Biomedical subjects

Patrick Weber

Publications and source records attributed to Patrick Weber.

9 recordsLinked to original sources

PubMed2006

Antibody repertoire development in fetal and neonatal piglets. XIII. Hybrid VH genes and the preimmune repertoire revisited.

The expressed porcine VH genes belong to the VH3 family (clan), four of which, VHA, VHB, VHC, and VHE, alone comprise approximately 80% of the preimmune repertoire. However, so-called "hybrid" VH genes that use CDR1 of one VH gene and the CDR2 of another are frequently encountered. We studied > 3000 cloned VDJs and found that such hybrids can contribute up to 10% of the preimmune repertoire. Based on the 1) recovery of hybrid VH genes from bacterial artificial chromosome clones, 2) frequency of occurrence of certain hybrids in the preimmune repertoire, and 3) failure to recover equal numbers of reciprocal hybrids, we concluded that some chimeric genes are present in the genome and are not PCR artifacts. Two chimeric germline genes (VHZ and VHY), together with VHF and the four genes mentioned above, constitute the major VH genes and these account for > 95% of the preimmune repertoire. Diversification of the preimmune IgG and IgM repertoires after environmental exposure was mainly due to somatic hypermutation of major VH genes with no evidence of gene conversion. Somatic hypermutation was 3- to 10-fold higher in CDRs than in framework regions, most were R mutations and transversions and transitions equally contributed. Data were used to 1) develop an index to quantify the degree of VH repertoire diversification and 2) establish a library of 29 putative porcine VH genes. One-third of these genes are chimeric genes and their sequences suggest that the porcine VH genome developed by duplication and splicing from a small number of prototypic genes.

Animals↗

PubMed2006

Influence of lignification and feruloylation of maize cell walls on the adsorption of heterocyclic aromatic amines.

Both epidemiological and experimental data indicate that a diet rich in fiber may reduce cancer risk. One possible mechanism is by adsorbing carcinogens and transporting them out of the body without metabolic activation. We investigated the role of fiber lignification and feruloylation on the adsorption of four of the most relevant heterocyclic aromatic amines in food: 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), and 2-amino-9H-pyrido[2,3-b]indole (AalphaC). Adsorption experiments, under conditions mimicking the small intestine, were carried out using nonlignified and artificially lignified primary maize walls with defined lignin and ferulate/diferulate concentrations and defined lignin compositions. Lignin concentration and composition both influenced the adsorption of heterocyclic aromatic amines, especially the more hydrophobic types. Heterocyclic aromatic amine adsorption increased with lignin concentration. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine and 2-amino-9H-pyrido[2,3-b]indole were better adsorbed by guaiacyl-rich lignins, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline by syringyl-rich lignins, whereas the adsorption of 2-amino-3-methylimidazo[4,5-f]quinoline was not clearly influenced by lignin composition. Nonlignified cell walls adsorbed lesser amounts of heterocyclic aromatic amines. Variations in cell wall feruloylation had no effect on heterocyclic aromatic amine adsorption.

Adsorption↗

PubMed2005

Health search engine with e-document analysis for reliable search results.

OBJECTIVE: After a review of the existing practical solution available to the citizen to retrieve eHealth document, the paper describes an original specialized search engine WRAPIN. METHOD: WRAPIN uses advanced cross lingual information retrieval technologies to check information quality by synthesizing medical concepts, conclusions and references contained in the health literature, to identify accurate, relevant sources. Thanks to MeSH terminology [1] (Medical Subject Headings from the U.S. National Library of Medicine) and advanced approaches such as conclusion extraction from structured document, reformulation of the query, WRAPIN offers to the user a privileged access to navigate through multilingual documents without language or medical prerequisites. RESULTS: The results of an evaluation conducted on the WRAPIN prototype show that results of the WRAPIN search engine are perceived as informative 65% (59% for a general-purpose search engine), reliable and trustworthy 72% (41% for the other engine) by users. But it leaves room for improvement such as the increase of database coverage, the explanation of the original functionalities and an audience adaptability. CONCLUSION: Thanks to evaluation outcomes, WRAPIN is now in exploitation on the HON web site (http://www.healthonnet.org), free of charge. Intended to the citizen it is a good alternative to general-purpose search engines when the user looks up trustworthy health and medical information or wants to check automatically a doubtful content of a Web page.

Europe↗

PubMed2005

Antibody repertoire development in fetal and neonatal piglets. IX. Three pathogen-associated molecular patterns act synergistically to allow germfree piglets to respond to type 2 thymus-independent and thymus-dependent antigens.

Newborn piglets maintained germfree (GF) cannot respond to either thymus-dependent (TD) or type 2 thymus-independent Ags (TI-2) unless colonized with bacteria. We show here that pathogen-associated molecular patterns (PAMPs), including muramyl dipeptide (MDP), LPS, and a B-class CpG oligonucleotide (CpG-B), can substitute for gut flora in the induction of neonatal immunoresponsiveness. These PAMPs alone or in combination had little effect on serum IgG and IgA levels, but CpG-B and CpG-B + MDP elevated total IgM levels 3- to 7-fold above that seen in colonized controls after booster immunization. Although only CpG-B could alone stimulate immunoresponsiveness, co-administration of LPS or MDP resulted in a 5-fold increase in the IgG response to both immunogens. Co-administered MDP did not promote secondary IgG responses to either Ag but instead pronounced secondary IgM responses to the epitopes of both immunogens. LPS co-administered with CpG-B may promote class switch recombination or cause differentiation of previously switched cells that become responsive after exposure to CpG-B. Primary and secondary IgG responses equally recognized the epitopes of the TI-2 and TD immunogens, whereas IgM responses favored the TI-2 epitope. Because PAMPs alone can result in Abs to 2,4,6-triitrophenyl and FLU without immunization, it suggests they alone cause differentiation of B cells of the preimmune repertoire. The finding that both bacterial PAMPs and colonization are capable of stimulating Ab responses in both immunized and nonimmunized piglets suggests that PAMPs derived from host flora may play a major role in awakening adaptive immunity in neonates.

Acetylmuramyl-Alanyl-Isoglutamine↗

PubMed2005

Antibody repertoire development in fetal and neonatal piglets. XI. The thymic B-cell repertoire develops independently from that in blood and mesenteric lymph nodes.

The origin and function of thymic B cells is currently unresolved. In the present study we compared V(H) gene repertoire diversification in >3500 cloned VDJs (from 11 animals at three time-points, using three to five animals per time-point) that were expressed with immunoglobulin (Ig)M, IgD, IgG, IgA and IgE in thymus, mesenteric lymph nodes (MLN) and peripheral blood B cells (PBB) of newborn piglets and 5-week-old isolator piglets maintained germfree (GF) or colonized with Escherichia coli. The results showed that the repertoire expressed with IgM, IgD, IgG and IgA in PBB and MLN remained polyclonal, undiversified and unselected in piglets maintained GF for 5 weeks, that age and colonization resulted in significant repertoire diversification of IgG and IgA in the MLN and of IgG in blood, that the thymic B-cell repertoire was polyclonal, unaffected by colonization and showed no clonal selection in any isotype, and that the thymic IgA and IgE repertoires were more diverse at birth than the repertoire of any isotype in MLN or PBB. IgD was seldom recovered from the PBB of newborn piglets or at any time-point in thymus, but was recovered in the MLN of all 11 animals examined. The IgD and IgM repertoires in all tissues remained polyclonal and unselected, although V(H) usage by IgD transcripts did not always parallel that of IgM in the same tissue. Therefore, isotype-switched B cells in the thymic medulla cannot be accounted for by immigration of B cells diversified by colonization of the gut, and thymic B cells undergo switch recombination and repertoire diversification before birth without clonal selection.

Animals↗

PubMed2004

Medical activities and statistics.

The evaluation of the medical activity is a major concern for hospitals and public health services. With the introduction of coding (IDC-10 and CHOP classifications) hospitals are now able to analyze their medical activity. A way to improve physicians' acceptance in analyzing their work is to give them valuable feedback information. Building statistics tools is costly and time consuming. Therefore introducing data warehouse tools is helpful. Nice Code is an easy-to-use software that helps medical encoding while immediately offering understandable statistics. In Switzerland, physicians demand real feedback based on the data transmitted at the "cantonal" or federal levels and more transparency in third payer's decisions. In this respect, several cantons decided to equip public health services and hospitals with this tool. The goal is to give, physicians and economists, powerful tools for analyzing the medical activity.

Hospital Information Systems↗

PubMed2002

Antibody repertoire development in fetal and neonatal piglets. VIII. Colonization is required for newborn piglets to make serum antibodies to T-dependent and type 2 T-independent antigens.

Cesarean-derived piglets were reared for 5 wk under germfree conditions or monoassociated with a benign Escherichia coli (G58-1) or a enterohemorrhagic strain (933D) derived from O157:H7, and immunized i.p. with the T-dependent (TD) Ags fluorescein-labeled (FL) keyhole limpet hemocyanin or trinitrophenylated (TNP) keyhole limpet hemocyanin and the type 2 T-independent Ags TNP-Ficoll or FL-Ficoll. Only colonized piglets showed an increase in serum IgG, IgA, and IgM and had serum Abs to FL, TNP, and colonizing bacteria. While serum Abs to FL or TNP appeared following colonization alone, secondary responses were restricted to piglets immunized using TD carriers. While animals colonized with 933D had significantly higher total serum IgG and IgM levels and specific IgG Abs than those colonized with G58-1, no differences were seen in serum IgA levels, B cell diversification in the ileal Peyer's patches, and specific activity (ELISA activity per micrograms of Ig) of pre-boost serum IgG and IgM anti-TNP and anti-FL Abs. Serum IgA Abs to TNP, FL, or bacteria were not detected. Ag-driven responses, as measured by an increase in specific Ab activity, were only observed in secondary responses to TD Ags and to colonizing, pathogenic E. coli. We propose that germline-encoded, isotype-switched B cells in newborn piglets differentiate to Ab-secreting cells 1) after stimulation by bacteria-activated APCs or 2) through direct stimulation by bacterial products. We further propose that Ag-driven systemic responses require both bacterial colonization and TD Ags translocated to the peritoneum.

Animals↗

PubMed2002

Secure exchange of medical data: requirements and solutions.

It is now common to access and to exchange data through computer networks. The major applications used are Web access and, e-mail. But while there is no security concern when accessing classical or anonymous data, the exchange of sensitive data (e.g. patient-related information) is subject to legal constraints. This paper summarizes the current legal obligations in Switzerland and presents state of the art techniques for applying the legal rules. A commercial implementation in Switzerland is taken as illustration.

Computer Security↗

PubMed2002

Multilingual approach to ICD10: on the need for a source reference database.

The distribution of ICD10 is of concern for thousand of developers in numerous countries. The absence of some basic features to facilitate the transfer and consequently to augment the quality of the delivered version is a constant characteristic. Errors, ambiguities, missing terms, unrecognised attributes are quite common, despite the efforts of some national centres doing their best to fill this gap. For other countries and languages, where such centres do not exist or do not have sufficient resources, this problem is even stronger. A reference ICD database is clearly a need today. The following features are to be made available out of an ICD database: exact count of terms, whether they are systematic, include, exclude or daggers and asterisks pairs, eventually at chapter level; exact count of notes, references and indirect exclusions; recommended structure of relational tables for ICD representation; basic structure of the classification at any level of detail. These features are somewhat language dependant and should be repeated for each one. This paper demonstrates the benefits of publishing such ICD reference information in order to improve the future ICD tools to be developed in numerous countries.

Database Management Systems↗