title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Multiple kinesin motors coordinate cytoplasmic RNA transport on a subpopulation of microtubules in Xenopus oocytes. | RNA localization is a widely conserved mechanism for generating cellular asymmetry. In Xenopus oocytes, microtubule-dependent transport of RNAs to the vegetal cortex underlies germ layer patterning. Although kinesin motors have been implicated in this process, the apparent polarity of the microtubule cytoskeleton has pointed instead to roles for minus-end-directed motors. To resolve this issue, we have analyzed participation of kinesin motors in vegetal RNA transport and identified a direct role for Xenopus kinesin-1. Moreover, in vivo interference and biochemical experiments reveal a key function for multiple motors, specifically kinesin-1 and kinesin-2, and suggest that these motors may interact during transport. Critically, we have discovered a subpopulation of microtubules with plus ends at the vegetal cortex, supporting roles for these kinesin motors in vegetal RNA transport. These results provide a new mechanistic basis for understanding directed RNA transport within the cytoplasm. | 18,771,961 |
First-trimester serum levels of soluble endoglin and soluble fms-like tyrosine kinase-1 as first-trimester markers for late-onset preeclampsia. | The aim of this investigation was to assess soluble endoglin (sEng) and soluble fms-like tyrosine kinase-1 (sFlt1) as first-trimester serum markers to predict preeclampsia. First-trimester sera were obtained from 46 women with subsequent late-onset preeclampsia and from 92 controls. sEng and sFlt1 concentrations were determined immunoanalytically. Correlation analysis with inhibin A and placental growth factor levels was performed. sEng and sFlt1 serum concentrations were higher in women with subsequent preeclampsia than in controls (mean +/- SD, sEng: 5.57 +/- 1.18 ng/mL vs 5.02 +/- 1.01 ng/mL, P = .009; sFlt1: 1764 +/- 757 pg/mL vs 1537 +/- 812 pg/mL, P = .036). Sensitivities and specificities for predicting preeclampsia were 63% and 57% for sEng and 64% and 56% for sFlt1, respectively. When sEng and inhibin A were combined, the sensitivity increased to 68%, whereas the specificity was 61%. sEng and sFlt1 are increased in the first trimester in women with subsequent late-onset preeclampsia and might therefore prove useful to predict preeclampsia. | 18,771,978 |
Obstetric management of hepatitis C-positive mothers: analysis of vertical transmission in 559 mother-infant pairs. | The objective of the study was to determine vertical transmission rates of hepatitis C in 2 tertiary level maternity units. This was a retrospective review of all hepatitis C-positive mothers and their pregnancy outcomes. Of 74,629 deliveries, 559 liveborn infants were born to 545 hepatitis C mothers; the rate of antenatal hepatitis C infection was 0.7%. In the neonatal period, 423 infants tested negative for hepatitis C ribonucleic acid (RNA) (75.7%), 18 were positive (3.2%), and 118 infants were not tested or were lost to follow-up (21.1%). The overall vertical transmission rate is 18 of 441 (4.1%, 95% confidence interval 2.3% to 5.9%). The vertical transmission rate for infants following vaginal delivery or emergency cesarean in labor was no different when compared with those delivered by planned cesarean (4.2% vs 3.0%, P = NS). Among women in whom hepatitis C RNA was detected antenatally, this finding remained (7.2% vs 5.3%, P = NS). No case of vertical transmission was noted among hepatitis C RNA-negative mothers. This study reports a vertical transmission rate for hepatitis C of 4.1%. These results do not support a recommendation of planned cesarean to reduce vertical transmission of hepatitis C infection. | 18,771,997 |
Dynamics of the dopaminergic system as a key component to the understanding of depression. | For decades, clinical treatment of depression has usually involved antidepressants that target noradrenergic and serotonergic neurotransmission. Over the past half century, no genuinely ground-breaking progress has been made in the pharmacological development of antidepressant drugs. Dopaminergic mesolimbic and mesocortical systems are involved in hedonia and motivation, two core symptoms of depression. However, their role in the pathophysiology of depression and their manipulation to treat depression has received little attention. Recent findings indicate the potential usefulness of monitoring limbic dopaminergic dynamics in combination with mathematical analysis. In this chapter comprehensive review of data from animal models, genetics, neuroimaging and human clinical trials that strengthen the case for dopaminergic dysfunction in the pathophysiology of major depression. This chapter focuses on recent convergence of data describing the fluctuation in activity of the mesolimbic dopaminergic system, and discusses its crucial role in manifestation of depressive-like behavior. Decoding the functionality of the dopaminergic system is important to the understanding of depression and the development of future efficient antidepressant treatments. | 18,772,037 |
Prospects for serotonin 5-HT2R pharmacotherapy in psychostimulant abuse. | The serotonin (5-HT) neurotransmitter system provides fundamental modulatory regulation of the limbic-corticostriatal circuitry known to be vital in the development of addiction as well as the aspects of addiction that hinder recovery and contribute to relapse. Thus, components of the 5-HT system may provide novel targets for the development of pharmacological treatments for psychostimulant dependence, which is associated with significant aberrations in dopamine (DA) neurotransmission. Two key modulators of DA signalling within the limbic-corticostriatal circuit are the 5-HT(2A) receptor (5-HT(2A)R) and the 5-HT(2C)R. These receptors are known to control the neurochemical and behavioural effects of psychostimulants, and in particular the in vivo effects of cocaine. Pre-clinical studies indicate that 5-HT(2A)R antagonists and/or 5-HT(2C)R agonists may effectively reduce craving and/or relapse, and likewise, enhance abstinence, while 5-HT(2C)R agonists may also effectively reduce cocaine intake in active cocaine users. At present, the progression of studies to probe the effectiveness of 5-HT(2A)R and 5-HT(2C)R ligands in the clinical setting is hindered by a lack of available, selective 5-HT(2A)R antagonists or 5-HT(2C)R agonists for use in human cocaine abusers. However, a number of selective 5-HT(2)R ligands currently under development, or in early clinical trials for psychiatric and/or neurological disorders, may soon be available for translational studies to explore their effectiveness in modulating drug use and dependence. | 18,772,040 |
Pharmacological inhibition of dopamine and serotonin activity blocks spontaneous and cocaine-activated behaviour. | The dopaminergic (DA) and serotonergic (5-HT) systems are modulatory transmitter systems that can influence a wide range of behavioural functions. Psychostimulant drugs increase both DA and 5-HT activity by substance-specific mechanisms and, consequently, can broadly influence behavioural and emotional processes in humans and animals. In this chapter, we examine psychostimulant drug effects from the perspective of DA-5-HT and environmental context interactions and anchor this analysis to changes in spontaneous behaviour. In our consideration of the DA and 5-HT transmitter systems, we focus on pharmacological manipulations that target DA and 5-HT autoreceptors. Autoreceptors provide negative feedback inhibitory control of DA and 5-HT neuronal activity so that pharmacological treatments that act on autoreceptors can regulate DA and 5-HT availability. Since psychostimulant drug effects are linked to DA and 5-HT availability, our analysis focuses on investigations that use autoreceptor pharmacology to unravel the complexity of psychostimulant drug action. The overall findings from the experimental manipulations of autoreceptor pharmacology were then used to discuss issues pertinent to drug development for the treatment of psychostimulant drug addiction. | 18,772,041 |
Serotonergic and dopaminergic modulation of attentional processes. | Disturbances in attentional processes are a common feature of several psychiatric disorders such as schizophrenia, attention deficit/hyperactivity disorder and Huntington's disease. The use of animal models has been useful in defining various candidate neural systems thus enabling us to translate basic laboratory science to the clinic and vice-versa. In this chapter, a comparative and integrated account is provided on the neuroanatomical and neurochemical modulation of basic behavioural operations such as selective attention, vigilance, set-shifting and executive control focusing on the comparative functions of the serotonin and dopamine systems in the cognitive control exerted by the prefrontal cortex. Specifically, we have reviewed evidence emerging from several behavioural paradigms in experimental animals and humans each of which centres on a different aspect of the attentional function. These paradigms offering both human and animal variants include the five-choice serial reaction time task (5CSRTT), attentional set-shifting and stop-signal reaction time task. In each case, the types of operation that are measured by the given paradigm and their neural correlates are defined. Then, the role of the ascending dopaminergic and serotonergic systems in the neurochemical modulation of its behavioural output are examined, and reference is made to clinical implications for neurological and neuropsychiatric disorders which exhibit deficits in these cognitive tests. | 18,772,049 |
Baseline low-density lipoprotein cholesterol is an important predictor of the benefit of intensive lipid-lowering therapy: a PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) analysis. | This study sought to determine whether the benefit of intensive lipid-lowering therapy (LLT) is dependent on baseline low-density lipoprotein cholesterol (LDL-C). Aggressive LDL-C reduction with statins improves cardiovascular outcomes in acute and chronic coronary heart disease (CHD). The importance of baseline LDL-C is unclear. We compared 2-year composites of death, myocardial infarction (MI), unstable angina, revascularization >30 days, and stroke (primary end point), and CHD death, MI, and revascularization >30 days (secondary end point) in 2,986 statin-naïve patients with recent acute coronary syndrome (ACS) randomized to atorvastatin 80 mg versus pravastatin 40 mg in the PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) study stratified by quartiles of baseline LDL-C. Multivariable models assessed whether the treatment benefit was dependent on baseline LDL-C. A significant reduction in the hazards of the primary (hazard ratio [HR]: 0.63, 95% confidence interval [CI]: 0.47 to 0.85, p = 0.002) and secondary (HR: 0.57, 95% CI: 0.42 to 0.79, p = 0.001) end points occurred in patients within the highest quartile (>132 mg/dl) of baseline LDL-C treated with atorvastatin 80 mg. The benefit of intensive therapy progressively declined as baseline LDL-C decreased. The lowest quartile (LDL-C < or =92 mg/dl) experienced similar rates of the primary (HR: 0.93, 95% CI: 0.69 to 1.25, p = 0.63) and secondary (HR: 0.98, 95% CI: 0.71 to 1.35, p = 0.89) end points. Adjusted interaction tests between treatment and highest versus lowest baseline LDL-C quartile were significant for the primary and secondary end points (p = 0.03 and p = 0.007, respectively). Analyzing baseline LDL-C as a continuous variable, atorvastatin 80 mg was associated with improved outcomes provided the baseline LDL-C was >66 mg/dl. A progressive reduction in the benefit of intensive LLT with atorvastatin 80 mg over pravastatin 40 mg occurred in statin-naïve ACS patients as baseline LDL-C declined. (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 [PROVE IT-TIMI 22]; NCT00382460). | 18,772,061 |
Evidence for involvement of calcitonin gene-related peptide in nitroglycerin response and association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism. | This study sought to determine whether calcitonin gene-related peptide (CGRP) is involved in glyceryl trinitrate (GTN) response in humans, and its association with mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys (ALDH2*2) polymorphism. In animal models, CGRP contributes to the cardiovascular effects of GTN. The enzyme principally responsible for GTN bioactivation is ALDH2. The common ALDH2*2 polymorphism is associated with a lack of GTN efficacy. In 18 ALDH2*2-genotyped Chinese volunteers, we observed the changes in plasma concentrations of CGRP after sublingual GTN administration and its correlation with GTN response, and assessed the expression of CGRP messenger ribonucleic acid (mRNA) in cultured peripheral blood mononuclear cells (PBMCs) pre-treated with 10(-5) mol/l GTN. In contrast to carriers of the ALDH2*2 allele, ALDH2*1/*1 homozygotes showed a significantly higher extent of absolute changes in both systolic blood pressure (DeltaSBP) and HR (DeltaHR) at several time points after GTN administration. Plasma concentrations of CGRP were increased significantly 12 min after GTN administration, the percentage increase in plasma concentrations of CGRP correlated positively with both DeltaSBP and DeltaHR, and percentage increase in plasma concentrations of CGRP was significantly higher in ALDH2*1/*1 homozygotes. In addition, PBMCs from ALDH2*1/*1 homozygotes showed a higher-fold increase in both CGRP I and CGRP II mRNA after GTN stimulation, and the GTN-induced increase in CGRP mRNA expression in PBMCs from ALDH2*1/*1 homozygotes was inhibited by the ALDH2 inhibitor chloral hydrate. We found that CGRP is associated with the cardiovascular effect of GTN through an ALDH2-dependent pathway in humans. | 18,772,068 |
Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. | Ginsenosides are a special group of triterpenoid saponins that can be classified into two groups by the skeleton of their aglycones, namely dammarane- and oleanane-type. Ginsenosides are found nearly exclusively in Panax species (ginseng) and up to now more than 150 naturally occurring ginsenosides have been isolated from roots, leaves/stems, fruits, and/or flower heads of ginseng. Ginsenosides have been the target of a lot of research as they are believed to be the main active principles behind the claims of ginsengs efficacy. The potential health effects of ginsenosides that are discussed in this chapter include anticarcinogenic, immunomodulatory, anti-inflammatory, antiallergic, antiatherosclerotic, antihypertensive, and antidiabetic effects as well as antistress activity and effects on the central nervous system. Ginsensoides can be metabolized in the stomach (acid hydrolysis) and in the gastrointestinal tract (bacterial hydrolysis) or transformed to other ginsenosides by drying and steaming of ginseng to more bioavailable and bioactive ginsenosides. The metabolization and transformation of intact ginsenosides, which seems to play an important role for their potential health effects, are discussed. Qualitative and quantitative analytical techniques for the analysis of ginsenosides are important in relation to quality control of ginseng products and plant material and for the determination of the effects of processing of plant material as well as for the determination of the metabolism and bioavailability of ginsenosides. Analytical techniques for the analysis of ginsenosides that are described in this chapter are thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) combined with various detectors, gas chromatography (GC), colorimetry, enzyme immunoassays (EIA), capillary electrophoresis (CE), nuclear magnetic resonance (NMR) spectroscopy, and spectrophotometric methods. | 18,772,102 |
Mature solid teratoma of the fallopian tube associated with uterine leiomyomas. | Benign solid teratomas within the fallopian tube are rare. The incidence of this kind of benign solid teratoma of the fallopian tube associated with intrauterine leiomyomas is extremely low and may complicate the clinical manifestations. Here, we report a 40-year-old female with periodic lower abdominal pain and hypermenorrhea who was found to have 3 nodules within the uterine myometrium and left distended fallopian tube. Final pathology revealed benign solid teratoma of the fallopian tube associated with 3 intrauterine leiomyomas. Primary teratoma of the fallopian tube is extremely uncommon. Gynecologic oncologists should be aware of the possibility of this disease entity when making differential diagnoses. | 18,772,124 |
High-output heart failure resulting from an obscure traumatic arteriovenous fistula. | Traumatic arteriovenous fistula (AVF) is not an uncommon disorder, but late discovery and the presentation of high-output heart failure is very rare. This patient did not know that he had traumatic AVF after a gunshot injury in the left thigh 14 years ago. The major presentation of the AVF was signs of heart failure. We performed surgical repair after making the diagnosis. The patient recovered with an uneventful course. This report stresses the importance of history-taking and physical examination in making the diagnosis of traumatic AVF. | 18,772,125 |
Lysophospholipid acyltransferases and arachidonate recycling in human neutrophils. | The cycle of deacylation and reacylation of phospholipids plays a critical role in regulating availability of arachidonic acid for eicosanoid production. The major yeast lysophospholipid acyltransferase, Ale1p, is related to mammalian membrane-bound O-acyltransferase (MBOAT) proteins. We expressed four human MBOATs in yeast strains lacking Ale1p and studied their acyl-CoA and lysophospholipid specificities using novel mass spectrometry-based enzyme assays. MBOAT1 is a lysophosphatidylserine (lyso-PS) acyltransferase with preference for oleoyl-CoA. MBOAT2 also prefers oleoyl-CoA, using lysophosphatidic acid and lysophosphatidylethanolamine as acyl acceptors. MBOAT5 prefers lysophosphatidylcholine and lyso-PS to incorporate linoleoyl and arachidonoyl chains. MBOAT7 is a lysophosphatidylinositol acyltransferase with remarkable specificity for arachidonoyl-CoA. MBOAT5 and MBOAT7 are particularly susceptible to inhibition by thimerosal. Human neutrophils express mRNA for these four enzymes, and neutrophil microsomes incorporate arachidonoyl chains into phosphatidylinositol, phosphatidylcholine, PS, and phosphatidylethanolamine in a thimerosal-sensitive manner. These results strongly implicate MBOAT5 and MBOAT7 in arachidonate recycling, thus regulating free arachidonic acid levels and leukotriene synthesis in neutrophils. | 18,772,128 |
TRAF6 specifically contributes to FcepsilonRI-mediated cytokine production but not mast cell degranulation. | TRAF6 (tumor necrosis factor-associated factor 6) is an essential adaptor downstream from the tumor necrosis factor (TNF) receptor and Toll-like receptor superfamily members. This molecule is critical for dendritic cell maturation and T cell homeostasis. Here we show that TRAF6 is important in high affinity IgE receptor, FcepsilonRI-mediated mast cell activation. In contrast to dendritic cells and T cells, TRAF6-deficient mast cells matured normally and showed normal IgE-dependent degranulation. Importantly, TRAF6-deficient mast cells showed impaired production of cytokine interleukin-6, CCL-9, interleukin-13, and TNF following FcepsilonRI aggregation. Chromatin immunoprecipitation assay showed decreased NF-kappaB p65 binding to CCL-9 and TNF promoters in TRAF6-deficient mast cells. Antigen and IgE-induced IkappaB phosphorylation and NF-kappaB p65 translocation to the nucleus were diminished in TRAF6-deficient mast cells. NF-kappaB luciferase activity in response to antigen and IgE stimulation was severely impaired in TRAF6-deficient mast cells. In addition, antigen and IgE-induced phosphorylation of mitogen-activated protein kinase p38 and JNK, but not ERK1/2, was significantly reduced in TRAF6-deficient mast cells. These results identified TRAF6 as an important signal transducer in FcepsilonRI-mediated signaling in mast cells. Our findings implicate TRAF6 as a new adaptor/regulator molecule for allergen-mediated inflammation in allergy. | 18,772,140 |
Disease-causing mutation in GPR54 reveals the importance of the second intracellular loop for class A G-protein-coupled receptor function. | The G-protein-coupled receptor (GPCR) GPR54 is essential for the development and maintenance of reproductive function in mammals. A point mutation (L148S) in the second intracellular loop (IL2) of GPR54 causes idiopathic hypogonadotropic hypogonadism, a disorder characterized by delayed puberty and infertility. Here, we characterize the molecular mechanism by which the L148S mutation causes disease and address the role of IL2 in Class A GPCR function. Biochemical, immunocytochemical, and pharmacological analysis demonstrates that the mutation does not affect the expression, ligand binding properties, or protein interaction network of GPR54. In contrast, diverse GPR54 functional responses are markedly inhibited by the L148S mutation. Importantly, the leucine residue at this position is highly conserved among class A GPCRs. Indeed, mutating the corresponding leucine of the alpha(1A)-AR recapitulates the effects observed with L148S GPR54, suggesting the critical importance of this hydrophobic IL2 residue for Class A GPCR functional coupling. Interestingly, co-immunoprecipitation studies indicate that L148S does not hinder the association of Galpha subunits with GPR54. However, fluorescence resonance energy transfer analysis strongly suggests that L148S impairs the ligand-induced catalytic activation of Galpha. Combining our data with a predictive Class A GPCR/Galpha model suggests that IL2 domains contain a conserved hydrophobic motif that, upon agonist stimulation, might stabilize the switch II region of Galpha. Such an interaction could promote opening of switch II of Galpha to facilitate GDP-GTP exchange and coupling to downstream signaling responses. Importantly, mutations that disrupt this key hydrophobic interface can manifest as human disease. | 18,772,143 |
FACTA: a text search engine for finding associated biomedical concepts. | FACTA is a text search engine for MEDLINE abstracts, which is designed particularly to help users browse biomedical concepts (e.g. genes/proteins, diseases, enzymes and chemical compounds) appearing in the documents retrieved by the query. The concepts are presented to the user in a tabular format and ranked based on the co-occurrence statistics. Unlike existing systems that provide similar functionality, FACTA pre-indexes not only the words but also the concepts mentioned in the documents, which enables the user to issue a flexible query (e.g. free keywords or Boolean combinations of keywords/concepts) and receive the results immediately even when the number of the documents that match the query is very large. The user can also view snippets from MEDLINE to get textual evidence of associations between the query terms and the concepts. The concept IDs and their names/synonyms for building the indexes were collected from several biomedical databases and thesauri, such as UniProt, BioThesaurus, UMLS, KEGG and DrugBank. The system is available at http://www.nactem.ac.uk/software/facta/ | 18,772,154 |
Isolation of small RNAs using biotinylated PNAs. | In this study, an RNA isolation method was developed using a biotinylated peptide nucleic acid (PNA) that is complementary to the target RNA. Using the biotinylated PNA method, we successfully isolated several RNAs from Escherichia coli and from human total RNA in pure form. Damage to the RNA appears to be negligible by this method because the method is rapid and does not require a high temperature treatment to facilitate RNA-PNA binding. | 18,772,156 |
First occurrence of KPC-2-possessing Klebsiella pneumoniae in a Greek hospital and recommendation for detection with boronic acid disc tests. | To investigate the first KPC carbapenemase-producing Klebsiella pneumoniae isolate from a Greek hospital, including phenotypic methods to aid recognition of this resistance type. A carbapenem-resistant clinical isolate of K. pneumoniae was recovered from a hospitalized Greek patient. Detailed susceptibility testing was carried out by the agar dilution method. The isolate was screened by phenotypic and genotypic assays for the presence of various beta-lactamases. Boronic acid disc tests were performed to show the ability of these tests to detect production of the KPC enzymes. The potential for conjugal transfer of carbapenem resistance was examined by biparental matings, plasmid analysis and PCR studies. The isolate possessed on the same self-transferable plasmid the KPC-2 carbapenemase and the SHV-12 extended-spectrum beta-lactamase. Although the isolate did not produce an AmpC-type enzyme, the production of KPC-2 was associated with positive boronic acid disc tests using cephamycins and cefotaxime as well as cefepime and carbapenems as substrates. KPC-2-possessing K. pneumoniae clinical isolates seem to have been introduced in our region. Boronic acid disc tests using boronic acid in combination with carbapenems or cefepime may help the phenotypic detection of KPC enzymes and their distinction from plasmid-mediated AmpC enzymes. | 18,772,158 |
Minilaparotomy radical cystoprostatectomy (Minilap RCP) in the surgical management of urinary bladder carcinoma: early experience. | To assess the feasibility of minilaparotomy for radical cystoprostatectomy (RCP) and urinary diversion in the management of urinary bladder carcinoma. A total of 45 consecutive patients with muscle invasive urinary bladder cancer underwent RCP and urinary diversion [32, 12 and 1 patients with pitchers pot orthotopic neobladder (NB), ileal conduit (IC) and sigma rectal pouch respectively], between May 2006 and June 2007, using 8-12 cm infraumbilical midline vertical incision from pubic symphysis, were prospectively analyzed for technical feasibility, operative time, blood loss, intraoperative and postoperative complications and return of bowel function. All the patients were males with average age of 59.65 years (44-79 years) and average body mass index of 23.97(17.7-29.5). The length of the incision was 8, 10 and 12 cm in 4, 39 and 2 patients, respectively. The average number of lymph nodes removed on the right and left side was 14 and 16, respectively. The average blood loss was 1046 ml (595-2100 ml). Return of bowel sounds was observed on an average by second postoperative day (1-5 days). Average postoperative stay was 14 days (range 10-24 days) for NB and 7 days (6-8 days) for IC patients. One (2.22%) patient died on the 18th postoperative day due to septicemia and acute renal failure. Minilaparotomy RCP is technically feasible without compromising the oncological principles. Complete removal of urachus and adequate clearance of pelvic lymph nodes is not difficult with the small incision. Early restoration of bowel function, early postoperative recovery and good cosmesis seem to be the main advantages. | 18,772,171 |
Comparison of inflammatory markers and angiographic outcomes after implantation of sirolimus and paclitaxel-eluting stents. | We compared the degree of systemic inflammation and its relation to the angiographic outcomes after drug-eluting stent (DES) implantations. We implanted a single DES in 79 stable angina patients (50 men; 60.4 (9.5) years of age; sirolimus-eluting stent (SES), n = 38; paclitaxel-eluting stent (PES), n = 41). The high-sensitivity C-reactive protein (hs-CRP) and interleukin 6 (IL-6) levels were determined before and at 24 hours, 72 hours, and 4 weeks after the percutaneous coronary intervention (PCI). An angiography and intravascular ultrasound (IVUS) were performed. The hs-CRP and IL-6 levels at baseline did not differ between the two groups. The hs-CRP increased significantly from baseline at 24 hours and 72 hours after the PCI in both groups and there was a significant increase in the IL-6 level at 24 hours after the PCI in both groups. However, there was no significant difference between the two groups in any of the hs-CRP or IL-6 measurements. At follow-up, the late lumen loss was significantly higher in the PES group than in the SES group (0.57 (0.56) mm vs 0.28 (0.58) mm, respectively, p = 0.020). The neointimal hyperplasia (NIH) volume in the PES group was significantly higher than that in the SES group (23.1 (22.7) vs 3.8 (7.1) mm(3), respectively, p = 0.000). The percentage luminal volume reduction was higher in the PES group than in the SES group (18.9 vs 3.9%, p = 0.002). The absolute values or change in the inflammatory markers did not correlate with the NIH or stent volume reduction. Our study showed that the benefits obtained from the SES, which reduce neointimal proliferation, are not probably mediated by the attenuation of the systemic inflammatory markers hs-CRP or IL-6. | 18,772,180 |
Differential origin of reticulospinal drive to motoneurons innervating trunk and hindlimb muscles in the mouse revealed by optical recording. | To better understand how the brainstem reticular formation controls and coordinates trunk and hindlimb muscle activity, we used optical recording to characterize the functional connections between medullary reticulospinal neurons and lumbar motoneurons of the L2 segment in the neonatal mouse. In an isolated brainstem-spinal cord preparation, synaptically induced calcium transients were visualized in individual MNs of the ipsilateral and contralateral medial and lateral motor columns (MMC, LMC) following focal electrical stimulation of the medullary reticular formation (MRF). Stimulation of the MRF elicited differential responses in MMC and LMC, according to a specific spatial organization. Stimulation of the medial MRF elicited responses predominantly in the LMC whereas stimulation of the lateral MRF elicited responses predominantly in the MMC. This reciprocal response pattern was observed on both the ipsilateral and contralateral sides of the spinal cord. To ascertain whether the regions stimulated contained reticulospinal neurons, we retrogradely labelled MRF neurons with axons coursing in different spinal funiculi, and compared the distributions of the labelled neurons to the stimulation sites. We found a large number of retrogradely labelled neurons within regions of the gigantocellularis reticular nucleus (including its pars ventralis and alpha) where most stimulation sites were located. The existence of a mediolateral organization within the MRF, whereby distinct populations of reticulospinal neurons predominantly influence medial or lateral motoneurons, provides an anatomical substrate for the differential control of trunk and hindlimb muscles. Such an organization introduces flexibility in the initiation and coordination of activity in the two sets of muscles that would satisfy many of the functional requirements that arise during postural and non-postural motor control in mammals. | 18,772,205 |
Tonic activation of group I mGluRs modulates inhibitory synaptic strength by regulating KCC2 activity. | The furosemide-sensitive potassium-chloride cotransporter (KCC2) plays an important role in establishing the intracellular chloride concentration in many neurons within the central nervous system. Consequently, modulation of KCC2 function will regulate the reversal potential for synaptic GABAergic inputs, thus setting the strength of inhibitory transmission. We show that tonic activation of group I metabotropic glutamate receptors (mGluR1s) regulates inhibitory synaptic strength via modulation of KCC2 function in pyramidal neurons of the hippocampal CA3 area. Specifically, group I mGluRs signal via activation of a protein kinase C-dependent pathway to alter KCC2 activity, thereby altering the intracellular chloride concentration, and thus inhibitory synaptic input. This interaction between the glutamatergic and chloride transport systems highlights a novel homeostatic mechanism whereby ambient glutamate levels directly regulate the inhibitory synaptic tone by setting the activity level of KCC2. Thus, mGluRs are poised to play a pivotal role in providing a direct interplay between the excitatory and inhibitory systems in the hippocampus. | 18,772,206 |
Kinetics and thermodynamics of salt-dependent T7 gene 2.5 protein binding to single- and double-stranded DNA. | Bacteriophage T7 gene 2.5 protein (gp2.5) is a single-stranded DNA (ssDNA)-binding protein that has essential roles in DNA replication, recombination and repair. However, it differs from other ssDNA-binding proteins by its weaker binding to ssDNA and lack of cooperative ssDNA binding. By studying the rate-dependent DNA melting force in the presence of gp2.5 and its deletion mutant lacking 26 C-terminal residues, we probe the kinetics and thermodynamics of gp2.5 binding to ssDNA and double-stranded DNA (dsDNA). These force measurements allow us to determine the binding rate of both proteins to ssDNA, as well as their equilibrium association constants to dsDNA. The salt dependence of dsDNA binding parallels that of ssDNA binding. We attribute the four orders of magnitude salt-independent differences between ssDNA and dsDNA binding to nonelectrostatic interactions involved only in ssDNA binding, in contrast to T4 gene 32 protein, which achieves preferential ssDNA binding primarily through cooperative interactions. The results support a model in which dimerization interactions must be broken for DNA binding, and gp2.5 monomers search dsDNA by 1D diffusion to bind ssDNA. We also quantitatively compare the salt-dependent ssDNA- and dsDNA-binding properties of the T4 and T7 ssDNA-binding proteins for the first time. | 18,772,224 |
Progesterone influence on neurite outgrowth involves microglia. | Progesterone (P4) antagonizes estradiol (E2) in synaptic remodeling in the hippocampus during the rat estrous cycle. To further understand how P4 modulates synaptic plasticity, we used entorhinal cortex lesions, which induce E2-dependent neurite sprouting in the hippocampus. In young ovariectomized rats, the E2-dependent entorhinal cortex lesion-induced sprouting was attenuated by concurrent treatment with P4 and E2. Microglial activation also showed the E2-P4 antagonism. These findings extend reports on the estrous cycle synaptic remodeling without lesions by showing the P4-E2 antagonism during simultaneous treatment with both E2 and P4. Glial mechanisms were analyzed with the wounding-in-a-dish model of cocultured glia and embryonic d-18 cortical neurons from rat. In cocultures of mixed glia (astrocytes plus 30% microglia), P4 antagonized the E2-dependent neurite outgrowth (number and length) and neuron viability in the presence of E2, as observed in vivo. However, removal of microglia (astrocyte-neuron coculture) abolished the antagonism of E2 by P4 on neuron sprouting. The P4 receptor antagonists ORG-31710 and RU-486 blocked the antagonism of P4 on E2-dependent sprouting. These findings suggest a new role for microglia in P4 antagonism of E2 in neuronal plasticity and show its dependence on progesterone receptors. These findings are also relevant to the inclusion of progestins in hormone therapy, which is controversial in relation to cognitive declines during aging and in Alzheimer's disease. | 18,772,232 |
Diet or exercise: what is more effective in preventing or reducing metabolic alterations? | The influence of diet and exercise on metabolic syndrome is controversial since fit individuals might also eat healthier foods. We evaluated the association of diet/exercise variation with reductions in metabolic variables and C-reactive protein (CRP) values in the experimental and control arms of a 1-year randomized lifestyle intervention trial performed in patients with multiple metabolic abnormalities. A prospective study of 169 cases and 166 controls after a lifestyle intervention was performed. In the intervention group, 15/169 (8.9%), 63/169 (37.3%), and 70/169 (41.4%) reached only dietary, only exercise, and dietary/exercise targets respectively. Reductions in weight, body mass index (BMI), and waist were significant only in patients who increased exercise. Most controls did not reach any target (131/166, 78.9%), while only few patients reached only dietary (13/166, 7.8%), only exercise (5/166, 3.0%), and dietary/exercise targets (17/166, 10.2%). Weight, BMI, and waist reduction was more pronounced in those reaching the exercise target. In the whole cohort, increased exercise was inversely associated with weight, BMI, waist, and CRP, increased saturated fat was directly associated with weight, BMI, waist, and diastolic pressure variations, while increased fiber intake was inversely associated with glucose values in a multiple regression model. After adjusting for waist changes, the associations between exercise and CRP (beta=-0.023; 95% CI -0.028 -0.017; P<0.001) and the associations between fiber and glucose (beta=-0.022; -0.031 -0.013; P<0.001) remained significant. Independent of weight reduction, exercise level and fiber intake are inversely associated with CRP and fasting glucose values respectively. Change in lifestyle may lower inflammation and prevent metabolic deterioration. | 18,772,269 |
Depression in patients with diabetes: does it impact clinical goals? | To examine whether depressive symptoms are associated with achievement of recommended goals for control of glucose, lipids, and blood pressure among patients with diabetes. We used a prospective cohort study of 1223 adults with diabetes that obtained self-reported depression symptoms from a survey. Medication use was obtained from claims data, and pharmacy and clinical data were obtained by manual review of paper medical records. Diabetes patients with depression symptoms were less likely to be at their glucose goal (43% vs 50%; P = .0176) but more likely to be at their blood pressure goal (57% vs 51%; P = .0435). The association between lipids and depression symptoms was related to a lower rate for low-density lipoprotein testing (56% vs 68%; P < .0001). Treatment with antidepressants resulted in a greater percentage achieving glucose and blood pressure goals but not lipid goals. Depression seems to have a variable impact on achieving these clinical goals, perhaps because the goals have differing measurement logistics and biological profiles. Further research is needed to learn whether better treatment of depressive symptoms leads to improvements in meeting diabetes clinical goals. | 18,772,293 |
Do guidelines for the diagnosis and monitoring of diabetes mellitus fulfill the criteria of evidence-based guideline development? | Although the methodological quality of therapeutic guidelines (GLs) has been criticized, little is known regarding the quality of GLs that make diagnostic recommendations. Therefore, we assessed the methodological quality of GLs providing diagnostic recommendations for managing diabetes mellitus (DM) and explored several reasons for differences in quality across these GLs. After systematic searches of published and electronic resources dated between 1999 and 2007, 26 DM GLs, published in English, were selected and scored for methodological quality using the AGREE Instrument. Subgroup analyses were performed based on the source, scope, length, origin, and date and type of publication of GLs. Using a checklist, we collected laboratory-specific items within GLs thought to be important for interpretation of test results. The 26 diagnostic GLs had significant shortcomings in methodological quality according to the AGREE criteria. GLs from agencies that had clear procedures for GL development, were longer than 50 pages, or were published in electronic databases were of higher quality. Diagnostic GLs contained more preanalytical or analytical information than combined (i.e., diagnostic and therapeutic) recommendations, but the overall quality was not significantly different. The quality of GLs did not show much improvement over the time period investigated. The methodological shortcomings of diagnostic GLs in DM raise questions regarding the validity of recommendations in these documents that may affect their implementation in practice. Our results suggest the need for standardization of GL terminology and for higher-quality, systematically developed recommendations based on explicit guideline development and reporting standards in laboratory medicine. | 18,772,309 |
IFATS collection: Fibroblast growth factor-2-induced hepatocyte growth factor secretion by adipose-derived stromal cells inhibits postinjury fibrogenesis through a c-Jun N-terminal kinase-dependent mechanism. | Adipose-derived stem/stromal cells (ASCs) not only function as tissue-specific progenitor cells but also are multipotent and secrete angiogenic growth factors, such as hepatocyte growth factor (HGF), under certain circumstances. However, the biological role and regulatory mechanism of this secretion have not been well studied. We focused on the role of ASCs in the process of adipose tissue injury and repair and found that among injury-associated growth factors, fibroblast growth factor-2 (FGF-2) strongly promoted ASC proliferation and HGF secretion through a c-Jun N-terminal kinase (JNK) signaling pathway. In a mouse model of ischemia-reperfusion injury of adipose tissue, regenerative changes following necrotic and apoptotic changes were seen for 2 weeks. Acute release of FGF-2 by injured adipose tissue was followed by upregulation of HGF. During the adipose tissue remodeling process, adipose-derived 5-bromo-2-deoxyuridine-positive cells were shown to be ASCs (CD31-CD34+). Inhibition of JNK signaling inhibited the activation of ASCs and delayed the remodeling process. In addition, inhibition of FGF-2 or JNK signaling prevented postinjury upregulation of HGF and led to increased fibrogenesis in the injured adipose tissue. Increased fibrogenesis also followed the administration of a neutralizing antibody against HGF. FGF-2 released from injured tissue acts through a JNK signaling pathway to stimulate ASCs to proliferate and secrete HGF, contributing to the regeneration of adipose tissue and suppression of fibrogenesis after injury. This study revealed a functional role for ASCs in the response to injury and provides new insight into the therapeutic potential of ASCs. | 18,772,314 |
Nanomolar concentrations of pregnenolone sulfate enhance striatal dopamine overflow in vivo. | The balance between GABA-mediated inhibitory and glutamate-mediated excitatory synaptic transmission represents a fundamental mechanism for controlling nervous system function, and modulators that can alter this balance may participate in the pathophysiology of neuropsychiatric disorders. Pregnenolone sulfate (PS) is a neuroactive steroid that can modulate the activity of ionotropic glutamate and GABA(A) receptors either positively or negatively, depending upon the particular receptor subtype, and modulates synaptic transmission in a variety of experimental systems. To evaluate the modulatory effect of PS in vivo, we infused PS into rat striatum for 20 min via a microdialysis probe while monitoring local extracellular dopamine (DA) levels. The results demonstrate that PS at low nanomolar concentrations significantly increases extracellular DA levels. The PS-induced increase in extracellular DA is antagonized by the N-methyl-d-aspartate (NMDA) receptor antagonist, d-AP5 [d-(-)-2-amino-5-phosphonopentanoic acid], but not by the sigma receptor antagonist, BD 1063 [1(-)[2-(3,4-dichlorophenyl)-ethyl]-4-methylpiperazine]. The results demonstrate that exogenous PS, at nanomolar concentrations, is able to increase DA overflow in the striatum through an NMDA receptor-mediated pathway. | 18,772,319 |
Hypoglossal premotor neurons of the intermediate medullary reticular region express cholinergic markers. | The inspiratory drive to hypoglossal (XII) motoneurons originates in the caudal medullary intermediate reticular (IRt) region. This drive is mainly glutamatergic, but little is known about the neurochemical features of IRt XII premotor neurons. Prompted by the evidence that XII motoneuronal activity is controlled by both muscarinic (M) and nicotinic cholinergic inputs and that the IRt region contains cells that express choline acetyltransferase (ChAT), a marker of cholinergic neurons, we investigated whether some IRt XII premotor neurons are cholinergic. In seven rats, we applied single-cell reverse transcription-polymerase chain reaction to acutely dissociated IRt neurons retrogradely labeled from the XII nucleus. We found that over half (21/37) of such neurons expressed mRNA for ChAT and one-third (13/37) also had M2 receptor mRNA. In contrast, among the IRt neurons not retrogradely labeled, only 4 of 29 expressed ChAT mRNA (P < 0.0008) and only 3 of 29 expressed M2 receptor mRNA (P < 0.04). The distributions of other cholinergic receptor mRNAs (M1, M3, M4, M5, and nicotinic alpha4-subunit) did not differ between IRt XII premotor neurons and unlabeled IRt neurons. In an additional three rats with retrograde tracers injected into the XII nucleus and ChAT immunohistochemistry, 5-11% of IRt XII premotor neurons located at, and caudal to, the area postrema were ChAT positive, and 27-48% of ChAT-positive caudal IRt neurons were retrogradely labeled from the XII nucleus. Thus the pre- and postsynaptic cholinergic effects previously described in XII motoneurons may originate, at least in part, in medullary IRt neurons. | 18,772,326 |
The role of p66Shc deletion in age-associated arterial dysfunction and disease states. | Accumulation of oxidative stress with age is hypothesized to be the primary causative mediator of age-associated diseases. Among different tissues, aging vessels are known to accumulate oxidative damage and undergo functional impairment. Oxidative stress affects the availability and/or balance of key regulators of vascular homeostasis and favors the development of cardiovascular disease. Reactive oxygen species are generated by different intracellular molecular pathways principally located in the cytoplasm and in the mitochondria. The mitochondrial enzyme p66Shc is an adaptor protein and plays an important role as a redox enzyme implicated in mitochondrial reactive oxygen species generation and translation of oxidative signals into apoptosis. Mice lacking p66Shc-/- gene display reduced production of intracellular oxidants and a 30% prolonged life span. For this reasons, a series of studies conceived to elucidate the function of p66Shc and its possible implication in age-associated cardiovascular diseases have been carried out. Indeed, p66Shc-/- mice have been shown to be protected from age-dependent endothelial dysfunction as well as age-related risk factors such as diabetes and hypercholesterolemia. This review focuses on delineating the role of the p66Shc adaptor protein and its potential implication in the pathophysiology of aging and age-related cardiovascular disease. | 18,772,327 |
Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome. | Microparticles are membrane vesicles that are released during cell activation and apoptosis. Elevated levels of microparticles occur in many cardiovascular diseases; therefore, we characterized circulating microparticles from both metabolic syndrome (MS) patients and healthy patients. We evaluated microparticle effects on endothelial function; however, links between circulating microparticles and endothelial dysfunction have not yet been demonstrated. Circulating microparticles and their cellular origins were examined by flow cytometry of blood samples from patients and healthy subjects. Microparticles were used either to treat human endothelial cells in vitro or to assess endothelium function in mice after intravenous injection. MS patients had increased circulating levels of microparticles compared with healthy patients, including microparticles from platelet, endothelial, erythrocyte, and procoagulant origins. In vitro treatment of endothelial cells with microparticles from MS patients reduced both nitric oxide (NO) and superoxide anion production, resulting in protein tyrosine nitration. These effects were associated with enhanced phosphorylation of endothelial NO synthase at the site of inhibition. The reduction of O2(-) was linked to both reduced expression of p47 phox of NADPH oxidase and overexpression of extracellular superoxide dismutase. The decrease in NO production was triggered by nonplatelet-derived microparticles. In vivo injection of MS microparticles into mice impaired endothelium-dependent relaxation and decreased endothelial NO synthase expression. These data provide evidence that circulating microparticles from MS patients influence endothelial dysfunction. | 18,772,329 |
Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis. | The endocannabinoid pathway plays an important role in the regulation of appetite and body weight, hepatic lipid metabolism, and fibrosis. Blockade of the endocannabinoid receptor CB1 with SR141716 promotes weight loss, reduces hepatocyte fatty acid synthesis, and is antifibrotic. D-4F, an apolipoprotein A-1 mimetic with antioxidant properties, is currently in clinical trials for the treatment of atherosclerosis. C57BL/6J mice were fed a high-fat diet for 7 months, followed by a 2.5-month treatment with either SR141716 or D-4F. SR141716 markedly improved body weight, liver weight, serum transaminases, insulin resistance, hyperglycemia, hypercholesterolemia, hyperleptinemia, and oxidative stress, accompanied by the significant prevention of fibrosis progression. D-4F improved hypercholesterolemia and hyperleptinemia without improvement in body weight, steatohepatitis, insulin resistance, or oxidative stress, and yet, there was significant prevention of fibrosis. D-4F prevented culture-induced activation of stellate cells in vitro. In summary, C57BL/6J mice given a high-fat diet developed features of metabolic syndrome with nonalcoholic steatohepatitis and fibrosis. Both SR141716 and D-4F prevented progression of fibrosis after onset of steatohepatitis, ie, a situation comparable to a common clinical scenario, with D-4F seeming to have a more general antifibrotic effect. Either compound therefore has the potential to be of clinical benefit. | 18,772,330 |
Smad-independent transforming growth factor-beta regulation of early growth response-1 and sustained expression in fibrosis: implications for scleroderma. | Transforming growth factor-beta (TGF-beta) plays a key role in scleroderma pathogenesis. The transcription factor early growth response-1 (Egr-1) mediates the stimulation of collagen transcription elicited by TGF-beta and is necessary for the development of pulmonary fibrosis in mice. Here, we report that TGF-beta causes a time- and dose-dependent increase in Egr-1 protein and mRNA levels and enhanced transcription of the Egr-1 gene via serum response elements in normal fibroblasts. The ability of TGF-beta to stimulate Egr-1 was preserved in Smad3-null mice and in explanted Smad3-null fibroblasts. The response was blocked by a specific mitogen-activated protein kinase kinase 1 (MEK1) inhibitor but not by an ALK5 kinase inhibitor. Furthermore, MEK1 was phosphorylated by TGF-beta, which was sufficient to drive Egr-1 transactivation. Stimulation by TGF-beta enhanced the transcriptional activity of Elk-1 via the MEK-extracellular signal-regulated kinase 1/2 pathway. Bleomycin-induced scleroderma in the mouse was accompanied by increased Egr-1 accumulation in lesional fibroblasts. Furthermore, biopsies of lesional skin and lung from patients with scleroderma showed increased Egr-1 levels, which were highest in early diffuse disease. Moreover, both Egr-1 mRNA and protein were elevated in explanted scleroderma skin fibroblasts in vitro. Together, these findings define a Smad-independent TGF-beta signal transduction mechanism that underlies the stimulation of Egr-1, demonstrate for the first time sustained Egr-1 up-regulation in fibrotic lesions and suggests that Egr-1 has a role in the induction and progression of fibrosis. | 18,772,333 |
The endothelin-converting enzyme-1/endothelin-1 pathway plays a critical role in inflammation-associated premature delivery in a mouse model. | Premature delivery occurs in 12% of all births and accounts for nearly half of long-term morbidity. Current therapeutic approaches to preterm delivery are ineffective and present serious risks to both mother and fetus. The single most common cause of preterm birth is infection. Previous in vitro investigations have shown that endothelin-1 (ET-1) is induced by inflammatory cytokines and that it increases myometrial smooth muscle tone. Furthermore, we have previously shown that both the endothelin-converting enzyme-1 (ECE-1) inhibitor, phosphoramidon, as well as a novel ET-1 receptor A antagonist synthesized by our group, control premature delivery in a mouse model of inflammation-associated preterm delivery. In the current work, we show that levels of both ET-1 and ECE-1 are increased in gestational tissues in E16.5 mice induced to deliver prematurely after lipopolysaccharide administration. We also show that premature delivery is controlled by treatment with the selective endothelin receptor A antagonist BQ-123 in a dose-dependent manner. Finally, we show here for the first time that premature delivery can be controlled using RNA silencing, by hydrodynamic transfection of E15 mice with ECE-1 RNAi. Taken together, these data support a critical role for the ECE-1/ET-1 system in inflammation-associated premature delivery. The ability to control premature delivery by antagonizing or silencing the ECE-1/ET-1 system offers a novel approach to an unmet clinical need. | 18,772,340 |
An unusual cause of atrial tachycardia in a young patient with lymphoma. | An 8-year-old girl who was recently diagnosed as having anaplastic large-cell lymphoma presented with atrial tachycardia and dilated cardiomyopathy, which is a contraindication for further treatment with cardio-toxic chemotherapy. After starting digoxin therapy, the dilated cardiomyopathy resolved. Repeated episodes of atrial tachycardia in this case were not caused by any common disorder but were due to mechanical stimulation by a central venous catheter. Central venous catheters are known to cause mainly ventricular arrhythmias. However, atrial tachycardia is a rare manifestation of arrhythmia due to mechanical stimulation of the heart by a central venous catheter, with potentially important cardiovascular consequences. | 18,772,357 |
Crosspresentation by nonhematopoietic and direct presentation by hematopoietic cells induce central tolerance to myelin basic protein. | Central tolerance plays a critical role in eliminating self-reactive T cells specific for peripheral antigens. Here we show that central tolerance of MHC class I-restricted T cells specific for classic myelin basic protein (MBP), a component of the myelin sheath, is mediated by both bone marrow (BM)-derived and nonBM-derived cells. Unexpectedly, BM-derived cells induce tolerance directly by using classic MBP that they synthesize, whereas nonBM-derived cells mediate tolerance by crosspresenting classic MBP acquired from an exogenous source. Thus, tolerance to tissue-specific antigens can involve multiple cell types and mechanisms in the thymus, which may account for the limited spectrum of autoimmune syndromes observed when expression of tissue-specific antigens is impaired only in thymic epithelial cells. | 18,772,374 |
A transcript profiling approach reveals an epicatechin-specific glucosyltransferase expressed in the seed coat of Medicago truncatula. | Expression of the Arabidopsis TRANSPARENT TESTA 2 (TT2) MYB family transcription factor leads to massive accumulation of proanthocyanidins (PAs) in hairy roots of Medicago truncatula. Microarray analysis showed that TT2 induces genes for flavonoid/PA biosynthesis, transcription factors, and a large number of genes of unknown function. A second microarray dataset identified genes that were preferentially expressed in the M. truncatula seed coat. Comparison of the two datasets defines target genes for steps that are yet unidentified in PA biosynthesis and accumulation. Of these genes, a glycosyltransferase, UGT72L1, was active specifically toward the PA precursor (-)-epicatechin, and its expression pattern in developing seeds correlated with the presence of epicatechin glucoside and accumulation of PAs. UGT72L1 may be involved in the production of epicatechin 3'-O-glucoside in the seed coat as a key step in PA biosynthesis or its regulation. | 18,772,380 |
Comment on "Fire-derived charcoal causes loss of forest humus". | Wardle et al. (Brevia, 2 May 2008, p. 629) reported that fire-derived charcoal can promote loss of forest humus and belowground carbon (C). However, C loss from charcoal-humus mixtures can be explained not only by accelerated loss of humus but also by loss of charcoal. It is also unclear whether such loss is related to mineralization to carbon dioxide or to physical export. | 18,772,418 |
Microcatheter contrast injections during intra-arterial thrombolysis may increase intracranial hemorrhage risk. | During intra-arterial revascularization, either guide catheter injections of contrast in the neck or microcatheter contrast injections (MCIs) at or beyond the site of an occlusion, can be used to visualize intracranial vasculature. Neurointerventionalists vary widely in their use of MCIs for a given circumstance. We tested the hypothesis that MCIs are a risk factor for intracranial hemorrhage (ICH) in the Interventional Management of Stroke (IMS) I and II trials of combined intravenous/IA recombinant tissue plasminogen activator therapy. All arteriograms with M1, M2, and ICA terminus occlusions were reanalyzed (n=98). The number of MCIs within or distal to the target occlusion was assigned. Postprocedure CTs were reviewed for contrast extravasation and ICH. Contrast extravasation was defined as a hyperdensity suggestive of contrast (Hounsfield unit >90) seen at 24 hours or present before 24 hours and persisting or replaced by ICH at 24 hours. In this IMS subset, the rate of any ICH was 58% (57 of 98). More MCIs were seen in the ICH group (median=2 versus 1; P=0.04). Increased MCIs were associated with higher ICH rates (P=0.03). MCIs remained associated with ICH in multivariable analysis (P=0.01) as did baseline CT edema/mass effect, atrial fibrillation, time to intravenous recombinant tissue plasminogen activator initiation, and Thrombolysis in Cerebral Infarction reperfusion score. MCIs were also associated with contrast extravasation in unadjusted and adjusted analyses. MCIs may risk ICH in the setting of combined intravenous/intra-arterial recombinant tissue plasminogen activator therapy, possibly due to contrast toxicity or pressure transmission by injections. MCIs should be minimized whenever possible. These findings will be tested prospectively in the IMS III trial. | 18,772,441 |
Association of longer telomeres with better health in centenarians. | Prior animal model studies have demonstrated an association between telomere length and longevity. Our study examines telomere length in centenarians in good health versus poor health. Using DNA from blood lymphocytes, telomere length was measured by quantitative polymerase chain reaction in 38 sex- and age-matched centenarians (ages 97-108). "Healthy" centenarians (n = 19) with physical function in the independent range and the absence of hypertension, congestive heart failure, myocardial infarction, peripheral vascular disease, dementia, cancer, stroke, chronic obstructive pulmonary disease, and diabetes were compared to centenarians with physical function limitations and > or =2 of the above conditions (n = 19). Healthy centenarians had significantly longer telomeres than did unhealthy centenarians (p =.0475). Our study demonstrated that investigations of the association between telomere length and exceptional longevity must take into account the health status of the individuals. This raises the possibility that perhaps it is not exceptional longevity but one's function and health that may be associated with telomere length. | 18,772,468 |
Trafficking pathways of mycolic acids: structures, origin, mechanism of formation, and storage form of mycobacteric acids. | Mycolic acids, the hallmark of mycobacteria and related bacteria, are major and specific components of their cell envelope and essential for the mycobacterial survival. Mycobacteria contain structurally related long-chain lipids, but the metabolic relationships between these various classes of compounds remain obscure. To address this question a series of C(35) to C(54) nonhydroxylated fatty acids (mycobacteric acids), ketones, and alcohols structurally related to the C(70-80) dicyclopropanated or diethylenic mycolic acids were characterized in three mycobacterial strains and their structures compared. The relationships between these long-chain acids and mycolic acids were established by following the in vivo traffic of (14)C labeled alpha-mycolic acids purified from the same mycobacterial species. The labeling was exclusively found in mycobacteric acids. The mechanism of this degradation was established by incorporation of (18)O(2) into long-chain lipids and shown to consist in the rupture of mycolic acids between carbon 3 and 4 by a Baeyer-Villiger-like reaction. We also demonstrated that mycobacteric acids occur exclusively in the triacylglycerol (TAG) fraction where one molecule of these acids esterifies one of the three hydroxyl groups of glycerol. Altogether, these data suggest that these compounds represent a pathway of metabolic energy that would be used by mycobacteria in particular circumstances. | 18,772,482 |
[Expression and SNP analysis of BRD7 gene in acute leukemia cells]. | To evaluate the expression level of BRD7 gene in bone marrow mononuclear cells (BMNCs) in patients with acute leukemia (AL) and to analyze BRD7 single nucleotide polymorphism(SNP). RT-PCR was used to detect BRD7 expression in patients with AL and normal bone marrow subjects. Single-strand conformation polymorphism and DNA sequence analysis were also used to identify BRD7 mutation or SNP to investigate the relation between BRD7 and AL. BRD7 mRNA in BMNCs from 52 patients with AL and 30 control subjects was expressed. The mRNA relative expression of BRD7 in patients with AL was higher than that of the control group (P=0.001). Three SNPs (C657A,C495T and A737G) in BRD7 gene coding region (447 approximately 844 bp) were found, and A737G was coupled with C495T . The allele frequencies of SNP C657A were not significantly different between AL and the control group. The genotype and the allele frequencies of the 2 coupled SNPs were significantly different (P<0.01). But there was no significant discrepancy among the mRNA expression levels of AA, AG, and GG genotypes in the leukemia group (P>0.05). Expression of BRD7 gene is up-regulated in AL cells. The 2 coupled SNPs (C495T and A737G ) in BRD7 gene coding region (447 approximately 844 bp) are correlated with AL, indicating that SNPs may be one of the genetic susceptibility factors of AL. | 18,772,500 |
Molecular mechanisms underlying the transition of cardiac hypertrophy to heart failure. | Heart failure is a condition in which the heart cannot supply enough blood to the body's organs, and is a final common consequence of various heart diseases. In the past 2 decades, much progress has been made in understanding the molecular and cellular processes that contribute to cardiac hypertrophy and heart failure, leading to the development of effective therapies. However, heart failure remains a leading cause of mortality worldwide and the precise molecular mechanisms that mediate the transition of cardiac hypertrophy to heart failure are largely undefined. This review discusses the potential mechanisms of heart failure progression focusing on (1) cardiac myocyte loss, (2) abnormalities of calcium handling, and (3) myocardial ischemia and hypoxia. These factors are closely related, and are considered to contribute to the pathogenesis of contractile dysfunction and heart failure in a cooperative manner. Elucidation of the molecular mechanisms underlying the transition of cardiac hypertrophy to heart failure will lead to the development of novel therapeutic strategies for heart diseases. | 18,772,527 |
[A case report of ball valve syndrome caused by the gastrointestinal stromal tumor arising from the muscularis mucosae in gastric fornix]. | An 83-year-old woman who was admitted to other hospital, was consulted us because of continuous tarry stool and abdominal fullness. On upper endoscopy, the submucosal tumor from greater curvature of gastric fornix invaginated into the duodenal bulbus, showing so-called "ball valve syndrome (BVS)". As the tumor incarcerted again on the following endoscoopy, she underwent laparoscopic partial gastrectomy. The submucosal tumor was diagnosed histologically as gastrointestinal stromal tumor (GIST) arising from the muscularis mucosae. This is the first report that GIST arising from the muscularis mucosae in gastric fornix showed a BVS. | 18,772,574 |
Effects of gender, gonadectomy and sex hormones on growth and plasma cholesterol level in rats. | No studies have clearly demonstrated how sex hormones are involved in the observed gender difference in growth and plasma cholesterol levels in animals fed hypercholesterolemic diets. This study was conducted to determine the effects of gender, gonadectomy (GNX), and sex hormones on growth, plasma cholesterol and cortisol levels in Sprague-Dawley rats. In the first of two experiments, equal numbers of male and female 4-week-old rats were divided into three groups: sham-operated control, GNX, or GNX + 17alpha-methyltestosterone (MT). The rats were fed a hypercholesterolemic diet for 4 weeks. In a second experiment, 24 GNX females were equally divided into three groups: control, 17beta-estradiol (E(2)), or MT. These rats were fed a normocholesterolemic diet for 3 weeks. The average total plasma cholesterol level in female rats was twice that in male rats. MT administration to GNX male and GNX female rats decreased plasma cholesterol levels by 23 and 45%, respectively. Weekly intramuscular injection of E(2) markedly suppressed growth while increasing plasma cortisol levels in GNX female rats. Testosterone decreases plasma cholesterol levels in rats fed a hypercholesterolemic diet and E(2) suppresses growth of rats, inducing the secretion of hormones that increase with stress. | 18,772,583 |
Methotrexate-loaded polymethylmethacrylate bone cement for local bone metastasis therapy: pilot animal study in the rabbit patellar groove. | Local chemotherapy is an option in bone metastasis treatment. On the other hand, evaluation of side effects on bone is a difficult issue in drug development and biomaterials research. Most animal models to date are inappropriate or not feasible. Rabbits are an alternative to other bigger mammals and have an appropriate bone structure compared to rats and mice. The patellar groove model of the rabbit offers a standardized and sensitive model to evaluate bone-compromising drug effects. We tested the system with a reproducible polymethacrylate implant as carrier and loaded this system with methotrexate. Three methotrexate concentrations were used in the test samples (250 mg, 1 g and 4 g per 40 g polymethacrylate bone cement; 2 per group) for a descriptive histology approach. Eight German giant rabbits were operated on both knees and received test and control implants in a randomized manner in this bilateral study design. The histological results after 35 days were convincing, encouraging the use in preclinical drug development and biomaterials research and warranting further development of this metastasis treatment approach. | 18,772,590 |
Angiographic and intravascular ultrasound assessment of immediate and 9-month efficacy of percutaneous transluminal renal artery balloon angioplasty with subsequent brachytherapy in patients with renovascular hypertension. | Scarce data exist concerning the long-term effect of renal balloon angioplasty (PTRA) enhanced by intravascular gamma-brachytherapy (IVBT) in patients with renovascular hypertension. The aim of this randomized study was to evaluate long-term outcome after PTRA with IVBT in patients with renal artery stenosis. 71 patients with renovascular hypertension were randomized into group I (PTRA + IVBT) or group II (PTRA). 9 patients who required stent implantation were excluded. Both baseline and 9-month follow-up quantitative computerized angiography and intravascular ultrasound (IVUS) analysis were performed to assess restenosis. During the 9-month follow-up, 3 patients died - 2 from group I and 1 from group II. The restenosis rate was 16.1% in group I and 32.1% in group II. The 9-month lumen loss in angiography was 1.2 +/- 0.7 and 1.7 +/- 0.7 mm (p = 0.004) and the area loss (IVUS) was 6.5 +/- 4.8 and 10.1 +/- 5.6 mm(2) in groups I and II, respectively (p = 0.01). eGFR increased both in group I (from 75 +/- 22 to 84 +/- 31 ml/min/1.73 m(2); p < 0.001) and in group II (from 74 +/- 23 to 77 +/- 23 ml/min/1.73 m(2); p = 0.04). Only the diastolic blood pressure in group I decreased significantly (65 +/- 17 and 77 +/- 18 mm Hg; p = 0.048). The rate of blood pressure normalization was low in both groups (6.1 and 6.9%). IVBT after PTRA with a self-centering source is a safe and effective method for prevention of restenosis in patients with renovascular hypertension. | 18,772,602 |
Growth hormone stimulates mechano growth factor expression and activates myoblast transformation in C2C12 cells. | Mechano growth factor (MGF) is an alternatively spliced variant of insulin-like growth factor-I (IGF-I). Previous reports have revealed that the MGF in skeletal muscles is induced by mechanical overload or muscle injury. In the present study, we examined the effect of growth hormone (GH) on MGF expression in C2C12 mouse muscle cell lines since GH is the principal regulator of IGF-I. The MGF mRNA increased 1 h following GH stimulation whereas IGF-IEa mRNA, which encodes a systemic type of IGF-I, increased 4 h following GH stimulation. The diverse expression of MGF and IGF-IEa was also observed in the case of muscle injury by using bupivacaine in the same cell line. Furthermore, GH induced the increase of MyoD as well as M-cadherin expression, the peak of which was parallel to that of MGF. These results indicate that GH directly and preferentially increased MGF prior to the IGF-IEa expression in C2C12 cells, which may lead to the activation of muscle satellite cells. | 18,772,608 |
The efficacy of reboxetine as an antidepressant, a meta-analysis of both continuous (mean HAM-D score) and dichotomous (response rate) outcomes. | Reboxetine is the first selective Norepinephrine Reuptake Inhibitor (NRI). There are limited numbers of quantitative synthesis studies of the efficacy of this drug in treating depressive disorders. We have meta-analyzed the efficacy of the reboxetine using both continuous and dichotomous outcome measures. Data was collected from the Pubmed search of English-language studies published from 1997 to 2007 and manual search of retrieved articles. We have searched for controlled clinical trials of reboxetine with any other antidepressant comparator or placebo in adults with depressive disorders using HAM-D scale for the outcome measure. After 11 studies were selected, separate meta-analyses for the active drug and for the placebo were performed using random effect model. The overall effect size compared with the other antidepressants was -0.06 (95%CI: -0.19; 0.08), with placebo -1.54 (95%CI: -2.23; -0.85). It was calculated using the final mean HAM-D score (continuous outcome). The pooled SD was used when the variance was not available. Pooled odds ratios for the response rates (dichotomous outcome) were 1.04 (95%CI: 0.75; 1.46) and 2.85 (95%CI: 1.88; 4.31) for the active drug and placebo comparisons accordingly. These results suggest that the efficacy of the reboxetine and the other antidepressants (SSRI, TCA and SNRI) on both measures does not differ while it is significantly superior to placebo. | 18,772,616 |
Predictive value of admission electrocardiography in patients with heart failure. | Admission electrocardiography (ECG) in heart failure (HF) patients provides important diagnostic information; however, there are limited data regarding the prognostic significance of ECG parameters for predicting cardiac events (CEs). The ECGs of 246 patients admitted with acute HF were evaluated for heart rate, rhythm, QRS and ST-T wave abnormalities, QTc duration, QT peak corrected (QTpc), T amplitude, and axis. The end points included rehospitalization for a CE or death during 30-day follow-up. There were 71 (29%) patients with CEs. In patients with CEs, atrial fibrillation (AF) was observed more frequently (27% vs 13%, respectively; P=.009) and QTpc was shorter (370+/-43 vs 386+/-44 ms, respectively; P=.020). Multivariate logistic regression analysis revealed that QTpc <or=360 ms and AF were predictive of CE after adjustment for clinical covariates. In conclusion, apart from AF, the presence of short QTpc <or=360 ms is independently associated with increased risk of rehospitalization or death in HF patients. | 18,772,621 |
Thermal therapy: a viable adjunct in the treatment of heart failure? | The aim of this work was to review and provide a summary of published literature on the clinical impact of thermal therapy (ie, warm water immersion, traditional sauna bathing, and dry infrared sauna) in patients with heart failure. Medline and Embase database literature searches were conducted, and studies that included measurement of heart failure-related clinical parameters were reviewed. Thermal therapy was found to have a positive impact on key heart failure-related parameters across multiple studies. Significant improvements were noted across a wide scope of heart failure-related parameters in the areas of (1) endothelial function, (2) hemodynamics, (3) cardiac geometry, (4) neurohormonal markers, and (5) quality of life. Of special note, thermal therapy also conveyed a strong antiarrhythmic effect in heart failure patients. The clinical evidence highlights repeatable and compelling data showing that thermal therapy may provide an important and viable adjunct in the treatment of heart failure. | 18,772,622 |
Characteristics, drug therapy, and outcomes from a database of 500,000 hospitalized patients with a discharge diagnosis of heart failure. | Knowledge related to acute heart failure (HF) and its management in "real-world" clinical practice is limited. The authors delineated characteristics and drug therapy for hospitalized HF patients and their association with clinical and economic outcomes. The NDCHealth (National Data Corporation, Atlanta, GA) database, containing billing data from a geographically diverse sample of approximately 300 hospitals, was screened for admissions in 2003 of either a primary or secondary discharge diagnosis of HF. Of 2.5 million admissions screened, 496,534 patients (19.7%) had a primary (131,057) or secondary (365,477) discharge diagnosis of HF. Mean age was 73.1+/-13.9 years, and 55.4% were women. Mean length of hospital stay was 8.7+/-28.6 days, and in-hospital mortality was 7.1%. Mean hospital cost per admission was dollars 18,667. Admissions with HF as a secondary diagnosis were associated with a worse prognosis. HF commonly exists in hospitalized patients and is associated with significant morbidity, mortality, and economic burden, irrespective of whether it is the primary diagnosis or a secondary comorbidity. | 18,772,626 |
Blood pressure control in patients with comorbidities. | Hypertension frequently coexists with obesity, diabetes, hyperlipidemia, or the metabolic syndrome; their association with cardiovascular disease is well established. The identification and management of these risk factors is an important part of the overall management of hypertensive patients. Because patients in these special populations are more predisposed to target organ damage (TOD), stringent targets for blood pressure (BP) control have been set in clinical guidelines. However, clinical trial and real-life evidence suggest that these targets are difficult to achieve. Patients with these comorbidities are more likely to require combination therapy, yet physicians are often reluctant to adjust the number and doses of medications to achieve target BP. There is a particular need for effective 24-hour BP control in these patients, due to the increased likelihood of nondipping status, which is a risk factor for TOD and mortality. Not all available antihypertensives are equally effective in controlling BP over 24 hours, and some may exacerbate underlying metabolic abnormalities. | 18,772,645 |
Receiving bad news: a phenomenological exploration of the lived experience of receiving a cancer diagnosis. | This article explores the process of coming to a place of knowing one's diagnosis of cancer. The study was guided by the philosophy of hermeneutic phenomenology, with data collected via unstructured in-depth interviews. This article focuses on 10 people who received a cancer diagnosis (recipients). The analysis of the recipient narratives offered an interpretation of the phenomenon of receiving bad news as a process occurring over a period of time and not as a one-off event in time. The concept of bad news as a trajectory was clearly evident in the narratives and was represented through 3 themes: "disturbance of the everyday world," "surfacing within the lived world," and "embodiment within the lived world." The findings are consistent with the literature addressing diagnosis and end-of-life issues. Understanding the phenomenon of "knowing" is crucial in helping the healthcare professional recognize the changing information and psychosocial needs of the recipient as they experience the trajectory of bad news. | 18,772,654 |
Implications of systematic review for breast cancer prediction. | Highly accurate and predictive models are essential components to promote early breast cancer screening in primary care or home care settings. This study was conducted to demonstrate how the relevant variable selection process influenced the predictive performance of the model to identify individuals at high risk for breast cancer. As such, as a strategy to increase the predictive performance of the models, a systematic review of previously published articles was conducted to select important risk factors for breast cancer. Through the systematic literature review and the application of variable selection methods, 13 final risk factors were identified. Logistic regression and naive Bayes predictive modeling techniques were used. Both models had higher predictive performances than previously developed models. It is believed that the systematic literature review process contributed to the identification of relevant variables and increased the predictive performance of the models. This study also implies that the naive Bayes was equivalent to and could be preferred over logistic regression. | 18,772,655 |
Enhancing hope among early female survivors of childhood cancer via the internet: a feasibility study. | The purpose of this research was to establish the feasibility of delivering the Hope Intervention Program (HIP) using a Web-based design among 6 female survivors of childhood cancer. The HIP is an 8-week program to foster and promote hope. Each session of the HIP has specific focus, goals, and activities that offer opportunities for participants to share and discuss issues of importance to them. The HIP was delivered online with the use of educational software that included Web cameras and voice and text chat capabilities. Feasibility was evaluated by examining how easily and effectively the software and hardware technology could be used to deliver the HIP and if meaningful dialogue and interactions among the study participants and the nurse interventionist could occur online. The evaluation of this study suggested that using a Web-based approach was effective in the delivery of the intervention, as evidenced by participants' evaluation of the program and their descriptive comments that reflect that the online sessions promoted intimate, meaningful human-to-human interactions to foster hope and build a trusting relationship among and between group members. The results of this study suggest that Web-based psychosocial nursing interventions for survivors of childhood survivors are feasible for nurse researchers to conduct. | 18,772,662 |
Pediatric strabismus imaging. | With both radiologists and ophthalmologists in mind, this article describes the best use of computed tomography and magnetic resonance imaging in the diagnosis of strabismus. Both computed tomography and magnetic resonance imaging are valuable tools in evaluation of strabismus, despite concerns about radiation exposure with computed tomography. Advancements in magnetic resonance imaging are being made and open new techniques that can be useful in the future evaluation of strabismus. Computed tomography and magnetic resonance imaging are safe tools in the evaluation of certain types of pediatric strabismus. The collaboration between imagers and ophthalmologists is essential in the development of feasible innovative methods of imaging that will advance diagnosis and monitoring in children with strabismus. | 18,772,668 |
Psychosocial characteristics of cancer patients who choose to attend an educational session on cancer-related fatigue. | Little is known about cancer patients who seek specific educational interventions on cancer-related fatigue (CRF). The objectives of this study were (1) to describe the level of CRF, and emotional distress; social support; coping styles; and quality of life of patients who chose to attend a 1-hour educational session on CRF and (2) to examine the relationship between the selected demographic, psychosocial, and treatment-related variables and CRF. A questionnaire-based survey of 41 cancer patients who volunteered after a 1-hour education session on CRF at the Tom Baker Cancer Centre was conducted. The sample consisted mostly of married white women who lived in an urban environment. The average age was 56 years, and participants had an average of 14 years of education; 78% of the sample reported moderate to severe fatigue, 27% had significant levels of emotional distress, and 63% had a problematic coping style. Higher fatigue was associated with emotional distress, poorer quality of life, hopelessness, and reduced social support. To conclude, patients who self-refer to an educational session on CRF present a wide range of emotional difficulties and problematic coping styles. Therefore, educational sessions with patients with CRF should emphasize coping with emotional distress and building a support system. | 18,772,666 |
Targeted monoclonal antibody therapy and radioimmunotherapy for lymphoproliferative disorders of the ocular adnexa. | The goal of this review is to update ophthalmologists and orbital and adnexal specialists with the emerging role of targeted monoclonal antibody therapy and radioimmunotherapy for orbital and adnexal non-Hodgkin's lymphoma and other lymphoproliferative disorders of the orbit. Rituximab as monotherapy for indolent lymphoma of the orbit and conjunctiva may be associated with good initial response, but the risk of distant relapse is about 50%. Rituximab may be used in combination with conventional chemotherapy, and such combination therapy may be associated with a higher durable response rate and improved progression-free survival compared with chemotherapy alone. Radioimmunotherapy using targeted monoclonal antibodies with radioactive conjugates is also associated with a more durable response rate than monotherapy with rituximab alone and may be an alternative for treatment of ocular adnexal lymphoma. Radioimmunoconjugates are associated with transient pancytopenia during the first 3 months after treatment. Rituximab monotherapy may be considered as an alternative to systemic steroids for treatment of orbital benign lymphoid hyperplasia. Targeted monoclonal antibody therapy is an intriguing new modality for treatment of orbital, eyelid, or conjunctival lymphoma and can be used in combination with radioimmunotherapy or standard chemotherapy for a more durable response. | 18,772,675 |
Ptosis repair options and algorithm. | The treatment options for ptosis are strictly surgical. Each patient needs to be individually assessed and treated. A surgeon needs to be familiar with all types of surgical repair to choose the best possible option for his/her particular patient. There are certain established surgeries in ptosis repair; however, there is no ideal surgical technique to treat every patient without any drawbacks. Several modifications of known techniques have been described to address the weaknesses of original applications. Also, new techniques such as orbicularis plication, levator readaptation, and new approaches in frontalis suspension surgery were presented. An algorithm showing the appropriate/most preferred ptosis surgery techniques is prepared based on the traditional knowledge and the latest publications. There have been many modifications and new proposals in the management of ptosis. The surgeon needs to be familiar with an algorithm for the appropriate surgical method. | 18,772,677 |
Response to oral supplementation in copper deficiency myeloneuropathy. | Neurological manifestations due to copper deficiency include ataxic myeloneuropathy that resembles subacute combined degeneration due to B12 deficiency. We report our experience in the treatment of 10 patients with copper deficiency myeloneuropathy and conclude that copper supplementation leads to stabilization rather than improvement in the neurological deficits. | 18,772,693 |
Low bone mineral density in spinal muscular atrophy. | Pathological fractures are common in pediatric neuromuscular disorders. Dual-energy x-ray absorptiometry has become the most accepted technique for the measurement of bone mineral density (BMD) in adults and children. Limited data are available on BMD in pediatric neuromuscular diseases except Duchenne muscular dystrophy. We retrospectively analyzed the results of all dual-energy x-ray absorptiometry scans done in a period of 23 months at a tertiary care pediatric neuromuscular center. BMD was performed on spine region L1-4. Osteopenia was classified as mild if the Z scores were between 0 and -1.5, moderate if Z scores were between -1.5 and -2.5, and severe if Z scores were > -2.5 standard deviation scores. Eighty-four dual-energy x-ray absorptiometry scans were performed on 79 patients between the ages of 4 months and 18 years with the mean age of 8 years. Z scores were used to compare their BMDs. BMD was lowest in patients with spinal muscular atrophy (SMA) with Z score of -2.25 +/- 0.31 standard deviation scores. The Z score for patients with Duchenne muscular dystrophy was -1.72 +/- 0.1. The BMD in nonambulatory patients with SMA was significantly decreased compared with ambulatory patients with SMA (P < 0.05). We conclude that osteopenia is common in children with neuromuscular disorders. Patients with SMA have the lowest BMD. | 18,772,695 |
Bifrontal versus bitemporal electroconvulsive therapy in severe manic patients. | To compare the efficacy and safety of moderate-dose bifrontal (BF) with low-dose bitemporal (BT) electroconvulsive therapy (ECT) in the treatment of patients with severe mania. In a parallel, double-blind, randomized clinical trial, 28 patients with severe mania admitted to a university hospital were assigned randomly to moderate-dose BF (n = 14) and low-dose BT (n= 14) ECT. The primary outcome measures included the Mini-Mental State Examination (MMSE) and the Young Mania Rating Scale (YMRS). All patients received at least 6 sessions of ECT. The 2 groups did not show any difference in their baseline MMSE or YMRS scores (P > 0.05). There was a significant difference between the MMSE scores of the BF compared with the BT group after both the sixth ECT (P < 0.05) and final ECT treatments (P < 0.05). Young Mania Rating Scale scores did not differ between the 2 groups after either the sixth or the last ECT sessions (P > 0.05). Moderate-dose BF ECT was as effective as BT ECT but was associated with fewer cognitive side effects in the treatment of patients with severe mania. | 18,772,704 |
[Peri-partum hemorrhage: surgical management]. | Surgeons must be aware of the surgical techniques necessary to control grave peri-partum hemorrhage which place the life of the mother in jeopardy; at times, surgery is the only life-saving solution in spite of all the medical, obstetrical, and interventional radiologic techniques which have been developed. Surgical indications and approaches must take into account several factors - the cause of the hemorrhage, the urgency defined by the hemodynamic status of the patient, the technical and human means available, and the obstetrical situation (vaginal versus caesarean delivery). When medical and obstetrical management along with fluid resuscitation prove inadequate, recourse to surgery is necessary. While hysterectomy and ligation of the hypogastric arteries are time-honored treatments of last recourse, newer techniques which are both simpler and less aggressive have been developed in recent years; these newer conservative techniques should be given first choice. | 18,772,729 |
[Impact of the French consensus guidelines on the management of colonic and rectal cancer: a population-based study]. | To compare the management of colorectal cancer (CRC) before and after the French consensus conferences of rectal cancer (RC) in 1994 and colonic cancer (CC) in 1998. From 344 CCR incident cases in 1992 and 545 in 2000, patient characteristics, tumor data, and diagnostic and treatment modalities were collected to compare the management of CRC. Post-operative mortality did not change significantly (4% in 1992 and 2.8% in 2000). No trends were observed in disease stage at diagnosis or rate of resection. For patients with CC (n=244 in 1992 and n=396 in 2000), the number of resection specimens with at least 12 lymph nodes increased from 11% in 1992 to 27% in 2000 (p<0.001). For CC with Dukes stage C and D, the use of chemotherapy increased significantly: for Dukes Stage C from 45% in 1992 to 55% in 2000; for Dukes Stage D from 37% in 1992 to 67% in 2000. For patients with RC (n=100 in 1992 and n=149 in 2000), no change in use of adjuvant radiotherapy was observed: 59% in 1992 versus 53.4% in 2000. Preoperative radiotherapy for RC was performed in 63% in 1992 and 75% in 2000 (p=0.7). The consensus guidelines appear to have moderately influenced management practices. A better diffusion of guidelines to practitioners and a systematic evaluation of actual practices would be helpful to improve their impact. | 18,772,733 |
[Cervical lymph nodes]. | Imaging plays a chief role in the care and monitoring of patients in cervico-facial oncology. The radiologist must know the anatomy of different lymph nodes as well as signs of malignancy (hypertrophy, enhancement, necrosis, capsular rupture, etc.). CT is still the first-line examination because of its high reliability, its accessibility and its ability to make an assessment of the upper aero digestive ways at the same time. Ultrasound is very accuracy, and allows the realization of cytoponction, but does not provide a complete exploration of the neck. MRI does not appear to be indicated for the first intention, but the new rapid sequences (STIR, diffusion) seem interesting. The PET-CT is useful in post-therapeutic management of patients, and probably in the initial staging, but its accessibility is poor. | 18,772,779 |
[Stab injury to the cervical cord: report of three cases]. | Retrospective review of the value of MR in the evaluation of stab injuries to the cervical cord in three patients admitted to our hospital. The mean patient age was 25 years old. Clinical examination showed hemiparesis in the first 2 cases and a Brown-Sequard syndrome in the third patient. Cervical spine radiographs showed no bony lesion. MR showed cord contusions for the first two patients with associated epidural hematoma in the second case, and cord laceration for the third case. MR of the cervical spine should be obtained in all patients with suspicion of cord injury following stab injury to the neck in the absence of bony lesion on plain radiographs or CT, even in the absence of neurological symptoms at the time of admission. | 18,772,788 |
[Cataract surgery and age-related maculopathy: benefits in terms of visual acuity and quality of life--a prospective study]. | To assess the benefits of cataract surgery in patients with age-related macular degeneration (AMD) in terms of visual acuity and quality of life. Forty-two eyes of 30 patients were included in this prospective study between October 2003 and January 2005. The eyes were divided into two groups: the first group (n=12) with geographic atrophy and neovascularization (late-stage AMD) and the second group (n=30) with drusen and retinal pigment epithelium abnormalities (early-stage AMD). Assessment included best corrected visual acuity (BCVA) and quality-of-life measures (VF-14 questionnaire) before surgery and BCVA and the VF-14 score after surgery. In the first group, there was no statistical difference but a trend toward improvement in BCVA (p>0.05). In terms of quality of life, there was a statistical difference between pre- and postoperative VF-14 (p=0.0078). In the second group, there was a statistical difference between pre- and postoperative BVCA (p<0.0001). In terms of quality of life, there was a statistical difference between pre- and postoperative VF-14 (p<0.0001). This study shows a benefit in terms of visual acuity and quality of life in the majority of patients with age-related maculopathy after cataract surgery, even in late-stage AMD. Indeed, we noted a marked improvement in visual acuity in cases of early-stage AMD and a slight improvement of visual acuity in late-stage AMD. Quality of life was improved at both stages. In conclusion, cataract surgery is justified in patients with AMD. | 18,772,807 |
[Polypoidal choroidal vasculopathy: clinical and angiographic features]. | To clarify the clinical and angiographic characteristics of idiopathic polypoidal choroidal vasculopathy (IPCV) and its natural course. Descriptive, prospective, consecutive case series of patients with presumed IPCV seen at Fort-de-France Hospital Center (French West Indies) between January and June 2006. All participants underwent complete eye examination and fluorescein and indocyanine green (ICG) angiography. The nature and location of the lesions were assessed in all eyes. Inclusion criteria were demonstration of characteristic lesions of IPCV on ICG angiography. Diagnosis of IPCV was made in 26 eyes of 14 patients, ten women and four men, all of Afro-Caribbean origin. The mean age was 77.4 years (range 60-92 years). Drusen were present in 13 eyes (50%), age-related macular degeneration (AMD) in one eye, and branch retinal vein occlusion in one eye. Twelve patients (85.7%) had bilateral involvement. Twelve eyes (46.2%) had visual acuity (VA) (Snellen) worse than 20/200, six eyes (23.1%) had VA between 20/200 and 20/100, and eight eyes (30.8%) had VA better than 20/100. On ICG angiography, lesions were predominantly located in the peripapillary area but also in the midperiphery, the macular and interpapillomacular areas, and the far periphery. Peripheral locations of IPCV and associations with drusen or AMD are not rare. The prognosis of the disease is poor in its natural course. Its etiology is unknown but genetic factors are probably involved. It is the main differential diagnosis for exudative AMD in black patients. | 18,772,808 |
[Folic acid in physiology and pathology]. | This paper presents current knowledge of the biological functions of folic acid, the effects of its deficiency in the organism, as well as the possibilities of its therapeutic use. Folic acid (folate, B9) is a vitamin of special importance in normal cellular functions. Tetrahydrofolate (TH4-folate) is the biologically active form of folic acid. The main role of folic acid in biochemistry is the single-carbon transfer reaction (e.g. transfer of a methyl, methylene, or formyl group). Folic acid is involved in the transformation of certain amino acids as well as in the synthesis of purines and dTMP (2'-deoxythymidine-5'-phosphate) needed for the synthesis of nucleic acid (DNA), required by all rapidly growing cells. In humans, folate deficiency results in serious pathologies, the most important of which are neural tube defects, megablastic anemia, acceleration of the arteriosclerotic process, changes in the central nervous system, and the development of certain types of cancer. To increase the intake of folic acid, preventive actions include dietary education, the main objectives of which are to increase the intake of natural folate in the daily diet, add folic acid to selected dietary products (e.g. fl our, pasta, rice), and encourage supplementation with folic acid-containing pharmaceuticals. | 18,772,846 |
[The role of matrix metalloproteinases in the pathogenesis of diabetes mellitus and progression of diabetes retinopathy]. | Matrix metalloproteinases (MMPs) comprise a family of over 20 structurally related proteins which are zinc-dependent and calcium-activated endopeptidases. The members of this family are able to degrade most extracellular matrix (ECM) proteins and are thus involved in tissue remodeling and contribute to cell migration by eliminating extracellular matrix and basement membrane barriers. Of the MMPs, MMP-2 and MMP-9 are especially active in the degradation of type IV collagen, the main constituent of the basement membrane. MMPs also cleave a variety of non-ECM proteins, including cytokines, chemokines, and growth factors. MMPs and their inhibitors (TIMPs) play important roles in physiological processes such as embryogenesis and wound healing; however, these enzymes are also involved in the pathogeneses of many diseases, such as cancer and atherosclerosis. In these pathological conditions the balance between MMPs and TIMPs shifts in favor of MMPs, resulting in excessive degradation of ECM. Research results published recently show that these enzymes can also be involved in the pathogenesis of diabetes mellitus and diabetic complications such as diabetic retinopathy. MMP-9 has the ability to degrade insulin and is able to activate IL-8, the main chemoattractant factor for neutrophils and monocytes. In addition, MMP-9 enables infl ammatory cell migration and pancreas colonization by eliminating the basement membrane barriers. Type IV collagenases are also important for endothelial cell invasion occurring during neovascularization (diabetic retinopathy), as angiogenesis needs extracellular matrix degradation; what is more, these enzymes are able to degrade pigment epithelium-derived factor, which is the principal antiangiogenic protein of the eye. | 18,772,849 |
PCR-based gene targeting in Candida albicans. | PCR-based gene-targeting approaches have increased the speed of gene function analyses in ascomycetous fungi, for example, in the diploid human fungal pathogen Candida albicans. Here we describe a protocol that utilizes Rapid-PCR to amplify all cassettes available with the previously reported pFA modules. With this protocol, sufficient quantities of any cassette for use in C. albicans transformation experiments can be reliably generated in 25-50 min using either of the two alternative optimized amplification conditions; cassette amplification by standard PCR methods typically takes 3-4 h and is likely to require optimization of amplification conditions for each cassette. Transformants that appear 2-4 d after transformation can be rapidly identified using Rapid-PCR on whole cells, eliminating the need for genomic DNA extraction. In total, less than a week is required for the deletion of one allele in C. albicans. Repeating this procedure will result in the generation of homozygous mutant strains. | 18,772,868 |
Neutral desorption sampling of biological surfaces for rapid chemical characterization by extractive electrospray ionization mass spectrometry. | Extractive electrospray ionization mass spectrometry (EESI-MS) allows the real-time, direct analysis of complex gaseous and liquid samples without any sample pretreatment under ambient conditions. By using a neutral desorption (ND) sampling gas beam to gently impact a surface, the analyte present on a surface can be efficiently sampled and then transported to the EESI source for soft ionization without any previous work-up. By separating the sampling process and the ionization process in both space and time, ion suppression effects are significantly decreased in ND-EESI-MS. Therefore, virtually any surface can be gently sampled in real time, allowing in vivo analysis of living objects while maintaining the native conditions of the sample. This greatly simplifies the procedure for the characterization of complex surfaces (e.g., plants, food, skin) and prevents potential chemical contamination, providing a unique platform for wide applications in multiple disciplines such as chemistry, biology and the life sciences. Here we present a complete description of a protocol for ND-EESI-MS for in vivo analysis of living objects, including equipment setup, reagent preparation, data acquisition and analysis steps. The data collection can be completed within a few minutes even though the time required for the entire analytical process, which largely depends on the preparation of samples and materials, takes slightly longer. | 18,772,874 |
Cripto recruits Furin and PACE4 and controls Nodal trafficking during proteolytic maturation. | The glycosylphosphatidylinositol (GPI)-anchored proteoglycan Cripto binds Nodal and its type I receptor Alk4 to activate Smad2,3 transcription factors, but a role during Nodal precursor processing has not been described. We show that Cripto also binds the proprotein convertases Furin and PACE4 and localizes Nodal processing at the cell surface. When coexpressed as in early embryonic cells, Cripto and uncleaved Nodal already associated during secretion, and a Cripto-interacting region in the Nodal propeptide potentiated the effect of proteolytic maturation on Nodal signalling. Disruption of the trans-Golgi network (TGN) by brefeldin A blocked secretion, but export of Cripto and Nodal to the cell surface was not inhibited, indicating that Nodal is exposed to extracellular convertases before entering the TGN/endosomal system. Density fractionation and antibody uptake experiments showed that Cripto guides the Nodal precursor in detergent-resistant membranes to endocytic microdomains marked by GFP-Flotillin. We conclude that Nodal processing and endocytosis are coupled in signal-receiving cells. | 18,772,886 |
Graphene 2.0. | Once the preserve of physicists, graphene is now attracting the attention of growing numbers of chemists, who are discovering new ways to produce this remarkable material. | 18,772,903 |
Enhanced combined tumor-specific oncolysis and suicide gene therapy for prostate cancer using M6 promoter. | Enzyme pro-drug suicide gene therapy has been hindered by inefficient viral delivery and gene transduction. To further explore the potential of this approach, we have developed AdIU1, a prostate-restricted replicative adenovirus (PRRA) armed with the herpes simplex virus thymidine kinase (HSV-TK). In our previous Ad-OC-TK/ACV phase I clinical trial, we demonstrated safety and proof of principle with a tissue-specific promoter-based TK/pro-drug therapy using a replication-defective adenovirus for the treatment of prostate cancer metastases. In this study, we aimed to inhibit the growth of androgen-independent (AI), PSA/PSMA-positive prostate cancer cells by AdIU1. In vitro the viability of an AI- PSA/PSMA-expressing prostate cancer cell line, CWR22rv, was significantly inhibited by treatment with AdIU1 plus GCV (10 microg ml(-1)), compared with AdIU1 treatment alone and also cytotoxicity was observed following treatment with AdIU1 plus GCV only in PSA/PSMA-positive CWR22rv and C4-2 cells, but not in the PSA/PSMA-negative cell line, DU-145. In vivo assessment of AdIU1 plus GCV treatment revealed a stronger therapeutic effect against CWR22rv tumors in nude mice than treatment with AdIU1 alone, AdE4PSESE1a alone or in combination with GCV. Our results demonstrate the therapeutic potential of specific-oncolysis and suicide gene therapy for AI-PSA/PSMA-positive prostate cancer gene therapy. | 18,772,902 |
An atomic-resolution nanomechanical mass sensor. | Mechanical resonators are widely used as inertial balances to detect small quantities of adsorbed mass through shifts in oscillation frequency. Advances in lithography and materials synthesis have enabled the fabrication of nanoscale mechanical resonators, which have been operated as precision force, position and mass sensors. Here we demonstrate a room-temperature, carbon-nanotube-based nanomechanical resonator with atomic mass resolution. This device is essentially a mass spectrometer with a mass sensitivity of 1.3 x 10(-25) kg Hz(-1/2) or, equivalently, 0.40 gold atoms Hz(-1/2). Using this extreme mass sensitivity, we observe atomic mass shot noise, which is analogous to the electronic shot noise measured in many semiconductor experiments. Unlike traditional mass spectrometers, nanomechanical mass spectrometers do not require the potentially destructive ionization of the test sample, are more sensitive to large molecules, and could eventually be incorporated on a chip. | 18,772,913 |
Highly conducting graphene sheets and Langmuir-Blodgett films. | Graphene is an intriguing material with properties that are distinct from those of other graphitic systems. The first samples of pristine graphene were obtained by 'peeling off' and epitaxial growth. Recently, the chemical reduction of graphite oxide was used to produce covalently functionalized single-layer graphene oxide. However, chemical approaches for the large-scale production of highly conducting graphene sheets remain elusive. Here, we report that the exfoliation-reintercalation-expansion of graphite can produce high-quality single-layer graphene sheets stably suspended in organic solvents. The graphene sheets exhibit high electrical conductance at room and cryogenic temperatures. Large amounts of graphene sheets in organic solvents are made into large transparent conducting films by Langmuir-Blodgett assembly in a layer-by-layer manner. The chemically derived, high-quality graphene sheets could lead to future scalable graphene devices. | 18,772,914 |
Revival of saprotrophic and mycorrhizal basidiomycete cultures after 20 years in cold storage in sterile water. | Vegetatively colonized agar cores of 69 basidiomycete fungus isolates (48 species in 30 genera and 17 families) were stored at 5 degrees C in tubes of sterile distilled water without manipulation for 20 years. These were represented by 34 isolates of saprotrophic fungi (29 species in 19 genera) and 35 isolates of mycorrhizal fungi (19 species in 11 genera). Viability was evaluated based on revived growth on agar media at room temperature. Fifty-seven of the 69 isolates (82.6%) grew vigorously when revived after storage for 20 years; of the 34 saprotrophic fungus isolates, 30 revived (88.2%); of the 35 mycorrhizal fungus isolates, 27 revived (77.1%). Thirteen isolates of Laccaria were all viable after 20 years, indicating cold storage in sterile water to be a good method for maintaining this important genus of mycorrhizal fungi. In general, however, mycorrhizal fungus species demonstrated lower viability than saprotrophic fungi. | 18,772,921 |
Differences in nitric oxide steady states between arginine, hypoxanthine, uracil auxotrophs (AHU) and non-AHU strains of Neisseria gonorrhoeae during anaerobic respiration in the presence of nitrite. | Neisseria gonorrhoeae can grow by anaerobic respiration using nitrite as an alternative electron acceptor. Under these growth conditions, N. gonorrhoeae produces and degrades nitric oxide (NO), an important host defense molecule. Laboratory strain F62 has been shown to establish and maintain a NO steady-state level that is a function of the nitrite reductase/NO reductase ratio and is independent of cell number. The nitrite reductase activities (122-197 nmol NO2 reduced x min(-1) x OD600(-1)) and NO reductase activities (88-155 nmol NO reduced x min(-1) x OD600(-1)) in a variety of gonococcal clinical isolates were similar to the specific activities seen in F62 (241 nmol NO2 reduced x min(-1) x OD600(-1) and 88 nmol NO reduced x min(-1) x OD600(-1), respectively). In seven gonococcal strains, the NO steady-state levels established in the presence of nitrite were similar to that of F62 (801-2121 nmol x L-1 NO), while six of the strains, identified as arginine, hypoxanthine, and uracil auxotrophs (AHU), that cause asymptomatic infection in men had either two- to threefold (373-579 nmol x L-1 NO) or about 100-fold (13-24 nmol x L-1 NO) lower NO steady-state concentrations. All tested strains in the presence of a NO donor, 2,2'-(hydroxynitrosohydrazono)bis-ethanimine/NO, quickly lowered and maintained NO levels in the noninflammatory range of NO (<300 nmol x L-1). The generation of a NO steady-state concentration was directly affected by alterations in respiratory control in both F62 and an AHU strain, although differences in membrane function are suspected to be responsible for NO steady-state level differences in AHU strains. | 18,772,926 |
Use of the 16S-23S ribosomal genes spacer region for the molecular typing of sphingomonads. | The ability of sphingomonads in drinking water to cause community- and hospital-acquired opportunistic infections has raised the need to establish reproducible identification assays. In this study, a total of 129 isolates recovered from drinking water with yellow- to orange-pigmented colonies were distributed among 10 biotypes on the basis of colony morphology. Polymorphisms, based on the amplification and restriction digestion of the intergenic transcribed spacer (ITS) region within the 10 assigned biotypes and 18 ATCC reference strains, were used to investigate the ability of this approach to differentiate closely related sphingomonads. ITS size, which ranged between 400 and 1100 bp, did not vary enough among the different genera. However, 16 distinct banding patterns within the ATCC reference strains and 9 within the 10 biotypes were obtained through ITS restriction digestion, and the majority of the tested biotypes produced patterns similar to those generated by the ATCC strains. To our knowledge, this study is not only the first comprehensive record of the size of the ITS region in sphingomonads, it is also the first study that describes the use of ITS restriction digestion to subtype those isolates. | 18,772,929 |
The Pic19 NBS-LRR gene family members are closely linked to Scmv1, but not involved in maize resistance to sugarcane mosaic virus. | Sugarcane mosaic virus (SCMV) is the causal pathogen for a severe mosaic virus disease of maize worldwide. In our previous research, the maize resistance gene analog (RGA) Pic19 and its three cognate BAC contigs were mapped to the same region as the SCMV resistance gene Scmv1. Here we report the isolation and characterization of the Pic19R gene family members from the inbred line FAP1360A, which shows complete resistance to SCMV. Two primer pairs were designed based on the conserved regions among the known Pic19 paralogs and used for rapid amplification of cDNA ends of FAP1360A. Six full-length cDNAs, corresponding to the Pic19R-1 to -6 paralogs, were obtained. Three of them (Pic19R-1 to -3) had uninterrupted coding sequences and were, therefore, regarded as candidates for the Scmv1 gene. A total of 18 positive BAC clones harboring the Pic19R-2 to -5 paralogs were obtained from the FAP1360A BAC library and assembled into two BAC contigs. Two markers, tagging Pic19R-2 and -3 and Pic19R-4, were developed and used to genotype a high-resolution mapping population segregating solely for the Scmv1 locus. Although closely linked, none of these three Pic19R paralogs co-segregated with the Scmv1 locus. Analysis of the Pic19R family indicated that the Pic19R-1 paralog is identical to the known Rxo1 gene conferring resistance to rice bacterial streak disease and none of the other Pic19R paralogs seems to be involved in resistance to SCMV. | 18,772,945 |
Effect of nano-scale crystal field on the broadening of Er3+- emission in sodium tellurite glass ceramics. | In this paper we report the effect of heat treatment of 10 mol% Na(2)O-89.5 mol% TeO(2) glass for studying the fluorescence and line broadening behavior of Er-ions in the glass-ceramic matrix. Controlled crystal growth measurements using the X-ray line broadening technique for samples heat treated in the temperature range of 583-693 K were carried out and compared with the photoluminescence studies. The influence of crystal growth on line broadening of (4)I(13/2) spectra and metastable lifetime of (4)I(13/2) level is compared for various heat treatment temperatures. The full-width-of- half maxima increase with increasing heat treatment temperature and then fall rapidly at high temperatures. | 18,772,961 |
Low loss elliptical core D-fiber to PANDA fiber fusion splicing. | Elliptical core D-fiber is difficult to fusion splice to other types of fiber due to its small core and D-shaped cladding. The presented method of splicing D-fiber to PANDA fiber involves using E-fiber in a bridge splice. The E-fiber core is expanded to match the mode of the PANDA fiber. The D-fiber is then connected to the E-fiber with a low temperature splice. Total system loss for fibers spliced using this method is 0.72 dB with a polarization crosstalk of less than 25 dB. | 18,772,964 |
Successive order, multiple scattering of two-term Henyey-Greenstein phase functions. | An analytic solution to the problem of determining photon direction after successive scatterings in an infinite, homogeneous, isotropic medium, where each scattering event is in accordance with a two-term Henyey-Greenstein phase function, is presented and compared against Monte Carlo simulation results. The photon direction is described by a probability density function of the dot product of the initial direction and the direction after multiple scattering events, and it is found that such a probability density function can be represented as a weighted series of one-term Henyey-Greenstein phase functions. | 18,772,974 |
Fast time-domain diffuse optical tomography using pseudorandom bit sequences. | We report a novel time-domain diffuse optical tomography to determine the optical properties in a faster speed than the conventional ones. Instead of using the ultrashort pulse laser, a 2.5 Gbps pseudorandom bit sequence is used to modulate the near-infrared light for tissue-like phantom illumination. The time-resolved signal can be retrieved very quickly by demodulation with the reference signal. The system impulse response has a full width at half maximum around 800 picoseconds and the 2-dimentional maps of optical properties can be obtained within a few seconds. The high signal-to-noise ratio and the environmental illumination insensitivity warrant a great potential for applications in clinical noninvasive breast cancer detection. | 18,772,975 |
Measuring the spatiotemporal electric field of tightly focused ultrashort pulses with sub-micron spatial resolution. | We demonstrate a powerful and practical spectral interferometer with near-field scanning microscopy (NSOM) probes for measuring the spatiotemporal electric field of tightly focused ultrashort pulses with high spatial and spectral resolution. Our measurements involved numerical apertures as high as 0.44 and yielded the spatiotemporal field at and around the foci produced by two microscope objectives and several different lenses. For the first time, we measure the spatiotemporal field of the Bessel-like X-shaped pulse caused by spherical aberrations and a "fore-runner pulse" due to chromatic aberrations. We observed spatial features smaller than 1 microm and verified these results with non-paraxial simulations. | 18,772,978 |
A photon-counting time-of-flight ranging technique developed for the avoidance of range ambiguity at gigahertz clock rates. | This paper describes a rapid data acquisition photon-counting time-of-flight ranging technique that is designed for the avoidance of range ambiguity, an issue commonly found in high repetition frequency time-off-light systems. The technique transmits a non-periodic pulse train based on the random bin filling of a high frequency time clock. A received pattern is formed from the arrival times of the returning single photons and the correlation between the transmitted and received patterns was used to identify the unique target time-of-flight. The paper describes experiments in laboratory and in free space at over several hundred meters range at clock frequencies of 1GHz. Unambiguous photon-counting range-finding is demonstrated with centimeter accuracy. | 18,772,980 |
Reconstructing subsurface electrical wave orientation from cardiac epi-fluorescence recordings: Monte Carlo versus diffusion approximation. | The development of voltage-sensitive dyes has revolutionized cardiac electrophysiology and made optical imaging of cardiac electrical activity possible. Photon diffusion models coupled to electrical excitation models have been successful in qualitatively predicting the shape of the optical action potential and its dependence on subsurface electrical wave orientation. However, the accuracy of the diffusion equation in the visible range, especially for thin tissue preparations, remains unclear. Here, we compare diffusion and Monte Carlo (MC) based models and we investigate the role of tissue thickness. All computational results are compared to experimental data obtained from intact guinea pig hearts. We show that the subsurface volume contributing to the epi-fluorescence signal extends deeper in the tissue when using MC models, resulting in longer optical upstroke durations which are in better agreement with experiments. The optical upstroke morphology, however, strongly correlates to the subsurface propagation direction independent of the model and is consistent with our experimental observations. | 18,772,987 |
Two-photon induced polymer nanomovement. | We present the first report of two-photon induced plastic surface deformation in solid polymer films. Exposure of azo polymer films, which absorb in the visible range (lambda(max) = 480 nm), to intense 920 nm irradiation leads to polarization dependent photofluidic polymer nanomovement caused by photoselective two-photon trans <-->cis isomerization. The deformations were induced by a gradient of light intensity; and strongly depend on the wavelength and the polarization direction of the incident laser light and the position of the focused spot with respect to the plane of the polymer film. | 18,773,020 |
Guidelines for palliative surgery of cholangiocarcinoma. | The aims of the guidelines are to help assess the evidence for palliation surgery in patients with cholangiocarcinoma (CCA). The guidelines are classified in accordance with the location of the primary lesion, i.e. intrahepatic, hilar, and distal. They are based on comprehensive literature surveys, including results from randomized controlled trials, systematic reviews and meta-analysis, and cohort, prospective, and retrospective studies. Intrahepatic CCA, i.e. resection of lymph-node-positive tumors and R1/R2 resections have not been shown to provide survival benefit: Evidence levels: 2b, 4; Recommendation grade C. Hilar CCA: R1 resection is justified as a very efficient palliation. Non-surgical biliary stenting is the first choice of palliative biliary drainage. Distal CCA: Resection of lymph-node-positive tumours and R1/R2 resections should be performed. Non-surgical stenting is regarded as the first choice of palliation for patients with short life expectancy. For patients with longer projected survival, surgical bypass should be considered. Palliative resections have a relevant beneficial impact on the outcome of patients with distal and hilar CCA. Non-surgical stenting is the first choice of palliative biliary drainage for patients with hilar CCA and for those with distal CCA and short life expectancy. For patients with distal CCA and longer projected survival, surgical bypass should be considered. | 18,773,044 |
Surgery for extrahepatic cholangiocarcinoma: predictors of survival. | The incidence of extrahepatic cholangiocarcinoma is increasing worldwide and is often in an advanced stage at diagnosis and difficult to treat. The TNM (tumor node metastasis) cancer staging system predicts survival on the basis of tumor histopathology and the presence of distant metastases. However, numerous prognostic factors have been described that are not included in the TNM system. This review focuses on the prognostic significance of clinical, surgical, and histopathological factors as reported in the literature. Overall, the most important independent prognostic factors for long-term survival are negative surgical margins, lymph node status, and differentiation grade of the tumor. Further improvement of staging systems and identification of prognostic factors are crucial if we are to better select patients for surgical and adjuvant therapy and, hence, increase the rate of curative resections. | 18,773,053 |
Development of a swine model of secondary liver tumor from a genetically induced swine fibroblast cell line. | Metastatic disease is the most common liver tumor. Although alternative therapies have been developed for non-surgical candidates, those therapies lacked ideal testing prior to clinical application because of a paucity of large animal models. The purpose of the present study was to develop a model for secondary liver tumor in a large animal. Fibroblasts were isolated from swine ear lobules and then transfected with amphotrophic retroviruses encoding human or murine genetic material (hTERT, p53(DD), cyclinD-1, CDK4(R24C), Myc (T58A), Ras(G12V)). Transformed cell lines were finally inoculated subcutaneously (s.c.) into: 1) immunodeficient mice (nude), 2) immunocompetent mice (wild type), 3) immunosuppressed swine (under tacrolimus or corticosteroids), 4) immunocompetent swine, and 5) into the liver and portal circulation of swine under steroid-based immunosuppression. In the murine model, tumor growth was evident in 100% of the nude mice (n=5), with a peak size of 20 mm (15.22+/-4.5 mm; mean+/-SD) at the time of sacrifice (3 weeks). Tumor growth was evident in 71% of the wild mice (n=21), with a peak size of 7.8 mm (4.19+/-1.1 mm) by the third week of growth. In the swine model, tumor growth was evident in 75% (3/4 ears; n=2) of swine under tacrolimus-based immunosuppression versus 50% of swine under steroids-based immunosuppression (n=2). Tumor growth was slow in two animals, while in one animal the tumor was larger with a peak growth of 42 mm at 3 weeks. The tumor pattern in the ear lobules was characterized by slow growth, with a peak size of 6-8 mm in the immunocompetent swine at 3 weeks. All tumors were shown to be malignant by histology. In contrast, inoculums of the transformed fibroblast cell line in swine livers showed no evidence of tumor growth at 3 weeks. Development of a transformed swine fibroblast cell line was successful, resulting in an in vivo malignant tumor. Cell line inoculums had tumorigenic properties in nude mice, wild-type mice, and immunosuppressed swine, as judged by uncontrolled cell growth, invasion of surrounding tissue, neoangiogenesis, and invasion of normal vasculature, resulting in the formation of tumor nodules. Such properties were not observed in swine upon inoculation into the liver/portal circulation. | 18,773,055 |
Staging cholangiocarcinoma by imaging studies. | Cholangiocarcinoma (CCA) is an adenocarcinoma that arises from the bile duct epithelium and is observed in the entire biliary tree (intrahepatic, hilum, and extrahepatic distal). The staging of this tumor differs depending on location. The role of imaging in the staging of hilar CCA is to assess the extent of ductal involvement by the tumor, hepatic artery, or portal venous involvement, the functional status and volumetric assessment of the underlying liver, and the regional or distant tumor extension. Complete assessment is done by combining magnetic resonance (MR) cholangiography and multidetector computed tomography (CT). Multidetector CT, in particular, is accurate for resectability and the negative predictive value (patients with disease classified as unresectable and in whom unresectability has been confirmed) is quite high: 85-100%. The role of imaging in the staging of intrahepatic CCA is to evaluate resectability based on the tumor itself, vascular involvement, regional and distal extension, and volumetric assessment of the contralateral liver, and to determine the prognostic factors. These factors are mainly: tumor size, the presence of satellite nodules, vascular involvement, and lymph nodes. CT and MR imaging (MRI) are keys and their results are comparable. In distal extrahepatic CCA due to tumor location, staging is focused mainly on the adjacent vessels (portal vein and hepatic artery), the hepatoduodenal ligament, the proximal and distal biliary extent, and pancreatic invasion. CT and MRI are mandatory. | 18,773,065 |
Identification of neural crest and glial enhancers at the mouse Sox10 locus through transgenesis in zebrafish. | Sox10 is a dynamically regulated transcription factor gene that is essential for the development of neural crest-derived and oligodendroglial populations. Developmental genes often require multiple regulatory sequences that integrate discrete and overlapping functions to coordinate their expression. To identify Sox10 cis-regulatory elements, we integrated multiple model systems, including cell-based screens and transposon-mediated transgensis in zebrafish, to scrutinize mammalian conserved, noncoding genomic segments at the mouse Sox10 locus. We demonstrate that eight of 11 Sox10 genomic elements direct reporter gene expression in transgenic zebrafish similar to patterns observed in transgenic mice, despite an absence of observable sequence conservation between mice and zebrafish. Multiple segments direct expression in overlapping populations of neural crest derivatives and glial cells, ranging from pan-Sox10 and pan-neural crest regulatory control to the modulation of expression in subpopulations of Sox10-expressing cells, including developing melanocytes and Schwann cells. Several sequences demonstrate overlapping spatial control, yet direct expression in incompletely overlapping developmental intervals. We were able to partially explain neural crest expression patterns by the presence of head to head SoxE family binding sites within two of the elements. Moreover, we were able to use this transcription factor binding site signature to identify the corresponding zebrafish enhancers in the absence of overall sequence homology. We demonstrate the utility of zebrafish transgenesis as a high-fidelity surrogate in the dissection of mammalian gene regulation, especially those with dynamically controlled developmental expression. | 18,773,071 |
Rhythm generation through period concatenation in rat somatosensory cortex. | Rhythmic voltage oscillations resulting from the summed activity of neuronal populations occur in many nervous systems. Contemporary observations suggest that coexistent oscillations interact and, in time, may switch in dominance. We recently reported an example of these interactions recorded from in vitro preparations of rat somatosensory cortex. We found that following an initial interval of coexistent gamma ( approximately 25 ms period) and beta2 ( approximately 40 ms period) rhythms in the superficial and deep cortical layers, respectively, a transition to a synchronous beta1 ( approximately 65 ms period) rhythm in all cortical layers occurred. We proposed that the switch to beta1 activity resulted from the novel mechanism of period concatenation of the faster rhythms: gamma period (25 ms)+beta2 period (40 ms) = beta1 period (65 ms). In this article, we investigate in greater detail the fundamental mechanisms of the beta1 rhythm. To do so we describe additional in vitro experiments that constrain a biologically realistic, yet simplified, computational model of the activity. We use the model to suggest that the dynamic building blocks (or motifs) of the gamma and beta2 rhythms combine to produce a beta1 oscillation that exhibits cross-frequency interactions. Through the combined approach of in vitro experiments and mathematical modeling we isolate the specific components that promote or destroy each rhythm. We propose that mechanisms vital to establishing the beta1 oscillation include strengthened connections between a population of deep layer intrinsically bursting cells and a transition from antidromic to orthodromic spike generation in these cells. We conclude that neural activity in the superficial and deep cortical layers may temporally combine to generate a slower oscillation. | 18,773,075 |
Toward a comprehensive approach to the collection and analysis of pica substances, with emphasis on geophagic materials. | Pica, the craving and subsequent consumption of non-food substances such as earth, charcoal, and raw starch, has been an enigma for more than 2000 years. Currently, there are little available data for testing major hypotheses about pica because of methodological limitations and lack of attention to the problem. In this paper we critically review procedures and guidelines for interviews and sample collection that are appropriate for a wide variety of pica substances. In addition, we outline methodologies for the physical, mineralogical, and chemical characterization of these substances, with particular focus on geophagic soils and clays. Many of these methods are standard procedures in anthropological, soil, or nutritional sciences, but have rarely or never been applied to the study of pica. Physical properties of geophagic materials including color, particle size distribution, consistency and dispersion/flocculation (coagulation) should be assessed by appropriate methods. Quantitative mineralogical analyses by X-ray diffraction should be made on bulk material as well as on separated clay fractions, and the various clay minerals should be characterized by a variety of supplementary tests. Concentrations of minerals should be determined using X-ray fluorescence for non-food substances and inductively coupled plasma-atomic emission spectroscopy for food-like substances. pH, salt content, cation exchange capacity, organic carbon content and labile forms of iron oxide should also be determined. Finally, analyses relating to biological interactions are recommended, including determination of the bioavailability of nutrients and other bioactive components from pica substances, as well as their detoxification capacities and parasitological profiles. This is the first review of appropriate methodologies for the study of human pica. The comprehensive and multi-disciplinary approach to the collection and analysis of pica substances detailed here is a necessary preliminary step to understanding the nutritional enigma of non-food consumption. | 18,773,081 |
Stability and dynamics of polycomb target sites in Drosophila development. | Polycomb-group (PcG) and Trithorax-group proteins together form a maintenance machinery that is responsible for stable heritable states of gene activity. While the best-studied target genes are the Hox genes of the Antennapedia and Bithorax complexes, a large number of key developmental genes are also Polycomb (Pc) targets, indicating a widespread role for this maintenance machinery in cell fate determination. We have studied the linkage between the binding of PcG proteins and the developmental regulation of gene expression using whole-genome mapping to identify sites bound by the PcG proteins, Pc and Pleiohomeotic (Pho), in the Drosophila embryo and in a more restricted tissue, the imaginal discs of the third thoracic segment. Our data provide support for the idea that Pho is a general component of the maintenance machinery, since the majority of Pc targets are also associated with Pho binding. We find, in general, considerable developmental stability of Pc and Pho binding at target genes and observe that Pc/Pho binding can be associated with both expressed and inactive genes. In particular, at the Hox complexes, both active and inactive genes have significant Pc and Pho binding. However, in comparison to inactive genes, the active Hox genes show reduced and altered binding profiles. During development, Pc target genes are not simply constantly associated with Pc/Pho binding, and we identify sets of genes with clear differential binding between embryo and imaginal disc. Using existing datasets, we show that for specific fate-determining genes of the haemocyte lineage, the active state is characterised by lack of Pc binding. Overall, our analysis suggests a dynamic relationship between Pc/Pho binding and gene transcription. Pc/Pho binding does not preclude transcription, but levels of Pc/Pho binding change during development, and loss of Pc/Pho binding can be associated with both stable gene activity and inactivity. | 18,773,083 |
Ultrasonically activated device for parenchymal division during open hepatectomy. | The use of new technological devices has gained popularity and has been proposed to improve the safety of liver resection. This study was designed to evaluate the usefulness of the ultrasonically activated device (USAD) during open liver resection. Indication for surgery, type of resection, need to perform a Pringle manoeuvre, operation time, blood loss, number of blood transfusions, morbidity and mortality rate were analyzed in 60 patients undergoing a formal open liver resection by means of USAD. The overall mean operation time was 172 minutes (range 120-255 min); an intermittent warm ischemia was applied in 9 cases (15%). The overall mean blood loss was 410 mL (median 400 mL, range 50-950 ml). A median of one blood transfusion was administered in six patients (10%). The mean hospital stay was 10.2 days (median 11, range 8-16). The overall morbidity rate was 20% (12 out of 60 patients). No in-hospital mortality was recorded. By subdividing the patients according to the presence or absence of cirrhosis no statistical significant differences were found between the two subgroups in all peri-and postoperative outcomes. In conclusion, though there is a lack of data based on well conducted controlled studies and further on a greater number of patients are needed, the utilization of USAD may help to minimize blood loss during liver resection regardless of the condition of the liver, even in case of cirrhosis. | 18,773,104 |
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