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STM stm has been used to T0 the structure of the noncrystalline globular protein vicilin molecules were deposited on amorphous carbon substrates and imaged both in air and in vacuo without additional sample preparation currentvoltage plots of an individual protein molecule are also reported the stm images are compared with conventional transmission electron micrographs and with a MM of vicilin based on smallangle synchrotron xray scattering data | MEDAL |
inhibitors of two zinc metallopeptidases angiotensin i CE ace and neutral metalloendopeptidase ep are antihypertensive agents in this issue of hypertension genden and molineaux report that yet another peptidase inhibitor metalloendopeptidase ec ep lowers blood pressure in normotensive rats in this editorial we discuss the possible role of kinins as common mediators of part of the vasodepressor action of these peptidase inhibitors genden and molineaux report that the marked fall in blood pressure caused by the ep inhibitor is almost abolished by a kinin receptor antagonist supporting the hypothesis that kinins play a role in the regulation of normal blood pressure we have confirmed that the ep inhibitor used by these investigators lowers blood pressure up to now ep has not been implicated in in vivo metabolism of kinins although a number of kininases have been identified our own previous work indicated that the metabolic pathway responsible for clearing kinins from the circulation involves the action of kininase ii angiotensin i converting enzyme and renal peptidases nevertheless the main metabolic pathway involved some other unidentified enzyme since in these experiments disappearance of kinins from the circulation was only marginally reduced by a cocktail of inhibitors of ace ep and CPN it could be that ep is involved in kinin metabolism however a number of questions need to be answered with regard to the mechanism by which the ep inhibitor lowers blood pressureabstract truncated at words | MEDAL |
anxiety sensitivity as has been implicated in the development and maintenance of a range of MH problems the development of the anxiety sensitivity index a psychometrically sound index of as has provided the opportunity to better understand how the lowerorder factors of as physical psychological and social concerns are associated with unique forms of psychopathology the present study investigated these associations among treatmentseeking adults with high as participants completed measures of as anxiety and depression multiple regression analyses controlling for other emotional disorder symptoms revealed unique associations between as subscales and certain types of psychopathology only physical concerns predicted unique variance in panic only cognitive concerns predicted unique variance in DS and social anxiety was predicted by only social concerns findings emphasize the importance of considering the multidimensional nature of as in understanding its role in anxiety and depression and their treatment | MEDAL |
spontaneous coronary artery dissection a rare cause of acute coronary syndrome is due to nonatherosclerotic coronary events and is probably underrecognized as a cause of myocardial infarction the condition typically affects premenopausal women who are otherwise healthy among more than reported cases recurrent dissection has been described times and only reports have documented multiple episodes of dissection involving different vascular territories we present the case of a woman in her s who over a year period presented times with coronary dissection in different V1 territories she was first treated conservatively then with stents and ultimately by means of CABG in addition to this case we discuss this rare condition and its management | MEDAL |
CS with CP bypass cpb is known to induce an immune response whose nature has been increasingly elucidated during the recent decade clinically patients usually show two to three of the four PS which define the socalled systemic inflammatory response syndrome sirs in addition all parameters of the innate nonspecific IS eg polymorphonuclear cells PE and complement are G1 this also applies to the Th1 mediators interleukin ilbeta and and RT CN factor tnfalpha within the adaptive TPS immune system a decrease of t lymphocytes and t helper th cells is observed whereas suppressor cytotoxic t cells and b cells appear to be nearly unaffected cytokine measurements provide more detailed information il and il which are important for the activation of the type thcell thmediated immune response are depressed following cardiac T0 in contrast il and transforming growth factorbeta essential to thmediated humoral or antiinflammatory immune response are upregulated in vivo tests eg delayed type hypersensitivity skin reaction and tetanus antibody production confirm the polarization of the adaptive immune response towards the th pathway however all these alterations usually do not result in clinical AEs therefore more information is needed about the immune response of patients at high preoperative risk or with serious perioperative complications to find out whether clinically relevant events are correlated to alterations of immune response for this purpose more readily available standardized methods for immunologic monitoring appear highly desirable | MEDAL |
singlecell mrna sequencing can uncover novel celltocell heterogeneity in gene expression C2 in seemingly homogeneous populations of cells however these experiments are prone to high C2 of unexplained technical noise creating new challenges for identifying genes that show genuine heterogeneous expression within the population of cells under study basics bayesian analysis of singlecell sequencing data is an integrated bayesian hierarchical MM where i cellspecific normalisation constants are estimated as part of the model parameters ii technical R2 is quantified based on spikein genes that are artificially introduced to each analysed cells lysate and iii the total variability of the expression counts is decomposed into technical and biological components basics also provides an intuitive PCD criterion for highly or lowly variable genes within the population of cells under T0 this is formalised by means of tail posterior probabilities associated to high or low biological celltocell variance contributions quantities that can be easily interpreted by users we demonstrate our method using gene expression measurements from mouse embryonic stem cells crossvalidation and meaningful enrichment of GO categories within genes classified as highly or lowly variable supports the tau of our RPA | MEDAL |
in addition to the biodegradation problems encountered in buildings SE of their occupants to moulds is responsible for numerous diseases infections invasive nosocomial aspergillosis immediate or delayed allergies foodborne infections and different types of irritation in this context the aim of our work has been to determine specific chemical tracers for fungal OD on construction materials more generally by detecting a specific chemical fingerprint of fungal OD our objective was to propose a microbiological alert system which could control systems andor procedures for the microbiological treatment of indoor areas we therefore characterized the chemical emissions from six types of construction material contaminated artificially by moulds chemical fingerprints were established for compounds arising specifically from fungal metabolism ethylhexanoic acid methyl ester octenol heptanol methylbutanol methylbutanol octadiene hfuranone heptene alphapinene methylisoborneol heptanone methylfuran methylfuran dimethyldisulfide methoxybenzene a terpenoid and three sesquiterpenes determining the origin of these compounds and their TPS links with a growth ATP or fungal species made it possible to judge the pertinence of choosing these compounds as tracers thus the detecting TPS VOCs emitted as from the second day of fungal growth demonstrated that this approach had the advantage of detecting fungal OD both reliably and rapidly before any visible signs of contamination could be detected | MEDAL |
atpinduced TG inhibition is accompanied by a selective decrease in the content of the tripeptide glutathione gsh within the cancer cells in vivo depletion of cellular gsh sensitizes tumours to chemotherapy and radiation but the usefulness of this depletion depends on whether the levels of gsh can be reduced in the tumour relative to normal tissues we report here that administration of atp in combination with diethylmaleate and xrays leads to complete regression of of EA tumours in mice this shows that an aggressive tumour can be eliminated by using a therapy based on modulation of gsh levels in CA cells | MEDAL |
the overall HFA composition of leaf lipids in a mutant of arabidopsis thaliana was characterized by elevated amounts of palmitic acid and a decreased amount of unsaturated carbon fatty acids as a consequence of a single nuclear mutation quantitative analysis of the HFA composition of individual lipids suggested that the mutant is deficient in the activity of a chloroplast omega HFA desaturase which normally introduces a double bond in carbon acyl chains esterified to monogalactosyldiacylglycerol mgd the mutant exhibited an increased ratio of to carbon fatty acids in mgd due to a change in the relative contribution of the prokaryotic and eukaryotic pathways of lipid biosynthesis this appears to be a regulated response to the loss of cp omega desaturase and presumably reflects a requirement for PUFA fatty acids for the normal assembly of chloroplast membranes the reduction in mass of prokaryotic mgd species involved both a reduction in synthesis of mgd by the prokaryotic pathway and increased turnover of mgd molecular species which contain | MEDAL |
fractions EC in either photosystem i or photosystem ii have been prepared from chloroplasts with digitonin a more detailed analysis of the decay kinetics of fluorescence excited by a picosecond laser pulse has been possible compared to experiments with unfractionated systems the photosystem i fractions show a very short component less than or equal to ps at room temperature which is apparently independent of pulse intensity over the range of photon densities used photons cm the photosystem ii fraction has a short initial lifetime at room temperature which is strongly intensitydependent approaching ps at low photon densities but decreasing to close to ps at the highest photon densities all of these room temperature decays appear to be nonexponential and may possibly be fitted by at t expression expected from a random diffusion of excitations via förster energy transfer on cooling to k lifetimes of both photosystem i and photosytem ii increase the lengthening with photosystem i being more striking the photosystem i decays become intensity dependent like the PS ii and at the lowest photon densities decays which are more nearly exponential within the exp error give initial lifetimes of about ns the nonexponential decays seen at high photon densities appear to fit a t expression | MEDAL |
in the present T0 we investigated the relationship between DS and serum zinc and magnesium level in antepartum and PP women all women received standard vitamin zinc and magnesium supplementation sixtysix Pr women in the czerwiakowski hospital in kraków were assessed for prepartum depressive symptoms using the beck depression inventory bdi sixtytwo and fiftyeight women were also assessed for PP DS using edinburgh PND rating scale epdrs at and days after delivery respectively serum zinc and magnesium levels were also determined at these time points however the number of examined subjects were diminished a significantly higher epdrs score by indicating severity of DS was found on the rd day T3 childbirth compared with the th postpartum day moreover the early postdelivery period rd day was characterized by a lower serum zinc concentration than that found on the th day T3 childbirth bdi scores assessed a month before childbirth revealed mild depressive PS which was accompanied by a serum zinc concentration similar to that found on the rd day after delivery no significant alterations were found in the magnesium C2 between these time points the present results demonstrated a relationship between severity of depressive symptoms and decreased serum zinc but not magnesium concentration in a very TPS type of affective disorder the PP depression | MEDAL |
Tc m sestamibi cardiac scintigraphy is widely used as a means of predicting myocardial viability in patients with chronic ischemic left ventricular lv dysfunction no data are available comparing the results of visual and quantitative analysis of tomographic imaging in the assessment of myocardial viability the aim of this T0 was to directly compare visual and quantitative analysis of resting sestamibi single photon emission computed tomography in the identification of viable myocardium in patients with chronic lv dysfunction | MEDAL |
given the generally poor outcome of T3 b cell CLL leukemia experimental approaches are warranted especially for younger patients in whom classical treatments have failed we therefore conducted a prospective singlecenter study using PCT eshap to prepare patients for hematopoietic stem cell collection and autologous stem cell transplantation as consolidation therapy twenty patients entered the study an adequate response to eshap was obtained in patients and sufficient stem cells for grafting were obtained in eight of the patients who underwent the collection procedure six of these grafted patients are alive in complete clinical remission a median of months Tx it should be noted that we were only able to graft of the patients enrolled in this study either because a new remission could not be obtained or because not enough hematopoietic stem cells could be collected this argues for stem cell collection as soon as a CR1 is obtained even if the autograft is done later in the course of the disease | MEDAL |
to T0 how quickly C2 proprioceptive information induced muscular responses in the lower leg to control posture in the standing human we investigated lower leg muscle electromyography and forceplate data from healthy normal subjects when perturbed by posterior neck muscle vibration at the onset of vibration the tibialis anterior muscle was G1 at latencies of ms whilst the triceps surae muscle was inhibited at the same latencies at offset the opposite pattern was observed these findings suggest that a shortlatency integrative system rather than a direct reflex mediates the cervical influence on posture the short latencies also imply that activation of postural muscles in response to vibration towards the neck muscles occurs faster than would be expected if it was caused only by a perceptive illusion of movement | MEDAL |
we investigated peroxisome proliferatoractivated receptorγ pparγ ligands effect on cell motility and the plasminogen activator system using normal mcfa and malignant mcfca cell lines ciglitazone reduced both woundinduced migration and chemotaxis however the effect was not reversed with pretreatment of cells with the pparγspecific antagonist gw immunoblot analysis of CS media showed ciglitazone decreased plasminogen activator inhibitor pai in both cell lines this effect was also unaltered by pparγ antagonism alternatively treatment with the Ï fatty acid AA ara but not the Ï fatty acid docosahexanoic acid increased both mcfa cell migration and cell surface upa activity pretreatment with a pparγ antagonist reversed these effects suggesting that ara mediates its effect on cell motility and upa activity through pparγ activation collectively the data suggest pparγ ligands have a differential effect on normal and malignant cell migration and the plasminogen activation system resulting from pparγdependent and pparγindependent effects | MEDAL |
headache is a common condition not always managed satisfactorily by primary care providers pcps in an effort to improve headache care the curitiba city hall in consortia with hospital de clÃnicas da universidade federal do paraná brazil developed an educational program directed to the pcps the goal of the project was to evaluate to update and to train the pcp on HA knowledge and care | MEDAL |
phagocytes are able to generate ROS species by an activatable NOX system we investigated the inhibition of nadph oxidase activation by a methoxysubstituted catechol apocynin oxygen uptake by neutrophils incubated with microm apocynin was completely inhibited at min T3 addition of serumtreated zymosan stz with a lagtime of inhibition of to min the lagtime of effect of apocynin in neutrophils relatively deficient of myeloperoxidase was about longer when compared with normal cells inhibition of the stzinduced RB by apocynin was also observed in human eosinophils but not in HAM immunoblots of PMNL CM isolated at and min T3 stz stimulation of neutrophils demonstrated translocation of the cytosolic oxidase components pphox and pphox to the membrane fraction translocation at min after stz stimulation was markedly reduced when the neutrophils had been incubated with microm apocynin but translocation was normal after min of stimulation these properties suggest that apocynin is an intracellular inhibitor of the assembly of nadph oxidase in neutrophils and eosinophils and that apocynin requires conversion by peroxidases to exert its inhibitory effect the capacity of neutrophils for intracellular killing of staphylococcus aureus was not affected by apocynin the potential therapeutic value of apocynin was demonstrated in vitro by its ability to protect secretory leukocyte proteinase inhibitor from oxidative inactivation by neutrophils | MEDAL |
muscarinic receptors in the rat CBF cortex cardiac atria and vas deferens were identified quantitated and characterized relative to phosphatidylinositol pi turnover as the functional response to stimulation of specific receptor subtypes receptor densities as determined by hqnb IB were ranked CBF cortex greater than vas deferens greater than HR using displacement of hqnb binding by the selective m and m muscarinic receptor M1 and diethylaminomethylpiperidinylacetyldihydro hpyrido b benzodiazepineone afdx respectively heterogeneous populations were found in the cerebral SC and VD the m receptor subtype predominated in the former and the m predominated in the latter an homogeneous m receptor population was present in the heart methacholinestimulated accumulation of h inositolphosphate was greater in the VD than in the cerebral SC whereas pi turnover was not enhanced in cardiac atria RES treatment of rats mg kg day for days increased muscarinic receptor density in the VD coincident with a shift in the low affinity pki for afdx to a value comparable to high affinity IB and abolished the enhanced pi hydrolysis in the cerebral cortex reserpine treatment shifted only the early portion of the methacholine doseresponse curve to the right these results are judged to be supportive of preferential coupling between the m muscarinic receptor AT1 and pi turnover | MEDAL |
aortic valve regurgitation ar imposes a severe volume overload to the left ventricle lv which results in dilation eccentric hypertrophy and eventually loss of CF little is known about the impact of ar on lv mRNA we therefore conducted a gene expression profiling T0 in the lv of rats with acute and severe ar we identified genes that were specifically upregulated and that were downregulated out of genes after wk of the upregulated genes a good proportion was related to the extracellular matrix we subsequently studied a subset of genes by quantitative rtpcr qrtpcr to see if the modulation seen in the lv T3 wk persisted in the CP after and mo and found that it did persist knowing that the adrenergic and reninangiotensin systems are overactivated in our animal MM we were interested to see if blocking those systems using metoprolol mgkgday and captopril mgkgday would alter the expression of some upregulated lv genes in ar rats T3 mo by qrtpcr we observed that upregulations of lv mrna C2 encoding for procollagens type i and iii fibronectin atrial natriuretic peptide transforming growth factorbeta and connective tissue growth factor were totally or partially reversed by this treatment these observations provide a molecular rationale for a medical strategy aiming these systems in the medical treatment of ar and expand the paradigm in the study of this form of lv volume overload | MEDAL |
a yearold man who had had a left upper lobectomy for mucoepidermoid lung carcinoma was admitted again months later because of enlargement of four small nodules in the left lower lobe a computed tomographyguided needle aspiration biopsy obtained insufficient material for diagnosis and because pulmonary metastases were suspected two of the four PT were extirpated intraoperative frozen section found the nodules to be intrapulmonary lymph nodes intrapulmonary lymph NO should be included in the differential diagnosis of coin lesions in the IP lung field | MEDAL |
objectivein the united states healthcare expenditures have been soaring at a concerning rate there has been an excessive use of postoperative radiographs after spine surgery and this has been a target for hospitals to reduce unnecessary costs however there are only limited data identifying the rate of instrumentation changes on radiographs after complex spine surgery involving ⥠level fusionsmethodsthe medical records of AD ⥠years old patients with spine deformity undergoing elective primary complex spinal F0 ⥠C2 for deformity correction at a L1 academic institution between and were reviewed patient demographics comorbidities and intra and postoperative complication rates were collected for each patient the authors reviewed the first subsequent postoperative and followup radiographs and determined whether revision of surgery was performed within years postoperatively the primary outcome investigated in this T0 was the rate of hardware changes on followup radiographsresultsthe majority of patients were female with a mean age of ± years and a body mass index of ± kgm parametric data are expressed as the mean ± sd the median number of F0 C2 was interquartile range with a mean length of surgery of ± minutes and an estimated blood loss of ± ml the mean length of hospital stay was ± days with a day readmission rate of postoperative and followup change in stability on radiographs days from operation included image ± days image ± days image ± days image ± days and image ± days the rd year after surgery had the highest rate of hardware revision followed by the nd year and the st year conclusionsthis T0 suggests that the rate of instrumentation changes on radiographs increases over time with no changes occurring at the first postoperative image in an era of costconscious healthcare fewer orders for early radiographs after complex spinal fusions ⥠C2 may not impact patient care and can reduce the overall use of healthcare resources | MEDAL |
chronic myeloid leukemia cml is a clonal multilineage myeloproliferative disease of stem cell origin characterized by the presence of the bcrabl oncoprotein a constitutively AS tyrosine kinase the actual treatment of cml patients in CP is the specific abl kinase inhibitor imatinib mesylate that induces of cytogenetic responses in earlyphase patients however resistance in LT treated patients occurs and the allogeneic stem cell transplantation remains the only curative treatment in resistant patients despite recent reports outlining the role of allogeneic A-NK nk cells as potent antileukemic effectors the mechanisms controlling the leukemic target recognition and lysis by A-NK cells have not been well identified the authors experimental data obtained on appropriate cellular models identify diverse mechanisms that could explain the increased nkcell susceptibility of bcrabl targets to nkmediated lysis they further delineate unexpected effects of the inhibition of the IMT kinase activity on the crosstalk between nk and cml leukemic cells the consequences of such discoveries are discussed in the context of combined treatments with antikinases as well as adoptive cellular therapy approaches in ML patients | MEDAL |
aerosols of mtc DTPA mtcdtpa used for measuring lung permeability and lung ventilation require a radioaerosol delivery system to produce an aerosol with reproducible size and radiochemical purity to test how well nebulizers meet this requirement RCP of aerosols produced with a jet and an US nebulizer was evaluated the activity median aerodynamic diameter amad and geometric standard deviation sigma g of radioaerosols were micron sigma g for the jet NEB and micron sigma g for the US nebulizer paper and liquid chromatographic assays were obtained on the mtcdtpa aerosol solute produced with each nebulizer the results of these tests showed L1 differences in radiochemical purity aerosols produced in the jet nebulizer consistently showed greater than of the radioactivity bound to the dtpa ligand whereas aerosols produced in the ultrasonic NEB showed less than of the radioactivity bound to dtpa the results support the need to test RCP of aerosols before using an aerosol NEB for pulmonary imaging and clearance studies | MEDAL |
the medicinal plant withania somnifera has been used for over centuries in indian ayurvedic medicine to treat a wide spectrum of disorders withaferin a wa a bioactive compound that is isolated from this plant has antiinflammatory immunomodulatory antiangiogenic and anticancer properties here we investigated MPM mpm suppressive effects of wa and the molecular mechanisms involved wa inhibited growth of the mu as well as patientderived mpm cells in part by decreasing the chymotryptic activity of the proteasome that resulted in increased levels of ubiquitinated proteins and proapoptotic proteasome target proteins p bax iκbα wa suppression of mpm growth also involved elevated apoptosis as evidenced by activation of proapoptotic p AS G1 protein kinase sapk and caspase elevated C2 of proapoptotic bax protein and PARP parp our studies including genearray based analyses further revealed that wa suppressed a number of cell growth and metastasispromoting genes including cmyc wa treatments also stimulated expression of the cell cycle and apoptosis RII protein carpccar a novel transducer of cell growth signaling knockdown of carp on the other hand interfered with mpm growth GABA effects of wa intraperitoneal administration of mgkg wa daily inhibited growth of mu mpm cellderived tumors in vivo in part by inhibiting proteasome activity and stimulating apoptosis together our in vitro and in vivo studies suggest that wa suppresses mpm growth by targeting multiple pathways that include blockage of proteasome activity and stimulation of apoptosis and thus holds promise as an antimpm agent | MEDAL |
ob/ob obob mice are protected from con ainduced hepatitis however it is unclear whether OB deficiency or obesity itself is responsible for this protection to address this question wildtype wt obese mice with high SS OB levels were generated by injection of gold thioglucose wt gtg both con ainjected wt and wt gtg mice developed hepatitis whereas no hepatic damage was observed in obob mice moreover tnfalpha and ifngamma levels as well as expression of the activation marker cd were elevated in CL mononuclear cells of wt and wt gtg mice but not in obob mice following administration of con a the CL of wt and wt gtg mice had the same percentage of nk t cells a lymphocyte population involved in con ainduced SH this population decreased equally in both wt and wt gtg mice T3 con a i.t. in contrast the CL of obob mice contained less nk t cells compared to wt and wt gtg mice furthermore no decrease in nk t cells was observed in con ainjected obob mice we conclude that leptindeficiency not obesity is responsible for protection from con ainduced SH | MEDAL |
coxsackievirus b cvb SCV h and ha differ by a single nonconserved CAA in the vp capsid region cbl mice INF with the h virus develop MC correlating with activation of t cells expressing the vγ Ti chain infecting mice with ha activates NK killer t nkt mcddtetramer tcrβ cells but not vγ t cells and fails to induce myocarditis ha infection preferentially activates m alternatively G1 macrophage and cdfoxp t regulatory cells whereas cdth ifnγ cells are suppressed by contrast h virus infection activates m Th1 and cdth cells but not t RII cells the m macrophage show significantly increased cdd expression compared to m macrophage the ability of nkt cells to suppress myocarditis was shown by adoptive transfer of purified nkt cells into hinfected nkt knockout jα KO mice which inhibited cardiac inflammation and increased t regulatory cell response cardiac virus titers were equivalent in all mouse strains indicating that neither vγ nor nkt cells participate in control of virus infection these data show that nkt and vγ cells crossregulate t RII cell responses during cvb infections and are the primary factor determining viral pathogenesis in this mouse MM | MEDAL |
steroidsulfatase activity was absent in the cultured fibroblasts of nine affected members of eight families with sexlinked ichthyosis an intermediate value of CEA was found in an obligate heterozygote henobarbital and methylcholantrene and finally by the chromatographic separation of fractions with enzymatic glucuronidating activity only for rhonitrophenol or only for morphine nalorphine in concentrations of x m and x m inhibited in vitro dendemethylation of morphine x m by the supernatant of rat liver homogenates while in concentration of x m it enhanced this reaction | MEDAL |
the authors describe a patient with a palpable anterior neck mass and a SM swelling at the level of the vocal cords computed tomography ct revealed a tumour of the laryngeal skeleton pathologic diagnosis was a moderately well differentiated chondrosarcoma | MEDAL |
il is a cytokine which not only suppresses cellular immunity but also stimulates the humoral response in certain animal models of autoimmunity il exerts a protective effect against autodestruction this T0 was to ascertain whether there could be a role for il in human autoimmune thyroid disease total rna was extracted from snapfrozen thyroid blocks from surgical specimens five normal five multinodular six graves and two hashimoto thyroids one euthyroid and one hypothyroid were studied approximately microg of total rna from each gland were RT with oligodt primers preplateau semiquantitative PCR reaction pcr was performed with TPS il primers pcr products were run on a agarose gel blotted onto a nhybond nylon membrane hybridized with a specific internal probe labelled with gammapatp and autoradiographed statistical analysis of densitometric values showed significantly higher il levels in the autoimmune than in the nonautoimmune PG in situ hybridization and immunohistochemistry showed that the il message was located within the infiltrating lymphomononuclear cells histological analysis revealed that the autoimmune thyroids with the highest il C2 were characterized by relevant degrees of b and t cell infiltration and also exhibited the greatest percentage of spontaneous hla class ii expression on thyrocytes il and neutralizing antiil antibodies were not able to regulate in vitro spontaneous or interferongamma ifngammaphytohaemagglutinin phainduced hla class ii on thyrocytes we conclude that in active autoimmune thyroiditis in addition to the well documented production of th cytokines threlated lymphokines can be detected simultaneously it can be envisaged that in this condition the role of il might be directed to the stimulation of b cell proliferation and antibody production rather than to the suppression of Th1 cytokine release | MEDAL |
the HFA hfa formulation of the inhaled corticosteroid FLU is a modification of the original chlorofluorocarbon cfc formulation hfa FLU replaces cfc with an hfa propellant and uses a builtin spacer in its pressurized metereddose inhaler the average hfa flunisolide particle size is microm compared with microm for the cfc formulation the smaller particle size improves lung targeting allowing a reduction in the hfa flunisolide dose relative to cfc flunisolide while maintaining comparable tau in a T0 of healthy men pharmacokinetic parameters were determined T3 single doses of microg cfc flunisolide delivered without a spacer microg hfa flunisolide delivered through a spacer and microg hfa flunisolide delivered without a spacer a standard noncompartmental analysis of the concentration data was performed and mean sd pharmacokinetic values were reported Tmax observed cmax were similar for the three treatments area under the curve up to the time corresponding to the last measurable concentration auctlast was similar for the cfc and hfa FLU plus spacer CG ng x hml and ng x hml respectively however auctlast for the hfa FLU without spacer group was comparatively lower than for the cfc group ng x hml observed cmax and auctlast for betaoh flunisolide the FP metabolite of flunisolide and an indicator of oropharyngeal deposition were significantly higher in the cfc flunisolide group than in either hfa FLU group | MEDAL |
the role of platelet fibrinogen receptors and plateletprotein interaction in platelet consumption during simulated CP bypass was investigated in five recirculation experiments with whole blood the PLT count fell to of initial values and in two experiments with blood from patients with BSS to of normal values however in three experiments with blood from the patients with glanzmanns thrombasthenia the platelet count decreased to of initial values the extent of platelet consumption in normal blood was diminished to only by addition of microm prostaglandin e pge experiments and to by precoating surfaces of the circuit with human albumin experiments betathromboglobulin antigen beta tg loss from platelets was associated with TP the extent of beta tg loss was significantly reduced by the addition of pge to blood or precoating surfaces with albumin proteins adsorbed on the surface of the circuit exposed to normal blood were removed with triton x some of these proteins were identified to be glycoprotein iiia gpiiia microgramsml beta tg microgramsml and fibrinogen microgramsml the amount of gpiiia recovered in the triton x eluates correlated with the number of platelets lost during recirculation these studies indicate that exposure of fibrinogen receptors associated with gpiibgpiiia complex contributes to PLT consumption during CP bypass | MEDAL |
there is a dramatic increase in total blood volume during healthy pregnancy the disproportionate expansion in CPV and RCM depending on iron status results in a decrease in haemoglobin concentration maximal at weeks gestation this should not fall below gdl at any time during pregnancy deficiency of essential haematinics arising from increased requirements and inadequate NI may have far reaching effects on mother fetus and neonate which bear no relationship to the impaired oxygen carrying capacity of the reduced cell mass pathological anaemia of pregnancy is due to over of cases to iron deficiency associated with depleted stores and deficient NI the single largest demand for iron arises from the increased red cell mass under the influence of erythropoietin tissue enzyme malfunction occurs even in the very first stages of iron deficiency before significant anaemia develops increased BL at delivery and preterm birth are observed associated complications offspring of iron deficient mothers have decreased iron stores and may develop anaemia in the first year of life studies have shown behavioural abnormalities in children with iron deficiency and poor performance in the bayley mental developmental index the poor performance in mental and motor development can be improved to the level of ironsufficient infants by treatment with ferrous sulphate folate deficiency often accompanies iron deficiency as they are both associated with a poor diet the haematological effects of folate deficiency are usually masked by iron deficiencyabstract truncated at words | MEDAL |
two enzymes of ketone body metabolism oxoacid coatransferase and hydroxybutyrate dehydrogenase were measured with ultramicromethods to map their activities along single dissected segments of mouse nephron oxoacid coatransferase activity was assayed with a radiochemical procedure by separating csuccinylcoa formed in the presence of acetoacetylcoa from csuccinate this procedure when compared to the spectrophotometric method resulted in similar MICs in mouse organ homogenates hydroxybutyrate dehydrogenase activity was determined with sufficient sensitivity by using nadhdependent luciferase the dehydrogenase exhibited only of the activity of the oxoacid coatransferase when measured in mouse kidney SC homogenates both enzymes were found to be present in all nephron structures studies the specific activity related to tubular protein which was determined in parallel in all segments dissected exhibited a typical distribution DP along the nephron both enzymes roughly paralleled each other along the structures of the distal nephron they exhibited high activities in the thick ascending limb of henles loop and the distal convoluted tubule but decreased to nearly in the segments of the collecting tubule in the PCT and straight tubule oxoacid coatransferase activity was almost equal in contrast hydroxybutyrate dehydrogenase increased by a factor of from the convoluted to the straight portion this heterogeneity along the S3 remained when pure dhydroxybutyrate was used as substrate but was not found when rat or rabbit nephron segments were analysed lowest MICs of enzymes were recovered from glomeruli and thin descending limbs of henles loop the results obtained allow for the conclusion that hydroxybutyrate and acetoacetate can be metabolized in all structures of the mouse nephron with different capacities in various segments with the exception of the relatively low activity of hydroxybutyrate dehydrogenase in the PT convoluted tubule the CSD pattern mirrors the CSD of mitochondria along the rat nephron the results point to the possible role of ketone bodies as SE fuels for nephron segments performing active transport processes | MEDAL |
parkinsons disease pd features selective loss of DA SN of the substantia nigra pars compacta accompanied by the accumulation and aggregation of alphasynuclein in lewy HB pten induced putative kinase gene pink mutations are the second most common genetic cause of autosomal recessive earlyonset FPD eopd a single nucleotide deletion in pink exon cdelg was identified in a consanguineous chinese family with eopd the homozygous deletion was cosegregated with disease in the family and resulted in a frameshift T3 codon with a premature termination at codon pkrfsx these findings have significant implications on genetic counseling for the family and may be helpful in considering potential pathogenesistargeted and diseasemodifying strategies which should further improve patient SQ of life | MEDAL |
authors sought to compare the efficacy of monotherapy versus combination antihypertensive therapy in elderly patients patients in this study aged to years were divided into CG and entered an week treatment period first group patients AML mgd increasing to mg second patients eprosartan mgd increasing to mg twice a day third patients amlodipine mgd and ind mgd increasing amlodipine to mgd fourth patients imidapril mgd and indapamide mgd imidapril doubled to mgd a greater drop in systolic and in diastolic blood pressure was obtained by combination of AML and indapamide compared with amlodipine or eprosartan monotherapy imidapril and indapamide showed similar tau compared with eprosartan monotherapy but not with AML monotherapy amlodipine and indapamide appeared more effective than imidapril and indapamide in diastolic blood pressure combination treatment with AML and indapamide or imidapril and ind effectively reduces blood pressure in elderly patients with essential hypertension | MEDAL |
the reactions of chloroauric acid haucl with inosineino guanosineguo triacetylinosinetrino triacetylguanosinetrguo and cytidinecyd were studied complexes of auiii and aui with these nucleosides have been isola was found to be greater than pure on polyacrylamide disc gels in the presence of sodium dodecyl sulfate the subunit mr from the electrophoretic procedure was estimated at approximately the isolated cytoplasmic fragment ws judged to be a dimer since i the unmodified fragment and its disulfidecrosslinked dimeric counterpart eluted in the same peak fraction from a sephacryl s GF column and ii the sedimentation velocity molecular weight of the native fragment was calculated to be approximately no evidence of either larger or smaller aggregates was obtained the frictional ratio of the fragment was measured at suggesting a highly elongated morphology the circular dichroism spectrum of the fragment corresponded to approximately alpha helix titration of the cytoplasmic fragment over the physiological ph range gave rise to a reversible fold increase in the intrinsic fluorescence quantum yield lambda ex nm lambda em nm between ph and computer analysis of the data yielded a temperaturedependent apparent pka of at degrees c and at degrees c both with hill coefficients less than or equal to calorimetric experiments revealed a similar sensitivity to ph where the denaturation temperature of the fragment titrated from degrees c at ph to degrees c at ph with an apparent pka of and a hill coefficient less than the enthalpies and widths at halfheight of the EMT were also exquisitely sensitive to ph the fluorescence and calorimetric data could all be described by the titration of a single ionizable group of apparent pka of at degrees c and delta pkadegrees c of the ionization of this critical group is suggested to exert significant control over the structurestability of the cytoplasmic domain of band | MEDAL |
several postmortem and neuroimaging studies suggest that central nicotinic and muscarinic acetylcholine receptors are important in both the pathophysiology and pharmacotherapy of schizophrenia however while AP drugs are routinely used in the therapeutics of schizophrenia little is known about their effects on the densities of these receptors when they are po for D2 periods of time a common practice in the clinical setting in the present study in rats the residual effects of prior chronic SE to representative first generation antipsychotics and second generation antipsychotics on the densities of high affinity nicotinic acetylcholine receptors and mACh receptor in the brain were investigated test subjects were treated with the first generation antipsychotics haloperidol mgkgday or chlorpromazine mgkgday or the second generation antipsychotics risperidone mgkgday or olanzapine mgkgday in drinking water for periods of or days given a drugfree washout period ie returned to normal drinking water for two weeks and then killed quantitative receptor ARG was subsequently performed using mum sagittal slices of whole brain incubated with hepibatidine hpirenzepine or hafdx to measure high affinity nicotinic acetylcholine receptors m and m mACh receptors respectively the most notable experimental result was a moderate but significant p increase in hafdx IB CS in a number of BB regions including SC hippocampus subiculum substantia innominata and thalamus associated with prior exposure to olanzapine for but not days olanzapine was also associated with a significantly higher density of hpirenzepine binding CS in cortex lamina i after days of prior drug exposure these data indicate that chronic treatment with a commonly used F2 AP olanzapine is associated with modest increases in m mACh receptors in memoryrelated BB regions that may eventually abate with longer periods of chronic drug SE | MEDAL |
the independent living movement represents a direct challenge to current notions of rehabilitation see the article by gerben dejong in this issue it is a unique challenge spearheaded not by new technical advances but by a new social awareness and not from within by medical personnel but from without by lay groups in another sense however it is but the latest evolution of an old theme in american lifethe notion of selfhelp this paper traces the PH of selfhelp to illuminate the problems and prospects of the IL movement | MEDAL |
we investigated the effect of escherichia coli ob ET on the adrenergic control of lipolysis in the human adipocyte adipose tissue was incubated in vitro with isoproterenol to stimulate the beta receptors clonidine to stimulate the alpha receptors and theophylline to stimulate the subreceptor mechanism using a dual radioisotope technique a lipolysis factor was calculated for each sample the basal lipolysis factor was significantly p less than decreased with endotoxin beta adrenergic receptor stimulation isoproterenol x to x m was significantly decreased an average of with e coli endotoxin the beta receptor responsiveness was also significantly p less than decreased but not the receptor sensitivity this indicated an alteration in the post beta receptor mechanism the various components of the post beta adrenergic mechanism were stimulated including the beta receptor the g protein adenylase cyclase and the lipase phosphorylase the results indicated a significant reduction of the beta receptor and a reduction in g protein stimulation thus the e coli endotoxin effect on the beta adrenergic mechanism is at the g protein the endotoxin had no effect on the alpha receptor stimulation nor the theophylline stimulation of the subreceptor lipolysis this study indicates that e coli endotoxin ob decreases in vitro beta adrenergic stimulation of human adipocyte lipolysis and this effect can be partially reversed by theophylline | MEDAL |
between two courses of single agent carboplatin had been given to patients with clinical stage i seminoma within an median follow up period of months out of patients were analyzed retrospectively during this period no recurrences had been noted and nobody of our patients died relapsrate survivalrate the carboplatintherapy was well tolerated myelosuppression after chemotherapy was mild who grade i the experienced acute toxic side effects max grade ii who during and T3 chemotherapy had been nausea vomiting and mild hairloss until now no long term side effects were noticed a standardized questionnaire had been used to evaluate the impairment of quality life after single agent carboplatin therapy after a minimum of one year follow up averagly of the asked patients showed no impairment of their quality of life whereas of the people experienced mild impairment of their SQ of life because of the shown low recurrence rate the minimal toxicity and no relevant impairment of the SQ of life single agent carboplatin therapy will be an alternative RPA for CSI seminoma | MEDAL |
to use published hypertension optimal treatment hot T0 data to evaluate changes in cardiovascular mortality in nondiabetic hypertensive patients according to the degree of reduction in their diastolic blood pressure | MEDAL |
lamotrigine is an antiepileptic and mood stabilizing drug that has been detected in wastewater groundwater surface water and drinking water at frequencies in surface water ranging from to because lamotrigine is a weak base pka that appears in two protonation states in natural waters this T0 examined the direct photodegradation of lamotrigine to mg l in simulated sunlight using liquid chromatographyuv diode array detection and buffered AQ solutions at ph and lamotrigines halflife varied little ± to ± h with solution ph but its specific CS absorption rate was times higher and its reaction quantum yield was times lower at ph versus ph in the estimated midday midsummer sunlight in denver co usa latitude °n lamotrigines estimated photodegradation rate was more than twice as fast at ph versus ph lamotrigines photoproducts were detected by liquid chromatographyuv diode array PCD and timeofflight mass spectrometry solution ph was shown to affect the identities and relative abundances of lamotrigines photoproducts some photoproducts appeared only in solutions containing protonated lamotrigine and others appeared only in solutions containing neutral lamotrigine as a result different reaction mechanisms were proposed finally lamotrigines reaction quantum yield ± à mol einstein at ph and other results suggested that lamotrigine and three photoproducts are approximately as resistant to direct photodegradation as CBZ a frequently detected pharmaceutical in surface waters | MEDAL |
segments of human RA atrial appendages preincubated with hnoradrenaline and superfused with physiological salt solution containing desipramine and corticosterone were used to examine whether the cardiac sympathetic SN are endowed with cannabinoid receptors and to further study pharmacological properties of presynaptic imidazoline receptors the cannabinoid cb receptor agonists cp hu and anandamide inhibited evoked hnoradrenaline PR the inhibition by cp and anandamide was abolished by the cb receptor antagonists sra microm and ly microm rauwolscine at the imidazoline receptorblocking concentration of microm abolished the inhibitory effect of cp and anandamide T3 blockade of alphaadrenoceptors with microm rauwolscine the imidazoline IB site ligand s which is the enantiomer of the racemic oxazoline derivative s exhibited low potency in inhibiting electrically evoked hnoradrenaline PR pic whereas the enantiomer s and the racemate s were ineffective in the presence of microm rauwolscine s did not significantly inhibit evoked release the imidazoline receptormediated inhibitory effect of bdf and aganodine on evoked hnoradrenaline PR was abolished by microm sra and by microm ly the GABA effect of moxonidine on evoked hnoradrenaline PR which is exclusively mediated via activation of alphaautoreceptors was not antagonized by microm sra in conclusion GABA cannabinoid B6 receptors are present on the sympathetic axon terminals of human atrial appendages presynaptic imidazoline receptors share the property of other receptors in that they can be stereoselectively activated the crossantagonism of imidazoline receptor agonistsantagonists with cb receptor antagonistsagonists suggests that these receptors may have certain binding domains in common or that they interact with each other in an unknown manner | MEDAL |
to determine the quality of singlepiece allpolymethylmethacrylate pmma intraocular lenses iols from eght generic manufacturers marketing their product in india this assessment of quality was made with respect to compliance with internationa standards for the manufacture of iols specifically those parameters most likely to affect patient postoperat ve visual acuity and the longterm biocompatibility of the implanted lens | MEDAL |
LM observations of the vomeronasal organ vno jacobsons organ of habu trimeresurus flavoviridis revealed that the organ was encased in the os vomeris and the vomeronasal cartilage on either side of the nasal septum habu vno was divided into a domeshaped portion mainly composed of a sensory epithelium se and a hemispherical mushroom body covered with a ciliated epithelium a narrow lumen leading to the oral cavity via the VN duct was made between the mushroom body and the se the se consisted of a supporting cell SL facing the lumen and the underlying sensory cell SL where a C1 number of cells piled up in columns V1 plexuses were found around the neck and bottom of the columns along the antero posterior axis of the vno the height of the columns reached its maximum in the middle of the dorsal and the median parts over micron and gradually decreased toward lateral each column contained undifferentiated basal cells sensory cells and satellite cells sensory cells had a round nucleus and prominent lipofuscin LG the sensory cells were arrayed in a stringlike arrangement cells situated in the neck region of columns contained a larger amount of LF granules distal processes of sensory cells passed through the cytoplasmic meshwork of supporting cells and terminated as small swellings aggregates of heterogeneous cell populations were observed in the antero lateral region of the dome a number of pigment cells were seen in the epineurium and the perivascular regions of the dorsal and lateral vnos goblet cells were present in the lateral boundary between the dome portion and the mushroom body present findings clarify the complex organization of the habu vno and the occurrence of the sensory columns similar to those reported in other snakes | MEDAL |
gene expression reprogramming governs cellular processes such as proliferation differentiation and cell migration through the complex and tightly regulated control of transcriptional cofactors that exist in multiprotein complexes here we describe scai suppressor of cancer cell invasion a novel and highly conserved protein that regulates invasive cell migration through threedimensional matrices scai acts on the rhoadia signal transduction pathway and localizes in the nucleus where it binds and inhibits the myocardinrelated transcription factor mal by forming a ternary complex with serum response factor srf genomewide expression analysis surprisingly reveals that one of the strongest upregulated genes T3 suppression of scai is betaintegrin decreased levels of scai are tightly correlated with increased invasive cell migration and scai is downregulated in several human tumours functional analysis of the betaintegrin gene strongly argues that scai is a novel transcriptional cofactor that controls gene expression downstream of dia to dictate changes in cell invasive behaviour | MEDAL |
these studies were performed to assess the chronic toxicity and oncogenicity of DDE glycol eg in rats and mice groups of fischer rats and cd mice per sex were fed diets yielding approximate dosages of or gkgday of eg two separate control groups in each study received no eg MR was increased in highdose male rats all of which died by days the following effects were also observed in high dose male rats reduced body weight gain increased water NI increased blood urea nitrogen and creatinine reduced erythrocyte count reduced hematocrit and hemoglobin increased neutrophil count increased UV reduced SG and ph urinary calcium Ox crystals and increased kidney weight were seen in all highdose rats uric acid crystals were seen in the urine of highdose female rats at and months histopathologic changes in highdose male rats included tubular cell PH tubular dilation peritubular nephritis parathyroid PH and generalized soft tissue mineralization fatty change of the liver was seen in high and intermediatedose female rats no clinical signs or gross or microscopic evidence of toxicity was seen in mice at the dosages used water intake and clinical pathologic parameters were not measured in the mouse T0 in these studies there was no evidence of an oncogenic effect of eg in rodents | MEDAL |
the fate of cases of apparently primary cardiomyopathy were studied by angiocardiography and coronary arteriography over a to year period with a mean of years correlations were established between the clinical paraclinical haemodynamic and angiocardiographic findings on the one hand and the quality and length of survival on the other among the criteria leading to an improved prognosis the most precise was the left ventricular ejection fraction | MEDAL |
a deviant habitual sleep duration sleep complaints frequent napping and snoring have all been suggested as potential risk AF for future coronary heart disease it has not been studied thoroughly however whether the association of these phenomena with coronary HR disease is confounded by type a behaviour or by a state of vital exhaustion the aim of the present study was to explore the association of the above sleep characteristics with the CR AF type a behaviour and vital exhaustion systematically the results indicated that type a behaviour was not associated with any of these sleep characteristics except with frequent waking exhausted subjects however reported chronic sleep complaints a short sleep duration and frequent napping significantly more often than vital subjects type a behaviour did not confound these associations the data support the assumption that these sleep characteristics can be considered as potential risk AF for coronary HR disease because of their association with vital exhaustion | MEDAL |
activating and inhibiting receptors of lymphocytes collect valuable information about their mikròs kósmos this information is essential to initiate or to turn off complex signaling pathways irrespective of these advances our knowledge on how these intracellular activation cascades are coordinated in a spatiotemporal manner is far from CR among multiple explanations the scaffolding proteins have emerged as a critical piece of this evolutionary tangram among many iqgap is one of the essential scaffolding proteins that coordinate multiple signaling pathways iqgap possesses multiple protein interaction motifs to achieve its scaffolding functions using these domains iqgap has been shown to regulate a number of essential cellular events this includes actin polymerization tubulin multimerization microtubule organizing center formation calciumcalmodulin signaling pakrafmekmediated erk activation formation of maestrosome EC and cdmediated signaling and GS kinaseadenomatous polyposis colimediated βcatenin activation in this review we summarize the recent developments and exciting new findings of cellular functions of iqgap | MEDAL |
swertifrancheside a new flavononexanthone glucoside isolated from swertia franchetiana betahydroxyaleuritolic acid phydroxybenzoate a triterpene isolated from the roots of maprounea africana and protolichesterinic acid an aliphatic alphamethylenegammalactone isolated from the lichen cetraria islandica were found to be potent inhibitors of the dna polymerase activity of HIV virus reverse transcriptase hiv rt with inhibitory doses ic values of and microm respectively they were not cytotoxic with cultured rat cells the kinetic mechanisms by which compounds inhibited hiv rt were studied as was their potential to inhibit other nucleic acid polymerases swertifrancheside bound to dna and was shown to be a competitive inhibitor with respect to templateprimer but a mixedtype competitive inhibitor with respect to ttp on the other hand betahydroxyaleuritolic acid phydroxybenzoate and protolichesterinic acid were mixedtype competitive inhibitors with respect to templateprimer and noncompetitive inhibitors with respect to ttp therefore the mechanism of action of betahydroxyaleuritolic acid phydroxybenzoate and protolichesterinic acid as hiv rt inhibitors involves nonspecific binding to the enzyme at nonsubstrate IB CS whereas swertifrancheside inhibits CEA by binding to the templateprimer | MEDAL |
during the last two centuries the spanish ibex capra pyrenaica has shown a significant demographic decline as a result of the progressive destruction of its natural habitat disease epidemics and uncontrolled hunting partial sequencing of the class ii mhc drb gene revealed that the spanish ibex has remarkably low levels of genetic variation at this locus with only six different drb alleles and an observed heterozygosity of the rates of nonsynonymous vs synonymous substitutions were significantly different in the PBR dnds p a feature that indicates that the drb gene is under positive selection a phylogenetic analysis of the spanish ibex and a set of domestic goat drb alleles revealed that the reported sequences represent four L1 allelic lineages the limited allelic repertoire of the drb gene in the spanish ibex is likely the direct result of the recent history of population bottlenecks and marked demographic decline of this species a genetic survey of microsatellite loci was consistent with this idea the spanish ibex subspecies c p hispanica and c p victoriae consistently showed considerably lower levels of microsatellite heterozygosity ho and allelic diversity mean number of alleles per locus than those reported in other wild ruminants this study demonstrates the significance of both NK selection and the demographic PH of populations in determining patterns of genetic R2 at mhc loci in addition our results emphasize the importance of locally adapted populations for the preservation of genetic diversity | MEDAL |
postural tachycardia syndrome pots is a dysautonomia defined by an exaggerated increase in heart rate upon changing posture it is associated with disturbances involving multiple organ systems including neurologic dermatologic and gastrointestinal gi symptoms previous studies identified gi complaints in these patients and showed gastric emptying and EA abnormalities however the full spectrum of gi symptoms and their impact on quality of life remains unclear | MEDAL |
ovarian CA is a highly lethal disease and its underlying biology is poorly understood prophylactic salpingooophorectomies in brca women have recently implicated the fimbria as a site of origin for highgrade serous carcinoma and its IEL precursors this suggests that at least some ovarian cancers probably the most aggressive ones may not originate in the ovary itself but rather may arise in the uterine tubes chronic inflammation is associated with carcinogenesis in several tissues including CL esophagogastric junction cardia and the uterine cervix the mechanisms underlying the relationship between inflammation and CA are complex and involve common pathways in addition to dna damage a critical source of uterine tube inflammation is infection with chlamydia trachomatis we hypothesize that ctrachomatis infection may be involved in chronic tubal inflammation and subsequent fimbrial carcinogenesis fimbrial intraepithelial precursors can evolve into high grade serous carcinomas that spread rapidly to the ovarian surface and peritoneum such PT may appear to be primary ovarian neoplasia though in reality being a secondary malignancy this hypothesis must be further investigated to understand the intracellular signaling pathways involved in CT infection and its healing and their relationship to carcinogenesis in order to discover potential therapeutic molecular targets if our hypothesis were confirmed salpingectomy instead of ovariectomy may also become the recommended surgery for high risk women | MEDAL |
affinity labeling of the rat pancreatic cholecystokinin cck receptor with decapeptide probes has identified an mr protein distinct from the mr component previously labeled with ibolton huntercck we have characterized the carbohydrate composition of this novel protein labeled with idtyrglynlecck and disuccinimidyl suberate by using chemical and enzymatic deglycosylation and lectin chromatography the mr component was demonstrated to be an nlinked sialoglycoprotein based on neuraminidase digestion to mr and endobetanacetylglucosaminidase f endo f digestion to mr this was distinct from the mr product of endo f digestion of the protein labeled with ibolton huntercck lack of an effect of endobetanacetylglucosaminidase h demonstrated the absence of nlinked simple OS while products of chemical day at which the drug is administered maximum toxicity occurs C2 at h further experimentation has shown that the amount of corticosteroid present in the blood has a profound effect on the toxicity of methotrexate in the rat if the endogenous production of corticosterone is suppressed by treatment with dexamethasone the toxicity of methotrexate is markedly increased at whatever clock time it is po however if constantly high plasma levels are achieved by giving supplementary corticosterone methotrexate toxicity is diminished regardless of what time it is given since the timing of maximum methotrexate toxicity corresponds to the circadian nadir of endogenous plasma corticosterone concentration in the rat the possibility that it might be related to corticosterone production must be considered whether this phenomenon occurs in man and has any clinical relevance has yet to be investigated | MEDAL |
ID of virulence determinants of viruses is of critical importance in virology in search of such determinants virologists traditionally utilize comparative genomics between a virulent and an avirulent virus strain and construct chimeras to map their locations subsequent comparison reveals sequence differences and through analyses of sitedirected mutants key residues are identified in the absence of a naturally occurring virulent strain an avirulent CS can be functionally converted to a virulent variant via an experimental evolutionary approach however the concern remains whether experimentally evolved virulence determinants mimic those that have evolved naturally to provide a direct comparison we exploited a plant rna virus soybean mosaic virus smv and its natural host soybean through a serial in vivo passage experiment the molecularly cloned genome of an avirulent smv CS was converted to virulent variants on functionally immune soybean genotypes harboring resistance factors from the complex rsv locus to endstage CL disease it usually develops in those with refractory ascites and is a manifestation of the nonosmotic PR of Arg vasopressin avp in the hospitalized cirrhotic patient hyponatremia is associated with increased disease severity and mortality in this article we review the pathophysiology of hyponatremia its clinical implications evaluation and treatment | MEDAL |
phytochromes are red and farred lightreversible photoreceptors for photomorphogenesis in plants phytochrome a is a dimeric chromopeptide that mediates very low fluence and high irradiance responses to analyze the surface properties of phytochrome a phya the epitopes of antiphya monoclonal antibodies were determined by variously engineered recombinant phya proteins and the dissociation constants of seven antiphya monoclonal antibodies with phya were measured using a SPR sprbased resonant mirror biosensor iasys purified oat phya was immobilized on the sensor surface using a carboxymethyl dextran cuvette in advance and the interactions of each chosen monoclonal antibody against phya in either RL absorbing form pr or farred light absorbing form pfr at different concentrations were monitored the IB profiles were analyzed using the fast fit program of iasys the resultant values of dissociation constants clearly demonstrated the differential affinities between the phya epitopes and the monoclonal antibodies dependent upon pr vs pfr conformations monoclonal antibody map preferentially recognized the epitope at amino acids in the pr form whereas maa map and marmar displayed preferential affinities for the pfrs surfaces at epitopes the hinge region between the n and cterminal domains hinge in pasi domain and CTD respectively the nterminal extension was not recognized by map and map suggesting that the NT extreme is not exposed in the native conformation of phya on the other hand the CTD becomes apparently exposed on prtopfr phototransformation suggesting an interdomain crosstalk the use of surface plasmon resonance spectroscopy offers a new approach to T0 the surface properties of phytochromes associated with the photoreversible structural changes as well as for the study of proteinprotein interactions of phytochromes with their interacting proteins involved in light signaling events in plants | MEDAL |
TR betadribofuranosylthiazolecarboxamide nsc an oncolytic drug inhibits imp dh IMP dehydrogenase ec reduces ST activity and ip inositol trisphosphate concentration and arrests the cell cycle chiefly in s phase genistein trihydroxyisoflavone an inhibitor of pip kinase phosphatidylinositol phosphate kinase ec IMT kinase and topoisomeraseii induces arrest in g andor early m phase in most carcinoma cells both drugs as single agents induce differentiation since tiazofurin and genistein attack different enzymic targets and arrest the Tc at different phases and they each induce differentiation we tested the hypothesis that tiazofurin might be synergistic with genistein in inducing differentiation HL-60 k cells were grown in suspension SC and were seeded in well culture plates in growth inhibition assays for TR and genistein ics drug concentration that inhibits of cell proliferation were and microm respectively for tiazofurin and genistein the concentrations of drug that induce differentiation in of the cells were and microm respectively various combinations of these two drugs were tested since tiazofurin decreased gtp concentration in cells by at hr C2 genistein to microm was added hr T3 tiazofurin to microm synergistic action on differentiation was obtained from all TR and genistein combinations and in most combinations on growth inhibition the percent of differentiating cells induced by genistein microm and tiazofurin microm as single agents increased and fold respectively of the control values the two drugs together caused fold elevation in inducing differentiation similar action was observed on inhibition of proliferation | MEDAL |
when human or animal tissue is to be investigated by xray microanalysis it is sometimes necessary to store the tissue between removal from the organism and freezing however when excised tissue is stored in buffer the elemental concentrations in the cell may change in the present T0 it was attempted to develop a storage buffer that would retain the cellular elemental concentrations close to their in situ values to start the nacl component in krebsringer buffer was exchanged for kgluconate and kcl for nacl this buffer was called a high k solution starting from this solution part of the kgluconate was replaced by an equivalent amount of nacl incubation of excised rat CL degrees c h in HK solution resulted in PR of cellular na k ca s and mg concentration most closely to the in situ state whereas cellular cl was retained best when the tissue was incubated in HK solution for rat submandibular gland incubation in high k solution resulted in optimal retention of cellular na k ca p s and mg while cl was retained best in a high k solution based on these results an optimally modified krebsringer solution for the CL would consist of mm k mm na and mm cl an optimally modified krebsringer bicarbonate solution for the submandibular gland would be composed of mm k mm na and mm cl T3 incubation in the modified solutions at degrees c cellular na mg s cl k and ca in both tissues were maintained close to the in situ state throughout a h incubation the cellular p concentration was reduced after incubation for h thereafter in the CL cells it remained at this lower level for the rest of the incubation whereas in the submandibular gland tissue it increased again after h the increase in cell volume oedema was less in tissue stored in the modified solutions than in the high k solutions incubation in high na buffers degrees c h resulted in a progressive increase in the percentage of cells showing TB uptake a similar increase in TB uptake was seen in the modified solution but this increase levelled off T3 h T3 cholinergic stimulation in high na solution degrees c min the expected decrease in cellular cl concentration was seen in SM gland cells that had previously been preserved degrees c h in the modified solution but not in those that had been preserved in the HK solution | MEDAL |
the purpose of this study was to examine the relationship between proposed correlation indices of CVR and corresponding changes of cerebrovascular reserve as measured by changes of pial arteriolar diameter mild and severe physiologic challenge was produced in piglets by AGA ventilation with foreign gas mixture and altered alveolar ventilation intracranial pressure icp arterial blood pressure abp and video micrometer recordings of pial arteriolar diameter were made serial values of icp and abp were used to compute the rho coefficient index corrx and the pressure reactivity index prx for the mild physiologic challenge experiments correlations between percent change index delta corrx and delta prx and percent NC of pial arteriolar diameter delta dia induced by mild challenges n were p and p ns respectively for asphyxia experiments serial values with respect to time of the correlation indices were correlated with delta dia obtained before during induction and REC the grand mean n rho values sd of the corrx and prx were p and p ns respectively in contrast to the prx index changes of the corrx index significantly correlated with changes of pial arteriolar diameter however corrx and prx were simultaneously high only during a state of maximum dilation these findings suggest that sudden salient increases of the corrx and prx indices induced by physiologic challenge are indicative of vigorous dilatory response of the cerebral arterioles and loss of CVR | MEDAL |
clear cell sarcoma ccs also known as malignant melanoma of soft parts is a rare type of soft tissue sarcoma which exhibits morphological immunohistochemical and ultrastructural similarity with malignant melanoma it is rarely localized in the intestine and the NK PH of this tumor is not yet clear | MEDAL |
recurrent abdominal pain in childhood is common and continues to be a diagnostic and therapeutic challenge it is usually attributed to a PET gastrointestinal disorder rather than an organic disease in most cases a comprehensive history and PCS examination should enable one to make a positive diagnosis of functional disorder the presence of alarm symptoms and signs such as WL gastrointestinal bleeding and chronic severe diarrhoea warrants further investigations and referral to a paediatric gastrointestinal specialist the mainstay of therapy in PET abdominal pain is education reassurance and avoidance of triggering factors while symptombased pharmacological therapy may be helpful in patients who do not respond to simple management it is best used on a timelimited basis due to the lack of good evidence of its tau the primary goal of therapy is a return to normal ADL rather than CR elimination of pain in recalcitrant cases psychological interventions such as cognitive behaviour therapy and relaxation training have proven to be efficacious | MEDAL |
the role of diltiazem on left ventricular systolic function was analyzed in patients with acute myocardial infarction treated with streptokinase being obtained for the total of the population higher lv global ejection fraction p lv regional shortening p and lv global shortening p for the treated group relative to the placebo group the p values were respectively and for patients that achieved timi antegrade coronary flow it is concluded that diltiazem is useful as adjuvant to streptokinase especially when antegrade coronary blood flow timi is obtained | MEDAL |
melanoma growth angiogenesis and M1 progression are strongly promoted by the inflammatory RT microenvironment due to high C2 of cytokine and chemokine secretion by the recruited inflammatory and stromal cells in addition platelets and molecular components of procoagulant pathways have been recently emerging as critical players of tumor growth and metastasis in particular thrombin through the activity of its receptor proteaseactivated receptor par regulates tumor cell adhesion to platelets and endothelial cells stimulates tumor angiogenesis and promotes RT growth and metastasis notably in many tumor types including melanoma par expression directly correlates with their metastatic phenotype and is directly responsible for the expression of interleukin matrix metalloproteinase mmp VE growth factor plateletderived growth factor and integrins another proinflammatory receptorligand pair plateletactivating factor paf and its receptor pafr have been shown to act as important modulators of RT cell adhesion to endothelial cells angiogenesis RT growth and metastasis paf is a bioactive lipid produced by a variety of cells from membrane glycerophospholipids in the same reaction that releases arachidonic acid and can be secreted by platelets inflammatory cells keratinocytes and EC cells we have demonstrated that in M1 melanoma cells paf stimulates the phosphorylation of cyclic adenosine monophosphate CREB protein creb and activating transcription factor atf which results in overexpression of mmp and membrane type mmp membrane type mmp since only M1 melanoma cells overexpress crebatf we propose that M1 melanoma cells are better equipped than their nonmetastatic counterparts to respond to paf within the RT microenvironment the evidence supporting the hypothesis that the two gprotein coupled receptors par and pafr contribute to the acquisition of the M1 phenotype of melanoma is presented and discussed | MEDAL |
during antibiotic treatments active residuals reaching the colon profoundly affect the bacterial flora resulting in the emergence of resistance to prevent these effects we developed an entericcoated formulated activatedcharcoal based product dav meant to deliver its adsorbent to the ileum and neutralize antibiotic residues in the proximal colon in a randomized control crossover T0 the plasma pharmacokinetics of the probe drugs amoxicillin mg absorbed in the PT intestine and SP mg metabolized from sulfasalazine in the cecum and rapidly absorbed were compared T3 a single administration in healthy subjects who had received dav uncoated formulated activated charcoal fac or water and hours before concomitantly with the probe drugs and hours thereafter the auc h of amoxicillin was reduced by more than when it was taken with fac but bioequivalent when it was taken with water or dav by contrast the auc h of sulfapyridine was reduced by more than when administered with either fac or dav in comparison with water the results show that dav can selectively adsorb drug compounds in the PT colon without interfering with drug absorption in the PT small intestine thereby constituting a proof of concept that dav actually functions in humans | MEDAL |
erythropoietin epo is a glycoprotein hormone and the principal regulator of IDE in the fetus newborn and AD epoalfa is erythropoietin manufactured by recombinant human dna technology rhepo T3 counseling a Pr woman with antijsb in her SS was started on rhepo ukg biweekly to prevent anemia AA to serial donations of her blood for fetal transfusions T3 a total of rhepo infusions and autologous donation of units of whole blood maternal hemoglobin prior to the elective cesarean section at weeks was gmdl SS epo concentration was determined in paired maternal and fetal blood samples before ultrasound guided intravascular transfusions in this alloimmunized jsbnegative and another rhd alloimmunized pregnancy to determine possible correlations between maternal and fetal SS epo rhepo prevented anemia in a patient who donated units of blood from weeks of pregnancy without inducing adverse biological effects such as hypertension or thrombotic complications in the placenta data presented in this T0 suggest that epo does not cross the human placenta | MEDAL |
photosynthetically active reaction center complexes were prepared from the green sulfur bacterium chlorobium vibrioforme ncimb and the content of quinones was determined by SE and highperformance liquid chromatography the analysis showed a stoichiometry of molecules of menaquinonereaction center no other quinones were detected in the isolated reaction centers whereas membrane S9 also contained chlorobiumquinone the possible involvement of quinones in electron transport was investigated by electron paramagnetic resonance epr spectroscopy a highly anisotropic radical was detected by qband epr spectroscopy in both membranes and isolated RCs following dark reduction with sodium dithionite and photoaccumulation at k at ghz the epr spectrum is characterized by a g tensor with gxx gyy gzz and delta b of mt consistent with its ID as a quinone this spectrum is highly similar in terms of g values and line widths to photoaccumulated a in PS i of synechococcus sp pcc the results indicate that menaquinone in the green sulfur bacterial reaction center is analogous to phylloquinone in PS i | MEDAL |
we prospectively analysed the CL histology and clinical data of patients with a clinical diagnosis of chronic SH there was more chronic AS hepatitis than CPH in both there were more men than women except in the subgroup of lupoid hepatitis where all were women as a group chronic persistent SH patients tended to have less severe CA in PSA CL function tests CHB infection accounted for of all patients of these were maori or polynesian although they only account for approximately of the european population in auckland this correlated with the known high SH b surface antigen carrier frequency in the maori and polynesian and the high incidence of primary hepatocellular carcinoma in this ethnic group the present T0 also showed there are relatively few chronic active hepatitis patients those with immunological CA lupoid SH who are likely to respond to steroid treatment | MEDAL |
longterm performance of implanted cardiovascular grafts can be ensured if living EC overgrows their surface surface modifications to implants are therefore being sought that can encourage endothelialization while preventing thrombus formation until the natural EC is formed in the present T0 heparin was covalently attached to a fibrin mesh grown from a PVC pvc ATP surface by the catalytic action of surface immobilized thrombin on a fibrinogen solution the coating prevented platelet activation thrombin generation and clot formation and reduced inflammatory reactions when exposed to fresh human whole blood circulating in a chandler loop model in addition in vitro seeded human UV and human saphenous vein endothelial cells showed considerably enhanced att and proliferation on the coating © wiley periodicals inc j biomed mater res part a a | MEDAL |
we studied the surface antigens of early and late CFU-GM cfugm from bone marrow and IP blood of patients with chronic granulocytic leukaemia in chronic phase cglcp using selected murine monoclonal antibodies mcabs in complement dependent cytotoxicity assay followed by culture in methyl cellulose the same panel of mcabs was used to determine the antigens on leukaemic blast cells from peripheral blood of patients with cgl in blastic transformation bt by complement mediated lysis and in vitro SC technique for clonogenic blasts cful and immunofluorescence assay for total blast population mcab for DR antigens l and mcabs my s s and reacted with cfvgm and cful in contrast mcabs pm and aml recognizing antigens on more mature myeloid cells did not react with these progenitor cells mcab s reacted with the majority of cful and a small proportion of early and late cfugm this mcab may be useful for the prediction of blastic transformation in cgl patients generally the CR of most mcabs was more heterogeneous with cful than with cfugm in individual patients the majority of mcabs included in our study reacted with a higher percentage of cful and cfugm than predominant blast cell population in individual patients perhaps because the detected antigens are expressed more strongly on dividing progenitors than on relatively nonproliferative progeny thus we interpret the results of these studies showing that the antigenic phenotypes of the blast colony progenitor cells in cglbt are very similar to but not MZ with those of cfugm from cglcp patients | MEDAL |
tests for resistance to human plasma were made on six clones of a stabilate of trypanosoma rhodesiense lump which was calculated to contain about resistant trypanosomes per million two of the clones were not resistant and four were only subresistant tests were also made on lines clones of a stabilate of polymorphic trypanosomes isolated from tsetse flies one of them etat had INF a laboratory worker and was found to be fully resistant to human plasma the other lines showed only low or moderate resistance resistance of a CS to human plasma often depends upon a small minority of resistant trypanosomes strains of polymorphic trypanosomes may be classified as fully resistant moderately resistant subresistant or CS to human plasma if they contain respectively all some eg one per hundred very few eg one per million or no individuals which are resistant | MEDAL |
in evaluating complex new technologies people are usually dependent on information provided by others for example experts or journalists and have to determine whether they can trust these information sources this article focuses on similarity as the basis for trust the first experiment n confirmed that a journalist writing about genetically modified gm food was trusted more when his attitude was congruent with that of his readers in addition the experiment showed that this effect was mediated by the perceived similarity of the journalist the second experiment n revealed that trust in a journalist writing about the focal domain of gm food was even influenced by him expressing a congruent attitude in an unrelated domain this result supports a GA similarity account of the congruence effect on trust as opposed to a confirmatory bias account | MEDAL |
environmental restriction or ED early in development can induce social cognitive affective and motor CA similar to those associated with autism conversely rearing animals in larger more complex environments results in enhanced BB structure and CF including increased BB weight dendritic branching neurogenesis gene expression and improved learning and memory moreover in animal models of cns insult eg gene deletion a more EC has att or prevented the sequelae of the insult of relevance is the prevention of seizures and attenuation of their neuropathological sequelae as a consequence of exposure to a more complex environment relatively little attention however has been given to the issue of CS periods associated with such effects the relative importance of social versus inanimate stimulation or the unique contribution of exercise our studies have examined the effects of environmental complexity on the development of the restricted repetitive behavior commonly observed in individuals with autism in this MM a more complex environment substantially attenuates the OD of the spontaneous and persistent stereotypies observed in deer mice reared in standard laboratory cages our findings support a CS period for such effects and suggest that early enrichment may have persistent neuroprotective effects after the animal is returned to a standard cage environment attenuation or prevention of repetitive behavior by environmental complexity was associated with increased neuronal metabolic activity increased dendritic spine density and elevated neurotrophin bdnf levels in BB regions that are part of corticalbasal ganglia circuitry these effects were not observed in limbic Az such as the hippocampus | MEDAL |
environments can NC in incremental fashions where a shift from one state to another occurs over multiple organismal generations the rate of the environmental NC is expected to influence how and how well populations adapt to the final environmental state we used a MM system the lytic rna bacteriophage Ï to investigate this question empirically we evolved viruses for thermostability by exposing them to heat shocks that increased to a maximum temperature at different rates we observed increases in the ability of many heatshocked populations to survive high temperature heat shocks on their first SE to the highest temperature populations that experienced a gradual increase in temperature had higher average survival than populations that experienced a rapid temperature increase however at the end of the experiment neither the survival of populations at the highest temperature nor the number of mutations per population varied significantly according to the rate of thermal NC we also evaluated mutations from the endpoint populations for their effects on viral thermostability and growth as expected some mutations did increase viral thermostability however other mutations decreased thermostability but increased growth rate suggesting that benefits of an increased replication rate may have sometimes outweighed the benefits of enhanced thermostability our T0 highlights the importance of considering the effects of multiple selective pressures even in environments where a single factor changes | MEDAL |
heart rate patterns of fetuses exposed to cocaine near the time of delivery were compared with patterns in controls decreased longterm variability and an increased frequency of contractions were observed more often in the cocaine group p and p respectively there were no significant differences in the frequency of fetal ART or decelerations although accelerations were less frequent the midazolam groups the difference was not statistically significant three hours T3 the procedure all patients were fully awake intranasal administration of midazolam therefore seemed to be an interesting alternative for GD fibroscopy because it was simple non traumatic well tolerated and did not result in arterial desaturation | MEDAL |
in this paper a comprehensive T0 of the fate of an antibiotic lincomycin in the aquatic environment is presented highresolution mass spectrometry was employed to assess the evolution of the process over time formation of intermediate EDC was followed by high performance liquid chromatographyhigh resolution mass spectrometry lchrms accurate masstocharge ratios of parent ions were reported with inaccuracy below mmu which guarantee the correct assignment of their molecular formula in all cases while their ms and ms spectra showed several structuraldiagnostic ions that allowed to characterize the different transformation products tps and to discriminate the isobaric species the simulation of phototransformation occurring in the aquatic environment and the ID of biotic and abiotic tps of the pharmaceutical compound were carried out in different experimental conditions dark experiments homogeneous photolysis and heterogeneous photocatalysis using titanium dioxide in order to recreate conditions similar to those found in the environment twentyone main species were identified afterwards lincomycin transformation several isomeric species were formed and characterized by analyzing ms and msn spectra and by comparison with parent molecule fragmentation pathways the major transformation process for lincomycin is hydroxylation either at nalkyl side chain or at the pyrrolidine moiety in addition oxidationreduction demethylation or cleavage of pyranose ring occurs based on this information and additional assessment of profiles over time of formationdisappearance of each species it was possible to recognize the transformation pathways followed by the drug | MEDAL |
to assess the prognostic significance of a newer histologic classification of HD disease hd microscope slides from the time of diagnosis of clinical stage ia or b iia or b and iiia patients were reviewed in years T3 their participation in a radiochemotherapeutic trial overall the diagnostic reproducibility of the rye classification by the same pathologist was confirmed however a new analysis showed an improvement in the differential diagnosis between hd and nonhodgkins lymphomas nhl by the ID of nhl amongst the patients originally diagnosed as hd most of the nhl identified on review had been classified originally as MC on review none of the new histological subtypes of hd was significant for prognosis of relapsefree survival or overall survival only identification of nhl was shown to have an independent prognostic value on relapse rate p and on overall survival p it is concluded that diagnosis of hd by itself remains in the sole histologic factor influencing the prognosis of these patients | MEDAL |
a new process configuration combining anaerobic digestion with ozonation and operated at long srt was studied with the objective of onsite reduction in sludge quantity and improving biogas recovery the process performance with respect to solid reduction efficiency and other important process parameters like accumulation of inorganic solids changes in sludge viscosity and dewatering characteristics were evaluated from the data of long term pilot scale continuous experiments conducted using a mixture of primary and AA municipal sewage sludge due to sludge ozonation and long srt high vss Kd efficiency of approximately was achieved at a reactor solid concentration of a high fraction of inorganic solid consisting mainly of acid insoluble and iron compounds was found to accumulate in the reactor the high inorganic content accumulated in the digested sludge did not however contribute to the observed increase in sludge viscosity at high solid concentration the sludge viscosity was largely found to depend on the organic solid concentration rather than the total solid content moreover higher inorganic content in the digested sludge resulted in better sludge dewaterability for a quick assessment of the economic feasibility of the new process an economic index based on the unit cost of digested sludge disposal to unit electric cost is proposed | MEDAL |
sixtyfour male lambs of two southern spanish breeds a dairy breed grazalema merino and a meat breed churra lebrijana were used to study the effects of slaughter weight and breed on meat traits and intramuscular and subcutaneous fat composition lambs were reared following a traditional production system without weaning and slaughtered when live weight reached kg suckling or kg CS meat from suckling lambs of both breeds had lower fat and myoglobin contents and was more tender and had higher scores for sustained juiciness in the sensory analysis fat from CS lambs had lower c and c C2 than fat from suckling lambs grazalema merino meat had higher fat and ash contents and its fat had higher conjugated LA acid content than churra lebrijana meat | MEDAL |
the neuronal ceroid lipofuscinoses ncls or batten disease are a group of at least nine autosomal recessively inherited monogenetic storage disorders because there are no ERP therapies available all forms of ncl invariably prove fatal T3 a prolonged period of disability indeed for the forms of ncl that are the result of mutations in transmembrane proteins the therapeutic outlook remains uniformly bleak this includes juvenile ncl jncl the most prevalent form of batten disease that is the result of mutations in the cln gene characterizing cln deficient mice is now revealing important clues about the pathogenesis of jncl this includes evidence for elevated levels of glutamate within the jncl cns and cell type selective sensitivity to alphaaminohydroxymethylisoxazolepropionate ampa type glu receptor overactivation these findings raise the possibility that ampareceptor blockade may potentially be beneficial in jncl this possibility has now begun to be tested in cln mutant mice using a single intraperitoneal injection of the noncompetitive ampa antagonist egis by kovács and pearce kovács ad pearce da attenuation of ampa receptor activity improves motor skills in a mouse model of juvenile batten disease exp neurol although a positive effect of upon motor coordination deficits in this mouse model of jncl is reported in this acute T0 it remains unclear whether egis provides any lasting benefit or effects upon other aspects of their disease phenotype although supplying the first evidence for any form of improvement in a diseaserelevant phenotype in cln mutant mice more detailed studies will be needed to determine whether these preliminary findings will translate into a successful therapy for either mu or human jncl | MEDAL |
therapeutic tau of the novel matrix metalloproteinase mmp inhibitor ro biphenylylnitrophenylpiperazinylpyrimidinetrione has been shown in various models of different tumor entities the tumor growthreducing effect has been demonstrated in the orthotopic rat prostate dunning model subline matlylu based on these results we investigated ro in combination with EM on the g subline of the dunning RT this subline is characterized by a low metastatic ability and androgen sensitivity tau was determined by recording tumor growth in vivo by magnetic resonance imaging mri RT cells were injected into the prostates of COP rats mri was performed at day and at day T3 tumor cell i.t. the duration of therapy was days with daily oral application of ro mgkg and four ip i.v. of EM mgkg histological evaluations were conducted to provide further information about the effects on tumor morphology orthotopic RT induction was successful in of the animals tumor volume calculations with mri showed a significant difference between the control CG the animals treated with ro and the animals treated with the combination of ro and EM the new mmp inhibitor ro reduces RT growth and provides a compatible therapeutic alternative for patients with prostate CA | MEDAL |
nowadays endoscopic diverticulotomy is the surgical RPA of the first choice in treatment of zenkers diverticulum we report our experience with this procedure and try to sum up recent recommendations for management of surgery and postoperative care data of patients with zenkers diverticulum treated by endoscopic carbon dioxide laser diverticulotomy at the department of otorhinolaryngology and head and neck surgery st faculty of medicine charles university UH motol prague czech republic were prospectively stored and followed in relatively short period from may to december the average length of diverticulum was mm the average duration of surgery was min the patients were fed via FF tube for days and antibiotics were po for days mean hospitalization time was days we observed one transient recurrent laryngeal nerve paralysis and no other serious complications recurrence rate was we recommend CR transection of the diverticular septum in one procedure systemic antibiotic treatment and exclusion of transoral intake for minimally days and contrast oesophagogram before resumption of oral intake to exclude fistula open diverticulectomy should be reserved for cases with inadequate endoscopic SE and for revision surgery for multiple recurrences from endoscopic diverticulotomies | MEDAL |
the crystalline structure dependence of enzymatic degradation SMB was investigated for the polymorphic polyhydroxypropionate php which has a basic backbone chemical structure of bacterial polyhydroxyalkanoates phas the php films consisting of the beta gamma andor deltaform crystal were cast or meltcrystallized as reported previously macromolecules macromolecules by controlling the molecular weight crystallization temperature andor temperature of the melt their thermal properties crystalline structures morphologies and c solid spinlattice relaxation dynamics were characterized by the differential scanning calorimetry the wideangle xray diffraction the smallangle xray scattering saxs and the c solidstate nmr spectra snmr respectively both the crystallinities and the lamellar thicknesses of php films were found to decrease roughly in the order of betaform or approximately gammaform deltaform from previous work which indicates that the pha enzymatic degradation depends onlres of various phinduced folded states of the protein severe structural perturbation including swelling of the protein is observed in the low phinduced conformer of hsa as evidenced from all the techniques used | MEDAL |
a broad battery of NP tests was given to AD epileptics treated primarily with phenytoin the patients were grouped according to degree of generalized nonepileptiform eeg abnormalities in waking eegs in patients classified as nonemild moderate or marked in terms of these eeg abnormalities performances on neuropsychological measures were contrasted statistically significant differences across the groups were found on of the NP variables an orderly decrease in performance occurred as a correlate of an increase in eeg CA these results were compared to a similar analysis of the correlates of topographic CSD of epileptiform discharges absent focal generalized it was discovered that degrees of generalized slow wave eeg CA were more potent in differentiating levels of NP performance than EDs nevertheless when discharges and degree of nonepileptiform abnormalities were simultaneously considered a maximal level of rho was reached | MEDAL |
this study was undertaken to evaluate the effect of chronic diuretic therapy with CTZ on the course of salt hypertension in hypertensionresistant r and hypertensionsensitive s strains of rats investigation of the effects of CTZ on blood pressure hour urinary na and aldosterone excretion and plasma renin activity pra produced the following observations chlorothiazide failed to prevent the development of salt hypertension in s rats T3 weeks s rats on high salt puls CTZ exhibited a rapid fall in blood pressure to levels indistinguishable from those of s rats on low salt CTZ significantly increased urinary na excretion only in s rats on high salt p less than chlorothiazide significantly increased pra and urinary aldosterone excretion in both strains on low or high salt diets p less than morbidity and mortality of salt hypertension were alleviated by CTZ treatment the unique aspect of this study is the finding that chlorothiazide did not abolish the hypertensiogenic action of salt in s rats | MEDAL |
an experiment was performed which examined movement planning and force transition control in six patients with parkinsons disease pd during a CS of five finger taps at either a fast ms or slow ms temporal speed the patients acted as their own controls and performed finger taps under three task conditions where all taps had to be of the same force intensity no AS where it was known that one of the taps had to be executed with an augmented force AS simple reaction time srt and where it was not known prior to initiation which one of the taps was to be more forcefully produced stress choice reaction time crt reaction time data revealed a betweencondition effect where stress srt was faster than stress crt and no stress was faster than both under both speed conditions the interval after the stressed tap was profoundly lengthened it was found that the lengthening was due to increases in both lift and dwell times for the slow tapping rate in contrast at the fast tapping rate proportionately more of the interval increase was due to the increase in lift time these findings suggest that patients with FPD when performing under a motor program mode have difficulty in initiating a CS and making a transitiontential for infection and knowledge deficits | MEDAL |
we analyzed the level of protein expression of two myogenic RII AF mrfs myod and myogenin in senile skeletal musclchemical markers of BR with ris treatment for OP were examined as a surrogate for the decrease in fracture risk greater decreases in bone resorption markers were associated with greater decreases in vertebral and nonvertebral fractures antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density early decreases in bone resorption may also play a role we tested this hypothesis by measuring two bone resorption markers the ctelopeptide of type i collagen ctx and the ntelopeptide of type i collagen ntx in OP patients in ris vertebral fracture trials we studied women with at least one vertebral deformity mean age years who received calcium and vitamin d if required and placebo or ris mg daily for years the reductions in urinary ctx median and ntx at months with risedronate therapy were significantly associated p with the reduction in vertebral fracture risk over year and over years the changes in both ctx and ntx accounted for approximately onehalf ctx ntx of risedronates effect in reducing the risk of vertebral fractures in the first year and approximately twothirds ctx ntx over years compared with PL the changes in ctx and ntx accounted for and respectively of risedronates effect in reducing the risk of nonvertebral fractures over years compared with placebo the relationships between vertebral fracture risk and changes from baseline in ctx and ntx were not linear p there was little further improvement in fracture benefit below a decrease of for ctx and for ntx the decrease in BR in patients taking risedronate accounts for a large proportion of the reduction in fracture risk there may be a level of bone resorption reduction below which there is no further fracture benefit | MEDAL |
the electrochemical SMB of arsecl and arse archoch choch in acetonitrile an containing tetrabutylammonium tetrafluoroborat tbafb as supporting electrolyte was studied on a stationary electrode spe in order to elucidate the electrode reactions linear potential scan cyclic voltammetry and controlledpotential coulometry were employed using a platinum electrode it is shown that arsecl and arse are reduced and Ox to arse arsear se and arsebf it is generally accepted that as final electrochemical reduction products the corresponding arse arse and se were formed the disappearance of the diorganoselenium and selenide in the course of the coulometric experiments was validated by measuring the limiting current of the voltammetric waves at spe and uv spectrometry | MEDAL |
we exposed erythrocytes in soluble hemoglobin and fe in which hydroxyl radical oh might be generated and measured low shear rate viscosity and viscoelasticity of EA suspensions at hct of the quantities of the lipid peroxidation product malonyldialdehyde mda for Ox samples were higher than that for control eg nmol and nmol n p respectively the viscosity values of oxidized erythrocyte suspensions for all tested shear rates were higher than those for the control samples p or better n dynamic viscosity eta of Ox erythrocyte samples was higher than that of control samples at the tested shear stress of mpa whereas it was not observed in elasticity values eta we tentatively concluded from the T0 that Ox erythrocytes would be more prone to form aggregates and increase viscosity of blood at low shear rates therefore they might impair blood flow in the microcirculation | MEDAL |
the efficacy of in vivo administration of a alphaandrostane and two betaandrostanes alpha and beta on cfugm and cfue mouse bone marrow stem cells was compared the subjects were two CG of swiss webster mice one normal group and one group in whom chronic aplastic anemia was induced by irradiation followed by mesenteric node lymphocyte grafting from cbl donor mice in normal animals the two types of androgens alpha and beta had the same efficacy and the injection of betaandrostane before that of alpha significantly increased its tau in aplastic mice alpha and betaandrostanes had the same tau on cfue but betaandrostanes were more efficient on the granulopoietic committed stem cells the efficacy of the association of the two EDC in aplastic mice was not superior to that of each drug CT which can be explained by the SD of the stem cell compartment induced by the stimulating effect of the first androgen | MEDAL |
there are limited studies on the prevalence and correlates of sexual risk SMB among adolescents in pacific island countries in order to inform public sexual and RH interventions the aim of this study was to assess the prevalence and correlates of various sexual risk behaviors among inschool adolescents in pacific island countries using data from the global schoolbased health survey in a crosssectional T0 schoolgoing adolescents boys and girls years old from fiji kiribati samoa and vanuatu were surveyed with a selfadministered questionnaire overall of students reported to ever had sex ranging from in vanuatu to in samoa and of those sexually active had an early sexual debut years had or more sexual partners during their lifetime had not used a condom at last sex had not used birth control at last sex and engaged in sexually risky behavior using a composite measure multivariate logistic regression found that male sex older age tobacco use alcohol use mental distress having no close friends and truancy were associated with several of or all sexual risk behaviors sexual and RH promotion programs are indicated to address the high risk of sexually transmitted infection hiv and pregnancy in this adolescent population | MEDAL |
there are two alternatives concerning the origin of life the origin may be heterotrophic or autotrophic the CE problem within the theory of an autotrophic origin is the first process of carbon fixation i here propose the hypothesis that this process is an autocatalytic cycle that can be retrodictively constructed from the extant reductive citric acid cycle by replacing thioesters by thioacids and by assuming that the required reducing power is obtained from the oxidative formation of pyrite fes this archaic cycle is strictly chemoautotrophic photoautotrophy is not required the cycle is catalytic for pyrite formation and autocatalytic for its own multiplication it is a consequence of this hypothesis that the postulated cycle cannot exist as a single isolated cycle but must be a member of a network of concatenated homologous cycles from which all anabolic pathways appear to have sprung | MEDAL |
to evaluate LT patient survival and causes of death T3 open or or endovascular er mesenteric revascularization for AS chronic mesenteric ischemia using propensity scorematched comparison and clinical risk stratification | MEDAL |
indomethacin is a widely used antiinflammatory drug with serious sideeffects this drug was used as a MM drug for the coating of agglomerates with a permeable film eudragit ne the agglomeration of the crystals increased the flowability of the bulk crystals the coating further improved the flowability and also the uniformity of the mass of the filled capsules the coating film also influenced the wetting of the samples the coating decreased the surface free energy and therefore reduced the adhesion forces between both the dry and the wet particles the modification of the flow properties and the even capsule filling can be explained by this phenomenon since coating film does not dissolve in the artificial gastric juice the dissolution test was performed only in the artificial intestinal juice the dissolution of indomethacin from the coated sample was changed significantly accordingly coating of the crystals can be performed in order to protect the mucosa of the gastrointestinal tract or to promote the preparation of solid dosage form | MEDAL |
the aim of the present T0 was to clarify the accuracy and limitation of functional magnetic resonance imaging fmri for the identification of the central sulcus affected by BT twelve NV and patients with intracranial PT adjacent to the central sulcus underwent fmri and magnetoencephalography meg three patients were evaluated again T3 surgery fmri was performed with a tesla scanner during repetitive opening and closing of each hand crosscorrelation function was used to identify activation Az and the central sulcus was defined as the nearest sulcus to the highest activation spots that were determined by elevating correlation coefficient threshold somatosensoryevoked fields were measured using a whole head meg system the CS was defined as the nearest sulcus to the nm for the median nerve stimulus fmri and meg coincided in defining the CS in all hemispheres of volunteers and all examined nonaffected hemispheres of patients the fmridefined central sulcus coincided with the megdefined CE sulcus in nine but did not in two affected hemispheres of patients the preoperative mismatch disappeared after surgery in one of the two patients the present study indicates that fmri successfully defined the CS in most of the patients with BT however in a few cases fmri was not reliable probably due to A-V flow changes by RT compression andor compensational activity by BB tissues surrounding the primary sensorimotor cortex for precise PET assessment of the brain affected by intracranial PT combination of fmri and meg will be recommended | MEDAL |
administration of spironolactone provides a beneficial effect in various animal models of renal injury in this T0 we investigated whether spironolactone prevents the progression of diabetic nephropathy through reduction of connective tissue growth factor ctgf synthesis in type ii diabetic rats in addition we evaluated the effect of aldosterone and spironolactone on ctgf and collagen production in cultured cells renal PET and morphologic changes were examined in otsuka longevans tokushima fatty rats with or without spironolactone treatment mgkgday for months as well as in nondiabetic agematched longevans tokushima otsuka rats spironolactone treatment did not induce any significant differences in body weight kidneybody weight ratio SS creatinine concentration blood glucose levels or systolic blood pressure however urinary protein and Al excretion were significantly decreased in the spironolactone treatment group which was associated with amelioration of glomerulosclerosis in addition renal ctgf collagen synthesis demonstrated marked decreases in the spironolactone TG in cultured mc and ptc aldosterone induced significant increases in ctgf gene expression and protein synthesis associated with increased collagen synthesis which was abolished by prior treatment with spironolactone however aldosterone treatment did not induce transforming growth factor tgfbeta overproduction and inhibition of tgfbeta by NT of tgfbeta protein did not significantly prevent aldosteroneinduced ctgf production these results suggest that the antifibrotic effects of spironolactone may be mediated by ctgf through a tgfbetaindependent pathway in this rat of diabetic nephropathy | MEDAL |
tp gene mutations occur in to hepatocellular carcinomas both the frequency and the type of p mutations in hcc vary according to geographical location of tumors a TPS mutation at codon aggagt was found at VHF in PT from high aflatoxinareas tp mutations in other geographic locations are less frequent and scattered on the exons encoding the CE region of the protein tp mutations observed in HCC carcinoma are accompanied by a loss of wildtype p function moreover the pser mutant appears to display a gain of function at some degree in addition to p inactivation by gene mutation there is growing evidence that the wildtype p functions can be inactivated by the hbx protein of hepatitis b virus the HCC functions of wildtype p protein are not entirely known the present data suggest that the dna damaging agents induce pdependent Tc arrest or apoptosis in cell lines derived from normal liver or hepatocellular carcinoma in contrast the SE of mice to genotoxic agents does not induce pdependent changes in normal adult CL this could be due to the fact that the hepatocytes of the AD liver are quiescent cells | MEDAL |
we have monitored extracellularly individual neurons in the V1 of weekold unparalyzed kittens with the aim of changing the ocular dominance of these cells during recording to do this we elicited conjugate eye movements using a BP stimulating electrode positioned in the internal medullary lamina iml of the TH during electrical stimulation of this region one eye was occluded and the other was visually activated with optimal stimuli receptive fields were studied subjectively and objectively and relative response strengths were assessed of cells studied in detail underwent changes on OD following conditioning periods of generally min control experiments suggest that this STDP is agerelated requires both visual stimulation and activation of pathways associated with EM and does not appear to be caused solely by increased arousal levels | MEDAL |
a large set of volatiles a metabolome was isolated by safe distillation from high priced rums prepared from sugar cane juice scj and high priced rums manufactured from sugar cane molasses scm the volatile fractions were first analyzed by comprehensive 2DE gas chromatography timeofflight mass spectrometry gcÃgctofms and the comprehensive template matching fingerprinting was used to extract the entire features present in the respective set of volatile compounds after raw data i.c.v. chemometrics was used to locate marker compounds following a sparsepartialleastsquares discriminant analysis splsda and a partialleastsquares discriminant analysis plsda were applied to a training data set for creating a model the model was validated using leaveoneout cross validation and tested over an independent data set to evaluate its predictive power the characteristic fingerprint resulted in a correct classification of sugar cane juice rums thus achieving the first aim of locating markers for these higher quality rums then pastprocessing ID within the discriminant features was done to characterize significant marker EDC as decanol γdodecalactone ethyl methylbutanoate ethyl nonanoate furancarboxaldehyde hexanol βionone and methylbutanol methyl decanoate octanol and undecanone quantitation of eight selected markers by stable isotope dilution astes in the inflammatory reaction in adipose tissue during obesity the exp evidence shows that lps is involved in the transition of macrophages from the m to the m phenotype in addition lps inside adipocytes may activate ICE this may induce a highly inflammatory type of programmed cell death ie pyroptosis which also occurs after infection with intracellular pathogens lipoproteins with or without lps are taken up by adipocytes C1 adipocytes are more metabolically AS and potentially more exposed to lps than small adipocytes are thus lps might be involved in defining the adipocyte death size and the formation of crownlike structures the adipocyte death size is reached when the intracellular concentration of lps initiates pyroptosis the mechanistic details remain to be elucidated but the observations indicate that adipocytes are stimulated to cell death by processes that involve lps from the gut microbiota there is a complex interplay between the composition of the diet and microbiota this influences the amount of lps that is translocated from the gut in particular the lipid content of a meal may correlate with the amount of lps built in to chylomicrons | MEDAL |
increased urinary methylglutaconic acid excretion is a relatively common finding in metabolic disorders especially in mitochondrial disorders in most cases methylglutaconic acid is only slightly elevated and accompanied by other disease specific metabolites there is however a group of disorders with significantly and consistently increased methylglutaconic acid excretion where the methylglutaconic aciduria is a hallmark of the phenotype and the key to diagnosis until now these disorders were labelled by roman numbers iv in the order of discovery regardless of pathomechanism especially the so called unspecified methylglutaconic aciduria type iv has been ever growing leading to biochemical and clinical diagnostic confusion therefore we propose the following pathomechanism based classification and a simplified diagnostic flow chart for these IEM with methylglutaconic aciduria as discriminative feature one should distinguish between primary methylglutaconic aciduria formerly known as type i methylglutaconylcoa hydratase deficiency auh defect due to defective leucine catabolism and thecurrently knownthree CG of AA methylglutaconic aciduria the latter should be further classified and named by their defective protein or the historical name as follows i defective phospholipid remodelling taz defect or barth syndrome serac defect or megdel syndrome and ii mitochondrial membrane associated disorders opa defect or costeff syndrome dnajc defect or dcma syndrome tmem defect the remaining patients with significant and consistent methylglutaconic aciduria in whom the above mentioned syndromes have been excluded should be referred to as not otherwise specified nos mgauria until elucidation of the underlying pathomechanism enables proper possibly extended classification | MEDAL |
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