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fibrillation potentials and positive sharp waves were recorded in the paralyzed muscles of patients with a CB of more than days duration in of the muscles these effects were attributed to axonal damage in addition to the local demyelinating block this conclusion being based on changes in the properties of the mu found EMG when recovery had taken place in the remaining of the muscles the denervationlike activity was thought to be an effect of the local demyelinating block alone the delay of the sensory action potential recorded above the presumed site of nerve compression most likely arises from a block of the largest myelinated nerve fibers this assumption is based on the fact that the amplitudes of the fastest and the slowerconducted components in the patients differed little from corresponding components in the normal nerve
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the myofibroblast is essential for the integrity of the rat body by virtue of its role in woundhealing but it can also threaten it by its ability to promote tumour progression it is an almost universal cellular component in rat lesions but not a typical component of normal untraumatised tissues partly because of its absence from T/N it has not been part of conventional histology teaching this has contributed to difficulties in appreciating the nature of the myofibroblast and defining it by scientists interested in the mechanism of disease and pathologists wanting to diagnose myofibroblastic rumours this paper documents the features of the myofibroblast with an emphasis on ultrastructure a baseline of understanding is first provided by a description of normal cells found in untraumatised tissues from which the myofibroblast has on occasion been postulated as arising or with which to varying degrees the myofibroblast has been confusedfibroblasts smoothmuscle cells endothelium pericytes myoepithelium and lymphoid reticulum cells the biology CS microscopy features and ultrastructure of the myofibroblast are then documented for comparison features emphasised for defining the myofibroblast include a spindled cell morphology an abundant matrix IS for alphasmoothmuscle actin in the absence of desmin and hcaldesmon and the eda splice variant of cellular fibronectin Rg endoplasmic reticulum peripherally located smoothmuscle type myofilaments a GA producing collagensecretion LG gap junctions and fibronexus junctions the fibronexus is emphasised as a distinctive organelle for identifying the myofibroblast and lamina is emphasised as absent the mechanism by which myofibroblasts arise in granulation tissue and promote tumour progression is discussed briefly and an appendix provides summaries of the involvement of myofibroblasts in nonneoplastic diseases
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antimicrobial therapy for episodes of bacteremia in an bed UH was prospectively evaluated for year to measure the impact of two factorsblood culture results and the therapy chosen by infectious diseases specialists idsson quality of treatment and outcome initial shock a simplified acute physiology score of and inappropriateness of the empirical treatment were independently associated with increased mortality empirical treatment was appropriate in of the episodes this proportion reached for the episodes treated by idss compared with for the others p T3 availability of blood culture results the proportion of appropriate treatments increased to with for idstreated patients and for other patients p idss more frequently shifted to oral antibiotics and used fewer broadspectrum drugs this study underlines the impact of blood SC results and of idss on the prescription of appropriate treatment for bacteremia and on the better use of antimicrobial drugs
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this study evaluates the effectiveness of dialectical behaviour therapy dbt for BL personality disorder bpd in an unselected comorbid population seeking month inpatient treatment we studied consecution of dapoxetine for urological indications including premature ejaculation it will make initial milestone and royalty payments to ppd genupro a portion of which will be paid to originator eli lilly ppd inc received a milestone payment relating to the ongoing development of dapoxetine for PE in july in december ppd and alza amended the dapoxetine license to allow ppd to receive a fixedsum cash payment apon nda approval in return for this alza will not have to make salesbased payments for a period of time following the approval of dapoxetine if dapoxetine is approved by the us fda for PE the drug will be marketed in the us by orthomcneil pharmaceutical inc in december alza corporation submitted a new drug application to the fda for dapoxetine hydrochloride in the treatment of premature ejaculation if approved by the fda dapoxetine hydrochloride will be marketed in the us by orthomcneil pharmaceutical inc johnson johnson plans to support the launch of dapoxetine for PE with a responsible directtoconsumer advertising campaign in may johnson johnson presented data from two phase iii trials involving dapoxetine for the treatment of premature ejaculation during the th annual scientific meeting of the american urological association aua results on drug interactions and pharmacodynamics of dapoxetine were also presented during this meeting dapoxetine also appears to be a useful adjunct to morphine lowering the threshold for analgesia although the compound itself has negligible analgesic activity in december ppd inc acquired from eli lilly and company the patents for dapoxetine for development in the field of genitourinary disorders under the terms of the PA with lilly ppd will pay lilly million us dollars in cash ppd will also pay lilly a royalty on net sales of dapoxetine in excess of a certain threshold of annual net sales as part of the transaction ppd and lilly terminated their existing license agreement for dapoxetine
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human immunodeficiency virus type hiv is characterized by high genetic R2 due to its high replication rate and the lack of proofreading activity of the reverse transcriptase enzyme on the basis of phylogenetic analysis performed on numerous isolates from all over the world hiv is subdivided into types subtypes subsubtypes circulating recombinant forms and unique recombinant forms no data are currently available about the circulation of hiv types in montenegro here we describe the genetic variability of hiv strains identified in plasma samples of patients from montenegro phylogenetic analysis on hiv sequences was carried out the prevalent circulating hiv subtype is b the strains were interspersed within the tree two main clades i and ii may suggest independent introductions of hiv AT1 b into montenegro although other epidemiological evidence will be needed to assume a small number of introductions no obvious evidence of clustering by residence age or sex was found data not shown nelfinavir resistance was found though LPV is the only pi administered continuous monitoring of HIV+ individuals is crucial to a better understand of the epidemiology of the b subtype in montenegro
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we herein report a case of metastasis to the thyroid from lung adenocarcinoma mimicking TC the thyroid tumor was palpated in the left lobe of the thyroid and diagnosed as primary TC by fineneedle aspiration cytology the patient also had a C1 pulmonary RT and tiny pulmonary nodules which were respectively diagnosed as moderately differentiated adenocarcinoma of the lung and intrapulmonary metastases from the main C1 lung carcinoma by the pathological examination of the biopsy specimens obtained by videoassisted thoracic surgery hemithyroidectomy with radical neck dissection was performed the thyroid RT was diagnosed as metastasis to the thyroid from A549 because it showed mucin production positive immunoreactivity for CEA antigen and negative immunoreactivities for thyroglobulin and calcitonin the patient received systemic chemotherapy and died of the disease year and months T3 the diagnosis was made
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alternative messenger rna mrna splicing is a fundamental process of gene regulation and PE in rna splicing are known to be associated with a variety of different diseases however there is currently a lack of quantitative technologies for monitoring mrna SVs in cells here we show that a combination of plasmonic dimer probes and hyperspectral imaging can be used to detect and quantify mrna SVs in living cells the probes are made from gold NPs functionalized with oligonucleotides and can hybridize to TPS mrna sequences forming nanoparticle dimers that exhibit distinct spectral shifts due to plasmonic coupling with this approach we show that the spatial and temporal CSD of three selected splice SCV of the breast cancer susceptibility gene brca can be monitored at singlecopy resolution by measuring the hybridization dynamics of the nanoplasmonic dimers our T0 provides insights into rna and its transport in living cells which could improve our understanding of cellular protein complexes pharmacogenomics genetic diagnosis and gene therapies
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we evaluated whether the SE of staphylococcus aureus to a subinhibitory concentration of penicillin and cefamandole could modify its susceptibility to rat serum AF and to the phagocytic activity of the isolated and perfused rat CL control or submic treated bacteria were added to the circulating medium which contained homologous serum and the disappearance of bacteria from the perfusate and their recovery in the liver was determined during the min exp time submic treated bacteria were more susceptible to the bactericidal activity of SS present in the perfusate however the CL of bacteria by the liver was decreased for penicillintreated organisms and unchanged for cefamandoletreated bacteria the data suggest that betalactam antibiotics at submic levels may modify s aureus susceptibility to host defense mechanisms
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activation of endothelial nitric oxide synthase enos in portal hypertensive pht gastric mucosa leads to hyperdynamic circulation and increased susceptibility to injury however the signaling mechanisms for enos activation in pht gastric mucosa and the role of tnfalpha in this signaling remain unknown in pht GM we studied enos phosphorylation at serine required for its activation association of the phosphatidylinositol kinase pi kinase and its downstream effector akt with enos and whether tnfalpha neutralization affects enos phosphorylation and pi kinaseakt activation to determine human relevance we used human microvascular EC cells to examine directly whether tnfalpha stimulates enos phosphorylation via pi kinase pht GM has significantly increased enos phosphorylation at serine by p membrane translocation p and phosphorylation p of p RII S1 of pi kinase by and respectively phosphorylation p and activity p of akt by and respectively and IB of akt to enos by as much as p NT antitnfalpha antibody significantly reduced p phosphorylation phosphorylation and activity of akt and enos phosphorylation in pht gastric mucosa to normal levels furthermore tnfalpha stimulated enos phosphorylation in human microvascular endothelial cells in conclusion these findings show that in pht GM tnfalpha stimulates enos phosphorylation at serine required for its activation via the pi kinaseakt ST pathway
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the prevalence of obesity is increasing in an alarming way while that of other risk AF hyperlipaemia arterial hypertension are tending to diminish amongst all of the AF involved in its OD two are outstanding because of their potential for modification an excessive calorie intake and a sedentary life style in spite of the recommendations in favour of regularly practising PCS exercise the principal problem in studying the prevalence of obesity is the scarcity of studies that analyse it in a global form in the first results of the monica project of the who were published with the observation that the prevalence was higher for men than for women and that it was greater in the mediterranean countries and the east of europe in comparison with the north and centrewest in a T0 was carried out by the institute of european food studies iefs in which individuals participated proceeding from representative samples of the member states of the EU its results showed that the higher prevalence of obesity was to be found in the united kingdom followed by spain while it was lower in italy france and sweden by sex the prevalence of obesity is somewhat greater amongst women while overweightedness was greater amongst men in spain the CSD of overweightedness and obesity amongst the different SES groups is similar to that of other regions with the percentage of obesity being highest amongst the elderly subjects of a lower socioeconomic level and the inhabitants of the north and northwest of spain
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CBZ is a useful antithyroid drug with a rare potentially fatal complication of agranulocytosis we report cases presenting with this problem one was treated supportively with barrier nursing and broad spectrum antibiotics and the other needed use of a haemopoietic growth factor rG-CSF gcsf as it is indeed possible for thyrotoxic patients who developed agranulocytosis with carbimazole to have the same complication with propylthiouracil once agranulocytosis had resolved both patients were treated with radioiodine to maintain euthyroidism carbimazoleinduced agranulocytosis usually spontaneously resolves within to weeks of stopping the drug the use of haemopoietic growth AF to stimulate the proliferation and differentiation of progenitor cells accelerates neutrophil REC as in our first case discussed we recognise that agranulocytosis from carbimazole is a rare lifethreatening complication instead of awaiting spontaneiolence are suggested
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background tivantinib is a nonatp competitive inhibitor of cmet RET that may have additional cytotoxic mechanisms including tubulin inhibition prostate cancer demonstrates higher cmet expression as the disease progresses to more T3 stages and to a castration resistant state methods patients pts with asymptomatic or minimally symptomatic mcrpc were assigned to either tivantinib mg po bid or PL p the primary endpoint was progression free survival pfs results of the pts enrolled tivantinib p received treatment and were evaluable median follow up is months range to months patients treated with tivantinib had significantly better pfs vs those treated with placebo medians mo vs mo respectively hr ci to p grade febrile neutropenia was seen in patient on tivantinib while grade and neutropenia was recorded in patient each on tivantinib and placebo grade sinus bradycardia was recorded in two men on the tivantinib arm conclusions tivantinib has mild toxicity and improved pfs in men with asymptomatic or minimally symptomatic mcrpc
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an overlap between subpopulations of nerve growth factor ngfresponsive and capsaicinsensitive dorsal root ganglion drg SNs has been suggested from a number of in vivo studies to examine this apparent link in more detail we compared the effects of capsaicin on AD rat drg neurons cultured in the presence or absence of ngf CAP sensitivity was assessed histochemically by a cobalt IF method by measuring capsaicininduced ca uptake and by electrophysiological recording of capsaicinevoked membrane currents when cultured with ngf approximately of these adult drg SN were capsaicinsensitive whereas AD sympathetic neurons or ganglionic nonneuronal cells were insensitive drg cultures grown in the absence of ngf however were essentially unresponsive to CAP capsaicin sensitivity could be regained fully within days of replacement of ngf these results indicate that at least in vitro ngf can modify the capsaicin sensitivity of adult drg neurons
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we recently demonstrated that PET inactivation of hras results in significant reduction in interleukin beta il betamediated effects on isolated beta cells since palmitoylation of ras has been implicated in its membrane targeting we examined the contributory roles of palmitoylation of ras in il betainduced nitric oxide no PR and subsequent activation of caspases preincubation of hitt or ins cells with cerulenin cer microm hr an inhibitor of protein palmitoylation significantly reduced il betainduced no release from these cells bromopalmitate a structurally distinct inhibitor of protein palmitoylation but not hydroxymyristic acid an inhibitor of protein myristoylation also reduced il betainduced no release from hit cells ilinduced inducible nitric oxide synthase gene expression was markedly att by cer further cer markedly reduced incorporation of hpalmitate into hras and caused significant accumulation of ras in the CF certreatment also prevented il betainduced activation of ICE in these cells moreover nmonomethyllarginine a known inhibitor of inducible nitric oxide synthase markedly inhibited ilinduced activation of caspase thus establishing a link between ilinduced no release and ICE activation depletion of MB cholesterol using methylbetacyclodextrin which also disrupts caveolar organization within the plasma membrane abolished il betainduced no release suggesting that il betamediated rasdependent signaling in these cells involves the intermediacy of caveolae and their key constituents eg caveolin in isolated beta cells confocal LM evidence indicated significant colocalization of ras with caveolin taken together our data provide the first evidence to indicate that palmitoylation of ras is essential for il betainduced cytotoxic effects on the islet beta cell
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to evaluate the occurrence of sleepdisordered PLB and to clarify the characteristics of sleep among patients with PWS syndrome pws overnight continuous eegpolysomnographic studies were performed in patients with pws males and females mean age years age range years unselected for sleep disturbance the baseline arterial oxygen saturation spo was with a nadir of the rapid EM rem RL was min the percent of total sleep time spent in sleep stages slow wave and rem were and respectively the respiratory disturbance index rdi was hr and desaturation index di was hr respectively ageadjusted bmi was associated with more severe hypoxemia during sleep baseline spo r p nadir sao r p rdi r p di r p and more sleep disruption arousal index r p there were no significant associations between gender or genotype pattern deletion vs uniparental disomy and the results of PSG sleep hypoxemia and sleep disruption are more prevalent in patients with pws than in NC obesity in these patients is associated with more severe sleepdisordered breathing
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reptilian nests can experience NK hypoxic and hypercapnic conditions we incubated alligator eggs at a femaleonly producing temperature °c in three conditions o co o co and o co alligator embryos chronically incubated in high co were markedly hypotensive blood pressure reduced by and had relatively massspecific enlarged hearts DM increased by lungs dry mass increased by and kidneys dry mass increased by this study is the first to chronically incubate reptilian eggs in hypercapnia and suggests that high co alters the cardiovascular phenotype of alligator embryos low blood pressure relatively enlarged NF as well as the relative size of the organs primarily responsible for acid base balance lungs and kidneys the lungs and kidneys are largely nonfunctional during embryonic development and the embryonic phenotype of increased relative mass may be a predictiveadaptation to metabolic or respiratory acidosis such as during exercise or high respiratory co this T0 demonstrates that phenotypic plasticity of alligator embryos incubated in high co may result in either preferential organ growth or maintenance of organ growth with reduced somatic growth
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vascular malformations of the CE NS are thought to originate from abnormal developmental processes during embryogenesis reports have cited the dynamic nature of these lesions and their maturation into other types of malformations herein we report on three patients with vascular malformations who exhibited dynamic alterations with stepwise progression of their lesions these cases lend support to the hypothesis that these malformations may constitute the spectrum of a single disease caused by alterations in a common developmental program and that accumulating injury eg by radiation may allow one malformation type to mature into another this concept warrants further investigation
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this T0 investigates the effect of preservation methods on the performance of bovine parietal pericardium grafts in a rat MM midventral full thickness abdominal wall defects of x cm in size were created in SD rats g which were divided into three CG of rats each the ABD defects of group one and two were repaired with lyophilized and glycerolized BP grafts while the defects of group three were repaired with expanded polytetrafluoroethylene eptfe mycro mesh as a positive control another group of rats underwent sham T0 and was used for comparison as negative control each group of rats n was divided into five subgroups n and killed at and weeks postsurgery for gross and morphological evaluations the rats tolerated the surgical procedure well with a total mortality of no serious postoperative clinical complications or signs of AAR were encountered adhesions between the grafts and the underlying visceral organs observed in the study were mostly results of postsurgical complications glycerol preservation delayed Kd and replacement of the grafts whereas lyophilization caused early resorption and replacement of the grafts the glycerolized grafts were replaced with thick dense fibrous tissue and the lyophilized grafts were replaced with thin loose fibrous tissue the healing characteristic of the BP grafts was similar to those of the shamoperated group and quite different from those of the eptfe mycro mesh the outcome of the present T0 confirmed the superiority of glycerolized bovine pericardium grafts over its lyophilized counter part
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elevated plasma levels of triglyceriderich lipoproteins tgrlp including very LDLs vldl CMs and their remnants are now acknowledged as risk AF for cardiovascular disease interactions of tgrlp with lipoprotein receptors on monocytes macrophages and endothelial cells may be mechanistically linked to this risk triglyceriderich lipoproteins from hypertriglyceridemic htg subjects have the abnormal ability to bind to lowdenisty lipoprotein receptors via apoe and plasma CMs from all subjects bind to a new distinct receptor for apob that is expressed specifically by monocytes macrophages and endothelial cells receptor IB and uptake of tgrlp by these cells are likely mechanisms involved in the formation of lipidfilled macrophagederived foam cells of AS lesions and for defective fibrinolysis due to EC dysfunction recognition of the atherothrombogenic potential of tgrlp may lead to improved interventions to lessen or prevent the often fatal sequelae of coronary atherosclerosis and thrombosis associated with elevated plasma triglyceride levels
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synthetic genetic circuits are programmed in living cells to perform predetermined cellular functions however designing higherorder genetic circuits for sophisticated AAA remains a substantial challenge here we program a genetic circuit that executes pavlovianlike conditioning an archetypical sequentiallogic CF in escherichia coli the circuit design is first specified by the subfunctions that are necessary for the single simultaneous conditioning and is further genetically implemented using four function modules during this process quantitative analysis is applied to the optimization of the modules and finetuning of the interconnections analogous to classical pavlovian conditioning the resultant circuit enables the cells to respond to a certain stimulus only after a conditioning process we show that although the conditioning is digital in ss observed on chromosome as well as suggestive association on chromosomes and nextgeneration dna sequencing of the exons of genes of seven regions identified multiple associated alleles on chromosome and p candidate genes located in the associated regions on chromosomes and included lama lrr and cola respectively the associated region on cfa contained candidate genes gdf comp and cilp in conclusion our T0 identified candidate genes that might affect susceptibility to canine hip dysplasia these genes are involved in hypertrophic differentiation of chondrocytes and EM integrity of basement membrane and cartilage the functions of the genes are in agreement with the notion that disruptions in endochondral bone formation in combination with soft tissue defects are involved in the etiology of hip dysplasia
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an experiment was designed to determine whether the respiratory PR of ST vapor as estimated from measurements of endexhaled air was the same during periods of both constant and fluctuating SE six human subjects were exposed to styrene inside a exp chamber a computercontrolled system was used to generate timevarying air concentrations of styrene over h in both multistep sequences of constant SE four subjects exposed to ppm of ST in min steps and fluctuating patterns representative of occupational exposures two subjects exposed to mean concentrations of styrene of ppm in the latter case lognormally distributed exposures which fit one of two firstorder AR models were generated at intervals of min it was found that the concentration of styrene in endexhaled air was reduced by about half if the subject inhaled one to three breaths of clean air prior to sampling this suggests that significant amounts of ST were desorbed from the lining of the lungs during the initial exhalation the PR of styrene vapor during constant exposures was and was independent of the level during each of the two sets of fluctuating SE the retention of ST was also constant and was independent of both the variance and autocorrelation coefficient however the PR of styrene during the fluctuating exposure estimates ranged from to was significantly higher than that observed during the constant exposuresabstract truncated at words
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a new CS of the genus promicromonospora capt was isolated from the surface sterilized root of callitrispreissii australian native pine tree this CS was a gramstainpositive aerobic actinobacterium with hyphae breaking up into fragments which were nonmotile rodlike coccoid elements phylogenetic DUE based on s rrna gene sequence analysis placed this isolate as a member of the family promicromonospora ceae and most closely to promicromonospora sukuve more difficult than in younger cohorts comprehensive geriatric assessment has been shown to improve outcomes and is now embedded in most ukbased services for traumatic hip fracture perioperative comprehensive geriatric assessment has been explored in other surgical disciplines and procedures and where evaluated has been associated with improved outcomes the need to support older patients with frailty undergoing surgery exceeds the capacity of specialist geriatricians other CG of healthcare professionals need to nurture the core competencies to support this group perioperatively
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this T0 was aimed at evaluating the in vitro effects of phosphodiesterase inhibitors and betaadrenoceptor agonists on spontaneous contractions of human term myometrium rolipram rp cyclopentyloxyndichloropyridilmethoxybenzamide and ro butoxymethoxybenzylimidozolidinone phosphodiesterase inhibitors inhibited spontaneous myometrial contractions emax approximately pd of and respectively salbutamol and formoterol were less ERP emax and respectively than phosphodiesterase inhibitors to reduce myometrial +dP/dt inhibitors of phosphodiesterase milrinone and siguazodan and zaprinast were marginally effective rolipram nm and siguazodan microm potentiated the response to salbutamol emax and and pd and respectively sodium nitroprusside pd and theophylline pd were effective inhibitors of myometrial contractions chromatographic separation of phosphodiesterase isoenzymes demonstrated that phosphodiesterase is predominant but other phosphodiesterase isoenzymes were also identified in conclusion phosphodiesterase inhibitors CT or combined with betaadrenoceptor agonists have potential interest as tocolytic agents
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myxomatous mitral valve disease mmvd is the most common acquired cardiac disorder found in dogs the disease process can lead to HF hf and has been found to be associated with oxidative stress and inflammation statins exert antioxidant and antiinflammatory effects in human hf patients however the beneficial effects of statins in mmvd dogs are still unclear thirty mmvd dogs were enrolled in the study and were divided into two CG mmvd without hf dogs n and mmvd with hf dogs n ATV mg kg
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alzheimers disease ad is a devastating neurodegenerative disorder and the most common cause of elderly dementia in an effort to contribute to the potential of molecular approaches to reduce degenerative processes we have tested the possibility that the neural adhesion molecule l ameliorates some characteristic cellular and molecular parameters associated with the disease in a mouse MM of ad threemonthold mice overexpressing mutated forms of amyloid F0 protein and presenilin under the control of a neuronspecific promoter received an i.t. of adenoassociated virus encoding the neuronal isoform of FL l aavl or as negative control green fluorescent protein aavgfp into the hippocampus and OC four months after virus injection the mice were analyzed for histological and PSA parameters of ad aavl i.t. decreased the aβ PI load C2 of aβ aβ ratio and astrogliosis compared with aavgfp controls aavl injected mice also had increased densities of GABA synaptic terminals on pyramidal cells in the hippocampus when compared with aavgfp controls numbers of microglial cellsmacrophages were similar in both groups but numbers of microglial cellsmacrophages per plaque were increased in aavl injected mice to probe for a molecular mechanism that may underlie these effects we analyzed whether l would directly and specifically interact with aβ in a labelfree binding assay concentration dependent IB of the extracellular domain of l but not of the close homolog of l to aβ and aβ was seen with the fibronectin type iii homologous repeats of l mediating this effect aggregation of aβ in vitro was reduced in the presence of the extracellular domain of l the combined observations indicate that l when overexpressed in SN and glia reduces several histopathological hallmarks of ad in mice possibly by reduction of aβ aggregation l thus appears to be a candidate molecule to ameliorate the pathology of ad when applied in therapeutically viable treatment schemes
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there has been a dearth of prospective randomized studies in essential or primary thrombocythemia et to date only two reports have been published cortelazzo et al reported the first T0 in the second is the MRC primary thrombocythemia trial mrc pt the results and implications of which are the subject of this article
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the accreditation council for graduate medical education has introduced farreaching changes to the educational requirements for postgraduate trainees over the past years these steps were taken to improve the SQ of education and to enhance patient safety this symposium will explore the design and implementation of these changes and determine if they are succeeding
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the aim of the study was to elucidate the role of nucleoside transport systems in the postischemic release of nucleosides and nucleobases accumulated by the rat liver during CS livers were preserved for h in eurocollins ec or in a lactobionatebased solution lbs without exogenous adenosine the rates of release of uric acid xanthine hypoxanthine inosine adenosine UR and cytidine were monitored during early reperfusion the greater part of the purines and pyrimidines up to was lost in the first min of reperfusion T3 storage in ec uric acid and xanthine formed more than of the total purines released nucleosides did not exceed of the total after storage in lbs hypoxanthine formed more than of purine efflux and the release of inosine and UR was increased times these changes were shown to be due to the presence of allopurinol in lbs dipyridamole an inhibitor of equilibrative nucleoside transporters decreased the efflux of UA after storage in ec but residual PR remained high dipyridamole exerted the most pronounced effect on the release of nucleosides inosine and uridine from livers stored in lbs the use of sodiumfree media for liver preservation and reperfusion did not alter the rates of purine and pyrimidine PR we conclude that equilibrative nucleoside transporters mediate the postischemic release of nucleosides and also but to a less degree of UA simple diffusion is an important factor in the release of nucleobases AS nanucleoside cotransport does not play an important role in early reperfusion
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as part of its AR to oxidative AS escherichia coli produces two inducible hydroperoxidases called hpi and hpii upon SE to sublethal levels of hydrogen peroxide hpi expression is induced at the transcriptional level by oxyr a member of the lysr family of autoregulators oxyr functioning as both a sensor and transducer contains a critical redoxsensitive cys residue that is oxidized by hydrogen peroxide this is thought to induce a conformational change in the tertiary structure of the oxyr tetramer altering its dnabinding specificity and resulting in an increase in the transcription of katg and several other oxyrdependent genes in contrast synthesis of the hpii enzyme is not induced by hydrogen peroxide expression of both hpi and hpii is growth phasedependent levels of hpi and hpii are fold higher in stationary phase than exponential phase cultures these growth phasedependent increases are largely dependent on rpos a stationary phase TPS sigma factor that is itself subject to complex transcriptional and posttranscriptional controls several metabolic signals have been proposed to activate the rpos regulon including hyperosmolarity weak acids HSL and udpglucose since both hpi and hpii are members of the rpos regulon elucidation of the mechanism of regulation of rpos should contribute to our GA understanding of hydroperoxidase regulation
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thiamine confers SVR acquired resistance sar on susceptible plants through priming leading to rapid counterattack against pathogen invasion and perturbation of disease progress priming reduces the metabolic cost required for constitutive expression of acquired resistance to investigate the effects of priming by B1 on defenserelated responses arabidopsis arabidopsis thaliana was treated with thiamine and effects of pathogen challenge on the production of active oxygen species callose deposition hypersensitive cell death and pathogenesisrelated prphe ammonialyase pal mRNA was analyzed thiamine did not induce cellular and molecular defense responses except for transient expression of pr per se however subsequent Pst challenge triggered pronounced cellular defense responses and advanced activation of prpal gene transcription B1 treatment and subsequent pathogen invasion triggered hydrogen peroxide accumulation callose induction and prpal transcription activation in arabidopsis mutants insensitive to JA jar ethylene etr or ABA abi but not in plants expressing bacterial nahg and lacking regulation of sar npr nonexpressor of pr genes moreover removal of hydrogen peroxide by catalase almost completely nullified cellular and molecular defense responses as well as sar abolishing bacterial propagation within plants our results indicated that priming is an important cellular mechanism in sar by thiamine and requires hydrogen peroxide and intact npr
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myocardial imaging with in labeled antimyosin monoclonal antibody antimyosin imaging has been reported to be useful in the noninvasive PCD of myocardial cell CN in dilated cardiomyopathy as well as in myocardial infarction and myocarditis we used antimyosin imaging to detect myocardial damage in patients with malignant lymphoma in whom adriamycin cardiotoxicity was suspected patients were injected with mbq of indium labeled antimyosin fab fraction fortyeight hours later planar imaging and singlephoton emission computed tomography were performed using a gamma camera with a medium energy general purpose collimator antimyosin imaging demonstrated diffuse myocardial uptake not only in one patient with congestive HF but also in another patient at the early stage without CHF antimyosin imaging may be a CS method for noninvasive visualization of myocardial cell damage and useful in the early diagnosis of specific heart muscle disease
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charcotmarietooth hereditary neuropathy is a heterogeneous syndrome associated with mutations in several different genes including IP myelin protein myelin p connexin and early growth response there is considerable variability in the phenotypic expression of this syndrome and the relationship of this R2 to mutation genotypes requires extensive analysis here we describe the phenotypes and genotypes of four new mutations underlying the CMT syndrome and document segregation with disease four families with CMT were ascertained examined and evaluated electrophysiologically each family had peripheral blood dna screened for mutations in myelin protein myelin p and connexin two families were found with new mutations in the myelin p gene st in the extracellular domain and kdel in the cytoplasmic domain all families showed segregation of the mutations with the charcotmarietooth phenotype as did a new family with the rare gr mutation in the membrane domain a yearold man with the st mutation demonstrated conduction block on electrophysiological testing a family with a novel sp mutation in the connexin gene had a neuropathy with very slow nerve conduction these new mutations in the myelin p and connexin genes help to clarify the pathophysiology of the clinical charcotmarietooth syndrome the st mutation in myelin p can be associated with CB and CMT should be part of the differential diagnosis of that phenomenon mutations in the cytoplasmic domain of myelin p can cause clinical neuropathy the sp mutation in the connexin gene can produce aspects of a demyelinating type of xlinked hereditary neuropathy
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this article aims at summarizing normal eeg criteria and their maturational DP in premature infants of to weeks gestational age although very premature infants with a normal outcome are not numerous their normal eeg patterns must be known as eeg constitutes a basis for neurological prognosis background activity is first discontinuous discontinuity decreases thereafter with increasing age so that some long periods of continuous activity may be observed in active sleep around weeks of age conversely interburst intervals become shorter and the proportion of time without eeg activity is decreasing based on eeg activity and eye movements a rough sleepstate differentiation was described as soon as weeks of gestational age and is CR achieved at weeks the main eeg figures are highvoltage delta waves of higher amplitude and slower frequency in younger infants temporal delta waves occur in sequences these are very characteristic of the very premature infant thereafter they become smaller less numerous and eventually disappear around weeks in contrast occipital delta waves remain numerous and of HV are usually BL and superimposed with fast rhythms the two types of FC delta waves that are observed in weeks prematures disappear with maturation bursts of synchronized delta waves are less numerous than localized delta waves and also disappear before weeks of age finally diffuse theta bursts are mainly recorded at weeks ga and become more localized in temporal Az with maturation at weeks they are observed on temporal areas mainly during slowwave sleep
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the folding kinetics of rdapocytochrome b is twostate but nativestate hydrogen exchange experiments show that there are discrete partially unfolded puf structures in equilibrium with the native state these puf structures are called hidden intermediates because they are not detected in kinetic experiments and they exist T3 the ratelimiting step structures of the mimics of hidden intermediates of rdapocytochrome b are resolved by nmr based upon their relative stability and structural features the folding mechanism was proposed to follow a TPS pathway unfolded â ratelimiting transition state â puf â puf â native investigating the roles of equilibrium puf structures in folding kinetics and their interrelationship not only deepens our understanding of the details of folding mechanism but also provides guides in protein design and prevention of misfolding we performed MD starting from a hidden intermediate and the native state of rdapocytochrome b in explicit solvent for a total of μs mainly with anton we validated our simulations by detailed comparison with experimental data and other computations we have verified that we sampled the post ratelimiting transition state region only markov state MM was used to analyze the simulation results we replace the TPS pathway MM with a network MM transitionpath theory was employed to calculate the net effective flux from the most unfolded state towards the most folded state in the network the proposed sequential folding pathway via puf then more SD more nativelike puf is one of the routes in our network but it is not dominant the dominant path visits puf without going through puf there is also a route from puf directly to the most folded state in the network without visiting puf our results indicate that the puf states are not necessarily sequential in the folding the L1 routes predicted in our network are testable by future experiments such as single molecule experiment
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the present T0 was undertaken to evaluate the role of propofol in altering PTZ induced seizure threshold in rats total WR were used to evaluate different parameters onset of action duration of seizure seizure severity score and number of seizure following propofol injection the present results showed that there was significant reduction in the time required for onset of seizure in propofol treated groups following ptz treatment if treated with propofol alone and mgkg there was no significant difference as compared to controls in seizure severity score assessment there was no significant difference with various doses of propofol CT treated CG but the difference was observed in propofol and mgkg treated groups following ptz treatment duration of seizure also significantly increased in propofol mgkg treated group but at mgkg of propofol treatment no significant difference was observed the present results showed that propofol ameliorate seizure threshold and caused prolongation of duration of seizure however further T0 and trials are needed to confirm the present results
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neonatal hypoxicischemic encephalopathy nhie is a dramatic perinatal complication associated with poor neurological prognosis despite neuroprotection by therapeutic HT in the absence of an available curative therapy we evaluated and compared readytouse human umbilical cord blood cells hucbc and bankable but allogeneic endothelial progenitors ecfc as cell therapy candidate for nhie we compared benefits of hucbc and ecfc transplantation hours after injury in male rat nhie MM based on the ricevannucci approach based on behavioral tests immunehistological assessment and metabolic imaging of BB perfusion using single photon emission computed tomography spect hucbc or ecfc administration provided equally early and sustained PET benefits up to weeks after injury these results were associated with total normalization of injured hemisphere cerebral blood flow assessed by spectct imaging in conclusion even if ecfc represent an efficient candidate hucbc autologous criteria and easier availability make them the ideal candidate for hypoxicischemic cell therapy stem cells translational medicine
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the effects of the two htreleasing drugs PCA and dfenfluramine on CE serotoninergic and dopaminergic systems were compared in adult rats both drugs mgkg ip hr before death produced a dosedependent reduction in C2 of ht but only pchloroamphetamine decreased the C2 of 5-HIAA acid hiaa in the hippocampus striatum and cerebral cortex within the dose range tested dfenfluramine did not affect the levels of da and of its metabolites dihydroxyphenylacetic acid dopac and homovanillic acid hva in brain by contrast pchloroamphetamine significantly increased the levels of da and hva and decreased the levels of dopac notably in the striatum as expected of a ht uptake inhibitor dfenfluramine at small doses mgkg prevented the SD of ht due to methylalphaethylmetatyramine h mgkg ip whereas at large doses mgkg dfenfluramine like PCA mgkg slightly enhanced the effect of h neither dfenfluramine mgkg nor PCA mgkg affected the depletion of da due to h these data indicate that pchloroamphetamine is a htreleasing drug at any dose between and mgkg whereas dfenfluramine acts as a ht uptake inhibitor at mgkg and as a ht releasing drug at larger doses on account of the potential neurotoxicity of htreleasing drugs but not ht uptake inhibitors it can be inferred that dfenfluramine is very probably devoid of any neurotoxic action in the dose range less than mgkg required for its anorectic action
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the present T0 investigates the potential use of haemocyte lysosomal fragility as a reliable indicator of toxic injury in snails subjected to herbicide atrazine two cytochemical assays were used the first one was based on microscopic observations of neutral red dye and the second one on a fluorescence spectroscopy approach using AO which had the advantage of being more reliable in assessing minor cell damage two sets of experiments were carried out in controlled laboratory conditions temperature photoperiod and in outdoor microcosms which produce more realistic ecological conditions an unequivocal relationship was shown linking atrazine exposure to lymnaea stagnalis haemocytes lysosomal permeability high temperatures also had a negative effect on the lysosomal membrane in the microcosms the response was affected by seasonal AF and led to an integrated cell response it was concluded that lysosomal sensitivity reflects environmental changes moreover the technique using acridine orange was shown to be sufficiently CS and reliable to serve as a lysosomal marker in a controlled environment
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mitochondrial atpsensitive potassium mitokatp channels play a key role in ischemic preconditioning of the heart however the mechanism of cardioprotection remains controversial we measured rhod fluorescence in adult rb ventricular cardiomyocytes as an index of mitochondrial matrix ca concentration cam using timelapse confocal microscopy to simulate ischemia and reperfusion ir cells were exposed to metabolic inhibition minutes followed by washout with control solution rhod fluorescence gradually increased during simulated ischemia and rose even further with reperfusion the mitokatp channel opener DZ attenuated the accumulation of cam during simulated ir ec micromoll these effects of diazoxide were blocked by the mitokatp channel antagonist hydroxydecanoate hd in contrast inhibitors of the mitochondrial PT mpt cyclosporin a and BKA did not alter cam accumulation during ischemia but markedly suppressed the surge in rhod fluorescence during reperfusion measurements of mitochondrial membrane potential deltapsim in permeabilized myocytes revealed that DZ depolarized deltapsim by at micromoll p in a hdinhibitable manner our data support the hypothesis that attenuation of mitochondrial ca overload as a consequence of partial mitochondrial membrane depolarization by mitokatp channels underlies cardioprotection furthermore mitokatp channels and the mpt differentially affect mitochondrial calcium homeostasis mitokatp channels suppress calcium accumulation during ir while the mpt comes into play only upon reperfusion
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immunization with PRP PRP prp has resulted in limited and VL antibody radioimmunoassay in infants younger than years of age although an h influenzae type b vaccine has been in use for several years it is not used now for the age group at greatest risk for disease in an effort to enhance immunogenicity prp has been coupled to various carrier proteins and to an outer membrane protein complex ompc from neisseria meningitidis group b the latter approach has yielded a vaccine that elicits a good antibody response T3 a single micrograms dose of vaccine in infants as young as months of age as measured by radioimmunoassay and immune bacteriolysis in this report we describe the results of a pilot study using this h influenzae type b conjugate vaccine pedvaxhib in children from months to years of age three different vaccine lots were examined for consistency of response sera were measured for antibody C2 by radioimmunoassay and for functional activity using an opsonophagocytic CA using human AD neutrophils these assays correlated well and demonstrated the excellent immune response and biologic activity of sera from infants vaccinated with this unique h influenzae type b conjugate vaccine
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we report on the first nuclear magnetic resonance nmr and electron paramagnetic resonance epr investigation of inorganic fullerenelike mos NPs spectra of bulk hmos samples have also been measured for comparison the similarity between the measured quadrupole coupling constants and chemical shielding anisotropy parameters for bulk and fullerenelike mos reflects the nearly MZ local crystalline environments of the mo atoms in these two materials epr measurements show that fullerenelike mos exhibits a larger density of dangling bonds carrying unpaired electrons indicative of them having a more defective structure than the bulk sample the latter observation explains the increase in the spinlattice relaxation rate observed in the nmr measurements for this sample in comparison with the bulk h mos ones
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listeria monocytogenes evades the antimicrobial mechanisms of macrophages by escaping from the phagosome into the cytosolic space via a unique cytolysin that targets the phagosomal membrane listeriolysin o llo encoded by hly gamma interferon Th1 which is known to play a pivotal role in the induction of thdependent protective immunity in mice appears to be produced depending on the bacterial VF to determine whether the llo molecule the major VF of l monocytogenes is indispensable or the escape of bacteria from the phagosome is sufficient to induce Th1 production we first constructed an hlydeleted mutant of l monocytogenes and then established isogenic l monocytogenes mutants expressing llo or ivanolysin o ilo encoded by ilo from listeria ivanovii lloexpressing l monocytogenes was highly capable of inducing ifngamma production and listeriaspecific protective immunity while the hlydeleted mutant was not in contrast the level of Th1 induced by iloexpressing l monocytogenes was significantly lower both in vitro and in vivo despite the ability of this strain to escape the phagosome and the intracellular multiplication at a level equivalent to that of lloexpressing l monocytogenes only a negligible level of protective immunity was induced in mice against challenge with llo and iloexpressing l monocytogenes these results clearly show that escape of the bacterium from the phagosome is a prerequisite but is not sufficient for the ifngammadependent th response against l monocytogenes and some distinct molecular nature of llo is indispensable for the final induction of Th1 that is essentially required to generate a thdependent immune response
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the causes and consequences of the insulin resistance that accompanies the polycystic ovary syndrome pcos are still controversial the hyperandrogenism does not appear any more as a causal factor but on the contrary is likely to be a consequence via the ovarian effects of hyperinsulinism these are still not clearly understood in their molecular aspects but their reality is undoubtful in view of some clinical studies which showed an improvement following by the reduction of hyperinsulinism therefore the aetiopathogenic role of the insulin resistance in pcos becomes more and more obvious but it cannot be split from the likely implication of the intraovarian growth factors and more especially the igf which could act synergistically with it moreover the presence of lh seems to be still a prerequisite to the ovarian action of insulin the therapeutical incidences of these hypothesis are obvious and should improve in the next future the medical management of pcos
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sixtyseven ABD operations for colon and rectal disorders were performed on patients years of age or older from january to june nine patients required multiple operations sixtytwo procedures percent were performed on patients in their ninth decade two operations were performed on patients years of age or older fortyfive patients percent were operated upon for carcinoma operations included segmental colectomy patients low anterior resection patients TAC patients and abdominoperineal resection patients forty patients were classified as asa class iii the majority were monitored in the surgical intensive ECU for a mean of days thirty patients were monitored with arterial catheters and with CE invasive monitoring OM was percent patients two patients died from diffuse carcinomatosis one patient had a fatal myocardial infarction the final death occurred from multisystem OF following anastomotic dehiscence twentyseven operations were performed without postoperative complications operations were followed by a single minor complication the average hospital stay was days all patients were admitted from home thirtythree returned home postoperatively were discharged to an extended care facility in conclusion elderly patients with colon and rectal disorders can be operated upon with acceptable morbidity and mortality age alone should not interdict surgical therapy
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interest in translational studies aimed at investigating biologic markers in predicting response to primary chemotherapy pct in breast CA has progressively increased we conducted a pilot T0 to evaluate feasibility of evaluating biomarkers of response to pct at one days T3 first cycle
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we present general expressions for the number of photons emitted by a fluorescent chromophore as a function of the intensity and the duration of illumination the aim is to find optimal conditions for detecting fluorescent molecules in the presence of both groundstate SD and photodestruction the key molecular parameters are the absorption coefficient epsilon the excited singletstate lifetime tau f the excited tripletstate tau kt the intersystem crossing rate ki and the intrinsic photodestruction time tau d when only singlet saturation and photochemistry are important the signaltonoise ratio depends on two fundamental variables k the ratio of the Ka ka to the observed fluorescence decay rate kf and tau the ratio of the duration of illumination taut to the intrinsic photodestruction time tau d equations are also developed for the more complicated cases when triplet formation and photochemistry are important this theory was tested by measuring the fluorescence from a solution of betaphycoerythrin flowed through a focused argon ion laser beam the dependence of the fluorescence on the incident CS intensity and the illumination time agrees well with the theoretical prediction for singlet saturation and photochemistry the signaltonoise ratio is optimal when the light intensity and the flow rate are adjusted so that both k and tau are close to unity x photons cm s and a transit time tau t of mus this analysis should be useful for optimizing fluorescence detection in dna sequencing chromatography fluorescence microscopy and singlemolecular fluorescence PCD
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snakes and their relationships with humans and other primates have attracted broad attention from multiple fields of T0 but not surprisingly from neuroscience despite the involvement of the visual system and strong behavioral and physiological evidence that humans and other primates can detect snakes faster than innocuous objects here we report the existence of SN in the primate medial and dorsolateral pulvinar that respond selectively to visual images of snakes compared with three other categories of stimuli monkey faces monkey hands and geometrical shapes snakes elicited the strongest fastest responses and the responses were not reduced by low spatial filtering these findings integrate neuroscience with evolutionary biology anthropology psychology herpetology and primatology by identifying a neurobiological basis for primates heightened visual sensitivity to snakes and adding a crucial component to the growing evolutionary perspective that snakes have long shaped our primate lineage
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phenobarbital is a lipophilic molecule used as a sedative and antiepileptic drug that elicits a multitude of effects in the liver including gross liver enlargement hepatocyte hypertrophy and induced expression of DME and other liverspecific genes the constitutive androstane receptor car nri and to a lesser extent the pregnane x receptor pxr nri are responsible for mediating induction of many phenobarbitalresponsive genes however carmediated transcriptional control of some genes is critically dependent on hepatocyte nuclear factor alpha hnfalpha nra which itself regulates multiple liverspecific genes involved in hepatic growth metabolism and differentiation we studied the effects of phenobarbital on hnfalpha expression in HCs and provide evidence that hnfalpha nuclear expression is regulated in response to phenobarbital realtime PCR reaction analyses revealed that hnfalpha mrna is modestly upregulated by phenobarbital in addition nuclear expression of hnfalpha protein is significantly elevated hours after the administration of phenobarbital in wildtype car and carpxr mice in vitro analysis revealed that phenobarbitalinduced hnfalpha expression is both time and dose dependent in addition the phosphatase inhibitor okadaic acid and the cacalmodulindependent protein kinase ii inhibitor kn block nuclear induction of hnfalpha by phenobarbital furthermore hnfalpha nuclear expression is enhanced by inhibition of cyclic ampdependent protein kinase a in conclusion induced nuclear expression of hnfalpha and car is an integral part of the phenobarbital response aimed at coordinated regulation of genes involved in drug metabolism and detoxification as well as maintenance of LF
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heparininduced TP hit is a serious complication of heparin use igg antibodies to complexes of platelet factor pf and heparin trigger the clinical manifestations of hit only a subset of these antibodies will activate platelets and these can only be identified with PLT aggregation PET assays heparininduced PLT aggregation hipa and cserotonin PR sra assays for hit are timeconsuming and complex to perform we have developed a whole blood impedance wbi test using the new multiplate analyser all samples referred to our laboratory over a month period were screened for heparinpf antibodies by an elisa method zymutest hia igg the ts score was used to assess hit pretest probability twenty antibody positive samples were further tested by all three functional assays light transmission aggregometry lta sra and wbi thirteen out of twenty samples were positive by lta patients and by wbi patients sra considered to be the gold standard was used as a crough a mechanism that involves ros production and suggests another important interaction between iron and cadmium metabolism
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in this present study we have attempted to grade soft tissue sarcomas on fineneedle aspiration cytology fnac material and then subsequently correlated our findings on histology sectiona total of cases of primary soft tissue sarcomas sts were graded and correlated with the subsequent histopathology sectionsfnac successfully diagnosed cases and four cases were reported as benign there were grade i grade ii and one grade iii cases on histopathology out of the grade i cases only three cases were graded correctly on cytology on fnac sarcomas were diagnosed correctly as grade ii tumors and one case was under diagnosed as benign there was a single case of grade iii sarcoma on histopathology which was correctly diagnosed and graded on fnacin majority of the sts it is possible to grade on fnac grade i sts is relatively difficult to grade than grade ii sts
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the HTLV human t lymphotropic virus type htlv promotes spastic paraparesis AD t cell leukaemia and other diseases recently some human micrornas mirnas have been described as important AF in hostvirus interactions this study compared mirna expression in control individuals asymptomatic htlv carriers and htlv associated myelopathy hamtropical spastic paraparesis patients the proviral load and tax protein expression were measured in order to characterize the patients hsamirb expression was significantly higher in patients than in controls p or in the ham group p therefore our findings suggest that mirb expression can be used to elucidate the mechanisms of viral replication and pathogenic processes
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acute renal failure is one of the serious complications of malaria with untoward consequences including increased risk of mortality this T0 was conducted to evaluate the incidence clinical features course outcome and predictors of mortality of ARF arf in children with malaria in the pediatric GA wards and intensive ECU of our medical center from january to december data of all children from month to years of age with confirmed malaria either on peripheral smear andor optimal test were reviewed those suffering from arf were selected for further study twelve eight plasmodium falciparum three plasmodium vivax and one mixed infection out of cases of confirmed malaria had arf in addition to arf most of the patients had at least one other manifestation of severe malaria nine patients recovered completely while died presence of associated cerebral malaria hyperbilirubinemia and DIC dic was a poor prognostic factor and predictor of mortality in conclusion arf can complicate both p falciparum and p vivax malaria malarial arf as an isolated complication has a good prognosis the presence of multiorgan involvement and delayed diagnosis increases morbidity and mortality
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over cases of hodgkins disease diagnosed between were used to examine incidence and time trends these data are part of the leukaemia research funds specialist data collection T0 which is the only large populationbased data set of its type in europe the age specific incidence curves showed different patterns for NS contrasted with all other subtypes combined nonnodular sclerosis for nodular sclerosis there was a female excess for young adults while for nonnodular sclerosis a gradual rise in incidence with age in both sexes was observed incidence varied over time showing a complex pattern with a decreasing trend in males in all ryesubtypes and no significant NC among females diagnosed with NS these complex patterns of change are different from those seen in other countries it is concluded that the results provide clear evidence of the heterogeneity of HD disease between the sexes and between subtypes which should be taken into account in future studies
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lower genital tract intraepithelial neoplasia was the predominant indication for co laser surgery in patients treated at wayne state university one hundred nineteen patients had C2 intraepithelial neoplasia cin iii and in the patients who were adequately followed the failure rate following the first treatment was secondary treatment with laser surgery cryosurgery or in one instance hysterectomy was effective in treating all persistent cin success in treating vaginal IEL neoplasia with laser surgery was most favorable in patients who had not had prior pelvic irradiation small less than cm vulvar IEL neoplasia iii was successfully treated in seven patients recalcitrant condyloma acuminata responded well to laser surgery in patients
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a total of respiratory specimens sputa bronchial and tracheal aspirates and BAL lavages from patients were tested for direct detection of mycobacterium tuberculosis complex by the genprobe amplified mycobacterium tuberculosis direct test mtd and the results were compared with those of the conventional methods of fluorescence microscopy and cultivation solid and radiometric media one series of specimens n was decontaminated with nacetyllcysteine nalcnaoh the other one n was decontaminated with sodium dodecyl lauryl sulfate sdsnaoh of the specimens decontaminated with nalc were mtd and culture positive were mtd and SC negative were mtd positive and SC negative and were mtd negative and SC positive indicating a sensitivity of and a specificity of for the mtd of the specimens decontaminated with sds were mtd and culture positive were mtd and SC negative were mtd positive and SC negative and was mtd negative and culture positive indicating a sensitivity of and a specificity of for the mtd after resolution of discrepant results by review of the patients clinical data the sensitivity of the mtd was the specificity was the positive predictive value was and the negative predictive value was for the nalc series the corresponding values were and respectively for the sds series in conclusion the mtd is a highly CS and TPS technique for detecting m tuberculosis complex within hours in both smearpositive and smearnegative respiratory specimens
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taz g was initially identified as the gene associated with barth syndrome and left ventricular noncompaction lvnc the purpose of this study was to investigate patients with lvnc for diseasecausing mutations in taz in japanese patients including families mutation analysis of taz was performed using dna sequencing a splice donor mutation was identified in two brothers with barth syndrome and lvnc and a sister who was asymptomatic however the variant was not identified in either parent or the maternal grandparents all of whom were asymptomatic due to the recurrent inheritance of this variant by each of the children we concluded that this was evidence of gonadal mosaicism in the obligate carrier mother the first reported occurrence of this in barth syndrome
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the consequences of the boundary conditions signal reflecting vs signal adsorbing on bacterial IC were addressed by a combined physics and microbiology approach a predictive biophysical model was devised that considered system size diffusion from given points signal molecule decay and boundary properties the theoretical predictions were tested with two experimental agarosegelbased setups for reflecting or absorbing boundaries nacyl homoserine lactone ahl concentration profiles were measured using the agrobacterium tumefaciens ntl bioassay and found to agree with model predictions the halflife of ahl was estimated to be days the absorbing vs reflecting nature of the boundaries drastically changed ahl concentration profiles the effect of a single nonreflecting boundary side was equivalent to a fold lower cell concentration results suggest that the kinetics of signal accumulation vs signal removal and their thresholdmediated phenotypic consequences are directly linked to the properties of biofilm boundaries stressing the relevance of the DWI sensing component in bacterial communication
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preadipocyte factor pref originally identified in mouse tl preadipocytes is known to play a key role in inhibiting the adipose conversion as a first step to study the involvement of the pref gene in IM adipose tissue OD in cattle which has an economic importance for beef cattle we have isolated the bovine pref cdna and genomic clones and characterized expression in abdominal adipose and promoter region of the bovine pref gene we have detected two bovine pref spliceisoforms prefc and prefa in AF tissue the rtpcr experiment revealed that the two isoforms are identified in neonatal but no in AD AF tissue suggesting agedependent suppression of the bovine pref gene expression in the form of prefc and prefa in abdominal fat tissue by mapping the RII region of this gene we have shown that at least two regions within bp UP of putative transcription start site are sufficient to confer promoter activity when accompanied by a short region including the transcription start site the chromosomal location of the pref gene was determined by fluorescence in situ hybridization fish the pref gene locates on bovine chromosome q
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an EMT emt enables epithelial tumor cells to break out of the primary tumor mass and to metastasize understanding the molecular mechanisms driving emt in more detail will provide important tools to interfere with the metastatic process to identify pharmacological modulators and druggable targets of emt we have established a novel multiparameter highcontent microscopybased CA and screened chemical compounds with MICs against known targets out of compounds we have identified drugs that block transforming growth factor beta tgfβinduced emt in normal mu MG epithelial cells nmumg the AS compounds include inhibitors against tgfβ receptors tgfbr rhoassociated protein kinases rock myosin ii src kinase and UR analogues among the emtrepressing compounds we identified a group of inhibitors targeting multiple receptor tyrosine kinases and biochemical profiling of these multikinase inhibitors reveals tgfbr as a thus far unknown target of their inhibitory spectrum these findings demonstrate the feasibility of a multiparameter highcontent microscopy screen to identify modulators and druggable targets of emt moreover the newly discovered offtarget effects of several receptor tyrosine kinase inhibitors have important consequences for in vitro and in vivo studies and might beneficially contribute to the therapeutic effects observed in vivo
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although pulmonary CF tests are used to evaluate acute changes in obstructive airway disease in patients with cystic fibrosis cf these tests are relatively difficult to perform in young children or severely ill patients and may be costly other standard tests eg the shwachmankulczycki and national institutes of health nih scoring systems evaluate disease severity and predict prognosis but do not measure daytoday changentractions induced by higher concentrations of et with ic values similar to those for contractions induced by thapsigargin or ionomycin these results show that the contractions and increases in cai of rat aortic smooth muscles at lower concentrations of et involve only one ca entry channel which is CS to skf and loe nscc whereas those at higher concentrations of et involve another ca entry channel which is sensitive to skf but resistant to loe socc in addition to the former channel
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guillainbarré syndrome gbs is an acute post infectious or disimmune illness that affects nerve roots and peripheral SN multicenter studies have clearly shown that plasma exchange pe provides valuable amelioration of gbs it was recently suggested that plasma perfusion pp on phenylalanine columns displays the same therapeutic effects of pe in neuroimmunologic disorders without the infectious risks linked with plasma replacement in this study the authors compared the tau of pe versus that of pp in two groups of patients suffering from gbs by investigating the clinical outcomes and the EP and cerebrospinal fluid findings of patients suffering from gbs underwent seven sessions of pe in a mean time of days group a six patients showing the same clinical pattern underwent three sessions of pp in a mean time of days group b data reported in group a show that pe stops the progressive worsening of the disease prevents the development of acute respiratory failure allows an early and significant clinical improvement with change in disability grade and improves motor conduction E/A and motor action potentials when recorded days T3 the end of treatment data in group b show that pp allows a slower and later improvement in disability grade and electrophysiologic data recorded at the end of treatment was worse after days finally it may be concluded that pe has beneficial effects on gbs in terms of time of recovery complication rate and relapses PP did not show the same results
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in male wistar rats extrahepatic cholestasis was induced by ligation and transsection of the common bile duct T3 and weeks of cholestasis the bile flow was restored by means of a RY choledochojejunostomy plasma levels of bilirubin alkaline phosphatase got and clotting factor x were measured weekly CL biopsies were taken at the time of restored bile flow as well as and weeks thereafter histochemical reaction for LDH and sirius red fba staining were used as measure for functional CL parenchyma and collagen respectively acid phosphatase alkaline phosphatase and nucleotidase MICs as well as the glycogen content were demonstrated in cryostat sections of the same biopsies after and weeks of common bile duct one levels of bilirubin ALP phosphatase and got significantly increased whereas levels of clotting factor x decreased rbf resulted in normalization of all these C2 to control range the volume density of functional parenchyma was found to be reduced to and of the control values following and weeks of common bile duct one respectively returning to and at weeks respectively T3 restored bile flow the collagen content increased significantly during cholestasis up to fold T3 weeks of common bile duct obstruction T3 restored bile flow a slight decrease of collagen was measured in some animals but in none of the three groups a return to normal values appeared cholestasis induced an alteration in localization andor activity of the three enzymes analyzed as well as a depletion of glycogen stores all changes in activity and distribution DP of the three enzymes as well as the glycogen depletion during CBD obstruction normalised after restored bile flow was performed however the longer CBD one had existed the longer period was needed for full REC in conclusion even T3 weeks of common bile duct obstruction the parenchymastroma relationship grossly normalized T3 restored bile flow with an almost complete restoration of the parenchyma and a concomitant REC of LF however collagen once formed did not disappear but remained as more condensed septa which apparently did not interfere with normal function
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we have developed a new tool called fastdnaml for constructing phylogenetic trees from dna sequences the program can be run on a wide variety of computers ranging from unix workstations to massively parallel systems and is available from the ribosomal database project rdp by anonymous ftp our program uses a maximum likelihood approach and is based on version of felsensteins dnaml program several enhancements including algorithmic changes significantly improve performance and reduce SM usage making it feasible to construct even very large trees trees containing taxa have been easily generated and phylogenetic estimates are possible even when hundreds of sequences exist we are currently using the tool to construct a phylogenetic tree based on small subunit rrna sequences from prokaryotes
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early invasive strategy is one of two methods of treatment of acute coronary syndromes without stsegment elevation nsteacs we aimed at assessing month outcomes and SQ of life in patients with nsteacs and multivessel PD disease cad who underwent percutaneous or surgical revascularization analyzed group comprised patients who were qualified for invasive treatment based on coronary angiography performed hours T3 admission and in whom longterm follow up data was available the inclusion criteria were rest angina within hours prior to admission and at least one of the following st segment depression or mm transient min stsegment elevation negative twaves or mmin at least contiguous leads positive serum cardiac markers patients with singlevessel cad or qualified for CT were excluded from the T0 we analysed the rate of adverse cardiac events death nonfatal myocardial infarction unstable angina repeated revascularization cardiovascular hospitalization at one year the SQ of life was assessed using shortform sf questionnaire the rate of death was vs ns myocardial infarction vs p unstable angina vs p repeated revascularization vs p and cardiovascular hospitalization vs p in the pci and cabg group respectively PCS component summary scores were vs p in the pci and cabg group respectively mental component summary scores were similar in both groups vs ns
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sphingosine and its analogs which inhibit protein kinase c pkc are known to be potent inducers of apoptosis in tumor cells however we were concerned that sphingosine might also interfere with antitumor cells of the IS therefore we evaluated the effect of sphingosine on activation of human monocytes by interleukin il for killing of leukemic cells monocytes purified by elutriation and adherence were activated with il or interferongamma Th1 in the presence or absence of sphingosine or another inhibitor for h then the monocytes were washed and the culture medium was replaced with fresh medium to remove the sphingosine hl and k leukemic cells were added to the mo cultures over the next h the cytotoxic activity of the monocytes towards the leukemic cells was assessed by means of an indiumreleasing CA ilactivated monocytes lysed of hl cells and of k cells sphingosine dihydrosphingosine DMS and the pkc inhibitor h inhibited the activation of monocytes by il blocking cytotoxic activity against the leukemic cells by approximately these inhibitors were not toxic to monocytes at the concentrations used in a pkc assay sphingosine and h inhibited pkc activity in iltreated monocytes thus sphingosines by inhibiting pkc activity inhibited activation of monocytes by il which inhibited the killing of leukemic cells
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staphylococcus aureus encoding pantonvalentine leukocidin pvl genes has become the cause of lifethreatening infections we describe a case of carotid cavernous fistula after bacteremia in a yearold male caused by a MSSA s aureus isolate carrying the pvl fnba and ebps genes and related to sequence type st the patienical trial outcomes analyzed in the last to years have been suboptimal with atenolol the worlds most popular β blocker several metaanalyses have suggested that despite lowering blood pressure any and all β blockers inadequately protect HT from cardiovascular events these phenomena have been attributed to ineffective lowering of central aortic or intervisit blood pressures or adverse metabolic effects particularly when combined with diuretics although there has never been a HH comparison of atenolol with any other β blocker in hypertensive patients indirect comparisons can be done with network and bayesian metaanalyses which suggest that heterogeneity of βblockers pharmacology also extends to outcomes although oncedaily atenolol as initial antihypertensive therapy may be unwise whether initial β blockers newer than atenolol reduce cardiovascular risk to the same extent as other antihypertensive drugs should be answered with more PCTs
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acute ethanol administration increases striatal dopamine PR and decreases cerebral glucose metabolism the a allele of the ankk taqia polymorphism is associated with lower DA tone and greater risk for alcoholism but the mechanisms are unclear we hypothesized that ethanol would be more reinforcing in men with the a S2 a than in men without it a as indicated by decreased anxiety and fatigue and altered activity in associated brain regions in a pilot T0 a and a men group drank ethanol mlkg or placebo beverages on each of days positron emission tomography with ffluorodeoxyglucose fdg was used to assess regional cerebral glucose metabolism as a measure of relative BB activity while participants performed a vigilance task significant findings were as follows ethanol decreased anxiety and fatigue in a men but increased them in a men ethanol increased activity in the striatum and insula of a men but reduced activity in the anterior cingulate of a men reduced anxiety and fatigue in a men were significantly associated with greater activity within a right orbitofrontal region previously implicated in cognitive control and less activity in structures associated with anxiety amygdala fatigue thalamus and cravingreinforcement striatum in contrast anxiety and fatigue changes were unrelated to brain activity in a men although these results require replication in a larger sample alcoholinduced negative reinforcement may explain the greater risk for alcoholism associated with the a S2
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the aim of this T0 was to evaluate the efficacy and safety of a combined chemotherapy regimen gemcitabine and cisplatin gc in the treatment of T3 urothelial carcinomas
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lipid fluidity in native and denatured SR and extracted lipids was monitored between and degrees c using transparinaric acid as a fluorescent probe in addition to a C1 increase in fluidity between and degree c in each system a phase NC centered near degrees c was observed in the extracted lipids but not in either the native or denatured CM a significant NC in FI near degrees c was observed in native sarcoplasmic reticulum membranes however when transparinaric acid was excited by SE transfer from tryptophan residues of the membrane protein when caatpase was subjected to proteolytic cleavage by TR as a CF of temperature a change in susceptibility was detected at about degrees c in the native CM but not in a solubilized preparation it is proposed that one or more structural changes in the microenvironment of caatpase in the native membrane occur between and degrees c which may be related to the NC in apparent activation energy which is observed for this enzyme
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the objective of this study was to evaluate the gum from hakea gibbosa hakea as a sustainedrelease and mucoadhesive component in buccal tablets following their application to the buccal mucosa of rabbits flatfaced core tablets containing either or mg of hakea and or mg of chlorpheniramine maleate cpm per tablet with either sodium bicarbonate or tartaric acid in a molar ratio were formulated using a direct compression technique and were coated with cutinar on all but one face the resulting plasma cpm concentration versus time profiles were determined following buccal application of the tablets in rabbits the strength of mucoadhesion of the tablets was also quantitated in terms of the force of detachment as a function of time following the application of the mucoadhesive buccal tablets the following values for several pharmacokinetic parameters were obtained the force of detachment for the mucoadhesive buccal tablets containing mg of hakea and either and mg cpm and mg hakea and mg cpm increaseduestionnaire format of the lequesnealgofunctional index in patients with oa of the lower extremities
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despite the advent of nonfluoroscopic technology fluoroscopy remains the cornerstone of imaging in most interventional EP procedures from diagnostic studies over ablation interventions to device implantation moreover many patients receive additional xray imaging such as cardiac computed tomography and others more and more complex procedures have the risk to increase the radiation exposure both for the patients and the operators the professional lifetime attributable excess CA risk may be around in for the operators the same as for a patient undergoing repetitive complex procedures moreover recent reports have also hinted at an excess risk of BB tumours among interventional cardiologists apart from evaluating the need for and justifying the use of radiation to assist their procedures physicians have to continuously explore ways to reduce the radiation exposure T3 an introduction on how to quantify the radiation exposure and defining its current magnitude in electrophysiology compared with the other sources of radiation this position paper wants to offer some very practical advice on how to reduce exposure to patients and staff the text describes how customization of the xray system workflow adaptations and shielding measures can be implemented in the cath uccessful diagnosis hinges on familiarity with mdct angiography and the D2 capabilities of VR and multiplanar reformation in this review we illustrate and describe key mdct findings of congenital inflammatory traumatic infectious and TE conditions affecting the mesenteric vasculature in adult patients
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high carbohydrate cho diets cause accumulation in plasma of larger triglyceride tgenriched very LD lipoprotein vldl particles in man the composition of the vldl is changed by such diets as well the source of the altered vldl particles is presumed to be the CL but the intestine is known to secrete vldl and vldl is also altered during its postsecretory catabolism to ascertain that the liver is a source of dietinduced vldl we fed rats cho and control diets and we examined plasma levels of lipids chemically and apoproteins ai apoai and b apob by specific radioimmunoassay ria vldl d less than and vldl density subfractions were isolated and their composition studied by ria column chromatography isoelectric focusing ief and PAGE livers from control and chofed rats were perfused in vitro whole perfusates and perfusate vldl were studied similary in the chofed rats plasma tg increased cholesterol and apoai remained unchanged and apob fell the vldl isolated were tg EC and less dense although total vldlprotein rose the proportion of vldlprotein that was apob and argininerich protein arp fell while apoc rose the apob content varied directly with density of particles arp subunits were not changed but relative proportions of apociii rose from to per cent of dye uptake on ief gels and apociii fell from to per cent thus cho feeding produced altered plasma vldl in the rat the perfused livers of the chofed rat secreted more tg but absolute secretory rates for cholesterol apob and apoai were unchanged the vldl isolated from perfusates were larger tgenriched and less dense although vldlprotein rose the proportion that was apob fell both apoc and arp rose arp subunits were unchanged while apociii rose from to per cent and apociii fell from to per cent in contrast to plasma apoc content was not increased relative to arp as in plasma content of apob varied with particle density thus cho feeding induced changes in hepatic perfusate vldl structure and composition that in GA paralleled those changes seen in plasma this strongly suggests that the action of diet on the CL is responsible for many of the changes seen in plasma vldl on the other hand the discrepancy between the vldlapoc content and subunit proportions of plasma and perfusate suggests that the discrepancy is due to postsecretory processing similarly the failure to see decreases in absolute hepatic apob secretion while plasma apob levels fell suggests that the postsecretory metabolism of apobcontaining lipoproteins is also altered by diet in addition the failure to see increases in hepatic vldlapob secretory rates at a time when vldltg and vldlprotein increased suggests that there is no tight coupling between the secretion of apob and lipids
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it has been shown that the echogenicity of blood varies during a flow cycle under pulsatile flow both in vitro and in vivo in GA the echogenicity of flowing whole blood increases during the early systole phase and then reduces to a minimum at late diastole while it has been postulated that this cyclic R2 is associated with the dynamics of erythrocyte aggregation the mechanisms underlying this increasing echogenicity with flow velocity remain uncertain the effect of flow acceleration has also been proposed as an explanation for this phenomenon but no TPS experiments have been conducted to test this hypothesis in addition the influence of US attenuation on the cyclic R2 of echogenicity requires clarification in the present study a couette flow system was designed to simulate blood flowing with different acceleration patterns and the flow velocity attenuation and backscattering coefficient were measured synchronously from and hematocrit porcine whole blood and erythrocyte suspensions using mhz ultrasound transducers the results showed ultrasonic attenuation exerted only minor effects on the echogenicity of blood under pulsatile flow conditions cyclic variations of echogenicity were clearly observed for whole blood with a hematocrit of but no variations were apparent for EA suspensions the echogenicity did not appear to be enhanced when instantaneous acceleration was applied to flowing blood in any case these findings show that flow acceleration does not promote erythrocyte aggregation even when a higher PV is applied to the blood comparison of the results obtained with different accelerations revealed that the cyclic variation in echogenicity observed during pulsatile blood flow may be jointly attributable to the effect of shear rate and the distribution of EA on aggregation
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thirtyone children hips were reviewed after having sustained a salter innominate osteotomy the average follow up was years the indication for the osteotomy was a persisting dysplasia after CT of congenital dislocation of the hip the x rays study allowed to describe the importance of the remodeling of the FA head the overall results were satisfactory in per cent of the cases the age of the patient at the time of surgery was important the results being much better in children under years of age the failures were mostly related to technical faults however some failures could not be predicted
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plasma fibronectin deficiency and reticuloendothelial phagocytic dysfunction are observed in critically ill and septic surgical trauma or burn patients with multiple OF they also appear to amplify altered lung VP with sepsis or intravascular coagulation this article highlights important aspects of plasma fibronectin which may relate to the aetiology of multiple organ failure in the septic injured patient
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a missense mutation in the cytoplasmic domain of the tolllike receptor tlr has been identified as the defect responsible for lipopolysaccharide lps hyporesponsiveness in C3 mice tlr and tlr have recently been implicated in lps signaling in studies where these receptors were overexpressed in lps nonresponsive human embryonic kidney cells however the signaling role of tlr or tlr in human cells with natural lps response remains largely undefined here we show that human dermal microvessel endothelial cells hmec and human umbilical vein endothelial cells express predominantly tlr but very weak tlr and respond vigorously to lps but not to mycobacterium tuberculosis kda lipoprotein transient transfection of nonsignaling mutant forms of tlr and antitlr monoclonal antibody inhibited lpsinduced nfkappab activation in hmec while a monoclonal antibody against tlr was ineffective in contrast to lps responsiveness the ability of hmec to respond to kda lipoprotein correlated with the expression of tlr transfection of tlr into hmec conferred responsiveness to kda lipoprotein these data indicate that tlr is the lps signaling receptor in hmec and that human EC cells ec express predominantly tlr and weak tlr which may explain why they do not respond to kda lipoprotein the differential expression of tlrs on human ec may have important implications in the participation of V1 ec in innate immune defense mechanisms against various infectious pathogens which may use different tlrs to signal
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phenelzine and imipramine were compared doubleblind in depressed inpatients a PL week preceded drug treatment this allowed early identification of PL NR who did not therefore enter the T0 after three weeks treatment the two drugs were equally ERP on hamilton beck and scl measures of depression and anxiety on the the scl scales of hostility and paranoia imipramine was more ERP in some patients phenelzine was associated with increased hostility measurement of mao inhibition and plasma TCA levels indicated that adequate doses were generally used mean mgday phenelzine and mgday imipramine
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specimens of hbac from human hemolysate contain more than six minor components which cannot be separated by conventional methods these components have differing characteristic properties and their levels fluctuate depending on the time the blood is drawn and the method of sample preparation used hbac exhibits unreasonable fluctuation and unexpectedly high C2 and is therefore not an accurate indicator of LT blood glucose control the six components of hbac were resolved by our new chromatographic technique using iex and designated by their eluting position and properties hbf lghb stghb lghb fr and fr hbf was alkaline resistant lghb and lghg were easily removed by treatment with saline or SC and increased after incubation with gl the level of lghb in the blood showed rapid and varied fluctuation on ogtt in both diabetics and control subjects more than hbf and lghb was present in of the control group n and in of the iddm group n stghb which was a major component of hbac was not affected by pretreatment with saline semicarbazide or gl in vitro the level of stghb in the blood showed little NC on ogtt hbac hitherto referred to as one SD component is an incorrect term used to denote the index of LT blood gl control it is important and warranted to use the level of SD glycohemoglobin stghb in future determinations following proper analytical methods
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carbonic anhydrase ca and mgdependent atpase and mgdependent hcostimulated atpase mghcoatpase MICs in rat DU mucosa and kidney cortex were examined with respect to thyroidal status administration of and micrograms thyroxine tkg per day sc for days decreased DU cytosol ca activity to of control with the former and with the latter dose while mghcoatpase activity in brush borders of duodenal mucosa was increased to of control by micrograms tkg ca and mghcoatpase activities in the cytosol and brush border of kidney cortex did not change C2 of t hypothyroidism induced by Tx for and weeks or administration of methimazole mgkg per day sc or peroral for and weeks all increased DU cytosol ca activity to about at weeks and at weeks T3 Tx and to about T3 the p.o. of mg methimazolekg per day for weeks while brush border mghcoatpase activity was decreased to of control weeks T3 Tx and to T3 the sc administration of mg methimazolekg day for weeks the increase in ca activity and the decrease in atpase activity after thyroidectomy were restored to normal levels by replacement with t neither enzyme activity in the kidney changed in hypothyroidism serum concentrations of t and cortisollike material increased T3 administration of t and SS concentrations of t aldosterone and cortisollike material all decreased in HT correlations were observed between duodenal ca and mghcoatpase MICs and serum concentrations of t p less than these results reveal that the decrease in ca activity and the increase in mghcoatpase activity of DU mucosa in hyperthyroidism are reversed in HT while both enzyme MICs in the kidney are unrelated to thyroidal status
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anisomeles indica popularly known in taiwan as yuchentsao has been traditionally used as an anticancer and antiinflammatory agent however little is known about its antimetastatic potential therefore we attempted in this study to examine the antimetastatic potential of a indica aqueous extract ai its isolated EDC apigenin ovatodiolide βsitosterol and acteoside in otetradecanoylphorbolacetate tpainduced human breast adenocarcinoma mcf cells among the test agents CE ai and pure compound apigenin potently suppressed the tpainduced mcf cells migration and invasion in addition ai and apigenin time and dosedependently down regulated the matrix metalloproteinase mmp enzymatic MICs and its mrna expression furthermore ai and apigenin also down regulated the nuclear factor nfκb subunit p and AP-1 ap S1 cfos proteins expression in nucleus and transcriptional activity of nfκb and ap this is the first report on the antimetastatic potential of a indica that suppressed the cancer cell invasion through the inhibition of mmp enzyme via nfκbap signaling taken together our data indicate that a indica can be considered as a source of new antimetastatic agent for food and pharmaceutical industries
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the purpose of this study was to determine the associations and predictive values of medical college admission test mcat component and composite scores prior to with us medical licensure exam usmle step and step clinical knowledge ck scores with a focus on whether students scoring low on the mcat were particularly likely to continue to score low on the usmle exams
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five patients with severe RA ICA are reported in whom leg ulcers were not apparently associated with vasculitis the conventional explanation for these ulcers deserves review patients with rheumatoid arthritis may develop gravitational leg ulceration and pressure sores on their legs in addition they may develop ulcers on the lower aspects of the legs and around the ankles which are well demarcated punched out painful and slow to heal these ulcers usually occur in patients with longstanding severe SP disease they are presently considered to be due to a necrotising arteritis causing dermal infarction since they are frequently associated with other clinical features of rheumatoid vasculitis wilkinson has commented that biopsies are seldom taken from leg ulcers in this paper we report five patients with severe rheumatoid ICA who developed such leg ulcers in the absence of other clinical evidence of vasculitis and in whom biopsies of the ulcers failed to reveal vasculitis a case is summarised as illustrative of the five patients whose relevant histories clinical findings and laboratory investigations are summarised in table
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the purpose of this series is to describe the sonographic findings in patients with intestinal one due to internal hernia
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alzheimer disease ad is characterized by EM impairment this T0 was aimed at assessing various aspects of EM and particularly sensitivity to semantic cuing in patients with various degrees of cognitive deterioration compared with normal elderly subjects one hundred thirtyone patients subdivided into four subgroups as a function of their minimental state examination score were included all subjects including normal elderly subject were given an EM test with controlled encodeviews three studies that we recently completed with boneinducing implants longterm clinical followup of allogeneic demineralized bone implants showed an average degree of resorption of implants used for dorsal nasal augmentation showed an average degree of resorption of increasing to T3 a month followup the efficacy of demineralized bone implants is dependent on many factors including site of implantation method of preparation etc transforming growth factorbeta tgfbeta is a regulator of bone formation we combined recombinant tgfbeta with demineralized bone powder in a rb facial augmentation model at weeks there was evidence of increased bone formation in the implants containing tgfbeta even though tgfbeta can increase bone formation in demineralized bone implants the overall boneinducing activity in these implants seems to be suboptimal osteoinductive factor extract ofe is a partially purified bone factor preparation that has been shown to form bone when implanted into rats using a collagenceramic carrier we implanted ofe into a rb facial augmentation MM at d histomorphometry revealed numerous osteoblasts and bone formation in the ofe implants the boneinducing activity of many partially purified osteoinductive preparations such as ofe is probably due to bone morphogenetic proteina bmpa which has been shown to induce bone formation in its recombinant form recombinant dna methodology provides the technology necessary to produce these molecules in their homogeneous form permitting evaluation of boneinducing activity in a preparation free of contaminants finally the ideal carrier must be devised to permit safe and ERP delivery of recombinant boneinducing AF
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neither the association between obstructive airways disease oad and sleep apneahypopnea sah nor the sleep consequences of each disorder alone and together have been characterized in an AD community setting our primary aims were to determine if there is an association between oad and sah and identify predictors of oxyhemoglobin desaturation during sleep in persons having oad with and without sah PSG and spirometry results from participants in the sleep heart AHS were analyzed oad was defined by a fevfvc value less than assessment of sah prevalence in oad was performed using thresholds of respiratory disturbance index rdi greater than and greater than a total of participants had oad that was predominantly mild fevfvc mean sd sah was not more prevalent in participants with oad than in those without oad versus with and without oad respectively at rdi threshold values greater than and versus with and without oad respectively at rdi threshold value greater than in the absence of sah the adjusted odds ratio for sleep desaturation total sleep time with saturation was greater than when fevfvc was less than participants with both oad and sah had greater sleep perturbation and desaturation than those with one disorder generally mild oad alone was associated with minimally altered sleep SQ we conclude that there is no association between generally mild oad and sah exclusive of sah and T3 adjusting for demographic AF and awake oxyhemoglobin saturation an fevfvc value less than is associated with increased risk of sleep desaturation desaturation is greater in persons with both oad and sah compared with each of these CT and individuals with generally mild oad and without sah in the community have minimally perturbed sleep
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since the discovery of antineutrophil cytoplasmic autoantibodies anca great strides have been made in elucidating the etiology and pathogenesis of disease in this article we review recent published key breakthroughs in understanding the pathogenesis of anca vasculitis including some that may lead to novel therapeutics these breakthroughs have occurred in multiple areas of investigation a EU genomewide association study gwas revealed the importance of the genetic contribution of proteinase pr and its endogenous inhibitor alpha antitrypsin as well as hla risk epigenetic modification of autoantigen genes appears to contribute to perpetuation of disease and possibly relapse risk autoantigen excision a novel method to detect autoantibody epitopes using mass spectrometry not only revealed pathogenic epitopes in myeloperoxidase mpoanca vasculitis and identified unique mpoanca responsible for the majority of ancanegative small vessel vasculitis but has vast applicability to other autoantibodymediated diseases an explosion of biomarker studies has revealed circulating cytokines and alternative complement pathway products that may predict active disease interestingly ACP blockade in the mu MM of disease is protective and a CT in humans using an oral alternative complement pathway inhibitor is underway increasing clarity of the role of b and TA in disease pathogenesis is ongoing b cell depleting agents have shown great utility in remission induction and maintenance and monitoring specific b cell subsets during the disease course may have predictive SP for remission maintenance despite these substantial advances more research is needed including but not limited to validation of existing discoveries as additional novel discoveries emerge so will novel therapies and it is with great hope that these collective insights will ultimately lead to prevention and cure
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this T0 was designed to investigate the repair of oxidative damage in nuclear dna sequences with different transcriptional MICs chinese hamster ovary cho cells were treated with the oxygen radical generator hypoxanthinexanthine oxidase hypxo damage and repair were evaluated in kb TRF containing either the dhfr gene a nontranscribed flanking region or the cfos gene using a quantitative southern blot technique damage to the sugarphosphate backbone and AP CS were detected by measuring their lability in alkali conditions lesions in dna bases were identified using the bacterial repair enzyme endonuclease iii which predominantly recognizes damage to thymines and cytosines and formamidopyrimidinedna glycosylase which recognizes oxoguanine and purines with fractured imidazole rings the results showed that similar amounts of all types of oxidative damage were produced in both the transcribed and nontranscribed sequences following a h exposure to the radical generator repair in all sequences was rapid with approximately removal of lesions observed by h therefore within these sequences the repair of oxidative lesions is much faster than that of other types of damage such as those induced by alkylating toxins and uv irradiation and the repair is not affected appreciably by transcriptional status
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pulmonary hypertension is a hemodynamic condition defined as a mean pulmonary i.a. pressure by rightsided heart catheterization of at least mm hg at rest it is classified into general CG based on the underlying cause with left ventricular failure and chronic obstructive pulmonary disease being of the most common causes in the united states although the specifics of the pathophysiology will vary with the cause appreciating the risks of pulmonary hypertension and RA ventricular failure is critical to appropriately evaluating and resuscitating pulmonary hypertension patients in the emergency department ed patients may present to the ed with complaints related to pulmonary hypertension or unrelated ones but this condition will affect all aspects of care exertional dyspnea is the most common symptom attributable to pulmonary hypertension but the latter should be considered in any ed patient with unexplained dyspnea on exertion syncope or signs of RVD patients with RA VVI failure are often volume overloaded and careful volume management is imperative especially in the setting of hypotension vasopressors and inotropes rather than fluid boluses are often required in shock to augment cardiac SO and reduce the risk of exacerbating RA ventricular ischemia intubation should be avoided if possible although hypoxemia and hypercapnia may also worsen rightsided HR CF emergency physicians should appreciate the role of pulmonary vasodilators in the treatment of PAH and recognize that patients receiving these medications may rapidly develop right ventricular faiand a MAP pressure of to mmhg data from consecutive highrisk cardiac surgical patients assigned to this protocol were compared with a matched cohort of consecutive highrisk cardiac surgical patients receiving usual care in baseline characteristics were similar in the two groups there was no significant difference in the duration of noradrenaline infusion in the shp cohort compared to historical controls median iqr hours versus hours p despite patients receiving more fluid in their first hours in the icu mean ml sd ± ml versus ml sd ± ml p the shp cohort had a higher rate of reintubation in versus in p the shp delivered significantly more fluid but did not reduce the duration of noradrenaline infusion compared to UC
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detection of benzyolecgonine the L1 metabolite of cocaine in the urinalysis conducted on the first day of an inpatient heroin detoxification treatment program was studied as a predictor of discharge against medical advice ama with this aim we conducted a chartreview procedure of heroin dependents dsmiiir who received methadone or dextropropoxyphene chlorhydrate to treat opioid withdrawal syndrome data were analyzed following a casecontrol design the patients who did not CR the treatment due to discharged ama were characterized by having achieved total heroin abstinence during fewer months from the timnd in this instance increased tau of the pde inhibitor with the pde inhibitor was not apparent p or il production from clones with th th and th phenotypes appeared equally CS to treatment with the pde inhibitor we conclude that the antiinflammatory effects of pde inhibitors may be mediated in part by downregulation of il
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the mechanical properties of a suspension can be dramatically altered by adding a small amount of a AA fluid that is immiscible with the bulk phase the substantial changes in the strength of these capillary suspensions arise due to the capillary force inducing a percolating particle network spatial information on the structure of the particle networks is obtained using confocal microscopy it is possible for the first time to visualize the different types of percolating structures of capillary suspensions in situ these capillary networks are unique from other types of particulate networks due to the nature of the capillary attraction we investigate the influence of the threephase CA on the structure of an oilbased capillary suspension with Si microspheres contact angles smaller than ° lead to pendular networks of particles connected with single capillary bridges or clusters comparable to the funicular state in wet granular matter whereas a different clustered structure the capillary state forms for angles larger than ° particle pair distribution functions are obtained by image analysis which demonstrate differences in the network microstructures when porous particles are used the pendular conformation also appears for apparent theta larger than ° the complex shear modulus can be correlated to these microstructural changes when the percolating structure is formed the complex shear modulus increases by nearly three decades pendular bridges lead to stronger networks than the capillary state network conformations but the capillary state clusters are nevertheless much stronger than pure suspensions without the added liquid
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the effect of dilute sodium XTT naoh on reed straw structural change at degreec temperature was evaluated in this study various concentrations of naoh to were used for i.c.v. of reed straw at degreec for min scanning electron microscopy atomic force microscopy and fourier transform infrared spectroscopy studies showed that and naoh pretreated sample exposed more cellulose SF compared with other treatments the cellulose crystalline index was increased by the to naoh treatments and slightly lowered by the naoh treatment due to destructing cellulose fibres two per cent naoh i.c.v. caused lignin removal whereas naoh pretreatment removed lignin besides reed straw when pretreated at and naoh resulted and hemicellulose removal respectively however the difference in removal of lignin and hemicellulose between and naoh treated reed straw was very marginal in addition very negligible increase of cellulose level was estimated amounting and in and naohtreated sample respectively moreover after h reducinmmune response of the infected host have led to the development of several new vaccines a number of which are already undergoing clinical trials these include preexposure prime vaccines which could replace bacille calmetteguérin bcg and preexposure booster vaccines given in addition to bcg infants are the target population of these two types of vaccines in addition several postexposure vaccines given during adolescence or adult life in addition to bcg as a priming vaccine during infancy are undergoing clinical testing therapeutic vaccines are currently being assessed for their potential to cure AS tb as an adjunct to chemotherapy bcg replacement vaccines are viable rBCG or doubledeletion mutants of mtb all booster vaccines are composed of one or several antigens either expressed by viral vectors or formulated with adjuvants therapeutic vaccines are killed mycobacterial preparations finally multivariate biomarkers and biosignatures are being generated from highthroughput data with the aim of providing better diagnostic tools to specifically determine tb progression here we provide a technical overview of these recent developments as well of the relevant computational approaches and highlight the obstacles that still need to be overcome
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in this experiment a new type of nutritional drinkmillet SM beveragewas developed based on combining skim milk with millet and nutritional resource utilization the effects of nahcoâ concentrations in soaking water g ml and g ml and blanching time and min on the physicochemical properties of millet skim milk were studied the parameter changes caused by the above treatment were evaluated via color analysis physicochemical analysis and sodium dodecyl sulfate polyacrylamide gel PACE sdspage soaking in water containing nahcoâ had a significant
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sensory SN in dorsal root ganglia drgs are the firstorder SN along the pathway conveying sensory information from the periphery to the CNS system the analysis of the morphological and physiological features of these neurons and their alterations in pathology is the necessary prerequisite to understand pain encoding mechanisms here we describe an in vitro procedure for combined morphofunctional analysis of mouse drgs freshly excised drgs obtained from adult mice were incubated in collagenase to dissolve the ensheathing connective capsule the Kd of the connective tissue facilitates both access to the SN by CP recording glass pipettes and the penetration of primary antibodies for immunohistochemical procedures the entire drgs were then imaged using a confocal microscope obtaining a fine d representation of their cytoarchitecture without requiring tissue sectioning thus our proposed wholemount preparation represents a flexible in vitro approach for both PET and phenotypic analysis of drg SN by at the same time preserving their neuroanatomical relationships
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a primary mechanistic hypothesis by which ambient air particles have a significant negative impact on human health is via the induction of pulmonary inflammatory responses mediated through the generation of reactive oxygen species ros OD of a biosensor for the assessment of particulate ros activity would be a significant advance in air pollution monitoring the objective of this T0 was to evaluate whether air particulates interact directly with protective enzymes involved in oxidative AS responses we performed CEA assays on four enzymes involved in oxidative AS responses cuzn superoxide dismutase mn superoxide dismutase glutathione peroxidase and glutathione reductase in the presence of particles of varying toxicities and found distinctive inhibition patterns on the basis of these findings we suggest a strategy for an enzyme bioassay that could be used to assess the potential of particles to generate rosinduced responses
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tamoxifen has long been an established adjuvant treatment in the management of advanced breast cancer studies carried out by the national surgical adjuvant breast and bowel project nsabp and other groups also established its use in the treatment of early breast cancer and subsequently as a riskreducing agent for the development of CL breast CA in breast cancer patients the nsabp began its investigation of tamoxifen as a preventive agent in the early s in women who had never had the disease with its breast cancer prevention trial p its second prevention study the star trial is currently under way
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the interactions of the anthelmintic agent AVM the anticonvulsant pentobarbital and the anxiolytic tracazolate with the GABA acid gaba receptor chloride ion channel complex in rat BB membrane were studied the results indicated that they all potentiated ligand IB to the gaba and benzodiazepine receptors the stimulatory effects of AVM and pentobarbital but not tracazolate on gaba receptor IB were inhibited by picrotoxin the effect of AVM was not additive with those of tracazolate and pentobarbital on the other hand the stimulatory effect of gaba on benzodiazepine IB was additive with those of AVM and pentobarbital but tracazolate and pentobarbital inhibited the effect of AVM in the receptor heat inactivation experiments avermectin ba and clonazepam protected gaba receptors whereas AVM and gaba protected benzodiazepine receptors tracazolate pentobarbital and picrotoxin did not protect either receptor these findings suggest that the recognition sites for the benzodiazepines AVM pentobarbital and PT are coupled allosterically to the gaba receptor chloride ion AChR in different ways the binding sites for avermectin ba may be partially shared by PT pentobarbital and tracazolate
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hepatic and renal excretion of individual bile acid conjugates were studied in four patients with extrahepatic cholestasis during weeks of percutaneous transhepatic drainage with bile refeeding the study involved isolation and determination by gas chromatographymass spectrometry of individual bile acids separated into glycine taurine and sulphate conjugates simultaneously in bile SS and urine in bile CA chenodeoxycholic and deoxycholic acids were chiefly found as glycine or taurine conjugates and in high concentrations which indicated a C1 capacity of the postcholestatic liver to excrete these conjugates a minor portion of cholic chenodeoxycholic and deoxycholic acids and all of lithocholic and betahydroxycholenic acids in the bile were recovered as sulphate conjugates the biliary concentration of sulphated bile acids was low but increased during drainage with refeeding of bile indicating a gradually more efficient hepatic elimination of sulphated bile acids the urinary concentrations of the individual bile acid conjugates decreased when the biliary concentration increased
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in most patients the LAD i.a. lad feeds the anterior aspect of the interventricular SP and a large segment of the anterior wall of the left ventricle it then passes around the left ventricular apex to supply that area as well however in some cases the lad is shorter and terminates either at or before the left VVI apex the latter in these cases is instead supplied by a long posterior descending PD pda originating from the right coronary artery rca at the crux then passing along the entire length of the posterior interventricular groove and either terminating at the apex or extending beyond it to pass upward in the anterior interventricular groove in this case report we describe a yearold man with an apical PD on AS myocardial perfusion imaging in whom diagnostic coronary angiography revealed that the LVA was supplied by a C1 obtuse marginal CB of the left circumflex coronary i.a. lcx instead of the lad
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effects of sematilide a novel class iii antiarrhythmic agent on the delayed rectifier k current ik were examined in guinea pig atrial myocytes using a Vc clamp technique sematilide inhibited both timedependent outward current upon depolarization and tail currents iktail at mv the concentration of sematilide required for a decrease in iktail was approximately microm the sematilidesensitive current obtained using a triangular voltage command exhibited marked inward rectification and had the maximum amplitude at mv these results suggest that sematilide inhibits rapidly activating ik in guinea pig atrial myocytes resulting in the prolongation of action potential duration and refractoriness
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sarcopenia is the agerelated loss of skeletal MM and function and is characterized by a reduction in MM and fiber crosssectional area alterations in muscle fiber type and mitochondrial functional changes in rhesus monkeys calorie restriction cr without malnutrition improves survival and delays the onset of ageassociated diseases and disorders including sarcopenia we present a longitudinal T0 on the impact of cr on early stage sarcopenia in the upper leg of monkeys from years to years of age using DEXA we show that cr delayed the development of maximum muscle mass and unlike control animals MM of the upper leg was preserved in cr animals during EP sarcopenia histochemical analyses of vastus lateralis muscle biopsies revealed that cr opposed agerelated changes in the proportion of type ii muscle SF and fiber crosssectional area in contrast the number of MF with mitochondrial ETS enzyme CA etsab was not significantly affected by cr laser capture microdissection of etsab SF and subsequent pcr analysis of the mitochondrial dna revealed C1 deletion mutations in SF with abnormal mitochondrial enzyme MICs cr did not prevent stochastic mitochondrial deletion mutations in MF but cr may have contributed to the maintenance of affected fibers
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