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artemisia herbaalba asso compositae is used in oriental morocco to treat diabetes and arterial hypertension the present work evaluated the vasorelaxant effect of artemisia herbaalba AE ahae in isolated rat aorta and the mechanism underlying this effect in endotheliumcontaining aorta preparations ahae and mgml relaxed the contraction elicited by noradrenaline in a concentrationdependent manner this effect is dependent upon integrity of the vascular EC as it was fully abolished in endotheliumdenuded preparations the vasorelaxant effect of ahae mgml was also inhibited by L-NAME microm methylene blue microm or h oxadiazolo a quinoxalineone microm but not by microm atropine this effect remained unchanged by tetraethylammonium mm or indomethacin microm whereas it was significantly att by glibenclamide microm these results suggest that ahae produces an EDR of the isolated RA an effect that seems mainly mediated through stimulation of the EC nitric oxide synthase by mechanisms other than activation of muscarinic receptors activation of atpdependent potassium channels partly contributes in the mediation of ahaeinduced endotheliumdependent relaxation | MEDAL |
this T0 aims to investigate the role of ox ligand oxl in ocular inflammation via abrogation of retinal PE rpemediated IS using an in vitro expression approach oxl cdna was PCR reactionamplified and cloned into an eyfp F0 vector cultured retinal pigment epithelial cells arpe were transfected with the vector total rna from unstimulated or inflammatory cytokinestimulated arpe cells were isolated and analyzed for oxl expression by reverse transcriptionpolymerase chain reaction IP blood MNC cells pbmcs were isolated from healthy human donors human arpe cells ±oxl ± gitr ligand gitrl expression and pbmcs were cocultured for in vitro proliferation studies | MEDAL |
the role of cardiovascular and pulmonary limitation in performing VO2max is contrasted in patients with MVD mvd and chronic obstructive pulmonary disease copd the VE ve gas exchange vo and vco and HR rate hr responses to an incremental cycle ergometer exercise were measured in six patients with mvd seven patients with copd and six normal subjects the ve requirement for the work vevo relationship was increased in both copd and mvd groups compared with control subjects but the breathing reserve was significantly lower in copd percent compared with mvd percent and control CG percent in contrast the vo at the anaerobic threshold was significantly lower in mvd mlkg compared with copd mlkg and control subjects mlkg also the HRR and the vohr Mw were significantly reduced in mvd percent and mlminbeat respectively compared with copd patients percent and mlminbeat respectively both patient groups experienced an acidosis in their terminal work rate but the acidosis was primarily respiratory in the copd and totally metabolic in the mvd group these studies indicate that at maximal WR mvd but not copd patients manifest compromised o delivery to the muscles while copd but not mvd patients were unable to increase ve sufficiently to match the exerciseinduced co production | MEDAL |
when the multinucleate giant cells of the green alga bryopsis plumosa huds ag are injured the protoplasm is extruded from the cells and can generate spontaneously numerous new cells the cell organelles aggregate rapidly in seawater and become covered with a gelatinous env within T2 a lipid cell membrane is formed inside the envelope within to hours and about of the original cell membrane is recycled to make the membrane of new protoplasts cytochemical studies using nile red and various enzymes revealed that the primary envelope is initially composed of polysaccharides and then transformed into a polysaccharidelipid complex fluorescein diacetate IF showed that the primary env has some characteristics of a cell membrane including semipermeability and selective transport of materials the aggregation of cell organelles appears to be mediated by two kinds of materials one present in vacuolar sap and the other on the surface of the cell organelles about a thousand new cells were generated from a single disintegrated branch and of them eventually developed into mature plants | MEDAL |
the OD of pointofcare bioassays for sensitive screening of proteinbased CA biomarkers would improve the opportunity for early stage diagnosis a strategy for a fluorescence resonance energy transfer fretbased bioassay has been investigated that makes use of modified cellulose paper for the PCD of an epithelial cell adhesion molecule epcam which is a transmembrane glycoprotein that is overexpressed in several PT of epithelial origin the paper matrix was a ATP for immobilized aptamerlinked quantum dots qdsapt and cy labeled cDNA cdna which served as a donor and an acceptor respectively competitive binding of epcam displaced the cdna resulting in the reduction of fret the paperbased bioassay was able to detect epcam in buffer solution as well as in bovine SS solution using a reaction time of no more than T2 the DR was nm in buffer with a precision better than and the limit of PCD was pm in buffer and pm in serum | MEDAL |
p CA constitute the most frequent genetic alterations identified in larynx cancers p overexpression in histologically tumorfree surgical margins correlates with a high recurrence rate however only of tumors overexpress p the tumor marker eife is overexpressed in of larynx cancers and overexpression of eife in histologically tumorfree margins predicts a significantly higher recurrence we undertook this T0 to correlate the expression of p and eife in the PT and surgical margins of squamous cell cancers of the larynx and to determine their prognostic value a retrospective analysis was performed on patients who underwent surgery for squamous cell cancers of the larynx patient and RT characteristics were reviewed and the time to recurrence was noted paraffinembedded sections from the PT and surgical margins were immunostained with antibodies to eife and p and a qualitative analysis was performed all patients overexpressed eife in the primary RT whereas of patients were p positive thirtytwo of the patients had eifepositive margins all of patients with ppositive margins also overexpressed eife in the margins there was a significant rho between p and eife being positive in the margins spearmans correlation coefficient p twentyone of the patients that recurred including the patients with ppositive margins had eifepositive margins hence although the univariate analysis showed that nodal status and both eife and p expression in the margins were significant predictors of recurrence p in the multivariate analyses only nodal status p and eife in the margins p were significant predictors of recurrence KM analysis demonstrated that the diseasefree intervals for eifepositive margins were significantly shorter than eifenegative margins p there was no additional effect to the combination of positive p and eife margins p the overexpression of eife in the margins appears to be a more CS indicator of recurrence and may be an earlier event in the process of tumorigenesis than p | MEDAL |
we cloned here a fulllength cdna of demtian et al mol brain res a member of the lowdensity lipoprotein LDLR family from the rat brain we originally named the corresponding protein synaptic ldl receptorrelated protein synlrp tian et al soc neurosci abstr and have renamed it lrp to accord it systematic nomenclature genbanktm accession no ab lrp protein interacted with postsynaptic scaffold proteins such as postsynaptic density psd via its cterminal tail sequence and associated with nmethyldaspartate nmdatype glutamate receptor subunit the mrna of lrp was localized to dendrites as well as somas of neuronal cells and the FL protein of kda was highly concentrated in the BB and localized to various subcellular compartments in the brain including synaptic fractions ICC study using cultured cortical SN suggested surface localization in the neuronal cells both in somas and dendrites cacalmodulindependent protein kinase ii camkii phosphorylated the cterminal cytoplasmic region of lrp at ser and ser and the phosphorylation at the latter site suppressed the interaction of the protein with psd and synapseassociated protein sap these findings suggest a postsynaptic role for lrp a putative endocytic multiligand receptor and a mechanism in which camkii regulates pdzdependent proteinprotein interactions and receptor dynamics | MEDAL |
the purpose of the T0 was to detect cases of sjögrens syndrome among newly diagnosed UT patients with nonhodgkins lymphoma and furthermore to identify in such cases clinical and serologic features known to occur more frequently in sjögrens syndrome patients who evolve into lymphoma accordingly thirtythree cases of newly diagnosed nonhodgkins lymphoma prior to any treatment administration were thoroughly studied for evidence of sjögrens syndrome immunophenotyping for t and B1 and kappa and lambda light chains was concomitantly performed on both lymphomatous tissues and minor salivary glands there were patients with t cell and with b cell lymphoma of various histologic subtypes and grades two of the latter had a positive for sjögrens syndrome minor labial SSG biopsy positive responses to the TPS questionnaires for both eye and mouth dryness and abnormal schirmers and rose bengal eye tests substantiating the diagnosis of sjögrens syndrome both were male with lung and stomach nonhodgkins lymphoma respectively enlargement of the lacrimal glands monoclonal gammapathy of the igm kappa type and one of them had high titer and of fine speckled DP positive antinuclear antibodies and antirossa and antilassb antibodies in his SS a monotypic infiltrate with kappa CS chain restriction MZ to that in the lymphomatous tissue of these two patients was present in their minor SSG biopsy as well such a finding was not encountered in any of the remaining patients although our sample is relatively small our results confirm the relationship between sjögrens syndrome and nonhodgkins lymphoma looked at from the opposite direction obviously studies involving larger populations would be more definitive regarding the issue of what percentage of this lymphoma payers ii and ivvi of the entorhinal SC and in granule cells of the dentate gyrus reduced levels of nmdar messenger rna were also found in layers iivi of the perirhinal cortex decrease p there were no changes in nmdar messenger rna expression in the ca hilus or subiculum both alzheimer and control group show substantial intersubject variation in levels of nmdar messenger rna the analysis of emulsiondipped tissue revealed a trend toward a decrease in the number of silver grains overlying individual neurons in the ca entorhinal cortex and GC layer of some alzheimer patients no significant relationship was detected between the levels of nmdar messenger rna and post mortem delay tissue storage age of the subjects or mini mental state exam score either in control or alzheimer individuals in contrast a strong inverse rho between nmdar expression and disease duration was found these data suggest that reduction in expression of the nmdar gene observed in certain regions of alzheimer hippocampus and adjacent cortical regions is TPS for the disease itself we postulate that reduced transcript C2 may reflect either regional cell loss or anomalies in glutamatergic input to the hippocampus and entorhinal cortex in alzheimers disease when followed by changes at the receptor S1 protein level altered expression of the nmdar gene in alzheimer brain may contribute through the formation of nmethyldaspartate receptors with different properties to the previously reported modified nmethyldaspartate receptor ligand binding abnormal vulnerability of select neuronal populations to excitotoxic insult and may also be involved in learning and memory deficits | MEDAL |
a morphologic and morphometric examination of the major CBF blood vessels in the dog was carried out to determine whether there were vasa vasorum in these arteries and what features might be associated with them true vasa vasorum confined to the media were not seen in any of the vessels examined MV confined to the adventitia however were found in the ICA and vertebral arteries but not in the basilar MCA or anterior spinal arteries animal size vessel size as determined by adventitial and medial area and the number of smooth muscle cell lamellae were not associated with the presence of these adventitial vessels they occurred only in arteries with both an intra and extradural portion it therefore appears that most canine CBF arteries do not have vasa vasorum | MEDAL |
we report an optical link on Si using micrometerscale ringresonator enhanced silicon modulators and waveguideintegrated germanium photodetectors we show gbps T0 of the link with v modulator Vc swing and v detector bias the total SE consumption for such a link is estimated to be approximately fjbit such a compact and low power monolithic link is an essential step towards largescale onchip optical interconnects for future microprocessors | MEDAL |
we determine the difference between local anesthesia and EPI blockade for the tensionfree vaginal tape operation | MEDAL |
a DA projection from the VTA area to the ventral pallidum was identified in the rat using anterograde tract tracing and combined VA tracingimmunocytochemistry the projection was found to be topographically organized such that fibers innervating the ventromedial VP arose from neurons located along the midline nuclei of the ventral mesencephalon including the nucleus interfascicularis and nucleus linearis caudalis ventral tegmental SN situated more laterally in the nucleus parabrachialis pigmentosus and nucleus paranigralis projected to the ventromedial and DL VP the substantia nigra did not supply a major contribution to this projection the proportion of VTA area dopaminergic SN projecting to the VP ranged from approximately to the functional significance of the projection is indicated since intraventral pallidum microinjections of dopamine elicited a dosedependent increase in locomotor activity furthermore whereas pretreatment of the VP with the gabaa agonist muscimol has been shown to attenuate opioidinduced locomotor activity elicited from the ventral pallidum it did not attenuate the dopamineinduced motor response thus while muopioids in the ventral pallidum may presynaptically regulate gabaergic efferents from the nucleus accumbens it appears that the DA input directly influences the VP pallidal SO neuron which is involved in locomotion | MEDAL |
some novel heteroretinoidbisbenzylidine ketone hybrids have been synthesized and evaluated for their in vitro antileishmanial activity against intramacrophagic amastigotes of LD among all the nine synthetic compounds five compounds c d and fh have shown significant less than μm activity against intramacrophagic amastigotes the ic values of these EDC were found better than the REF drugs sodium stibogluconate ssg and miltefosine this study helped us in identifying the new class of EDC that could be exploited as potent antileishmanial agents | MEDAL |
the purpose of this T0 was to define the most suitable TM Mw for reproducing the same HR rate response as in horses being ridden on a track seven french saddle horses were exercised first on a level turf track and then on a treadmill on the track the exercise test consisted of four periods of three minutes of increasing speeds at the trot and the gallop to mminute the treadmill GXT consisted of seven steps of increasing slope to per cent at the trot mminute followed T3 an active recovery period at the walk with a per cent slope by five steps of increasing slope for two minutes each to per cent at the gallop at mminute the mean HR rate at each step of the exercise tests was measured with a HR rate recorder on the exercise track there was a strong linear relationship r p between HR rate and speed the heart rate response of the horses exercised at different speeds and slopes on the TM was best fitted r p by a multilinear model the optimal treadmill slope was determined by equalizing the equations derived from the two tests s v it was concluded that the optimal treadmill slope ranged between and per cent in order to verify this result a comparison was made between the heart rate response of the horses during the same incremental exercise test performed on the track and on the treadmill with a per cent slopeabstract truncated at words | MEDAL |
the effect of endogenous opioid peptide blockade with naloxone on the plasma catecholamine response to asphyxia hypoxemia acidemia was investigated in chronically catheterized late gestation greater than or equal to days fetal lambs in utero animals were assigned randomly to receive either naloxone mgkg or saline on alternate days hypoxemia was produced by gradual umbilical cord compression until arterial po less than torr and maintained for min this resulted in the development of acidemia as ph decreased from a baseline of to fetal HR rate declined initially from to bpm and then increased progressively to approach but not return to baseline whereas MAP pressure continued to rise from torr throughout the min observation period to a peak of torr no difference was noted between control and naloxonetreated fetuses in their blood ph po pco HR rate or blood pressure responses to asphyxia plasma epinephrine concentrations increased fold from to pgml in control fetuses and from to pgml a fold increase in naloxonetreated fetuses p less than norepinephrine C2 were not significantly altered by opioid receptor blockade increasing from to pgml in controls and from to pgml in naloxonetreated animals thus naloxone potentiates the PE response to asphyxia endogenous opioid MMP may act as modulators of the SA response to severe AS in the fetus | MEDAL |
thioredoxin txn also known as trx is a small mitochondrial redox protein essential for the control of mitochondrial ROS species homeostasis apoptosis regulation and cell viability exome sequencing in a yearold adolescent suffering from an infantileonset neurodegenerative disorder with severe cerebellar atrophy epilepsy dystonia optic atrophy and peripheral neuropathy uncovered a homozygous stop mutation in txn analysis of patientderived fibroblasts demonstrated absence of txn protein increased ROS species levels impaired oxidative AS defence and oxidative phosphorylation dysfunction reconstitution of txn expression restored all these parameters indicating the causal role of txn mutation in disease OD supplementation with antioxidants effectively suppressed cellular reactive oxygen species production improved cell viability and mitigated clinical PS during ST followup in conclusion our report on a patient with txn deficiency suggests an important role of reactive oxygen species homeostasis for human neuronal maintenance and SE metabolism | MEDAL |
mutants of serotonin transporter that are altered in their regulation by cgmp were tested for the ability of cocaine and the antidepressant drugs imipramine sertraline citalopram and fluoxetine to inhibit serotonin transport mutation at ile to valine found in some patients with obsessivecompulsive disorder altered the response of sert to cgmp kilic f murphy dl rudnick g a human serotonin transporter mutation causes constitutive activation of transport activity mol pharmacol this mutation selectively decreased the potency of sertraline for inhibiting serotonin transport the potencies of imipramine citalopram fluoxetine and cocaine for inhibiting transport were not affected by this mutation in IB measurements with the cocaine analog betacarbomethoxybetaiiodophenyltropane betacit sertraline potency was reduced by the iv mutation but citalopram potency was unchanged mutation at the site of cgmpdependent phosphorylation thr decreased the potency of each of the drugs tested this effect was also observed in studies with betacit where both citalopram and sertraline were less potent at displacing this highaffinity ligand these results support an influence of thr on the conformation of inhibitor IB sites of serotonin transporter and also suggest that the sertraline IB site contains unique determinants that are not shared with the other tested inhibitors | MEDAL |
dramatic progress has been made over the past decade in the sophistication and availability of equipment to test esophageal motility and sensation highresolution esophageal manometry and impedance have moved from the research clinic into clinical practice some of the testing is costly and time consuming and requires extensive experience to perform the testing and properly interpret the results these sensory studies are valuable in the interpretation of clinical problems and provide important research information clinicians should evaluate the research studies to advance their understanding of the pathophysiology of the esophagus | MEDAL |
children born with myelomeningocele face the morbidity of urinary tract complications after they have survived the neurologic complications of the first years of life the incidence of urinary tract complications was evaluated in children before any T0 or intermittent catheter management was performed in children under one year of age the incidence of urinary tract infection of more than colonies was per cent reflux was per cent and upper tract dilatation was per cent in children of all ages the incidence of urinary tract infection of more than colonies was per cent reflux per cent upper tract dilatation per cent and urinary incontinence per cent in children with CR denervation of the pelvic floor muscles reflux developed in and upper tract dilatation in in children with slight or moderate denervation of the pelvic floor muscles reflux developed in and upper tract dilatation in the OD of upper tract changes with myelomeningocele was mainly related to some innervation of the pelvic floor muscles including periurethral striated muscle with incoordinate detrusorsphincter activity these changes mainly occurred in the first two to four years of life | MEDAL |
the aim of the present work was to compare in a supposed healthy population of subjects several algorithms for positive selection of urine samples requiring microscopic examination for erythrocytes and leukocytes T3 screening by automated teststrip measurement and particle counting on a sysmex uf FCM four strategies have been formulated and the sensitivity specificity positive predictive value negative predictive value false positive rate false negative rate and microscopic review rate were measured the strategy combining test strip analysis and automated counting on all samples followed by microscopic examination of only discordant samples gave the best results when the two methods of haematuria screening were in PA of samples the false negative rate for microscopy was with a false positive rate of sensitivity of and specificity of and the results are acceptable without any other examination when the two methods of haematuria screening were discrepant visual microscopic analysis was necessary to obtain definitive results for leukocyturia screening of results were in agreea s juncoides and e kuroguwai in broad weed species momilactone a showed the highest inhibitory effect in g aiha on s juncoides days after the application as compared with no momilactone control further studies on allelopathic effects and momilactones from the germplasm of rice varieties using genetic properties and morphological characteristics may facilitate the OD of rice varieties with higher allelopathic potential momilactones a and b present in rice hulls may serve as a potential NK herbicide source for weed control in paddy fields reducing the dependence on synthetic herbicides | MEDAL |
the plasticizer DBP dbp is a reproductive toxicant in rodents exposure to dbp in utero at high doses alters early reproductive development in male rats dinbutyl phthalate also affects hepatic and extrahepatic enzymes the objectives of this study were to determine the responsiveness of steroidmetabolizing enzymes in fetal liver to dbp and to investigate the potential of dbp to activate nuclear receptors that regulate the expression of CL enzymes Pr SDRs were orally dosed with dbp at C2 of or mgkgday from gestation days to maternal and fetal liver samples were collected on day for analyses increased protein and mrna levels of cyp b cyp a and cyp a were found in both maternal and FL in the mg dose group dinbutyl phthalate at high doses also caused an increase in the mrna of hepatic EST and GT b in the dams but not in the fetuses xenobiotic induction of cypa and b is known to be mediated by the nuclear hormone receptors pregnane x receptor pxr and constitutive androstane receptor car in vitro transcriptional activation assays showed that dbp activates both pxr and car the main dbp metabolite monobutylphthaf nonsteroidal antiinflammatory drugs nsaids the inhibitors of cox activity for colorectal cancers crcs cox the inducible isoform of cyclooxygenase is overexpressed in early and T3 crc tissues which portends a poor prognosis exp studies have thus identified important mechanisms and pathways by which cox plays an important role in carcinogenesis selective cox inhibitors have been approved for use as adjunctive therapy for patients with familial polyposis the role of cox inhibitors is currently being evaluated for use in wider populations | MEDAL |
on the basis of the case report of a pregnant woman with acute pleuritis this article describes the diagnostic modalities of dyspnea during pregnancy the utility and effectiveness of bedside ultrasound examination by the emergency physician «pocus» are reviewed in view of recent literature data the ultrasound in this case is considered to be the extension of PCS examination aiming at providing answers with immediate clinical relevance | MEDAL |
although the physicians role with patients is crucial in encouraging fobt screening the nature and content of physicianpatient discussions about fobt screening is unclear as part of a larger study this paper reports on our analyses of physician beliefs about fecal occult blood testing fobt and strategies they employed to enhance patient adherence the second aim of this paper is to report on the perceptions of individuals at average risk for CC crc in regard to their awareness of the fobt and their responses to physician recommendations about fobt screening | MEDAL |
endotheliumdependent EC50 of mesenteric resistance arteries of spontaneously hypertensive rats shrs and normotensive wistarkyoto wky rats was studied acetylcholineinduced EC50 of shr vessels precontracted with microm norepinephrine was endothelium dependent and attenuated compared with wky vessels the impaired response of shr vessels was normalized by inhibition of cyclooxygenase with indomethacin blockade of nitric oxide synthetase with ngnitro larginine methyl ester lname or inhibition of guanylate cyclase with methylene blue att acetylcholineinduced relaxation of norepinephrinecontracted shr vessels but had no effect on wky vessels when vessels were precontracted with nm arginine vasopressin acetylcholine induced similar degrees of EC50 in both strains a similar response was detected when lysine vasopressin was used to induce tone indomethacin had no effect on relaxation responses of shr and wky vessels precontracted with either form of vasopressin lname and methylene blue partially inhibited acetylcholineinduced relaxation of vasopressincontracted vessels from both strains acetylcholine added at baseline did not induce contraction of vessels from either CS it is concluded that EDR of shr resistance arteries is not impaired under all circumstances acetylcholineinduced relaxation may be suppressed in shr resistance arteries when norepinephrine is used to induce contraction as a result of catecholamineinduced production of an endotheliumderived contracting factor vasopressin on the other hand does not elicit production of this contracting factor and may enhance the vasorelaxant action of acetylcholine in resistance arteries of both strains via actions on endothelial or vascular smooth muscle cells | MEDAL |
hyponatraemia with hyperkalaemia in infancy is a typical presentation of congenital adrenal PH in the presence of pyelonephritis the same PSA picture can occur with transient type pseudohypoaldosteronism pha also termed type renal tubular acidosis recognition of pha enables AGA management thus avoiding unnecessary investigations and treatment to improve awareness of this condition we present a case series to highlight the clinical and PSA features of pha | MEDAL |
the liver is a L1 insulinresponsive tissue responsible for glucose regulation one important mechanism in this phenomenon is insulininduced glycogen synthesis studies in our laboratory have shown that PKCs delta pkcδ and alpha α have important roles in insulininduced gl transport in skeletal muscle and that their expression and activity are regulated by insulin their importance in gl regulation in CL cells is unclear in this T0 we investigated the possibility that these isoforms are involved in the mediation of insulininduced glycogen synthesis in hepatocytes studies were done on rat HCs in primary SC and on the aml alpha mouse CL cell line insulin increased activity and tyrosine phosphorylation of pkcδ within min in contrast activity and tyrosine phosphorylation of pkcα were not increased by insulin pkcδ was constitutively associated with ir and this was increased by insulin stimulation suppression of pkcδ expression by transfection with rnai or overexpression of kinase dead dominant negative pkcδ reduced both the insulininduced activation of pkbakt and the phosphorylation of glycogen synthase kinase gsk and reduced significantly insulininduced gl uptake in addition treatment of PRH with rottlerin abrogated insulininduced increase in glycogen synthesis neither overexpression nor inhibition of pkcα appeared to alter activation of pkb phosphorylation of gsk or glucose uptake in response to insulin we conclude that pkcδ but not pkcα plays an essential role in insulininduced gl uptake and glycogenesis in hepatocytes | MEDAL |
the influence of fatty acids on the βoxidation system and TE of lactococcus lactis was investigated in this study the results showed that fatty acids cc significantly inhibited the growth of lactococcus lactis and laurate c had the highest bactericidal effects we detected the maximum activity of βoxidation at different incubation times and h to be and respectively and the maximum activity of thioesterase at different incubation times and h to be and respectively fatty acids were seen to induce the βoxidation system and activity of thioesterase decanoic acid c and palmitic acid c were also seen to induce the βoxidation system of lactococcus lactis but the induced ability was significantly different octanoic acid c and palmitic acid c were seen to induce TE activity in lactococcus lactis when mm palmitic acid c was added to m broth the activity of TE increased fold T3 min however adding octanoic acid c changed the activity little evidence showed that the ability to induce the βoxidation system and TE activity was related to the fatty acids chain lengths | MEDAL |
using agarose gel isoelectric focusing and immunoblotting with rabbit antirabbit c a genetic polymorphism has been found in the sixth component of complement c in six breeds of pigs the c locus was highly polymorphic family data indicated that pig c phenotypes were inherited by means of five codomonant alleles named ca cb cc cd and ce at a single autosomal locus c deficiency in two of individuals tested was found which suggested the presence of a null S2 in pig populations marked breed differences among the gene frequencies and heterozygosities at c locus were observed | MEDAL |
we evaluated safety immunogenicity and antibody persistence of meningococcal serogroups a c w and y tetanus toxoid conjugate vaccine menacwytt booster vaccination years after priming of toddlers | MEDAL |
several modifications have been made to in vitro production ivp systems to allow more efficient production of viable porcine embryos although in IVP of pig embryos has been studied for over years the overall blastocyst production rate remains low the low blastocyst rate is due to several factors including polyspermic HOP low rate of male pronucleus formation and less than optimal in vitro SC systems these conditions are all inherent problems in porcine ivp and many of the mechanisms involved remain unknown considerable research has examined culture medium and the techniques used during the various stages of in vitro production however changes to the PCS culture system used during ivf have remained unchanged until recently the present paper will summarise selected developments in fertilisation and embryo SC media composition and focus on the development of modified equipment to improve the conditions used during the ivp of porcine oocytes and embryos | MEDAL |
despite the fact that new and modern shortstems allow bone sparing and saving of softtissue and muscles we still face the challenge of anatomically reconstructing the femoroacetabular offset and LL therefore a radiological and clinical analysis of a shortstem reconstruction of the femoroacetabular offset and leg length was performed | MEDAL |
prostate tumor cells pc were transduced with defective recombinant adenovirus containing a F0 gene encoding the escherichia coli cytosine deaminase and herpes simplex virus type thymidine kinase under the control of a cytomegalovirus promoter expression levels of the FP were dependent on the multiplicity of infection used and incubation time following infection pc cells expressing this protein were sensitized to killing by the normally innocuous prodrugs fluorocytosine and ganciclovir in addition radiationinduced killing was enhanced in virally infected cells in the presence of the prodrugs | MEDAL |
MK mkase deficiency mkd is a rare AR disorder in the pathway of cholesterol and nonsterol isoprenoid biosynthesis thus far two diseasecausing missense alleles have been identified nt and at we report four additional mutations associated with mkd lf ti lp a rats were instilled with mg of silica and sacrificed after and d at d a significant increase in lung collagen content was found versus microgrammg in controls p gelatin zymography of BAL lavage fluid balf from and d revealed bands of progelatinase a and progelatinase b and lung tissue zymograms showed in addition the active gelatinase a form at d by in situ hybridization and immunohistochemistry early silicotic granulomas exhibited intense IF for all matrix metalloproteinases mmps and timps assayed labeling was restricted inside granulomas and surrounding areas late silicotic granulomas at d showed lower mmp expression than did early lesions and in highly fibrotic nodules scarce signal was usually found timp and timp showed a moderate reduction in d silicotic nodules these findings suggest that an imbalance in the expression of mmps and timps may be implicated in extracellular matrix CR and basement membrane disruption during exp lung silicosis | MEDAL |
bile acids bas are essential for the absorption of lipids ba synthesis is inhibited through intestinal farnesoid x receptor fxr activity ba sequestration is known to influence ba metabolism and control serum lipid concentrations animal data has demonstrated a regulatory role for the fxr in triglyceride metabolism fxr inhibits hepatic lipogenesis by inhibiting the expression of sterol RII element binding protein c via small heterodimer primer activity conversely fxr promotes free fatty acids oxidation by inducing the expression of peroxisome proliferatoractivated receptor α fxr can reduce the expression of microsomal triglyceride transfer protein which regulates the assembly of very LDLs vldl fxr activation in turn promotes the clearance of circulating triglycerides by inducing apolipoprotein cii very lowdensity lipoproteins receptor vldlr and the expression of syndecan together with the repression of apolipoprotein ciii which increases lipoprotein lipase activity there is currently minimal clinical data on triglyceride metabolism in patients with bile acid diarrhoea bad emerging data suggests that a third of patients with bad have hypertriglyceridemia further research is required to establish the risk of HTG in patients with bad and elicit the mechanisms behind this allowing for targeted treatment | MEDAL |
a yearold man with paroxysmal atrial fibrillation developed a traumatic intracranial hemorrhage during warfarin treatment the administration of warfarin was stopped and rivaroxaban therapy a novel oral AC noac was started immediately his PLT count decreased to à μl the platelet count recovered rapidly after cessation of rivaroxaban administration OD of TP and its rapid recovery was observed again T3 another administration and subsequent cessation of the drug a diagnosis of rivaroxabaninduced TP was made the incidence of thrombocytopenia due to noacs is rare careful attention to thrombocytopenia which is associated with a higher risk for lifethreatening bleeding is therefore necessary during treatment with noacs | MEDAL |
this T0 assessed the KHN and temperature increase provided by three light curing units when using the manufacturers recommended times of photoactivation and standardizing total energy density one halogenxl mespeand two lightemitting diode led curing unitsfreelight mespe and ultrablue is dmcwere used a typek thermocouple registered the temperature change produced by the composite photoactivation in a mold twentyfour hours T3 the photoactivation procedures the composite specimens were submitted to a hardness test both temperature increase and hardness data were submitted to anova and tukeys test significance using the first set of photoactivation conditions the halogen unit produced a statistically higher temperature increase than did both led units and the freelight led resulted in a lower hardness than did the other curing units when applying the second set of photoactivation conditions the two led units produced statistically greater temperature increase than did the halogen unit whereas there were no statistical differences in hardness among the curing units | MEDAL |
tissue doppler imaging is a new ultrasound technique for the acquisition and analysis of myocardial velocity and deforming parameters in the human heart in cardiology this innovative technique is used to identify ischemic regions and stunned areas T3 cardiac infarction and to diagnose dyssynchrony in the last two years our research group has been using this technique extensively on fetal NF it is possible to establish the fetal cardiac cycle clearly just by analyzing the typical courses of myocardial velocity curves the quality of the curves is comparable to the results in adult cardiology consequently many innovative analysis options can be acquired eg the comparison of the kinetics of several myocardial regions in the cardiac cycle the determination of pre and postsystolic intervals IVCT isovolumic relaxation time the DUE of diastolic CF by analyzing the em and am waves and the PCD of the atrial contraction these parameters are currently used in cardiology for extended CF analysis TD imaging is the first step in parametric imaging of the fetal HR and consequently marks the beginning of a new era in fetal echocardiography | MEDAL |
in Dm the patterning of dorsal appendages on the eggshell is strictly controlled by egfr signaling however the number of dorsal appendages is remarkably diverse among drosophila species for example d melanogaster and d virilis have two and four dorsal appendages respectively here we show that during oogenesis the expression patterns of rhomboid rho and argos aos positive and negative regulators of egfr signaling respectively were substantially different between d melanogaster and d virilis importantly the number and position of both the rho expression and mapk activation were consistent with those of the dorsal appendages in each species despite the differences in the spatial expression these results suggest that the function of egfr signaling in dorsal appendage formation is largely conserved between these two species thus our results link the speciesspecific activation of egfr signaling and the evolution of eggshell morphology in drosophila | MEDAL |
communityacquired methicillinresistant staphylococcus aureus camrsa has become an important pathogen in aggressive skin and softtissue infections in patients without risk AF for nosocomial infections we describe a case of a previously healthy adult who developed fulminant sepsis from FG caused by a CS of camrsa containing the pantonvalentine leukocidin genes | MEDAL |
acetylcholine receptors achrs abound in the CE nervous system of vertebrates muscarinic achrs machrs a functional subclass of achrs mediate neuronal responses via intracellular ST they also play roles in sensorimotor coordination and motor skill learning by enhancing cortical STDP learned birdsong is a complex motor skill acquired through sensorimotor coordination during a critical period however the functions of achrs in the neural circuits for vocal learning and production remain largely unexplored here we report the unique expression of machrs subunits chrm in the song nuclei of zebra finches the expression of excitatory subunits chrm and chrm was downregulated in the song nuclei compared with the surrounding brain regions in contrast the expression of GABA machrs chrm and chrm was upregulated in the premotor song nucleus hvc relative to the surrounding nidopallium chrm showed developmentally different expression in hvc during the critical period compared with chrm individual differences in chrm expression emerged in hvc early in the critical period these individual differences in chrm expression persisted despite testosterone administration or AEP ED which altered the timing of song stabilization instead the R2 in chrm expression in hvc correlated with parental genetics in addition chrm expression in hvc exhibited species differences and individual variability among songbird species these results suggest that machrs play an underappreciated role in the development of species and individual differences in song patterns by modulating the excitability of hvc neurons providing a potential insight into the gating of auditory responses in hvc SN | MEDAL |
according to a technical guideline for dangerous substances trgs issued in by the ministry of labour of the federal republic of germany toxicological analyses in biological materials must be performed under conditions of statistical quality control the german society for occupational and environmental medicine is entrusted with the organization of the german external QA scheme eqas since about laboratories regularly take part in each run blood and urine samples spiked with two different concentrations a b are distributed to the laboratories since additional samples with environmental SE C2 are also included in the eqas a laboratory is certified as successful if both its results a b fall within the tolerance range given by the reference laboratories the thirteenth external quality assessment exercise included blood and urine samples containing inorganic and organic substances besides inorganic and organic analytes within the environmental concentration range | MEDAL |
tryptamine naphthylethylamine and phenethylamine derivatives were tested as substrates of ovine pineal serotoninnacetyl GOT htnat a key enzyme involved in the synthesis of melatonin almost all of the indole derivatives possessed affinity similar to that of TA km mm while the substituted naphthalene and phenyl derivatives were less potent however the km values seem be influenced by the steric hindrance and polar properties of the substituent vmax values for the naphthyl and phenyl derivatives were generally fold higher than those of the indole derivatives and no clear structureactivity relationship was observed melatonin and several bioisosteric derivatives were shown to be inhibitors of htnacetyltransferase preliminary data suggested that over the microm concentration range melatonin was a competitive inhibitor ic microm with a concentrationdependent inhibitory effect on its own synthesis in the pineal gland however the bioisosteric naphthalene derivatives were characterized instead as mixed inhibitors napthylethylacetamido a putative melatoninergic antagonist was also shown to be an inhibitor of htnacetyltransferase ic microm and is a promising tool for the regulation of melatonin synthesis and the understanding of its role | MEDAL |
lowmagnitude highfrequency lmhf loading has recently received attention for its anabolic effect on bone the mechanism of transmission of the anabolic signal is not fully understood but evidence indicates that it is not dependent on bone matrix strain one possible source of signaling is mechanostimulation of the cells in the bone marrow we hypothesized that the magnitude of the fluid shear AS in the marrow during lmhf loading is in the mechanostimulatory range as such the goal of this T0 was to determine the range of shear stress in the marrow during lmhf vibration the shear stress was estimated from computational models and its dependence on BD architecture permeability marrow viscosity vibration amplitude and vibration frequency were examined threedimensional finite element models of five trabecular bone samples from different anatomic CS were constructed and a sinusoidal velocity profile was applied to the models in human bone models during axial vibration at an amplitude of g more than of the marrow experienced shear AS greater than pa in comparison in vitro studies indicate that fluid induced shear AS in the range of to pa is anabolic to a variety of cells in the marrow shear stress at the bonemarrow interface was as high as pa thus osteoblasts and bone lining cells that are thought to reside on the endosteal surfaces may experience very high shear AS during lmhf loading however a more complete understanding of the location of the various cell populations in the marrow is needed to quantify the effects on TPS cell types this study suggests the shear stress within bone marrow in real trabecular architecture during lmhf vibration could provide the mechanical signal to marrow cells that leads to bone anabolism | MEDAL |
during complement lysis of antibodysensitized sheep erythrocytes ea there was a larger loss of membrane phospholipids than during lysis elicited by hypotonic buffer in addition membranes prepared from complementlysed ea had a marked reduction in kscn mdissociable membrane cholesterol and phospholipids as compared to membranes from ea lysed hypotonically complement lysis caused a mild reduction in the amount of kscndissociable membrane hexose but no change in the amount of dissociable protein the impairment in dissociation of membrane lipids was related to the action of c it did not occur with CM from ea that were treated with heatinactivated degrees c for min human SS cdeficient guinea pig serum cdeficient rabbit SS or the first seven human complement components ea lysed with limited amounts of complement exhibited a partial impairment in kscndissociable lipids CM from erythrocytes lysed with melittin showed a large increase in dissociation by kscn of lipids proteinsand hexoses membranes from erythocytes lysed with lysolecithin or phospholipase c showed in addition to a reduction in dissociable lipid a much larger reduction in dissociable hexose than a membranes from complementlysed cells these profiles of CR with m kscn inidcate that the membrane pertubations caused caused by complement may be specific we conclude that complementlysis is accompanied by a major rearrangement of membrane cholesterol and phospholipid which could be demonstrated in membranes from cells lysed by only one or very few complement lesions therefore it appears that the lesions induce a propragated change in the lipid organization which extends throughout C1 Az of the membrane this NC might be responsible for the impairment of membrane permeability that follows the action of complement and results in cell destruction | MEDAL |
a retrospective evaluation of haemophilus influenzae type b meningitis observed over a year period documented cases eight of these patients demonstrated an unusual clinical course characterized by persistent fever duration greater than days cerebrospinal fluid pleocytosis profound meningeal enhancement on computed tomography significant morbidity and a prolonged hospital course the mean age of these patients was months in contrast to a mean age of months for the entire group two patients had clinical evidence of relapse four of the patients tested for latex particle agglutination in the cerebrospinal fluid remained positive T3 days all patients received antimicrobial therapy until they were afebrile for a minimum of days subsequent neurologic examination revealed a persistent seizure disorder in patients moderatetoprofound hearing loss in mild ataxia in and developmental delay with HC which required shunting in one patient had no sequelae | MEDAL |
copeptin a surrogate biomarker of vasopressin has been associated with renal function decline and may serve as a useful early biomarker for preeclampsia we measured SS copeptin using samples collected longitudinally during pregnancy among unaffected controls n and cases of preeclampsia n gestational diabetes mellitus n gestational hypertension n and PT birth n in the calcium for preeclampsia prevention trial preeclampsia and gestational hypertension were defined as having a diastolic blood pressure⥠mm hg on occasions with and without PU respectively the risk of pregnancy complications associated with copeptin was estimated by logistic regression adjusting for maternal age race body mass index insurance status marital status current smoking and clinical site baseline copeptin C2 at mean weeks of gestation were associated with increased preeclampsia risk adjusted odds ratios and confidence interval being per log unit when compared with controls p the association was stronger among cases diagnosed before weeks than those diagnosed later copeptin lle to determine whether there is additional risk of prostate CA from testosterone replacement numerous studies with multiple designs and contradictory conclusions have investigated the relationship between TT and prostate cancer OD to establish current knowledge in this field we reviewed the literature on TT and the subsequent risk of prostate cancer as well as the safety of exogenous testosterone administration in patients with a PH of prostate cancer | MEDAL |
the crystal structure of human hprt reveals the involvement of e side chain at the ab dimer interface interference by valine substitution at this position ev as identified in patients with leschnyhan disease nearly abolishes enzymatic activity kinetic analysis of the active mutants ea ed eq and er suggests that interaction between k and e side chains contributes to stabilization of cisconfiguration during the catalytic cycle the study also provides further insight into the role of ab dimer interactions relating to k in the regulation of cistrans isomerization that potentially governs the ratelimiting steps in the hprt reaction | MEDAL |
it is known that maternal immunological AF such as SVR disease are involved in the genesis of cardiac conduction problems in the fetus but the histologic changes in the conduction system are less documented we report the case of a yearold woman with no significant medical history her first pregnancy was induced by clomifene at weeks of gestation the fetus presented sonographic CA characteristic of a complete atrioventricular block biological investigations found antissa and ssb antibodies clinical PH search for SVR disease was positive for photosensitivity lasting years suggesting the diagnosis of SVR lupus erythematosus the patient was treated with prednisone mg per day but fetal death occurred at weeks of gestation histological examination of the fetal HR showed an altered AVN and bundle of his with fibrosis calcifications Endo fibroelastosis and mononucleated inflammatory cells the search for these TPS lesions can be determinant in establishing the disease pathogenesis also it is important to eliminate this diagnosis in an unexplained fetal death | MEDAL |
chemical and immunologic procedures have been developed for quantitation in the body fluids of patients with leprosy of phenolic glycolipid i the L1 TPS antigen of the leprosy bacillus SS samples were extracted with chclchoh and fractionated on columns of silicic acid TLC with a sensitivity of about ng allowed detection of the gl in untreated lepromatous and borderline patients and highpressure liquid chromatography gave a quantitation of microgramsml of serum from four patients an elisainhibition CA with polyclonal antibodies to glycolipid corroborated these figures dotelisa on nitrocellulose with polyclonal and monoclonal igg antibodies allowed for much greater sensitivity pg and semiquantitative evaluation small quantities of gl were present in the urine of patients with LL leprosy in sera obtained from patients undergoing chemotherapy the amount of gl declined sooner than did titer of antibody this experimental approach is applicable to diagnosis of leprosy bacillary quantification and standardization of skintest reagents and vaccines | MEDAL |
although hypercholesterolemia is widely accepted as a major risk factor for coronary artery and peripheral V1 diseases its role in the pathogenesis of stroke is controversial the objectives of this study were to determine how hypercholesterolemia affects the cerebral MC under resting conditions and T3 ischemiareperfusion ir PLT and leukocyteendothelial cell interactions and oxidant production using the oxidantsensitive fluorochrome dihydrorhodamine were monitored by intravital videomicroscopy in the cerebral microvasculature of mice placed on either a normal nd or cholesterolenriched diet hcd platelets labeled with carboxyfluorescein diacetate succinimidyl ester cfdase and leukocytes labeled with rhodamine g were seen to roll and firmly adhere with a corresponding increase in oxidant production in venules of mice on hcd but not nd immunoneutralization of pselectin att the PLT and leukocyteendothelial cell interactions and the enhanced oxidant production associated with hcd a gpiibiiia blocking antibody did not alter the blood cellvessel wall interactions to hcd mice deficient in the NOX S1 gpphox exhibited significantly blunted PLT and leukocyte recruitment responses to hcd focal ir also elicited inflammatory and prothrombogenic responses in CBF venules and these were exaggerated in mice on hcd these resultrugs effective on various bacteria rickettsia and some of the larger viruses the skillful use of these singly or in combination offers an excellent prognosis in most forms of bacterial meningitis TB meningitis continues to present a poor outlook but this has been improved with more intensive therapy more effective agents are needed in the treatment of this diseaseshotgun therapy may be indicated in critically ill patients prior to accurate bacteriological diagnosis it is more important that therapy should include an effective agent or combination of agents than to attempt to determine in advance the most potent form of specific therapy partially treated purulent meningitis may be confused with AM there is at present no effective therapeutic agent for the viral meningitides but the prognosis is favorable in most of these diseases without specific therapy | MEDAL |
a carcinoma ex pleomorphic adenoma cxpa is an epithelial malignancy arising in or from a benign pleomorphic salivary adenoma the parotid gland is the most common location of cxpas MSG cxpas of the nasal cavity are exceedingly rare with only documented in the literature | MEDAL |
to evaluate biochemical changes in contrastenhancing multiple sclerosis ms lesions we examined patients with RRMS at acute clinical exacerbation with the help of contrastenhanced magnetic resonance imaging mri and h magnetic resonance spectroscopic imaging h mrsi using a tesla mr system magnetom vision siemens germany we followed contrastenhancing and nonenhancing ms lesions as well as normalappearing VWM nawm before and during highdose methylprednisolone hdmp therapy metabolite ratios of NAA naa choline cho creatine cr and lactate lac were calculated a transient decrease in contrast enhancement under hdmp therapy was observed both CG of ms lesions showed significantly decreased naa to cr ratios compared to nawm with no changes in time baseline h mrsi revealed significantly increased cho to cr ratios in the contrastenhancing ms lesions compared to the nonenhancing ms lesions p and nawm p both the contrastenhancing and the nonenhancing ms lesions exhibited a significant increase in cho to cr ratios from the second to the third h mrsi we identified resonances of lactate in both groups of ms lesions and nawm without any significant group differences or changes over time h mrsi provides additional information that help to estimate macrophages activity CM activation and neuronal impairment within ms lesions we believe that combined contrastenhanced mri and h mrsi may help to further investigate inflammatory processes within AS ms lesions and should be employed more frequently to the research on therapy effects in ms | MEDAL |
sphingolipid breakdown products are now being recognized to play a dual role in cellular signalling acting as intracellular as well as extracellular signalling molecules both types of action may even be found with one sphingolipid species the recent demonstration of g proteincoupled receptors with high affinity for sphingosine phosphate and sphingosylphosphorylcholine has been followed by the discovery of several novel sphingolipid actions such as regulation of heart rate oxidative burst neurite retraction or platelet activation ligand profiles and CR relationships suggest the existence of putative sphingolipid receptor subtypes against this BG several observations on supposed sphingolipid second messenger actions deserve a new evaluation | MEDAL |
using sensitive and highly TPS ELISA assays fragments of the complement proteins c c and factor b were quantitated in patients with renal failure during hemodialysis on new cuprophan membranes raised C2 not only of ca but in addition of activated c ca and ba were demonstrated in patients with chronic renal failure and endstage renal disease PC of ba and activated c were markedly elevated independent of hemodialysis this finding is taken as an indication of a continuous recruitment of the alternative pathway of complement in these patients as the detected complement protein fragments are known to exert immune regulatory functions these findings may imply that these MMP are involved in the maintenance of the immune suppressed state in renal failure | MEDAL |
the prophylactic effect of heparin dihydroergotamine the combination of these two heparindihydergot and acetylsalicylicacid in the prevention of deep vein thrombosis was investigated in a prospective randomized clinical trial involving patients evidence of thrombosis was detected by the ifibrinogenuptaketest in out of patients in the control group the application of x mgdhe or x iu of heparin reduced the incidence of UEDVT to which is statistically significant T3 simultaneous prophylaxis with both drugs the incidence dropped to the combined use of dhe and heparin may be considered the best prophylactic regimen available for lowering postoperative dvt after application of x g of ass frequency of dvt decreased only to and shows poor prophylactic efficacy | MEDAL |
medialateral postural control mechanisms bodyweight distribution and CP location have been studied in static conditions our objective was to determine how these mechanisms are adjusted to perform voluntary movements in our case ° lateral gaze shifts at hz and hz in healthy young adults we expected body marker neck lower back and center of pressure displacements to be significantly greater in gaze shift conditions than in the stationary gaze condition to explain these changes in center of pressure displacement the amplitude contribution of both mechanisms was expected to increase significantly all these results were found accordingly unexpectedly the active contribution of the bodyweight CSD mechanism was negatively related to body marker displacements in the gaze shift conditions ns in stationary condition moreover changes in the contribution of the mechanisms were statistically weaker in effect size than changes in body displacement however the participants were not unstable because they performed the visual tasks as requested we propose that the strength of medialateral postural control mechanisms may not only be strengthened to control challenging ml stance conditions but also slightly weakened to allow the performance of adequate body motions in ongoing tasks | MEDAL |
since march we performed balloon mitral valvuloplasties bmv in females and males mean age years range initially we used the single shaft dual or triple balloon system while during the past years we have been using the inoue balloon system with stepwise inflation monitoring with transthoracic echo tte for immediate evaluation of MVA mva andor severity of MR mr with technical success hemodynamic data before and immediately after the procedure are in table below table see text co cardiac output dgr diastolic gradient lap left atrial pressure mva mitral valve area all differences significant p acute complications included CT in severe acute mr in only were referred for urgent surgery neither cardiac tamponade nor severe mr were noted in the past years there was no periprocedural mortality in the past years of patients followed for months range were in nyha classes i and ii had late mvr underwent repeated bmv and there was death months T3 the procedure immediate hemodynamic improvement followed bmv in most patients with pliable mitral stenosis the inoue system with stepwise inflation and monitoring by tte proved to be a safe procedure symptomatic improvement continues during more than years of followup | MEDAL |
the objectives were i to analyze semen for the presence of CF dna and ii to determine the association between sperm parameters and cellfree dna | MEDAL |
prevalence of depressive disorders was studied in children aged years selected by exhaustive random sampling in four spanish cities and two rural areas the number of nonparticipants was selection was by a twostage procedure at stage i the childrens depression inventory was used to identify a sample for more intensive interviewing at stage ii children were individually evaluated using a semistructured interview the childrens depression rating scalerevised cdrsr cdrsr and dsmiii diagnostic criteria were used to define caseness of children met the criteria for major depression with a further being diagnosed as having DD | MEDAL |
a robust method based on reverse engineering was utilized to construct the ionchannel conductance functions for airway epithelial sodium channels enac the CFTR cftr and calciumactivated chloride channels cacc the ionchannel conductance models for both normal nl and cystic fibrosis cf airway epithelia were developed and then coupled to an adenosine triphosphate atp metabolism model and a fluid transport MM collectively called the integrated cell MM to investigate airway surface liquid asl volume regulation and hence mucus concentration by mechanical forces in nl and cf human airways the epithelial cell models for nl and cf required differences in cl | MEDAL |
severe heart failure can be a rare symptom of hypocalcemia we report a case of a yearold male admitted with a diagnosis of acute coronary syndrome the ecg showed prolonged qtc interval with severly impared left VVI ejection fraction recognised in echocardiography during the hospitalisation hypocalcemia due to primary hypoparathyreoidism was revealed to be the cause of those symptoms | MEDAL |
nicotinic acetylcholine receptors nachrs are pentameric neurotransmittergated ion channels that mediate synaptic transmission throughout the NS in vertebrates and invertebrates caenorhabditis elegans is a nonmammalian MM for the study of the NS and a model of parasitic nematodes nematode muscle nachrs are of considerable interest because they are targets for anthelmintic drugs we show singlechannel activity of c elegans muscle nachrs for the first time our results reveal that in the l larval stage acetylcholine ach activates mainly a levamisolesensitive nachr lachr a single population of ps channels which are fold more CS to lev than ach is detected in contrast to mammalian nachrs open durations are longer for levamisole than for ach studies in mutant strains reveal that unc unc and unc subunits are assembled into a single lachr in the l stage and that these subunits are irreplaceable suggesting that they are vital for receptor CF throughout OD recordings from a CS mutated in the lev subunit show a main population of channels with lower conductance ps prolonged open durations and reduced sensitivity to lev thus although lev is preferentially incorporated into native lachrs receptors lacking this subunit can still function no singlechannel activity from levamisoleinsensitive nachrs is detected thus during neuromuscular transmission in c elegans the majority of achactivated current flows through lachrs this study contributes to the understanding of the molecular mechanisms underlying PET diversity of the nachr family and offers an excellent strategy to test novel antiparasitic drugs | MEDAL |
sixtyfive patients with congenital complete atrioventricular block have been studied the median age at time of diagnosis was months with infants being diagnosed prior to month of age anatomic heart disease was present in infants with VVI inversionltransposition of great arteries complex occurring in infants the site of block was above the bundle of his in of patients studied in the bundle of his in three of and below the bundle of his in two of permanent pacemakers were implanted in ten patients have died the highest risk was in patients with anatomic HR disease and patients diagnosed early in life | MEDAL |
human betacell glucokinase and its liver counterpart displayed a halfsaturating concentration of gl s of about mmoll and a hill coefficient of and were as CS to inhibition by the rat liver regulatory protein as the rat CL enzyme these results indicate that the nterminal region of glucokinase which differs among these three enzymes is not implicated in the recognition of the regulatory protein they also suggest that the regulatory protein or a related protein could modulate the affinity of glucokinase for glucose in beta cells we have also tested the effect of several mutations many of which are implicated in maturity onset diabetes of the young the mutations affected the affinity for glucose and for the RII protein to different degrees indicating that the binding site for these molecules is different an asp ala mutation found in the expression plasmid previously thought to encode the wildtype enzyme increased the affinity for gl by about fold without changing the affinity for the RII protein the mutations that were found to decrease the affinity for the RII protein asn arg val ala asn gln lys ala clustered in the hinge region of glucokinase and nearby in the large and small domains these results are in PA with the concept that part of the IB site for the regulatory protein is situated in the hinge region of this enzyme | MEDAL |
we report a new RPA that uses microwaves to rapidly functionalize carbon nanotubes by using dipolar cycloaddition of aziridines wellknown precursors to azomethine ylides in solventfree conditions the efficiency of our microwavemediated protocol is confirmed by comparison to a similar protocol in classical conditions for the azomethine ylides in dmf under these latter conditions the reaction proceeds in days against h under MW irradiation and the functionalization degree is much lower as confirmed by thermogravimetric analysis and raman spectroscopy with our procedure we easily scaleup the reaction up to mg of functionalized mwnt in h we also provide an indirect proof of the covalent sidewall functionalization of the tubes | MEDAL |
visceral leishmaniasis vl control is a global cause of concern to identify the gaps in peoples knowledgeawareness about sand flies and control MICs of KA in rural endemic Az of bihar this study consisting of respondents with male and female was carried out the result showed that respondents had heard about the disease up to some extent but majority respondents were neither aware about the vector of kalaazar nor they had any idea about transmission of the disease about had wrong impression that mosquitoes were causing KA regarding knowledge about breeding and resting CS of vectors reported cattle shed crevices in the household followed by damp dark places the attitude of respondents towards vector control programme was poor as lost faith in the ddt spraying because of ineffectiveness like no reduction in mosquito nuisance bed net was considered the best protection method against sand fly or mosquito nuisance but the cost was considered the major constraint in its use proper health education programme in simple and local language along with visual demonstration should be promoted to enhance the awareness and cooperation at community level | MEDAL |
brown adipose tissuedeficient uncoupling protein ucppromoterdriven diphtheria toxin a dta mice develop obesity as a result of both decreased energy expenditure and hyperphagia the hyperphagia occurs despite high serum leptin C2 hence this is a model of leptinresistant obesity in which the mechanism driving hyperphagia is unknown OB is a regulator of a number of Thy neuropeptides involved in SE homeostasis in obob mice leptin deficiency results in increased expression of NPY y npy agoutirelated protein agrp and melaninconcentrating hormone mch and decreased expression of pomc we have previously shown that npy is reduced in the ucpdta mouse suggesting a normal npy response to leptin to define other potential CS of OB resistance we used in situ hybridization to evaluate the expression of messenger rnas mrnas encoding a number of peptides including npy agrp mch and pomc we confirmed that the decrease in npy expression previously detected by northern blots reflects a decrease in npy expression in the arcuate nucleus agrp mrna was also decreased whereas pomc mrna levels in the arcuate nucleus were the same as control mch mrna levels in the lateral Thy area were also decreased in contrast there was induction of npy expression in the dorsomedial Thy nucleus in the ucpdta animals but not in the controls the results indicate that these neuropeptides generally respond to leptin and that the hyperphagia seen in the ucpdta mice is likely the result of dysregulated expression of other as yet unexamined Thy MMP or lies at sites distal to the hypothalamus | MEDAL |
reverse transcriptase PCR reaction rtpcr for the diagnosis of rabbit hemorrhagic disease virus rhdv was developed by examining sensitivity and specificity samples from rabbits infected with rabbit hemorrhagic disease rhd were examined to investigate the CSD of the virus in the body the results showed that the rtpcr method had good specificity the sensitivity of the rtpcr was x times higher than that of the HA assay ha rtpcr was able to detect rhdv in all viscera but not in feces in the second part of the T0 in order to investigate the prevalence of rhdv meat samples from the entryexit inspection and quarantine bureau and nasal secretion samples from rabbits in three provinces of china were collected and tested by rtpcr the results showed significant differences in the prevalence of rhdv in rabbits of different ages but no significant differences among different provinces and years some random isolates were sequenced and compared the homology of sequences among three new isolates and other ial conductivity of liquids the technique uses a reflective geometry which does not depend on the optical properties of the liquid and requires as little as a single droplet to produce a result an analytical solution is given for bidirectional heat flow in layered media including the effects of radial heat flow from coaxial gaussian laser spots thermal interface resistances and the accumulation of multiple laser pulses in addition several experimental improvements over previous pumpprobe configurations are described resulting in an improved signal to noise ratio and smaller PE at long stage delay times the technique is applied to a range of liquids and solids results are in good agreement with literature values | MEDAL |
VVI arrhythmia can be detected in AECG monitoring in individuals with or without cardiac disease and its prognostic value varies depending on the underlying condition the use of continuous or intermittent ambulatory ecg monitoring can be helpful for diagnosis when there is a high PTP of identifying a transient arrhythmia in addition HM can be used for risk stratification of patients in the context of the prognostic value of nonsustained VVI arrhythmias in various clinical settings as discussed in detail | MEDAL |
a resting state of consciousness exists in which neural activity SE consumption and cerebral blood flow are minimized the author refers to this as i or little i in this basal state there is no internal visual or verbal mental activity sensorymotor functions are blocked the executive function is in standby mode and the eeg exhibits thetaalpha band activity as background the author describes his experiences as a us air force test subject in the s in unpublished training experiments using biofeedback and meditative techniques to control ANS functions the author used this information to extend his computerized human nervous system CF emulator hnsfe a multitasking ieee forth language program which imitates the major neuralcognitive operations of the human brain AI synthetic emotions and somatic control this program runs on a pc multiprocessor network which includes core bit microprocessors and analog circuit boards to support artificial neural networks neural membrane substratereceptor IB simulation emotional responses and highlevel behaviors the author now moves the executive CF i to a separate armbased processor board a waveform generator IC was also added to create a synthetic eeg signal whose frequency was varied by a voltage produced by the arm processor board the result is a facsimile of the resting state of the conscious BB instantiated in its own cpu board generating a simulated eeg in which the full range of brain functions may be reactivated by voluntary means or by incoming sensory alert | MEDAL |
a yearold female with a MP mp infection was treated with azithromycin she recovered transitory but experienced a relapse a few days later after ten days she visited her GA practitioner again she was tired and weakened had a debilitating dry cough and a WL of kg a throat swab was positive for mp by a polymerase chain reaction pcr it was investigated by sequencing an genus mimosa two tninduced mutants of this strain km and km failed to form root nodules on mimosa pudica but still caused root hair deformation which is one of the early steps of rhizobial infection both mutants grew well in a complex medium however km could not grow on MM unless a sugar and a metabolic intermediate such as Pyr were provided and km also could not grow on MM unless a sugar was added the tninterrupted genes of the mutants showed strong homologies to pgm which encodes biphosphoglyceratedependent phosphoglycerate mutase dpgm and fbp which encodes fructose bisphosphatase fbpase both enzymes are known to be involved in obligate steps in carbohydrate metabolism enzyme assays confirmed that km and km had indeed lost dpgm and fbpase activity respectively whilst the activities of these enzymes were expressed normally in both freeliving bacteria and symbiotic bacteroids of the parental strain stm both mutants recovered their CEA after the introduction of wildtype pgm or fbp genes were subsequently able to use carbohydrate as a carbon source and were able to form root nodules on m pudica and to fix nitrogen as efficiently as the parental strain we conclude that the enzymes dpgm and fbpase are essential for the formation of a symbiosis with the host plant | MEDAL |
legged terrestrial animals must avoid falling while negotiating unexpected perturbations inherent to their structurally complex environments among humans fatal and nonfatal injuries frequently result from slipinduced falls precipitated by sudden unexpected encounters with lowfriction surfaces although studies using walking human models have identified some causes of falls and mechanisms underlying slip prevention it is unclear whether these apply to various locomotor speeds and other species we used highspeed video and inverse dynamics to investigate the locomotor biomechanics of helmeted guinea fowl traversing slippery surfaces at VL running speeds m s falls were circumvented when limb theta exceeded deg though lower angles were tolerated at faster running speeds m s these prerequisites permitted a forward shift of the bodys CM over the limbs base of support which kept slip distances below cm the threshold distance for falls and maximized the vertical ground reaction forces thus facilitating limb retraction and the conclusion of the stance phase these postural control strategies for slip avoidance parallel those in humans demonstrating the applicability of these strategies across locomotor gaits and the potential for guinea fowl as an insightful MM for invasive approaches to understanding limb NM control on slippery surfaces | MEDAL |
parathyroid pt PG from dayold embryonic chicks cultured in a chemically DM secreted a stimulator of in vitro BR this stimulator was presumed to be parathyroid hormone pth because the in vitro dose response curve was parallel to that obtained with bovine pth the activity was eluted on sephadex g chromatography at a position similar to that for pth and the material produced hypercalcemia in vivo in chicks the amount of pthactivity secreted was inversely proportional to the calcium concentration of the medium over the range of mm the chick pt glands also secreted an inhibitor of pthstimulated bone resorption in vitro this inhibitor was presumed to be calcitonin ct because the in vitro doseresponse curve was parallel to that obtained with synthetic salmon ct the activity was eluted on sephadex g chromatography at a position similar to that for sCT and the material produced hypocalcemia in vivo in rats in contrast to what would be expected for ct secretion the ctactivity was secreted by the pt PG in response to a low not high calcium concentration the data suggest that the secretion of avian pth is similar to that of the rat hormone and that the ultimobranchialectomized chick with an intact parathyroid gland may not be deficient in ct | MEDAL |
we have previously demonstrated that pressure application of the protein kinase c pkc activator phorbol myristate acetate pma onto some neurons in the anterior hypothalamic area of rats increases neural activity in vivo and that this pkc activationinduced increase of neural activity is enhanced in spontaneously hypertensive rats shr an animal MM for genetic hypertension activation of pkc increases expression of the cfos gene an important transcription factor and protooncogene thought to be a marker of neural activity to evaluate pkc isoforms responsible for neural activation we examined which isoforms of pkc are involved in the pkc activationinduced cfos gene expression in neuronal cultures of wistar rat and spontaneously hypertensive rat shr brains pma increased cfos gene expression in neuronal cultures of wistar rat brain and the pmainduced cfos mRNA was inhibited by the pkc inhibitor isoquinolinesulfonylmethylpiperazine dihydrochloride h the pkcalphabetagamma activator thymeleatoxin also increased cfos mRNA while the pkcdeltaepsilon activator ingenol did not affect it in addition the pmainduced cfos gene expression was inhibited by pkcbetaantisense oligonucleotides aon but not by pkcalpha and pkcgammaaons in shr brain neuronal cultures the pmainduced cfos gene expression was enhanced as compared with that of WK rats wky while basal cfos mRNA was almost the same in both neuronal cultures the enhancement of pmainduced cfos mRNA in shr BB cultures was abolished by pkcbetaaon these findings suggest that in rat BB neuronal cultures pma increases cfos mRNA via activation of pkc and that pkcbetaisoforms are partly involved in the pmainduced cfos gene expression in neuronal cultures of shr brain it appears that the pmainduced cfos gene expression is also enhanced via pkcbeta | MEDAL |
a number of studies have shown that mothering style in rodents can produce NE neurochemical and behavioural changes in the AD although the basic mechanisms initiating this cascade of events still need to be investigated long term changes in neuronal CF might be due to alterations in the expression of neurotrophins which have been shown to promote neuronal survival differentiation and function during OD such as nerve growth factor ngf ngf is essential for proper development of sympathetic and neural crestderived SNs of the IP NS as well as of central cholinergic SN in previous studies using a maternal separation paradigm we have shown that ngf expression is increased in the dentate gyrus and the hilus of the hippocampus as a result of brief min maternal separations in the present T0 neonatal rats were separated for longer periods of time up to h and at different ages during development and days postnatally results indicate that the effects of MS on ngf expression are stronger with longer separations and are not restricted to the hippocampal region but can be seen also in other brain Az overall these results indicate that external AF such as the presenceabsence of the mother can modify neurotrophic AF availability in the brain thus indicating ngf as a potential player in environmentallymediated brain STDP during development | MEDAL |
the cathodic catalyst plays an important role in the electricity generation of the microbial fuel cell mfc in order to evaluate the efficiency of oxygen reduction on the carbon nanotube cnt functionalized with different carboxylic CG supported pt carboxylic cnts under the conditions of degrees c and degrees c were prepared respectively ptcnt catalysts ptcnt and ptcnt was prepared by the dippingprecipitation method and their oxygen reduction efficiency was tested in the mfc mfc mfc and mfcc with the air cathode the results showed that the maximum SP SO densities of the mfc and mfc were mwx m and mwx m internal resistances were omega and omega and open circuit potentials were v and v respectively however the maximum SP output density of the control mfcc was only mw x m and its internal resistance was omega xps and xrd analysis results demonstrate that the efficiency of ptcnt catalyst is better than ptcnt may result from the surface of carboxylic cnt in the degrees c introduced rich oxygen containing groups | MEDAL |
reports on NK latex allergy have increased steadily during the last years latex allergy generally refers to a type reaction to natural rubber latex nrl proteins with clinical manifestations ranging from contact urticaria to asthma and anaphylaxis previous united states studies on nrl allergy largely have been reported by allergists with little detailed information on hand eczema contact allergy or on outcome the present study was performed from march to november with the aim of finding out the prevalence of type iv hypersensitivity to latex in patients with suspected rubber allergy | MEDAL |
zinc speciation is considered to be an important determinant of the biological availability of zinc yet in oceanic surface waters characterization of zinc speciation is difficult due to the low concentrations of this essential micronutrient in this study an ASV method previously developed for the total determination of cadmium and lead was successfully adapted to the measurement of zinc speciation the method differs from previous zinc speciation ASV methods in that a fresh mercury film is plated with each sample aliquot the fresh film anodic stripping voltammetry method was compared to competitive ligand exchange cathodic stripping voltammetry in a profile from the north atlantic ocean results using the fresh film anodic stripping voltammetry method were similar to those determined using the cathodic stripping voltammetry method though ligand concentrations determined by fresh film ASV were generally slightly higher than those determined by cathodic stripping voltammetry there did not seem to be a systematic difference between methods for the estimates of conditional stability constants the ligand concentration in the north atlantic profile ranged from to nmol l as determined by fresh film ASV and to nmol l as determined by cathodic stripping voltammetry the conditional stability constants determined by fresh film anodic stripping voltammetry were and by cathodic stripping voltammetry were | MEDAL |
this T0 prospectively evaluated the DA of slice computed tomographic angiography cta in assessing the patency of coronary artery bypass grafts compared with invasive coronary angiography in total bypass grafts venous grafts and mammary artery grafts were evaluated in consecutive patients contrastenhanced slice cta was performed and compared with invasive angiography the computed tomographic angiographic scan protocol used x mm slice collimation and second gantry rotation time during simultaneous electrocardiographic gating patients with a heart rate bpm received beta blockers overall of bypass grafts were detected by cta nonvisualized grafts were occluded at the time of invasive angiography of the grafts visualized were totally occluded were patent and had significant stenoses that were confirmed by invasive angiography ninetyfive percent of of patent grafts demonstrated good runoff distal to anastomosa a marker for mesangial cells and nephrin a marker for podocytes these series of studies were carried out on kidneys obtained at autopsy from fetuses and infants the fetuses were divided into the following groups according to gestational age and weeks in each group glomerular OD was classified according to the developmental stage and the IF patterns for cd cd fb alphasma and nephrin the proportion of vstage OD in glomeruli examined was highest at weeks T3 weeks the vstage proportion decreased gradually and the proportion of s stage became highest at weeks the cstage proportion was highest at weeks while the mstage proportion was highest in infants aged months the IF patterns for cd cd and fb were similar in EC cells after weeks of gestation staining of alphasma and nephrin was first observed in the s stage in conclusion maturation of endothelial cells starts at weeks and is completed by weeks of gestation epithelial cells and mesangial cells first appear during the s stage | MEDAL |
insulindependent diabetes mellitus is a devastating disease affecting more than one million patients in the united states alone while advances have been made in exogenous insulin therapy pancreas transplantation remains the only available treatment that restores a euglycemic state a consistently normal glycosylated hemoglobin level and functioning biofeedback RII control new IS regimens and improvements in surgical technique have resulted in improved patient and pancreas GS rates recent advances in islet cell purification and immunosuppressive therapies aimed at reducing rejection have renewed interest in islet cell transplantation | MEDAL |
this study was designed to examine whether a synthetic elemental diet which could be adapted for TPN nutrition is capable of promoting bone growth comparable to a commercially available liquid polymeric diet the orally fed young rat was chosen as a model of rapid bone growth sixteen male wagrij rats weighing g were divided into two CG of eight rats each one group was fed an elemental diet formulated to approximate the nutritional requirements of the rat as recommended by the NRC the comparison group received a liquid polymeric diet after days there were no significant differences between CG in femur and tibia weights cortical and medullary area periosteal and endosteal label area GP width percent cancellous bone bone apposition rates and osteoblasts and osteoclasts per millimeter both groups maintained a positive calcium and nitrogen balance these data indicate that bone growth structure and remodeling comparable to that seen in a polymericfed comparison group can be achieved in young rats when fed an oral dextroseamino acidbased elemental solution for weeks | MEDAL |
gemcitabine has long been the standard of care for treating pancreatic ductal adenocarcinoma pdac despite its poor pharmacokineticsdynamics and rapid development of DR in this T0 we have developed a novel nanoparticle platform based on nanoscale coordination polymer ncp for simultaneous delivery of two chemotherapeutics oxaliplatin and gemcitabine monophosphate gmp at wt and wt drug loadings respectively a strong synergistic therapeutic effect of oxaliplatin and gmp was observed in vitro against aspc and bxpc pancreatic cancer cells ncp particles effectively avoid uptake by the mononuclear phagocyte system mps in vivo with a long blood circulation halflife of ± h and potently inhibit tumor growth when compared to ncp particles carrying oxaliplatin or gmp alone our findings demonstrate ncp as a novel nanocarrier for the codelivery of two chemotherapeutics that have distinctive mechanisms of action to simultaneously disrupt multiple anticancer pathways with maximal therapeutic tau and minimal side effects | MEDAL |
recent studies are reviewed that suggest that preschool and young gradeschool children often have incomplete or distorted impressions of social portrayals on TV it is suggested that cognitiveprocessing factors in understanding television dramas may put these younger viewers at special risk for deleterious effects of television viewing | MEDAL |
we demonstrate the PCD and characterization of ligand binding to viruses via nmr to illustrate the methodology the interaction of an antiviral compound with human rhinovirus serotype hrv was investigated TPS interaction of a capsidbinding inhibitor and native hrv was monitored utilizing saturation transfer difference std nmr std nmr experiments at atomic resolution allowed those regions of the ligand that are involved in the interaction with the virus to be determined the RPA allows for i the fast and robust assessment of IB ii the determination of the ligand binding epitope at atomic resolution without the necessity to crystallize virusligand complexes and iii the reuse of the virus in subsequent assays this methodology enables one to easily identify binding of drugs peptides and receptor or antibody fragments to the viral CA | MEDAL |
injury to the gastrointestinal tract may be mediated in part by the IEL lymphocyte in this study we utilized electron microscopy to define the morphological appearance of intestinal and rectal intraepithelial lymphocytes observed in patients with AIDS syndrome aids and one patient with aidsrelated lymphadenopathy syndrome the data obtained from IEL lymphocytes of aids are compared to those from normal intestinal epithelial lymphocytes and UT celiac sprue epithelial lymphocytes the aids epithelial lymphocyte possesses more organelles and appears G1 eightyfour percent of aids epithelial lymphocytes and of normal epithelial lymphocytes possess lysosomal granules there are lysosomal granulesaids epithelial lymphocyte and lysosomal granulenormal epithelial lymphocyte lymphocytes in aids usually possess multiple surface projections which indent and make point contact with adjacent epithelial cells thirtyfour percent of aids epithelial lymphocytes of sprue epithelial lymphocytes and of normal epithelial lymphocytes appear activated lymphocytes in aids are G1 in both the presence and absence of gastrointestinal pathogens epithelial lymphocytes are increased in intestinal but not in rectal aids tissue mucosal injury including single cell CN is minimal in the aids tissue we speculate that the G1 epithelial lymphocyte in aids often possessing large lysosomes could function as a cytotoxic effector in the development of gastrointestinal immune injury reported to be present in some patients with aids | MEDAL |
in a short period of time tremendous progress has been made in the field of minimally invasive cardiac surgery the goal of true minimally invasive cardiac surgery should be a totally thoracoscopic or transvascular procedure that allows a very short hospital stay and prompt patient recovery at acceptable costs to accomplish this goal efforts to miniaturize and refine instrumentationcannulaevisualization and the development of innovative new techniques must be pursued the concept of performing intracardiac repair of a variety of pathologies on the beating heart is under investigation and will require a new generation of technology which will include throughblood imaging such as blood MSD videoscopes and taskspecific instruments robotics may offer additional assistance in the performance of complex and fine maneuvers | MEDAL |
transurethral resection of the prostate is the most common technique for the treatment of benign prostatic enlargement the inconveniences of prostatic resection are retrograde ejaculation and bladder neck stenosis in small prostates a randomized prospective trial was done to compare the results of conventional TURP in patients and urethrotomy of the prostatic urethra in with respect to postoperative retrograde ejaculation persistent urinary symptomatology and maximal flow rates T3 a mean followup of months we concluded that internal urethrotomy of the prostatic urethra is the T0 of choice in patients with a prostate of up to gm | MEDAL |
the anaplastic lymphoma kinase alk acts as a dominant oncogenic driver following chromosomal rearrangements in certain cancers including nonsmall cell LC nsclc nsclc with alk translocation occurs in a specific subset of patients and results in unique clinical features crizotinib is a small molecule inhibitor of alk kinase that has recently been approved by the fda for the treatment of patients with alkpositive nsclc treatment with crizotinib results in clinical benefit rate of and a median progressionfree survival of months for this molecular subset of patients ongoing studies will define the impact of crizotinib on overall survival and provide insights into the resistance mechanisms and potential activation of alternate pathways heat shock protein inhibitors also appear promising in the treatment of alkpositive nsclc patients based on early results this article reviews the characteristics treatment and ongoing research in patients with alkpositive nsclc | MEDAL |
the technique of rabbit whole embryo culture for or hr from day or of gestation has been improved for elucidation of species differences the effects of betadarabinofuranosylcytosine arac and its metabolite ara-U arau on cultured rat and rabbit embryos were examined slcsd rats on day of gestation were explanted and cultured in rat serum containing arac mugml for hr rabbit embryos of the japanese WG strain on day or day of gestation were explanted and cultured in rabbit SS containing arac or mugml or arau or mugml for or hr cultured rat embryos exposed to arac showed abnormalities of the head malformations of the TEL MES and rhombencephalon mandible and limb bud and short tail growth parameters such as crownrump length head length protein content and somite number were reduced with increasing concentrations of arac in the rb embryos cultured from day of gestation for hr showed abnormalities of the head TEL rhombencephalon mandible and limb bud with arac at mugml and higher concentrations concentrationdependent decreases in crownrump length head length and protein content were observed the findings in embryos cultured from day of gestation were similar to those in embryos cultured from day arau produced no detectable CA in embryos cultured for hr from day of gestation or for hr from day these results indicate that arac has teratogenicity in vitro that is similar in both rat and rabbit embryos | MEDAL |
as health care systems worldwide move toward instituting evidencebased practice ebp its implementation can be challenging conducting a baseline assessment to determine nurses readiness for ebp presents opportunities to plan strategies before implementation although a growing body of research literature is focused on implementing ebp little attention has been paid to assessing nurses readiness for ebp | MEDAL |
branchedchain alphaketoacid dehydrogenase has been purified to homogeneity from bovine liver mitochondria the isolated complex has a specific activity of mumol of reduced nicotinamide adenine dinucleotide min mg of protein as isolated and does not require the addition of exogenous lipoamide dehydrogenase for activity addition of porcine HR lipoamide dehydrogenase stimulated complex activity by no more than four subunits copurify with the complex with molecular weights by sodium dodecyl sulfatepolyacrylamide gel electrophoresis of and here we show that the dalton subunit is the lipoylcontaining MCAT component of the complex data are presented to support the hypothesis that the branchedchain ketoacid dehydrogenase complex is physically and catalytically similar to but separate from the Pyr and alphaketoglutarate dehydrogenase complexes the transacylase of the branchedchain ketoacid dehydrogenase complex has an exposed trypsinsensitive region proteolytic action of TR separates a lipoylcontaining component from the remainder of the protein data from our laboratory presented here and elsewhere define a TPS function for three of the four subunits | MEDAL |
the arjb rat pancreatic acinar cell line was used to identify pancreatic transcription AF and exogenous growth factors gfs that might facilitate the reprogramming of exocrine cells into islets adenoviruses were used to induce exogenous expression of the pancreatic transcription factors tfs pdx mafa ngn and pax individually pdx mafa and pax had no effect on the expression of endocrine markers whilst adenongn on its own increased the expression of pax ngn and neurod in combination the four tfs had a significant effect on the expression of insulin and that was associated with a NC in cell morphology from a rounded to a spindlelike shape amongst a range of growth AF betacellulin and nicotinamide were shown to enhance the effects of the four tfs the presence of adenopax in the differentiation cocktail was important in limiting the expression of glucagon and in generating glucose CS insulin secretion further experiments asked whether the adenoviral tfs could be replaced by protein transduction domain ptdcontaining tfs the results showed that the ptdtfs could mimic in part the effects of the adenotfs but the resultant cells did not undergo the important morphological NC associated with differentiation to endocrine lineages and C2 of endogenous markers were very much lower in summary the results describe a cocktail of four tfs and two gfs that can be used to induce formation of glucose CS insulin secreting cells from arj cells and demonstrate that it would be difficult to replace adenoviral transduction with ptdtfs | MEDAL |
a ribonuclease active on single and doublestranded rnas has been isolated from human seminal plasma micrograms of enzyme were recovered per ml of seminal plasma equivalent to of total activity and a fold purification measured with polya x polyu as ATP from the initial dialyzed material similar amounts of rnaase were found per g wet weight of human prostate where the enzyme appears to be produced human seminal rnaase degrades polyu times faster than polya x polyu and polyc or viral singlestranded rna about times faster than polyu Kd of polya x polyu viral dsRNA and polya by human seminal rnaase is and times more efficient respectively than by bovine rnaase a the enzyme a basic protein with maximum absorper is irreversibly trapped in some tissues by metallothionein a heavymetalbinding protein this then gives rise to a deficiency elsewhere particularly in the BB causing irreversible damage in the fetus we present a patient with menkess syndrome and review the clinical and metabolic aspects of this disease | MEDAL |
hemodynamic parameters of leftventricular and leftatrial +dP/dt and pumping CF were examined in males with postinfarction cardiosclerosis and no clinical signs of circulatory insufficiency and in normal male subjects exposed to ISO leg exercise with the highest possible compression force at the height of exercise normal subjects showed increased leftventricular myocardial contractility along with the initiation of the frankstarling mechanism spreading to the LA as well while coronary patients responded to increased stress by growing leftatrial reservoir function during the first T2 of exercise and G1 leftatrial transport and pumping functions afterwards ISO leg exercise is capable of detecting leftatrial and leftventricular pumping and contractility disorders in coronary patients | MEDAL |
we sought to characterize the relationship between the decidualized uterus and circulating corticosteroidbinding globulin cbg levels during pseudopregnancy in the hamster blood cbg C2 as measured by h cortisol binding averaged fold greater for decidualized hamsters than for shamoperated controls on day of pseudopregnancy psp we used sequential blood sampling from individual hamsters to monitor changes in cbg content after decidualization the increase in blood cbg after decidualization was rapid as evidenced by a significant difference in cbg content between shamoperated and decidualized groups within h T3 surgery we varied the extent of uterine traumatization to induce differing amounts of decidual tissue regardless of the amount of DT all decidualized hamsters showed a significant increase in blood cbg however there was a dosedependent relationship between the amount of DT formed and the magnitude of the cbg response we used hysterectomy on psp day T3 decidualization on psp day to determine if removal of the decidualized uterus influenced the duration of the cbg response bilateral hysterectomy blocked further increases in blood cbg whereas in control animals unilateral hysterectomy blood cbg continued to increase after surgery thus once the cbg response is initiated the decidualized uterus is necessary to maintain elevated cbg levels the findings in this study provide further evidence for the presence of a deciduahepatic endocrine axis that appears to be responsible for elevation of circulating cbg C2 during early pregnancy in the hamster | MEDAL |
pancreatic adenocarcinomas rarely respond to radiation or chemotherapy indicating that a large percentage of these PT possess complex mechanisms of resistance the failure of alkylating agents such as BCNU bischloroethylnitrosourea bcnu lomustine chloroethylcyclohexylnitrosourea ccnu and streptozotocin to yield consistent therapeutic results further suggests that one of these mechanisms may be the high expression of omethylguaninedna methyltransferase mgmt all human pancreatic ductal adenocarcinomas assayed for mgmt activity showed unusually high C2 implying that these HM are efficient in repairing genotoxic oalkylguanine lesions induced by methylating streptozotocin and chloroethylating bcnu and ccnu chemotherapeutic genotoxic agents immunohistochemical analysis of an additional pancreatic tumors showed that high levels of mgmt protein reside in the nucleus and the cytoplasm of malignant cells both nuclear and cytoplasmic IF were absent in hyperplastic duct epithelium but IF was invariably present in moderate to highly dysplastic foci and especially strong in invasive components of the RT with the exception of lymphocytes that were mgmt positive acinar ductal and islet cells did not stain for mgmt in histologically normal pancreata these data indicate that mgmt activity is upregulated in dysplastic epithelium and its expression increases during RT progression reaching the highest C2 in the invasive components of the RT resistance of pancreatic tumor cells to alkylating agents was verified with four pancreatic tumor cell lines capan cfpac panc and miapaca having mgmt levels of and fmolmg protein respectively were resistant to bcnu but their resistance declined sharply following i.c.v. with the mgmt inhibitor obenzylguanine obg on the other hand panc and miapaca could not be eradicated with nmethylnitrosourea mnu at concentrations as high as mm even when pretreated with obg these two lines were shown to be modified genetically in microsatellite sequences by mnu and are believed to have a defective MMR which may explain their resistance to methylating agents failure of pancreatic PT to respond to nitrosoureas is related to high levels of mgmt expression and in some cases to genomic instability however these tumors can be sensitized to chloroethylating drugs and eradicated following the beta of mgmt activity by obg or homologous mgmt inhibitors | MEDAL |
recent studies have implicated a crucial role for tissue transglutaminase tg in the pathogenesis of celiac sprue a disorder of the small intestine triggered in genetically susceptible individuals by dietary SE to gluten proteolytically SD peptide inhibitors of human tg were designed containing acivicin or alternatively DON don as warheads in biochemical and cellbased assays the best of these inhibitors acpqpdonlpfnh was considerably more potent and selective than other tg inhibitors reported to date selective pharmacological inhibition of extracellular tg should be useful in exploring the mechanistic implications of tgcatalyzed modification of dietary gluten a phenomenon of considerable relevance in CS | MEDAL |
arrhythmogenic RA VVI dysplasiacardiomyopathy is recognized as an important cause of death in young patients particularly athletes in the past years cardiac mri techniques have evolved rapidly in an attempt to improve the noninvasive diagnosis of this disorder steadystate free precession sequences and more rapid fat saturation techniques have permitted a comprehensive and welltolerated examination the first formal testing of diagnostic accuracy among a broad range of readers has recently been completed despite these advances limited spatial resolution and interobserver variability have prevented successful implementation of these methods future approaches may include highfield imaging at tesla and viability imaging to improve diagnostic accuracy | MEDAL |
the growth of children with malignant disease was studied over a or year period and compared with the growth of NC matched for age and sex by calculation of the sigma score the mean standard deviation score of the children with leukaemia fell in the first year of treatment and thereafter showed little NC remaining below the normal this effect was related to cranial and craniospinal irradiation but not to age or duration of chemotherapy the loss in eventual height attained was small and does not suggest any LT interference with growth hormone production | MEDAL |
analysis of surface marker of cells after intratumor injection with nocardia rubra cell wall skeleton ncws resulted in gradually increasing percentage of macrophage pan t and bocd cells proportion of bocd cells gradually increased from th day and then decreased from th day T3 the injection fresh tumor infiltrated cells obtained from lymphatic nodule at days after injection of ncws showed cytotoxic activity against bovine leukemia cell L1 but this activity decreased with the time of cultivation and no activity could be detected after days cultivation these cultured cells were injected twice to lymphatic nodule at one week interval for adoptive immunotherapy and found to induce CR regression of nodule after weeks from first i.t. | MEDAL |
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