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typically clinical mastitis is coded as the presence or absence of disease in a given lactation and records are analyzed with either linear models or binary threshold models because the presence of mastitis may include cows with multiple episodes there is a loss of information when counts are treated as binary responses poisson models are appropriated for random variables measured as the number of events and although these models are used extensively in studying the epidemiology of mastitis they have rarely been used for studying the genetic aspects of mastitis ordinal threshold models are pertinent for ordered categorical responses although one can hypothesize that the number of clinical mastitis episodes per animal reflects a continuous underlying increase in mastitis susceptibility these models have rarely been used in genetic analysis of mastitis the objective of this study was to compare probit poisson and ordinal threshold models for the genetic DUE of us holstein sires for CM mastitis was measured as a binary trait or as the number of mastitis cases data from firstparity cows recorded in onfarm herd management software were gathered edited and processed for the present T0 the cows were daughters of sires distributed over herds predictive ability was assessed via a fold crossvalidation using loss functions mean squared error of prediction msep as the end point and a cost difference function the heritability estimates were for mastitis measured as a binary trait in the probit MM and and for the number of mastitis cases in the ordinal threshold and poisson models respectively because of scale differences only the probit and ordinal threshold models are directly comparable among healthy animals msep was smallest for the probit MM and the cost function was smallest for the ordinal threshold model among diseased animals msep and the cost function were smallest for the poisson model followed by the ordinal threshold model in GA the models for count variables more accurately identified diseased animals and more accurately predicted mastitis costs healthy animals were more accurately identified by the probit model | MEDAL |
distention of the rat distal esophagus evokes an arterial pressor and a cardioaccelerator response that depends upon activation of a vagal afferent projection to the nucleus tractus solitarii nts the present T0 aimed to determine in urethaneanesthetized rats if the afferent limb of this reflex a relays in the nts subdivision known ro receive esophageal afferents and b utilizes glutamatergic synapses to this end tetrodotoxin or the glu antagonists gammadglutamylglycine dinitroquinoxalinedione dnqx and aminophosphonovaleric acid ap were applied to the nts extraventricular surface rostral to the obex all four agents inhibited both components of the reflex dnqx or ap produced a similar reversible inhibition upon pressure ejection in the vagal esophageal afferent projection area application of tetrodotoxin to the DM oblongata caudal to the area postrema ap was ineffective basal heart rate hr except in the case of ap and blood pressure increased upon nts surface application of the antagonists but not T3 intrants ejection at corresponding dorsal nts CS focal excitation of solitarial neurons with glu evoked SH and cardiac slowing at adjacent ventral CS in the nts subnucleus centralis ntsc andor its immediate vicinity glu elicited an arterial pressor response that coincided with an esophageal contraction in most but not all cases in conclusion afferent fibers of the esophagocardiovascular reflex ecvr probably terminate in the vicinity of esophageal PM SN comprising the ntsc and activate secondorder SN via glutamate receptors of both the nmda and nonnmda AT1 | MEDAL |
the decision of whether or not to treat a ventricular extrasystole depends in the first instance on the benign or severe nature of the disorder and on whether there is subjacent cardiopathy the results of hour holter monitoring exercise tolerance tests and clinical and echographic examinations will define the pathological character of a VVI extrasystole and will indicate any subjacent cardiopathy EP exploration with programmed stimulation should be reserved for socalled lethal cases of arrhythmia such as attacks of sustained VVI ART IC is by far the most frequent cause of VES the two L1 risks of SD after myocardial infarction are due to left ventricular dysfunction and repetitive andor complex VVI extrasystoles as well as to attacks of VVI tachycardia HR patients presenting these disorders must receive urgent treatment with antiarrhythmics isolated monomorphic ventricular extrasystoles are also treated in heart patients at risk if their frequency is greater than per hour measured by hour HM in the absence of subjacent cardiopathies the therapeutic indications are much less well defined approximately five per cent of subjects in a normal population present VVI eell as on mature cells circulating in the blood in pnh | MEDAL |
drug attrition rates have increased in past years resulting in growing costs for the pharmaceutical industry and consumers the reasons for this include the lack of in vitro models that correlate with clinical results and poor preclinical toxicity screening assays the in vitro production of human cardiac progenitor cells and cardiomyocytes from human pluripotent stem cells provides an amenable source of cells for applications in drug discovery disease modeling regenerative medicine and cardiotoxicity screening in addition the ability to derive humaninduced pluripotent stem cells from somatic tissues combined with current highthroughput screening and pharmacogenomics may help realize the use of these cells to fulfill the potential of personalized medicine in this review we discuss the use of CFU-S stem celnments and tolerate similar environmental temperatures this study indicated that sea bass and common sole can acclimatize to new thermal conditions adjusting their cellular process in a different manner | MEDAL |
the effect of the anticholinergic agent emepronium bromide cetiprin was studied in a double blind crossover T0 of a group of elderly patients with urinary incontinence and uninhibited bladder contractions during cystometry there was no statistically significant difference between the subjective effect of emepronium bromide and that of placebo and no change in the cystometric parameters the overall subjective cure or improvement rate was the effect of anticholinergic drugs in the treatment of urinary incontinence in elderly patients with uninhibited bladder contractions might to some extent be due to an improvement in the patients understanding and acceptance of the bladder disorders | MEDAL |
the effects of orally and intravenously administered doses of polyethyleneimine were observed in chloraloseurethananesthetized dogs polyethyleneimine produced an initial augmentation of rhythmic segmenting gastric antral contractions a copious flow of gastric mucus increased segmenting and propulsive activities of the small and large intestines and occasional micturition and defecation the gastric corpus and fundic regions became relaxed and enlarged these events were associated with the prompt appearance of retching the retching response to p.o. could only be abolished by bilateral vagotomy or bilateral sympathectomy the skeletal muscle component of retching was blocked by tubocurarine i.v. of chlorpromazine blocked the retching response and gastric corporal atonia to either intravenous or oral doses of polyethyleneimine either oral or i.v. of polyethyleneimine produced no detectable changes in the lead ii ecg but was associated with marked transient reductions in both mean and pulsatile arterial BPs these depressor effects showed clear tachyphylaxis in all cases where gi effects were noted QO2 was augmented and erratic in a manner associated with the retching responses | MEDAL |
the isolated perfused glomerulus technique was used to T0 pressure dependence of renin PR in single microdissected rb glomeruli with IN afferent arteriole and IN bowmans capsule renin release from individual afferentglomerular units was measured in minute intervals while AA pressure was either decreased from to to mm hg or increased from to to mm hg there was a clear inverse relation of RR and afferent pressure mean RR rate was times higher at than at mm hg and times higher at than at mm hg to evaluate the possible role of wall stretch in mediating this response inner and outer afferent arteriolar diameters were measured by videomicroscopy outer afferent diameter remained constant between and mm hg whereas inner diameter exhibited a slight increase changes of afferent arteriolar wall stretch however did not correlate with changes of renin release these data for the first time directly demonstrate the existence of a renin baroceptor at the level of the renal afferent arteriole they furthermore suggest that this baroceptor is not a stretch receptor | MEDAL |
throughout ophthalmic history it has been shown that progress has gone hand in hand with technological breakthroughs in the past fluorescein angiography and fundus photographs were the most commonly used imaging modalities in the management of diabetic macular edema dme today despite the moderate correlation between macular thickness and functional outcomes spectral domain OCT sdoct has become the dme workhorse in clinical practice several sdoct biomarkers have been looked at including presence of epiretinal membrane vitreomacular adhesion disorganization of the inner retinal layers central macular thickness integrity of the ellipsoid layer and subretinal fluid among others emerging imaging modalities include fundus autofluorescence macular pigment optical density fluorescence lifetime imaging ophthalmoscopy oct angiography and adaptive optics technological advances in imaging of the posterior segment of the eye have enabled ophthalmologists to develop hypotheses about pathological mechanisms of disease monitor disease progression and assess response to treatment spectral domain oct is the most commonly performed imaging modality in the management of dme however reliable biomarkers have yet to be identified machine learning may provide treatment algorithms based on multimodal imaging | MEDAL |
a silverstaining technique specific for demonstrating nucleolus organizer regions nor showed that the achromatic stalks of the acrocentric autosomes of the human complement represent the nors some R2 in number of stained stalks is observed from celltocell and from individualtoindividual the silverstained masses may extend beyond the stalks and cover the satellites especially in chromosomes with short stalks or minute satellites | MEDAL |
dosing of anticancer drugs in adults is mostly adjusted to estimated body surface area or body weight dose normalisation to body size is assumed to decrease the interindividual pharmacokinetic and pharmacodynamic variability this RPA is rarely validated before approval theoritically body size should be used only if it has been demonstrated that it constitues a significant factor affecting clinical variability recent studies have shown a posteriori that several marketed anticancer agents could be po at a fixed dose moreover the abandon of BS area in dosing of new drugs in phase i trials has been recommended at the present time body size continues to be used in the dosing of new agents in AD patients this review presents the concepts and the limits of weight and body surface areabased dosing of anticancer drugs in adult patients | MEDAL |
heating salmonella typhimurium in ethylenediaminetetraacetate was found to dissociate its antigens into forms that are nonsedimentable at x g the treatment caused a marked increase in the rate of immunoreaction and the sensitivity in an enzyme immunoassay for the detection of salmonella antigens the method permits the extraction of salmonella antigens from solidrich samples and the preparation of solidfree samples by means of centrifugation when the level of the antigens in the supernatant was too low for the immunoassay the antigens were readily concentrated by passing a C1 volume of the supernatant through a macroporous hydrophobic cloth coated with antisalmonella antibody using this method the PCD of as few as salmonella cells per gram of chicken meat was possible within a total of h which included h of enrichment in either TT selenite cystine or nutrient broths | MEDAL |
the present T0 was designed to investigate the putative anxiolytic effects of moclobemide moc a reversible inhibitor of type a MA oxidase enzyme rima antidepressant in an exp MM of anxiety in mice the test selected was the lightdark aversion test in the present investigation an anxiogeniclike SMB was induced by CS alone as the stimulus standard version of the test or by pretreatment with a subconvulsant dose of pentylenetetrazole ptz mgkg ip min before testing enhanced version of the test in mice the effect of repeated administration for weeks of moc and mgkg ip was compared with those of selegiline sel and mgkg ip an irreversible and selective maob inhibitor for comparative purpose the chronic effect of an established reference anxiolytic such as lorazepam lor and mgkg ip was also evaluated results demonstrated that ptztreated mice showed a decrease in the number of EMT as well as in the time spent in the lit area when compared with vehicle controls an effect characteristic of an anxiogenic response this anxiogeniclike behavior was reduced by chronic administration of lor as well as moc suggesting an anxiolyticlike effect as shown in the standard version of the test in addition the increased aversion of mice for the CS compartment of the lightdark box was significantly reduced compared to ptztreated mice or VH controls sel failed to significantly alter the anxiogeniclike behavior induced by subconvulsant doses of ptz these data provide additional evidence for the anxiolyticlike effects of moc administered chronically in the mouse | MEDAL |
a mitochondrial dna deletion in a case of kearnssayre syndrome is described the deletion is bracketed by direct repeats that were unusual in that one of them was located nucleotides from the deletion seam and both were conserved which should not occur in slip replication or illegitimate elongation the deleted region was demarcated on the deletion side by sequences that could be predicted to form hairpin structures the side of the deletion was flanked by a sequence homologous to a nucleotide piece of the conserved sequence block ii of the dloop this arrangement around the deletion in KSS bears some resemblance to the arrangement in the pearson marrowpancreas syndrome described by a rötig et al genomics | MEDAL |
the carboxylterminal portion of simian virus large t antigen is essential for productive infection of cv and cvp green monkey A6 mutant dla lacking base pairs at map units was positive for viral dna replication but unable to form plaques in cvp cells j tornow and cn cole j virol in this report the defect of dla is further defined simian virus late mrnas were transcribed polyadenylated spliced and transported in dlainfected cells but the level of CPs produced in INF cv green monkey A6 was extremely low dla C1 t antigen lacks those residues known to be required for adenovirus helper CF and the block to productive infection by dla occurs at the same stage of infection as the block to productive adenovirus infection of cv cells these results suggest that the adenovirus helper CF is required for productive infection by simian virus mutant dla was able to grow on the vero and bsc lines of african green monkey kidney cells additional mutants affecting the carboxylterminal portion of LT were prepared mutant inv contains an inversion of the dna between the bamhi and bcli CS to map units this inversion causes transposition of the carboxylterminal amino acids of LT antigen and the carboxylterminal amino acids of vp this mutant was viable even though the essential information absent from dla C1 t antigen has been transferred to the CT of vp of inv the vp polypeptide carrying this carboxylterminal portion of LT could overcome the defect of dla this indicates that the CT of LT antigen is a separate and separable functional domain | MEDAL |
we report two cases of fatal intoxications with mercury one intentional and the other allegedly resulting from a drug formulation mistake both cases occurred in the year of the first case refers to a man who ingested a great portion of a mercuric chloride solution he attended a hospital emergency submitted to treatment but died T3 days in the second case a woman applied on the chest skin an ointment containing a great quantity of mercury bromide T3 days of treatment in the hospital she died in both cases samples of tissues and organs were collected at autopsy for mercury analysis because methylation of mercury in humans after exposure to metallic or inorganic mercury is almost unknown both total mercury and methylmercury were quantified in the postmortem samples the quantifications were carried out by cold vapour generation atomic absorption spectrometry for total mercury and by hplcuv for methylmercury the total mercury contents found in the postmortem fluid and tissue samples were consentaneous with mercury poisoning for the first case the concentrations found expressed in microgg wet weight were in the CL lung and BB and for blood microgml for the second case the concentrations expressed in microgg wet weight were in the CL lung brain kidney stomach spleen and HR and for blood and urine and microgml respectively only in the first case was methylmercury found and quantified in liver microgg wet weight and in blood microgml samples | MEDAL |
it has become increasingly clear that low C2 of antibiotics present in many environments can select for resistant bacteria yet the evolutionary pathways for resistance OD during SE to low amounts of antibiotics remain poorly defined here we show that salmonella enterica exposed to submic C2 of streptomycin evolved highlevel resistance via novel mechanisms that are different from those observed during lethal selections during lethal selection only rpsl mutations are found whereas at submic selection resistance is generated by several smalleffect resistance mutations that combined confer highlevel resistance via three different mechaynthesis of various sulphurcontaining biomolecules accumulating evidence has revealed another important feature of persulphides their potent reducing activity which implies that they are implicated in the regulation of redox signalling and antioxidant functions in this chapter we discuss the biological occurrence and possible biosynthetic mechanisms of cysssh and related persulphides and we include descriptions of recent advances in the analytical methods that have been used to detect and quantitate persulphide species we also discuss the antioxidant activity of persulphide species that contributes to protecting cells from reactive oxygen speciesassociated damage and we examine the signalling roles of cysssh in bacteria | MEDAL |
healthrelated quality of life hrqol measurement aims to capture the complete subjective health state of the patients and to comprehensively evaluate treatment outcomes the aim of this T0 was to assess using the d hrqol instrument hrqol in a sample of chronic pain patients referred to the multidisciplinary pain clinic of the helsinki UH during to the d results of the chronic pain patients were compared with those of a matched GP to analyse the properties of the d the results were compared with the preadmission questionnaire of the pain clinic containing questions about background AF aspects of the pain and its impact on life the mean d score of the chronic pain patients was one of the lowest reported using d vs in the GA population it equalled the score of advanced CA patients in palliative care the d scores were normally distributed and d showed both statistically and clinically significant discriminative power in painrelated background AF VAS scale on PI VAS scale on painrelated distress and the impact of pain on daily life correlated well with the d score pain intensity did not have independent predictive value on the score the results indicate heavy perceived burden of illness in CPPs in CS of the questions analysed d appears CS and discriminative in CPPs in tertiary care instead of PI the impaired hrqol in CP was mainly because of the psychosocial aspects of pain | MEDAL |
the hematopoietic growth factor granulocyte colonystimulating factor gcsf has become one of the few growth factors approved for clinical use it has therapeutic potential for numerous neurodegenerative diseases however at present the cellular effects of gcsf on the CNS system remain unclear and in need of investigation in the present study we used SCI a neurodegenerative MM to examine the effects of intrathecal it gcsf on glial cell microglia and astrocyte activation and neuroprotective factor expression including glial cell linederived neurotrophic factor gdnf and V1 EC growth factor a vegfa protein expression our results indicate that it gcsf could enhance ischemiainduced microglial activation and inhibit ischemiainduced astrocyte activation both gdnf and vegfa are upregulated after injury and it gcsf could enhance gdnf and vegfa expressions T3 injury interestingly our results indicate that performing it gcsf alone on normal animals could have the effect of microglial and astrocyte activation and enhanced gdnf and vegfa expressions furthermore through laser scanning confocal microscopy we found that astrocytes may contribute to the majority of gdnf and vegfa expressions of gcsf after spinal cord ischemia overall this gcsfinduced upregulation suggests that activation of endogenous neuroprotective mechanisms could resist neurodegenerative insults these observations demonstrate the cellular mechanism of it gcsf after spinal cord ischemia and confirm the neuroprotective effect of gcsf after SCI injury | MEDAL |
we evaluated the possibility that in some patients with obstructive SA the initial polysomnogram may be negative we reviewed PSGs performed at the MCG from to and found nine patients whose initial polysomnogram was negative but whose repeat polysomnogram confirmed obstructive SA all nine patients five women and four men average age years had an apnea index of less than fewer than five apneic episodes per hour and had a total of fewer than apneic episodes during the initial overnight PSG the change in average weight was not significant three patients had received shortterm oxygen therapy and two of these three received nasal CPAP prior to the initial T0 the time that patients spent supine increased from min in the initial T0 to min in the second but this was not significant p comparison of the initial and diagnostic PSGs showed significantly reduced TST from h to h p and reduced rapid EM rem sleep time from h to h p in the initial study we conclude that in a small subset of patients with obstructive sleep apnea the initial PSG may be falsely negative which could be due to previous therapy a reduction in TST and rem sleep or other unidentified factors | MEDAL |
the relatives of newborn children with nonsyndromic cleft lip with or without cleft palate cl p of with isolated cleft palate cp and of equal numbers of appropriate controls were screened for the presence of the same or different malformations the main findings were as follows the frequency of familial cases of cl p was much higher than the prevalence of this malformation among the relatives of controls the sibs of cl p subjects showed a higher prevalence of this condition than their parents v the degree of genetic determination of this condition should be high to and the data in GA favour a multifactorial MM of inheritance with different thresholds between sexes however the action of dominant genes cannot be excluded since selection or dominant genes or both could be postulated to explain the parentsib difference the frequency of other malformations was also significantly raised in the families of cl p probands as compared to controls v the prevalence of these other malformations was higher among sibs than parents of cl p babies a general susceptibility to malformations and different exposure to selective agents may explain these latter findings none of the comparisons involving cp children yielded significant results | MEDAL |
pregnancy is a special clinical state with several normal physiological changes that influence body organs including the liver MLD can cause significant morbidity and mortality in both pregnant women and their infants this review summarizes liver diseases that are unique to pregnancy we discuss clinical conditions that are seen only in pregnant women and involve the CL from hyperemesis gravidarum that happens in out of pregnancies and ICP prevalence to the more frequent condition of preeclampsia prevalence and its severe form hemolysis elevated liver enzymes and a low platelet count syndrome of pregnancies with preeclampsia to the rare entity of acute fatty liver of pregnancy incidence of per to deliveries although pathogeneses behind the development of these aliments are not fully understood theories have been proposed some propose the special physiological changes that accompany pregnancy as a precipitant others suggest a constellation of factors including both the mother and her fetus that come together to trigger those unique conditions reaching a timely and accurate diagnosis of such conditions can be challenging the timing of the condition in relation toward which trimester it starts at is a key accurate diagnosis can be made using TPS clinical findings and blood tests some entities have welldefined criteria that help not only in making the diagnosis but also in classifying the disease according to its severity management of these conditions range from simple medical remedies to measures such as immediate termination of the pregnancy in TPS conditions it is prudent to have expert obstetric and medical specialists teaming up to help improve the outcomes | MEDAL |
gastric gland component cells were electronmicroscopically and immunoelectronmicroscopically examined with highpressure freezing followed by FS and a lowtemperature embedding resin method and compared to that of the conventional chemicalfixation method the rat gastric gland was highpressure frozen freezesubstituted with acetonecontaining osmium or acrolein and embedded in epon or lowicryl km respectively using the highpressure freezing method the vitreous freezing range reached the depth of microns from the surface the ultrathin sections from both procedures embedding in epon and lowicryl km were doubly stained with uranyl acetate and lead acetate and histochemically or IHC stained respectively in comparison to the conventional chemical fixation method excellent results were obtained with respect to ultrastructural preservation the stainings performed in this experiment included periodic acidthiocarbohydrazidesilver proteinate IF cationic colloidal cold at ph IF helix pomatia lectinstaining antialpha or beta S1 antibodies of hkatpase immunostaining and pepsinogen IS the staining intensity of those was stronger than that of the conventional immersionchemical fixation method in addition to these results the labels also showed good TPS localization in this paper we provide a description of the highpressure freezing followed by FS and lowtemperature embedding resin method compared to the conventional chemicalfixation method our results suggest that this method is a suitable tool for ultrastructural and histochemicalimmunohistochemical studies at high resolution | MEDAL |
SVR vasculitides can cause retinal V1 pathology including cottonwool spots retinal hemorrhages V1 occlusion and capillary nonperfusion two main causes of visual decline include macular edema and retinal neovascularization presumably both of these complications are caused by increased intraocular levels of V1 growth and permeability AF we report a patient with occlusive retinal vasculitis associated with mixed connective tissue disease who was treated with intravitreal bevacizumab for chronic macular edema one month after treatment visual acuity improved from to and foveal thickness decreased from microns to microns this effect persisted for at least months after treatment no complications including increased retinal ischemia were observed | MEDAL |
we previously cloned and sequenced nqr operon encoding the natranslocating nadhquinone reductase nqr from the marine bacterium vibrio alginolyticus a gene cluster very similar to nqr operon was found to exist in the genome of haemophilus influenzae rd we examined the membrane fraction from h influenzae and the RC of h influenzae was found to contain a nadependent nqr that is essentially identical to those found in the marine v alginolyticus these results indicate that quite similar to the saltloving marine bacteria the bloodloving h influenzae has a redoxdriven na pump and utilizes na circulation for SE coupling | MEDAL |
this report presents the recommendations of a who expert committee commissioned to coordinate MICs leading to the adoption of international recommendations for the production and control of vaccines and other biologicals and the establishment of international biological reference materials following a brief introduction the report summarizes a number of general issues brought to the attention of the committee the next part of the report of particular relevance to manufacturers and national regulatory authorities outlines the discussions held on the OD of revised who recommendations and guidelines for a number of vaccines blood products and related substances TPS discussion Az included the development of who guidance on the quality safety and tau of poliomyelitis vaccines recombinant malaria vaccines diphtheria vaccines tetanus vaccines combined vaccines based on diphtheria and tetanus vaccines and JE vaccines subsequent sections of the report then provide information on the current status and proposed development of international REF materials in the Az of vaccines and related substances blood products and related substances in vitro diagnostic device reagents biotherapeutics other than blood products and antibiotics a series of annexes are then presented which include an updated list of who recommendations guidelines and other documents on biological substances used in medicine annex followed by a series of who recommendations and guidelines adopted on the advice of the EC annexes all additions made during the meeting to the list of international standards and REF reagents for biological substances maintained by who are then summarized in annex and are also available at httpwww whointbiologicals | MEDAL |
prolonged asymptomatic carriage of vancomycinresistant enterococci vre in the gastrointestinal tract and the lack of effective decolonization regimen perpetuate the endemicity of vre in the healthcare settings | MEDAL |
amyloid formation of the plasma protein transthyretin ttr has been linked to familial amyloid polyneuropathy and senile systemic amyloidosis IB of ligands within its natural hormone IB site can stabilize the tetrameric structure and impair amyloid formation we have recently shown that the flavonoid luteolin stabilizes ttr in human plasma with a very high selectivity luteolin however is inactivated in vivo via glucuronidation for which the preferred site is the hydroxy group at position on its aromatic aring we have evaluated the properties of two luteolin variants in which the hydroxy group has been exchanged for a chlorine cllut or a methoxy group meolut using an in vitro model based on human CL microsomes we verified that these modifications increase the persistence of the drug crystal structure determinations show that cllut binds similarly to luteolin the larger meo substituent cannot be accommodated within the same space as the chlorine or OH group and as a result meolut binds in the opposite direction with the methoxy group in position facing the solvent both cllut and meolut qualify as highaffinity binders but in contrast to luteolin they display a highly nonspecific binding to other plasma components the IB of the two conformations and the keyinteractions to ttr are discussed in detail taken together these results show a proofofconcept that the persistence of luteolin towards enzymatic modification can be increased we reveal two alternative highaffinity IB modes of luteolin to ttr and that modification in position is restricted only to small substituents if the original orientation of luteolin should be preserved in addition the present work provides a GA and convenient method to evaluate the efficacy of ttrstabilizing drugs under conditions similar to an in vivo environment | MEDAL |
a rare case of extradural nasal and orbital extension of malignant glioma is presented the development of malignant changes was observed during years the mode of transdural extension was via the olfactory nerve where it was directly destructive in all four cases that have been reported to date the biological malignancy of transdurally extending glioma is also described | MEDAL |
available data support the idea that the neonatal lupus erythematosus syndrome results from an autoantibody produced in the mother and passed across the placenta to the fetus despite the evidence for the presence of the rossa autoantigen both in the skin and heart and the almost universal presence of the rossa autoantibody in mothers of infants with neonatal lupus there are emerging data to suggest that lassb and rarely nrnp antibodies play an important pathologic role in some cases of the neonatal lupus syndrome | MEDAL |
to investigate the effect of caffeine infusion on superior mesenteric artery sma blood flow E/A bfv in preterm infants | MEDAL |
shp small heterodimer partner nrb is an atypical orphan nr nuclear receptor that functions as a transcriptional corepressor by interacting with a diverse set of nrs and transcriptional factors hnf hepatocyte nuclear factor is a key regulatory factor in pancreatic OD endocrine differentiation and the formation of the biliary tract as well as glucose metabolism in this T0 we have investigated the CF of shp as a putative repressor of hnf using transient transfection assays we have shown that shp represses the transcriptional activity of hnf confocal microscopy revealed that both shp and hnf colocalize in the nuclei of cells shp physically interacted with hnf in proteinprotein association assays in vitro emsas electrophoretic mobilityshift assays and chip chromatin immunoprecipitation assays demonstrated that shp inhibits the dnabinding activity of hnf to an hnfresponse PE consensus CS and the hnf target region of the endogenous gpase glucose phosphatase promoter respectively northern blot analysis of hnf target genes in cells infected with adenoviral vectors for shp and shp sirnas small GABA rnas indicated that shp represses the expression of endogenous gpase and pepck phosphoenolpyruvate carboxykinase our results suggest that hnf is a novel target of shp in the regulation of gluconeogenesis | MEDAL |
glycogen a branched polymer of glucose functions as an energy reserve in many living organisms CA in glycogen metabolism usually excessive accumulation can be caused genetically most often through mutation of the enzymes directly involved in synthesis and degradation of the CP leading to a variety of glycogen storage diseases gsds microscopic visualization of glycogen deposits in cells and tissues is important for the study of normal glycogen metabolism as well as diagnosis of gsds here we describe a method for the detection of glycogen using a renewable recombinant protein which contains the carbohydratebinding module cbm from starchbinding domain containing protein stbd we generated a FP containing g lutathione stransferase a cm c eptitope and the tbd bm gysc for use as a glycogenbinding probe which can be detected with AA antibodies against glutathione stransferase or cmyc by enzymelinked immunosorbent CA we demonstrate that gysc binds glycogen and two other polymers of glucose amylopectin and amylose immunofluorescence IF of cultured cells indicate a gyscspecific signal that is colocalized with signals obtained with antiglycogen or antiglycogen synthase antibodies gyscpositive staining inside of lysosomes is observed in individual muscle fibers isolated from mice deficient in lysosomal enzyme acid alphaglucosidase a wellcharacterized MM of gsd ii pompe disease colocalized gysc and glycogen signals are also found in muscle SF isolated from mice deficient in malin a model for lafora disease these data indicate that gysc is a novel probe that can be used to study glycogen metabolism under normal and pathological conditions | MEDAL |
most sym plasmidlocalized nodulation genes of rhizobium leguminosarum bv viciae are only expressed upon activation of the nodd protein by plant flavonoids eg naringenin s a j zaat c a wijffelman h p spaink a a n van brussel and b j j lugtenberg j bacteriol as part of a T0 on the mechanism of nodd protein activation the mechanism of uptake and the intracellular fate of hnaringenin were studied naringenin was accumulated by rhizobium cells without apparent metabolic conversion to an foldhigher concentration in a process which did not require any of the other sym plasmidlocalized nod genes naringenin accumulation was nonsaturable highly reversible and not inhibited by the presence of other flavonoids or the metabolic inhibitors potassium cyanide sodium azide dinitrophenol and carbonyl cyanide mchlorophenylhydrazone these data indicate an accumulation mechanism without high affinity sites which does not use cellular SE in vitro naringenin has high affinity for the CM this binding was ph dependent very high at ph and not present anymore at ph a similar ph dependency was found for the affinity of naringenin for the olive oil fraction of a biphasic olive oilwater system phdependent changes in the uv spectrum indicate ionization of naringenin at high ph to a negatively charged form since it has recently been shown that the nodd gene product is located in the cytoplasmic membrane h r m schlaman h p spaink r j h okker and b j j lugtenberg j bacteriol in press our data are consistent with a MM in which the unionized form of naringenin accumulates in the CM and activates in a metabolically unaltered form the nodd protein | MEDAL |
the autosomal dominantly inherited disease NF type nf is caused by mutations of a large gene comprising exons which code for a protein with amino acids called neurofibromin employing an expressed polymorphic site in exon of the neurofibromin gene the expression of its alleles was analysed quantitatively by scanning radioactive rtpcr fragments of this exon prepared from the rna of fibroblast cell cultures from nf patients and of WBCs from one nf patient thirteen of the rna preparations yielded unequal amounts of the allelic messages the deviations of the expression ratios aa from ranged from to the allelic messages were equally represented in the rna S9 from five informative HD apart from fibroblasts this phenomenon could also be detected in keratinocytes MC from normally pigmented skin and melanocytes from a caféaulait spot of one patient only one of three patients affected by stop mutations exhibited unequal allelic expression when nuclear rna from of the patients was examined equal amounts of the primary transcripts were found average ratio aa sem indicating that unequal expression on the level of mrna was not caused by mutations affecting transcriptional regulation the ratio of the amount of neurofibromin to that of p gap did not seem to be correlated with the extent of unequal allelic expression | MEDAL |
the distribution and cytoarchitectonic pattern of the magno and parvocellular hypothalamic nuclei of the cobra naja naja are described at the lightmicroscopic level with respect to their tinctorial affinity to paraldehyde fuchsin af as a representative of the gomoritype of stains the MCNs belong to the afpositive and the parvocellular SN to the afnegative elements in addition to the supraoptic and paraventricular nuclei proper two accessory aggregations of magnocellular neurons the nucleus retrochiasmaticus and nucleus circularis can be identified although in a peculiar location they may be regarded as subunits of the supraopticoparaventricular NS complex as many as afnegative nuclear Az are identified in the hypothalamus of the cobra the nucleus periventricularis hypothalami of earlier authors is subdivided into several circumscribed neuronal complexes the nucleus arcuatus nucleus hypothalamicus lateralis and nucleus lateralis recessus infundibuli are well developed an attempt is made to interpret the significance of these nuclei on a comparative and phylogenetic basis | MEDAL |
butenediol bdd a L1 metabolite of butadiene bd can readily be Ox to hydroxymethnce peak width and the minimum device size is derived in good PA with simulations measurements indicate a negligible NC in shape of the resonance peak from nm at a degrees angle of incidence to nm at a degrees angle with a full width at halfmaximum of nm in this range the shift of the peak wavelength is linear with respect to changes in the angle of incidence | MEDAL |
the multicenter european radiofrequency survey merfs retrospectively analysed the incidence of procedurerelated complications in patients who had undergone radiofrequency catheter ablation in european institutions between and of these patients underwent modification of the atrioventricular node to cure AVN reentrant tachycardia this report presents a detailed analysis of the incidence of CR atrioventricular block with respect to the target site and the number of patients reported per institution the most common complication of modification of the AVN was the unintended induction of CR atrioventricular block of patients in of patients detailed information about the approached target site for modification of the atrioventricular node was available CAVB occurred significantly more often in patients who underwent ablation of the FP or in whom ablation of the slow and fast pathway was attempted T3 failure at the initial site than in patients who underwent SP ablation p the overall incidence of complete atrioventricular block was significantly higher in centres with limited experience in RF modification of the AVN or patients treated GI n compared to centres that had treated patients group ii n p in addition in those patients in whom the target site was available the incidence of CAVB after FP ablation was significantly higher in GI n patients when compared to group ii n patients vs p and also tended to be higher after SP ablation in group i in GI vs in group ii p ns | MEDAL |
pseudomatching the selection of the correct comparison stimulus without dependence on presentation of a sample CS- was demonstrated in monkeys being TR ostensibly on a matchingtosample shockavoidance tast pseudomatiching occurred whenever the problem sets were not fully counterbalanced for key position and correct symbol and seemed to represent memorization of specific CS- configurations some animals showed the capacity to memorize hundreds of different choice problems as indicated by test trials on which the samples were omitted to prevent pseudomatching contamination of matchingtosample behavior one must arrange full counterbalancing and randomization of stimuli and reinforcements pseudomatiching test trials are also recommended | MEDAL |
the effects of CP on the bioenergetics and activity of monoamine oxidase in mitochondria from the BB of the rat were examined oxidation rates of glu and succinate were investigated in the presence of chlorphentermine mm in small concentrations mm chlorphentermine decreased the RCR and the adenosine diphosphate oxygen adpo ratio and stimulated state four QO2 state three respiration and the uncoupled state were also decreased but to a lesser degree in the presence of larger concentrations of chlorphentermine mm the respiration in states four three and in the uncoupled state as well as the respiratory control ratio and adpo ratio were decreased significantly these data indicate that CP functions as an uncoupler of oxidative phosphorylation oxidation of norepinephrine serotonin octopamine tyramine and dopamine by MAO-A mao an enzyme marker of the outer mitochondrial membrane was inhibited in the presence of to mm of chlorphentermine oxidation of TA and BZ was unaffected a kinetic study of the oxidation of serotonin in the absence and presence of CP mm indicated that both the vmax and km were affected this drug is an inhibitor of MA oxidase of mitochondria of the BB with mixed type inhibition these combined data show that CP affects PSA processes in both inner and outer mitochondrial CM | MEDAL |
the adherence of several GN uropathogens to human uroepithelial cells was examined with scanning and transmission electron microscopy and in vitro adhesion assays the bacteria studied demonstrated different extracellular structures fimbria and glycocalyx human uroepithelial cells were obtained from a bladder RT cell line t and from different groups of patients including those with no history of urinary tract infection controls recurrent urinary tract infection acute cystitis and bladder tumors before and T3 rBCG therapy results from these comparative studies showed that bacteria with extracellular structures adhered better than those bacteria without extracellular structures it also was shown that uroepithelial cells obtained from patients with recurrent urinary tract infection and with acute cystitis were more susceptible to bacterial adherence than the uroepithelial cells of the controls there were significant increases of to fold in mean adherence in the former CG p equals and there was no significant difference in bacterial adherence between the t cells and the bladder tumor cells before rBCG treatment however in both CG after treatment with bacillus calmetteguerin the mean adherence increased to fold p equals times a survey of bladder tumor patients also showed a fold increase in the incidence of acquired urinary tract infection after bacillus calmetteguerin therapy these results reveal a corregainst staphylococci it had activity similar to that of cefotaxime and ceftizoxime against group a and b streptococci and streptococcus pneumoniae it did not inhibit streptococcus faecalis or listeria spp cefmenoxime had activity similar to that of cefotaxime ceftizoxime ceftazidime and moxalactam against escherichia coli citrobacter diversus klebsiella proteus mirabilis salmonella and shigella it inhibited betalactamasepositive and negative isolates at less than or equal to microgramml cefmenoxime was somewhat less active than moxalactam or ceftizoxime against enterobacter cloacae enterobacter aerogenes and enterobacter agglomerans but was more active than cefotaxime ceftizoxime or ceftazidime against morganella minimum GABA concentration for of isolates microgramml proteus vulgaris and providencia spp it was as active as CZX was against serratia pseudomonas spp and bacteroides spp were relatively resistant minimum inhibitory concentration for of isolates greater than microgramsml the compound was SD to the common plasmid betalactamases such as that of tem it was stable to most chromosomally mediated betalactamases which act primarily as cephalosporinases but was hydrolyzed by bacteroides and acinetobacter | MEDAL |
total elbow arthroplasty remains the most definitive PET procedure for patients with endstage painful arthritis of the elbow complication rates have historically been quite high and early revision was not uncommon a greater understanding of elbow anatomy and kinematics has led to advances in prosthetic design and surgical technique the success of modern elbow arthroplasty for lowdemand patients with RA arthritis has approached that of hip and knee arthroplasty mechanical failures have been noted to increase as a complication of both longevity and the use of elbow arthroplasty in a younger higherdemand patient population as the indications for total elbow arthroplasty widen to include more complex situations it becomes more important to precisely recreate the flexionextension axis of the elbow to optimally balance muscle forces and ligaments in an effort to improve implant durability advances in implant modularity and instrumentation can make determination and recreation of the flexionextension axis more reliable and reproducible an anatomic convertible implant allows the surgeon great versatility in choosing to perform hemiarthroplasty or unlinked or linked TEA with assurance that later revision can be performed without the compulsory removal of wellfixed components conversion from an unlinked to a linked constraint and visa versa can be performed at any time if late conversion is required it can be performed in a minimally invasive fashion | MEDAL |
the readiness potential preceding voluntary movement is modulated by the mode of movement selection ie it has a higher amplitude preceding freely selected than before prescribed movements praamstra p stegeman df horstink mwim brunia chm and cools ar MRPs preceding voluntary movement are modulated by the mode of movement selection exp brain res one cortical area that is likely to be involved in this modulation is the SMA area sma recent attempts to elucidate the neural generators of the readiness potential using spatiotemporal dipole source analysis however failed to establish a significant sma contribution to the RP this might be explained by a failure of the proposed analyses to discriminate between sma and motor SC contributions to the readiness potential we applied a dipole source analysis approach that better separates these overlapping source activities the resulting source MM includes an sma source generating premovement activity consistent with evidence from intracranial recordings in humans the sma source accounts almost CR for the modulation of the RP by different modes of movement selection on the basis of these results the relation between scalprecorded movementrelated activity intracranially recorded potentials and findings from functional imaging studies of voluntary movement appears more transparent than suggested by previous dipole source analyses of premovement potentials | MEDAL |
rats susceptible sjr and resistance rjr to the hypertensive effect of salt were weaned at days of age and placed on a high salt intake blood pressure measured at and weeks of age after weeks of high salt NI demonstrated a slight increase in rjr rats and a highly significant increase in sjr rats urinary fee nordeoxycorticosterone nordoc C2 measured in weekly urine collections were found to be markedly elevated in sjr rats compared to C2 in rjr rats since nordoc has been shown to be a potent mineralocorticoid the results suggest that elevated production of nordoc may have a role in hypertension in rats susceptible to the hypertensive effects of salt | MEDAL |
prostate cancer is known to be affected by the heavy metal levels and oxidative damage of the body yet there are very few studies which look into the way it occurs the aim of this T0 was to determine whether blood and tissue lead pb cadmium cd and Se se levels are associated with oxidative damage in the context of prostate CA progression and development seventynine patients comprising patients with BPH bph patients with malignant prostatic carcinoma malign ca patients with lowgrade PIN lgpin and patients with highgrade PIN hgpin diagnosed on the basis of their clinical profile transrectal ultrasonography and histopathology were included in this T0 cd and pb C2 in whole blood were found to be increased in patients with hgpin compared with the bph group also the levels of cd in whole blood and tissue were found to be increasing in patients with malign ca unlike bph patients moreover the C2 of malondialdehyde mda in plasma and tissue were significantly increased in malign ca lgpin and hgpin than those in bph however the levels of tissue pb were found to be decreasing in bph unlike the malign ca and hgpin patients and the levels of tissue protein carbonyls in malign ca were significantly lower than those in hgpin the levels of tissue reduced glutathione gsh in malign ca were significantly lower than those in bph additionally the C2 of se in SS and tissue in lgpin were significantly lower than those in bph the serum se C2 in hgpin were also significantly lower than those in bph and malign ca CG furthermore the concentrations of serum se in lgpin were significantly lower than those in malign ca from the pearson rho analysis there were significant positive correlations between tissue cd and mda levels in malign ca lgpin and hgpin and between the tissue pb and tissue mda and protein carbonyl C2 in malign ca blood pb and tissue pb were also significantly positively correlated with plasma mda and protein carbonyl C2 in malign ca in addition blood pb was significantly positively correlated with tissue mda and protein carbonyl levels in malign ca and a significant positive rho was also found between blood cd and plasma protein carbonyls and tissue mda in lgpin we observed that altered prooxidantantioxidant balance and heavy metal levels may lead to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis these findings indicate that changes in the levels of pb cd se mda protein carbonyls and gsh in the blood andor tissue are related to the prostatic carcinoma development and progression although triggering one of the mentioned changes is unknown therefore further study is required to determine the exact steps of the process and clarify the roles of different substances in order to obtain a more detailed explanation of the phenomenon | MEDAL |
the ability to detect sudden changes in the environment is critical for survival hearing is hypothesized to play a L1 role in this process by serving as an early warning device rapidly directing attention to new events here we investigate listeners sensitivity to changes in complex acoustic sceneswhat makes certain events popout and grab attention while others remain unnoticed we use artificial scenes populated by multiple puretone components each with a unique frequency and amplitude modulation rate importantly these scenes lack semantic attributes which may have confounded previous studies thus allowing us to probe lowlevel processes involved in AEP NC perception our results reveal a striking difference between appear and disappear events listeners are remarkably tuned to object appearance change PCD and identification performance are at ceiling response times are short with little effect of scenesize suggesting a popout process in contrast listeners have difficulty detecting disappearing objects even in small scenes performance rapidly deteriorates with growing scenesize response times are slow and even when change is detected the changed component is rarely successfully identified we also measured NC detection performance when a noise or silent gap was inserted at the time of NC or when the scene was interrupted by a distractor that occurred at the time of change but did not mask any scene elements gaps adversely affeeng possesses the neuroprotective effects in this T0 we tried to explore the effect of rg on promoting differentiation of mouse embryonic stem es cells towards the neuronal lineage and its potential role involved in glucocorticoid receptor gr activation rg treatment induced a remarkable increase in the population of neuronlike cells in a timedependent manner more than of rgtreated EBs ebs differentiated into neuronlike cells on d furthermore the gradually increased protein expression of neurofilament nefm and βtubulin iii a neuronal specific protein was determined gr expression gradually increased during the differentiation course ru an antagonist of gr could efficiently block the neurogenesispromoting activity of rg on the other side rg stimulated the phosphorylation of erk and akt at different time points through gr activationdependent mechanisms treatment of both u an inhibitor of mek and ly an inhibitor of pi k hampered the neuronal differentiation induced by rg meantime u further decreased rginduced pakt expression in conclusion rg possesses the effects on inducing differentiation of mouse es cells into SN in vitro via the grmekerkpi kakt signaling pathway | MEDAL |
chronic granulomatous disease cgd is a primary phagocyte immunodeficiency it is often accompanied by an exuberant and aberrant inflammatory response with granulomata and obstruction of the gastrointestinal and GU tracts and inflammatory bowel disease although corticosteroids are successful in managing the obstructive and inflammatory disorders of cgd they are not ordinarily used for the management of infection because of the possibility of further compromising the patients immune system | MEDAL |
we investigated the influence of bias in the estimates of the population pharmacokinetic parameters on the performance of bayesian FB in achieving a desired drug serum concentration three specific cases were considered i steadystate case ii lidocaine example and iii mexiletine example whereas in the first case both the FB and the desired concentration represented steadystate values in the lidocaine and mexiletine examples the FB concentration was assumed to be sampled shortly T3 starting therapy rmse was used as a measure of predictive performance for the simple steadystate case the relationship between rmse and bias in the parameter estimates describing the prior CSD could be derived analytically MC simulations were used to explore the two nonsteadystate situations in GA the performance of bayesian feedback to predict serum concentrations was relatively insensitive to bad populatior i on cholesterol sidechain cleavage activity and the synthesis of cytochrome pscc and Ad were investigated in primary cultures of swine ovarian GCs nanomolar concentrations of pure human somatomedin c stimulated biosynthesis of progesterone and alphahydroxypregnenone moreover in the presence of exogenous sterol substrate for SCC somatomedin c significantly enhanced pregnenolone biosynthesis in a time and dosedependent manner this augmentation of PET cholesterol sidechain cleavage activity was accompanied by a dosedependent fold increase in smethionine incorporation into specific immunoprecipitable cytochrome pscc and Ad micromolar concentrations of insulin but not proinsulin or desoctapeptide also induced synthesis of cholesterol sidechain cleavage constituents by fold these results demonstrate that an insulinlike growth factor somatomedin c exerts discrete differentiating effects on ovarian cells characterized by increased synthesis of immunospecific cytochrome pscc and adrenodoxin thus we infer that somatomedin c may serve a critical role in the differentiation of steroidogenic cells in the rat ovary | MEDAL |
the objective of this study was to compare HS for short HV transection with conventional ligation during recipient hepatectomy with caval preservation sixteen patients undergoing elective living donor liver transplantation were randomized into CG we recorded number diameter and location of each short HV procedure time central venous pressure and degree of CL failure C-P and MM for end stage liver disease scores as an end point we observed the intraoperative and postoperative one rates of the transected veins we transected veins of mean diameter of ± mm range mm mean number of short hepatic veins in each person was range HS was safe for veins with a diameter ⤠mm these veins were more prone to bleeding with conventional ligation bleeding rate was higher T3 ligation of veins in the upper half than the lower half of the cava vs p both total and per vessel procedure time did not differ between the groups no postoperative one complications occurred transection of veins with a diameter ⤠mm by HS was as safe as conventional ligation HS transection of small hepatic veins ⤠mm can be even safer than conventional control by knot tying particularly in narrow Az | MEDAL |
quantitative control of aroma generation during the MR presents great scientific and industrial interest although there have been many studies conducted in simplified model systems the results are difficult to apply to complex food systems where the presence of other components can have a significant impact in this work an aqueous extract of defatted beef CL was chosen as a simplified food matrix for studying the kinetics of the MR aliquots of the extract were heated under different time and temperature conditions and analyzed for sugars amino acids and methylbutanals which are important maillardderived aroma compounds formed in cooked meat multiresponse kinetic modeling based on a simplified mechanistic pathway gave a good fit with the experimental data but only when additional steps were introduced to take into account the interactions of glucose and glucosederived intermediates with protein and other amino EDC this emphasizes the significant role of the food matrix in controlling the maillard reaction | MEDAL |
skin biopsies of uremic patients patients on continuous ambulatory PD capd on hemodialysis hd patients with endstage renal disease esrd before initiation of dialysis treatmentand healthy volunteers were investigated to determine the number of langerhans cells lc by LM after IF for s protein the epidermal lc count was significantly lower in patients on capd mean lcmm p and patients on hd mean lcmm p compared to controls mean lcmm and uremic patients before initiation of dialysis treatment mean lcmm the difference between lc counts of capd and hd patients did not reach statistical significance p there was no relation between lc count and age p or epidermal width p no statistically significant rho could be demonstrated between duration of dialysis and lc count r p lc counts of capd patients with diabetes mellitus n were not significantly different from those of nondiabetics n p lc counts seem to be normal in uremic patients before dialysis treatment the reduction in lc density in the skin of dialysis patients may contribute to immunodeficiency of uremic patients on regular dialysis treatment | MEDAL |
familial adenomatous polyposis fap is the second most common inherited predisposition to colorectal cancer crc associated with the development of hundreds to thousands of adenomas in the colon and rectum mutations in apc are found in polyposis patients with fap in the remaining no genetic diagnosis can be provided suggesting other genes or mechanisms that render apc inactive may be responsible copy number variants cnvs remain to be investigated in fap and may account for disease in a proportion of polyposis patients a cohort of polyposis patients and controls were screened for cnvs using the m microarray affymetrix with data analysed using chas affymetrix a total of cnvs were identified unique to the polyposis cohort suggesting their involvement in crc risk we specifically identified cnvs in four unrelated polyposis patients among crc susceptibility genes apc dcc mlh and ctnnb which are likely to have contributed to disease development in these patients a recurrent deletion was observed at position p in of the patients screened that was of particular interest further investigation is necessary to fully understand the role of these SCV in crc risk given the high prevalence among the patients screened | MEDAL |
following either standardized stapled resection of an ileal blind loop terminus beagles or construction of a colorectal anastomosis beagles half the subjects immediately were fed an ED vivonex hn gastrointestinal gi motility and absorption were maintained by exclusion of swallowed air controls received the same rate of FF solution containing only the electrolyte components four days postoperatively the fed beagles colorectal anastomosis had over double the bursting pressure of the control mm hg p less than at this time the mature collagen content of the fed subjects ileal wound was undiminished from that of normal ileum versus contrasting with the decrease of this structural component ohp in the wounds of the unfed controls microgramg of tissue p less than similarly the wounds of fed but not unfed subjects had a doubling p less than in concentration of collagen precursors and new collagen the catabolic and lag phases as noted in unfed exp animals appeared to be reflections of the relative starvation that accompanied the intestinal wounding with maintenance of gi function and immediate full enteral nutrition accelerated healing was noted relative to the previously considered norm | MEDAL |
the efficiency of using the natural antioxidant mexidol in a combined therapy of parkinsons disease has been evaluated in a group of patients including females and males the drug was po in the form of infusions ml of a solution per ml of physiological solution over a period of days the clinical dynamics was evaluated in terms of the universal parkinsonism disease rate scale updrs and using the data of electromyography and electroneuromyography the day treatmeteolytic cleavages of the app protein that together lead to the generation of the alzheimers diseaseassociated abeta peptide it is widely believed that halting the production of abeta peptide by inhibition of bace is an attractive therapeutic modality for the treatment of alzheimers disease bace is an aspartyl protease and there is significant effort in the pharmaceutical community to apply traditional design methods to the OD of active sitedirected inhibitors of this enzyme we report here the discovery of a ligand binding pocket within the catalytic domain of bace that is distinct from the enzymatic active site ie an exosite peptides initially identified from combinatorial phage peptide libraries contain the sequence ypyfilpli and bind specifically to this exosite even in the presence of saturating concentrations of active sitedirected inhibitors IB of peptides to the bace exosite leads to a concentrationdependent inhibition of proteolysis for apprelated proteinbased substrates of bace the discovery of this exosite opens new opportunities for the ID and OD of novel and potentially selective small molecule inhibitors of bace that act through exosite rather than active site binding interactions | MEDAL |
placentae from normal term pregnancies from normal preterm pregnancies and from pregnancies complicated by preeclampsia have been analysed by computerized histometry an immunoperoxidase technique was used to stain specifically human PL in the ST the percentage and mass of syncytiotrophoblast were measured using an image analysing computer the percentage of syncytiotrophoblast was found to be remarkably constant throughout gestation strong evidence was found that a linear relationship exists between syncytiotrophoblast mass and gestation period and that on average preeclampsia placentae have a lower percentage and a reduced mass of ST | MEDAL |
management of chronic pain is not a simple task pain is a complex multifaceted perceptual experience for ERP management the physician needs the patients cooperation and personal commitment many chronic pain patients become preoccupied with their pain and gradually lose interest in social activities or they may use their pain to avoid anxietyproducing situations CP therapy instituted by the primary care physician demands a coordinated approach using pharmacologic and nonpharmacologic treatment methods when necessary appropriate treatment by subspecialty physicians and by psychologists and other paramedical personnel should be coordinated | MEDAL |
the diagnosis of occupational asthma oa can be challenging and needs a stepwise approach however the predictive value of the methacholine challenge has never been addressed specifically in this context | MEDAL |
ivermectin is a macrocyclic lactone fermentation product and actinomycete streptomyces avermitilis that possesses an unusually broad spectrum of potent activity against several species of nematodes arachnids and insects that parasitize domestic animals from clinical trials in humans it has been found to be microfilaricidal killing microfilariae of onchocerca volvulus the parasite causing onchocerciasis and interrupting its transmission by the black fly vector dermal microfilariae density in patients are reduced to near zero levels for months T3 a single oral dose of ivermectin mgkg its precise mechanism of action is unknown it has a time to maximum concentration of h and an elimination halflife of h when compared with an oral solution the tablet dosage form has a RBV of approximately percent not much is known about its metabolism in humans and the unchanged drug is ND in the urine controlled PCTs have shown ivermectin to be associated with milder side effects than diethylcarbamazine the current drug of choice for onchocerciasis therapy it does not cause the severe mazzotitype anaphylactoid reactions that are associated with diethylcarbamazine use ivermectin is ERP safer and more tolerable than diethylcarbamazine it should therefore replace diethylcarbamazine as the drug of choice for onchocerciasis therapy | MEDAL |
in a nonselected population comprising women an evaluation was performed of the ultrasonic measurement of the biparietal diameter compared with a reliable last menstrual period as the basis for estimation of the day of delivery in women with a reliable menstrual PH and spontaneous ON of labor the ultrasound estimate was the significantly better predictor of the day of delivery in of cases and the LMP estimate was the better predictor in of cases the percentages of women who delivered within days of the predicted day were and for the ultrasound and the last menstrual period estimations respectively there was a significantly narrower CSD of births according to the ultrasound estimate p the proportion of estimated postterm births was using the ultrasound method and using the last menstrual period method p even when the difference between the methods in predicting the day of delivery was less than days the ultrasound method was better than the last menstrual period method it is concluded that ultrasonic measurement of the biparietal diameter between and weeks of pregnancy is the best method for the estimation of the day of delivery and should be used as a routine procedure | MEDAL |
a preliminary T0 of a modified microconcentric NEB cei cetac as the sample introduction device of capillary PACE inductively coupled plasma mass spectrometry ceicpms for the determination of monophosphate nucleotides is described the monophosphate nucleotides studied include adenosine monophosphate amp guanosine monophosphate gmp UR monophosphate ump and inosine monophosphate imp the species studied were well separated using a cm length x microm id fused silica capillary while the applied Vc was set at kv and a mmol l ammonium citratecitric acid buffer ph containing mv cationic CP hexadimethrine bromide PB was used as the electrophoretic buffer the electroosmotic flow was reversed by flushing the fused Si capillary with mv polybrene to accelerate separation the detection limit of various species studied was in the range of microg p ml which corresponded to the absolute PCD limit of pg p based on the i.t. volume of nl we determined the concentrations of nucleotides in twoy inexpensive and a rapid method of pathologic DUE of primary or M1 hepatic masses the specificity and the positive predictive value of fnac is very high however the sensitivity of the procedure widely ranges between to the two L1 areas of diagnostic difficulties are differentiation of benign and nonneoplastic hepatic nodules from well differentiated hcc and ID of obviously malignant cells as hcc cholangiocarcinoma or metastasis preparation of cell blocks immunohistochemical stains and application of other ancillary techniques are often helpful in difficult cases in presence of characteristic features a diagnosis of hcc can be established on fnac however a negative result does not exclude malignancy the role of pathologic diagnosis in the assessment of C1 hepatic masses is well established however its role in the evaluation of small hepatic nodules cm detected during surveillance of high risk patients is still evolving considering the overall advantages and costanalysis fnac can be suggested as the initial method of choice for evaluation of hepatic masses in most clinical settings however the final choice of the diagnostic procedure should be decided on the basis of working clinical diagnosis and the institutional experience | MEDAL |
noninvasive studies are useful but limited in detecting rejection among cardiac allograft recipients because an elevated MG level is a CS indicator of CN in acute myocardial infarction we postulated that myoglobin levels might correlate with the presence absence or degree of AAR therefore we prospectively measured MG levels at the time of endomyocardial biopsy in heart Tx and correlated these C2 with biopsy scores grade through grade there was no significant difference in mean myoglobin levels among patients with grade biopsy scores and those with grade through grade scores serial myoglobin C2 and endomyocardial biopsy specimens were obtained in five patients during a to week period no significant directional NC in myoglobin levels appeared to correlate with changes in endomyocardial biopsy score in addition a normal myoglobin level did not exclude nor did an elevated level confirm any grade of AAR we conclude that neither the absolute level nor a directional NC in serum myoglobin is useful in identifying AAR among heart Tx | MEDAL |
conventional control methods based on testandslaughter policies have in several countries led to the successful eradication of BTB in cattle however new approaches for control of bovine tuberculosis are required in developing countries and those with a wildlife reservoir of infection recent developments include improved diagnostics and evaluation of new vaccination strategies | MEDAL |
the ear is one of the most complex organs in the human body sound is a CS of pressure waves which propagates through a compressible media such as air the pinna concentrates the sound waves into the EAM in this canal the sound is conducted to the tympanic membrane the Tty membrane transforms the pressure variations into mechanical displacements which are then transmitted to the ossicles the vibration of the stapes footplate creates pressure waves in the fluid inside the cochlea these pressure waves stimulate the hair cells generating electrical signals which are sent to the BB through the CN where they are decoded in this work a threedimensional FEM MM of the human ear is developed the model incorporates the Tty membrane ossicular bones part of temporal bone external AEP meatus and tympanic cavity ME ligaments and tendons cochlear fluid skin ear cartilage jaw and the air in EAM and Tty cavity using the FEM the magnitude and the phase angle of the umbo and stapes footplate MSD are calculated two slightly different models are used one MM takes into consideration the presence of air in the external auditory meatus while the other does not the ME sound transfer function is determined for a stimulus of db spl applied to the outer surface of the air in the external AEP meatus the obtained results are compared with previously published data in the literature this study highlights the importance of EAM in the sound transmission the pressure gain is calculated for the EAM | MEDAL |
ovarian follicular dynamics were monitored in surgically modified red deer hinds ovaries adhered to vaginal wall by transvaginal realtime ultrasonography during the luteal cycle anoestrus and induction of superovulation all hinds showed evidence of regular luteal plasma progesterone cyclicity during the breeding season although luteal tissue was not observed on the ultrasonograms during the normal luteal cycle days total numbers of follicles mm did not vary significantly by day range of means p a single C1 or mm follicle was usually present on all days except immediately after ovulation day however the appearance of new follicles or mm was not random and was greatest on day and day p tracking of individual follicles revealed irregular waves of emergence and disappearance of the largest follicle with either one n two n or three n waves observed across nine luteal cycles new follicles or mm emerged after regression or ovulation of a C1 follicle suggesting a dominance effect there were no significant differences in the overall mean numbers of follicles during early mid and late anoestrus september november and april respectively but F2 turnover was more rapid during midanoestrus as evidenced by a significantly greater number of new small mm follicles p administration of superovulatory doses of ovine fsh during the breeding season resulted in a marked increase in the appearance of new follicles within h of initiation of the injection regimen by termination at h the time of progesterone withdrawal the mean number of follicles mm was significantly higher than for control hinds versus p while most follicles ovulated progressively days later about persisted beyond this period the study demonstrated the presence of discrete patterns of antral follicle growth and regression during the breeding and nonbreeding seasons with the luteal cycle characterized by a variable number of DF waves anoestrus represents a period of dynamic changes in follicular turnover | MEDAL |
neoadjuvant chemotherapy of epirubicin plus paclitaxel was po to patients including a cycle group of patients and a cycle group of patients with LABC cases of stage iib of stage iiia of stage iiib to compare efficacy and toxicity of cycle and cycle regimens all patients were female they were treated with epirubicin mgm on day by iv followed by paclitaxel mgm by hour continuous infusion on day repeated every weeks premedication with dexamethasone ondansetron diphenhydramine and cimetidine were po to prevent gastroenteritic and allergic reactions before chemotherapy thirtynine patients were given cycles and thirtysix were given cycles of this regimen one of patients had CR response had partial response and had no NC in the cycle group in addition of patients had complete response including who had pathologic complete response had partial response and had no NC the response rates were in the cycle group and in the cycle group there were no progressive disease in these groups however a higher proportion of pr was observed in stage ii patients than in stage iii patients twelve of patients underwent breast conserving surgery as tumor size had become smaller and downstaging was realized T3 neoadjuvant chemotherapy in addition axillary lymph nodes were palpable in all patients before neoadjuvant chemotherapy with the et regimen but in the cycle group and in the cycle group became impalpable conversely L1 toxicities including leukopenia and gastroenteric reactions were similar in both groups but myalgia arthralgia neurotoxicity and alopecia were more severe in the cycle group than in the cycle group in the present T0 neoadjuvant chemotherapy with a cycle et regimen was more ERP than with a cycle regimen in down staging locally T3 breast cancer although L1 toxicities were more severe in the cycle group than in the cycle group the regimen was tolerable and safe | MEDAL |
clinical translation of PA pa imaging can be facilitated by integration with commercial ultrasound us scanners to enable dualmodality imaging an arraybased us scanner was modified for handheld pa imaging the performance was benchmarked in terms of signaltonoise ratio snr axial spatial resolution and sensitivity pa images of a tube filled with methylene blue mb approx mm and placed at various depths in chicken tissue were acquired a cm penetration depth was achieved with an db snr using a laser fluence of mj cm only oneseventh of the safety limit mj cm an axial resolution of approximately μm was maintained at all imaging depths the pa sensitivity to mb placed cm deep in chicken tissue was less than μm further T3 intradermal i.t. of mb approx mm a rat sentinel lymph node was clearly identified in vivo beneath a cm thick SL of chicken breast the accumulated concentration of mb in the node was estimated to be approximately mm the noiseequivalent sensitivities approx cm depth were and μm ex vivo and in vivo respectively these results support the use of this pa system for noninvasive mapping and imageguided needle biopsy of sentinel nodes in breast CA patients | MEDAL |
renal scintigraphy represents the optimal modality for the detection of renal scars mtechnetiumglucoheptonate is rapidly accumulated by the kidney through glomerular filtration and active transport by renal tubular cells this permits rapid visualization of the renal parenchyma in the EP to minute images and subsequent imaging of the collecting system and ureters about to per cent of the injected activity remains in the kidney labeling the cells of the PCT tubules late phase or to hour images the late phase has been used more commonly to assess renal PC damage early and late phase glucoheptonate scanning was performed in children as part of the DUE of recurrent febrile urinary tract infections with or without a history of vesicoureteral reflux interobserver reliability to interpret glucoheptonate scans was good early per cent aobtained from aotus monkeys that had been repeatedly INF with asexual p falciparum from one of four strains the capacity of these sera to block in vitro cytoadherence of infected erythrocytes and agglutinate intact INF cells was determined the sera were also used to immunoprecipitate protein antigens from detergent extracts of isurface labeled or biosynthetically radiolabeled infected erythrocytes for each serumantigen combination precipitation of only one protein correlated with the ability of the serum to interfere with cytoadherence and agglutinate INF cells this malarial protein denoted pf emp p falciparumerythrocytemembraneprotein bore strainspecific epitopes on the cell surface and displayed size heterogeneity mr approximately pf emp was strongly labeled by cellsurface radioiodination but was a quantitatively very minor malarial protein pf emp was distinguished by its size surface accessibility and antigenic properties from a more predominant malarial protein in the same size range pf emp that is under the infected EM at knobs monoclonal antibodies and rabbit antisera raised against pf emp were used to show that this size heterogeneous antigen was indistinguishable from the previously described mesa mature parasite INF erythrocyte surface antigen identified by precipitation with rb antisera raised against the mesa hexapeptide repeats antibodies raised against pf emp mesa did not precipitate pf emp we conclude that pf emp is either directly responsible for the cytoadherence phenomenon or is very closely associated with another as yet unidentified PET molecule pf emp mesa must have a structural propertyfunction that is important under the host CM | MEDAL |
the purpose of this study was to determine the role of ventricular size or contractility in the effectiveness of dynamic cardiac compression in terms of the pressurevolume relationship and myocardial oxygen consumption in isolated crosscirculated dog NF the ventricle was directly compressed during systole for the volume run measurements for slope of the endsystolic pressurevolume relation PVA EW coronary blood flow and myocardial oxygen consumption were achieved before and during a fixed amount of dynamic cardiac compression left VVI volume was then increased while stroke volume was kept constant and measurements were repeated for the +dP/dt run T3 the control measurements were taken dP/dt was significantly increased or decreased by infusion of either dobutamine or propranolol into the coronary circulation measurements were repeated before and during dynamic cardiac compression at the control level of EDV and stroke volumes dynamic cardiac compression significantly increased Mw of the endsystolic pressurevolume relation pressurevolume area and external work p whereas coronary blood flow and myocardial oxygen consumption were not affected the increase in PVA caused by dynamic cardiac compression was greater with the larger volume despite the significant differences in the native dP/dt the increases in Mw of the endsystolic pressurevolume relation PVA and EW did not differ among the three CG we conclude that dynamic cardiac compression enhances LVSP CF independent of ventricular +dP/dt and without affecting coronary blood flow or myocardial oxygen consumption mechanical enhancement is more effective in the dilated heart | MEDAL |
during the past decade there has been a resurgence of interest in the OD of oral macrolide and fluoroquinolone antimicrobial agents azithromycin and clarithromycin are two new oral macrolides whose pharmacokinetics compared with those of erythromycin are characterized by improved oral BA increased tissue penetration and persistence and longer elimination halflives a limited number of interactions with other drugs have been reported for azithromycin and clarithromycin the most common adverse reactions to the new macrolide agents include nausea diarrhea and abdominal pain norfloxacin ciprofloxacin ofloxacin temafloxacin and lomefloxacin are the oral fluoroquinolones that have been marketed in the united states thus far in comparison to NAL the newer fluoroquinolones have improved pharmacokinetic properties including greater oral absorption increased Cmax and Az under the curve higher tissue concentrations and longer t1/2 divalent or trivalent cations can alter the absorption of all fluoroquinolones some of the fluoroquinolones norfloxacin ciprofloxacin and ofloxacin can inhibit the cytochrome p enzyme system and thereby cause increased SS concentrations of drugs like theophylline and caffeine adverse reactions to the fluoroquinolones primarily involve the gastrointestinal system skin and CNS system | MEDAL |
focus group discussions and a minisurvey in kebbi state nigeria revealed poor knowledge of obstetric complications lack of confidence in health services and cultural barriers to seeking care | MEDAL |
patients with proven SI were subjected to surgical treatment which combined both sling and stameypereyra techniques a cm long and cm wide sling of bulgarian polyamide mesh was placed under the urethrovesical junction using a small vaginal incision two long polyamide sutures were tied to either end of the mesh and were retrieved from the vagina to the abdomen by pereyra needle inserted through two small suprapubic incisions and guided by the vaginal forefinger the technique of the procedure is described a total number of patients were operated on two of them has their suspending sutures cut postoperatively because of prolonged UR the remaining were continent the technique proposed combines the advantages of the sling procedures high efficiency especially in cases of severe and recurrent incontinence and the simplicity of stameypereyra suspension technique on the other hand the bulgarian polyamide mesh showed very good qualities no infection AAR or sling erosion were observed | MEDAL |
rapid WL following RY gastric bypass rygbp for the treatment of obesity can increase the incidence of cholelithiasis formation nevertheless routine simultaneous cholecystectomy at the time of bariatric surgery remains controversial however in case of delayed occurrence of common bile duct cbd stones the difficulty to reach endoscopically the biliary tract T3 rygbp should be kept in mind we here report the case of a patient who presented with cbd stones seven years T3 gastric banding followed five T2 by rygbp without associated cholecystectomy our approach of transgastric laparoscopic assisted ERCP followed by sphincterotomy and balloon stones extraction is illustrated | MEDAL |
dopaminebetahydroxylase dbh was purified from rat AM by a series of steps including sedimentation of membranes extraction with nbutanol AS fractionation gel chromatography and IEC disk gel electrophoresis revealed two protein bands both of which were active antiserum was prepared against homogeneously purified bovine adrenal and rat adrenal dbh ouchterlony ID enzyme NT and complement fixation tests demonstrated that the respective homologous antisera were monospecific and of high titer AS to bovine dbh was only to fold more potent than preimmune serum in inhibition of rat dbh activity complement fixation tests demonstrate that AS to bovine dbh has a fold lower immunoreactivity with rat dbh than with bovine dbh | MEDAL |
a subgenomic cdna clone from human rhinovirus hrv comprising the noncoding region and the first nucleotides of the coding CS has been inserted into a vector under the control of the t promoter and rna was transcribed deletions in the noncoding CS modulated viral polyprotein synthesis significantly in a reticulocyte lysate system removal of the first nucleotides had little effect but deletion of a further nucleotides to significantly increased the efficiency of the translation process further deletion to nucleotide almost abolished translation suggesting an essential role for the to nucleotide sequence the efficiency of the translation process can also be influenced by the addition of ribosomal salt wash prepared from uninfected hela cells | MEDAL |
in a randomized crossover multiple dose study ten healthy volunteers received the recommended dosages of cotrimoxazole mg trimethoprim and mg sulfamethoxazole and cotrifamole mg TMP and mg sulfamoxole for five days each urinary C2 of trimethoprim and each sulfonamide were measured daily for five days the urinary ratios of trimethoprim and sulfonamide for both formulations were consistently lower than those considered optimal for synergy concentration of trimethoprim in the urine from both S9 was found to be greatly in excess of the mic for trimethoprimsensitive urinary pathogens approximately microgramml the sulfonamide levels achieved were not consistently in excess of their mic approximately microgramml for either preparation | MEDAL |
oxygen plays a CE role in wound healing the hypothesis of this study was that the administration of a perfluorocarbon emulsion which dissolves oxygen will increase subcutaneous tissue oxygen tension psqo in normovolemic and hemorrhaged animals in the first set of experiments psqo was measured with a polarographic oxygen electrode along the dorsum of normovolemicanesthetized rats n PLB supplemental oxygen T3 baseline equilibration of tissue oxygen tension perflubron emulsion n or saline control n was po PFB administration increased psqo by mmhg whereas saline administration had no effect mmhg in a second set of experiments psqo n was measured in rats breathing percent oxygen after being bled percent of their blood volume creating hypovolemic rats allowed for the T0 of the effect of PFB emulsion administration on subcutaneous oxygen tension in tissues with compromised blood flow PFB w/o/w was only ERP at increasing oxygen tension in tissues with oxygen extractions less then vol these findings agree with those results analytically predicted based on the oxygen solubility of the perflubron w/o/w | MEDAL |
duchenne muscular dystrophy is the most common and most severe form of childhood LGMD resulting in early loss of ambulation between the ages of and years and death in the teens and twenties despite the phenomenal advances made in the understanding of the molecular genetics of the disease no definitive cure has been found of all of the therapeutic drugs studied in DMD only prednisone seems to have the potential for providing interim PET improvement for boys with DMD muscular dystrophy while they wait for a cure with gene or cell therapy there is still no consensus regarding recommending CSs as ST for boys this is an evidencebased review of all of the studies of CSs prednisone deflazacort and oxandrolone in duchenne muscular dystrophy from this review it is clear that until a definitive treatment for DMD is available the use of deflazacort and prednisone with judicious dietary control and close clinical monitoring for side effects seems the best intervention for interim preservation of CF in such a common devastating disorder of young growing boys | MEDAL |
quantitative changes in the gastric mast cells in ulcer diathesis and especially in the OD of acute ulceration have already been studied qualitative changes may be assesed by alcian safranin blue stain which permits one to distinguish two sub groups the blue mast cells and the red mast cells which alone undergo degranulation this report describes the modifications in number and aspect of the mast cells of the stomach of the white rat T3 stress due to restraint at VL intervals after highly selective vagotomy the density of the mast cells and their appearance depend partly on vagal nerve supply T3 highly SV their density increases while the initially unbalanced proportion of red and blue mast cells becomes normal in the long term T3 AS there is a reduction in the number of mast cells and above all disappearance of the red forms whether the rats are vagotomised or not this study takes into consideration multifactorial problems which intervene in the etiology of stress ulcers and the necessity of continuing the T0 of the consequences of vagotomy | MEDAL |
as it is still unclear to what extent parental drinking is a predictor of childrens alcohol use we tested the association of specific PWS and maternal drinking patterns with both initiation and development of adolescent alcohol use longitudinal data four annual measurements of parentchild dyads n have been used parental drinking patterns have been identified using latent class analysis the association of parental drinking patterns with the initiation and development of year olds drinking have been examined with latent growth curve modeling only two out of six parental drinking patterns were related to adolescent drinking that is having a heavy drinking father or two heavy episodic drinking parents particularly predicts early and heavier adolescent drinking when controlled for parenting behaviors and background variables such as adolescent gender age and socioeconomic status ses these findings remained significant interaction analyses revealed that the influence of parental heavy episodic drinking differs across gender and is especially strong among adolescents with lower ses thus parental heavy episodic drinking and not so much the freqsis complex tsc | MEDAL |
proteolytic enzymes appear to have an essential role in multiple phases of mammalian fertilization several observations suggest that the plasminogen activatorplasmin system might also play a role in mammalian fertilization movement characteristics of bovine sperm incubated with different concentrations of plasmin were investigated using a computerassisted automated semen analysis system sperm were incubated up to h in a modified tyrodes medium control and and muml of plasmin the percentage motile sperm was significantly higher at h for sperm incubated in and mu of PL relative to sperm incubated in control medium lateral head displacement alh curvilinear velocity beat cross frequency path velocity and straight L1 velocity vsl of sperm treated with mu of plasmin for h were increased after h of incubation sperm treated with mu of PL showed an increase in alh but a decrease in vsl straightness and linearity the effect of plasmin on most motility parameters appears to be direct since all these parameters were affected at h of incubation our results support the notion of hyperactivation of bovine spermatozoa following incubation with different concentrations of PL the present work provides additional information to further characterize motility movement of bovine sperm associated with final preparation for fertilization | MEDAL |
a year old man presented with headaches computed tomography scanning revealed an enhancing subdural mass extending from the skull base to the convexity thought to represent an enplaque meningioma pathologic study revealed extraaxial subdural granulomatous inflammation consistent with neurosarcoidosis | MEDAL |
the influence of spent medium from immature mouse sertoli cells scm on testosterone production by purified leydig cells was investigated and compared to that of avp a potent local modulator of leydig cell steroidogenesis scm inhibited in a dosedependent manner the hcgstimulated testosterone production but was ineffective in basal conditions as is known for avp i a lag period of h was prerequisite for scm to inhibit leydig cell function ii the main effect of scm was located at a step beyond the receptoradenylate cyclase system since the hcg and bromocampstimulated testosterone productions were similarly affected the possibility that the effect of scm may be related to avplike molecules is also supported by the observations that at maximal concentrations the inhibitory effects of avp and scm were not additive and that the inhibition of testosterone production was largely reversed by the presence of betamercaptobeta betacyclopentamethylenepropionyl ometyrargvasopressin a selective vasopressor antagonist these data indicate that sertoli cells produce in vitro potent inhibitory AF of leydig cell steroidogenesis they provide additional evidence that one of these bioactive factors has an effect on leydig cell function similar to that of avp | MEDAL |
crossneutralisation has been demonstrated for haemorrhagic venoms including echis spp and cerastes spp and for australia elapid procoagulant toxins a previous study showed that commercial tiger snake antivenom tsav was able to neutralise the systemic effects of the egyptian cobra naja haje in vivo but it is unclear if this was true crossneutralisation the aim of the current study was to determine whether tsav can neutralise the in vitro neurotoxic effects of n haje venom both notechis scutatus μgml and n haje μgml venoms caused inhibition of indirect supramaximal v hz msec twitches of the chick biventer cervicis nervemuscle preparation with t values ie the time to produce inhibition of the original twitch height of ± min n and ± min n this effect at μgml was significantly attenuated by the prior addition of tsav uml a comparison of the reversephase hplc profiles of both venoms showed some similarities with peak elution times and sdspage analysis elucidated comparable bands across both venoms further analysis using WB indicated tsav was able to detect n haje venom and enzyme immunoassay showed that inhouse biotinylated polyclonal monovalent n scutatus antibodies were able to detect n haje venom these findings demonstrate crossneutralisation between different and geographically separated snakes supporting potential immunological similarities in snake toxin groups for a large range of snakes this provides more evidence that antivenoms could be developed against TPS toxin groups to cover a large range of snakes | MEDAL |
the group a streptococcal sequela ARF arf has been associated with immunological crossreactivity between streptococcal and heart proteins to identify streptococcus pyogenes genes that encode a myosin crossreactive antigens recognized by arf sera a genomic library from an emm deletion CS t was screened with a single arf SS a positively identified lambda embl clone t produced a protein which reacted with myosinspecific antibodies affinity purified from individual arf sera the recombinant protein was initially estimated to be kda in size by sodium dodecyl sulfatepolyacrylamide gel electrophoresis however upon CS analysis it had a molecular mass equivalent to kda sera from patients with streptococcal infections acute glomerulonephritis and arf were reactive with the recombinant kda protein however individual sera from healthy persons were negative or demonstrated low C2 of reactivity with the kda antigen the gene encoding the kda myosincrossreactive antigen was subcloned and its nucleotide CS was determined by using a combined strategy of dna sequencing of the cloned gene and nterminal amino acid sequencing of the protein expressed in escherichia coli the aminoterminal CS deduced from the nucleotide CS of an open reading frame was identical to that determined from the kda protein expressed in e coli the gene encoded amino acids with a calculated molecular weight of no cleavable signal peptide was detected with the kda protein expressed in e coli the deduced CAA CS of the kda protein did not exhibit significant similarity to any known streptococcal proteins however it was found to be MZ and similar over CAA residues to the beta chain of mouse H-2 complex class ii antigen iau similar degrees of homology to the beta chains of other murine and human class ii haplotypes were found mouse antiia sera reacted with the recombinant kda protein about five times more strongly than normal mouse sera in the enzymelinked immunosorbent assay southern hybridization experiments using a probe for the gene encoding the kda protein showed that the gene was present and conserved among pathogenic CG a c and g of streptococci these data suggest that the streptococcal protein which is distinct from the emm may have structural features in common with the beta chain of the class ii antigens as well as myosin and may play an important role in the pathogenesis of streptococcal infections | MEDAL |
PE are a diverse group of plantderived compounds that structurally or functionally mimic mammalian estrogens and show potential benefits for human health the number of articles published on phytoestrogens has risen dramatically in the past couple decades further research continues to demonstrate the biological complexity of phytoestrogens which belong to several different chemical classes and act through diverse mechanisms this paper discusses the classification of PE methods of identification their proposed mechanisms of action and botanical sources for PE the effects of phytoestrogens on breast and prostate cancers cardiovascular disease menopausal symptoms and osteoporosis will also be examined including research on benefits and risks | MEDAL |
the present T0 extended previous work by examining whether disturbances in the circadian rhythms of prolactin prl and thyroidstimulating hormone tsh distinguish patients with premenstrual dysphoric disorder pmdd from normal volunteers in addition the effects of therapeutic interventions with early and late partial sleep deprivation were explored both prl and tsh levels were measured every min from h to h during midfollicular and late luteal menstrual cycle phases in pmdd patients and NV hormone levels were measured again T3 a randomized crossover trial of early sleep h versus late sleep h partial sleep deprivation po in two separate luteal phases compared with NV pmdd patients had higher prl concentrations consistent with previous findings tsh rhythms occurred earlier in pmdd than in normal subjects prl C2 decreased and tsh levels increased with sleep deprivation compared with baseline conditions the timing of prl secretion shifted earlier with late sleep ED and later with early sleep deprivation although circadian disturbances of prl and tsh were found in pmdd patients compared with normal volunteers the therapeutic effects of early and late sleep ED do not appear to be mediated by correcting these disturbances | MEDAL |
locally advanced prostate tumours ie those that extend beyond the prostate gland but are not M1 often carry a poor prognosis between and of patients die within years after diagnosis various treatments are proposed to improve their prognosis which treatments have a proven survival benefit and what are their adverse effects to answer these questions we reviewed the literature using the standard prescrire methodology prostatectomy has not been evaluated in controlled trials versus either watchful waiting or radiation therapy CT prostatectomy is mainly proposed to patients who are in good general health five years after prostatectomy mortality from prostate CA is between and depending on the studythreequarters of patients who have surgery at this stage experience erectile dysfunction and at least of patients develop urinary incontinence EBRT CT has not been compared with WW or prostatectomy external beam radiation therapy has documented benefits in patients with T4 prostate CA treated with gonadorelin agonists preventing to deaths from all causes T3 to years of followup among treated patients however about of patients experience erectile dysfunction about symptomatic radiation proctitis and about urinary incontinence when combined with prostatectomy radiation therapy did not affect the year survival rate but prolonged survival by about years in a trial with more than years of followup when used without concomitant androgen suppression antiandrogens have no proven impact on overall survival in patients with locally advanced prostate CA in the absence of radical prostatectomy or radiation therapy androgen suppression by means of orchiectomy or gonadorelin agonist has a minimal impact on overall survival among patients with T4 CA in one randomised trial AS in combination with prostatectomy prolonged median survival by about years among patients with lymph node involvement in another randomised trial treatment with a gonadorelin agonist and flutamide for months started before radiation therapy reduced the year overall MR to versus after radiation therapy alone androgen suppression for at least years T3 radiation therapy prevented to deaths from all causes per patients during to years of followup in three randomised trials that provided similar results shorter durations of treatment appeared to be less effective in other RCT the adverse effects of gonadorelin agonists often undermine patients quality of life due to hot flushes loss of libido erectile dysfunction gynaecomastia OP weight gain cardiovascular events and diabetes in mid european clinical practice guidelines recommend a combination of radiation therapy and AS for to years for most patients with T4 prostate cancer before choosing between therapeutic options it is crucial to take into account the patients priorities in terms of treatment tau and adverse effects and reversibility of adverse effects | MEDAL |
labile blood products labile blood products are therapeutic products produced from blood which do not have the characteristics of drugs this category of products include PRC platelets as well as white cell concentrates and frozen fresh plasma packed red cells and platelet concentrates these products used to be prepared from total blood specific components can be selected using a cell separator apheresis this process has made available PLT apheresis products white RCCs and fresh plasma for therapeutic indications the major impact of apheresis on blood donation has been to reduce the number of donors required for PLT transfusion plasma in france plasma is produced from total blood by fractionation in order to assure the production of bloodderived drugs albumin coagulation factors immunoglobulins biological glue viral inactivation concerns only detergent solvant viroinactivated plasma no therapeutic process has been fully validated for other labile blood products transformation and characteristics labile blood products may undergo several types of transformation deplasmatization plasma volume reduction cyropreservation irradiation since april all labile cellular blood products produced in france must be leukocytedepleted additional donorrelated characterization phenotype cmv negative may also be determined | MEDAL |
a new NH and a new monoterpene were isolated from the seeds of clausena lansium together with four known ones the structures of the new EDC were elucidated by extensive spectroscopic analyses the absolute configurations of and were determined by optical rotation and the modified moshers method | MEDAL |
familial ALS is a degenerative motor neuron disease associated in some cases with the presence of a mutant form of cuzn superoxide dismutase we have studied the stability of the glyglu mutant in extracts of red cells obtained from members of a family with a PH of the disease extracts containing the mutant had an average of normal superoxide dismutase activity on heating at degrees c these extracts lost activity at twice the rate of extracts containing only the normal enzyme decreased heat stability was also evident on native PAGE with activity staining this showed selective loss of first the mutant homodimer and then the heterodimer of the enzyme decreased stability intracellularly could be a factor in motor neuron degeneration | MEDAL |
novel influenza a hn virus which emerged in and highly pathogenic hn virus identified since pose challenges to public health and necessitate quest for new antiinfluenza compounds anthraquinone derivatives like aloeemodin emodin and chrysophanol reportedly exhibit antiviral activity this study probes their GABA mechanism and effect against influenza a virus of three AQ derivatives aloeemodin with a lower cytotoxicity showed concentrationdependently reducing virusinduced cp effect and inhibiting replication of influenza a in mdck cells GABA concentration value of aloeemodin on virus yield was less than μgml proteomics and western blot of mdck cells indicated aloeemodin upregulating galectin and thioredoxin as well as downregulating nucleoside diphosphate kinase a western blot and quantitative pcr confirmed aloeemodin upregulating galectin expression recombinant galectin augmented expression of antiviral genes ifnβ ifnγ pkr and oas in infected cells agreeing with expression DP of those treated with aloeemodin galectin also inhibited influenza a virus replication proteomic analysis of treated cells indicated galectin upregulation as one antiinfluenza a virus action by aloeemodin since galectin exhibited cytokinelike regulatory actions via jakstat pathways aloeemodin also restored nsinhibited statmediated antiviral responses in transfected cells eg stat phosphorylation of interferon ifn stimulation response element isredriven promoter rnadependent protein kinase pkr and oligoadenylate synthetase oas expression treatment with aloeemodin could control influenza infection in humans | MEDAL |
there are three directions in pathogenetic treatment of chronic prostatitis cp which is conducted in parallel to etiotropic one antimicrobial GA immunological improving arterial inflow and VO creation of prostatic secretion outflow and that of seminal vesicles by means of contractions of the pelvic and perineal muscles muscular fibers of the prostatic gland the latter two directions can be managed with physiotherapy it is proposed to use combination of drugs with physiotherapy conducted by means of the devices see text | MEDAL |
the aim of our study was to evaluate whether captopril po at night can shift the circadian blood pressure bp from a nondipper to a dipper pattern in adequately controlled HT who continued their antihypertensive therapy in a prospective randomized double blind placebocontrolled designed T0 we enrolled treated adequately controlled nondipping hypertensive patients all patients were randomly assigned to mg captopril or PL treatment po at night in case of nondippers the dosage of captopril or PL was doubled T3 two weeks of treatment while for dippers antihypertensive regimens were not changed T3 another two weeks all patients underwent ABP monitoring our results show that at the end of the active treatment period the prevalence of a dipping diurnal bp pattern in the captopril group was significantly higher than that in the PG p nighttime bp nightday bp ratio nighttime bp load and h systolic bp were significantly lower T3 weeks nighttime captopril treatment compared to baseline in conclusion the present T0 demonstrates for the first time that captopril administered at night can restore the diurnal bp rhythm and decrease the elevated nightday bp ratio in appropriately controlled nondipper hypertensive patients these results were mainly due to the decrease of nighttime bp | MEDAL |
mandatory prescreening for the identification of risk AF and prevention of sudden CD scd is a widely debated topic within academic literature in addition the effective emergency management of sudden cardiac arrest sca has reported lower survival outcomes with bystander cpr with aed application although improvements such as strategic placements of aed units and handsonly compression only cpr are being made | MEDAL |
recent studies have shown that increased epidermal hydroxymethylglutaryl coenzyme a hmg coa reductase activity is crucial for the barrier recovery response that follows solventinduced barrier perturbation upregulation of this enzyme leads to increased cholesterologenesis formation and secretion of cholesterolenriched lamellar HB and barrier repair topical lovastatininduced inhibition of hmg coa reductase activity both delays the acute barrierrepair response as well as leading to a chronic barrier abnormality when applied repeatedly to IN skin presently we assessed the effects of repeated topical applications of two different TPS inhibitors of hmg coa reductase on barrier CF the lamellar bodysecretory system and SC intercellular domains with functional and morphologic parameters oncedaily applications of lovastatin or fluindostatin xu sandoz for d to IN hairless mouse epidermis produced a progressive abnormality in barrier CF transepidermal water loss greater than in treated versus less than mgcmh for weakly AS analogues or VH controls the barrier defect was preceded by alterations in lamellar body internal structure and a partial failure of lamellar body secretion into the SC interstices further confirmed by enzyme cytochemistry moreover the deposition of abnormal lamellar body contents resulted in the formation of clefts in the intercellular spaces at the stratum granulosumstratum corneum interface resulting in increased permeability through these domains shown by lanthanum perfusion applications of irritants even when producing a barrier abnormality did not alter the lamellar body sec system coapplications of cholesterol with the inhibitors reversed both the barrier abnormality and the CA in the lamellar body sec system that occur with the inhibitor alone finally membrane bilayer structures in the midtoouter stratum corneum of inhibitortreated specimens appeared normal but the intercellular domains displayed enormously expanded lacunae however because similar dilatations also occurred in vehicletreated samples they can be attributed to the VH alone these studies provide further evidence that the inhibitorinduced defect in barrier function a is initiated by inhibition of hmg coa reductase b can be attributed to defects in both lamellar body structure and deposition with resultant CA in intercellular membrane domains in the lower SC and c is further enhanced by permissive effects of the VH on the permeability of the outer stratum corneum | MEDAL |
the diagnosis of hypertension in children relies upon blood pressure distribution tables adjusted for gender age and height unlike in adults TPS blood pressure C2 corresponding to longterm adverse outcomes in children have not been established however there are known surrogate markers of target organ injury associated with elevated blood pressure such as left ventricular hypertrophy retinal changes thickening of the carotid artery wall cognitive changes and even evidence of early atherosclerosis moreover there is corroboration that hypertension in children predicts AD hypertensionin view of the global childhood obesity epidemic in conjunction with the wellestablished association of obesity and hypertension evaluation of blood pressure in the pediatric population has become an important health concern with this insight efforts continue worldwide to accurately measure determine prevalence and monitor recent trends of hypertension in children and adolescents | MEDAL |
the deposition of Nb metals on soft andor flexible substrates is vital for several emerging applications including flexible electronics and the fabrication of soft bionic implants in this paper we describe a new strategy for the deposition of platinum electrodes on a range of materials including insulators and flexible polymers the strategy is enabled by two principle advances the introduction of a novel low temperature strategy for reducing chloroplatinic acid to Pt using nitrogen plasma the development of a chloroplatinic acid based liquid ink formulation utilizing DDE glycol as both ink carrier and reducing agent for versatile printing at nanoscale resolution using DPN dpn the ink formulation has been printed and reduced upon si glass ito ge pdms and parylene c the plasma treatment effects reduction of the F0 patterns in situ without subjecting the substrate to destructively high temperatures feature size is controlled via dwell time and degree of ink loading and Pt features with nm dimensions could be routinely achieved on si reduction of the ink to platinum was confirmed by energy dispersive xray spectroscopy eds elemental analysis and xray diffraction xrd measurements feature morphology was characterized by optical microscopy sem and afm the high electrochemical activity of individually printed pt features was characterized using scanning EC microscopy secm | MEDAL |
hyaluronic acid production by group a streptococci is regulated by transcriptional control in this study transposon mutagenesis of an unencapsulated CS yielded an encapsulated mutant two genes homologous to sensors and response regulators of bacterial twocomponent systems were identified downstream of the transposon IS inactivation of the putative sensor gene csrs in three different unencapsulated strains yielded encapsulated mutant strains electrophoretic mobility shift assays determined AF in a cytoplasmic extract of an unencapsulated GAS CS was IB to a dsDNA dna fragment derived from the has operon promoter in contrast similarly prepared cytoplasmic extracts from a csrs deletion mutant did not shift the fragment the putative response regulator csrr was partially purified and was shown to bind the has Pu fragment the affinity and specificity of csrr for the fragment were increased significantly T3 incubation with acetyl phosphate dnase i footprinting determined that the acetyl phosphatetreated csrr was IB to key sequences in the promoter and the coding region of hasa therefore a twocomponent system is repressing the production of hyaluronic acid in group a streptococci using a phosphorylationdependent binding interaction between the response regulator csrr and the promoter region of the has operon | MEDAL |
the role of macrophages in the regulation of inflammation and immunity is in part due to their secretory repertoire among the important mediators released by macrophages are the products of both the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism the principal focus of this paper is the mechanism by which bacterial lipopolysaccharides lps regulate metabolism in macrophages lps has the capacity to prime macrophages for greatly enhanced metabolism when the cells are subsequently challenged with a spectrum of triggers concomitant with priming lps also promotes the covalent attachment of myristic acid to a set of macrophage proteins the time and concentration dependence of lpsinduced protein myristoylation is consistent with a role for myristoylation in lps priming of the cascade one of the myristoylated proteins is a k k mr protein kinase c substrate which associates with membranes upon myristoylation lpsprimed macrophages show greatly increased phosphorylation of the k protein when the cells are subsequently treated with protein kinase c activating phorbol esters it is proposed that the myristoylation of the k protein promotes its att to the membrane where it is more closely associated with G1 protein kinase c pkc an association which would ensure more efficient catalysis during the mobilization and oxygenation of this paper also examines protein myristoylation during tcellmediated activation of macrophages immuneactivated macrophages have an enhanced capacity to kill several infectious agents by oxidative mechanisms the lymphokine gammainterferon ifn gamma rapidly induces the myristoylation of a k protein this k protein is also myristoylated in murine macrophages that have been G1 in vivo by intraperitoneal injection of corynebacterium parvum suggesting that it may be an important intermediate in the activation of macrophages for enhanced microbicidal capacity | MEDAL |
we substantiate by numerical and analytical calculations that the recently discovered superconductivity below k in borondoped diamond is caused by electronphonon coupling of the same type as in mgb albeit in three dimensions holes at the top of the zonecentered degenerate sigmabonding valenceband couple strongly to the optical bondstretching modes the increase from two to 3D reduces the mode softening crucial for tc reaching k in mgb even if diamond had the same bare coupling constant as mgb which could be achieved with doping tc would be only k superconductivity above k in si ge requires hole doping beyond | MEDAL |
RLS periodic limb movements in sleep and periodic limb movement disorder are a group of conditions that merit awareness from the medical community these disorders are commonly encountered yet are often confused and misdiagnosed by HCPs it is imperative that health care providers are able to recognize these conditions to accurately diagnose manage and appropriately refer patients | MEDAL |
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