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we studied the efficacy and safety of transurethral needle ablation of the prostate for treatment of symptomatic benign prostatic hyperplasia bph
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proteaseactivated receptor par mediates the thrombininduced proliferation and hypertrophy of V1 smooth muscle cells a role of rac in the regulation of par expression was investigated
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mesoporous silicon is a biocompatible biodegradable material that is receiving increased attention for pharmaceutical applications due to its extensive TPS surface this feature enables to load a variety of drugs in mesoporous Si devices by simple adsorptionbased procedures in this work we have addressed the fabrication and characterization of two new mesoporous silicon devices prepared by electrochemistry and intended for protein delivery namely i mesoporous Si MPs and ii chitosancoated mesoporous silicon MPs both carriers were investigated for their capacity to load a therapeutic protein insulin and a model antigen bovine serum albumin by adsorption our results show that mesoporous Si MPs prepared by EC methods present moderate affinity for insulin and high affinity for Al however mesoporous silicon presents an extensive capacity to load both proteins leading to systems were protein could represent the L1 mass fraction of the formulation the possibility to form a chitosan coating on the microparticles surface was confirmed both qualitatively by atomic force microscopy and quantitatively by a colorimetric method mesoporous Si microparticles with mean pore size of nm released the loaded insulin quickly but not instantaneously this profile could be slowed to a certain extent by the chitosan coating modification with their high protein loading their capacity to provide a controllednancy the site and mode of detrimental glucocorticoid action in pregnancy is not established because circulating prolactin is important for progesterone secretion and pregnancy establishment we also hypothesised that AS negatively impacts on prolactin and its NE control systems in early pregnant mice basal prolactin secretion was profoundly inhibited by either immune or fasting stress in early pregnancy prolactin release is inhibited by tonic dopamine release from tuberoinfundibular tida neurones however immune AS did not increase tida neurone activity in the ME in Pr mice measured by dihydroxyphenylacetic acid dopac content and the dopacdopamine ratio by contrast both immune AS and fasting caused weak induction of fos in tida neurones however fos induction does not always reflect dopamine secretion taken together the data suggest that the stressevoked profound reduction in prolactin secretion does not involve substantially increased dopamine activity as anticipated in pregnancy there was also att recruitment of parvocellular paraventricular nucleus neurones and increased activation of BS NE nuclei T3 immune stress indicating that other mechanisms may be involved in the suppression of prolactin secretion in summary low prolactin and increased circulating glucocorticoids together may partly explain how a mothers endocrine system mediates stressinduced pregnancy failure
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the developmental capacity of oocytes matured in vitro following isolation at the GV from freshly killed mice control was compared with that of oocytes isolated from the carcasses of mice killed and hr earlier the yield of IN cumulus cellenclosed oocytes decreased as the interval between death of the animal and removal of the ovary increased after hr of SC of medium containing folliclestimulating hormone the frequency of germinal vesicle breakdown extrusion of a polar body and cumulus expansion was equivalent in oocytes of all groups the frequency of development of inseminated ova to cell stage embryos in the control and hr postmortem groups was the same but declined markedly in the and hr groups there was also no difference in the frequency of blastocyst development from cell stage embryos between the control and hr postmortem groups but the cell embryos in the hr postmortem group did not develop to blastocysts thirtysix percent of the cell stage embryos from the hr postmortem group developed to live young after transfer to foster mothers follicles of hr postmortem ovaries showed degeneration manifested as prominent crystalline inclusions within the oocytes and many pyknotic granulosa cells the crystals disappeared within hr of SC and the secondary oocytes appeared normal the cultured oocytecumulus cell complexes therefore reversed degenerative changes induced by the death of the animal this T0 demonstrates the feasibility of recovering developmentally competent oocytes from valuable recently deceased zoological agricultural and endangered mammals
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patterning of the vertebrate NT depends on intercellular signals emanating from sources such as the notochord and the FP the secreted protein sonic Hh and the EM protein vitronectin are both expressed in these signalling centres and have both been implicated in the generation of ventral SN the proteolytic processing of sonic Hh is fundamental for its signalling properties this processing generates two secreted MMP with all the inducing activity of shh residing in the highly conserved kda aminoterminal peptide nshh here we show that vitronectin is also proteolitically processed in the embryonic chick notochord FP and ventral NT and that this processing is spatiotemporally correlated with the generation of motor SN the processing of vitronectin produces two fragments of kda and kda as previously described for vitronectin isolated from chick yolk the kda fragment lacks the heparinbinding domain and the integrinbinding domain rgd present in the nonprocessed vitronectin glycoprotein here we show that nshh binds to the three forms of vitronectin and kda isolated from embryonic tissue although is preferentially associated with the kda form furthermore in cultures of dissociated neuroepithelial cells the combined addition of nshh and vitronectin significantly increases the extent of motor neuron differentiation as compared to the low or absent inducing capabilities of either nshh or vitronectin alone thus we conclude that the differentiation of motor neurons is enhanced by the synergistic action of nshh and vitronectin and that vitronectin may be necessary for the proper presentation of the morphogen nshh to one of its target cells the differentiating motor neurons
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genomic rna of positivestrand rna viruses replicate via cDNA ie negativestrand rna in MB replication complexes before RC formation virusencoded replication proteins specifically recognize genomic rna molecules and recruit them to sites of replication moreover in many of these viruses selection of replication templates by the replication proteins occurs preferentially in cis this property is advantageous to the viruses in several aspects of viral replication and evolution but the underlying molecular mechanisms have not been characterized here we used an in vitro translation system to show that a kda replication protein of tobacco mosaic virus tmv a positivestrand rna virus binds a terminal â¼nucleotide region of tmv rna cotranslationally but not posttranslationally tmv mutants that carried nucleotide changes in the terminal region and showed a defect in the IB were unable to synthesize negativestrand rna indicating that this IB is essential for template selection a cterminally truncated kda protein but not the FL kda protein was able to posttranslationally bind tmv rna in vitro suggesting that binding of the kda protein to the nucleotide region occurs during translation and before synthesis of the cterminal GABA domain we also show that binding of the kda protein prevents further translation of the bound tmv rna these data provide a mechanistic explanation of how the kda protein selects replication templates in cis and how fatal collision between translating ribosomes and negativestrand rnasynthesizing polymerases on the genomic rna is avoided
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we examined the in vivo mechanisms of amylininduced resistance in concious rats n during min euglycemic insulinclamp pmolkgmin studies amylin or pmolkgmin plasma concentration from x to x m infusion determined a reduction in glucose uptake vs vs and vs mumolkgmin at or pmolkgmin respectively p less than versus insulin alone whereas pmolkgmin amylin infusion plasma concn x m failed to affect insulinmediated glucose disposal after amylin infusion the contribution of wholrinciple of the enzyme immunoassay the sfc assay was used to quantitate ovalbumin oaspecific antibodysecreting cells asc in pigs that had been primed and boosted with oa the sfc CA was also used to quantitate trinitrophenyl tnpspecific asc in chickens that had been primed with tnpconjugated keyhole lympet haemocyanin tnpklh although the classical plaqueforming cell pfc CA cannot reliably detect isotopespecific asc in pigs and chickens it can detect these cells in mice therefore we compared the oa and tnpspecific sfc assays with pfc assays that were specific for these antigens in mice the T0 demonstrated that the sfc assay is superior to the pfc CA in detecting both oaspecific asc and tnpspecific asc the frequencies of oaspecific and tnpspecific sfc detected in mice were of the same order of magnitude as those detected in pigs and chickens we concluded that the sfc assay is the better method for quantitating asc in pigs chickens and probably all domestic animals for which isotypespecific monoclonal antibodies are available
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niguldipine inhibited specific ibe IB more potently in membrane preparations from rat tissues EC in the alpha a subtype hippocampus and VD than those with the alpha b AT1 liver and spleen inhibition curves for niguldipine were better fit by a twosite MM in most tissues although kl values for each site varied markedly between tissues the potency of this lipophilic drug was highly dependent on tissue concentration probably accounting for most of this variability pretreatment of membranes with chloroethylclonidine cec to inactivate the alpha b subtype did not completely eliminate the LA CS for niguldipine particularly in heart saturation analysis showed that niguldipine competitively inhibited both alpha a and alpha b subtypes however substantial MK-801 inhibition was also observed in several tissues analysis of inhibition curves for methylurapidil gave similar proportions of alpha a and alpha b receptor sites as were calculated for niguldipine in various tissues although niguldipine and methylurapidil revealed variable proportions of low affinity sites in cecpretreated hippocampus and HR this was not observed with inhibition curves for wb and phentolamine these results are generally consistent with the previously defined alpha a and alpha b subtypes methylurapidil currently appears to be the best antagonist for discriminating these subtypes niguldipine shows similar selectivity but is complicated by a high lipophilicity however the persistence of LA CS for methylurapidil and niguldipine T3 cec i.c.v. and the noncompetitive effects of niguldipine in some tissues raise the possibility of an additional subtypes of alpha adrenergic receptors in rat tissues
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the national influenza immunization program of offered an ideal opportunity to test the capability of the system in the united states for production and CSD of maximal amounts of inactivated influenza virus vaccine of carefully regulated SQ the four licensed manufacturers were able to produce and distribute greater than million doses of vaccine per week over a week period assays showed that the SQ of these vaccines was comparable to or exceeded that of vaccines produced in recent years under less stressful circumstances because of the extensive PCTs conducted as part of the program it was possible to make an unprecedented DUE of the significance of various laboratory tests of vaccines in relation to their pertinence in prediction of immunogenicity and reactivity for humans this experience demonstrated the superiority of immunodiffusion methods as compared with the standard chick cellagglutination method for CA of vaccine potency qualitative differences in immunogenicity between wholevirus and disruptedvirus vaccines were recognized that are not measured by in vitro potency tests the results also indicated that influenza viral components are responsible for most febrile reactions to the vaccine
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mechanisms accounting for the fact that the eye tends to become and remain emmetropic have been proposed for the developing eye but no such mechanisms have been proposed for the adult eye in the study reported here refractive component data published by sorsby and his coworkers were reanalyzed in terms of the variations in these components with age included in the analysis are component data for one eye of each of subjects from age to age years whose ocular refraction was between plano and d the results of this analysis show that the axial length of the eye appears to decrease during the adult years of life concurrently with a decrease in anterior chamber depth and an increase in the refractive power of both the cornea and the lens it is proposed that a reduction in the AL of the AD eye serves as an emmetropizing mechanism occurring in harmony with the increase in the refracting power of the eye which would otherwise cause the refraction of the eye to move in the myopic direction
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intracellular potentials cl activity and membrane resistances were measured in necturus small intestinal epithelium during cl replacement experiments using conventional or cl selective doublebarrelled microelectrodes a GCl located in the apical membrane and G1 by cyclic nucleotides is demonstrated by ionsubstitution experiments the mean mucosal membrane potential em was mv removal of cl from the mucosal medium by replacement with gluconate evoked a sudden depolarization of em and an immediate increase in the fractional resistance of the mucosal membrane frm the size of the NC in em varied between and mv corresponding to cl to k permeability ratios between and it was inversely related to the initial frm which ranged from to prolonged incubation in lowcl solutions led to a reversal of the initial depolarization and to a sustained hyperpolarization accompanied by a marked increase in frm the new value of em was close to the k equilibrium potential consistent with a SD of cellular cl and the preponderance of a k membrane permeability in the absence of cl this emphasizes the role of cl in establishing em removal of mucosal cl produced a fast decrease in [Cl-]i as measured with cl selective microelectrodes the efflux was consistent with electrodiffusion across the mucosal membrane changes in em paralleled changes in intracellular cl activity indicating the presence of a large cl conductance dibutyryl cAMP or forskolin produced a slow depolarization a decrease in frm and an increased change in intracellular potential in low mucosal cl which on average corresponds to an approximately fold increase in the relative cl permeability these results are consistent with an activation of apical cl conductance the selectivity of cl channels of necturus enterocytes to different anions was obtained from potential measurements the CS of permeabilities was scn greater than i greater than or equal to br greater than no greater than cl much greater than hco greater than gluconate this is consistent with a model involving a weak interaction of the anions with the selectivity filter the selectivity of the anion conductance was maintained after activation with cyclic nucleotides suggesting a single channel for the permeation of the different anions tested rather than parallel channels derivatives of ANT which are potent inhibitors of cl channels in other systems failed to block the apical GCl of necturus enterocytes GCl was also insensitive to furosemideabstract truncated at words
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the erythrocytes of rats treated with dihydroxycholecalciferol or dihydroxycholecalciferol glycoside showed decreased levels of 2,3-DPG the same result has been obtained in vitro indicating a direct effect of the sterol on the red cell the glycoside is less AS than the free sterol in vivo and more active in vitro the decreased levels of diphosphoglycerate induced tissue hypoxia as shown by a higher plasma lactatepyruvate ratio and a three fold increase in plasma erythropoietin concentration
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ID of patients at low risk presenting to the emergency department with CP is a continuing challenge we examined a cohort of lowrisk women with negative cardiac injury markers electrocardiogram with normal results and clinical stability we hypothesized that these patients can be safely and accurately managed in a CP unit cpu may not require predischarge cardiac testing and have an excellent shortterm prognosis the primary end point was L1 cardiovascular events during index admission or followup mean age of the women was ± years to years no patient had a cardiovascular event in the cpu and none of the patients followed for months had a late cardiovascular event most did not receive predischarge cardiac testing the remaining patients had predischarge exercise treadmill test stress imaging or cardiac catheterization of those patients who underwent TM testing almost had no exerciseinduced chest pain and approximately had functional capacity to mets in addition patients were discharged from the cpu T3 hours and n within to hours in conclusion this group of lowrisk women was safely and accurately managed in the cpu and discharged promptly there were no cardiac events on index admission or month followup and in most patients predischarge cardiac testing was unnecessary
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the repeatability and sensitivity of doppler ultrasonographic measurement of lateral digital arterial and A-V blood flow has not been previously determined doppler ultrasonography was used to measure blood flow within the forelimb lateral digital vessels in one normal adult thoroughbred horse on six occasions and in six normal AD TB horses on three occasions each occasion being at least h apart to determine the within and betweenhorse R2 the values obtained from the RA and LL digital vessels did not differ significantly the withinhorse coefficients of variation cv for arterial and A-V measurements were all acceptable the betweenhorse cv were acceptable for all parameters except tava average velocity of first peak of arterial waveform and tavb average velocity of remainder of arterial waveform the withinhorse intraclass correlation coefficients icc demonstrated excellent repeatability or for all parameters except A-V diameter the betweenhorse icc demonstrated good to excellent repeatability or for all parameters except tavb doppler ultrasonography can detect differences of and ml min in digital arterial and A-V flow respectively using measurements from six horses on three occasions power p thus the technique is sufficiently repeatable and sensitive to be able to detect changes in flow during different physiological or pathological states or following pharmacologic intervention
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review the analysis of a protein nutrition of russias population during last five years and ways of its rationalization are presented the scientific background for prosperity of using of soy bean proteins products of their processing and existing of products and halffinished products received from soy is given experimental data on biological value and bioavailability of soy bean proteins and results of clinical evaluation of curative and preventive effects of these various soy products are discussed
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nhydroxynndiacetylbenzidine nhodabz has been shown to be an in vitro metabolite of benzidine in several rodent species and may represent the proximate form of the carcinogen like other arylhydroxamic acids nhodabz may be converted to an ultimate carcinogenic electrophile by metabolic osulfonation in hepatic cytosol to investigate this possibility CL cytosols from rats mice and hamsters were assayed for their ability to catalyze the phosphoadenosine phosphosulfatedependent metabolism of nhodabz and the formation of an adduct with methionine for comparative purposes sulfotransferase activity for nhydroxyacetylaminofluorene nhoaf was also measured in the rat nhodabz and nhoaaf were metabolized at rates of and nmol of arylhydroxamic acid lost per in per mg of protein respectively in the mouse these rates were nmol for nhodabz and less than nmol for nhoaaf sulfotransferase activity for these substrates in hamster CL cytosol could not be detected less than nmolminmg the inclusion of Met in sulfotransferase incubation mixtures and subsequent heating resulted in the formation of methylmercapto arylamides from both nhodabz and nhoaaf from to of the nhodabz metabolized was trapped and recovered as an adduct while to of the nhoaaf metabolized was similarly obtained a methylmercaptonndiacetylbenzidine derivative was also obtained by reaction of nacetoxynndiacetylbenzidigation
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kinins are metabolized by metallopeptidases present in different tissues the aim of this study was to evaluate employing functional studies in isolated human umbilical vein the possible participation of angiotensinconverting enzyme neutral endopeptidase and APP as an inactivation pathway of bradykinin as well as assess if the EC SL is involved in this process CRCs to BK were constructed T3 min incubation period on human UV rings with and without endothelium and enzymatic inhibitors were applied min before construction of CRCs the presence of EC was confirmed by histological studies bradykinininduced contractile responses were potentiated in human UV without endothelium when compared to IN tissues application of captopril μm angiotensinconverting enzyme inhibitor or phosphoramidon μm NEP inhibitor induced a leftward shift of bradykininelicited responses in human UV with endothelium while no effect was observed in tissues denuded of EC under the same treatment exposure to apstatin μm aminopeptidase p inhibitor did not potentiate bradykinininduced effects in intact human umbilical vein when angiotensinconverting enzyme and neutral endopeptidase were concomitantly inhibited there was a higher potentiation of bradykininelicited responses compared to the effects observed under individual inhibition of either enzyme moreover CR curves to fr a nonpeptidic bradykinin b receptor agonist were not modified under dual enzymatic inhibition in conclusion our results demonstrate for the first time the functional relevance of angiotensinconverting enzyme and NEP localized on the endothelial SL acting concurrently as a BK inactivating pathway in isolated human UV
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a shifting fluid level sfl was detected by a and bscans in eyes all eyes had a hemorrhage into the vitreous in of the eyes the vitreous hemorrhage resulted from proliferative diabetic retinopathy in and seven eyes respectively the hemorrhage was a complication of closed vitrectomy and SB procedures in eight eyes the hemorrhage resulted from severe penetrating ocular trauma the sfl was characterized by a highamplitude echo on ascan and straight horizontal or vertical linear echo on horizontal or vertical bscan respectively it showed a typical shift toward the most posterior portion of the globe when the eye was moved in the different positions of gaze the sfl was overlying the retina in eyes and was suspected to be subretinal in five eyes sfl represented a SL of sedimented red blood cells on the surface of the retina or choroid
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mutations in cystic fibrosis transductance regulator gene cftr are known to result in some forms of male infertility an association between cftr gene mutations and obstructive azoospermia in cystic fibrosis cf and in congenital unilateral and bilateral absence of vas deferens cuavd cbavd has been proven however the role of cftr gene mutations in the etiology of nonobstructive azoospermia as well as in the regulation of spermatogenesis remains unsolved
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the treatment of rats with single subcutaneous sc doses of mercuric chloride mgkg plus potassium dichromate mgkg resulted in greater effects on water consumption urine volume body weight and urinary electrolyte excretion than produced by mercuric chloride CT the dose of potassium dichromate CT had no effects on renal function urine volume at hr was increased twofold over mercuric chloride CT similarly potassium excretion by these animals at hr was significantly decreased compared to controls these animals were oliguric by hr after the i.t. urine osmolality of rats receiving the combination of the metals remained lower than controls throughout the day experimental period measurement of renal arterial blood flow by EM flow probe T3 subcutaneous injection of saline mercuric chloride mgkg potassium dichromate mgkg or the combination produced no change over a hr period at hr and at hr and the glomerular filtration rate gfr of these rats was not affected over the same period of time
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TNF is considered to play a pivotal role in many inflammatory and illness states in our previous study we found that nimesulide a cox selective inhibitor prevents the lipopolysaccharideinduced elevation in plasma tnfalpha in rats the present study was undertaken to elucidate the effect of nimesulide on tnfalpha levels in the paw exudate of rats pretreated with lipopolysaccharide lps rats were injected subplantar with lps microgpaw in the right hind which resulted in a prominent increase in paw exudate tnfalpha levels peaked at one hour post injection in rats pretreated with nimesulide mgkg ip the elevation in TNF in the paw exudate was significantly reduced as compared to the lps treated group these results further stress the multiple antiinflammatory effects of nimesulide
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the influence of varying concentrations of two amine reducing agents commonly used in commercial lightcured composites nndimethylptoluidine dmpt and nndimethylaminoethyl methacrylate dmaema on the DC dc knoop hardness and compressive and transverse strengths of an unfilled lightcured resin was investigated the dc obtained from employing two different internal standard peaks carbonyl co at cm and URE nh at cm was compared the resin consisted of wt TEGDMA tegdma and wt bismethacryloxyethoxycarbonylaminotrimeth ylhexane udma activated with mol camphorquinone cq and varying concentrations of either dmpt or dmaema the dc calculated by use of either co or nh absorption peak as an internal reference showed similar values for both amines the physical properties were directly related to dc and appeared to reach maximal values at an aminecq molar ratio of the dc however appeared to reach a maximum at an aminecq molar ratio of generally for the same aminecq molar ratios the polymers formulated with dmaema had greater dcs and better PCS properties than those formulated with dmpt
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we report the retrospective outcomes of unrelated donor urd transplants in patients with ALL leukemia all in CR1 cr who received transplants between and median age was years range years a total of had a white blood RCC wbc more than x l extramedullary disease achieved cr more than weeks from diagnosis had adverse cytogenetics and had tcell one a total of were hla wellmatched partially matched with their donors and were hlamismatched at month median followup incidences of acute grade iv iii to iv and chronic graftversushost disease were and respectively fiveyear treatmentrelated mortality trm relapse and overall survival were and respectively in multivariate analyses trm was significantly higher with hlamismatched donors and tcell depletion relapse risk was higher if the diagnostic wbc was more than x l AF associated with poorer survival included wbc more than x l more than weeks to cr cytomegalovirus seropositivity hla mismatching and tcell SD nearly of adults with all in cr survive years T3 urd transplantation relapse risks were modest trm is the major cause of treatment failure selecting closely hlamatched urd and reducing trm should improve results
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the perceived position of a moving target at a particular point in time indicated by a flash is often judged to be different from its actual location here we show that the position of a target moving in depth is also systematically mislocalized we used three types of targets moving in depth at a range of speeds from to cms i a target realistically rendered that included concordant looming disparity and perspective cues ii a random dot surface whose depth was defined by disparity without concordant perspective or looming cues iii a surface of dynamic random dots whose deand invasion they also coopt macrophage traits these include a wide diversity of molecules and pathways regulating adhesion matrix alterations neoangiogenesis motility chemotaxis immune signaling pathways and even multidrug resistance proteins evidence is presented that these traits could be generated through macrophagetumor cell F0 fusion has been reported in numerous animal tumor models and was recently documented in human cases F0 could also account for the high degree of aneuploidy and plasticity in CA and for immune evasion one common trait of myeloidtumor fusion is the high expression of betabranched nglycans used by macrophages in SVR migration betabranched oligosaccharides have long been associated with metastasis in animal models and were recently found to be common in a wide diversity of human cancers we suggest that betabranched OS in human cancer may reflect widespread RT cell fusion viewing the CA cell as a myeloid hybrid provides new approaches towards understanding and treating this complex disease
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we compared intravenously administered ciprofloxacin with ceftazidime in a randomized doubleblind T0 patients received ciprofloxacin mg intravenously every hours or ceftazidime g intravenously every eight hours with PL infusions to maintain blinding therapy with metronidazole was added for suspected or documented intraabdominal infection thirtytwo of the ciprofloxacintreated patients were evaluable for determination of efficacy and had bacterial isolates from sites thirtysix of the ceftazidime patients were evaluable for determination of efficacy and had bacterial isolates from sites seven of bacteremic patients had no identifiable primary focus the most commonly isolated pathogens were escherichia coli streptococcus pneumoniae staphylococcus aureus and klebsiella pneumoniae cure rates and bacteriologic eradication rates were comparable nine patients did not improve patients with treatment failures in the ciprofloxacin group included a quadriplegic patient with relapse of urinary tract infection with bacteremia k pneumoniae another patient with bacteremia pseudomonas aeruginosa pneumonia proteus vulgaris and urinary tract infection p vulgaris providencia sp died on the first treatment day the third patient s aureus and streptococcus pneumoniae pneumonia had a new aspiration pneumonia develop on the third day the pneumococcus also persisted undrained s pneumoniae empyema caused the fourth ciprofloxacin TF and the fifth patient had a relapse of s aureus pneumonia with bacteremia one ceftazidimetreated patient died of pneumococcal pneumonia on the first day another had persistent SE and listeria bacteremia despite hours of treatment two other patients had pneumonia s aureus and p aeruginosa respectively and completed full courses of ceftazidime therapy without improvement five patients had pneumococcal bacteremia four patients were cured one of two patients in the ciprofloxacin group and three of three patients in the ceftazidime group significant increases in the number of platelets four patients with ciprofloxacin treatment one patient with ceftazidime treatment and declines in the number of platelets one patient with ciprofloxacin treatment one patient with ceftazidime treatment were observed intravenously po ciprofloxacin is comparable with ceftazidime and is a safe and effective antibiotic for the treatment of patients with serious infections including bacteremia
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reelin a secreted glycoprotein was recently demonstrated to be involved in the pathogenesis of CA however its oncogenic MICs in nonhodgkin lymphoma nhl remain unclear therefore we aimed to evaluate the PET role of reelin in nhl and the underlying molecular mechanisms in the present study we analyzed reelin expression in lymphoma tissues and cell lines using immunohistochemistry immunofluorescence staining qrtpcr and western blotting then the expression of reelin was silenced with short hairpin rna shrnaexpressing plasmid in the nhl cell line a the effects of reelin SD on cell growth migration and invasion in vitro were determined by cck and transwell assays FC was used to examine the cell cycle status and cellular apoptosis hoechst fluorescence staining was used to analyze morphologic changes caused by apoptosis the second messenger camp was analyzed by elisa in addition we used nude mice to evaluate the tumorigenic ability of reelin aberrant upregulated levels of mrna and protein of reelin were observed in lymphoma tissues and cell lines knockdown of reelin suppressed lymphoma growth migration and invasion ability of a furthermore reelin SD induced cell cycle arrest in gg phase and promoted apoptosis of a cells further analysis indicated that knockdown of reelin downregulated the expression of cdk and il and activated caspase in shreelin group elisa CA showed camp at a lower level in shreelin group sq a camp pathway inhibitor treated a cells and revealed likely effects the RT size in a mouse model injected shreelin was significantly smaller than controls there results suggest that reelin played essential roles in the development of lymphoma and might be a potential drug target in lymphoma
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recent studies indicated an enhanced expression of endothelin et in the kidney contralateral to the vascular clip in twokidney oneclip kc goldblatt hypertension we proposed that the enhanced intrarenal et production might be responsible for altered haemodynamic and excretory capability of the unclipped kidney uk of kc renovascular hypertensive rats therefore we examined the changes in arterial pressure and SRF in the clipped ck and uk simultaneously in response to chronic administration of the selective eta receptor blocker a given orally at a dose of mgkgday for weeks starting from the beginning of the th week of clipping SP averaged mmhg in control rats n and mmhg in treated rats n and the difference was not statistically different glomerular filtration rate gfr renal plasma flow rpf and renal V1 resistance rvr in the uk were not different between control and treated CG data were then analyzed by classifying rats as moderate hypertensives map mmhg and severe hypertensives map mmhg in the moderately hypertensive group average map was mmhg and mmhg in control n and treated n CG respectively in the severely hypertensive group average map was mmhg and mmhg in control n and treated n CG respectively gfr and rpf were significantly improved in the uk of only the severely hypertensives who received the antagonist however the eta antagonist blunted the sodium loss in both ck and uk of severely hypertensive rats we conclude that eta receptors do not play a role in the progression of hypertension in kc renovascular hypertensive rats yet eta receptors play an important role in altering renal hemodynamics of the unclipped kidneys in severe degrees of renovascular hypertension
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the age dependence of the oval cell response and bile duct carcinomas of male f rats exposed to a cyclic choline deficiencyethionine cde diet weeks on week off supports the concept of loss of potential of liver stem cells to form cancers with aging livers of rats exposed at weeks of age demonstrated a robust and widespread oval cell proliferation followed by cholangiofibrosis and bile duct metaplasia with extensive mucinous cysts throughout all lobes and induction of cholangiocarcinomas ccas in seven of eight rats livers of rats exposed beginning at weeks of age had much less oval cell response and cholangiofibrosis with only of rats developing a cca livers in old months when started rats remained virtually unaffected with minimal oval cell proliferation only occasional and small foci of ductular dysplasia and none of rats developed ccas in contrast to most published studies using uninterrupted CD plus a carcinogen HCC carcinoma hcc was not observed under the conditions of this study
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patients with pagets disease were treated with disodium etidronate at an oral dose of mgkgd and followed up for an average of years each course of treatment lasted months and was repeated once or several times per cent of the patients with PS had improved by the end of the follow up period and per cent of the asymptomatic patients showed none of the complications that might have been expected preventive treatment with etidronate not been undertaken the course of the disease deteriorated in of the patients between start and finish of the study but the result was sometimes incomplete or in some doubt for patients receiving treatment the annual incidence of coxarthropathy was per cent in patients with medullary involvement indicated by spasmodic paraparesis during the initial assessment oral disodium etidronate always had a curative effect in patients with cranial involvement the condition worsened fairly frequently with hypoacusis arising or deteriorating in per cent of the patients twenty three fractures occurred including in pagetic bone with an incidence of respectively and per cent patientyears the risk of fracture did not seem to be increased when etidronate was used at a low dose among the side effects observed there was a delayed increase in bone pain in per cent of the patients the PS generally resolving except in one case where a fracture occurredabstract truncated at words
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the role of cardiovascular risk reduction in patients with diabetes mellitus is significant as several AF have been found to promote accelerated atherosclerosis in persons with diabetes including hyperglycemiainduced endothelial dysfunction impaired fibrinolysis increased PLT aggregation PI instability dysfunctional arterial CR and fibrotic and calcified CAs recent attention has focused on identifying a cardiovascular biomarker that would propose a better noninvasive way to detect or visualize subclinical cardiovascular disease and prevent cardiovascular events this article reviews the use of commonly used cardiovascular risk assessment tools and emerging biomarkers including coronary artery calcium scanning metabolomics genomics and the role of optimal revascularization and risk reduction strategies and their impact on reducing risk in patients with cardiovascular disease and diabetes
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one hundred and twentyseven male patients were subjected to antiulcer surgery for duodenal ulcer resistant to hreceptor antagonist treatment fiftyfour group a had been on conservative treatment for up to months while the remaining group b had been on conservative treatment for more than and up to months of the group a underwent truncal vagotomy with pyloroplasty group a and highly SV group a of group b underwent truncal vagotomy with pyloroplasty group b and HSV group b followup ranged between and months mean months there were one ulcer recurrence in group a none in group a nine in group b and five in group b the difference between group a and group b being statistically significant p less than there was significantly higher nonulcerassociated morbidity T3 truncal than after highly SV p less than no significant difference in the degree of PAO reduction was observed between the patients with and those without ulcer recurrence these findings show that the administration of hreceptor antagonists for more than months in duodenal ulcer patients who however fail to have their ulcer healed is associated with high recurrence rate T3 vagotomy it is suggested that such patients should undergo vagotomy as soon as they fulfill the criteria of resistance to hreceptor antagonists if CT has lasted for more than months vagotomy plus antrectomy has to be considered as the surgical treatment for these patients with the possible cost of higher nonulcerassociated morbidity
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a mechanistic pathway for the formation of the structurally characterized manganeseamidehydrazide pinned butterfly complex mnμphnnphκnnμphnnphκnnμnhphl l thf py is proposed and supported by the use of labeling studies kinetic measurements kinetic competition experiments kinetic isotope effects and HAT reagent substitution and via the isolation and characterization of intermediates using xray diffraction and electron paramagnetic resonance spectroscopy the data support a formation mechanism whereby bisbistrimethylsilylamidomanganeseii mnnr where r sime reacts with nndiphenylhydrazine phnhnhph via initial proton transfer followed by reductive nn bond cleavage to form a longlived mniv imido multinuclear complex coordinating solvents activate this cluster for abstraction of hydrogen atoms from an additional equivalent of phnhnhph resulting in a mniiphenylamido dimer mnμnhphnrl this dimeric complex further assembles in fast steps with two additional equivalents of phnhnhph replacing the terminal silylamido ligands with ηhydrazine ligands to give a dimeric mnμnhphphnnhphl intermediate and finally the addition of two additional equivalents of mnnr and phnhnhph gives the pinned butterfly cluster
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the pathogenesis of idiopathic pulmonary arterial hypertension pah remains poorly understood the present authors recently reported that mice with vasoactive intestinal peptide vip gene disruption show a spontaneous phenotype of pah with pulmonary vascular remodelling and lung inflammation to explore the underlying molecular mechanisms in this MM it was examined whether absence of the vip gene might alter the expression of additional genes involved in the pathogenesis of pah as singlegene deletions in the absence of hypoxia rarely result in significant pulmonary vascular remodelling lung tissue from mice with targeted disruption of the VIP gene vip mice and from control mice was subjected to wholegenome gene microarray analysis and the results validated with quantitative RT pcr lungs from vip mice showed a wide range of significant gene expression alterations including overexpression of genes that promote pulmonary V1 smooth muscle cell proliferation underexpression of antiproliferative genes and upregulation of proinflammatory genes in conclusion vasoactive intestinal phighest frequency of expression with positive IS in n n n and n of cases respectively we studied the role of alphavbeta in detroit human pharyngeal carcinoma cells in vitro and in vivo prominent alphavbeta expression was detected on RT xenografts at the tumorstroma interface resembling the expression on human head and neck carcinomas nonetheless coculturing cells in vitro with matrix proteins did not upregulate alphavbeta expression detroit cells showed alphavbetadependent adhesion and activation of transforming growth factorbeta tgfbeta that was inhibited with an alphavbeta blocking antibody g although both recombinant soluble tgfbeta receptor typeii rstgfbeta riifc and g inhibited tgfbetamediated smad phosphorylation in vitro there was no effect on proliferation conversely in vivo g and rstgfbeta riifc inhibited xenograft RT growth by n p and n p respectively suggesting a role for the microenvironment in this response however stromal collagen and smooth SMA content in xenograft sections were unchanged with treatments although further studies are required to consolidate in vitro and in vivo results and define the mechanisms of RT inhibition by alphavbeta antibodies our findings support a role for alphavbeta in human CA and underscore the therapeutic potential of CF blocking alphavbeta antibodies
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a novel horizontal MM is presented for multitrait analysis of longitudinal traits through random regression analysis combined with single recorded traits weekly adfi on test for danish duroc landrace and yorkshire boars were available from the national test station and were collected from to kg bw single recorded production traits of adg from birth to kg bw adg adg from to kg bw adg and lean meat percentage lmp were available from breeding herds or the national test station the horizontal model combined random regression analysis of feed NI fi with single recorded traits of adg lmp and adg in the horizontal MM the fi data were horizontally structured with fi on each week as a trait the additive genetic and litter effects were modeled to be common across different fi records by reducing the rank of the covariance matrices using second and firstorder legendre polynomials of age on test respectively the fixed effect and random residual variance were estimated for each weekly fi trait residual FI rfi was derived from the conditional distribution of fi given the breeding values of adg and lmp the heritability of fi varied by week on test in duroc to landrace to and yorkshire to the heritability of rfi was lowest and highest in wk and respectively in duroc and wk and and and respectively in landrace and yorkshire the proportion of fi genetic variance explained by rfi ranged from to in duroc from to in landrace and from to in yorkshire average daily gain from to kg bw and adg heritabilities were moderate in duroc and respectively landrace and respectively and yorkshire and respectively lean meat percentage heritability was moderate in duroc and large in landrace and yorkshire the genetic rho of fi with adg increased by week on test followed by a decrease from wk in duroc and a decrease in dam L1 breeds defining rfi as genetically independent of production traits leads to consistent and easy interpretable breeding values the genetic parameters of traits in the feed efficiency complex and their dynamics over the test period showed breed differences that could be related to the fatness and growth potential of the breeds the horizontal model can be used to simultaneously analyze repeated and single recorded traits through proper modeling of the environmental variances and covariances
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the long arm of the y chromosome contains nonoverlapping regions termed azoospermia factor azf with great influence on male fertility microdeletions at these regions minimise the males ability to father offsprings in this preliminary T0 we attempted to screen the presence or absence of twenty y chromosomes sequencetagged CS sts associated with fertility in infertile and down syndrome ds males genomic dna from fertile infertile and karyotyped ds males was extracted and amplified in multiplex PCR reaction pcr containing primer pairs that amplify yspecific sts that cover PET regions associated with azf and spermatogenesisrelated genes our results indicated the integrity of the y chromosome at the fertility markers for both the fertile and down syndrome males however the results of the infertile males showed the presence of microdeletions at these yspecific sts three samples showed y chromosome microdeletion when blood and seminal fluid genomic dna were assayed while two samples showed microdeletion only when seminal fluid genomic dna was assayed the current study demonstrated that the molecular genetic aspect of infertility should be given proper attention when dealing with infertility cases furthermore our results indicate the importance of genetic counselling in managing infertility cases
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ED is one of the prime challenges confronting the treating physician its prevalence is directly proportional to aging it is imperative to comprehend the intricate mechanism of erection in order to individualize the approach to management thus it is appropriate to evaluate the etiology of erectile dysfunction normal aging as well as psychogenic V1 neurogenic and endocrinologic causes andor those due to structural abnormalities of the penis should be considered when evaluating details to determine its probable cause an increasing use of drugs a legacy of civilization has considerably compounded the problem therapy for erectile dysfunction apart from psychosexual counseling includes medical treatment by alpha adrenoceptor antagonists dopamine agonists phosphodiesterase type inhibitors sublingual AP hydrochloride or HT transdermal or transurethral corporeal drug delivery are other possible treatment modalities vacuum devices and surgical approaches are considered relevant only in refractory cases
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the formation of a highmolecular weight complex between Sp and factin depends on the presence of a third CSK constituent protein electron microscopy shows that in this ternary complex the AFs are linked by bridges which have the appearance of Sp the spectrin must be in the tetrameric state for such bridges to form the dimer is evidently univalent for it binds but forms no crosslinks gactin also fails to form extended complexes it is inferred that in the native cytoskeleton the spectrin is tetrameric and associated with and probably oligomers of actin
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the recent advances in the antiviral therapy of HC have significantly lowered the threshold for offering such therapy to patients sustained virological response rates of are achieved T3 weeks of combination therapy with peginterferon alpha and ribavirin in patients with TT infection in patients with a TT or infection weeks of combination therapy leads to a SR rate of almost the us NIH consensus states that every patient with hepatitis c should be considered for antiviral therapy identification of the patients selection for therapy the provision of good information guidance of the patient during therapy and a successful management of SE lead to better treatment compliance and are of paramount importance in obtaining maximal therapeutic efficacy supportive guidance during SA withdrawal programmes and the adequate use of selective serotonin reuptake inhibitors should be part of these measures
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objective to evaluate thirdyear pharmacy students ability to effectively design and apply root cause analysis rca to a sentinel event and to analyze student responses for Az of proficiency and deficiency methods this study involved a comprehensive review of rca key assessments from students in spring the performance assessments consisted of a review of each students rca worksheet and flow diagram as well as the page narrative reflection results the majority of students were able to successfully design an rca but had challenges with components factfinding session disclosure plan and a flow diagram several students perceived challenges to conducting a formal rca in certain health care settings which included assembling an rca team and gathering relevant facts a lack of transparencysafe environment within organizations and creating a plan for multiplesequential errors conclusion most students were able to design an rca process but encountered difficulty with some components students also identified challenges in applying the approach in certain health care arenas
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we studied the nature of diffuse type of SPs sp in the brains of six autopsied subjects with alzheimertype dementia atd the densities of sp in the entorhinal cortex were evaluated using serial sections stained by four different methods compared with beta protein IS as a reference the modified bielschowsky stain and the periodic acidmethenamine silver pam stain labeled similar numbers of sp whereas the bodian stain labeled only a minor proportion of these the vast majority of bodiannegative plaques were diffuse plaques which were seen as illdefined areas of fine fibrillar material T3 beta protein immunostain with formic acid i.c.v. modified bielschowsky stain and pam stain they were not stained by congo red or periodic acidschiff stains double staining using bodian and beta protein methods demonstrated that diffuse plaques were free of swollen neurites argyrophilia of the diffuse plaques shown by the modified bielschowsky and pam stains became undetectable when sections were pretreated with formic acid such treatment made the diffuse plaques immunoreactive to beta protein antiserum suggesting that diffuse plaques consisted mainly of amyloid but not neuritic components the diffuse plaques were distributed in various cortical Az and in the amygdala and comprised a considerable population of the sp in the atd brains
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the aim of this study is to compare the efficacy of selective laser trabeculoplasty as initial or adjunctive treatment for primary openangle glaucoma in a retrospective chart review
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adjuvant radiotherapy for breast CA can lead to late cardiac complications the highest radiation doses are likely to be to the anterior portion of the HR including the left anterior descending coronary artery lad the purpose of this work was to assess the radiation doses delivered to the heart and the lad in respirationadapted radiotherapy of patients with leftsided breast CA
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the assessment of pulmonary CF including ventilation and perfusion status is important in addition to the evaluation of structural changes of the lung parenchyma in various pulmonary diseases the dualenergy computed tomography dect technique can provide the pulmonary functional information and high resolution anatomic information simultaneously the application of dect for the evaluation of pulmonary function has been investigated in various pulmonary diseases such as pulmonary embolism asthma and chronic obstructive lung disease and so on in this review article we will present principles and technical aspects of dect along with clinical applications for the assessment pulmonary function in various lung diseases
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the bifunctional enzyme DHF reductasethymidylate synthase dhfrts carries out two distinct reactions with the dihydrofolate produced by the tscatalyzed reaction acting as the ATP for the dhfrcatalyzed reaction BD simulation techniques were used to investigate the possible role of electrostatics in determining efficient channeling of the ATP by explicitly simulating ATP diffusion between the two active sites with a substrate charge of almost all ATP molecules leaving the ts active site reached the dhfr ac effects of age on mlss in male subjects age yr range yr height cm range cm body mass kg range kg performing an incremental load test to determine Wmax and several constant load tests for mlss measurement on a cycle ergometer mlss mmoll range to mmoll and mlss intensity related to maximal workload range were independent of age mlss HR rate min range min decreased p with increasing age whereas absolute w range w and relative mlss workload wkg range to wkg and absolute w range w and relative Wmax wkg range to wkg increased p with age the age independence of mlss supports the theory that NM AF may contribute to the frequently observed changes in response to given exercise with physical maturity more than changes in oxidative metabolism andor glycolysis
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the committee on the family of the group for the advancement of psychiatry has introduced the global assessment of relational SF-36 garf a scale that describes and quantifies the relational context within which patients live and problems occur the garf is intended to serve as a device that alerts clinicians to pay attention to the DUE not only of individuals but also of relational functioning in this article we describe from a historicals perspective the scientific and political context within which this scale was developed the garf is analogous to axis v of the dsm gaf scale global assessment of functioning that is used to assess individual SF-36 the garf is a composite derivative of three L1 dimensionalized constructs namely joint problem solving organization and emotional climate we provide five clinical vignettes to illustrate the process of arriving at garf ratings finally we discuss caveats and limitations for use of the garf at present and make recommendations for research projects and training methods that may enhance the value of this instrument in the future
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CH is a common postmortem finding in owl monkeys in most cases the animals do not exhibit clinical signs until the disease is advanced making antemortem diagnosis of subclinical disease difficult and treatment unrewarding we obtained echocardiograms electrocardiograms and thoracic radiographs from members of a colony of owl monkeys that previously was identified as showing a incidence of gross myocardial hypertrophy at necropsy to assess the usefulness of these modalities for antemortem diagnosis no single modality was sufficiently CS and TPS to detect all monkeys with CH electrocardiography was the least sensitive method for detecting owl monkeys with hypertrophic cardiomyopathy thoracic radiographs were more CS than was electrocardiography in this context but cannot detect animals with CH without an enlarged cardiac silhouette echocardiography was the most CS method for identifying CH in owl monkeys the most useful parameters suggestive of left VVI hypertrophy in our owl monkeys were an increased average left VVI wall thickness to chamber radius ratio and an increased calculated left VVI myocardial mass parameters suggestive of dilative cardiomyopathy were an increased average LVMM and a decreased average ratio of left ventricular free wall thickness to left ventricular chamber radius when all noninvasive diagnostic modalities PE echocardiography electrocardiography and thoracic radiography were used concurrently the probability of detecting hypertrophic cardiomyopathy in owl monkeys was increased greatly
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the nasal cavity and sinus system is extensive but its examination is limited listening to PLB and respiration can afford useful clues to underlying abnormality examination of the nasal cavity may reveal the pale swollen mucosa of allergic rhinitis or the overdeveloped lining seen in perennial rhinorrhoea and hypertropic rhinitis localised hypertrophy gives rise to the nasal polyp which usually forms in the region of the ethmoid sinus atrophic rhinitis is a destructive condition of the nasal lining sinusitis may be open or closed presenting with localised pain and MSD of the eye in the case of frontal or ethmoidal abscess or mucocoele deformities of the external nose or nasal SP are often encountered during examination epistaxis may be caused by bleeding simply from kiesselbachs vessels or may be an early feature of telangiectasia or cardiovascular diseases tumors are rarely found but include papillomata and the mucous membrane melanoma
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the purpose of this T0 was to evaluate the agreement among spectraldomain optical coherence tomography standard automated perimetry sap and optic disc stereo photography in the PCD of glaucomatous progression
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multiple logistic regression models were used in a crosssectional T0 to determine the relation of fasting glycemia to angiographically assessed coronary i.a. disease cad in men aged to years who were stratified according to fasting blood glucose concentrations mmoll and to mmoll or to mgdl waist circumference vs or cm and fasting triglyceridemia vs or mmoll or vs or mgdl for this purpose nondiabetic IFG was defined as from to mmoll to mgdl compared with normoglycemic controls fasting glycemia mmoll or mgdl without PH of cad in the absence of HTG waist IFG was not predictive of cad however the risk of cad was markedly higher among subjects characterized by both the hypertriglyceridemic waist phenotype and the presence of IFG odds ratio confidence intervals to p compared with the normoglycemic group with low waist circumferences and triglyceride C2 thus the results of the present study emphasizes the importance of other underlying metabolic abnormalities such as abdominal obesity and related atherogenic dyslipidemia in the modulation of the cad risk associated with HG
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the pulmonary donor pool would increase substantially if lungs could be safely Tx after cessation of circulation to determine whether the addition of the free radical scavenger dimethylthiourea to the perfusate of cadaver lungs could improve VG CF canine donors were sacrificed and lungs retrieved hours after death in a blinded fashion DMTU was added to the modified eurocollins solution and infused into recipients n perioperatively a PL was included in the perfusate of control animals n donor animals were ventilated with oxygen only during flush and harvest recipients were rendered dependent upon the single left transplanted lung by occlusion of the RPA and bronchus hour after transplantation ventilation was maintained at a constant inspiratory oxygen fraction of recipients were followed up for hours or until death three of conn be carried out during a single workingday the method was tested by typing a set of homozygous cell lines as well as a local panel previously typed by pcroligotyping also patients waiting for transplantation were typed to test the method in a routine setting the results suggest that this kind of RPA gives reliable DR types and works well in the routine use
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to study the effect of chronic ethanol administration on the enzyme activities involved in the glycosylation processes glycosidases and glycosyltransferases we used week ethanoltreated female wistar rats and paircontrol rats biological material was MF of microsomes and plasma membrane obtained by subcellular fractionation technique ethanol treatment increased with statistical significance the vmax of nacetylbetadglucosaminidase p less than betadglucuronidase and alphadmannosidase p less than MICs from microsomal fractions and likewise it increased the km value of betadglucuronidase p less than in vitro doses of ethanol m were added to delucidate hypothetical membrane tolerance responses however in vitro addition of ethanol provoked no differential effects in treated and UT rats glycosyltransferase assays were carried out using csugar derivatives we detected several glycosyltransferase MICs in both microsome and BPM fractions chronic ethanol SE appeared to affect nacetylneuraminyltransferase activity from both membrane fractions producing a greatly increased incorporation in the presence of ASF glucosyl and mannosyltransferase activities from BPM fractions were also altered by ethanol treatment producing an increased CEA when reaction was performed in the presence of phosphatidylcholine dolicholphosphate liposomes
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several methods were developed for the solidphase synthesis spps of coloured peptides and peptide libraries at first a bifunctional red compound nethylntertbutyloxycarbonylaminopropylaminophenylazobe nzoic acid bocepab was coupled with chloromethyl resin to obtain a new solid support suitable for spps using boc chemistry MMP synthesized on this coloured resin had the chromophore at their ctermini nterminally coloured MMP were synthesized on a traditional solid support coupled with chromophoric carboxylic acid before cleavage a model pentapeptide phealavalleugly and its ten derivatives were synthesized and their properties studied it was found that the presence of chromophores decreases the water solubility of MMP however insertion of solubilizing tags pentalysine sequences or polyoxyethyl chains into the molecule of any coloured derivative resulted in enhancement of the solubility the rphplc hydrophobicity indexes phi of the coloured MMP were also determined because phi values are closely related to their water solubility a coloured pentapeptide library was synthesized using the portioningmixing method each component of this library contained the red azo dye epab and the pentalysine tag before the last coupling step the samples were not mixed all of the sublibraries obtained T3 cleavage were readily soluble in water giving intense red solutions the effect of chromophore epab andor pentalysine solubilizing tag on the biological activity was also studied potencies of the bovine neurotensin fragment and its different coloured and pentalysine derivatives were compared in isolated longitudinal muscle strips of guinea pig ileum it was shown that the hexapeptide with pentalysine tag had almost the same activity as the fragment itself the activity of the epabderivative was found to be rather low however the presence of the solubilizing tag in the coloured hexapeptide compensated the negative effect of the chromophore
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to review available evidence about the safety and efficacy of alemtuzumab for induction of IS in HR transplant recipients
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we showed previously that lselectindependent recirculation of naive cd cells is essential for development of primary responses in PN recent studies suggest that lselectin is also required for lymphocyte entry into gut mucosal NALT that include peyers patches and MES CL NO here we show that antilselectin antibody mel inhibited homing of a rigorously purified homogenous population of naive cd cells into both of these tissues as well as PN directly demonstrating a role for this receptor in regulating entry into gutassociated sites however in intact animals treatment with mel resulted in the loss of naive cd cells cdrbhi cdlo from PN but not PPs whereas MES lymph nodes were intermediate in this regard in mice primed by parenteral immunization with KLH klh primary cd responses were readily detected in both peyers patches and MES CL nodes and were not affected by SE to mel indeed similar frequencies of klhspecific cd cells were recovered from both of these tissues irrespective of mel treatment the results indicate that interactions with lselectin can be circumvented to allow entry of naive cd cells into PPs but not PN
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a rat series of nonapeptides and their acetylated versions were successfully prepared using solidphase synthetic techniques each nonapeptide was rich in alphaalphadialkylated amino acids one aminopiperidinecarboxylic acid api and six alphaaminoisobutyric acid aib residues and also included lysines or lysine analogs two residues the incorporation of the protected dipeptide fluorenylmethyloxycarbonyl fmocaibaiboh improved the purity and overall yields of these de novo designed MMP the helix preference of each nonapeptide was investigated in six different solvent environments and each MMP antimicrobial activity and cytotoxicity were studied the helical amphipathic design of these peptides was born out most prominently in the nterminally acetylated MMP most of the peptides exhibited modest activity against escherichia coli and no activity against staphylococcus aureus the nonacetylated peptides concentrations or microm and the acetylated peptides concentrations or microm did not exhibit any significant cytotoxicity with normal nonactivated mu macrophages
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the sorption course of anthracene acene into brønstedacidic medium pore mfi zeolites was monitored by in situ epr and diffuse reflectance uvvisible absorption over one year weighed amounts of solid acene were merely exposed to hnzsm hnalonsion with the following brønsted acid site bas densities n dehydrated at k under argon the weighed amounts correspond to acene per zeolite unit cell acene is found to be incorporated as IN molecules in purely siliceous mfi silicalite monte carlo simulations indicate that acene lies in the intersection of straight and zigzag channels in contrast the presence of bass on the inner surface of channels induces spontaneous ionization of acene ionization potential ev the CS as acenehnzsm is caused by the strong coulombic field gradient of siohal bas in the absence of any Le acid site the rate and yield of ionization are found to increase dramatically with bas density increase the stabilization of acenehnzsm is explained by the tight fit between the rodshape acene and the channel dimensions and especially by the compartmentalization of ejected electrons as aloh centers away from the initial site of ionization the final CR occurs after more than one l and acquired forms that afflict patients these patients show a lengthening of the repolarization phase of the cardiac cycle which can be best visualized on an electrocardiogram ecg the ecg changes can include qt interval the time between the start of the q wave and the end of the t wave as seen on an ecg and t wave abnormalities as well as progression to TP and VVI fibrillation the ecg changes are most commonly elicited by physical activity ES and certain medications this condition represents a challenge for the oral and maxillofacial surgeon patients with lqts must receive proper medical management and a controlled and anxietyfree surgical environment the purpose of this article was to present a review of lqts and provide recommendations for effective surgical management additionally a case report of a patient with lqts treated by one of the authors has been included
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the objective of this study is to describe aspects of healthrelated quality of life hrqol in mexican patients with antineutrophil cytoplasmicassociated vasculitis aav crosssectional comparison study includes patients with established aav and a comparison group with rheumatoid ICA ra chronic kidney disease ckd and healthy subjects variables considered were sociodemographic data comorbidities laboratory SLEDAI damage and physicians and patients global assessment phga and ptga the following measurements were done pittsburg sleep QI multidimesional fatigue inventory mfi HAD scale short form questionnaire sf and health assessment questionnaire patients with aav were included median age years and female significant differences were found only in the bodily pain domain of the sf p aspects of disease relevant for aav patients were fatigue and lack of energy visual CA neuropathy RI ICA and sinusitis greater total score on mfi p and worse ptga p were associated with worse physical health higher phga values were associated with worse PCS SQ of life p greater fatigue score p greater anxietydepression score p and worse ptga p were associated with worse mental health quality of life no differences were found in prevalence of sleep impairment anxiety depression or disability between CG aav patients experienced more general and PCS fatigue p and reduced activity p than HS but similar to ra and ckd patients vasculitis has negative effects on patients PCS and mental hrqol
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monodisperse αfeo porous nanospheres with uniform shape and size have been synthesized via a facile templatefree route xray diffraction xrd SEM microscopy sem transmission electron microscopy tem highresolution tem hrtem and raman spectroscopy were employed to characterize the product showing the high quality of the asprepared αfeo porous nanospheres furthermore the αfeo porous nanospheres can selectively detect ethanol formaldehyde and acetic acid with a rapid response and high sensitivity from a series of flammable and toxiccorrosive gases indicating their potential applications for high sensitivity gas sensors
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pathological gambling pg shares clinical characteristics such as craving and loss of control with substance use disorders and is thus considered a behavioral addiction while functional alterations in the mesolimbic reward system have been correlated with craving and relapse in substance use disorders only a few studies have examined this brain circuit in pg and no direct comparison has been conducted so far thus we investigated the neuronal correlates of reward processing in pg in contrast to alcoholdependent ad patients and healthy subjects eighteen pg patients ad patients and controls were investigated with a monetary incentive delay task in which visual cues predict the consequence monetary gain avoidance of loss none of a fast response to a subsequent target stimulus PET magnetic resonance imaging data were analyzed to account for possible confounding factors such as local gray matter volume activity in the right VS during loss anticipation was increased in pg patients compared with controls and ad patients moreover pg patients showed decreased activation in the RA VS and RA medial prefrontal SC during successful loss avoidance compared with controls which was inversely associated with severity of gambling behavior thus despite neurobiolximab treatment this condition is caused by the reactivation of varicella zoster virus infection in the geniculate ganglion of facial nerve in the hosts IS she was treated immediately with valaciclovir and hydrocortisone and the complete recovery was achieved at months after the onset this is the first report of ramsay hunt syndrome as an adverse effect of infliximab in RA ICA
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angiogenic properties have been shown in preinvasive cervical lesions our goal was to determine the angiogenesis in cervical IEL neoplasms cin the relationship between microvessel counts histopathological parameters and the clinical outcome in invasive CC comparison of microvessel counts from normal epithelium with that from cin and invasive carcinoma showed significant increases in precancerous lesions and invasive CA p microvessel density assessed by cd immunostaining was found to be associated with the overall survival in women with clinical stage ib CC p there was a significant association of microvessel density p with relapsefree survival in patients with regional CL node metastasis
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benzodiazepine bdz EDC are a group of ampa receptor inhibitors and are drug candidates for treating neurological diseases involving excessive ampa receptor activity we investigated the mechanism by which gluaqflip receptor channel opening is inhibited by two bdz derivatives ie aminophenyldihydroethylenedioxyhbenzodiazepinone bdz and its aminochlorophenyl analogue bdz both EDC have a ethylenedioxy moiety instead of the methylenedioxy feature present in the structure of gyki the prototypic bdz compound using a laserpulse photolysis approach with a time resolution of μs and a rapid solution flow technique we chiation by gata and its overexpression increases hemoglobin production rates in vitro however the role of abcme in erythropoiesis in vivo is unknown here we report for the first time that erythrocyte development in mice requires abcme abcme mice die at day of gestation showing nearly complete eradication of primitive IDE and lack of hemoglobinized cells at day abcme erythroid cells fail to differentiate because they exhibit a marked increase in apoptosis both in vivo and ex vivo erythroid precursors are particularly CS to oxidative AS and abcme in the heart and its yeast ortholog multidrug resistancelike have been shown to protect against oxidative AS thus we hypothesized that increased apoptosis in abcme erythroid precursors was caused by oxidative stress within this context abcme deletion causes an increase in mitochondrial O2- and protein carbonylation in erythroid precursors furthermore treatment of abcme erythroid progenitors with the mitochondrial antioxidant mntbap superoxide dismutase mimetic supports survival ex vivo differentiation and increased hemoglobin production altogether our findings demonstrate that abcme is essential for erythropoiesis in vivo
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the aim of this study was to evaluate the PET role of the interaction between the sternocleidomastoid muscles and the mandibular corners ism in the context of the stomatognathic apparatus
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day morning i.v. to pubertal male rats of polypeptide epithalamin preparation obtained from cattle epiphysis in dose of mg g body mass induced the increase of serotonin epiphyseal concentration night peak nacetylserotonin and melatonin and didnt produce any essential influence on methoxytryptamine oxy and methoxyindoleacetic acid level it has been concluded that epiphyseal MMP and indoles interact according to ultrashort connection epiphyseal peptides point of application is the reaction of tryptophan transformation into serotonin and its further metabolism in nacetylserotonin and melatonin it has been suggested that the increase of epiphyseal melatonin production is on the basis of epithalamin therapeutic action
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we estimated selfreported secondhand smoke shs SE in california at home and at work
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neuronal migration is an essential feature of the developing NS but the intracellular signaling mechanisms that regulate this process are poorly understood during the formation of the ENS ens in the moth manduca sexta the migration of an identified set of neurons the ep cells is regulated in part by the heterotrimeric guanylnucleotide IB PG protein goalpha using an in vivo SC preparation for developing embryos that allows direct access to the ens we have shown that ep cell migration is similarly regulated by intracellular ca treatments that increased intracellular ca inhibited the migratory process whereas buffering intracellular ca induced aberrant migration onto inappropriate pathways imaging the spontaneous changes in intracellular ca within individual ep cells showed that actively migrating neurons exhibited only small fluctuations in intracellular ca in contrast SN that had reached the end of migration displayed large transient ca spikes similar ca spikes were induced in the ep cells by g protein stimulation an effect that was reversed by removal of external ca stimulation of go in individual ep cells by i.t. of either activated goalpha subunits or mastoparan also inhibited migration in a cadependent manner these results suggest that the regulation of neuronal migration by g proteins involves a cadependent process requiring ca influx
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fiftyone cases of acquired immunodeficiency syndrome aidsrelated primary BB lymphomas arpbl were investigated for clinical characteristics HIV virus hivassociated disorders histopathologic features IP epsteinbarr virus ebv infection and when frozen tissue was available oncogene rearrangements arpbl occurred late in the course of aids and were usually associated with other SVR or cerebral disorders and with a low level of cd lymphocytes all cases were high grade lymphomas according to the WF or updated kiel classification and often displayed a multifocal pattern thirty cases were classified as immunoblastic with plasmacytic differentiation cases were LCLs with an immunoblastic component or CB polymorphic lymphomas and were small noncleaved nonburkitt lymphomas working formulation this latter category is classified as burkittslike lymphoma in the real nomenclature one case could not be classified because of necrosis arpbl showed a high level expression of activation and adhesion molecules the presence of ebv was detected if so female relatives might be able to withstand greater impairments than men before developing psychotic PS consequently in a sample that was limited to nonpsychotic relativesas in the present studythere could be overrepresentation of both less impaired men and more impaired women alternative explanations and limitations of the T0 are also discussed
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dipolyunsaturated phosphatidylcholines from bovine retina contain a whole series of unusual fatty acids methyl esters from these acids are very strongly retained on polar and nonpolar GLC stationary phases on thin layers of silicaagno they separate as tetra penta and hexaenoic fatty acid methyl esters T3 hydrogenation the three polyunsaturated fractions give the same series of saturated methyl esters having or carbon atoms high pressure liquid chromatography as well as gasliquid chromatography indicates that the new components of the three fractions are evencarbon homologs of well known polyenoic fatty acids of the n and n families since they behave as series of carbon tetraenoic n pentaenoic n and n and hexaenoic n fatty acids their occurrence in phospholipid molecules also having docosahexaenoate explains the separation of major dipolyunsaturated phosphatidylcholines from retina into dodecaenoic undecaenoic and decaenoic fractions after argentation thin SL chromatography using high pressure liquid chromatography the latter are resolved into individual species having double bonds and carbon atoms the unusual pcs are thus endowed not only with the highest degree of unsaturation but with the longest hydrocarbon chains yet reported for vertebrate glycerophospholipids it is shown that phosphatidylcholines containing the novel fatty acids are highly concentrated in photoreceptor CM and that they occur in the retina of vertebrates so distant in evolution as fish birds and various mammals
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isoproturon is a selective herbicide belonging to the phenylurea family and widely used for pre and postemergence control of annual weeds soil amendments eg SOCs or dissolved organic matter may affect environmental SMB and BA of pesticides however whether the physiochemical process of isoproturon in soils is affected by organic amendments and how it is affected in different soil types are unknown to evaluate the impact of low molecular weight organic acids lmwoa and dissolved organic matter dom on sorptiondesorption and mobility of isoproturon in soils comprehensive analyses were performed using two distinct soil types eutric gleysols and hap udic cambisols our analysis revealed that adsorption of isoproturon in eutric gleysols was depressed and desorption and mobility of isoproturon were promoted in the presence of dom and lmwoa however the opposite result was observed with hap udic cambisols suggesting that the soil type affected predominantly the physiochemical process we also characterized differential components of the soils using threedimensional excitationemission matrix eem fluorescence spectroscopy and fourier transform infrared ftir spectroscopy and show that the two soils displayed different intensity of absorption bands for several PET groups
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human uterine C2 carcinomas yum antagonists produce a nearly uniform cessation of both tonic and phasic coronary responses regardless of whether different vasoconstrictors receptors or pathways of ca delivery are involved thus our animal experiments as well as successful clinical trials highlight the outstanding efficacy of calcium antagonists in NT all types of extramural coronary artery spasm this action of calcium antagonists seems to be the predominant haemodynamic factor in relieving or preventing acute ischemic episodes especially in coronary heart disease with spastic components
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we have developed a procedure for the determination of a common mutation in exon of the human lipoprotein lipase lpl gene the mutation is due to a cg transversion which creates a premature termination codon serter and results in a truncated lpl molecule lacking the CT dipeptide sergly the mutation can be detected by polymerase chain reaction pcr amplification of exon using a modified amplimer that produces a bp product containing a site for the restriction enzyme hinf in the presence of the mutation g S2 the g S2 was in strong linkage disequilibrium with a hindiii restriction fragment length polymorphism rflp S2 in intron genotype determinations for the mutation can be performed by pcr amplification of genomic dna digestion with hinf and analysis of the products by polyacrylamide gel PACE the allelic frequency of the serter mutation in normal male caucasian controls was the frequency of the mutation was lower in a group of subjects with primary hypertriglyceridemia compared to NL controls
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hemoblot a new immunological faecal occult blood test produced by gamma angleur belgium was characterized and compared with another immunological test hemeselect smithkline diagnostics usa and with a guaiac test hemoccult ii smithkline diagnostics the analytical sensitivity of hemoblot is mg haemoglobing faeces and the test is specific for human haemoglobin in addition symptomatic patients who had to undergo a colonoscopy were tested using the three tests two criteria were considered for the analysis the blood criterion any pathology likely to cause colorectal or other one and the precancerouscancerous criterion the pathology being either a colorectal polyp cm or a CC considering both criteria the sensitivity of hemoblot was significantly higher than the sensitivity of hemoccult and respectively for the blood criterion and and for the precancerouscancerous criterion sensitivity and specificity did not differ statistically between hemoblot and hemeselect but hemoblot was faster and simpler to perform it could be widely used in mass screening
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the objective of this T0 was to characterize blaoxa harbouring acinetobacter indicuslike strains from cattle including genomic and phylogenetic analyses antimicrobial susceptibility testing and evaluation of pathogenicity in vitro and in vivo nasal and rectal swabs n from cattle in germany were screened for carbapenemnonsusceptible acinetobacter spp thereby two carbapenem resistant acinetobacter spp from the nasal cavities of two calves could be isolated malditof mass spectrometry and s rdna sequencing identified these isolates as a indicuslike a phylogenetic tree based on partial rpob sequences indicated closest relation of the two bovine isolates to the a indicus type strain at and human clinical a indicus isolates while whole genome comparison revealed considerable intraspecies diversity high mimimum GABA concentrations were observed for carbapenems and other antibiotics including fluoroquinolones and gentamicin whole genome sequencing and pcr mapping revealed that both isolates harboured blaoxa localized on the chromosome and surrounded by interrupted tn transposon structures since the pathogenic potential of a indicus is unknown pathogenicity was assessed employing the galleria g mellonella infection MM and an in vitro cytotoxicity assay using a human lung epithelial cells pathogenicity in vivo g mellonella killing CA and in vitro cytotoxicity assay of the two a indicuslike isolates was lower compared to a baumannii atcc and similar to a lwoffii atcc the reduced pathogenicity of a indicus compared to a baumannii correlated with the absence of important virulence genes encoding like phospholipase cc acinetobactin outer membrane protein baua rndtype efflux system proteins aders and adeab or the trimeric autotransporter adhesin ata the emergence of carbapenemresistant a indicuslike strains from cattle carrying blaoxa on transposable elements and revealing genetic relatedness to isolates from human clinical sources requires further investigations regarding the pathogenic potential genomic characteristics zoonotic risk and putative additional sources of this new acinetobacter species
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the aim of this T0 was to establish the value of indirect ct venography ctv in clinical practice within the uk
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an episode of diarrhea causes WL and a temporary cessation of growth in infants and children diarrhea is accompained by malabsorption of sugars nitrogen fats and micronutrients the mechanisms by which acute diarrheal disease produce malabsorption have not been studied carefully the nutritional costs of malabsorption may pose a major threat if diarrhea becomes chronic or recurrent the hydrogen breath test for carbohydrate malabsorption does not require intubation or blood drawing and can be used in children to help clarify the importance of carbohydrate intolerance in the duration and perpetuation of acute diarrhea and IBO
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cellulose NCs cncs are promising biosourced building blocks for the production of high performance materials in the last ten years cncs have been used in conjunction with polymers for the design of multilayered thin films via the layerbylayer assembly technique herein CP chains have been replaced with positively charged inorganic gibbsite nanoplatelets gn to form hybrid nanoparticleonly composite films a combination of atomic force microscopy and neutron reflectivity experiments was exploited to investigate the growth and structure of the films data show that the growth and density of gncnc films can be tuned over a wide range during preparation by varying the ionic strength in the cnc suspension and the film drying protocol specifically thin and dense multilayered films or very thick more porous mixed slabs as well as intermediate internal structures could be obtained in a predictable manner the influence of key physicochemical parameters on the multilayer film buildup was elucidated and the film architecture was linked to the dominating interaction forces between the components the degree of structural control over these hybrid nanoparticleonly films is much higher than that reported for cncpolymer films which offers new properties and potential applications as serelated mechanical responses two different models a finite element MM and a CP mechanical MM were used to simulate the mechanical responses force loading and deformation experienced by the hp at heelstrike both excessive force loading and deformation are believed to be detrimental to the heel pad in the simulation the corresponding force loading deformation and net effect the adding of the normalized force loading and deformation were calculated for each hps value two models found consistent trends that the stiffer the hp the greater the force loading and the lower the deformation in contrast a softer hp experienced a lower force loading and a greater deformation both the force loading and deformation were at medium levels and the net effect was minimal at a hps value between the highest and lowest values used in the simulation the modeling result suggested that the optimum hps should be in a state at which both the force loading and deformation were at medium C2 and the net effect was minimal in terms of the healthrelated mechanical responses the abnormal level of hps either too high or too low may correlate to respective pathologies
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antioxidant activity of MRPs mrps derived from four sugaramino acid maillard reaction model systems glucose glc or ribose rib reacted with glycine gly and llysine lys were examined in terms of chemical properties and molecular weight fractionation of MRP ribamino acid model systems produced mrps with higher antioxidant activity than glcamino acid MM mrps p riblys ribgly glclys glcgly in the same sugar or same CAA MM systems antioxidant activity of mrps was negatively related to the final ph fluorescent intensity and the content of dicarbonyl EDC antioxidant activity positively related to the production of latestage browning mrps fraction i from the glclys MM system separated by gel filtration chromatography had the highest oxygen radical absorbance capacity orac value micromol troloxg mrp fraction iv from the riblys MM system had a higher orac value compared to fraction iii this result indicated that high molecular weight mrps do not necessarily have higher antioxidant activity compared to low molecular weight mrps
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leukocyte transendothelial migration tem is absolutely fundamental to the inflammatory response and involves initial pseudopod protrusion and subsequent polarised migration across inflamed EC ezrinradixinmoesin erm proteins are expressed in leukocytes and mediate cell shape changes and polarity the spatiotemporal organisation of erm proteins with their targets and their individual contribution to protrusion during tem has never been explored here we show that blocking IB of moesin to phosphatidylinositol bisphosphate pip
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the aim of this work was the estimation of resveratrol content in two successive extracts etoac and meoh of peanuts arachis hypogaea l pericarp of egypt by tlc and hplc methods results showed the presence of and microgml RES in etoac and meoh extracts respectively the in vitro carbohydrate hydrolyzing enzyme inhibition activity showed higher percentage of inhibition of alphaamylase alphaglucosidase and betagalactosidase with etoac and than with meoh extract and but lower than the standard RES concentration and and the reference acarbose and it could be concluded that the content of resveratrol in peanut pericarp is related to the percentage of inhibition activity of carbohydrate hydrolyzing enzymes these results strongly reflect the benefit of using peanut pericarp the waste product as a natural antidiabetic agent
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a yearold woman presented to the emergency department with a week history of anorexia fatigue general malaise and a day history of fever clinical examination revealed livedo reticularis across the anterior aspect of her knees and a pansystolic murmur laboratory DUE found neutrophil leucocytosis elevated c reactive protein and blood cultures grew streptococcus acidominimus transthoracic echocardiography displayed vegetation on the mitral valve and a left atrial myxoma she was treated with intravenous benzylpenicibased upon AS and coping theory this study examined whether perceived family support protects the impact of negative emotional experience with dyslexia on selfesteem
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the authors describe four patients with symptomatic lung disease morphologically representing a septal capillary injury syndrome temporally associated with serologic and SC evidence of AS cytomegalovirus cmv infection but without classic cp changes the authors conducted a thorough review of clinical data microscopic examination and in situ hybridization to detect cmv mrna encoding IE1 protein the assay detects transcripts that encode early and immediate early proteins in two cases additional tissue was available for direct immunofluorescent studies the disease process in each of the patients was morphologically indistinguishable from the DP of organ injury associated with AD including a small vessel microvascular injury syndrome involving skin and lung and immune complex mediated glomerulonephritis cytopenias were seen in all cases most commonly thrombocytopenia all treated patients demonstrated improvement on combined ganciclovir and lowdose steroid therapy cmv infection may be of pathogenetic importance in some cases of AH especially when accompanied by peripheral blood cytopenia in otherwise healthy patients and if clinical worsening occurs in the setting of a traditional immunosuppressive regimen typically used to treat vasculitis
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we developed an CA using a realtime QPCR rqpcr for the quantitative assessment of minimal residual disease mrd in childhood lymphoid malignancies by using a consensus vregion probe combining a allelespecific oligonucleotide aso reverse primer our strategy employs a set consisting of a consensus vregion probe an aso reverse primer and a patientspecific forward primer for clonal antigenreceptor igh immunoglobulin heavy chain tcr tcell receptor gene rearrangements ighaso and tcraso rqpcr assays the limit of PCD in both assays was copies of the target cell equivalents we tested the assays in childhood malignancies cases of B-ALL and of nonhodgkins lymphoma high correlation coefficients of the standard curves and pcr efficiency were achieved with all primerprobe sets in of the patients aso primers could not be designed because there was no junctional nsequence the quantitative data suggest that the copy number of clonal BCR markedly decreased T3 induction therapy in of patients and that patient relapsed and died of the disease consensus probes make it possible to examine a C1 number of patients with only a limited number of probes the strategy used for ighaso and tcraso rqpcr assays is accurate and reliable in the clinical prospective study of mrd in childhood lymphoid malignancies
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in a case of bilateral recurrent haemorrhagic pleural effusion due to asymptomatic pancreatitis the diagnosis was suggested by the presence of amylase in the PF when other possible causes had been excluded abdominal computed tomography and laparotomy confirmed the diagnosis no communications could be seen between the peritoneal and pleural space at LAP
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the worlds oceans are a global reservoir of persistent organic pollutants to which humans and other animals are exposed although it is well known that these pollutants are potentially hazardous to human and environmental health their impacts remain incompletely understood we examined how persistent organic pollutants interact with the drug efflux transporter pglycoprotein pgp an evolutionarily conserved defense protein that is essential for protection against environmental toxicants we identified specific congeners of organochlorine pesticides polychlorinated biphenyls and PBDEs that inhibit mouse and human pgp and determined their environmental C2 in yellowfin tuna from the gulf of mexico in addition we solved the cocrystal structure of pgp bound to one of these inhibitory pollutants pbde polybrominated diphenyl ether providing the first view of pollutant IB to a drug transporter the results demonstrate the potential for SB and inhibition of rat pgp by ubiquitous congeners of persistent organic pollutants present in fish and other foods and argue for further consideration of transporter inhibition in the assessment of the risk of SE to these chemicals
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the optimal method of providing safe and ERP sedation for outpatients undergoing lengthy dental operations is unclear we provided MAC conscious sedation for consecutive dental implant procedures using intravenous midazolam and fentanyl as primary pharmacologic agents midazolam was po by multiple intermittent i.t. or via continuous infusion the dose of midazolam required for the induction of sedation ranged from mg to mg maintenance of adequate sedation required a mean midazolam administration rate of mgh to mgh and a mean fentanyl administration rate of mcgh to mcgh continuous monitoring allowed for rapid detection and treatment of separate hemodynamic and respiratory problems there was no evidence of patient injury and all patients returned home on the day of surgery a postoperative telephone survey revealed that of patients had complete amnesia for operative events were satisfied with monitored anesthesia care and would desire a similar anesthetic technique for future procedures
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purification of proteins containing disordered regions and participating in transient complexes is often challenging because of the small amounts available after purification their heterogeneity instability andor poor solubility to circumvent these difficulties we set up a methodology that enables the production of stable complexes in large amounts for structural and functional studies in this chapter we describe the methodology used to establish the best cell culture conditions and buffer compositions to optimize soluble protein production and their stabilization through protein complex formation two examples of challenging protein families are described namely the human steroid nuclear receptors and the hiv preintegration complexes
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several different in vivo and in vitro bioassays are used to evaluate melanosome transfer efficacy from MC to keratinocytes however these methods are complicated and time consuming here we report on a simple rapid direct and reliable in vitro method for observing the process of melanosome transfer from melanocytes to KCs first we selected and tested a melanoma cell L1 rpmi that can normally synthesize melanin and transfer from mature melanosomes to KCs in vitro we cocultured these cells with a human ovarian teratoma transformed epidermal carcinoma cell L1 which is also capable of accepting melanosomes transferred from melanocytes as in normal keratinocytes the cells were cocultured for h and double labeled with fitcconjugated antibody against the melanosomeassociated protein trp and with cyconjugated antibody against the keratinocytespecific marker keratin the cells were examineduse we have analyzed the distribution of various subsets of alternatively spliced exons based on their inclusion level and evolutionary PH versus increasing intron length alternative exons may be included in either a L1 or minor fraction of all transcripts known as majorform and minorform exons respectively we find that majorform exons are seven to eightfold more likely to be contained in short introns nt than minorform exons which occur preferentially in longer introns since minorform exons are more likely to be novel approximately this implied that novel exons arise more frequently in longer introns to test this hypothesis we used whole genome alignments to classify exons according to their phylogenetic age we find that older exons ie exons that are conserved in all mammals predominate at shorter intron lengths for both major and minorform exons in contrast exons that arose recently during primate evolution are more prevalent at longer intron lengths nt this suggests that the observed rho of longer intron lengths with alternatively spliced exons may be at least partly due to biases in the probability of exon creation which is higher in long introns
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our objective was to assess efficacy and tolerance of thrombolysis using mgkg of alteplase in patients with massive pulmonary embolism defined as the association of a pulmonary embolism with shock we retrospectively included patients presenting with a MPE confirmed by either scintigraphy or SCT patients were treated on the basis of a standard rationale followed by thrombolysis with mgkg tPA over a period of minutes hospital mortality vital signs before and hours after thrombolysis and incidence of hemorrhagic events were recorded five patients died of these deaths occurred during the first hours T3 hospital admission systolic and diastolic blood pressure sp were significantly improved hours after the beginning of thrombolysis five minor hemorrhagic events occurred this study demonstrates that for patients with pulmonary embolism and shock a bolus treatment with alteplase is potentially effective and well tolerated
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herpes simplex virus hsv has several potential advantages as a vector for delivering genes to the nervous system the virus naturally infects and remains latent in SN and has evolved the ability of highly efficient retrograde transport from the site of infection at the periphery to the site of latency in the spinal ganglia hsv is a C1 virus potentially allowing the IS of multiple or very C1 transgenes furthermore hsv does not integrate into the host chromosome removing any potential for insertional activation or inactivation of cellular genes however the OD of hsv vectors for the CNS system that exploit these properties has been problematical this has mainly been due to either vector toxicity or an inability to maintain Tg expression here we report the OD of highly disabled versions of hsv deleted for icp icp and icpopen reading frame p and with an inactivating mutation in vp these viruses express only minimal C2 of any of the immediateearly genes in noncomplementing cells transgene expression is maintained for extended periods with promoter systems containing elements from the hsv latencyassociated transcript promoter j a palmer et al j virol unlike lessdisabled viruses these vectors allow highly effective gene delivery both to neurons in culture and to the CE NS in vivo gene delivery in vivo is further enhanced by the VA transport capabilities of hsv here the vector is efficiently transported from the site of inoculation to connected CS within the nervous system this is demonstrated by gene delivery to both the striatum and substantia nigra following striatal inoculation to the spinal cord spinal ganglia and brainstem following injection into the spinal cord and to retinal ganglion SN following i.t. into the superior colliculus and TH
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EC barrier dysfunction leads to increased EC permeability and is an early step in the OD of vascular inflammatory diseases such as atherosclerosis interferonγ ifnγ a proinflammatory cytokine is known to cause increased endothelial permeability however the mechanisms by which ifnγ disrupts the endothelial barrier have not been clarified this study aimed to investigate how ifnγ impairs the EC barrier integrity by specifically examining the roles of caldesmon adherens junctions ajs and p mitogenactivated protein map kinase in ifnγinduced EC barrier dysfunction ifnγ exhibited a biphasic effect on caldesmon localization and both the structural organization and protein expression of ajs in the EP h ifnγ induced the formation of peripheral caldesmon bands and discontinuous ajs while aj protein expression was unchanged interestingly ifnγ also stimulated caldesmon phosphorylation resulting in actin dissociation from caldesmon at h conversely changes seen in the late phase h included cytoplasmic caldesmon dispersal aj linearization and junctional area reduction which were associated with reduced membrane cytoskeletal and total aj protein expression in addition ifnγ enhanced myosin IB to caldesmon at h and persisted up to h furthermore inhibition of p map kinase by sb did not reverse either the early or late phase changes observed these data suggest that ifnγ may activate signaling molecules other than p map kinase in conclusion our findings enhance the current understanding of how ifnγ disrupts EC barrier CF and reveal potential therapeutic targets such as caldesmon and ajs for the treatment of ifnγassociated V1 inflammatory diseases
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LI describes a process by which preexposure of a stimulus without consequence retards the learning of subsequent conditioned associations with that CS- it is well established that latent inhibition in rats is impaired by increased dopamine function and potentiated by reduced dopamine function previous evidence has suggested that these effects are modulated via the mesoaccumbens dopamine projections we have now undertaken three experiments to examine this issue directly especially in the CS of one study in which LI was reported to be unaffected by direct i.t. of amphetamine into the accumbens LI was studied using the effect of preexposure of a tone CS- on the subsequent formation of a CER to the tone hydroxydopamineinduced lesions of dopamine terminals in the nucleus accumbens resulted in potentiation of latent inhibition bilateral local injections of the dopamine antagonist haloperidol into the nucleus accumbens microgside before conditioning also potentiated LI moreover such injections were able to reverse the disruptive effect of SVR amphetamine mgkg ip on latent inhibition BL local injection of amphetamine microgside into the nucleus accumbens before conditioning was able to disrupt LI provided that it was preceded by a SVR i.t. of amphetamine mgkg h earlierwe conclude that the attenuation of latent inhibition by increased dopamine function in the nucleus accumbens is brought about by impulsedependent release of the neurotransmitter occurring at the time of conditioning the previously reported failure to disrupt latent inhibition with intraaccumbens amphetamine is probably due to impulseindependent release of dopamine the implications of these conclusions for theories linking disrupted LI to the attentional deficits in schizophrenia and to the dopamine theory of this disorder are discussed
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CAN can is a byproduct of chlorination of drinking water epidemiological studies indicate that it might present a hazard to human health the present T0 was designed to investigate the potential adverse effects of intrauterine SE to can on fetal body weight and development of the MSK system in mice at gestation day Pr mice were given can or mgkgday till gestation day uteri were then examined and live fetuses were collected weighed and evaluated for any malformations high doses of can mgkg significantly elevated fetal anomalies and reduced fetal viability CAN at a dose of mgkg did not affect fetal viability and significantly reduced fetal body weight subsequent experimentation was performed using this dose level histological examination of fetal axial skeleton indicated that can resulted in delayed appearance of endochondral ossification centers widening of the vertebrae and destruction of the calcified zone in addition the skeletal MF were markedly distorted were small in size and were widely separated by connective tissue both connective tissue perimysium and endomysium were less cellular compared with control sections the histological findings were further confirmed by assessing the morphometric changes ratios of calcified cartilage to noncalcified cartilage areas in both control and canexposed CG were determined also skeletal muscle fiber diameter of canexposed fetuses was significantly decreased compared with control group in conclusion intrauterine SE to low C2 of can decreases fetal body weight and induces malformations in the MSK system in mice
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a computerbased highresolution highspeed system is described for the digitization of TV images of human gbanded chromosomes online directly from a TSM the digitized data are processed by a computer to determine the TL and CEN index of individual chromosomes and to obtain an integrated density profile representing the band pattern the density profile is reduced by the computer to a series of dark and CS bands each with a defined position width and density the results are displayed by the computer on a TV monitor in a ze reduction of denatured dna an easily measurable effect in e coli wildtype cells was carcinogeninduced repair polymerization when initiated by nacetoxynacetylaminofluorene or bromomethylbenzaanthracene it depended upon an atprequiring step ctp gtp or utp did not substitute for atp dna repair synthesis was inhibited by pchloromercuribenzoate and quinacrine in uvra uvrb and uvrc mutants no carcinogenstimulated dna synthesis could be detected indicating that steps involved in pyrimidine dimer excision are also involved in chemorepair in reca recb and recc mutant cells repair synthesis was stimulated by the carcinogens to a normal extent this evidence excludes the atpdependent recbc deoxyribonuclease and reca gene products as playing an important role in carcinogeninduced excision repair pola cells showed drastically reduced C2 of rapair polymerization indicating that dna polymerase i is the main polymerizing enzyme as determined by dna size reduction in ALP sucrose gradients the arylalkylating carcinogens caused endonucleolytic cleavage of endogenous dna in wildtype cells this incision step was most effectively performed in the ADP utp ctp and gtp were only slightly effective incision was inhibited by PCMB and quinacrine when exposed to the arylalkylating carcinogens uvra uvrb and uvrc mutant cells did not perform the incision step in the ADP suggesting the involvement of the respective gene products in the initiation of chemorepair
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the sulfation of psyllium was carried out with sulfur trioxidepyridine in DMF three sulfated PSY derivatives named sp sp and sp were characterized by sulfur content determination elemental analysis ftir and surface charge analysis the sulfated derivatives were also evaluated for their morphological and rheological properties water uptake capacities swelling volumes and in vitro bile acidbinding abilities the results showed that sulfation reduced the gelling capacity of PSY and the viscosity of its solution and significantly increased its bile acidbinding capacity sulfation might also increase the water uptake ability of PSY but might decrease its swelling capacity the three sulfated psyllium derivatives had in vitro IB capacities against CA and chenodeoxycholic acids comparable to that of cholestyramine resin on a per same as it is weight basis the bile acidbinding capacity of sp was about fold of that observed for the original psyllium preparation under the same assay conditions the results from this T0 suggest that sulfation is a possible approach to obtain novel psyllium derivatives with desirable physicochemical functional and biological properties for utilization in functional foods or supplemental and pharmaceutical products
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the general architecture of the MA was studied at the ultrastructural level in drosophila cultured cells its two main characteristics are a very polarized spindle and a strong compartmentalization ensured by large remnants of the nuclear env such compartmentalization has previously been reported for the rapid syncytial divisions of the early embryo a similar finding in these cells with a long cycle strongly suggests that this organization constitutes a general mechanism for mitosis in drosophila we followed the modifications of these structures after a heat shock of or min at degrees c contrary to interphase cells MI cells appear very CS to hyperthermia this stress treatment induced a disruption of the MI spindle a reappearance and an extension of the GA an inactivation of microtubule nucleation and a disorganization of the centrosome this organelle seems the first to be affected by the heat shock response the centrosome is not only inactivated but also is structurally affected during the recovery phase T3 HS the MI cells presented a remarkable ringshaped accumulation of electrondense material around the centrioles we conclude that in drosophila cells the mitotic phase and more specifically the centrosome are targets of the AS response
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several lines of evidence support the involvement of protein IMT phosphatase receptor type beta ptprb in addiction generally ptps interact with both neuronal receptors and cell adhesion molecules and appear to play roles in neurite growth and neuronal differentiation we previously identified a role of the cell adhesion molecule nrcam in polysubstance abuse vulnerability in humans as well as in the rewarding effects of abused drugs in animals furthermore we have identified genomic regions containing several CAMs as polysubstance abuse vulnerability loci by wholegenome association study the present study of HSA loci revealed that the sergly polymorphism in ptprb is associated with SA vulnerability in three independent casecontrol samples europeanamerican from coga families usa n p europeanamerican from maryland usa n p and africanamerican from maryland usa n p however this polymorphism was not associated with alcoholism in japanese subjects n p to confirm the importance of ptprb in responses to drugs of abuse the expression of ptprb in mouse BB was examined after chronic morphine treatment and found to be upregulated in some BB regions thus ptprb is an addictionassociated and drugregulated gene whose SCV may affect substance abuse vulnerability
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various treatment procedures for oral leukoplakia have been reported however T3 some treatments oral leukoplakia show recurrence andor malignant transformation even following complete resection furthermore patients with OL may develop new lesions in other oral cavity locations laser surgery for oral mucosal lesions has been reported to have many advantages and it is widely used in the treatment of oral leukoplakia in previous studies recurrence and malignant transformation from the lesion have occasionally been observed following laser surgery we reviewed the records of OL patients treated with laser surgery to assess its clinical usefulness it has been reported that the rate of recurrence was while malignant transformation was for oral leukoplakia treated with laser surgery in the present study there was recurrence and malignant transformation after laser surgery this was similar to previous findings this suggests that nonhomogeneous leukoplakia on nonkeratinized epithelia ie the tongue mucosa has a high risk for malignant transformation so lesions should be excised T3 detecting abnormal epithelia using vital tissue staining the wound healing process after laser surgery was satisfactory and no significant complications were observed management of oral leukoplakia prevents not only recurrence and malignant transformation but also postoperative dysfunction laser surgery is an excellent procedure that is able to overcome these problems
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ion mobility spectrometers have found widespread use for the screening of explosives chemical warfare agents and illicit drugs these instruments often rely on drifttime calibrants to perform qualitative ID such calibrants are suitable to determine the reduced mobility of EDC but may not necessarily provide information on instrument performance these calibrants are often internal and behave in a fashion similar to that of analytes in terms of sensitivity to a variety of instrumental and environmental variations ideally test materials used to evaluate instrument performance would be insensitive to these changes current calibrants are sometimes not designed to satisfy these requirements and although several instrument test materials are also in use a consensus has not been reached on best practices a rat series of tetraalkylammonium salts has been proposed as one alternative instrumental test material set and has been successfully used for electrospray IMS imsms experiments this T0 extends these analyses to thermal desorption ims instruments the reduced mobility k values for these EDC measured on a thermal desorption ims SF-36 are reported and are similar to those reported for electrospray ims the R2 of daily instrument response to these EDC is small further supporting their use as test materials the ionization SMB and thermal profile of the EDC in the thermal desorption process are discussed
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the passage via the LRT of the macromolecule bovine SS Al bsa mol wt and the nonapeptide deaminocysteinedarginine vasopressin ddavp mol wt was assessed for h T3 intratracheal instillation in young developing pigs the plasma C2 of immunoreactive bsa increased with time reaching a maximum between h after instillation and the main portion of bsa in plasma appeared IN as assessed by crossed immunoelectrophoresis the ddavp levels reached a maximum T3 h the time to reach maximal plasma C2 increased with the age of the pig for bsa while no such effect was observed for ddavp the total lung passage as calculated by dividing the area under the plasma leveltime curve obtained T3 intratracheal instillation with that obtained after i.v. elimination curve showed no significant differences with age for bsa in the newborn in the dayold and in the dayold pigs for ddavp a significant decrease in the total passage was obtained with age from in the newborn pigs to in the dayold pigs p and to p in the dayold pigs the T0 showed that the marker molecules bsa and ddavp passed over the porcine lung into the blood circulation in high amounts apparently inversely related to their molecular size the total lung passage of ddavp but not that of bsa was affected by changes with age indicating that these two markers might traverse the lung epithelium via different routes that are differently affected during PN development
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AD is a very serious condition mainly caused by degenerative diseases of the connective tissue and hypertension ascending aortic dissection as a consequence of aortitis in association with GCA is very rarely seen in this article we report on the successful surgical repair of a stanford type a aortic dissection caused by giant cell arteritis in a yearold patient we could visualize this dissection via echocardiography and computed tomography histopathology confirmed this rare complication of giant cell aortitis
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marine alginates are well established in wound management compared with different modern wound dressings marine alginates cannot prove superior effects on wound healing alginates from bacteria have never been studied for medical applications so far although the microbial polymer raises expectations for improved IB of wound AF because of its unique oacetylation due to its possible positive effects on wound healing alginates from bacteria might be a superior future medical product for clinical use to prove the IB capacity of microbial alginates to pathophysiological AF in chronic wounds we processed microbial alginate MF produced from fermentation of the soil bacterium azotobacter vinelandii atcc into needle web dressings and compared them with commercial dressings made of marine alginate four dressings were assessed marine alginate dressings containing either ionic silver or zincmanganesecalcium and microbial alginate dressings with and without nanosilver all dressings were tested in an in vitro approach for influence on chronic wound parameters such as elastase matrix metalloproteases tumour CN factorα interleukin and free radical formation despite the alginate origin or addition of antimicrobials all dressings were able to reduce the concentration of the proinflammatory cytokines tnfα and il however microbial alginate was found to bind considerable larger amounts of PE and mntly the reactive CG distributed in individual domains could be used as anchor sites to further incorporate PET units in an orthogonal fashion leading to welldefined multicompartment systems the strategy provides a new and efficient route to construct welldefined PET multicompartment systems with great flexibility and extendibility
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