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in situ hybridization histochemistry was used to determine the laminar distribution of d d d d and d dopamine receptor mrnas in the primate prefrontal cortex and to compare striatal and cortical C2 of these messages within the same tissue sections all five subtypes of dopamine receptor mrna are present in both the monkey striatum and the cerebral cortex but in different proportions within each structure thus levels of d and d mrnas are noticeably stronger in the striatum than in the cortex whereas d and d expression is clearly higher in the SC the d transcripts appear nearly equivalent in the striatum and the cortex a L1 finding is that within the prefrontal cortex mrnas encoding all dopamine receptor subtypes are expressed most strongly in SL v this laminar pattern of mrna CSD does not hold in all cortical regions the relatively high levels of mrnas encoding known dopamine receptor subtypes in the primate cerebral SC including the d receptor underscore the importance of this structure as a target for therapeutic actions of antipsychotic drugs further their prominence in SL v of the prefrontal SC which contains the corticostriatal and corticotectal projection SN provides a neural basis for DA regulation of the descending control systems | MEDAL |
imposex is a disorder caused by organotins mainly tributyltin which results in the appearance of male sexual characteristics in females of gastropod mollusks the main objective of this work was to make a critical analysis of the relationship between imposex and butyltin body burdens in nucella lapillus and nassarius reticulatus specifically this study evaluates possible additive effects among butyltins proposes scales of effects based on robust statistical criteria as alternatives to existing ones and defines the body burdens of tbt in n lapillus and n reticulatus corresponding to the assessment classes acs of the vas deferens sequence index vdsi established by ospar data of organotin body burdens and biological effects was retrieved from the ices dataset and from scientific literature all responses except the percentage of females displaying imposex impf in nucella lapillus showed a sigmoidal profile regarding to the body burden of mono mbt di dbt and TBT and sum of BTs sumbts tbt and the sumbts were better indicators of the vdsi or relative penis size indexrelative penis length index rpsirpli responses than mbt or dbt in most cases from a statistical point of view rpsirpli and vdsi were better indicators of contamination by tbt than impf although both rpsi and rpli showed lower sensitivity than vdsi the model used for describing the joint effect of BTs provided a statistically significant fitting to the data assuming a null effect for both mbt and dbt for n lapillus and a lower toxic contribution of mbt and dbt with respect to tbt for n reticulatus rpsi or rpli values equivalent to the acs for vdsi were proposed as alternative criteria when measuring moderate to high C2 of imposex tbt concentrations in n reticulatus and n lapillus tissues corresponding to the acs were calculated and provided valuable information for crossspecies comparisons | MEDAL |
this study sought to determine whether neurogenic inflammation occurs in the airways by examining the effects of capsaicin or substance p on microvascular plasma leakage in the trachea and lungs of male pathogenfree cbl mice single bolus intravenous i.v. of capsaicin and micromol kg iv or substance p and nmol kg iv failed to induce significant leakage in the trachea assessed as extravasation of evans blue dye but did induce leakage in the urinary bladder and skin i.c.v. with captopril mg kg iv a selective inhibitor of angiotensin converting enzyme ace either CT or in combination with phosphoramidon mg kg iv a selective inhibitor of neutral endopeptidase nep increased baseline leakage of evans blue in the absence of any exogenous inflammatory mediator the increase was reversed by the bradykinin b receptor antagonist hoe mg kg iv after pretreatment with phosphoramidon and captopril capsaicin increased the EB leakage above the baseline in the trachea but not in the lung this increase was reversed by the tachykinin nk receptor antagonist sr mg kg iv but not by the nk receptor antagonist sr mg kg iv experiments using monastral blue pigment as a tracer localized the leakage to postcapillary venules in the trachea and intrapulmonary bronchi although the labelled vessels were less numerous in mice than in comparably treated rats blood vessels of the pulmonary circulation were not labelled we conclude that neurogenic inflammation can occur in airways of pathogenfree mice but only T3 the inhibition of enzymes that normally degrade inflammatory peptides neurogenic inflammation does not involve the pulmonary microvasculature | MEDAL |
many mechanisms have been proposed to explain the caries preventive effect of xylitol as a total or partial dietary sugar substitute this article reviews the current knowledge of the effect of xylitol on the microbial population of dental plaque particularly on mutans streptococci in the CS of an ecological concept of the oral environment and of the potential clinical significance a noncariogenic commensal PI flora constitutes the biotic component of a balanced ecosystem compatible with dental health dietary sugars particularly SU and sugar substitutes are abiotic environmental factors that can shift the delicate balance of the ecosystem towards a more or less cariogenic microbiota most dietary sugars are fermented by PI microorganisms favour the establishment of a cariogenic microflora and contribute to bacterial virulence the vast majority of PI bacteria however are incapable of fermenting xylitol into cariogenic acid endproducts there is no evidence that the PI microbiota can adapt to metabolise xylitol or can be enriched with xylitolmetabolising cells even T3 long SE to xylitol accumulated intracellularly as a nonmetabolisable metabolite by mutans streptococci xylitol inhibits its growth in vitro and reduces the amount of plaque and the number of MS in both the plaque and saliva of xylitol consumers when present in the oral environment xylitol not only prevents a shift of the bacterial community towards a more cariogenic microflora but also selects for a mutants population that was shown to have weakened VFs in preliminary in vitro experiments and in rats further research is needed to fully understand the clinical importance in the prevention of caries of this xylitolselected population | MEDAL |
thromboangiitis obliterans tao is often cited as an extreme phenotype of vasculopathy and tobacco dependence although tobacco SE is essential to progression of arterial ischemia in tao expert opinion differs regarding the degree of tobacco dependence in this population the authors designed a prospective casecontrol T0 to test the hypothesis that subjects with tao have a greater degree of tobacco dependence than control subjects with coronary atherosclerosis PD disease cad do subjects with tao n confirmed by angiography biopsy or noninvasive arterial testing or cad n diagnosed by coronary angiography were mailed a standardized questionnaire regarding tobacco use to which and responded respectively the degree of tobacco dependence in each group was ascertained by several methods including the fagerström test for NIC dependence questionnaire the tao group was younger at index date year of first diagnosis for tao patients year of percutaneous transluminal coronary angioplasty ptca for cad patients tao vs cad yr p but the groups did not differ in age at first tobacco SE tao vs cad yr p current tobacco use at time of survey tao vs cad p or fagerström score tao vs cad p kaplanmeier curves showed no significant difference in time to topping tobacco use T3 first diagnosis p tao subjects smoked fewer cigarettes per day than cad subjects tao vs cad cigarettesday p among current smokers n tao subjects also smoked fewer cigarettesday vs p and were more likely to have made a serious attempt to stop vs p in contrast to case reports of extreme tobacco dependence in the tao population the degree of tobacco dependence in subjects with tao is similar to that in subjects with cad | MEDAL |
microwave assisted DA cycloaddition of brnbenzylpyridinone with methyl acrylate is described to gain an easy access to bromobenzyloxoaza or carbomethoxy bicyclooctenes the preparation of the ibogaine analogue desethylendohydroxymethyldemethoxyibogaine is described by stereoselective hydrogenation of the cc double bond biological evaluation showed an interesting in vitro binding profile toward dopamine transporter serotonin transporter and opioid receptor systems accompanied by an antiwithdrawal effect in mice for hydroxymethyl indolylazabicyclooctene the simplification of the ibogaine structure appears as a promising RPA toward the design of EDC that could reduce the withdrawal symptoms | MEDAL |
two splice CS on the human papillomavirus type hpv genome are used exclusively by the late CA protein l mrnas sd and sa these splice CS are suppressed in mitotic cells this study showed that serineargininerich protein c srpc also named sfrs activated both sd and sa and induced production of l mrna activation of hpv l mrna splicing by srpc required an intact arginineserinerepeat rs domain of srpc in addition to this effect srpc could enhance l mrna production indirectly by inhibiting the early splice site sa which competed with the late splice site sa srpc bound directly to sequences downstream of sa suggesting that srpc inhibited the enhancer at sa and caused a redirection of splicing to the late splice site sa this GABA effect of srpc was independent of its rs domain these results suggest that srpc can activate hpv l mrna expression via a bimodal mechanism directly by stimulating splicing to late splice sites and indirectly by inhibiting competing early splice CS | MEDAL |
the mechanism of atrial fibrillation af in patients with normal heart remains unclear while exogenous adenosine can trigger af nothing is known about the behavior of endogenous adenosine plasma level apl at the ON of af and during ablation procedure ninetyone patients with paroxysmal af males ± years with persistent af males ± years and controls were included among paroxysmal patients i medical therapy CT was performed in cases and ablation procedure in af was spontaneously resolutive in cases ii underwent ablation procedure and blood was collected simultaneously in a brachial vein and in the LA were spontaneously in sinus rhythm while were in SR T3 direct current cardioversion among persistent patients i in patients blood samples were collected in a brachial vein before and T3 direct current cardioversion ii in patients blood samples were collected simultaneously in a brachial vein and in LA before and T3 cardioversion during ablation procedure cvapl was higher in patients with persistent af vs patients with PAF median range vs μm p in patients with paroxysmal af laapl increased during the af episode vs μm p and normalized in SR after dccv in patients with persistent af laapl was higher than cvapl vs μm p and both normalized in SR cvapl vs μm p laapl vs μm p the occurrence of af is associated with a strong increase of apl in the atrium the cause of this increase needs further investigations | MEDAL |
hepatitis b virus nucleotide sequences derived from a hepatocellular carcinoma with free and multiply integrated viral dnas were determined based on a comparison within the xgene region cloned free viral dna previously had been attributed to two distinct groups of prec minus genomes the comparison of the CR sequence identified one of the genome equivalents as a recombinant between members of these groups four different integrated viral dna elements were cloned and analysed similarity to either one of two dnas representing the two groups of free viral dna on one hand and the presence of certain mutations only on integrated dna on the other hand allowed to recognize distinct segments within the integrants the data suggest a contribution of different but related genotypes to contiguous stretches of integrated viral dna via HR on this basis an evolutionary relationship between free and integrated dnas of the prec and the prec minus TT could be recognized when short sequence segments were compared the observed coexistence on a given integrated dna of segments homologous to free viral dna and of segments rat to another integrated dna is consistent with a long lasting association of individual genotypes with dividing cells and multiple integration events being the result of a series of steps not separated by a long time span | MEDAL |
multidrugresistant plasmodium falciparum is widespread in cambodia the in vitro susceptibilities of cambodian isolates to chloroquine quinine MQ HF pyrimethamine cycloguanil pyronaridine artemisinin arteether AM and artelinate were studied using a semimicrotest on day and after days of culture the cultureadapted isolates were all resistant to chloroquine pyrimethamine and cycloguanil the susceptibility to quinine was generally low three isolates were resistant to mefloquine a comparison of susceptibility to cycloguanil quinine and mefloquine prior to and T3 culture adaptation showed a trend toward a higher resistance level in some isolates halofantrine pyronaridine and ART derivatives were highly active against the multidrugresistant cambodian isolates with very similar GABA concentrations ic these results confirm the presence of multidrugresistant p falciparum isolates in cambodia and indicate that quinine and mefloquineresistant populations of the parasite may already exist in the field the high in vitro MICs of halofantrine pyronaridine and artemisinin derivatives indicate their potential usefulness for the treatment of multidrugresistant malaria | MEDAL |
microencapsulation of islets is a proceduischemic stroke we prospectively studied consecutive patients who were admitted with AIS males age ± years the severity of stroke was assessed at admission with the national institutes of health stroke scale nihss moderatesevere stroke was defined as nihss ⥠the outcome was assessed with dependency rates at discharge modified rankin scale between and and with inhospital mortality independent predictors of moderatesevere stroke were age relative risk rr confidence interval ci p atrial fibrillation rr ci p heart rate rr ci p logtriglyceride tg C2 rr ci p and highdensity lipoprotein cholesterol hdlc levels rr ci p L1 lipids did not predict dependency at discharge independent predictors of inhospital mortality were atrial fibrillation rr ci p diastolic blood pressure rr ci p logtg C2 rr ci p and nihss at admission rr ci p MDA-LDL cholesterol C2 were not associated with stroke severity or outcome lower tg and hdlc C2 are associated with more severe stroke lower tg levels also appear to predict inhospital mortality in patients with AIS | MEDAL |
the influence of the linoleic acid C2 of diets containing partially hydrogenated marine oils hmo rich in isomeric and fatty acids on the HFA profiles of lipids from rat CL HR and adipose tissue was examined five CG of rats were fed diets containing wt fat hmo vegetable oils in these dietrhotic patients necropsied at hôpital beaujon from to the overall prevalence of cholelithiasis was significantly higher in cirrhotic than in non cirrhotic patients p and p respectively the prevalence of cholelithiasis was higher in cirrhotic than in non cirrhotic patients whether male or female and at any age except in women over years and in men over years in these groups the prevalence of cholelithiasis in non cirrhotic patients was especially high and therefore did not significantly differ from that in cirrhotic patients the cause of cirrhosis did not significantly influence the prevalence of cholelithiasis however although the number of studied patients was small the prevalence of cholelithiasis seemed to be particularly high in PBC the prevalence of cholecystectomy was lower in cirrhotic than in non cirrhotic patients which suggests that cholelithiasis might be less often symptomatic andor less often complicated in the former than in the latter | MEDAL |
as one of the main serotonergic ht projections to the forebrain the dorsal raphe nucleus drn has been implicated in disorders of anxiety and depression although the nucleus contains the densest population of ht SN in the BB at least of cells within this structure are nonserotonergic including a C1 population of nitric oxide synthase nos containing neurons the drn has a unique topographical efferent organization and can also be divided into subregions based on rostrocaudal and mediolateral dimensions nos is colocalized with ht in the midline drn but nospositive cells in the lateral wing lw of the nucleus do not express ht interestingly the nos lw neuronal population is immediately rostral to and in L1 with the ACh lateral dorsal tegmental nucleus ldt we used immunohistochemical methods to investigate the potential serotonergic regulation of nos lw neurons and also the association of this cell grouping to the ldt our results indicate that of nos lw neurons express the inhibitory hta receptor and are ACh the findings suggest this assembly of cells is a rostral extension of the ldt one that it is subject to regulation by ht release as such the present study suggests a link between ht signaling activation of cholinergicnos SN and the AS response including the pathophysiology underlying anxiety and depression | MEDAL |
the transcriptional represser mnt is a PET antagonist of the protooncoprotein myc both mnt and myc utilise max as an obligate partner for dna binding and mycmax and mntmax complexes compete for occupancy at ebox dna sequences in promoter regions we have previously shown in transgenic mouse models that the phenotype and kinetics of ON of haemopoietic tumours varies with the level of myc expression we reasoned that a decrease in the level of mnt would increase the functional level of myc and accelerate mycdriven tumorigenesis we tested the impact of reduced mnt in three models of myc transgenic mice and in p | MEDAL |
interferonalpha ifnalpha therapy was compared with bone marrow transplantation bmt in patients with chronic myelogenous one cml in a multicenter prospective study of evaluable patients received ifnalpha and received allogeneic bmt of whom received transplants from human leukocyte antigen hlaidentical related donors and from hlamatched unrelated donors CR hematologic response was achieved by patients in the ifnalpha group and in the bmt group in the ifnalpha group a CCR was induced in patients a partial cytogenetic response in and a minor cytogenetic response in at a median followup of months in the ifnalpha group the predicted year survival rate was and the predicted year rate of remaining in chronic phase was in the bmt group the predicted year survival rate was for relateddonor bmt and for unrelateddonor bmt among low sokalrisk patients year survival did not differ between ifnalpha therapy and bmt irrespective of age in higher sokalrisk patients survival for relateddonor bmt and unrelateddonor bmt tended to be better than that with ifnalpha therapy in younger patients on the other hand in older patients survival in the bmt group especially for those receiving unrelateddonor bmt appeared to be VPI to that in the ifnalpha group unrelateddonor bmt can be recommended for highrisk younger patients however for older patients it should be performed after careful consideration of prognostic AF such as age sokal score and response to ifnalpha | MEDAL |
to investigate the interrelation of heavy metals and the influence on next generation total mercury and methylmercury lead Cd manganese copper zinc and iron were determined in the maternal blood placenta umbilical cord and UC blood samples were collected at delivery from pregnant women who were living in the city of nagoya located in the CE district of japan during and total mercury and methylmercury cadmium and iron were higher in cord blood than in maternal blood whereas copper and zinc were lower significant positive correlations were observed between maternal and cord blood with regard to total mercury and methylmercury lead cadmium and manganese contents significant correlations were also observed between many pairs of metals particularly in umbilical cord and its blood | MEDAL |
autologous chondrocyte implantation aci is used worldwide in the treatment of cartilage defects in the knee several demographic and injuryspecific risk AF have been identified that can affect the success of aci treatment however the discovery of predictive biomarkers in this field has thus far been overlooked | MEDAL |
acute myelogenous leukemia is the most common type of acute one in adults the condition is lethal within a few months without treatment but most young patients reach CR remission with chemotherapy many of them will relapse after a while but an increasing number of young people survive for a long time | MEDAL |
tuberculosis tb of the ribs is extremely rare and its diagnosis is often delayed due to the late appearance of radiologic signs although antituberculous drugs are the mainstay of treatment surgery has a definite therapeutic role in recalcitrant or recurrent cases a yearold boy with scrofuloderma of the chest wall due to underlying tb of the rib who responded partially to antituberculous treatment is reported surgical resection of the affected rib led to CR resolution early diagnosis of tb of this rare site and the role of surgical intervention in such cases is emphasized | MEDAL |
normal bone marrow obtained at harvest for bone marrow transplantation was passed over a ficoll density gradient to obtain the MNC fraction these cells were incubated with antit cell monoclonal antibodies mab antihulym and antihulym plus rb complement washed and the degree of t cell SD was assessed by SC in phytohemagglutinin by FC and by limiting dilution analysis the optimal protocol for t cell SD was found to be a stage incubation with cycles of complement treatment using a DBMC concentration as low as possible the precise conditions of complement dilution and incubation temperature depended on the batch of complement used and had to be assessed for each batch of the methods used for assessing t cell contamination SC in pha was found to be inappropriate due to large R2 in background proliferation of treated and UT bone marrow cells flow cytometry was accurate for residual t cell content of greater than corresponding to a depletion of TA but could not detect lower C2 of t cell contamination the limit dilution assay was found to be by far the most sensitive being capable of detecting a t cell contamination of in cells when combined with FC on UT marrow for calculation of the CE it gave very accurate determinations of residual t cell content of marrow | MEDAL |
standard methods for describing the intensity CSD of mechanical and acoustic wave fields in the high frequency asymptotic limit are often based on flow transport equations common techniques are statistical energy analysis employed mostly in the context of vibroacoustics and ray tracing a popular tool in architectural acoustics dynamical SE analysis makes it possible to interpolate between standard statistical SE analysis and full ray tracing containing both of these methods as limiting cases in this work a version of dynamical energy analysis based on a chebyshev basis expansion of the perronfrobenius operator governing the ray dynamics is introduced it is shown that the technique can efficiently deal with multicomponent systems overcoming typical geometrical limitations present in SEA results are compared with stateoftheart hpadaptive discontinuous galerkin FEM simulations | MEDAL |
subjects with diabetes have a greatly increased risk of chd which is only partially related to their elevated gl other AF such as insulin resistance and dyslipidemia are likely to be important the type of dyslipidemia that is most characteristic of type diabetic subjects is elevated triglycerides and decreased hdl cholesterol levels although all lipoproteins have compositional abnormalities surprisingly few good prospective studies of lipoprotein levels in relation to chd have been done in NIDDM available studies suggest that low hdl cholesterol may be the most important risk factor for chd in observational studies in studies in which total cholesterol and triglyceride were done cholesterol and triglycerides were risk factors for chd although triglycerides were often a stronger predictor however the strength of triglyceride as a risk factor for chd may depend partially on its association with other variables eg hypertension plasminogen activator inhibitor pai etc in PCTs in diabetic subjects ldl reduction with statins has led to significant reductions in chd incidence in addition overall mortality was reduced with statin therapy although the results were not statistically significant GEM has led to reductions in chd incidence in diabetic subjects although the results were not statistically significant perhaps because of low sample size regarding lipoproteins and chd risk in diabetic patients the very positive results of statin trials point to ldl cholesterol being more important than previous realized apparently having a BL high ldl cholesterol between and mgdl in a diabetic patient is equivalent to a much higher ldl cholesterol in terms of chd risk for a nondiabetic subject therefore the primary target of therapy in diabetic patients is lowering ldl cholesterol or possibly nonhdl cholesterol statins are the preferred pharmacological agent in this situation once ldl cholesterol levels have been lowered attention can be given to treatment of residual HTG and low hdl the goal here is weight reduction and increased exercise however for selected patients combining a fibric acid or lowdose NIC with a statin also can be considered reduction of ldl levels should take priority over reduction of triglycerides in CHL because of the proven safety of the statin class of drugs as well as greater reduction in chd incidence | MEDAL |
to determine the medical consequences and economic impact of caring for patients injured after motor vehicle crashes mvc involving stolen cars | MEDAL |
riftia pachyptila is one of the most specialized invertebrate hosts of chemoautotrophic symbionts crucial to the SF-36 of this symbiosis is how these worms cope with fluctuating ion concentrations internal sulfate C2 in r pachyptila appear comparable with other benthic marine invertebrates despite the production of sulfate internally by means of the bacterial oxidation of hydrogen sulfide suggesting that these worms are able to eliminate sulfate effectively internal chloride C2 appear comparable however CF chloride levels decrease significantly as the amount of CF bicarbonate increases demonstrating a stoichiometry we believe this shift in chloride out of the body fluids is needed to compensate for changes in EC balance caused by the large increase up to and greater than mmol l in negatively charged bicarbonate riftia pachyptila fits the GA DP of monovalent ion concentrations that is seen in other benthic marine invertebrates with a high na k ratio extracellularly and low na k ratio intracellularly extracellular ph values of and for coelomic fluid and V1 blood respectively as well as intracellular ph values of and for plume and trophosome tissue respectively were measured on the basis of significant decreases in extracellular ph and in some cases na and k in worms exposed to carbonyl cyanide mchlorophenylhydrazone sodium vanadate and nethylmaleimide we suggest that high concentrations of hatpases perhaps nah or khatpases are involved in h beta in these animals | MEDAL |
nude mice serve as critical hosts for transplantation of xenogeneic cells for in vivo analysis of various biological processes because investigators typically select one or two immunodeficient mouse strains as recipients no comprehensive T0 has been published documenting differences in human tumor engraftment taking advantage of the increased metastatic potential of rhocexpressing human a melanoma cells we evaluate four immunodeficient mouse strains severe combined immunodeficiency scid nonobese diabetic nodscid nodscid betamnull and nodscid ilrgammanull as xenograft tumor recipients | MEDAL |
of children with glomerulonephritis with infected ventriculoatrial shunt had improved renal function after antibiotic therapy and removal of the INF shunt patient with endoextracapillary proliferative glomerulonephritis with glomerular crescents developed a rapidly progressive renal insufficiency renal failure was successfully managed by hemodialysis and kidney transplantation patient died from extrarenal causes in the course of a septic episode | MEDAL |
allogeneic haematopoietic stemcell transplantation hsct is the only curative treatment for myelofibrosis we report an analysis of the société française de greffe de moelle et de thérapie cellulaire sfgmtc registry including patients with myelofibrosis transplanted between and potential risk factors affecting engraftment nonrelapse mortality nrm overall survival os and progressionfree survival pfs were analysed one hundred and fortyseven patients aged median years diagnosed with primary or AA myelofibrosis underwent hsct of patients were transplanted from a matched sibling donor the conditioning regimen was myeloablative in of patients ninety percent of the patients engrafted AF affecting favourably engraftment were splenectomy before hsct human leucocyte antigen hla matched MSD peripheral stem cell use as source of stem cells and absence of pretransplant thrombocytopenia fouryear os pfs and nrm survival were confidence interval ci ci and ci respectively MVA indicated that hlaidentical sibling donor chronic phase disease and splenectomy in men had favourable impact on os | MEDAL |
as one of the three major human pathogens that cause schistosomiasis schistosoma japonicum is the only one that is endemic in china despite great progress on schistosomiasis control over the past years in china s japonicum transmission still occurs in certain endemic regions which causes significant public health problems and enormous economic losses during different life stages parasites are able to survive dramatic osmolality changes between its vector FW and mammal host however the molecular mechanism of parasite osmoregulation remains unknown to address this challenging question we report the first cloning of an s japonicum aquaglyceroporin sjaqp from an isolate from jiangsu province china expressing sjaqp in xenopus oocytes facilitated the permeation of water glycerol and urea the water permeability of sjaqp was inhibited by mm hgcl | MEDAL |
crystal structures of the klenow fragment kf of dna polymerase i from escherichia coli complexed with dNTP dntp or with pyrophosphate ppi determined to a resolution by xray crystallography show these molecules binding within the cleft of the polymerase domain and surrounded by residues previously implicated in dntp binding the dntp binds adjacent to the ohelix ollis d l brick p hamlin r xuong n g steitz t a a nature with its triphosphate moiety anchored by three positively charged residues arg arg and lys plus his and gln the dntp IB site observed in the crystal is consistent with the results of chemical modification including crosslinking and is also near many of the CAA residues whose mutation affects catalysis polesky a h steitz t a grindley n d f joyce c m j biol chem polesky a h dahlberg m e benkovic s j grindley n d f joyce c m j biol chem however we conclude that the position of at least the dnmp moiety of dntp in the binary complex is not likely to be the same as in its catalytically relevant complex with primertemplate dna | MEDAL |
a patient with cALL all hypereosinophilic syndrome and t qq translocation is described even with intensive treatment only short periods of pCR were achieved recurrence of the leukaemia was always accompanied by the appearance of eosinophilic granulocytes in the blood and in the bone marrow although there is no exp proof we assume that the hypereosinophilic syndrome is causally related to the chromosome aberration translocation of the gmcsf gene from chromosome no to chromosome no might have led to the deregulation of the gene by enhancer sequences of the immunoglobulin heavychain region on chromosome no with the consequence of an overproduction of neutrophilic and particularly eosinophilic granulocytes furthermore stimulation of the leukaemic cell clone may have occurred by this translocation the similarity of the clinical course with cases described in the literature suggests that this condition is a unique entity of all | MEDAL |
swiss t cells express receptors for both the polypeptide epidermal growth factor egf and the tetradecapeptide bombesin and respond mitogenically to these substances these cells thus provide a system to analyze potential ST pathways involved in mitogenic stimulation here we have determined and compared the early ionic responses elicited by egf and bombesin andimportant medical problem in spite of its benignity even well known clinical characteristics and therapy of subacute thyroiditis etiology and pathogenetic mechanisms are not well estimated the group of chronical thyroiditis described as autoimmune thyroiditis indicates on etiology of this heterogeneous group of thyroid diseases modern aspects of therapy are shown at the end of the T0 | MEDAL |
we have previously evaluated and reported numerous classes of linear and cyclic peptides containing hydrophobic and hydrophilic segments for intracellular delivery of multiple molecular cargos herein a combination of histidine and tryptophan amino acids were designed and evaluated for their efficiency in intracellular delivery of cellimpermeable phosphopeptides and the antihiv drug emtricitabine two new decapeptides with linear and cyclic natures both containing alternate tryptophan and histidine residues were synthesized using fmoctbu solidphase chemistry the MMP were characterized and purified by using matrixassisted LDI maldi spectroscopy and highperformance liquid chromatography hplc respectively these peptides did not show significant toxicity up to µm in ovarian cancer skov and leukemia cancer ccrfcem cells furthermore the cellular uptake of a fluorescence fâlabeled cellimpermeable phosphopeptide fâgpyeei was enhanced in the presence of linear whâ and cyclic whâ by and fold respectively compared to the uptake of the phosphopeptide CT the cellular uptake was not significantly changed in the presence of endocytosis inhibitors furthermore the intracellular uptake of the fluorescentlylabeled antihiv drug FTC fâftc by linear whâ and cyclic whâ in skov cancer cell lines was found to be enhanced by and fold respectively compared to that of the drug alone fluorescent uptake experiments confirmed the localization of fâgpyeeiloaded cyclic whâ intracellularly in the skov CA cell L1 T3 h of incubation thus these data demonstrated that whâ containing tryptophan and histidine enhanced the cellular uptake of fâgpyeei and FTC | MEDAL |
the effects of angiotensin ii and its precursors angiotensin i and tetradecapeptide renin substrate were investigated in isolated segments of the rat caudal artery each peptide constricted the rat caudal i.a. and also enhanced vasoconstrictor responses to sympathetic nerve stimulation hz s the threshold concentrations for each peptide in enhancing sympathetic vasoconstrictor responses were lower than those required to produce vasoconstriction TDP renin ATP was the least potent of the three peptides and had the slowest ON of action angiotensin ii and angiotensin i each enhanced noradrenergic transmission to the same degree whether perfused through the lumen or added to the adventitial surface of the artery in contrast TDP RS was more potent when applied to the adventitial surface the effects of angiotensin i were blocked by the converting enzyme inhibitor enalaprilat whereas the effects of tetradecapeptide renin ATP were unaltered by enalaprilat or by the renin inhibitors pepstatin or a decapeptide renin inhibitor these findings suggest that tetradecapeptide RS and angiotensin i may be converted to angiotensin ii within the rat caudal i.a. with subsequent enhancement of NE neuroeffector function however the enzyme responsible for the conversion of tetradecapeptide RS cannot be determined from the present findings | MEDAL |
response to selection for up u and d to wk gain in rats on average daily gain adg average daily feed intake adi gainfeed gf BC bc fasting VO2 per unit metabolic size mr and partial efficiency of weight gain adgfg was evaluated T3 generations of mass selection at wk weaning litters representing f crosses of two replicates within each of the u d and control c selection lines were divided within sexes between bulkfeeder and tubefeeder cage types for recording FI until wk of age rats from tubefeeder cages representing littersline were utilized for mr and bc data response in adg was asymmetrical higher for u line but only lower in d L1 compared with c L1 correlated responses were positive and significant in both u and d lines for adi and and gf and line differences in mr were not significant but both selected lines were slightly higher than c line in mr at wk of age and the reverse at wk of age over the period of to wk of age maintenance requirements per unit metabolic size and adgfg were and above for the u and and for d lines relative to c line females of both selected lines were fatter than c L1 p less than at wk of age but only d L1 males were fatter than c line | MEDAL |
recent work eg nairne pandeirada has shown that words are remembered better when they have been processed for their survival value in a grasslands context than when processed in other contexts it has been suggested that this is because human SM systems were shaped by evolution specifically to help humans survive thus far the survival processing advantage has mainly been shown with grasslands contexts which are thought to be particularly relevant to human evolution the present study demonstrated the survival processing advantage with other contexts eg lost in a jungle including with contexts that should not in and of themselves be relevant to human evolution eg lost in outer space we further examined whether implied SI plays a critical role in the survival advantage to memory by comparing scenarios in which the person is CT versus with other people present eg lost at sea CT or with others and whether the perceived source of danger is social isolation or other human attackers a survival advantage was shown in both the isolation and the group settings and whether the primary source of danger was isolation or other human attackers did not matter these findings suggest that the survival advantage in SM is not dependent on evolutionarily relevant physical contexts eg grasslands or particular sources of perceived danger SI vs perceived attackers showing the advantage to be robust and applicable to a variety of scenarios | MEDAL |
although progesterone plays an essential role in ovulation and the luteiniziation of the primate F2 the expression of cellular components required for progesterone synthesis and their control is not well defined this T0 was designed to determine the time course and gonadotrophin versus steroid regulation of the transcription of genes involved in progesterone synthesis in periovulatory follicles granulosa cells or whole ovaries were obtained from macaques undergoing controlled ovarian stimulation either before h or up to h following the administration of an ovulatory human chorionic GTH hcg bolus with or without a betahydroxysteroid dehydrogenase betahsd inhibitor with or without a nonmetabolizable progestin granulosa cell concentrations of LD lipoprotein receptor ldlr and steroidogenic acute regulatory protein star mrna increased transiently h following hcg administration p at which time steroid SD tended to reduce star mrna p at h posthcg progesterone suppressed the ldlr mrna C2 p p sidechain cleavage pscc mrna decreased in a timedependent fashion up to h whereas betahsd mrna increased within h of hcg administration p in a steroidindependent manner whole ovarian CYP17 pc and granulosa cell p aromatase parom mrna declined in a timedependent fashion by h after hcg administration steroid SD increased parom mrna although progestin replacement did not return aromatase to control values p these data demonstrate diverse patterns of steroidogenic enzyme expression that generally reflect the conversion of the macaque periovulatory follicle from an oestrogen to progesterone producing gland although mrnas associated with progesterone synthesis and metabolism are primarily regulated by gonadotrophins cholesterol uptake and utilization may be modulated locally by steroids in luteinizing granulosa cells | MEDAL |
west nile virus wnv infection can cause severe potentially fatal neurologic illnesses including encephalitis and meningitis acute wnv infection also has been associated with acute flaccid paralysis afp attributed to a peripheral demyelinating process guillainbarré syndrome gbs or to an anterior myelitis however the exact etiology of afp has not been assessed thoroughly with EP laboratory and neuroimaging data this report describes six cases of wnvassociated afp in which clinical and electrophysiologic findings suggest a pathologic process involving anterior horn cells and motor axons similar to that seen in acute poliomyelitis clinicians should evaluate patients with afp for evidence of wnv infection and conduct tests to differentiate gbs from other causes of afp | MEDAL |
human papillomavirus hpv are responsible of an important morbidity and mortality hpv is a significant source of morbidity and mortality hpv is the most common sexually transmitted infection adolescents are at highrisk for hpv acquisition biologic and epidemiologic studies have demonstrated that hpv infection is a necessary but nonsufficient cause of cervical CA and genital warts the vast majority of C2 cancers contain highrisk hpv type and approximately contain hpv types or hpv types or are responsible for approximately of genital warts thus a vaccine that could prevent prophylactic vaccines based on the use of viruslike particles vlps obtained by autoassembly of l are under PCTs two vaccines are currently evaluated cervarix glaxosmithkline biologics a bivalent vaccine against hpv and and gardasil merck co a quadrivalent vaccine against hpv and phase i ii and iii studies have demonstrated that both vaccines are well tolerated and provide an excellent immunogenicity with approximately year followup both vaccines have been ERP in preventing persistent infection with targeted hpv types and in preventing cervical intraepithelial lesions the optimal target for vaccination is probably yearold girls | MEDAL |
measures of impairment of oxygenation can be affected by the inspired oxygen fraction | MEDAL |
the nature of protective immunity against typhoid fever in man is not at present well understood work on animal models and earlier studies from this laboratory indicate an important protective role for cellular immunity the present work attempts to T0 the efficacy of the conventional typhoid vaccine in inducing specific cellular and humoral immune responses the study on fiftyeight new army recruits and thirtyone civilian volunteers showed adequate humoral responses after vaccination however vaccination failed to induce a significant cellular immune response in addition a transient suppression of cellular immunity was observed in the immediate PV period in ten subjects who possessed NK cellular immunity before vaccination these findings indicate the need for improving the typhoid vaccine so that it will induce cellular immunity as well as a humoral response it also points to the necessity for obtaining detailed knowledge of the postvaccination anergy as it could be important in timing public health programmes | MEDAL |
our study determined the LT clinical radiographic and computed tomography scanning results of highflexion mobilebearing and fixedbearing total knee arthroplasties tkas in the same younger patients in addition the survivorship and complication rates of both CG were evaluated | MEDAL |
the role of one in the pathogenesis of AA was studied by measuring the pressure in the appendix perioperatively in patients operated on with an appendectomy because of suspected acute appendicitis the technique used involved inserting a fine needle through the apex into the appendix lumen and measuring the hydrostatic pressure required to inject saline solution in three patients with a gangrenous appendix found at T0 and in two patients with a phlegmonous appendix there were signs of one of the appendix lumen as revealed by increased pressure within it in patients with a phlegmonous appendix found at T0 no signs of obstruction were found these experimental data suggest that obstruction is not an important causative agent of AA but might develop as a result of the inflammatory process | MEDAL |
acne fulminans af is a very rare severe form of acne seen in young males characterized by a sudden and explosive ON of hemorrhagic pustules and ulceration on the trunk systemic features in the form of fever polyarthropathy malaise erythema nodosum and painful osteolytic bone involvement with leukocytosis and an elevated EA sedimentation rate CT of af includes CSs or IS agents for the initial phase followed by isotretinoin AS ats purebred cats british shorthairs and persians were overrepresented it is currently unclear if this represents a true breed predisposition or a higher likelihood of owners of purebred cats seeking referral for advanced diagnostic imaging procedures | MEDAL |
the RPE rpe is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina to gain insight into the mechanisms controlling gl metabolism in rpe and its possible relationship to retinopathy we studied the influence of different gl concentrations on glycogen and lactate C2 and co production in rpe from normal and streptozotocintreated diabetic rats incubation of normal rpe in the absence of glucose caused a decrease in lactate production and glycogen content in normal rpe increasing gl concentrations from mm to mm caused a fourfold increase in gl accumulation and co yield as well as reduction in lactate and glycogen production in rpe from diabetic rats glucose accumulation did not increase in the presence of HG substrate but it showed a four and a sevenfold increase in co production through the mitochondrial and pentose phosphate pathways respectively we found high glycogen C2 in rpe which can be used as an energy reserve for rpe itself andor NR findings further show that the rpe possesses a high oxidative capacity the large increase in glucose shunting to the PPP in diabetic retina exposed to high glucose suggests a need for reducing capacity consistent with increased oxidative stress | MEDAL |
to assess the conditioning effect ce of selfetch adhesives of different pH applied to thick and thin smear SL sl the corresponding resin tags rt and hybrid layer hl | MEDAL |
the lipolytic MICs of streptomyces isolates were determined in TB and rhodamineb agar lipase MICs were also measured with pnitrophenyl palmitate pnpp as a substrate the strain of streptomyces bambergiensis oc used in this T0 was selected among strains of streptomyces from mucc as the best lipase producer the incubation conditions were optimized and the inoculum amount incubation period effect of carbon and nitrogen sources and rates of mgso and caco were investigated lipsb the lipase produced by s bambergiensis oc strain was partially purified with AS precipitation dialysis and gel filtration chromatography fold and with umg specific activity the optimal ph and temperature for lipsb were determined as and °c respectively the lipase has high stability in all ph and temperature values used in this T0 while lipsb was slightly activated in the presence of βmercaptoethanol it was slightly reduced by pmsf the enzyme conserved approximately of its activity at the end of h in the presence of methanol and ethanol since lipsb displays high activity in the thermophilic conditions and stability in the presence of organic solvents this lipase can catalyse the biodiesel production from olive oil by the transesterification reactions | MEDAL |
here we present a new method to rapidly quantify tryptophan trp in proteins animal feed mehaden fishmeal cell cultures and fermentation broths trp is separated from common amino acids by anionexchange chromatography in min and directly detected by integrated pulsed amperometry the estimated lower PCD limit for this method is pmol ALP m naoh hydrolysates can be directly injected and therefore we used this method to determine the optimum ALP hydrolysis conditions for the PR of trp from a model protein bovine serum Al bsa this method accurately determined the trp content of bsa and fishmeal high levels of glucose ww do not interfere with the chromatography or decrease recovery of trp we used this method to monitor free trp during an escherichia coli fermentation | MEDAL |
an enzymelinked immunosorbent CA elisa which used methylumbelliferyl phosphate as an enzyme substrate was used to quantify two plant CKs this assay detected as little as pmol approximately pg of cytokinin in microplate wells coated with a cytokininovalbumin conjugate the method measured competition between free cytokinin and the bound conjugate for reaction with monoclonal anticytokinin antibodies and used a standard curve prepared by use of known amounts of free cytokinin to quantify hormone C2 in unknown samples standard curves which consisted of logitlog plots of fluorescence units versus picomoles of competing cytokinin measured from to pmol approximately picograms of zothiol c content of unfertilized s purpuratus eggs is mumol eggs equivalent to approximately mm average concentration the glutathione gsh gssg content is mumol eggs in this species high ovothiol C2 persisted for the first weeks of embryonic development ovothiol and glutathione account for virtually all of the trichloroacetic acid solublesh groups in the egg these results are compared to several previous studiesabstract truncated at words | MEDAL |
this T0 was undertaken in order to evaluate histopathological and immunohistochemical cytokeratins aeae characteristics of parametrial invasion in patients with early stage CC | MEDAL |
interest in essential CAA analogues developed as a means of diverting ammonia nitrogen into protein synthesis in patients with chronic renal failure urea cycle enzyme defects and hepatic failure longterm practical therapeutic value has so far only been proved in children with urea cycle defects recent work confirms that the alphaketo acid of leucine in particular alters protein turnover and may prove of wide practical application to improve nitrogen balance in postoperative patients and others with severe illness | MEDAL |
human ovarian PT derived from a cells growing as subcutaneous xenografts in nude mice develop melphalanresistant cells T3 a single treatment of the TB animal with the drug caffrey zhang and frenkel submitted for publication treatment of the animals with selenite by ip injection prevented the OD of primary resistance to melphalan as well as crossresistance to cisplatin selenite treatment also prevented the melphalaninduced increase in the cellular level of glutathione in contrast selenite po sc or in drinking water had relatively little effect on the OD of resistance the results in this animal MM suggest that selenite may be clinically useful in preventing the development of drug resistance during chemotherapy of CA | MEDAL |
vitamin d vitd deficiency is linked to many disease states including rickets and CA and vitd supplementation to improve response to cancer therapy has been explored supplementation may be most appropriate for dogs with suboptimal vitd concentrations in dogs the primary source of vitd is diet predominantly via commercial dog food our goal was to determine how food source and supplements affect ohd concentrations the storage form of vitd SS was collected from clinically healthy dogs and pet owners were surveyed about food source and supplements SS ohd concentration was measured using a quantitative chemiluminescent assay liason diasorin stillwater mn | MEDAL |
lipoid pneumonia results from the pulmonary accumulation of endogenous or exogenous lipids host tissue reactions to the inhaled substances differ according to their chemical characteristics symptoms can vary significantly among individuals ranging from asymptomatic to severe lifethreatening disease acute sometimes fatal cases can occur but the disease is usually indolent possible complications include superinfection by nontuberculous mycobacteria pulmonary fibrosis respiratory insufficiency cor pulmonale and hypercalcemia the radiological findings are nonspecific and the disease presents with VL patterns and CSD for this reason ELP may mimic many other diseases the diagnosis of exogenous lipoid pneumonia is based on a PH of exposure to oil characteristic radiological findings and the presence of lipidladen macrophages on sputum or bal analysis highresolution computed tomography hrct is the best imaging modality for the diagnosis of ELP the most characteristic ct finding in lp is the presence of negative attenuation values within areas of consolidation there are currently no studies in the literature that define the best therapeutic option however there is a consensus that the key measure is identifying and discontinuing exposure to the offending agent treatment in patients without clinical PS remains controversial but in patients with diffuse pulmonary damage aggressive therapies have been reported they include whole lung lavage systemic corticosteroids and thoracoscopy with surgical debridement | MEDAL |
the present T0 was undertaken to examine possible changes in subjective appraisal and CNS system processing indexed by painrelated CBF evoked potentials n p of incoming noxious information in painfree control volunteers and subjects suffering from rightside cervicobrachial pain cbs detection threshold and CBF evoked potentials were recorded in response to noxious co laser stimulation of the right and left hands the results indicate that when compared to controls cbs subjects exhibit an elevation in detection threshold intensity and a reduction in the amplitude of the p peak following laser stimulation of the pain affected side there were also differences in the choice of qualitative descriptor for laser stimuli although not in the subjective rating of CS- intensity these changes were not apparent for responses on the unaffected limb the severity of clinical pain was found to be related to the magnitude of reduction in p amplitude only on the pain affected side conversely feelings of anxiety were associated with higher amplitude responses on both the RA and left sides suggesting a more generalized relationship between these AF we interpret these findings to indicate an alteration in central NS processing and subjective appraisal of acute experimental pain in subjects with chronic cbs moreover these alterations appear to be restricted to pain affected pathways and are more related to the severity of clinical pain than to GA mood state | MEDAL |
in r edgar hopesimpson proposed that a seasonal CS- intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza solar radiation triggers robust seasonal vitamin d production in the skin vitamin d deficiency is common in the winter and activated vitamin d ohd a steroid hormone has profound effects on human immunity ohd acts as an IS modulator preventing excessive expression of inflammatory cytokines and increasing the OB potential of macrophages perhaps most importantly it dramatically stimulates the expression of potent antimicrobial MMP which exist in neutrophils monocytes A-NK cells and in epithelial cells lining theeii trisphenanthroline complexes at about v and v respectively the electrocatalytic oxidative properties of guanine by feii bisterpyridine complex was measured by amperometry method using the rotating disk electrodes electropolymerization of feii trisaminophenanthroline complex produced thin polymer films on gold and GC electrodes the electrochemical quartz crystal microbalance eqcm and cyclic voltammetry were used to study the in situ growth of the CP the polyfeiinhphen exhibited a good electrocatalytic oxidation towards guanine and also for the mixture of guanine and adenine too | MEDAL |
photoaffinity labeling with alphamethylhpromegestone hr is an ERP technique for the covalent labeling of the Rp pr which allows monitoring of the steroid receptor complex under denaturing conditions the present study was initiated to evaluate whether photolabeled pr could be used also as a marker for pr under nondenaturing conditions accordingly the effect of irradiation on each component of the reaction was evaluated separately when hr CT was irradiated there was a rapid less than min light dependent destruction of hr as evident from increased formation of a more polar 3H product on tlc and a concomitant decrease in the ability of the irradiated preparation to bind to pr when rabbit uterine pr was irradiated in the absence of steroid a gradual decrease in the binding capacity was observed reaching of the nonirradiated control in min the optimal irradiation time for covalent hrpr complex formation was determined by irradiation for up to min and separation of the products by sodium dodecylsulfate sdspolyacrylamide gel electrophoresis specific labeling of proteins of mr and was observed with the rate of labeling of the two being similar and reaching a plateau by min of irradiation the photolabeling efficiency ranged from to SU gradient UC of photolabeled pr revealed that both the irradiated sample and the nonirradiated control sedimented to the same position subsequent sdspolyacrylamide gel electrophoresis of the sucrose gradient peak from the photolabeled sample showed the presence of both labeled proteins of mr and in addition photolabeled rabbit uterine pr mr and could be immunoprecipitated with a guinea pig AS raised against rb uterine pr analysis of the photoaffinity labeling procedure in our system revealed that the photodestruction of hr was very rapid however maximal labeling with hr was obtainable with minimal photodestruction of pr which suggests that photolabeled receptor can be used as a marker for pr under nondenaturing conditions | MEDAL |
methylglyoxal is present at low C2 in most cells as a byproduct of glycolysis and a product of lipid and CAA catabolism the most widely accepted method for measurement of MG involves the derivatization of methylglyoxal with diaminobenzene derivatives such as OPD followed by quantification of the resulting quinoxaline with highperformance liquid chromatography hplc here we describe the modification of this procedure for the measurement of free intra and extracellular methylglyoxal in animal cells grown in SC cell harvest and sample volume measurement techniques were developed solidphase extraction prior to methylglyoxal derivatization reduced interferences unique to CC such as the PH red indicator dye used in most cell SC media and extended the useful life of the hplc column in addition this extraction step significantly lessened the interference represented by oxidative degradation of nucleic acids to MG by PCA under CA conditions the concentration of free intracellular MG in chinese hamster ovary cho cells grown in SC ranged from microm mean standard deviations n to microm mean standard deviations n the concentration of free extracellular MG in the growth medium was microm mean standard deviations n severalfold less than that found inside the cell a possible explanation for the difference between measured free intracellular and extracellular methylglyoxal C2 is that the assay for free intracellular methylglyoxal also measures some reversibly bound methylglyoxal | MEDAL |
phosphatidylinositol is metabolized with a halflife of about h in lens epithelial cells of dayold embryonic chickens when these cells differentiate to form lens fiber cells however phosphatidylinositol turnover virtually ceases the present T0 was undertaken to determine whether there is a similar change in the metabolism of phosphatidylcholine and phosphatidylethanolamine porthophosphate was injected into dayold chicken embryos and the incorporation of label into phosphatidylcholine and phosphatidylethanolamine was followed for h the specific MICs of the precursors phosphorylcholine and PE were also measured during this time the data were then analysed by means of a simple kinetic model to determine the rate of synthesis and the halflife of each phospholipid the results showed that phosphatidylcholine is synthesized at a rate of about x mols per cell in the LECs and x mols per cell in the fiber cells phosphatidylethanolamine is synthesized at approximately x mols per cell in the epithelial cells and x mols per cell in the fiber cells both phospholipids are stable in both the epithelial cells and in the fiber cells with halflives of h or greater thus although phosphatidylcholine phosphatidylethanolamine and phosphatidylinositol all experience an increase in synthesis following lens fiber formation the previously observed decrease in phosphatidylinositol turnover accompanying differentiation is a TPS effect | MEDAL |
recent studies suggest that MB the most common malignant BB RT of childhood is comprised of four disease variants the wip oncogene is overexpressed in group and tumors which contain medulloblastomas with the most aggressive clinical SMB our data demonstrate increased wip expression in metastatic medulloblastomas and VPI PFS and overall survival of patients with wip highexpressing MB microarray analysis identified upregulation of genes involved in tumor metastasis including the g proteincoupled receptor cxcr in MB cells with high wip expression stimulation with the X4 ligand sdfα activated pi kinase signaling and promoted growth and invasion of wip highexpressing medulloblastoma cells in a pdependent manner when xenografted into the cerebellum of nude mice medulloblastoma cells with SD or endogenous high wip expression exhibited strong expression of cxcr and G1 akt in primary and invasive tumor cells wip or cxcr knockdown inhibited MB growth and invasion wip knockdown also improved the survival of mice xenografted with wip highexpressing medulloblastoma cells wip knockdown inhibited cell surface localization of cxcr by suppressing expression of the g protein receptor kinase grk restoration of wildtype grk promoted ser phosphorylation of X4 and inhibited the growth of wipstable medulloblastoma cells conversely grk knockdown inhibited ser phosphorylation of cxcr increased cell surface localization of cxcr and promoted the growth of MB cells with low wip expression these results demonstrate crosstalk among wip cxcr and grk which may be important for the aggressive phenotype of a subclass of MBs in children | MEDAL |
this T0 quantifies lung water in acute hemorrhagic pancreatitis to determine the degree to which pulmonary dysfunction occurs subclinically before alterations in the arterial blood gases can be measured pancreatitis was induced in ten dogs by injecting mlkg of bile into the pancreatic ducts which had been surgically cannulated pulmonary and systemic blood gases and BPs HR rate EVLW and lung RBF were studied over hours while cardiac SO and mean arterial pressure were maintained at control values by ringers lactate infusion the percentage of water in lung tissue was determined at the time of sacrifice using gravimetric measurements MAP pressure cardiac output and pulmonary capillary wedge pressure reflecting intravascular volume status did not change through at the experiment by contrast major disturbances were measured in the pulmonary bed with pulmonary i.a. pressures rising from mmhg to mmhg over hours p less than peripheral V1 resistance rose from units to units p less than whereas bronchial blood flow to the lung fell significantly these changes in pulmonary hemodynamics were not reflected by changes in the arterial blood gases PaO2 was maintained during hours of pancreatitis the partial pressure of carbon dioxide and the SS ph did not NC significantly there was however a progressive rise in extravascular lung water measured by the doubledilution technique from mlkg at control to mlkg p less than at hours this was confirmed by direct gravimetric measurements which revealed an increase in the water content of the lung from to over the course of the experiment arterial blood gases therefore do not necessarily reflect the pulmonary deterioration in acute pancreatitis these data supported a mechanism of lung dysfunction independent of the circulatory compromise which often accompanies the disease in the clinical setting | MEDAL |
these studies were conducted to determine how plasma LD lipoprotein ldl cholesterol C2 respond to dietary cholesterol fed in increasing amounts with either CO or CO diets in high as compared to low ldl responding baboons and to determine how apolipoprotein apo b transcription levels are modulated in response to dietary lipids eight high and eight low ldl responding pedigreed adult baboons balanced for sire age sex and weight were challenged for successive week periods with increasing levels of dietary cholesterol combined with either CO or CO at the end of each dietary period plasma and lipoprotein lipids apob apoai and hepatic mrna levels for apolipoproteins were measured as dietary cholesterol increased plasma cholesterol concentrations mostly ldl cholesterol increased in both phenotypes and with both types of fat but phenotypic differences were greater with coconut oil there was not a consistent DR relationship of plasma or ldl cholesterol C2 to increasing intakes of dietary cholesterol neither dietary cholesterol type of dietcreb to h after the i.t. compared with that of saline in a dosedependent manner at doses from to micrograms however no significant alterations were found in IB of probes for other different transcription factors tested following the injection of nmda up to h T3 the administration these included promoterspecific transcription factor nuclear factor kappa b activator protein and octamer binding protein potentiation of the ap and creb IB was prevented in a dosedependent manner by the administration of either of the MK-801 nmda antagonist methyldihydrohdibenzoadcycloheptenimine the nmda antagonist dleaminopropylphosphonopentenoic acid the glycine antagonist dichlorokynurenic acid or the proposed polyamine antagonist ifenprodil in contrast the ap IB was not consistently affected up to h following intracerebroventricular injections of other agonists including dlalphaaminohydroxymethylisoxazolepropionic kainic and aminocyclopentanetransdicarboxylic acids in contrast to the severity of convulsive seizures by the former excitants these results support the proposal that an intracerebroventricular injection of nmda may selectively potentiate dna IB MICs of both ap and creb through in vivo activation of the nmda BCR in the mu brain | MEDAL |
exerciseinduced asthma eia is characterised by transient airway obstruction occurring after strenuous exertion a fall of or more in the fev T3 exercise is diagnostic inhalation of C1 volumes of dry cold air during exercise leads to loss of heat and water from the bronchial mucosa and airway cooling and drying proposed mechanisms for bronchoconstriction include i mucosal drying and increased osmolarity stimulating mast cell degranulation and ii rapid airway rewarming T3 exercise causing vascular congestion increased permeability and oedema leading to obstruction eia symptoms start after exercise peak to T2 after exercise and spontaneously resolve in about T2 a refractory period of up to hours T3 REC during which repeat exercise causes less bronchospasm has bproline iminopeptidase from xanthomonas campestris pv citri is a serine peptidase that catalyses the removal of nterminal proline residues from MMP with high specificity we have solved its threedimensional structure by multiple isomorphous replacement and refined it to a crystallographic rfactor of using xray data to a resolution the protein is folded into two contiguous domains the larger domain shows the general topology of the alphabeta hydrolase fold with a CE eightstranded betasheet flanked by two helices and the nterminal residues on one side and by four helices on the other side the smaller domain is placed on top of the larger domain and essentially consists of six helices the AS site located at the end of a deep pocket at the interface between both domains includes a catalytic triad of ser asp and his cys located at the bottom of the active site very close to the catalytic triad presumably accounts for the inhibition by thiolspecific reagents the overall topology of this iminopeptidase is very similar to that of yeast serine carboxypeptidase the striking secondary structure similarity to human lymphocytic POP and dipeptidyl peptidase iv makes this proline iminopeptidase structure a suitable MM for the threedimensional structure of other peptidases of this family | MEDAL |
using a functional lactose permease mutant devoid of cys residues cless permease each CAA residue in putative TM helix vii and the flanking cytoplasmic and periplasmic regions from leu to glu was replaced individually with cys of the singlecys mutants exhibit high transport activity accumulating lactose to of the steadystate observed with cless permease in contrast permease with cys in place of ala or tyr exhibits low but significant activity and cys substitution for asp or asp yields permease molecules with little or no activity due to disruption of chargeneutralizing interactions between asp and lys or asp and lys respectively immunological analysis reveals that membrane levels of the mutant proteins are comparable to that of cless permease with the exception of tyrcys which exhibits reduced but significant levels of permease finally the effect of nethylmaleimide nem was tested on each mutant and the results indicate that the transport activity of the great majority of the mutants is not affected by the alkylating agent remarkably the six positions where cys replacements render the permease highly sensitive to inactivation by nem are confined to the cterminal half of helix vii a region that is strongly conserved among transport proteins rat to lactose permease the results demonstrate that although no residue per se in the region scanned is essential structural features of the c terminus of helix vii may be important for transport activity | MEDAL |
purine degradation occurs during strenuous muscle exercise and plasma levels of hypoxanthine hx purine degradation intermediate increase GDP Kd has not been investigated in HT htn the present study determined whether purine nucleotide degradation is altered in patients with htn CP exercise test was performed with serial measurements in blood lactate and plasma hx in patients men and women with essential htn world health organization who class i to ii mean age years and age sexmatched normal subjects exercise was terminated either by severe fatigue or excess blood pressure increase peak work rate wr normal v htn v w not significant ns was not different but peak oxygen uptake peak vo v mlminkg p and anaerobic threshold were lower in patients with htn resting levels of blood lactate and plasma hx were similar but the increment from rest to peak exercise delta for lactate delta lactate v mmoll p and for hx delta hx v micromoll p were significantly smaller in patients with htn when normalized by the peak wr delta hxpeak wr v micromollw p was significantly lower in patients with htn patients with htn exhibited reduced hx response to exercise with impaired exercise capacity the exerciseinduced changes in plasma hx were smaller in patients with ht when normalized with peak wr these results suggest that the purine nucleotide degradation is reduced in patients with htn | MEDAL |
using the immunohistochemical pap method gabaimmunopositive cells were revealed in horizontal and transverse sections of lamprey spinal cord the most numerous intensively stained small oval cells were located in the dorsal part of the spinal cord the larger cells with long nonbranching processes were located at the border of lateral column the main part of which is composed of gabaimmunonegative cells some of the largest but less intensively stained cells were observed in the lateral part of the spinal cord beyond the cell column and in the ventrolateral corner of transverse sections the latter are identified as previously described edge cells functional identification of the remaining gabaimmunopositive cells is rather difficult some of them may be glial elements | MEDAL |
in the present prospective study we have evaluated the sensitivity specificity and predictive value of the bengal rose and indirect immunofluorescence iif in patients with a bacteriological diagnosis of brucellosis the sensitivity of the bengal rose was and its specificity iif had a sensitivity of and a specificity of when the polyvalent antiigs conjugate was used the combined parallel use of bengal rose and iifigs resulted in a sensitivity of and a specificity of there was a good correlation between bengal rose and serum agglutination test r on the contrary there were not good correlations between the FL conjugates and bengal rose agglutination and coombs test in conclusion the combined use of bengal rose as a screening test and iif as a confirmation T0 is a good diagnostic strategy for human brucellosis | MEDAL |
kolbs learning style inventory and environmental press questionnaire were used to study thirdyear baccalaureate nursing students learning styles and perceptions of environmental press differences in medicalsurgical and psychiatric nursing settings from the experiential learning theory perspective evidence for a hypothesized match between predominating student learning styles and predominating environmental press was sought as hypothesized student learning styles were found to be predominantly concrete as was the predominating environmental press in both nursing settings medicalsurgical and psychiatric nursing settings did not differ significantly from environmental press a profile of competencies felt to be important in nursing emerged with concrete peopleoriented competencies rating higher than abstract competencies | MEDAL |
herein the role of il in the induction and maintenance of oral tolerance was evaluated the results show that mice treated with moab antiil are permissive to the induction of oral tolerance to ova antiil treatment did not reverse the in vitro blocking of t cell proliferative response found in orallytolerized mice and orallyinduced tolerance could not be broken by antiil treatment taken together these results suggest that il is not a fundamental cytokine for the establishment and maintenance of OT | MEDAL |
in this study a new type of polydimethylsiloxanemodified chitosan pmsc amphiphilic hydrogel was developed as a soft ATP to explore cellular responses for dermal reconstruction the hydrogel wettability mechanical stiffness and topography were controllable through manipulation of the degree of esterification de between hydrophobic polydimethylsiloxane pdms and hydrophilic nocarboxymethylchitosan nocc based on microphase separation the incorporation of pdms into nocc increased the stiffness of the hybrid through the formation of selfassembled aggregates which also provided anchor sites for cell adhesion as the de exceeded the size of the pdmsrich aggregates changed from nanoscale to microscale subsequently the hierarchical architecture resulted in an increase in the tensile modulus of the hybrid gel up to fourfold which simultaneously provided mechanotopographic guidance and allowed the cells to completely spread to form spindle shapes instead of forming a spherical morphology as on nocc de the results revealed that the incorporation of hydrophobic pdms not only impeded acidic damage resulting from nocc but also acted as an adhesion modification agent to facilitate longterm cell adhesion and proliferation on the soft ATP as proved by the promotion on longterm typei collagen production the pmsc hybrid with selfassembled mechanotopography offers great promise as an advanced scaffold material for use in healing applications | MEDAL |
the emergence of influenza a viruses which had acquired resistance to rimantadine during a clinical trial c b hall r dolin c l gala d m markovitz y q zhang p h madore f a disney w b talpey j l green a b francis and m e pichichero pediatrics provided the opportunity to determine the genetic basis of this phenomenon analysis of reassortant viruses generated with a resistant clinical isolate hn and the susceptible influenza asingapore hn virus indicated that rna segment coding for matrix and m proteins conferred the resistant phenotype resistant viruses isolated from seven patients each contained a single NC in the nucleotide sequence coding for the emm which resulted in substitutions in amino acid two viruses or five viruses in the TM domain of the molecule these changes occurred in locations identified in AIV selected for resistance to amantadine in tissue culture and indicate a common mechanism of action of the two EDC in CC and during chemotherapeutic use | MEDAL |
a novel compound as which inhibits acylcoa cholesterol acyltransferase acat was isolated from the culture broth of a fungus scedosporium sp spc as inhibited acat activity in an enzyme CA system using rb liver microsomes with an ic value of microm as also inhibited cholesterol ester formation in hepg caco and thp cells with ic values of and microm respectively | MEDAL |
peripheral lymphedema is a chronic progressive and debilitating disorder that results from abnormal lymphatic drainage advances in microsurgical techniques have led to the OD of new treatment options for LE that benefit from preoperative imaging to select the most AGA surgical repair magnetic resonance mr lymphangiography is a noninvasive imaging modality capable of providing highresolution d images of the lower extremities to define the severity and extent of lymphedema and depict individual lymphatic channels the mr examination consists of primary sequences the first is a d heavily tweighted CS to depict the severity and extent of the lymphedema the second is a fatsuppressed d SPGR sequence performed T3 the intracutaneous injection of an extracellular gadoliniumbased mr UCA as venous enhancement almost always occurs one of the interpretative challenges is differentiating enhancing lymphatic channels from SF veins mr techniques that can help with A-V contamination include the addition of a contrastenhanced mr venogram to the examination protocol or the use of an ironbased bloodpool contrast agent to selectively suppress venous enhancement | MEDAL |
a sFv phage display library was constructed from spleen cells of mice immunized with a soluble form of a human VE growth factor vegf receptor kinase insert domaincontaining receptor kdr after two rounds of biopanning of the clones recovered were specifically reactive to kdr subsequent selection identified two clones that blocked vegf binding to kdr the clones were expressed in escherichia coli and purified as soluble singlechain fv scfv antibodies the affinities of the scfv for IB to kdr were determined by biacore analysis x x m one scfv pc was shown to inhibit vegfinduced kdr phosphorylation and vegfstimulated dna synthesis in human umbilical vein EC cells there is much exp evidence to suggest that the vegfkdrflk pathway plays an important role in tumor angiogenesis a process that is essential for RT growth and metastasis the antibodies discussed here which block vegf binding to kdr have potential clinical application in the treatment of cancer and other diseases where pathological angiogenesis is involved | MEDAL |
elevation of cyclic gmp by muscarinic agonists has been suggested to be responsible for the negative inotropic effects of these agents in cardiac muscle and for the endotheliumdependent relaxation caused by these agents in V1 smooth muscle these relationships were studied by monitoring the effects of muscarinic agonists on tension and cyclic gmp levels in rb left atrial strips and aortic rings in the presence and absence of the cyclic gmp lowering agent ly ly completely blocked both the cyclic gmp increase and the EC50 caused by acetylcholine in rabbit aortic rings with intact EC cells acetylcholineinduced cyclic gmp elevation and relaxation in these preparations were also blocked by quinacrine and nordihydroguaiaretic acid ndga but neither response was blocked by the lipoxygenase inhibitor u in the experiments with rb left atrium ly blocked the acetylcholineinduced cyclic gmp elevation but did not block the negative inotropic effects of the drug quinacrine ndga and a guanylate cyclase inhibitor methylene blue failed to block either the cyclic gmp increase or the decrease in CF caused by carbachol in atrial strips these results support the suggestion that an increase in cyclic gmp may be responsible for the endotheliumdependent EC50 of rb aorta by muscarinic agonists but not for the direct negative inotropic effects of these drugs in rb atrium muscarinic agents appear to increase cyclic gmp C2 in rabbit atrium and aorta by different mechanisms although both are blocked by ly they differ not only in their requirements for EC cells but also in their susceptibility to other blocking agents | MEDAL |
the report of the national coordinating group on PIC nhs executive recommended that GA AD intensive care units in district GA hospitals should no longer continue to care for critically ill children apart from providing resuscitation prior to transfer to a specialist centre this recommendation was made despite a lack of outcome data in the uk to support this conclusion we wish to report our outcome data from one such unit over a fouryear period we have prospectively used paediatric risk of mortality scoring to estimate the risk of death for children cared for in our AD unit in a district general hospital dgh and have compared this with the observed outcome the observed mortality of deaths was less than the predicted mortality of deaths our results suggest that an adult unit can provide a paediatric intensive care service that is associated with an acceptable outcome in terms of mortality these data suggest that the role of such units with regard to the provision of paediatric intensive care should be considered further | MEDAL |
the a line of V1 smooth muscle cells has na dependent transport systems for alanine proline and pi whereas uptake of leucine myoinositol and dglucose is na independent when a cells were incubated for h in medium made hypertonic by addition of SU there was a marked increase in nadependent transport of alanine and proline but no chanion high levels of uric acid produced by a xanthine oxidasecatalyzed reaction are found in human plasma we studied whether uric acid could alter xanthine oxidase activity in plasma obtained from eight adults and eight neonates known amounts of UA were added to xanthine and xanthine oxidasesupplemented buffer and plasma and the production of uric acid and superoxide was determined uric acid and microm decreased the oxidation of xanthine to UA in AD plasma by and and formation of superoxide by and respectively compared with plasma without uric acid in newborn plasma a similar DP and extent of inhibition was observed superoxide formation however was inhibited to a greater extent than in AD plasma endogenous xanthine oxidase was detected in newborn plasma in nine additional neonates using hplc these results indicate that uric acid is an ERP inhibitor of the formation of superoxide and hydrogen peroxide by xanthine oxidase at the C2 found in HP plasma uric acid may play an important role in attenuating the oxidantmediated tissue damage caused by xanthine oxidase released into the circulation during ischemiareperfusion | MEDAL |
CLL leukemia cll is characterized by a highly variable clinical course this retrospective study is planned to assess the prognostic value of serum free CS chain sflc levels and flc ratio flcr in cll | MEDAL |
pulsed amperometric PCD pad is useful for detection of cephalosporins following separation on a c column using an acetate buffer solvent with a small percentage of organic modifier under these conditions the indirect pad mode worked better than direct pad with ipad outperforming both a gradient program was demonstrated that allowed separation and sensitive electrochemical detection of eleven different cephalosporins with widely differing side chain structures the cephalosporins could be detected to submicromolar C2 with this separation applications of the method for quantitation of pharmaceutical formulations and for monitoring cephalexin in PS were demonstrated to improve the detectability of cephalexin an oncolumn concentration scheme using separate concentration and elution solvents was applied to porcine serum | MEDAL |
numerous mutations causing EO alzheimers disease have been identified in the presenilin ps genes particularly the ps gene like the mutations identified within the betaamyloid APP ps mutations cause the increased generation of a highly neurotoxic variant of amyloid betapeptide ps proteins are proteolytically processed to an nterminal approximately kda ntf and a CT approximately kda fragment ctf that form a heterodimeric complex we demonstrate that this complex is resistant to proteolytic degradation whereas the fulllength precursor is rapidly degraded degradation of the ps holoprotein is CS to inhibitors of the proteasome formation of a heterodimeric complex is ic blood flow since intrapulmonary arteriovenous fistulas were not demonstrated angiographically in any of our patients the intrapulmonary righttoleft shunt is probably due to low ratios of perfusion to ventilation in some pulmonary segments the intracardiac RLS was due to leaks across the interatrial baffle collaterals between SVR and PVs and to the coronary sinus draining to the PV atrium | MEDAL |
attachingeffacing lesioninducing escherichia albertii and the related but nonattachingeffacing organism hafnia alvei are both implicated as enteric pathogens in humans however effects of these bacteria on epithelial cells are not wellcharacterized related enteropathogens including EHEC oh decrease epithelial barrier CF by disrupting intercellular tight junctions in polarized epithelia therefore this T0 assessed epithelial barrier CF and tight junction protein CSD in polarized epithelia following bacterial infections polarized epithelial mdcki and TA grown on filter supports were INF apically with e coli oh e albertii and h alvei for h at degrees c all strains decreased transepithelial electrical resistance and increased permeability to a dextran probe in a host celldependent manner immunofluorescence microscopy showed that both e coli oh and e albertii but not h alvei caused a RD of the tight junction protein zona occludens in contrast to e coli oh e albertii and h alvei did not redistribute claudin western blotting of whole cell protein extracts demonstrated that each bacterium caused differential changes in tight junction protein expression dependent on the host cell these findings demonstrate that e albertii and h alvei are candidate enteric pathogens that have both strainspecific and host epithelial celldependent effects | MEDAL |
in a study of breast cancer patients tumour p protein expression was determined by immunohistochemistry using the monoclonal antibody pab patient lymph node status and blooms grade were determined and both oestrogen and progesterone status assessed also by immunohistochemistry CL node status tumour grade and Rp status all had a significant influence on survival patients with ppositive tumours showed poorer survival but this did not achieve significance p protein expression showed a significant relationship to high tumour grade and a weak correlation with negative oestrogen receptor status the data suggest that p protein expression may be a marker of more aggressive carcinomas but that the prognostic SP of expression is likely to be weak and unlikely therefore to be of clinical value the results do not resolve whether detectable p protein expression represents a random product of dedifferentiation or an important feature of the malignant phenotype playing a key role in tumour behaviour the number of patients in our study is small however and investigation of a larger series is clearly indicated | MEDAL |
we have shown that draxin is a repulsive axon guidance molecule for a variety of neuron classes and that genetic deletion of draxin in mice results in the absence of all forebrain commissures moreover we also identified a secreted molecule tsukushi tsk that belongs to the small leucinerich proteoglycan family slrp and inhibits signaling molecules such as bmp and wnt tsk KO show malformation of the CC cc and agenesis of the anterior commissure ac suggesting the importance of tsk function in forebrain commissure formation there is a possibility that the combined CF of these two proteins is essential for the formation of these commissures in this study we investigate this possibility by generating draxintsk doubly heterozygous mice and comparing their forebrain commissure phenotypes with those of singly heterozygous mice we found that although draxin and tsk did not interact directly their genetic interaction was evident from the significantly higher prevalence of cc malformation and es recent data provide convincing evidence that leptin has a beneficial influence on glucose homeostasis studies suggest that leptin could be used as an adjunct of insulin therapy in insulindeficient diabetes thereby providing an insight into the therapeutic implications of OB as an antidiabetic agent extensive research will be needed to determine LT safety and efficacy of such a therapy | MEDAL |
the distribution of hphysostigmine phy has been studied in the rat brain subcellular fractions at various time intervals following iv i.t. hphy or its metabolites rapidly accumulate into the cytoplasm of cells and penetrates the intracellular compartments kinetic studies of the subcellular distribution of radioactivity ra per gm of rat BB following iv injection of hphy show peak concentrations at min in all subcellular fractions with the exception of mitochondria in the mitochondrial fraction the ra C2 continue to rise from dpmgm at min to dpmgm at min p less than the cytosol contains the highest ra dpmgm at min which declined to dpmgm at min ra in synaptosome microsomes and myelin increases from to min and declines at min in vitro studies did not show a greater uptake of ra by the mitochondrial or synaptosomal fractions the finding of relatively high concentrations of ra in the mitochondrial fraction at min increases the likelihood that phy or its metabolites could interfere with the physiological CF of this organelle | MEDAL |
we describe a novel ion exchange chromatographic technique suitable for largescale preparation of viruses and other biomacromolecular assemblies in highly purified form the method which utilizes AE on either of two commercially available cellulose cartridges is applied to the escherichia coli bacteriophage prd viral particles eluted from both qma and deae cartridges retain infectivity and exhibit greater homogeneity of composition as judged by gel PACE and electron microscopy than particles purified by rate zonal SU gradient centrifugation the ion exchange protocols are rapid requiring less than min elution time and permit retrieval of the purified viral particles at high concentration in AQ media without centrifugal pelleting the present method is particularly well suited to the preparation of milligram to decigram quantities of virus sufficient for many biophysical structural analyses including investigations by solution spectroscopic and crystal diffraction techniques the feasibility and advantages of the ion exchange chromatographic procedure are demonstrated by application of laser raman spectroscopy to ion exchange purified prd virions and subviral assemblies | MEDAL |
funding for this summary was contributed by the laura and john arnold foundation blue shield of california and california health care foundation to the institute for clinical and economic review icer an independent organization that evaluates the evidence on the value of health care interventions icers annual policy summit is supported by dues from aetna ahip anthem blue shield of california cvs caremark express scripts harvard pilgrim health care cambia health solutions united healthcare KP premera blue cross astrazeneca genentech glaxosmithkline johnson johnson merck national pharmaceutical council prime therapeutics sanofi spark therapeutics health care service corporation editas alnylam regeneron mallinkrodt biogen healthpartners and novartis synnott kumar adair rind and pearson are employees of icer which provided grants to the UC san francisco and the university of colorado to perform work for these analyses tice and walsh are employed by the university of california san francisco and campbell and whittington are employed by the university of llergens is a risk factor for allergic sensitization and allergic sensitization is a risk factor for allergic asthma however apart from indoor mold SE as a risk factor for childhood asthma there is insufficient evidence to conclude that the associations between allergen exposure and asthma development are causal a new challenge for research is to analyze the huge amount of data derived from the metagenomic characterization of the environmental and human microbiome to understand the role of interactions between viruses bacteria and allergens in the development of asthma it is recognized that prenatal and PN exposure to air pollution and maternal smoking increase the risk of developing asthma in children in adults the data are scarce and the results remain controversial as regards these exposures and asthma incidence further research is needed to appraise the effect of SE to phenols phthalates and perfluorinated compounds which are widespread in the environment and may be associated with asthma especially in children frequent use of chemicals for home cleaning especially in the form of sprays which is a common practice at the population level is a risk factor for the OD of AD asthma the domestic use of cleaning products might also be a risk factor for asthma in children exposed at home the chemicals involved in these relationships are still to be identified OA is a major phenotype of adult asthma a significant part of these asthma cases might relate to occupational SE to cleaning products while there is evidence of associations between diet during pregnancy or during childhood and the risk of developing asthma in children the data in adults are insufficient beyond genetic AF BC is influenced by dietary choices and physical activity further research is needed to clarify the complex interplay between these nutritional AF and asthma OD the new challenge for research is to decipher the role of all the environmental factors to which the individual is exposed since conception exposome in the OD of asthma using a holistic approach | MEDAL |
normally hearing blind students and matched normalsighted students were compared with regard to differential AEP sensitivity and AR thresholds DUE of ITDs for directional hearing and ARTs showed no differences between the groups the difference limen for intensity when interpreted by the sisi test and the DL for frequency revealed a slightly optimizing trend in the blind group however differences missed statistical significance as to difference limen for intensity and in the orange also as to difference limen for frequency any superior hearing of the blind was not mirrored by a corresponding superiority in peripheral supraliminal performance | MEDAL |
the ODI odi has become one of the principal conditionspecific outcome measures used in the management of spinal disorders this review is based on publications using the odi identified from the authors personal databases the science citation index and hand searches of spine and current textbooks of spinal disorders | MEDAL |
we used FC and a dnabinding dye efflux assay to isolate a SP sp of cells with SC characteristics from the human pancreatic HEp-2 panc nonobese diabeticsevere combined immunodeficiency mouse xenograft experiments showed that sp cells were EC in RT initiating capability compared with nonsp cells cultured sp cells were able to differentiate into daughter cells and nonsp cells through asymmetric division our T0 demonstrated highaffinity IB of alphabungarotoxin alphabgtx was established alphabgtxhtars and used to purify alphabgtxhtars in a lipid environment for use in structural studies using photoaffinity labeling alphabgtxhtars were expressed robustly pmol of hbrl binding CS approximately microg of receptor per milligram of protein and displayed the same functional properties as wildtype receptors serotonin ec microm while ialphabgtx bound to the alphabgtxhtars with high affinity kd nm application of nonradioactive alphabgtx up to microm had no effect on serotonininduced current responses alphabgtxhtars were purified on an alphabgtxderivatized affinity column from detergent extracts in milligram quantities and at approximately purity the hydrophobic photolabel trifluoromethylmiiodophenyldiazirine itid was used to identify the amino acids at the lipidprotein interface of purified and lipidreconstituted alphabgtxhtars itid photoincorporation into the alphabgtxhtar subunit was initially mapped to S1 proteolytic fragments of kda containing the m TM segment and approximately of incorporated i and kda containing the mm transmembrane segments within the m segment itid labeled ser equivalent to the itidlabeled residue thr at the lipidexposed face of the torpedo nicotinic acetylcholine receptor nachr alpham alphahelix these results provide a first definition of the surface of the htar m helix that is exposed to lipid and establish that this surface is equivalent to the surface exposed to lipid in the torpedo nachr | MEDAL |
previous studies having shown differences in the clinical presentation of hyperthyroidism in the young and in the over sixtyyears old patients we studied the presentation of HT of late onset without previous thyroid disorder to determine if it continued to NC with age after years two hundred and ninety cases of hyperthyroidism presenting after the age of years without a previous PH of goitre collected in the department of NM of the pitié hospital between january and may were analysed retrospectively there was no significant rho between age and HR rate or total circulating thyroxine t and triiodothyronine t concentration a positive rho with WL and a negative rho with i fixation were observed it was higher in cases of atrial fibrillation and HT with normal thyroid scintigraphy GD with goitre was associated with the most overt signs of thyrotoxicosis and the highest hormonal concentrations contrarily to TA the t but not t concentration correlated positively with HR rate t and t were positively correlated with WL and this rho remained significant at constant t and t concentrations | MEDAL |
HVS has been shown to possess a thymidylate synthase ts gene that is unusual in its transcriptional regulation although ts is believed to be required for viral dna synthesis the tsspecific kb mrna was found most abundantly during the late phases of asynchronous virus replication in permissive cultures to study the kinetics of gene activation the ts promoter and RII sequences were cloned UP of the chloramphenicol acetyltransferase cat gene no cat expression or transcripts were found after transfection of F0 genes into permissive owl monkey kidney omk cells however the promoter was strongly activated when cat plasmids were cotransfected with intact herpesvirus saimiri virion dna or were transferred to omk cells that were lytically INF with herpesvirus saimiri or a related herpesvirus herpesvirus ateles cat was expressed at reduced levels in cultures when viral dna replication was inhibited by phosphonoacetic acid this indicates that the gene is G1 during the DE phase however the highest amounts of mrna were present in the late period of replication deletion analyses localized essential response elements for trans activation in the promoter UP region between nucleotides and they consisted of related TRs and perfect palindromes a CS with two overlapping palindromes of and bp was found to be a L1 target for activation of the herpesvirus saimiri ts promoter these palindromes did not have any significant homologies with known sequences of herpesviruses or cellular dna the bp palindrome had however a certain structural similarity with a conserved sequence of the eresponsive cis CS that is required for transcription regulation of early papillomavirus genes | MEDAL |
cyclic stretching experiments on OB cells have proven to be a useful tool in understanding the underlying mechanisms of load transduction at the boneimplant surface however most experimental setups use silicone rubber substrates which are atypical for orthopedic and dental implant materials therefore we investigated the responses of osteoblastlike cells to loading on titanium ticoated versus plain silicone substrates ticoated substrates were made by a RF magnetron sputtering process and characterized using rutherford backscattering spectrometry xray photoelectron spectroscopy and contactangle measurements osteoblastlike cells cultured from rat bone marrow were seeded on both types of substrates and stretched for h continuously subsequently cell proliferation ALP phosphatase activity and calcium content were measured for up to days T3 seeding in addition CS scanning electron and confocal laser scanning micrographs were made the results showed that our ti coating had a thickness of nm and contained tioxygen as however further characterization proved that the silicone material had a tendency to resurface through the coating OB cells proliferated faster on the ticoated substrates but differentiation was slower compared with the silicone substrates it was concluded that that there was a definitive influence of the ATP material in mechanical AS models therefore extrapolation of results obtained using silicone substrates cannot be translated directly toward the situation of metallic implant materials | MEDAL |
magnetic resonance imaging mri of rodents can be expected to be a growing application particularly when translatory imaging research from mouse to man is envisioned t highfield human wholebody mr e total surface area by comparing healthy infants born at term with healthy young adults we demonstrate that PN cortical expansion is strikingly nonuniform regions of lateral temporal parietal and frontal SC expand nearly twice as much as other regions in the insular and medial occipital cortex this differential PN expansion may reflect regional differences in the maturity of dendritic and synaptic architecture at birth andor in the complexity of dendritic and synaptic architecture in adults this expression may also be associated with differential sensitivity of cortical circuits to childhood experience and insults by comparing human and macaque monkey CBF SC we infer that the pattern of human evolutionary expansion is remarkably similar to the DP of human PN expansion to account for this correspondence we hypothesize that it is beneficial for regions of recent evolutionary expansion to remain less mature at birth perhaps to increase the influence of postnatal experience on the development of these regions or to focus prenatal resources on regions most important for early survival | MEDAL |
the effect of FS and endothelial cell growth factor on the healing of defects of the avascular portion of canine menisci was investigated in menisci of AD mongrel dogs the defects were treated in one of three ways group the defect was left empty group the defect was filled with Fn sealant and group the defect was filled with fibrin sealant and EC cell growth factor the healing process was evaluated macroscopically and histologically at intervals of and weeks the average percentage of each defect that was filled with connective tissue was in group in group and in group in the early phase of this repair the extrinsic pannuslike tissue that contained many capillary vessels D2 from the meniscosynovial junction into the defect subsequently organized fibrous connective tissue was formed which had changed to cartilaginous tissue at to weeks the combination of Fn sealant and EC cell growth factor enhanced the neovascularization and formation of granulation tissue which accounted for the increased healing level in the avascular portion of the meniscus | MEDAL |
with the rate of aging rising each year the number of patients with dementia increases the latest study released by the ministry of health labour and welfare estimated that as of there were a total of million people with PSD in japan with of aged and over of aged and over of aged and over and of aged and over dementia includes alzheimers disease which makes up the most cases DLB frontotemporal dementia and cerebrovascular PSD which is caused by a CBF infarction or cerebral hemorrhage hypothyroidism NPH and depression also impair cognitive functions and therefore these pathological conditions are easily mistaken for dementia methods that can easily distinguish between these diseases have been devised early and accurate diagnoses are very important for patients and their families as there are a number of diseases that can be treated in addition although japan only has medicines that delay the advance of alzheimers disease in recent years efforts have been made to prevent the onset of alzheimers disease through reducing the potential for diabetes high blood pressure obesity and depression quitting smoking and improving physical and intellectual MICs at the annual meeting last year we reported the results of a survey at our health counseling center on the quality of life a person wants as dementia progresses the survey had some surprising results twothirds of the people surveyed preferred to be in a group home or an T3 medical center rather than in their own homes onethird of the respondents expressed a desire to be at home the survey showed that if possible a person diagnosed with dementia will stay at home however where this is not possible they have no choice other than to resign themselves to leaving home furthermore patients with PSD feel that the medication that will allow them to continue their lifestyle at home for long periods is limited home care for PSD is said to be more difficult than palliative care at home for patients with terminal CA this paper reports on one case in which medication was not and could not be used because the symptoms were too severe however home care could be continued by preventing the patient s wife from feeling isolated and being able to cope with the prolonged crisis through the environmental improvement | MEDAL |
recent data and hypotheses concerning the CE oculomotor pathways are reviewed lateral and vertical eye movements are discussed successively beginning in each case with the final common pathway and then progressing step by step along the main supranuclear tracts selectively involved in the types of eye movements vestibular movements saccades and smooth pursuit it is now established that the final common pathway of lateral eye movements in frontaleyed species is the abducens nucleus which controls not only the ipsilateral lateral rectus but also through the internuclear SN almost all the conjugate lateral activity of the opposite MR the ascending tract of deiters providing direct excitatory vestibular signals to the medial rectus MNs could either have totally regressed in man or would play only a minor functional role likewise a direct inhibition of the MR motoneurons now seems unlikely or ineffective the EC50 of this muscle resulting essentially from the disfacilitation mediated by the abducens internuclear neurons this particular mechanism could be explained by the fact that the medial rectus MNs also receive messages of convergence a slow disjunctive movement independent of lateral eye movements convergence is performed by excitatory Rt neurons near the oculomotor nucleus and by inhibitory pathways projecting onto the abducens MNs perhaps passing through the internuclear SN of the oculomotor nucleus the PM relay of horizontal reflex eye movements is the medial VN mvn which contains excitatory and GABA SN projecting onto the contralateral and ipsilateral abducens nuclei respectively afferences of the mvn arise from the labyrinth through the vestibular nerve vestibuloocular reflex the neck through the dorsal part of the medullary tegmentum cervicoocular reflex the peripheral retina and the visual pathways for the vestibular contribution of optokinetic nystagmus perhaps via the PT the nucleus reticularis tegmenti pontis nrtp andor the nucleus PH nph visuoocular reflex the PM relay for all ipsilateral saccades is the paramedian PRF prf which excites the ipsilateral abducens nucleus and inhibits the contralateral abducens nucleus via the burst GABA neurons located ventrally to the ipsilateral abducens nucleusabstract truncated at words | MEDAL |
the insect MMP LMS pedvdhvflrfamide and dromyosuppressin tdvdhvflrfamide have identical chemical sequences with the exception of the nterminal amino acid both inhibit spontaneous contraction of insect visceral muscles SN in the hypocerebral ganglion of horn fly hematobia irritans l and SD fly stomoxys calcitrans l were found to contain material immunoreactive to antiserum produced against the cterminal of LMS but not to the nterminal of dromyossuppressin two C1 lateral clusters containing cells linked dorsally and ventrally by chains of cells encircled the anterior surface of the proventriculus and were immunoreactive of leucomyosuppressin and fmrfamide antisera axons from these cells were traced to the wall of the aorta and over the surface of the proventriculus ultrastructural analysis revealed these cells contained a singular type of elementary sec granule that contained material of relatively low electron density both in the cell body and at the axon terminals | MEDAL |
Jv by isolated perfused rb PT convoluted tubules is accompanied by an electrical potential difference pd negative in the lumen when the tubule is bathed by rabbit SS and perfused with an ultrafitrate of that serum in contrast the pd is positive when the perfusate composition approximates that of fluid in the LP tubule in vivo which lacks glucose amino acids and bicarbonate the principal purpose of the present studies was to investigate the characteristics of fluid absorption under these conditions proximal convoluted tubules were dissected from rb kidneys and perfused in vitro when the pd was positive the mean net fluid absorption was nl mm minus min minus the positive pd is caused by a chloride concentration difference across the tubule epithelium higher in the lumen than in the bath beta of the chloride concentration difference by replacing the bicarbonate in the bath as well as in the perfusate with chloride caused the pd to fall to zero without a significant NC in the rate of fluid absorption therefore neither the positive pd nor the chloride concentration difference is significantly related to the Jv ouabain inhibited fluid absorption under all of the above conditions making it likely that the Jv is due to AS sodium transport although the results are consistent with the generally accepted view that active sodium transport is a major driving force for Jv the mechanism of anion chloride transport is uncertain owing to the lack of correlation between Jv and the transepithelial pd | MEDAL |
electronic energy transfer plays an important role in many types of organic electronic devices forstertype theories of exciton DWI provide a way to calculate DWI constants and lengths but their applicability to amorphous CP systems must be evaluated in this paper the perylenediimide dye lumogen red in a polymethyl methacrylate host matrix is used to test theories of exciton motion over lumogen red concentrations clrs ranging from x to x m two experimental quantities are measured first TR anisotropy decays in films containing only lumogen red provide an estimate of the initial energy transfer rate from the photoexcited molecule second the lumogen red lifetime decays in mixed systems where the dyes malachite green and rhodamine act as SE acceptors are measured to estimate the diffusive quenching of the exciton from the anisotropy measurements it is found that theory accurately predicts both the clr concentration dependence of the polarization decay time taupol as well as its magnitude to within the theory also predicts that the diffusive quenching rate is proportional to clralpha where alpha ranges between and experimentally it is found that alpha when malachite green is used as an acceptor and alpha when rhodamine is the acceptor on the basis of the theory that correctly describes the anisotropy data the exciton DWI constant is projected to be nmns by use of several different analysis methods for the quenching data the experimental diffusion constant is found to be in the range of nmns thus the theory successfully describes the early time anisotropy data but fails to quantitatively describe the quenching experiments which are CS to motion on longer time scales the data are consistent with the idea that orientational and energetic disorder leads to a timedependent exciton migration rate suggesting that simple DWI models cannot accurately describe exciton motion within this system | MEDAL |
infectious mononucleosis im is associated with the risk of developing multiple sclerosis ms using databases of hospital admissions for england we investigated the femaletomale ratios fmrs for admission to hospital for im and ms stratified by age males were more frequently admitted for im for all age CG apart from ages fmr confidence interval ci and BL significantly at ages fmr ci this intriguing aspect of im epidemiology in adolescence the atypical female excess may be linked to the SR of ms where females predominate from adolescence | MEDAL |
this paper reviews the current status of information on diagnostic and therapeutic management of penile fractures focusing on the controversy between surgical vs CT of this uncommon injury penile fracture commonly defined as a rupture of the tunica albuginea and CC is a serious urological disorder demanding surgical management the diagnostic procedure classically consists of history taking physical examination and urinary status determination of the extent of severity and location of the rupture in the tunica albuginea takes foremost priority and requires additional imaging procedures such as ultrasound or cavernosography which will impart enough diagnostic information for the correct choice of treatment in some cases the urethra is injured as well immediate surgical repair offers CR REC for patients with penile fracture in most cases even in the presence of urethral injury although penile fracture is easily recognized and can therefore be classified as a firstlook diagnosis therapy remains controversial to date the correct therapeutical approach is a vital factor in management as the associated significant morbidity can result in complete loss of erectile CF painful erections or penis deviation early surgical treatment is strongly recommended because of the excellent results shorter hospitalization less morbidity and an early return to sexual activity | MEDAL |