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Selected AbstractsElectrophysiologicai Characteristics of the Atrium in Sinus Node Dysfunction With and Without Postpacing Atrial FihriliationPACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 3 2000ANTONIO DE SISTI DE SISTI, A., ET AL.: Electrophysiologicai Characteristics of the Atrium in Sinus Node Dysfunction With and Without Postpacing Atrial Fibrillation . In patients with sinus node dysfunction (SND) with or without associated paroxysmal atrial fibrillation (AF), the effectiveness of atrial pacing in reducing the incidence of AF is not definitive. In addition, despite several studies involving large populations of implanted patients, little attention has been paid to the electrophysioiogicai (EP) atrial substrate and the effect of permanent atrial pacing. The aim of this study is to correlate EP data and the risk of AF after DDD device implantation. We reviewed FP data of 38 consecutive patients with SND. mean age 70 ± 8 years, who were investigated free of antiarrhythmic treatment, for the evaluation of the atrial substrate. We also considered as control group 25 subjects, mean age 63 ± 14 years, referred to our EP laboratory for unexplained syncope or various atrioventricular disturbances. Following pharmacological washout and at a drive cycle length of 600 ms. effective and functional refractory periods (ERP, FRP), Sl-Al and S2-A2 latency, Al and A2 conduction duration, and latent vulnerability index (EHP/A2) were measured. AF induction was tested with up to three extrastimuli at paced cycle lengths of 600 and 400 ms in 20 patients. Induction of sustained AF (> 30 seconds) was considered as the endpoint. P wave duration on the surface ECG in lead II/Vl was also measured. DDD pacing mode was chosen in all patients with the minimal atrial rate programmed between 60 and 75 beats/min (mean 64 ± 4 beats/min). After implantation, the patients were followed-up for 29 ± 17 months and clinically documented occurrence of AF was determined. When comparing patients with SND and subjects of the control group, we did not find any significant statistical differences in terms of ERP (237 ± 33 vs 250 ± 29 ms), FRP (276 ± 30 vs 280 ± 32 ms) and Sl-Al (39 ± 16 vs 33 ± 11 ms) and S2-A2 latency (69 ± 24 vs 63 ± 25 ms). In contrast, we observed significant differences regarding Al (55 ± 19 vs 39 ± 13 ms; P < 0.001), A2 (95 ± 34 vs 57 ± 18 ms; P < 0.001) and P wave duration (104 ± 18 vs 94 ± 15 ms; P < 0.05), and ERP/A2 (2.8 ± 1.2 vs 4.8 ± 1.6; P < 0.001). When comparing patients with (n = 11) or without (n =27) postpacing AF occurrence, we did not find any difference with reference to ERP, FRP. Sl-Al, S2-A2, Al duration, or follow-up duration. In patients with postpacing AF occurrence, A2 was longer (116 ± 41 vs 87 ± 27 ms; P < 0.01), FRP/A2 lower (2.1 ± 0.4 vs 3.1 ± 1.4; P < 0.05), P wave more prolonged (116 ± 22 vs 99 ± 14 ms; P < 0.01), and preexisting AF history predominant (6/11 vs 5/27 patients; P < 0.05). No difference was observed between patients with (n = 8) and without (n = 12) AF induction during the EP study. In patients with SND, the atrial refractoriness appears normal and the most important abnormality concerns conduction slowing disturbances. Persistence of AF despite pacing stresses the importance of mechanisms responsible for AF not entirely brady-dependent. In this setting, more prolonged atrial conduction disturbances, responsible for a low vulnerability index, and a preexisting history of AF enable us to identify a high risk patient group for AF in the follow-up. sinus node dysfunction, atrial fibrillation, electrophysiologicai study, atrial pacing [source] Hydrodynamics and mass transfer coefficient in activated sludge aerated stirred column reactor: experimental analysis and modelingBIOTECHNOLOGY & BIOENGINEERING, Issue 4 2005Bo Jin Abstract The aerated stirred reactor (ASR) has been widely used in biochemical and wastewater treatment processes. The information describing how the activated sludge properties and operation conditions affect the hydrodynamics and mass transfer coefficient is missing in the literature. The aim of this study was to investigate the influence of flow regime, superficial gas velocity (UG), power consumption unit (P/VL), sludge loading, and apparent viscosity (,ap) of activated sludge fluid on the mixing time (tm), gas hold-up (,), and volumetric mass transfer coefficient (kLa) in an activated sludge aerated stirred column reactor (ASCR). The activated sludge fluid performed a non-Newtonian rheological behavior. The sludge loading significantly affected the fluid hydrodynamics and mass transfer. With an increase in the UG and P/VL, the , and kLa increased, and the tm, decreased. The ,, kLa, and tm, were influenced dramatically as the flow regime changed from homogeneous to heterogeneous patterns. The proposed mathematical models predicted the experimental results well under experimental conditions, indicating that the UG, P/VL, and ,ap had significant impact on the tm, ,, and kLa. These models were able to give the tm, ,, and kLa values with an error around ±8%, and always less than ±10%. © 2005 Wiley Periodicals, Inc. [source] Close association of CD8+/CD38bright with HIV-1 replication and complex relationship with CD4+ T-cell count,CYTOMETRY, Issue 4 2009Edouard Tuaillon Abstract Background: Measuring lymphocyte activation provides information in addition to CD4+ T-cell count for immune monitoring of HIV-1 infected patients. CD38 is a well-established activation marker that is generally analyzed on the whole population of CD8+ T-cells. Focusing specifically on CD38 high expression (CD8+/CD38bright) may be an interesting surrogate gating strategy because CD38bright characterizes principally activated memory cells. Methods: CD8+/CD38bright was investigated in 1,353 HIV-1 infected patients over a one-year period to establish relevant cutoff values and clarify the relationships of this marker with HIV-1 RNA viral load (VL) and CD4+ T-cell count. Results: The CD8+/CD38bright (>8,500 CD38 binding site per cells) is well correlated with HIV-1 VL (r = 0.87, P < 0.001) in this longitudinal follow-up of nonimmunodepressed patients that initiated antiviral therapy (ART). In aviremic patients on ART, the marker was highly predictive of VL rebound (sensitivity 93%, specificity 64% for a VL level of detection >200 copies/ml). While the CD8+/CD38bright moderately correlated with CD4+ T-cell count independently of the VL (r = ,0.37, P < 0.001), it increased dramatically in aviremic patient groups that exhibited profound CD4+ T-cell depletion (median 39% for CD4+ T-cell counts <50/mm3). This result indicates that other additional immunological and/or viral factors than readily detectable HIV-1 replication appears to be involved in T-cell activation of immunodepressed individuals. Conclusions: CD8+/CD38bright is an effective marker for monitoring T-cell activation, which is a central factor of HIV-1 pathogenesis. This gating strategy requires only a single additional staining in conventional four color CD4 protocols. © 2008 Clinical Cytometry Society [source] In vivo muscle architecture and size of the rectus femoris and vastus lateralis in children and adolescents with cerebral palsyDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 10 2009NOELLE G MOREAU PHD PT Aim, Our aim was to investigate muscle architecture and size of the rectus femoris (RF) and vastus lateralis (VL) in children and adolescents with cerebral palsy (CP) compared with age-matched typically developing participants. Method, Muscle architecture and size were measured with ultrasound imaging in 18 participants with spastic CP (9 females, 9 males; age range 7.5,19y; mean age 12y [SD 3y 2mo]) within Gross Motor Function Classification System levels I (n=4), II (n=2), III (n=9), and IV (n=3) and 12 typically developing participants (10 females, 2 males; age range 7,20y; mean age 12y 4mo [SD 3y 11mo]). Exclusion criteria were orthopedic surgery or neurosurgery within 6 months before testing or botulinum toxin injections to the quadriceps within 3 months before testing. Results, RF cross-sectional area was significantly lower (48%), RF and VL muscle thickness 30% lower, RF fascicle length 27% lower, and VL fascicle angle 3° less in participants with CP compared to the typically developing participants (p<0.05). Intraclass correlation coefficients were ,0.93 (CP) and , 0.88 (typical development), indicating excellent reliability. Interpretation, These results provide the first evidence of altered muscle architecture and size of the RF and VL in CP, similar to patterns observed with disuse and aging. These alterations may play a significant role in the decreased capacity for force generation as well as decreased shortening velocity and range of motion over which the quadriceps can act. [source] Quantitation of reduced glutathione and cysteine in human immunodeficiency virus-infected patientsELECTROPHORESIS, Issue 10-11 2004Elena Sbrana Abstract Plasma viral load (VL) values and CD4+ cell count are employed clinically for initiation of therapy in the treatment of patients infected with human immunodeficiency virus (HIV), as previous clinical studies have shown a marked prevalence of acquired immunodeficiency sydrome (AIDS) development in seropositive individuals with VL values over 30,000 copies/mL. Many studies have shown that reduced glutathione (GSH) and cysteine (Cys) deficiency play an important role in the infection. We have developed capillary zone electrophoresis (CZE)-based assays and have used them to investigate the relationship between plasma and intracellular thiol levels and HIV-1 viremia in plasma. Blood samples from healthy volunteers and seropositive patients undergoing different antiretroviral regimes were analyzed in the study. The VL assay was based on CZE-UV detection of viral RNA at 260 nm. Determination of endogenous reduced Cys and GSH was achieved by CZE-UV detection of their mercurial complexes at 200 nm. We found that a decrease in GSH and Cys levels may be associated with disease progress. In fact, reduced GSH and Cys levels appear progressively reduced with increasing VL. [source] The role of interface framework residues in determining antibody VH/VL interaction strength and antigen-binding affinityFEBS JOURNAL, Issue 10 2006Kenji Masuda While many antibodies with strong antigen-binding affinity have stable variable regions with a strong antibody heavy chain variable region fragment (VH)/antibody light chain variable region fragment (VL) interaction, the anti-lysozyme IgG HyHEL-10 has a fairly strong affinity, yet a very weak VH/VL interaction strength, in the absence of antigen. To investigate the possible relationship between antigen-binding affinity and VH/VL interaction strength, a novel phage display system that can switch two display modes was employed. We focused on the two framework region 2 regions of the HyHEL-10 VH and VL, facing each other at the domain interface, and a combinatorial library was made in which each framework region 2 residue was mixed with that of D1.3, which has a far stronger VH/VL interaction. The phagemid library, encoding VH gene 7 and VL amber codon gene 9, was used to transform TG-1 (sup+), and the phages displaying functional variable regions were selected. The selected phages were then used to infect a nonsuppressing strain, and the culture supernatant containing VH -displaying phages and soluble VL fragment was used to evaluate the VH/VL interaction strength. The results clearly showed the existence of a key framework region 2 residue (H39) that strongly affects VH/VL interaction strength, and a marked positive correlation between the antigen-binding affinity and the VH/VL interaction, especially in the presence of a set of particular VL residues. The effect of the H39 mutation on the wild-type variable region was also confirmed by a SPR biosensor as a several-fold increase in antigen-binding affinity owing to an increased association rate, while a slight decrease was observed for the single-chain variable region. [source] Immune response to leishmania: paradox rather than paradigmFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2007Parul Tripathi Abstract The leishmaniases are a group of diseases caused by protozoan parasites of the genus Leishmania. Various Leishmania species can cause human infection, producing a spectrum of clinical manifestations. It is estimated that 350 million people are at risk, with a global yearly incidence of 1,1.5 million for cutaneous and 500 000 for visceral leishmaniasis (VL). VL is a major cause of morbidity and mortality in East Africa and the Indian subcontinent. Coinfection with HIV enhances the risk of the disease. The only control measure currently available in India is case detection and treatment with antimonial drugs, which are expensive, not always available and cannot be self-administered. Newer drugs like oral miltefosine have not become widely available. Vector and reservoir control is difficult due to the elusive nature of the vector and the diversity of the animal reservoir. A detailed knowledge of immune response to the parasite would help in designing prophylactic and therapeutic strategies against this infection. [source] Times of sand: Sedimentary history and archaeology at the Sigatoka Dunes, FijiGEOARCHAEOLOGY: AN INTERNATIONAL JOURNAL, Issue 2 2006Atholl Anderson The orthodox archaeological sequence at the Sigatoka Dunes site (VL 16/1) in Fiji proposes three phases of occupation spanning Fijian prehistory, each associated with a period of dune stability. It has been taken as the standard model of Fijian prehistory for more than 30 years. Recently, however, it has been argued that there is no stratigraphic support for three discrete levels and that the occupation history was fragmented, complex, and continuous within a volatile dune system. We present new data, from optical and radiocarbon dating, to argue that a three-phase model, although somewhat more complex in detail, remains the most robust interpretation of site history. The longest stable phase (Level 2) began 2500,2300 cal yr B.P. and is possibly associated with relatively low ENSO frequency. Substantial sand dune accumulation began after ,1300 cal yr B.P. © 2006 Wiley Periodicals, Inc. [source] How reliable is an undetectable viral load?HIV MEDICINE, Issue 8 2009C Combescure Objectives An article by the Swiss AIDS Commission states that patients with stably suppressed viraemia [i.e. several successive HIV-1 RNA plasma concentrations (viral loads, VL) below the limits of detection during 6 months or more of highly active antiretroviral therapy (HAART)] are unlikely to be infectious. Questions then arise: how reliable is the undetectability of the VL, given the history of measures? What factors determine reliability? Methods We assessed the probability (henceforth termed reliability) that the n+1 VL would exceed 50 or 1000 HIV-1 RNA copies/mL when the nth one had been <50 copies/mL in 6168 patients of the Swiss HIV Cohort Study who were continuing to take HAART between 2003 and 2007. General estimating equations were used to analyse potential factors of reliability. Results With a cut-off at 50 copies/mL, reliability was 84.5% (n=1), increasing to 94.5% (n=5). Compliance, the current type of HAART and the first antiretroviral therapy (ART) received (HAART or not) were predictive factors of reliability. With a cut-off at 1000 copies/mL, reliability was 97.5% (n=1), increasing to 99.1% (n=4). Chart review revealed that patients had stopped their treatment, admitted to major problems with compliance or were taking non-HAART ART in 72.2% of these cases. Viral escape caused by resistance was found in 5.6%. No explanation was found in the charts of 22.2% of cases. Conclusions After several successive VLs at <50 copies/mL, reliability reaches approximately 94% with a cut-off of 50 copies/mL and approximately 99% with a cut-off at 1000 copies/mL. Compliance is the most important factor predicting reliability. [source] British HIV Association (BHIVA) national cohort outcomes audit of patients commencing antiretrovirals from naïveHIV MEDICINE, Issue 6 2009E Street Objectives The aim of this work was to audit the extent to which routine HIV care in the UK conforms with British HIV Association (BHIVA) guidelines and specifically the proportion of patients starting highly active antiretroviral therapy (HAART) who achieve the outcome of virological suppression below 50 HIV-1 RNA copies/mL within 6 months. Methods A prospective cohort review of adults with HIV infection who started antiretroviral therapy (ART) for the first time between April and September 2006 was carried out using structured questionnaire forms. Results A total of 1170 adults from 122 clinical sites participated in the review. Of these patients, 699 (59.7%) started ART at CD4 counts <200 cells/,L and 193 (16.5%) had not been tested for HIV drug resistance. Excluding patients with valid reasons for stopping short-term ART, 795 (73.5%) of 1081 patients had an undetectable viral load (VL) at follow-up. Detectable VL was strongly associated with pretreatment CD4 count below 50 cells/,L and pretreatment VL above 100 000 copies/mL, and was not associated with clinic location or case load. About a quarter of patients did not have a VL measurement during the first 6 weeks after starting ART. Conclusions The majority of patients who initiated ART at sites participating in this UK national audit were managed within the BHIVA guidelines and achieved virological suppression below 50 copies/mL around 6 months after commencing treatment. Poor VL outcomes were associated with very low CD4 cell count and/or high VL at baseline but not with clinic case load or location. There is an urgent need to diagnose patients at an earlier stage of their HIV disease. [source] Pediculosis capitis in northern JordanINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2000Zuhair S. Amr BSc Background Little is known about the prevalence of pediculosis among school students in northern Jordan. Objective To study the incidence of pediculosis among school students of different socio-economic levels in northern Jordan. Method A total of 2519 school students of both sexes enrolled in eight elementary governmental schools were examined for the presence of Pediculus capitis. Schools were grouped into four socio-economic classes: very low (VL), low (L), medium (M), and high (H). The chi-squared test was performed to analyze the results. Results Overall, 338 students (13.4%) were infested with nits, immature or adult P. capitis. Girls showed a higher prevalence (14.5%) than boys (11.1%). Statistical analysis for socio-economic classes and infestation rates yielded a significant effect of the four classes on infestation. This conclusion was evident among schoolgirls, where infestation rates were 28.8%, 18.9%, 6.1%, and 0.2% in VL, L, M, and H socio-economic classes, respectively. Schoolchildren in the age group 8,9 years exhibited higher prevalence rates (16% in boys and 22.1% in girls), while prevalences declined to 10.2% and 6.6% among boys and girls aged 10,12 years, respectively. Conclusions This study reveals that socio-economic status is a major factor influencing the occurrence of pediculosis among school students of both sexes in Jordan. A national campaign should be implemented to enhance public awareness. [source] Selective sampling for approximate clustering of very large data setsINTERNATIONAL JOURNAL OF INTELLIGENT SYSTEMS, Issue 3 2008Liang Wang A key challenge in pattern recognition is how to scale the computational efficiency of clustering algorithms on large data sets. The extension of non-Euclidean relational fuzzy c-means (NERF) clustering to very large (VL = unloadable) relational data is called the extended NERF (eNERF) clustering algorithm, which comprises four phases: (i) finding distinguished features that monitor progressive sampling; (ii) progressively sampling from a N × N relational matrix RN to obtain a n × n sample matrix Rn; (iii) clustering Rn with literal NERF; and (iv) extending the clusters in Rn to the remainder of the relational data. Previously published examples on several fairly small data sets suggest that eNERF is feasible for truly large data sets. However, it seems that phases (i) and (ii), i.e., finding Rn, are not very practical because the sample size n often turns out to be roughly 50% of n, and this over-sampling defeats the whole purpose of eNERF. In this paper, we examine the performance of the sampling scheme of eNERF with respect to different parameters. We propose a modified sampling scheme for use with eNERF that combines simple random sampling with (parts of) the sampling procedures used by eNERF and a related algorithm sVAT (scalable visual assessment of clustering tendency). We demonstrate that our modified sampling scheme can eliminate over-sampling of the original progressive sampling scheme, thus enabling the processing of truly VL data. Numerical experiments on a distance matrix of a set of 3,000,000 vectors drawn from a mixture of 5 bivariate normal distributions demonstrate the feasibility and effectiveness of the proposed sampling method. We also find that actually running eNERF on a data set of this size is very costly in terms of computation time. Thus, our results demonstrate that further modification of eNERF, especially the extension stage, will be needed before it is truly practical for VL data. © 2008 Wiley Periodicals, Inc. [source] Diagnostic performance of the variant lymphocyte flag of the Abbott Cell-Dyn 4000 haematology analyserINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 1 2004J. J. M. L. Hoffmann Summary Background: In addition to differential cell counts, modern haematology analysers generate suspect flags if abnormal cells are detected. Reports on validation of suspect flags are scarce. We have routine experience with the Abbott Cell-Dyn 4000 analyser for over 5 years and have previously demonstrated the utility of the blast flag. Here we report a similar study on the performance of the analyser's Variant Lymphocyte (VL) flag. Aim of the study: Evaluation of the diagnostic performance of the Cell-Dyn 4000 VL flag, as compared with lymphocyte morphology in blood smears. In addition, we investigated the usefulness of the numerical VL flag confidence index as provided by the analyser. Materials and methods: All samples generating a VL flag were reviewed over a 5-month period. We also reviewed smears from patients with known lymphoid disorders, even if the analyser did not flag the sample. Two experienced investigators assessed lymphocyte morphology independently. Results: In total, 187 samples were included in the study, of which 183 had a VL flag and four had not. Of the 183 flagged samples, 83 appeared to have abnormal lymphocyte morphology and 100, normal lymphocyte morphology. The sensitivity of the VL flag for detecting abnormal lymphocytes was 0.95 and the positive predictive value was 0.44. Using ROC analysis of the VL flag confidence index, the area under the ROC curve was 0.58 (95% confidence interval 0.50,0.65). Conclusions: The Cell-Dyn VL flag has reasonable sensitivity but a high false-positive rate. In addition, its performance is insufficient for detecting clinically relevant abnormal lymphocytes. As the VL flag appeared to rely mainly on numerical criteria, it has no added value over numerical criteria defined by the laboratory. [source] Intra- and intermuscular variation in human quadriceps femoris architecture assessed in vivoJOURNAL OF ANATOMY, Issue 3 2006Anthony J. Blazevich Abstract Despite the functional importance of the human quadriceps femoris in movements such as running, jumping, lifting and climbing, and the known effects of muscle architecture on muscle function, no research has fully described the complex architecture of this muscle group. We used ultrasound imaging techniques to measure muscle thickness, fascicle angle and fascicle length at multiple regions of the four quadriceps muscles in vivo in 31 recreationally active, but non-strength-trained adult men and women. Our analyses revealed a reasonable similarity in the superficial quadriceps muscles, which is suggestive of functional similarity (at least during the uni-joint knee extension task) given that they act via a common tendon. The deep vastus intermedius (VI) is architecturally dissimilar and therefore probably serves a different function(s). Architecture varies significantly along the length of the superficial muscles, which has implications for the accuracy of models that assume a constant intramuscular architecture. It might also have consequences for the efficiency of intra- and intermuscular force transmission. Our results provide some evidence that subjects with a given architecture of one superficial muscle, relative to the rest of the subject sample, also have a similar architecture in other superficial muscles. However, this is not necessarily true for vastus lateralis (VL), and was not the case for VI. Therefore, the relative architecture of one muscle cannot confidently be used to estimate the relative architecture of another. To confirm this, we calculated a value of whole quadriceps architecture by four different methods. Regardless of the method used, we found that the absolute or relative architecture of one muscle could not be used as an indicator of whole quadriceps architecture, although vastus medialis, possibly in concert with VL and the anterior portion of VI, could be used to provide a useful snapshot. Importantly, our estimates of whole quadriceps architecture show a gender difference in whole quadriceps muscle thickness, and that muscle thickness is positively correlated with fascicle angle whereas fascicle length is negatively, although weakly, correlated with fascicle angle. These results are supportive of the validity of estimates of whole quadriceps architecture. These data are interpreted with respect to their implications for neural control strategies, region-specific adaptations in muscle size in response to training, and gender-dependent differences in the response to exercise training. [source] Effects of vegetable feed ingredients on bone health in Atlantic salmonJOURNAL OF APPLIED ICHTHYOLOGY, Issue 2 2010P. G. Fjelldal Summary The aim of the present study was to examine if dietary inclusion of vegetable lipids (VL) and proteins (VP) influenced markers of bone health in Atlantic salmon. Triplicate groups were fed one of four different diets; 100% fish protein (FP) and fish lipids (FL) (FPFL), 80% VP and 35% VL (80VP35VL), 40% VP and 70% VL (40VP70VL), or 80% VP and 70% VL (80VP70VL) for 12 months on-growth in sea water. Fish were analyzed for vertebral bone mineralization (mineral content, as % of bone dry weight), vertebral deformities (radiology), vertebral bone mRNA expression of factors involved in mineralization (bone gla protein, bgp) and growth regulation (igf-I and growth hormone receptor), as well as plasma vitamin D metabolites. The fish grew from 0.35 to 4 kg during the experimental period. At the end of the experiment, significantly lower prevalence of fish with one or more deformed vertebrae was observed in the 80VP70VL group (11%) compared to the other groups (33,43%). There was a significant higher relative expression of igf -I mRNA in vertebral bone of fish fed the 80VP70VL diet compared to control fish (FPFL), while the other genes studied were unaffected. Elevated plasma 25-hydroxyvitamin D3 recorded in the marine feed group is discussed as a predictor for later development of bone deformities. In conclusion, the present study shows that high inclusion levels of vegetable lipids and proteins may have a positive effect on bone health in Atlantic salmon postsmolts. [source] Recombinant shark natural antibodies to thyroglobulinJOURNAL OF MOLECULAR RECOGNITION, Issue 5 2005Samuel F. Schluter Abstract As cartilaginous fish are the vertebrates most distal from man to produce antibodies, fundamental information regarding conservation and variation of the antigen binding site should be gained by comparing the properties of antibodies directed against the same antigen from the two species. Since monoclonal cell lines cannot be generated using shark B cells, we isolated antigen binding recombinant single chain Fv antibodies (scFv) comprising of the complete variable regions from shark light and heavy chains. Thyroglobulin was used as the selecting antigen as both sharks and humans express natural antibodies to mammalian thyroglobulin in the absence of purposeful immunization. We report that recombinant sandbar shark (Carcharhinus plumbeus) scFvs that bind bovine thyroglobulin consist of heavy chain variable regions (VH) homologous to those of the human VHIII subset and light chain variable regions (VL) homologous to those of the human V,6 subgroup. The homology within the frameworks is sufficient to enable the building of three-dimensional models of the shark VH/VL structure using established human structures as templates. In natural antibodies of both species, the major variability lies in the third complementarity determining region (CDR3) of both VH and VL. Copyright © 2005 John Wiley & Sons, Ltd. [source] Structural basis for preferential binding of non- ortho -substituted polychlorinated biphenyls by the monoclonal antibody S2B1JOURNAL OF MOLECULAR RECOGNITION, Issue 4 2005Jean-Luc Pellequer Abstract Polychlorinated biphenyls (PCBs) are a family of 209 isomers (congeners) with a wide range of toxic effects. In structural terms, they are of two types: those with and those without chlorines at the ortho positions (2, 2,, 6 and 6,). Only 20 congeners have no ortho chlorines. Three of these are bound by the aryl hydrocarbon receptor and are one to four orders of magnitude more toxic than all others. A monoclonal antibody, S2B1, and its recombinant Fab have high selectivity and nanomolar binding affinities for two of the most toxic non- ortho -chlorinated PCBs, 3,4,3,,4,-tetrachlorobiphenyl and 3,4,3,,4,,5,-pentachlorobiphenyl. To investigate the basis for these properties, we built a three-dimensional structure model of the S2B1 variable fragment (Fv) based on the high-resolution crystallographic structures of antibodies 48G7 and N1G9. Two plausible conformations for the complementarity-determining region (CDR) H3 loop led to two putative PCB-binding pockets with very different shapes (models A and B). Docking studies using molecular mechanics and potentials of mean force (PMF) indicated that model B was most consistent with the selectivity observed for S2B1 in competition ELISAs. The binding site in model B had a deep, narrow pocket between VL and VH, with a slight constriction at the top that opened into a wider pocket between CDRs H1 and H3 on the antibody surface. This binding site resembles those of esterolytic antibodies that bind haptens with phenyl rings. One phenyl ring of the PCB fits into the deep pocket, and the other ring is bound in the shallower one. The bound PCB is surrounded by the side chains of TyrL91, TyrL96 and TrpH98, and it has a ,-cation interaction with ArgL46. The tight fit of the binding pocket around the ortho positions of the bound PCBs indicates that steric hindrance of ortho chlorines in the binding site, rather than induced conformational change of the PCBs, is responsible for the selectivity of S2B1. Copyright © 2005 John Wiley & Sons, Ltd. [source] Comparative radical production and cytotoxicity induced by camphorquinone and 9-fluorenone against human pulp fibroblastsJOURNAL OF ORAL REHABILITATION, Issue 12 2004T. Atsumi summary, Camphorquinone (CQ) is widely used as a photo-initiator in dental materials; however, its cytotoxicity against human pulp fibroblasts (HPF) and particularly the effects of 2-dimethylaminoethyl methacrylate (DMA), a reducing agent and visible light (VL) irradiation on it remain unknown. So we investigated the cytotoxic and reactive oxygen species (ROS)-producing effects of CQ with or without DMA, in the presence or absence of VL on HPF cells. The free-radical production activity of CQ was measured by two different methods [using diphenylpicryl hydrazyl and galvinoxyl]. The phase-transition properties of dipalmitoylphosphatidyl choline (DPPC) liposomes, as a model for biomembranes, induced by CQ were investigated by differential scanning calorimetry. These findings were compared with those of 9-fluorenone (9F), an aromatic photo-initiator with long conjugated groups. Camphorquinone with VL irradiation increased the radical production, whereas 9F with VL irradiation increased ROS production, as well as effecting changes in the DPPC phase-transition properties. The cytotoxicity of CQ towards HPF cells was smaller than that of 9F despite greater radical production. The addition of DMA to the photosensitizer enhanced the free-radical production without increasing the ROS level or the cytotoxicity. Camphorquinone/DMA is a valuable combination for the polymerization of dental resins. [source] Measurement of varus,valgus and internal,external rotational knee laxities in vivo,Part II: relationship with anterior,posterior and general joint laxity in males and femalesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 8 2007Sandra J. Shultz Abstract We examined sex differences in general joint laxity (GJL), and anterior,posterior displacement (ANT,POST), varus,valgus rotation (VR,VL), and internal,external rotation (INT,EXT) knee laxities, and determined whether greater ANT and GJL predicted greater VR,VL and INT,EXT. Twenty subjects were measured for GJL, and scored on a scale of 0,9. ANT and POST were measured using a standard knee arthrometer at 133 N. VR,VL and INT,EXT were measured using a custom joint laxity testing device, defined as the angular displacements (deg) of the tibia relative to the femur produced by 0,10 Nm of varus,valgus torques, and 0,5 Nm of internal,external torques, respectively. INT,EXT were measured during both non-weight-bearing (NWB) and weight-bearing (WB,=,40% body weight) conditions while VR,VL were measured NWB. All laxity measures were greater for females compared to males except for POST. ANT and GJL positively predicted 62.5% of the variance in VR,VL and 41.8% of the variance in WB INT,EXT. ANT was the sole predictor of INT,EXT in NWB, explaining 42.3% of the variance. These findings suggest that subjects who score higher on clinical measures of GJL and ANT are also likely to have greater VR,VL and INT,EXT knee laxities. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:989,996, 2007 [source] Age-related changes in electromyographic quadriceps activity during stair descentJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2005Rana S. Hinman Abstract Purpose: To determine the effects of age on (i) the onset of vastus medialis obliquus (VMO) activity relative to that of vastus lateralis (VL) and (ii) the onset of quadriceps activity in terminal swing relative to heel-strike, during stair descent. Methods: Sixty-six healthy men and women with no known knee pathology were recruited from the community and the University of Melbourne. Thirty-three older people aged over 50 (mean (SD) 68 (8) years) and 33 younger people aged under 40 (mean (SD) 25 (4) years) participated. Surface electromyography (EMG) was used to record muscle activity during stair descent. Muscle onset was identified from individual EMG traces with a computer algorithm and validated visually. Results: Both younger and older participants demonstrated a relatively synchronous onset of VMO and VL (i.e. within 10ms of each other) with no differences between the age groups evident (P = 0.262). However older participants activated their quadriceps significantly earlier than the younger group (P < 0.001) even when differences in body mass and speed of stair descent were accounted for. Conclusion: Age-related changes in quadriceps activity are apparent. The clinical implications of such changes are unknown, but increases in joint loading are possible. Earlier quadriceps activation may compensate for balance and strength impairments in older people during challenging activities. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Simultaneous feedforward recruitment of the vasti in untrained postural tasks can be restored by physical therapyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 3 2003Sallie M. Cowan Abstract Background and purpose: Physical therapy rehabilitation strategies are commonly directed at the alteration of muscle recruitment in functional movements. The aim of this study was to investigate whether feedforward strategies of the vasti in people with patellofemoral pain syndrome can be changed by a physical therapy treatment program in a randomised, double blind, placebo controlled trial. Subjects: Forty (25 female, 15 male) subjects aged 40 yrs or less (27.2 ± 7.8 yrs). Methods: Subjects were allocated to either a placebo treatment or a physical therapy intervention program. The postural challenge used as the outcome measure was not included in the training program. Electromyography (EMG) onsets of vastus medialis obliquus (VMO), vastus lateralis (VL), tibialis anterior and soleus were assessed before and after the six week standardised treatment programs. Results: At baseline the EMG onset of VL occurred prior to that of VMO in both subject groups. Following physical therapy intervention there was a significant change in the time of onset of EMG of VMO compared to VL with the onsets occurring simultaneously. This change was associated with a reduction in symptoms. In contrast, following placebo intervention the EMG onset of VL still occurred prior to that of VMO. Conclusion and discussion: The results indicate that the feedforward strategy used by the central nervous system to control the patella can be restored. Importantly, the data suggest that this intervention produced a change that was transferred to a task that was not specifically included in the training program. Furthermore, the change in motor control was associated with clinical improvement in symptoms. © 2002 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Multiple steady states in distillation: Effect of VL(L)E inaccuraciesAICHE JOURNAL, Issue 5 2000Nikolaos Bekiaris Output multiplicities in heterogeneous azeotropic distillation columns were studied. The accuracy of the thermodynamic description is a key factor that determines if multiplicities can be observed in numerical simulations. The descriptions used in the multiplicity-related literature are analyzed. The ,/, analysis of Bekiaris et al. (1996) was used to check implications of inaccuracies in the reported thermodynamics on the existence of multiplicities in azeotropic distillation. On this basis, guidelines are derived concerning what features of thermodynamic descriptions need special attention for use in multiplicity prediction and simulation. Secondly, numerical studies on output multiplicities in heterogeneous azeotropic distillation in the literature were compared to the ,/, predictions wherever possible. The ,/, analysis was used to derive the relations between the reported multiplicities and to identify the physical phenomena causing them. [source] Preparation and Growth Mechanism of Molybdenum Trioxide WhiskerJOURNAL OF THE AMERICAN CERAMIC SOCIETY, Issue 8 2002Jianqiang Li A new whisker, ,-MoO3, was fabricated via molybdenum thread oxidation at 973, 1023, and 1173 K. Various morphologies of the whiskers, such as flakelike, platelike, and needlelike, were observed under different fabrication conditions. The lateral surfaces of the whiskers were close-packed (010) plane, and the growth direction was (001), which related to the unique layered structure of the ,-MoO3 crystal. Growth of the MoO3 whiskers was attributed to a vapor-liquid-solid (VLS) mechanism at 1023 and 1173 K, whereas, at 973 K, growth was attributed to a vapor-liquid (VL) mechanism. [source] Performance of sequence analysis, INNO-LiPA line probe assays and AFFIGENE assays in the detection of hepatitis B virus polymerase and precore/core promoter mutationsJOURNAL OF VIRAL HEPATITIS, Issue 6 2006A. Olivero Summary., In this study, we compare results obtained by sequences analysis and commercial kits in the detection of hepatitis B virus (HBV) polymerase and precore (PC) and core promoter mutations. A total of 23 serum samples from lamivudine treated patients were tested for polymerase mutations by direct sequencing, INNO-LiPA HBV DR and AFFIGENE HBV DE/3TC. Full concordance among the three assays was observed in 63% of the total analysed codons. Concordant results were obtained between sequencing and LiPA in 80%, between sequencing and AFFIGENE in 73% and between LiPA and AFFIGENE in 74% of all tested codons. All discrepancies were observed in mixed population samples in which AFFIGENE and LiPA detected additional viral variants not revealed by sequence. In two patients, with serial samples, LiPA detected earlier than sequence and AFFIGENE an emerging mutate strain. PC and core promoter viral variants were detected in 28 serum samples collected from 14 HBV inactive carriers and from 14 hepatitis B patients with chronic liver disease. Direct sequencing, INNO-LiPA HBV PreCore and AFFIGENE HBV MUTANT VL 19 showed fully coincident results in 88% of tested positions. These findings showed that all assays evaluated were sensitive and accurate tools to analyse HBV genomic variability. Sequence analysis is essential to study new emerging mutations as LiPA and AFFIGENE assays are more easily useful in clinical laboratories to detect the appearance of well-characterized HBV variants. [source] Phlebotomus (Adlerius) halepensis vector competence for Leishmania major and Le. tropicaMEDICAL AND VETERINARY ENTOMOLOGY, Issue 3 2003J. Sádlová Abstract., In Eurasia, phlebotomine sandflies of the subgenus Adlerius (Diptera: Psychodidae) comprise about 20 known species. Some are suspected vectors of visceral leishmaniasis (VL) and at least one species has been implicated as a vector of cutaneous leishmaniasis (CL). We tested Phlebotomus (Adlerius) halepensis Theodor (Jordan strain) for CL vector competence, compared with three standard vectors: Phlebotomus (Phlebotomus) duboscqi N-L. from Senegal, Phlebotomus (Paraphlebotomus) sergenti Parrot from Turkey and the Neotropical Lutzomyia longipalpis (L. & N) (Jacobina strain). Sandfly females were membrane-fed on amastigote suspensions of Leishmania major Y. & S. and Le. tropica (Wright) (Kinetoplastida: Trypanosomatidae) and examined for parasite development 3, 6 and 10 days post-infection. Phlebotomus halepensis showed high susceptibility to both leishmanias, supporting typical suprapylarian parasite development similar to the other vectors. Phlebotomus halepensis infection rates were ,90% for Le. major and ,80% for Le. tropica, with high parasite densities. Development of infections was relatively fast, colonizing the thoracic midgut by 6 days post-bloodmeal in every case and reaching the stomodeal valve in >80% of flies. In late-stage infections, 10 days post-bloodmeal, nearly all P. halepensis females had cardia and stomodeal valve filled with very high numbers of parasites and some Le. tropica -infected females had promastigotes in the pharynx and proboscis. Host choice experiments in the laboratory showed that P. halepensis females fed readily on rat or rabbit and preferred the human forearm. In view of its vector competence and partial anthropophily, we infer that P. halepensis is a potential vector of cutaneous as well as visceral leishmaniases. [source] Prolonged vastus lateralis denervation after botulinum toxin type A injectionMOVEMENT DISORDERS, Issue 3 2010FRACP, John W Dunne MBBS (Hons) Abstract Intramuscular injection of botulinum toxin (BoNT) produces reversible blockade of neuromuscular transmission. In animal experimental models, recovery begins within four weeks and is usually complete by twelve weeks. We present evidence of prolonged denervation following BoNT injection of the vastus lateralis (VL) muscle to correct quadriceps muscle imbalance in patients with chronic anterior knee pain. Needle electromyography data were obtained from 10 subjects who had received a single BoNT treatment 5 to 19 months earlier as part of a clinical trial. Insertional and spontaneous activity, recruitment, and motor unit action potentials were examined. Clear differences between the injected and non-injected VL muscles, which correlated with the time since injection, were identified in all subjects. All 10 subjects studied with needle EMG showed evidence of persisting denervation in the BoNT-A injected VL muscle beyond the period of neuromotor recovery expected from animal experimental studies. © 2010 Movement Disorder Society [source] Motor thalamic circuits in primates with emphasis on the area targeted in treatment of movement disordersMOVEMENT DISORDERS, Issue S3 2002Igor A. Ilinsky MD Abstract The ventral region of the motor thalamus that receives cerebellar afferents has been and still is the target of stereotactic interventions for movement disorders. According to Hassler, this area includes ventro-oralis posterior (Vop) and ventral intermedius (Vim) nuclei, although some investigators believe that Vop is associated with the pallidothalamic pathway. We sought to correlate our experimental data on distribution of nigral, pallidal, and cerebellar afferents to the monkey thalamus with Hassler's motor thalamic parcelations. We concluded that Hassler's parcelations retained their value, although some adjustments were needed to relate them to the current neuroanatomic data; particularly, the cerebellothalamic zone that represents the monkey ventral lateral nucleus (VL) corresponds topographically to Hassler's Vop, Vim, and most of Voi. Electron microscopic tracing studies have shown very complex circuitry in this region of the monkey thalamus, as the cerebellar and cortical afferents innervating it are engaged in complex synapses with thalamocortical projection neurons, and this interaction is strongly modulated by local circuit neurons and the input from the reticular thalamic nucleus, which are both inhibitory and ,-aminobutyric acid (GABA)ergic. Spinothalamic afferents also reach the VL, but this input is less studied in the monkey. The circuitry subserving the activity of thalamocortical projection neurons in the VL should be considered while interpreting the functional data obtained in stereotactic surgery. © 2002 Movement Disorder Society [source] Linearity and reliability of the mechanomyographic amplitude versus dynamic torque relationships for the superficial quadriceps femoris musclesMUSCLE AND NERVE, Issue 3 2010Matthew S. Stock MS Abstract The purpose of this investigation was to examine the linearity and reliability of the mechanomyographic (MMG) amplitude versus dynamic torque relationships for the vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM) muscles. Nine healthy men and 11 healthy women performed submaximal to maximal, concentric, isokinetic muscle actions of the leg extensors at 30° s,1 on two occasions. Surface MMG signals were detected from the VL, RF, and VM of the dominant thigh during both trials. The ranges of the coefficients of determination for the MMG amplitude versus dynamic torque relationships were 0.01,0.94 for the VL, 0.01,0.84 for the RF, and 0.19,0.96 for the VM. The intraclass correlation coefficients for the linear MMG amplitude versus torque slope coefficients were 0.823 (VL), 0.792 (RF), and 0.927 (VM). These results indicate that, when analyzed for individual subjects, the MMG amplitude versus dynamic torque relationships demonstrated inconsistent linearity. When using MMG in the clinical setting, dynamic muscle actions of the superficial quadriceps femoris muscles do not appear to be appropriate for assessing changes in muscle function during strength training. Muscle Nerve, 2009 [source] Brief Definitive Report: Human visceral leishmaniasis is not associated with expansion or accumulation of Foxp3+ CD4 cells in blood or spleenPARASITE IMMUNOLOGY, Issue 7 2010R. MAURYA Summary Natural regulatory T cells (CD4+ CD25+ Foxp3+), natural regulatory T cells (nTreg), play an important role in the regulation of inflammatory immune responses. However, the immunosuppressive properties of nTreg may unfavourably affect the host's ability to clear certain infections. In human visceral leishmaniasis (VL), reports on the frequency and function of nTreg are not conclusive. A limitation of our own previous studies that did not indicate a major role for Foxp3+ nTreg in VL pathogenesis was that Foxp3 was measured by mRNA expression alone, as other tools were not available at the time. We have in this study assessed CD4+CD25+Foxp3+ cells in splenic aspirates and peripheral blood mononuclear cells (PBMC) from an extensive series of patients with VL and endemic controls (EC) by flow cytometry (FACS). The results do not show increased frequencies of Foxp3+ cells in patient with VL pre- and post-treatment, neither were they elevated when compared to PBMC of EC. We conclude that active VL is not associated with increased frequencies of peripheral Foxp3 Treg or accumulation at the site of infection. [source] Elevated levels of IgG3 and IgG4 subclass in paediatric cases of kala azarPARASITE IMMUNOLOGY, Issue 8 2008N. A. ANSARI SUMMARY Visceral leishmaniasis (VL) or Kala azar (KA) is a systemic disease caused by the parasites of the Leishmania donovani complex. Control measures rely on treatment with antileishmanial agents, however, fraught with problems such as toxicity or drug resistance. The incidence rate is on the rise for children, for reasons yet undefined. Previously we have shown significantly elevated level of IL-10 in children compared to adult KA cases. Here, antileishmanial antibody and C-reactive protein (CRP) levels were investigated in paediatrics and adult patients of KA and post-KA dermal leishmaniasis (PKDL). Level of IgG4 was significantly elevated in PKDL compared to KA, although total IgG and IgG1 were significantly lower. The antileishmania antibody levels of subclass IgG3 and IgG4 were found significantly elevated in paediatrics, however, levels of IgG, IgG1, IgG2 and CRP were comparable in paediatric and adult KA cases. In case of PKDL, levels of IgG and it subclass were similar in the two groups. No significant difference in antileishmanial antibody level was noticed between macular or polymorphic cases of PKDL. The differential antibody intensity in paediatric cases, together with significant level of circulating IL-10, could be considered as a marker of differential disease susceptibility. [source] | |||||||||||||||||||||||||||||||||||||||||||||||||