text
stringlengths 10
10.1k
| source
stringclasses 1
value |
|---|---|
the oxidation of lowdensity lipoprotein ldl is central to current theories on the initiation and progression of atherosclerosis type diabetes is associated with an increase in oxidative stress which may be responsible for the increased susceptibility to coronary heart disease seen in type diabetes highdensity lipoprotein hdl associated paraoxonase pon can retard the oxidation of ldl | MEDAL |
the DR relationship of oral famotidine at doses up to mg was evaluated in healthy male subjects to assess the extent and duration of inhibition of mealstimulated intragastric acid secretion each subject received single oral administrations of famotidine and mg and placebo in a doubleblind randomized crossover fashion i.g. ph was measured every seconds for hours and expressed as the mean ph for each minute interval standard highprotein meals were provided hour before each dose of T0 drug and at and hours postdose the mean intragastric ph was significantly higher T3 famotidine doses and mg than T3 PL at times to to and to hours postdose respectively there were no significant differences in mean ph seen between famotidine mg versus PL the range of the ph means between and hours postdose was PL to famotidine mg to mg to mg to and mg to there was a statistically significant linear doseresponse relationship between FAM dose and intragastric ph between and hours and from to hours T3 ingestion | MEDAL |
an impairment of muscle glutamine metabolism in response to dexamethasone dex occurs with aging to better characterize this alteration we have investigated muscle glutamine PR with regard to muscle glutamine production net PB de novo glutamine synthesis in AD and old glucocorticoidtreated rats male SDRs or mo old were divided into seven groups three CG received mgkg of dex QD by intraperitoneal i.t. for or days three groups were pair fed to the three treated CG respectively and one control group of healthy rats was fed ad libitum muscle glutamine synthetase activity increased earlier in old rats day than in AD rats day whereas an increase in muscle glutamine release occurred later in old rats day than in adult dextreated rats day consequently muscle glutamine concentration decreased later in old rats day than in adults day finally net muscle protein breakdown increased only in old dextreated rats day in conclusion the impairment of muscle glutamine metabolism is due to a combination of an increase in glutamine production and a delayed increase in glutamine release | MEDAL |
insulindependent diabetes mellitus is a multigenic autoimmune disease for which one of the best animal models is the NOD nod mouse strain in both humans and nod mice major histocompatibility complex genes are implicated as risk factors in the disease process other susceptibility genes are also involved and a number have been mapped in the mouse to specific chromosomal locations to identify further susceptibility genes diabetic backcross mice produced after crossing nodlt to the nondiabetic strains sjl and B6 b were examined for markers not previously associated with disease susceptibility linkage was found to loci on chromosomes and of the candidate loci on chromosome the gene encoding the nah exchanger nhe was the most likely since the nod allele was different from that of both nondiabetic strains nod lymphocytes were found to have a higher level of nah exchange activity than lymphocytes from either b or sjl mice since the chromosome susceptibility gene is recessive the b S2 should prevent diabetes this prediction was tested in fourthgeneration backcross mice selected for retention of the b S2 at nhe mice homozygous for nhe developed diabetes T3 cyclophosphamide treatment but heterozygotes were largely protected from disease these results implicate the nah exchanger antiporter in the development of type diabetes and may provide a screening test for atrisk individuals as well as offering prospects for disease prevention | MEDAL |
glucosylceramide synthase gcs is an important target for clinical drug development for the treatment of lysosomal storage disorders and a promising target for combating type diabetes iminosugars are useful leads for the OD of gcs inhibitors however the ERP iminosugar type gcs inhibitors reported have some unwanted crossreactivity toward other glycoprocessing enzymes in particular iminosugar type gcs inhibitors often also inhibit to some extent human acid glucosylceramidase gba and the nonlysosomal glucosylceramidase gba the two enzymes known to process glucosylceramide of these gba itself is a potential drug target for the treatment of the lysosomal storage disorder gaucher disease and selective gba inhibitors are sought T3 as potential chemical chaperones the physiological importance of gba in glucosylceramide processing in relation to disease states is less clear and here selective inhibitors can be of use as chemical knockout entities in this communication we report our identification of a highly potent and selective nalkylated lidoconfigured iminosugar in particular the selectivity of for gcs over gba is striking | MEDAL |
the term lateonset schizophrenia was first coined by manfred bleuler to describe a form of schizophrenia with an ON between the ages of and this concept has been adopted by german psychiatry until recently british and american psychiatrists had little interest in this patient group however they often used the term lateonset schizophrenia interchangeably with late paraphrenia or as a generic term for both these diseases even though the concept of late paraphrenia is quite different from that of LOS late paraphrenia is a british concept that includes all delusional disorders starting T3 age this confusion of terms and concepts is even more important now because recent neuroimaging and neuropsychological studies suggest that an organic ATP probably exists in most cases of late paraphrenia while only minor organic abnormalities can be found in lateonset schizophrenia we believe it is of utmost importance to establish a clear boundary between lateonset schizophrenia and other delusional disorders in middle and old age because the confusion in terminology and concepts is a serious impediment to comparative international research | MEDAL |
the C2 of CMZ in plasma and tissue were determined T3 i.t. of a dose of mgkg into the zone of the wound of each of patients undergoing appendectomy the mean plasma levels of cefmetazole at the start and end of surgery and min T3 dosage were and microgramsml respectively concentrations of the drug were and microgramsg in skin and microgramsg in subcutaneous tissue and and microgramsg in muscle | MEDAL |
familial partial lipodystrophy due to lmna lamin ac mutations is a rare disorder characterized by a selective loss of adipose tissue and insulin resistance dyslipidemia and severe diabetes often occur during its evolution only isolated and contradictory case reports have been published on the obstetrical prognosis in lipodystrophy the aim of our T0 was to compare the fertility and occurrence of obstetrical complications of women with familial partial lipodystrophy due to lmna lamin ac mutations with those of nonaffected relatives women from the GA population and women with polycystic ovary syndrome pcos | MEDAL |
loss of CF mutations in pink typically lead to early ON parkinson disease pd zebrafish danio rerio are emerging as a powerful new vertebrate MM to study neurodegenerative diseases we used a pink mutant pink zebrafish L1 with a premature stop mutation y in the pink kinase domain to identify molecular mechanisms leading to mitochondrial dysfunction and loss of dopaminergic SN in pink deficiency | MEDAL |
fuscopeptins are phytotoxic amphiphilic lipodepsipeptides containing CAA residues they are produced by the plant pathogenic bacterium pseudomonas fuscovaginae in two forms a and b which differ only in the number of methylene groups in the fatty acid chain their covalent structure and biological properties have been reported previously cd and nmr spectroscopy investigations in solution revealed the absence of identifiable elements of secondary and tertiary structure for these molecules fuscopeptin b appears to be completely unstructured in aqueous solution and has a large molecular flexibility a dramatic conformational NC was observed upon addition of trifluoroethanol this study reports the CR interpretation of the twodimensional nmr spectra and the noe results obtained for fuscopeptin b in watertrifluoroethanol solutions the signals relative to the peptidic moiety are MZ to those observed for fuscopeptin a the results of this investigation were used to determine the solution structure of fuscopeptin b by computer simulations applying distance geometry and SA procedures in watertrifluoroethanol solutions the peptidic region appears to have a partly helical structure the lactonic ring assumes defined conformations very similar to those already reported for other lipodepsipeptides the structure for fuscopeptin b in solution is also valid for fuscopeptin a because of the negligible structural difference between the two metabolites | MEDAL |
cortical cerebellar BCs are SD postmitotic cells hence they are liable to endure agerelated changes since the cerebellum is a vital organ for the postural control equilibrium and motor coordination we aimed to determine the quantitative morphological changes in those interneurons with the ageing process using unbiased techniques material from the cerebellar cortex crus i and crus ii was collected from female rats aged and mo animals per each age group fixed by intracardiac perfusion and processed for transmission electron microscopy using conventional techniques serial semithin sections were obtained blocks from each rat enabling the determination of the numberweighted mean nuclear volume by the nucleator method on ultrathin sections cell profiles from each animal were photographed the volume density of the nucleus ground substance mitochondria GA golgi and dense HB db and the mean surface density of the rough endoplasmic reticulum rer were determined by point counting using a morphometric grid the mean total volumes of the soma and organelles and the mean total SA of the rer sn rer were then calculated the results were analysed with way anova posthoc pairwise comparisons of group means were performed using the newmankeuls test the relation between age and each of the parameters was studied by SRA significant agerelated changes were observed for the mean volumes of the soma ground substance golgi db and sn rer positive linear trends were found for the mean volumes of the ground substance golgi and db a negative linear trend was found for the sn rer these results indicate that rat cerebellar basket cells endure important agerelated changes the significant decrease in the sn rer may be responsible for a reduction in the rate of protein synthesis additionally it may be implicated in a cascade of events leading to cell damage due to the excitotoxic activity of glu which could interfere in the SF-36 of the complex cerebellar neuronal network | MEDAL |
phylloquinone functions as the electron transfer cofactor at the a site of PS i we have isolated and characterized a mutant of chlamydomonas reinhardtii mend that is deficient in mend which encodes succinylhydroxycyclohexadienecarboxylate synthase an enzyme that catalyzes the first specific step of the K1 biosynthetic pathway the mutant is photosynthetically active but lightsensitive analysis of total pigments by mass spectrometry reveals that K1 is absent in mend but plastoquinone levels are not affected this is further confirmed by the rescue of mend by addition of K1 to the growth medium analysis of electron transfer by absorption spectroscopy indicates that plastoquinone replaces phylloquinone in PS i and that electron transfer from a to the ironsulfur centers is slowed down at least fold consistent with a replacement of phylloquinone by PQ the size of the free plastoquinone pool of mend is reduced by in contrast to cyanobacterial menddeficient mutants photosystem i accumulates normally in mend whereas the level of PS ii declines this decrease is because of reduced synthesis of the photosystem ii core subunits the relationship between plastoquinone occupancy of the a site in PS i and the reduced accumulation of PS ii is discussed | MEDAL |
sixty indepth interviews with mothers living in a urban slum of morocco probed resistances to practicing modern methods of fertility control and began to shed light on some of the reasons FP programs often fail to reach illiterate target populations economic insecurity and the disintegration of the support networks of the traditional D2 family complicate the difficult lives of young mothers in the urban slum while such AF tend to encourage sm a drink of water to man one normocholesterolemic man dissipated a mildly nonfamilial hypercholesterolemic man dissipated and a FH man dissipated of a dose of cmevalonate in hours calculated as a per cent of the renantiomer the observations support the hypothesis of the existence of a metabolic shunt of intermediates of sterol biosynthesis derived from mevalonate not leading to sterols | MEDAL |
tau protein is a microtubuleassociated protein that is present in axons elevated tau protein C2 in CSF fluid or SS are associated with several CNS system diseases and can indicate neuronal injury | MEDAL |
critical care is an important component of inpatient and combat casualty care and it is a L1 contributor to us healthcare costs regular SE to critically ill and injured patients may directly contribute to wartime skills PR for military CGs data describing critical care services in the military health system mhs however is lacking this T0 was undertaken to describe mhs critical care services their resource utilization and differences in care practices amongst military treatment facilities mtfs | MEDAL |
we have previously shown that patch test S9 of polymeric diphenylmethane diisocyanate pmdi are more stable than S9 of diphenylmethanediisocyanate mdi this study was conducted to i investigate whether pmdis yield as many positive reactions as mdi ii T0 concurrent reactions to mdi and diaminodiphenylmethane mda and iii follow the course of positive reactions during weeks it was shown that pmdis detect as many positive reactions as mdi thus they are better patch test agents being more stable than S9 of mdi we recommend that pmdis with a monomer content of at least is used in petrolatum pet ie monomer patch test concentration approximately it was shown that reactions to mdi and pmdis appear late and we recommend readings on both day d and d mda was shown to be a good marker for mdi and patch testing with mda in pet can be used instead of pmdi concomitant reactions to mdi and mda are probably not caused by conversion of mdi into mda by reaction with water another explanation is a path of reactions leading to ureas and mdi conjugates with skin constituents which are hydrolysed into mda this complex process depends upon several factors and might explain why positive mdi reactions appear T3 d | MEDAL |
to characterize the transcriptional effects of human hfsh and hcg on the pomc gene primary rat GCs were transiently transfected with a chloramphenicol AT cat reporter plasmid under the control of the pomc promoter and region pomccat contains a fragment of the rat pomc gene extending from nucleotide to nucleotide fused to the cat gene treatment of pomccattransfected cells with either hfsh ngml or hcg ngml significantly increased cat enzyme activity however neither hcg nor hfsh increased cat CEA in cells transfected with psvcat a reporter plasmid under the control of the sv virus promoter and region the phosphodiesterase inhibitor isobutylmethylxanthine or the nonhydrolyzable camp analog campchlorothiophenyl significantly increased cat activity in pomccattransfected GCs human fsh stimulated transcription and h T3 treatment but fsh stimulation at the two earlier time points was to fold greater than that at h gonadotropinstimulated steroidogenesis was equivalent in pomccattransfected GCs untransfected and mocktransfected cells this indicates that transfection left the physiological hormone response intact these data demonstrate the following basepairs of the rat pomc gene are enough to confer gonadotropin stimulation on the cat marker gene in GCs although the pomc promotor lacks a well conserved camp response element either of two different pharmacological manipulations of GCs that raise intracellular camp can also stimulate pomcdriven cat expression transfected primary cultures of GCs provide a nontransformed physiologically relevant model with which to T0 hormoneregulated gene expressionabstract truncated at words | MEDAL |
acid ceramidase acdase metabolizes ceramide to sphingosine leading to sphingosine phosphate production reportedly acdase has been upregulated in prostate cancer however its RII mechanism remains unclear lncap androgensensitive prostate cancer cell L1 but not pc and du androgenunresponsive cell lines exhibited the highest acdase protein among three cell lines asah mrna level was not correlated with acdase protein expression and the promoter activity did not show androgen dependency suggesting the posttranscriptional regulation of acdase in lncap cells based on these results lncap was analysed further casodex androgen receptor antagonist and charcoalstripped fcs csfcs decreased acdase protein and activity whereas dihydrotestosterone in csfcs SC increased acdase protein and enzyme activity mg a proteasome inhibitor prevented the decrease of acdase protein when cultured in csfcs suggesting the involvement of ubiquitinproteasome system reportedly usp a deubiquitinase plays an important role in lncap cells usp sirna decreased acdase protein whereas usp overexpression increased acdase protein of lncap cells however skp an ubiquitin e ligase known to be active in prostate CA did not affect androgendependent acdase expression in lncap cells thus acdase regulation by androgen in LNCaP lncap cells is mainly due to its prolonged protein halflife by androgenstimulated usp expression | MEDAL |
preterm delivery represents an important cause of infant morbidity and mortality various tocolytics have been studied with the objective of stopping PT labor increasing gestational age at delivery and preventing complications related to preterm birth | MEDAL |
individuals with PET lower urinary tract disorders including IC icbladder pain syndrome bps and overactive bladder oab often report symptom eg urinary frequency worsening due to AS one member of the transient receptor potential ion channel vanilloid family trpv has recently been implicated in UB dysfunction disorders including oab and icbps these studies address the role of trpv in stressinduced bladder dysfunction using an animal MM of stress in male rats to induce stress rats were exposed to days of repeated variate AS rvs QPCR data demonstrated significant p ⤠increases in trpv transcript levels in urothelium but not detrusor smooth muscle western blot analyses of split urinary bladders ie urothelium and detrusor showed significant p ⤠increases in trpv protein expression levels in urothelial tissues but not detrusor smooth muscle we previously showed that rvs produces bladder dysfunction characterized by decreased BC and increased voiding frequency the functional role of trpv in rvsinduced bladder dysfunction was evaluated using continuous open outlet intravesical infusion of saline in conjunction with administration of a trpv agonist gska μm a trpv antagonist hc μm or VH dmso in saline in control and rvstreated rats bladder capacity void volume and intercontraction interval significantly decreased following intravesical instillation of gska in control rats and significantly p ⤠increased following administration of hc in rvstreated rats these results demonstrate increased trpv expression in the urothelium following rvs and that trpv blockade ameliorates rvsinduced bladder dysfunction consistent with the role of trpv as a promising target for bladder CF disorders | MEDAL |
ten women with normal pregnancies who underwent an elective cesarean section received orally mg of aminophylline every hours for hours prior to surgery the levels of aminophylline and caffeine were measured in maternal and cord sera and in amniotic fluids the mean level of aminophylline sd in MS was microgramsml and in cord SS microgramsml the mean aminophylline level in amniotic fluids was microgramsml the serum aminophylline levels were within the therapeutic level range caffeine C2 in those specimens ranged between traces to microgramsml which correspond to the normal dietary range | MEDAL |
experiments were conducted on albino rats of age groups and monthold a study was made of the influence of prolonged administration of hydrocortisone on the activity of glucosophosphatase fructosodiphosphatase and the synthesis of rna fractionated by the thermic PH method an increase of the enzyme activity of the SRA of the relative specific radioactivity of the rna fractions was less pronounced in old rats a comparatively early occurrence of the phenomenon of disruption of the inductive mechanisms of the hormonal stimulation was observed in the same age group | MEDAL |
transplantation of pancreatic islets has great potential for treating type i diabetes ex vivo GT may promote revascularization or inhibit apoptosis of the islets and promote VG in this T0 we investigated the feasibility of nonviral gene delivery using enhanced green FL protein egfp and human VE growth factor hvegf expression plasmids as MM reporter and therapeutic genes lipofectaminepdna and superfectpdna complexes showed high transfection efficiency in rapidly dividing jurkat cells but low transfection in nondividing human islets lipofectaminepcaggshvegf transfected islets showed relatively higher C2 of hvegf than in those transfected with lipofectaminepcmsegfp complexes or glucose to exclude endogenously secreted hvegf real time rtpcr experiment was repeated using pcaggs vectorspecific forward primer o sabin and the second was in the rna polymerase region nucleotide positions and the recombination had introduced six sabin derived amino acids into the sabin capsid environment in the carboxyl terminus of vp the CR genome of the recombinant virus differed from corresponding parental sabin strains at nucleotide positions nine of them resulting in an CAA substitution four substitutions were in the capsid proteins and five were in the region encoding the nonstructural proteins one CAA was changed in the antigenic site b and two in site b in addition the whole antigenic site a was replaced by sabin specific amino acids but the antigenic characteristics of the s did not show type specific features NT antibody titres in sera from finnish children immunized with the inactivated poliovirus vaccine were not lower against the recombinant virus than against sabin our results suggest that the chimeric virus was most likely generated by recombination events in the vaccinee rather than representing progeny of circulating vaccinederived virus | MEDAL |
the notion that prolonged ethanol consumption promotes hepatocellular damage through interactions with iron was evaluated in rats fed ethanol with or without supplemental dietary CI the individual and combined prooxidant potential of these agents was evaluated in terms of their ability to perturb iron homeostasis and initiate HCC injury spraguedawely rats received a high fat liquid diet for weeks supplemented with ethanolderived calories alcohol group to wv carbonyl iron iron group ethanol plus carbonyl iron alcohol iron group or a diet containing carbohydratederived isocaloric calories control group hepatic and serum nonheme iron stores were significantly elevated p in all treatment CG compared with the controls catalytically AS lowmolecular weight iron was detected in rats consuming alcohol and was markedly elevated p in rats ingesting iron CT or iron in combination with alcohol elevations in SS alt indicated significant HCC injury in rats ingesting only alcohol but was most prominent in the rats consuming ethanol in combination with iron p significant hepatic fatty infiltration increased hydroxyproline content and perturbations in reduced glutathione were also observed in the alcohol and iron treatment groups histochemical assessment of hepatic iron sequestration revealed that alcohol feeding resulted in deposition of ferric iron in the centrilobular area of the liver lobule this unique alcoholmediated iron deposition was histologically graded above control group and was observed in both hepatocytes and KCs data presented herein suggest that alcohol alone or in combination with iron results in rather specific lobular patterns of hepatic iron deposition relevant to iron overload observed in human alcoholics furthermore data suggest that alcohol and ironinitiated prefibrotic events occur before extensive HCC necrosis | MEDAL |
the cornea is one of the most highly innervated tissues in the rat host we hypothesized changes to cornea innervation through chemical sympathectomy would significantly alter the host response to the neurotropic viral pathogen herpes simplex virus type hsv following ocular infection mice treated with hydroxydopamine hydrobromide displayed reduced tyrosine hydroxylasepositive fibers residing in the cornea sympathectomized mice were also found to show a transient rise in virus recovered in infected tissues and succumbed to infection in greater numbers whereas there were no differences in infiltrating leukocyte populations including hsvspecific Tc lymphocytes in the INF tissue an increase in substance p and a decrease in Th1 levels in the TG ganglion but not BB stem of SX mice were noted sympathectomized mice treated with the neurokinin receptor antagonist l had delayed mortality implicating the involvement of substance p in hsvmediated death | MEDAL |
inflammation plays a L1 role in many diseases for instance in arteriosclerosis rheumatoid arthritis autoimmune disorders and CA since many plants contain compounds with antiinflammatory activity their consumption may be able to prevent the development of inflammatorybased diseases edible ferns are some of the most important wild vegetables in china and have traditionally been used both for dietary and therapeutic purposes in this study we investigated the antiinflammatory and antioxidant potential of fern extracts from matteuccia struthiopteris osmundajaponica matteuccia orientalis and pteridium aquilinum intended for use as nutraceuticals two modes of action were investigated the inhibition of the Th1 gene expression of interleukin beta ilβ and interleukin il and the mRNA of inos by lpselicited macrophages the results showed a decrease of ilβ gene expression for the five fern extracts this effect was more pronounced for the extracts prepared from the roots of o japonica ic of µgml and the young fronds of m orientalis µgml regarding the indirect measurement of no via inos mRNA an interesting decrease of was obtained with the extract of m orientalis fronds at a low concentration µgml compared with p aquilinum fronds µgml and leaves of o japonica the latter showed a higher decrease but at a high concentration of extract µgml the five fern extracts were also evaluated for their ability to scavenge diphenyllpicrylhydrazyl dpph radicals and azinobisethylbenzothiazolinesulfonic acid abts all fern extracts exhibited antioxidant effects but the roots of o japonica and the fronds of m orientalis were most efficient the hplcms analysis of the constituents of the fern extracts confirmed the presence of CGA caffeic acid pcoumaric acid ferulic acid kaempferol and apigenin molecules known to exhibit antiinflammatory andor antioxidant properties | MEDAL |
approximate entropy apen is frequently used to identify changes in the complexity of ISO force records with ageing and disease different signal acquisition and processing parameters have been used making comparison or confirmation of results difficult this study determined the effect of sampling and parameter choices by examining changes in apen values across a range of submaximal isometric contractions of the first dorsal interosseus reducing the sample rate by decimation changed both the value and DP of apen values dramatically the pattern of apen values across the range of effort levels was not CS to the filter cutoff frequency or the criterion used to extract the section of data for analysis the complexity increased with increasing effort levels using a fixed r value which accounts for measurement noise but decreased with increasing effort level when r was set to of the standard deviation of force it is recommended ISO force records are sampled at frequencies hz template length m is set to and r set to measurement system noise or sd depending on physiological process to be distinguished it is demonstrated that changes in apen across effort levels are related to changes in force gecular and PCS signals are orchestrated in space and time to sculpt multiple cell types into PET tissues and organs the complex and dynamic nature of the process has hindered studies aimed at delineating morphogenetic mechanisms in vivo particularly in mammals recent demonstrations of stem celldriven tissue assembly in culture offer a powerful new tool for modeling and dissecting organogenesis however despite the highly organotypic nature of stem cellderived tissues substantial differences set them apart from their in vivo counterparts probably owing to the altered microenvironment in which they reside and the lack of mesenchymal influences advances in the biomaterials and microtechnology fields have for example afforded a high degree of spatiotemporal control over the cellular microenvironment making it possible to interrogate the effects of individual microenvironmental components in a modular fashion and rapidly identify organspecific synthetic culture models hence bioengineering approaches promise to bridge the gap between stem celldriven tissue formation in SC and morphogenesis in vivo offering mechanistic insight into organogenesis and unveiling powerful new models for drug discovery as well as strategies for tissue regeneration in the clinic we draw on several examples of stem cellderived organoids to illustrate how bioengineering can contribute to tissue formation ex vivo we also discuss the challenges that lie ahead and potential ways to overcome them | MEDAL |
pc is a member of the eukaryotic family of subtilisinlike proteases which is thought to participate in the processing of prohormones and proneuropeptides in NE cells pc is synthesized as a kda prepropolypeptide the nhterminal signal sequence is removed during segregation within the endoplasmic reticulum where glycosylation occurs to generate a kda propolypeptide a combination of SDM and a cellfree translationtranslocation system from xenopus eggs was used to investigate the processing of the propc precursor the kda polypeptide underwent slow cleavage after the sequence arglyslysarg to generate a kda mature enzyme cleavage was blocked when the tetrabasic CS was deleted pcm or when the active site asp was changed to asn pcm this latter observation suggested that cleavage of the kda propolypeptide to the mature kda enzyme was autocatalytic incubation of the pcm mutant with the wild type pc precursor resulted in cleavage of both the wild type polypeptide and the catalytically inactive pcm mutant this indicates that cleavage could occur through an intermolecular reaction the results also demonstrate that the novel xenopus egg extract translationtranslocation system represents a powerful CF method for studying proteolytic processing of propolypeptides | MEDAL |
picomolar concentrations of NT caused concentrationdependent contractions of the longitudinal musculature of the fundus of the rat stomach the ec of NT was approximately nm on a molar basis neurotensin was about times more potent than hydroxytryptamine ht and approximately times as AS as acetylcholine in producing similar contractions studies with structurally related MMP indicated that whereas the carboxy terminal portion of NT was essential for biological activity a substantial part of its amino terminus end could be removed without affecting its potency the ec for the neurotensin fragment was identical to that of NT however its or fragments were completely inactive tetrodotoxin did not modify the potency of NT or structurally related analogues suggesting that the neurotensin receptor is probably located on the smooth muscle membrane in addition the potency of NT in contracting the fundus was not modified by i.c.v. with atropine methysergide or diphenhydramine fade to the contractile response of NT was followed by the development of tachyphylaxis desensitization was concentrationdependent and characterized by a shift in the agonist concentrationresponse curve to the RA and downwards desensitization with a priming concentration of neurotensin approx ec caused a substantial blockade of its excitability there was crossdesensitization between NT and the contractile activity of NT or xenopsin but not with angiotensin ii bradykinin substance p acetylcholine ht or histamine pretreatment of the fundus strip with verapamil microm antagonized in a concentrationdependent fashion the neurotensininduced contractions but not the muscular contractions caused by acetylcholine it is concluded that NT activates a specific excitatory receptor probably located on the CM of the smooth muscles of the rat fundus in addition we suggest that this receptor is somehow related to a voltagedependent calcium channel CS to verapamil | MEDAL |
the aim of the study was to screen the enterobacteriaceae flora of meat for the presence of bacteria harbouring the yersinia highpathogenicity island hpi | MEDAL |
fractures of the pyramid longitudinal fractures in the majority of cases lead to a damage of the facial nerve in the surrounding of the geniculate ganglion this area has to be controlled surgically when a FN paralysis occurs after a head injury | MEDAL |
comparisons were made between the kinetics and steadystate properties of the sodium conductance changes and of the sodium gating currents in the squid giant axon perfused with caesium fluoride and maintained at a high membrane holding potential the conductance measurements were made with reduced external sodium and as much electrical compensation as possible in order to minimize PE caused by the series resistance after an initial delay of musec whose size was a function of the holding potential and pulse amplitude the conductance rise on depolarization followed cube law kinetics values of the time constant taum as defined by hodgkin huxley b were determined for membrane potentials ranging between and mv they lay on a nearly symmetrical bellshaped curve with maximum at degrees c of just under musec at mv values of the gating current time constant tauv were determined over the same potential range and found to lie on a very similar bellshaped curve a computed leastsquares best fit gave the maximum as musec also falling at about mv the midpoint of the minfinity curve lay at mv and its slope at this point was mv another series of measurements on intact axons gave a midpotential of mv in the perfused axons the state of the membrane was better described by the constant field equation than by gna recalculation of minfinity from pna shifted the curve about mv in a positive direction | MEDAL |
highly specific antisera and RP hplc were used to examine the nature and CSD of gonadotropinreleasing hormone gnrh in the brains and plasma of three species of rana frog previously reported to vary in the types and BB distributions of gnrh the three species examined rana pipiens rana esculenta and rana ridibunda exhibit differences in total concentration and relative concentrations of gnrh in brain Az but all three contain the mammalian and chickenii forms of gnrh mgnrh and cgnrhii both forms were found in the TEL and diencephalon but mgnrh is consistently the most abundant form in the preoptichypothalamic area eg ratios of mgnrhcgnrhii in hypothalamusmedian eminence whereas cgnrhii is the most abundant in the TEL and the only form measured in the cerebellum and medulla the total content of cgnrhii in the whole brain is about times higher than that of mgnrh due to the larger size of the areas outside the preoptichypothalamic area these GA patterns were the same for adults and juveniles we found no evidence of a third form of gnrh corresponding to salmon gnrh in hypothalamus or other brain areas of r esculenta as previously reported these analyses also revealed the presence otic herniated disc with chymopapain patients were reexamined by magnetic resonance imaging mri at a mean followup of months welldefined mri findings before chemonucleolysis were compared with those T3 the procedure by an independent observer five mri parameters were assessed no significant NC was noted in the signal intensity of the affected disc the extent of osteochondrosis and endplate reaction of the affected segment the height of the affected disc as well as the size of the disc herniation were reduced significantly the loss of the height is seen as a direct result of chymopapain activity whereas the alteration of the size of the herniation seems to depend on the NK PH of a disc herniation and is probably not a simple result of the treatment | MEDAL |
ampa receptors mediate rapid glutamatergic synaptic transmission in the rat cochlear nuclei neurons receive excitatory input from either AEP nerve fibers PFs or both fiber systems the PET correlates of differences in the source of input were examined by recording ampa receptormediated miniature epscs mepscs in wholecell voltageclamp mode from identified neurons bushy octopus and tstellate cells of the VCN vcn and tuberculoventral cells of the dorsal cochlear nucleus dcn receive most of their excitatory input from the AEP nerve fusiform cells receive excitatory inputs from both the AEP nerve and PFs cartwheel cells receive excitatory input from parallel SF CT mepscs from bushy octopus tstellate and tuberculoventral cells had significantly faster decay time constants msec than did those from fusiform and cartwheel cells msec some fusiform cells had two populations of mepscs with distinct time courses mepscs in cells with AEP nerve input alone were inhibited by philanthotoxin a blocker of calciumpermeable ampa receptors whereas mepscs in cells with parallel fiber input were not thus ampa receptors postsynaptic to the auditory nerve differ from those postsynaptic to parallel fibers both in channelgating kinetics and in their permeability to calcium these results confirm the conclusion that synaptic ampa receptors are specialized according to the source of input hunter et al rubio and wenthold wang et al | MEDAL |
the prefrontal cortex plays a key role in the perception of painful stimuli including those emerging from the viscera colorectal distension is a noninvasive CS- used to T0 visceral pain processing in the NS visceral hypersensitivity is one of the main characteristics of the functional bowel disorder IBS ibs moreover recent human neuroimaging studies have emphasized the importance of altered brain activity and circuitry in the manifestation of ibs symptom severity and reaction to visceral stimuli it is unclear whether animal models of visceral hypersensitivity display a similar response therefore in the present study we have used cfos protein immunoreactivity as an indicator of cell activation to compare the response of the viscerally hypersensitive wistarkyoto wky rat and control spraguedawley sd rat strains to colorectal distension crd a noxious visceral CS- several corticolimbic structures were analysed including the PL SC IL cortex and the rostral and caudal anterior cingulate cortices moreover visceral hypersensitivity was also assessed behaviourally in both strains as previously described wky rats had a lower pain threshold than sd controls in response to crd in all BB regions analysed SE to crd induced an increase in cfos activation in both the wky and sd rats however an exaggerated cell activation was found in the PL infralimbic and rostral anterior cingulate cortices of the wky rat compared to sd animals no significant difference was found in caudal anterior cingulate cortex activation when the strains were compared these results demonstrate to our knowledge for the first time an augmented colorectal distensioninduced prefrontal cortex activity in wky rats similar to that seen in ibs patients further supporting the use of this strain as a MM in which to study braingut axis dysregulation observed in ibs | MEDAL |
the first triboelectricnanogenerator tengbased selfpowered implantable drugdelivery system is presented pumping flow rates from to µl min | MEDAL |
historically chemotherapy has remained the most commonly utilized therapy in patients with metastatic cancers in prostate cancer chemotherapy has been reserved for patients whose M1 becomes resistant to first line castration or androgen ED while chemotherapy palliates decreases SS prostate specific antigen and improves survival it is associated with significant side effects and is only suitable for approximately of patients with castrateresistant prostate CA on that basis exploration of other therapeutic options such as active secondary hormone therapy bone targeted treatments and immunotherapy are important until recently immunotherapy has had no role in the treatment of solid HM aside from renal cancer and melanoma the fdaapproved autologous cellular immunotherapy sipuleucelt has demonstrated efficacy in improving overall survival in patients with metastatic castrateresistant prostate CA in RCTs the proposed mechanism of action is reliant on activating the patients own antigen presenting cells apcs to prostatic acid phosphatase pap fused with rGM-CSF gmcsf and subsequent triggered tcell response to pap on the surface of prostate CA cells the how mand how do i and how many using separate SMB chains to target the frames we taught children with autism to emit mands for information with behavior chain and assessed generalization with the remaining behavior chains SMB chains that the participants were unable to perform independently and that produced a desirable outcome for the participant eg tornado water were used to contrive the relevant motivating operation for all participants mands for information generalized across motivating operations and response topographies | MEDAL |
ovine interferon tau ifn tau is a type i interferon that was originally identified as ovine trophoblast protein and is associated with the maternal recognition of pregnancy in sheep additionally ifn tau possesses potent antiviral and antiproliferative activity without the corresponding toxicity found in known ifn alpha s structurefunction studies with SP have identified three discontinuous functional sites on the protein that are involved in receptor interaction and biological activity however the structural relationship of these regions is unknown therefore a model relationship of these regions is unknown therefore a MM of the d structure of ifn tau would be useful in interpretation of existing data and the design of future structurefunction studies combining information from circular dichroism cd of both the full length recombinant ifn tau and SP representing regions of the ifn tau molecule with sequence homology of ifn tau to ifn beta a protein of known d structure we have constructed a MM of ifn tau using distance geometry and energy minimization methods the most striking feature of this model is that functionally active domains of ifn tau discontinuous in the primary structure are localized to one side of the molecule and found to be spatially contiguous this observation is consistent with multiple binding sites on ifn tau interacting simultaneously with the ifn tau receptor | MEDAL |
adenovirus ad replicative complexes form at discrete sites on the NM nm through the interaction of ad preterminal protein ptp the nm is a highly saltresistant fibrillar network which is known to anchor transcription mrna splicing and dna replication complexes incubation of ratp with nm to which ptp was bound caused the PR of ptp as a ptpnm complex with a size of to kda incubation with AMP-PNP ramppnp showed no significant PR indicating that ratp hydrolysis was required with nm extracts it was shown that a ptpnm complex which was capable of IB ad origin dna could be reconstituted in vitro a number of highmolecularweight nm proteins ranging in size from to kda were identified on far western blots for their ability to bind ptp ratpdependent release of ptp from the nm was inhibited in a dosedependent fashion by the addition of tyrosine kinase inhibitors such as quercetin methyldihydroxycinnamate or genistein nmmediated phosphorylation of a polyglu tyr ATP was also significantly abrogated by the addition of these EDC ratpdependent PR of ad dna termini bound to the nm via ptp was also blocked by the addition of these inhibitors these results indicate that a IMT kinase mechanism controls the release of ptp from its IB CS on the nm these data support the concept that phosphorylation may play a key role in the modulation of ptp IB sites on the nm | MEDAL |
a yearold man with a restenotic lesion of the mid lad was scheduled for wiktor stent placement the ivus revealed circumferential severe calcification two conventional noncompliant angioplasty balloons inflated to high pressures failed to achieved sufficient dilatation and both ruptured at this point we selected OHP inflation of the cutting balloon the cutting balloon achieved adequate dilation for stenting and proved to be useful in predilating a circumferential heavily calcified lesion | MEDAL |
there continues to be uncertainty regarding the relative biological effectiveness rbe values that should be used in charged particle radiotherapy cpt prescriptions using protons and heavier ions this uncertainty could potentially offset the physical dose advantage gained by exploiting the bragg peak effect and it needs to be clearly understood by clinicians and physicists this paper introduces a combined radiobiological and PCS sparing factor s this factor includes the ratio of the most relevant physical doses in tumour and normal tissues in combination with their respective rbe values and can be extended to contain the uncertainties in rbe s AF can be used to study in a simplified way for tentative modelling those clinical situations in which highlinear energy transfer let irradiations are likely to prove preferable over their lowlet counterparts for a matched tumour isoeffect in cases where cpt achieves an excellent degree of T/N sparing the radiobiological AF become less important and any uncertainties in the tumour and healthy tissue rbe values are correspondingly less problematic when less T/N sparing can be achieved however the rbe uncertainties assume greater relevance and will affect the reliability of the doseprescription methodology more research is required to provide accurate rbe estimation focusing attention on the associated statistical uncertainties and potential differences in rbe between different tissue types | MEDAL |
terpenoids are the largest and most structurally diverse family of natural products found in nature yet their presence in bacteria is underappreciated the carbon skeletons of terpenoids are generated through carbocationdependent cyclization cascades catalyzed by terpene synthases tss type i and type ii tss initiate cyclization via diphosphate ionization and protonation respectively and protein structures of both types are known most plant diterpene synthases dtss possess three αhelical domains αβγ which are thought to have arisen from the fusion of discrete ancestral bacterial type i tss α and type ii tss βγ type ii dtss of bacterial origin of which there are no structurally characterized members are a missing piece in the structural evolution of tss here we report the first crystal structure of a type ii dts from bacteria ptmt from streptomyces platensis cb was verified as an entcopalyl diphosphate synthase involved in the biosynthesis of platensimycin and platencin the crystal structure of ptmt was solved at a resolution of å and docking studies suggest the catalytically AS conformation of geranylgeranyl diphosphate ggpp sitedirected mutagenesis confirmed residues involved in IB the diphosphate moiety of ggpp and identified dxxxxe as a potential mgbinding motif for type ii dtss of bacterial origin finally both the shape and physicochemical properties of the active sites are responsible for determining specific catalytic outcomes of tss the structure of ptmt fundamentally advances the knowledge of bacterial tss their mechanisms and their role in the evolution of tss | MEDAL |
the positive inotropic effect of CG has been attributed to inhibition of the nakatpase accumulation of intracellular sodium and enhanced calcium availability due to naca exchange however few measurements of intracellular sodium in the functioning left ventricle following ouabain exposure at therapeutic doses are available our exp objective was to quantitate the relationship between contractile state and intracellular sodium measured by na nuclear magnetic resonance spectroscopy or atomic absorption in the intact HR isolated guineapig NF perfused in the langendorff mode were paced and then exposed to ouabain xm for min leftventricular pressure was monitored continuously intracellular sodium was measured either at min intervals throughout the perfusion by shift reagentaided na nuclear magnetic resonance spectroscopy in the beating heart or following minutes of perfusion by AA in myocardial tissue while treatment with ouabain was associated with almost a twofold rise in developed pressure there was no significant increase in intracellular sodium measured by either technique thus the PIE of ouabain in this model is not associated with significant changes in bulk intracellular sodium however these results do not exclude the possibility of shifts between intracellular pools which would not be detected in bulk measurements or changes in nmrinvisible intracellular pools which are not detectable by single quantum spectroscopy techniques | MEDAL |
torsion of a Pr uterus is rare but torsion of a nonpregnant uterus is extremely rare abdominal pain is the L1 symptom other PS include vaginal bleeding urinary tract PS and gastrointestinal manifestations we present a case of a yearold WG nullipara who presented at the ER with acute urinary retention medical PH revealed that the patient carried the disease of myotonic dystrophy which was diagnosed two years before physical examination revealed a tender distended bladder which was easily catheterized draining ml of clear urine the abdomen was soft with no muscle guarding or rebound tenderness a palpable large dense mass occupying the culdesac was found during bimanual examination abdominal ultrasound examination revealed a large intramural leiomyoma approximately cm in diameter in the posterior wall of the uterus which repelled the bladder in neurological examination the muscular tone and reflexes were reduced in the lower extremities myotonic phenomenon was not found the patient was thought to suffer from myotonic dystrophy and therefore the possibilities for pulmonary and cardiac complications or malignant hyperthermia had to be kept in mind during the anaesthetic management the patient underwent an exploratory lapaer region the decreased amide HX for residues within camp IB domain a and for residues which include the pseudosubstrate GABA site support the prediction that these two regions represent the conserved primary and peripheral csubunit binding CS an increase in amide HX for a broad area within campbinding domain b and a narrow area within campbinding domain a residues suggest that csubunit binding transmits longdistance conformational changes throughout the protein | MEDAL |
to investigate whether glucagon affects the xylitolinduced increase in the production of purine bases hypoxanthine xanthine and uric acid the present T0 was performed with five HS i.v. of ml xylitol increased the plasma concentration and urinary excretion of purine bases erythrocyte concentrations of adenosine monophosphate amp and adenosine diphosphate adp and blood concentrations of glyceraldehydephosphate gap dihydroxyacetone phosphate dhap fructosebisphosphate fbp and lactic acid it decreased the blood concentration of pyruvic acid and the plasma concentration and urinary excretion of inorganic phosphate however intravenous administration of mg glucagon together with xylitol reduced the xylitolinduced changes in oxypurines pyruvic acid gabp dhap and fbp whereas it promoted the xylitolinduced increase in the urinary excretion of total purine bases and did not affect the xylitolinduced increase in the plasma concentration of total purine bases in addition in vitro T0 demonstrated that sodium Pyr prevented the xylitolinduced Kd of adenine nucleotides in erythrocytes these results suggested that gluconeogenesis due to glucagon increased the production of pyruvic acid accelerated the conversion of nadh to nad and thereby prevented both the xylitolinduced Kd of adenine nucleotides in organs similar to erythrocytes and the inhibition of xanthine dehydrogenase in the liver and small intestine resulting in decreases in the plasma concentration and urinary excretion of oxypurines however it was also suggested that in the CL storing glycogen glucagoninduced glycogenolysis accumulated sugar phosphates resulting in purine degradation since the xylitolinduced increase in the nadhnad ratio partially blocked glycolysis at the level of gabp dehydrogenase therefore administration of glucagon together with xylitol may synergistically increase purine Kd more than xylitol alone despite decreases in the plasma concentration and urinary excretion of oxypurines | MEDAL |
established renal epithelial cell lines of human pig and dog origin llcpk mdck were examined in terms of nephrotoxicity and ability to biotransform cyclosporine a csa all three cell lines exhibited a comparable concentration dependent cytotoxicity to csa treatment alterations in cell CF included a decreased transport of lysine an inhibition of growth and an activation of lysosomal and mitochondrial activity as indicated by the increased uptake of neutral red nr and increased reduction of the tetrazolium dye mtt at microm csa increased leakage of lactic dehydrogenase and MICs of gammaglutamyl transpeptidase ggt and nacetylbetadhexosaminidase were observed at h and microm csa a discrimination between csa and the less nephrotoxic cyclosporinecsh was shown for dna synthesis and nr uptake the contribution of extrarenal parameters on kidney cell function was studied by the addition of medium from HCs exposed to csa to the kidney cell lines a more potent inhibition of dna synthesis and enhanced reduction of mtt resulted than by addition of equimolar csa directly to the A6 these data indicate that hepatocyte constituents present in the medium due to csa treatment affect kidney cell function additionally the presence of csa metabolites may contribute to the csainduced nephrotoxicity the vascular nephrotoxicity induced by csa an increased deposition of platelets in the renal arterioles was mimicked by cocultures of ECM and platelets csa increased the aggregability and adherence of platelets to the ECM whereas csh had no effect | MEDAL |
minimally invasive cardiac surgery has captured the interest and attention of cardiac surgeons throughout the world we reviewed our experience of minimal access cardiac operations performed through a lower median ministernotomy between january and august congenital valvular coronary aneurysmal and other operations were performed via a to cm lower ministernotomy in consecutive patients no special instruments were required four patients died and reoperations were necessary complications occurred in patients the mean CP bypass time was min crossclamp time was min time to extubation was h and total chest drainage was mlkg blood transfusions of ml were needed in patients postoperative hospital stay was days our experience shows that many types of cardiac operations can be performed through a lower ministernotomy this technique results in less trauma quick recovery and reduces the risk of infection and BL it is a safe and easy procedure that can bring about favorable early outcomes in a wide range of cardiac operations | MEDAL |
cell signaling by coagulation factor xa xa contributes to Th1 responses in vivo this study characterizes the signaling mechanism of xa in a hela cell line that expresses proteaseactivated receptor par but not par or xa induced nfkappab in hela cells efficiently but with delayed kinetics compared to thrombin this delay caused no difference in mRNA patterns as determined by highdensity microarray analysis both proteases prominently induced the angiogenesispromoting gene cyr and connective tissue growth factor inhibition of par cleavage abolished map kinase phosphorylation and gene induction by xa demonstrating that xa signals through par and not through a novel member of the par family activation of cell surface prothrombin with the snake venom enzyme ecarin also produced pardependent signaling however though the response to ecarin was completely blocked by the thrombin inhibitor hirudin the response to xa was not this suggests that the xa response is not mediated by locally generated thrombin the concentration dependence of xa for par activation is consistent with previously characterized xamediated par signaling suggesting that local concentration of xa on the cell surface rather than sequencespecific recognition of the par scissile bond determines receptor cleavage this T0 demonstrates that par cleavage by xa can elicit the same cellular response as thrombin but mechanistic differences in receptor recognition may be crucial for specific roles for xa in signaling during spatial or temporal separation from thrombin generation | MEDAL |
according to ultrastructure size and location within the dorsal cortex of lacerta galloti six basic types of neuronal somata are described in this T0 in the outer plexiform layer only few neuronal somata with nuclear invaginations can be detected type a in the granular stratum large neuronal somata type b receiving axosomatic synapses and covered by ependymoglial ramifications represent of all somata of the DC in the IPL a heterogeneous population of somata according to their ultrastructure can be detected these are big neuronal somata type c neuronal somata with nuclear invaginations type d neuronal somata having many dense core LDV type e and neuronal somata associated to the ependymal layer type f there also CG or nests of neuronal somata closely attached and partially covered by ependymoglial branches can be seen because of the simple cytoarchitectonic scheme of this DC location of somata frequency and biometrical characteristics they have been used to make comparisons with neuronal types defined by golgi impregnations in the DC of lacerta galloti regidor nevertheless grouped neuronal somata of the inner plexiform SL are difficult to correlate also the presence of immature neuronal somata in this area leads to the possibility of existing a subependymary zone remaining some embryonary characteristics | MEDAL |
alphamelanocytestimulating hormone alphamsh alphamelanotropin nledphealphamsh and related fragment analogues acnledphealphamshnh and acnledphealphamshnh were studied for their ability to stimulate tyrosinase activity in cloudman s mouse melanoma cells in TC all of the melanotropins stimulated tyrosinase activity in a dosedependent manner nledphealphamsh was about times more active than alphamsh as determined from the minimal effective dose med required to activate the enzyme above control basal levels the med of this analogue to significantly stimulate tyr activity at and h of incubation was m whereas the med of alphamsh was m at each of these times the maximum tyrosinase activity achieved from the time of initial incubation in the presence of nledphealphamsh was approximately and fold greater than control C2 at and h respectively the nledphesubstituted fragment analogues were at least as AS as the tridecapeptide analogue and therefore at least fold more active than alphamsh in stimulating enzyme activity these nledphesubstituted analogues were more active in the melanoma tyrosinase CA than in the melanoma adenylate cyclase assay or other normal melanocyte frog and lizard skin bioassays | MEDAL |
cowden syndrome also known as multiple hamartoma syndrome is a rare autosomal dominant disorder characterized by multiple hamartomas and a high risk of OD of malignancy oral findings such as papillomatous lesions and fibromas are common features however a periodontal phenotype has not been reported previously therefore this report presents a case of gingival overgrowth associated with cowden syndrome its successful surgical management and the month followup results additionally we discuss the implications for clinicians a yearold woman was referred to the department of periodontics piracicaba dental school presenting with generalized GO a detailed dental and medical PH and clinical examination confirmed the systemic diagnosis of cowden syndrome histology radiographs and clinical data document the entire clinical RPA and followup clinically there were minor signs of recurrence of gingival overgrowth in a month period T3 gingivectomy however papular lesions reappeared in keratinized gingiva immediately T3 healing no signs of BL related to the systemic condition were observed radiographically histologically a dense connective tissue with a moderate chronic inflammatory infiltrate and epithelial acanthosis which is characteristic of gingival hyperplasia were demonstrated GO may occur as an oral phenotype related to cowden syndrome and can be successfully treated by means of external bevel gingivectomy followed by regular maintenance therapy contributing to the patients wellbeing both functionally and esthetically | MEDAL |
african trypanosomes are protozoan parasites that evade the host immune system by varying their dense antigenic coat the variant SU vsg is expressed exclusively from telomerelinked ESs that contain in addition to the vsg gene a number of open reading frames termed expression site associated genes esags here we demonstrate by complementation of a yeast mutant deleted for adenylate cyclase cyr that an esag from trypanosoma equiperdum encodes an adenylate cyclase furthermore we report that adjacent to adenylate cyclase in the expression site is a separate open reading frame that encodes a protein sequence motif similar to the leucinerich repeat RD of saccharomyces cerevisiae and Sp adenylate cyclases the finding of two adjacent open reading frames homologous to a single enzyme in yeast suggests that the two expression site encoded proteins may interact to regulate adenylate cyclase activity during the course of an infection | MEDAL |
the authors examined the relationship between neuronal densities glial cell densities and the glial cellneuron ratio in the ca and ca HPC subfields and preoperative and postoperative memory function in patients who had undergone a temporal lobectomy RA rtl left ltl for the relief of medically intractable epilepsy the ltl group performed more poorly than the rtl group on a list learning and story recall task preoperatively and postoperatively both the rtl and ltl groups performed more poorly on the story recall task postoperatively in the ltl group neuronal densities in the ca subfield were significantly correlated with the preoperative scores on the immediate r p and delayed r p recall of the story there were no significant correlations in the ltl group between the ca and ca cell counts and VIQ or scores on a measure of naming ability none of the cell density measures in the ca and ca subfields were significantly correlated with the preoperative NP test scores in the rtl group postoperative decline in verbal recall was associated with the excision of a relatively IN left hippocampus with high neuronal and low glial cell densities in the ca subfield the excision of a relatively intact right hippocampus was also associated with a postoperative deterioration in verbal recall | MEDAL |
studies of the recent decade including sequencing of numerous human genome regions allowed a great progress in PCD of new tumor suppressor genes tsg and development of new means of their ID and analysis ERP methods of genome scanning and tsg identification combine dna array techniques and subtraction hybridization alternative ways take advantage of new extrachromosomal vector systems pete petr and the PET gene inacoinflammatory cytokines and membrane MPs released from G1 host cells tissue factor plays an important role in initiating thrombosis associated with inflammation during infection sepsis and organ transplant rejection recent findings suggest that tissue factor can also CF as a receptor and thus may be important in cell signaling the present minireview will focus on the role of tissue factor in the pathogenesis of septic shock infectious endocarditis and invasive aspergillosis as determined by both in vivo and in vitro models | MEDAL |
bioaugmentationassisted phytoextraction may enhance the phytoextraction efficiency thanks to larger metal mobilization by microbial metabolites green FL proteintagged cells of pseudomonas aeruginosa pseudomonas fluorescens or ralstonia metallidurans able to produce siderophores were inoculated in an agricultural soil containing cr mg kg and pb mg kg and maize was cultivated bacteria were inoculated as free or immobilized cells in caalginate beads with SM in the aim at improving both the bacterial survival and the in situ siderophore production SM addition increased inoculated pseudomonads concentration in soil soil inoculation with free cells of r metallidurans supplied with skim milk increased cr accumulation in maize shoots by a factor of and inoculation with immobilized p aeruginosa cells supplied with SM increased cr and pb uptake by maize shoots by a factor of and respectively however total metal taken up by the whole plant decreases almost always with bioaugmentation translocation factor also increased with p aeruginosa or r metallidurans by a factor of up to inoculated bacteria concentration in soil was correlated with metals in the exchangeable fraction cr and pb concentrations in the exchangeable fraction were correlated with metal contents in shoots or roots our results suggest that bioaugmentationassisted phytoextraction is a relevant method in the aim at increasing the phytoextraction rate which usually limits the use of phytoremediation technologies | MEDAL |
we have identified the membraneactive regions of the severe acute respiratory syndrome coronavirus sars cov spike glycoprotein by determining the effect on model membrane integrity of a mer sars cov spike glycoprotein peptide library by monitoring the effect of this peptide library on membrane leakage in model membranes we have identified three regions on the sars cov spike glycoprotein with membraneinteracting capabilities region located immediately upstream of heptad repeat hr and suggested to be the fusion peptide region located between hr and hr which would be analogous to the loop domain of human immunodeficiency virus type and region which would correspond to the pretransmembrane region the identification of these membraneactive regions which are capable of modifying the biophysical properties of phospholipid CM supports their direct role in sars covmediated membrane F0 as well as facilitating the future OD of sars cov entry inhibitors | MEDAL |
kaposis sarcoma ksassociated herpesvirus openreading frame orf encodes a latencyassociated nuclear antigen lana that is the basis for several serologic assays immunoreactive epitopes were searched for by peptide mapping and cleavable biotinylated mer peptides offset by residues were synthesized and screened with human SS samples by elisa the initial screen which used highly reactive serum diluted identified immunoreactive peptides these were subsequently tested on additional SS samples diluted thirteen MMP were more reactive with SS samples from patients with ks than with control serum samples no single epitope was recognized by most ks patient SS samples combined use of these peptides did not increase test sensitivity to that of current indirect immunofluorescence assays for lana for comparison fulllength orf was expressed in bacteria and analyzed by western blot the overall sensitivity was range among us patients with classic ks to among italian patients with classic ks these studies suggest that lana immunoreactivity may be due to variations in patient response or conformational epitopes | MEDAL |
several different genomic and nongenomic mechanisms are known to mediate the important antiinflammatory and immunomodulatory effects of glucocorticoids gc genomic effects are the most important while the clinical relevance of nongenomic actions is still a matter of debate we therefore investigated whether beclometasone and clobetasol are particularly suitable for topical application because of their TPS spectrum of genomic and nongenomic actions for these purposes we compared effects on oxygen consumption as measured with a clark electrode nonspecific nongenomic glucocorticoid effects on interleukin synthesis by means of elisa genomic effects and on apoptosis using flow cytometry nongenomic and genomic effects in quiescent and mitogenstimulated pbmc beclometasone and clobetasol indeed had stronger effects on the oxygen consumption of quiescent and stimulated cells at lower concentrations and m but were less potent at higher concentrations and m in comparison with dexamethasone also in terms of genomic potency topical gc were more effective than dexamethasone at and m but gave similar results at higher concentrations the ability of all three gc to induce apoptosis was found to be concentrationdependent and similar at concentrations between and m but compared with m dexamethasone topical gc at m were significantly more ERP at inducing apoptosis in both pbmc and jurkat tcells these results show that topical gc have different concentrationgenomicnongenomic effectratios compared with dexamethasone besides to the wellknown genomic effects there are also significant nongenomic effects of topical glucocorticoids that already at low concentrations might be more therapeutically relevant in certain clinical conditions than currently assumed | MEDAL |
the unstirred ferroin fephen catalyzed belousovzhabotinsky bz reaction is the prototype oscillatory chemical system reaction media with added br appear red reduced low fephen during an induction period of several T2 followed by the spontaneous formation of pacemaker CS which oscillate between a blue oxidized state high fephen and the red reduced state and generate target patterns of con outwardly moving waves of oxidation blue autooscillatory behavior is also seen in the oregonator model of field koros and noyes fkn a robust reduced model that captures qualitative bz kinetics in the autooscillatory regime however the oregonator MM predicts a blue oxidized induction phase here we develop a generalized oregonatorlike model with no explicit bifurcation parameter that yields the observed transition from a red initial state to oscillatory dynamics and displays a new bifurcation mechanism not seen in the original oregonator | MEDAL |
changes in plasma lipid and apolipoprotein profiles were evaluated in healthy unfit subjects vopeak mlkgmin women men at baseline and following endurance exercise training the exercise protocol consisted of a week endurance exercise training program days week minsession or hrmax subjects were randomly assigned to consume an egg n eggsweek or noegg n eggsweekbased eucaloric standardized diet for weeks both diets were macronutrient balanced carbohydrate fat protein gkgday and individually designed for weight maintenance plasma lipids were measured twice within the same week at baseline and following exercise training at baseline subjects were NL with values of and mg dl for total cholesterol ldl cholesterol and hdl cholesterol and triglyceride concentrations respectively a twoway anova was used to analyze diet and exercise effects and interactions in both CG endurance exercise training resulted in a significant increase in hdlc p a decrease in apo b concentrations p and reductions in plasma cetp activity p plasma ldlc decreased by p no main effects of diet or interactions with plasma lipids or apo b concentrations were observed these data demonstrate that endurance training improved the plasma lipid profiles of previously unfit NL subjects independent of dietary cholesterol NI from eggs | MEDAL |
IMT aminotransferase activity increased during conversion of serum depleted quiescent reuber h rat hepatoma cells into the proliferative state increased activity coincides with the actual increase of cells into s phase the rate of tyrosine aminotransferase synthesis along the Tc was studied the rate of enzyme synthesis fluctuated through the Tc but could not explain the increase of specific activity apparently CEA is predominantly regulated by a posttranslational event intracellular levels of cyclic amp and cyclic gmp were measured at various times of g and s phases in the early part of the cell cycle tyrosine aminotransferase decreased while intracellular levels of cyclic amp increased at later stages cAMP rises concurrently with increased rates of enzyme synthesis induction of TAT by nodibutyryladenosine monophosphate btcamp was studied inducibility by btcamp fluctuated through the cell cycle alternation of positive and negative control of TAT synthesis was observed in early serum induced cells btcamp increased CEA without any increased rate of enzyme synthesis on the contrary a decreased rate of synthesis was observed the data support the view that alternation of positive and negative control of IMT aminotransferase synthesis and temporary posttranslational control of enzyme activity determine the enzyme level during the transition of quiescent hepatoma cells into proliferation | MEDAL |
a CS of wistar rats was inbred in our laboratory for its susceptibility to sound the seizures are characterized by one or two wild running fits which terminate in a tonic DF with open mouth followed by a catatonic state during the tonic phase of the seizure the cortical eeg is flattened for to s then a slow and regular lowvoltage cs activity is observed during to s when these animals are submitted to daily soundstimulations the behavioral as well as the eeg manifestations of the audiogenic seizures change progressively T3 to exposures the wild running becomes disorganized by occurrence of myoclonic jerks of the limbs and the body in some animals the tonic extension disappears and a myoclonic seizure develops progressively with facial and forelimb clonus rearing and falling in other animals the tonic phase still occurs and is followed by a generalized clonic phase during both the myoclonic and the tonicoclonic seizures rhythmic spikes polyspikes and spike and waves of high amplitude cs during to s are observed on eeg recordings these eeg modifications often outlast the sound stimulation the pharmacological reactivity in rats exposed to single or repeated audiogenic seizures is similar phenytoin and carbamazepine suppress both kinds of seizures at low doses whereas ethosuximide is efficacio obtained in angiographic examinations of patients with blunt traumas of the abdomen | MEDAL |
an avidity test for measles igg was developed and applied to the study of igg immunoglobulin maturation kinetics in followup sera from patients with known acute primary and convalescent measles and sera frtry in the AD mouse brain strong hybridization was detected in cerebellum hippocampus substantia nigra sn and CBF cortex in mouse cerebellum hybridization was detected in granule cells purkinje cells and in cells of the deep cerebellar nuclei dcn in human cerebellum hybridization was detected in the granule cell layer in the mouse gcap is expressed at least as early as embryonic day e in the CNS system cns | MEDAL |
the relation between overall survival time os and response level cr r pr mr sd was analysed in multiple myeloma patients from prospective finnish leukaemia group trials treated with CC the primary regimen was either melphalan and prednisolone or combination chemotherapy with melphalan as a main component both the influence of the pretreatment AF in patients with different levels of responses and the aspects related to chemotherapy were analysed the patients aged up to yr and the older patients were dealt with as separate groups irrespective of the primary chemotherapy regimen the level of response was not significantly influencing in the os time and this was true in both age categories the median os of the patients up to yr of age who had any response was months compared to the months of those with pd p the corresponding figures for the older patients were and months p respectively the pretreatment prognosticators for the patients with minimal responses were not more favourable than for patients with responses at higher C2 the prolonged primary chemotherapy was favourable in patients having responses less than pr accordingly the primary goal of conventional chemotherapy for multiple myeloma is stabilization of disease not the level of response | MEDAL |
it has been reported that the degeneration of cochlear hair cells is the typical cause of presbycusis or agerelated hearing loss however the molecular mechanisms that mediate cochlear HC apoptosis are not yet fully understood and there is no ERP treatment for this disorder micrornas mirnas or mirs have been increasingly shown to be associated with agerelated diseases and are emerging as promising therapeutic targets in this T0 we investigated whether mirb is involved in the degeneration of cochlear hair cells to examine our hypothesis nuclear IF and terminal deoxynucleotidyl GOT dutp nickend labeling tunel were used to quantify the HC counts rtqpcr and western blot analysis were used to examine mirbsirtuin sirtproliferatoractivated receptorgamma coactivator α pgcâα signaling in cochlear hair cells we found that there was a significant degeneration of cochlear hair cells and a higher expression of mirb in aged B6 mice compared with young mice there was also an agerelated decrease in the expression of sirt and pgcâα in the inner ear cell L1 heioc mirb overexpression by transfection with mirb mimic inhibited sirt and pgcâα expression leading to an increase in mitochondrial dysfunction and apoptosis moreover the inhibition of mirb by transfection with mirb inhibitor increased sirt and pgcâα expression while it decreased apoptosis taken together our findings support a link between agerelated cochlear hair cell apoptosis and mirbsirtpgcâα signaling which may present an attractive pharmacological target for the development of novel drugs for the treatment of agerelated hearing loss | MEDAL |
WFS also known as didmoad diabetes insipidus diabetes mellitus optic atrophy deafness is an autosomal recessive disorder characterized by the association of childhood nonimmune insulindependent diabetes mellitus dm with progressive bilateral optic atrophy additional PS including signs of severe neurodegeneration and psychiatric illness are likely to evolve over time resulting in premature death we report on two siblings of turkish origin from our diabetes clinic who were diagnosed with wolfram syndrome after years and years duration of dm respectively subtle PS such as attitude changes growing reading difficulties in the history of children or adolescents with antibody negative and ketone negative dm should alert the treating physician and lead to reevaluation of the diagnosis keeping in mind that not all juvenile dm is type dm | MEDAL |
human recombinant tissue inhibitor of MPs rtimp at microm was found to stimulate the growth of normal human KCs in primary cultures on a plastic support and to markedly increase their growth on a 3D SC system the skin equivalent as shown by histology dna measurements and planimetry in contrast rtimp had no effect on the growth of normal human fibroblasts the growth of keratinocytes on extracellular matrix components produced by KCs cultured in the presence or absence of rtimp was similar suggesting that rtimp does not stimulate keratinocyte growth by modifying either the quantity or the composition of the extracellular matrix deposited rtimp was labeled with iodine in order to T0 its interaction with keratinocytes in culture binding of i rtimp to KCs was found to be temperature and time dependent under steadystate conditions at degrees c one class of specific rtimp IB CS was identified with kd of nm and sitescell such findings are in keeping with the known potentiating effect of timp on BFU-E and indicate that this protein has at least two distinct activities | MEDAL |
with regards to research animal models related to immune thrombocytopenia itp there is an extensive literature of over publications published since it appears that many of these models either confirm what has been found in human itp or in some instances are the first to describe a phenomenon related to itp that is still of relevance today in human medicine these models will undoubtedly play a significant role in the future research of human itp particularly related to understanding of the pathogenesis of the disorder and the OD of novel therapeutics this review will highlight some of the L1 animal models utilized for itp research and will present a somewhat historical aspect of the subject | MEDAL |
humoral and cellular immune CR are reported for two neuroendocrine autoantigensglutamic acid decarboxylase gad and the protein IMT phosphatase iain a patient with the autoimmune type of stiffman syndrome and insulin dependent diabetes iddm | MEDAL |
we report the cloning of a glycoside hydrolase family ghf gene of rice oryza sativa l cv sasanishiki oscela corresponding to the auxininduced kda endobetaglucanase egase this enzyme reveals a broad substrate specificity with respect to sugar backbones glucose and xylose in betaglycans of type ii cell wall oscela encodes a CAA polypeptide and is an ortholog of tomcel a tomato egase containing a carbohydratebinding module cbm CS at its cterminus the expression of four rice egase genes including oscela showed different patterns of organ specificity and responses to auxin oscela was preferentially expressed during the initiation of lateral roots or subcultured root calli but was hardly expressed during auxininduced coleoptile elongation or in seed calli in contrast to osceld a korrigan kor homolog in situ localization of oscela transcripts demonstrated that its expression was specifically upregulated in lateral root primordia lrp RNA blotting analysis showed the presence of a single product of oscela in contrast both MS analyses of peptide fragments from purified kda egase proteins and immunogel blot analysis of egase proteins in root extracts using two antibodies against internal peptide sequences of oscela revealed that the entire cbm region was posttranslationally truncated from the kda nascent protein to generate kda egase isoforms analyses of auxin concentration and time course dependence of accumulation of two egase isoforms suggested that the translation and posttranslational cbm truncation of the oscela gene may participate in lateral root development | MEDAL |
the authors report a case of malignant lymphoma small lymphocytic type involving the lymphoid stroma of a warthins tumor of the PG this was confirmed by the presence of a monoclonal IgH chain gene rearrangement demonstrated by southern blot hybridization of dna extracted from PET similar techniques showed only germline immunoglobulin gene bands in two control cases of warthins tumor | MEDAL |
puberty involves a series of morphological physiological and behavioural changes during the last part of the juvenile period that culminates in the attainment of fertility the activation of the pituitarygonadal axis by increased hypothalamic secretion of gonadotrophinreleasing hormone gnrh is an essential step in the process the current hypothesis postulates that a loss of transsynaptic inhibition and a rise in excitatory inputs are responsible for the activation of gnrh release similarly a shift in the balance in the expression of puberty activating and puberty GABA genes exists during the pubertal transition in addition recent evidence suggests that the epigenetic machinery controls this genetic balance giving rise to the tantalising possibility that epigenetics serves as a relay of environmental signals known for many years to modulate pubertal development here we review the contribution of epigenetics as a regulatory mechanism in the hypothalamic control of female puberty | MEDAL |
there is a clinical need for a tissueengineered vascular VG tevg and combining stem cells with biodegradable tubular scaffolds appears to be a promising RPA the goal of this study was to characterize the incorporation of musclederived stem cells mdscs within tubular polyester urethane urea peuu scaffolds in vitro to understand their interaction and to evaluate the mechanical properties of the constructs for V1 applications porous peuu scaffolds were seeded with mdscs using our recently described rotational vacuum seeding device and cultured inside a spinner flask for or days cell viability number distribution and phenotype were assessed along with the suture retention strength and uniaxial mechanical behavior of the tevgs the seeding device allowed rapid even CSD of cells within the scaffolds T3 days the constructs appeared completely populated with cells that were spread within the polymer cells underwent a population doubling of fold with a population doubling time of h stem cell antigen sca expression by the cells remained high T3 DIC vs at day while cd expression was reduced vs at day and MHC chain expression was scarce not quantified the estimated burst strength of the tevg constructs was mm hg and suture PR strength was n we conclude from this study that mdscs can be rapidly seeded within porous biodegradable tubular scaffolds while maintaining cell viability and high proliferation rates and without losing SC phenotype for up to days of invitro culture the successful integration of these steps is thought necessary to provide rapid availability of tevgs which is essential for clinical translation | MEDAL |
antiphospholipid antibodies can influence the results of clotting tests in a subset of patients which can be a L1 obstacle in monitoring warfarin the aim was to determine if pointofcare testing of the international normalized ratio inr is influenced by antiphospholipid antibodies we compared patients receiving warfarin for a diagnosis of antiphospholipid antibody syndrome aps to patients receiving warfarin for atrial fibrillation to evaluate the consistency between inr results obtained by different methods inr results obtained by finger stick capillary wholeblood and venipuncture noncitrated and citrated wholeblood were compared with our laboratory plasmabased prothrombin time CA five patients with aps and both elevated antibetaglycoprotein i C2 and positive lupus anticoagulants had nonmeasurable protime inr results and generally higher hemochron signature inr results than the plasmabased method but the corresponding chromogenic factor x results were not supratherapeutic for the remaining patients differences between the plasmabased inr and the pointofcare inr results ranged from to the differences were similar for patients with aps and atrial fibrillation for all inr comparisons with the exception of the plasmabased method compared with the protime which showed a mean absolute difference of for aps patients and of for atrial fibrillation patients p in a subset ofaps patients the protime system will not yield an inr result and the hemochron signature citrate and noncitrate wholeblood inr results will exhibit elevated inr results for this subset of aps patients we suggest using an alternative method to monitor warfarin | MEDAL |
this study was done to test whether subitizing versus counting are attention demanding based on whether they can be performed during the attentional blink ab erps were recorded while participants performed a task requiring them to judge the number of dots presented and this judgment task either followed the presentation of a taskrelevant item in a rapid CS- presentation stream dualtask or the potential target was task irrelevant singletask the behavioral data demonstrated that t accuracies decreased as a function of the number of dots not only in counting range but also in subitizing range the erp results showed a delayed p component in the dualtask condition and this was equally true for both subitizing and counting conditions furthermore the p amplitude was reduced during the ab and this was still equally true for both the subitizing and counting conditions the present results suggest that both subitizing and counting require attention and that subitizing is not a purely preattentive process | MEDAL |
matrix metalloproteinases mmps may contribute to the OD of EM genetic variations in several mmp promoters may influence the transcription and expression of mmps the purpose of the present T0 was to assess how gene polymorphisms in the mmp and mmp promoters affect the risk of OD of EM we genotyped women with endometriosis and control subjects in north china there was a significant difference in frequency of the mmp genotype between cases and controls p the g homozygote in endometriosis and controls was significantly different p the frequency of the g allele among affected women was significantly higher than among the healthy controls p however the overall genotype and allelotype distribution of the mmp single nucleotide polymorphism snp in patients was not different from that of controls p or mmp and mmp polymorphisms were in linkage disequilibrium in cases and controls d p the haplotype frequency distribution derived from these two polymorphisms was significantly different between cases and controls p the haplotype analysis suggested an implication of both mmp and mmp polymorphisms in the susceptibility to EM we conclude that the mmp promoter snp and mmp ga haplotype may modify susceptibility to endometriosis but that the mmp promoter snp is unlikely to be associated with EM in the population of north china | MEDAL |
condyloma acuminatum is a viral infection of near epidemic proportions both men and women are affected equally most lesions are on the external genitalia and the mucous CM of the urethra or the vagina a rare occurrencv was similar to that in intact cats in contrast rsna map and hr decreased significantly following BUP mgkg iv during nitrous oxidehalothane anesthesia cardiovascular depression following BUP iv during nitrous oxidehalothane anesthesia may be caused by both a decreased sympathetic activity and a direct myocardial depression | MEDAL |
embryonic stem cells escs can be propagated indefinitely in SC while retaining the ability to differentiate into any cell type in the organism the molecular and cellular mechanisms underlying esc pluripotency are however poorly understood we characterize a population of early mesodermspecified em progenitors that is generated from mouse escs by bone morphogenetic protein stimulation we further show that CFU-S escs are actively regenerated from em progenitors by the action of the divergent homeodomaincontaining protein nanog which in turn is upregulated in em progenitors by the combined action of leukemia inhibitory factor and the early mesoderm transcription factor tbrachyury tiates was developed it involves a reaction of suitably protected nucleosides with triethylammonium phosphinate in the presence of pivaloyl chloride followed by selenization of the intermediate nucleoside phosphinates with triphenylphosphine selenide to produce the corresponding nucleoside hphosphonoselenoates in yields | MEDAL |
tumorassociated macrophages tams play an important role in the immune response to cancer but the mechanisms by which the tumor microenvironment controls tams and t cell immunity are not CR understood here we report that kynurenine produced by glioblastoma cells activates aryl hydrocarbon receptor ahr in tams to modulate their CF and t cell immunity ahr promotes ccr expression driving tam recruitment in response to ccl ahr also drives the expression of klf and suppresses nfκb activation in tams finally ahr drives the expression of the ectonucleotidase cd in tams which promotes cd | MEDAL |
oxyhemoglobin desaturation in patients with sickle cell disease has been proposed as a possible mechanism in the initiaton of vascoocclusive pain crises nocturnal oxyhemoglobin desaturation nod has been described with a prevalence of up to in children and adolescents with sickle cell disease the objective of this T0 was to evaluate the mechanisms of nocturnal oxyhemoglobin desaturation in sickle cell disease and determine the role of obstructive sleep apnea we performed channel PSGs and pulmonary function testing in patients with sickle cell disease ages years who had documented desaturation on home oximetry studies the median saturation awake was quartile range median saturation during rem sleep was and during nonrem sleep the median respiratory disturbance index was low quartile range twelve patients had no obstructive apnea recorded while patients had a total of or episodes during the entire T0 the median snoring time was of total sleep time quartile range there was no correlation between number of obstructive apneas and mean sleeping saturation r p there was no rho between pulmonary CF data and prevalence of nod there was a strong positive rho between sleeping and awake saturation r p we conclude that while nocturnal oxyhemoglobin desaturation may be common in children and adolescents with sickle cell disease upper AO does not appear to play an important role in its genesis | MEDAL |
AML leukemia aml in people over age is characterized by adverse cytogenetic characteristics prior myelodysplasia and phenotypic features predictive of poor response to induction chemotherapy and brief leukemiafree survival because increased treatmentrelated toxicity complicates both induction and consolidation chemotherapy most studies of aml in the elderly focus on induction regimens designed to reduce toxicity consolidation usually consists of a repeat cycle of conventionaldose induction chemotherapy older patients who achieve complete remission may represent a select population clinically distinct from patients receiving induction therapy regardless of the consolidation regimen the duration of pCR is months to months with longterm leukemiafree survival rates of percent to percent in the ucla experience patients over age who received consolidation chemotherapy and pretreatment characteristics similar to elderly patients undergoing induction postremission treatment varied from standarddose arac to highdose arac consolidation followed by autologous stemcell transplantation LFS appears to be longer with highdose arac and autologous stemcell transplantation further randomized studies should be conducted to determine the feasibility of and response to postremission treatment | MEDAL |
diverse environmental and physiological factors are known to induce the transcription of a set of genes encoding special protective molecules known as molecular chaperones within our cells literature abounds in evidence regarding the varied roles these guides can effectively perform in our system highly conserved through evolution from the prokaryotes to the eukaryotes these make perfect study tools for verifying their role in both the pathogenesis as well as the therapeutics of varied neurodegenerative autoimmune and potentially malignant disorders and varied cancer states we present a concise review of this ever dynamic molecule highlighting the probable role in a potentially malignant disorder oral lichen planus | MEDAL |
ssulfonated gammaglobulin ggs derived from human gammaglobulin by selective sulfonation retains the dimensional structure and antibody activity of s gammaglobulin ggs does not bind with complement and is therefore suitable for i.v. fc activity is recovered through in vivo conversion to IN globulin following iv administration a total of administrations of ggs was made to patients with primary immunodeficiency syndrome the frequency of episodes of fever cough and infections suffered by those patients who had been treated with other globulin preparations for about one year before the administration of ggs was compared with that following replacement ggs therapy for about one year symptomatic relief on administration of ggs was confirmed to be excellent the administration of mgkgbw of ggs resulted in the igg level rising to mgdl with a decrease to mgdl after one week the igg level at two weeks was mgdl it is possible to maintain an igg level of mgdl by administration of mgkgbw of ggs once every weeks | MEDAL |
ST reduction in plasma tryptophan TD produces a relapse of depressive PS in of previously depressed patients recently recovered with serotonin reuptake inhibitor treatment TD does not consistently increase DS in unmedicated depressed patients or in depressed patients whose PS are remitted with a norepinephrine reuptake inhibitor these data suggest that SRI treatment itself may confer vulnerability to the OD of depressive PS during tryptophan depletion in order to further investigate this possibility six HI underwent doubleblind placebocontrolled tryptophan depletion before and following six weeks of treatment with fluoxetine mgday no increased vulnerability to the moodlowering effects of TD occurred as a result of fluoxetine treatment additionally fluoxetine treatment itself was not associated with changes in mood or quality of life in these healthy volunteers these data indicate that SRI treatment CT does not produce the depressive effects of TD that are observed in serotonin reuptake inhibitortreated depressed and obsessive compulsive disorder patients | MEDAL |
laparoscopic cholecystectomy lsc is being performed increasingly often the carbon dioxide cavity increases endexpiratory carbon dioxide exco which can be regulated by mechanical ventilation because about carbon dioxide remains in the patient at the end of surgery we were interested in its influence on spontaneous respiration patients and methods fifteen patients classed as asa and undergoing lsc were compared with patients also asa undergoing laparotomy for cholecystectomy lap all patients had balanced anaesthesia with FE enflurane nitrous oxide and vecuronium after surgery they were extubated when spontaneous QO2 and vigilance were adequate in the next h we continuously determined exco in the expired air through an intranasal catheter and oxygen saturation sat respiratory rate rr and heart rate hr using oscar datex and ohmeda braun apparatus while the patients were breathing room air the blood pressure bp was determined intermittently postoperative pain treatment was standardized results the CG were reduced comparable with respect of the anthropometric data because the weight was significantly higher in the lap group fentanyl consumption was also significantly higher in the lap group reflecting the more pronounced trauma than with lsc mean exco was mmhg after lsc and mmhg after lap p less than or equal to continuously decreasing in the lsc group and increasing in the lap group to mmhg T3 h mean rr was min after lsc and min after lap during this period p less than or equal to there were no differences in sat hr min and bp mmhg discussion and conclusions the remaining carbon dioxide T3 lsc has important implications for postoperative spontaneous respiration probably due to an activation of carbon dioxide receptors rr is increased to eliminate residual carbon dioxide this is confirmed by a significantly increased exco compared with that in the lap group this effect lasts at least h exco being comparable in both groups but rr is still increased after lsc this different respiratory pattern does not affect sat being normal without hypoxic episodes cardiovascular parameters were also normal without group differences we conclude that the carbon dioxide peritoneal cavity has important consequences for postoperative ventilation using our anaesthetic technique and postoperative treatment exco reaches normal values after about h due to an increased rr if other methods eg stronger opioids which decrease carbon dioxide response are used this effect may even be prolonged and more pronounced we are now performing an investigation to evaluate this effect | MEDAL |
the T0 compared quality and freezability of stallion semen during breeding and nonbreeding seasons ejaculates were collected twice per week from four stallions during may n and december n the semen was mixed with SM extender centrifuged and resuspended in fresh extender aliquots of this sperm suspension were separated from extender and diluted in talp medium for sperm DUE or with cryoextender type gent or a combination of triladyl and skim milk samples of ml were cryopreserved in straws using a programmed freezer parameters of sperm quality were evaluated before and T3 freezingthawing these included percentages of motile spermatozoa and of morphological IN sperm typical injuries were demonstrated by scanning electron microscopy sem the acrosomal status was visualised using fitcconjugated peanut agglutinin and the acrosome reaction was induced by A23187 the chromatin stability was estimated by acridine orange test in winter the average percentages of motile and morphologically normal sperm and respectively were higher than during the breeding season in may and p after freezingthawing the proportions of vital and IN sperm decreased significantly the number of motile sperm declined to and in may and december range and of morphologically intact sperm to in both seasons results of sem showed typical membrane ruptures in the acrosomal region and some sperm with abnormal necks the proportion of frozen sperm with spontaneous acrosome reaction was higher during winter versus suggesting a higher degree of membrane reactivity percentages of spermatozoa with denaturated chromatin were minimal and showed minimal differences between fresh and frozen state stallions or seasons an additional decondensation treatment with papain and dte revealed a slightly enhanced number of spermatozoa with denaturable dna T3 cryopreservation especially in december the influence of cryoextenders was not significant for most sperm parameters but there was a high R2 between the stallions altogether the influence of AF on the quality of spermatozoa has the following rank order cryopreservation stallion season different cellular structures seem to have different susceptibilities to physicochemical stress the cryopreservation of sperm during december results in survival rates similar to those measured during the breeding season even more important for successful preservation is the selection of suitable semen donors | MEDAL |
prothoracicotropic hormone ptth is a brain neuropeptide that stimulates the prothoracic glands to synthesize ecdysone an event that leads to insect molting both cAMP camp and calcium have been implicated in ptth action with current evidence favoring camp as the messenger directly regulating ecdysone synthesis to further define the role of camp in ptth action the activity of campdependent protein kinase camppk was examined in prothoracic PG from two developmental stages of the tobacco hornworm manduca sexta day fifth instar larvae and day pupae prothoracic PG at each of these stages of OD possess two forms of camppk which resemble the vertebrate type i and type ii isozymes with the latter being the predominant form greater than marked developmental differences exist in the degree of activation of soluble camppk following in vitro SE of the PGs to ptth in larval PG soluble camppk is activated within min of initial exposure to doses of ptth that stimulate ecdysone synthesis by contrast activation of soluble camppk in pupal glands occurs only when ptth is po in the presence of a phosphodiesterase inhibitor developmental differences in the activation of camppk by ptth were qualitatively identical to previously observed differences in ptthstimulated accumulation of intracellular camp the results suggest an involvement of soluble camppk in the response of day fifth instar larval prothoracic PG to ptth but indicate a difference in the nature intracellular location or time course of activation of hormonesensitive protein kinase in day pupal PG | MEDAL |
phosphorylation of the dalton myosin light chain is necessary for force generation but not for force maintenance the purpose of this study was to determine if the magnitude of the transient in S1 light chain phosphorylation affected force maintenance in swine carotid medial strips strips were either depolarized with k and then exposed to a ca channel blocker normal MLCP transient or were exposed to the ca channel blocker before k depolarization blunted myosin light chain phosphorylation transient the level of force maintained was the same regardless of the experimental protocol indicating that the prior PH of myosin light chain phosphorylation did not affect the maintained force whereas the phasic response to k depolarization of strips pretreated with ca channel blocker was depressed in those treated with verapamil only minimal effects were observed with nifedipine these findings suggest an additional action for verapamil besides ca channel blockade | MEDAL |
we examined the sensory properties of cells in the anterior bank of the caudal part of the superior temporal sulcus caudal sts in anesthetized paralyzed monkeys to visual AEP and somesthetic stimuli in the anterior bank of the caudal sts there were three regions distinguishable from each other and also from the middle temporal area mt in the floor of the sts and area tpt in the superior temporal gyrus the three regions were located approximately in the respective inner middle and outer thirds of the anterior bank of the caudal sts these three regions are referred to from the inner to the outer as the medial superior temporal region mst the mostly unresponsive region and the caudal sts polysensory region cstp respectively the extent of mst and its response properties agreed with previous studies cells in mst responded exclusively to visual stimuli had large visual receptive fields rfs and nearly all showed directional selectivity in the mostly unresponsive region three quarters of cells were unresponsive to any stimulus used in this study a quarter of the cells responded to only visual stimuli and most did not show directional selectivity for moving stimuli several DS cells responded to movements of threedimensional objects but not of projected stimuli the response properties of cells in the superficial cortex of the caudal superior temporal gyrus a part of area tpt external to cstp were different from those of cells in the three regions in the anterior bank of the sts cells in tpt were exclusively auditory and had much larger auditory rfs mean degrees than those of acousticallydriven cstp cells mean degrees the cstp contained unimodal visual AEP and somesthetic cells as well as multimodal cells of two or all three modalities the sensory properties of cstp cells were as follows out of cells recorded cells were unimodal visual AEP and somesthetic cells were bimodal visualauditory visualsomesthetic and auditorysomesthetic and four cells were trimodal visual and auditory responses were more frequent than somesthetic responses the ratio of the population of cells driven by visual auditory somesthetic stimuli was visual rfs were large mean diameter degrees but twothirds were limited to the CL visual hemifield about half the cells showed DS for moving visual stimuli none showed selectivity for particular visual shapesabstract truncated at words | MEDAL |
from to patients with unilateral operable breast CA t t t were treated with breast conservation and irradiation at the gustave roussy institute or at the henri mondor hospital the minimum followup is years most patients with t greater than cm underwent radiation therapy with the RT in place while the greater part of patients with t less than cm received radiation therapy after tumorectomy the breast and draining CL node Az received widefield telecobalt irradiation to gy the dose to the tumor site was boosted using iridium implantation additional irradiation was given to the internal mammary and lower axillary nodes using an electron beam the years ned survival rate was and for t t and t PT respectively the ned survival for t less than or equal to cm was the local recurrence rate was and for t t and t tumors respectively of the patients with local recurrence underwent surgical salvage complications were rare cosmetic results were satisfactory in most patients including the t group the proportion of breasts conserved among patients living ned at years was and for t t and t tumors respectively in after almost years experience using breast conserving techniques we modified our treatment policies in close collaboration with our surgical team hel cbye extending the indications for tumorectomy and associating routine surgical exploration of the lower axilla | MEDAL |
treatment of patients with acute ML aml who do not wish to accept blood product transfusion including jehovahs witnesses is extremely challenging the use of conventional chemotherapy for induction of pCR cr results in profound anemia and TP requiring frequent transfusions of blood products without which such treatment will be lifethreatening finding a well tolerable minimally myelosuppressive induction regimen for such patients with aml is a clear example of area of unmet medical need here we report a successful treatment of a yearold jehovahs witness with newly diagnosed aml with pegasparaginase vincristine and methylprednisolone the aml was characterized with normal karyotype and mutations in isocitrate dehydrogenase idhargser nucleophosmin npmtrpcysfs and neuroblastoma ras viral oncogene homolog nrasgyva T3 one day cycle of treatment the patient achieved complete remission with incomplete count recovery cri and after the second cycle he achieved cr with full blood count REC the patient has never received any blood products notwithstanding that myeloperoxidaseinduced oxidative degradation of vincristine results in its lack of activity as monotherapy in aml its combination with corticosteroid and asparaginase has resulted in a robust remission in this patient diminished steroid clearance by asparaginase activity as well as reduction in serum glutamine level induced by glutaminase enzymatic activity of asparaginase may have contributed to ERP killing of the myeloblasts that carry idhnpmnras mutations in conclusion asparaginasecontaining regimens which are approved for treatment of ALL one all but not aml can be used to treat patients with aml who do not accept ABT | MEDAL |
in mental health care both clinical and scientific decisions are based on withinsubject comparisons of test scores on the same selfreport questionnaire at different points in time to establish the validity of test score comparisons over time longitudinal measurement invariance should be established the current study tested whether the item beck scale for suicide ideation bss is measurement invariant mi over time as the first five items of the scale are often used to screen for the presence of suicidal thoughts we also tested a model consisting of only the first five items psychiatric in and outpatients n completed the questionnaire upon admission and T3 months by means of confirmatory FA cfa we tested whether the parameters of a single factor model were equal over time all fit indices indicated that both the item questionnaire and the fiveitem screener were measurement invariant over time this means that changes in testscores over time can be attributed to true changes in the construct of interest these findings legitimate the use of the item scale and the fiveitem screener in longitudinal assessments | MEDAL |
to compare the usefulness of power doppler imaging and color doppler imaging in the V1 DUE of gastrointestinal lesions patients with focal gastrointestinal tract lesions were examined with both SP and color doppler imaging two reviewers blinded to the diagnosis compared intramural vascularity detected by each of these methods SP doppler imaging detected flow in patients with nonischemic lesions whereas CD imaging detected flow in only patients neither modality detected flow in three patients with transmural infarction but only PD imaging detected minimal flow in the two patients with reversible ischemia power doppler imaging improves visualization of intramural gastrointestinal vascularity increasing the level of confidence in differentiating ICM from nonischemic lesions | MEDAL |
empirical antibiotic treatment is selected to target causative bacteria with antibiotics to which they are not resistant we analysed the increase in bacterial resistance among individual patients associated with antibiotic SE in the month prior to infection onset compared to unexposed patients from a series of prospective cohort studies in the period at beilinson hospital israel consecutive patients suspected of infection were included we analysed resistance to antibiotics in bacterial isolates from patients with clinically significant and microbiologically documented infections starting antibiotics after obtaining cultures n in GN bacteria significantly higher rates of resistance was associated with exposure to antibiotics while no significant associations were found for grampositive bacteria significant odds ratios ors for increased resistance to classes of antibiotics ranged from to in GNB from patients exposed to any antibiotics with quinolones having the highest or followed by aminoglycosides penicillins with βlactamase inhibitor and cephalosporins the majority of significant associations also had significant ors T3 SE to another class of antibiotics indicating a substantial effect of crossresistance in conclusion increased resistance was observed following exposure to antibiotics both from the same class and from other classes the results indicate a reason to adjust the expected coverage of empirical antibiotic treatments for patients recently exposed to antibiotics with some antibiotics being more affected than others | MEDAL |
telomeres are repetitive dna sequences located at the ends of chromosomes telomeres are shortened by repeated cell divisions and by oxidative dna damage and cells with critically shortened telomeres cannot divide we hypothesized that chronic GE reflux disease gerdinduced injury of the esophageal squamous epithelium results in progressive telomeric shortening that eventually might interfere with mucosal healing to address our hypothesis we compared telomere length and TA in biopsy specimens of esophageal squamous epithelium from gerd patients and CP endoscopic biopsies were taken from the esophageal squamous epithelium of patients with gerd longsegment barretts esophagus lsbe shortsegment ssbe gerd without barretts esophagus and control patients without gerd telomere length was assessed using the terminal restriction fragment assay and telomerase activity was studied by the pcrbased TRAP CA patients with gerd had significantly shorter telomeres in the distal esophagus than controls vs se kbp p among the patients with gerd telomere length in the distal esophagus did not differ significantly in those with and without barretts esophagus lsbe ssbe gerd without be kbp no significant differences in telomerase activity in the distal esophagus were noted between patients with gerd and controls vs rius telomeres in the squamous epithelium of the distal esophagus of patients who have gerd with and without barretts esophagus are significantly shorter than those of patients without gerd despite similar levels of telomerase activity | MEDAL |
the use of fouriertransform midinfrared ftir spectroscopy is of interest to the dairy industry worldwide for predicting milk composition and other novel traits that are difficult or expensive to measure directly although there are many valuable applications for ftir spectra noise from differences in spectral responses between instruments is problematic because it reduces prediction accuracy if ignored the purpose of this study was to develop strategies to reduce the impact of noise and to compare methods for standardizing ftir spectra in order to reduce betweeninstrument R2 in multipleinstrument networks noise levels in bands of the infrared spectrum caused by the water content of milk were characterized and a method for identifying and removing outliers was developed two standardization methods were assessed and compared piecewise direct standardization pds which related spectra on a primary instrument to spectra on other secondary instruments using MZ milkbased REF samples n analyzed across the instruments and retroactive percentile standardization rps whereby percentiles of observed spectra from routine milk test samples n were used to map and exploit primary and secondaryinstrument relationships different applications of each method were studied to determine the optimal way to implement each method across time industrystandard predictions of milk components from spectra records were regressed against predictions from spectra before and T3 standardization using pds or rps the pds RPA resulted in an overall decrease in root mean square error between industrystandard predictions and predictions from spectra from to g ml for fat from to g ml for protein and from to g ml for lactose reductions in prediction error for rps were similar but less consistent than those for pds across time but similar reductions were achieved when pds coefficients were updated monthly and separate primary instruments were assigned for the north and south islands of new zealand we demonstrated that the pds RPA is the most consistent method to reduce prediction PE across time we also showed that the rps approach is sensitive to shifts in milk composition but can be used to reduce prediction PE provided that secondaryinstrument spectra are standardized to a primary instrument with samples of broadly equivalent milk composition AGA implementation of either of these approaches will improve the SQ of predictions based on ftir spectra for various downstream applications | MEDAL |
in this paper it is demonstrated that the effects of acoustic attenuation may play a significant role in establishing the quality of tomographic optoacoustic reconstructions accordingly spatially dependent reduction of signal amplitude leads to quantification errors in the reconstructed CSD of the optical absorption coefficient while signal broadening causes loss of image resolution here we propose a correction algorithm for accounting for attenuation effects which is applicable in both the time and frequency domains it is further investigated which part of the optoacoustic signal spectrum is practically affected by those effects in realistic imaging scenarios the validity and benefits of the suggested modelling and correction approaches are experimentally validated in phantom measurements | MEDAL |
a yearold woman was referred to our department for evaluation of an incidental adrenal mass an ABD ct scan revealed a cm RA adrenal mass the patient had been diagnosed with hypertension years earlier and had taken antihypertensive medications intermittently her PE demonstrated a round face CE obesity and mild hypertension SS CAs renin aldosterone acth and h urinefree cortisol vanillylmandelic acid levels were within normal limits however serum cortisol level was markedly elevated and the CR was disturbed successive lowdose and highdose dexamethasone suppression tests were ordered for DUE of a SF-36 adrenal incidentaloma about h after taking the second dose of mg dexamethasone she suddenly developed NV palpitations and anxiety with severe hypertension on the same day we measured serum CAs which were markedly elevated an elective laparoscopic right adrenalectomy was performed and pathologic examination confirmed the diagnosis of pheochromocytoma one week T3 surgery serum and urine catecholamine C2 returned to normal the patient has remained normotensive without any medications and clinically well patients with adrenal incidentalomas may have a PET mass that does not always manifest as a full symptomatic disease during the investigation of AI pheochromocytoma should ideally be ruled out before administering corticosteroids | MEDAL |
the presence of a congenital anomaly in coronary arteries can be the cause of a defective coronary flow and ischaemic PS although they are rare we must suspect them in the presence of major CE in young people a single PD is present if the entire coronary system arises from a solitary ostium its presence is regarded as having little clinical significance and it is usually a fortuitous finding on coronary angiography we report the case of a patient with effort anginal PS with a single coronary artery arising from the RA sinus of valsalva without obstructive atherosclerotic lesions | MEDAL |
EP exploration was carried out in patients before and during administration of vincristine sulphate mgm body surface area the patients had stage iii or iv lymphoreticulosarcoma and received one injection of vincristine weekly for weeks compared with i.c.v. findings motor and SCV as well as delay in triceps surae h reflex remained unchanged sensory nerve amplitude and density of distal muscle electromyographic recordings rapidly decreased the amplitude of distal tendinous reflexes rapidly diminished whereas that of the h reflex remained SD these results being similar to those observed in exp acrylamide toxicity where a dying back hemopathy has been demonstrated it is suggested that the neuropathy induced by vincristine in man is of the same type | MEDAL |