Seasonal variation of chemical characteristics of fine particulate matter at a high-elevation subtropical forest in East Asia.

The aim of this study was to chemically characterize the fine particulate matter (PM2.5) at a subtropical forest in East Asia under the influences of anthropogenic and biogenic sources and a complex topographic setting. Four seasonal campaigns were conducted at the Xitou Experimental Forest in central Taiwan from the winter of 2013 to the autumn of 2014. The results indicated that the ambient levels and chemical features of PM2.5 exhibited pronounced seasonal variations. Non-sea-salt sulfate (nss-SO42-) constituted the major component of PM2.5, followed by ammonium (NH4+) and nitrate (NO3-) during winter, summer and autumn. However, it was revealed that the mass fraction of NO3- increased to be comparable with that of nss-SO42- in springtime. The mass contribution of secondary organic carbon (SOC) to PM2.5 peaked in summer (13.2%), inferring the importance of enhanced photo-oxidation reactions in SOC formation. Diurnal variations of O3 and SO2 coincided with each other, suggesting the transport of aged pollutants from distant sources, whereas CO and NOx were shown to be under the influences of both local and regional sources. Notably high sulfur oxidation ratio (SOR) and nitrogen oxidation ratio (NOR) were observed, which were 0.93 ±â€¯0.05 and 0.39 ±â€¯0.20, respectively. Precursor gases (i.e. SO2 and NOx) could be converted to sulfate and nitrate during the transport by the uphill winds. Furthermore, due to the high relative humidity at Xitou, enhanced aqueous-phase and/or heterogeneous reactions could further contribute to the formation of sulfate and nitrate at the site. This study demonstrated the significant transport of urban pollutants to a subtropical forest by the mountain-valley circulations as well as the long-range transport from regional sources, whereas the implications of which for regional climate change necessitated further investigation.

A semi-automated vascular access system for preclinical models.

Murine models are used extensively in biological and translational research. For many of these studies it is necessary to access the vasculature for the injection of biologically active agents. Among the possible methods for accessing the mouse vasculature, tail vein injections are a routine but critical step for many experimental protocols. To perform successful tail vein injections, a high skill set and experience is required, leaving most scientists ill-suited to perform this task. This can lead to a high variability between injections, which can impact experimental results. To allow more scientists to perform tail vein injections and to decrease the variability between injections, a vascular access system (VAS) that semi-automatically inserts a needle into the tail vein of a mouse was developed. The VAS uses near infrared light, image processing techniques, computer controlled motors, and a pressure feedback system to insert the needle and to validate its proper placement within the vein. The VAS was tested by injecting a commonly used radiolabeled probe (FDG) into the tail veins of five mice. These mice were then imaged using micro-positron emission tomography to measure the percentage of the injected probe remaining in the tail. These studies showed that, on average, the VAS leaves 3.4% of the injected probe in the tail. With these preliminary results, the VAS system demonstrates the potential for improving the accuracy of tail vein injections in mice.

Robot-assisted intraocular surgery: development of the IRISS and feasibility studies in an animal model.

PURPOSE: The aim of this study is to develop a novel robotic surgical platform, the IRISS (Intraocular Robotic Interventional and Surgical System), capable of performing both anterior and posterior segment intraocular surgery, and assess its performance in terms of range of motion, speed of motion, accuracy, and overall capacities. PATIENTS AND METHODS: To test the feasibility of performing 'bimanual' intraocular surgical tasks using the IRISS, we defined four steps out of typical anterior (phacoemulsification) and posterior (pars plana vitrectomy (PPV)) segment surgery. Selected phacoemulsification steps included construction of a continuous curvilinear capsulorhexis and cortex removal in infusion-aspiration (I/A) mode. Vitrectomy steps consisted of performing a core PPV, followed by aspiration of the posterior hyaloid with the vitreous cutter to induce a posterior vitreous detachment (PVD) assisted with triamcinolone, and simulation of the microcannulation of a temporal retinal vein. For each evaluation, the duration and the successful completion of the task with or without complications or involuntary events was assessed. RESULTS: Intraocular procedures were successfully performed on 16 porcine eyes. Four eyes underwent creation of a round, curvilinear anterior capsulorhexis without radialization. Four eyes had I/A of lens cortical material completed without posterior capsular tear. Four eyes completed 23-gauge PPV followed by successful PVD induction without any complications. Finally, simulation of microcannulation of a temporal retinal vein was successfully achieved in four eyes without any retinal tears/perforations noted. CONCLUSION: Robotic-assisted intraocular surgery with the IRISS may be technically feasible in humans. Further studies are pending to improve this particular surgical platform.

MEK inhibition enhances ABT-737-induced leukemia cell apoptosis via prevention of ERK-activated MCL-1 induction and modulation of MCL-1/BIM complex.

Recently, strategies for acute myeloid leukemia (AML) therapy have been developed that target anti-apoptotic BCL2 family members using BH3-mimetic drugs such as ABT-737. Though effective against BCL2 and BCL-X(L), ABT-737 poorly inhibits MCL-1. Here we report that, unexpectedly, ABT-737 induces activation of the extracellular receptor activated kinase and induction of MCL-1 in AML cells. MEK inhibitors such as PD0325901 and CI-1040 have been used successfully to suppress MCL-1. We report that PD0325901 blocked ABT-737-induced MCL-1 expression, and when combined with ABT-737 resulted in potent synergistic killing of AML-derived cell lines, primary AML blast and CD34+38-123+ progenitor/stem cells. Finally, we tested the combination of ABT-737 and CI-1040 in a murine xenograft model using MOLM-13 human leukemia cells.Whereas control mice and CI-1040-treated mice exhibited progressive leukemia growth, ABT-737, and to a significantly greater extent, ABT-737+CI-1040 exerted major anti-leukemia activity. Collectively, results demonstrated unexpected anti-apoptotic interaction between the BCL2 family-targeted BH3-mimetic ABT-737 and mitogen-activated protein kinase signaling in AML cells: the BH3 mimetic is not only restrained in its activity by MCL-1, but also induces its expression. However, concomitant inhibition by BH3 mimetics and MEK inhibitors could abrogate this effect and may be developed into a novel and effective therapeutic strategy for patients with AML.

Distribution of lysosome-associated membrane proteins-1 and -2, and cathepsin D in eosinophilic granular bodies: possible relationship to cyst development in pilocytic astrocytomas.

Pilocytic astrocytomas are usually cystic; cyst formation within these tumours may result in increased intracranial pressure, due to the effect of their mass, and contribute to cerebral damage. Eosinophilic granular bodies (EGBs) are produced abundantly in pilocytic astrocytomas but their role in disease progression remains unknown. Immunohistochemistry studies showed EGBs to exhibit pronounced reactivity to antibodies against lysosome-associated membrane proteins (LAMP)-1 and LAMP-2, and the lysosomal enzyme cathepsin D. Both LAMP-1 and LAMP-2 showed peripheral rim and granular staining patterns. The EGBs were scattered widely across cysts and, where EGBs aggregated in clusters, were usually close to areas of fluid in the cysts. Most EGBs had nuclei either attached or close by, indicating that the EGBs may be derived from anucleated astrocytes. The results suggest that EGBs, together with other factors, may play a role in the development of cysts in pilocytic astrocytomas.

Selective FLT3 inhibitor FI-700 neutralizes Mcl-1 and enhances p53-mediated apoptosis in AML cells with activating mutations of FLT3 through Mcl-1/Noxa axis.

Treatment using Fms-like tyrosine kinase-3 (FLT3) inhibitors is a promising approach to overcome the dismal prognosis of acute myeloid leukemia (AML) with activating FLT3 mutations. Current trials are combining FLT3 inhibitors with p53-activating conventional chemotherapy. The mechanisms of cytotoxicity of FLT3 inhibitors are poorly understood. We investigated the interaction of FLT3 and p53 pathways after their simultaneous blockade using the selective FLT3 inhibitor FI-700 and the MDM2 inhibitor Nutlin-3 in AML. We found that FI-700 immediately reduced antiapoptotic Mcl-1 levels and enhanced Nutlin-induced p53-mediated mitochondrial apoptosis in FLT3/internal tandem duplication cells through the Mcl-1/Noxa axis. FI-700 induced proteasome-mediated degradation of Mcl-1, resulting in the reduced ability of Mcl-1 to sequester proapoptotic Bim. Nutlin-3 induced Noxa, which displaced Bim from Mcl-1. The FI-700/Nutlin-3 combination profoundly activated Bax and induced apoptosis. Our findings suggest that FI-700 actively enhances p53 signaling toward mitochondrial apoptosis and that a combination strategy aimed at inhibiting FLT3 and activating p53 signaling could potentially be effective in AML.

Biodegradation of phthalate esters in compost-amended soil.

In this study, we investigated the biodegradation of the phthalate acid esters (PAEs) di-n-butyl phthalate (DBP) and di-(2-ethyl hexyl) phthalate (DEHP) in compost and compost-amended soil. DBP (50 mg kg(-1)) and DEHP (50 mg kg(-1)) were added to the two types of compost (straw and animal manure) and subsequently added to the soil; they were tested as a single compound and in combination. Optimal PAE degradation in soil was at pH 7 and 30 degrees C. The degradation of PAE was enhanced when DBP and DEHP were simultaneously present in the soil. The addition of either of the two types of compost individually also improved the rate of PAE degradation. Compost samples were separated into fractions with various particle size ranges, which spanned from 0.1-0.45 to 500-2000 microm. We observed that the compost fractions with smaller particle sizes demonstrated higher PAE degradation rates. When the different compost fractions were added to soil, however, compost particle size had no significant effect on the rate of PAE degradation.

Multiple symmetric lipomatosis in two chinese patients, one typical and one unusual.

Multiple symmetric lipomatosis (MSL; Madelung disease) is an uncommon disorder with diffuse multiple symmetrical unencapsulated accumulations of fat located in the neck and the upper trunk. MSL usually occurs in middle aged Caucasian men of Mediterranean ancestry with a history of alcoholism. In the past decade, an increasing number of cases in the Chinese population have been reported which appear to be limited to the head and neck regions. We describe two Chinese patients with MSL who have a history of alcoholism. The MR and CT findings disclosed that one patient had the typical accumulation of unencapsulated fat in the neck and upper back, while the other patient had more than the typical neck involvement and an unusual distribution of fat in the scrotum.

The soluble leptin receptor of regular exercisers.

This study examined the concentrations and the relationships of soluble leptin receptor (sLR) and leptin levels among both physically active people and lean sedentary persons. Information collected for this study came from twelve joggers (JOG), ten weight trainers (WET) and eleven lean sedentary persons (CON). Regular exercisers were defined as those who consistently participated in jogging or weight training 30 minutes a day, at least four times a week, for a period of no less than three years prior to the study. The CON group was defined as exercising, at most, one time per week, less than 20 minutes each time if at all. Leptin and sLR were analyzed using enzyme-linked immunosorbent assay. The results show the BMI of the WET group to be higher than the other groups, yet their percent body fat was not significantly different. Although sLR levels of the JOG group were higher than the WET and CON groups, their free leptin index (FLI) did not show a significant difference. The sLR levels for joggers were higher than the weight trainers. The sLR concentration or the ratio of sLR to fat mass may be an alternative index to FLI for comparing physically active and lean people.

Color Doppler twinkling artifact related to chronic pancreatitis with parenchymal calcification.

Color Doppler twinkling artifact is known as a rapidly changing mixture of red and blue behind certain strongly reflecting structures. This artifact has been described behind calcifications in various tissues. We describe a case of twinkling artifact related to chronic pancreatitis with parenchymal calcification.

Altered hepatic and muscle substrate utilization provoked by GLUT4 ablation.

Studies were conducted to explore altered substrate utilization and metabolism in GLUT4 null mice. Liver fatty acid synthase mRNA and fatty acid synthesis rates were dramatically increased in GLUT4 null mice compared with control mice and were supported by increased rates of the pentose phosphate pathway oxidative phase and sterol regulatory binding protein mRNA expression. Increased GLUT2 protein content, glucokinase mRNA, and glucose-6-phosphate in GLUT4 null mice may provide substrate for the enhanced fatty acid synthesis. Increased fatty acid synthesis, however, did not lead to hepatic triglyceride accumulation in GLUT4 null mice because of increased hepatic triglyceride secretion rates. GLUT4 null mice rapidly cleared orally administered olive oil, had reduced serum triglyceride concentrations in the fed and the fasted state, and increased skeletal muscle lipoprotein lipase when compared with controls. Oleate oxidation rates were increased in GLUT4 null skeletal muscle in association with mitochondrial hyperplasia/hypertrophy. This study demonstrated that GLUT4 null mice had increased hepatic glucose uptake and conversion into triglyceride for subsequent use by muscle. The ability of GLUT4 null mice to alter hepatic carbohydrate and lipid metabolism to provide proper nutrients for peripheral tissues may explain (in part) their ability to resist diabetes when fed a normal diet.

Regulation and targeting of antiapoptotic XIAP in acute myeloid leukemia.

XIAP is a member of the inhibitors-of-apoptosis family of proteins, which inhibit caspases and block cell death, with prognostic importance in AML. Here we demonstrate that cytokines regulate the expression of XIAP in leukemic cell lines and primary AML blasts. Inhibition of phosphatidylinositol-3 kinase (PI3K) with LY294002 and of the mitogen-activated protein kinase (MAPK) cascade by PD98059 resulted in decreased XIAP levels (34+/-8.7 and 23+/-5.7%, respectively). We then generated OCI-AML3 cells with constitutively phosphorylated Akt (p473-Akt) by retroviral gene transfer. Neither these nor Akt inhibitor-treated OCI-AML3 cells showed changes in XIAP levels, suggesting that XIAP expression is regulated by PI3K downstream effectors other than Akt. The induction of XIAP expression by cytokines through PI3K/MAPK pathways is consistent with its role in cell survival. Exposure of leukemic cells to chemotherapeutic agents decreased XIAP protein levels by caspase-dependent XIAP cleavage. Targeting XIAP by XIAP antisense oligonucleotide resulted in downregulation of XIAP, activation of caspases and cell death, and sensitized HL-60 cells to Ara-C. Our results suggest that XIAP is regulated by cytokines through PI3K, and to a lesser degree through MAPK pathways. Selective downregulation of XIAP expression might be of therapeutic benefit to leukemic patients.

Abnormal 201Tl myocardial single photon emission computed tomography in energetic male patients with myocardial bridge.

Myocardial bridge is a relatively benign condition where a major coronary artery is bridged by a band of muscle and narrows during systole, particularly during rapid heart rates. Its clinical presentation and electrocardiogram (ECG) changes overlap with that of coronary artery disease. 201Tl myocardial perfusion imaging is thus frequently prescribed for further evaluation. This retrospective study was carried out to determine the 201Tl image patterns in patients with myocardial bridge. A total of 17 male patients (aged from 30 to 63 years) who had a positive exercise ECG and angiographic evidence of myocardial bridge in the mid-third of the left anterior descending coronary artery were recruited. Most of them were robust and received routine physical check-ups. They had no known heart disease or medication that affected cardiac function. The patients' clinical presentations, echocardiograph and exercise ECG findings were analysed. 201Tl single photon emission computed tomography (SPECT) was performed by intravenous injection of 201Tl (111 MBq) immediately following stress (treadmill or dipyridamole induced) and 4 h after stress, using a fixed, right angle camera equipped with a low energy, general purpose collimator. The images were interpreted independently by two experienced nuclear medicine physicians. Nine of the 17 patients had anterior chest pain during exercise. All patients had an abnormal ECG during exercise, including ST-T wave depression in leads II, III and aVF, and v4-6. Except for eight patients revealing reversible perfusion defect (R), 16 of the 17 patients also exhibited a partial reversible perfusion defect (PR) or a significant reverse redistribution (RR) scan pattern in the anterior or inferior walls of the left ventricle. Myocardial bridge should be taken into consideration in energetic male patients who had abnormal exercise ECGs and the corresponding patterns of Tl SPECT abnormalities including R, PR and RR.

Levels of interferon-gamma and interleukin-2 receptor-alpha for bronchoalveolar lavage fluid and serum were correlated with clinical grade and treatment of pulmonary tuberculosis.

OBJECTIVE: We investigated possible correlations for interferon-gamma (IFN-gamma) and soluble interleukin-2 receptor-alpha (sIL-2R-alpha) levels in bronchoalveolar lavage fluid (BALF), and clinical grade of pulmonary tuberculosis (TB), which is determined by factors such as extent of pulmonary involvement, fever and loss of body weight. DESIGN: In order to explore these correlations and address associated questions, BALF was collected from 45 patients presenting with active pulmonary TB and 14 healthy controls. Repetitive BALF was collected in 17 patients after 3 months of anti-tuberculosis chemotherapy. The epithelial lining fluid (ELF) levels for IFN-gamma and sIL-2R-alpha were measured using enzyme-linked immunosorbent assay (ELISA) after standardization with urea. RESULTS: Patients with higher-grade pulmonary TB (i.e., with more advanced pulmonary involvement, fever or body weight loss), revealed significantly higher ELF levels for IFN-gamma and sIL-2R-alpha compared to those with lower grade pulmonary TB. Similar results were also determined for sIL-2R-alpha serum levels, but not for IFN-gamma serum levels. After anti-tuberculosis chemotherapy the elevated cytokine levels for ELF and serum significantly decreased in accordance with radiographic improvement. CONCLUSIONS: ELF levels of IFN-gamma and sIL-2R-alpha were correlated with disease grading of pulmonary TB and decreased after anti-tuberculosis chemotherapy.

Change in demographic picture and increase of drug resistance in pulmonarytuberculosis in a 10-year interval in Taiwan.

BACKGROUND: This study was designed to compare the change in demographics, medical characteristics and drug resistance of patients with active pulmonary tuberculosis (TB) between two time periods within a 10-year interval. PATIENTS AND METHODS: We retrospectively reviewed the clinical records and chest radiographs of 1,826 patients with active pulmonary TB for two time periods from 1992-1996 (n = 884) and 1982-1986 (n = 942). RESULTS: The mean age was significantly higher and there were significantly more female patients in the 1992-1996 period than in the 1982-1986 period. In the 1992-1996 period, there were significantly fewer patients with the main complaints of cough, fever and body weight loss at the time of diagnosis but significantly more patients who had diabetes mellitus, obstructive airway disease, cancer other than lung cancer or who were on corticosteroid therapy. During the 1992-1996 period, single drug resistance against isoniazid (INH), rifampin (RIF) and streptomycin increased by 0.5%, 3% and 0.7%, respectively. Multiple drug resistance against both INH and RIF increased by 2% in the 1992-1996 period. A history of pulmonary TB and extensive pulmonary involvement were two significant factors for drug resistance against INH, RIF or ethambutol (EMB). CONCLUSION: In the 1992-1996 period, the mean age of patients and number of female patients significantly increased. There were more patients with diabetes mellitus, obstructive airway diseases, cancer other than lung cancer and prior steroid therapy but fewer patients presenting with classic clinical symptoms of TB. In consideration of the high prevalence and increasing rate of single and multiple drug resistance, we recommend an initial four-drug regimen (INH, RIF, EMB, pyrazinamide) for the treatment of pulmonary TB in Taiwan.

Combined bronchoalveolar lavage and polymerase chain reaction in the diagnosis of pulmonary tuberculosis in smear-negative patients.

SETTING: The polymerase chain reaction (PCR) may be sensitive and specific for the diagnosis of tuberculosis, but most reports are of studies conducted in well-controlled laboratories. A study to evaluate the clinical value of bronchoalveolar lavage (BAL) combined with PCR was necessary. OBJECTIVE: One hundred and thirty one patients were recruited into the study from March 1994 to February 1997. DESIGN: Patients with a positive acid-fast stain on sputum smear were recruited into group A as positive controls, patients with lung cancer and a negative acid-fast stain on sputum smear were put into group B as negative controls, and patients who had clinical symptoms of pulmonary TB without sputum or with negative smear results were the investigating group. PCR was performed on the sputum samples from group A and B patients and on the BAL fluid from those in group C. RESULTS: The sensitivity of PCR was 96% in group A, and the specificity was 100% in group B. The sensitivity of PCR in the BAL fluid from the group C patients was 36% and the specificity was 96%; the positive predictive value was 94% and the negative predictive value was 45%. CONCLUSION: BAL plus PCR is useful in the rapid diagnosis of pulmonary TB in non-productive or smear-negative patients.

Risk factors for pneumothorax and bleeding after CT-guided percutaneous coaxial cutting needle biopsy of lung lesions.

PURPOSE: To evaluate risk factors for pneumothorax and bleeding after computed tomography (CT)-guided percutaneous coaxial cutting needle biopsy of lung lesions. MATERIALS AND METHODS: This study involved 117 consecutive patients with 117 intrapulmonary lesions. Statistical analysis of factors related to patient characteristics, lung lesions, and biopsy technique was performed to determine possible contribution to the occurrence of pneumothorax and bleeding. Interactions between related factors were considered to prevent colinearity. RESULTS: Pneumothorax occurred in 12% (14 of 117) of patients. Needle aspiration of two moderate asymptomatic pneumothoraces were performed; there was no chest tube insertion. Lesion depth (P =.0097), measured from the pleural puncture site to the edge of the intrapulmonary lesion along the needle path, was the single significant predictor of pneumothorax. The highest risk of pneumothorax occurred in subpleural lesions 2 cm or shorter in depth (this represented 33% of lung lesions but caused 71% of all pneumothoraces; OR = 7.1; 95% CI, 1.3-50.8). Bleeding presented as lung parenchyma hemorrhage and hemoptysis in 30 patients (26%). Hemoptysis occurred in four patients (3%). Univariate analysis identified lesion depth (P <.0001), lesion size (P <.015), and pathology type (P =.007) as risk factors for bleeding. Multivariate logistic regression analysis identified lesion depth as the most important risk factor, with the highest bleeding risk for lesions more than 2 cm deep (14% of lesions caused 46% of all bleeding; OR = 17.3; 95% CI, 3.3-121.4). CONCLUSIONS: In CT-guided coaxial cutting needle biopsy, lesion depth is the single predictor for risk of pneumothorax, which occurs at the highest rate in subpleural lesions. Increased risk of bleeding occurs in lesions deeper than 2 cm.