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a wisconsin foundations aggressive approach to patent licensing is damaging its reputation compromising its own universitys research collaborations and stymieing stem cell research | MEDAL |
human immune interferongamma huifngamma labeled with p was used to study the structure of Th1 receptor when phuifngamma was bound and crosslinked to Th1 the receptor of human cells with a bifunctional crosslinker disuccinimidyl suberate dss a single diffused plabeled band corresponding to the ifngammareceptor complex was visualized by sdspolyacrylamide gel electrophoresis and ARG the size of the phuifngammareceptor complex was about kd separation of crosslinked complex in reducing and nonreducing gels showed no size differences suggee is reduced with increasingly positive MPs in cells loaded with either citrate or dpa DPA pyridinedicarboxylic acid inactivation is negligible or absent for small depolarizations in the range of membrane potentials where maximum current flows mv a monophasic slow time course of inactivation is observed at more positive MPs inactivation is slowed the amount of inactivation under this condition is related to the current density of the cell conditions which for a given membrane potential reduce the amplitude of ica such as extracellular application of blocking ions co cd a conditioning depolarization or rundown of cachannels lead to a slowing or a complete removal of inactivation in cells dialysed with citrate or dpa respectively cells loaded with these ca chelators did not show any symptom of Vc dependent inactivation of ica under the conditions described action potentials were recorded in the current clamp mode upon dialysis with egta the typical triangular shaped atrial action potential develops a plateau of to ms in duration with citratecontaining pipette solutions the action potential duration usually is several seconds the results for the first time demonstrate that inactivation of cardiac ica can be considerably slowed or even removed they provide further strong support for the hypothesis that inactivation of this current depends on ca entry rather than membrane potential the fast phase of inactivation observed with egta nta possibly reflects the slow kinetics of the IB reaction of this type of ca chelators | MEDAL |
pulmonary vein pv isolation is a technically challenging intervention for this reason integration of threedimensional imaging with computed tomography ct or magnetic resonance imaging mri in order to enhance effectiveness and safety has been widely adopted a novel imaging approachintraprocedural rotational angiography and reconstruction of the left atrium and pvsis feasible and provides high anatomic accuracy | MEDAL |
the contact sensitizing potential of hydroxymethylphenylbenzotriazole tinuvin p was investigated using the murine local CL node assay llna and the mouse ear swelling test with some modification in the induction procedure modified mest topical exposure of the ears to tinuvin p in acetoneolive oil aoo for consecutive days induced no increase in auricular CL node weight and lymph node cell proliferation in the llna tinuvin p was negative and its sensitizing potential was determined as not strong in the modified mest mice were sensitized with a combination of an intradermal injection of tinuvin p in freunds complete adjuvant into the shaved abdomen and topical application of tinuvin p in aoo on both ears for consecutive days the ear thickness in mice previously treated with tinuvin p increased significantly on challenge with tinuvin p a crossreaction test between tinuvin p and various substituted benzotriazole ultraviolet CS uv absorbers was performed challenge with these benzotriazole compounds on the ears of the mice previously sensitized to tinuvin p showed no increase in ear thickness these data indicated that tinuvin p had a contact sensitizing ability while tinuvin psensitized mice did not crossreact with the other benzotriazole uv absorbers | MEDAL |
the new targeted agent bevacizumab in combination with cisplatin and gemcitabine and a third generation chemotherapy pemetrexed combined with cisplatin are approved as firstline treatment for patients with advanced nonsquamous nonsmall cell lung CA nsclc as no headtohead comparison of these treatments exists this study aimed to compare the effectiveness of the two treatments using an indirect treatment comparison RPA an indirect comparison on PFS pfs was performed for two relevant RCT using a wellaccepted adjusted indirect comparison method the results were used in a statistical disease model markov model to extrapolate the longterm effectiveness of the two treatments a hazard ratio of for pfs for bevacizumab plus cisplatin and gemcitabine was calculated suggesting that this treatment is associated with a lower risk of disease progression and death compared with pemetrexed plus cisplatin treatment the markov MM predicted that bevacizumab plus cisplatin and gemcitabine resulted in months additional pfs and overall survival compared with pemetrexed plus cisplatin based on this analysis bevacizumab plus cisplatin and gemcitabine is more effective than pemetrexed plus cisplatin for patients with T3 nonsquamous nsclc and should be considered as one of the preferred targeted treatments of choice for these patients | MEDAL |
dexrazoxane is a bidentate chelator of divalent cations i.c.v. with short infusions of DEX prior to bolus doxorubicin has been shown to lessen the incidence and severity of anthracyclineassociated cardiac toxicity however because of rapid diffusionmediated cellular uptake and the short plasma halflife of DEX combined with prolonged cellular PR of doxorubicin dexrazoxane may be more ERP when po as a continuous infusion thus a phase i pharmacokinetic trial of a h infusion of DEX was performed DEX doses were escalated in cohorts of to patients per dose level all patients received granulocytecolony MSF at a dose of microgkgday starting h after completion of the dexrazoxane infusion plasma samples were collected and analyzed for DEX by highperformance liquid chromatography urine collections were performed at baseline and during the infusion to determine the renal clearance of dexrazoxane and the excretion rate of divalent cations twentytwo patients were enrolled at doses ranging from to mgmday grade and toxicities included grade thrombocytopenia in patients treated at mgmday grade thrombocytopenia and grade nausea and vomiting in patient treated at mgmday grade diarrhea and grade NV in patient treated at mgmday and grade hypertension in patient treated at mgmday steadystate dexrazoxane levels ranged from microgl microm to microgl microm dexrazoxane plasma clss and elimination t were lhm and h respectively the mean percentage of po DEX recovered in the urine at Css was range urinary iron and zinc excretion during the DEX infusion increased in of and of patients by a median of and fold respectively these results suggest that dexrazoxane as a h infusion can be safely administered with granulocytecolony MSF at doses that achieve plasma C2 that have been demonstrated previously to inhibit topoisomerase ii activity and to induce apoptosis in vitro additional studies will be required to determine whether the combination of continuous infusions of dexrazoxane and doxorubicin would provide enhanced cardioprotection compared with the currently recommended bolus or short infusion schedules | MEDAL |
as assessed by the lipopolysaccharide lpsspecific chromogenic limulus amoebocyte lysate lal assay helicobacter pylori lps extracted by the phenolwater procedure showed full potency to coagulate lal as did lps from salmonella minnesota and escherichia coli however i.c.v. of h pylori lps with polymyxin b which easily destroys the endotoxic activity of enterobacterial lpslipid a had little effect on the lal coagulation activity although the same treatment of e coli lps markedly diminished its activity the h pylori lps induced very weak production of nitric oxide no or tumour necrosis factor tnf by mu macrophages and tnf by human peripheral whole blood in vitro in comparison with s minnesota lps these findings indicate that h pylori lps has the unique endotoxic characteristic of retaining full lal coagulation activity with polymyxin b resistance despite losing its endotoxic potencies such as the ability to induce no and tnf production | MEDAL |
to measure the effect of the HIV virus hiv epidemic on mortality from opportunistic infections ois in national multiplecause death certificate data were examined using two approaches first for each oi the percentage of deaths with hiv infection reported as the underlying cause was calculated second the ageadjusted rate of death per million population was compared with the rate predicted from a MM of rates in or as available the percentage of deaths with hiv as the underlying cause and the ratio of observed to predicted death rates were as follows toxoplasmosis and cryptosporidiosisisosporiasis and infinite PML and pneumocystosis and cytomegalovirus disease and nontuberculous mycobacteriosis and cryptococcosis and and histoplasmosis and thus the hiv epidemic has greatly increased mortality from several ois | MEDAL |
the human gastrointestinal tract hosts a diverse network of microorganisms collectively known as the microbiota that plays an important role in health and disease for instance the intestinal microbiota can prevent invading microbes from colonizing the gastrointestinal tract a phenomenon known as colonization resistance perturbations to the microbiota such as antibiotic administration can alter microbial composition and result in the loss of colonization resistance consequently the host may be rendered susceptible to colonization by a pathogen this is a particularly relevant concern in the hospital setting where antibiotic use and antibioticresistant pathogen SE are more frequent many nosocomial infections arise from gastrointestinal colonization due to their resistance to antibiotics treatment is often very challenging however recent studies have demonstrated that manipulating the commensal microbiota can prevent and treat various infections in the intestine in this review we discuss the members of the microbiota as well as the mechanisms that govern CR against specific pathogens we also review the effects of antibiotics on the microbiota as well as the unique epidemiology of ICP that renders them a particularly highrisk population to intestinal nosocomial infections | MEDAL |
using a threedimensional electromechanical MM of the canine ventricles with dyssynchronous HF we investigated the relationship between severity of valve regurgitation and VVI mechanical responses the results demonstrated that endsystolic tension in the SP and left ventricular free wall was significantly lower under the condition of mitral regurgitation mr than under AR ar stroke work in ar was higher than that in mr on the other hand the difference in stroke volume between the two conditions was not significant indicating that ar may cause worse pumping efficiency than mr in terms of consumed SE and performed work | MEDAL |
in order to estimate the influence of adaptational processes during pregnancy and post partum on micturition uroflowparameters and PVR were examined in healthy women comparisons were made between women in the st nd and rd trimester of pregnancy women who were between and days post partum and nonpregnant fertile women compared with the control group the mean flow was significantly lower during the and trimester time taken to achieve maximum flow was significantly higher after spontaneous delivery compared with the control group during pregnancy and after delivery an increase in flow time could be shown during the rd trimester time taken to achieve maximum flow was noticeably higher than in the other CG both mean and maximum flow were lower during pregnancy and T3 spontaneous delivery than in the control group residual urine increased mainly during the trimester and showed the highest value after delivery as all the investigated differences stayed within the standardized values uroflowmetric investigations and ultrasonic residual urine estimation during pregnancy and T3 delivery are only necessary if suspicious symptoms on the part of the urinary tract exist | MEDAL |
idioventricular tachycardia ivt occurred in a patient with angina pectoris on three separate occasions associated with stress induced angina it occurred immediately after a masters test a treadmill exercise test and following an episode of paroxysmal atrial tachycardia which was precipitated by endocardial pacing his bundle electrograms demonstrated that the rhythm was ventricular in origin cardiac catheterization documented the presence of severe coronary i.a. disease idioventricular ART is often seen with acute myocardial infarction it is rarely seen with angina or with exercise testing to our knowledge this is the first reported case of ivt which could be repeatedly produced by stress induced angina | MEDAL |
physical treatment SMT and massages are often recommended to treat migraine as a prophylactic therapy clinical experience and theoretical concepts support their usefulness however data on these therapies are scarce on the basis of the available studies it is impossible to determine whether or not these therapies are ERP there is a lack of welldesigned prospective RCTs with a sufficiently long followup to observe these therapies due to the high acceptance of physical treatment on the one hand and preconceptions about drug treatment on the other these types of therapies may be an alternative option for some patients if their tau is established a costbenefit analysis of theses therapies should consider the long amount of time required for them compared with drug intake | MEDAL |
this T0 describes the biological properties of a CS of virus isolated from tissues of a goat with leukoencephalomyelitisarthritis the agent is a retrovirus having a virionassociated reverse transcriptase enzyme and an antigenic determinants which crossreacts with the p of visnamaedi viruses morphogenesis of the virus is also similar to visna virus in terms of virus assembly and the multinucleated giant cell formation which accompanies replication of the latter virus despite its cytopathogenic property the goat agent was not lytic in goat cell culture causing instead a productive infection which persisted through multiple subcultures of the cells the virus replicated incompletely in sheep cell cultures but could be rescued from the latter weeks T3 inoculation by cocultivation with goat cells our data suggest that this CS of goat leukoencephalitis virus is a variant of the ovine retroviruses with a host range limited to the goat | MEDAL |
children were included in protocol fralle from june to september disease free survival for the all protocol is and overall survival various clinical and laboratory features at the time of diagnosis have been correlated with prognosis they provide a potential mean to stratify patients into treatment subgroups according their or of treatment failure the identification of these prognostic factors has been an essential PE in the design of current therapeutic trials prognostic characteristics of childhood all include age white blood RCC RT burden cytogénétics chromosome count and chromosomal translocation IP and early response to treatment molecular biology has been the revolution of the last two decades permitting the cloning of the genes involved in the leukemic process finally the new molecular techniques allow a CS diagnostic approach to minimal residual disease mrd the better PCD of mrd must allow a more rational basis for therapeutic intensification for a subset of poor responder patients a decrease in therapy of very good responders can also be envisaged | MEDAL |
various food products of plant origin were investigated for the occurrence of natural mutagens using the salmonellamicrosome CA in GA food plants were FD and subsequently extracted with a number of solvents solvents were evaporated and the residues obtained were tested for mutagenicity in addition to smix gut flora extracts were applied for metabolic activation from bracken fern pteridium aquilinum a novel mutagen designated aquilide a was isolated and its chemical structure was identified aquilide a requires activation to become mutagenic this activation occurs spontaneously at ph C2 above G1 aquilide a was found to be genotoxic in cultured rat cells natural mutagens were detected in out of vegetables investigated in addition broad beans vicia faba were found to be mutagenic T3 treatment with nitrite all mutagenic vegetables showed marked intercultivar variations from lettuce and string beans quercetin was isolated T3 chemical hydrolysis and in rhubarb emodin an anthraquinon was detected the mutagenic activity of these two compounds was further investigated using cultured rat cells quercetin and emodin responded negative or weakly positive in the systems applied the genotoxic properties of a number of pyrrolizidin alkaloids which are reported to occur in various flowering plants and as a result occur in honey and some herbal preparations were studied using a cocultivation system of v V79 and primary cultures of chick embryo HCs pccehv all four PAs investigated were found to be potent inducers of sces in this test system antimutagenic effects of butylated hydroxyanisole bha and indolecarbinol ic were detected using the pccehv cocultivation system this indicates that the cocultivation system described can be a valuable tool for the screening of various products for potential anticarcinogenic properties extracts of lettuce and string beans and a number of natural chemicals were found to reduce the mutagenic activity of cigarette smoke condensate and benzo a Py bap as detected in the salmonellamicrosome assay intercultivar variation with respect to the antimutagenic activity observed was less pronounced than the variation noted for the mutagenic activity of these vegetables measures which may result in a reduction of the SE to a number of NK mutagens are discussed | MEDAL |
the aims of this work were to develop quinine qnloaded NC to evaluate their efficacy in vivo and to determine their pharmacokinetics and EA partition coefficient plasmodium bergheiinfected wistar rats were used to evaluate the tau of qnloaded nanocapsules using different dosing regimens pharmacokinetics was evaluated T3 i.v. of free or nanoencapsulated qn mgkg to infected rats the qn partition coefficient into p bergheiinfected erythrocytes was evaluated qnloaded nanocapsules presented an adequate particle size nm narrow particle CSD negative zeta potential mv and high drug content and encapsulation efficiency i.v. of qnloaded nanocapsules at mgkgday to infected rats resulted in survival representing an almost reduction compared with the free qn effective dose mgkgday the pharmacokinetic parameters of ncorresponding to the exons of genes in samples in total mb were sequenced in the context of this largescale T0 we obtained a false positive rate of approximately in bp and a false negative rate of approximately | MEDAL |
the transcription factor camp responsive element binding protein creb is important in regulating immediateearly genes and some lateeffector genes involved in neuroplasticity in response to IP injury and stressful insults partial PNI elicited neuropathic pain is accompanied by increased phosphorylation of creb in the ipsilateral spinal cord DH ma and quirion pain miletic et al pain the aim of this study is to determine whether increased phosphorylation of creb in the DH contributes to the pathogenesis of neuropathic pain three weeks following partial sciatic nerve ligation psnl daily intrathecal i.t. of antisense creb oligodeoxynucleotide odn microgday for days significantly attenuated tactile allodynia the attenuation lasted for more than days total creb and pCREB in both ipsilateral and contralateral dorsal horn SN were dramatically reduced in antisense odn injected psnl rats week after i.t. the extent of reduction of total creb and phosphorylated creb containing cells in the dorsal horn ipsilateral to injury was greater than in the CL DH these data suggest that phosphorylation of creb is an important contributie site of injection and the production of morphological CA in these cells as judged by staining techniques for antibody content these locally assembled cells are not AS in the formation of antibody wax injected in mineral oil results in a remarkable systematized stimulation of the RES the greatly increased serum antibody levels demonstrated T3 the use of tubercle bacillary wax in antigen mixtures is attributed to a widespread proliferation of plasma cell elements in the lymphatic glands spleen and CL | MEDAL |
a new compound hydroxybenzoyl quinazolinhone and four known compounds were isolated from a marine fungus penicillium oxalicum f the structure of the new compound was elucidated based on the spectroscopic analysis bioactivity assays showed that hydroxybenzyl quinazolinhone and methyl hydroxyphenylacetate had potent inhibitory activity against tobacco mosaic virus tmv and the new compound had moderate LIA against tmv and human gastric CA cell sgc | MEDAL |
the course of the disease CL caused by the intracellular protozoan parasite leishmania tropica differs markedly amongst various common inbred mouse strains after intradermal injection of x promastigotes to young female TPS pathogenfree spf derived mice persistent infection characterized by an expanding ulcerous lesion is seen in balbc and dba mice in the strains cbah chhe and aj lesions resolve within weeks and in cb mice no real lesion typical of CL develops at the injection site nzb mice are highly resistant macrophages harvested from the thioglycollatestimulated peritoneal cavity of nzb and cb mice appear to differ from macrophages of the other mouse strains in not supporting multiplication of l tropica organisms in vitro nevertheless hypothymic nude nunu mice of B6 TT as well as cbahnunu and balbcnunu mice develop C1 lesions with metastases to other cutaneous and visceral locations in the IN mice in which infection resolves spontaneously resistance to reinfection is CR using mouse antipromastigote sera and an indirect FAT in carefully controlled experiments l tropica antigens were detected on in vitro INF macrophages of both highly susceptible balbc and relatively resistant cbah genotypes T3 incubation with a crude soluble antigen preparation from cultured promastigotes infected balbc macrophages differed from INF cbah macrophages and uninfected macrophages of both genotypes in being unable to sensitize syngeneic recipients for a delayedtype DTH to that antigen when infected and uninfected macrophages were used as blocking cells in an in vitro alloreactive cytotoxic t cell system involving cells from congenic mice evidence was obtained for reduced hd expression on INF macrophages of the susceptible mouse strains balbc the data in this MM system of cutaneous leishmaniasis raise the possibility that genetic susceptibility is associated with both a permissive macrophage and defective t cell recognition of parasite antigens on INF macrophages defective recognition may be the result of reduced functional expression of hd antigens on infected balbc macrophages required for efficient recognition by syngeneic t cells of one or more subpopulations | MEDAL |
experiments were performed on eight rabbits to T0 the effects of acetylcholine on interneuronal intracortical interactions multineuronal activity was recorded in the motor cortex during local iontophoretic administration of acetylcholine and PS interneuronal connections were identified by crosscorrelation analysis a role for acetylcholine in intracortical connection reorganization processes is proposed these studies demonstrated that acetylcholine has an activating effect on intracortical connections application of acetylcholinel cells eventually the melanoma cells IC with the EC cells at this stage many endothelial filament bundles terminated at contacts between the EC cells and the transmigrating melanoma cell suggesting AS interactions between the two cell types upon contact with the MG melanoma cells began to spread beneath the EC displaying a fibroblastic morphology with prominent SFs to reestablish the ML adjacent endothelial cells extended processes over the melanoma MCT necrosis factor alpha did not affect the transmigration of melanoma cells from cell lines isolated from several stages of metastasis however TN factor did promote the transmigration of melanoma cells derived from a nonmetastatic lesion these results thus define cell attachment and cell penetration of the ML as two distinct steps in transmigration and suggest that tumor necrosis factor may enhance the metastatic potential of RT cells | MEDAL |
in this paper we investigate the quest for a single target which remains fixed in a lattice by a set of independent walkers the target exhibits fluctuating SMB between a trap and an ordinary site of the lattice whereas the walkers perform an intermittent kind of search strategy our searchers carry out their movements in one of two states between which they switch randomly one of these states the exploratory phase is a symmetric nearestneighbor random walk and the other state the relocating phase is a symmetric nextnearestneighbor random walk by using the multistate continuoustime randomwalk approach we are able to show that for dynamical targets the intermittent strategy despite the simplicity of the kinetics chosen for searching improves detection in comparison to displacements in a single state we have obtained analytic results which can be numerically evaluated for the survival probability and for the lifetime of the target thus we have studied the dependence of these quantities both in terms of the transition probability that describes the dynamics of the target and in terms of the parameter that characterizes the walkers intermittency in addition to our analytical approach we have implemented monte carlo simulations finding excellent PA between the theoreticalnumerical results and simulations | MEDAL |
the topographic CSD of epidurally recorded flashed visual evoked potentials veps in unanesthetized rabbits was studied using montages veps with linked ears reference and source derivation were compared with the linkedears REF n of veps which consisted of slow potentials and superimposed oscillations were recorded diffusely over the head when source derivation was used the slow negative potentials of n present on the recordings in p and p were not obtained in f fz and f in a digital filtering T0 of the oscillatory potentials n in oscillatory potentials which were recorded diffusely over the head were localized to the VC by source derivation it was concluded that n in the OPs generated from the VC are enhanced and localized with source derivation | MEDAL |
the effects of silicone oil and perfluorocarbon liquids used in retinal reattachment surgery were studied in vitro using rat retinal cultures seeded on microporous inserts these inserts allow the cell SL to be in contact with the material to be tested on the apical side and with the nutrient medium on the basal side the materials tested were silicone oil the perfluorocarbons perfluorophenanthrene and perfluoroctane and hydroxypropylmethylcellulose perfluorophenanthrene the heaviest of the compounds induced a very precocious detachment of the cell SL all the other tested biomaterials were compatible with cell survival and did not alter the structural organization of the retinal cultures as revealed by SEM microscopy of NO regions regardless of the procedure used for the nucleolar visualization early stages of the granulopoietic compartment and particularly myeloblasts of raeb patients were characterized by reduction of the nucleolar number expressed by the nucleolar coefficient the values of which resembled those described previously in acute myeloid leukemias the reduced values of the nucleolar coefficient of these cells in silver stained specimens of raeb patients were accompanied by a decreased number of clusters of silver stained particles representing interphasic silver stained nucleolus organizer regions agnors the reduction of these clusters was also described previously in leukemic cells in addition the differences in the values of the nucleolar coefficient of granulocytic precursors between specimens stained for rna and those stained with the silver reaction might reflect changing composition and proportions of nucleolar components in the course of the granulocytic OD | MEDAL |
we determined the electrical constants of epicardial and Endo S9 from both normal and hypertrophied rat hearts this was done by comparative analysis of the spatial decay of steadystate electronic voltage deflection produced by i.t. of a hyperpolarizing constantcurrent pulse we used a 2DE finite disk MM to obtain the apparent Rm rmapp and internal longitudinal resistivity ri rmapp was significantly larger in epicardial omega cm than Endo preparations from normal hearts this regional difference disappeared in hypertrophied hearts epicardium Endo omega cm ri was similar for normal Endo omega cm and epicardial preparations as well as for hypertrophied Endo and epicardial S9 we determined the ERP membrane capacity ceff by measuring the ratio of applied charge to the displacement of membrane potential ceff was larger for normal NF Epi micro fcm endocardium than for hypertrophied NF Epi endocardium from the values for ceff we calculated the effective membrane resistance rmeff rmeff was larger for normal epicardium omega cm Endo than for hypertrophied Epi endocardium preparations our results show that the amount of electrically effective membrane area is decreased in hypertrophied myocardium despite the increased TA per hypertrophied cell one functional implication of this finding is that activation of contraction by spread of surface electrical depolarization into the ttubules may be impaired in hypertrophied cardiac muscle | MEDAL |
insulininduced hypoglycemia itt is currently the goldstandard test for the diagnosis of adult growth hormone deficiency ghd itt is often contraindicated however particularly in conditions that are also common in patients with suspected ghd used CT ghreleasing hormone ghrh has no diagnostic value owing to withinsubject R2 and the inability to distinguish ghd from normal subjects when combined with Arg however ghrh becomes a potent and reproducible test which is unaffected by gender and aging showing excellent specificity the ghrh arginine arg test distinguishes ghd patients from normal subjects and is at least as CS as itt provided that AGA cutoff limits are considered its reliability for retesting ghd has also been demonstrated the ghrharg test can also be performed in a shorter procedure resulting in potential for cost reduction synthetic gh secretagogues ghss possess a strong and reproducible ghreleasing effect and synergize with ghrh the combination of ghrh and a peptidyl ghs such as hexarelin or ghreleasing peptide has recently been shown as another reliable test for the diagnosis of adult ghd again provided that the cutoff limit is AGA to the potency of the test thus ghrh combined with either Arg or ghs is a potential tool for the diagnosis of adult ghd | MEDAL |
two synthetic CBs win rdihydromethylmorpholinylmethylpyrol debenzoxazinylnaphthalenylmethanone monomethanesulfonate and mgkg ip and cp ardimethylheptylhydroxyhydroxypropyl cyclohexylphenol ardimethylheptylhydroxyhydroxypropyl cyclohexylphenol and mgkg ip inhibited acetylcholine PR in the rat hippocampus the inhibition was prevented by the cannabinoid receptor antagonist sr a npiperidinyl chlorophenyldichlorophenylmethylhpyrazolecarboxamide hcl at the dose of mgkg ip higher doses of sr a and mgkg ip themselves increased hippocampal acetylcholine PR suggesting that acetylcholine output is tonically inhibited by endogenous cannabinoids the results also suggest that the negative effects of marijuana on learning and memory may depend on cannabinoid receptormediated inhibition of acetylcholine PR | MEDAL |
human βdefensin hbd is an antimicrobial peptide with high activity and broad spectrum activity hbd expression may be highly elevated by microorganisms and inflammation we reported that the majority of common vaccines used including valent pneumococcal polysaccharide vaccine Hib and split influenza virus vaccine could induce the expression of hbd in epithelial cells among them the valent PPV was effective at a lower concentration µgml while haemophilus influenzae type b vaccine and split influenza virus vaccine were effective at the concentration of µgml however bacteriostatic experiments revealed that the split influenza virus vaccine was capable of inducing the highest antimicrobial activity the medium of the valent PPV TG had a higher antimicrobial activity than the medium of the Hib vaccine TG the transcriptional regulator of hbd that is the nfκb S1 had a high level of activity while the normal epithelial cells showed barely detectable activity indicating that these vaccines have potential for clinical application | MEDAL |
although the ironchelating protein LF is secreted by the seminal LDV the precise role of lactoferrin in semen is unclear this study aimed to determine whether there is any association between seminal LF concentrations and normal and abnormal semen samples with and without leucocytospermia lactoferrin concentrations were measured by radial immunodiffusion of semen samples from men attending a regional andrology referral center routine seminal analysis including the presence of leucocytospermia was also performed results showed increased seminal lactoferrin in samples showing oligospermia mg ml and oligoasthenospermia mg ml compared to normospermic samples mg ml there were no significant differences in seminal lactoferrin between normospermic samples and azoospermic samples or asthenospermic samples with normal sperm density although there was a trend toward increased LF concentration with leucocytospermia this was not significant possible causes for raised lactoferrin in association with oligospermia are discussed | MEDAL |
the clinical records and histologic material of consecutive patients with MH were reviewed the age of the patients ranged from months to years median years there were males and females lymph node and liver enlargement fever and skin nodules were the most common PCS findings and leukocytosis was frequently the most abnormal laboratory test seven of patients died and their survival ranged from to months median months T3 histopathologic diagnosis the histologic findings on CL NO spleen liver bone marrow and skin were investigated with special REF to both the cellular composition and the pattern of N0 vascular invasion of small perinodal vessels was observed in fatal cases the absence of capsular invasion and the lack of cohesiveness among atypical proliferating histiocytes of malignant histiocytosis appeared to be inconstant sequential lymph node biopsies revealed in later stages the extension of the histiocytic proliferation from the sinuses into the cords and the complete obliteration of the nodal structures the radiologic investigations yielded numerous pathologic findings that were consistent with the dissemination of the disease CR response to initial treatment was achieved in patients that were treated with radiotherapy andor chemotherapy complete response with chemotherapy was achieved only when the treatment included adriamycin the histologic and clinical features of the present series provide future evidence for the recognition of MH as a distinct clinical and pathologic entity | MEDAL |
a highly symptomatic yearold woman with rheumatic mitral valvular stenosis was referred for cardiac catheterization following the procedure it was decided to perform a mitral valvuloplasty with a balloon catheter an isolated transarterial approach through the right FA was used a sones catheter was introduced into the left atrium and through it a long tefloncoated guide wire was placed into this cavity the sones catheter was removed and an mm diameter balloon catheter was placed under the mitral valve and inflated several times for about sec each the pulmonary wedge and pulmonary artery pressures were significantly lower than the prevalvuloplasty ones the angiograms showed better mitral valve opening | MEDAL |
group a meningococcal disease has been an important public health problem in subsaharan africa for over a century outbreaks occur there annually and large epidemics occur at intervals ranging between and y the meningitis vaccine project was established in with funding from the gates foundation with the goal of developing testing licensing and introducing an affordable group a meningococcal conjugate vaccine into africa from to a monovalent group a conjugate vaccine menafrivactm was developed at the serum institute of india ltd through an innovative publicprivate partnership preclinical studies of the new conjugate vaccine were completed in and a phase T0 began in india in phase studies in african y olds were completed in showing the new meningococcal a conjugate vaccine to be as safe as currently licensed meningococcal polysaccharide vaccines but much more immunogenic T3 indian market authorization december and who prequalification june menafrivactm was introduced at public health scale using a single µg dose in individuals y of age in burkina faso mali and niger in december we summarize the laboratory and clinical studies leading to prequalification of menafrivactm the epidemic season ended with no reported case of group a meningitis in vaccinated individuals | MEDAL |
the present study was aimed at establishing behavioral differences between three inbred mouse strains ssvhsd cbljolahsd fvbnhsd and two f hybrid lines derived from them x cbl and x fvb the choice of the given strains was based on the frequent use of these mice in transgenic research for the behavioral phenotyping we employed a test battery consisting of the following models elevated plusmaze epm open field of lightdark exploration spontaneous locomotor activity rotarod rr porsolts forcedswimming test fst and morris water task significant variations between the strains were established in all tests ALB was more pronounced in the ssv and x B6 mice the fvbn mice were spontaneously hyperactive the best coordination ability was demonstrated by the B6 and x B6 groups a good performance in the learning test was established in both hybrid lines and the ssv mice whereas the wellknown CVI of the fvb CS was confirmed by low performance in spatial and nonspatial tasks differences related to the gender were revealed occasionally most importantly x B6 males had a higher anxiety level than their female counterparts in the epm several other gender dissociations suggest the strain and task specificity in conclusion we would like to highlight the importance of the genetic BG and gender of mice for the molecular biological and pharmacological studies and also the need for wellestablished testing protocols to obtain wide information at the first stage of behavioral screening of GM mice | MEDAL |
a total of fresh clinical isolates were used to test a rapid method for determining lysine arginine and ODC as well as arginine dihydrolase activity the conventional møller decarboxylase BB was tested in parallel with the rapid method on enterobacteriaceae and nonfermentative gramnegative rods the agar method was tested in parallel on enterobacteriaceae and nonfermentors all media were checked at halfhour or hourly intervals for up to eight hours with the final reading taken after incubation for hours at degrees c the rapid method detected positive decarboxylase or dihydrolase reactions that were not detected by the møller BB and more than the agar medium when testing enterobacteriaceae the corresponding figures for the nonfermentative gramnegative rods were three and two respectively lysine and ornithine decarboxylase were generally detected by the rapid BB in two to four hours incubation while the arginine decarboxylase and dihydrolase were slower and required six to eight hours this compares with overnight incubation as the general rule for the møller BB and agar decarboxylases the comparable accuracy of the rapid method with conventional techniques and the shorter incubation time required for detection of positive reactions make this procedure well suited to a routine clinical laboratory | MEDAL |
drinking water contaminated with As a human carcinogen is a worldwide health issue an understanding of cellular signaling events in response to As SE and rational designing of strategies to reduce As damages by modulating signaling events are important to fight against arsenicinduced diseases previously we reported that activation of the nrfmediated cellular defense pathway confers protection against toxic effects induced by sodium arsenite asiii or monomethylarsonous acid mmaiii paradoxically As has been reported to induce the nrfdependent signaling pathway here we report the unique mechanism of nrf induction by As similar to tertbutylhydroquinone tbhq or sulforaphane sf arsenic induced the nrfdependent response through enhancing nrf protein levels by inhibiting nrf ubiquitination and Kd however the detailed action of arsenic in nrf induction is different from that of tbhq or sf arsenic markedly enhanced the interaction between keap and cul subunits of the e ubiquitin ligase for nrf which led to impaired dynamic assemblydisassembly of the e ubiquitin ligase and thus decreased its ligase activity furthermore induction of nrf by arsenic is independent of the previously identified c residue in keap that is required for nrf activation by tbhq or sf distinct mechanisms of nrf activation by seemingly harmful and beneficial reagents provide a molecular basis to design nrfactivating agents for therapeutic intervention | MEDAL |
the BB and spine foundation bsf has produced a web based information access toolkit for health and social care professionals and primary care trust service commissioners to support implementation of the national service FR for long term neurological conditions | MEDAL |
the effect of exposure to pesticides among children in a nicaraguan community in the path of rain water runoff from a C1 cropdusting airport was evaluated by measuring plasma cholinesterase mean ChE in children in the path of runoff was international unitsml bloodmin lower than the iumlmin measured in a group of children from an unexposed community difference iumlmin ci six of the exposed children had abnormally low cholinesterase levels a possible explanation for this physiological effect of SE to pesticides is the dermal absorption which may have occurred among children playing barefoot in puddles grossly contaminated by runoff from the airport drinking water from a well in the exposed community demonstrated low level residues of cholinesteraseinhibiting pesticides although contamination with toxaphene not a cholinesterase inhibitor exceeded by over fold the united states environmental protection agency maximum permissible concentration in drinking water the difficulty in measuring health effects resulting from environmental pesticide contamination and in controlling SE resulting from the rapidly increasinme analysis of CR sequenced genomes the analysis reveals a surprising plasticity of the glycolytic pathway isoenzymes in different species are identified and compared deviations from the textbook standard are detailed several potential pharmacological targets and bypasses such as the entnerdoudoroff pathway to glycolysis are examined and compared in the different species archaean bacterial and parasite TPS adaptations are identified and described | MEDAL |
to determine whether dexfenfluramine is a ATP of CYP2D6 cypd its disposition has been studied in nine extensive em and eight PMs pm of debrisoquine following a mg dose of dexfenfluramine hydrochloride urine was collected in all subjects for h postdose and plasma samples were collected in subjects six ems and five pms dexfenfluramine and nordexfenfluramine were measured in urine by hplc and in plasma by gc urinary REC of dexfenfluramine was greater in pms than ems micrograms vs micrograms ci of difference p whereas that of nordexfenfluramine was similar in both phenotypes pm micrograms vs micrograms dexfenfluramine auc was higher in pms micrograms l h than ems micrograms l h the apparent oral clearance of dexfenfluramine was greater in ems than pms l h vs l h ci of difference p the renal clearance was similar in both phenotypes ems l h pms l h indicating that the higher urinary recovery of dexfenfluramine in pms reflects higher plasma concentrations rather than phenotype differences in the renal handling of dexfenfluramine the apparent nonrenal clearance of dexfenfluramine was substantially lower p ci of difference in pms l h than ems l h there was a significant inverse rho rs ci n p between the debrisoquine metabolic ratio and the apparent nonrenal clearance of dexfenfluramine pms had a higher incidence of adverse effects nausea and vomiting than ems in conclusion the metabolism of dexfenfluramine is impaired in pms thus cypd the isoenzyme deficient in poor metabolizers of DBQ must catalyse at least one pathway of dexfenfluramine biotransformation | MEDAL |
we have used the rat formalin test to compare the antinociceptive properties of several voltageactivated na channel blockers the antiarrhthymic mexiletine and mgkg ip att flinching behaviour in both first and second phases of the test compared with VH p the anticonvulsants lamotrigine and mgkg ip and CBZ mgkg ip also inhibited second phase flinching behaviour compared with VH p although phenytoin up to mgkg ip was without effect riluzole mgkg ip in contrast to lubeluzole up to mgkg ip also inhibited second phase flinching behaviour compared with vehicle p when tested against an acute thermal nociceptive CS- mexiletine lubeluzole and riluzole exhibited antinociceptive effects the antinociceptive doses used in the formalin test produced no motor impairment in the rotarod test thus voltageactivated na channel blockers can attenuate nociceptive behaviour in the formalin test and a specific mechanism of action on hH1 CF may be required for this to occur | MEDAL |
objective CSF fluid csf rhinorrhea is among the most common complications following TSS for sellar region lesions the aim of this T0 was to review the authors institutional experience in identifying repairing and treating csf leaks associated with direct endonasal transsphenoidal operations methods the authors performed a retrospective review of cases involving surgical treatment of PIT adenomas and other sellar lesions at the USC between december and march inclusion criteria included all pathology of the sellar region approached via a direct microscopic or endoscopic endonasal transsphenoidal approach demographics pathology intraoperative and postoperative csf leak rates and other complications were recorded and analyzed a literature review of the incidence of csf leaks associated with the direct endonasal transsphenoidal RPA to PIT lesions was conducted results a total of patients met the inclusion criteria and their cases were subsequently analyzed preoperative diagnoses included PIT adenomas in cases rathkes cleft cyst in and other sellar lesions in lesions with a diameter ⥠cm made up of the series intraoperative repair of an identified csf leak was performed in cases using autologous fat fascia or both an additional patients underwent empirical sellar reconstruction without evidence of an intraoperative csf leak postoperative csf leaks developed in patients including of the overall group in whom no intraoperative leak was identified among the patients who developed a postoperative csf leak were noted to have intraoperative leak and underwent sellar repair while the remaining did not have an intraoperative leak or sellar repair no patients who underwent empirical sellar repair without an intraoperative leak developed a postoperative leak eight patients underwent additional surgery reoperation rate for csf leak repair and were successfully treated with lumbar drainage or lumbar puncture alone the incidence of postoperative csf rhinorrhea in this series was compared with that in other reported series that met inclusion criteria with incidence rates ranging between and conclusions in this large series half of the patients who developed postoperative csf rhinorrhea had no evidence of intraoperative csf leakage unidentified intraoperative csf leaks andor delayed developmeice as high in gactin p that reflected an increase in affinity upon reaching the ar spermatozoa plcζ was partially released from the cell it was concluded that actin cytoskeleton dynamics control the migration of plcζ during capacitation and leads to its partial release at ar spermatozoa it is suggested that liberated plcζ could reach the egg and favour fertilization | MEDAL |
in healthy humans there is an apparent dissociation between cognitive and affective consequences of reduced brain serotonin ht as rapid tryptophan depletion rtd causes alterations in a consistent constellation of cognitive processes in the GA absence of mood deterioration this T0 aimed to investigate possible neural mechanisms underlying this relative dissociation by measuring the effects of reduced ht on regional cerebral blood flow rcbf a total of healthy euthymic male subjects mean age years without a personal or family PH of affective disorder had mood ratings and single photon emission computed tomography scans with the rcbf tracer mtchmpao under reduced ht rtd and control conditions across individuals modest positive and negative changes in subjective happiness associated with rtd were significantly correlated with change of rcbf in a cluster comprising subgenual affective ACC acc and associated regions brodmanns area ba posterior ba and caudate nucleus and VS spm p QTc the covariation was such that increasing sadness was associated with increased rcbf and vice versa independent of mood change rtd was associated with reduced rcbf in the dorsal cognitive acc ba spm p QTc the subgenual prefrontal SC and dorsal acc are important components of the VP and dorsal neural systems that regulate and integrate affective and cognitive functions the results therefore suggest that the dissociation between affective and cognitive consequences of rtd may possibly be attributable to differential effects of reduced ht on these neural systems | MEDAL |
proximal row carpectomy was performed in wrists with old unreduced perilunate dislocations and in wrists with kienböcks disease one failure was converted to wrist arthrodesis and patients were lost to followup the remaining patients were reexamined T3 years average ranges of wrist motion were degrees of DF degrees of palmar flexion degrees of radial deviation and degrees of ulnar deviation GS averaged two thirds of the uninvolved hand pain relief was achieved in patients who all returned to their previous occupations the results according to cooneys criteria were good fair and poor | MEDAL |
the effects of Sp and methoctramine a selective m muscarinic receptor antagonist were studied on the highaffinity gtpase activity of g proteins and on ligand binding to m muscarinic receptors in pig heart sarcolemma the spontaneous gtp hydrolysis by pig HR sarcolemma and its stimulation by mastoparan or carbachol were prevented by pertussis toxin and inhibited by methoctramine ics and microm respectively and Sp ics and microm Sp and methoctramine also inhibited spontaneous gtp hydrolysis by rat peritoneal mast cell CM which do not respond to carbachol the neutral muscarinic antagonists afdx and atropine did not modify the inhibitory effect of high concentrations of methoctramine indicating that this effect was not related to the antagonist binding site of M2 we suggest that methoctramine behaves as a receptor antagonist at nanomolar concentrations and interacts with g proteins at micromolar concentrations spermine did not modify the binding of the 3H muscarinic antagonist hnms but decreased the IB of the agonist hoxom spermine elicited a rightward shift of the carbacholhnms IB isotherm with a decrease in the proportion of CS with highaffinity for carbachol suggesting that PAs uncouple gi proteins from receptors the inhibition of gtpase activity by PAs preventing the reassociation of alpha and betagamma subunits of gi proteins might sustain the RII effect of gi subunits on downstream effectors the level of intracellular PAs might be important for the control of the transduction of extracellular signals through gi proteincoupled receptors | MEDAL |
the presence of lymphoid nodules in bone marrow biopsy was investigated at diagnosis in patients with chronic myeloproliferative disorders mpd twelve out of patients with idiopathic myelofibrosis im showed such a feature versus two out of with phpositive CML two of with polycythaemia vera and one of with essential thrombocythaemia the difference between im and the remaining mpd being statistically significant p less than when im patients were compared for their initial characteristics according to the presence or not of bone marrow lymphoid nodules patients with such a histological finding showed significantly lower values for either wbc counts number of primitive cells in the blood and LDH C2 moreover it was observed that virtually all patients with lymphoid nodules were in the nonmyelosclerotic phases of im finally among the of im patients investigated for circulating immune complexes who gave a positive test a significant association between this immunological abnormality and bone marrow lymphoid nodules was found the above results reinforce the immunological significance of the finding of bone marrow lymphoid nodules in im and give support to the hypothesis of an immune component in the pathogenesis of the disorder | MEDAL |
the SD fly stomoxys calcitrans l diptera muscidae is one of the most significant biting flies that affect cattle the use of traditional insecticides for SD fly control has only a limited success owing to the insects unique FF behaviours and immature OD CS a laboratory study was conducted to evaluate the effects of two insect growth regulator igr products pyriproxyfen and buprofezin on the OD of the immature stages of the SD fly and the effects of pyriproxyfen on oviposition and egg hatch both pyriproxyfen and buprofezin had significant GABA effects on immature development the lc s of pyriproxyfen and buprofezin were and ppm respectively topical treatment of AD females with different doses of pyriproxyfen had significant negative effects on both female oviposition and egg hatching when and dayold females were treated and the effects were dose dependent a significant reduction in the mean number of eggs laid was observed only at the highest pyriproxyfen dose µgfly and egg hatch was unaffected by pyriproxyfen treatment when dayold females were treated results from the present T0 indicate that pyriproxyfen has the potential to be used as part of an integrated stable fly management programme | MEDAL |
the present series of experiments was designed to examine in the anesthetized cat the extent to which the synaptic tau of knee joint afferents is modified during the state of central sensitization produced by the i.t. of CAP into the hindlimb plantar cushion we found that the intradermic i.t. of capsaicin increased the n and n components of the focal potentials produced by stimulation of intermediate and HT myelinated fibers in the posterior articular nerve pan respectively this facilitation lasted several hours had about the same time course as the paw inflammation and was more evident for the n and n potentials recorded within the intermediate zone in the l than in the l spinal segments the capsaicininduced facilitation of the n focal potentials which are assumed to be generated by activation of SF signaling joint position suggests that nociception may affect the processing of proprioceptive and somatosensory information and probably also movement in addition the increased effectiveness of these afferents could activate besides neurons in the intermediate region neurons located in the more SF layers of the DH as a consequence normal joint movements could produce pain representing a secondary hyperalgesia the capsaicininduced increased efficacy of the pan afferents producing the n focal potentials together with the reduced postactivation depression that follows high frequency autogenetic stimulation of these afferents could further contribute to the pain sensation from noninflamed joints during skin inflammation in humans the persistence after capsaicin of the inhibitory effects produced by stimulation of cutaneous SN innervating noninflamed skin regions may account for the reported reduction of the articular pain sensations produced by transcutaneous stimulation | MEDAL |
patients with inoperable nonsmallcell lung CA nsclc were randomly assigned to receive one of three dosage regimens VDS and cisplatin vp mitomycin vindesine and cisplatin mvp or etoposide and cisplatin AC with vindesine and MMC epvm in assessable patients the response rates were vp mvp and epvm the addition of MMC to the vp regimen did not significantly improve the response rate the response rate was significantly lower with the epvm regimen than with the mvp regimen p less than the median survival times were vp weeks mvp weeks and epvm weeks these differences were not significant WHO or iv thrombocytopenia was significantly greater p less than in mvp patients than in the vp other toxicities were similar in the three groups analyses of prognostic factors showed that treatment with mvp sex and histologic classification squamous cell carcinoma were predictive of improved response important AF for improved survival according to the cox regression analysis were the stage of disease performance status sex WL before diagnosis and hemoglobin concentration | MEDAL |
antibodies and antibody domains are ideal agents for targeting the surface of cells and fusion proteins between celltargeting domains and cytotoxic proteins may be particularly effective therapeutic reagents we constructed a family of immunofusion proteins linking the humanized fab fab or singlechain antibody form of the h antibody which recognizes the cd antigen on the surface of human TA with the plant ribosomeinactivating protein gelonin to maximize the product yield and simplify the production process each FP was linked to a bacterial signal CS for expression in e coli as a secreted protein more than F0 genes were assembled with antibody domains and gelonin in various PCS orientations each immunofusion accumulated in the bacterial culture supernatant in a properly folded active form bacteria transformed with each fusion gene were then grown in a fermentor and product was recovered from the cellfree fermentation BB by column chromatography all of the immunofusion proteins were purified by a single process and each was tested for cytotoxicity toward antigenpositive human cells a compact cgmp fermentation area was built to manufacture these fusion proteins our integrated approach to microbial protein production including molecular genetics bacterial fermentation and initial isolation is described in detail | MEDAL |
gliadin a component of wheat gluten known to be an important factor in the etiology of celiac disease is related to several other diseases through its enhancing effect on intestinal paracellular permeability we investigated the significance of gliadin in nonsteroidal antiinflammatory drug nsaidinduced smallintestinal damage in mice weekold cbl male mice were divided into the following groups SD group in which mice were fed with wheatcontaining standard rodent diet ce glutenfree diet group in which mice were fed with GFD aina and gliadinadministered group in which mice fed with glutenfree diet were administered with gliadin mgkg bw each group was subdivided into negative healthy control group and nsaidtreated group to some mice fed with GFD and administered with gliadin epidermal growth factor receptor egfr IMT kinase inhibitor was administered for clarification of the significance of egfr in nsaidinduced SI damage and IP in mice fed with a GFD indomethacin or diclofenac induced very mild mucosal damage in the small intestine compared with that in mice fed with a wheatcontaining standard diet gliadin exacerbated the nsaidinduced smallintestinal damage in mice fed with a GFD with the administration of indomethacin mpo activity a marker of neutrophil infiltration into the mucosa and mrna expression level of TN factor α and interleukinβ in the small intestine were higher in the gliadinadministered mice gliadin increased the intestinal paracellular permeability without indomethacin administration fold and further increased the permeability T3 indomethacin administration fold gliadin induced phosphorylation of epidermal growth factor receptor egfr in smallintestinal tissues and erlotinib an egfr IMT kinase inhibitor attenuated the indomethacininduced intestinal damage and permeability exacerbated by gliadin accompanied by inhibition of egfr phosphorylation these results suggest that gliadin plays an important role in the induction and exacerbation of nsaidinduced smallintestinal damage and that increase in IP via the egfr signalling pathway is involved in its mechanism | MEDAL |
SE of female mice to testosterone resulted in aggressive SMB as a CF of breeding line in two lines of mice selectively bred for high turku aggressive ta and low turku nonaggressive tna levels of aggressiveness female ta mice that received a single i.t. of TP tp mg in ml peanut oil on the second day of life and starting at days of age received daily injections for seven consecutive days displayed aggressive SMB on a level comparable to that of socially isolated males of the same line whereas control ta females injected with ml peanut oil and tpexposed tna females were totally nonaggressive the level of aggressiveness was assessed by means of dyadic tests against intact male opponents early and AD SE to tp did not lead to increased aggressiveness in male tna mice fighting experience in combination with prolonged tp treatment changed the aggressiveness of the tpexposed ta females leading to decreased aggressiveness in defeated animals the genetically correlated low level of aggressiveness of tna male and female mice was unaffected by any combination of tp exposure learning and social isolation it is concluded that differences in testosterone CR of target organs other than those which are y chromosome determined ie the testes are responsible for the aggressiveness in the strains studied | MEDAL |
although trans fatty acids tfas may increase the risk of dyslipidemia and coronary i.a. disease cad limited data are available on their association with heart failure hf | MEDAL |
in the current study we examined the association between polymorphisms in the omethylguaninedna methyltransferase gene mgmt and the risk for roles in immune responses and can be distinguished in two major subsets myeloid and PDCs although the presence of dc in all IP organs including the kidney has been well documented no accurate estimates of dc subsets in human kidneys have been reported this T0 shows a detailed analysis of dc subsets in cryosections of human renal tissue the SC of normal kidneys contains at least two different DR MDC subtypes characterized by bdcadcsign and bdcadcsign the staining for dcsign completely overlapped with cd in the renal interstitium unexpectedly bdcadcsign plasmacytoid dcs are also abundantly present both subsets are located in the tubulointerstitium often with a VHF around but rarely observed within glomeruli quantification of bdca dcsign and bdca cells in normal human renal tissue pretransplant biopsy living donors n revealed that bdca is about four times as frequently present as bdca a preliminary crosssectional analysis of dc in diseased kidneys including rejection and immunoglobulin a nephropathy revealed that the number of dc as well as their anatomical CSD might NC under pathophysiological conditions in conclusion we show that human kidneys contain a dense network of myeloid and plasmacytoid dcs and provide the tools for phenotyping and enumeration of these cells to better understand interindividual differences in immune responses | MEDAL |
to calibrate a wholebody counter it is necessary to find a determination method for peak efficiencies of detectors used in the WBC for this purpose peak efficiencies of a ge semiconductor detector for point and volume sources were evaluated in the photon SE range kev by MC simulation and experiment it was found that the calculated peak efficiency curves as a CF of SE without modelling of the actual sensitive region of the detector are similar in shape to those measured the calculated peak efficiencies of the detector having an apparent dead SL mm were also found to agree with the exp values deviations from consequently the simulation method for peak efficiencies was validated in addition an optimum design fldenberg and slob ecotox environ safety an overall predicted noeffect concentration pnec for the plantatmosphere compartment of microg m dbp was calculated the pnec was calculated using the mean and sigma of the noec for four of the tested species and an extrapolation factor in addition to changes in leaf colour leaf crinkling and growth reduction a number of not quantified observations are described indicating that dbp affects the physiology as well as the morphology of these species | MEDAL |
the avidinbiotin immunohistochemical abc method was applied to the diagnosis of alveolar hydatid disease in patients from the hyperendemic region of western alaska the test was TPS for larval cestodes of the genus echinococcus and exhibited high sensitivity a negative reaction was obtained in all cases in which spontaneous death of the larval cestode had occurred results were inconsistent in sections of lesions from patients who had received LT therapy with mebendazole because of the persistence of antigens for a considerable time following the death of the parasite | MEDAL |
a case of patient with PS of ll roots affliction and iv cranial nerve lesion caused by meningeal carcinomatosis secondary to giant cell lung CA is presented the clinical features diagnosis methods and therapeutic possibilities in this case are commented on | MEDAL |
the T0 addresses the relationship of plasma arachidonic acid and thromboxane production with the dietary compliance in treated phenylketonuric patients whose veganlike dietary DP makes them a useful MM to evaluate the effects of the neartotal avoidance of animal fats thirteen treated phenylketonuric children were compared with twelve HCs for AA NI plasma fatty acids and platelet thromboxane b production assessed as accumulation of this eicosanoid in serum the calculated NI of AA acid was lower in phenylketonurics than in controls and this was associated with lower C2 in plasma lipids plasma arachidonic acid concentrations and SS thromboxane b C2 correlated with the last months phenylalanine C2 taken as negative indicator of dietary compliance a direct relationship between plasma AA concentration and thromboxane b production was observed only in phenylketonuric patients r p while wellcompliant pku subjects have low AA and thromboxane concentrations in plasma the low compliance with animal food avoidance evoking higher phenylalanine C2 results in elevation of both plasma AA and serum thromboxane b this gives support to the hypothesis that the consumption of animal fats may affect the production of AA acidderived PLT eicosanoids | MEDAL |
a simple reliable and sensitive gas chromatographymass spectrometry method for the quantification of volatile and nonvolatile BA in port wines and grape juices was developed and evaluated the method was based on a previously reported twophase derivatization procedure with isobutyl chloroformate in a toluene medium which provides a quantitative reaction in min following the derivatization step the excess of reagent was eliminated by treatment with alkaline methanol the derivatization procedure was performed directly on ml of sample avoiding any fastidious and timeconsuming cleanup SE steps the method allows the simultaneous quantification of amines which can be found in wines methylamine dimethylamine ethylamine diethylamine propylamine isopropylamine butylamine isobutylamine amylamine isoamylamine methylbutylamine hexylamine pyrrolidine piperidine morpholine diaminopropane putrescine cadaverine diaminohexane phenylethylamine histamine and tyramine because of the fact that histamine and tyramine derivatives are degraded during the isobutyl chloroformate elimination step the corresponding determination was made T3 removal of the excess of derivatizing reagent by evaporating an aliquot of the toluene layer obtained T3 the reaction the presented method showed excellent analytical characteristics in what linearity recovery repeatability and limit of detections were respected it was used to assess the concentration of BA in juice grapes and tawny and vintage port wines with different aging times on the whole the total content of amines in port wines was low most of the amines found in wines have their origin in the raw material used for their elaboration so the port winemaking process is not proipate in a second cme bias study | MEDAL |
thioredoxininteracting protein txnip is upregulated by high gl and is associated with oxidative stress it has been implicated in hyperglycemiainduced βcell dysfunction and apoptosis as high glucose and oxidative AS mediate diabetic nephropathy dn the contribution of txnip was investigated in renal mesangial cell ROS species ros generation and collagen synthesis to determine the role of txnip mouse mesangial cells mc cultured from wildtype ch and txnipdeficient hcb mice were incubated in hg confocal microscopy was used to measure total and mitochondrial ros production dcf and mitosox and CIV trx and NOX activities were assayed and nadph oxidase isoforms nox and nox and antioxidant enzymes were determined by immunoblotting ch mc exposed to hg elicited a significant increase in cellular and mitochondrial ros as well as nox protein expression and NOX activation whereas hcb mc showed no response trx activity was att by hg only in ch mc these defects in hcb mc were not due to increased antioxidant enzymes or scavenging of ros but associated with decreased ros generation adenovirusmediated overexpression of txnip in hcb mc and txnip knockdown with sirna in ch confirmed the TPS role of txnip collagen iv accumulation in hg was markedly reduced in hcb cells txnip is a critical component of the hgros signaling pathway required for the induction of mitochondrial and total cell ros and the NOX isoform nox txnip is a potential target to prevent dn | MEDAL |
renal CF was assessed in unrestrained conscious rats during either their AS period ie the hours of darkness or their inactive period on the following day measurements were repeated after inactin anaesthesia and preparation for clearance studies in rats anaesthetized during their AS period preparation for clearance studies had no effect on inulin clearance used as a measure of glomerular filtration rate CLi used as an estimate of endproximal fluid delivery or fractional lithium excretion in rats anaesthetized during their inactive period the same procedures resulted in increases in all three variables to reach values indistinguishable from those in animals studied during their active period in both CG of rats there were increases in the fractional reabsorption of sodium and water in the distal nephron and in the urinary excretion of potassium it is concluded that in anaesthetized rats prepared for clearance studies rates of glomerular filtration and APR as indicated by lithium clearance are similar to those in conscious animals during their AS period | MEDAL |
employing the new concept of systolic myocardial stiffness this study addresses the questions of linearity of the endsystolic stressstrain relations in left VVI hypertrophy and the preload dependence of fiber shortening rate pressure overload hypertrophy was induced in six puppies by banding the ascending aorta ultrasonic crystals were implanted for measurement of short axis and wall thickness in the six dogs with hypertrophy and in five control dogs a pressure catheter was inserted through the apex for left VVI pressure measurement load was altered by graded infusions of phenylephrine in the setting of betaadrenergic blockade linearity of the endsystolic stressstrain relations was observed in all cases and preloadcorrected shortening rateafterload rel seek warmth may lead to the formation of additional pockets increased ventilation is an expensive solution to the problems associated with indoor air pollution however more thorough mixing of indoor air may reduce the effects of these clouds of pollutants | MEDAL |
H-2 complex expression of G1 peripheral blood lymphocytes of captive african green monkeys from barbados and from africa were analue within its local environment all pairs are characterized by their dihedral angles AA structure and number of neighboring residues as a function of residue type each residue pair preference is expressed for all amino acids of the profiled residue and is weighted by the compatibility of the environment residue with its own local environment the rp method produces an initial profilesequence alignment which is then refined by converting the initial profile into a profile of a target sequence threaded into the structure of the initial profile we have tested this method by evaluating alignments of sequences with known d structures using structural superposition alignments as REF rpsequence alignments are or correct on average for sequences whose d structure pairs superimpose with an rms deviation of or a the average improvement in correctness during this iterative refinement is the rpsequence alignments are compared with sequencesequence and d profilesequence alignments when all three methods are combined on average or of the alignments are correct for pairs of d structures that superimpose within a a d model of hisa is predicted with the combined method | MEDAL |
a new SLM extractor for bioanalytical sample preparation is presented the extractor consists of a PP HF mounted inside a ptfe tube by means of a crossconnector and a teeconnector all parts are commercially available inexpensive and easily assembled an organic solvent in the pores of the fiber forms a liquid membrane that separates the sample which is pumped along the outside of the fiber from the acceptor phase which is pumped inside the length of the hollow fiber may easily be varied to meet different demands on extractive surface and extract volumes to test the system the strongly acidic plasticizerflame retardant metabolite diphenyl phosphate ester dphp with a pka value of was extracted from urine dphp was protonated using m hydrochloric acid and extracted into an acceptor phase at ph thirty extractions were made with the same liquid membrane without any decrease in extraction efficiency and with a relative standard deviation an analyte concentration enrichment of times was achieved in the extraction step giving a limit of PCD sn of microgml with lcesims and microgml with ceuv the effects on SE efficiency using different sample ph organic solvents sample PFR and lengths of the fiber were evaluated | MEDAL |
the inflammation which follows cryotherapy is a significant disadvantage of this therapeutic modality to date the only treatment shown to reduce this inflammation is application of topical corticoids we have therefore conducted a pilot study to investigate whether i.c.v. with the free radical scavengers vitamins c and e might alleviate the signs and symptoms of inflammation following liquid nitrogen cryotherapy of common warts we undertook a randomized doubleblind placebocontrolled parallel group T0 we recruited adult patients of whom returned for DUE treatments comprised vitamin c mg and VE iu daily or matching PL for days prior to cryotherapy to a hand wart oedema volume erythema level pain intensity and the presence or absence of blistering were assessed h after cryotherapy there were no significant differences between the two treatment CG in any of the parameters assessed this T0 yielded no suggestion of benefit from the use of i.c.v. with free radical scavengers in conjunction with liquid nitrogen cryotherapy | MEDAL |
perinatal hypoxicischemic HIVE hie is associated with high neonatal mortality and severe longterm neurologic morbidity yet the mechanisms of BB injury in infants with hie remain largely elusive the present T0 determined a novel mechanism of microrna mir in silencing endogenous neuroprotection and increasing hypoxicischemic brain injury in neonatal rats the T0 further revealed a potential therapeutic effect of mir inhibition using cDNA locked nucleic acid oligonucleotides mirlna in dayold neonatal rats in the ricevannucci model the underlying mechanisms were investigated with intracerebroventricular i.t. icv of mir mimic mirlna glucocorticoid receptor gr agonist and antagonist luciferase reporter gene CA was conducted for identification of mir targeting gr untranslated region the results showed that the hi treatment significantly increased mir levels in the BB and mir mimic significantly decreased gr protein abundance and exacerbated hi brain injury in the pups mirlna administration via icv h T3 the hi insult significantly decreased BB mir levels increased gr protein abundance reduced hiinduced neuronal death and brain IS and improved LT neurological function REC of importance the intranasal delivery of mirlna h after the hi insult produced similar effects in decreasing hiinduced neonatal BB injury and improving neurological CF later in life altogether the present T0 provides evidence of a novel mechanism of mir in a neonatal hi brain injury MM and suggests a potential therapeutic approach of mir inhibition in the treatment of neonatal hie | MEDAL |
in this randomized controlled trial group BT bt n was compared to group supportive therapy st n in the treatment of trichotillomania ttm both treatments were also compared to a naturally occurring waiting period the time period that participants waited for groups to form participants completing group bt experienced significantly greater decreases in selfreported hairpulling symptoms and clinicianrated hair loss severity than did those in group st decreases were significantly greater after treatment than T3 the naturalistic waiting period in addition a significantly higher percentage of those in the bt than st condition were rated as much improved or very much improved on the clinical global impression scale at PT however despite substantial symptom improvement ttm severity remained problematic at PT specifically few participants in either treatment met criteria for clinically significant change at posttreatment in addition relapse of symptoms occurred over the month followup period results provided partial support for the shortterm tau of group bt however the group format may not maximize the tau of bt for ttm thus it is recommended that future bt research test either individual therapy or a combination of group and individual formats for ttm | MEDAL |
androgenetic alopecia is one of the most common forms of hair loss AA is a common autoimmune disorder which causes hair loss it has been previously reported that both alopecia disorders can have negative effects on SQ of life however only a few studies have compared the effects of the two disorders | MEDAL |
we report an unmarried woman with PTC thyroid CA the patient was a yearold woman who had neck tumor the ultrasonography us ct and ABC abc were performed the diagnosis of the tumor was papillary carcinoma of thyroid the total Tx plus lymph NO dissection da were performed two years T3 the first T0 we recognized CL NO swelling at her right neck the us guided abc was performed the diagnosis was the metastasis of lymph node from TC we performed CL NO dissection again three years after the first T0 we detected the swelleing of CL NO again at her RA neck we performed lymph NO dissection again we recommended a therapeutic use of iodine radioisotopes however she rejected the therapy because she strongly wanted to be Pr generally speaking it is difficult to determine the therapeutic use of iodine radioisotopes for unmarried women after seven years from the first T0 she delivered a baby girl we plan to use of iodine radioisotopes for adjuvant therapy when she delivers her nd baby this case suggested that a treatment strategy for unmarried thyroid cancer patients should be made thoughtfully with care | MEDAL |
to assess the prevalence of SR in VA patients with this diagnosis who had undergone coronary arteriography in the hospital and a followup of at least year were studied patients with coronary bypass surgery or myocardial infarction were excluded remission was diagnosed in of the patients who had been anginafree and had had no treatment for more than months mean the other patients were receiving medical treatment had been anginafree for at least months mean and angina persisted in the persistent angina group had a lower prevalence of organic coronary stenoses or greater of versus of and of for the other two groups p less than and a longer PH of rest angina before admission the remission group contained more patients of versus of p less than whose attacks had been documented only by provocative testing rest angina recurred when calcium antagonist drugs were discontinued in of instances within month in patients and later in patients remission was eventually attained in of the patients in whom these drugs were stopped these results indicate that remission is a frequent outcome of variant angina this fact should be considered in the DUE of the longterm results of treatment and in the planning of care for an individual patient | MEDAL |
in the previous study takeda et al neurosci lett we reported that the T3 glycation end products ages in the external space of neuronal perikarya extraneuroperikaryal age deposits were significantly abundant in the alzheimers BB in this T0 we investigated the spatial relationship of the extraneuroperikaryal age carboxymethyllysine and pentosidine deposits in astrocytes and microglial cells in the alzheimers disease brain using double immunolabelling for ages and astrocyte or microglial cell markers most of the extraneuroperikaryal age deposits were colocalized with GFA proteinpositive astrocytes age depositbearing astrocytes also contained gomoripositive LG furthermore some of the extraneuroperikaryal age deposits were colocalized with microglial cells these extraneuroperikaryal ages may activate astrocyte and microglia and play a role in pathogenesis of alzheimers disease | MEDAL |
the biggest challenge to GT is how to efficiently deliver the desired therapeutic gene into a sufficient number of recipient cells to achieve significant clinical efficacy here we identified a partially purified extract from rat muscle probably containing myoblast specific F0 factors msf which significantly enhanced fusion of donor myoblast with host muscle fibers once incorporated the introduced genetic construct could instruct the machinery of the hybrid cells to express the desired proteins rat satellite cells containing a plasmid carrying a marker bone morphogenetic protein bmp coding sequence were used as foreign gene delivery vehicle brdu labeling of the msfpretreated satellite cells allowed tracing the fate of the GM satellite cells in the host muscles immunohistochemistry using antibmp antibody demonstrated the translation of the introduced gene construct it was demonstrated that in the presence of msf numerous brdu positive nuclei and the expression of bmp polypeptides could be observed in host hybrid fibers while in the control group using RS to replace msf containing fraction only a few brdu positive signals were detected the expression of osteocalcin and the elevated alkaline phosphatase activity detected in the hybrid fibers indicated the proper folding secretion and PTM of the expressed foreign protein this strategy of enhanced myoblastmediated gene transfer would break the major barrier in current practice of normal or engineered myoblast transplantation in the management of genetic muscle diseases or systemic genetic disorders | MEDAL |
it has been shown in vitro that saccharomyces cerevisiae strand exchange protein sep promotes the transfer of one strand of a linear duplex dna to a homologous ssDNA circle sep also has an exonuclease active on dna and rna by using exonuclease iiitreated linear duplex dna with various lengths of singlestranded tail as well as ca to inhibit the exonuclease activity of sep we show that the processivity of exonuclease activity of sep is greater than previously reported the results in this work also demonstrate that the joint molecule between the linear duplex and singlestranded circle observed from the seppromoted strand transfer reaction is just the pairing between the long singlestranded tail of the linear duplex dna generated by the exonuclease activity of sep and the singlestranded circular dna when a synthetic holliday junction was used as ATP branch migration facilitated by sep could not be detected finally using electron microscopy no alphastructure a joint molecule with displaced ssDNA tail that indicates branch migration could be observed the results imply that sep cannot promote CB migration in vitro further investigation is needed to determine the role of sep in recombination in vivo | MEDAL |
the optical and morphological properties of lustrous metal selfhealing liquidlike nanofilms were systematically studied for different applications eg optical mirrors or filters these nanofilms were formed by a OS selfassembly methodology of gold nanoparticles aunps at immiscible wateroil interfaces previously reported by our group we investigated a host of exp variables and herein report their influence on the optical properties of nanofilms aunp mean diameter interfacial aunp surface coverage nature of the organic solvent and nature of the lipophilic organic molecule that caps the aunps in the interfacial nanofilm to probe the interfacial gold nanofilms we used in situ uvvisnir spectroscopy and optical microscopy as well as ex situ sem and tem of interfacial gold nanofilms transferred to Si substrates techniques the interfacial aunp surface coverage strongly influenced the morphology of the interfacial nanofilms and in turn their maximum reflectance and absorbance we observed three distinct morphological regimes i smooth d monolayers of floating islands of aunps at low surface coveragowed that sex seemed to modify the effects of humidity on outpatient visits for allergic conjunctivitis but not for no o or temperature people younger than were found to be susceptible to changes of all four parameters while those older than were only consistently affected by no C2 our findings revealed that higher levels of ambient no o and temperature increase the chances of outpatient visits for allergic conjunctivitis ambient air pollution and weather changes may contribute to the worsening of allergic conjunctivitis | MEDAL |
although the primary cause of acute coronary syndrome is AS disease it is important to include other causes of AIM this report describes the case of a yearold man with acute myeloid one who was referred to our cardiology department for treatment of acute myocardial infarction with st segment elevation on an electrocardiogram portable echocardiography showed large Az of vegetation on the anterior mitral leaflet while coronary angiography demonstrated the total occlusion of the LAD i.a. a histologic examination of the embolectomy specimen confirmed the presence of aspergillus fungal thrombi this report highlights a rare case of fatal aspergillus endocarditis with myocardial infarction due to embolism in an immunosuppressed patient | MEDAL |
this T0 evaluated the effect of early application of intraaortic balloon pump iabp counterpulsation in patients with stsegment elevation acute myocardial infarction stemi scheduled for elective percutaneous coronary MI pci | MEDAL |
female rats have a higher threshold than males for seizures induced by the convulsant pentylenetetrazol a gabaa receptorchloride AChR blocker no sex difference was observed for the anticonvulsant MICs of ethanol or diazepam to protect against pentylenetetrazol seizures ovariectomy reduces the pentylenetetrazol ST of females to that of males in contrast females have a lower threshold than males to electroshock seizures pentylenetetrazol receptors were compared in males and females and gonadectomized animals by binding of several radioligands to the gabaa BCR no differences were found for these four groups of animals in the binding of hflunitrazepam to the benzodiazepine CS and stbutyl bicyclophosphorothionate stbps to the chloride channelconvulsant sites in membrane homogenates nor for allosteric modulation of IB by gaba the steroid anesthetic alphaxalone or the benzodiazepine ro in tissue section autoradiography no difference was observed for these same assays nor for the IB of hmuscimol in the presence and absence of alphaxalone in several major regions we conclude that circulating female sex hormones possibly neurosteroid metabolites of progesterone known to interact directly with the gabaa receptor complex are involved in the sex differences in pentylenetetrazol seizure susceptibility | MEDAL |
neural apoptosisregulated convertaseproprotein convertase subtilisinkexin like narcpcsk is a proprotein convertase recently described to play a major role in cholesterol homeostasis through enhanced degradation of the lowdensity lipoprotein receptor ldlr and possibly in neural development herein we investiimental conditions needed to use human ileal mucosa for in vitro absorption studies are described intestinal mucosa contains leptin receptors and OB inhibits galactose absorption suggesting a new site for leptins modulation of body mass the enhancer PE for the apob gene is located much farther from its structural gene in the intestine than in the liver | MEDAL |
repetition priming is a nonconscious form of memory that is accompanied by reductions in neural activity when an experience is repeated to date however there is no direct evidence that these neural reductions underlie the behavioral advantage afforded to repeated material here we demonstrate a causal linkage between neural and behavioral priming in humans fmri PET magnetic resonance imaging was used in combination with transcranial magnetic stimulation tms to target and disrupt activity in the left frontal cortex during repeated classification of objects leftfrontal tms disrupted both the neural and behavioral markers of priming neural priming in early sensory regions was unaffected by leftfrontal tmsa finding that provides evidence for separable conceptual and perceptual components of priming | MEDAL |
cleavage of amyloidbeta precursor protein app by alphabeta and gammasecretases releases an extracellular fragment called apps small abeta MMP and a short app intracellular domain that may provide a transcriptional signal analogous to the notch ICD notch cleavage is G1 by extracellular ligands on the cell surface but the cellular localization of app cleavage remains unclear we now show that in transfected cultured cells the BPM snare protein syntaxin a when expressed as a fulllength protein disrupts the golgi apparatus and blocks transgolgi traffic and exocytosis in contrast truncated syntaxin a selectively abolishes exocytosis but has no apparent effect on transgolgi traffic or golgi structure whereas further truncated syntaxins a and a have no effect on either exocytosis or golgi traffic using these syntaxin a fragments we demonstrated that blocking transgolgi traffic greatly impairs app cleavage and aicddependent nuclear signaling whereas blocking exocytosis CT does not affect either process even though secretion of apps and abeta peptide is abolished our data suggest that different from notch cleavage of app is independent of cell surface regulation by extracellular ligands but may be controlled by intracellular signaling | MEDAL |
strategies to recover myocardium in therapeutically unresponsive patients are again under scrutiny including techniques developed in the pioneering days of cardiothoracic surgery such as retroperfusion via the coronary sinusthe beck procedure an underestimated aspect of retroperfusion is the formation of new vessels this early observation of neoangiogenesis may be an important mechanism in observed benefits we hypothesized that periodic pressure elevation in coronary veins induces an analogy to shear AS angiogenic pulses by activating venous endothelium pulsatile stretch on A-V EC can be achieved easily by a pressurecontrolled intermittent balloon blockade of the coronary sinus outflow | MEDAL |
AEDs probably act by preventing the spread of the abnormal paroxysmal activity from the epileptogenic focus to surrounding normal SN an investigation of the mechanism of action of established anticonvulsant drugs on normal neuronal systems may therefore offer useful insights into the pathogenesis of the seizure disorders that these drugs serve to control antiabsence drugs ethosuximide valproate depress Rt inhibitory pathways drugs ERP against GTC seizures phenytoin carbamazepine valproate depress reticular excitatory pathways drugs that are also ERP against TG neuralgia phenytoin carbamazepine also depress afferent excitation and facilitate segmental inhibition in the TG complex drses to lps which occurred during the first wks were observed whereas the responses to pg protein a cw and pwm continued to increase for wks and the increases were high and significant in most cases there was no change in the dose response and kinetics patterns characteristic for each stimulant during ontogeny ontogenic development of autoantibodysecreting cells was different from the development of cells secreting all ig and antisrbc antibodies the increases in the numbers of cells secreting igm antidna and igm antibromelintreated mouse rbc antibodies in response to lps and pg during postnatal development were larger than the increases of all igmsecreting cells in contrast the increases of igm antidna secreting cells in response to protein a and pwm were smaller than the increases of all igmsecreting cells the frequencies of cells secreting antidna antibodies in lps and pgstimulated cultures were low in newborns and continued to increase until wks of age but they were high and did not change throughout ontogeny in protein astimulated cultures changes in the frequencies of antirbc antibodysecreting cells were less distinct and mostly insignificant PN changes in mitogenic responses were smaller and not correlated with the development of polyclonal ig responses our data indicate different modes of ontogenic OD of the ability of cells to produce polyclonal ig autoantibodies and heteroantibodies and to synthesize dna in response to different stimulants | MEDAL |
ten normal wakeful young average age years male subjects received positron emission tomographic pet scans to minutes T3 an infusion of d fdeoxyglucose in order to assess localized cerebral glucose metabolic rates during silent visual and other sensory imagery and cognitive mentation the typescripts of the verbal reports limited to T2 of this type of mentation including freeassociations to all the silent mental events were blindly contentanalyzed to provide objective measures of various kinds of anxiety and hostility many significant positive and negative correlations were found in medial cortical lateral cortical and subcortical GM and WG matter areas between the magnitude of the anxiety and hostility aroused in the silent mental processes and localized CBF gl metabolic rates clearly SE consumption in the BB as judged from localized gl metabolic rates is highly influenced by the quality and quantity of emotionally tinged private reveries and mental events occurring spontaneously within human subjects brain areas involved with the processing of language sensation cognition SM and emotional reactions appear to be involved especially in these significant correlations the implications of such findings in the neurosciences and behavioral sciences are discussed | MEDAL |
primary open angle glaucoma is an important type of glaucoma as it is one of the most common causes of blindness previous studies have demonstrated that in glaucomatous patients the human trabecular meshwork htm is markedly stiffened the purpose of the present study was to determine the RII role of yesassociated protein yap and transcriptional coactivator with pdzbinding motif taz in htm cells primary htm cells were cultured with different concentrations of dexamethasone dex and the expression levels of yap and taz were evaluated using reverse transcriptionquantitative PCR reaction and western blotting the results revealed that dex increased the expression of yap and taz in a dosedependent manner in addition the western blot analysis of cytoskeletonassociated proteins revealed that the inhibition of yap andor taz using small interfering rna resulted in the increased expression of collagen i and decreased expression of fibronectin laminin and CIV the expression of βcatenin a key protein in the wnt pathway was also observed to be regulated by yap and taz a ethynyldeoxyuridine IF assay indicated that yap and taz induced the proliferation of htm cells the investigation of crosslinked actin network formation by the htm cells demonstrated that the knockdown of yap and taz genes rescued htm cells from cytoskeletal reorganization furthermore functional DUE of a htm cell monolayer using a permeability CA demonstrated that the inhibition of yap and taz attenuated the dexinduced impairment of permeability these findings suggest that yap and taz play pivotal roles in the dexinduced cytoskeletal changes of htm cells and reveal novel potential mechanisms for the OD and progression of glaucoma | MEDAL |
the rate of cl secretion by human airway epithelium is determined in part by apical cell membrane GCl in cystic fibrosis airway epithelia defective regulation of cl conductance decreases the capability to secrete cl here we report that extracytosolic atp in the luminal bath of cultured human airway epithelia increased transepithelial cl secretion and apical membrane cl permeability singlechannel studies in excised membrane patches revealed that atp increased the open probability of outward rectifying cl channels the latter effect occurs through a receptor mechanism that requires no identified soluble second messengers and is insensitive to probes of g protein CF these results demonstrate a mode of regulation of anion channels by binding atp at the extracellular surface regulation of GCl by external atp is preserved in cystic fibrosis airway epithelia | MEDAL |
the immobilization of gold NPs in AE resin and their quantitative retrieval by means of a cationic SF cetylpyridinium chloride is studied the resinbound gold nanoparticles rau have been used successfully as a solidphase catalyst for the reduction of nitrophenol by sodium borohydride at the end of the reaction the solid matrix remains G1 and separated from the product the recycling of catalyst particles T3 the quantitative reduction of nitrophenol and the recovery of gold nanoparticles with unaffected particle morphology from the resinbound gold nanoparticle entity have been reported | MEDAL |
by the method of tenaxta absorbent adsorption combined with gcms this paper analyzed the changes of the diurnal rhythm of the volatiles in the healthy branches and batocera horsfieldidamaged branches of viburnum awabuki and betula luminifera and EAG technique was used to perform a comparative analysis on the electroantennogram eag responses of unmated male and female b horsfieldi to the volatiles T3 the FF by b horsfieldi there was a decrease in the contents of limonene nonanal hexadecane butyl acrylate and methylbutanoic acid in damaged branches of v awabuki and in the neohexane and hexadecane contents in damaged branches of b luminifera simultaneously new materials such as permethyl a octyl alcohol iodo decanal hexanal and bioallethrin etc were newly synthesized in the damaged branches the eag response values of unmated male and female b horsfieldi adults to the volatiles in the damaged branches of b luminifera were the highest being mv and mv while to the healthy branches of v awabuki were the lowest being mv and mv respectively as for the time period the eag response values of the adults to the volatiles were the lowest from to which accorded with the feeding behaviors of the adults i e taking food in the field in early morning or at dusk | MEDAL |
the purpose of this prospective T0 was to measure patients ability to open a purse take out money and count it in order to identify persons in need of increased health care the T0 population consisted of patients mean age range in two settings consecutively admitted geriatric hospital patients who could return home and communitydwelling patients aged years or older none was completely dependent on others nor severely demented time for task performance was measured further assessment included the minimental state examination mmse barthel index of adl instrumental activities of daily living iadl SES grip strength williams board test and medication profile the timed test of money counting ttmc was reliable interrater and intrarater and s development of a deformity AA to the potential tethering effect in twelve extremities a diaphyseal osteotomy of the tibia also was performed to correct tibial bowing and to improve the mechanical alignment of the extremity at the time of followup the patients who had had a syme amputation had more problems related to reformation of the calcaneus instability of the heel pad prosthetic suspension and excessive length of the residual extremity the modified boyd amputation improved the CF of the heel pad and the prosthetic suspension and provided the optimum length of the residual extremity we also found that an early diaphyseal osteotomy of the tibia to correct severe bowing improved prosthetic fitting this T0 did not support the concept that early resection of the fibular anlage or a diaphyseal osteotomy of the tibia prevents the development of hypoplasia of the lateral FA condyle and associated genu valgum deformity | MEDAL |
among children with univentricular circulation who underwent total cavopulmonary connection glenn or fontan over a years period january april we found two patients who had diffuse coronary fistulisation of their myocardium we also report an additional third case from oak lawn illinois usa one of the children had documented normal CAs and myocardium at catheterisation prior to OD of the fistulisation process the same child also developed extensive venovenous collaterals all children had evidence of elevated pulmonary arterial pressures and were treated with a combination of pulmonary vasodilators the presence of chronic hypoxaemia and elevated filling pressures could potentially have contributed to coronary endothelial dysfunction thereby giving rise to the coronary vasculopathy and myocardial fistulisation alternatively this myocardial fistulisation process may be present from early in life and not recognised this may necessitate early referral for orthotopic cardiac transplantation diffuse fistulisation of the myocardium in children and young adults with univentricular circulation may be an underrecognised occurrence and coronary angiography should be considered in these patients | MEDAL |
URS has enhanced the diagnosis and treatment of upper urinary tract disorders however the irrigation necessary for visualization and distention of the lumen may increase renal pelvic pressure resulting in pyelovenous lymphatic backflow we report a case of renal pelvic transitional cell carcinoma that may have migrated to submucosal venous and lymphatic spaces during flexible ureterorenoscopy | MEDAL |
we have examined the possibility of assessing primary bile acid pool sizes from the spillover of the bile acids into SVR blood after intestinal exposure to the total endogenous bile acid pool the studies were carried out in HS bile acid spillover was calculated as the integrated area under the curve of bile acid conjugates in SS of each primary bile acid class in response to a welldefined sustained cholecystokinininduced stimulus of the enterohepatic circulation for min causing complete GB emptying serum levels of each species of primary bile acid conjugates were measured by two specific and CS radioimmunoassays one for conjugated CA and one for conjugated chenodeoxycholate primary bile acid pool sizes determined with ccholic acid and cchenodeoxycholic acid according to lindstedt acta physiol scand served as REF bile acid conjugates of both species reached a peak min after the start of the cholecystokinin infusion probably reflecting simultaneous intestinal absorption of both primary bile acids in this model highly significant linear correlations were found between the integrated areas under the curve and primary bile acid pool sizes which were closer for chenodeoxycholate n r p less than than for cholate n r p less than abstract truncated at words | MEDAL |
vandetanib is a multitargeted RET inhibitor that is in clinical development for the treatment of solid tumours this preclinical study examined the inhibition of two key signalling pathways vegfr egfr at drug concentrations similar to those achieved in the clinic and their contribution to direct and indirect antitumour effects of vandetanib for in vitro studies receptor phosphorylation waecd draft guideline fet and was based on the exposure of newly fertilized eggs to and mgl of tcf for days the fish acute test followed the oecd guideline and was based on the exposure of AD fish to and mgl of tcf for days daphnia sp immobilization CA followed the oecd guideline and was based on the SE of juvenile daphnids to and μgl of tcf for days and the algae growth inhibition assay followed the oecd guideline and was based on the SE of the two species to and mgl of tcf for days biomarker levels were measured T3 h exposure to tcf in zebrafish early life stages and adults and after h exposure in d magna tested organisms seem to have dissimilar sensitivities towards tcf SE d magna hlc μgl was the most CS organism followed by early life stages and adults of zebrafish hlc and mgl respectively and finally by the algae p subcapitata hlc mgl and c vulgaris no effect observed as daphnids are a source of food for organisms of higher trophic C2 the impairment on its population is prone to have consequences in the entire ecosystem the biomarker MICs measured in daphnids and fish seemed to be useful tools in the assessment of trichlorfon effects especially che activity which was the most CS biomarker tested for all organisms trichlorfon was teratogenic for zebrafish embryos leading to anomalies in the absorption of the YS spine bending and pericardial oedemas the present research suggests that further work is urgently needed in order to monitor environmental concentrations of trichlorfon and to test the long term effects of environmentally realistic concentrations of this compound | MEDAL |
thieanisylzhexen diynyl AN thda an enediyne compound was identified in our laboratory as a novel antineoplastic agent against HL-60 k cells thdainduced apoptosis was associated with the upregulation of bax downregulation of xlinked inhibitor of apoptosis xiap as well as the activation of ICE and caspase in addition the mitogenactivated protein family kinases including cjun NT kinase jnk and extracellular signalregulated protein kinase erk kinases and the transcription factor cjun were all activated by phosphorylation T3 h SE to thda phosphorylation activation of jnk and erk kinases by thda was blocked by an erk inhibitor pd or a jnk inhibitor jnk respectively suggesting that thdainduced apoptosis in k cells is erk and jnk dependent moreover the blockade of erk and jnk also att the modulation of bax and xiap as well as the activation of caspase and caspase induced by thda these findings suggest that the activation of jnk and erk is involved in the thdainduced apoptosis of k cells therefore this investigation for the first time uncovered the biological properties of this novel antitumor enediyne | MEDAL |
platinumii complexes with an nheterocyclic carbene and a cyclometalating phenyl ligand cc are excellent candidates as efficient blue triplet emitters for oled applications the electronic and photophysical properties of these complexes can be finetuned with the objective to increase the quantum yields and lower the phosphorescence decay times we found that platinum complexes with an imidazopyrazine cc ligand and bulky acetylacetonates are skyblue triplet emitters characterised by an almost unitary quantum yield and short phosphorescence decay times | MEDAL |
a case of leukoencephalopathy induced by FT an antineoplastic derivative of fu is reported the patient received mg of FT po for days before excision of RC after the operation gait disturbance and mental abnormalities appeared he became akinetic and mute within a few days following readministration of tegafur serial studies of BB ct somatosensory evoked potentials sep were made and myelin basic proteins mbp in the cerebrospinal fluid were measured the level of mbp was about twice the normal value and the central conduction time cct of sep was prolonged at admission the value of mbp and cct improved with recovery from akinetic mutism | MEDAL |
selective neurodegeneration accompanied by mitochondrial dysfunction characterizes neurodegenerative disorders such as alzheimers and parkinsons diseases thiamine deficiency td in rats is a model for the study of cellular and molecular mechanisms that lead to selective neuronal loss caused by chronic oxidative deficits neurodegeneration in tdrats develops over a period of to days and can be partially reversed by B1 administration the aim of this T0 was to characterize the invivo progression of neurodegeneration and the neuronal rescue processes in td using t magnetic resonance mapping and DTI dti each rat was scanned prior to td induction day before the appearance of neurological PS day during the symptomatic stage days and and during the recuperation period days and timedependent lesions were revealed mainly in the thalamus and the VPI colliculi early decrease in the fractional anisotropy fa was found on day in the VPI colliculi and to a lesser degree in the thalamus while the earliest detectable changes in the t parameter occurred only on day fa values in the thalamus remained significantly low after B1 restoration suggesting irreversible disarrangement and replacement of neuronal structures while t values in the FC cortex demonstrated no lesions fa values significantly increased on days and an enlargement of the lateral ventricles was observed and persevered during the REC period this longitudinal mri T0 demonstrated that in td mri can detect neurodegeneration and neuronal recovery dti is more sensitive than t mapping in the early detection of td lesions | MEDAL |
mottled tohoku atpamotohm or motohm is an xlinked mutation with mottled pigmentation in heterozygous motohm females and is embryonic lethal at e in hemizygous motohmy males copper C2 were low in the BB and high in the intestine of motohm mice two congenic strains with icr or B6 b BG were produced for genetic and phenotypic analyses and revealed that motohm females with icr BG survived until adulthood while most with b background died within days T3 birth the motohmy males with both backgrounds died at around e massive hemorrhage was shown in the YS cavity with irregular att between the mesoderm and the endothelial cells of blood vessels in the embryos at e suggesting that this irregular attachment causes embryonic lethality the motohm mutant had a bp deletion between intron and exon of the atpa gene motohmy males with the wildtype atpa cdna Tg were rescued from embryonic lethality confirming that the motohm mutant is caused by the defect in the atpa gene this mutant mouse is the most severe MM of human menkes disease in mo mice established to date and one of the useful models for understanding the gene function of menkes disease | MEDAL |
conduction through the AVN avn is assessed during electrophysiology T0 by relating the SO to the input generated by an A2 this extrastimulus scans electrical diastole of the heart to enable output to be plotted against input using this technique we compared two mathematical models of the avn a rectangular hyperbola and a decaying exponential respectively the models were compared in curves from patients with only one avn transmission pathway SE of the estimate were usually trials less with the exponential model suggesting this the preferred algorithm for further OD | MEDAL |
inflammationinduced procoagulant changes and alterations in platelet activity appear to play an important role in thromboembolic complications of L3 endocarditis ie the aim of this T0 was to investigate SVR coagulation activity fibrinolytic capacity and platelet activation in ie patients with and without embolic events by measuring the plasma C2 of prothrombin fragment TAT complex plasminogen activator inhibitor betathromboglobulin and platelet factor the T0 included consecutive patients with definite ie according to the duke criteria among them had L1 embolic events PC of prothrombin fragment vs and nmoll p respectively and TAT vs and ngml p respectively were elevated in patients with embolic events compared with both patients without embolic events and control subjects similarly patients with embolic events had increased plasma C2 of betathromboglobulin vs and ngml p respectively and PF4 vs and ngml p respectively compared with those without embolic events and the control group embolic patients also had higher plasminogen activator inhibitor levels than both nonembolic patients and healthy subjects vs and ngml p respectively in conclusion ie patients with subsequent thromboembolism have increased SVR coagulation activation enhanced platelet activitydamage and impaired fibrinolysis the resulting imbalance produces a sustained hypercoagulable state that may contribute to the increased risk of TE events in this particular group | MEDAL |
in photosynthetic chains the kinetics of fluorescence yield depends on the photochemical rates at the level of both photosystem i and ii and thus on the absorption cross section of the photosynthetic units as well as on the coupling between light harvesting complexes and photosynthetic traps a new setup is described which at variance with the commonly used setups uses of a weakly absorbed light source lightemitting diodes with maximum SO at nm to excite the photosynthetic electron chain and probe the resulting fluorescence yield changes and their time course this RPA optimizes the homogeneity of the exciting CS throughout the leaf and we show that this homogeneity narrows the distribution of the photochemical rates although the exciting CS is weakly absorbed the possibility to tune the intensity of the light emitting diodes allows one to reach photochemical rates ranging from s to s rendering experimentally accessible different PET regimes the variations of the fluorescence yield induced by the photosynthetic activity are qualitatively and quantitatively discussed when illuminating darkadapted leaves by a weak light the kinetics of fluorescence changes displays a pronounced plateau which precedes the fluorescence increase reflecting the full reduction of the plastoquinone pool we ascribe this plateau to the TD needed to reduce the photosystem i electron acceptors | MEDAL |
cull cows n of similar age from angus and hereford breed types were assigned to one of four feeding periods or d and subdivided into two CG one implanted with synovexh and a nonimplanted control cows were fed a high energy diet and slaughtered at the end of each feeding period average daily gain and feed efficiency were evaluated on each animal during the trial the following carcass traits were evaluated usda yield and quality grade characteristics boning yield muscle weights bone weights ph and warnerbratzler shear force of the longissimus muscle the left side of each carcass was boned and proximate analysis was determined no significant implant effects were encountered for any of the traits evaluated therefore data were pooled and evaluated by feeding period on with the possibility that surfaceactive lipids in dairy milk such as phospholipids may account for a significant portion of milks antiulcer activity by maintaining the hydrophobicity of the luminal surface of the GM in the presence of a damaging agent | MEDAL |
the expression of interleukin receptors il r on human IP t cells was studied by the IB CA with ilabeled recombinant human interleukin il alpha and il beta and by the flow cytofluorometry with the fluorescein isothiocyanate fitcconjugated il alpha IP BL expressed only few il r without any stimulations when they were stimulated with concanavalin a con a il rpositive cells began to increase by hr reached the maximum level at hr and then gradually decreased the kinetics of the expression of il alpha r and il beta r showed the same DP furthermore the IB of ilabeled il alpha to il r on TA was inhibited by the addition of either cold il alpha or il beta but not by interleukin or interferons the similar results were observed in the binding of ilabeled il beta these results suggest that il r on human IP TA reactive for il alpha and il beta were identical by scatchard plot analysis the numbers of il r were estimated as and molecules per cell before and T3 con a stimulation respectively and their kd values were x m and x m when purified t cells CT were stimulated with con a il r were only marginally expressed however by the addition of monocytes il r were expressed on t cells in a dosedependent manner the maximum response was induced in the presence of monocytes the maximum il rpositive t cells were approximately by the detection of the flow cytofluorometry with fitcconjugated il alpha this enhancing activity of il r expression on t cells by monocytes was inhibited by the addition of an antihladr antibody or by the treatment of monocytes with the antihladr EAC furthermore t cell proliferative responses induced with il and con a were also enhanced by the addition of hladrpositive monocytes these results suggest that il r are expressed as the result of monocytet cell interaction in the early stage of t cell activation and the expression of il r on TA and the responsiveness of t cells for il require the accessory function of hladrpositive monocytes | MEDAL |
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