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Background: Pulmonary vascular function is impaired with increased pulmonary blood flow (PBF). We hypothesized that a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist would mitigate this effect., Methods: An aorta-to-pulmonary-artery shunt was placed in 11 fetal lambs. Lambs received the PPAR-γ agonist rosiglitazone (RG, 3 mg/kg/d, n = 6) or vehicle (n = 5) for 4 wk. Lung tissue from five normal 4-wk-old lambs was used for comparisons., Results: At 4 wk, pulmonary artery pressure (PAP) and vascular resistance (PVR) decreased with inhaled nitric oxide (NO) in RG- and vehicle-treated shunt lambs. PAP and PVR decreased with acetylcholine (Ach) in RG-treated, but not vehicle-treated, shunt lambs. In vehicle-treated shunt lambs, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, rac1, superoxide, and 3-nitrotyrosine (3-NT) levels were increased, and Ser1177 endothelial NO synthase (eNOS) protein was decreased as compared with normal lambs. In RG-treated shunt lambs, NOx, Ser1177 eNOS protein, and eNOS activity were increased, and NADPH activity, rac1, superoxide levels, and 3-NT levels were decreased, as compared with vehicle-treated shunt lambs. PPAR-γ protein expression was lower in vehicle-treated shunt lambs than in normal and RG-treated shunt lambs., Conclusion: The PPAR-γ agonist RG prevents the loss of agonist-induced endothelium-dependent pulmonary vascular relaxation in lambs with increased PBF, in part, due to decreased oxidative stress and/or increased NO production.

Chromosome enumeration in interphase and metaphase cells using fluorescence in situ hybridization (FISH) is an established procedure for the rapid and accurate cytogenetic analysis of cell nuclei and polar bodies, the unambiguous gender determination, as well as the definition of tumor-specific signatures. Present bottlenecks in the procedure are a limited number of commercial, non-isotopically labeled probes that can be combined in multiplex FISH assays and the relatively high price and effort to develop additional probes. We describe a streamlined approach for rapid probe definition, synthesis and validation, which is based on the analysis of publicly available DNA sequence information, also known as "database mining". Examples of probe preparation for the human gonosomes and chromosome 16 as a selected autosome outline the probe selection strategy, define a timeline for expedited probe production and compare this novel selection strategy to more conventional probe cloning protocols.

Hypertension can induce left ventricular hypertrophy (LVH), and the nitric oxide (NO) pathway plays an important role in the pathogenesis of cardiac hypertrophy. This study aimed to examine whether KMUP-1, a novel xanthine-based derivative, could inhibit LVH in spontaneously hypertensive rats (SHRs) and to investigate potential mechanisms underlying its antihypertrophic effects. Two groups of animals with chronic or subacute LVH were treated. In the chronic LVH group, KMUP-1 (10 or 30 mg/kg/d orally) was administered for 28 days to both normotensive rats and SHRs. In the subacute LVH group, KMUP-1 (0.5 mg/kg/d intraperitoneally) or sildenafil (0.7 mg/kg/d intraperitoneally) was administered for 10 days with or without co-treatment with the nitric oxide synthase (NOS) inhibitor N-omega-nitro-l-arginine (L-NNA; 20 mg/L orally). After treatment, the effects of KMUP-1 or sildenafil on hypertension, cardiac hypertrophy, survival, expression of the NO/soluble guanylate cyclase (sGC)/protein kinase G (NO/sGC/PKG) pathway in the aorta andleft ventricle, and calcineurin A/extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in the left ventricle were examined. In the chronic LVH group, the SHRs developed hypertension with LVH over the 28 days. KMUP-1 attenuated the hypertension and LVH, increased survival rate, enhanced endothelial NOS/cyclic guanosine monophosphate/PKG (eNOS/cGMP/PKG) and decreased inducible NOS (iNOS) expression in the aorta and left ventricle of the SHRs. In the subacute LVH group, both KMUP-1 and sildenafil administered for 10 days attenuated the LVH in SHRs, with enhanced eNOS/cGMP/PKG and suppressed iNOS/calcineurin A/ERK1/2 expression in the left ventricle. In addition, both KMUP-1 and sildenafil attenuated L-NNA-induced LVH. KMUP-1 inhibition of hypertension-induced LVH with associated upregulation of eNOS, downregulation of iNOS in both the aorta and left ventricle, and attenuation of calcineurin A and ERK1/2 signaling in the left ventricle., (Copyright © 2012. Published by Elsevier B.V.)

Background: This study was conducted to determine the effect of ultrasound (US)-guided percutaneous access for percutaneous endovascular abdominal aortic aneurysm repair (PEVAR) on conversion to open repair by femoral cutdown. We also sought to identify other risk factors associated with failure of percutaneous access and conversion to femoral cutdowns., Methods: This is a single-center, retrospective review of 101 patients who underwent PEVAR between January 1, 2005 and July 31, 2009 (56 months). Risk factors that were evaluated for unsuccessful PEVAR included gender, age (≤65 and ≥66 years), US-guided percutaneous access, mechanical failure, abdominal aortic aneurysm size, and the following comorbidities: diabetes, hypertension, vessel calcification, and obesity (body mass index: ≥30 kg/m(2))., Results: There were 10 (9.9%) conversions from percutaneous to femoral cutdown, yielding a success rate of 90.1% for a total percutaneous approach. Each converted patient had one groin converted, resulting in a cutdown rate per groin of 10/202 (5%). There were no 30-day mortalities. Univariate analysis showed that hypertension (P = 0.261), age ≥66 years (P = 0.741), current smoking history (P = 0.649), past smoking history (P = .093), diabetes (P = 0.908), vessel calcification (P = 0.8281), and body mass index ≥30 kg/m(2) (P = 0.052) did not significantly predict conversion to endovascular aortic aneurysm repair (EVAR). Mechanical failure significantly predicted conversion to cutdown EVAR (P = 0.0002), whereas US-guided percutaneous access influenced successful PEVAR (P = 0.030). Multivariate analysis showed that mechanical failure significantly predicted conversion to cutdown EVAR (P = 0.003) and US-guided percutaneous access influenced successful PEVAR (P = 0.040) after adjusting for smoking history and obesity., Conclusion: PEVAR is a viable option for aortic aneurysm repair that may be improved with US-guided percutaneous access by reducing the rate of femoral cutdowns., (Copyright © 2012 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Objective: The objective was to examine hyperlipidemia among Taiwanese patients with schizophrenia., Methods: We obtained a random sample of 766,427 subjects aged ≥18 years in 2005. Subjects with at least one primary diagnosis of schizophrenia and with a primary or secondary diagnosis of hyperlipidemia or medication for hyperlipidemia were identified. We compared the prevalence and incidence of hyperlipidemia in schizophrenic patients with the general population., Results: The prevalence of hyperlipidemia in patients with schizophrenia was higher than that in the general population (8.15% vs. 8.10%; odds ratio 1.17; 95% confidence interval, 1.04-1.31) in 2005. Compared with the general population, schizophrenic patients had a higher prevalence of hyperlipidemia in individuals aged <50 years, among those with higher insurance amount, and among persons living in northern and central regions and in urban areas. The average annual incidence of hyperlipidemia in schizophrenic patients with second-generation antipsychotic use from 2006 to 2008 was higher than that in the general population (1.57% vs. 1.29%; odds ratio 1.31; 95% confidence interval, 1.11-1.55)., Conclusions: Patients with schizophrenia had a much higher prevalence of hyperlipidemia in young adulthood than that in the general population. Schizophrenic patients with second-generation antipsychotic exposure had a higher incidence of hyperlipidemia than individuals in the general population., (Copyright © 2012 Elsevier Inc. All rights reserved.)

An implantable micromachined neural probe with multichannel electrode arrays for both neural signal recording and electrical stimulation was designed, simulated and experimentally validated for deep brain stimulation (DBS) applications. The developed probe has a rough three-dimensional microstructure on the electrode surface to maximize the electrode-tissue contact area. The flexible, polyimide-based microelectrode arrays were each composed of a long shaft (14.9 mm in length) and 16 electrodes (5 µm thick and with a diameter of 16 µm). The ability of these arrays to record and stimulate specific areas in a rat brain was evaluated. Moreover, we have developed a finite element model (FEM) applied to an electric field to evaluate the volume of tissue activated (VTA) by DBS as a function of the stimulation parameters. The signal-to-noise ratio ranged from 4.4 to 5 over a 50 day recording period, indicating that the laboratory-designed neural probe is reliable and may be used successfully for long-term recordings. The somatosensory evoked potential (SSEP) obtained by thalamic stimulations and in vivo electrode-electrolyte interface impedance measurements was stable for 50 days and demonstrated that the neural probe is feasible for long-term stimulation. A strongly linear (positive correlation) relationship was observed among the simulated VTA, the absolute value of the SSEP during the 200 ms post-stimulus period (ΣSSEP) and c-Fos expression, indicating that the simulated VTA has perfect sensitivity to predict the evoked responses (c-Fos expression). This laboratory-designed neural probe and its FEM simulation represent a simple, functionally effective technique for studying DBS and neural recordings in animal models.

Objective: To evaluate the effects on neonatal outcomes between very-low-birth-weight (VLBW) preterm newborns with and without maternal use of antenatal corticosteroids (ACS)., Methods: We retrospectively reviewed medical records of VLBW premature infants who were admitted to Kaohsiung Medical University Hospital between 1999 and 2008. A total of 256 infants were enrolled in this study. A total of 174 neonates did not receive any ACS, and 82 neonates received ACS. A total of 37 neonates received one dose of ACS, and 45 neonates received more than one dose of ACS, referred to as "multiple-dose ACS." In addition, these 82 infants were divided to betamethasone group (n=8) and dexamethasone group (n=50) with 24 infants excluded because of inadequate information., Results: Neonates with multiple-dose ACS had lower incidence of surfactant use and lower rate of intubation than neonates without ACS. There were no differences in the occurrences of intraventricular hemorrhage, necrotizing enterocolitis, retinopathy of prematurity, sepsis, and chronic lung disease with one-dose vs. multiple-dose ACS and in the betamethasone group vs. the dexamethasone group., Conclusions: ACS reduces the need for exogenous surfactant, and the need for endotracheal tube insertion at birth in VLBW premature infants., (Copyright © 2012. Published by Elsevier B.V.)

The newborn screening of homocystinuria in Taiwan has never been formally reported before. Since 1984, out of 5 million newborns screened, only 3 newborns (Han Taiwanese) suffering from homocystinuria were detected in this newborn screening program. Four mutations (p.R121L [c.362G>T], p.E176K [c.526G>A], p.V320G [c.959T>G] and p.G259D [c.776G>A]) were identified in these 3 patients. Unexpectedly, we recently found 8 patients presenting with homocystinuria in an Austronesian Taiwanese Tao tribe. Out of them, three patients participated in the newborn screening program but were unidentified by the current newborn homocystinuria (using methionine as a marker) screening. All the Tao patients are homozygous for a new p.D47E (c.141T>A) mutation. Among the 428 adult islanders screened for the D47E mutation, approximately 1 in 7.78 is a carrier of the mutation, and an estimated 1 in 240 islanders suffered from homocystinuria. This is the highest known prevalence of homocystinuria worldwide. The result of expression studies of all the mutations identified in Taiwan revealed that, except for p.D47E mutation, all mutations were severely limited in their ability to form functional tetramers. The clinical manifestations of the Tao patients varied widely, despite sharing the same mutation and very similar genetic and environmental backgrounds. Comparisons of clinical and biochemical phenotypes of these patients were presented in this report., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Oxidative stress has been widely implicated in the pathogenesis of hypoxia/reoxygenation (H/R) injury. San-Huang-Xie-Xin-Tang (SHXT), a widely used traditional Chinese medication, has been shown to possess antioxidant effects. Here, we investigated whether SHXT and its main component baicalin can attenuate oxidative stress induced by H/R injury. H9c2 rat ventricular cells were exposed to SHXT or baicalin followed by hypoxia for 24 h and/or reoxygenation for 8 h. Pretreatment with SHXT and baicalin both significantly prevented cell death and production of reactive oxygen species induced by hypoxia or H/R in H9c2 cardiomyoctes. In addition, SHXT and baicalin also inhibited hypoxia- or H/R-induced apoptosis, with associated decreased Bax protein, increased Bcl-2 protein, and decreased caspase-3 activity. Furthermore, we found that hypoxia and H/R decreased endothelial nitric oxide synthase (eNOS) expression and nitrite production, and these effects were counteracted by SHXT and baicalein. Finally, SHXT inhibited H/R-induced activation of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation in H9c2 rat ventricular cells. The present study demonstrates for the first time that SHXT can protect cardiomyocytes from H/R injury via inhibition of oxidative stress-induced apoptosis. These cardioprotective effects are possibly mediated through eNOS enhancement and p38 MAPK and JNK-dependent signaling pathways.

Acute lymphoblastic leukemia (ALL) is the most common cancer in children. ALL frequently involves the central nervous system and testicles, but has also been reported to metastasize to the liver and lung. We report a case of a 4-year-old African-American male with a previous history of ALL and hematopoietic stem cell transplant who presented with decreased arm movement and abdominal pain with relapse of primary disease into the brachial plexus and pancreas.

Few medical schools require a stand-alone course to develop knowledge and skills relevant to substance use disorders (SUDs). The authors successfully initiated a new course for second-year medical students that used screening, brief intervention, and referral to treatment (SBIRT) as the course foundation. The 15-hour course (39 faculty teaching hours) arose from collaboration between faculty in Departments of Medicine and Psychiatry and included 5 hours of direct patient interaction during clinical demonstrations and in small-group skills development. Pre- and post-exam results suggest that the course had a significant impact on knowledge about SUDs. The authors' experience demonstrates that collaboration between 2 clinical departments can produce a successful second-year medical student course based in SBIRT principles.

Introduction: After a traumatic event, a significant proportion of victims develop psychiatric disorders. Trauma has been an important ailment among workers. This study aimed to determine the prevalence of post-traumatic stress disorder (PTSD) and other psychiatric disorders at three months after occupational injuries., Methods: Our study candidates were injured workers in Taiwan who were hospitalized for 3 days or longer and received hospitalization benefits from the Labor Insurance program. A two-staged survey study was conducted. A self-reported questionnaire including the Brief Symptom Rating Scale (BSRS-50) and Post-traumatic Symptom Checklist (PTSC) was sent to workers at 3 months after injury. Those who met the criteria were recruited for the second stage phone interview with a psychiatrist using the Mini-international Neuropsychiatrie Interview (MINI)., Results: A total of 2001 workers completed the questionnaire (response rate 45.5%). Among them, 357 (17.8%) fulfilled the criteria for the MINI interview and were invited. A total of 148 (41.5%) completed the phone interview. The estimated rates of PTSD, partial PTSD (PPTSD), major depression, comorbid PTSD/PPTSD and major depression, and either PTSD/PPTSD or major depression were 2.7, 4.1, 3.0, 2.3, and 7.5%, respectively. The estimated rates of either PTSD/PPTSD or major depression among workers who suffered from intracranial injury, fracture, burn, crushing injury, and open wound of upper limbs were 10.4, 6.9, 5.9, 5.8 and 0%, respectively., Conclusions: At three months after occupational injuries, a significant proportion of workers suffered from psychiatric disorders. The rates of psychiatric disorders occurring after intracranial injuries were significantly higher than those occurring after non-intracranial injuries.

Background: Employment insecurity and workplace injustice are important psychosocial hazards. However, few studies of these associations have been conducted in Chinese-speaking populations., Purpose: This study evaluated the psychometric properties of a Chinese version of employment insecurity and workplace justice scales, and examined their associations with the levels of workers' burnout status in Taiwanese workers., Method: Study subjects were participants in a national survey of employees in Taiwan, consisting of 9,636 men and 7,406 women. A self-administered questionnaire was used to assess employment insecurity (six items) and workplace justice (nine items), as well as other psychosocial work characteristics. After the survey was completed, in-depth interviews with 10 employees were conducted for a qualitative evaluation., Results: Cronbach's α was 0.87 or greater for the workplace justice scale and 0.76 or greater for the employment insecurity scale, indicating satisfactory internal consistencies. Exploratory factor analyses revealed a factor pattern consistent with the theoretically assumed structure, except that the items with statements in reversed direction were loaded on separated factors. Higher levels of employment insecurity and lower levels of workplace justice were associated with higher burnout scores. However, results from the qualitative interviews suggested that some questionnaire items contained double-barreled questions, and some questions were misinterpreted or considered irrelevant by participants., Conclusion: The Chinese version of employment insecurity and workplace justice scales were found to have satisfactory reliability and validity. However, improvement of these scales is still needed.

Using various animal models, studies have greatly expanded our understanding of perinatal hypoxia-induced neuronal injury in the newborn at the cellular/molecular levels. However, the synapse-basis pathogenesis and therapeutic strategy for such detrimental alterations in the neonatal brain remain to be addressed. We investigated whether the damaged synaptic efficacy and neurogenesis within hippocampal CA1 region (an essential integration area for mammalian learning and memory) of the neonatal rat brain after perinatal hypoxia were restored by granulocyte-colony stimulating factor (G-CSF) therapy. Ten-day-old (P10) rat pups were subjected to experimentally perinatal hypoxia. G-CSF (10, 30, or 50 μg/kg, single injection/d, P11-16) was s.c. administered to neonatal rats which were analyzed on P17. Perinatal hypoxia reduced the expression in pRaf-pERK1/2-pCREB(Ser-133) signaling, the synaptic complex of postsynaptic density protein-95 (PSD-95) with N-methyl-D-aspartate receptor (NMDAR) subunits (NR1, NR2A, and NR2B), synaptic efficacy, and neurogenesis. A representatively effective dosage of G-CSF (30 μg/kg) alleviated the perinatal hypoxia-induced detrimental changes and improved the performance in long-term cognitive function. In summary, our results suggest a novel concept that synaptic efficacy defects exist in the neonatal brain previously exposed to perinatal hypoxia and that G-CSF could be a clinical potential for the synapse-basis recovery in the perinatal hypoxia suffers.

Objectives: Unilateral hyperlucent lung on chest radiograph is uncommon in children. It is often found incidentally and always refers to Swyer-James syndrome, with decrease in pulmonary vascularity and air trapping during expiration. However, it may occasionally mimic other serious lung diseases such as pulmonary hypoplasia/aplasia, defect of pulmonary artery, and other primary pulmonary disorders. In this study, we hypothesized that there would be characteristic patterns in pulmonary ventilation and perfusion scintigraphy (V/Q scan) in children with unilateral hyperlucency on chest film, which could play an important role in differential diagnosis of this disease group explicitly., Methods: Children with unilateral hyperlucency on chest radiograph had a detailed clinical examination and underwent echocardiography, chest computed tomography, selective pulmonary angiogram, flexible bronchoscopy, and pulmonary V/Q scan., Results: A total of 10 cases were enrolled, including two cases of unilateral pulmonary artery agenesis, three cases of Swyer-James syndrome, two cases of agenesis of the right lung, one case of lobar emphysema, and two cases of tetralogy of fallot with left pulmonary artery stenosis. Besides, an overview of children with unilateral hyperlucent lung is provided, reviewing nine studies (171 patients), including our clinical experience, and finally an algorithm for diagnosis unilateral hyperlucent lung is proposed, based on the characteristics of V/Q scan., Conclusion: We chose a descriptive approach to the V/Q scan in children with unilateral hyperlucent lung on chest radiograph. This result enables us to promote the V/Q scan as a first-line tool in evaluating these patients and to avoid further unnecessary procedures.

The photoluminescence (PL) of well dispersed molecules of a conjugated polymer, poly[2-methoxy-5-((2'-ethylhexyl)oxy)-1,4-phenylene-vinylene] (MEH-PPV), in an optically inert matrix manifested dramatic increases when the individual molecular strands were fully stretched. The PL increase rose with stretching and may reach several folds when the mechanical strain of the matrix polymer went beyond 550%. Strong polarization effects indicate that stretching individual polymer chains was responsible for the PL enhancement. This effect was attributed to suppression of electron-phonon interactions in the stress-rigidified polymer chain segments and may be useful for efficiency-enhanced polymer-based optoelectronic devices., (© 2011 American Chemical Society)

Objective: Labedipinedilol-A, a novel calcium antagonist, has been previously demonstrated to have pleiotropic protective effects in the cardiovascular system. This study aimed to investigate its cytoprotective effects in rat vascular smooth muscle cells (VSMCs) treated with lysophosphatidylcholine (lysoPC), a key lipid component mediating atherogenesis., Methods and Results: VSMCs were incubated with lysoPC with or without labedipinedilol-A pretreatment to determine its effects on lysoPC-induced cell death, Ca(2+) influx, oxidative stress, MAPK signaling and apoptosis. Labedipinedilol-A attenuated lysoPC-induced cell death and Ca(2+) influx. It also reduced reactive oxygen species (ROS) production evoked by lysoPC and down-regulated expressions of NAD(P)H oxidase subunits, Nox1 and Rac1. Moreover, it inhibited lysoPC-induced phosphorylation of MAPK including ERK1/2, JNK, and p38. It mitigated the dissipation of mitochondrial transmembrane potential induced by lysoPC. Lastly, labedipinedilol-A inhibited lysoPC-induced apoptosis with attenuation of caspase-3/-9 activations and modulation of Bax/Bcl-2 protein expressions., Conclusion: Labedipinedilol-A can suppress lysoPC-induced VSMCs death via reducing ROS production and anti-apoptosis. These protective effects are potentially mediated through the inhibition of Ca(2+) influx, down-regulation of the NAD(P)H oxidase subunits (Nox1/Rac1) and MAPK signaling, and attenuation of mitochondrial depolarization. Thus, labedipinedilol-A may have a valuable role in the preventing atherosclerosis associated with hyperlipidemia., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

This work designed and fabricated an optical pickup system based on optical films using the roll-to-roll process. The design combined the advantages of the stacked and planar optical pickup system. Two blazed gratings were used as beam splitters for bending the optical path, while a cylindrical lens was used for astigmatic focus-error detection. The proposed design effectively reduces overall system configuration, component cost, and fabrication complexity.

Ewing sarcoma family tumors (ESFT) are aggressive bone and soft tissue tumors that express EWS-ETS fusion genes as driver mutations. Although the histogenesis of ESFT is controversial, mesenchymal (MSC) and/or neural crest (NCSC) stem cells have been implicated as cells of origin. For the current study we evaluated the consequences of EWS-FLI1 expression in human embryonic stem cell-derived NCSC (hNCSC). Ectopic expression of EWS-FLI1 in undifferentiated hNCSC and their neuro-mesenchymal stem cell (hNC-MSC) progeny was readily tolerated and led to altered expression of both well established as well as novel EWS-FLI1 target genes. Importantly, whole genome expression profiling studies revealed that the molecular signature of established ESFT is more similar to hNCSC than any other normal tissue, including MSC, indicating that maintenance or reactivation of the NCSC program is a feature of ESFT pathogenesis. Consistent with this hypothesis, EWS-FLI1 induced hNCSC genes as well as the polycomb proteins BMI-1 and EZH2 in hNC-MSC. In addition, up-regulation of BMI-1 was associated with avoidance of cellular senescence and reversible silencing of p16. Together these studies confirm that, unlike terminally differentiated cells but consistent with bone marrow-derived MSC, NCSC tolerate expression of EWS-FLI1 and ectopic expression of the oncogene initiates transition to an ESFT-like state. In addition, to our knowledge this is the first demonstration that EWS-FLI1-mediated induction of BMI-1 and epigenetic silencing of p16 might be critical early initiating events in ESFT tumorigenesis.

The polycomb group family protein BMI-1 is overexpressed by and functions as an oncogene in many different human cancers. We have previously shown that BMI-1 promotes the tumorigenicity of Ewing sarcoma family tumors (ESFTs) and that this is mediated independently of CDKN2A repression. In this study, we have discovered that high levels of BMI-1 confer resistance to contact inhibition in ESFT cells. Using stable retroviral transduction, we evaluated the consequences of BMI-1 knockdown on the growth of CDKN2A wild-type and mutant ESFT cells in subconfluent and confluent conditions. Although knockdown of BMI-1 had no effect on proliferation in low-density cultures, at high cell densities it resulted in cell cycle arrest and death. The normal cell contact inhibition response is mediated, in large part, by the recently described Hippo pathway which functions to inhibit cell proliferation and promote cell death by inactivating the Yes-Associated Protein (YAP). Significantly, we found that YAP levels, activity and expression did not diminish in confluent ESFT cells that expressed high levels of BMI-1. In contrast, YAP expression and nuclear localization were reduced in confluent BMI-1 knockdown cells suggesting that silencing of BMI-1 restored contact inhibition by restoring normal activation of the Hippo-YAP growth-suppressor pathway. Importantly, knockdown of YAP in ESFT cells resulted in profound inhibition of cell proliferation and anchorage-independent colony formation suggesting that stabilization and continued expression of YAP is critical for ESFT growth and tumorigenicity. Together, these studies reveal a previously unrecognized link between BMI-1, contact inhibition and the Hippo-YAP pathway and suggest that resistance to contact inhibition in BMI-1 overexpressing cancer cells may be in part a result of Hippo inhibition and aberrant stabilization of YAP.

Eugenol and isoeugenol, two components of clover oil, have been reported to possess several biomedical properties, such as anti-inflammatory, antimicrobial and antioxidant effects. This study aims to examine the anti-inflammatory effects of eugenol, isoeugenol and four of their derivatives on expression of inducible nitric oxide synthase (iNOS) activated by lipopolysaccharide (LPS) in mouse macrophages (RAW 264.7), and to investigate molecular mechanisms underlying these effects. We found that two derivatives, eugenolol and glyceryl-isoeugenol, had potent inhibitory effects on LPS-induced upregulation of nitrite levels, iNOS protein and iNOS mRNA. In addition, they both suppressed the release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) induced by LPS. Moreover, they both attenuated the DNA binding of NF-kB and AP-1, phosphorylation of inhibitory kB-alpha (IkB-alpha), and nuclear translocation of p65 protein induced by LPS. Finally, we demonstrated that glyceryl-isoeugenol suppressed the phosphorylation of ERK1/2, JNK and p38 MAPK, whereas eugenolol suppressed the phosphorylation of ERK1/2 and p38 MAPK. Taken together, these results suggest that that eugenolol and glyceryl-isoeugenol suppress LPS-induced iNOS expression by down-regulating NF-kB and AP-1 through inhibition of MAPKs and Akt/IkB-alpha signaling pathways. Thus, this study implies that eugenolol and glyceryl-isoeugenol may provide therapeutic benefits for inflammatory diseases.

Interleukin 6 is the in vivo growth factor of myeloma cells. In response to IL-6 stimulation, the PI3K/AKT signaling pathway is activated in these cells. With comparative proteomic approaches, this study reveals many putative downstream effectors of the PI3K/AKT pathway. Mass spectrometry analysis of excised protein spots from 2-dimensional gel allowed the identification of proteins such as β-Actin, cyclophilin A, E3 SUMO-protein ligase PIAS-NY protein, HSP 27, PML, and transforming growth factor β-2. Among these putative effectors, β-Actin was chosen for further characterization. Phosphorylation of β-Actin by AKT upon IL-6 stimulation was confirmed by western blotting using a phospho-AKT substrate antibody. Interestingly, IL-6 significantly increased cell migration (P < 0.05) and the content of filamentous actin (P < 0.05). Therefore, IL-6 stimulation could have effects on the migration of myeloma cells, and the phosphorylation of β-Actin is probably involved in the process.

Background: A new engineering intervention measure, an embracing air curtain device (EACD), was used to increase the capture efficiency of cooker hoods and reduce cooking oil fume (COF) exposure in Chinese restaurants., Methods: An EACD was installed in six Chinese restaurants where the cooks complained of COF exposure. Before- and after-installation measurements were taken to compare changes in particulate matter (PM) and polycyclic aromatic hydrocarbons (PAHs) in kitchen air, and changes in levels of urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA). The association between PM and PAHs in air and 8-OHdG and MDA in urine was evaluated by linear mixed-effects regression analysis., Results: Results showed that geometric mean kitchen air levels of PM(10), PM(2.5), PM(1.0) and total particulate PAHs were significantly reduced after the EACDs were introduced. Urinary levels of 8-OHdG and MDA in cooks were also significantly lower after EACD instalment. PM(2.5), PM(1.0) and benzo(a)pyrene (BaP) levels were positively associated with urinary 8-OHdG levels after adjusting for key personal covariates. Urinary MDA levels in cooks were also positively associated with BaP levels after adjusting for key personal covariates., Conclusion: This study demonstrates that the EACD is effective for reducing COF and oxidative stress levels in cooks working in Chinese kitchens.

Purpose: Ewing sarcoma family tumors (ESFT) are aggressive tumors of putative stem cell origin for which prognostic biomarkers and novel treatments are needed. In several human cancers, high expression of the polycomb protein BMI-1 is associated with poor outcome. We have assessed the potential clinical significance of BMI-1 expression level in ESFT., Experimental Design: BMI-1 expression was assessed in 130 tumors by immunostaining and associations with clinical features and outcome determined. The molecular signatures of BMI-1-low and BMI-1-high tumors were compared using microarrays and differentially activated canonical pathways identified by gene-specific enrichment analysis. Automated quantitative analysis of phosphoproteins was used to assess relative levels of pathway activation. Sensitivity to IGF1-R inhibition was determined using MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assays., Results: BMI-1 is overexpressed by the vast majority of ESFTs. However, in 20% of cases, BMI-1 levels are low to undetectable. Significantly, although clinical presentation and outcome were similar between BMI-1-high and BMI-1-low tumors, whole genome expression array analysis showed marked differences in their respective gene expression profiles. Gene-specific enrichment analysis identified that several cancer-associated canonical biological pathways, including IGF1, mTOR, and WNT, are significantly downregulated in BMI-1-low compared with BMI-1-high tumors. Consistent with these in vivo data, the response to IGF1-R inhibition in vitro was diminished in BMI-1-low compared with BMI-1-high ESFT cells., Conclusion: ESFT that do not overexpress BMI-1 represent a novel subclass with a distinct molecular profile and altered activation of and dependence on cancer-associated biological pathways., (©2010 AACR.)

San-Huang-Xie-Xin-Tang (SHXT) is a traditional Chinese medication consisting of three herbs, namely Coptidis rhizome, Scutellariae radix and Rhei rhizome. This study aimed to examine the cardioprotective effects of SHXT in a rat model of acute myocardial apoptosis induced by ischemia/reperfusion (I/R). Vehicle (intravenous saline) or SHXT (intravenous or oral) was administered prior to I/R (occlusion of left coronary artery for 45 min followed by reperfusion for 2 h). In the vehicle group, myocardial I/R caused myocardial infarction with increased plasma cardiac enzymes, severe arrhythmia and mortality. Myocardial apoptosis was induced by I/R as evidenced by DNA ladder and Bcl-2/Bax ratio. In the SHXT group, we found that SHXT significantly reduced plasma levels of cardiac enzymes, arrhythmia scores (from 5 ± 1 to 2 ± 1, P < .01) and mortality rate (from 53 to 0%, P < .01). In addition, pretreatment with intravenous SHXT reduced the infarct size dose-dependently when compared with the vehicle group (10 mg kg(-1): 14.0 ± 0.2 versus 44.5 ± 5.0%, and 30 mg kg(-1): 6.2 ± 1.2% versus 44.5 ± 5.0%, both P < .01). Similarly, oral administration of SHXT reduced the infarct size dose-dependently. Furthermore, SHXT markedly decreased the apoptosis induced by I/R with increased Bcl-2/Bax ratio. Finally, we found that SHXT counteracted the I/R-induced downstream signaling, resulting in increased myocardial eNOS expression and plasma nitrite, and decreased activation of ERK1/2, p38 and JNK. These data suggest that SHXT has cardioprotective effects against I/R-induced apoptosis, and that these effects are mediated, at least in part, by eNOS and MAPK pathways.

Ethylene is a gaseous hormone important for adaptation and survival in plants. To further understand the signaling and regulatory network of ethylene, we used a phenotype-based screening strategy to identify chemical compounds interfering with the ethylene response in Arabidopsis thaliana. By screening a collection of 10,000 structurally diverse small molecules, we identified compounds suppressing the constitutive triple response phenotype in the ethylene overproducer mutant eto1-4. The compounds reduced the expression of a reporter gene responsive to ethylene and the otherwise elevated level of ethylene in eto1-4. Structure and function analysis revealed that the compounds contained a quinazolinone backbone. Further studies with genetic mutants and transgenic plants involved in the ethylene pathway showed that the compounds inhibited ethylene biosynthesis at the step of converting S-adenosylmethionine to 1-aminocyclopropane-1-carboxylic acid (ACC) by ACC synthase. Biochemical studies with in vitro activity assay and enzyme kinetics analysis indicated that a representative compound was an uncompetitive inhibitor of ACC synthase. Finally, global gene expression profiling uncovered a significant number of genes that were co-regulated by the compounds and aminoethoxyvinylglycine, a potent inhibitor of ACC synthase. The use of chemical screening is feasible in identifying small molecules modulating the ethylene response in Arabidopsis seedlings. The discovery of such chemical compounds will be useful in ethylene research and can offer potentially useful agrochemicals for quality improvement in post-harvest agriculture.

Newborn screening for Fabry disease in Taiwan Chinese has revealed a high incidence of the late-onset GLA mutation IVS4 + 919G→A (∼1 in 1,500-1,600 males). We studied 94 adults with this mutation [22 men, 72 women; mean age: men 57.8 ± 6.0 (range 42-68), women 39.1 ± 14.1 years (range 19-82)]. Plasma α-galactosidase A activity assay was 10.4 ± 11.2% of normal in the men and 48.6 ± 19.5% of normal in the women. Echocardiography in 90 of the adults revealed left ventricular hypertrophy (LVH) in 19 (21%), including 14 of 21 men (67%) and 5 of 69 women (7%). Microalbuminuria, based on the urine albumin-to-creatinine ratio measured on at least two occasions, was present in 17 of 86 subjects (20%) (men: 5/20, 25%; women 12/66, 18%). At least one ocular manifestation consistent with Fabry disease was present in 41 of 52 subjects (79%) who underwent ophthalmologic examination, including 8 (15%) with conjunctival vessel tortuosity, 15 (29%) with cornea verticillata, 10 (19%) with Fabry cataract, and 34 (65%) with retinal vessel tortuosity. Among subjects over 40 years of age, men were more likely than women to have LVH [14/21 (67%) vs 5/25 (20%), p < 0.001]. Cardiovascular, renal and ocular abnormalities are highly prevalent in adult Taiwan Chinese subjects with the Fabry mutation IVS4 + 919G→A. Our findings contribute to the limited understanding of the course of this late-onset disease variant and underscore the need for close follow up in such patients.

Postobstructive pulmonary edema is life-threatening, and results from a sudden episode of upper airway obstruction. Croup is generally thought to be a benign condition, but occasionally it can develop into postobstructive pulmonary edema. We present a case of a 5-year-old boy with recurrent croup, who was diagnosed with postobstructive pulmonary edema. Our experience alerts pediatricians to this easily misdiagnosed disease., (Copyright © 2010 Elsevier. Published by Elsevier B.V. All rights reserved.)

Retrograde superior mesenteric artery stenting (ROMS) represents a significant development in the treatment of acute mesenteric ischemia. Compared to traditional surgical mesenteric bypass, ROMS is a less invasive technique that avoids many complications associated with emergent mesenteric bypass. This case report illustrates that retrograde superior mesenteric artery (SMA) stenting is an option for the treatment of acute mesenteric ischemia for patients in extremis.

The clinical observation and treatment of young children with sitosterolemia has rarely been reported. We report clinical, biochemical, and molecular genetic observations and treatment outcomes for five Chinese children from four separate families presenting with sitosterolemia in whom we identified two new (Y329X, G269R) and three known (R446X, N437K, R389H) mutations in the ABCG5 gene. The R389H mutation was found in 50% of alleles. Three of these five patients received cholestyramine therapy with a very good response. However, all patients discontinued this therapy because of poor compliance. Finally, all patients were on ezetimibe therapy and had satisfactory total serum cholesterol levels, though their plant sterol levels were still higher than normal. Another noteworthy finding is that a female infant had a serum cholesterol level of 654 mg/dl at 7 months of age, despite being breast fed (with very tiny amounts of plant sterols) since birth and undergoing 4 months of ezetimibe administration. Although she failed to respond to ezetimibe during this period, she did show improvement when the therapy was started again at 2 years of age. It is possible that another 23-month-old female patient also responded more slowly to ezetimibe treatment than older patients.

Objectives: To determine whether B-type natriuretic peptide (BNP) predicts indomethacin responsiveness in premature neonates with patent ductus arteriosus (PDA)., Study Design: Premature neonates receiving indomethacin for an echocardiograhically large (diameter>1.5 mm) and clinically significant PDA were prospectively studied. All neonates underwent paired echocardiography and BNP measurements at baseline and 24 hours after each dose of indomethacin. After treatment, neonates who responded (with closed or insignificant PDA) and neonates who did not respond (with persistent significant PDA requiring surgical ligation) were compared., Results: Thirty-one premature neonates (mean gestational age, 30 weeks) underwent 119 paired echocardiography and BNP determinations. Mean BNP levels (1286+/-986 pg/mL) associated with significant PDA (n=96) were higher than those associated with closed or insignificant PDA (n=23; 118+/-124 pg/mL; P<.001). Twenty-three neonates responded and 8 neonates did not respond to indomethacin. Mean baseline BNP levels were higher in neonates who were non-responders (2234+/-991 pg/mL) than neonates who were responders (983+/-814 pg/mL; P=.001). A baseline BNP level>1805 pg/mL had a sensitivity rate of 88% and a specificity rate of 87% for predicting indomethacin non-responsiveness (P=.003)., Conclusions: High baseline BNP levels predict poor responses to indomethacin and the need for surgery in premature neonates with PDA., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Acute partial compression of the fetal ductus arteriosus (DA) results in an initial abrupt increase in pulmonary blood flow (PBF), which is followed by a significant reduction in PBF to baseline values over the ensuing 2-4 h. We have previously demonstrated that this potent vasoconstricting response is due, in part, to an endothelin-1 (ET-1)-mediated decrease in nitric oxide synthase (NOS) activity. In addition, in vitro data demonstrate that ET-1 increases superoxide levels in pulmonary arterial smooth muscle cells and that oxidative stress alters NOS activity. Therefore, the objectives of this study were to determine the potential role of superoxide in the alterations of hemodynamics and NOS activity following acute ductal constriction in the late-gestation fetal lamb. Eighteen anesthetized near-term fetal lambs were instrumented, and a lung biopsy was performed. After a 48-h recovery, acute constriction of the DA was performed by inflating a vascular occluder. Polyethylene glycol-superoxide dismutase (PEG-SOD; 1,000-1,500 units/kg, n = 7) or PEG-alone (vehicle control group, n = 5) was injected into the pulmonary artery before ductal constriction. Six animals had a sham operation. In PEG-alone-treated lambs, acute ductal constriction rapidly decreased pulmonary vascular resistance (PVR) by 88%. However, by 4 h, PVR returned to preconstriction baseline. This vasoconstriction was associated with an increase in lung superoxide levels (82%), a decrease in total NOS activity (50%), and an increase in P-eNOS-Thr495 (52%) (P < 0.05). PEG-SOD prevented the increase of superoxide after ductal constriction, attenuated the vasoconstriction, preserved NOS activity, and increased P-eNOS Ser1177 (307%, P < 0.05). Sham procedure induced no changes. These data suggest that an acute decrease in NOS activity that is mediated, in part, by increased superoxide levels, and alterations in the phosphorylation status of the endothelial NOS isoform, underlie the pulmonary vascular response to acute ductal constriction.

Ilio-iliac arteriovenous (AV) fistula is a rare complication after lumbar diskectomy. Endovascular repair of such fistulas is a growing trend in vascular surgery. This is a case report of an endovascular exclusion of an ilio-iliac AV fistula in a 51-year-old male. This man presented with high-output congestive heart failure and ascites. The AV fistula was discovered 17 years after a lumbar diskectomy. Computed topography (CT) revealed a right common iliac artery pseudoaneurysm connecting to the left common iliac vein. The fistula was repaired using a bifurcated Gore Excluder endograft. There were follow-up CT scans at 6 and 10 months confirming exclusion of the AV fistula. Endovascular AV fistula repair offers a safe, effective method for managing ilio-iliac AV fistulas., (Copyright 2010 Annals of Vascular Surgery Inc. Published by Elsevier Inc. All rights reserved.)

Pt contact on p-Si nanowires (NWs) using Ga-ion-induced deposition by a focused ion beam was formed with a specific contact resistance (rho(c)) of 1.54 x 10(-6) Omega cm(2). Ohmic behavior is caused by Ga-ion-induced amorphization of Si NWs underneath the Pt contact. A very low Schottky barrier height associated with interface states raised from Pt-amorphized Si junction and with an image force induced by the applied bias can be implemented to elucidate ultralow rho(c). The value of rho(c) lower than that of any known contact to Si NWs demonstrates a practical method for integrating NWs in devices and circuits.

Dynamics of fluorescent diamond nanoparticles in HeLa cells has been studied with two-photon fluorescence correlation spectroscopy (FCS). Fluorescent nanodiamond (FND) is an excellent fluorescent probe for bioimaging application, but they are often trapped in endosomes after cellular uptake. The entrapment prohibits FCS from being performed in a time frame of 60 s. Herein, we show that the encapsulation of FNDs within a lipid layer enhances the diffusion of the particles in the cytoplasm by more than one order of magnitude, and particles as small as 40 nm can be probed individually with high image contrast by two-photon excited luminescence. The development of the technique together with single particle tracking through one-photon excitation allows probing of both short-term and long-term dynamics of single FNDs in living cells.

Background and Purpose: To determine whether KMUP-1, a novel xanthine-based derivative, attenuates isoprenaline (ISO)-induced cardiac hypertrophy in rats, and if so, whether the anti-hypertrophic effect is mediated by the nitric oxide (NO) pathway., Experimental Approach: In vivo, cardiac hypertrophy was induced by injection of ISO (5 mg.kg(-1).day(-1), s.c.) for 10 days in Wistar rats. In the treatment group, KMUP-1 was administered 1 h before ISO. After 10 days, effects of KMUP-1 on survival, cardiac hypertrophy and fibrosis, the NO/guanosine 3'5'-cyclic monophosphate (cGMP)/protein kinase G (PKG) and hypertrophy signalling pathways [calcineurin A and extracellular signal-regulated kinase (ERK)1/2] were examined. To investigate the role of nitric oxide synthase (NOS) in the effects of KMUP-1, a NOS inhibitor, N(omega)-nitro-L-arginine (L-NNA) was co-administered with KMUP-1. In vitro, anti-hypertrophic effects of KMUP-1 were studied in ISO-induced hypertrophic neonatal rat cardiomyocytes., Key Results: In vivo, KMUP-1 pretreatment attenuated the cardiac hypertrophy and fibrosis and improved the survival of ISO-treated rats. Plasma NOx (nitrite and nitrate) and cardiac endothelial NOS, cGMP and PKG were all increased by KMUP-1. The activation of hypertrophic signalling by calcineurin A and ERK1/2 in ISO-treated rats was also attenuated by KMUP-1. All these effects of KMUP-1 were inhibited by simultaneous administration of L-NNA. Similarly, in vitro, KMUP-1 attenuated hypertrophic responses and signalling induced by ISO in neonatal rat cardiomyocytes., Conclusions and Implications: KMUP-1 attenuates the cardiac hypertrophy in rats induced by administration of ISO. These effects are mediated, at least in part, by NOS activation. This novel agent, which targets the NO/cGMP pathway, has a potential role in the prevention of cardiac hypertrophy.

Pneumomediastinum, the leakage of air or gas into the mediastinum, can be a primary or secondary diagnosis. Although spontaneous pneumomediastinum (SPM) is uncommon in pediatric respiratory disorders, it is potentially life-threatening. In this study, we investigated the associations between various etiologies and clinical presentations, hospital length-of-stay, and clinical outcomes of SPM. From January 2004 to December 2007, we collected medical records and chest films from 23 pediatric patients with SPM. Results showed that increased hospital length-of-stay was significantly associated with asthma (p = 0.035), dyspnea/tachypnea (p = 0.01), and emergent visit (p = 0.04). Dysphagia was associated with shorter hospital stay (p = 0.058). Besides, the disorder was misdiagnosed initially in 21% of patients. In conclusion, there may be close relationships between the predisposing factors of SPM and its clinical manifestations. The high rate of misdiagnosis highlights the importance of careful examination and history taking in pediatric patients with chest pain.

Centrosymmetric furan-containing cyclophandienes 3 and 4, synthesized by our furan annulation protocol, have been shown to exhibit extraordinarily large Stokes shifts and second-order nonlinear optical beta values. The beta values for 3 and 4 measured at 1.32 mum are 208 and 530x10(-30) esu, respectively. The beta values of 3 and 4 are similar to those of respective cyclophenes 1 a and 7 in which strong hyperpoarizable interactions between two twisted pi-systems (oligoaryl and bridging double bond) might take place. Symmetry breaking due to the resonance contribution (cf. 2) and the unique structural features of 3 and 4 has been used to account for this unusual photophysical behavior.

Lower respiratory tract infections associated with wheezing are not uncommon in infants and young children. Among the wheezing-associated disorders, allergic etiologies are more commonly encountered than anatomic anomalies. We present a 3-year-old girl with a sudden attack of asthmatic symptoms including dyspnea, cyanosis and diffuse wheezing Based on a history of choking, and atelectasis in the right upper lobe detected by chest films, flexible tracheobronchoscopy was arranged and incidentally detected a stenotic orifice in the right upper lobe bronchus. Multidetector-row spiral computed tomography and pulmonary scintigraphy subsequently also disclosed the focal stenosis. She suffered from recurrent wheezing, pneumonia and lung atelectasis during 1 year of follow-up. We emphasize the diagnosis, clinical course and management of focal stenosis in the right upper lobe bronchus.

Vibrio vulnificus infection is an uncommon but potentially fatal disease in children such that prompt recognition has prognostic implications. We describe here the case of a 9-year-old female with thalassemia and iron overload who presented with septic arthritis as an atypical initial manifestation of fatal V. vulnificus septicemia. This report underscores the possibility of septic arthritis as an early manifestation of V. vulnificus septicemia. Pediatricians should be alert to this extremely invasive disease, especially in children with iron overload.

Background: Thyroglobulin (TG) defect is a rare cause of congenital hypothyroidism. Although only 44 mutations of the human TG gene have been identified, we have suspected a TG defect in 38% of Taiwan Chinese children/adolescents presenting with moderate or severe thyroidal dyshormonogenesis., Study Objective: The aim of the study is to report the discovery of new TG gene mutations and associated clinical manifestations of the defective TG protein., Patients and Results: In seven patients from six families, we detected six new TG gene mutations, including c.1348delT, p.R432X (c.1351C>T), g.IVS3 + 2T>G, c.1712delT, p.Q1765X (c.5350C>T), and c.6047delA. The c.1348delT and p.R432X mutations were the most common, detected in 33 and 25%, respectively, of alleles studied. Haplotype analysis suggested that the c.1348delT and g.IVS3 + 2T>G mutations are due to founder effects, whereas p.R432X is probably due to independently recurrent de novo mutations. mRNA transcript of the g.IVS3 + 2T>G mutant, detected in whole blood by reverse transcription-nested PCR, showed skipping of exon 3 (98-bp deletion) and a frameshift, with a terminal signal after 17 altered amino acid residues., Conclusions: TG defects have an important role in severe thyroidal dyshormonogenesis (pretreatment, or after a 3-wk T(4) withdrawal, plasma T(4) < or = 30 nmol/liter) in Taiwanese. Its genetic characteristics are markedly different from those described in other populations presenting with mutations of the TG gene.

The optical absorption spectra of a graphene monolayer in the presence of a modulated electric field are investigated by the gradient approximation with tight-binding model. Such a field could strongly affect the low-energy electronic and optical properties. The low-energy bands exhibit two kinds of band-edge states (micro and upsilon), which lead to many prominent asymmetric peaks in the density of states (DOS). The finite DOS at omega = 0 implies that a single layer graphene in the presence of modulated electric fields would become a semimetallic one. The low-frequency optical absorption spectra display rich peaks and they vanish at omega = 0. Such absorption peaks mainly result from the two kinds of band-edge states and could be divided into two groups. However, they could not be ascribed to an obvious selection rule. It is worth noting that the optical absorption spectra could show anisotropic features in different modulated directions. The predicted results could be verified by the experimental measurements.

Objectives: To determine B-type natriuretic peptide (BNP) levels in infants and children with acute lung injury (ALI), and to investigate associations between BNP levels and clinical outcome., Design: Prospective observational study., Subjects: After informed consent, plasma was collected from 48 pediatric patients on day 1 of ALI., Methodology: Plasma BNP levels were measured by immunoassay on day 1 of ALI in 48 pediatric patients. Associations between BNP levels and outcome were determined., Results: The mean PaO(2)/FiO(2) at the onset of ALI was 155 (+/-74) and BNP values ranged from 5 to 2,060 pg/ml with a mean of 109 (+/-311). BNP levels were inversely correlated with ventilator-free days (Spearman rho -0.30, P = 0.04), and positively correlated with exhaled tidal volume (Spearman rho 0.44, P = 0.02). BNP levels were higher in patients receiving inotropic support (n = 12) than patients not receiving inotropic support (n = 33, P = 0.02). BNP levels were correlated with PRISM III scores (Spearman rho 0.55, P < 0.001) and PELOD scores (Spearman rho 0.4, P = 0.006). Mortality for the cohort was 15%. BNP levels were higher in non-survivors (n = 7) than survivors (n = 41, P = 0.055)., Conclusions: BNP levels are elevated in children with ALI/ARDS early in the disease course, and increased levels are associated with worse clinical outcome.

Here, we studied the functional role of a chloroplast alkaline alpha-galactosidase (OsAkalphaGal) in the breakdown of thylakoid membranes during rice (Oryza sativa) leaf senescence. We assayed the enzyme activity of recombinant OsAkalphaGal with different natural substrates and examined the effect of ectopic OsAkalphaGal expression in rice plants. Recombinant OsAkalphaGal showed at least a two-fold greater substrate-binding affinity and a 10-fold greater turnover rate to galactolipid digalactosyl diacylglycerol than the raffinose family of oligosaccharides (verbascose, stachyose, raffinose) and melibiose. The OsAkalphaGal null mutant (osakalphagal) displayed a delayed leaf senescence phenotype. OsAkalphaGal complementation in osakalphagal recovered OsAkalphaGal expression and showed a senescence phenotype similar to that of wild-type plants. Transgenic plants overexpressing OsAkalphaGal (UbiP-OsAkalphaGal) exhibited retarded plant growth and development, and showed a pale-green phenotype coupled with a reduced chlorophyll content to 42% in newly unfolded leaves. UbiP-OsAkalphaGal leaves also showed a 29-fold increase in alkaline alpha-galactosidase activity compared with wild-type leaves. An ultrastructural study of Ubi-OsAkalphaGal chloroplasts in newly unfolded leaves revealed abnormal grana organization. Our findings strongly suggest that OsAkalphaGal is a thylakoid membrane-degrading enzyme involved in the degradation of digalactosyl diacylglycerol during rice leaf senescence.