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Early Response (early + response)

Distribution by Scientific Domains

Medical Sciences	51%
Life Sciences	28%
Chemistry	8%
4 Other Domains	13%

Distribution within Medical Sciences

Psychiatry	21%
Immunology	15%
Oncology & Radiotherapy	9%

Terms modified by Early Response

early response gene

Selected Abstracts

Early response and 8-week treatment outcome in GAD ,

DEPRESSION AND ANXIETY, Issue 8 2006
Moira Rynn M.D.
Abstract Our objective was to compare the predictive value of early response to treatment outcome in patients with generalized anxiety disorder (GAD) treated with benzodiazepines, serotonin receptor (5HT-1A) partial agonists, or placebo. Data from two double-blind GAD studies were combined. Subjects were evaluated with the Hamilton Anxiety Scale (HAM-A) and the Clinical Global Impression of Improvement (CGI-I) scale over 8 weeks. Categories of response at weeks 1 and 2 were defined by the HAM-A total score. Analyses of covariance and Kaplan,Meier survival analyses were the primary analyses used to assess 8-week end point treatment outcomes as a function of early improvement. HAM-A change from baseline to weeks 1 and 2 significantly predicted last observation carried forward (LOCF) response at week 8 for both medications and for placebo (P<.001). Early improvement was a strong predictor for treatment outcome irrespective of whether active medication or placebo was the treatment agent. Depression and Anxiety 23:461,465, 2006. Published 2006 Wiley-Liss, Inc. [source]

Early response as predictor of final remission in elderly depressed patients

INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 11 2009
Rob M. Kok
Abstract Background Several studies have attempted to predict the final response or remission based on improvement during the early course of treatment of major depression. There is however a great variation in cut offs used to define early response and in the optimal week to predict final results. Objective To compare different cut offs at different time points early in the treatment of elderly depressed patients. Method A 12 week randomised, controlled trial in 81 elderly inpatients with DSM,IV major depression comparing venlafaxine with nortriptyline. At least 20, 25, 30 or 50% improvement was analysed after 1, 3 and 5 weeks using the Hamilton Depression Rating Scale and the Montgomery Asberg Depression Rating Scale. We plotted sensitivity against 1,specificity and calculated areas under the curve (AUCs). Results The highest percentage of correctly classified patients is found using at least 50% decrease as cut off in week 5, with acceptable sensitivity (81.8%) and specificity (87.4%). In week 5, the AUCs were 0.891 (95% CI 0.798,0.984) and 0.866 (95% CI 0.789,0.983) for the HAM-D and MADRS, respectively. Conclusions Combining the results from our study and the other studies addressing this issue, we suggest that the treatment should be changed in the elderly if after 3,4 weeks less than 30% improvement in depression score has been achieved. Copyright © 2009 John Wiley & Sons, Ltd. [source]

A rapid technique for assessing the suitability of areas for invasive species applied to New Zealand's rivers

DIVERSITY AND DISTRIBUTIONS, Issue 2 2008
Cathy Kilroy
ABSTRACT Early responses to incursions of non-indigenous species (NIS) into new areas include modelling and surveillance to define the organisms' potential and actual distributions. For well-studied invasive species, predictive models can be developed based on quantitative data describing environmental tolerances. In late 2004, an invasive freshwater diatom Didymosphenia geminata, an NIS for which we had no such quantitative data, was detected in a New Zealand river. We describe a procedure used to rapidly develop a classification of suitability for all New Zealand's rivers, based on two sources of information. First, from a review of the limited available literature and unpublished data, we determined that temperature, hydrological and substrate stability, light availability, and water pH were the most important environmental gradients determining D. geminata's broad-scale distribution and capacity for establishing and forming blooms in rivers. The second information source was a GIS-based river network developed for a national classification of New Zealand's rivers, with associated data describing environmental characteristics of each section of the network. We used six variables that were available for every section of the network as surrogates for the environmental gradients that determine suitability. We then determined the environmental distance of all the river sections in the network from our assessment of the optimal conditions conducive to D. geminata blooms. The analysis suggested that > 70% of New Zealand's river sections (stream order > 3) fell into the two highest suitability categories (on a five-point scale). At the time of writing, D. geminata had spread to 12 catchments, all of which were within these two categories. The technique is applicable in initial responses to incursions of NIS where quantitative information is limited, and makes optimal use of available qualitative information. Our assessment contributed to evaluations of the potential ecological, social, and economic impacts of D. geminata and is currently being used to stratify site selection for ongoing surveillance. [source]

Early responses associated with chronic pathology in murine schistosomiasis

PARASITE IMMUNOLOGY, Issue 5 2007
C. B. CÊTRE-SOSSAH
SUMMARY Inbred male CBA/J mice infected with Schistosoma mansoni develop either hypersplenomegaly syndrome (HSS) or moderate splenomegaly syndrome (MSS) by 20 weeks of infection. Pathologically and immunologically, MSS and HSS closely parallel the intestinal and hepatosplenic clinical forms of schistosomiasis in humans, respectively. By 6 weeks after infection, mice that eventually will become MSS develop T cell-stimulatory, cross-reactive idiotypes (CRI) while HSS mice never produce CRI. Because presence of CRI is useful to predict degree of chronic pathology, we used this measure to investigate what other early immunological events occurred in animals destined to develop severe morbidity. At 8 weeks of infection, there was a strong inverse correlation between CRI and splenomegaly, egg counts, and liver hydroxyproline. Similarly, phorbol myristate acetate (PMA)- and ionomycin-stimulated intracellular cytokine expression of IL-4, IL-5, and GM-CSF in splenic CD4+ T cells was inversely correlated with serum CRI and directly correlated with spleen size. In contrast, spleen cell intracellular TNF-, and peritoneal cell production of nitric oxide demonstrated positive correlations with CRI and inverse correlations with measures of morbidity. Surprisingly, IL-10 and IFN-, were not correlated with CRI levels. These studies link chronic pathology to certain immunological responses during the acute phase of schistosomiasis. [source]

Letters to the editor

PERFORMANCE IMPROVEMENT, Issue 5 2007
Article first published online: 3 MAY 200
Editor's note: The editor welcomes letters from all readers wishing to comment on articles in this issue of Performance Improvement. Early responses have the best chance of being published. Please be concise and include your title and organizational affiliation. Performance Improvement reserves the right to select, solicit, and edit letters. Send letters to pijeditor@ispi.org. [source]

Early response and 8-week treatment outcome in GAD ,

Life-cycle exposure of fathead minnows (Pimephales promelas) to an ethinylestradiol concentration below 1 ng/L reduces egg fertilization success and demasculinizes males

ENVIRONMENTAL TOXICOLOGY, Issue 2 2005
Joanne L. Parrott
Abstract Forty-eight hours after fertilization, fathead minnow (Pimephales promelas) eggs were exposed to the synthetic estrogen 17,-ethinylestradiol (EE2) at nominal concentrations of 0.32 and 0.96 ng/L and measured concentrations of 3.5, 9.6, and 23 ng/L. The fish were observed through the larval, juvenile, and adult stages. Growth, secondary sex characteristics, the liver somatic index, the gonadosomatic index, and fecundity were examined after several lengths of exposure. No significant changes were seen in fry or juvenile growth from 8 to 30 days posthatch (dph). An increase in the ovipositor index (a female secondary sex characteristic) was the most sensitive early response at 60 dph and was seen in fish exposed to EE2 concentrations , 3.5 ng/L. Continuation of the EE2 exposure until 150 dph, through maturation and reproduction, allowed measurement of two sensitive end points: decreased egg fertilization and sex ratio (skewed toward females), both of which were significantly affected at the lowest EE2 concentration tested, 0.32 ng/L. The next most sensitive end point was demasculinization (decreased male secondary sex characteristic index) of males exposed to an EE2 concentration of 0.96 ng/L. The effects of low concentrations of EE2 (0.32 and 0.96 ng/L) were manifested in male fish (decreased male sex characteristics and reduced egg fertilization success), whereas female fish showed no changes in the gonadosomatic index. Exposure to higher EE2 concentrations negatively affected females, as shown by a reduced gonadosomatic index at 150 dph in fish exposed to ,3.5 ng/L EE2. Although there were some end points that showed changes at 60 dph, the reproductive end points and external sex characteristics measured in mature fish at 150 dph were more sensitive, with response thresholds of EE2 ranging from 0.32 to 0.96 ng/L. The concentrations of EE2 that negatively affected fathead minnows were similar to or lower than those detected in many municipal wastewater effluents. In conclusion, life-cycle exposure of fathead minnows proved to be a very sensitive bioassay, and responses were seen at concentrations of less than 1 ng/L, which are environmentally relevant concentrations of EE2. © 2005 Government of Canada. Exclusive worldwide publication rights in the article have been transferred to John Wiley & Sons, Inc. Environ Toxicol 20: 131,141, 2005. [source]

Highly active antiretroviral therapy (HAART) among HIV-infected drug users: a prospective cohort study of sexual risk and injecting behaviour

ADDICTION, Issue 3 2006
Colette Smit
ABSTRACT Aims To study sexual risk and injecting behaviour among HIV-infected drug users (DU) receiving highly active antiretroviral therapy (HAART)., Design and setting As part of an ongoing prospective cohort study, HIV-infected DU who commenced HAART (n = 67) were matched with those not starting HAART (n = 130) on CD4 cell counts, duration of cohort participation, age and calendar year of visit. Immunological and virological responses of the HAART-treated DU were compared with the HAART-treated homosexual men from the same cohort (n = 212). Measurements Trends in behaviour and therapeutic response were tested with a logistic regression model adjusted for repeated measurements and a piecewise random effects model, respectively. Findings Non-HAART users reported more episodes of injecting than HAART users. In both groups injecting declined over time with no effect of HAART initiation. Before HAART initiation an increase in sexual risk behaviour was observed among those who had been assigned to receive HAART; their sexual risk behaviour declined thereafter. No change in sexual risk behaviour was found among non-HAART users. Relative to homosexual men, DU had a similar initial therapeutic response, but DU started HAART at lower CD4 cell counts and higher viral load levels. Conclusion DU who are treated with HAART are not increasing their risk behaviour, and their early response to HAART is similar to homosexual men. However, before the treated DU received HAART they were seen to inject less often than those not treated with HAART. This suggests that selection of potential HAART starters is based on limited drug use. Although the DU who commence HAART are a selected group, our results show that HIV-infected DU can be treated effectively. [source]

Vagal motor neurons in rats respond to noxious and physiological gastrointestinal distention differentially

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2002
Xueguo Zhang
Abstract Low-pressure gastrointestinal distention modulates gastrointestinal function by a vago-vagal reflex. Noxious visceral distention, as seen in an obstruction of the gastrointestinal tract, causes abdominal pain, vomiting and affective changes. Using single neuron recording and intracellular injection techniques, we characterized the neuronal responses of neurons in the dorsal motor nucleus of the vagus (DMNV) to low- and high-pressure distentions of stomach and duodenum. Low-pressure gastric distention inhibited the mean activity of the DMNV neurons whereas high-pressure gastric distention excited many neurons. Of 47 DMNV neurons, low-pressure gastric distention inhibited 39, excited four, and did not affect four neurons. High-pressure gastric distention inhibited 26, excited 20, and left one unaffected. Thirteen of the 39 DMNV neurons inhibited by low-pressure distention of the stomach reversed their response to excitation during high-pressure gastric distention. Among 47 DMNV neurons, low-pressure duodenal distention inhibited 30, excited 10, and did not affect the remaining seven neurons. High-pressure distention of the duodenum inhibited 25 and excited 22 neurons. Eight DMNV neurons inhibited by low-pressure duodenal distention were excited in early response to high-pressure distention of the duodenum. High-pressure duodenal distention caused an early excitation and late inhibition in the mean activity of the DMNV neurons while low-pressure duodenal distention only produced late inhibition. These results suggest that different reflexes are present between physiological distention and noxious stimulation of gastrointestinal tract. [source]

A Smart Nanoprobe Based On Fluorescence-Quenching PEGylated Nanogels Containing Gold Nanoparticles for Monitoring the Response to Cancer Therapy

ADVANCED FUNCTIONAL MATERIALS, Issue 6 2009
Motoi Oishi
Abstract A biocompatible, caspase-3-responsive, and fluorescence-quenching smart apoptosis nanoprobe based on a PEGylated nanogel that contains gold nanoparticles (GNPs) (fluorescence quenchers) in the cross-linked polyamine gel core and fluorescein isothiocyanate (FITC)-labeled DEVD peptides at the tethered PEG chain ends is prepared for monitoring the cancer response to therapy. FITC,DEVD,nanogel,GNP shows very little fluorescence in the absence of activated caspase-3 (normal cells) through the fluorescence resonance energy transfer (FRET) process between the GNPs and the FITC molecules, while pronounced fluorescence signals are observed in apoptotic cells because of the cleavage of the DEVD peptide by activated caspase-3 present in the cells, which results in the release of FITC molecules. Thus, remarkable quenching and dequenching of fluorescence signals in response to activated caspase-3 is observed. Apoptotic cells are detected in human hepatocyte (HuH-7) multicellular tumor spheroids (MCTSs), a commonly used three-dimensional in vitro model mimicking the in vivo biology of tumors, as early as one day post-treatment with staurosporine, an apoptosis-inducing agent; while growth inhibition (i.e., change in size) of the HuH-7 MCTSs is only observed after a delay of three days (i.e., on day 4). This demonstrates the effectiveness of the FITC,DEVD,nanogel,GNP probe as a smart nanoprobe for real-time monitoring as well as a more rapid assessment of the early response to cancer therapy. [source]

Parallel activation of field CA2 and dentate gyrus by synaptically elicited perforant path volleys

HIPPOCAMPUS, Issue 8 2004
Renata Bartesaghi
Abstract Previous studies showed that dorsal psalterium (PSD) volleys to the entorhinal cortex (ENT) activated in layer II perforant path neurons projecting to the dentate gyrus. The discharge of layer II neurons was followed by the sequential activation of the dentate gyrus (DG), field CA3, field CA1. The aim of the present study was to ascertain whether in this experimental model field, CA2, a largely ignored sector, is activated either directly by perforant path volleys and/or indirectly by recurrent hippocampal projections. Field potentials evoked by single-shock PSD stimulation were recorded in anesthetized guinea pigs from ENT, DG, fields CA2, CA1, and CA3. Current source-density (CSD) analysis was used to localize the input/s to field CA2. The results showed the presence in field CA2 of an early population spike superimposed on a slow wave (early response) and of a late and smaller population spike, superimposed on a slow wave (late response). CSD analysis during the early CA2 response showed a current sink in stratum lacunosum-moleculare, followed by a sink moving from stratum radiatum to stratum pyramidale, suggesting that this response represented the activation and discharge of CA2 pyramidal neurons, mediated by perforant path fibers to this field. CSD analysis during the late response showed a current sink in middle stratum radiatum of CA2 followed by a sink moving from inner stratum radiatum to stratum pyramidale, suggesting that this response was mediated by Schaffer collaterals from field CA3. No early population spike was evoked in CA3. However, an early current sink of small magnitude was evoked in stratum lacunosum-moleculare of CA3, suggesting the presence of synaptic currents mediated by perforant path fibers to this field. The results provide novel information about the perforant path system, by showing that dorsal psalterium volleys to the entorhinal cortex activate perforant path neurons that evoke the parallel discharge of granule cells and CA2 pyramidal neurons and depolarization, but no discharge of CA3 pyramidal neurons. Consequently, field CA2 may mediate the direct transfer of ENT signals to hippocampal and extrahippocampal structures in parallel with the DG-CA3-CA1 system and may provide a security factor in situations in which the latter is disrupted. © 2004 Wiley-Liss, Inc. [source]

Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4

IMMUNOLOGY, Issue 2 2004
Eva M. Pålsson-McDermott
Summary An understanding of lipopolysaccharide (LPS) signal transduction is a key goal in the effort to provide a molecular basis for the lethal effect of LPS during septic shock and point the way to novel therapies. Rapid progress in this field during the last 6 years has resulted in the discovery of not only the receptor for LPS , Toll-like receptor 4 (TLR4) , but also in a better appreciation of the complexity of the signalling pathways activated by LPS. Soon after the discovery of TLR4, the formation of a receptor complex in response to LPS, consisting of dimerized TLR4 and MD-2, was described. Intracellular events following the formation of this receptor complex depend on different sets of adapters. An early response, which is dependent on MyD88 and MyD88-like adapter (Mal), leads to the activation of nuclear factor-,B (NF-,B). A later response to LPS makes use of TIR-domain-containing adapter-inducing interferon-, (TRIF) and TRIF-related adapter molecule (TRAM), and leads to the late activation of NF-,B and IRF3, and to the induction of cytokines, chemokines, and other transcription factors. As LPS signal transduction is an area of intense research and rapid progress, this review is intended to sum up our present understanding of the events following LPS binding to TLR4, and we also attempt to create a model of the signalling pathways activated by LPS. [source]

Predictors of early response to infliximab in patients with ulcerative colitis

INFLAMMATORY BOWEL DISEASES, Issue 2 2007
Marc Ferrante MD
Abstract Background: Our objective is to report the outcome of infliximab (IFX) in ulcerative colitis (UC) patients from a single center and to identify predictors of early clinical response. Methods: The first 100 UC patients (45 female; median age, 37.9 years) who received IFX at a single center were included. Eighty-four patients received 5 mg/kg IFX, and 37 patients received a 3-dose IFX induction at weeks 0, 2, and 6. The Mayo endoscopic subscore, assessed by sigmoidoscopy before inclusion, was 1, 2, and 3 in 5%, 52%, and 43% of patients, respectively. Sixty percent had pancolitis, 63% were on concomitant immunosuppressive therapy, 9% were active smokers, 64% had C-reactive protein ,5 mg/dL, and 44% were pANCA+/ASCA,. Five patients received IFX because of severe acute colitis refractory to intravenous corticosteroids. Results: Early complete and partial clinical responses were observed in 41% and 24% of patients. Patients with early clinical response were significantly younger than nonresponders (median age, 35.7 versus 41.6 years, P = 0.041). Patients who were pANCA+/ASCA, had a significantly lower early clinical response (55% versus 76%; odds ratio [OR] = 0.40 (0.16,0.99), P = 0.049). Concomitant immunosuppressive therapy and the use of an IFX induction scheme did not influence early clinical response. Only 1 of 5 patients who received IFX for acute steroid-refractory colitis required colectomy within 2 months. Conclusions: IFX is an efficient therapy in UC, as shown by 65% early clinical response. A pANCA+/ASCA, serotype and an older age at first IFX infusion are associated with a suboptimal early clinical response. (Inflamm Bowel Dis 2006) [source]

Signalling responses linked to betulinic acid-induced apoptosis are antagonized by MEK inhibitor U0126 in adherent or 3D spheroid melanoma irrespective of p53 status

INTERNATIONAL JOURNAL OF CANCER, Issue 5 2006
Manuel Rieber
Abstract MEK1/2 inhibitors like U0126 can potentiate or antagonize the antitumor activity of cytotoxic agents such as cisplatin, paclitaxel or vinblastine, depending on the drug or the target cells. We now investigated whether U0126, differentially regulates melanoma signaling in response to UV radiation or betulinic acid, a drug lethal against melanoma. This report shows that U0126 inhibits early response (ERK) kinase activation and cyclin A expression in wt p53 C8161 melanoma exposed to either UV radiation or betulinic acid. However, U0126 does not protect from UV damage, but counteracts betulinic acid-mediated apoptosis in the same cells. Protection from the latter drug by joint treatment with U0126 was also evident in wt p53 MelJuso melanoma and mutant p53 WM164 melanoma. The latter cells were the most responsive to betulinic acid, showing a selective decline in the cdk4 protein, without a comparable change in other key cell cycle proteins like cdc2, cdk2, cdk7 or cyclin A, prior to apoptosis-associated PARP fragmentation. Laser scanning cytometry also showed that betulinic acid induced a significant increase in chromatin condensation in WM164 melanoma irrespective of whether they were in adherent form or as multicellular spheroids. All these betulinic acid-induced changes were counteracted by U0126. Our data show for the first time that (a) cdk4 protein is an early target of betulinic acid-induced apoptosis and (b) unrestricted ERK signaling favours betulinic acid-induced apoptosis, but this is counteracted by U0126, partly through counteracting chromatin condensation and restoring Akt activation decreased by betulinic acid treatment. © 2005 Wiley-Liss, Inc. [source]

Early response as predictor of final remission in elderly depressed patients

Interactions between FGF and Wnt signals and Tbx3 gene expression in mammary gland initiation in mouse embryos

JOURNAL OF ANATOMY, Issue 1 2004
Maxwell C. Eblaghie
Abstract Interactions between Wnts, Fgfs and Tbx genes are involved in limb initiation and the same gene families have been implicated in mammary gland development. Here we explore how these genes act together in mammary gland initiation. We compared expression of Tbx3, the gene associated with the human condition ulnar,mammary syndrome, expression of the gene encoding the dual-specificity MAPK phosphatase Pyst1/MKP3, which is an early response to FGFR1 signalling (as judged by sensitivity to the SU5402 inhibitor), and expression of Lef1, encoding a transcription factor mediating Wnt signalling and the earliest gene so far known to be expressed in mammary gland development. We found that Tbx3 is expressed earlier than Lef1 and that Pyst1 is also expressed early but only transiently. Patterns of expression of Tbx3, Pyst1 and Lef1 in different glands suggest that the order of mammary gland initiation is 3, 4, 1, 2 and 5. Consistent with expression of Pyst1 in the mammary gland, we detected expression of Fgfr1b, Fgf8 and Fgf9 in both surface ectoderm and mammary bud epithelium, and Fgf4 and Fgf17 in mammary bud epithelium. Beads soaked in FGF-8 applied to the flank of mouse embryos, at a stage just prior to mammary bud initiation, induce expression of Pyst1 and Lef1 and maintain Tbx3 expression in flank tissue surrounding the bead. Grafting beads soaked in the FGFR1 inhibitor, SU5402, abolishes Tbx3, Pyst1 and Lef1 expression, supporting the idea that FGFR1 signalling is required for early mammary gland initiation. We also showed that blocking Wnt signalling abolishes Tbx3 expression but not Pyst1 expression. These data, taken together with previous findings, suggest a model in which Tbx3 expression is induced and maintained in early gland initiation by both Wnt and Fgf signalling through FGFR1. [source]

Up-regulation of heat shock protein HSP 20 in the hippocampus as an early response to hypoxia of the newborn

JOURNAL OF NEUROCHEMISTRY, Issue 2 2006
Jean-Claude David
Abstract Hypoxia is an important challenge for newborn mammals. Stress generated at the brain level under low oxygenation conditions results in up-regulation of heat shock proteins (HSPs) and other stress proteins. The aim of the present work was to determine the effect of hypoxia in the newborn on some newly described small molecular weight HSPs (HSP 20 and B8) in the hippocampus, cortex and cerebellum of newborn piglets. These effects will be compared with those of other closely related proteins such as ,B crystallin, HSP 27, heme oxygenase (HO)-1, HO-2, cyclooxygenase (COX)-1 and COX-2. The piglets were submitted to hypoxia (5% O2; 95% N2) over either 1 or 4 h, with recovery periods ranging from 0 to 68 h. Western blot analysis showed that HSP 20 was rapidly induced only in the hippocampus, long before hypoxia-inducible transcription factor HIF-1,, while HSP 27 was rapidly induced in the cortex and cerebellum. Vascular epithelial growth factor was increased simultaneously in the three regions. Moreover, an increase in the expression of, respectively, HO-1 and COX-2 was observed later, but at the same time, in the three regions tested. It appears that HSP 20 can be an early marker of hypoxia in the hippocampus. The other small HSPs or stress proteins display different temporal patterns of up-regulation (HSP 27 and HO-1, COX-2) or do not show changes in their expressions (,B crystallin, HSP B8, HO-2 and COX-1). [source]

IMPACT OF IRON LIMITATION ON THE PHOTOSYNTHETIC APPARATUS OF THE DIATOM CHAETOCEROS MUELLERI (BACILLARIOPHYCEAE)

JOURNAL OF PHYCOLOGY, Issue 6 2001
Margaret Davey
Iron starvation induced marked increases in flavodoxin abundance and decreases in light-saturated and light-limited photosynthesis rates in the diatom Chaetoceros muelleri. Consistent with the substitution of flavodoxin for ferredoxin as an early response to iron starvation, increases of flavodoxin abundance were observed before declines of cell division rate or chl a specific photosynthesis rates. Changes in the abundance of flavodoxin after the addition of iron to iron-starved cells indicated that flavodoxin was not actively degraded under iron-replete conditions. Greater declines in light-saturated oxygen evolution rates than dark oxygen consumption rates indicated that the mitochondrial electron transfer chain was not affected as greatly by iron starvation as the photosynthetic electron transfer chain. The carbon:nitrogen ratio was unaffected by iron starvation, suggesting that photosynthetic electron transfer was a primary target of iron starvation and that reductions in nitrate assimilation were due to energy limitation (the C:N ratio would be expected to rise under nitrogen-limited but energy-replete conditions). Parallel changes were observed in the maximum light-saturated photosynthesis rate and the light-limited initial slope of the photosynthesis-light curve during iron starvation and recovery. The lowest photosynthesis rates were observed in iron-starved cells and the highest values in iron-replete cells. The light saturation parameter, Ik, was not affected by iron starvation, nor was the chl-to-C ratio markedly reduced. These observations were consistent with iron starvation having a similar or greater effect on photochemical charge separation in PSII than on downstream electron transfer steps. Declines of the ratio of variable to maximum fluorescence in iron-starved cells were consistent with PSII being a primary target of iron starvation. The functional cross-section of PSII was affected only marginally (<20%) by iron starvation, with the largest values observed in iron-starved cells. The rate constant for electron transfer calculated from fast repetition rate fluorescence was found to covary with the light-saturated photosynthesis rate; it was lowest in the most severely starved cells. [source]

Treatment of chronic hepatitis C virus infection in patients with cirrhosis

JOURNAL OF VIRAL HEPATITIS, Issue 5 2000
Zeuzem
Chronic hepatitis C virus (HCV) infection eventually leads to cirrhosis in 20,30% of patients and to hepatocellular carcinoma (HCC) in 1,5% of patients. Rates of sustained virological response with standard interferon-, (IFN-,) are low in patients without cirrhosis (generally < 20%) and are even lower in those with cirrhosis. Combination therapy with IFN and ribavirin improves response rates in patients with chronic hepatitis C without cirrhosis, and the results from subgroups of HCV-infected patients with advanced fibrosis or cirrhosis are encouraging. Importantly, treatment with IFN slows progression of liver fibrosis, regardless of HCV genotype or early response to therapy, and reduces the risk of HCC by two- to fivefold. The risk of development of HCC is also lower in patients who show at least a partial response to IFN therapy compared with those who show no response. There is a clear need for more definitive studies of treatment in patients with chronic hepatitis C and cirrhosis, ideally using therapies with greater efficacy. Nonetheless, based on the potential to slow the progression of liver fibrosis (regardless of treatment response) and to reduce the risk of HCC, a greater number of HCV-infected patients with cirrhosis should be considered as candidates for IFN treatment. Preliminary data indicate that pegylated IFNs have improved virological response rates and may have additional clinical benefits in the prevention or reduction of fibrosis and retardation of progression of cirrhosis and HCC in these patients. [source]

Early detection of radiation therapy response in non-Hodgkin's lymphoma xenografts by in vivo1H magnetic resonance spectroscopy and imaging

NMR IN BIOMEDICINE, Issue 6 2010
Seung-Cheol Lee
Abstract The purpose of the study was to investigate the capability of 1H MRS and MRI methods for detecting early response to radiation therapy in non-Hodgkin's lymphoma (NHL). Studies were performed on the WSU-DLCL2 xenograft model in nude mice of human diffuse large B-cell lymphoma, the most common form of NHL. Radiation treatment was applied as a single 15,Gy dose to the tumor. Tumor lactate, lipids, total choline, T2 and apparent diffusion coefficients (ADC) were measured before treatment and at 24,h and 72,h after radiation. A Hadamard-encoded slice-selective multiple quantum coherence spectroscopy sequence was used for detecting lactate (Lac) while a stimulated echo acquisition mode sequence was used for detection of total choline (tCho) and lipids. T2 - and diffusion-weighted imaging sequences were used for measuring T2 and ADC. Within 24,h after radiation, significant changes were observed in the normalized integrated resonance intensities of Lac and the methylenes of lipids. Lac/H2O decreased by 38,±,15% (p,=,0.03), and lipid (1.3,ppm, CH2)/H2O increased by 57,±,14% (p,=,0.01). At 72,h after radiation, tCho/H2O decreased by 45,±,14% (p,=,0.01), and lipid (2.8,ppm, polyunsaturated fatty acid)/H2O increased by 970,±,36% (p,=,0.001). ADC increased by 14,±,2% (p,=,0.003), and T2 did not change significantly. Tumor growth delay and regression were observed thereafter. This study enabled comparison of the relative sensitivities of various 1H MRS and MRI indices to radiation and suggests that 1H MRS/MRI measurements detect early responses to radiation that precede tumor volume changes. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Recent advances in breast MRI and MRS

NMR IN BIOMEDICINE, Issue 1 2009
S. Sinha
Abstract Breast MRI is an area of intense research and is fast becoming an important tool for the diagnosis of breast cancer. This review covers recent advances in breast MRI, MRS, and image post-processing and analysis. Several studies have explored a multi-parametric approach to breast imaging that combines analysis of traditional contrast enhancement patterns and lesion architecture with novel methods such as diffusion, perfusion, and spectroscopy to increase the specificity of breast MRI studies. Diffusion-weighted MRI shows some potential for increasing the specificity of breast lesion diagnosis and is even more promise for monitoring early response to therapy. MRS also has great potential for increasing specificity and for therapeutic monitoring. A limited number of studies have evaluated perfusion imaging based on first-pass contrast bolus tracking, and these clearly identify that vascular indices have great potential to increase specificity. The review also covers the relatively new acquisition technique of MR elastography for breast lesion characterization. A brief survey of image processing algorithms tailored for breast MR, including registration of serial dynamic images, segmentation and extraction of morphological features of breast lesions, and contrast uptake modeling, is also included. Recent advances in MRI, MRS, and automated image analysis have increased the utility of breast MR in diagnosis, screening, management, and therapy monitoring of breast cancer. Copyright © 2008 John Wiley & Sons, Ltd. [source]

Comparison of gallium and PET scans at diagnosis and follow-up of pediatric patients with Hodgkin lymphoma

PEDIATRIC BLOOD & CANCER, Issue 2 2008
Melissa Hines-Thomas BS
Abstract Background Positron emission tomography (PET) and gallium scans facilitate diagnosis and staging, evaluation of response to therapy, and monitoring for relapse in Hodgkin lymphoma (HL), but have not been compared in pediatric HL. Procedure We performed concurrent PET and gallium scans on 44 pediatric HL patients at diagnosis, early response, off chemotherapy, and off-therapy evaluations. PET and gallium scans were compared to each other and to computed tomography (CT) alone to determine whether either modality led to a change in stage or modified the results of the early response evaluation, which was used to determine the radiation dose. Results PET upstaged four patients at diagnosis (2 from stage I to II, one II to III, and one III to IV), but did not lead to a change in therapy in any of them. It changed response category in two patients at early response evaluation, leading to a change in radiation dose for 1 patient (25.5 Gy instead of 15 Gy to the spleen). Gallium did not change the stage of treatment for any patient. The negative predictive values for eventual lymphoma relapse of PET and gallium scans at off therapy were 89% and 83%, respectively; the positive predictive value of PET at off therapy is 29%. Conclusion PET appears to be superior to gallium in pediatric HL; future studies will determine the optimal timing of PET to assess early response and the utility of quantitative interpretation of the avidity of specific nodal sites. Pediatr Blood Cancer 2008;51:198,203. © 2008 Wiley-Liss, Inc. [source]

Molecular analysis of resistance mechanisms to Orobanche cumana in sunflower

PLANT PATHOLOGY, Issue 3 2007
P. Letousey
Resistance to the dicotyledenous parasite Orobanche cumana in sunflower is characterized by a low number of parasitic attachments and a confinement of the parasite in host tissues leading to its necrosis. To help understand what determines such resistance mechanisms, molecular, biochemical and histological approaches were employed before (early response) and after (late response) attachment of the broomrape parasite to susceptible (2603) and resistant (LR1) sunflower genotypes. The expression patterns of 11 defence-related genes known to be involved in different metabolic pathways (phenylpropanoids, jasmonate, ethylene) and/or in resistance mechanisms against microorganisms were investigated. RT-PCR and cDNA blot experiments revealed that the resistant genotype exhibited a stronger overall defence response against O. cumana than the susceptible one, involving marker genes of the jasmonate (JA) and salicylic acid (SA) pathways. Among them, the SA-responsive gene, def. (defensin), appeared to be characteristic of LR1 sunflower resistance. However, no JA accumulation and similar SA contents (250,300 ng g,1 FW) were measured by GC/MS in both genotypes, parasitized or not. In addition, three cDNAs, isolated by a suppression-subtractive hybridization, were shown to be strongly induced only in the resistant genotype 8 days post-inoculation, when the first O. cumana attachments occurred. These genes, putatively encoding a methionine synthase, a glutathione S-transferase and a quinone oxidoreductase, might be involved in detoxification of reactive oxygen species, suggesting the occurrence of an oxidative burst during the incompatible interaction. Finally, host cell-wall modifications leading to parasite-confinement were correlated with more intense callose depositions in the resistant genotype, concomitant with over-expression of the callose synthase cDNA HaGSL1. [source]

CO2 limitation induces specific redox-dependent protein phosphorylation in Chlamydomonas reinhardtii

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 9 2006
Maria V. Turkina
Abstract Acclimation of the green alga Chlamydomonas reinhardtii to limiting environmental CO2 induced specific protein phosphorylation at the surface of photosynthetic thylakoid membranes. Four phosphopeptides were identified and sequenced by nanospray quadrupole TOF MS from the cells acclimating to limiting CO2. One phosphopeptide originated from a protein that has not been annotated. We found that this unknown expressed protein (UEP) was encoded in the genome of C.,reinhardtii. Three other phosphorylated peptides belonged to Lci5 protein encoded by the low-CO2 -inducible gene,5 (lci5). The phosphorylation sites were mapped in the tandem repeats of Lci5 ensuring phosphorylation of four serine and three threonine residues in the protein. Immunoblotting with Lci5-specific antibodies revealed that Lci5 was localized in chloroplast and confined to the stromal side of the thylakoid membranes. Phosphorylation of Lci5 and UEP occurred strictly at limiting CO2; it required reduction of electron carriers in the thylakoid membrane, but was not induced by light. Both proteins were phosphorylated in the low-CO2 -exposed algal mutant deficient in the light-activated protein kinase,Stt7. Phosphorylation of previously unknown basic proteins UEP and Lci5 by specific redox-dependent protein kinase(s) in the photosynthetic membranes reveals the early response of green algae to limitation in the environmental inorganic carbon. [source]

Proteomic analysis of the response of the human neutrophil-like cell line NB-4 after exposure to anthrax lethal toxin

PROTEOMICS - CLINICAL APPLICATIONS, Issue 10 2007
Jun X. Wheeler
Abstract We used 2-D DIGE to analyze the early response of NB-4 cells, a human promyelotic leukemia cell line, exposed to lethal toxin from Bacillus anthracis at the proteome level. After a 2,h exposure, cells were still viable and 43% of spots (n,=,1042) showed a significant change in protein level. We identified 59 spots whose expression had changed significantly, and these reflected cytoskeleton damage, mitochondrial lysis and endoplasmic reticulum stress. Actin filament assembly was disrupted as evidenced by an increase in both actin subunits and phosphorylated cofilin, whilst levels of tropomyosin, tropomodulin and actin related protein 2/3 complex subunit decreased. Lower levels of ATP synthase subunits and mitochondrial inner membrane protein were identified as markers of mitochondrial lysis. Levels of various stress response proteins rose and, uniquely, levels of Ca2+ binding proteins such as translationally controlled tumor protein rose and hippocalcin-like protein 1 decreased. This response may have mitigated effects brought about by mitochondrial lysis and endoplasmic reticulum stress, and delayed or prevented apoptosis in NB-4 cells. These results resemble findings of similar proteomics studies in murine macrophages, although quantitative differences were observed. [source]

Efficacy of risperidone in the treatment of delirium in elderly patients

PSYCHOGERIATRICS, Issue 2 2008
Koji IKEZAWA
Abstract Background:, Despite increasing recognition of delirium as a serious complication of physical illness, little has been reported in this area. Interest has been raised in treatment options other than haloperidol, such as atypical antipsychotic agents. Methods:, A 2-week open-label trial of risperidone for the treatment of delirium was conducted to assess the efficacy and tolerance of this medication in elderly patients. Twenty-two patients with DSM-IV-defined delirium were investigated. All patients had the hyperactive,hyperalert variant of delirium. Patients received a fixed dose of risperidone (mean 1.5 ± 0.7 mg; range 0.5,3 mg). Delirium was assessed using the Delirium Rating Scale (DRS) at baseline and on Days 1, 3, 5, 7, and 14 after the initiation of risperidone treatment. Clinical and demographic data, as well as risperidone therapy related information, were collected. Results:, Delirium resolved in all patients over the course of treatment. The mean period over which delirium resolved was 4.0 ± 2.9 days. The mean DRS score at baseline was 20.7 ± 3.0. The DRS score improved from baseline to Day 1 of treatment and continued to improve until the study end-point. Mild side-effects were present in 27.3% of patients. Stepwise logistic regression identified a decrease of 2 points or higher on the DRS on Day 1 associated with side-effects. There were no significant differences in the response to treatment with the different doses of risperidone used. Conclusion:, Our findings indicate that low-dose risperidone (0.5,3.0 mg/day) is effective and safe for the treatment of delirium in elderly patients, and that an early response on Day 1 of treatment may be associated with side-effects in these patients. [source]

Early signaling through the Arabidopsis pattern recognition receptors FLS2 and EFR involves Ca2+ -associated opening of plasma membrane anion channels

THE PLANT JOURNAL, Issue 3 2010
Elena Jeworutzki
Summary The perception of microbes by plants involves highly conserved molecular signatures that are absent from the host and that are collectively referred to as microbe-associated molecular patterns (MAMPs). The Arabidopsis pattern recognition receptors FLAGELLIN-SENSING 2 (FLS2) and EF-Tu receptor (EFR) represent genetically well studied paradigms that mediate defense against bacterial pathogens. Stimulation of these receptors through their cognate ligands, bacterial flagellin or bacterial elongation factor Tu, leads to a defense response and ultimately to increased resistance. However, little is known about the early signaling pathway of these receptors. Here, we characterize this early response in situ, using an electrophysiological approach. In line with a release of negatively charged molecules, voltage recordings of microelectrode-impaled mesophyll cells and root hairs of Col-0 Arabidopsis plants revealed rapid, dose-dependent membrane potential depolarizations in response to either flg22 or elf18. Using ion-selective microelectrodes, pronounced anion currents were recorded upon application of flg22 and elf18, indicating that the signaling cascades initiated by each of the two receptors converge on the same plasma membrane ion channels. Combined calcium imaging and electrophysiological measurements revealed that the depolarization was superimposed by an increase in cytosolic calcium that was indispensable for depolarization. NADPH oxidase mutants were still depolarized upon elicitor stimulation, suggesting a reactive oxygen species-independent membrane potential response. Furthermore, electrical signaling in response to either flg22 or elf 18 critically depends on the activity of the FLS2-associated receptor-like kinase BAK1, suggesting that activation of FLS2 and EFR lead to BAK1-dependent, calcium-associated plasma membrane anion channel opening as an initial step in the pathogen defense pathway. [source]

Substantial early, but nonprogressive neuronal loss in multiple sclerosis (ms) spinal cord,

ANNALS OF NEUROLOGY, Issue 5 2009
Lucas Schirmer MD
Research in multiple sclerosis (MS) has recently been focusing on the extent of neuroaxonal damage and its contribution to disease outcome. In the present study, we examined spinal cord tissue from 30 clinically well-characterized MS patients. MS, amyotrophic lateral sclerosis (ALS), and control spinal cord tissue were subjected to morphometric analysis and immunohistochemistry for markers of cell damage and regeneration. Data were related to disease duration and age at death. Here, we present evidence for substantial, nonprogressive neuronal loss on the cervical and lumbar levels early in the disease course of MS. Chromatolytic neurons and immunoreactivity for c-Jun and GAP43 were observed in the ventral gray matter in and adjacent to actively demyelinating lesions, pointing toward neuronal damage and regeneration as an early response to lesion formation. Ann Neurol 2009;66:698,704 [source]

Gene expression profiling during early response to injury and microbial challenges in the silkworm, Bombyx mori

ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY (ELECTRONIC), Issue 1 2009
Fei Liu
Abstract To identify Bombyx mori genes involved in the early response to injury and microbial challenge, we performed genome-wide gene expression-profiling experiments using oligonucleotide DNA microarrays. Of approximately 23,000 genes examined, 465 displayed changes in mRNA expression levels. Of these, 306 were induced and 159 were repressed in response to injury (injection with phosphate buffer saline) or challenges by Gram-negative (Serratia marcescens), Gram-positive bacteria (Staphylococcus aureus), or fungus (Beauveria bassiana). Many of these differentially expressed genes can be assigned to specific functional groups of the innate immune response, including recognition, signaling, melanization and coagulation, and antimicrobial peptides. Seventeen percent of differentially expressed genes encode proteins with no obvious similarity to known functional domains. Of particular interest is a member of the juvenile hormone-binding protein family, which was highly induced by both injury and microbial challenges. The possible role of juvenile hormone in innate immunity is discussed. © 2009 Wiley Periodicals, Inc. [source]

18F-fluorodeoxyglucose positron emission tomography/computed tomography in the evaluation of early response in a primary hepatic lymphoma

BRITISH JOURNAL OF HAEMATOLOGY, Issue 6 2006
Amalia De Renzo
No abstract is available for this article. [source]