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PubMed1992

Immunological reactivity of a human immunodeficiency virus type I derived peptide representing a consensus sequence of the GP120 major neutralizing region V3.

To reduce the opportunities for human immunodeficiency virus type 1 (HIV-1) to evade vaccine induced immunity, the development of subunit vaccines must focus on the characterization of immunogenic epitopes, which are major targets for the immune system. The most dominant site for elicitation of neutralising immune response is located on the external envelope glycoprotein gp120 within the third variable domain (V3). To overcome virus type specificity of antibodies directed to the V3-domain we designed a 36 amino acids long gp120/V3-consensus peptide (V3-C36) based on published biological data and sequence comparisons of various HIV-1 virus isolates. This peptide contains a conserved core sequence which is suggested to form a surface-exposed beta-turn. This peptide also includes T-cell epitopes defined in mice and humans, an ADCC-epitope and two highly conserved cysteine residues which were oxidized to form a cystine derivate, thus allowing correct peptide folding. In ELISA-tests, this peptide reacts with at least 90% of randomly selected sera of European and African patients infected with HIV-1 and is recognized by three different HIV-1/V3 "type-specific" antisera (MN, RF, IIIB-strain). Using this peptide as immunogen in rabbits, antisera could be raised with highly cross-reactive and HIV-1/IIIB strain neutralizing properties. Moreover, HTLV/HIV-1/IIIB specific cytotoxic T-lymphocytes (CTLs) of BALB/c mice infected with a gp120 recombinant vaccinia virus recognized the central 16- and 12-mer peptides of the V3-C36 consensus peptide in cytolytic assays, indicating perfect compatibility of the consensus peptide with the IIIB-primed CTLs. The DNA-sequence encoding the V3-consensus loop region might be an important component in newly designed recombinant subunit vaccines. In addition, due to its broad serological reactivity, the V3-consensus peptide might play an important role in special diagnostic purposes.

AIDS Vaccines↗
PubMed2003

The development and evaluation of consensus chloroplast primer pairs that possess highly variable sequence regions in a diverse array of plant taxa.

Although universal or consensus chloroplast primers are available, they are limited by their number and genomic distribution. Therefore, a set of consensus chloroplast primer pairs for simple sequence repeats (ccSSRs) analysis was constructed from tobacco (Nicotiana tabacum L.) chloroplast sequences. These were then tested for their general utility in the genetic analysis of a diverse array of plant taxa. In order to increase the number of ccSSRs beyond that previously reported, the target sequences for SSR motifs was set at A or T ( n >/= 7) mononucleotide repeats. Each SSR sequence motif, along with +/-200-bp flanking sequences from the first of each mononucleotide base repeat, was screened for homologies with chloroplast DNA sequences of other plant species in GenBank databases using BLAST search procedures. Twenty three putative marker loci that possessed conserved flanking sequence spans were selected for consensus primer pair construction using commercially available computer algorithms. All primer pairs produced amplicons after PCR employing genomic DNA from members of the Cucurbitaceae (six species) and Solanaceae (four species). Sixteen, 22 and 19 of the initial 23 primer pairs were successively amplified by PCR using template DNA from species of the Apiaceae (two species), Brassicaceae (one species) and Fabaceae (two species), respectively. Twenty of 23 primer pairs were also functional in three monocot species of the Liliaceae [onion (Allium cepa L.) and garlic (Allium sativum L.)], and the Poaceae [oat (Avena sativa L.)]. Sequence analysis of selected ccSSR fragments suggests that ccSSR length and sequence variation could be useful as a tool for investigating the genetic relationships within a genus or closely related taxa (i.e., tribal level). In order to provide for a marker system having significant coverage of the cucumber chloroplast genome, ccSSR primers were strategically "recombined" and named recombined consensus chloroplast primers (RCCP) for PCR analysis. Successful amplification after extended-length PCR of 16 RCCP primer pairs from cucumber ( Cucumis sativus L.) DNA suggested that the amplicons detected are representative of the cucumber chloroplast genome. These RCCP pairs, therefore, could be useful as an initial molecular tool for investigation of traits related to a chloroplast gene(s) in cucumber, and other closely related species.

Base Sequence↗
PubMed2004

A high-density microsatellite consensus map for bread wheat (Triticum aestivum L.).

A microsatellite consensus map was constructed by joining four independent genetic maps of bread wheat. Three of the maps were F(1)-derived, doubled-haploid line populations and the fourth population was 'Synthetic' x 'Opata', an F(6)-derived, recombinant-inbred line population. Microsatellite markers from different research groups including the Wheat Microsatellite Consortium, GWM, GDM, CFA, CFD, and BARC were used in the mapping. A sufficient number of common loci between genetic maps, ranging from 52 to 232 loci, were mapped on different populations to facilitate joining the maps. Four genetic maps were developed using MapMaker V3.0 and JoinMap V3.0. The software CMap, a comparative map viewer, was used to align the four maps and identify potential errors based on consensus. JoinMap V3.0 was used to calculate marker order and recombination distances based on the consensus of the four maps. A total of 1,235 microsatellite loci were mapped, covering 2,569 cM, giving an average interval distance of 2.2 cM. This consensus map represents the highest-density public microsatellite map of wheat and is accompanied by an allele database showing the parent allele sizes for every marker mapped. This enables users to predict allele sizes in new breeding populations and develop molecular breeding and genomics strategies.

Bread↗
PubMed2000

Laparoscopic fundoplication for gastro-oesophageal reflux disease - a consensus development conference and the evidence-based benefit.

The aim of this paper is to demonstrate an example of evidence-based medicine for a clinically relevant and frequent disease - gastro-oesophageal reflux disease - for which an increasing number of laparoscopic operations is performed. A consensus development conference was performed on this topic in 1996. During the following 3-year period, increase of knowledge shown by the number of publications was monitored and the consecutive changes of the consensus as well as its consequences and impact were analysed. The six published randomised clinical trials revealed important information about the technique of the laparoscopic operation focussing on the gastric fundic mobilisation and the modification of the anti-reflux wrap. Five consecutive consensus conferences were performed and published. Citations of the 1996 consensus conference could not be found in the major surgical journals - not even by participants of the conference. The responsibility of societies to run such conferences continues.

Consensus Statements as Topic↗
PubMed2005

Consensus guidelines for validation of virtual reality surgical simulators.

The Work Group for Evaluation and Implementation of Simulators and Skills Training Programmes is a newly formed sub-group of the European Association of Endoscopic Surgeons (EAES). This work group undertook a review of validation evidence for surgical simulators and the resulting consensus is presented in this article. Using clinical guidelines criteria, the evidence for validation for six different simulators was rated and subsequently translated to a level of recommendation for each system. The simulators could be divided into two basic types; systems for laparoscopic general surgery and flexible gastrointestinal endoscopy. Selection of simulators for inclusion in this consensus was based on their availability and relatively widespread usage as of July 2004. Whilst level 2 recommendations were achieved for a few systems, it was clear that there was an overall lack of published validation studies with rigorous experimental methodology. Since the consensus meeting, there have been a number of new articles, system upgrades and new devices available. The work group intends to update these consensus guidelines on a regular basis, with the resulting article available on the EAES website (http://www.eaes-eur.org ).

Computer Simulation↗
PubMed2002

The NIH Consensus concept of chronic prostatitis/chronic pelvic pain syndrome compared with traditional concepts of nonbacterial prostatitis and prostatodynia.

The new National Institutes of Health (NIH) consensus classification identifies chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) based on the presence or absence of leukocytes in expressed prostatic secretions (EPS), postprostatic massage urine (VB3), or seminal fluid analysis. The purpose of this review is to determine the effect of the new classification on the proportion of symptomatic patients diagnosed with inflammation. We compare and contrast the new consensus classification with the traditional classification of prostatitis syndromes, then review how these changes effect patient classification in our clinical practice. Thorough clinical and microbiologic examination of 140 patients attending the University of Washington Prostatitis Clinic included evaluation of first void urine, mid-stream urine, EPS, VB3, and semen specimens. Inflammation was documented in 111 (26%) of 420 samples including 39 EPS samples, 32 VB3 samples, and 40 SFA specimens. Of the 140 patients, 73 (52%) had inflammatory CP/CPPS according to the NIH consensus criteria, but only 39 (28%) had nonbacterial prostatitis according to traditional EPS criteria (P < 0.001). The new NIH consensus concept of inflammatory CP/CPPS includes almost twice as many patients as the traditional category of nonbacterial prostatitis.

Chronic Disease↗
PubMed1992

Interpreting consensus sequences based on plurality rule.

Our goal is to help researchers interpret the results of a function, based on the concept of plurality rule, that calculates a consensus of a profile of molecular bases. By expressing the plurality rule function as a composition of simpler functions, we obtain both an algorithm to calculate the consensus result and an upper bound on the number of nonequivalent results. Consequently, when used to analyze molecular sequences such as DNA or RNA, the plurality rule function yields at most 48 nonequivalent consensus results. For problems of reasonable size, we describe an algorithm to calculate the probability that each consensus result would occur if the bases were equally likely to appear at every position of the plurality rule function's input profile.

Algorithms↗
PubMed1992

Ugandan HIV-1 V3 loop sequences closely related to the U.S./European consensus.

The third variable (V3) loop of the human immunodeficiency virus type 1 (HIV-1) envelope protein is an important determinant for virus neutralization and cell tropism. V3 loop sequences from uncultured lymphocytes obtained in 1990 from 22 Ugandan HIV-1-infected patients could, with the exception of two patients' sequences, be divided into two groups (A and B) on the basis the V3 loop size and sequence. The V3 loop consensus sequences from both groups showed a high degree of homology to a U.S./European consensus, a characteristic also reflected by the results of peptide serology. In the case of group B the difference in sequence was only five amino acids. In contrast, the V3-flanking regions for both groups showed greater homology to an earlier (1986/1987) Ugandan consensus. The discovery of these two new Ugandan V3 loop genotypes, which are closely related to the U.S./European consensus, has implications for the understanding of the evolution of HIV-1 and for the future design of a vaccine for use in Africa.

Amino Acid Sequence↗
PubMed1992

Usefulness of consensus conferences: the case of albumin.

The usefulness of consensus conferences has been questioned. We have assessed the impact of a 1989 consensus conference about the treatment of hypovolaemia on prescribing practice at our hospital. Data available from the blood bank enabled us to follow albumin use and costs by department between 1987 and 1991. Medical journals, direct mail, and meetings were used to disseminate the recommendations of the consensus conference, which were that the only indications for albumin are massive haemorrhage, plasmapheresis, massive hypoalbuminaemia, and volume expansion in pregnancy; for hypovolaemia caused by septic shock or vasoplegia, fluid gelatins and crystalloids should be used. In the year after the conference, and in subsequent years, albumin use and costs were 40% lower than before the conference, even though total medical expenditure continued to rise and numbers of patients admitted did not change. We believe that consensus conferences can be a useful means of improving medical practice. The features that ensured success in this programme were the small number of prescribers, the homogeneous setting, and the frequent restatement of the recommendations.

Consensus Statements as Topic↗
PubMed2004

Identification and functional analysis of consensus androgen response elements in human prostate cancer cells.

Androgen receptor (AR) recognizes and binds to 15-bp palindromic androgen response element (ARE) sequences with high affinity in vitro, which consist of two hexameric half-sites arranged as inverted repeats with a 3-bp spacer. Although a few near-consensus ARE sequences have been actually identified in the transcriptional regulatory regions of androgen-responsive genes, it has been unclear whether the exact consensus sequences function as bona fide AREs in vivo. A genome-wide in silico screening of palindromic AREs identified 563 exact consensus sequences in the human genome. The distribution of perfect palindromic AREs among the chromosomes is basically consistent with the length of chromosomes. Using human prostate cancer cell line LNCaP treated with a synthetic androgen R1881 as a model, in vivo AR binding abilities of 21 consensus AREs were analyzed by chromatin immunoprecipitation. Of 21 genomic fragments containing perfect AREs in chromosome X, 8 fragments recruited more ARs (>4-fold enrichment) even compared with the proximal ARE region of prostate-specific antigen. A couple of proximal genes or putative transcripts in the vicinity of the perfect AREs were found to be androgen-responsive analyzed by quantitative RT-PCR. Our results suggest that some of perfect palindromic AREs could function as in vivo AR binding sites in the human genome and regulate gene transcription.

Androgens↗
PubMed2005

Multilocus consensus genetic maps (MCGM): formulation, algorithms, and results.

In process of creating genetic maps different labs/research groups obtain overlapping parts of the map. Merging these parts into one integrative map is based on looking for maximum shared marker orders among the maps. Really, not all shared markers of such maps have consensus order that obstructs building of the integrative maps. In this paper we propose a new approach to build verified multilocus consensus genetic maps in which shared markers always are integrated in stable consensus order. The approach is based on combined analysis of initial mapping data rather than manipulating with previously constructed maps. We show that more effective and reliable solutions may be obtained based on "synchronized ordering" facilitated by cycles of "re-sampling-->ordering-->removing unstable markers". The proposed formulation of consensus genetic mapping can be considered as a version of traveling salesperson problem (TSP) that we refer to as synchronized-TSP. From the viewpoint of optimization, synchronized-TSP belongs to discrete constrained optimization problems. Earlier we developed new powerful and fast guided evolution strategy algorithms for some types of discrete constrained optimization. These algorithms were used here as a basis for solving more challenging problems of consensual marker ordering.

Algorithms↗
PubMed2006

Derivation of the consensus DNA-binding sequence for p63 reveals unique requirements that are distinct from p53.

p63 is a member of the p53 family of proteins and plays an important role in epithelial development and differentiation. Although some p63 binding sites in the regulatory elements of epithelial genes have been identified, the optimal DNA-binding sequence has not been ascertained for this transcription factor. Here, we identify the preferred DNA-binding site of p63 by performing in vitro DNA selection experiments. Our analysis shows that the optimal p63 DNA-binding consensus motif consists of a CA(T)TG core and an AT-rich 5' and 3' flanking sequence. Gel shift and competition experiments demonstrate that there are specific sequence requirements that confer high DNA-binding affinity for p63 and that significant deviation from the consensus sequences result in poor or no binding. This pattern of DNA-binding is similar for both recombinant p63 and the endogenous protein present in keratinocyte nuclear extracts. Furthermore, we show that the consensus sequence is distinctly different from that of p53, particularly in the flanking sequences. Identification of the p63 consensus DNA-binding sequence will facilitate the validation of in vivo p63-responsive elements that mediate transcriptional regulation of a wide variety of target genes.

Animals↗
PubMed2025

Operationalizing the Wilson-Jungner principles for the genomics era: Consensus recommendations from the International Consortium on Newborn Sequencing.

PURPOSE: For decades, the selection of disorders included in newborn screening (NBS) programs has been guided by principles published by Wilson and Jungner in 1968. As research explores the expansion of conditions included in NBS through genomic sequencing, there is a critical need for updated recommendations to address the opportunities and complexities of genomic data. METHODS: The International Consortium on Newborn Sequencing includes leaders from over 16 research projects investigating genomic NBS across the United Kingdom, Europe, United States, and Oceania. Consortium members were invited to participate in a modified Delphi study, aggregating opinion on the selection of conditions for genomic NBS through 3 rounds of online questionnaires, with feedback provided to participants between rounds. RESULTS: In round 1, 94 participants completed the questionnaire, and 10 of 43 statements reached consensus. In round 2, 81 participants completed the questionnaire, and 14 of 27 statements reached consensus. In round 3, 68 participants completed the questionnaire, and all 10 statements reached 72% or more consensus. CONCLUSION: The 10 consensus recommendations developed in this study can guide future research and public health programs performing genomic NBS. This process also identified key areas of participant discordance, highlighting important topics for future research.

Humans↗
PubMed2004

A new definition for the consensus sequence of the peroxisome targeting signal type 2.

All organisms except the nematode Caenorhabditis elegans have been shown to possess an import system for peroxisomal proteins containing a peroxisome targeting signal type 2 (PTS2). The currently accepted consensus sequence for this amino-terminal nonapeptide is -(R/K)(L/V/I)X(5)(H/Q)(L/A)-. Some C.elegans proteins contain putative PTS2 motifs, including the ortholog (CeMeK) of human mevalonate kinase, an enzyme known to be targeted by PTS2 to mammalian peroxisomes. We cloned the gene for CeMeK (open reading frame Y42G9A.4) and examined the subcellular localization of CeMeK and of two other proteins with putative PTS2s at their amino termini encoded by the open reading frames D1053.2 and W10G11.11. All three proteins localized to the cytosol, confirming and extending the finding that C.elegans lacks PTS2-dependent peroxisomal protein import. The putative PTS2s of the proteins encoded by D1053.2 and W10G11.11 did not function in targeting to peroxisomes in yeast or mammalian cells, suggesting that the current PTS2 consensus sequence is too broad. Analysis of available experimental data on both functional and nonfunctional PTS2s led to two re-evaluated PTS2 consensus sequences: -R(L/V/I/Q)XX(L/V/I/H)(L/S/G/A)X(H/Q)(L/A)-, describes the most common variants of PTS2, while -(R/K)(L/V/I/Q)XX(L/V/I/H/Q)(L/S/G/A/K)X(H/Q)(L/A/F)-, describes essentially all variants of PTS2. These redefined PTS2 consensus sequences will facilitate the identification of proteins of unknown cellular localization as possible peroxisomal proteins.

Amino Acid Sequence↗
PubMed2004

Beyond consensus: statistical free energies reveal hidden interactions in the design of a TPR motif.

Consensus design methods have been used successfully to engineer proteins with a particular fold, and moreover to engineer thermostable exemplars of particular folds. Here, we consider how a statistical free energy approach can expand upon current methods of phylogenetic design. As an example, we have analyzed the tetratricopeptide repeat (TPR) motif, using multiple sequence alignment to identify the significance of each position in the TPR. The results provide information above and beyond that revealed by consensus design alone, especially at poorly conserved positions. A particularly striking finding is that certain residues, which TPR-peptide co-crystal structures show are in direct contact with the ligand, display a marked hypervariability. This suggests a novel means of identifying ligand-binding sites, and also implies that TPRs generally function as ligand-binding domains. Using perturbation analysis (or statistical coupling analysis), we examined site-site interactions within the TPR motif. Correlated occurrences of amino acid residues at poorly conserved positions explain how TPRs achieve their near-neutral surface charge distributions, and why a TPR designed from straight consensus has an unusually high net charge. Networks of interacting sites revealed that TPRs fall into two unrecognized families with distinct sets of interactions related to the identity of position 7 (Leu or Lys/Arg). Statistical free energy analysis provides a more complete description of "What makes a TPR a TPR?" than consensus alone, and it suggests general approaches to extend and improve the phylogenetic design of proteins.

Amino Acid Motifs↗
PubMed1999

Consensus on renal cortical scintigraphy in children with urinary tract infection. Scientific Committee of Radionuclides in Nephrourology.

A questionnaire related to cortical scintigraphy in children with urinary tract infection was submitted to 30 experts. A wide consensus was reached on several issues related to planar images: 99mTc dimercapto succinic acid (DMSA) appears as the most appropriate tracer for renal imaging; dynamic tracers are considered to be inferior, in particular 99mTc diethylenetriaminepentaacetate, which is not recommended. The general opinion is that DMSA scintigraphy is not feasible with a minimal dose below 15 MBq, whereas the maximum dose should not be higher than 110 MBq. The dose schedule generally is based on body surface area, and sedation is only exceptionally given to children. Images are obtained 2 to 3 hours after injection, preferably with high resolution collimators; pinhole images are used by only half of the experts. Posterior and posterior oblique views are used by most of the experts, and the posterior view is acquired in supine positions. At least 200.000 kcounts or 5 minute acquisition is required for nonzoomed images. As a quality control, experts check the presence of blurred or double outlines on the DMSA images. Color images are not used and experts report on film or directly on the computer screen. As far as normal DMSA images are concerned, most experts agree on several normal variants. Hydronephrosis is not a contraindication for DMSA scintigraphy but constitutes a pitfall. Differential renal function generally is measured, but no consensus is reached whether or not background should be subtracted. Most of the experts consider 45% as the lowest normal value. A consensus is reached on some scintigraphic aspects that are likely to improve and on some others that probably represent persistent sequelae. There is a wide consensus for the systematic use of DMSA scintigraphy for detection of renal sequelae, whereas only 58% of the experts are systematically performing this examination during the acute phase of infection.

Child↗
PubMed2004

[Primary treatment of Parkinson's disease: the application of the March 2000 consensus rules in the Nord Pas-de-Calais area].

INTRODUCTION: For Parkinson's disease, the choice of the initial treatment is essentially between L-Dopa and dopaminergic agonists. Selegilin, anticholinergic and amantadine can be used for subjects with moderate symptoms. The first French consensus conference, held in 2000, elaborated decision-making rules which take into account both the age and disease severity. The aim of our study was to evaluate the impact of these recommendations on treatments prescribed for de novo parkinsonian patients in the Nord-Pas de Calais area, comparing initial prescriptions before and after the conference. METHODS: Three groups of 50 patients whose diagnosis of Parkinson's disease had been establish in three periods (1985-1992, 1993-1999, and after July 2000, date of the national publication of the consensus) were constituted. RESULTS: For these 3 groups, the initial treatment complied with the 2000 recommendations for 58, 84 and 82 percent of the patients respectively. The prescriptions of agonists increased progressively while the prescriptions of L-Dopa decreased for younger patients, in concordance with the consensus, but also for older patients, in opposition with the recommendations, though without any increase in the incidence of side effects. The non dopaminergic treatments were almost discarded as initial treatment. CONCLUSION: Prescription habits have gradually changed over the past 10 years. Changes were linked to the elaboration of the national consensus conference guidelines and to the apparent desire to decrease L-Dopa prescriptions.

Aged↗
PubMed2002

International consensus on palliative radiotherapy endpoints for future clinical trials in bone metastases.

PURPOSE: To reach a consensus on a set of optimal endpoint measurements for future external beam radiotherapy trials in bone metastases. METHODS: An International Bone Metastases Consensus Working Party invited principal investigators and individuals with a recognized interest in bone metastases to participate in the two surveys and a panel meeting on their preference of choice of optimal endpoints. RESULTS: Consensus has been reached on the following: (a) eligibility criteria for future trials; (b) pain and analgesic assessments; (c) radiation techniques; (d) follow-up and timing of assessments; (e) parameters at follow-up; (f) endpoints; (g) re-irradiation; and (h) statistical analysis. CONCLUSIONS: Based on the available literature and the clinical experience of the working party members, an acceptable set of endpoints has been agreed upon for future clinical trials to promote consistency in reporting. It is intended that the consensus will be re-examined every 5 years. Areas of further research were identified.

Bone Neoplasms↗