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PubMed2002

Prediction of partial membrane protein topologies using a consensus approach.

We have developed a method to reliably identify partial membrane protein topologies using the consensus of five topology prediction methods. When evaluated on a test set of experimentally characterized proteins, we find that approximately 90% of the partial consensus topologies are correctly predicted in membrane proteins from prokaryotic as well as eukaryotic organisms. Whole-genome analysis reveals that a reliable partial consensus topology can be predicted for approximately 70% of all membrane proteins in a typical bacterial genome and for approximately 55% of all membrane proteins in a typical eukaryotic genome. The average fraction of sequence length covered by a partial consensus topology is 44% for the prokaryotic proteins and 17% for the eukaryotic proteins in our test set, and similar numbers are found when the algorithm is applied to whole genomes. Reliably predicted partial topologies may simplify experimental determinations of membrane protein topology.

Computational Biology↗
PubMed2004

A proposal for case definitions and outcome measures in studies of infantile spasms and West syndrome: consensus statement of the West Delphi group.

PURPOSE: To reach a broad consensus on case definitions, outcomes, and outcome measures that will ease future study design and facilitate comparison of data from different studies of infantile spasms and West syndrome. METHODS: Persons who had recently presented or published first-author original research in this field were invited to participate in an e-mail Delphi process and to invite other investigators or clinicians who they thought might participate. RESULTS: The process consisted of six rounds, anonymous except to the facilitator. In total, responses were received from 46 participants. The final statement was approved by 31 participants from 15 countries. It concluded that the primary clinical outcome, cessation of spasms, should denote absence of witnessed spasms from within 14 days of commencement of treatment, and for > or =28 consecutive days from the last witnessed spasm. Primary electroclinical outcome denotes cessation of spasms with resolution of hypsarrhythmia. West syndrome should be a defined subset of the syndrome of infantile spasms. An infantile spasms single-spasm variant should be recognized. Ways are suggested of handling subtle spasms in the context of clinical studies. It proposes a standard for reporting modifying and atypical features of hypsarrhythmia, a minimal set of baseline characteristics and outcomes that should be reported in trials of infantile spasms, and suggests a standard definition of relapse. Consensus was not reached on a definition of hypsarrhythmia. CONCLUSIONS: We reached a clear consensus on many aspects of study design for the investigation of infantile spasms, although incomplete consensus was found on how to define EEG criteria.

Child, Preschool↗
PubMed2003

Development of consensus fluorogenically labeled probes of the immunoglobulin heavy-chain gene for detecting minimal residual disease in B-cell non-Hodgkin lymphomas.

We have examined 72 patients with B-cell non-Hodgkin lymphoma (B-NHL) in order to search for consensus sequences of the immunoglobulin heavy chain (IgH) gene, and developed consensus fluorogenically labeled probes for use in an allele-specific oligonucleotide (ASO) real-time quantitative polymerase chain reaction (RQ-PCR) assay of minimal residual disease (MRD). We detected a clonal IgH variable region (VH) sequence in 51 (70.8%) of the 72 B-NHLs, the most frequent VH gene usages being VH3 and VH4 (45/51, 88.2%). It was possible to design three consensus fluorogenic probes for the VH3 gene and one for the VH4 gene avoiding these hypermutations. Our sequencing results suggested that consensus fluorogenic probes would be best based on the 5'-side of the framework region 3 (FR3) because the frequency of somatic hypermutations was significantly lower in the regions on which the probes were based than in the remaining parts of FR3 (P < 0.05). Nineteen (54.3%) of 35 B-NHLs with the VH3 gene and 5 (50%) of 10 with the VH4 gene had sequences identical to at least one of these probes. We found that probes containing one base substitution were still applicable for a MRD study, whereas those containing two or more were not. Therefore, our four probes were applicable for 37 (82.2%) of the 45 patients with VH3 or VH4. This limited number of probes makes a large-scale study of MRD in B-NHL more feasible.

Adult↗
PubMed2004

A consensus protocol for the determination of the threshold doses for allergenic foods: how much is too much?

BACKGROUND: While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult. OBJECTIVE: A roundtable conference was convened to develop a consensus clinical protocol for low-dose challenge trials for the estimation of threshold doses for specific allergenic foods. METHODS: In May 2002, 20 clinical allergists and other interested parties were invited to participate in a roundtable conference to develop consensus of the key elements of a clinical protocol for low-dose challenge trials. RESULTS: A consensus protocol was developed. Patients with convincing histories of food allergies and supporting diagnostic evidence including past challenge trials or high CAP-RAST scores can be enrolled in low-dose challenge trials. Care must be taken with younger patients to assure that they have not outgrown their food allergy. An approach was developed for the medication status of patients entering such trials. Challenge materials must be standardized, for example, partially defatted peanut flour composed of equal amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish). Challenge materials must be appropriately blinded with sensory evaluation used to confirm the adequacy of blinding. A double-blind, placebo-controlled design should be used for low-dose challenge trials. Low-dose challenge trials would begin at doses of 10 microg of the allergenic food and would continue with doses of 100 microg and 1 mg followed by specific higher doses up to 100 mg depending upon the expert judgement of the physician; even higher doses might be applied to assure that the patient is indeed reactive to the particular food. A 30-min time interval would be used between doses, and reactive doses would be expressed as both discrete and cumulative doses. The goal of each challenge would be to develop objective symptoms; trials should not be discontinued on the basis of subjective symptoms only. Statistically, a minimum of 29 patients would be enrolled in low-dose challenge trials for each allergenic food because 0 reactors out of 29 patients at a particular dose allow the conclusion that there is 95% certainty that 90% of allergic individuals will not react to that dose. CONCLUSION: A consensus protocol was developed. Using this protocol, it will be possible to estimate threshold doses for allergenic foods, the lowest amount that elicits mild, objective symptoms in highly sensitive individuals.

Allergens↗
PubMed2006

Theories about consensus-based conservation.

"Conservation and the Myth of Consensus" (Peterson et al. 2005) levels several serious indictments against consensus-based approaches to environmental decision making. Namely, the authors argue that consensus processes (1) reinforce apathy and ignorance of conservation issues; (2) legitimize damage to the environment; (3) quash public debate about conservation; (4) solidify the existing balance of power in favor of prodevelopment forces; and (5) block progress toward an ecologically sustainable future. Careful scrutiny of consensus-based approaches is important, especially considering their surging use in conservation policy. In the spirit of advancing the debate further, I review some of the limitations of the essay and its modes of inquiry.

Consensus↗
PubMed2001

Shared expectations for protection of identifiable health care information: report of a national consensus process.

OBJECTIVE: The Ethical Force Program is a collaborative effort to create performance measures for ethics in health care. This report lays out areas of consensus that may be amenable to performance measurement on protecting the privacy, confidentiality and security of identifiable health information. DESIGN: Iterative consensus development process. PARTICIPANTS: The program's oversight body and its expert panel on privacy include national leaders representing the perspectives of physicians, patients, purchasers, health plans, hospitals, and medical ethicists as well as public health, law, and medical informatics experts. METHODS AND MAIN RESULTS: The oversight body appointed a national Expert Advisory Panel on Privacy and Confidentiality in September 1998. This group compiled and reviewed existing norms, including governmental reports and legal standards, professional association policies, private organization statements and policies, accreditation standards, and ethical opinions. A set of specific and assessable expectations for ethical conduct in this domain was then drafted and refined through 7 meetings over 16 months. In the final 2 iterations, each expectation was graded on a scale of 1 to 10 by each oversight body member on whether it was: (1) important, (2) universally applicable, (3) feasible to measure, and (4) realistic to implement. The expectations that did not score more than 7 (mean) on all 4 scales were reconsidered and retained only if the entire oversight body agreed that they should be used as potential subjects for performance measurement. Consensus was achieved on 34 specific expectations. The expectations fell into 8 content areas, addressing the need for transparency of policies and practices, consent for use and disclosure of identifiable information, limitations on information that can be collected and by whom, individual access to one's own health records, security requirements for storage and transfer of information, provisions to ensure ongoing data quality, limitations on how identifiable information may be used, and provisions for meaningful accountability. CONCLUSIONS: This process established consensus on 34 measurable ethical expectations for the protection of privacy and confidentiality in health care. These expectations should apply to any organization with access to personally identifiable health information, including managed care organizations, physician groups, hospitals, other provider organizations, and purchasers. Performance measurement on these expectations may improve accountability across the health care system.

Confidentiality↗
PubMed2001

Novel sigmaF-dependent genes of Escherichia coli found using a specified promoter consensus.

Availability of whole genome information opens new bioinformatics approaches to study global regulation. We developed a program, named ScanProm, that allows to search a genome database for promoter consensus elements. The program uses a multiple alignment of previously identified components of a regulon as an input and generates a consensus profile. The profile is then optimized by adjusting the cutoff value for position-specific similarity assessment and used for a genome scan to search for unknown members of the regulon. The candidates obtained are scored by their similarity to the consensus profile. The ScanProm program was applied to search for novel members of the class III flagellar regulon of Escherichia coli. The search template included the previously defined 4 bp (-35) and 8 bp (-10) promoter elements, presumably recognized by the flagellar-specific sigmaF, with additional 4 bp at the 3' of the -35 consensus. The majority of highly scoring candidates obtained from the whole genome sequence scan were known class III genes, although several new genes were also identified. We tested 10 novel highly scoring candidate class III genes by cloning their promoter fragments into a fusion vector designed to monitor the transcriptional activity with lacZ. Two of these genes, b2737(ygbK) and ppdAB, were found to be dependent on FlhDC, the master regulator of the flagellar genes. The regulation of these genes by sigmaF was further confirmed by comparing their expression in the wild-type and fliA backgrounds. An overproduction or inactivation of these genes did not exhibit any notable phenotypes in motility or chemotaxis.

Base Sequence↗
PubMed2006

Consensus statement on injury definitions and data collection procedures in studies of football (soccer) injuries.

Variations in definitions and methodologies have created differences in the results and conclusions obtained from studies of football injuries; this has made inter-study comparisons difficult. An Injury Consensus Group was established under the auspices of FIFA Medical Assessment and Research Centre. Using a nominal group consensus model approach, a working document that identified the key issues related to definitions, methodology and implementation was discussed by members of the group during a 2-day meeting. Following this meeting, iterative draft statements were prepared and circulated to members of the group for comment before the final consensus statement was produced. Definitions of injury, recurrent injury, severity and training and match exposures in football together with criteria for classifying injuries in terms of location, type, diagnosis and causation are proposed. Proforma for recording players' baseline information, injuries and training and match exposures are presented. Recommendations are made on how the incidence of match and training injuries should be reported and a checklist of issues and information that should be included in published reports of studies of football injuries is presented. The definitions and methodology proposed in the consensus statement will ensure that consistent and comparable results will be obtained from studies of football injuries.

Athletic Injuries↗
PubMed1995

A consensus promoter sequence for Caulobacter crescentus genes involved in biosynthetic and housekeeping functions.

Caulobacter crescentus differentiates prior to each cell division to form two different daughter cells: a monoflagellated swarmer cell and a nonmotile stalked cell. Thus, one might expect that developmentally expressed genes would be regulated by mechanisms different from those used to regulate the expression of the biosynthetic genes. To determine a consensus promoter sequence for genes involved in biosynthetic or housekeeping functions, DNA fragments containing the regulatory regions of the ilvD, ilvR, cysC, pleC, and fdxA genes were cloned. S1 nuclease protection mapping and primer extension techniques were used to identify the transcription initiation sites. Comparison of the regulatory regions of these genes with those of the published sequences of the ilvBN, rrnA, trpFBA, dnaA, dnaK, hemE, and rsaA genes has resulted in the identification of a putative promoter consensus sequence. The -35 region contains the sequence TTGACGS, which is similar to the Escherichia coli -35 region, while the -10 region, GCTANAWC, has a more balanced GC content than the corresponding region in E. coli. Oligonucleotide-directed site-specific mutagenesis of both the ilvBN and pleC promoters indicates that mutations that make a promoter more like the consensus result in increased promoter activity, while mutations decreasing similarity to the consensus result in decreased promoter activity.

Bacterial Proteins↗
PubMed1992

Mutagenic analysis of the coronavirus intergenic consensus sequence.

Previously, a system in which an intergenic region from mouse hepatitis virus (MHV) inserted into an MHV defective interfering (DI) RNA led to transcription of a subgenomic DI RNA in helper virus-infected cells was established. In the present study, a DI cDNA containing one UCUAAAC consensus sequence in the middle of the 0.3-kb-long intergenic region located between genes 6 and 7 was constructed. From this DI cDNA clone, 21 mutant DI RNAs were constructed so that each of the seven consensus sequence nucleotides was changed individually to the three alternative bases. These mutants were used to define how changes in the integrity of MHV transcription consensus sequence UCUAAAC affected mRNA transcription. Except for two mutants with the sequences UGUAAAC and UCGAAAC, all of the mutants supported efficient subgenomic DI RNA transcription. This indicated that MHV transcription regulation was sufficiently flexible to recognize altered consensus sequences. Next, these and other mutants were used to examine the leader-body fusion site on the subgenomic DI RNAs. Sequence analysis demonstrated that all subgenomic DI RNAs analyzed contained two pentanucleotide sequences; the first sequence seemed to be contributed by the leader, and the leader-body fusion most likely took place at either the first or the second nucleotide of the second sequence. This observation was not consistent with the proposed coronavirus transcription model (S. C. Baker and M. M. C. Lai, EMBO J. 9:4173-4179, 1990) which states that nucleotide mismatch can be corrected by RNA polymerase proofreading activity.

Base Sequence↗
PubMed2001

Effect of intragenic rearrangement and changes in the 3' consensus sequence on NSP1 expression and rotavirus replication.

The nonpolyadenylated mRNAs of rotavirus are templates for the synthesis of protein and the segmented double-stranded RNA (dsRNA) genome. During serial passage of simian SA11 rotaviruses in cell culture, two variants emerged with gene 5 dsRNAs containing large (1.1 and 0.5 kb) sequence duplications within the open reading frame (ORF) for NSP1. Due to the sequence rearrangements, both variants encoded only C-truncated forms of NSP1. Comparison of these and other variants encoding defective NSP1 with their corresponding wild-type viruses indicated that the inability to encode authentic NSP1 results in a small-plaque phenotype. Thus, although nonessential, NSP1 probably plays an active role in rotavirus replication in cell culture. In determining the sequences of the gene 5 dsRNAs of the SA11 variants and wild-type viruses, it was unexpectedly found that their 3' termini ended with 5'-UGAACC-3' instead of the 3' consensus sequence 5'-UGACC-3', which is present on the mRNAs of nearly all other group A rotaviruses. Cell-free assays indicated that the A insertion into the 3' consensus sequence interfered with its ability to promote dsRNA synthesis and to function as a translation enhancer. The results provide evidence that the 3' consensus sequence of the gene 5 dsRNAs of SA11 rotaviruses has undergone a mutation causing it to operate suboptimally in RNA replication and in the expression of NSP1 during the virus life cycle. Indeed, just as rotavirus variants which encode defective NSP1 appear to have a selective advantage over those encoding wild-type NSP1 in cell culture, it may be that the atypical 3' end of SA11 gene 5 has been selected for because it promotes the expression of lower levels of NSP1 than the 3' consensus sequence.

Amino Acid Sequence↗
PubMed1994

Hox proteins have different affinities for a consensus DNA site that correlate with the positions of their genes on the hox cluster.

The hox genes, members of a family of essential developmental regulators, have the intriguing property that their expression in the developing murine embryo is colinear with their chromosomal organization. Members of the hox gene family share a conserved DNA binding domain, termed the homeodomain, which mediates interactions of Hox proteins with DNA regulatory elements in the transcriptional control regions of target genes. In this study, we characterized the DNA binding properties of five representative members of the Hox family: HoxA5, HoxB4, HoxA7, HoxC8, and HoxB1. To facilitate a comparative analysis of their DNA binding properties, we produced the homeodomain regions of these Hox proteins in Escherichia coli and obtained highly purified polypeptides. We showed that these Hox proteins interact in vitro with a common consensus DNA site that contains the motif (C/G)TAATTG. We further showed that the Hox proteins recognize the consensus DNA site in vivo, as determined by their ability to activate transcription through this site in transient transfection assays. Although they interact optimally with the consensus DNA site, the Hox proteins exhibit subtle, but distinct, preferences for DNA sites that contain variations of the nucleotides within the consensus motif. In addition to their modest differences in DNA binding specificities, the Hox proteins also vary in their relative affinities for DNA. Intriguingly, their relative affinities correlate with the positions of their respective genes on the hox cluster. These findings suggest that subtle differences in DNA binding specificity combined with differences in DNA binding affinity constitute features of the "Hox code" that contribute to the selective functions of Hox proteins during murine embryogenesis.

Amino Acid Sequence↗
PubMed2005

EULAR/PReS endorsed consensus criteria for the classification of childhood vasculitides.

BACKGROUND: There has been a lack of appropriate classification criteria for vasculitis in children. OBJECTIVE: To develop a widely accepted general classification for the vasculitides observed in children and specific and realistic classification criteria for common childhood vasculitides (Henoch-Schönlein purpura (HSP), Kawasaki disease (KD), childhood polyarteritis nodosa (PAN), Wegener's granulomatosis (WG), and Takayasu arteritis (TA)). METHODS: The project was divided into two phases: (1) the Delphi technique was used to gather opinions from a wide spectrum of paediatric rheumatologists and nephrologists; (2) a consensus conference using nominal group technique was held. Ten international experts, all paediatricians, met for the consensus conference. Agreement of at least 80% of the participants was defined as consensus. RESULTS: Consensus was reached to base the general working classification for childhood vasculitides on vessel size. The small vessel disease was further subcategorised into "granulomatous" and "non-granulomatous." Final criteria were developed to classify a child as HSP, KD, childhood PAN, WG, or TA, with changes introduced based on paediatric experience. Mandatory criteria were suggested for all diseases except WG. CONCLUSIONS: It is hoped that the suggested criteria will be widely accepted around the world because of the reliable techniques used and the international and multispecialist composition of the expert group involved.

Child↗
PubMed2003

An evidence and consensus based guideline for the management of a child after a seizure.

OBJECTIVE: An evidence and consensus based guideline for the management of the child who presents to hospital having had a seizure. It does not deal with the child who is still seizing. The guideline is intended for use by junior doctors, and was developed for this common problem (5% of all paediatric medical attenders) where variation in practice occurs. OPTIONS: Assessment, investigations (biochemistry, lumbar puncture, serum anticonvulsant levels, EEG in particular), and/or admission are examined. OUTCOMES: The guideline aims to direct junior doctors in recognising those children who are at higher risk of serious intracranial pathology including infection, and conversely to recognise those children at low risk who are safe to go home. EVIDENCE: A systematic review of the literature was performed. Articles were identified using the electronic data bases Medline (from 1966 to June 1998), Embase (from 1980 to June 1998) and Cochrane (to June 1998), and selected if they investigated the specified clinical question. Personal reviews were excluded. Selected articles were appraised, graded, and synthesised qualitatively. Statements of recommendation were made. CONSENSUS: An anonymous, postal Delphi consensus development was used. A national panel of 30 medical and nursing staff regularly caring for these children were asked to grade their agreement with the statements generated. They were sent the relevant original publications, the appraisals, and literature review. On the second and third rounds they were asked whether they wished to re-grade their agreement in the light of other panellists' responses. Consensus was defined as 83% of panellists agreeing with the statement. Recommendations in brief: For afebrile seizures all children should have their blood pressure recorded, but no other investigations are routine although a seizing or somnolent child should have blood glucose measured; all children under 1 year should be admitted. For seizures with fever, clinical signs indicating the need to treat as meningitis are given. Children should be admitted if they are under 18 months old, have had a complex seizure, or after pretreatment with antibiotics. VALIDATION: The guideline has undergone implementation and evaluation in a paediatric accident and emergency department, the results of which will be published separately. Only one alteration was made to the guideline as a result of this validation process, which is included here.

Algorithms↗
PubMed1999

Gastric precancerous lesions: heading for an international consensus.

As pathological criteria lie at the foundation for the classification of many diseases, a crucial requisite for such classifications to be valid is that their morphological basis be standardised. Inadequately standardised diagnostic criteria result in unacceptable interobserver variation, a factor that may influence both individual patient care and the evaluation of clinical protocols. One of the most important goals in gastric diseases today is to establish whether cure of Helicobacter pylori is an effective preventive measure against gastric cancer. To tackle this issue it is necessary to measure reliably intermediate outcomes, specifically gastric atrophy and dysplasia. However, there is little agreement on what gastric atrophy and atrophic gastritis are, and treatment and follow up results obtained at one clinical centre are often radically different from those obtained at another. Similarly, studies that examine the fate of dysplastic lesions in the stomach show a great divergence of outcomes between Europe and North America and Japan, where the concept of dysplasia has different connotations. To reach a consensus on the definitions and diagnostic criteria for atrophy and atrophic gastritis, a group of gastrointestinal pathologists and gastroenterologists met in Houston, Texas, USA, in February 1998. Substantive progress was made, but several problems remained, and a study aimed at resolving the issues that seem to stand in the way of an international agreement is currently underway. To fulfil the need for a broad discussion on the diagnostic differences of gastric dysplasia and cancer between East and West, an international group of pathologists gathered in Padova, Italy, in the spring of 1998. Their main objectives were: (1) to agree on the definitions of the spectrum of gastric preneoplastic lesions; (2) to establish an international glossary for gastric precancerous lesions; and (3) to test the consensus and eventually generate guidelines useful to clinicians for the development of management strategies. A consensus was achieved on the definition of gastric dysplasia as preinvasive neoplasia. Other validation studies are underway. The experiences achieved in the search for an international consensus on the phenotypes of atrophic gastritis and gastric dysplasia may represent a model in dealing with the new scenario of a modern evidence-based pathology.

Atrophy↗
PubMed2006

Multidisciplinary consensus on the terminology and classification of complaints of the arm, neck and/or shoulder.

BACKGROUND: There is no universally accepted way of labelling or defining upper-extremity musculoskeletal disorders. A variety of names are used and many different classification systems have been introduced. OBJECTIVE: To agree on an "unambiguous language" concerning the terminology and classification that can be used by all relevant medical and paramedical disciplines in the Netherlands. METHODS: A Delphi consensus strategy was initiated. The outcomes of a multidisciplinary conference were used as a starting point. In total, 47 experts in the field of upper-extremity musculoskeletal disorders were delegated by 11 medical and paramedical professional associations to form the expert panel for the Delphi consensus strategy. Each Delphi round consisted of a questionnaire, an analysis and a feedback report. RESULTS: After three Delphi rounds, consensus was achieved. The experts reported the consensus in a model. This so-called CANS model describes the term, definition and classification of complaints of arm, neck and/or shoulder (CANS) and helps professionals to classify patients unambiguously. CANS is defined as "musculoskeletal complaints of arm, neck and/or shoulder not caused by acute trauma or by any systemic disease". The experts classified 23 disorders as specific CANS, because they were judged as diagnosable disorders. All other complaints were called non-specific CANS. In addition, the experts defined "alert symptoms" on the top of the model. CONCLUSIONS: The use of the CANS model can increase accurate and meaningful communication among healthcare workers, and may also have a positive influence on the quality of scientific research, by enabling comparison of data of different studies.

Arm↗
PubMed2001

Formal consensus: the development of a national clinical guideline.

BACKGROUND: There is currently a political enthusiasm for the development and use of clinical guidelines despite, paradoxically, there being relatively few healthcare issues that have a sound research evidence base. As decisions have to be made even where there is an undetermined evidence base and that limiting recommendations to where evidence exists may reduce the scope of guidelines, thus limiting their value to practitioners, guideline developers have to rely on various different sources of evidence and adapt their methods accordingly. This paper outlines a method for guideline development which incorporates a consensus process devised to tackle the challenges of a variable research evidence base for the development of a national clinical guideline on risk assessment and prevention of pressure ulcers. METHOD: To inform the recommendations of the guideline a formal consensus process based on a nominal group technique was used to incorporate three strands of evidence: research, clinical expertise, and patient experience. RESULTS: The recommendations for this guideline were derived directly from the statements agreed in the formal consensus process and from key evidence-based findings from the systematic reviews. The existing format of the statements that participants had rated allowed a straightforward revision to "active" recommendations, thus reducing further risk of subjectivity entering into the process. CONCLUSIONS: The method outlined proved to be a practical and systematic way of integrating a number of different evidence sources. The resultant guideline is a mixture of research based and consensus based recommendations. Given the lack of available guidance on how to mix research with expert opinion and patient experiences, the method used for the development of this guideline has been outlined so that other guideline developers may use, adapt, and test it further.

Adult↗
PubMed1995

Recognition of consensus CHO structure in ligands for selectins by novel antibody against sialyl Lewis X.

The selectins (L, E, and P) play an important role in the earliest events of the inflammatory response, leading to the "rolling" phenomenon. All selectins react with sialyl Lewis X (SLex) in vitro, possibly suggesting that their ligands have a consensus structure. 2H5 is a monoclonal antibody against SLex that blocks L-selectin-mediated adhesion. 2H5 inhibited adhesion of HL-60 cells to P- and E-selectin-producing COS cells in vitro and immunoprecipitated a P-selectin glycoprotein ligand-1-like glycoprotein from HL-60 cell lysate, suggesting that it recognizes a functional consensus structure on the ligands for all selectins. 2H5 reacted not only with human but also with rat and mouse neutrophils. 2H5 is the first antibody against SLex that recognizes neutrophils of nonhuman mammals. The carbohydrate structure recognized by 2H5 was present not only on high endothelial venules of rat lymphoid organs but also on the endothelial cells of nonlymphoid organs. Furthermore, administration of the antibody markedly inhibited L- and P-selectin-mediated neutrophil rolling and adhesion in rat mesenteric venules in vivo. These results provide evidence for the presence of a consensus carbohydrate structure on the ligands for all selectins. The consensus structure thus has the potential to serve as a therapeutic target.

Animals↗