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the nonkeratinized epithelia of the ocular surface are constantly challenged by environmental insults such as smoke dust and airborne pathogens tears are the sole physical protective barrier for the ocular surface production of tears in inadequate quantity or of inadequate quality results in constant irritation of the ocular surface leading to dry eye disease also referred to as keratoconjunctivitis sicca kcs inflammation of the LG such as occurs in sjogren syndrome SA chronic graftversushost disease and other pathological conditions results in inadequate secretion of the AQ layer of the tear film and is a leading cause of dry eye disease the hallmarks of LG inflammation are the presence of immune cell infiltrates loss of acinar epithelial cells the secreting cells and increased production of Th1 cytokines to date the mechanisms leading to acinar cell loss and the associated decline in lacrimal gland secretion are still poorly understood it is also not understood why the remaining lacrimal gland cells are unable to proliferate in order to regenerate a SF-36 lacrimal gland this article reviews recent advances in exocrine tissue injury and repair with emphasis on the roles of PCD and stemprogenitor cells
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deficits in language comprehension have been widely reported in children with autism spectrum disorders asd with behavioral and neuroimaging studies finding increased reliance on visuospatial processing to aid in language comprehension however no T0 to date has taken advantage of this strength in visuospatial processing to improve language comprehension difficulties in asd this T0 used a translational neuroimaging RPA to test the role of a visual imagerybased reading MI in improving the brain circuitry underlying language processing in children with asd fMRI mri in a longitudinal T0 design was used to investigate interventionrelated change in sentence comprehension brain activation and PET connectivity in three groups of participants age years an EG of asd children asdexp a waitlist control group of asd children asdwlc and a group of typically developing control children T3 MI the asdexp group showed significant increase in activity in visual and language areas and righthemisphere language area homologues putamen and TH suggestive of compensatory routes to increase proficiency in reading comprehension additionally asd children who had the most improvement in reading comprehension after intervention showed greater functional connectivity between lefthemisphere language Az the middle temporal gyrus and VPI frontal gyrus while reading high imagery senter pupil size also varies due to pragmatic manipulations in two pupillometry experiments we investigated whether pupil diameter was sensitive to increased processing demands as a result of comprehending an indirect request versus a direct statement AD participants were presented with picturesentence combinations that could be interpreted either as an indirect request a picture of a window with the sentence its very hot here or as a statement a picture of a window with the sentence its very nice here based on the hypothesis that understanding indirect utterances requires additional inferences to be made on the part of the listener we predicted a larger pupil diameter for indirect requests than statements the results of both experiments are consistent with this expectation we suggest that the increase in pupil size reflects additional processing demands for the comprehension of indirect requests as compared to statements this research demonstrates the usefulness of pupillometry as a tool for experimental research in pragmatics
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invasive cardiovascular procedures such as percutaneous translumenal coronary angioplasty ptca and aortocoronary bypass surgery acbs that are currently employed in treating the coronary stenosis or occlusion caused by atherosclerosis represent a major therapeutic advance for managing coronary heart disease chd however the cellular proliferative response and associated intimal PH that can follow the damage to blood vessels that occurs with these procedures leads to late complications which cannot be effectively controlled by presently available drugs hence a new RPA is required for managing these complications termed restenosis in the case of ptca or stenosis in the case of acbs existing drug therapy is reviewed and some new approaches to this problem are provided herein further studies of growth factors and other substances that influence the cellular proliferative response that follows injury to the blood vessel wall could lead to the OD of ERP therapy inhibition of IH andor acceleration of EC cell regrowth provide a basis for such new approaches plateletderived growth factor pdgf and basic FB growth factor bfgf as well as endotheliumderived relaxing factors edrf and CGRP-LI cgrp are among the substances discussed modification of certain currently available drugs eg caantagonists could also be of value in meeting this therapeutic demand
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to assess whether chest ultrasound us can be useful in the diagnosis of lobar BAC we retrospectively analyzed the us patterns of eight patients with bronchioloalveolar carcinoma presenting with lobar consolidation for comparison patients with lobar consolidation of a benign etiology were also analyzed we found that the us patterns of lobar BAC had a characteristic homogeneous echogenic pattern the airbronchograms and airalveolograms were scarce when compared to benign consolidation the sensitivity of using these us criteria in discriminating lobar BAC was and the specificity was we also assessed the yield of usguided transthoracic cutting biopsies in the diagnosis of lobar BAC the diagnostic rate of the usguided cutting biopsy was which was superior to other diagnostic procedures such as sputum cytology fiberoptic bronchoscopy with brushing or biopsy and TNA cytology none of the patients developed complications we conclude that the distinct us pattern for lobar bronchioloalveolar carcinoma is a helpful diagnostic sign and the usguided biopsy is a useful RPA in the diagnosis of lobar BAC
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the best treatment option for liver metastases is CR surgical resection unfortunately at the time of diagnosis not all patients are candidates for R0 electrolytic therapy ect is a novel nonthermal method of tissue destruction we evaluated its safety and effectiveness in comparison with radiofrequency ablation rfa
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a rb tcell line bj has been derived from a new zealand white rb infected with alcelaphine herpes virus which has the characteristics of a lymphokine activated killer lak cell the surface phenotype of this cell L1 has been studied by FC using a panel of monoclonal antibodies mab to rb leucocyte surface markers and compared with that of another rb tcell L1 rl transformed with herpes virus ateles the expression of a number of markers is common to the two lines these include the rb analogues of cdacd cd cd and cd three antigens are expressed on bj but not rl one of these is recognized by a mab thought to recognize cd while a second is a class ii rdq molecule the third antigen is expressed on thymocytes a subset of TA neutrophils and platelets but its molecular nature is unknown these two cell lines should prove useful in preparing reagents which recognize subsets of rb t cells and for studying the mechanism of herpes virusinduced lymphoid cell deregulation
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we have analyzed the mRNA profile of monocytes in response to a HP cell wall fraction of mycobacterium bovis bcg a clinically approved adjuvant known as bcg cell wall skeleton bcgcws it is composed of mycolic acid arabinogalactan and peptidoglycan and confers tolllike receptor tlr and tlrdependent signaling that induces monocytes to differentiate into antigenpresenting cells apcs here we report differential gene expression analysis with bcgcwsstimulated versus nonstimulated monocytes bcgcws exerted massive induction of genes regulated by tlr signaling marked gene RII characteristics in bcgcwsstimulated cells compared to lipopolysaccharide lpsstimulated cells follow i spliced mrnas encoding soluble forms of trem and trem recently discovered inflammatorysignalamplifying receptors were regulated by bcgcws resulting in their differential expression ii the genes for zinciron transporter protein ziplike family proteins hke and liv were induced exclusively by bcgcws iii interleukin il rather than ilp was induced by bcgcws while interferoninducible genes were induced only by lps by RNA and reverse transcriptionpcr analyses we confirmed the differential expression of more than bcgcws RII genes and their expression was compared with that of lps and other known tlr ligands a battery of genes responded rapidly and for a short time to lps but for a long time to bcgcws structural analysis of the identified novel or hypothetical proteins revealed that some are potential candidates as signaling mediators or transcriptional regulators hence bcgcws may profoundly modulate apc responses in a way distinct from that of lps leading to possible advantages for its adjuvantactive therapeutic potential
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alterations in the cutaneous vasomotion function caused by scald burns to a large area on the flank were observed and quantified in a dorsal skin flap window with a hamster model subsequent to chronic implantation of the window chamber to provide direct microscopic observation of blood flow for an entire thickness of skin control measurements of vasoactivity in a defined network of arterioles were taken by means of a digital video image splitter over a period of several days a degrees c second water scald was then effected over to of the total body surface area and the vasoactivity was remeasured in the targeted set of sites at serial time intervals for to days data were acquired directly into a computer and analyzed for both the magnitude and time pattern of diameter fluctuations during minute observation periods average and standard deviations of diameters were computed and the prony power spectral analysis method was applied to identify the presence and strength of fluctuation frequencies in general vasomotion was suppressed for several hours subsequent to the burn and the activity was dominated by much slower contractions than control no direction of vessel diameter changes prevailed uniformly throughout the peripheral malso found that pre or PT with ta both lead to a similar reduction of kda protein phosphorylation and that the tpastimulated dna synthesis was also inhibited by ta in a dosedependent manner suggesting that the blockage of protein phosphorylation by ta was of biological significance in conclusion the work presented here demonstrated that the antitumor promoting effect of ta was not mediated by competing for the binding site with PDBu or interrupting the pkc translocation but rather by effectively blocking phosphorylation by membranebound pkc possibly through altering the biophysical properties of the membrane environment
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the antibiotic diazooxolnorleucine don an analogue of lglutamine causes limb malformations in several species including mice this report shows that don also interferes with differentiation of cartilaginous rudiments of mouse limb buds grown as organ cultures for to days in medium containing the teratogen don mugml inhibits growth of the explants and interferes with production of normal matrix by chondrocytes the cartilage of dontreated cultures exhibits a striking lack of matrix compared with that of control explants which contains abundant metachromatic matrix differentiation of OBs and secretion of osteoid around the scapula and humerus are enhanced by don the direct effects of don on growth and chondrogenesis which can be prevented by addition of lglutamine mgml to the medium can be attributed to the known interference of don in lglutaminedependent steps in metabolism the possible relationships between these effects of don in vitro and the malformations produced in vivo are discussed
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three female sibs had cerebellar hypoplasia facial dysmorphism comprising a high forehead lowset posteriorly rotated ears a prominent upper lip and receding chin and variable internal abnormalities two of the cases had deficient lobulation of the lungs two had an atrial septal defect of the HR and developmental abnormalities of the urinary system or internal genitalia one had holoprosencephaly all had normal chromosomes this syndrome does not seem to have been reported before and may be inherited in an autosomal recessive manner
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exp were conducted to evaluate the effect of LL on performance and nutrient digestibility of nursery pigs and to determine the effects of fat encapsulation by spray drying in diets fed in either meal or pelleted form in exp pigs d of age kg bw were allotted to one of four dietary treatments asfed basis control with no added lard control with added lard treatment with LL and treatment with LL in a d experiment added lard decreased adg p and adfi p during d to and overall lysolecithin improved adg linearly p during d to and overall but did not affect adfi or gf addition of lard decreased the digestibility of dm p and cp p and increased p fat digestibility when measured on d lysolecithin at but not tended to improve the digestibility of fat p on d digestibilities of dm fat cp p p and ge p were increased with the addition of lard and LL supplementation linearly decreased digestibilities of dm p ge p cp and p p in exp pigs d of age kg bw were allotted to one of six treatments in a x factorial randomized complete block design AF included level asfed basis and source of fat control diet with lard control diet with additional lard and control diet with additional lard from encapsulated spraydried fat and diet form pelleted or meal addition of lard decreased FI during d to p d to p and overall p and improved gf for d to p and overall p encapsulated spraydried lard increased adg p and gf p during d to compared with the equivalent amount of fat as unprocessed lard pelleting increased adg p during d to decreased FI during d to p and overall p and increased gf during all periods p fat digestibility was increased p with supplementation of lard and this effect was greater when diets were fed in meal form interaction p pelleting increased the digestibility of dm om and fat p results indicate that growth performance may be improved by lysolecithin supplementation to diets with added lard and by encapsulation of lard through spray drying
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despite the increasing incidence of cervical artery dissection cad due to chiropractic manipulation of the C2 spine risk factors predisposing to vascular damage are still unknown in the present study we measured fasting tHcy thcy concentration in subjects with manipulationrelated cad selected from a larger series of patients with spontaneous dissection of the neck arteries scad and in a group of control subjects ct mthfr genotypes and insbp cbs genotypes were also determined median thcy levels were significantly p higher in patients with manipulationrelated cad micromoll range to compared with controls micromoll range to and not significantly different p from those observed in patients with scad micromoll range to no significant difference in the CSD of genotypes was observed in the three CG hyperhomocysteinemia may represent a potential risk factor for manipulationrelated cad leading to structural abnormalities of the arterial wall and increasing the susceptibility to mechanical stress
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a major role of tnf in pulmonary fibrosis is supported by the following evidences obtained from PF induced in mice by bleomycin or silica particles these diseases are associated with a marked and lasting increase of the tnf mrna within the lung they can be prevented by a treatment with anti tnf antibody or aggravated by a perfusion of mouse recombinant tnf an infusion of TNF can reproduce the alterations observed during pulmonary fibrosis such as growth of fibroblasts collagen deposition cell necrosis
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a number of clinical and research situations arise that require the integration of complex multidimensional performancerelated information to determine a single quantity such as disease severity or risk level for subsequent OD of a disease this process is generally carried out either by relying on a subjective gestalt approach or by using rating scales that combine scores for component measures using an additive process without justification concepts from general systems performance theory have provided insights into this problem teaching that a fundamentally multiplicative method of integrating components is often appropriate in this paper concepts and previous supportive exp work are reviewed in the context of the quantitative characterization of disease severity a FPD T0 n is presented that mimics the twocondition situation encountered in the CT of a new drug or other therapy traditional and performance theorybased composite scores are computed for each condition on and off medications and compared with emphasis on the different quantitative pictures conveyed by each approach it is concluded that performance theory based composites are not only more CS to therapeutic agents experimentally but also have superior conceptual validity compared to traditional forms of singlenumber composites
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the cost effectiveness of performing routine neonatal cranial ultrasound scans to diagnose intraventricular haemorrhage ivh on cohorts of high risk infants is in question in the early s cranial ultrasound scans were performed on preterm infants to expand knowledge of the incidence aetiology pathogenesis and evolution of ivh in many neonatal units high risk infants are scanned on days and and prior to discharge for extremely low birthweight elbw infants CUS scanning is often used as a surrogate for assessment of neurodevelopmental outcome with information from meta analyses used to counsel parents about the likelihood of subsequent neurosensory disability
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carotid intimamedia thickness imt is a subclinical marker of atherosclerosis and a strong predictor of stroke pericardial fat pf the fat depot around the HR has been associated with several atherosclerosis risk factors we sought to examine the association between carotid imt and pf and to examine whether such an association is independent from common atherosclerosis risk AF including measures of overall adiposity
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bracken ferns are some of the most widespread ferns in the world causing immense problems for land managers foresters and rangers bracken is suspected of causing cancer in humans due to its content of the carcinogen PT ingestion of bracken or food and drinking water contaminated with PT may be the cause the aim of this T0 was to monitor the content of ptaquiloside in bracken stands from britain to obtain a better understanding of the ptaquiloside dynamics and to evaluate the environmental implications of using different cutting regimes in bracken management the ptaquiloside content in fronds ranged between and μgg corresponding to a PT load in the standing biomass of up to mgm in mature fronds ptaquiloside was also found in the underground rhizome system μgg and in decaying litter μgg the amount of PT present in bracken stands at any given time is difficult to predict and did not show any correlations with edaphic growth factors the content of ptaquiloside turned out to be higher in fronds emerging T3 cutting compared to uncut fronds environmental risk assessment and bracken management must therefore be based on actual and site TPS determinations of the PT content care must be taken to avoid leaching from cut ferns to aquifers and other recipients and appropriate precautionary measures must be taken to protect staff from exposure to bracken dust
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recent OD of highthroughput analytical techniques has made it possible to qualitatively identify a number of metabolites simultaneously correlation and multivariate analyses such as principal component analysis have been widely used to analyse those data and evaluate correlations among the metabolic profiles however these analyses cannot simultaneously carry out ID of metabolic reaction networks and prediction of dynamic behaviour of metabolites in the networks the present study therefore proposes a new RPA consisting of a combination of statistical technique and mathematical modelling RPA to identify and predict a probable metabolic reaction network from timeseries data of metabolite concentrations and simultaneously construct its mathematical model firstly regression functions are fitted to experimental data by the locally estimated scatter plot smoothing method secondly the fitted result is analysed by the bivariate granger causality test to determine which metabolites cause the change in other metabolite concentrations and remove less related metabolites thirdly ssystem equations are formed by using the remaining metabolites within the FR of biochemical systems theory finally parameters including rate constants and kinetic orders are estimated by the levenbergmarquardt algorithm the estimation is iterated by setting insignificant kinetic orders at zero ie removing insignificant metabolites consequently a reaction network structure is identified and its mathematical model is obtained our RPA is validated using a generic inhibition and activation MM and its practical application is tested using a simplified model of the glycolysis of lactococcus lactis mg for which actual timeseries data of metabolite concentrations are available the results indicate the usefulness of our approach and suggest a probable pathway for the production of lactate and acetate the results also indicate that the approach pinpoints a probable strong inhibition of lactate on the glycolysis pathway
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to evaluate the prevalence risk factors possible etiology prognosis and management of proteinuria in renal SPK recipients we studied adult renal transplant recipient patients randomly selected from our center patients were reviewed retrospectively and patients were followedup prospectively for a period of one year the patients were classified into three groups according to the results of UA and spot urinary albumin creatinine ratio group a patients with normoalbuminuria group b patients with microalbuminuria and group c patients with macroalbuminuria persistent posttransplantation proteinuria was detected in patients the etiology of posttransplantation proteinuria included chronic allograft dysfunction in patients AR in patients SPK glomerulopathy in eight patients glomerular disease in patients and other etiology in patients proteinuric paxperiences may be explained in part by genebysex interactions
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interaction of nanoparticles with food matrix components may cause unpredictable health complications using an improved caco cellbased in vitro coculture MM the potential of quercetin as one of the L1 food flavonoids to alter the effect of silver nanoparticles agnps nm in the Caco-2 mucosa at real life concentrations was investigated agnps μgml decreased cell viability and reduced thiol groups induced oxidativenitrosative stress and lipid peroxidation and led to activity changes of various antioxidant enzymes after h SE the contribution of ag ions within the concentrations released from NPs was shown to be less important compared to agnps while leading to inflammatory response in the intestines agnps paradoxically also showed a potential antiinfammatory effect manifested in downregulated il C2 quercetin coadministered with agnps led to a reduction of cytotoxicity oxidative AS and recovered metabolic activity of caco cells suggesting the protective effects of this flavonoid against the harmful effect of agnps quercetin not only alleviated the effect of agnps on the gastrointestinal cells but also demonstrated a potential to serve as a tool for reversible modulation of intestinal permeability
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as deubiquitinases several ubiquitin specific protease members have been reported to mediate tumorigenesis although ubiquitin specific protease usp was previously demonstrated to suppress p transcriptional activity and dna repair its role in carcinogenesis remains elusive in this T0 we sought to define a novel role of usp in tumorigenesis it was found that usp was significantly upregulated in HCC carcinoma hcc cells and most clinical specimens further functional investigation also showed that usp knockdown suppressed cell proliferation migration drug resistance and induced apoptosis on the other hand usp overexpression promoted colony formation migration DR and tumorigenesis additionally the inactivated p
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lglutamate appears to be a major excitatory neurotransmitter in the hypothalamus its action is mediated via ionotropic and metabotropic glutamate receptors mglur eight mglurs have already been cloned in the present study the hypothalamic distribution of mglura has been investigated by immunocytochemistry using monoclonal antibodies recently produced by some of the present authors t j g r k t k the observations have been compared with findings obtained with a polyclonal antibody a widespread and heterogeneous CSD of mglura was found with the monoclonal antibodies intense immunolabelling of perikarya and dendrites occurred in several hypothalamic cell groups including the suprachiasmatic anterior periventricular anterior hypothalamic posterior part paraventricular supraoptic arcuate tuberal magnocellular dorsomedial and mammillary nuclei particularly in the medial it was only the ventromedial nucleus in which several perikarya were stained by the polyclonal antibody but appeared to be negative by the monoclonal antibodies the findings fit extremely well with the data on the Thy CSD of mglur mrna with the exception of the ventromedial nucleus it remains to be elucidated whether alternatively spliced variants of mglur mglurb and c are expressed in this nucleus further they confirm the results of former immunohistochemical studies in addition they indicate that a significant part of the NE region of the hypothalamus including the paraventricular supraoptic and arcuate nuclei also contains mglur suggesting that this receptor may play a role also in NE regulation
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feline bone marrow cells can be EC for erythroid and myeloid progenitors by counterflow centrifugal elutriation cce and subsequent treatment of the cce fractions with the SBA sba lectin separation of cce fractions into sba and sba populations yielded cells EC for bfue and cfugm progenitors respectively differential analyses revealed a high percentage of erythroid lineage cells in the sba fractions and in the sba fractions a high concentration of myeloid cells of varying maturation stages the latter cells but not the cfugm progenitors could be removed by immunomagnetic depletion from cce fractions using a monoclonal antibody mab TPS for cd cells in feline bone marrow resulting also in a population containing predominantly erythroid differentiating cells mice were immunized with cce fractions EC for erythroid lineage cells and the splenocytes fused with spo cells for hybridoma OD supernatant SC fluids from hybridomas were analyzed by FC with whole bone marrow and select ccesba fractions as the target cells those hybridomas suggestive of containing the desired antibodies as indicated by the percentage IF were subcloned and the mabs utilized in clonogenic assays treatment of bone marrow cells or cce fractions with the mabs followed by immunomagnetic depletions led to identification of two k and q reactive with the bfue progenitor and one k reactive only with latedifferentiating erythroid lineage cells thus removal of cells from a ccesba suspension reactive with k or q led to greater than reductions of the bfue progenitors and a population EC for cfugm removal of cells reactive with mab k however led to a marked enrichment fold of both bfue and cfugm progenitors
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tuberculosis is an ancient human scourge that continues to be an important public health problem worldwide the increasing number of multidrugresistant mdr m tuberculosis isolates from both aids and nonaids patients is an ominous trend that threatens tuberculosis eradication programs both in the us and overseas new antituberculosis vaccines with therapeutic properties are urgently needed for HIV virusinfected individuals as well as health care professionals likely to be exposed to mdr tubercle bacilli recombinant dna vaccines bearing protective genes from virulent m tuberculosis are being developed using shuttle phasmids to transfer genetic material from one mycobacterial species to another improved CA procedures are needed to measure the protection afforded by these new vaccines under exp and field test conditions tuberculosis vaccine development should be given a high priority in current medical research goals
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the method of somatic hybridization was used to generate a panel of hybridomas producing monoclonal antiidiotypic antibodies monoaiab imitating biological effects of human alphainterferons hifalpha induction of syngeneic antiidiotypic antibodies in balbc mice was achieved with monoclonal antibodies mca if capable of NT three kinds of hifalpha lymphoblastoid leukocyte geneticengineering the screening of monoaiab was done by determinations of antiviral activity avactivity of S9 from growing hybrid cell cultures caused by the cp effect of doses of mouse encephalomyocarditis virus memc by a micromethod in vero cells grown in well plates monoaiab were found to neutralize mca if and not to bind with immunosorbent of staphylococcal reagent containing protein a and balbc mouse immunoglobulins it was shown that monoaiab possessed avactivity against memc and vesicular stomatitis viruses and were not VPI in this activity to commercial preparations of leukocyte ifalpha monoaiab had tissue speciesspecificity triggering the mechanism of avactivity in human and simian cells as well as bovine A6 mdvk line imitating hifalpha in this effect
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the lightinduced reaction of the bluf BL photoreceptor using flavin adenine dinucleotide photoreceptor pixd from synechocystis sp pcc slr was investigated using the timeresolved transient grating method a conformational change coupled with a volume contraction of ml mol was observed with a time constant of ms following photoexcitation at a weak excitation light intensity there were no further changes in volume and diffusion coefficient d the determined dvalue à m s suggests that pixd exists as a decamer in solution and this oligomeric state was confirmed by sizeexclusion chromatography and blue native polyacrylamide gel electrophoresis surprisingly by increasing the excitation laser power we observed a large increase in d with a time constant of ms following the volume contraction reaction the dvalue of this photoproduct species à m s is close to that of the pixd dimer combined with transient grating and sizeexclusion chromatography measurements under lightilluminated conditions the lightinduced increase in d was attributed to a transient dissociation reaction of the pixd decamer to a dimer for the mamutated pixd no volume or dchange was observed furthermore we showed that the ma mutant did not form the decamer but only the dimer in the dark state these results indicate that the formation of the decamer and the conformational NC around the met residue are important factors that control the regulation of the downstream ST by the pixd photoreceptor
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an immuneinflammatory challenge can affect reproduction at the level of the hypothalamus PIT gland or gonads nonetheless the L1 impact is thought to occur within the BB or the pituitary gland the present T0 was designed to examine the effect of intravenous iv lipopolysaccharide lps i.t. on the expression of gonadotropinreleasing hormone gnrh and the gonadotropinreleasing hormone receptor gnrhr genes in the Thy structures where gnrh SN are located as well as in the anterior PIT gland ap of anestrous ewes we also determined the effect of lps on luteinizing hormone lh PR it was found that iv lps injection significantly decreased gnrh and gnrhr mrnas levels in the preoptic area por and por respectively and median eminence and respectively por endotoxin injection decreased plasma lh concentration por and gnrhr mRNA por in the ap together these observations indicate that inflammatory challenge can affect the reproductive system at the hypothalamic level through modulation of the activity of gnrhergic SN as well as at the level of the ap via inhibition of lh secretion orand through reduction of the sensitivity of gnrh reactive pituitary cells to gnrh stimulation the presence of gnrh mrna in the median eminence the hypothalamic structure where gnrhergic SN terminals are located suggests that the axonal transport of gnrh mrna may occur in these SN this phenomenon could play an important role in the physiology of gnrh neurons our data demonstrate that immune stress could be important inhibitor of this process
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a novel method has been developed to allow the accurate determination of equilibrium gasphase structures from experimental data thus allowing direct comparison with theory this new method is illustrated through the example of sodium chloride vapor at k using this approach the equilibrium structures of the monomer nacl and the dimer nacl together with the fraction of vapor existing as dimer have been determined by gasphase electron diffraction supplemented with data from microwave spectroscopy and ab initio calculations rootmeansquare amplitudes of vibration u and distance corrections ra re have been calculated explicitly from the ab initio potentialenergy surfaces corresponding to the vibrational modes of the monomer and dimer these u and ra re values essentially include all of the effects associated with largeamplitude modes of vibration and anharmonicity using them we have been able to relate the ra distances from a gasphase electron diffraction experiment directly to the re distances from ab initio calculations vibrational amplitudes and distance corrections are compared with those obtained by previous methods using both purely harmonic force fields and those including cubic anharmonic contributions and the diffterm labor that subsides in response to tocolysis and who subsequently deliver at term are considered to have false PT labor however the episode of preterm labor may represent the uterine response ie uterine contractions to an insult not severe enough to trigger PT parturition but which may put the fetus at risk for additional pregnancy complications including growth restriction the objective of this T0 was to compare the frequency of smallforgestationalage sga neonates among patients with an episode of increased uterine contractility who delivered at term and those who delivered PT
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the relative potencies of dopamine receptor agonists in causing stereotypy in rats when injected into the olfactory tubercles and contralateral rotation when injected unilaterally into the Cd nucleus of rats with lesions of the nigrostriatal dopamine pathway were determined the actions of some agonists in eliciting these responses following peripheral injection and the relative potencies of dopamine IL-1ra in inhibiting them were also determined dopamine AP and amino and ADTN a dtn a dtn and nn dipropyl a dtn induced both responses in contrast tetrahydrodihydroxyphenylhbenzazepine hcl sk f whether injected intracerebrally or peripherally induced CL rotation but not stereotypy contralateral rotation and stereotypy induced by apomorphine or nn dipropyl a dtn were inhibited by haloperidol PIM and fluphenazine but these drugs failed to inhibit rotation induced by sk f clozapine inhibited rotation induced by sk f AP or nn dipropyl a dtn but failed to inhibit stereotypy loxapine was more potent in inhibiting stereotypy than rotation whereas clothiapine inhibited rotation and stereotypy at similar doses irrespective of the agonist used to elicit the response contralateral rotation induced by sk f was not inhibited by yohimbine prazosin atropine methysergide mepyramine or propranolol the results provide evidence that contralateral rotation induced by dopamine receptor agonists is mediated by two different classes of dopamine receptors and that these receptors differ from those mediating the stereotypy response the receptors mediating these responses appear classifiable in terms of their sensitivity to the agonist actions of sk f or AP respectively sk f sensitive receptors are susceptible to blockade by CLZ but are not blocked by haloperidol pimozide or FLU apomorphinesensitive receptors are susceptible to blockade by haloperidol pimozide and FLU but appear divisible into two subclasses depending on whether or not they are blocked by CLZ and on their sensitivity to blockade by loxapine
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the cribari matrix method cmm is the standard to identify potential overtriage and undertriage but requires case reviews to correct for the fact that injury severity score does not account for physiology or comorbidities nor is it well correlated with resource consumption further the secondary reviews introduce undesirable subjectivity this T0 assessed if the standardized triage assessment tool stata combination of the cmm and the need for trauma interventioncould more accurately determine overtriage and undertriage than the cmm alone
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the characteristics of thermophilic anaerobic sequencing batch reactor asbr treating thermalhydrolyzed sewage sludge were investigated the results showed that increasing the olr cod of the thermophilic asbr treating thermalhydrolyzed sewage sludge from kgm x d to kgm x d lead to the acidification of the reactor with the accumulation of the volatile HFA vfa and the drop of the ph and gas production this acidification is recoverability the olrcod of the thermophilic asbr treating thermalhydrolyzed sewage sludge can reach to kgm x d T3 the system was recovered under the olrcod of and kgm x d the methane yield chcodinput of thermophilic asbr were and ml respectively there are significant linear relationship among olr and mpr the methane yield with the increase of the olr the methane production rate increased while the methane yield reduced
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a yearold woman in good GA health presented a massive intestinal and Tc ischemia with rapid postoperative death due to mesenteric inflammatory venoocclusive disease MES inflammatory venoocclusive disease first described in is a vasculitis of unknown etiology limited to the mesenteric area affecting exclusively veins and venules and sparing arteries histologically there are acute lesions of lymphocytic andor necrotizing sometimes granulomatous phlebitis and chronic lesions of myointimal hyperplasia reducing the lumen of the veins in this case polymorphonuclear eosinophils were particularly numerous
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isolated angiitis of the central nervous system may occur more frequently and with a more favorable outcome than has previously been described during the past years we diagnosed this condition in patients ranging in age from to years whose initial presenting PS included severe HA transient focal neurologic deficits or seizures the diagnosis was established in all cases by characteristic angiographic findings all patients were initially treated with highdose steroids one patient later required the addition of an IS agent all patients responded initially to the CS and were in clinical remission while receiving either a small dose of steroids or no medication after a mean followup of months one patient died months after diagnosis presumably of an intracerebral hemorrhage this experience suggests that the diagnosis of isolated angiitis of the CNS system should be considered in any young person complaining of persistent headache transient focal neurologic deficits or seizures angiography usually yields characteristic diagnostic findings treatment should consist of highdose CS with the addition of IS agents only in cases where CS are ineffective
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a crosssectional survey of primaryschool children in bahrain was conducted to estimate the prevalence of goitre and ID according to age sex and area of residence during januarymay children were randomly chosen from all government schools children were examined for goitre and of those were randomly selected for UI level assessment only children had goitre although median urinary iodine was above microgl of children had low urinary iodine levels although ID does not pose a significant public health problem in bahrain education about the nutritional value of iodized salts in the prevention of this disorder could increase public awareness
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bovine cardiac myosin atpase activity was rapidly inactivated by the purine disulfide analog of atpdithiobisinosinyl imidodiphosphate kinetic investigations showed that this analog acted as a sitespecific reagent at degrees with a ki of mum and a halflife of min at saturating inhibitor concentrations concentrations to mum of atp adenylyl imidodiphosphate amppnp or adp that saturated the AS site caused an enhancement in the rate of inactivation indicating the purine disulfide analog was not reacting at the active site under these conditions saturation kinetic data were still observed with ki values remaining unchanged mum but with the halflife of inactivation decreasing to min atp and min amppnp at saturating inhibitor concentrations at concentrations greater than mm atp amppnp or adp there was a decrease in the rate of inactivation implying protection by these nucleotides however saturation kinetics of inactivation could no longer be demonstrated implying a change in the mechanism of inactivation a comparison of the inactivation of the mg ca and edtaatpase MICs of cardiac S1 after modification by the purine disulfide analog showed that the mg and caatpase MICs plateaued at approximately and respectively while the edtaatpase activity continued to decrease to below this evidence supports the suggestion that the purine disulfide analog was not reacting at the AS site equilibrium dialysis experiments were used to measure the IB of hamppnp to native cardiac S1 the thiopurine nucleotidemodified S1 and the derivative formed by displacing the thiopurine nucleotide by cyanide the antihypertensive effect of atenonol and pra are no longer significant on longterm treatment
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inflammation results in an early and maintained elevation in nerve growth factor ngf C2 in inflamed tissues NT the action of the increased ngf with specific antingf antibodies substantially diminishes inflammatory hypersensitivity indicating that this neurotrophin is a key mediator in the production of inflammatory pain the hyperalgesic actions of ngf may in part be the consequence of an increase in sensitivity of the IP terminals of high threshold nociceptors either as a result of a direct action of ngf on trka expressing sensory fibres or indirectly via the PR of sensitizing mediators from trka expressing inflammatory cells and postganglionic sympathetic neurons ngf is also however retrogradely transported in sensory SN to the dorsal root ganglion where it alters transcription of a number of proteins and peptides this chapter reviews evidence suggesting that an ngfmediated modification of mRNA in the dorsal root ganglion during inflammation is CE to the pathophysiology of persistent pain the phenotype changes produced by ngf during inflammation include elevation of neuropeptides which may amplify sensory input signals in the spinal cord and augment neurogenic inflammation in the periphery and the upregulation of growth related molecules which may lead to a hyperinnervation of injured tissue by promoting terminal sprouting
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probiotics are live microbial organisms that are present in foods or dietary supplements and that confer health benefits to the host when ingested in sufficient quantities probiotics can be bacterial eg bifidobacteria spp and lactobacillus spp or yeasts eg saccharomyces boulardii the administration of probiotics is often believed to be by and large beneficial for individuals with inflammatory or infectious diseases of the gastrointestinal tract these positive effects are generally attributed to the ability of probiotics to regulate intestinal permeability normalize host intestinal flora improve gut immune barrier CF and equilibrate the balance between Th1 and antiinflammatory cytokines of note however these claims are not always substantiated by findings from properly conducted PCTs of particular importance even when results from RCTs support the beneficial effects of a particular probiotic for a TPS indication the benefits achieved by the probiotic are generally not translatable to other probiotic formulations this review discusses the gastrointestinal indications for probiotic use and describes the level of evidence that supports the use of specific probiotics for these indications several indications are addressed including enteric infections gastritis caused by helicobacter pylori infection NEC inflammatory bowel diseases and IBS
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to propose a simple accurate method for measuring t in flowing blood and the arterial input function aif and to evaluate the impact on DCE-MRI dcemri quantification of pharmacokinetic parameters
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stable single αhelical sah domains exist in a number of unconventional myosin isoforms as well as other proteins these domains are formed from sequences rich in charged residues arg lys and glu they can be hundreds of residues long and in isolation they can tolerate significant changes in ph and salt concentration without loss in helicity here we describe methods for the preparation and purification of sah domains and sah domaincontaining constructs using the S1 sah domain as an example we go on to describe the use of circular dichroism spectroscopy and force spectroscopy with the atomic force TSM for the elucidation of structural and mechanical properties of these unusual helical species
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growth factors play a role in wound healing and tumour growth the aim of this study was to compare the effect of partial hepatectomy ph and laparotomy on serum levels of growth AF and acutephase proteins in patients with colorectal liver metastases and to correlate these C2 with prognosis T3 ph
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the in vitro production of ghb was observed in freshly collected untreated whole blood samples using glass bdvacutainers and polypropylene smonovettes ghb concentrations were determined daily over a period of one week and after and weeks again furthermore the ghb concentration in untreated random whole blood samples stored at °c for a longer period of time samples month samples month and samples month was also determined for comparison the in vitro production of ghb in freshly collected and prepared serum samples was observed ghb serum concentrations were determined three times over a period of one week and once again after six weeks sample preparation was performed by means of methanolic extraction following the precipitation of whole blood and SS samples a methanolic standard calibration was done in a low range of μgml lod lloq for quantification a spiked blood bank serum with a determined ghb concentration of μgml was used QTc calibrations in the range of μgml were used lod μgml lloq μgml REC high level μgml low level μgml
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study design and OD are presented for an investigation of risk factors for senile cataract in a collaborative indous casecontrol T0 in new delhi india this T0 emphasizes the relationship of nutritional status as ascertained by biochemical assessment on plasma and red blood cells and by dietary PH to TPS cataract types nuclear cortical posterior subcapsular
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novel tetracationic diviologen compounds of the general formula chchnvchvchnch where v bipyridinium and n or were investigated as electrochemical reporters of dna duplex formation these compounds bind to both singlestranded dna ssdna and doublestranded dna dsdna when the dna is either present in solution or immobilized at electrode surfaces binding to thiolated ssdna and dsdna immobilized at au electrodes was characterized using the electrochemical response for the reduction of the v state to the v viologen radical cation state an analysis of the charge for this reduction provided isotherms and binding constants for binding of these diviologens to both forms of immobilized dna saturation of the binding is achieved at solution concentrations near microm for both the n and diviologens IB to ssdna is driven by electrostatic charge NT for the n case the binding is cooperative in the presence of dsdna the n diviologen exhibits a unique reduction potential for the v redox couple that is shifted approximately mv negative of that in the presence of ssdna this new EC signature is attributed to the reduction of viologen CG bound in the minor groove of the dna duplex for dsdna in solution an increase in the thermal denaturation temperature tm from to degrees c as a function of the n diviologen concentration confirmed its interaction with the duplex circular dichroism cd spectroscopy also was used to investigate the binding of both the v and v redox states of the n diviologen to dsdna in solution for the v state a cd signal was observed that is consistent with the presence of facetoface pi dimers of the viologen groups this unambiguously demonstrates the IB of this redox state of the diviologen in the dsdna minor groove and the formation of such dimers in the minor groove
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prenatal diagnosis of fragile x syndrome identifying full mutations has been described here we report on a case of a prenatal test concerning a normal male carrier of the fragile x syndrome SB analysis of the fragile x gene resulted in the ID of a premutation in dna isolated from the chorionic villus sample using a PCR reaction pcrbased CA the cgg repeat length was determined to be cgg repeat units confirmation of this premutation in the CV sample was based on the cytogenetic analysis of the expression of the fragile site at xq applied on a cordocentesisderived blood sample
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some districts of bihar especially muzzaffarpur district have been known to be affected by annual outbreak called locally as acute encephalitis syndrome aes which became one of the major health concerns in bihar due to its high fatality and complications several hypotheses like bat virus heat stroke pesticide exposure and the presence of a compound methylenecyclopropyl glycine mcpg in litchi have been proposed by different investigators for aes when the investigators examined the symptoms signs and the epidemiological data bat virus and HS hypothesis were ruled out two L1 hypotheses which remain in question were the SE to pesticides or mcpg present in litchi therefore this study was designed to check the presence of both in the muzzaffarpur samples of ripe and semi ripe litchi fruits the fruit cover of ripe and semi ripe litchi showed the traces of malathion μgg and ppddt μgg while no pesticide residues were detected in the pulp of ripe or semi ripe litchi thereby ruling out the possibility of pesticide exposure in children of muzzaffarpur however mcpg was detected in the pulp of semi ripe μgg and ripe litchi fruits μgg further when the human condition was simulated in animals there was deprivation in body weight and gl C2 in starved litchi seed dosed rats causing hypoglycemia these results suggest that the cause of hypoglycemic encephalopathy in muzzaffarpur is related to the consumption of semi ripe and ripe litchi fruits by undernourished children
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from excised dog lungs we isolated airtight the intrapulmonary main bronchi cm in length with beads according to the technique described by takishima et al j appl physiol except for the most distal bronchus in which a retrograde catheter was inserted into the pleural surface of the lung air flowed from the retrograde catheter to the isolated main lobar bronchi at a given transpulmonary pressure pl with variable dynamic rates of driving pressure we studied isovolume pressureflow ivpf curves in the isolated intrapulmonary bronchi the ivpf curves showed maximum expiratory flow vmax and negative effort dependence vmax increased with increased pl and with increased dynamic rate of driving pressure and decreased with increased IP airway resistance added to the VA catheter bronchograms showed that DC occurred near the outlet of the isolated bronchi when the isolated bronchi were dissected free from the surrounding parenchyma vmax decreased by compared with vmax in IN bronchi we concluded that vmax in intrapulmonary bronchi is preserved by mechanical interdependence between bronchi and parenchyma
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the present study was designed to define the role of nitric oxide no in RT MC through the direct intravital microcirculatory observations T3 administration of no synthase nos inhibitor and no donor both regionally and systemically more specifically we tested the following hypotheses endogenous no derived from RT V1 endothelium andor tumor cells increases andor maintains tumor blood flow decreases leukocyteendothelial interactions and increases VP exogenous no can increase tumor blood flow via vessel dilatation and decrease leukocyteendothelial interactions and no production and tissue responses to no are tumor dependent to this end a murine mammary adenocarcinoma mcaiv and a Caco-2 lst were implanted in the dorsal skinfold chamber in ch and severe combined nude mice respectively and observed by means of intravital fluorescence microscopy both regional and SVR inhibition of endogenous no by n omeganitrolarginine methyl ester lname mumoll superfusion or mgkg intravenously significantly decreased vessel diameter and local blood flow rate the diameter NC was dominant on the arteriolar side superfusion of no donor Sp no mumoll increased RT vessel diameter and flow rate whereas SVR i.t. of Sp no mgkg had no significant effect on these parameters rolling and stable adhesion of WBCs were significantly increased by i.v. of lname in untreated animals both mcaiv and lst RT vessels were leaky to Al SVR no inhibition significantly attenuated RT VP of mcaiv but not of lst tumor immunohistochemical studies using polyclonal antibodies to endothelial nos and inducible nos revealed a diffuse pattern of positive labeling in both mcaiv and lst tumors nitrite and nitrate levels in RT ISF of mcaiv but not of lst were significantly higher than that in normal subcutaneous interstitial fluid these results support our hypotheses regarding the microcirculatory response to no in tumors modulation of no level in PT is a potential strategy for altering tumor hemodynamics and thus improving oxygen drug gene vector and effector cell delivery to solid tumors
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since the dawn of endovascular aortic aneurysm repair evar starting from its initial report in there has been a significant evolution in stent VG design and delivery systems complications mostly endoleaks and reintervention rates T3 evar remain amongst the most challenging aspects in comparison with traditional open repair the use of a sacanchoring endograft changes the RPA of aneurysm exclusion the nellix⢠endovascular aneurysm sealing system endologix inc irvine ca consists of balloon expandable stents surrounded by endobags that are filled with a polymer thereby sealing the aneurysm by sealing the aneurysm sac instead of exclusion with only proximal and distal fixation the risk of stent migration and endoleaks is theoretically diminished current investigational use is aimed to confirm clinical success decreased complication and AA intervention rates compared to conventional endovascular repair
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we have cloned and sequenced the structural genes encoding the delta sterol desaturase erg gene and the alphamethyl sterol demethylase erg gene from candida glabrata l leu single and double mutants of these genes were created by gene deletion the phenotypes of these mutants including sterol profiles aerobic viabilities antifungal susceptibilities and generation times were studied CS ld erg deltaleu accumulated mainly ergostadien betaol was aerobically viable and remained susceptible to antifungal agents but had a slower generation time than its parent CS llud leu erg deltaura strains required medium supplemented with ergosterol and an anaerobic environment for growth a spontaneous aerobically viable mutant lludr ltium hexamethyl propyleneamineoxime singlephoton emission computed tomography spect in children with electroclinical features of frontal lobe epilepsy fle ictal spect demonstrated unilateral frontal hyperperfusion in of children one lobar two frontocentral six DL six frontopolar three orbitofrontal one medial frontal and one insula concordant with electroclinical lateralization in of hyperperfusion was evident in the ipsilateral BG in of and the contralateral cerebellum in of children interictal spect showed unilateral localized FC hypoperfusion concordant with electroclinical lateralization in only two of children ictal spect localization to the frontocentral media frontal or dorsolateral regions was associated with asymmetric tonic posturing CL headeye deviation and unilateral clonic jerking p ictal spect localization to the frontopolar or orbitofrontal regions was associated with vocalization hyperventilation truncal flexion and complex gestural automatisms p or ictal spect has the potential to localize seizures in patients with intractable fle and advance understanding of the in vivo anatomicoclinical relationships of frontal lobe seizures
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kidney androgenregulated protein kap a proximal tubule androgenregulated gene codes for a protein of unknown function
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the outcome of patients with follicular lymphoma fl has improved over the last two decades through the introduction of anticd monoclonal antibodies usually used in combination with chemotherapy however patients with fl still experience multiple relapses requiring several lines of treatment early toxicity of chemotherapy is a significant concern and as the life expectancy of patients with fl is increasing late toxicities become an increasingly important concern progress made in understanding the biology of fl especially dysregulation of intracellular pathways and immunological antitumor responses recently allowed for the development of innovative chemofree therapeutic approaches in this report different options such as new anticd antibodies antibodies targeting other CSA bispecific antibodies immunomodulation idiotype vaccine and other targeted therapies are presented the article also highlights how although promising in early phase studies the costeffectiveness of new agents will have to be justified in phase iii trials furthermore chemofree regimen might not mean toxicityfree treatment and monitoring of early and late toxicities is required
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general practitioners are frequently consulted to assess a variety of skin lesions actinic keratoses account for an important number of those discovered spontaneously by physicians especially in elderly patients they then wonder whether or not they should treat these precancerous lesions which may become invasive and may transform into squamous cell carcinoma however there are clear therapeutic guidelines in place when patients present with only a small area of actinic keratosis that shows no signs of malignancy when patients experience no discomfort from the lesions or when they have not consulted the general practitioner because of this condition watchful waiting is a justifiable course of action
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an electric discharge was made through a gas mixture of n cm hg h cm hg and co cm hg over an aqueous solution ml ph of adenosine m and phosphate m in a liter vessel simulating primitive earth conditions amp was produced at a constant rate in the so a psychological technique of great potency for reducing pain increasing patients lifeenhancing attitudes and helping patients deal with death and separation ultimately the value of hypnosis lies in enabling an individual to potentiate inner capacities for creating psychological quiescence and physical comfort for a suffering CA patient relief that comes from within can provide a muchneeded experience of personal efficacy and strength
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adaptations of arm and thigh muscle hypertrophy to different LT periodized resistance training programs and the influence of upper body resistance training were examined
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rats TR on a DMTP dmtp task displayed mediating SMB during delays to solve the task infusion of the ACh antagonist scopolamine into the medial prefrontal SC area mpfc dose dependently impaired performance independent of delay these results indicate that scopolamine does not specifically affect WM infusion of the cholinesterase inhibitor physostigmine muscarinic subtype IL-1ra the dopamine d antagonist sch and of the gabaa receptor antagonist BIC did not affect performance in the dmtp task in a posthoc analysis scopolamine was found to impair discriminability in a delaydependent manner only in animals that used mediating behavior in the majority of the trials furthermore a time sampling method indicated that scopolamine infusions into the mpfc disrupted mediating SMB during the task results suggest that cholinergic systems in the mpfc play a role in directing attention to task relevant behavior
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NPC npc is a progressive neurodegenerative disorder with characteristic storage of glycolipids in the BB this study investigated cellular origin and temporal changes of monosialoganglioside storage in the balbc npcnih mouse brain by immunohistochemistry antigm gave positive staining of the hippocampus TH cerebellar molecular and purkinje cell layers in the week old npc mouse brain and in general the staining progressively diminished in an agedependent manner antigm gave positive staining of the hippocampus thalamus cerebellar GC SL and BS nuclei in the week old npc mouse BB in contrast to gm gm IF in these regions except for the hippocampus progressively augmented in an agedependent manner double labeling experiments with antibodies against glial fibrillary acidic protein and lysozyme showed localization of gm and gm in reactive astrocytes and macrophages respectively thus in the npc mouse BB gm accumulated primarily in neurons and astrocytes whereas gm accumulated primarily in SN and macrophages temporal profiles of storage were different from each other and depended on the cell type presumably reflecting both developmental changes and progression of the disease process we also investigated subcellular CS of storage in primarycultured purkinje cells from the neonatal npc mouse by immunocytochemistry in npc PCs gm accumulated both in the cytoplasm and dendrites whereas gm showed punctuate accumulation in perinuclear LDV thus subcellular sites of storage were also different between gm and gm in npc neurons
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previous studies have suggested the relation of particular frequency bands such as theta hz alpha hz beta hz or gamma hz to cognitive functions however there has been controversy over which bands are specifically related to attention we used the ANT to separate three anatomically defined BB networks that carry out the functions of alerting orienting and executive control of attention highdensity scalp electrical recording was performed to record synchronous oscillatory activity and PS analyses based on PET magnetic resonance imaging constrained dipole modeling were conducted for each attentional network we found that each attentional network has a distinct set of oscillations related to its activity the alerting network showed a specific decrease in theta alpha and betaband activity ms after a WS the orienting network showed an increase in gammaband activity at approximately ms after a spatial cue indicating the location of a target the executive control network revealed a complex pattern when a target was surrounded with incongruent flankers compared with congruent flankers there was an early ms increase in gammaband activity a later ms decrease in beta and low gammaband activity T3 the target ON and a decrease of all frequency bands before response followed by an increase T3 the response these data demonstrate that attention is not related to any single frequency band but that each network has a distinct oscillatory activity and time course
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we measured maximal static inspiratory and expiratory pressures pimax and pemax in patients with cystic fibrosis cf and normal control subjects to determine whether chronic hyperinflation and malnutrition reduce pimax and pimaxpemax respectively in addition we examined the effect of posture on pressures generated we used a diminution in pemax as an index of a malnutrition effect on pressures generated the patients with cf although significantly hyperinflated ratio of residual volume to TLC generated pimax values similar to those of the control subjects p greater than despite evidence of malnutrition mean body mass percentile the pemax values of patients with cf and those of control subjects were comparable p greater than there was no postural effect on pressures generated in the normal subjects or the cf group as a whole we conclude that respiratory muscle strength is normal or supranormal in cf despite chronic hyperinflation and malnutrition
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mitochondrial uncoupling protein a polytopic integral protein of the inner membrane is initially made in the cytoplasm as a soluble polypeptide amino acids lacking a cleavable targeting signal peptide earlier studies liu x bell a w freeman k b and shore g c j cell biol identified internal regions of the molecule that are critical for targeting and membrane IS here we demonstrate that the ability of uncoupling protein to insert into the IM is abrogated when the molecule is fused behind the matrixtargeting signal of preornithine carbamyltransferase the hybrid protein was imported across the IM and deposited in the matrix where it was processed in this context however the processed product remained in the matrix and was incapable of inserting into the inner membrane
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serial sections from epoxy resinembedded rat APs were sequentially immunostained for endorphin metenkephalin and growth hormone respectively we found that metenkephalin immunoreactivity was confined to the growth hormone producing cells corticotropinendorphin cells in the anterior PIT from both normal and ADX did not contain any metenkephalin immunoreactivity when anterior PIT cells were maintained in monolayer culture for days metenkephalin immunoreactivity was still located in the growth hormoneproducing cells although the IF was weaker than in the somatotrophs in PIT tissue fixed immediately T3 death of the animals this suggested that somatotrophs synthesize metenkephalin however this cannot be proved conclusively until biosynthesis experiments have been performed the following conclusions were drawn from these findings i anterior PIT metenkephalin is not an SE artifact derived from betaendorphin with which it shares the nhterminal pentapeptide sequence ii in the anterior PIT betaendorphin is not the F0 to metenkephalin metenkephalin in somatotrophs may be of brain origin and in the somatotrophs may be bound to intracellllar receptors as has been shown for luteotropin releasing hormone in gonadotropic cells
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the effects of VF changes and ocular hypertension on visual evoked potentials were investigated by photopic erg and by luminance and patternreversal eps on glaucomatous and on normal eyes the problem was approached by way of four investigations firstly which nerve structures are affected by glaucoma and how do visual field defects caused by glaucoma influence the ep the results show a PET diminution of all intraocular nerve structures in which the prelaminary part of the optic nerve is most affected the eps especially the patternreversal eps are markedly diminished if the VF defects extend inside the degree boundary differences in the VF defects of both eyes and the course of the sickness can be well observed by the eps secondly which preoperative prognosis for visual acuity produced by the ep can be given to patients who have a dense cataract in addition to glaucoma a postoperative improvement of the VA can be expected if the leps are within the standard deviation if the ep is distinctly diminished and does not increase with increasing CS- intensity then there is no hope for an improvement of the VA T3 the T0 thirdly does a decrease of intraocular pressure in chronic and acute glaucoma influence the ep in acute glaucoma with pressure levels of mmhg or more and sometimes in chronic glaucoma with pressure levels of about mmhg an increase of the amplitude of the ep and an improvement of the VF could be noticed T3 pressure regulation fourthly what is the behaviour of the ep in normal and glaucomatous eyes at experimentally elevated intraocular pressure the amplitudes of the erg components show a gradual decrease in normal as well as in glaucomatous eyes when intraocular pressure is increased and are maintained when intraocular pressure reaches systolic ophthalmic blood pressure on the other hand the eps show a strong decrease in amplitude when intraocular pressure exceeds the mean ophthalmic blood pressure particularly in the case of glaucomatous eyes
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cell adhesion molecules mediate numerous developmental processes necessary for the segregation and organization of tissues here we show that the zebrafish biber bib mutant encodes a dominant allele at the ncadherin locus when knocked down with antisense oligonucleotides bib mutants phenocopy parachute pac null alleles demonstrating that bib is a gainoffunction mutation the mutant phenotype disrupts normal cellcell contacts throughout the mesoderm as well as the ectoderm during gastrulation stages cells of the mesodermal germ layer converge slowly during segmentation stages the borders between paraxial and axial tissues are irregular and somite borders do not form later myotomes are fused during neurulation the NT is disorganized although weaker all traits present in bib mutants were found in pac mutants when the distribution of ncadherin mrna was analyzed to distinguish mesodermal from neuroectodermal expression we found that ncadherin is strongly expressed in the yolk cell and hypoblast in the early gastrula just preceding the appearance of the bib mesodermal defects only later is ncadherin expressed in the anlage of the cns where it is found as a radial gradient in the forming neural SP hence besides a wellestablished role in neural and somite morphogenesis ncadherin is essential for morphogenesis of the mesodermal germ layer during gastrulation
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inherited immune deficiencies are a heterogeneous group of diseases that can be either isolated with the immune defect being the exclusive manifestation or associated with other abnormalities we report on two sisters born to consanguineous parents of srilankan descent who presented in infancy with immunodeficiency GD and fatal lung fibrosis immune studies demonstrated combined humoral and cellular CA including reduced immunoglobulin production an absence of lymphoid tissue markedly reduced tlymphocyte numbers and function and reduced newly thymusderived tcells both infants succumbed to rapidly progressive lung fibrosis autopsy showed dysgenetic gonads bearing no discernible oocytes in both karyotypes were normal female xx comparative genome hybridization and analysis of genes known to be associated with severe immune defects in infancy or gonadal dysgenesis showed no abnormality the distinct findings in these two sisters have not been reported before and thus suggest a hitherto unknown autosomal recessive condition that includes immune dysfunction gonadal dysgenesis and PF
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we have studied the dynamic structure of thin approximately a few nanometers liquid films of a nearly spherical nonpolar molecule tetrakisethylhexoxysilane tehos by using a combination of atomic force microscopy afm and FCS fcs ultrasensitive interferometerbased afm was used to determine the stiffness force gradient and the damping coefficient of the liquid film the experiments show oscillations in the damping coefficient with a period of approximately nm which is consistent with the molecular dimension of tehos as well as previous xray reflectivity measurements additionally we performed fcs experiments for direct determination of the molecular dynamics within the liquid film from the fluctuation autocorrelation curve we measured the translational diffusion of the probe molecule embedded within the fluid film formed on a solid ATP the autocorrelation function was best fitted with two components which indicate that the dynamics are heterogeneous in nature however the heterogeneity is not as pronounced as had been previously observed for molecularly thin liquid films sandwiched between two solid substrates
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with the exceptions of bacillus cereus and bacillus anthracis bacillus species are generally perceived to be inconsequential however the relevance of other bacillus species as food poisoning organisms and etiological agents in nongastrointestinal infections is being increasingly recognized eleven bacillus species isolated from veterinary samples associated with severe nongastrointestinal infections were assessed for the presence and expression of diarrheagenic enterotoxins and other potential VFs pcr studies revealed the presence of dna sequences encoding hemolysin bl hbl enterotoxin complex and b cereus enterotoxin t bcet in five b cereus strains and in bacillus coagulans nb enterotoxin hbl was also harbored by bacillus polymyxa nb T3 h of growth in BB HR infusion broth all seven bacillus isolates carrying genes encoding enterotoxin hbl produced this toxin cellfree supernatant fluidch had received carrageenan exhibited a reduced degree of pleural exudation polymorphonuclear cell migration lung myeloperoxidase activity an index of neutrophil infiltration was significantly reduced in loko mice in comparison with lowt lungtissue sections from carrageenantreated lowt mice showed positive staining for ICAM-1 icam vascular cell adhesion molecule vcam pselectin and eselectin which were mainly localized around vessels the intensity and degree of icam vcam pselectin and eselectin were markedly reduced in tissue section from carrageenanloko mice which also improved the histological status of the inflamed lungs taken together our results clearly demonstrate that lo modulates neutrophil infiltration in the acute lung inflammation
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to evaluate the clinical effects of bovine lactoferrin on staphylococcal mastitis in holstein cows during the early nonlactating period mammary quarters were selected randomly from cows on dairy farms twelve quarters were infused intramammarily with bovine LF twentynine quarters were infused with antibiotic as a control in the bovine lactoferrininfused group of mastitic quarters were cured at days T3 calving compared with in the control group furthermore the changes in mammary secretion induced by the infusion of bLF were investigated mean numbers of staphylococci in MG secretions were significantly decreased in both bovine lactoferrininfused quarters and antibioticinfused control quarters p unlike in the control quarters the mean total cell concentration in the MG secretions increased in bovine lactoferrininfused quarters similar results were obtained in healthy quarters which were infused with bLF in these quarters the cell population contained mainly phagocytes such as polymorphonuclear leukocytes and cells positive for cdb which is known as a complement receptor the mean concentration of c in MG secretions was significantly increased in mastitic quarters infused with bovine LF p but showed no significant NC in mastitic control quarters these results suggested that bovine lactoferrin treatment for staphylococcal mastitis in the early nonlactating period might increase the rate of cure through the induction of innate immunity in the host
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the application of phosphorodiamidate technology to pyrimidine and purine nucleosides with anticancer activity to potentially overcome the resistance mechanisms associated with parent nucleosides is reported sixteen symmetrical phosphorodiamidates were prepared from the NK amino acids lalanine and glycine all the compounds were evaluated for their cytotoxic activity against a wide panel of solid and leukaemic tumour cell lines in addition a carboxypeptidase y CA was performed on a representative phosphorodiamidate in order to reveal the putative bioactivation pathway for the reported phosphorodiamidatetype prodrugs
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the pharmacokinetics of CFS in the fluids of the ear and eye as well as in SS were studied T3 IM administration of and mgkg to eight CG of six guinea pigs a retention of CFS in the inner earsimilar to that of the aminoglycoside antibiotics was observed as the measured PL concentrations of cefsulodin and gentamicin are comparable on a weight for weight basis and as the clinical dosage of cefsulodin is much higher than that of gentamicin the perilymph concentrations of CFS reached in man are probably much higher than those of gentamicin the results obtained are compared to those of mezlocillin azlocillin and fosfomycin finally the importance of the cefsulodin perilymph concentrations in the treatment and prophylaxis of infectious inner ear complications due to the most common pathogens of COM as well as in the treatment of certain eye infections is discussed
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abstract positron emission tomographic pet studies of normal humans undergoing TPS cognitive activation paradigms have identified a region of the anterior cingulate cortex as a component of an anterior midline attentional system involved in highlevel processing selection however deficits in attention have not been demonstrated in patients following bilateral anterior cingulotomy a procedure that results in lesions of adjacent anterior cingulate SC task paradigms used in pet studies that recruit the ACC were applied to NCs and to a patient before and after cingulotomy to provide highly sensitive and functionally targeted reaction time measures of attentional performance in contrast to unchanged performance in several NP measures this patient demonstrated specific deficits in attention during the subacute postoperative period which resolved spontaneously several months T3 surgery such impairment is consistent with the evolving view of the anterior cingulates involvement in highlevel processing selection these data show the feasibility of using information from pet activation studies of normals in the design of novel chronometric tasks useful for probing abnormalities in specific cognitive operations associated with discrete cortical regions
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during mitosis adherent cells round uonformation than the unbound form during simulations for both the unbound and bound gp the C1 concerted motions derived from essential dynamics ed analyses can influence the sizeshape of the ligandbinding channelcavity of gp and therefore were related to its functional properties the differences in motion direction between certain structural components of these two forms of gp were related to the conformational interconversion between them the free SE calculations based on the metadynamics simulations reveal a more rugged and complex free SE landscape fel for the unbound than for the bound gp implying that gp has a richer conformational diversity in the unbound form the estimated free energy difference of â¼ kjmol between the global minimum free energy states of the unbound and bound gp indicates that gp can transform spontaneously from the unbound to bound states revealing that the bound state represents a highprobability ground state for gp and explaining why the unbound state resists crystallization our results provide insight into the dynamicsandfunction relationship of gp and facilitate understandings of the thermodynamics kinetics and conformational control mechanism of hiv gp
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the objective was to study the effects of patientspecific vaccine immunotherapy po with either interferongamma Th1 or granulocytemacrophage colony MSF gmcsf in patients with M1 CA shortterm cell lines were established from CA tissue resected from patients with M1 cancer for use as autologous RT cell vaccines successful cultures were expanded to to x cells irradiated and cryopreserved in aliquots of cells for intradermal testing of delayed RT hypersensitivity and cells for subcutaneous vaccinations the study design was that of a randomized phase trial patients were stratified by RT type and by whether they had measurable disease at the time vaccination was to commence and then randomized to receive either miu ifngamma subcutaneously or microg gmcsf subcutaneously at the time of each RT cell vaccination following a baseline test of delayedtype hypersensitivity dth to an intradermal injection of irradiated ATC patients received weekly subcutaneous i.v. of cells had a repeat dth test at week then received monthly vaccinations for months a positive dth test was defined as at least mm of induration survival was determined from the first dth test there were patients enrolled with a median followup of over years the most prevalent diagnoses were melanoma renal cell carcinoma and softtissue sarcoma there were patients men women average age years randomized to Th1 and men women average age years to gmcsf the average numbers of vaccine and adjuvant i.v. were and respectively for the patients who received Th1 the objective response rate was of for patients who received gmcsf the response rate was of only eight patients four from each arm had a positive baseline dth reaction to autologous RT the RT dth test converted from negative to positive in of of the Th1 group and of of the gmcsf group with patients deceased in the Th1 arm and in the gmcsf arm the year and year survival rates were and for the ifngamma arm and and for the gmcsf arm nsd both adjuvants were well tolerated and results were similar in both arms of the T0 both adjuvants were associated with a to rate of dth conversion and a year survival rate immune recognition of autologous RT can be induced with this RPA
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deep rought mutants which produce very defectiveelated epitope as il murine aht did not efficiently inhibit proliferation of tlymphocytes in mitogen and mlr pbmc stimulation assays in contrast the chimeric aht antibodies containing a human igg constant region had substantially more antiproliferative activity than their mu iggi counterparts our results indicated that the human Fc of the chimeric antibodies interacted more efficiently than the mu Fc with effector components present in the pbmc cultures this conclusion was supported by our observation that fab generated from the chimeric antibodies did not efficiently inhibit proliferation in the pbmc assays and the chimeric antibodies did not inhibit proliferation of an antigen specific il dependent human tcell clone stimulated in the absence of pbmc
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SVR cytotoxic chemotherapy remains the mainstay of MBC however prognosis and overall survival is unfavorable due to inadequate treatment response andor unacceptable toxicity natural EDC and their AS metabolites receive increasing attention as possible adjuvant therapy with CA chemotherapeutics to improve treatment response survival rates and SQ of life of breast cancer patients this T0 investigated the combination of FS lignans secoisolariciresinol and enterolactone with classic chemotherapeutic agents docetaxel doxorubicin and carboplatin with different mechanisms of action to determine whether flaxseed lignans could enhance the cytotoxic effect of such drugs in the MBC cell lines skbr and mdamb the exp data suggests that FS lignans significantly enhanced the ability of chemotherapeutic agents to cause cytotoxicity in skbr and mdamb BCCs a three compound combination study found that enterolactone and metformin together in combination with relatively low concentrations of chemotherapeutic drugs were able to significantly decrease cancer cell viability compared to low concentrations of the individual chemotherapeutic drug CT our in vitro DUE suggests a future direction in improving chemotherapeutic efficacy in breast cancer by adjuvant therapy with the FS lignans
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the effects of the administration of methyl clofenapate methylpchlorophenylphenoxymethylpropionate on the inducibility of hepatic microbody peroxisome proliferation and catalase synthesis were studied in male rats and in both sexes of wild type csa CS and acatalasemic csb CS mice these investigations included electron microscopic examination of livers assay of CL cat quantitation of catalase protein by immunotitration procedure and measurements of SS cholesterol and glycerideglycerol levels in all groups of animals administration of methyl clofenapate at dietary concentrations of and produced a significant and sustained increase in number of hepatic microbody peroxisome profiles there was no appreciable increase in mitochondrial population but several mitochondria were markedly enlarged and possessed numerous cristae the hepatic microbody proliferation in male rats and in both sexes of wild type mice following methyl clofenapate administration was associated with a twofold increase in catalase activity and in the concentration of catalase protein the increase in microbody population in acatalasemic mice however was not accompanied by a significant elevation of the cat which is due to the unusual heat lability of the mutant catalase enzyme a marked decrease in SS cholesterol and glycerideglycerol levels was observed in male rats following methyl clofenapate administration which paralleled the increase in liver cat in both strains of mice there was a significant reduction in serum glycerideglycerol concentrations all the above effects of methyl clofenapate were fully reversed when the drug was withdrawn from the diet of male wild type mice the demonstration of microbody proliferation and catalase induction with hypolipidemic compounds cpib nafenopin and in these studies with methyl clofenapate suggests a possible but as yet unclarified relationship between microbodies and hypolipidemia
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the amount of the immunoreactive protein for the tissue inhibitor of the matrix metalloproteinase timp was studied prospectively from the i.c.v. sera of breast carcinoma patients using an enzymelinked immunoassay elisa the T0 consisted of patients with a primary breast carcinoma diagnosed between and the median followup time was more than years and routine adjuvant treatment was not used in the primary treatment high timp ngml was found to correlate with a poor RFS survival rfs in primary nodenegative breast carcinoma T3 years of the followup only of the patients with a high preoperative serum timplevel were free of the relapse whereas of the patients with a low serum timp enjoyed a long rfstime log rank p high serum timp also indicated poor rfs p and overall survival p in stage i breast carcinoma in KM analysis the rfs was in patients with a low serum level of timp compared to in patients with a high serum concentration of timp in conclusion preoperative high SS timp levels predict poor outcome in primary breast carcinoma in multivariate analysis preoperative high SS timp increases the risk of relapse fold during the first years of followup in primary nodenegative breast carcinoma
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miciii is a versatile program system to support gamma spectrometry data management and data collection for experiments using the radioactive microsphere technique it is mainly written in pascal and running on a minicomputer hierarchical organ dissection schemes are used for unique classification and identification of samples for each series of experiments up to different nuclides and up to different organ dissection schemes can be handled simultaneously sample weights are collected online and sample radioactivities are measured automatically by gamma spectrometry under process control the spectra with a resolution of channels are analyzed using a modified linear regression technique and a strategy to compensate for global spectrum shifts the spectrum deconvolution algorithm was evaluated by calculating the REC indices for known nuclide mixtures and compared to the stripping method matrix method and a LR technique using window counts REC values produced by miciii are better balanced than those of the other methods miciii showed the smallest dispersion of the recovery index and exhibited least error accumulation in case of spectrum shift miciii computes regional blood flow and arteriovenous shunt and provides interfaces to customized programs or statistical software packages for further analysis it has successfully been employed in more than experiments
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in the present work we aimed to elaborate an exp MM to evaluate and quantify the shortterm memory in exp animals in this case in mice it seemed ideal to us the employment of a spontaneous behaviour ie the reexploration of the hole board automatically recorded by animals which had previously explored at a h interval the data obtained show that when reexploring the animals show a statistically significant decrease compared to the previous exploration it can be concluded that the animals had a mnestical PR and that it can be validly quantified this shows the validity of this exp MM in order to study the ST memory in mice
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mutations in the human ectodysplasina eda are responsible for the most common form of the ectodermal dysplasia and the defective orthologous gene in mice produces the tabby phenotype suggesting its vital role in the OD of hair SGs and teeth among several eda splice isoforms the most common and the longest eda splice isoforms edaa and edaa differing by only two amino acids activate nfkappabpromoted transcription by IB to distinct receptors edar and xedar the extent to which any particular isoform is sufficient for the formation of hair sweat PG or teeth has remained unclear here we report that transgenic expression of the mouse edaa isoform in Ta edaless males rescued OD of several skin appendages the transgenic tabby mice showed almost complete restoration of hair growth dermal ridges sweat glands and molars the number of hair follicles in the transgenic mice is the same as in wildtype though the development of follicles and associated glands varies from indistinguishable from wildtype to smaller andor only partially formed these results suggest that the other eda isoforms may not be absolutely required for skin appendage formation but consistent with distinctive temporal and spatial expression of the edaa isoform are likely required for AGA timing and completeness of OD our data provide the first direct physiological evidence that edaa is a key regulator of hair follicle and sweat gland initiation its soluble ligand form could aid in deriving therapeutic reagents for conditions affecting hair and sweat gland formation
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plants possess very large numbers of biosynthetic cytochrome p enzymes in spite of the importance of these enzymes for the synthesis of bioactive plant AA metabolites only two plant p structures has been obtained to date isoflavone synthase ifs is a membraneassociated cytochrome p enzyme catalyzing the entrypoint reaction into isoflavonoid biosynthesis ifs from the model legume medicago truncatula cypc was engineered by deleting the membranespanning domain and inserting a hydrophilic polypeptide in the nterminus and a four histidine tag at the cterminus the truncated form exhibited dramatically enhanced expression and solubility the engineered enzyme was expressed in escherichia coli xlblue cells and was purified by ni
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DPE was as effective as adrenaline as an eyedrop for glaucoma it was responsible for fewer SE through SE did occur it had an additive effect when used with timolol maleate and in of patients on LT medication with both drugs a rise of pressure of mmhg or more occurred when dipivalyl epinephrine was stopped as sole therapy DPE was ERP in chronic simple openangle glaucoma ocular hypertension and pseudoexfoliative glaucoma and may be useful on its own in the latter two conditions in lowtension glaucoma it seemed the best therapy when combined with timolol headache and ocular pain were uncommon but prominent side effects
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approximately one half of prescribed radiotherapy is given for palliation of symptoms due to incurable cancer distressing PS including pain bleeding and obstruction can often be relieved with minimal toxic effects painful osseous metastasis is common in oncologic practice ninety percent of patients with symptomatic bone metastases obtain some PR with a lowdose brief course of palliative radiotherapy one half of the responding patients may experience CR PR a single dose of cgy in the setting of painful bone metastasis may provide pain control comparable to more protracted treatment at a higher dose of radiation patients with lytic disease in weightbearing bones particularly in the presence of cortical destruction should be considered for prophylactic surgical stabilization of their condition routinely a brief fractionated course of radiotherapy is given postoperatively pain due to multiple BM uncontrolled by analgesics can be managed with single doses of halfbody irradiation doses of cgy delivered to the upper halfbody above the umbilicus and cgy to the lower halfbody from the umbilicus to the middle of the femur will provide some pain relief in of patients halfbody techniques have been investigated as prophylactic treatment as a complement to localfield irradiation and as fractionated rather than singledose therapy although intravenous administration of strontium has been associated with myelosuppression this treatment has been shown a to relieve pain due to BM and b to delay OD of new painful sites recent data from phase iii trials demonstrated that BPs have a role in reducing skeletal morbidity due to bone metastasis bone pain was reduced and the incidence of pathologic fracture and the need for future radiotherapy was decreased radiotherapy relieves clinical symptoms in to of patients with BB metastases brief treatment schedules eg cgy in five fractions over week are as ERP as more prolonged therapy patients with solitary brain metastasis and no extracranial disease or controlled extracranial disease should be considered for surgical resection because phase iii data indicate enhanced survival with such an RPA wholebrain radiotherapy is routinely po postoperatively a phase iii T0 is examining the impact of accelerated fractionated doses of radiotherapy two treatments per day on survival of patients with brain metastases stereotaxic radiosurgical treatment is becoming increasingly available and permits delivery of radiation to metastatic intracranial RT with minimal SE of normal surrounding brain this treatment is most commonly used at the time of a solitary recurrence of disease in patients who previously received wholebrain radiotherapy a role for this modality in newly diagnosed brain metastases remains to be defined chest PS are common in patients with T4 LC and are effectively palliated with one cgy or two cgy one fraction doses of radiation to the thoracic inlet and mediastinum chest pain and hemoptysis are more effectively palliated than cough and dyspnea in patients with stage iii CA there is no compelling evidence that radiotherapy confers a survival advantage and it may be reasonable to administer thoracic radiotherapy only when the patient has significant PS and the goal is to achieve control of these symptoms approximately of the cases of superior VC syndrome are due to lung CA and smallcell LC is the most common histologic type a histologic diagnosis should be obtained before treatment is started because detection of lymphoma or smallcell carcinoma would necessitate systemic therapy eighty percent of the patients with VC syndrome due to malignant disease achieve symptom relief with a brief fractionated palliative course of rad
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plasmaimmunoreactive trypsin irt was measured by radioimmunoassay in patients with chronic renal failure were on conservative treatment onregular haemodialysis and on regular haemofiltration irt levels were elevated in those with raised plasma creatinine and there was a significant positive correlation to plasma creatinine concentrations r p less than irt levels were not significantly altered by haemodialysis or haemofiltration it is concluded that the kidney plays an important role in the metabolism of plasma trypsin since plasma irt levels may be elevated in patients with chronic renal failure the irt determination may be misleading in diagnosing acute and CP in the presence of kidney disease
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tertoctylphenol op is a prevalent environmental pollutant that has been shown to exert both toxic and estrogenic effects on mammalian cells the effects of op on the reproductive system of AD male vertebrates are virtually unknown in the present T0 we investigated the effects of chronic SE to op on reproductive hormone secretion in the AD male rat and compared the results qualitatively with those observed in other male rats treated chronically with estrogen we injected corn oil VH or op or mg or estradiol valerate ev or microg in oil sc into moold male rats thrice weekly for either or mo the mg dosage of op and one or both dosages of ev had the following effects decreased anterior pituitary gland apg and SS lh and fsh concentrations increased apg and serum prolactin prl concentrations increased apgbody weight ratios decreased ST concentrations decreased hematocrit and decreased food consumption and body weight gain to evaluate the response of the hypothalamusapg to gonadal removal we orchidectomized some of the rats T3 the end of treatment and decapitated them wk later in orchidectomized controls SS lh and fsh concentrations rose markedly and SS prl concentrations decreased similar changem intracellular vesicular structures to the BPM the precise nature of these intracellular glut stores has however remained poorly defined using an established skeletalmuscle fractionation procedure we present evidence for the existence of two distinct intracellular glut compartments we have shown that T3 fractionation of crude muscle CM on a discontinuous SU gradient the majority of the glut immunoreactivity was largely present in two sucrose fractions and ww SU denoted f and f respectively containing intracellular CM of different buoyant densities here we show that these fractions contained and of the crude membrane glut CR respectively and could be further discriminated on the basis of their immunoreactivity against TPS subcellular antigen markers membranes from the f fraction were highly EC in transferrin receptor tfr and annexin ii two markers of the early endosome compartment whereas they were significantly depleted of both glut and the alphasubunit of nakatpase two cellsurface markers insulin treatment resulted in a significant reduction in glut content in CM from the f fraction whereas the amount of glut in the less dense f fraction remained unaffected by insulin immunoprecipitation of glutcontaining LDV from both intracellular fractions revealed that tfr was present in glut LDV isolated from membranes from the f fraction in contrast glut LDV from the f fraction were devoid of tfr the aminopeptidase vp was present in glut LDV from both f and f however LDV isolated from f contained over twice as much vp per unit of glut than those isolated from f the PSA colocalization of vpglut was further substantiated by doubleimmunogold labelling of ultrathin muscle sections overall our data indicate the presence of at least two internal glut pools one possibly derived from an endosomal recycling compartment and the other representing a specialized insulinsensitive glut storage pool both pools contain vp
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a deoxyribonuclease activity has been identified in the nuclei of the human cervical carcinoma hela this activity has the novel property of existing as a single strand TPS endo and exodeoxyribonuclease activity these MICs are ionic strength CS with retardation of activity occurring at mm nacl and above with the mn ion preferred over the mg ion as activating cation this activity extensively damages dna via its single strand nicking and gaping activity the method used to solubilize this activity as well as the enzymes characteristics are discussed
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the effects of lowlevel cadmium cd administration to rats on animal health CL and kidney thiols metallothionein and glutathione reductase gssg reductase and their modulation by cysteine as a possible protector and diethyl maleate as a possible potentiator have been investigated SD rats were treated with sodium or cd acetate micrograms cdkg orally five times a week for weeks a second group of animals received cysteine mgkg po before each gavage while a third group received DEM dem mgkg ip in addition to sodium or cd acetate when rats were treated with Cd alone neither WG nor SS parameters indicative of hepato or nephrotoxicity were affected however acidsoluble thiols primarily glutathione were decreased by about in CL only a tendency to a decrease in hepatic protein thiols was also noted no changes were observed for hepatic or renal metallothionein in response to this low level of cadmium administration CT or in combination with the other treatments animals receiving cysteine either alone or with Cd showed decreased body weight gain but no change in serum parameters acidsoluble thiols in CL were lower in cysteinetreated rats and cysteine cd while kidney thiols were unaffected administration of dem CT or with cd did not cause any alteration in body weight gain when given dem cd however an increase in SB was observed which suggests interference with hepatobiliary CF acidsoluble thiols were decreased by dem CT and dem cd in liver while renal thiols showed no change our data indicate that lowlevel cd gavage decreases hepatic cellular thiols but not those of kidney cysteine gavage does not protect from the cdrelated effect indeed cysteine itself was found to reduce acidsoluble thiols under the exp conditions this was observed only in liver as was the decrease in thiols due to dem treatment dem administration together with cd resulted in signs of liver toxicity there is no indication that inhibition of gssg reductase by cd might be involved in the thioldecreasing effect of shortterm repeated lowlevel gavage of cd to rats
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a system for interstitial photodynamic therapy with deltaaminolaevulinic acid and multiple optical fibers has been developed the system enables photodynamic treatment of large embedded RT volumes and utilizes realtime measurements to allow online dosimetry important parameters such as light fluence rate sensitizer fluorescence intensity and changes in local blood oxygen saturation are measured with the same fibers that deliver the therapeutic light data from the first clinical treatments on nodular BCCs indicate a major treatmentinduced light absorption increase rapid sensitizer photobleaching and a relatively constant global tissue oxygen saturation level during the treatment
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use of the fluorescenceactivated cell sorter proved to be an accurate and highly efficient means for cloning babesia parasites these qualities were examined by separating a mixed population of babesiainfected bovine erythrocytes composed of two isolates with different karyotypes direct evidence of polymorphism was detected during comparison of the resultant clones
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we compared the effects of AMI wr on the cytotoxicity of mafosfamide or hydroperoxycyclophosphamide hc in normal marrow progenitor cells cfugm and leukaemic progenitor cells cful during ex vivo purging for ABMT transplantation abmt mononuclear cells mnc were incubated with amifostine mgml for min washed and subsequently tested for their sensitivity to MAF or hc micrograms mncml the ld was significantly higher among amifostinetreated cells for pcmcfugm in of patients and for rcfugm in of patients p in contrast AMI exhibited no protective effects upon cful the results of this T0 will show that AMI protects normal late and early progenitor cells for the toxic effects of cyclophosphamide derivatives while preserving their antileukaemic effects these results suggest that AMI has therapeutic value as a protective agent for normal marrow progenitor cells during exvivo purging of bone marrow for abmt
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ischaemic preconditioning has not been demonstrated to reduce IS following global ischaemia in murine myocardium eighteen mouse hearts were isolated perfused in the langendorff mode and randomised to control or preconditioning groups preconditioned hearts received four periods of five T2 global ischaemia with five minutes of intervening reperfusion control NF were perfused normally during this period both CG were then subjected to minutes global ischaemia followed by T2 reperfusion IS contractile recovery and ldh leakage were assessed mean IS was reduced from of ventricular volume controls to in PC hearts p a small improvement in contractile REC was also observed of baseline in controls in PC hearts p PR of ldh did not differ significantly between groups this study confirms for the first time that ischaemic preconditioning can delay the ON of myocardial necrosis following global ischaemia in the isolated mouse HR
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the subjective physiological and behavioral effects of nalbuphine an opioid mixed agonistantagonist analgesic naloxone and hydromorphone were studied on AD male methadonedependent volunteers living on a clinical research ward the purpose was to assess nalbuphines agonist properties vs antagonist properties relative to a standard agonist HM and a standard antagonist naloxone in opioiddependent subjects drug conditions included saline PL nalbuphine hydrochloride and mg naloxone hydrochloride and mg and hydromorphone hydrochloride and mg drug conditions given by im injection were tested in five subjects under doubleblind conditions in hr exp sessions physiologic measures were monitored continuously before and for hr after drug administration pupil diameter and subject and observerrated behavioral responses were measured intermittently over this same period hydromorphone increased ratings significantly on subjective measures typical of morphinelike effects naloxone precipitated opioid abstinence which was measurable on several subject and observerrated behavioral measures and physiological measures nalbuphine produced effects which were qualitatively similar to the effects of naloxone and showed no evidence of opioid agonist effects in these methadonedependent subjects the withdrawal syndrome precipitated by nalbuphine was indistinguishable from that produced by na ligation e restored sr in four of four dogs after mgkg ode restored sr in four of four dogs T3 mgkg and mode restored sr in four of four dogs after mgkg thus ode and mode have antiarrhythmic activity which may contribute to the effects of e in patients with cardiac arrhythmias
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ten healthy female subjects performed maximum exercise on a bicycle in an ALT chamber during normoxia and hypobaric hypoxia simulating altitudes of and m the increases in systolic blood pressure responses were reduced with the degree of hypobaric hypoxia whereas HR rate and diastolic pressure responses were unchanged the increases in blood levels of aldosterone plasma renin activity adrenaline noradrenaline neuropeptidey and vasoactive intestinal peptide were similar at the different simulated altitudes angiotensinconverting enzyme and vasoactive intestinal peptide levels were not affected by hypoxia or maximum exercise the present results suggest that the decreases in systolic blood pressure responses during hypobaric hypoxia could not be explained by altered responses of the measured vasoactive substances from the reninangiotensin gastrointestinal and autonomic nervous systems
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we studied adolescent and adult patients with cystic fibrosis cf and control subjects to determine if the prevalence of atopy and bronchial hyperreactivity was increased in this disease results showed that atopic PS as defined by PH were more frequently present in the cf patients prick testing of the skin produced positive reactions in of the cf group and of the control subjects p less than and the mean number of reactions per subject was significantly higher in the former group p less than reactions to fungal antigens were strikingly positive in the cf group the cf patients had a significantly higher mean serum igg p less than ige p less than and higher mean eosinophil count p less than clearcut bronchial hyperreactivity was demonstrated in the cf group compared with control subjects bronchial provocation with micrograms of histamine led to a greater than fall in the preinhalation fev in of the cf subjects compared with of the control group with a mean percentage fall of and respectively p less than in the cf group a greater than rise in pefr occurred in after inhalation of the parasympatholytic IB micrograms and in after inhalation of the sympathomimetic fenoterol micrograms no correlation was found between bronchial CR and atopic status hla phenotype pattern or disease severity the cause of the increased prevalence of atopy and bronchial reactivity in cf patients remains unknown however it is clear that a trial of bronchodilator therapy is warranted in adolescents and young adults with cf
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haploid germ cells spermatids and spermatozoa develop in the testis after IT has been established therefore they contain various autoimmunogenic antigens but the testis is known to be an immunologically privileged organ in particular the bloodtestis barrier formed by sertoli cells protects autoimmunogenic haploid germ cells from attack by the autoimmune system experimental autoimmune orchitis eao a breakdown of the testicular immune privilege leading to immunological male infertility has been ordinarily induced in mice by immunization twice with testicular antigenscomplete freunds adjuvant cfabordetella pertussis bp we previously found that two subcutaneous injections of viable syngeneic testicular germ cells induced murine eao without the use of cfabp in both eao models the lesions are characterized by spermatogenic disturbance with lymphocytic inflammation and a second immunization with testicular antigens is critical for the disease induction in the present study we found that only one placement of a syngeneic donors testes epididymides and vasa deferentia tev into the ABD cavity or subcutaneous space was sufficient to induce eao on the recipients testes in mice it was also noted that the placement of tev induced only orchitis without epididymovasitis while the serum autoantibodies were reactive with haploid germ cells existing throughout the tev furthermore the tev placed in the abdominal cavity rather than the subcutaneous space was effective in inducing severe eao and the aj CS was most susceptible to the tevinduced eao among the three strains examined the model of eao induced by the placement of the donors tev into the ABD cavity in aj mice will be helpful for the further analyses of testicular autoimmunity
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in severe inflammatory response various blood and tissue cells including polymorphonuclear granulocytes release lysosomal proteinases extracellularly and into the circulation such enzymes as well as normally intracellular oxidizing agents produced during phagocytosis enhance the inflammatory response by degrading connective tissue structures membrane constituents and soluble proteins by proteolysis or oxidation we first used polymorphonuclear elastase e as a marker of such PR reactions the liberated proteinase competes with susceptible substrates including alpha proteinase inhibitor alpha pi and alpha macroglobulin and is eliminated finally as inactive enzymeinhibitor complexes by the RES using an enzymelinked immunosorbent CA we determined the plasma C2 of ealpha pi following major abdominal surgery multiple trauma and pancreatogenic shock whereas the operative trauma was followed by up to fold increase of the ealpha pi postoperative septicemia was associated with a to fold increase the increase of ealpha pi and a concomitant decrease of plasma AF such as AT iii clotting factor xiii and alpha macroglobulin were correlated multiple trauma causes a substantial increase of ealpha pi up to hours after accident the released PE seems to correlate with severity of injury but assessing the relationship to consumption of plasma factors is complicated by concomitant transfusions in AP peaks of ealpha pi coincide with a massive consumption of antithrombin iii and alpha macroglobulin during shock
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serotonin has been implicated to play an important role in regulating emotions and behavior and it is well accepted that the platelet serotonergic system mirrors the presynaptic central serotonergic system since prevalence of psychiatric problems increases with age and women are known to be more vulnerable than men the present investigation was carried out to T0 the relationship between serotonin activity and age in women C2 of serotonin hydroxytryptamine ht and its metabolite hydroxyindoleacetic acid hiaa were measured in platelets and plasma in women n aged years women aged years and women aged years there was a significant age difference between the two CG mean years in the younger and years in the older women respectively p PLT ht as well as hiaa levels were significantly higher in older women as compared to those in the younger women ng platelets in younger vs in older women p and in younger vs ng platelets in older women p respectively pearson correlation coefficients determined in the combined group n showed a significant positive rho between platelet ht and age r p plasma ht levels on the other hand were lower in older women compared to those in the younger women in younger vs ngml plasma in older women p and a significant negative correlation was observed between plasma ht and age r p plasma hiaa concentration did not differ between the two groups PLT ht levels in the younger group were independent of ethnicity since high serotonin activity has also been associated with psychiatric problems our results of increased concentration of PLT ht as well as hiaa with age may have implications in predisposing aging women to behavioralpsychiatric problems
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childhood psychosocial challenges ie adversities mental and substance use disorders social challenges may relate to the ON of obesity and extreme obesity identifying the types of psychosocial challenges most strongly associated with obesity could advance etiologic understanding and help target prevention efforts using a nationally representative sample of us adults n the present T0 evaluates relationships between childhood psychosocial challenges and OD of obesity and extreme obesity after mutually controlling childhood poverty was a risk in men or and a significantly stronger one in women or maltreatment increased odds of obesity in both men and women or ci and specifically increased odds of extreme obesity in women or early childrearing before age was an independent risk factor in both men or and women or not finishing high school was the strongest childhood psychosocial challenge risk factor for extreme obesity in both men or and women or psychiatric disorders mdd anxiety disorder ptsd before age were not independently associated with adult obesity in men nor women but substance use disorders alcohol or drug were inversely associated with AD obesity individuals who have experienced childhood adversities and social challenges are at increased risk for obesity previous findings also indicate that these individuals respond poorly to traditional weight management strategies it is critical to identify the reasons for these elevated weight problems and to develop interventions that are appropriately tailored to mitigate the obesity burden faced by this vulnerable population
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an analytical procedure was developed for the fast screening of diuretics acetazolamide althiazide amiloride bendroflumethiazide bumetanide canrenoic acid chlorthalidone chlorthiazide clopamide ethacrynic acid furosemide hydrochlorthiazide hydroflumethiazide indapamide TA trichlormethiazide and a masking agent PB in human urine the whole method involves three analytical steps including liquidliquid extraction of the analytes from the matrix their reaction with methyl iodide at degrees c for h to form methyl derivatives analysis of the resulting mixture by fast gas chromatographyelectron impact mass spectrometry fast gceims the analytical method was validated by determining selectivity linearity accuracy intra and inter assay precision extraction efficiencies and signal to noise ratio sn at the lowest calibration level lcl for all candidate analytes the analytical performances of three SE procedures and five combination of derivatization parameters were compared in order to probe the conditions for speeding up the sample preparation step limits of detection lod were evaluated in both eims and ecnims electron capture negative ionization mass spectrometry modes indicating better sensitivity for most of the analytes using the latter ionization technique the use of short columns and high carrier gas velocity in fast gcms produced efficient separation of the analytes in less than min resulting in a drastic reduction of the analysis time while a resolution comparable to that obtained from classic gc conditions is maintained fast quadrupole ms electronics allows high scan rates and ERP data acquisition both in scan and selected ion monitoring modes
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CW is widely used to treat municipal sewage however lack of carbon source always constraints the application of constructed wetland in advanced tailwater treatment process bark was used as the filler and external carbon source of CW in the study and the effects of hydraulic PR time hrt on no
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the efficacy safety and pharmacokinetic parameters of a mg oral dose of cetamolol hydrochloride betacor a new synthetic cardioselective betaadrenoceptor antagonist with intrinsic sympathomimetic activity were evaluated by studying HT with normal renal function or different degrees of renal impairment C2 of cetamolol serial blood and urine sample collections as well as vital sign determinations for the next hours were performed in all patients with the exception of urine collection which was not possible in hemodialysis patients results indicate that cetamolols pharmacokinetic parameters are significantly changed in patients who have moderate or severe renal impairment specifically as the severity of RI increased the maximum serum concentration cmax and the area under the serum concentrationtime curve auc increased whereas the renal clearance clr urinary excretion and total body clearance cl decreased additionally significant direct or inverse correlations for auc cl clr and urinary excretion with creatinine clearance clcr were demonstrated in the subjects with mild renal impairment the trends toward changes in the cetamolol pharmacokinetic parameters were evident though small and not statistically significant although anuric patients on hemodialysis still retained the ability metabolically to clear cetamolol at a rate of about onethird of that found in normal subjects reductions in blood pressure and heart rate also were found to be greater and more prolonged as the severity of RI increased there were no adverse drug or toxic effects noted in any of the study patients based on these findings dosing recommendations are suggested for patients who have compromised renal CF because of the effects of renal CF on the pharmacokinetics of cetamolol
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growth in the number of AS patients on the kidney SPK WL has slowed projections based on the most recent year data suggest the total waiting list will grow at a rate of registrations per year whereas the AS WL will increase at less than onesixth that rate or registrations per year the last years have seen a small trend toward improved unadjusted allograft survival for living and deceased donor kidneys since the overall number of pancreas transplants has declined among pancreas recipients those with simultaneous KP transplants experienced the highest pancreas graft survival rates in response to the ongoing shortage of deceased donor organs the us health resources and services administration launched the organ donation breakthrough collaborative in september and the organ transplantation breakthrough collaborative otbc in october the dsa challenge is prominent among the goals adopted by the otbc its premise were each of the existing donation service Az to increase the number of kidney transplants performed within their boundaries by per month an additional transplants over current annual C2 would result such an increase could potentially eliminate the national kidney transplantation waiting list by
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