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Relevant Changes (relevant + change)
Selected AbstractsEMPIRICAL COMPARISON OF G MATRIX TEST STATISTICS: FINDING BIOLOGICALLY RELEVANT CHANGEEVOLUTION, Issue 10 2009Brittny Calsbeek A central assumption of quantitative genetic theory is that the breeder's equation (R=GP,1S) accurately predicts the evolutionary response to selection. Recent studies highlight the fact that the additive genetic variance,covariance matrix (G) may change over time, rendering the breeder's equation incapable of predicting evolutionary change over more than a few generations. Although some consensus on whether G changes over time has been reached, multiple, often-incompatible methods for comparing G matrices are currently used. A major challenge of G matrix comparison is determining the biological relevance of observed change. Here, we develop a "selection skewers"G matrix comparison statistic that uses the breeder's equation to compare the response to selection given two G matrices while holding selection intensity constant. We present a bootstrap algorithm that determines the significance of G matrix differences using the selection skewers method, random skewers, Mantel's and Bartlett's tests, and eigenanalysis. We then compare these methods by applying the bootstrap to a dataset of laboratory populations of Tribolium castaneum. We find that the results of matrix comparison statistics are inconsistent based on differing a priori goals of each test, and that the selection skewers method is useful for identifying biologically relevant G matrix differences. [source] Differential protein expression on the cell surface of colorectal cancer cells associated to tumor metastasisPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 5 2010Jose Luis Luque-García Abstract Progression to metastasis is the critical point in colorectal cancer (CRC) survival. However, the proteome associated to CRC metastasis is very poorly understood at the moment. In this study, we used stable isotope labeling by amino acids in cell culture to compare two CRC cell lines: KM12C and KM12SM, representing poorly versus highly metastatic potential, to find and quantify the differences in protein expression, mostly at the cell surface level. After biotinylation followed by affinity purification, membrane proteins were separated by SDS-PAGE and analyzed using nanoflow LC-ESI-LTQ. A total of 291 membrane and membrane-associated proteins were identified with a p value<0.01, from which 60 proteins were found to be differentially expressed by more than 1.5-fold. We identified a number of cell signaling, CDs, integrins and other cell adhesion molecules (cadherin 17, junction plakoglobin (JUP)) among the most deregulated proteins. They were validated by Western blot, confocal microscopy and flow cytometry analysis. Immunohistochemical analysis of paired tumoral samples confirmed that these differentially expressed proteins were also altered in human tumoral tissues. A good correlation with a major abundance in late tumor stages was observed for JUP and 17-,-hydroxysteroid dehydrogenase type 8 (HSD17B8). Moreover, the combined increase in JUP, occludin and F11 receptor expression together with cadherin 17 expression could suggest a reversion to a more epithelial phenotype in highly metastatic cells. Relevant changes were observed also at the metabolic level in the pentose phosphate pathway and several amino acid transporters. In summary, the identified proteins provide us with a better understanding of the events involved in liver colonization and CRC metastasis. [source] Changes in Quality-of-Life After Pacemaker Implantation: Responsiveness of the Aquarel QuestionnairePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2001MONIQUE A. M. STOFMEEL STOFMEEL, M.A.M., et al.: Changes in Quality-of-Life After Pacemaker Implantation: Responsiveness of the Aquarel Questionnaire. Before being introduced for widespread use, health status instruments should be evaluated for reliability, validity, and responsiveness to relevant clinical changes. In a previous study the validity and reliability of Aquarel, a disease-specific quality-of-life (QOL) questionnaire for pacemaker patients, were tested and found satisfactory. The purpose of this study was to assess the sensitivity to change in health of Aquarel. A cohort of 51 patients was assessed at baseline and at 4,6 weeks after pacemaker implantation. We compared the sensitivity to change over time on the Aquarel scores to the scores on the SF-36 using various techniques (t -test value, effect size, standard error of measurement). Using the 1-standard error of measurement (SEM) criterion for clinically relevant change, Aquarel seemed to provide better classification of patients compared to the SF-36 alone. This study supports the value of Aquarel as a disease-specific measure of QOL in pacemaker patients. [source] Low Systemic Absorption and Good Tolerability of Pimecrolimus, Administered as 1% Cream (Elidel®) in Infants with Atopic Dermatitis , A Multicenter, 3-Week, Open-Label StudyPEDIATRIC DERMATOLOGY, Issue 5 2005Doris Staab M.D. Here we evaluate pimecrolimus blood concentrations and tolerability to pimecrolimus cream 1% in 22 infants below 2 years of age with atopic dermatitis (10,92% body surface area affected at baseline). Efficacy was assessed as a secondary objective. Pimecrolimus cream 1% was applied twice daily for 3 weeks. Blood concentrations were low, typically (96% of total 100 concentrations measured) below 2 ng/mL, the majority (71%) remaining below 0.5 ng/mL. The highest concentration observed was 2.26 ng/mL. At steady state, there was no indication of accumulation. Pimecrolimus was well tolerated locally and systemically, with no serious adverse events recorded. Most adverse events recorded (35 in 17/22 patients) were typical of the young pediatric population studied, of mild to moderate severity, and not considered to be study-medication related, with the exception of four local adverse effects limited to the site of cream application. No clinically relevant change was observed in physical examination, vital signs, or laboratory safety parameters. A rapid onset of therapeutic effect was observed within the first four days of treatment. Pimecrolimus cream 1% is well tolerated in infants 3 to 23 months of age treated for 3 weeks, and results in minimal systemic exposure. [source] Determination of the minimal clinically important difference in rheumatoid arthritis joint damage of the Sharp/van der Heijde and Larsen/Scott scoring methods by clinical experts and comparison with the smallest detectable differenceARTHRITIS & RHEUMATISM, Issue 4 2002Karin Bruynesteyn Objective To assess the minimal clinically important difference (MCID) in joint damage on hand and foot radiographs of patients with early rheumatoid arthritis (RA) as assessed with the Sharp/van der Heijde and Larsen/Scott methods, and to study how the smallest detectable difference (SDD) relates to the MCID for each method. Methods The judgments of an international panel of experts on the clinical relevance of progression of joint damage as seen on sets of radiographs obtained at 1-year intervals in 4 clinical settings (early versus late RA and mild versus high disease activity) were used as the external criterion, which was compared with the progression scores as determined by the 2 scoring methods. Progression scores with the highest combined sensitivity and specificity for detecting clinically relevant progression represented the MCID. Subsequently, the sensitivity and specificity of the scoring methods were determined when using the SDD as the threshold for relevant progression, and these were compared with the sensitivity and specificity of the MCID. Results The panel judged changes in joint damage around the level of the SDD (5.0) of the Sharp/van der Heijde method as minimal clinically important, resulting in satisfactory sensitivity (mean 79%) and specificity (mean 84%) for detecting clinically important progression in the 4 clinical settings when using the SDD as the threshold value. The MCID (mean 2.3) of the Larsen/Scott method was much smaller than its SDD (5.8), and the sensitivity for detecting clinically important progression by applying the SDD as threshold was consequently low (mean 51%), accompanied by high specificity (mean 99%). Conclusion This study suggests that the SDD of the Sharp/van der Heijde method can be used as the MCID, i.e., as the threshold level for individual response criteria. The SDD of the Larsen/Scott method, however, turned out to be too insensitive to use as the threshold for individual clinically relevant change. [source] Are conventional pressure-flow measurements dependent upon filled volume?BJU INTERNATIONAL, Issue 3 2005Kanagasabai Sahadevan OBJECTIVE To determine, in a prospective study, whether detrusor pressure (pdet.Qmax) and maximum urinary flow rate (Qmax) measurements obtained after filling to maximum cystometric capacity (MCC) differ from those obtained with filling restricted to average voided volume (Vvoid), as standard protocols for pressure flow studies (PFS) mandate bladder filling until the subject has a strong desire to void, which aids standardization but further divorces the test from real-life experience. PATIENTS AND METHODS After calculating the appropriate sample size, 84 patients attending for PFS with an adequately completed 3-day frequency-volume chart were recruited. Each underwent two consecutive PFS with filling to MCC and average Vvoid in a random order, and measurements of pdet.Qmax and Qmax were compared. For men, the agreement for a diagnosis of obstruction between the tests was also assessed. RESULTS Complete data were obtained from 76 (90%) of the patients, with a mean (range) age of 64 (20,94) years. The mean (sd) difference between MCC and average Vvoid was 134 (113) mL (P < 0.01). There were no significant differences between estimates of Qmax, at ,,0.1 (3) mL/s (P = 0.75), and of pdet.Qmax, at ,,1 (13) cmH2O (P = 0.91), obtained within each patient. For men there was 91% agreement (32 of 35) in the classification of obstruction. CONCLUSIONS Restriction of filling to the average Vvoid during PFS allows a closer approximation to normal voiding and results in no clinically relevant change to the value of standard pressure-flow measurements or alters individual classification of obstruction. [source] Reproducibility evaluation of gross and net walking efficiency in children with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2007Merel-Anne Brehm MSc In evaluating energy cost (EC) of walking, referred to as walking efficiency, the use of net measurement protocols (i.e. net=gross-resting) has recently been recommended. However, nothing is known about the comparative reproducibility of net protocols and the commonly used gross protocols. Ten minutes of resting and 5 minutes of walking at a self-selected speed were used to determine gross and net EC in 13 children with spastic cerebral palsy (CP; seven males, six females; mean age 8y 7mo [SD 3y 4mo], range 4y 1mo,13y) and in 10 children (three males, seven females) with typical development. In the former, their Gross Motor Function Classification System levels ranged from Level I to Level III; and seven had hemiplegia and six diplegia. There were four repeated sessions on different days, with periods of 1 week between sessions. Reproducibility was assessed for speed, and gross and net EC, by using the standard error of measurement. The results of this preliminary study showed that EC measurements were more variable for children with CP than for children with typical development. Furthermore, in both groups there was considerably more variability in the net measurements than in the gross measurements. We conclude that, on the basis of the methodology used, the use of gross EC, rather than net EC, seems a more sensitive measure of walking efficiency to detect clinically relevant changes in an individual child with CP. [source] Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a randomized controlled trialEPILEPSIA, Issue 3 2009Péter Halász Summary Purpose:, To evaluate the efficacy and safety of lacosamide (200 and 400 mg/day) when added to one to three concomitant antiepileptic drugs (AEDs) in patients with uncontrolled partial-onset seizures. Methods:, This multicenter, double-blind, placebo-controlled trial randomized patients (age 16,70 years) with partial-onset seizures with or without secondary generalization to placebo, lacosamide 200, or lacosamide 400 mg/day. The trial consisted of an 8-week baseline, a 4-week titration, and a 12-week maintenance period. Results:, Four hundred eighty-five patients were randomized and received trial medication. Among these, 87% were taking two or more concomitant AEDs. Median percent reduction in seizure frequency per 28 days from baseline to maintenance period (intent-to-treat, ITT) was 20.5% for placebo, 35.3% for lacosamide 200 mg/day (p = 0.02), and 36.4% for 400 mg/day (p = 0.03). In the per protocol population, the reductions were 35.3% for lacosamide 200 mg/day (p = 0.04) and 44.9% for 400 mg/day (p = 0.01) compared to placebo (25.4%). The 50% responder rate for lacosamide 400 mg/day (40.5%) was significant (p = 0.01) over placebo (25.8%), but was not for 200 mg/day (35.0%). In the per protocol population, the 50% responder rate for lacosamide 400 mg/day (46.3%) was significant (p < 0.01) compared with the placebo responder rate (27.5%). Dose-related adverse events (AEs) included dizziness, nausea, and vomiting. Clinically relevant changes in the mean plasma concentrations of commonly used AEDs were not observed. Discussion:, Results of this trial demonstrated the efficacy and tolerability of adjunctive lacosamide 200 and 400 mg/day and support that lacosamide may be an advantageous option for the treatment of partial-onset seizures in patients with epilepsy. [source] Creatine has no beneficial effect on skeletal muscle energy metabolism in patients with single mitochondrial DNA deletions: a placebo-controlled, double-blind 31P-MRS crossover studyEUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2005C. Kornblum The purpose of our randomized, double-blind, placebo-controlled crossover study in 15 patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns,Sayre syndrome (KSS) because of single large-scale mitochondrial (mt) DNA deletions was to determine whether oral creatine (Cr) monohydrate can improve skeletal muscle energy metabolism in vivo. Each treatment phase with Cr in a dosage of 150 mg/kg body weight/day or placebo lasted 6 weeks. The effect of Cr was estimated by phosphorus-31 magnetic resonance spectroscopy (31P-MRS), clinical and laboratory tests. 31P-MRS analysis prior to treatment showed clear evidence of severe mitochondrial dysfunction. However, there were no relevant changes in 31P-MRS parameters under Cr. In particular, phosphocreatine (PCr)/ATP at rest did not increase, and there was no facilitation of post-exercise PCr recovery. Clinical scores and laboratory tests did not alter significantly under Cr, which was tolerated without major side-effects in all patients. Cr supplementation did not improve skeletal muscle oxidative phosphorylation in our series of patients. However, one explanation for our negative findings may be the short study duration or the limited number of patients included. [source] Abnormal associative encoding in orbitofrontal neurons in cocaine-experienced rats during decision-makingEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 9 2006Thomas A. Stalnaker Abstract Recent evidence has linked exposure to addictive drugs to an inability to employ information about adverse consequences, or outcomes, to control behavior. For instance, addicts and drug-experienced animals fail to adapt their behavior to avoid adverse outcomes in gambling and reversal tasks or after changes in the value of expected rewards. These deficits are similar to those caused by damage to the orbitofrontal cortex, suggesting that addictive drugs may cause long-lasting changes in the representation of outcome associations in a circuit that includes the orbitofrontal cortex. Here we test this hypothesis by recording from orbitofrontal neurons in a discrimination task in rats previously exposed to cocaine (30 mg/kg i.p. for 14 days). We found that orbitofrontal neurons recorded in cocaine-experienced rats failed to signal the adverse outcome at the time a decision was made in the task. The loss of this signal was associated with abnormal changes in response latencies on aversive trials. Furthermore, upon reversal of the cue,outcome associations, orbitofrontal neurons in cocaine-treated rats with enduring reversal impairments failed to reverse their cue-selectivity, while orbitofrontal neurons in cocaine-treated rats with normal performance showed an increase in the plasticity of cue-selective firing after reversal. These results provide direct neurophysiological evidence that exposure to cocaine can cause behaviorally relevant changes in the processing of associative information in a circuit that includes the orbitofrontal cortex. [source] Time-resolved fluorescence analysis of the recombinant photosystem II antenna complex CP29FEBS JOURNAL, Issue 2 2001Effects of zeaxanthin, phosphorylation Nonradiative dissipation of excitation energy is the major photoprotective mechanism in plants. The formation of zeaxanthin in the antenna of photosystem II has been shown to correlate with the onset of nonphotochemical quenching in vivo. We have used recombinant CP29 protein, over-expressed in Escherichia coli and refolded in vitro with purified pigments, to obtain a protein indistinguishable from the native complex extracted from thylakoids, binding either violaxanthin or zeaxanthin together with lutein. These recombinant proteins and the native CP29 were used to measure steady-state chlorophyll fluorescence emission and fluorescence decay kinetics. We found that the presence of zeaxanthin bound to CP29 induces a ,,35% decrease in fluorescence yield with respect to the control proteins (the native and zeaxanthin-free reconstituted proteins). Fluorescence decay kinetics showed that four components are always present but lifetimes (,) as well as relative fluorescence quantum yields (rfqy) of the two long-lived components (,3 and ,4) are modified by the presence of zeaxanthin. The most relevant changes are observed in the rfqy of ,3 and in the average lifetime (, 2.4 ns with zeaxanthin and 3.2,3.4 ns in the control proteins). When studied in vitro, no significant effect of acidic pH (5.2,5.3) is observed on chlorophyll a fluorescence yield or kinetics. The data presented show that recombinant CP29 is able to bind zeaxanthin and this protein-bound zeaxanthin induces a significant quenching effect. [source] Canopy recovery after drought dieback in holm-oak Mediterranean forests of Catalonia (NE Spain)GLOBAL CHANGE BIOLOGY, Issue 12 2004Francisco Lloret Abstract Climate change is likely to produce more frequent and longer droughts in the Mediterranean region, like that of 1994, which produced important changes in the Quercus ilex forests, with up to 76% of the trees showing complete canopy dieback. At the landscape level, a mosaic of responses to the drought was observed, linked to the distribution of lithological substrates. Damage to the dominant tree species (Q. ilex) and the most common understorey shrub (Erica arborea) was more noticeable on the compact substrates (breccia) than on the fissured ones (schist). This result was consistent with observations documenting deeper root penetration in schist than in breccia materials, allowing the plants growing on fissured substrates to use water from deeper soil levels. Smaller plants were more vulnerable to drought than larger plants in the trees, but not in the shrubs. Overall, Q. ilex was more affected than E. arborea. The resilience of the system was evaluated from the canopy recovery 1 year after the episode. Stump and crown resprouting was fairly extensive, but the damage pattern in relation to substrate, plant size, and species remained similar. The effect of recurrent drought episodes was studied on vegetation patches of Q. ilex located on mountain slopes and surrounded by bare rock. We observed that plants that resprouted weakly after a previous drought in 1985 were more likely to die or to produce poor regeneration in 1995 than plants that had resprouted vigorously. Vegetation patches located on the lower part of the slope were also less damaged than patches situated uphill. The study provides evidence of relevant changes in forest canopy as a consequence of extreme climate events. The distribution of this effect across the landscape is mediated by lithological substrate, causing patchy patterns. The results also support the hypothesis that recurrent droughts can produce a progressive loss of resilience, by depleting the ability of surviving plants to regenerate. [source] Effect of Antipsychotic Withdrawal on Behavior and Sleep/Wake Activity in Nursing Home Residents with Dementia: A Randomized, Placebo-Controlled, Double-Blinded Study The Bergen District Nursing Home StudyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2004Sabine Ruths MD Objectives: To explore the effect on sleep/wake activity and on behavioral and psychological symptoms of the withdrawal of antipsychotic medications from nursing home (NH) patients with dementia. Design: Randomized, placebo-controlled, double-blind trial. Setting: NHs in Bergen, Norway. Participants: Thirty patients (mean age 83.5) taking haloperidol, risperidone, or olanzapine for nonpsychotic symptoms. Intervention: Study participants were randomly assigned to withdrawal (intervention group) or continued treatment with antipsychotic medications (reference group) for 4 consecutive weeks. Measurements: Behavioral rating using the Neuropsychiatric Inventory Questionnaire (NPI-Q) and actigraphy. Results: After antipsychotic withdrawal, behavioral scores remained stable or improved in 11 of 15 patients, whereas four had worsening scores. Actigraphy revealed decreased sleep efficiency after drug discontinuation and increased 24-hour and night activity in both groups. Actigraphy records of nighttime and daytime activity indicated sleep problems and restlessness, in terms of the NPI-Q. One patient was restarted on antipsychotics. Conclusion: Antipsychotic drug withdrawal affected activity and sleep efficiency over the short term. Increases in total activity and impaired sleep quality after drug discontinuation should be monitored, because the long-term effect of these changes is not known. The NPI-Q and actigraphy are feasible tools that disclose relevant changes occurring during antipsychotic withdrawal in NH patients with dementia. Their use in clinical practice should be substantiated by larger studies. [source] Thermal analysis of merino wool fibres without internal lipidsJOURNAL OF APPLIED POLYMER SCIENCE, Issue 1 2007M. Martí Abstract Merino wool is made up of cuticle and cortical cells held together by the cell membrane complex (CMC), which contains a small amount of internal lipids (IWL) (1.5% by mass). IWL have been extracted from wool on account of their considerable dermatological interest owing to their proportion of ceramides. IWL have been extracted by different methods and solvents, methanol and acetone at laboratory and pilot plant levels. Thermal analysis of these extracted wool fibers is presented using thermogravimetry (TG) and differential scanning calorimetry (DSC). TG provides a measurement of the weight loss of the sample as a function of time and temperature. DSC gives information about possible structure modification of extracted wool fibers. Thermoporometry was applied to evaluate the pore size distribution of extracted wool fibers. The results showed that the extraction process increased the pore size distribution and the cumulated pore volume, which is consistent with some changes in the extracted wool CMC. Extracted fiber becomes more hydrophilic and absorbs a large amount of water. We can conclude that the lipid extraction of wool produced no relevant changes in the crystalline fraction when extracted with acetone. However, part of the amorphous keratin material was extracted with methanol, the rest of the crystalline material becoming more stable. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci 104: 545,551, 2007 [source] Mandibular overdentures supported by two Brĺnemark, IMZ or ITI implants: a ten-year prospective randomized studyJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 9 2009Henny J. A. Meijer Abstract Objectives: The aim of this prospective comparative study was to evaluate the survival rate, condition of peri-implant tissues, patient satisfaction and surgical and prosthetic aftercare of the IMZ-implant system (two-stage cylinder type), the Brĺnemark-implant system (two-stage screw type) and the ITI-implant system (one-stage screw type) supporting a mandibular overdenture during a 10-year follow-up period. Materials and Methods: Three groups of 30 edentulous patients were treated with two endosseous implants in the interforaminal region of the mandible. Clinical and radiographic parameters were evaluated immediately after completion of the prosthetic treatment and after 1, 5 and 10 years of functional loading. Prosthetic and surgical aftercare was scored during the evaluation period, as well as patient satisfaction. Results: The 10-year survival rate was 93% for the IMZ group, 98% for the Brĺnemark group and 100% for the ITI group (IMZ Age-Related Changes in Drinking Patterns From Mid- to Older Age: Results From the Wisconsin Longitudinal StudyALCOHOLISM, Issue 7 2010Rachel C. Molander Background:, Drinking has generally been shown to decline with age in older adults. However, results vary depending on the measure of alcohol consumption used and the study population. The goals of this study were to (i) describe changes in drinking in a current cohort of older adults using a variety of measures of drinking and (ii) examine a number of different possible predictors of change. Methods:, This is a longitudinal study of a community-based sample surveyed at 2 time points, ages 53 and 64 years. We estimated a series of logistic regressions to predict change and stability in drinking categories of nondrinking, moderate drinking, and heavy drinking. Linear regressions were used to predict change in past-month drinking days, past-month average drinks per drinking day, and past-month total drinks. Results:, From age 53 to 64, average drinks per drinking day and heavy drinking decreased. Frequency of drinking increased for men and women, and total drinks per month increased for men. The most consistent predictors of drinking changes were gender, health, and education. Other factors predicted drinking change but were not consistent across drinking measures including: adolescent IQ, income, lifetime history of alcohol-related problems, religious service attendance, depression, debt, and changes in employment. Conclusions:, Heavy drinking decreases with age, but we may see more frequent moderate drinking with current and upcoming cohorts of older adults. Components of quantity and frequency of drinking change differently. Composite measures of total alcohol consumption may not be adequate for describing relevant changes in drinking over time. A number of factors predicted patterns of change in drinking and warrant further exploration. [source] Changes in inhibitory activity and secondary conformation of soybean trypsin inhibitors induced by tea polyphenol complexationJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 14 2009Huihua Huang Abstract BACKGROUND: Tea polyphenol (TP) is a new food additive for antioxidant application, while soybean is an important resource for food and feed processing. It is therefore of rational and practical significance to investigate the influence of TP on soybean trypsin inhibitors (TIs). The aim of this study was to determine the effects of TP on the inhibitory activity of Kunitz (KTI) and Bowman,Birk (BBTI) TIs and to reveal the relationship between the inhibitory activity and conformation of KTI and BBTI by measurement of circular dichroism (CD) spectra. RESULTS: KTI and BBTI were found to be partially deactivated by TP. BBTI exhibited stronger resistance than KTI to TP deactivation. The unchanged KM value of trypsin for benzoyl- DL -arginine- p -nitroanilide hydrolysis indicated that KTI and BBTI inhibited trypsin in a non-competitive pattern when complexed with TP. As the TP/TI ratio was increased and the inhibitory activity of KTI and BBTI decreased, the conformation of KTI and BBTI showed relevant changes and the major CD negative bands shifted progressively towards the near-UV region. CONCLUSION: These results show the deactivation effects of TP on KTI and BBTI and reveal preliminarily the relationship between the inhibitory activity and secondary structure of KTI and BBTI. Copyright © 2009 Society of Chemical Industry [source] CSRP2, TIMP-1, and SM22, promoter fragments direct hepatic stellate cell-specific transgene expression in vitro, but not in vivoLIVER INTERNATIONAL, Issue 1 2004Jens Herrmann Abstract: Background/Aims: The activation of hepatic stellate cells (HSC) and their transdifferentiation into myofibroblasts (MFB) is the key step for development of liver fibrosis. Over the past several years, significant progress has been made in the understanding of the critical pathways involved incells undergoing activation. Cellular activation in the course of transdifferentiation involves, among other biochemical modifications, functionally relevant changes in the control of gene expression. These include the up-regulation of transcription factors, different extracellular matrix proteins, cell adhesion molecules, smooth muscle specific genes, and proteins involved in matrix remodelling, or cytoskeletal organization. The corresponding regulatory elements of these genes have afforded us the opportunity to express transgenes with antifibrotic potential in a cell type- and/or transdifferentiation-dependent manner. Methods: In the present study, we have tested several promoters for their ability to mediate cell-specific expression, including those for CSRP2, SM22,, and TIMP-1 (CSRP2, gene encoding the LIM domain protein CRP2; SM22,, smooth muscle-specific gene encoding a 22-kDa protein; TIMP-1, gene encoding the tissue inhibitor of metalloproteinases-1), which in liver are specifically expressed in HSC or become strongly activated during the acute remodelling into MFB. We constructed adenoviral reporter vectors in which relevant portions of the promoters were fused to the green fluorescent protein. Results and Conclusion: Our experiments demonstrate that each of these promoters is sufficient to achieve strong or partially selective expression in vitro but none is able to direct a specific or inducible expression of transgenes in HSC/MFB in vivo. [source] Comparison between impairment and disability scales in immune-mediated polyneuropathiesMUSCLE AND NERVE, Issue 1 2003Ingemar S.J. Merkies MD Abstract The ability of a scale to detect clinical relevant changes over time, i.e., its "responsiveness," may help clinicians to choose among valid and reliable measures. Therefore, we investigated the responsiveness' rank ordering (best to worse) of six selected valid and reliable scales, namely the Medical Research Council (MRC)-sumscore, sensory-sumscore, grip-strength (Vigorimeter), nine-hole peg, ten-meters walking, and a disability-sumscore, in immune-mediated polyneuropathies. Patients with newly diagnosed Guillain,Barré syndrome (n = 7) or chronic inflammatory demyelinating polyneuropathy (n = 13) were examined over 52 weeks. Responsiveness of each scale was measured using different methods (effect-size, standardized response mean score, Wilcoxon matched-pairs signed-rank, and a newly devised Schmitz's distribution-free responsiveness score), and the obtained scores in each method were plotted against the follow-up period, thus allowing area-under-the-curve calculations (higher area-under-the-curve indicating better responsiveness). Also, longitudinal correlations were performed between the scales' values and patients' own clinical judgments (deteriorated, unchanged, improved) (higher correlation = better responsiveness). A consistent rank ordering was observed in each technique with the disability-sumscore, MRC-sumscore, and Vigorimeter being among the best responsive scales. Hence, the primary use of these measures is suggested in studies of immune-mediated polyneuropathies. Muscle Nerve 28: 93,100, 2003 [source] Quality of life and use of red cell transfusion in patients with myelodysplastic syndromes.AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009A systematic review The main treatment for many patients with Myelodysplastic Syndromes (MDS) remains red cell transfusion to attenuate the symptoms of chronic anemia. Fatigue can reduce a patient's health related quality of life (HRQoL), but there is little understanding of the optimal use of transfusions to improve this. A systematic review was performed to identify and appraise publications reporting the use of HRQoL instruments in patients with MDS. A total of 17 separate studies were identified that used 14 HRQoL instruments, but only one MDS disease specific HRQoL instrument (QOL-E) was reported. Two well established HRQoL instruments were most often used in MDS research (variants of the Functional Assessment of Cancer Therapy (FACT) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30)). Several common problems were identified in the published literature including a lack of power calculations to detect clinically relevant changes, small sample sizes and significant attrition rates for completion of HRQoL assessments, all of which limit the strength of any conclusions. There is no consensus on the optimal transfusion regimen to improve HRQoL in transfusion-dependent MDS. Future research into HRQoL within MDS is a pressing requirement. Studies should focus on the domains that are of most clinical importance to the patient as well as traditional quantitative changes of hemoglobin concentration. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source] Impact of Annealing on the Conductivity of Amorphous Carbon Films Incorporating Copper and Gold Nanoparticles Deposited by Pulsed Dual Cathodic ArcPLASMA PROCESSES AND POLYMERS, Issue S1 2009Jose Luis Endrino Abstract The influence of annealing in argon at 300,°C on the conductivity, phase stability and electronic structure of hydrogen-free amorphous carbon (a-C) films containing copper (a-C:Cu) and gold (a-C:Au) nanoclusters was investigated. The motivation of this work is twofold: (1) to study the thermal stability of a-C:Cu and a-C:Au films and (2) to point out the relevance of X-ray absorption near edge structure (XANES) technique to study the structural evolution of metal-doped a-C nanocomposites. The films were produced at room temperature using a selective-bias pulsed dual-cathode arc deposition technique. Compositional analysis was performed with secondary neutral mass spectroscopy whereas grazing incidence X-ray diffraction (GIXRD) was used to monitor phase transformation and identify the dispersion or agglomeration of the crystallites within the carbon matrix. XANES spectra at the C-K was used to investigate the effect of annealing in argon on the electronic structure of the a-C matrix, while Cu K and Au L-edges were investigated on a-C:Cu and a-C:Au samples, respectively, to study the nanocluster evolution. XANES showed that the a-C host matrix increased its graphitic character and that stress was relieved upon annealing. No relevant changes were observed in the Au arrangements in a-C:Au films. In the case of the a-C:Cu samples, the Cu-K XANES spectra indicated the formation of Cu2O crystals which correlated well with GIXRD spectra and the decrease in conductivity. [source] Early events of Bacillus anthracis germination identified by time-course quantitative proteomicsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 19 2006Pratik Jagtap Abstract Germination of Bacillus anthracis spores involves rehydration of the spore interior and rapid degradation of several of the protective layers, including the spore coat. Here, we examine the temporal changes that occur during B. anthracis spore germination using an isobaric tagging system. Over the course of 17,min from the onset of germination, the levels of at least 19 spore proteins significantly decrease. Included are acid-soluble proteins, several known and predicted coat proteins, and proteins of unknown function. Over half of these proteins are small (less than 100 amino acids) and would have been undetectable by conventional gel-based analysis. We also identified 20 proteins, whose levels modestly increased at the later time points when metabolism has likely resumed. Taken together, our data show that isobaric labeling of complex mixtures is particularly effective for temporal studies. Furthermore, we describe a rigorous statistical approach to define relevant changes that takes into account the nature of data obtained from multidimensional protein identification technology coupled with the use of isobaric tags. This study provides an expanded list of the proteins that may be involved in germination of the B. anthracis spore and their relative levels during germination. [source] The effect of age, gender, and body mass index on the pharmacokinetics and pharmacodynamics of vildagliptin in healthy volunteersBRITISH JOURNAL OF CLINICAL PHARMACOLOGY, Issue 3 2008Yan-Ling He What is already known about this subject ,,Vildagliptin is a new, potent, and selective inhibitor of DPP-4. ,,The efficacy and safety of vildagliptin in type 2 diabetes has been intensively studied in diverse subject populations. ,,There has been little information published about the pharmacokinetics and pharmacodynamics of vildagliptin. What this study adds ,,No clinically relevant changes in pharmacokinetics or pharmacodynamics were observed between young and elderly, male and female, or high body mass index (BMI) and low BMI subjects. ,,The results suggest that no dose modification is necessary for vildagliptin based on the age, gender, or BMI of a subject. Aims To evaluate the effect of age, gender, and body mass index (BMI) on the pharmacokinetics and pharmacodynamics of vildagliptin. Methods Forty healthy subjects received a single oral dose of 100 mg vildagliptin to assess the effects of age, gender, and BMI on the pharmacokinetics and pharmacodynamics, reflected by the time course of inhibition of DPP-4 activity, of vildagliptin. Results Peak concentration and exposure (AUC(0,,)) of vildagliptin were 17% (90% CI 2, 35%) and 31% (90% CI 18, 45%) higher in elderly vs. young subjects. Renal clearance was reduced by 32% (90% CI 17, 45%) in elderly subjects. The pharmacokinetics of vildagliptin were not significantly influenced by gender or BMI. Inhibition of DPP-4 activity was similar regardless of age, gender, or BMI. Conclusions The pharmacokinetics of a single oral 100 mg dose of vildagliptin were not affected by gender and BMI. Exposure to vildagliptin was higher in elderly patients, but this was not associated with any difference in the effect of DPP-4 inhibition. Based on these results, no vildagliptin dose adjustment is necessary for age, gender, or BMI. [source]
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