title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Co-solvent effects on structure and function properties of savinase: solvent-induced thermal stabilization. | The industrial utilization of savinase is mainly constrained by its stability limitations. In the present study, the irreversible thermoinactivation of savinase has been evaluated at 70 degrees C, and various possible mechanisms for irreversible thermoinactivation of savinase were examined. The main process seemed to be autodigestion of savinase at higher temperatures. To improve the thermal stability of the enzyme, the effect of two co-solvents (sorbitol and trehalose) on the enzyme's activity and stability was investigated. Both osmolytes prevented the autolysis of savinase at 70 degrees C without inactivating the enzyme; furthermore, the structural and kinetic stabilities of the enzyme increased in the presence of additives. | 18,955,077 |
Recurrence quantification analysis of surface electromyographic signal: sensitivity to potentiation and neuromuscular fatigue. | This study aimed to assess the capacity of recurrence quantification analysis (RQA) to detect potentiation and to determine the fatigue components to which RQA is sensitive. Fifteen men were divided in two groups [8 endurance-trained athletes (END) and 7 power-trained athletes (POW)]. They performed a 10-min intermittent (5s contraction, 5s rest) knee extension exercise at 50% of their maximal voluntary isometric contraction. Muscular fatigue and potentiation were evaluated with neurostimulation technique. Mechanical (peak torque, Pt) and electrophysiological (M-wave) responses following electrical stimulation of the femoral nerve were measured at rest and every 10s throughout exercise. Vastus lateralis muscle activity (root mean square, RMS) was recorded during each contraction, and RMS was normalized to M-wave area (RMS/M). During contraction, muscle activity was analyzed with RQA to obtain the percentage of determinism (%Det). At the beginning of exercise, a significant Pt increase (+52%, P<0.001) was observed in both groups, indicating potentiation. At this time, %Det remained constant in both groups, indicating that RQA did not detect potentiation. Thereafter, Pt decreased in POW from 5min 30s of exercise (-30%, P<0.001), reflecting impairment in excitation-contraction coupling, and %Det increased from 3min 30s (P<0.01). In END, Pt remained high and %Det was unchanged. These two results indicated that RQA detected the peripheral component of fatigue. Conversely, RQA did not detect central adaptation to fatigue since %Det remained constant when a significant increase in RMS/M (P<0.01) appeared in END. | 18,955,082 |
Comparison of HPV detection technologies: Hybrid capture 2, PreTect HPV-Proofer and analysis of HPV DNA viral load in HPV16, HPV18 and HPV33 E6/E7 mRNA positive specimens. | Human papillomavirus (HPV) testing using molecular methods in liquid based cytology (LBC) specimens may be useful as an adjunct to cervical screening by cytology. We compared the positivity rate of the commercially available HPV DNA method hybrid capture 2 (hc2) and the commercially available E6/E7 mRNA method PreTect HPV-Proofer in cytological specimens (n=299). LBC specimens collected (n=299) represented the following cervical cytological disease categories: Normal (n=60), borderline nuclear abnormalities (BNA) (n=34), CIN1 (n=121), CIN2 (n=60), CIN3 (n=24). Overall, 69% (205/299) of the cases were positive by hc2 and 38% (112/299) of the cases were positive by PreTect HPV-Proofer. Concordance rates between the two tests were highest in the high-grade cytology cases (CIN2: 67% and CIN3: 83%) and the normal cytology cases (88%) and lowest in the BNA and CIN1 categories (56% and 52%). HPV DNA viral load analyses were carried out on HPV16 (n=55), HPV18 (n=9) and HPV33 (n=13) samples that were positive by PreTect HPV-Proofer. The sensitivity and specificity of PreTect HPV-Proofer and the hc2 DNA test for the detection of high-grade cytology (i.e. CIN2+) were 71.4% and 75.8% vs 100% and 43.7%, respectively. The relatively low detection rate observed by PreTect HPV-Proofer in the whole range of cytological positive cases, combined with a relatively higher specificity and PPV, suggests that PreTect HPV-Proofer may be more useful than hc2 for triage and in predicting high-grade disease. | 18,955,086 |
Molecular cloning, functional characterization and localization of an annexin from a fish gill fluke Microcotyle sebastis (Platyhelminthes: Monogenea). | The full cDNA of an annexin gene from Microcotyle sebastis (MsANX) was cloned for the first time in monogeneans. The cDNA of MsANX comprises 1199bp with a 29bp 5' untranslated region, an open reading frame of 1062bp, and a 108bp 3' untranslated region. The recombinantly produced MsANX bound phosphatidylserine vesicles in the presence of Ca2+, whereas no MsANX was precipitated in the absence of free Ca2+. Phylogenetically, MsANX formed a cluster with human annexin A13, known as the earliest annexin in vertebrates and expressed mainly in the intestine. The localization of MsANX in M. sebastis was analyzed by Western blotting and immunohistochemistry using the antiserum raised against the recombinant MsANX. In Western blot analysis, rat antiserum bound to a protein corresponding to the MsANX in size when worm crude extracts were used as antigens, but no bands were detected by the antiserum when the excretory/secretory proteins of worms were used as antigens. In immunohistochemistry analysis, significant antibody binding annexin was found in the ovarian region, the pharynx and the intestinal caecum of the worm. Interestingly, the alimentary canal location of MsANX was similar to the location of human annexin A13, and further research is needed to trace evolutionary relationship among helminthic annexins and human annexin A13. Also it remains to be investigated whether immunization of naïve fish with the recombinant MsANX can induce protective immune responses against M. sebastis infection. | 18,955,089 |
Safety evaluation of an IPP tripeptide-containing milk protein hydrolysate. | Tensguard is a milk protein hydrolysate containing the lactotripeptide IPP. It is derived from cow's milk, which is present in the human diet and has a safe history of consumption. The final Tensguard product, a supplement or a functional food ingredient, is intended for use by people who want to follow a healthy diet and lifestyle in order to manage their blood pressure. The safety-in-use of commercial lactotripeptide-containing products has been confirmed in several in vitro and in vivo toxicity studies and in studies with humans. To support the safety, Tensguard was examined in three in vitro genotoxicity tests (bacterial reverse mutation test, mammalian cell gene mutation test and mammalian chromosomal aberration test) and in a 90-day repeated-dose oral toxicity study in rats. The genotoxicity tests confirm that Tensguard is not mutagenic or clastogenic. The NOAEL from the 90-day study was at the highest dose tested, i.e. 4% in the diet. The NOAEL is equivalent to an overall mean intake of 2 g Tensguard/kg body weight/day and corresponds to 40 mg IPP/kg body weight/day. This is 141-fold higher than the maximal anticipated intake. In conclusion, Tensguard is safe under the conditions of intended use. | 18,955,104 |
Fear-conditioned respiration and its association to cardiac reactivity. | This study aimed to investigate ventilatory correlates of conditioned fear responses. Respiratory, end-tidal carbon dioxide pressure (PetCO(2)) and heart rate changes were studied in a differential fear-conditioning paradigm. Forty-two participants viewed pictures of faces. One picture (CS+) was followed by a human scream (US) during the acquisition phase, but not in a subsequent extinction phase. Conditioning of PetCO(2) (decrease), respiratory cycle time (decrease) and inspiratory duty time (increase) was established and subsequently extinguished. When participants were clustered according to their conditioned PetCO(2) responses during acquisition, only a group showing a conditioned decrease in PetCO(2) showed also a differential cardiac acceleration, a decrease in expiratory duration and an increase in inspiratory duty time in response to the CS+. These results suggest that preparation for defensive action is characterized by a tendency towards hyperventilation and cardiac acceleration. | 18,955,105 |
Sequence-dependence and prediction of nucleotide solvent accessibility in double stranded DNA. | Solvent accessibility of amino acid residues in proteins has been widely studied and many methods for its prediction from sequence and evolutionary information are available. Some of the advantages of studying amino acid solvent accessibility also apply to DNA. However, currently there are no methods to estimate the solvent accessibility of nucleotides, as most works on DNA structures have focused on elastic deformations and other structural attributes. In this work, an attempt has been made to analyze the distribution of different nucleotides in various accessibility ranges. Effect of neighboring nucleotides on the predictability of exposure has been evaluated by developing a linear perceptron model that takes sequence information as the input. Five different types of solvent accessibility (overall nucleotide, side chain, main chain, polar and non-polar) have been predicted. From the analysis, it is observed that Thymine stands out in terms of its higher exposed surface area, particularly its side chain and non-polar atoms. It is also concluded that the solvent accessibility of a nucleotide strongly depends on its sequence neighbors and can be predicted with fair success using this information. | 18,955,120 |
In vitro release and characterization of chitosan films as dexamethasone carrier. | Chitosan, a biodegradable and biocompatible polysaccharide, is a potentially useful material in various fields. We produced mono and bilayer chitosan films containing dexamethasone as a drug carrier for controlled release. The chitosan drug-loaded films were produced by a casting/solvent evaporation technique using 2 wt% acetic acid solution and distilled water and they were dried at room temperature. These films were characterized by release and swelling studies, DSC and ATR-FTIR. The total profile for water absorption was similar for the types of films developed. ATR-FTIR analysis showed little change in the band position of the O--H and N--H stretching from dexamethasone and chitosan, respectively. DSC analysis from bilayer film indicates that the dexamethasone peak was shifted from 256 to 240 degrees C. These results suggested an interaction between hydroxyl and amino groups of chitosan and hydroxyl groups of dexamethasone. In the drug release studies it was observed 89.6% release from the monolayer film in 8h and 84% from the bilayer film in 4 weeks. These results suggested that the chitosan sheet prepared in this study is a promising delivery carrier for dexamethasone. | 18,955,123 |
Fiber-types of sarcomeric proteins expressed in cultured myogenic cells are modulated by the dose of myogenin activity. | The myogenic basic helix-loop-helix regulatory factors (MRFs) maintain commitment of proliferating cells to the skeletal myogenic lineage, and contribute to activation of transcription of muscle-specific genes in myocytes and muscle fibers. A clear role for any or all of the MRFs in muscle fiber-type determination, however, has not emerged from expression or genetic studies. During fetal, neonatal and adult life, diversification of muscle fiber types, and the dynamics of slow or fast fiber type adaptation and growth, are controlled by exogenous factors, including innervation, work load, and hormonal signaling. In contrast, stereotypical development of muscle fibers preferentially expressing slow or fast isoforms of sarcomeric proteins in the embryo occurs in the absence of these factors, and appears to be mediated both by input from the surrounding interstitial milieu, as well by cell autonomous mechanisms. We report here that diversification of myogenic cells in culture towards the expression of fast or slow skeletal muscle fiber types can be determined by the activity and dose of at least one MRF, myogenin. The dose of myogenin is modulated by two parameters: the phosphorylation state of the transcriptional activation domains, and the level of expression. Low doses of myogenin promoted a fast phenotype, whereas higher doses promoted a slow phenotype, and further studies suggested that diversification is mediated by both transcriptional and post-transcriptional mechanisms. The potential for dose or numeration signaling by basic helix-loop-helix regulators has been revealed by studies in Drosophila melanogaster, while the present results support the notion that this mechanism may be more commonly employed to generate subdiversity among developing cell types. | 18,955,131 |
The Hippo-YAP pathway: new connections between regulation of organ size and cancer. | The control of organ size is a basic biological question. In the past several years, the Hippo signaling pathway has been delineated and shown to be crucial in control of organ size in both Drosophila and mammals. Acting downstream of the Hippo pathway is the Yki/YAP/TAZ transcription co-activators. In mammalian cells, the Hippo pathway kinase cascade inhibits YAP and its paralog TAZ by phosphorylation and promotion of their cytoplasmic localization. The TEAD family transcription factors have recently been identified as evolutionarily conserved key mediators of YAP biological functions. yap is a candidate oncogene, and several other components of the Hippo pathway are tumor suppressors. Dysregulation of the Hippo pathway contributes to the loss of contact inhibition observed in cancer cells. Therefore, the Hippo-YAP pathway connects the regulation of organ size and tumorigenesis. | 18,955,139 |
Naltrexone aversion and treatment efficacy are greatest in humans and rats that actively consume high levels of alcohol. | The opioid antagonist naltrexone is the standard pharmacotherapy for alcoholism, although compliance is often low. The mechanism by which naltrexone reduces drinking is yet unclear. Here we show that in active alcoholics the magnitude of naltrexone treatment efficacy is correlated with the level of naltrexone-induced aversive side effects. This correlation is not observed when subjects are sober, but emerges following alcohol administration, when subjects are intoxicated. In contrast, there is no correlation following placebo administration. To clarify these results, naltrexone was administered to ethanol-consuming rats prior to quantification of naltrexone aversion. Ethanol consumption preceding naltrexone treatment was again correlated with subsequent naltrexone-induced aversion, and this aversion correlated with subsequent decrease in ethanol consumption. In contrast, when naltrexone was given to ethanol-free rats, aversion was not predictive of ethanol consumption. We conclude that naltrexone treatment efficacy is greater during active ethanol consumption and may be partly due to aversive side effects. | 18,955,144 |
Assessing mitochondrial outer membrane permeabilization during apoptosis. | Mitochondria play a pivotal role in the regulation of apoptosis. An imbalance in apoptosis can lead to disease. Unscheduled apoptosis has been linked to neurodegeneration while inhibition of apoptosis can cause cancer. An early and key event during apoptosis is the release of factors from mitochondria. In apoptosis the mitochondrial outer membrane becomes permeable, leading to release of apoptogenic factors into the cytosol. One such factor, cytochrome c, is an electron carrier of the respiratory chain normally trapped within the mitochondrial intermembrane space. Many apoptotic studies investigate mitochondrial outer membrane permeabilization (MOMP) by monitoring the release of cytochrome c. Here, we describe three reliable techniques that detect cytochrome c release from mitochondria, through subcellular fractionation or immunocytochemistry and fluorescence microscopy, or isolated mitochondria and recombinant Bax and t-Bid proteins in vitro. These techniques will help to identify mechanisms and characterize factors regulating MOMP. | 18,955,145 |
GintGRX1, the first characterized glomeromycotan glutaredoxin, is a multifunctional enzyme that responds to oxidative stress. | Glutaredoxins (GRXs) are small proteins with glutathione-dependent disulfide oxidoreductase activity involved in cellular defense against oxidative stress. This work reports the identification and characterization of the first glomeromycotan dithiol glutaredoxin gene from the fungus Glomus intraradices. The corresponding gene, named GintGRX1, shares high sequence similarity with previously described fungal GRXs. GintGRX1 contains the characteristic dithiol active site CPYC. By using a yeast expression system, we found that GintGRX1 encodes a multifunctional protein with oxidoreductase, peroxidase and glutathione S-transferase activity. GintGRX1 partially reverted sensitivity to superoxide radicals of the Deltagrx1Deltagrx2Saccharomyces cerevisiae strain. GintGRX1 was transcriptionally regulated by paraquat but not by hydrogen peroxide. Copper induced an accumulation of reactive oxygen species in the extraradical mycelium of G. intraradices and up-regulation of GintGRX1 transcript levels. These data suggest a role for GintGRX1 in protecting the fungus against the oxidative damage induced directly by the superoxide anion or indirectly by copper. | 18,955,149 |
Expression of genes encoding laccase and manganese-dependent peroxidase in the fungus Ceriporiopsis subvermispora is mediated by an ACE1-like copper-fist transcription factor. | The effect of copper on the expression of genes encoding the ligninolytic enzymes laccase (lcs) and manganese peroxidase (mnp) in Ceriporiopsis subvermispora was evaluated. This metal increased transcript levels of lcs, mnp1 and mnp2. This finding was not unexpected in the case of lcs, since its promoter contains a putative ACE element. Originally characterized in the yeast Saccharomyces cerevisiae, ACE is the target sequence of the ACE1 copper-responsive transcription factor in this microorganism. Analysis of the promoter regions of mnp genes revealed the presence of formerly unnoticed ACE elements. Based on the ace1 gene from Phanerochaete chrysosporium, we isolated and characterized an ACE1-like transcription factor from C. subvermispora (Cs-ACE1) through complementation of a S. cerevisiae ace1Delta strain. Surprisingly, ACE1 factors from both basidiomycetes exhibit substantial differences, not only structurally but also in their ability to complement the aforementioned yeast strain. Specific binding of Cs-ACE1 to its cognate DNA sequence was confirmed by electrophoretic mobility-shift assays. | 18,955,150 |
Predicting mortality in patients with bleeding peptic ulcers after therapeutic endoscopy. | Despite advances in management of patients with bleeding peptic ulcers, mortality is still 10%. This study aimed to identify predictive factors and to develop a prediction model for mortality among patients with bleeding peptic ulcers. Consecutive patients with endoscopic stigmata of active bleeding, visible vessels, or adherent clots were recruited, and risk factors for mortality were identified in this deprivation cohort by using multiple stepwise logistic regression. A prediction model was then built on the basis of these factors and validated in the evaluation cohort. From 1993 to 2003, 3220 patients with bleeding peptic ulcers were treated. Two hundred eighty-four of the patients developed rebleeding (8.8%); emergency surgery was performed on 47 of these patients, whereas others were managed with endoscopic retreatment. Two hundred twenty-nine of these sustained in-hospital death (7.1%). In patients older than 70 years, presence of comorbidity, more than 1 listed comorbidity, hematemesis on presentation, systolic blood pressure below 100 mm Hg, in-hospital bleeding, rebleeding, and need for surgery were significant predictors for mortality. Helicobacter pylori-related ulcers had lower risk of mortality. The receiver operating characteristic curve comparing the prediction of mortality with actual mortality showed an area under the curve of 0.842. From 2004 to 2006, data were collected prospectively from a second cohort of patients with bleeding peptic ulcers, and mortality was predicted by using the model developed. The receiver operating characteristic curve showed an area under the curve of 0.729. Among patients with bleeding peptic ulcers after endoscopic hemostasis, advanced age, presence of listed comorbidity, multiple comorbidities, hypovolemic shock, in-hospital bleeding, rebleeding, and need for surgery successfully predicted in-hospital mortality. | 18,955,161 |
Recurrent syncope due to carotid sinus hypersensitivity and sick sinus syndrome. | Syncope is a sudden and brief loss of consciousness with postural tone. Its recovery is usually spontaneous. There are various causes of syncope including cardiac, vascular, neurologic, metabolic and miscellaneous origins. The tracing is usually time-consuming and costly. The diagnosis of carotid sinus syncope may sometimes be difficult since the symptoms are nonspecific, especially in older persons. Here, we report the case of a 72-year-old woman who sought medical attention at our hospital due to repeated syncope episodes over the previous 5 years. Neurologic examinations showed negative results (including brain computed tomography). Twenty-four-hour ambulatory electrocardiogram monitoring showed atrial and ventricular premature contractions only. Electrophysiologic study disclosed prolonged corrected sinus node recovery time (1,737 ms) with poor atrioventricular conduction. Drop of blood pressure together with sinus bradycardia developed after left side carotid sinus massage. Both carotid sinus hypersensitivity with sick sinus syndrome contributed to this patient's syncope, and after pacemaker placement together with selective serotonin reuptake inhibitor treatment, she was free from syncope thereafter. | 18,955,189 |
Antioxidant activity of 45 Chinese herbs and the relationship with their TCM characteristics. | Here, 45 Chinese herbs that regulate blood circulation were analyzed for antioxidant activity using the oxygen radical absorbance capacity (ORAC) assay. A recent publication by Ou et al. identified a close relationship between in vitro antioxidant activity and classification of Chinese herbs as yin or yang. The 45 Chinese herbs in this study could be assigned the traditional characteristics of natures (cold, cool, hot and warm), flavors (pungent, sweet, sour, bitter and salty) and functions (arresting bleeding, promoting blood flow to relieve stasis, nourishing blood and clearing away heat from blood). These characteristics are generalized according to the theory of yin and yang. We identified a broad range, 40-1990 micromol Trolox Equivalent/g herbs, of antioxidant activity in water extracts. There was no significant correlation between ORAC values and natures or functions of the herbs. There was a significant relationship between flavors and ORAC values. Bitter and/or sour herbs had the highest ORAC values, pungent and/or sweet herbs the lowest. Other flavors had intermediate values. Flavors also correspond with the yin/yang relationship and our results are supportive of the earlier publication. We reported for the first time antioxidant properties of many Chinese herbs. High antioxidant herbs were identified as Spatholobus suberectus vine (1990 micromol TE/g), Sanguisorba officinalis root (1940 micromol TE/g), Agrimonia pilosa herb (1440 micromol TE/g), Artemisia anomala herb (1400 micromol TE/g), Salvia miltiorrhiza root (1320 micromol TE/g) and Nelembo nucifera leaf (1300 micromol TE/g). Antioxidant capacity appears to correlate with the flavors of herbs identified within the formal TCM classification system and may be a useful guide in describing their utility and biochemical mechanism of action. | 18,955,214 |
Brazilian red propolis--chemical composition and botanical origin. | Propolis contains resinous substances collected by honey bees from various plant sources and has been used as a traditional folk medicine since ca 300 BC. Nowadays, the use of evidence-based complementary and alternative medicine (CAM) is increasing rapidly and so is the use of propolis in order to treat or support the treatment of various diseases. Much attention has been focused on propolis from Populus sp. (Salicaceae) and Baccharis dracunculifolia (Asteracea), but scientific information about the numerous other types of propolis is still sparse. We gathered six samples of red propolis in five states of Northeastern Brazil. The beehives were located near woody perennial shrubs along the sea and river shores. The bees were observed to collect red resinous exudates on Dalbergia ecastophyllum (L) Taub. (Leguminosae) to make propolis. The flavonoids of propolis and red resinous exudates were investigated using reversed-phase high-performance liquid chromatography and reversed-phase high-performance thin-layer chromatography. We conclude that the botanical origin of the reddish propolis is D. ecastophyllum. In areas where this source (D. ecastophyllum) was scarce or missing, bees were collecting resinous material from other plants. Propolis, which contained the chemical constituents from the main botanical origin, showed higher antimicrobial activity. | 18,955,226 |
Evaluation of Antioxidant Properties of Phaulopsis fascisepala C.B.Cl. (Acanthaceae). | The antioxidant activities of crude extract of Phaulopsis fascisepala leaf were evaluated and compared with alpha-tocopherol and BHT as synthetic antioxidants and ascorbic acid as natural-based antioxidant. In vitro, we studied its antioxidative activities, radical-scavenging effects, Fe(2+)-chelating ability and reducing power. The total phenolic content was determined and expressed in gallic acid equivalent. The extract showed variable activities in all of these in vitro tests. The antioxidant effect of P. fascisepala was strongly dose dependent, increased with increasing leaf extract dose and then leveled off with further increase in extract dose. Compared to other antioxidants used in the study, alpha-Tocopherol, ascorbic acid and BHT, P. fascisepala leaf extract showed less scavenging effect on alpha,alpha,-diphenyl-beta-picrylhydrazyl (DPPH) radical and less reducing power on Fe(3+)/ferricyanide complex but better Fe(2+)-chelating ability. These results revealed the in vitro antioxidant activity of P. fascisepala. Further investigations are necessary to verify these activities in vivo. | 18,955,238 |
Mistletoe Preparation Iscador: Are there Methodological Concerns with Respect to Controlled Clinical Trials? | In Europe many cancer patients use complementary therapies, particularly mistletoe. Only a few controlled clinical trials have been performed with the mistletoe preparation Iscador as a complementary treatment for cancer, many of them with medium to low quality due to methodological shortcomings. Reasons for some quality concerns, particularly discontinuation of treatment and/or participation and premature termination are analyzed. Analysis is based on controlled clinical trials dealing with Iscador. Data stem from the archive of published and ongoing research of the <<Verein für Krebsforschung>> (Society for Cancer Research) in Arlesheim, Switzerland. Controlled clinical studies with cancer patients that were started after 01.01.1990 or were not completed by then have been evaluated. Fifty-six controlled studies are documented, 24 of them randomized and 32 non-randomized. Nine of the randomized studies were done by matched-pair design, the others by conventional parallel group design; six of the last were terminated prematurely primarily for slow recruitment due to patient preferences and compliance of physicians. Patient and physician preference seem to be important factors limiting recruitment for randomized trials and hence implementation. This adds to the overall unwillingness of participation by patients with serious diseases. A well-balanced mix of designs using different research methods and outcomes is suggested combined with analyses, in countries where mistletoe therapy in general or Iscador in particular is unknown or not available. | 18,955,241 |
Influence of Honey on the Suppression of Human Low Density Lipoprotein (LDL) Peroxidation (In vitro). | The antioxidant activity of four honey samples from different floral sources (Acacia, Coriander, Sider and Palm) were evaluated with three different assays; DPPH free radical scavenging assay, superoxide anion generated in xanthine-xanthine oxidase (XOD) system and low density lipoprotein (LDL) peroxidation assay. The dark Palm and Sider honeys had the highest antioxidant activity in the DPPH assay. But all the honey samples exhibited more or less the same highly significant antioxidant activity within the concentration of 1mg honey/1 ml in XOD system and LDL peroxidation assays. The chemical composition of these samples was investigated by GC/MS and HPLC analysis, 11 compounds being new to honey. The GC/MS revealed the presence of 90 compounds, mainly aliphatic acids (37 compounds), which represent 54.73, 8.72, 22.87 and 64.10% and phenolic acids (15 compound) 2.3, 1.02, 2.07 and 11.68% for Acacia, Coriander, Sider and Palm honeys. In HPLC analysis, 19 flavonoids were identified. Coriander and Sider honeys were characterized by the presence of large amounts of flavonoids. | 18,955,249 |
Assessment of antimalarial activity against Plasmodium falciparum and phytochemical screening of some Yemeni medicinal plants. | Developing countries, where malaria is one of the most prevalent diseases, still rely on traditional medicine as a source for the treatment of this disease. In the present study, six selected plants (Acalypha fruticosa, Azadirachta indica, Cissus rotundifolia, Echium rauwalfii, Dendrosicyos socotrana and Boswellia elongata) commonly used in Yemen by traditional healers for the treatment of malaria as well as other diseases, were collected from different localities of Yemen, dried and extracted with methanol and water successfully. The antiplasmodial activity of the extracts was evaluated against fresh clinical isolates of Plasmodium falciparum. The selectivity parameters to evaluate the efficacy of these medicinal plants were measured by in vitro micro test (Mark III) according to World Health Organization (WHO) 1996 & WHO 2001 protocols of antimalarial drug tests. Among the investigated 12 extracts, three were found to have significant antiplasmodial activity with IC(50) values less than 4 microg/ml, namely the water extracts of A. fruticosa, A. indica and D. socotrana. Six extracts showed moderate activity with IC(50) values ranging from 10 to 30 microg/ml and three appeared to be inactive with IC(50) values more than 30 microg/ml. In addition, preliminary phytochemical screening of the methanolic and aqueous extracts indicated the presence of saponins, tannins, flavonoids, terpenoids, polysaccharides and peptides. | 18,955,251 |
Acori graminei rhizoma ameliorated ibotenic acid-induced amnesia in rats. | In the present study, we investigated the effects of Acori graminei rhizoma (AGR) on learning and memory for the Morris water maze task and on the central cholinergic system of the rats with excitotoxic medial septum (MS) lesion. On the water maze test, the rats were trained to find a platform that was in a fixed position during 6 days and then they received a 60 s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesioning of the MS impaired the performance on the maze test and it caused degeneration of choline acetyltransferase and acetylcholine esterase in the hippocampus, which are markers of the central cholinergic system. Daily administrations of AGR (100 mg kg(-1), i.p.) for 21 consecutive days produced reversals of the ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus that was induced by ibotenic acid. These results demonstrated that AGR ameliorated learning and memory deficits through their effects on the central nervous system, and neuroprotection was partly evaluated through the effect of AGR on the cholinergic system. Our studies suggest that AGR can possibly be used as treatment for Alzheimer's disease. | 18,955,253 |
Oral Administration of Ren-Shen-Yang-Rong-Tang 'Ninjin'yoeito' Protects Against Hematotoxicity and Induces Immature Erythroid Progenitor Cells in 5-Fluorouracil-induced Anemia. | The purpose of this study was to investigate the efficacy of four different Japanese and Chinese herbal prescriptions, Ren-Shen-Yang-Rong-Tang (Ninjin'yoeito, NYT), Chai-Hu-Gui-Zhi-Gan-Jiang-Tang (Saikokeishikankyoto, SKKT), Si-Jun-Zi-Tang (Shikunshito, SKT) and Si-Wu-Tang (Shimotsuto, SMT), which are traditionally used for anemia and fatigue, against hematotoxicity in mice treated with 5-fluorouracil (5-FU). NYT 1-100 mg kg(-1) day(-1) injected orally for 7 consecutive days before and after 5-FU injection significantly suppressed reductions in red blood cell, white blood cell and platelet counts in peripheral blood, and accelerated their recovery. Administration of SKKT also produced a slight but significant improvement in 5-FU-induced erythrocytopenia, whereas SMT and SKT could not prevent anemia. Oral injection of NYT also inhibited 5-FU-induced decreases in peripheral reticulocyte and bone marrow cell counts on day 10, and markedly hastened their recovery on day 20, in a dose-dependent manner. Erythroid progenitor colonies, such as colony forming units-erythroid and burst forming units-erythroid, formed by marrow cells from mice treated with 5-FU were significantly increased by oral administration of NYT. These findings suggest that NYT has the potential to protect against hematotoxicity, and also has hematopoietic activity, through stimulation of immature erythroid progenitor cell differentiation. | 18,955,264 |
Regulation of Caspase-3 and Bcl-2 Expression in Dalton's Lymphoma Ascites Cells by Abrin. | The role of abrin, a toxic lectin isolated from seeds of Abrus precatorius Linn in inducing apoptosis in murine Dalton's Lymphoma Ascites (DLA) cells was evaluated. Abrin when incubated at the concentration of 10 ng per million DLA cells could bring about cell death as typical morphological changes with apoptosis. However, necrotic cell death dominated when a higher dose of abrin was used. DNA samples, isolated from DLA cells treated with abrin showed fragmentation. Abrin brought about induction of apoptosis by stimulating the expression of pro-apoptotic Caspase-3, at the same time blocking the expression of Bcl-2, which is an anti apoptotic gene. However, the expression of tumor suppressor gene p53 has not been observed in control and abrin-treated DLA cells. Results suggested that abrin effectively induced apoptotic changes in the tumor cells that led to cellular death. | 18,955,274 |
Pogostemon cablin as ROS Scavenger in Oxidant-induced Cell Death of Human Neuroglioma Cells. | Reactive oxygen species (ROS) have been implicated in the pathogenesis of a wide range of acute and long-term neurodegenerative diseases. This study was undertaken to examine the efficacy of Pogostemon cablin, a well-known herb in Korean traditional medicine, on ROS-induced brain cell injury. Pogostemon cablin effectively protected human neuroglioma cell line A172 against both the necrotic and apoptotic cell death induced by hydrogen peroxide (H(2)O(2)). The effect of Pogostemon cablin was dose dependent at concentrations ranging from 0.2 to 5 mg ml(-1). Pogostemon cablin significantly prevented depletion of cellular ATP and activation of poly ADP-ribose polymerase induced by H(2)O(2). The preservation of functional integrity of mitochondria upon the treatment of Pogostemon cablin was also confirmed by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2-H-tetrazolium bromide assay. Furthermore, Pogostemon cablin significantly prevented H(2)O(2)-induced release of cytochrome c into cytosol. Determination of intracellular ROS showed that Pogostemon cablin might exert its role as a powerful scavenger of intracellular ROS. The present study suggests the beneficial effect of Pogostemon cablin on ROS-induced neuroglial cell injury. The action of Pogostemon cablin as a ROS-scavenger might underlie the mechanism. | 18,955,302 |
Acupuncture effects on cardiac functions measured by cardiac magnetic resonance imaging in a feline model. | The usefulness of acupuncture (AP) as a complementary and/or alternative therapy in animals is well established but more research is needed on its clinical efficacy relative to conventional therapy, and on the underlying mechanisms of the effects of AP. Cardiac magnetic resonance imaging (CMRI), an important tool in monitoring cardiovascular diseases, provides a reliable method to monitor the effects of AP on the cardiovascular system. This controlled experiment monitored the effect electro-acupuncture (EA) at bilateral acupoint Neiguan (PC6) on recovery time after ketamine/xylazine cocktail anesthesia in healthy cats. The CMRI data established the basic feline cardiac function index (CFI), including cardiac output and major vessel velocity. To evaluate the effect of EA on the functions of the autonomic nervous and cardiovascular systems, heart rate, respiration rate, electrocardiogram and pulse rate were also measured. Ketamine/xylazine cocktail anesthesia caused a transient hypertension in the cats; EA inhibited this anesthetic-induced hypertension and shortened the post-anesthesia recovery time. Our data support existing knowledge on the cardiovascular benefits of EA at PC6, and also provide strong evidence for the combination of anesthesia and EA to shorten post-anesthesia recovery time and counter the negative effects of anesthetics on cardiac physiology. | 18,955,311 |
Lipid Lowering Activity of Anthocephalus indicus Root in Hyperlipidemic Rats. | The lipid lowering activity of Anthocephalus indicus (family Rubiaceae; Hindi name Kadamba) root extract has been studied in triton WR-1339 induced hyperlipidemia in rats. In this model, feeding with root extract (500 mg kg(-1) b.w.) lowered plasma lipids and reactivated post-heparin lipolytic activity in hyperlipidemic rats. Furthermore, the root extract (50-500 μM) inhibited the generation of superoxide anions and hydroxyl radicals, in both enzymic and non-enzymic systems, in vitro. The results of the present study demonstrated both lipid lowering and antioxidant activities in root extract of A. indicus, which could help prevention of hyperlipidemia and related diseases. | 18,955,320 |
The Role of Dual-trained Conventional/Complementary Physicians as Mediators of Integration in Primary Care. | A growing number of physicians study complementary and alternative medicine (CAM). Limited data are available on perspectives of physicians with dual training in conventional medicine and CAM, on issues of communication and collaboration with CAM practitioners (CAMPs). Questionnaires were administered to primary care physicians employed in the largest health maintenance organization (HMO) in Israel and to MD and non-MD CAM practitioners employed by a CAM-related agency of the same HMO. Data for statistical analysis were available from 333 primary care physicians (PCPs) and 241 CAM practitioners. Thirty-one of the 241 CAMPs were dual-trained physicians employed in a CAM-related agency as practitioners and/or triage-consultants. Dual trained physicians and CAMPs shared similar attitudes and supported, more so than PCPs, collaborative physician-CAM practitioner teamwork in clinical practice, medical education and research. Nevertheless, dual trained physicians supported a physician-dominant teamwork model (similar to the PCPs' approach) in contrast to non-MD CAM practitioners who mainly supported a co-directed teamwork model. Compared to PCPs and non-MD CAM practitioners, dual trained physicians supported significantly more a medical/referral letter as the preferred means of doctor-CAM practitioner communication. Dual trained physicians have a unique outlook toward CAM integration and physician-practitioner collaboration, compared to non-MD CAM practitioners and PCPs. More studies are warranted to explore the role of dual trained physicians as mediators of integration. | 18,955,339 |
Traditional Arabic and Islamic Medicine, a Re-emerging Health Aid. | Complementary medicine is a formal method of health care in most countries of the ancient world. It is expected to become more widely integrated into the modern medical system, including the medical curriculum. Despite the perception of modern medicine as more efficacious, traditional medicine continues to be practiced. More than 70% of the developing world's population still depends primarily on the complementary and alternative systems of medicine (CAM). In rural areas, cultural beliefs and practices often lead to self-care, home remedies or consultation with traditional healers. Herbal medicine can be broadly classified into four basic systems as follows: Traditional Chinese Herbalism, Ayurvedic Herbalism, Western Herbalism-which originally came from Greece and Rome to Europe and then spread to North and South America and Traditional Arabic and Islamic Medicine (TAIM). There is no doubt that today the concept of Arabic traditional herbal medicine is a part of modern life in the Middle East, and it is acquiring worldwide respect, with growing interest among traditional herbalists and the scientific community. TAIM therapies have shown remarkable success in healing acute as well as chronic diseases and have been utilized by people in most countries of the Mediterranean who have faith in spiritual healers. TAIM is the first choice for many in dealing with ailments such as infertility, epilepsy, psychosomatic troubles and depression. In parallel, issues of efficacy and safety of complementary medicine have become increasingly important and supervision of the techniques and procedures used is required for commercial as well as traditional uses. More research is therefore needed to understand this type of medicine and ensure its safe usage. The present review will discuss the status of traditional Arab medicine (particularly herbal medicine), including the efficacy and toxicity of specific medicinal preparations, with an emphasis on the modern in vitro and in vivo techniques. | 18,955,344 |
An international comparison of attitudes toward traditional and modern medicine in a chinese and an american clinic setting. | Introduction. International comparative research on traditional medicine (TM) offers a useful method for examining differences in patient characteristics and can provide insight into: (i) more universal characteristics which may cross cultures and international borders; (ii) unique characteristics influenced by regional/national factors; and (iii) cultural values of immigrant populations. To explore these issues TM patients from the United States and China were compared. Methods. Data collection took place at two TM college clinics. A convenience sample of 128 patients in China and 127 patients in the United States completed a 28-item questionnaire. Results. There was a marked similarity between the two patient groups in terms of the biological characteristics of age and gender. Musculoskeletal issues were the most common presenting complaints in the United States; while in China TM was used for a more diverse array of conditions. The majority of patients in both countries had initially used allopathic medicine (AM); significantly, more of the United States respondents stopped allopathic treatment after beginning traditional treatment. In comparing the two countries, patients in China were significantly more satisfied with AM and American patients significantly more satisfied with TM. In comparing the two medicines, the patient samples in both countries were significantly more satisfied with TM than AM. Discussion. Although treatment often originated with allopathic providers, many patients sought alternatives presumably to find the best solution to their problems. This tendency toward self-assignment suggests that a pluralistic healthcare system may provide the greatest satisfaction resulting from personal choice and improved outcomes. | 18,955,368 |
Echocardiographic optimization of the atrioventricular and interventricular intervals during cardiac resynchronization. | An optimized atrioventricular (AV) interval can maximize the benefits of cardiac resynchronization therapy (CRT). If programmed poorly, it may curtail beneficial effects of CRT. AV optimization will not convert non-responder to responder, but may convert under-responder to improved status. There are many echocardiographic techniques for AV optimization but there is no universally accepted gold standard. The optimal AV delay varies with time, necessitating periodic re-evaluation. As the optimal AV delay may lengthen on exercise, a rate-adaptive AV delay should not be routinely programmed. Intra- and interatrial conduction delays may require AV junctional ablation when AV optimization is impossible in patients with a poor clinical response. Fusion with the spontaneous QRS complex may be acceptable on a trial basis to seek a better clinical response or with a short PR interval. Routine VV optimization is presently controversial but programming may prove beneficial in some patients with a suboptimal CRT response where no cause is found. It may partially compensate for less than optimal left ventricular (LV) lead position and may correct for heterogeneous ventricular activation including a prolonged LV latency interval and slow conduction (scarring) near the LV pacing site. VV timing is generally programmed using the aortic velocity-time integral, and long-term variations of the optimal value necessitate periodic re-evaluation. | 18,955,406 |
Evaluation of daily online set-up errors and organ displacement uncertainty during conformal radiation treatment of the prostate. | We have studied and analysed the magnitude of interfraction set-up errors and gold seed marker and prostate displacement in 118 patients using three gold seeds implanted within the prostate. Set-up errors and gold seed marker displacements were determined from bony anatomy and gold seed marker mismatch between the electronic portal image and the simulation digitally reconstructed radiograph (DRR), respectively. Prostate displacement relative to bony anatomy was determined from the difference between gold seed marker and bony anatomy displacement. Daily online repositioning of patients was accomplished through image matching using Varian Portal-Vision software. A total of 4878 electronic portal images and 236 DRRs from 118 patients were acquired over the course of the study. The means and standard deviations of the systematic error of gold seed marker displacement of 118 patients were 2.1+/-2.7 mm for anteroposterior (AP), -0.5+/-1.7 mm for left-right (L-R), and 1.0+/-1.9 mm for superoinferior (SI) directions; the random errors were 3.2 mm (0.9-4.9 mm) for AP, 1.9 mm (0.7-5.3 mm) for L-R, and 2.1 mm (0.7-4.5 mm) for SI directions. The mean and standard deviation of the isocentre set-up systematic error of 20 patients was 1.2+/-2.2 mm for AP, -0.1+/-1.4 mm for L-R, and -0.8+/-2.6 mm for SI directions. The isocentre set-up random errors were 1.6 mm (1.2-4.8 mm) for AP, 1.3 mm (0.6-2.5 mm) for L-R and 1.3 mm (1.0-2.6 mm) for SI directions. The mean and standard deviation of the prostate displacement systematic error relative to bony anatomy was 0.0+/-1.4 mm for AP, 0.0+/-1.1 mm for L-R and -0.2+/-2.4 mm for SI directions. Prostate displacement random errors were 1.5 mm (1.2-3.3 mm) for AP, 0.9 mm (0.4-1.5 mm) for L-R and 1.4 mm (1.2-2.4 mm) for SI directions. | 18,955,413 |
Sharp recanalization of central venous occlusions: a useful technique for haemodialysis line insertion. | Central venous occlusions can be difficult to traverse using conventional catheter and wire techniques. We describe six procedures in five patients using a technique of "sharp" recanalization and subsequent line insertion. The technique was successful in all of the cases, with the line functional for a mean duration of 13 months. This technique can permit successful dialysis catheter placement in patients who have failed with traditional techniques. | 18,955,417 |
Effect of pre-operative physiotherapy in patients with end-stage osteoarthritis undergoing hip arthroplasty. | To examine the effect of pre-operative physiotherapy before hip arthroplasty in patients with end-stage hip osteoarthritis. A prospective randomized controlled study. Physical medicine and rehabilitation and orthopaedic departments of Policlinico Gemelli of Rome. Twenty-three patients randomized in study and control groups. The study group took part in an educational and physiotherapy programme one month before surgery. Both groups took part in the same inpatient rehabilitation programme after surgery. Both groups were evaluated one month (T0) and the day before arthroplasty (T1), after 15 days (T2), four weeks (T3) and three months (T4) post surgery, using the Barthel Index, the Short Form-36 (SF-36), the Western Ontario and McMaster Osteoarthritis Index (WOMAC), the Hip Harris Score (HHS), visual analogue scale (VAS), the British Medical Research Council (BMRC) measures of hip abductor and quadriceps strength and range of hip abduction and external rotation. There were no significant differences between groups with regard to the Barthel Index, SF-36, WOMAC and HHS at T4. The study group presented significant improvements of the SF-36 physical composite score at T1. The hip external rotation was significantly higher in the study group at each evaluation and the visual analogue scale values were lower at T1, T3 and T4. Pre-operative physiotherapy in patients undergoing hip arthroplasty does not improve impairment and health-related quality of life after intervention. Physiotherapy and educational therapy may be useful for end-stage osteoarthritis. | 18,955,429 |
How much do the benefits cost? Effects of a home-based training programme on cardiovascular fitness, quality of life, programme cost and adherence for patients with coronary disease. | To evaluate cost, adherence and effects on cardiovascular function and quality of life of a home-based cardiac rehabilitation programme for patients with coronary disease. A randomized, prospective controlled trial. Department of Rehabilitation, University Hospital, Brazil. Thirty-nine low-risk patients were assigned to a home exercise training group (n = 19) or a control group (n = 20). The home group performed home-based training for three months with biweekly telephone monitoring. The aerobic capacity and the quality of life (Medical Outcomes Study 36-Item Short Form Survey (SF-36)) of all patients were evaluated before and after the three-month period. Adherence was evaluated weekly. Programme cost was estimated using the Brazilian Classification of Medical Procedures. After training, the home group had higher peak Vo2 from 28.8 (6.4) to 31.7 (8.1) mL/kg per minute, peak heart rate from 135 (22) to 143 (20) bpm, work rate from 4780 (2021) to 7103 (3057) kpm/min and exercise time from 11.5 (1.9) to 13.6 (2.3) minutes (P < or = .05). The control group showed reduction in peak Vo2 from 28.6 (6.6) to 26.8 (7.2) mL/kg per minute, peak Vo2 pulse from 15.5 (3.9) to 14.3 (3.8) mL/bpm and exercise time from 11.5 (2.3) to 11.4 (2.7) minutes (P < or = 0.05). The home group reported improvements in all domains of SF-36. The control group showed improvement in only three domains of SF-36. In the home group the average cost per patient was US$502.71 and the adherence achieved 100%. The programme seems to provide an efficient low-cost approach to cardiac rehabilitation in low-risk patients. | 18,955,430 |
Cohort study of fatty acid synthase expression and patient survival in colon cancer. | Energy balance seems to be important in the pathogenesis of colon cancer. Fatty acid synthase (FASN) is physiologically regulated by energy balance and is often upregulated in colorectal cancer. Nonetheless, the influence of FASN expression on patient outcome is uncertain. Using the database of 647 patients with colon cancer in two independent cohort studies, FASN overexpression was detected in 84 tumors (13%) by immunohistochemistry. Cox proportional hazards models calculated hazard ratios (HRs) of colon cancer-specific and overall mortalities, adjusted for patient characteristics and related tumoral features, including KRAS, BRAF, p53, microsatellite instability and the CpG island methylation phenotype. There were 279 deaths, including 160 colon cancer-specific deaths. FASN overexpression was associated with a significant reduction in colon cancer-specific mortality by both univariate and multivariate analyses (adjusted HR, 0.41; 95% CI, 0.19 to 0.89) and an insignificant trend toward improved overall mortality (adjusted HR, 0.75; 95% CI, 0.50 to 1.13). Notably, the effect of FASN expression on mortality might be different according to body mass index (BMI; P(interaction) = .019); the adjusted HR of overall mortality for FASN overexpression was 0.63 (95% CI, 0.39 to 1.02) among patients with BMI less than 27.5 kg/m(2) and 2.91 (95% CI, 1.19 to 7.12) among those with BMI >or= 27.5 kg/m(2). Moreover, the adverse effect of moderate overweight/obesity on overall survival was limited to FASN-positive tumors (adjusted HR, 4.10; 95% CI, 1.14 to 14.8; BMI >or= 27.5 kg/m(2) v < 27.5 kg/m(2)). CONCLUSION Among nonobese patients with colon cancer, tumoral FASN overexpression is associated with improved survival, whereas among moderately overweight or obese patients (BMI >or= 27.5 kg/m(2)), FASN overexpression may predict a worse outcome. | 18,955,444 |
Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177. | Epidermal growth factor receptor (EGFR) amplification in glioblastoma multiforme (GBM) is a common occurrence and is associated with treatment resistance. Erlotinib, a selective EGFR inhibitor, was combined with temozolomide (TMZ) and radiotherapy (RT) in a phase I/II trial. Adults not taking enzyme-inducing anticonvulsants after resection or biopsy of GBM were treated with erlotinib (150 mg daily) until progression. Erlotinib was delivered alone for 1 week, then concurrently with TMZ (75 mg mg/m(2) daily) and RT (60 Gy), and finally, concurrently with up to six cycles of adjuvant TMZ (200 mg/m(2) daily for 5 days every 28 days). The primary end point was survival at 1 year. Ninety-seven eligible patients were accrued with a median follow-up time of 22.2 months. By definition, the primary end point was successfully met with a median survival time of 15.3 months. However, there was no sign of benefit in overall survival when comparing N0177 with the RT/TMZ arm of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981/22981 (recursive partitioning analysis [RPA] class III, 19 v 21 months; RPA class IV, 16 v 16 months; RPA class V, 8 v 10 months, respectively). Presence of diarrhea, rash, and EGFRvIII, p53, phosphatase and tensin homolog (PTEN), combination EGFR and PTEN, and EGFR amplification status were not predictive (P > .05) of survival. Although the primary end point was successfully met using nitrosourea-based (pre-TMZ) chemotherapy era historic controls, there was no sign of benefit compared with TMZ era controls. Analyses of molecular subsets did not reveal cohorts of patients sensitive to erlotinib. TMZ chemotherapy combined with RT resulted in improved outcomes compared with historical controls who received nitrosourea-based chemotherapies. | 18,955,445 |
Impact of disease risk on efficacy of matched related bone marrow transplantation for pediatric acute myeloid leukemia: the Children's Oncology Group. | There is considerable variation in the use of HLA-matched related bone marrow transplantation (BMT) for the treatment of pediatric patients with newly diagnosed acute myeloid leukemia (AML). Some oncologists have argued that BMT should be offered to most patients in first complete remission (CR). Others have maintained that transplantation in first remission should be reserved for patients with high-risk disease. We performed this study to determine how disease risk influences the efficacy of BMT. We combined data from four cooperative group clinical trials: Pediatric Oncology Group 8821, Children's Cancer Group (CCG) 2891, CCG 2961, and Medical Research Council 10. Using cytogenetics and the percentage of marrow blasts after the first course of chemotherapy, patients were stratified into favorable, intermediate, and poor-risk disease groups. Patients who could not be risk classified were analyzed separately. Outcomes for patients assigned to BMT and for patients assigned to chemotherapy alone were compared. The data set included 1,373 pediatric patients with AML in first CR. In the intermediate-risk group, the estimated disease-free survival at 8 years for patients who did not undergo transplantation was 39% +/- 5% (2 SE), whereas it was 58% +/- 7% for BMT patients. The estimated overall survival for patients who did not undergo transplantation was 51% +/- 5%, whereas it was 62% +/- 7% for BMT patients. Both differences were significant (P < .01). There were no significant differences for survival in the other two risk groups or in the non-risk-stratified patients. Our study indicates that HLA-matched related BMT is an effective treatment for pediatric patients with intermediate-risk AML in first CR. | 18,955,460 |
Human polymorphonuclear neutrophil responses to Burkholderia pseudomallei in healthy and diabetic subjects. | The major predisposing factor for melioidosis is diabetes mellitus, but no immunological mechanisms have been investigated to explain this. In this study, polymorphonuclear neutrophil (PMN) responses to Burkholderia pseudomallei, the causative agent of melioidosis, in healthy and diabetic Thai subjects were determined by flow cytometry. The results showed that B. pseudomallei displayed reduced uptake by PMNs compared to Salmonella enterica serovar Typhimurium and Escherichia coli. Additionally, intracellular survival of B. pseudomallei was detected throughout a 24-h period, indicating the intrinsic resistance of B. pseudomallei to killing by PMNs. Moreover, PMNs from diabetic subjects displayed impaired phagocytosis of B. pseudomallei, reduced migration in response to interleukin-8, and an inability to delay apoptosis. These data show that B. pseudomallei is intrinsically resistant to phagocytosis and killing by PMNs. These observations, together with the impaired migration and apoptosis in diabetes mellitus, may explain host susceptibility in melioidosis. | 18,955,471 |
Inactivation of G-protein-coupled receptor 48 (Gpr48/Lgr4) impairs definitive erythropoiesis at midgestation through down-regulation of the ATF4 signaling pathway. | G-protein-coupled receptors (GPCRs), one of the most versatile groups of cell surface receptors, can recognize specific ligands from neural, hormonal, and paracrine organs and regulate cell growth, proliferation, and differentiation. Gpr48/LGR4 is a recently identified orphan GPCR with unknown functions. To reveal the functions of Gpr48 in vivo, we generated Gpr48-/- mice and found that Gpr48-/- fetuses displayed transient anemia during midgestation and abnormal definitive erythropoiesis. The dramatic decrease of definitive erythroid precursors (Ter119pos population) in Gpr48-/- fetal liver at E13.5 was confirmed by histological analysis and blood smear assays. Real-time PCR analyses showed that in Gpr48-/- mice both adult hemoglobin alpha and beta chains were decreased while embryonic hemoglobin chains (zeta, betaH1, and epsilony) were increased, providing another evidence for the impairment of definitive erythropoiesis. Furthermore, proliferation was suppressed in Gpr48-/- fetal liver with decreased c-Myc and cyclin D1 expression, whereas apoptosis was unaffected. ATF4, a key transcription factor in erythropoiesis, was down-regulated in Gpr48-/- fetal livers during midgestation stage through the cAMP-PKA-CREB pathway, suggesting that Gpr48 regulated definitive erythropoiesis through ATF4-mediated definitive erythropoiesis. | 18,955,481 |
Human anti-gold antibodies: biofunctionalization of gold nanoparticles and surfaces with anti-gold antibodies. | The interface molecules designed to exhibit molecular recognitions between different species have become attractive tools for the bottom-up fabrication and hybridization of nanostructured units. Here, we focus on antibodies with high binding ability and specificity to construct a novel biomolecule interface for recognizing an inorganic material. Careful selection from a phage-displayed library of variable region heavy and light Fv chains of human antibodies using enzyme-linked immunosorbent assay and surface plasmon resonance assay resulted in the identification of an antibody fragment, A14P-b2, with high affinity (KD = 1.7 nm) and specificity for gold materials. Our results indicated the potential usefulness of human antibody libraries and the effectiveness of the antibody framework for recognizing bulk material surfaces. Construction of bivalent and bispecific antibodies on the A14P-b2 platform with high affinity by means of fusion technology enabled the functionalization of gold nanoparticles and allowed selective protein accumulation on gold spots patterned on a silicon substrate. This type of antibody engineering is potentially applicable to bio-inspired materials and nanobiosensing. | 18,955,492 |
Study of the in vitro activities of rifaximin and comparator agents against 536 anaerobic intestinal bacteria from the perspective of potential utility in pathology involving bowel flora. | Rifaximin, ampicillin-sulbactam, neomycin, nitazoxanide, teicoplanin, and vancomycin were tested against 536 strains of anaerobic bacteria. The overall MIC of rifaximin at which 50% of strains were inhibited was 0.25 microg/ml. Ninety percent of the strains tested were inhibited by 256 microg/ml of rifaximin or less, an activity equivalent to those of teicoplanin and vancomycin but less than those of nitazoxanide and ampicillin-sulbactam. | 18,955,526 |
Plasmid-mediated 16S rRNA methylases in aminoglycoside-resistant Enterobacteriaceae isolates in Shanghai, China. | High-level resistance to aminoglycosides produced by 16S rRNA methylases in Enterobacteriaceae isolates was investigated. The prevalences of armA in Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae were 0.6%, 3.0%, and 10%, respectively. rmtB was more prevalent than armA. Pulsed-field gel electrophoresis patterns indicated that armA and rmtB have spread horizontally and clonally. | 18,955,532 |
Correlating echinocandin MIC and kinetic inhibition of fks1 mutant glucan synthases for Candida albicans: implications for interpretive breakpoints. | A detailed kinetic characterization of echinocandin inhibition was performed for mutant 1,3-beta-d-glucan synthase enzymes from clinical isolates of Candida albicans with nine different FKS1 mutations resulting in high MICs. Among 14 mutant Fks1p enzymes studied, the kinetic parameters 50% inhibitory concentration and K(i) increased 50-fold to several thousandfold relative to those for the wild type. Enzymes with mutations at Ser645 (S645P, S645Y, and S645F) within hot spot 1 showed the most prominent decrease in sensitivity, while those with mutations at the N- and C-terminal ends of hot spot 1 generally retained greater sensitivity to all three drugs. Kinetic inhibitions by caspofungin, micafungin, and anidulafungin were comparable among the fks1 mutant enzymes, although absolute values did vary with specific mutations. Amino acid substitutions in Fks1p did not alter K(m) values, although some mutations decreased the V(max). Given the association of FKS1 mutations with clinical resistance, an evaluation of the kinetic parameters for the inhibition of mutant 1,3-beta-D-glucan synthase as a function of the MIC enabled an independent evaluation of the recently adopted susceptibility breakpoint for echinocandin drugs. Overall, a breakpoint MIC of >or=2 microg/ml for caspofungin captured nearly 100% of fks1 C. albicans strains when a kinetic inhibition rise threshold of <or=50-fold for the K(i) was used as a measure of susceptibility. A similar MIC breakpoint for micafungin and anidulafungin was less inclusive, and a projected MIC of >or=0.5 microg/ml was required for >95% coverage of clinical isolates. However, when MIC determinations were performed in the presence of 50% serum, all fks1 mutants showed MIC values of >or=2 microg/ml for the three echinocandin drugs. The 1,3-beta-D-glucan synthase kinetic inhibition data support the proposed susceptibility breakpoint for caspofungin in C. albicans, but a lower susceptibility breakpoint (<or=0.5 microg/ml) may be more appropriate for anidulafungin and micafungin. Overall, the data indicate that MIC testing with caspofungin may serve as a surrogate marker for resistance among the class of echinocandin drugs. | 18,955,538 |
Effects of feeding polyclonal antibody preparations on rumen fermentation patterns, performance, and carcass characteristics of feedlot steers. | In a previous study, preparations of polyclonal antibodies (PAP) against Fusobacterium necrophorum (PAP-Fn) or Streptococcus bovis (PAP-Sb) were successful in decreasing ruminal counts of target bacteria and increasing ruminal pH in steers fed high-grain diets. The objective of this study was to evaluate the effects of feeding PAP-Fn or PAP-Sb on performance, carcass characteristics, and ruminal fermentation variables of feedlot steers. In Exp. 1, during 2 consecutive years, 226 or 192 Angus and Angus crossbred steers were fed a high-grain diet containing either PAP-Sb or PAP-Fn, or both. When measured on a BW basis, steers fed only PAP-Sb had a greater G:F (P < 0.05) than those fed no PAP. Nevertheless, when both PAP were fed, feed efficiency was similar (P > 0.10) to steers fed no PAP or only PAP-Sb. Steers receiving PAP-Fn (alone or in combination with PAP-Sb) had a decreased (P < 0.05) dressing percentage. Steers receiving PAP-Fn (alone or in combination with PAP-Sb) had a decreased severity of liver abscess (P < 0.05). No differences (P > 0.10) were observed in any other carcass characteristics. In Exp. 2, sixteen ruminally cannulated Angus crossbred steers (BW = 665 +/- 86 kg) were fed a high-grain diet containing either PAP-Sb or PAP-Fn, or both. Feeding only PAP-Fn or PAP-Sb for 19 d decreased (P < 0.05) ruminal counts of S. bovis when compared with steers fed both or no PAP. The ruminal counts of F. necrophorum in steers fed PAP-Fn alone or in combination with PAP-Sb were decreased by 98% (P < 0.05) after 19 d, when compared with the counts in control steers. Mean daily ruminal pH was greater (P < 0.05) in steers fed both PAP when compared with feeding either or no PAP. Ruminal pH in the first 4 h after feeding was greater (P < 0.05) for steers receiving PAP-Fn alone or in combination with PAP-Sb. Steers receiving either PAP alone or in combination had less (P < 0.05) ruminal NH(3)-N concentrations in the first 4 h after feeding when compared with those of control steers. Polyclonal antibody preparations against S. bovis were effective in enhancing G:F of steers fed high-grain diets, but dressing percentage was decreased. Mechanisms of enhancement of G:F remain unknown but may be related to changes in ruminal counts of target bacteria and associated effects on ruminal fermentation products. | 18,955,541 |
Endothelial adhesion receptors are recruited to adherent leukocytes by inclusion in preformed tetraspanin nanoplatforms. | VCAM-1 and ICAM-1, receptors for leukocyte integrins, are recruited to cell-cell contact sites on the apical membrane of activated endothelial cells. In this study, we show that this recruitment is independent of ligand engagement, actin cytoskeleton anchorage, and heterodimer formation. Instead, VCAM-1 and ICAM-1 are recruited by inclusion within specialized preformed tetraspanin-enriched microdomains, which act as endothelial adhesive platforms (EAPs). Using advanced analytical fluorescence techniques, we have characterized the diffusion properties at the single-molecule level, nanoscale organization, and specific intradomain molecular interactions of EAPs in living primary endothelial cells. This study provides compelling evidence for the existence of EAPs as physical entities at the plasma membrane, distinct from lipid rafts. Scanning electron microscopy of immunogold-labeled samples treated with a specific tetraspanin-blocking peptide identify nanoclustering of VCAM-1 and ICAM-1 within EAPs as a novel mechanism for supramolecular organization that regulates the leukocyte integrin-binding capacity of both endothelial receptors during extravasation. | 18,955,551 |
Segregation and activation of myosin IIB creates a rear in migrating cells. | We have found that MLC-dependent activation of myosin IIB in migrating cells is required to form an extended rear, which coincides with increased directional migration. Activated myosin IIB localizes prominently at the cell rear and produces large, stable actin filament bundles and adhesions, which locally inhibit protrusion and define the morphology of the tail. Myosin IIA forms de novo filaments away from the myosin IIB-enriched center and back to form regions that support protrusion. The positioning and dynamics of myosin IIA and IIB depend on the self-assembly regions in their coiled-coil C terminus. COS7 and B16 melanoma cells lack myosin IIA and IIB, respectively; and show isoform-specific front-back polarity in migrating cells. These studies demonstrate the role of MLC activation and myosin isoforms in creating a cell rear, the segregation of isoforms during filament assembly and their differential effects on adhesion and protrusion, and a key role for the noncontractile region of the isoforms in determining their localization and function. | 18,955,554 |
Stable and dynamic microtubules coordinately shape the myosin activation zone during cytokinetic furrow formation. | The cytokinetic furrow arises from spatial and temporal regulation of cortical contractility. To test the role microtubules play in furrow specification, we studied myosin II activation in echinoderm zygotes by assessing serine19-phosphorylated regulatory light chain (pRLC) localization after precisely timed drug treatments. Cortical pRLC was globally depressed before cytokinesis, then elevated only at the equator. We implicated cell cycle biochemistry (not microtubules) in pRLC depression, and differential microtubule stability in localizing the subsequent myosin activation. With no microtubules, pRLC accumulation occurred globally instead of equatorially, and loss of just dynamic microtubules increased equatorial pRLC recruitment. Nocodazole treatment revealed a population of stable astral microtubules that formed during anaphase; among these, those aimed toward the equator grew longer, and their tips coincided with cortical pRLC accumulation. Shrinking the mitotic apparatus with colchicine revealed pRLC suppression near dynamic microtubule arrays. We conclude that opposite effects of stable versus dynamic microtubules focuses myosin activation to the cell equator during cytokinesis. | 18,955,555 |
Amelioration of epidermolysis bullosa by transfer of wild-type bone marrow cells. | The recessive dystrophic form of epidermolysis bullosa (RDEB) is a disorder of incurable skin fragility and blistering caused by mutations in the type VII collagen gene (Col7a1). The absence of type VII collagen production leads to the loss of adhesion at the basement membrane zone due to the absence of anchoring fibrils, which are composed of type VII collagen. We report that wild-type, congenic bone marrow cells homed to damaged skin, produced type VII collagen protein and anchoring fibrils, ameliorated skin fragility, and reduced lethality in the murine model of RDEB generated by targeted Col7a1 disruption. These data provide the first evidence that a population of marrow cells can correct the basement membrane zone defect found in mice with RDEB and offer a potentially valuable approach for treatment of human RDEB and other extracellular matrix disorders. | 18,955,559 |
HIV-associated lymphomas and gamma-herpesviruses. | Among the most common HIV-associated lymphomas are Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) with immunoblastic-plasmacytoid differentiation (also involving the central nervous system). Lymphomas occurring specifically in HIV-positive patients include primary effusion lymphoma (PEL) and its solid variants, plasmablastic lymphoma of the oral cavity type and large B-cell lymphoma arising in Kaposi sarcoma herpesvirus (KSHV)-associated multicentric Castleman disease. These lymphomas together with BL and DLBCL with immunoblastic-plasmacytoid differentiation frequently carry EBV infection and display a phenotype related to plasma cells. EBV infection occurs at different rates in different lymphoma types, whereas KSHV is specifically associated with PEL, which usually occurs in the setting of profound immunosuppression. The current knowledge about HIV-associated lymphomas can be summarized in the following key points: (1) lymphomas specifically occurring in patients with HIV infection are closely linked to other viral diseases; (2) AIDS lymphomas fall in a spectrum of B-cell differentiation where those associated with EBV or KSHV commonly exhibit plasmablastic differentiation; and (3) prognosis for patients with lymphomas and concomitant HIV infection could be improved using better combined chemotherapy protocols incorporating anticancer treatments and antiretroviral drugs. | 18,955,561 |
Investigation and management of hypertriglyceridaemia. | While the precise definition of hypertriglyceridaemia remains contentious, the condition is becoming more common in western populations as the prevalence of obesity and diabetes mellitus rise. Although there is strong epidemiological evidence that hypertriglyceridaemia is an independent risk factor for cardiovascular disease, it is has been difficult to demonstrate this by drug intervention studies, as drugs that reduce triglycerides also raise high density lipoprotein cholesterol. Precise target values have also been difficult to agree, although several of the new guidelines for coronary risk management now include triglycerides. The causes of hypertriglyceridaemia are numerous. The more severe forms have a genetic basis, and may lead to an increased risk of pancreatitis. Several types of hypertriglyceridaemia are familial and are associated with increased cardiovascular risk. Secondary causes of hypertriglyceridaemia are also numerous and it is important to exclude these before starting treatment with specific triglyceride-lowering agents. Lifestyle management is also very effective and includes weight reduction, restricted alcohol and fat intake and exercise. | 18,955,574 |
Increased oxidant activity mediates vascular dysfunction in vibration injury. | Occupational exposure to hand-operated vibrating tools causes a spectrum of pathological changes in the vascular, neurological, and musculoskeletal systems described as the hand-arm vibration syndrome (HAVS). Experiments were performed to determine the effects of acute vibration on the function of digital arteries. Rats paws were exposed to a vibrating platform (4 h, 125 Hz, constant acceleration of 49 m/s(2) root mean squared), and digital artery function was assessed subsequently in vitro using a pressure myograph system. Constriction to phenylephrine or 5-hydroxytryptamine was reduced in digital arteries from vibrated paws. However, after endothelium denudation, constriction to the agonists was no longer impaired in vibrated arteries. Inhibition of nitric-oxide synthase (NOS) with N(omega)-nitro-l-arginine methyl ester (l-NAME) increased constriction to phenylephrine or 5-hydroxytryptamine in vibrated but not control arteries and abolished the vibration-induced depression in constrictor responses. However, nitric oxide (NO) activity, determined using the NO-sensitive probe 4-amino-5-methylamino-2', 7'-difluorofluorescein, was reduced in vibrated compared with control arteries. Endogenous levels of reactive oxygen species (ROS), determined using the ROS-sensitive probe 5-(and 6)-chloromethyl-2',7'-dichlorodihydro-fluorescein, were increased in vibrated compared with control arteries. The increased ROS levels were abolished by L-NAME or by catalase, which degrades extracellular hydrogen peroxide. Catalase also increased constriction to phenylephrine or 5-hydroxytryptamine in vibrated but not control arteries and abolished the vibration-induced depression in constrictor responses. The results suggest that acute vibration causes vascular dysfunction in digital arteries by increasing ROS levels, which is probably mediated by uncoupling of endothelial NOS. Therefore, therapeutic strategies to inhibit ROS or augment NO activity may be beneficial in HAVS. | 18,955,588 |
Measurements of the BKCa channel's high-affinity Ca2+ binding constants: effects of membrane voltage. | It has been established that the large conductance Ca(2+)-activated K(+) channel contains two types of high-affinity Ca(2+) binding sites, termed the Ca(2+) bowl and the RCK1 site. The affinities of these sites, and how they change as the channel opens, is still a subject of some debate. Previous estimates of these affinities have relied on fitting a series of conductance-voltage relations determined over a series of Ca(2+) concentrations with models of channel gating that include both voltage sensing and Ca(2+) binding. This approach requires that some model of voltage sensing be chosen, and differences in the choice of voltage-sensing model may underlie the different estimates that have been produced. Here, to better determine these affinities we have measured Ca(2+) dose-response curves of channel activity at constant voltage for the wild-type mSlo channel (minus its low-affinity Ca(2+) binding site) and for channels that have had one or the other Ca(2+) binding site disabled via mutation. To accurately determine these dose-response curves we have used a series of 22 Ca(2+) concentrations, and we have used unitary current recordings, coupled with changes in channel expression level, to measure open probability over five orders of magnitude. Our results indicate that at -80 mV the Ca(2+) bowl has higher affinity for Ca(2+) than does the RCK1 site in both the opened and closed conformations of the channel, and that the binding of Ca(2+) to the RCK1 site is voltage dependent, whereas at the Ca(2+) bowl it is not. | 18,955,592 |
Standards of practice in UK emergency departments before, during and after conscious sedation. | The agents used for conscious sedation are well known to have potentially serious complications. It is recommended that patients receiving them should be objectively monitored until it is deemed safe. An audit of our departmental practices led us to conduct a national questionnaire to determine how we compared with other units in the UK. All 211 UK emergency departments (EDs) seeing >40,000 patients/year were contacted and asked to take part in a telephone questionnaire. Interviewees were asked questions regarding which agents were used within their department, the types and duration of monitoring, whether or not patients were fasted, what consent was recorded, the number of staff present and who they were, and what follow-up arrangements were used. 183 departments (87%) completed the questionnaire. Opiates (77%) and benzodiazepines (97%) were the most commonly used agents. Heart rate/blood pressure monitoring (95%), ECG (86%) and pulse oximetry (97%) were used in the majority of cases. Other monitoring modalities, particularly neurological, were either used or documented infrequently. 112 departments (61%) monitored their patients for a set time (4-360 min; mean 97 min). The remainder were monitored until the patient scored a certain Glasgow Coma Score or was subjectively deemed fit. Only 24 departments (13%) ensured that their patients were fasted. 62 departments (34%) did not formally record either written or verbal consent. 80 departments (44%) had 2 members of staff present; the remainder had a minimum of 3. All departments had at least 1 ED doctor and nurse. 174 departments (95%) used fracture clinic follow-up. For conscious sedation, 51 departments (28%) had set proformas and 54 departments (30%) had set policies. Certain practices were applied in most departments but none were universal, with most being subject to wide variation. The local results reflected this, suggesting that a variation may exist both within and between individual units. | 18,955,604 |
Knowledge of signs, treatment and need for urgent management in patients presenting with an acute ischaemic stroke or transient ischaemic attack: a prospective study. | To assess stroke awareness among patients presenting to the emergency department with an acute ischaemic stroke or transient ischaemic attack (TIA). A consecutive cohort of patients presenting with a cerebrovascular event was prospectively enrolled over a 15-month period and questionnaires were administered. If the patient was unable to respond to the questions or answer the questionnaire, it was administered to the primary caregiver. Comprehension of having a cerebrovascular event, reason for delay in presentation, mode of arrival and knowledge of treatment modalities were determined. Only 42% of 400 patients thought they were having a stroke or TIA. The median time to presentation was 3.4 h. Delayed presentation was almost equal in men and women. When asked about onset, 19.4% thought that a stroke came on gradually and only 51.9% thought immediate presentation was crucial. 20.8% of patients had heard of thrombolysis. Community knowledge of ischaemic stroke needs to be enhanced so that individuals present earlier, leading to timely management. | 18,955,606 |
Audit of oxygen use in emergency ambulances and in a hospital emergency department. | Oxygen is widely used but poorly studied in emergency medicine, with a limited evidence base for its use in specific conditions. There are safety concerns about the underuse of oxygen in patients with critical illness and its overuse in conditions such as chronic obstructive pulmonary disease (COPD). A baseline audit was required to assess current practice prior to the introduction of new national emergency oxygen guidelines in late 2008. The use of pulse oximetry and oxygen therapy was audited in patients brought by ambulance to the "majors" section of the emergency department (ED) in a university hospital. Oxygen therapy in the ambulance and the ED was subsequently documented. Oxygen use in ambulances was compared with Joint Royal Colleges Ambulance Liaison Committee (JRCALC) guidance and with subsequent patient management. The ambulance and ED records of 1022 patients were audited manually. Oxygen saturation (SpO(2)) was recorded for 90% of patients, 17% of whom had SpO(2) <94% at some time and 7% had SpO(2) <90%, including 33% of patients with COPD and 5.5% of patients without COPD. 34% of patients received oxygen in the ambulance and almost half of these had oxygen discontinued in the ED. Only 62% of ambulance oxygen use was in accordance with JRCALC guidance, but most "undertreated" patients were stable normoxaemic patients for whom guidance recommends high-flow oxygen. Only 58% of patients with COPD were correctly identified in the ambulance and 73% of these patients were treated with flow rates >4 l/min (equivalent to >35% oxygen). Oxygen use in ambulances is very common, equivalent to 2.2 million episodes annually in the UK. The quality of oxygen use is suboptimal, especially for patients with COPD. Emergency oxygen therapy will become simpler when new evidence-based UK emergency oxygen guidelines are published, and it is hoped that future audits will show better protocol adherence. | 18,955,625 |
Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. | A wide variety of oral diabetes medications are currently available for the treatment of type 2 diabetes mellitus, but it is unclear how these agents compare with respect to long-term cardiovascular risk. Our objective was to systematically examine the peer-reviewed literature on the cardiovascular risk associated with oral agents (second-generation sulfonylureas, biguanides, thiazolidinediones, and meglitinides) for treating adults with type 2 diabetes. We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, from inception through January 19, 2006. Forty publications of controlled trials that reported information on cardiovascular events (primarily myocardial infarction and stroke) met our inclusion criteria. Using standardized protocols, 2 reviewers serially abstracted data from each article. Trials were first described qualitatively. For comparisons with 4 or more independent trials, results were pooled quantitatively using the Mantel-Haenszel method. Results are presented as odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Treatment with metformin hydrochloride was associated with a decreased risk of cardiovascular mortality (pooled OR, 0.74; 95% CI, 0.62-0.89) compared with any other oral diabetes agent or placebo; the results for cardiovascular morbidity and all-cause mortality were similar but not statistically significant. No other significant associations of oral diabetes agents with fatal or nonfatal cardiovascular disease or all-cause mortality were observed. When compared with any other agent or placebo, rosiglitazone was the only diabetes agent associated with an increased risk of cardiovascular morbidity or mortality, but this result was not statistically significant (OR, 1.68; 95% CI, 0.92-3.06). Meta-analysis suggested that, compared with other oral diabetes agents and placebo, metformin was moderately protective and rosiglitazone possibly harmful, but lack of power prohibited firmer conclusions. Larger, long-term studies taken to hard end points and better reporting of cardiovascular events in short-term studies will be required to draw firm conclusions about major clinical benefits and risks related to oral diabetes agents. | 18,955,635 |
Identification of cardiac troponin I sequence motifs leading to heart failure by induction of myocardial inflammation and fibrosis. | Despite the widespread use of cardiac troponins for diagnosis of myocyte injury and risk stratification in acute cardiac disorders, little is known about the long-term effects of the released troponins on cardiac function. Recently, we showed that an autoimmune response to cardiac troponin I (cTnI) induces severe inflammation and subsequent fibrosis in the myocardium. This autoimmune disorder predisposes to heart failure and cardiac death in mice. To investigate the role of cTnI-specific T cells, T cells were isolated from splenocytes of mice immunized with murine cTnI (mcTnI). Wild-type mice that received mcTnI-specific T cells showed high mcTnI-specific antibody titers, increased production of the proinflammatory cytokines interleukin-1beta and tumor necrosis factor-alpha, severe inflammation and fibrosis in the myocardium, and reduced fractional shortening. To identify the antigenic determinants of troponin I responsible for the observed inflammation, fibrosis, and heart failure, 16 overlapping 16mer to 18mer peptides covering the entire amino acid sequence of mcTnI (211 residues) were synthesized. Only mice immunized with residues 105 to 122 of mcTnI developed significant inflammation and fibrosis in the myocardium, with increased expression of the inflammatory chemokines RANTES, monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, macrophage inflammatory protein-2, T-cell activation-3, and eotaxin and the chemokine receptors CCR1, CCR2, and CCR5. Mice immunized with the corresponding human cTnI residues 104 to 121 and the mcTnI residues 131 to 148 developed milder disease. Transfer of troponin I-specific T cells can induce inflammation and fibrosis in wild-type mice, which leads to deterioration of contractile function. Furthermore, 2 sequence motifs of cTnI that induce inflammation and fibrosis in the myocardium are characterized. | 18,955,666 |
Changes in caregiver strain over time in young adolescents with ADHD: the role of oppositional and delinquent behavior. | The objectives of this study were to identify the relationships between caregiver strain among parents of young adolescents with ADHD and child characteristics during a 1-year period. Parents of 52 middle-school-aged youth with ADHD participated in this study and completed two evaluations 1 year apart. Ratings of oppositional and delinquent behavior best predicted levels of caregiver strain, and change over time did not significantly add to the equation. Patterns of change in caregiver strain indicated important individual differences. Oppositional, delinquent behavior was the best predictor of caregiver strain and suggests that preventing and treating these child behavior problems should be a high priority when working with young adolescents with ADHD. Given the variability in parent responses to changes in oppositional and delinquent behavior, it may also be important to address personal coping strategies for parents of youth exhibiting high rates of these behaviors. | 18,955,733 |
Empirical dead-time corrections for synchrotron sources. | An experimental comparison of models for performing dead-time corrections of photon-counting detectors at synchrotron sources is presented. The performance of several detectors in the three operating modes of the Advanced Photon Source is systematically compared, with particular emphasis on asymmetric fill patterns. Several simple and well known correction formulas are evaluated. The results demonstrate the critical importance of detector speed and synchrotron fill pattern in selecting the proper dead-time correction. | 18,955,768 |
Epidemiological and genetic characterization of methicillin-resistant Staphylococcus aureus isolates from the ear discharge of outpatients with chronic otitis media. | The origin of methicillin-resistant Staphylococcus aureus (MRSA) strains from otolaryngology outpatients has not been evaluated yet in Korea. We analyzed epidemiologic and genetic characteristics of MRSA isolates from the ear discharge of 64 outpatients with chronic otitis media in a Korean University Hospital during 2004. MRSA strains were grouped as either from the initial visit (n=33) or the follow-up visit (n=31) based on the timing of isolation. Healthcare-associated risk factors were frequently present among patients of the initial visit group, especially prior visit to primary clinic (79%) and antibiotic use (73%). SCCmec typing and multilocus sequence typing results showed that two genotypes, ST5-MRSA-II and ST239-MRSAIII, were prevalent in both the initial visit (73% vs. 24%) and the follow-up visit (55% vs. 42%). Pulsed-field gel electrophoresis identified eight types, including two major types shared by both groups. We conclude that majority of MRSA strains from ear discharge of chronic otitis media belonged to nosocomial clones that might be circulating in the community. This is the first report of the genetic analysis of MRSA strains from otolaryngology practices in Korea. | 18,955,778 |
Epidemiology of complex regional pain syndrome: a retrospective chart review of 150 Korean patients. | Complex regional pain syndrome (CRPS) is a chronically painful and disabling disorder. However, no data are available even on the epidemiology of CRPS in Korea. This study was undertaken to retrospectively assess the epidemiologic characteristics of CRPS in 150 consecutive patients at a tertiary chronic pain center from March 2002 to February 2006. Information was obtained regarding patients' demographics, nature of injury, and treatment modalities. Seventy-one percent of patients had CRPS type I. The mean 11-point verbal numerical rating scale score at initial examinations and at the time of study were 8.0 and 5.7, respectively. Thirty-two percent of patients showed no change or increase in pain intensity during follow-up at our pain center. The mean duration of CRPS symptoms prior to our pain center evaluation and prior to the time of study were 27 months and 50 months, respectively. These patients had seen on average 5 different physicians before being referred to our center. This study shows that the majority of CRPS patients were referred to our center after more than 2 yr of symptoms. The clinical implication of such delayed transfer and strategies to avoid this problem are discussed. | 18,955,780 |
Association of UCP1 genetic polymorphisms with blood pressure among Korean female subjects. | Recent studies have provided some clues with regard to the relationship existing between uncoupling protein 1 (UCP1) and blood pressure in animal experiments. In an attempt to determine the genetic polymorphisms that are associated with blood pressure in humans, we have analyzed genetic polymorphisms in UCP1 gene. In this study, we assessed the association between UCP1 genotypes and systolic blood pressure (SBP) and diastolic blood pressure (DBP), in a population comprised of 832 Korean female subjects, using a general linear model, which was adjusted for age and body mass index (BMI). Among 4 genetic polymorphisms and the haplotypes constructed from them, haplotype3 of UCP1, UCP1-ht3[GAGA], evidenced significant associations with SBP (p=0.005) and DBP (p=0.013). However, this haplotype was not significantly associated with obesity phenotypes, including BMI or fat mass (p>0.05), thereby suggesting that its association with blood pressure was independent of obesity phenotypes. | 18,955,781 |
Low frequency and variability of FLT3 mutations in Korean patients with acute myeloid leukemia. | FLT3 mutations are common genetic changes, and are reported to have prognostic significance in acute myeloid leukemia (AML). The FLT3 internal tandem duplication (ITD) and the D835 activating mutation in the tyrosine kinase domain (TKD) were analyzed by polymerase chain reaction (PCR) in the genomic DNA of Korean patients with AML at diagnosis and during follow-up. There were 226 patients with AML enrolled between March 1996 and August 2005. The incidence of ITD and TKD at diagnosis was 13% (29/226) and 3% (6/226). When compared to Western and other Asian patients with AML, Korean patients had a lower frequency by about two-thirds of ITD and TKD. Among the non-M3 cases (N=203), the patients with an ITD had a significantly shorter event-free survival when compared with those without an ITD (p=0.0079). Among 54 relapsed patients, 9 patients had the FLT3 ITD at diagnosis. Six patients demonstrated a reappearance of the ITD and 3 patients remained negative at relapse. One patient, among 45 patients who relapsed, had a negative baseline ITD but acquired a de novo ITD at relapse. There were 101 samples from 93 patients in remission; they were all negative for an ITD. Among 34 patients who failed to achieve a remission, five patients had a persistent ITD and one patient had a de novo ITD. These results support the concept of resistance of FLT3 ITD leukemic clones to chemotherapy. Therefore, effective therapy with FLT3 targeting agents may improve the prognosis of non-M3 AML patients with the FLT3 mutation. | 18,955,790 |
Efficient cultivation conditions for human limbal epithelial cells. | To compare the stem niche in different culture conditions of limbal epithelial cells, the suspended human limbal epithelial cells (HLECs) were seeded on the 3T3-pretreated plates and the other suspended cells were plated on amniotic membranes (AMs) which were either cryo-preserved or freeze-dried. All were cultured for 10 to 12 days. Reverse transcription-polymerase chain reaction (RT-PCR) for ATP-binding cassette, subfamily G, member 2 (ABCG2), p63, cytokeratin 12, and connexin 43 were performed in cultivated HLECs and their expression levels were compared. The mRNA expression of all markers examined showed no statistically significant differences between the cells on cryo-preserved and on freeze-dried AM. The expression of p63 and cytokeratin 12 in cultivated cells on AMs were significantly lower than those in 3T3-cocultured cells on RT-PCR and immunofluorescent staining. Cultivated HLECs on AMs showed reduced proliferation and differentiation while maintaining stem-property regardless of the preservative method of AM. | 18,955,795 |
Fetal choledochal cyst diagnosed at 22 weeks of gestation by three-dimensional ultrasonography: a case report. | Choledochal cyst is a cystic or fusiform dilatation of the extra- or intrahepatic bile duct that has rarely been reported in prenatal cases. Here we report a fetus with choledochal cyst diagnosed prenatally by three-dimensional (3-D) ultrasonography at 22 weeks of gestation. We demonstrated an image of choledochal cyst by using a new ultrasound technique, a 3-D multislice view. After close intrauterine followup, surgery was successfully performed and postoperative course was uneventful. | 18,955,804 |
Removable partial denture in a cleft lip and palate patient: a case report. | This clinical report described the oral rehabilitation of a cleft lip and palate patient with removable partial denture. Although implant-supported fixed treatment was presented as part of the optimum treatment plan to achieve the best result, the patient declined this option due to the significant financial burden. Persons with a congenital or craniofacial defect are unique, and oral problems must be evaluated individually to the most ideal treatment. The changes in appearance, function, and psychological wellbeing have an enormous impact on patients' personal lives and are rewarding for the maxillofacial prosthodontist providing this care. | 18,955,808 |
Increased yield of high-purity and active tetrameric recombinant human EC-SOD by solid phase refolding. | Superoxide dismutase (SOD) removes damaging reactive oxygen species from the cellular environment by catalyzing the dismutation of two superoxide radicals to hydrogen peroxide and oxygen. Extracellular superoxide dismutase (EC-SOD) is a tetramer and is present in the extracellular space and to a lesser extent in the extracellular fluids. Increasing therapeutic applications for recombinant human extracellular superoxide dismutase (rEC-SOD) has broadened interest in optimizing methods for its purification, with a native conformation of tetramer. We describe a solid phase refolding procedure that combines immobilized metal affinity chromatography (IMAC) and gel filtration chromatography in the purification of rEC-SOD from Escherichia coli. The purified rEC-SOD tetramer from the Ni(2+)-column chromatography is refolded in Tris buffer. This method yields greater than 90% of the tetramer form. Greater than 99% purity is achieved with further purification over a Superose 12PC 3.2/30 column to obtain the tetramer and specific activities as determined via DCFHDA assay. The improved yield of rEC-SOD in a simple chromatographic purification procedure promises to enhance the development and therapeutic application of this biologically potent molecule. | 18,955,813 |
Penicillium griseofulvum F1959, high-production strain of pyripyropene a, specific inhibitor of acyl-CoA: cholesterol acyltransferase 2. | Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes cholesterol esterification and plays an important role in the intestinal absorption of cholesterol, hepatic production of lipoproteins, and accumulation of cholesteryl ester within cells. During the course of screening to find ACAT inhibitors from microbial sources, the present authors isolated pyripyropene A from Penicillium griseofulvum F1959. Pyripyropene A, an ACAT2-specific inhibitor, has already been produced from Aspergillus fumigatus. Yet, Aspergillus fumigatus is a pathogen and only produces a limited amount of pyripyropene A, making the isolation of pyripyropene A troublesome. In contrast, Penicillium griseofulvum F1959 was found to produce approximately 28 times more pyripyropene A than Aspergillus fumigatus, plus this report also describes the ideal conditions for the production of pyripyropene A by Penicillium griseofulvum F1959 and its subsequent purification. | 18,955,816 |
Development of surface plasmon resonance immunosensor through metal ion affinity and mixed self-assembled monolayer. | An immunosensor based on surface plasmon resonance (SPR) with enhanced performance was developed through a mixed self-assembled monolayer. A mixture of 16- mercaptohexadecanic acid (16-MHA) and 1-undecanethiol with various molar ratios was self-assembled on gold (Au) surface and the carboxylic acid groups of 16-MHA were then coordinated to Zn ions by exposing the substrate to an ethanolic solution of Zn(NO(3))(2)d6H2O. The antibody was immobilized on the SPR surface by exposing the functionalized substrate to the desired solution of antibody in phosphatebuffered saline (PBS) molecules. The film formation in series was confirmed by SPR and atomic force microscopy (AFM). The functionalized surface was applied to develop an SPR immunosensor for detecting human serum albumin (HSA) and the estimated detection limit (DL) was 4.27 nM. The limit value concentration can be well measured between ill and healthy conditions. | 18,955,822 |
Aetiology and management of extrahepatic portal vein obstruction in children: King's College Hospital experience. | To study a single-centre experience of the management of extrahepatic portal vein obstruction (EHPVO) in children during the last 3 decades. The medical records of 108 children (67 male, median age 4.75 years, range = 1 day-16.3 years) presenting with EHPVO between 1979 and 2005 were reviewed retrospectively. Extended prothrombotic screening performed in 30 patients revealed low protein C activity (6 patients), low free protein S (2), and a positive lupus anticoagulant (1); factor V Leiden mutations and the JAK2V617F mutation were not identified. Associated congenital anomalies were found in 26 of the 108 children (24%). Clinical presentation included splenomegaly in 98 (91%) and ascites in 3 (3%). Elevation of liver enzymes and prolonged international normalized ratio were seen in 13 (12%) and 14 (13%) children, respectively. Haematological parameters of hypersplenism were present in 13 (12%). Bleeding occurred in 83 (77%) patients with a median age of 4.58 (0.02-16.37) years. On first endoscopy, oesophageal varices were present in 92 patients; of those subjects, 70 (76%) received sclerotherapy, 5 (5%) had band ligation, and 16 (17%) received both. Complications of endoscopy occurred in 34 (37%) patients: oesophageal ulcers in 16, oesophageal stricture in 10, both in 7, and erosive gastritis in 1. Seventeen (16%) children underwent shunt surgery for uncontrolled bleeding at a median age of 9.7 (5.2-23.7) years. The aetiology of EHPVO in the majority of patients remains unknown. Sclerotherapy and banding are effective treatments for bleeding varices with good long-term outcome. Procoagulant state is an infrequent cause of EHPVO in children. | 18,955,865 |
Sterol profiling in red blood cell membranes and plasma of newborns receiving total parenteral nutrition. | Total parenteral nutrition (TPN) is a lifesaving therapy in children with intestinal failure, frequently complicated by liver dysfunction. Plant sterols (phytosterols) of lipid emulsions have been supposed to contribute to cholestasis in TPN-treated children. The present study aimed to evaluate the plasma and red blood cell membrane (RBCM) phytosterol levels in newborns after a short period of TPN. Phytosterols, cholesterol, and other sterol levels were quantified by gas chromatography-mass spectrometry in 15 healthy control infants, 22 patients after TPN, and 11 patients before TPN. Sterols of lipid emulsions were quantified. Plasma and RBCM phytosterol levels were, respectively, on average 56 micromol/L and 83 micromol/g per protein in patients after TPN, 13 micromol/L and 15 micromol/g per protein in patients before TPN, and 9 micromol/L and 13 micromoL/g per protein in control infants (P < 0.05 for differences). The days of TPN and the total amount of infused lipids correlated significantly with RBCM phytosterol (P < 0.05); correlations for plasma were positive but not significant. No correlation was observed with plasma bilirubin, gamma-glutamyltransferase, or alanine transaminase. Plasma and RBCM phytosterols increase significantly in newborns after a short period of TPN. Higher phytosterol levels were observed in some patients that could have been due to their individual variability in phytosterol metabolism and/or clearance. A greater accumulation of phytosterols in membranes may induce TPN-related cholestasis. | 18,955,867 |
[Suspension diverticulopexy for Zenker's diverticulum]. | Zenker's diverticulum is an unusual condition. Its treatment requires surgery but there is no consensus regarding the various operative techniques. Through an open cervical approach, the diverticulum can be either resected or suspended with or without a concurrent myotomy of the cricopharyngeus muscle. An innovative option is endoscopic trans-oral stapled esophago-diverticulostomy. and method: We retrospectively reviewed a consecutive series of 36 patients operated on between 1988 and 2006. Median age was 77.5 years and M/F sex ratio was 1.4. Through an open neck approach, diverticulectomy without cricopharyngeal myotomy was performed in 7 patients, diverticulectomy with myotomy in 11, and diverticulopexy with myotomy in 18. Morbidity rate was 13.8%. One fistula and one recurrence occurred in both diverticulectomy groups with and without myotomy. There was no morbidity after suspension diverticulopexy which also allowed earlier oral feeding (1 vs. 6 days) and shortened hospitalization (6 vs. 13.5 days). Diverticulopexy with cricopharyngeus myotomy is an effective, reliable, and reproducible technique for the correction of Zenker's diverticula smaller than 5 cm. Diverticulectomy should be reserved for larger diverticula. Technical improvements of transoral stapled diverticulostomy are still required before it can be promoted as an alternative therapy. | 18,955,924 |
[Morbidity/mortality review: usefulness and shortcomings]. | The Morbidity-Mortality Conference is a formalized exercise validated by the Haute Autorité de Santé (HAS) whose aim is to improve the quality and safety of care through periodic (weekly or monthly) analysis of deaths and complications. In France, no data is available concerning the implementation of the MMC methodology despite the interest of the National Institute of Healthcare Quality (HAS) in using the MMC as part of the physician recredentialling process and of hospital accreditation (mandatory in France since the laws of 2005 and 1997 respectively). We aimed to study the experience and perceptions of physicians with this specific methodology in the context of a large regional project aimed to improve clinical risk management. A one page questionnaire with eight confidential questions and a space for free commentary was sent to 150 hospitals in the north of France. We received 83 responses from 29 hospitals (range: 1-14 responses per hospital). Analysis of unexpected adverse events is performed mainly in informal meetings (76%) and mandatory reports (77%); the MMC methodology is rarely used (11%). The analysis of adverse events is considered to be an important tool for the improvement of patient care and safety (90%) and continuing education (61%), and it results in modification of care protocols (70%) or organizational change (71%). Lack of knowledge of the MMC methodology (66%) and lack of available time (50%) are the main obstacles to the adoption of the MMC. Fear that the findings of the MMC could be available for use in litigation (1%) was not an obstacle. Physicians interested in implementing the MMC are motivated by a desire for improved patient safety (86%) and care management on the surgical service (54%). Self-responsibility is more important than the mandatory process for re-credentialing. The implementation of the MMC requires specific measures such as teaching and support. | 18,955,926 |
The p53 family and programmed cell death. | The p53 tumor suppressor continues to hold distinction as the most frequently mutated gene in human cancer. The ability of p53 to induce programmed cell death, or apoptosis, of cells exposed to environmental or oncogenic stress constitutes a major pathway whereby p53 exerts its tumor suppressor function. In the past decade, we have discovered that p53 is not alone in its mission to destroy damaged or aberrantly proliferating cells: it has two homologs, p63 and p73, that in various cellular contexts and stresses contribute to this process. In this review, the mechanisms whereby p53, and in some cases p63 and p73, induce apoptosis are discussed. Other reviews have focused more extensively on the contribution of individual p53-regulated genes to apoptosis induction by this protein, whereas in this review, we focus more on those factors that mediate the decision between growth arrest and apoptosis by p53, p63 and p73, and on the post-translational modifications and protein-protein interactions that influence this decision. | 18,955,976 |
Model-guided design of ligand-regulated RNAi for programmable control of gene expression. | Progress in constructing biological networks will rely on the development of more advanced components that can be predictably modified to yield optimal system performance. We have engineered an RNA-based platform, which we call an shRNA switch, that provides for integrated ligand control of RNA interference (RNAi) by modular coupling of an aptamer, competing strand, and small hairpin (sh)RNA stem into a single component that links ligand concentration and target gene expression levels. A combined experimental and mathematical modelling approach identified multiple tuning strategies and moves towards a predictable framework for the forward design of shRNA switches. The utility of our platform is highlighted by the demonstration of fine-tuning, multi-input control, and model-guided design of shRNA switches with an optimized dynamic range. Thus, shRNA switches can serve as an advanced component for the construction of complex biological systems and offer a controlled means of activating RNAi in disease therapeutics. | 18,956,013 |
Quantitative trait loci associated with lettuce seed germination under different temperature and light environments. | Temperature and light are primary environmental cues affecting seed germination. To elucidate the genetic architecture underlying lettuce (Lactuca sativa L.) seed germination under different environmental conditions, an F8 recombinant inbred line population consisting of 131 families was phenotyped for final germination and germination rate. Seeds were imbibed in water at 20 degrees C under continuous red light (20-Rc), 20 degrees C continuous dark (20-Dc), 31.5 degrees C continuous red light (31.5-Rc), 31.5 degrees C continuous dark (31.5-Dc), or 20 degrees C far-red light for 24 h followed by continuous dark (20-FRc-Dc). Thirty-eight quantitative trait loci (QTL) were identified from two seed maturation environments: 10 for final germination and 28 for germination rate. The amount of variation attributed to an individual QTL ranged from 9.3% to 17.2% and from 5.6% to 26.2% for final germination and germination rate, respectively. Path analysis indicated that factors affecting germination under 31.5-Rc or 31.5-Dc are largely the same, and these appear to differ from those employed under 20-FRc-Dc. QTL and path analysis support the notion of common and unique factors for germination under diverse temperature and light regimes. A highly significant effect of the seed maturation environment on subsequent germination capacity under environmental stress was observed. | 18,956,026 |
Meiotic events in Oenothera - a non-standard pattern of chromosome behaviour. | The genus Oenothera shows an intriguing extent of permanent translocation heterozygosity. Reciprocal translocations of chromosome arms in species or populations result in various kinds of chromosome multivalents in diakinesis. Early meiotic events conditioning such chromosome behaviour are poorly understood. We found a surprising uniformity of the leptotene-diplotene period, regardless of the chromosome configuration at diakinesis (ring of 14, 7 bivalents, mixture of bivalents and multivalents). It appears that the earliest chromosome interactions at Oenothera meiosis are untypical, since they involve pericentromeric regions. During early leptotene, proximal chromosome parts cluster and form a highly polarized Rabl configuration. Telomeres associated in pairs were seen at zygotene. The high degree of polarization of meiotic nuclei continues for an exceptionally long period, i.e., during zygotene-pachytene into the diplotene contraction stage. The Rabl-polarized meiotic architecture and clustering of pericentromeres suggest a high complexity of karyotypes, not only in structural heterozygotes but also in bivalent-forming homozygous species. | 18,956,028 |
Bisucaberin biosynthesis: an adenylating domain of the BibC multi-enzyme catalyzes cyclodimerization of N-hydroxy-N-succinylcadaverine. | The bisucaberin biosynthetic gene cluster has been identified in Vibrio salmonicida and a domain from within the BibC multienzyme encoded by the cluster has been shown to catalyse ATP-dependent dimerisation and macrocyclisation of N-hydroxy-N-succinylcadaverine to form bisucaberin. | 18,956,041 |
One-pot synthesis of benzo[c]carbazoles by photochemical annulation of 2-chloroindole-3-carbaldehydes. | A novel and efficient procedure for the synthesis of benzo[c]carbazoles has been achieved in moderate to high yields by the one-pot photochemical annulations of 2-chloroindole-3-carbaldehydes by styrenes via photodechlorination-initiated coupling of 2-chloroindole-3-carbaldehydes with styrenes, electrocyclic reactions and deformylative aromatization in the presence of pyridine. | 18,956,060 |
High-conversion-efficiency organic dye-sensitized solar cells with a novel indoline dye. | An indoline dye (D205), the synthesis method of which is disclosed in this report, gave high-efficiency organic dye-sensitized solar cells (9.52%) using an anti-aggregation reagent (chenodeoxycholic acid). | 18,956,066 |
Photochromic oligothienoacene derivatives with photo-switchable luminescence properties and computational studies. | Photochromic thieno[3,2-b]thiophenes and dithieno[3,2-b:2',3'-d]thiophene with photo-switchable luminescence properties have been synthesized using a Suzuki cross-coupling reaction; their electronic structures, and photochromic and luminescence behaviour have also been studied. | 18,956,069 |
Palladium-catalyzed carboboration of alkynes using chloroborane and organozirconium reagents. | Three-component coupling of bis(dialkylamino)chloroborane, alkynes and organozirconium reagents proceeded in the presence of palladium catalysts, leading to the formation of stereo-defined alkenylborane derivatives via cis-carboboration of carbon-carbon triple bonds. | 18,956,076 |
Site-selectivity of protonation in gaseous toluene. | The favoured protonation sites leading to isomeric toluenium ions have been assayed, envisaging the mildest possible route for proton transfer to naked toluene. | 18,956,084 |
Spin-orbit configuration interaction study of the ultraviolet photofragmentation of XeH+. | The multireference spin-orbit CI method is employed to calculate potential energy curves for the ground and low-lying excited states of the XeH+ cation. For the first time, the spin-orbit interaction is taken into account and electric dipole moments are computed for transitions to the states responsible for the first absorption continuum (A band) of XeH+. On this basis, the partial and total absorption spectra in this energy range are obtained. It is found that the A-band absorption is dominated by the spin-forbidden b3Pi0+ <-- X1sigma+ parallel transition, while perpendicular transitions to the B(1)Pi and b(3)Pi(1) states are significantly weaker. The Gamma(nu) branching ratio defined as the ratio of the Xe+(2P(1/2)) yield to the total yield of the Xe+ cations from the XeH+ photodissociation is calculated for the (42-80) x 10(3) spectral range. It is shown that Gamma(nu) increases smoothly from <0.2 in the red and blue tails of the band to its maximum of 0.92 in the middle of the band, at E approximately 51.4 x 10(3) cm(-1). The high Gamma(nu) values correspond to the predominant formation of the spin-excited Xe+(2P(1/2)) ions that may be used to obtain IR laser generation at the Xe+(2P(1/2) - 2P(3/2)) transition. The calculated XeH+ data are compared with those for the isovalent ArH+, KrH+, and HI systems. | 18,956,105 |
A temperature dependence kinetic study of O(1D) + CH4: overall rate coefficient and product yields. | Using a recently-developed chemiluminescence technique for monitoring O(1D), the rate coefficient, k1, of the important atmospheric reaction O(1D) + CH4 --> products has been determined over a wide temperature range, 227 to 450 K. The rate coefficient was shown to be independent of temperature, having a value of (1.91 +/- 0.08) x 10(-10) cm3 s(-1); the quoted uncertainties are with 95% confidence. This highly precise value, based on an extended set of determinations with very low scatter, is significantly greater, 26%, than current recommended values. Secondly, the fraction of O(1D) quenched to O(3P) by CH4, k(1q)/k1, was precisely determined from chemiluminescence decays over the temperature range 236 to 340 K. A temperature independent value for k(1q)/k1 of 0.002 +/- 0.003 was found. Finally, LIF detection of OH has been applied to accurately determine the product branching fraction to OH of O(1D) + CH4 at room temperature. Our value, k(1a)/k1 = 0.76 +/- 0.08 (95% confidence), is in line with recent determinations by other groups. | 18,956,106 |
Theoretical study of the dynamics of hyperthermal collisions of Ar with a fluorinated alkanethiolate self-assembled monolayer. | We present a classical-trajectory study of the dynamics of energy exchange in collisions between hyperthermal Ar (6-12 eV collision energy) and a fluorinated self-assembled monolayer (SAM). Product translational-energy, polar-angle, and azimuthal-angle distributions as a function of collision energy and incidence angle are presented to provide a detailed description of the gas/surface energy exchange dynamics. Our results indicate that while the properties of the scattered Ar atom at normal and 30 degrees incidence are notably similar and essentially independent of collision energy in the 6-12 eV range, the dynamics of energy exchange when Ar impinges at 60 degrees are remarkably different and depend on collision energy. This behavior is understood via analysis of the microscopic mechanism of the collisions. Three main collision mechanisms-direct collisions without surface penetration, direct collisions involving surface penetration, and surface-penetrating non-direct collisions-are found to govern the dynamics, and the ratio of these mechanisms determines the properties of the scattered Ar atom. Our study also reveals that the Ar atoms that penetrate the organic monolayer do not desorb following a direct-ejection mechanism proposed in recent studies of Xe collisions with a hydrogenated SAM. The vast amount of energy transferred to the surface found in the calculations lends support to recent experiments showing degradation of fluorinated surfaces in collisions with hyperthermal Ar. | 18,956,114 |
Occupational exposure to dust, gases and fumes, a family history of asthma and impaired respiratory health. | This study assessed the impact of occupational exposure to dust, gases, and fumes on respiratory symptoms, obstructive lung diseases, or the use of asthma medication among persons with and without a family history of asthma. A population-based cohort was followed for 10 years. This study included all 1739 men and 1594 women occupationally active at the first survey. Exposure and respiratory health were assessed from questionnaires. Multiple logistic regression was used to estimate the effects in relation to occupational groups, with age, gender, and smoking habits as possible confounders, using both cross-sectional and longitudinal analyses. The susceptibility to impaired respiratory health was determined from a family history of asthma. A family history of asthma was reported by 27% of the men and 34% of the women. Both occupational exposure and a family history of asthma were associated with impaired respiratory health. The etiologic fractions showed that up to about 70% of the symptoms could be explained by a family history of asthma among those exposed to low levels of air pollutants, as well as among those with high exposure. However, high exposure contributed up to 35% of the symptoms both among those with and among those without a family history of asthma. The study indicates that the relative risk of occupational exposure to pollutants is similar for both persons with and those without a family history of asthma. The relative risk for impaired respiratory health after exposure to occupational air pollutants seems to be similar for persons with and those without a susceptibility to impaired respiratory health. | 18,956,125 |
Vagal neural crest provides inhibitory neurotransmission to the chick embryo cloaca. | The intrinsic innervation of the developing chick cloaca originates in the vagal and sacral regions of the neural tube. Its major inhibitory neurotransmitters are nitric oxide (NO) and vasoactive intestinal peptide (VIP). It has previously been shown that the majority of neurons in the chick embryo cloaca are derived from vagal neural crest cells. This study aimed to identify the phenotype of these vagal-derived neurons using quail-chick chimeras. Chicken embryos were incubated until the 10-12 somite stage. The vagal neural tube was then microsurgically ablated in ovo and replaced with the vagal neural tube from age-matched quail embryos. Quail-chick chimera embryos were harvested at E12, and E14, and fixed and embedded in paraffin wax, and serially sectioned. Immunohistochemistry was performed using human natural killer-1 (HNK-1), quail-cell-specific perinuclear (QCPN), NOS and VIP antibodies. Expression of NOS and VIP neurons in the developing chick embryo cloaca was also further analysed using immunohistochemistry. HNK-1 labelled all ganglia in the myenteric and submucosal plexuses of the cloaca, whilst the quail-specific QCPN antibody labelled all ganglia derived from the transplanted quail vagal neural tube. NOS- and VIP-immunoreactive neurons appeared to make up a large proportion of the quail-derived vagal neural crest cells. Both NOS and VIP expression was seen to increase throughout development. This data suggests for the first time that the inhibitory neurons in the chick cloaca primarily originate in the vagal neural crest, thus providing new insights into the developmental origin of the intrinsic innervation of the developing cloaca. | 18,956,196 |
A comparison of the reliability and stability of oro-lingual swallowing pressures in patients with head and neck cancer and healthy adults. | The ability to measure normality and abnormality and to accurately assess true changes in swallowing function over time, is important for the management of dysphagia. Despite this, there is a paucity of information regarding the stability and reliability of measurements tools used for dysphagia research. As both head and neck (H&N) cancer and its treatment(s) have been shown to significantly affect deglutitive tongue function, it is important that we have a reliable method to measure swallowing tongue function in this population. In this study we evaluate the reliability and stability of oro-lingual swallowing pressures captured from H&N cancer patients and from healthy, age- and gender-matched controls using the Kay Swallowing Workstation (KSW) fixed, three-transducer tongue pressure array. Significant differences between the two samples (H&N cancer and controls), with respect to mean peak oro-lingual pressures were recorded during swallowing. Furthermore, reliability of these measures was lower in H&N cancer patients. These differences highlight the importance of obtaining information about the reliability of dysphagia assessment tools with the specific population with whom they will be used. | 18,956,230 |
Phytolacca americana from contaminated and noncontaminated soils of South Korea: effects of elevated temperature, CO(2) and simulated acid rain on plant growth response. | Chemical analyses performed on the invasive weed Phytolacca americana (pokeweed) growing in industrially contaminated (Ulsan) and noncontaminated (Suwon) sites in South Korea indicated that the levels of phenolic compounds and various elements that include some heavy metals (Al, As, B, Cd, Co, Cu, Fe, Mn, Ni, Pb, and Zn) were statistically higher in Ulsan soils compared to Suwon soils with Al being the highest (>1,116 mg/l compared to 432 mg/l). Analysis of metals and nutrients (K, Na, Ca, Mg, Cl, NH(4), N, P, S) in plant tissues indicated that accumulation occurred dominantly in plant leaves with Al levels being 33.8 times higher in Ulsan plants (PaU) compared to Suwon plants (PaS). The ability of PaU and PaS to tolerate stress was evaluated under controlled conditions by varying atmospheric CO(2) and temperature and soil pH. When grown in pH 6.4 soils, the highest growth rate of PaU and PaS plants occurred at elevated (30 degrees C) and non-elevated (25 degrees C) temperatures, respectively. Both PaU and PaS plants showed the highest and lowest growth rates when exposed to atmospheric CO(2) levels of 360 and 650 ppm, respectively. The impact of soil pH (2-6.4) on seed germination rates, plant growth, chlorophyll content, and the accumulation of phenolics were measured to assess the effects of industrial pollution and global-warming-related stresses on plants. The highest seed germination rate and chlorophyll content occurred at pH 2.0 for both PaU and PaS plants. Increased pH from 2-5 correlated to increased phenolic compounds and decreased chlorophyll content. However, at pH 6.4, a marked decrease in phenolic compounds, was observed and chlorophyll content increased. These results suggest that although plants from Ulsan and Suwon sites are the same species, they differ in the ability to deal with various stresses. | 18,956,232 |
Transcription and activation under environmental stress of the complex telomeric repeats of Chironomus thummi. | In contrast to their traditional role, telomeres seem to behave as transcriptionally active regions. RNAs complementary to the short DNA repeats characteristic of telomerase-maintained telomeres have recently been identified in various mammalian cell lines, representing a new and unexpected element in telomere architecture. Here, we report the existence of transcripts complementary to telomeric sequences characteristic of Chironomus thummi telomeres. As in other Diptera, the non-canonical telomeres of chironomids lack the simple telomerase repeats and have instead more complex repetitive sequences. Northern blots of total RNA hybridized with telomere probes and RT-PCR with telomere-specific tailed primers confirm the existence of small non-coding RNAs of around 200 bp, the size of the DNA repeated telomeric unit. Telomere transcripts are heterogeneous in length, and they appear as a ladder pattern that probably corresponds to multimers of the repeat. Moreover, telomeres are activated under conditions of environmental stress, such as heat shock, appearing highly decondensed and densely labelled with acetylated H4 histone, as well as with RNA polymerase II antibodies, both marks of transcriptional activity. Changes in the expression levels of telomeric RNA were detected after heat shock. These findings provide evidence that transcriptional activity of the repetitive telomere sequences is an evolutionarily conserved feature, not limited to telomerase telomeres. The functional significance of this non-coding RNA as a new additional element in the context of telomere biology remains to be explained. | 18,956,244 |
Quality of life in noncompliant adults with phenylketonuria after resumption of the diet. | Discontinuation of dietary therapy in adults with phenylketonuria can lead to neuropsychological abnormalities and emotional problems. The aim of our study was to assess the change in quality of life in adult patients returning to the diet and to define the reasons for failure in diet resumption. Quality of life was assessed by means of the Psychological General Well-Being Index before study entry and subsequently after 3 and 9 months. Reasons for failure in diet resumption were analysed. 53 patients participated in the study. Initial quality of life assessment revealed severe distress in 17%, moderate distress in 28% and positive well-being in 55% of them. In the majority of patients with severe or moderate distress, improvement of subjective well-being was observed (especially in the domains of anxiety and depressiveness) if they managed to return to the diet (blood phenylalanine concentrations before study entry 0.78-1.62 mmol/L, mean 1.16 mmol/L; average blood phenylalanine concentration decrease by 0.42 mmol/L). Only 29 persons managed to maintain the diet for at least 3 months and only 10 participants finished the entire 9-month study protocol. Problems with dietary treatment while at work, the high cost of low-protein products and poor knowledge regarding proper diet were the most important factors responsible for failure in resumption of diet. Interpersonal differences exist between adult patients on relaxed diet, in some of whom quality of life often remains good, while others can suffer from severe emotional distress. Returning to diet increases quality of life in the majority of patients. | 18,956,249 |
Nutritional management of PKU with glycomacropeptide from cheese whey. | Individuals with phenylketonuria (PKU) must follow a lifelong low-phenylalanine (Phe) diet to prevent neurological impairment. Compliance with the low-Phe diet is often poor owing to restriction in natural foods and the requirement for consumption of a Phe-free amino acid formula or medical food. Glycomacropeptide (GMP), a natural protein produced during cheese-making, is uniquely suited to a low-Phe diet because when isolated from cheese whey it contains minimal Phe (2.5-5 mg Phe/g protein). This paper reviews progress in evaluating the safety, acceptability and efficacy of GMP in the nutritional management of PKU. A variety of foods and beverages can be made with GMP to improve the taste, variety and convenience of the PKU diet. Sensory studies in individuals with PKU demonstrate that GMP foods are acceptable alternatives to amino acid medical foods. Studies in the PKU mouse model demonstrate that GMP supplemented with limiting indispensable amino acids provides a nutritionally adequate source of protein and improves the metabolic phenotype by reducing concentrations of Phe in plasma and brain. A case report in an adult with classical PKU who followed the GMP diet for 10 weeks at home indicates safety, acceptability of GMP food products, a 13-14% reduction in blood Phe levels (p<0.05) and improved distribution of dietary protein throughout the day compared with the amino acid diet. In summary, food products made with GMP that is supplemented with limiting indispensable amino acids provide a palatable alternative source of protein that may improve dietary compliance and metabolic control of PKU. | 18,956,251 |
Transcobalamin (TC) deficiency--potential cause of bone marrow failure in childhood. | It is unusual for inborn errors of metabolism to be considered in the investigative work-up of pancytopenia. We report a family in which the proband presented with failure to thrive at 2 months of age and subsequent bone marrow failure. A previous sibling had died at 7 months of age with suspected leukaemia. Haematological findings in the proband were significant for pancytopenia, and bone marrow aspiration showed dysplastic changes in all cell lineages. Urinary organic acid analysis revealed elevated methylmalonic acid. The synthesis of transcobalamin II (transcobalamin, TC) by cultured fibroblasts was markedly reduced, confirming the diagnosis of TC deficiency. The proband and his younger asymptomatic sister (also found to have TC deficiency) were homozygous for R399X (c.1195C>T), a novel mutation resulting in the loss of the C- terminal 29 amino acids of TC, a highly conserved region. Response to parenteral vitamin B(12) in the proband was dramatic. At 6 years 3 months of age, physical examination is normal and developmental level is age appropriate. His sister is clinically asymptomatic and is also developing normally. Propionylcarnitine concentrations were not elevated in the newborn screening cards from the proband and sister, but that was for specimens retrieved from storage after 7 years and 5 years, respectively. Inherited and acquired cobalamin disorders should both be considered in the differential diagnosis of bone marrow failure syndromes in young children. Early detection of the metabolic causes of bone marrow failure can ensure prompt recovery in some cases involving the vitamin B(12) pathway. | 18,956,254 |
Strategies targeting telomerase inhibition. | Telomerase plays a pivotal role in cellular immortality and tumorigenesis. Its activity is normally not detectable in most somatic cells while it is reactivated in the vast majority of cancer cells. Therefore, inhibition of telomerase has been viewed as a promising anticancer approach due to its specificity for cancer cells. Studies so far have shown that telomerase inhibition can inhibit the proliferation of cancer cells or cause apoptosis while it has no effect on most normal cells. Strategies currently being applied to induce telomerase inhibition target virtually all of the major components of the ribonucleoprotein holoenzyme and related cell signal pathways that regulate its activity. These strategies include inhibition of telomerase through targeting at the telomerase reverse transcriptase (TERT) catalytic subunit, the telomerase RNA (TR) component, and associated proteins. Other strategies have been developed to target the proteins associated with telomerase at the telomeric ends of chromosomes such as tankyrase. The specific mechanisms that mediate those inhibition effects include small molecules, antisense RNA, and ribozymes. Although the beneficial evidence of telomerase inhibition is obvious, limitations of strategies remain to be resolved to increase the feasibility of clinical application. This analysis will summarize recent developments of strategies in telomerase inhibition. | 18,956,258 |
Expression and secretion of RANTES (CCL5) in human adipocytes in response to immunological stimuli and hypoxia. | Obesity and related disorders represent states of systemic low-grade inflammation. Chemokine secretion by adipocytes may initiate leukocyte infiltration in obese adipose tissue and thus mediate an important step in the establishment of chronic immune activation. The chemokine RANTES (regulated upon activation normal T cell expressed and secreted)/CCL5 is a chemoattractant for various leukocyte subsets. This study was designed to examine whether RANTES is expressed and released by human adipocytes and how its expression is regulated. RANTES expression under basal conditions was studied in mature adipocytes. Cells were therefore challenged with lipopolysaccharide (LPS), interferon (IFN)-gamma, interleukin (IL)-4, monocyte chemoattractant protein (MCP)-1 or exposed to low oxygen pressure. RANTES was expressed and secreted constitutively in most samples of mature adipocytes from the omental and the subcutaneous depot. RANTES release was dependent on adipocyte size and also seemed to be higher from cells of obese donors. Hypoxia (4% O (2)) caused an approximately 36% increase of RANTES release. Human adipocytes express the chemokine RANTES and are thus identified as a novel cellular source of this immune mediator. LPS and IFNgamma do not seem to play a significant role for the expression of RANTES in contrast to moderate hypoxia, which points to a distinct role in the innate immune system. | 18,956,302 |
The enigmatic role of the ankyrin repeat domain 1 gene in heart development and disease. | It has been proposed that the ankyrin repeat domain 1 (ANKRD1) factor (also known as CARP) plays a critical role in transcriptional regulation, myofibrillar assembly and stretch sensing during heart development and cardiac insults. ANKRD1/CARP has also been reported to negatively regulate cardiac gene expression in cell-based promoter-reporter assays. Consequently, rapid up-regulation of the ankrd1 gene in myocardium in response to developmental stimuli or pathological insults has tended to be interpreted in the context of the inhibitory effects of ANKRD1 on cardiomyocyte gene expression. Surprisingly, a total ankrd1 knockout resulted in a complete lack of phenotype, suggesting that ANKRD1/CARP is not crucial for regulation of cardiac gene expression in vivo. In this essay, we summarize (1) the accumulated evidence for the apparent multifunctional properties of this enigmatic protein, (2) the distinct chamber-dependent regulation of ankrd1 expression patterns in the heart, both during development and cardiac injury, and (3) ANKRD1 involvement in networks regulating adaptation of the myocardium to stress. Whenever feasible, we present the results obtained in patients together with those obtained in the relevant animal and cellular models. A close examination of the findings still fails to define ANKRD1 as a negative regulator of cardiac gene expression in vivo, but rather indicates that its augmented expression can represent an adaptive response of the myocardium to stress both during development and various heart insults. | 18,956,313 |
Expression of a retinal homeobox (Rx) gene during planarian regeneration. | Retinal homeobox (Rx) genes, with representatives in vertebrates and invertebrates, encode fundamental regulators of early eye and brain formation. Here we describe the spatio-temporal expression profile of a candidate planarian orthologue of Rx during regeneration in Dugesia japonica and Schmidtea mediterranea. Although low levels of Rx transcripts were found throughout the body of intact planarians, high levels of Rx expression were specific to regenerating tissue in both head and tail fragments. We also observed that Rx was never expressed in the simple rhabdomeric planarian eyes, supporting the notion that only formation of eyes that use the ciliary type of photoreceptors requires Rx function. | 18,956,344 |
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