknown substitution(s) in amplified DNA fragments, whereas PCR–single strand conformation polymorphism (SSCP) can be used for both. Materials and Methods Three-hundred unrelated blood donors of the AB phenotype were enrolled. Four pairs of primers were designed to constitute two sets of multiplex PCRs: this amplifies four fragments spanning the entire exon 6 and its immediate flanking regions, nucleotides 432–1065, as well as the 3′ untranslated region of exon 7 of the ABO gene. The SSCP electrophoresis was carried out on a 12·5% polyacrylamide gel in a GenePhor electrophoresis unit. For those with unexpected banding patterns, SSCP analyses were performed in duplicate and samples were cloned and sequenced for exons 6 and 7. Results Seven samples were noted to have six variant alleles, of which five have not been previously reported in the literature. Of these five novel variants, four were derived from the B allele, while the other derived from the A allele. Conclusions By using PCR–SSCP, five novel A/B alleles were found. [ABSTRACT FROM AUTHOR]

Aim To investigate the tissue type plasminogen activator (t-PA) activity in human pulp cells stimulated with Porphyromonas endodontalis ( P. endodontalis) in the absence or presence of p38 inhibitor SB203580, mitogen-activated protein kinase kinase (MEK) inhibitor U0126 and phosphatidylinositaol 3-kinase (PI3K) inhibitor LY294002. Methodology The supernatants of P. endodontalis were used to evaluate t-PA activity in human pulp cells using casein zymography and enzyme-linked immunosorbent assay (ELISA). Furthermore, to search for possible signal transduction pathways, SB203580, U0126 and LY294002 were added to test how they modulated the t-PA activity. Results The main casein secreted by human pulp cells migrated at 70 kDa and represented t-PA. Secretion of t-PA was found to be stimulated with P. endodontalis during 2-day cultured period ( P < 0.05). From the results of casein zymography and ELISA, SB203580 and U0126 significantly reduced the P. endodontalis stimulated t-PA production respectively ( P < 0.05). However, LY294002 lacked the ability to change the P. endodontalis stimulated t-PA production ( P > 0.05). Conclusions Porphyromonas endodontalis enhances t-PA production in human pulp cells, and the signal transduction pathways p38 and MEK are involved in the inhibition of t-PA. [ABSTRACT FROM AUTHOR]

2IgB7-H3 has recently been identified as a new member of the B7 family. Its expression at the protein level remains largely unknown due to the lack of the specific monoclonal antibody (mAb). To characterize the expression of 2IgB7-H3, we newly generated two mouse antihuman 2IgB7-H3 mAbs (4H7 and 21D4). We found the constitutive expression of 2IgB7-H3 on a series of tumor cell lines. Furthermore, the expression was examined on monocyte-derived dendritic cells (Mo-DCs) and DCs from CD34+ hematopoietic progenitor cells (HPC) by means of mAb staining. The results showed that 2IgB7-H3 was expressed on Mo-DCs at a high and stable level during differentiation in vitro. With the maturation of DCs from CD34+ HPCs, the expression of the molecule was upregulated. However, the 2IgB7-H3 was not expressed on fresh isolated T and B lymphocytes, monocytes, or CD34+ HPCs. These results suggested that 2IgB7-H3 may be a valuable surface antigen for the detection of DCs. [ABSTRACT FROM AUTHOR]

Huang F-M, Tsai C-H, Chen Y-J, Liu C-M, Chou M-Y, Chang Y-C.Upregulation of tissue-type plasminogen activator in inflamed human dental pulps.International Endodontic Journal,38, 328–333, 2005.To compare tissue-type plasminogen activator (t-PA) expression in normal human pulp and inflamed human pulp tissue specimens.Thirty pulpal tissue specimens (13 normal and 17 inflamed pulps) were obtained from extracted third molars. The levels of t-PA between normal pulp and inflamed pulp tissues were compared using the quantitative reverse-transcriptase polymerase chain reaction analysis. In addition, immunohistochemistry was used to identify thein situlocalization of t-PA expression in pulp specimens. Wilcoxon–Mann–Whitney rank sum test was applied for the statistical analysis of the results.t-PA mRNA gene was found more in inflamed pulps when compared with normal pulp tissue (P < 0.05). The results from immunohistochemistry demonstrated that t-PA expression was significantly higher in the inflamed pulp (P = 0.025). t-PA stain was detected in the fibroblasts, inflammatory infiltrates and endothelial cells.t-PA expression was significantly higher in inflamed pulp tissue. t-PA may play an important role in the pathogenesis of pulpal inflammation. [ABSTRACT FROM AUTHOR]

Cytokines play an important role in regulating fibroblast function and is likely to play a key role in regulating the initiation and progression of scarring in any fibrotic disease. Interleukin-6 (IL-6) has been implicated in the development of a variety of fibrotic diseases. The aim of this study was to compare IL-6 expression in fibroblasts cultured from normal human buccal mucosa and oral submucous fibrosis (OSF) specimens and further explore the potential mechanism that may lead to induce IL-6 expression.mRNA level of IL-6 in fibroblasts from OSF was compared with normal buccal mucosa. The effects of arecoline, the major areca nut alkaloid, on IL-6 expression in normal human buccal mucosa fibroblasts (BMFs) were measuredin vitro. mRNA was quantified with AlphaImager 2000. To determine whether glutathione (GSH) levels were important in the induction of IL-6 by arecoline, we pretreated cells with 2-oxothiazolidine-4-carboxylic acid (OTZ) to boost GSH levels or with buthionine sulfoximine (BSO) to deplete GSH.Fibroblasts derived from OSF exhibited higher IL-6 gene expression than BMF in mRNA levels (P < 0.05). The exposure of quiescent BMF to arecoline resulted in the elevation of IL-6 mRNA expression in a dose-dependent manner (P < 0.05). IL-6 gene regulated by arecoline correlated with intracellular GSH levels in BMF. Arecoline at a concentration of 129 μM induced about 2.7-fold IL-6 mRNA levels over the 6-h incubation period. However, BSO enhanced the IL-6 mRNA levels by 3.9-fold (P < 0.05). In addition, OTZ was found to marginally reduce the arecoline-induced IL-6 expression by about 1.7-fold (P < 0.05).Taken together, these results suggest that IL-6 expression is significantly upregulated in OSF fibroblasts in areca quid chewers and arecoline may be responsible for the enhanced IL-6 expression. In addition, the regulation of IL-6 expression induced by arecoline is critically dependent on the intracellular GSH concentrations. [ABSTRACT FROM AUTHOR]

Abstract Vivipary with precocious seedlings in mangrove plants was thought to be a hindrance to long-range dispersal. To examine the extent of seedling dispersal across oceans, we investigated the phylogeny and genetic structure among East Asiatic populations of Kandelia candel based on organelle DNAs. In total, three, 28 and seven haplotypes of the chloroplast DNA (cpDNA) atp B-rbc L spacer, cpDNA trn L-trn F spacer, and mitochondrial DNA (mtDNA) internal transcribed spacer (ITS) were identified, respectively, from 202 individuals. Three data sets suggested consistent phylogenies recovering two differentiated lineages corresponding to geographical regions, i.e. northern South-China-Sea + East-China-Sea region and southern South-China-Sea region (Sarawak). Phylogenetically, the Sarawak population was closely related to the Ranong population of western Peninsula Malaysia instead of other South-China-Sea populations, indicating its possible origin from the Indian Ocean Rim. No geographical subdivision was detected within the northern geographical region. An analysis of molecular variance (amova) revealed low levels of genetic differentiation between and within mainland and island populations (ΦCT = 0.015, ΦSC = 0.037), indicating conspicuous long-distance seedling dispersal across oceans. Significant linkage disequilibrium excluded the possibility of recurrent homoplasious mutations as the major force causing phylogenetic discrepancy between mtDNA and the trn L-trn F spacer within the northern region. Instead, relative ages of alleles contributed to nonrandom chlorotype–mitotype associations and tree inconsistency. Widespread distribution and random associations (χ2 = 0.822, P = 0.189) of eight hypothetical ancestral cytotypes indicated the panmixis of populations of the northern geographical region as a whole. In contrast, rare and recently evolved alleles were restricted to marginal populations, revealing... [ABSTRACT FROM AUTHOR]

An extracellular protein was isolated from a species of soil-borne fungi (Trichoderma viride) and its amino acid composition has been determined. The protein is acidic with a molecular mass of 14 200 daltons and is given the trivial name tricholin. Tricholin is a potent inhibitor of cell-free protein synthesis. When rabbit reticulocyte lysate was incubated with tricholin at a concentration of 6.3. x 10-7 M, it completely abolished the capacity of the lysate to support protein synthesis. The inhibition appears to be due to its reaction to ribosomes, since it generates a specific cleavage product, an α-sarcin RNA fragment, from reticulocyte ribosomal RNA. This reaction to ribosomes mimics that of α-sarcin. The antibody α-sarcin strongly cross-reacts with tricholin, while the antibody of tricholin shows a weak reaction with α-sarcin. [ABSTRACT FROM AUTHOR]