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contractions of single motor units in the gastrocnemius soleus and pretibial flexor muscles were elicited by intracellular stimulation of the innervating motoneurones kittens being and weeks of age were used the aim was to establish the pattern of PN differentiation of the AD motor unit types burke et al hammarberg and kellerth b in the developing type s units of the soleus muscle the mean value for ICT showed a transient decrease during the early postnatal period but the twitch halfrelaxation time hrt the duration of motoneurone postspike afterhyperpolarization ahp and the susceptibility to fatigue remained virtually unchanged during the age period studied in the units of the developing fast twitch muscles the ICT hrt and susceptibility to fatigue were significantly different from those of the soleus units already at week of age at weeks of age the contractile characteristics typical of the AD type ff and fr units were attained the ahp duration gradually decreased up to weeks of age and it was then considerably shorter than both at week of age and in the AD stage
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previous studies of the ferret visual SC indicate that the development of DS requires visual experience here we used twophoton calcium imaging to T0 the OD of direction selectivity in SL neurons of the mouse visual cortex in vivo surprisingly just T3 eye opening nearly all orientationselective SN were also direction selective during later development the number of SN responding to drifting gratings increased in parallel with the fraction of neurons that were orientation but not direction selective our experiments demonstrate that direction selectivity develops normally in DR mice indicating that the early OD of DS is independent of visual experience furthermore remarkable PET similarities exist between the OD of direction selectivity in cortical neurons and the previously reported OD of DS in the mouse retina together these findings provide strong evidence that the OD of orientation and DS in the mouse BB is distinctly different from that in ferrets
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killer cell lectinlike receptor g klrg is a type ii TM glycoprotein inhibitory receptor belonging to the c type lectinlike superfamily klrg exists both as a monomer and as a disulfidelinked homodimer this wellconserved receptor is found on the most mature and recently activated nk cells as well as on a subset of effectormemory t cells using klrg tetramer as well as other methods e n and rcadherins were identified as klrg ligands these cadependent cellcell adhesion molecules comprises of an extracellular domain containing five cadherin repeats responsible for cellcell interactions a TM domain and a cytoplasmic domain that is linked to the actin cytoskeleton generation of the klrg tetramer was essential to the identification of the klrg ligands klrg tetramer is also a unique tool to elucidate the roles cadherin and klrg play in regulating the immune response and tissue integrity
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the role of nmethyldaspartate nmda receptors in SM processes was examined using a yshaped maze and a stepthrough PA task in mice in the ymaze the total number of arm entries which represents locomotor activity and alternation behaviour thought to reflect working memory were measured competitive nmda antagonists cgs cisphosphonomethylpiperidinecarboxylate and cpp carboxypiperazinylpropylphosphate impaired spontaneous alternation at doses which reduced locomotion of mice nmethyldaspartate prevented the impairment of alternation and decrease of locomotor activity produced by cgs and cpp these results suggest that nmdadependent processes are involved in the mechanisms of WM in contrast the MK-801 nmda antagonist mk methyldihydrohdibenzoadcycloheptanimine maleate dramatically enhanced the total number of arm entries while reducing alternation behaviour nmethyldaspartate had no effect on mk induced enhancement of locomotor activity and impairment of alternation in the passive avoidance task mice were TR to avoid entry into the dark compartment at doses which impaired working memory in the alternation task cpp cgs and mk reduced acquisition when po before training nmethyldaspartate antagonized the effect of cpp cgs and mk neither cpp nor mk affected retention when po immediately after training or before testing retention nmethyldaspartate had no effect on PR with highintensity shock but facilitated PR with LI shockabstract truncated at words
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the principal objective of this article is to present evidence for the numerical and biological importance of cell death in tumour growth and regression much of this death has the morphology of apoptosis a process observed elsewhere in biology in a variety of circumstances recent studies on the mechanism of apoptosis in nonneoplastic cells suggest that a relatively small number of TPS intracellular changes are involved two of these are described endonuclease activation within the nucleus which coincides with the characteristic morphological changes there and altered expression of surface carbohydrates which may be responsible for the swift recognition and phagocytosis of apoptotic cells it seems probable that similar events occur during the apoptosis of tumour cells further knowledge of the control of these endogenous mechanisms for effecting cell death could lead to powerful new means of controlling the growth of tumours
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we reviewed the autopsy material of patients with rheumatoid ICA ra and studied the cardiac changes is these patients SVR vasculitis was observed in cases among patients with ra in cases we found vasculitis of the subepicardial andor intramural coronary vessels coronary arteritis or arteriolotis has led to multifocal small andor C1 myocardial infarctions in cases and was the cause of progressive cardiac insufficiency the direct cause of death multifocal circumscribed myocardial infarction reported in rheumatoid disease in cases RN were found in the myocardium of them related to vasculitis we suggest that rheumatoid nodules are the most severe form of necrotizing granulomatous vasculitis pathognomic nodular rheumatoid pericarditis was seen in cases and diffuse rheumatoid pericarditis in another case pathognomic nodular valvulitis was found in cases RA nodules localized to the epi myo or Endo were observed on patients generalized secondary amyloidosis was observed in of the patients with ra AA was prevalent in the HR in of cases relative frequency
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CC crc is the second leading cause of cancer death crc screening with a fecal immunochemical test fit is important as occult blood may be detected to offer iowa research network members in family physician offices the opportunity to provide fits at no charge to patients in need and determine how many of the tests would be handed out to patients and how many would be returned to the office eight family physician offices agreed to participate and twoday fits were provided potentially providing patients a crc screening test one hundred and eighty of the fits were handed out to patients of the patients who returned at least one card had negative results were positive and were ind of patients with a positive result had a followup colonoscopy providing fits at no charge to the offices was an expensive endeavor implementing this forced a NC in office routine and the type of FOBT used less than half of the fits were given out to patients and of those given out about half of the patients returned a fit for those who returned fits and had positive findings followedup with a colonoscopy office nurses implementing the crc screening need to be included in the planning of the type of FOBT used and receptive to the project
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an episode of suboptimal growth poor feathering and behavioural CA in broilers in scotland during the winter of is described this was considered to be associated with mouldcontaminated maize and wheat components of the feed from which fusaria were isolated in persistently high numbers four species fusarium culmorum f tricinctum f nivale and f moniliforme were identified CF extracts of the raw materials and of an artificial medium in which three of the fusarium species were cultured proved toxic to tissue cultures of a human epithelial cell line hep ii TPS ID by thin SL chromatography of the mycotoxins deoxynivalenol zearalenone and diacetoxyscirpenol was achieved in some extracts in addition several other areas of the chromatograms were found to be toxic in the hep ii cell system and these may contain toxins for which standards were not available or alternatively previously uncharacterised fungal metabolites it was concluded that the toxins produced by the fusaria were major contributing AF to the disease PS shown by the birds
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a female infant with severe mental retardation general hypotonicity and a PH of generalised oedema cyanosis HR murmur and nystagmus in the first days of life was found to have both a translocation and a deletion her karyotype was xxdeltp ter leads to qq leads to qterpter leads to qq leads to q ter the karyotype of both parents was normal the proposita is the result of a three break point exchange and is monosomic for part of the dark band q q of chromosome it is suggested that in cases with mental retardation and apparent balanced de novo reciprocal translocation a small undetected deletion in one of the chromosomes involved in the translocation could explain the mental retardation
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a specific lcms method was developed for separation identification and characterization of the processrelated substances and degradation products in tofacitinib citrate the separation was achieved on a lichrospher c column mm×mm μm by linear gradient elution of ammonium acetate solution ph adjusted to by formic acid and acetonitrile at a flow rate of mlmin forced Kd studies were conducted under hydrolytic acidic basic oxidative photolytic and thermal stress conditions as described in ich it was found that tofacitinib was SD under photolytic condition but degraded obviously in acidic basic thermal and oxidative conditions the high resolution tofms and msms were used for determination and structural identification of the related substances eleven major related substances were detected and identified as five processrelated substances and six Kd products and three of them were further synthesized and characterized by nmr spectroscopy the most plausible mechanisms involved in the formation of the related substances were also proposed since related substances have a signipational functioning social interaction and interpersonal relationships in patients with schizophrenia past researchers have reported reduced alpha and increased theta and delta spectral powers on quantitative eeg recordings in those with prominent negative symptoms
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this T0 was undertaken to characterize the adhesion of lst colon adenocarcinoma cells to h tnfalphastimulated human umbilical vein EC cells huvecs under flow in the presence and absence of platelets and erythrocytes cell IB to huvecs was significantly enhanced by simultaneous perfusion of thrombinactivated but not resting platelets this increase was achieved via a platelet bridging mechanism whereby a previously tethered lst cell primary tether captures a freeflowing cell secondary tether that subsequently attaches to the EC downstream of the already adherent cell the total number of RT cells tethering to huvecs and the percentage of secondary tethers relative to the total aein convertase egl indicating that the protein was efficiently targeted to the peptidergic sec pathway timelapse epifluorescence microscopy of idagfp revealed that dcvs moved in a saltatory and bidirectional manner dcv velocity profiles exhibited multiple distinct peaks suggesting the participation of multiple molecular motors with distinct properties differences between velocity profiles for axonal and dendritic processes furthermore suggested a polarized distribution of the molecular transport machinery study of a number of candidate mutants identified the kinesin unc kifa as the microtubule motor that is specifically responsible for anterograde axonal transport of dcvs at velocities of microms microms
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origins of dna replication are key genetic elements yet their identification remains elusive in most organisms in previous work we found that centromeres contain origins of replication oris that are determined epigenetically in the pathogenic yeast candida albicans in this study we used origin recognition complex orc binding and nucleosome occupancy patterns in saccharomyces cerevisiae and kluyveromyces lactis to train a machine learning algorithm to predict the position of AS arm noncentromeric origins in the c albicans genome the MM identified bona fide AS origins as determined by the presence of RIs on nondenaturing 2DE d gels importantly these origins function at their native chromosomal loci and also as autonomously replicating sequences arss on a linear plasmid a miniars screen identified at least one and often two ars regions of ≥ bp within each bona fide origin furthermore a bp acrich consensus motif was associated with the predicted origins and conferred autonomous replicating activity to the miniarss thus while centromeres and the origins associated with them are epigenetic arm origins are dependent upon critical dna features such as a IB site for orc and a propensity for nucleosome exclusion
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nociceptive stimulation has been considered to affect the expression of genes encoding endogenous neuropeptides and their receptors the effect of electric stimulation of the tooth pulp andor periaqueductal gray pag in rats on mrna levels of the selected neuropeptides and opioid receptors ors was investigated in comparison with control group without stimulation the C2 of mrna for the selected neuropeptides galanin gal vasopressin avp oxytocin ot substance p sp somatostatin som VIP vip endomorphin em and opioid receptors mor dor and kor in mesencephalic Thy and thalamic tissues were determined by realtime pcr it was demonstrated that in the control group expression of the tested neuropeptides was at a very low level in the mesencephalon and thalamus but at the higher level in the hypothalamus the highest expression of ors was observed in the MES nociceptive TP stimulation had the strongest effect in the hypothalamus elevating mrna C2 of all tested neuropeptides except som electric stimulation of pag either did not NC or downregulated mrna levels of the neuropeptides in the cerebral structures simultaneous stimulation of pag and tooth pulp either did not affect mrna C2 of the investigated neuropeptides or caused their slight decrease versus tooth pulp stimulation the noxious stimulation of TP increased also the C2 of or mrnas while stimulation of pag had the opposite effect the above results demonstrated that TP stimulation significantly upregulated the mrna levels for a number of neuropeptides and all three types of ors in the rat BB which would result in more potent antinociception in contrast pag stimulation downregulated the mrna levels of several neuropeptides and ors in the CBF tissues which would cause decreased synthesis of ors the obtained results represent a new insight into the mechanism of orofacial pain
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we consider bayesian methodology for comparing two or more unlabeled point sets application of the technique to a set of steroid molecules illustrates its potential utility involving the comparison of molecules in chemoinformatics and bioinformatics we initially match a pair of molecules where one molecule is regarded as random and the other fixed a type of mixture model is proposed for the point set coordinates and the parameters of the distribution are a labeling matrix indicating which pairs of points match and a concentration parameter an important property of the likelihood is that it is invariant under rotations and translations of the data bayesian inference for the parameters is carried out using markov chain MC simulation and it is demonstrated that the procedure works well on the steroid data the posterior CSD is difficult to simulate from due to multiple local modes and we also use additional data partial charges on atoms to help with this task an approximation is considered for speeding up the simulation algorithm and the approximating fast algorithm leads to essentially identical inference to that under the exact method for our data extensions to multiple molecule alignment are also introduced and an algorithm is described which also works well on the steroid data set after all the steroid molecules have been matched exploratory data analysis is carried out to examine which molecules are similar also further bayesian inference for the multiple alignment problem is considered
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acetyllcarnitine alc is known to affect several aspects of neuronal activity to evaluate the NE actions of this compound several endocrinological parameters were followed in alctreated and control animals during recovery from darkinduced anestrus in treated animals serum luteinizing hormone lh and prolactin C2 were higher than those of controls during the proestrous and estrous phases of the cycle and SS estradiol levels were higher during estrus no significant changes were observed in SS levels of folliclestimulating hormone and progesterone uterine weight was increased in alctreated rats during proestrus and estrus but not in diestrus the basal release of gonadotropinreleasing hormone gnrh from perifused hypothalamic slices of alctreated animals was elevated at proestrus and diestrus and gnrh PR elicited by HK was higher during all three phases of the cycle the basal release of lh from perifused pituitaries of treated animals was elevated in diestrus and the lh response to gnrh was higher in estrus and diestrus i depolarization with k caused increased lh secretion during proestrus and estrus in treated animals in contrast to these effects of alc treatment in vivo no direct effects of alc were observed during short or longterm treatment of cultured pituitary cells these results indicate that alc treatment influences hypothalamopituitary function in a cycle stagedependent manner and increases the sec activity of gonadotrophs and lactotrophs since no effects of alc on basal and agonistinduced sec responses of gonadotrophs were observed in vitro it is probable that its effects on gonadotropin PR are related to enhancement of gnrh neuronal CF in the hypothalamus
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the spontaneously hypertensive sh rat has an exaggerated sympathetic discharge which may result from an enhanced neuronal excitability in the central NS to test this hypothesis we examined the EP properties of neurons in the medial region of the nucleus of the solitary tract mnts a CE nucleus involved in the processing of baroreceptor afferent information in sh rats and normotensive spraguedawley sd rats an in vitro brainstem slice preparation was used to record intracellularly from SN in monthold sh rats and SN in monthold sd rats between the two groups there was no significant differences in resting membrane potential input resistance and spontaneous firing frequency or in action potential amplitude duration and afterhyperpolarization ahp there were no significant differences in SFA and posttetanic hyperpolarization pth delayed excitation de a manifestation of acurrent occurred in in sh and sd mnts neurons but the duration of de was significantly p shorter in sh mnts neurons we propose that att expression of IA may contribute to increased sympathetic drive in sh rats
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xeroderma pigmentosum xp variant patients are genetically predisposed to sunlightinduced skin cancer fibroblasts derived from these patients are extremely CS to the mutagenic effect of uv radiation and are abnormally slow in replicating dna containing uvinduced photoproducts however unlike cells from the majority of xp patients xp variant cells have a normal or nearly normal rate of nucleotide excision repair of such damage to determine whether their uv hypermutability reflected a slower rate of excision of photoproducts specifically during early s phase when the target gene for mutations ie the hypoxanthine guanine phosphoribosyltransferase gene hprt is replicated we synchronized 2C populations of normal and xp variant fibroblasts irradiated them in early s phase and compared the rate of loss of cyclobutane pyrimidine dimers and pyrimidinepyrimidones from dna during s phase there was no difference both removed of the pyrimidinepyrimidones within h and of the dimers within h there was also no difference between the two cell lines in the rate of repair during g phase to determine whether the hypermutability resulted from abnormal errorprone replication of dna containing photoproducts we determined the spectra of mutations induced in the coding region of the hprt gene of xp variant cells irradiated in early s and g phases and compared with those found in normal cells the majority of the mutations in both types of cells were base substitutions but the two types of cells differed significantly from each other in the kinds of substitutions but the two types differed significantly from each other in the kinds of substitutions observed either in mutants from s phase p or from g phase p in the variant cells the substitutions were mainly transversions in s in g in the normal cells irradiated in s the majority of the substitutions were gc at and most involved cc photoproducts in the transcribed strand in the variant cells irradiated in s substitutions involving cytosine in the TS were gc ta transversions exclusively gc at transitions made up a much smaller fraction of the substitutions than in normal cells p and all of them involved photoproducts located in the nontranscribed strand the data strongly suggest that xp variant cells are much less likely than normal cells to incorporate either damp or dgmp opposite the pyrimidines involved in photoproducts this would account for their significantly higher frequency of mutants and might explain their abnormal delay in replicating a uvdamaged template
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many viruses including members of several poxvirus genera encode inhibitors that block apoptosis by simultaneously IB the proapoptotic bcl proteins bak and bax the OPV vaccinia virus encodes the bcllike f protein which sequesters bak but not bax however n a potent virulence factor is reported to be Bcl-2 and to interact with bax here we investigated whether vaccinia virus inhibits bakbaxdependent apoptosis via the cooperative action of f and n we found that western reserve wr and δnl viruses inhibited drug and infectioninduced apoptosis equally meanwhile infections with δfl or δnlfl virus resulted in similar levels of bax activation and apoptosis outside the context of infection n did not block drug or baxinduced cell death or interact with bax in addition to f and n vaccinia virus encodes further structural homologs of bcl proteins that are conserved in orthopoxviruses including a a b c c B6 k and n however we found that these do not associate with bax or inhibit druginduced cell death based on our findings that n is not an y and administrative data to examine needsadjusted rates of prescription drug use by people of different ethnic CG
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we studied the buffer mechanism of human whole blood by means of a titration experiment under the open condition in which blood is exposed to carbon dioxide gas van slyke proposed the theory of a blood buffer mechanism in j biol chem however his theory is not applicable to our experiments because it did not take into consideration the effects of changes in volume and the concentration of bicarbonate ion in the buffer as a result of titration we studied the blood buffer mechanism theoretically by using graphical representation and developed a theory which we then applied to our experiments buffer value as defined by van slyke is the quantity of the base deltanohv in the sample without volume NC in gram equivalent per liter required to NC one unit in ph based on our blood buffer theory we obtain the experimental buffer value betaprime prime or minute which is the r vitamin and trace element on a subsample of subjects the mean standard deviation concentrations of plasma betacarotene alphatocopherol vitamin c Se and zinc among participants who were randomly assigned to receive a daily supplementation with betacarotene vitamin e VC Se and zinc for years were significantly higher than those who were assigned to receive PL specifically the mean concentrations among men in the MI group were micromoll for betacarotene micromoll for alphatocopherol microg ml for VC micromoll for selenium and micromoll for zinc the mean concentrations among women in the MI were micromoll for betacarotene micromoll for alphatocopherol microgml for vitamin c micromoll for Se and micromoll for zinc the values observed for betacarotene and VE in the supplementation group T3 years of intervention are those that have been associated with the lowest risk of cancer in observational studies they are definitely lower than concentrations reported in intervention studies showing an apparent negative effect of high levels of betacarotene supplementation on the lung cancer incidence rate in highrisk subjects initial level multiplied by data from the followup will ascertain if any plausible reduction in the incidence rate of cancers may be associated with such amounts of antioxidant agents
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for the patient scheduled for head and neck cancer surgery careful assessment of the airway demonstrates the most AGA course of action for securing the airway before surgery begins often the patient may be anesthetized safely before intubation of the tr the patient may require an awake examination of the airway under sedation and topical analgesia or an awake fiberoptic intubation before the induction of GA to secure the airway in some patients a tracheostomy may be needed T3 the T0 extubation of the trachea requires careful attention and may be even more of a challenge than the original intubation current principles and techniques for the anesthetic management of the patient undergoing HNC surgery are reviewed emphasis is placed on avoiding the airway problems associated with this kind of surgery
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the hypolipidemic and antiatherogenic effects of different NIC derivatives were studied five rb CG maintained on an atherogenic diet were given simultaneously various NIC derivatives mgkg body weightday nicotinic acid xantinolnicotinate betapyridylcarbinol or pirozadil bistrimethoxybenzoate pyridindiyldimethylene all EDC showed a clear hypocholesterolemic and antiatherogenic effect as measured by serum cholesterol and by planimetric DUE of the aortic lesions in terms of percent surface area affected in the aortas and coronary lumen the simultaneously observed elevation of the hdlldl cholesterol ratio of the aortic tissue possibly indicates an antiatherogenic effect of these changes
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in patients with marfan syndrome mfs distal AD can necessitate thoracoabdominal aortic aneurysm taaa repair in survivors of acute debakey type i dissection and those with debakey type iii dissection we examined outcomes of surgical repair of taaa in patients with mfs with distal aortic dissection
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we applied fMRI fmri to map the somatotopic organization of the primary motor cortex using voluntary movements of the hand arm and foot eight RH HS performed selfpaced repetitive flexionextension movements of the limbs while undergoing echoplanar imaging four subjects performed movements of the RA fingers and toes while the remaining subjects performed movements of the right fingers and elbow joint there was statistically significant PET activity in the left primary motor SC in all subjects the pattern of functional activity followed a topographic representation finger movements resulted in signal intensity changes over the convexity of the left motor SC whereas toe movements produced changes either at the interhemispheric fissure or on the dorsolateral surface adjacent to the interhemispheric fissure elbow movements overlapped the more medial signal intensity changes observed with finger movements functionally active regions were confined to the cortical ribbon and followed the gyral anatomy closely these findings indicate that fmri is capable of generating somatotopic maps of the primary motor cortex in individual subjects
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in an adequate environment primary avian tendon cells are capable of retaining both the full expression of differentiated function and a correct morphological orientation for week in SC at HD and in the presence of ascorbate they are fully stabiluced by intraductal injection of fresh trypsinbileblood mixture in addition the cya was localized histochemically in the pancreas basal camp concentration and cya activity were pmolesmg wet tissue and pmolesmg proteinmin respectively the AP drastically reduced the adenyl cyclase activity at T2 to pmolesmg proteinmin and totally suppressed cya activity at T2 T3 the onset of one without affecting camp levels the presence of sodium fluoride in the incubation medium prolonged the enzyme activity up to T2 the progressive disappearance of cya activity presumably resulted from the destruction of cellular integrity caused by autodigestion by the active proteolytic enzymes released during pancreatitis
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eye movements were induced by stimulating the ventral bank of the AES aes of chloraloseanesthetized cats intracortical microstimulation of this SC evoked centering movements of both eyes the RL of eye movement was ms range ms and the intensity of stimulation was microa range microa the evoked eye movements persisted T3 ablation of the CP FC eye field of both sides these results suggest that the ventral bank of the aes is involved in the control of eye movements
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bladder substitution in whole or in part represents a growing field within the specialty of surgery the principles and procedures associated with bladder augmentation are well established and include the use of spatulated rather than IN bowel segments and appreciation of the importance of adequate protection of the augmented bladder from urinary extravasation by means of both the suprapubic and ureteral catheter drainage the principles pertinent to continent urinary diversion by means of total bladder replacement have not been as well defined problems still exist with each of the described procedures there has yet to be an operative technique that will allow for orthotopic micturition that is free from the difficulty of enuresis with those operations employing a continent abdominal stoma requiring intermittent catheterization the competence of the continence mechanism is not assured in every case nevertheless the psychologic advantages of freedom from urinary collection devices can stimulate patients to seek out total bladder substitution when facing cystectomy an additional large patient group already diverted by means of urinary conduits is seeking conversion to total bladder substitution it is certain that this large patient population will stimulate the operative technique of bladder substitution so that we will have a dependable procedure to employ in future years
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tomato and cucumber seedlings were distributed into groups five for each plant of plants each the plants were irrigated for weeks with primary treated wastewater group a secondary treated wastewater group b chlorinated secondary treated wastewater group c a fertilizer dilution group f and tap water group m all precautions were taken to secure that there was no direct contact between the wastewater and the edible portions of the crops during this period and on a weekly basis the height and number of leaves was monitored while at the end the dry weight of leaves stems and roots for each plant of each group was measured based on these growth parameters both types of plant in groups a and f recorded the most significant OD compared to the other three groups the plants irrigated with tap water recorded the smallest development in every case plants in groups b and c were similar with a slight but not significant superiority for the plants irrigated with AA treated wastewater probably as a result of some phytotoxic effects of residual chloride in the chlorinated wastewater the presence of nutrients and specifically nitrogen in the various solutions explains the differences satisfactorily the vegetables grown on the plants of each group were harvested and their surface tissue analyzed for total coliforms tc and enterococci ec tomatoes grown on the plants of CG a and b recorded the highest values for tc with and cfug respectively whereas for cucumbers those values were and cfug respectively enterococci were detected on the surface of harvested vegetables from groups a and b but the small number of cases and their random character cannot support any strong relations between the used wastewater and their presence the tc values in group c were very low far lower than those if group f no ec were found in either group c or group f these primary results suggested that irrigation with AGA disinfected wastewater even of such highrisk cultivations of vegetables eaten raw should not be discarded completely as unsafe but be reconsidered and studied further however the use of undisinfected wastewater in such greenhouse cultivations where all safety precautions have been taken to prevent any contact of the fruits with the soil or the wastewater does not prove to be safe
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atrial natriuretic peptide is a peptide regulating salt and water balance originally isolated from the cardiac atrium where it is synthesised as part of a precursor molecule in specialised myocardial cells the myocardium extends into the extrapulmonary part of the PVs in many species including man in some small mammals however such as the rat mouse and bat it extends further to veins in the peripheral parts of the lung since this myocardial SL is continuous with that in the atrium we have looked for the possible expression of the atrial natriuretic peptide gene in this tissue in rats strong immunoreactivity was seen for both the peptide and the n terminal CS cardiodilatin of its precursor in extrapulmonary veins and in intrapulmonary veins extending into the lung as far as the second branching point where it was localised in the dense cored LG by electron microscopy in ISH showed atrial natriuretic peptide messenger rna at identical sites chromatography and radioimmunoassay of extracts of extrapulmonary and intrapulmonary veins showed most of the atrial natriuretic peptide immunoreactivity to be in the uncleaved precursor molecule form thus the peptide is synthesised in veins both outside and inside the lung and these extraatrial CS may be an important additional source of circulating atrial natriuretic peptide
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vardenafil selectively inhibits phosphodiesterase type pde an enzyme which hydrolyses cyclic guanosine monophosphate in the cavernosum tissue of the penis inhibition of pde results in increased arterial blood flow leading to enlargement of the corpus cavernosum because of the increased tumescence veins are compressed between the CC and the TA resulting in an erection vardenafil has a high bioavailabilty and is rapidly absorbed an erection of rigidity was maintained for approximately twice as long following visual stimulation in patients treated with vardenafil or mg than in recipients of placebo in a C1 placebocontrolled trial in patients with mild to severe erectile dysfunction ed vardenafil or mg taken as needed over a week period significantly improved the scores in questions and of the international index of EF iief the rate of successful attempts at intercourse with ejaculation was also significantly higher with vardenafil to than in the placebo group and significantly more patients treated with vardenafil than PL responded yes to a global assessment question gaq asking if treatment had improved erections in a week trial in men with ed of varied aetiologies and severity patients receiving vardenafil or mg experienced significantly improved erections with of vardenafil mg recipients reporting improved EF assessed using the gaq compared with of PL recipients treatment with vardenafil also significantly improved scores in response to questions and of the iief compared with PL a week trial in men with ed associated with diabetes mellitus demonstrated that treatment with vardenafil mg compared with placebo significantly improved iief EF domain scores and the rate of positive NR to the erectile improvement gaq similar results were reported in a placebocontrolled trial of vardenafil to mg involving patients with ed T3 radical prostatectomy AEs associated with vardenafil were those commonly associated with pde inhibitors headache flushing dyspepsia and rhinitis these were mostly dosedependent and mild to moderate in intensity
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a controlled clinical T0 on the outcome of family MI in chronic schizophrenics is being carried out in athens all subjects participating in the study reside with their families and attend a vocational rehabilitation unit those belonging to families characterized by high expressed emotion ee are randomly assigned to either the experimental or the control condition the former receive family MI combined with individual treatment the latter individual treatment CT subjects have entered the T0 and relatives were interviewed with the CFI patients were found to belong to high ee families the present article presents the results of the baseline assessment it was found that the ee status of the family was significantly associated with measures of psychopathology and SF bprs gas das number of residual symptoms further analyses revealed that these associations exist only when all key relatives express high ee the implications of these findings are discussed
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andersens syndrome as is a rare disorder characterized by a triad of PS periodic paralysis cardiac arrhythmia and bone developmental defects most of the patients carry mutations on the inward rectifier BK kir encoded by the kcnj gene kcnj knockout mice are lethal at birth preventing hence thorough investigations of the physiological and pathophysiological events we have generated induced pluripotent stem ips cells from healthy as well as from as patient muscular biopsies using the fourgene cassette required for cellular reprogramming oct sox klf and cmyc the generated asips cells exhibited the gold standard requirement for ips cells expression of genetics and surface CFU-S markers strong alkaline phosphatase activity selfrenewal and could be differentiated by the formation of embryoid bodies ebs into the three germ layers sequencing of the entire coding CS of the kcnj gene in asips cells revealed that the reprogramming process did not revert the andersens syndromeassociated mutation moreover no difference was observed between control and asips cells in terms of pluripotent markers expression selfrenewal and three germ layer differentiation interestingly expression of osteogenic markers are lower in ebdifferentiated asips compared to control ips cells our results showed that the kir channel is not important for the reprogramming process and the early step of the development in vitro however the osteogenic machinery appears to be hastened in asips cells strongly indicating that the generated asips cells could be a good model to better understand the as pathophysiology
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the ophthalmologists main task in the interdisciplinary approach to vertigo is the examination of ocular motility to rule out CE ocular motility disorders further neuroophthalmological examinations eg pupil reactions and optic disc may provide unspecific findings that can be helpful the ophthalmologist may be able to deliver puzzlesolving key findings in some multidisciplinary diseases eg cogan i vogtkoyanagiharada disease and behcets disease ocular alterations do not cause vertigo but a variety of more diffuse complaints that some patients refer to as vertigo
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to identify PSA markers for salt tolerance two contrasting cultivars of rice oryza sativa l differing in salt tolerance were analyzed for various parameters pokkali a salttolerant cultivar showed considerably lower level of ho as compared to ir a CS cultivar and such a physiology may be ascribed to the higher activity of enzymes in pokkali which either directly or indirectly are involved in the detoxification of ho enzyme MICs and the isoenzyme DP of antioxidant enzymes also showed higher activity of different types and forms in pokkali as compared to ir suggesting that pokkali possesses a more efficient AOD system to cope up with saltinduced oxidative stress further pokkali exhibited a higher gshgssg ratio along with a higher ratio of reduced ascorbateoxidized ascorbate as compared to ir under nacl AS in addition the activity of methylglyoxal detoxification system GLO i and ii was significantly higher in pokkali as compared to ir as reduced glutathione is involved in the ascorbateglutathione pathway as well as in the MG detoxification pathway it may be a point of interaction between these two our results suggest that both ascorbate and glutathione homeostasis modulated also via GLO enzymes can be considered as biomarkers for salt tolerance in pokkali rice in addition status of reactive oxygen species and oxidative dna damage can serve as a quick and sensitive biomarker for screening against salt and other abiotic stresses in crop plants
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we report an unusual case of PRS in which medically refractory focal epilepsy with ongoing EPC epc arose from the hemisphere contralateral to the side of facial atrophy unilateral cerebral involvement was confirmed by multimodal brain imaging as well as by EEG eeg and magnetoencephalography meg while in many cases of PRS the side of cerebral involvement is ipsilateral to that of the cutaneous lesion these discordant exceptions imply that other yet undefined mechanisms may be responsible for the distribution of the cutaneous and CBF pathologies
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airway protection is a critically important function that preventslimits the intrusion of foreign material into the pulmonary tree a host of different behaviors participate in this process the control coordination and execution of these behaviors is a complex process that has recently received increased attention data from human clinical and animal studies support the concept of a coordinated neural control system that governs the appropriate expression and sequencing of airway protective behaviors our current knowledge of the proposed neural control network for breathing cough swallow and other airway protective behaviors indicates that it is a highly complex system that can rewire reconfigure itself to perform several different functions computational modeling and simulation have been used as tools to investigate this system the results of modeling efforts have yielded motor output patterns of upper airway and respiratory muscles that are very similar to those recorded in vivo regulation and coordination of multiple different airway protective behaviors have been successfully simulated outcomes of simulation efforts support the hypothesis that computational modeling of airway protection can yield important testable hypotheses regarding brainstem neural network functions and organization modeling of complex systems can be challenging but the eyes and body affected patients suffer blurred vision during head movement postural instability and chronic disequilibrium while individuals with some residual sensation often compensate for their loss through rehabilitation exercises those who fail to do so are left with no adequate treatment options an implantable neuroelectronic vestibular prosthesis that emulates the normal labyrinth by sensing head movement and modulating activity on AGA branches of the vestibular nerve could significantly improve SQ of life for these otherwise chronically dizzy patients this brief review describes the impact and current management of BL loss of vestibular sensation animal studies supporting the feasibility of prosthetic vestibular stimulation and a vestibular prosthesis designed to restore sensation of head rotation in all directions similar to a cochlear implant in concept and size the johns hopkins multichannel vestibular prosthesis mvp includes miniature gyroscopes to sense head rotation a microcontroller to process inputs and control CS- timing and current sources switched between pairs of electrodes implanted within the vestibular labyrinth in rodents and rhesus monkeys rendered bilaterally vestibulardeficient via treatment with gentamicin andor plugging of semicircular canals the mvp partially restores the vestibuloocular reflex for head rotations about any axis of rotation in dimensional space our efforts now focus on addressing issues prerequisite to human implantation including refinement of electrode designs and surgical technique to enhance CS- selectivity and preserve cochlear CF optimization of stimulus protocols and reduction of device size and SP consumption
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while the characterization of the biosynthetic pathway of monoterpene indole alkaloids mias in leaves of catharanthus roseus is now reaching completion only two enzymes from the root counterpart dedicated to tabersonine metabolism have been identified to date namely tabersonine hydroxylase th and minovincine oacetyltransferase mat albeit the recombinant mat catalyzes mia acetylation at low efficiency in vitro we demonstrated that mat was inactive when expressed in yeast and in planta suggesting an alternative CF for this enzyme therefore through transcriptomic analysis of periwinkle adventitious roots several other bahd acyltransferase candidates were identified based on the correlation of their expression profile with th and found to localize in small genomic clusters only one named tabersonine derivative oacetyltransferase tat was able to acetylate the hydroxytabersonine derivatives from roots such as minovincinine and hörhammericine following expression in yeast kinetic studies also showed that the recombinant tat was TPS for root mias and displayed an up to fold higher catalytic efficiency than mat in addition gene expression analysis protein subcellular localization and rat expression in nicotiana benthamiana were in agreement with the prominent role of tat in acetylation of rootspecific mias thereby redefining the molecular determinants of the root mia biosynthetic pathway finally identification of tat provided a convenient tool for metabolic engineering of mias in yeast enabling efficiently mixing different biosynthetic modules spatially separated in the whole plant this combinatorial synthesis associating several enzymes from catharanthus roseus resulted in the conversion of tabersonine in tailormade mias bearing both leaf and roottype decorations
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met is a RET often overexpressed or mutated in human cancer upon activation by its ligand the HGF met controls several cell functions such as proliferation migration and survival through the activation of multiple pathways upon ligand binding met rapidly internalizes and continues to signal from endosomal compartments prior to its degradation importantly this endosomal signaling has recently been shown to be involved in tumorigenesis and experimental metastasis consequently interfering with met endosomal signaling may provide a novel therapeutic RPA in cancer treatment however there is a need for additional studies in various exp models to confirm this and find the most specific ways of achieving it thus outlined in this review are the techniques and tools we have been using to T0 met endocytosis and met endosomal signaling
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pathological aggregates of tau protein are found in several neurodegenerative diseases termed tauopathies increasing evidence indicates that tau oligomer species rather than the C1 amyloid cytoplasmic inclusions relevant for histopathological diagnosis might be crucial for cellular damage and neurodegeneration trivalent metal ions and polyanionic structures like heparin or AA have been shown to induce tau aggregation however little is known about early processes of tau aggregation in this study we applied fluorescence correlation spectroscopy fcs and scanning for intensely fluorescent targets sift to investigate oligomer formation of tau at nanomolar protein concentrations at the singleparticle level our results indicate that the formation of distinct tau oligomers is induced by the trivalent metal ions fe and al and by organic solvents like dmso respectively in contrast bivalent metal ions cu zn mn ca mg had no effect while dmsoinduced small tau oligomers are relatively stable in solution dynamic CR can be initiated by nonionic detergents moreover al induces rapid formation of a different oligomer species of larger size our results provide further insights into early tau oligomerization and aggregation dynamics
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one hundred ninety patients were considered for surgical treatment of uncontrolled partial seizures twentyseven had intracranial mass lesions detected during preoperative evaluation seizures were present for a mean of years sixty percent of the patients had prior negative radiologic studies the lesions included neoplasms and nonneoplastic structural nonatrophic lesions refractory simple partial seizures and a changing neurologic examination were more commonly associated with neoplasms treatment included biopsy and radiation mass resection or subtotal lobectomy although any form of treatment gave better seizure control patients undergoing subtotal lobectomy had more than reduction in seizures
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in human fetus newborn infant and adult hypothalami antibodies to ovine CRF stain a paraventriculoinfundibular neuroglandular pathway the perikarya are located in the PVH nucleus they mainly project to the VP and lateral areas of the ME eminential corticoliberinpositive MF appear during the th week of fetal life and increase in number during the following weeks perikarya were first revealed in the th week in some areas of the median eminence CRF vasopressin or metenkephalinimmunoreactive terminals are similarly distributed sequential stainings or staining comparison of contiguous semithin sections failed to prove the coexpression of CRF and metenkephalin immunoreactivities in MF but indicated that CRF and vasopressin immunoreactivities may be coexpressed in a few fibres those methods enabled us to observe in the PVH nucleus perikarya revealed by corticoliberin and vasopressin antisera our results suggest a possible release of corticoliberin in portal vessels of the ME beginning in the th week of fetal life ie weeks later than appearance of the corticotrophs in the PIT establishment of a corticoliberin hypothalamic control of pituitary corticotrophs at mid gestation agrees with previous physiological and teratological studies abundance as well as IS intensity of the CRF processes in the infant and AD median eminence attest to the physiological importance of this system close vicinity of corticoliberin vasopressin and metenkephalin fibres in some eminential areas and coexpression of corticoliberin and vasopressin immunoreactivities in some SN are morphological correlates of functional relations which were reported
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longterm observational studies assessing the incidence of type i gastric carcinoid typeigc in patients with chronic atrophic gastritis are few
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hyponatremia is the most frequently observed electrolyte abnormality in clinical practice and its frequency is almost double in hospitalized CA patients as a subset of cancer hyponatremia is quite common in LC patients and it is often coupled with the diagnosis of syndrome of inappropriate antidiuretic hormone secretion the presence of hyponatremia is consequential in that its presence adversely affects cancer patients prognosis and outcomes limited data suggest that correcting hyponatremia in lung cancer patients can increase response to anticancer treatment may help reduce length of hospital stay and cost and reduce morbidity and mortality the type of treatment for hyponatremia depends on several factors the key AF are the duration and severity of neurological PS of hyponatremia and the status of ECV when hyponatremia is caused by syndrome of inappropriate ADH hypertonic saline is indicated for acute symptomatic cases whereas fluid restriction is recommended in chronic asymptomatic hyponatremia the latter allows a slower rate of correction thus avoiding the dreaded complication of ODS fluid restriction is however insufficient or impractical and often the use of pharmacological therapy such as V2 hormone receptor antagonists becomes necessary availability of these antagonists as an effective treatment in the management of hyponatremia has been a L1 breakthrough and furthermore its clinical or investigational use in cancerrelated hyponatremia may offer a potential opportunity to gain further insights into the prognostic impact of hyponatremia correction on CA patients outcomes tolvaptan is a prototype of adh IL-1ra that acts at renal tubular C2 to increase free water excretion without inducing major systemic electrolyte CA such as hypokalemia or alkalosis the aim of this paper is to provide a brief review while focusing on CA hyponatremia of the epidemiology of hyponatremia and its pathophysiology and diagnostic approaches and of the pharmacokinetics of tolvaptan and its clinical tau safety and compliance
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elevated C2 of total dissolved gas tdg may occur downstream of dams during the spill process these high levels would increase the incidence of gas bubble disease in fish and cause severe environmental impacts with increasing numbers of cascade hydropower stations being built or planned the cumulative effects of tdg SS are becoming increasingly prominent the tdg saturation CSD in the downstream reaches of the jinsha river was studied to investigate the cumulative effects of tdg supersaturation resulting from the cascade hydropower stations a comparison of the effects of the joint operation and the single T0 of two hydropower stations xld and xjb was performed to analyze the risk degree to fish posed by tdg SS the results showed that water with supersaturated tdg generated at the upstream cascade can be transported to the downstream SP station leading to cumulative tdg SS effects compared with the single T0 of xjb the joint operation of both stations produced a much higher tdg saturation downstream of xjb especially during the nonflood discharge period moreover the duration of high tdg saturation and the lengths of the lethal and sublethal areas were much higher in the joint operation scenario posing a greater threat to fish and severely damaging the environment this work provides a scientific basis for strategies to reduce tdg supersaturation to the permissible level and minimize the potential risk of supersaturated tdg
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although the association between malignant disease and thrombosis was first recognised by trousseau in many aspects of this complex relationship are still obscure cancer patients have an increased risk of developing thrombosis similarly patients presenting with idiopathic venous thromboembolism are considered to have a higher risk of developing CA however no data exist that warrant thorough screening for cancer in these patientsapart from history taking physical examination routine investigations and chest xray tumour cells activate the blood coagulation system either by directly stimulating thrombin formation or by inducing mononuclear cells to synthesise procoagulants both CA cells and chemotherapeutic agents damage the endothelium by further enhancing the hypercoagulable state of malignancy with few exceptions the diagnosis and treatment of thrombosis in CA patients are the same as in patients without cancer CA patients are considered eligible for primary prevention of venous thromboembolism when they are receiving chemotherapy if they have indwelling CE venous catheters when they are immobilised and more importantly when they undergo surgery AA prevention in recurrent VT may require the administration of oral anticoagulants or in cases of resistance to warfarin adjusted doses of heparin
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nonsteroidal antiinflammatory drugs nsaids inhibit cyclooxygenase cox activity and are considered to exert antitumor actions in a variety of cancer cells although the effects are unlikely entirely due to cox inhibition because clinical observations suggest that hepatocyte growth factor hgf can promote metastasis of hepatoma cells while stimulating tumor invasiveness we investigated the effect of aspirin and ns a selective cox inhibitor on hgfmediated invasiveness of hepg human hepatoma cells hgf stimulated the invasiveness of hepg cells in matrigel cell invasion CA together with increased expression of matrix metalloproteinase mmp addition of aspirin or ns similar to pd which acts as a TPS inhibitor of MAP kinaseextracellular signalregulated kinase mek an uppp synthase obtained from wholebody preparations of the lepidopteran insect manduca sexta the larval enzyme was separated from isopentenyl diphosphate ipp isomerase phosphatase and ggpp synthase by preparative isoelectric focusing and was further purified by deae sepharose hydroxyapatite and size exclusion chromatography wholebody m sexta fpp synthase has a native molecular weight of kda and consists of two subunits of kda as seen with other prenyltransferases the enzyme has an absolute requirement for divalent cation and both mn and mg stimulated activity although the former was GABA at higher concentrations insect fpp synthase catalyzes the condensation of ipp km microm with both dimethylallyl diphosphate and GPP km microm the enzyme requires the presence of detergent glycerol and nonspecific proteinprotein interactions for stability and maximum catalytic activity
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critical periods are times of pronounced brain STDP during a critical period in the postnatal development of the visual cortex the occlusion of one eye triggers a rapid reorganization of neuronal responses a process known as ocular dominance plasticity we have shown that the transplantation of inhibitory neurons induces ocular dominance plasticity after the critical period Tx inhibitory neurons receive excitatory synapses make inhibitory synapses onto host cortical neurons and promote STDP when they reach a cellular age equivalent to that of endogenous inhibitory neurons during the normal critical period these findings suggest that OD plasticity is regulated by the execution of a maturational program intrinsic to inhibitory SN by inducing STDP inhibitory neuron transplantation may facilitate BB repair
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carbon IDA ida electrodes with features sizes down to μm were fabricated by controlled pyrolysis of patterned photoresist cyclic voltammetry of reversible redox species produced the expected steadystate currents the collection efficiency depends on the ida electrode spacing which ranged from around to μm with the smaller dimensions achieving higher collection efficiencies of up to the signal amplification because of redox cycling makes it possible to detect species at relatively low concentrations molar and the small spacing allows PCD of transient electrogenerated species with much shorter lifetimes submillisecond digital simulation software that accounts for both the width and height of electrode elements as well as the electrode spacing was developed to MM the ida electrode response the simulations are in quantitative PA with exp data for both a simple fast one electron redox reaction and an electron transfer with a following chemical reaction at the idas with larger gaps whereas currents measured for the smallest ida electrodes that were larger than the simulated currents are attributed to convection from induced charge electrokinetic flow
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this study aimed to determine the factors associated with response to intraarticular steroid injection iasi in patients with knee joint OA one hundred seventyfour female patients age ranging from to years diagnosed to have OA of the knee joint were given iasi response to iasi was assessed by using womac and vas at weeks weeks and months at months the subjects were categorized as responders PR and nonresponders to treatment by iasi various factors were narrowed down to see their effect on response namely age bmi smoking habits comorbidities presence of clinical effusion radiographic score local knee tenderness ROM and SES status one hundred twentyfour patients completed the T0 showed or more improvement in womac score at months post iasi therapy whereas of oa patients had more than improvement in vas score out of all factors ROM local knee tenderness and radiographic score of the affected joint are the three parameters which can predict the improvement in womac score T3 months of iasi therapy p p and p respectively age of the patient can predict improvement in vas at months post iasi p we conclude that age range of movement local knee tenderness and radiographic score of the affected joint can predict response to iasi T3 months of iasi therapy
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in this paper we have conducted a preliminary T0 of the applied clinical decision support cds features in adopted computerized physician order entry cpoe systems the T0 was conducted in three hospitals in riyadh the capital city of saudi arabia the results show that the adoption of cpoe with a CDS system cdss is not yet mature cpoe systems allow physicians to enter their medication orders electronically but many of the applied cpoe systems do not contain alerts to advise physicians of potentially dangerous interactions caused by incorrect medications hospitals are advised to enhance the role of cdss with the cpoe to reduce medication PE improve patients safety and increase information quality
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adult stem cells maintain organ systems throughout the course of life and facilitate repair T3 injury or disease a fundamental property of stem and progenitor cell division is the capacity to retain a proliferative state or generate differentiated daughter cells however little is currently known about signals that regulate the balance between these processes here we characterize a proliferating cellular compartment in the AD drosophila midgut using genetic mosaic analysis we demonstrate that differentiated cells in the epithelium arise from a common lineage furthermore we show that reduction of notch signalling leads to an increase in the number of midgut progenitor cells whereas activation of the notch pathway leads to a decrease in proliferation thus the midgut progenitors default state is proliferation which is inhibited through the notch signalling pathway the ability to identify manipulate and genetically trace cell lineages in the midgut should lead to the discovery of additional genes that regulate stem and progenitor cell biology in the gastrointestinal tractwever it did not affect the salivary secretion induced by pilocarpine applied peripherally we conclude that peripherally applied pilocarpine affects the parotid glands and the thirst center in the CNS system while it may induce salivary secretion mainly via IP responses but water NI mainly via the central NS
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anomalous origin of the left PD arising from the pulmonary artery alcapa or blandwhitegarland syndrome is a rare but serious congenital coronary i.a. anomaly with a poor prognosis without surgical repair there are two types of alcapa syndrome infant type and AD type we present a rare case of a yearold female patient with isolated left anterior descending i.a. origin from the pulmonary artery coronary computed tomography angiography revealed giant and tortuous CAs with many collaterals between the left and right coronary system the patient refused any surgical treatment
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this study analysed correlations between poststroke QEEG qeeg indices and cognitionspecific PET outcome measures results were compared between qeeg indices calculated from the standard versus frontal or posterior electrodes to assess the feasibility and efficacy of employing a reduced electrode montage restingstate eeg was recorded at the bedside within h after onset of PS of M1 ischaemic stroke confirmed radiologically RP for delta theta alpha and beta deltaalpha ratio dar and pairwisederived BB symmetry index pdbsi were averaged over all electrodes global over f f f f FC and p p t t posterior the functional independence measure and PET assessment measure fimfam was po at mean days poststroke total items and cognitionspecific items fimfam scores were correlated with qeeg indices using spearmans coefficient with a bonferroni correction twentyfive patients were recruited died within months and was lost to followup hence cases female left hemisphere mean age years range were analysed two qeeg indices demonstrated highlysignificant correlations with cognitive outcomes frontal dar ρ p ≤ and global relative alpha power ρ p ≤ after correction there were no other significant correlations alpha activity particularly frontally may index poststroke attentional capacity which appears to be a key determinant of PET and cognitive outcomes likewise frontal delta pathophysiology influences such outcomes pending further studies dar from frontal electrodes may inform early screening for postmca stroke cognitive deficits and thereby clinical decisions
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the motion of amoeboid cells is characterized by cytoplasmic streaming and by membrane protrusions and retractions which occur even in the absence of interactions with a substratum cell translocation requires in addition a transmission mechanism wherein the SP produced by the cytoplasmic engine is applied to the substratum in a highly controlled fashion through specific adhesion proteins here we present a simple mechanochemical model that tries to capture the physical essence of these complex biomolecular processes our MM is based on the continuum equations for a viscous and reactive twophase fluid MM with moving boundaries and on force balance equations that average the stochastic interactions between actin polymers and membrane proteins in this paper we present a new derivation and analysis of these equations based on minimization of a SP functional this derivation also leads to a clear formulation and classification of the kinds of boundary conditions that should be specified at free surfaces and at the sites of interaction of the cell and the substratum numerical simulations of a onedimensional lamella reveal that even this extremely simplified MM is capable of producing several typical features of cell motility these include periodic ruffle formation protrusionretraction cycles centripetal flow and cellsubstratum traction forces
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we compared three challenge models for the assessment of atrophic rhinitis ar vaccines combined infection with bordetella bronchiseptica bb and PM pm application of acetic acid aa to the nasal mucosa followed by pm infection and bb infection CT two vaccines were tested using standardized criteria notably nasal lesion scores the vaccines provided different C2 of protection in the bb and the aapm challenges but were similar in the combined bbpm challenge it is clear that the aapm MM shows the protective value of only the pm component whereas the single bb challenge reflects the protective value merely of the bb component of a combined vaccine these results suggest that the best assessment of protection is provided if the two specific challenges are performed separately
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previous work has shown that adhesion of anchoragedependent cells to fibronectin via integrin alpha beta leads to activation of the nah antiporter and a rise in intracellular ph phi we now show that adhesion of bovine capillary endothelial cells bce to fibrinogen collagens type iii iv and v laminin and vitronectin ligands that bind other members of the integrin family resulted in significant elevations in phi other ligands basic fibroblast growth factor concanavalin a and thrombin which bind cells when immobilized on plastic but that do not bind integrins and do not support cell growth do not elevate phi adhesion to an antibody against Int alpha v beta also elevates phi adhesion of IP human t lymphocytes to an antibody against the integrin lfa induced a rise in phi antibodies to cd or icam had only slight effects on phi whereas an antibody to the t cell BCR that strongly activates t cells induced a large increase in phi we conclude that elevation of phi by integrins is specific and is a property shared by many members of the Int family
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acute and prolonged critical illness are different metabolic and NE paradigms and should perhaps be approached with different therapeutic strategies the initial endocrine response consists primarily of an activated release of anterior PIT hormones and peripheral inactivation of anabolic pathways thought to provide substrates for survival while anabolism is postponed and to activate the immune cascade while the host is being protected against deleterious effects of the latter there is still no solid basis for hormonal MI in the acute phase of illness the development of modern intensive care now enables survival of previously lethal conditions and unmasked previously unknown disorders such as the wasting syndrome of chronic intensive caredependency in the CP of critical illness we documented a uniformly impaired pulsatile secretion of anterior pituitary hormones at least in part of Thy origin to correlate positively with reduced activity of target tissues an acute event complicating the chronic phase of illness may evoke mixed acuteprolonged endocrine patterns which are difficult to interpret and account for some of the apparent paradoxes in the literature it is unlikely that the reduced neuroendocrine stimulation distinctively present in the chronic phase of illness has been selected by evolution and should accordingly be considered as timehonoured and appropriate the hypothesis of inappropriate NE dysfunction can be validated by studying the effects either of combined peripheral hormonal substitution or of hypophysiotropic releasing peptide administration we demonstrated that selected pituitarydependent axes can be reactivated in the chronic phase of critical illness with preserved peripheral responsiveness intervening at the hypothalamicpituitary level appears to be a safer strategy compared to administration of peripheral hormones as presence of active feedback inhibition prevents overtreatment on an individual basis at a time when it is difficultif not impossibleto determine what is a normal or optimal level of circulating peripheral hormones whether this novel endocrine strategy will result in beneficial metabolic effects and ultimately will stimulate the recovery process in those patients who need it most remains to be elucidated
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resident cardiac scapositive stem cells may differentiate into cardiomyocytes to improve the function of damaged hearts however little is known about the inducers and molecular mechanisms underlying the myogenic conversion of sca stem cells here we report that sphingosylphosphorylchols elp concentration ph and most importantly salt effects heavily influence the transition temperature here we explore the chemical synthesis of a series of mer peptides consisting of pentameric elp repeats with hydrophobic as well as charged guest residues such as isoleucine leucine alanine lysine andor glutamate all prepared by bocbased SP peptide synthesis these guest residues expand the available toolbox of synthetic elps and provide elps that can be chemically modified and tuned to TPS environments an nterminal cysteine is added allowing disulfidebased crosslinking of elps and to link synthetic elps to a recombinantly produced protein using native chemical ligation transition temperatures of all synthetic elps and the fusion construct were determined by measuring turbidity in solution and spanned a large temperature range between and °c providing synthetically accessible elps with transition temperatures suitable for in vitro and in vivo applications cycling between their soluble and aggregate state has been observed at least times without significant loss of material for all synthetic elps copyright © EU peptide society and john wiley sons ltd
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an investigation was made into whether recent vaccination of cattle with tissue culture RPV would cause IS and lead to more frequent or more severe infection with trypanosomes in animals grazing in tsetseinfested areas herds of cattle on galana ranch in kenya were divided with approximately half of each herd being vaccinated with tissue SC rinderpest virus strain kabete o while the rest remained unvaccinated the herds were then exposed to the risk of natural infection with trypanosomes on the ranch three experiments were performed during different seasons infections with trypanosoma congolense and trypanosoma vivax were frequently detected but there was no evidence that vaccinated animals were more likely to acquire trypanosome infections or to show a more severe disease than unvaccinated cattle it is concluded that TC rinderpest vaccine does not cause IS and can safely be used in cattle likely to be exposed to tsetse flies and trypanosomosis
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preoperative simulation using threedimensional d reconstructions have been suggested to enhance surgical planning of hepatectomy evidence on its benefits for hepatectomy patients remains limited this systematic review examined the use and impact of preoperative simulation and intraoperative navigation on hepatectomy outcomes a systematical searched electronic databases for studies reporting on the use and results of simulation and navigation for hepatectomy was performed the primary outcome was NC in operative plan based on simulation AA outcomes included operating time min estimated blood loss surgical margins day postoperative morbidity and mortality and studyspecific outcomes from citations we included studies including patients all were observational cohort studies no study compared hepatectomy with and without simulation all studies performed d reconstruction and segmentation most commonly with volumetrics measurements in six studies reporting intraoperative navigation five relied on ultrasound and one on a resection map of two studies reporting on it the resection line was changed intraoperatively in one third of patients based on simulation virtually predicted liver volumes pearson correlation r to and surgical margins r to correlated highly with actual ones in eight studies heterogeneity of the included studies precluded metaanalysis preoperative simulation seems accurate in measuring volumetrics and surgical margins current studies lack intraoperative transposition of simulation for direct navigation simulation appears useful planning of hepatectomies but further work is warranted focusing on the development of improved tools and appraisal of their clinical impact compared to traditional resection
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upon hormone stimulation the sst somatostatin receptor couples to aca through gio proteins and undergoes rapid endocytosis via clathrincoated pits in this T0 we determined the relationship between the ability of ligands to induce sst receptor internalization and inhibit aca immunocytochemical studies demonstrated that peptide agonists such as somatostatin cortistatin octreotide vapreotide ke tyrcycloddiaminobutyric acidargphephedtrplysthrphe and som cyclodiaminoethylcarbamoylhydroxyprolinephenylglycinedtrplysobenzylltyrphe and nonpeptide agonists such as l stimulated the rapid endocytosis of sst receptors in human embryonic kidney and chok cells in contrast two antagonists did not induce receptor endocytosis by themselves and completely blocked agonist stimulation using a quantitative ELISA CA to measure sst receptor sequestration we found that peptide agonists varied by more than fold in their potencies but exhibited the same efficacy as somatostatin in contrast l did not induce maximal receptor internalization it is interesting that although betaarrestin was recruited to cell surface sst receptors after stimulation with either somatostatin or l the betaarrestinreceptor complex dissociated earlier in the endocytic pathway with the nonpeptide ligand although all agonists including l produced the same maximal inhibition of cAMP the potency ratio for inhibition of cyclic amp and stimulation of receptor endocytosis varied by fold in GA native MMP showed similar potencies for cAMP inhibition and receptor endocytosis whereas short therapeutic analogs were substantially more potent at inhibiting cyclic amp synthesis these results demonstrate that the activity of somatostatin analogs to regulate receptor endocytosis and signaling are not tightly linked and provide compelling evidence for the induction of agonist specific states of the sst receptor
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senescence marker protein smp plays an important role in intracellular ca homeostasis the aim of the present T0 was to investigate the effects of estrogens on CL apoptotic damage and changes in smp expression induced by a high saturated HFA diet hsfd ovariectomized mice ovx and shamoperated mice sham were randomly divided into five CG sham fed a normal diet shamnd sham fed hsfd shamhsfd ovx fed nd ovxnd ovx fed hsfd ovxhsfd and ovx fed hsfd with βestradiol e supplementation using an implanted slowrelease pellet ovxhsfde after weeks markers of endoplasmic reticulum er stress and apoptosis and C2 of TN factorα tnfα and smp expression were investigated compared with shamnd ovxhsfd mice showed significantly increased spliced xbox protein sxbp phosphorylated eukaryotic initiation factorα peifα glucoseregulated protein gpr CHOP chop cytosolic cytochrome c caspase activity and tnfα and significantly decreased smp these differences in ovxhsfd mice were restored to the C2 of shamnd mice by e supplementation these results suggest that e supplementation attenuates hsfdinduced CL apoptotic death in ovariectomized mice by upregulating smp
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a synthetic oligonucleotide was used to isolate mouse brain cdna clones coding for a brain isoform of the alpha S1 of the voltagesensitive ca channel twentysix independent cdna clones were isolated and sequenced all the cdna clones reported here showed high homology to the rat BB class c cdna sequence snutch t p tomlinson w j leonard j p and gilbert m m neuron comparison of the individual mouse BB class c mbc cdna sequences indicated the presence of four regions within the alpha S1 coding sequence where AS can take place in mouse brain and raise the possibility that combinatorial arrangement of these splice variants could give rise to a heterogenous class of mbc transcripts RNA blot analysis demonstrated that mbc mrna sequences could be detected in highest abundance in mouse heart at lower levels in mouse BB and spinal cord and not at all in CL or skeletal muscle an expression vector for one isoform of the mbc alpha subunit cdna was constructed using the human cytomegalovirus promoter to direct expression and this expression vector was used in a novel transfection CA of primary cultures of bovine adrenal BCC transfection of the mbc alpha S1 expression vector increased the secretion of hGH derived from a cotransfected human growth hormone expression vector T3 stimulation with elevated k or the dihydropyridine agonist bay k these experiments suggest that this isoform of the mbc alpha subunit is functional in the transfected chromaffin cells and that the number of ca channels is a limiting component in the secretion from chromaffin cells in culture
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buprenorphine a muopioid receptor partial agonist has been shown to be safe and ERP for treatment of opioid dependence a novel implantable formulation of buprenorphine probuphine using a CP matrix sustainedrelease technology has been developed to offer treatment for opioid dependence while minimizing risks of patient noncompliance and illicit diversion the goal of the current T0 was to conduct an initial openlabel evaluation of the safety pharmacokinetics and tau of two doses of probuphine in subjects with opioid dependence maintained on sublingual buprenorphine two doses of probuphine were evaluated in heroindependent volunteers switched from daily sublingual buprenorphine dosing to either two or four probuphine implants based upon their buprenorphine daily maintenance dose of mg or mg respectively and were monitored for months probuphine implants provided continuous Css delivery of buprenorphine until their removal at months withdrawal PS and craving remained low throughout the months for the subjects an average of of urines were opioidnegative across the month treatment period ISRs were present in half of patients but none were serious no safety concerns were evident these results suggest that probuphine implants offer significant promise for enhancing delivery of effective opioid substitution treatment while minimizing risk for abuse of medication
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pulmonary edema cardiac enlargement and respiratory insufficiency may occur in patients with acute one the mechanisms are complex and incompletely understood but probable etiologic AF include fluid overload left ventricular failure impaired respiratory excursion and microatelectasis and a nonspecific response of the lung to various types of pulmonary injury including SH intravenous crystalloids and the effects of circulating pancreatic enzymes recognition of the association of pulmonary edema and respiratory insufficiency with one is importance because early treatment with positive pressure breathing careful fluid management and diuretics and CSs may prevent the OD of irreversible respiratory failure
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AD are characterized by various circulating autoantibodies especially antinuclear antibodies ana it has been a longstanding issue as to whether andor how ana interact with epidermal cells to produce skin lesions of these ana the antissaro antibody is the most closely associated with photosensitivity in patients with SLE erythematosus sle and its subgroups including SCLE scle and neonatal lupus erythematosus nle ssaro antigens are present in the nucleus and cytoplasm and interestingly ultraviolet b uvb light translocates these antigens to the surface of the cultured KCs thus antissaro antibodies in the sera can bind to the relevant antigens expressed on the uvbirradiated KC surface and have been speculated to be an important inducer of antibodydependent keratinocyte damage this interaction between the antissaro antibodies and uvbirradiated keratinocytes may induce the skin lesions through a cytotoxic mechanism this review will focus on the involvement of antibodydependent cellular cytotoxicity in the pathogenesis of the skin lesions observed in photosensitive cutaneous lupus erythematosus
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the early potential of GT is slowly becoming realized following the recent treatment of patients with severe CID and ocular diseases however at present the field of GT is tempered by the toxicity issues mainly that of the integrated retroviral vector used in most trials whichrm dihedral angles of and ° respectively with the triazole ring an intramolecular ch⋯s hydrogenbonding contact generates an s ring motif in the crystal packing pairs of nh⋯s hydrogen bonds link neighbouring molecules into inversion dimers forming r ring motifs the crystal structure is further stabilized by ch⋯π interactions
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the OD of robust genetic tools to manipulate borrelia burgdorferi the etiologic agent of LD now allows investigators to assess the roles of individual genes in the context of experimental lyme borreliosis this unit is devoted to the description of experimental approaches that are available for the molecular genetic analysis of b burgdorferi with an emphasis on cultivation electrotransformation selection of desired mutants and genetic complementation of acquired mutants the intent is to provide a consensus protocol that encapsulates the methodologies currently employed by the b burgdorferi research community and describe pertinent issues that must be accounted for when working with these pathogenic spirochetal bacteria
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early adverse experiences are well understood to affect development and wellbeing placing individuals at risk for negative physical and MH outcomes a growing literature documents the effects of adversity on developing neurobiological systems fewer studies have examined AS neurobiology to understand how to mitigate the effects of early adversity this review summarizes the research on three neurobiological systems relevant to interventions for populations experiencing high C2 of early adversity the hypothalamicadrenalpituitary axis the prefrontal cortex regions involved in EF and the system involved in threat detection and response particularly the amygdala also discussed is the emerging field of epigenetics and related interventions to mitigate early adversity further emphasized is the need for MI research to integrate knowledge about the neurobiological effects of prenatal stressors eg drug use alcohol SE and early adversity the review concludes with a discussion of the implications of this research topic for clinical psychology practice and public policy
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inflammation is a primary defense process against various extracellular stimuli such as viruses pathogens foods and environmental pollutants when cells respond to stimuli for short periods of time it results in acute or physiological inflammation however if the stimulation is sustained for longer time or a pathological state occurs it is known as chronic or pathological inflammation several studies have shown that tumorigenesis in the gastrointestinal gi tract is closely associated with chronic inflammation for which abnormal cellular alterations that accompany chronic inflammation such as oxidative stresses gene mutations epigenetic changes and inflammatory cytokines are shared with carcinogenic processes which forms a critical crosslink between chronic inflammation and carcinogenesis transforming growth factor tgfbeta is a multipotent cytokine that plays an important role in regulation of cell growth apoptosis and differentiation most importantly tgfbeta is a strong antiinflammatory cytokine that regulates the OD of effector cells tgfbeta has a suppressive effect on carcinogenesis under normal conditions by inhibiting abnormal cell growth but on the other hanin and rhein affecting migration and invasion in scc cells are not clear in the present T0 we investigated whether or not emodin aloeemodin and rhein inhibited migration and invasion of scc cells herein we demonstrate that emodin aloeemodin and RH inhibit the protein C2 and activities of matrix metalloproteinase mmp but did not affect mRNA of mmp however they inhibited the gene expression of mmp and all also inhibited the migration and invasion of human tongue CA scc cells mmp gelatinaseb plays an important role and is the most associated with RT migration invasion and metastasis in various human cancers results from zymography and western blotting showed that emodin aloeemodin and RH treatment decrease the C2 of mmp uPA upa in a concentrationdependent manner the order of inhibition of associated protein levels and gene expression of migration and invasion in scc cells are emodin aloeemodin RH our results provide new insight into the mechanisms by which emodin aloeemodin and rhein inhibit tongue cancers in conclusion these findings suggest that molecular targeting of mmp mrna expression by emodin aloeemodin and rhein might be a useful strategy for chemoprevention andor chemotherapeutics of tongue cancers
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NFs nf are detected in the cerebrospinal fluid of multiple sclerosis ms patients and their concentration correlates with disease severity we recently demonstrated that nf and coisolated proteins increase the proliferation and differentiation of oligodendrocytes ol in vitro if these proteins are released in the extracellular environment in ms they might then regulate remyelination by ol to test this hypothesis we took advantage of a paradigm of ol toxic injury using lysophosphatidyl choline lpc which decreases proliferation and differentiation of surviving cells and destroys myelinlike membranes in ol cultures that have been treated with lpc nf fractions as well as tubulin tub significantly improved REC the number of ol progenitors olp ab cells increased by and their proliferation by whereas differentiated cnp and mature mbp cells increased by compared to cultures treated with lpc alone when added at the time of lpc treatment nf and tub protected ol from lpc toxicity they increased olp by as well as the number of cnp and mbp ol by respectively compared to cultures treated only with lpc these effects were specific since irrelevant proteins actin skin proteins were ineffective this demonstrates that nf and tub protect ol and increase olp proliferation as well as their survival when challenged with lpc without delaying differentiation and maturation in vitro thus nf and tub delivered following axonal damage in ms could participate in the reguldisease directed differentiation of hesc has been performed using many different methods often via neural precursor intermediates generated from aggregates of hesc we describe here a protocol based on commercially available reusable silicone micromolds and two small molecule growth factor inhibitors to simply and reproducibly generate human neurons from hesc hundreds of neurospheres were generated with a single pipettation of hesc into agarose multiwell plates made with the micromolds this was followed by suspension culture with two medium changes and plating of clumps cut from the neurospheres on laminincoated coverslips T3 two weeks of terminal differentiation of cells expressed neuronal proteins and many of the neurons expressed markers of peripheral SNs the neurons made with this method underwent productive infection with the humanspecific pathogenic virus varicella zoster demonstrating the utility of the SN for addressing clinically relevant research questions this simple method should allow laboratories experienced in growing human CFU-S cells to easily generate SN for studies of nerve cell biology and pathology
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from the three ET et functions ME protection secretion clearance and ME ventilation the VE function is unanimously considered the most important one because proper hearing is established only when Tty membrane compliance is normal this requires equilibrium between the ME and ambient gas pressure which makes the normal functioning of active et opening of critical importance there are several methods and tests that can assess such a complex and VL mechanism sonotubometry is one such method despite the fact that it has been continuously improved in the last years it is not yet systematically used to evaluate the et VE CF because its measurement pattern context mapping patient clinic data medication treatment validation reproducibility and value for clinic practice have not yet been fully consolidated and integrated in a knowledgebased serviceoriented system that can provide decision support or even diagnostic the paper reviews the role of tubal sonometry as a noninvasive physiologic and easy to use method in assessing the ventilatory CF and investigates the validity and reproducibility of a measuring pattern and test in a group of children the paper describes the test DP used and the computerbased platform based on digital signal processing dsp for sound acquisition and lowlevel processing artificial intelligence techniques to extract significant sound features from sonotubograms and learn a manifold context database results are reported from test series carried out in HC a similar study between tests is included in the final discussions section
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decision making is central to health policy and medical practice because health outcomes are probabilistic most decisions are made under conditions of uncertainty this review considers two classes of decisions in health care decisions made by providers on behalf of patients and shared decisions between patients and providers considerable evidence suggests wide regional variation exists in services received by patients evidencebased guidelines that incorporate quality of life and patient preferences may help address this problem systematic costeffectiveness analysis can be used to improve resource allocation decisions shared medical decision making seeks to engage patients and providers in a collaborative process to choose clinical options that reflect patient preferences although some evidence indicates patients want an active role in making decisions other evidence suggests that some patients prefer a passive role decision aids hold promise for improving individual decisions but there are still few systematic evaluations of these aids several directions for future research are offered
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the unicellular marine alga dunaliella salina is a most interesting green cell factory for the production of carotenes and lipids under extreme environment conditions however the SC conditions and their productivity are the L1 challenges faced by researchers which still need to be addressed in this T0 we investigated the effect of bicarbonate amendment on biomass photosynthetic act two volumes centrifuged with and without cushion and frozen with conventional and two prototype drum and directional methods using ml straws for the conventional and drum and ml flat straws for both the drum and directional cushioned centrifugation increased total motility ± vs ± p and mean velocity ± vs ± p when compared to not cushioned centrifugation estimated after cooling the sperm at ⁰c for min before freezing cushioned centrifugation also increased p spermatozoa with polarized mitochondrial CM ± vs ± and intact plasmaticacrosomal CM ± vs ± of frozenthawed sperm with respect to not cushioned centrifugation however no effects of the centrifugation were evidenced for CP kinetic parameters flat straws had negative effect for almost all the parameters analyzed at thawing t and T3 hours incubation at ⁰c t₁ while the drum method with paillettes did not show appreciable affects the variability among stallions was relevant to variance for kinetics and membrane status while the variability among ejaculates was minor to factorial analysis identified three relevant AF with different informational content factor represented by CM status factor by kinetics estimated at t₀ and factor by kinetics estimated at t₁ cushioned centrifugation had some beneficial effects for the membrane status of the frozenthawed sperm while the use of flat straws needs to be improved
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visual functions of neurologically impaired children with permanent cerebral CVI cvi can be difficult to determine this T0 investigated the behavioural profile of cvi children by means of ethological observations in order to gain a better understanding of their visual functions
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magnesium sulphate has been used in the acute treatment of migraines some studies found it to be a highly ERP medication in the acute control of migraine pain and associated symptoms this randomized doubleblind placebocontrolled study assesses the effect of magnesium sulphate on the pain and associated symptoms in patients with migraine without aura and migraine with aura sixty patients in each group were assigned at random to receive magnesium sulphate mg intravenously or PS ml we used seven parameters of analgesic evaluation and an CAS to assess nausea photophobia and phonophobia in the migraine without aura group there was no statistically significant difference in the patients who received magnesium sulphate vs PL in PR the analgesic therapeutic gain was and number needed to treat was at h there was also no statistical difference in relief of nausea we did observe a significant lower intensity of photophobia and phonophobia in patients who received magnesium sulphate in the migraine with aura group patients receiving magnesium sulphate presented a statistically significant improvement of pain and of all associated PS compared with controls the analgesic therapeutic gain was at h a smaller number of patients continued to have aura in the magnesium sulphate group compared with placebo h T3 the administration of medication our data support the idea that magnesium sulphate can be used for the treatment of all symptoms in migraine with aura or as an adjuvant therapy for associated symptoms in patients with migraine without aura
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familiar xanthomatosis hypercholesterolemia in homozygous or heterozygous two or more defects in ldl receptors forms are rare the cholesterol C2 are frequently above mgdl the management of these patients includes odd procedures such as ileal bypass to control of levels of cholesterol we present a case of pregnancy in patient with familiar hypercholesterolemia fh and coronary and cerebral atherosclerosis who had undergone ileal bypass five years prior during pregnancy there were no clinical signs or symptoms related to coronary or CBF atherosclerosis and we did not observe obstetric complications nevertheless the C2 of cholesterol and triglyceride increased significantly to mgdl and mgdl face the unknown prognosis of this clinical situation we decided to hospitalize the patient and to prescribe prolonged rest dietary measures and specific therapy this RPA permitted her to reach the end of pregnancy without maternal and fetal complications the pahe electromyographic response T3 mivacurium had recovered to approximately of the baseline a continuous infusion of mivacurium was given to maintain neuromuscular blockade the plasma concentration of mg in blood of the mg group was meql higher than that meql of the nonmg group p the infusion rates of mivacurium of mg and nonmg groups were and meq x kg x min respectively in addition the recovery indexes of the mg and nonmg CG were and min respectively we conclude that a smaller dose of mivacurium should be infused to patients receiving mg
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this paper investigates the incorporation of the spatial covariance of the pericardial potentials assumed known a priori as a regularization function when computing the pericardial potential distribution from observed body surface potentials the resulting inverse solutions are compared with those using as a regularization function the norm of the solution the norm of the surface laplacian of the solution as well as with those based on using the truncated singular value decomposition the study uses a realistic source MM to simulate potentials throughout the qrsinterval this source is placed in an anatomically accurate inhomogeneous volume conductor model of the torso the use of a single value of the regularization parameter is shown to be feasible for data incorporating noise the use of the spatial covariance is demonstrated to result in a RE over the entire qrs interval as low as L1 PE are demonstrated to result if the effect of the inhomogeneity of the lungs is ignored the spatial covariance based inverse is shown to be more robust with respect to the perturbations noise inhomogeneity than the other estimators included in this T0
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aberrant retinal expression of V1 endothelial growth factor vegf leading to neovascularization is a CE feature of agerelated macular degeneration and diabetic retinopathy two leading causes of vision loss oxidative AS is suggested to occur in retinal tissue during agerelated macular degeneration and diabetic retinopathy and is suspected in the mechanism of vegf expression in these diseases arsenite a thiolreactive oxidative stressor induces vegf expression by a hifalphaindependent mechanism previously we demonstrated that homocysteine an endoplasmic reticulum stressor increases vegf transcription by a mechanism dependent upon activating transcription factor atf because atf is expressed in response to oxidative stress we hypothesized that atf was also responsible for increased vegf transcription in response to arsenite we now show that arsenite increased steady state levels of vegf mrna and activated transcription from a vegf promoter construct arsenite induced eifalpha phosphorylation resulting in increased atf protein levels inactivation or loss of atf greatly diminished the vegf response to arsenite treatment overexpression of atf was sufficient to activate the vegf promoter and arsenite cooperated with exogenous atf to further activate the promoter a complex containing atf binds a dna element at bp relative to the vegf transcription start site and dna CBA is increased by arsenite treatment in addition the ability of a thiol antioxidant nacetylcysteine to inhibit the effect of arsenite on vegf expression coincided with its ability to inhibit phosphorylation of eifalpha and atf protein expression thus arseniteinduced upregulation of vegf gene transcription occurs by an atfdependent mechanism
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to evaluate the effect of lowdose aspirin use in OD recipients with an endometrial thickness of mm
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tracking the former location of a radioactive source represents an attractive attribute in tral inducible sites in committed th cells the mechanism of il gene silencing is associated with a closed chromatin structure the lack of an HS site at the promoter region and the OD of repressive histone modification near the il promoter and introns and we confirm that the majority of hs sites coincide with conserved noncoding sequences cnss identified by comparative genomic CS alignment between human and mouse genomes potential transcription factor IB CS were located by comparing cnss with the transfac DB predicted in vivo binding of specific AF on the cns locus were confirmed by chromatin IP assays our results suggest that the combination of hs site and comparative genomic approaches allows ID of regulatory elements involved in differential il gene expression between th and th cells during t cell differentiation
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azelaic acid aza is used in the treatment of acne however side effects and low compliance have been associated with several topical treatments with aza nanotechnology presents a strategy that can overcome these problems polymeric NPs can control drug release and targeting and reduce local drug toxicity the aim of this T0 was to produce and evaluate an innovative topical treatment for acne with azaloaded polydllactideglycolide copolymer nanoparticles a soft white powder of NPs was prepared the mean size of loaded nanoparticles was nm and zeta potential was negative spherical nanoparticles were observed by SEM microscopy encapsulation efficiency was around and a strong interaction between the CP and the drug was confirmed by differential scanning calorimetric analysis in vitro drug release studies suggested a controlled and pulsatile PR profile system efficacy tests suggested similar results between the loaded nanoparticles and the nonencapsulated drug against the most common bacteria associated with acne cytotoxicity of azaloaded NPs was concentration dependent although not pronounced the occluded patch test seemed to indicate that the formulation excipients were safe and thus azaloaded nanoparticles appear to be an efficient and safe treatment for acne
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multiple sclerosis ms is an inflammatory disease of the cns that is associated with demyelination and axonal loss resulting in severe neurological handicap current ms therapies mostly target neuroinflammation but have only a little impact on cns myelin repair progress toward treatments that enhance remyelination would therefore represent major advances in ms treatment here we examined the ability of tfa a new synthetic compound belonging to TOC longchain fatty alcohols to promote oligodendrocyte regeneration and remyelination in experimental models of ms we showed that tfa significantly ameliorates neurological deficit and severity of myelin oligodendrocyte glycoproteininduced EAE eae in mice histological evaluation of mouse eae spinal cords showed that tfa treatment reduces inflammation astrogliosis and myelin loss additionally we demonstrated that tfa accelerates remyelination of focal demyelinated lesions induced by lysolecithin i.v. we also found that this compound induces the differentiation of OPCs into mature oligodendrocytes through the inhibition of the notchjagged signaling pathway altogether our data provide important proof of principle indicating that tfa could be a potential therapeutic compound for myelin repair in ms
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the prognosis for patients with pancreatic adenocarcinoma remains dismal the operative management of patients with pancreatic adenocarcinoma treated over a year period was reviewed biliary bypass was associated with a high OM percent cholecystojejunostomy was associated with a percent incidence of recurrent obstructive jaundice before death therefore it is recommended that when feasible a choledochojejunostomy be performed a percent incidence of duodenal obstruction was observed in patients who did not routinely undergo prophylactic gastroenterostomy survival was short in all patients whether or not a resection was performed the mean survival after biliary bypass was months a significant problem was observed in patients who underwent pancreaticoduodenectomy RT was present at the line of transection of the pancreas in the majority of patients thus it is strongly recommended that frozen section examination of the SM of the pancreas be carried out routinely if a Px is performed newer techniques of palliation for patients with pancreatic carcinoma such as fine needle aspiration biopsy guided by computerized axial tomography and internal or external biliary stenting are encouraged due to the high operative mortality and short survival of all patients with pancreatic adenocarcinoma there were no LTS T3 radical pancreaticoduodenectomy in this series
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LA acidderived radicals which are formed in the reaction of LA with soybean lipoxygenase were trapped with NB and the resulting radical adducts were analysed by hplcepr and liquid chromatographythermosprayms three nitrosobenzene radical adducts peaks i ii and iii were detected these gave the following parent ion masses for peak i for peak ii and for peak iii the masses of peaks i and ii correspond to the LA radicals with one more oxygen atom lo the radicals are probably carboncentred because the use of o did not result in an additional hyperfine splitting computer simulation of the peak i radical adduct epr spectrum also suggested that the radical is carboncentred the peak i radical was also detected in the reaction of hydroperoxylinoleic acid with feso from the above results peak i is probably the epoxylinoleic acid radical an hplcepr experiment using hlinoleic acid suggested that the epoxylinoleic acid radical is a ccentred radical peak ii is possibly an isomer of peak i peak iii which was observed in the reaction mixture without soybean lipoxygenase corresponds to a linoleic acid radical l the epoxylinoleic acid radical epoxylinolenic acid radical and epoxyarachidonic acid radical were also detected in the reactions of LA linolenic acid and AA acid respectively with soybean lipoxygenase using nitrosobenzene and methylnitrosopropane as spintrapping agents
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at least two investigators have demonstrated a reduction in o SE during induced HT cain and bradley j appl physiol schumacker et al j appl physiol we hypothesized that administration of pentoxiphylline ptx a theobromine that lowers blood viscosity and has vasodilator effects would increase o extraction during hypothermia to test this hypothesis we studied o transport in anesthetized paralyzed MV beagles exposed to hypoxic hypoxia during either normothermia degrees c HT degrees c or HT ptx degrees c and ptx mgkgh measurements included arterial and mixed A-V po hemoglobin concentration and saturation cardiac SO SVR V1 resistance svr blood viscosity and o consumption vo critical C2 of o delivery do the product of arterial o content and cardiac output were determined by a system of linear regression HT significantly decreased base L1 cardiac output do and vo while increasing svr and BV addition of ptx increased cardiac SO and vo and returned svr and BV to normothermic C2 HT CT failed to significantly reduce the critical level of do but addition of ptx did normothermia sd mlkgmin HT hypothermia ptx p less than analysis of variance the o extraction ratio vodo at the critical level of do was decreased during hypothermia CT NT hypothermia hypothermia ptx p less than abstract truncated at words
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eucalyptus hemicellulose was hydrolyzed by treating eucalyptus wood chips with sulfuric acid the hydrolyzate was used as the substrate to produce singlecell protein by growing paecilomyces variotii ioc for or h the influences of rice bran AS and fermentation time were verified by a fullfactorial CE composite design at the optimum process conditions the cell concentration was gl which was obtained when the microorganisms were cultivated for h in a medium composed of gl RB gl nitrogen and gl sodium phosphate the mathematical model y x x xx x x describes biomass production by p variotii in eucalyptus hemicellulosic hydrolyzate with a determination coefficient of r where x and x are ammonium sulfate and fermentation time respectively
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perioperative hemostatic management is increasingly important in otolaryngology this review summarizes the key elements of perioperative risk stratification thromboprophylaxis and therapies for bridging of antithrombotic treatment it gives a practical advise based on the current literature with an emphasis for patients undergoing earnosethroat surgery
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monoclonal antibodies against several human leucocyte CSA were prepared and characterized bm a noncytotoxic antibody against betamicroglobulin mem and mem against immunoglobulin kappatype CS chains mem memg and memb all against a monomorphic determinant in mhc class ii antigens presumably DR dependent on the association of alpha and beta chains mem and mem against a monocyte antigen of kda mem against a kda antigen expressed on all leucocytes mem against the t antigen of the cytotoxicsuppressor tlymphocyte subpopulation mem against the t antigen of t lymphocytes
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nitrite and nitrate are common inorganic salts in the diet and drinking water it is generally believed that excessive NI of these substances may result in methemoglobinemia or other diseases however the traditional PCD methods for nitrite and nitrate in dairy products restrain their applications to routine analysis due to the presence of certain limitations in order to solve this problem an improved national food safety standard method for the determination of NO(x) in dairy products has been studied T3 water extraction protein precipitation and centrifugation the supernatant was cleaned up by a solid phase SE spe column the eluent mainly composed of sodium XTT with acetonitrile as organic modifier external water mode was used for suppressor an as column was used as the analytical column and the oven temperature was degrees c while the cell temperature was degrees c the PCD wavelength was nm and the injection volume was microl the results showed that good linearity existed when the concentrations of NO(x) were between and mgl respectively the LOD of nitrite and nitrate were and mgkg respectively when using a conductivity detector while the values were only and mgkg using an ultraviolet uv detector the recoveries were between and when analyzing dairy products it is a simple fast and highly sensitive way for nitrite and nitrate detections
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studies of mutated retinoblastoma rb proteins in human RT cells potentially reveal regions of the normal rb gene product that are required for its cancer suppression CF we here characterize a mutated rb protein of mr p from a primary smallcell lung carcinoma unlike normal rb protein pprb p was unphosphorylated and unable to bind t antigen of sv both in vivo and in vitro on the other hand nuclear localization and dna binding activity were preserved in the ATM p was immunoprecipitable with four separate polyclonal antibodies recognizing different epitopes of the rb polypeptide suggesting the presence of most exons in their correct reading frame following reverse transcription and in vitro amplification rb mrna from this tumor was shown to lack nucleotides encoded by exon analysis of genomic dna from this RT showed that exon and its flanking splice donor and acceptor sequences were present and entirely normal however a base pair bp region containing the splice donor site of intron was deleted instead exon was joined directly to exon during mrna processing via a cryptic splice donor site exon was presumably skipped because the preceding mutated intron was of insufficient length less than bp for normal rb mrna processing these results demonstrate that loss of a single small exon disrupts several important biochemical properties of rb protein in addition sequence features of the bp SD suggest involvement of a novel deletional mechanism
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PD disease can be diagnosed from stress and delayed images of myocardial single photon emission computed tomography spect using technetium mtetrofosmin tctf however the negative predictive value of stress spect images after a single i.t. of a low tracer dose remains unknown thus the present T0 investigates whether normal stress spect results predict EFS
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the discharge properties of pulmonary stretch receptors psr were studied in spontaneously PLB pentobarbital sodiumanesthetized cats during eupneic breathing of psr both tonically and phasically active were recruited in the first third of inspiration none were recruited in the last third linear equations adequately expressed the relation between instantaneous discharge frequency and inspired volume in eupnea during co rebreathing both tidal volume and peak psr discharge frequency were inversely related to TI at fixed volumes less than ml above PET residual capacity instantaneous psr discharge frequency either did not NC or decreased with increases in flow above ml increases in discharge frequency accompanied increases in flow spikess per mls during progressive hypocapnic hypoxia discharge frequency increased on average at all volumes with increases in flow spikess per mls during both conditions as with eupnea increases in frequency were linearly related to increments in tidal volume therefore tidal volume CT can be used to estimate psr FB to the respiratory centers provided that its instantaneous value is appropriately scaled to account for the different effects of co and hypocapnic hypoxia on psr discharge
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a yearold male presented with vision loss and behavioral changes he had Tm pupils with no reaction to CS and normal funduscopic examination cranial magnetic resonance imaging revealed BL cortical lesions at po lobes elevated measles antibody titers in the CSF fluid confirmed the diagnosis of subacute sclerosing panencephalitis despite oral inosiplex and supportive care patient developed generalized seizures with frequent myoclonic jerks and rapidly progressed into coma cortical blindness in subacute sclerosing panencephalitis can be an early indicator for fulminant course
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gestational trophoblastic tumours group together the CR hydatidiform mole CP and partial mole with fetus invasive mole and choriocarcinoma genetically trophoblastic tumours can arise in different ways they can derive from normal zygotes with the maternal and paternal haplotype NP or from a triploid zygote PM or from an xx zygote possessing only a duplicated male haplotype and no maternal contribution complete mole the low malignancy rate in partial mole compared to the CM to remains unknown further analysis of the genetics of these tumours may well contribute to the understanding of the process of carcinogenesis
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the nucleus TS nts and dorsal motor nucleus of the VN dmv constitute sensory and motor nuclei of the dorsal vagal complex respectively we used wholecell patchclamp recordings from dmv SN in rat brain slices and three methods of stimulation electrical glutamate microdrop glu photostimulation to test the hypothesis that convergent excitatory and inhibitory inputs to dmv neurons originate from intact SN in multiple nts areas electrical stimulation of the nts resulted in evoked excitatory and inhibitory postsynaptic currents eepscs and eipscs in dmv neurons stimulation of the dorsal nts with glutamate microdrops which selectively stimulates the soma and dendrites of IN neurons resulted in of dmv neurons receiving eepscs receiving eipscs and receiving convergent excitatory and GABA inputs glutamate photostimulation allowed selective activation of IN neurons in multiple discrete Az of the nts and resulted in of dmv SN receiving eepscs receiving eipscs and receiving both inputs data obtained by stimulation of multiple nts areas support the hypothesis that there are anatomically convergent inputs to dmv neurons originating from intact SN within the nts these data support the hypothesis that there is transfer of convergent information from the nts to the dmv implying that significant sensorymotor processing occurs within the brainstem
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the regulation of the number of extrajunctional acetylcholine ach receptors was assayed by ilabelled alphabungarotoxin IB CS in denervated rat diaphragm muscle in culture sustained k depolarization does not eliminate extrajunctional ach receptors in fact muscle cultured in highk medium normal cl for days exhibits a greater IB capacity than controls under conditions in which the [Cl-]i concentration is unaltered highklowcl medium this effect of highk medium on the number of extrajunctional ach receptors is blocked the number of extrajunctional receptors increases h after exposure to highknormal cl medium similar to the time course of the initial appearance of extrajunctional receptors in the DNX diaphragm muscle in vivo or in organ SC in normal media highknormal cl medium did not alter the rate of receptor Kd electrical stimulation of DNX muscle strips cultured in lowca medium containing d eliminated extrajunctional receptors as efficiently as stimulation of muscles in control medium electrical stimulation did not reduce the extrajunctional ach receptor population in glyceroltreated uncoupled muscles to the same extent as in UT muscles the extrajunctional ach receptor content of denervated muscle cultured for days in and mmcaffeine was reduced by about half respectively denervated muscle cultured in mmcaffeine did not differ from control DNX muscle other agents which may alter intracellular cyclic nucleotide levels dbcGMP dibutyryl cyclic amp papaverine and sodium nitroprusside did not mimic the effect of caffeine or electrical stimulation in lowering the C2 of extrajunctional ach receptors we conclude that intracellular ca PR from the sarcoplasmic reticulum is necessary for the beta of extrajunctional ach receptors in DNX muscle the levels of [Cl-]i also influence the population of extrajunctional receptors conditions which lead to higher levels of intracellular cl result in greater rates of synthesis of ach receptors
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a highresolution structure of the histidinecontaining phosphocarrier protein hpr from staphylococcus aureus was obtained by hn multidimensional nuclear magnetic resonance nmr spectroscopy on the basis of structural restraints twentythree hydrogen bonds in hpr could be directly detected by polarization transfer from the amide nitrogen to the carbonyl carbon involved in the hydrogen bond differential L1 broadening was used to characterize the interaction of hpr with the hpr kinasephosphorylase hprkp of staphylococcus xylosus which is responsible for phosphorylationdephosphorylation of the hydroxyl group of the regulatory serine residue at position the dissociation constant kd was determined to be mm at k from the nmr data assuming independent IB the data are consistent with a stoichiometry of hpr molecule per hprkp monomer in solution using transversal relaxation optimized spectroscopyheteronuclear single quantum rho we mapped the interaction site of the two proteins in the kda complex as expected it covers the region around ser and the small helix b following this residue in addition hprkp also binds to the second phosphorylation site of hpr at position this interaction may be essential for the recognition of the phosphorylation state of his and the phosphorylationdependent regulation of the kinasephosphorylase activity in accordance with this observation the recently published xray structure of the hprhprk core protein complex from lactobacillus casei shows interactions with the two phosphorylation CS however the nmr data also suggest differences for the FL protein from s xylosus there are no indications for an interaction with the residues preceding the regulatory ser residue thr to lys in the protein of s xylosus in contrast it seems to interact with the cterminal helix of hpr in solution an interaction which is not observed for the complex of hpr with the core of hprkp of l casei in crystals
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the short term metabolic effects of the in vivo administration of plateletderived growth factor have been examined in the liver of the rat mealfed male WR weighing between g received an intraperitoneal injection of plateletderived growth factor units g weight transforming growth factorbeta ng g weight or saline at min T3 i.t. the livers were freezeclamped samples of the tissue were subsequently assayed for metabolite content and enzyme MICs plateletderived growth factor i.t. caused an elevation in the CL content of pyruvate from to mumolg wet weight liver p less than or equal to and an increase in the cytosolic phosphorylation potential sigma atpsigma adpsigma pi from to p less than or equal to in addition an increase in the hepatic content of the hexose monophosphate pathway metabolites phosphogluconate to mumolg wet weight p less than or equal to ribulose phosphate to mumolg wet weight p less than or equal to and combined sedoheptulose phosphate and ribose phosphate to mumolg wet weight p less than or equal to was observed the elevation in the HMP metabolites resulted from a fold elevation in the activity of glucosephosphate dehydrogenase ec when measured in a crude TH kinetic analysis performed on partially purified glucosephosphate dehydrogenase demonstrated no significant NC in the km of the enzyme for either nadp or glucose phosphate while a fold increase in the vmax was observed in view of the rapidity of the change in total measured CEA and increase in the vmax of glucosephosphate dehydrogenase it is postulated that plateletderived growth factor causes a covalent modification of the existing enzyme transforming growth factorbeta caused no NC in the hepatic metabolite content in the treated animals when compared to saline treated controls
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we examined the effect of nnntrimethylsphingosine tms on the interleukin beta il betainduced eselectin expression in HUVE cells huvec incubation of huvec with tms microm resulted in a concentrationdependent inhibition of il betainduced eselectin expression sphingosine or nndimethylsphingosine had no effects on the expression electrophoretic mobility shift CA revealed that tms inhibited il betainduced nfkappa b activation which is essential for eselectin expression this GABA effect of tms on il betadependent endothelial cell activation may partly explain the known antiinflammatory or antimetastatic effect of tms in vivo
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estrogenhydroxylase eh activity was measured by a direct product isolation CA in punch biopsy specimens obtained from nine nuclear regions from forebrain of AD male rats tritiated CE were isolated from incubations of tissues with hestradiol from all regions studied the amount of hydroxyestradiol ohe formed equaled or exceeded that of hydroxyestradiol ohe there were significant regional differences in the amounts of catechol estrogen produced the difference was nearly fold between the arcuatemedian eminence arcme and the MPO nucleus pom regions with the highest and lowest TPS MICs respectively vs pmolmg protein min ohe mean sem n the supraoptic nucleus was the site of second highest concentrations of eh activity pmol ohemg protein min estrogenh activity in the PVH pvn and PV peri nuclear regions though only about half that in the son was significantly greater than in the remaining brain Az nucleus interstitialis striae terminalis caudate AH and medial preoptic nuclei and cortex the arcme the region with the highest eh activity is where the DA neurones and terminals from the gnrh SN are concentrated the functions regulated by these two classes of neurones the secretion of prolactin and gonadotrophins respectively have been the subject of most of the previous studies aimed at establishing the role of catechol estrogen formation in the hypothalamusabstract truncated at words
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