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Biomedical subjects

M E Devey

Publications and source records attributed to M E Devey.

At least 19 recordsLinked to original sources
PubMed2004

Detection and verification of quantitative trait loci for resistance to Dothistroma needle blight in Pinus radiata.

Six related radiata pine ( Pinus radiata) full-sib families were used to detect and independently verify quantitative trait loci (QTLs) for resistance to Dothistroma needle blight, caused by Dothistroma septospora. The detection families had from 26 to 30 individuals each, and had either a common maternal (31053) or paternal (31032) parent; one family (cross 4) consisted of progeny from both parents, 31053 x 31032. Approximately 200 additional progeny from cross 4 were clonally replicated and planted at two sites, with at least five to seven ramets of each individual per site. Marker segregation data were collected from a total of 250 RFLP and microsatellite markers, and single factor ANOVAs were conducted separately for each family and marker. A number of putative associations were observed, some across more than one family. Permutation tests were used to confirm expected probabilities of multiple associations based on chance alone. Seven markers representing at least four QTLs for resistance to Dothistroma were identified as being significant in more than one family; one of these was significant at P<0.05 in three families and highly significant at P<0.01 in a fourth. Further confirmation was obtained by testing those markers that were significant in more than one of the detection families (or highly significant in cross 4) in the clonally replicated progeny from cross 4. Four QTL positions were verified in the clonal populations, with a total percent variation accounted for of 12.5.

Analysis of Variance↗
PubMed2003

QTL associations for density and diameter in Pinus radiata and the potential for marker-aided selection.

A large full-sib family of radiata pine ( Pinus radiata Donn. ex D. Don) was used for quantitative trait locus (QTL) detection and independent verification. QTL detection experiments were carried out for juvenile wood density (JWD) and stem diameter at breast height (DBH) using selective genotyping. Evenly spaced RFLP and microsatellite markers were selected from an existing linkage map. QTLs were verified in an independent set of progeny from the same family. Based on map location, at least eight QTL positions for JWD and two for DBH were detected and verified. The percent variance accounted for by the markers ranged from 0.78% to 3.58%, suggesting a genomic architecture of many genes with small effect. Two unrelated "bridging" families were chosen as candidates for marker-aided selection (MAS), and six microsatellite markers showing an association with JWD or DBH were tested in these families. Of these, four markers showed a consistent association with JWD in one or both of the bridging families. Results from this study provide a basis for MAS in P. radiata.

Analysis of Variance↗
PubMed2002

A set of microsatellite markers for fingerprinting and breeding applications in Pinus radiata.

Fifty microsatellite markers were developed and characterized in Pinus radiata, and from among these, a subset of 10 easily scored and highly polymorphic markers was selected for use in fingerprinting, quality control, and breeding applications. The markers were characterized based on reliable and reproducible amplification, observed and expected heterozygosities, number of alleles, a low frequency of null alleles, and a lack of close linkage with other selected markers. Allele numbers and frequencies were estimated using 24 first-generation breeding clones from Australia and New Zealand. Observed heterozygosities for the selected markers were all greater than 0.67, and there was an average of 10.5 alleles/locus. The occurrence of null alleles was checked with megagametophytes from mother trees for loci that appeared to be homozygous. The 10 markers are not closely linked (r < 0.20 and LOD > 3) to each other. The selected microsatellites fall into three discrete size classes, and with appropriate selection of fluorescent dyes for 5' end labeling, can be multiplexed with up to 6 markers/sample on an ABI PRISM 310 or similar instrument.

Alleles↗
PubMed1999

Bibliometric methods for the evaluation of arthritis research.

This study uses bibliometric methods to evaluate the magnitude and quality of publications in arthritis research in the UK and compare this with that of other countries. Arthritis research was defined by publication in a specialist journal or by specific title key words or address. Outputs from 13 countries between 1988 and 1995 were analysed by number, research level (from clinical to basic) and potential impact on other researchers (from low to high). The UK has a strong presence in arthritis research and the highest relative commitment of all the countries studied. UK output was more clinical than that of other countries, except Spain, and was of relatively high impact. A second study examined UK arthritis papers supported by different funding sources, including government, private-non-profit and industry. Papers with funding acknowledgements were of significantly higher impact and less clinical than those without. The Arthritis Research Campaign was the leading funder in the UK with high-impact papers which, over the 8 yr period, have become more clinical than those supported by other funding sources, except hospital trusts.

Arthritis↗
PubMed1995

Random amplified polymorphic DNA markers tightly linked to a gene for resistance to white pine blister rust in sugar pine.

We have genetically mapped a gene for resistance to white pine blister rust (Cronartium ribicola Fisch.) in sugar pine (Pinus lambertiana Dougl.) by using an approach which relies on three factors: (i) the ability to assay for genetic markers in the haploid stage of the host's life cycle, using megagametophyte seed tissue; (ii) a simple and clearly defined pathosystem; and (iii) the use of random amplified polymorphic DNA (RAPD) markers that can be quickly and efficiently evaluated. Resistance to white pine blister rust in sugar pine is known to be controlled by a single dominant gene (R). Maternal segregation of R and dominant RAPD markers were scored simultaneously following collection of megagametophytes for DNA assays and seedling inoculation with C. ribicola. Bulked samples of haploid megagametophyte DNA from resistant and susceptible offspring of segregating full-sib and half-sib families were used to evaluate 800 random decanucleotide primers. Ten loci linked with the gene for resistance to white pine blister rust were identified and segregation data were obtained from five families. Six of the linked markers were within 5 centimorgans of the gene, and one marker was 0.9 centimorgan from R. These and other markers derived by this approach may provide starting points for map-based cloning of this important gene.

Journal Article↗
PubMed1994

Occurrence and inheritance of microsatellites in Pinus radiata.

Microsatellites are an important class of DNA marker because of their abundance and length hypervariability. As part of a project mapping the Pinus radiata genome, we have characterized some of the microsatellites in this species. Southern blots were screened with oligonucleotide probes [(CA)10, (GA)10, (GAA)9, (CAA)8, (CAC)5, (GACA)4] to assess their abundance. CA and GA were the most abundant microsatellites, while GAA was least abundant. A genomic library in lambda ZAP, covering 9 x 10(4) kb, was screened with a combined poly(CA) + poly(GA) probe and yielded 120 positives, approximately one CA or GA microsatellite every 750 kb of the P. radiata genome. It was found that 25% of the positives were embedded within highly repetitive DNA. Four of the five subclones sequenced contained compound microsatellites, with TA predominating as the additional repeat. Segregation analysis of PCR products for two microsatellites, PR4.6 and PR9.3, in 96 progeny of a controlled outcross verified simple Mendelian inheritance. Both loci are highly polymorphic with Polymorphism Information Content values of 0.63 and 0.70 for PR4.6 and PR9.3, respectively. These results indicate that microsatellites are abundant in a conifer genome and can be valuable markers for pine mapping, fingerprinting, and population genetic studies.

Base Sequence↗
PubMed1993

The functional affinities of antibodies of different IgG subclasses to dietary antigens in mothers and their babies.

The quantity and functional affinities of IgG1 and IgG4 antibodies to the dietary antigens casein and ovalbumin were measured in unselected mothers and their 1-year-old infants. In these infants, the titre of IgG antibodies to both antigens was highest in the IgG1 subclass, while in their mothers the titre of IgG1 and IgG4 antibodies to these foods was similar. High affinity IgG4 responses to both casein and ovalbumin were frequently found in mothers, whilst IgG1 responses, particularly to ovalbumin, were of low functional affinity. By contrast, in the 1-year-old infants, the functional affinity of IgG1 antibody to ovalbumin was substantially higher than in their mothers (Student's paired t-test, P < 0.001), indicating that higher affinity IgG1 antibody was produced on first exposure to ovalbumin rather than following chronic exposure. The effect of antigenic load on affinity maturation was further investigated by comparing the affinity of IgG1 antibody to casein in bottle, mixed and breast fed infants. Bottle fed infants had significantly higher-affinity IgG1 antibodies to casein compared with breast or mixed fed infants (Student's unpaired t-test, P < 0.01 and 0.02), suggesting that antigen exposure via the gut was able to drive the affinity maturation process. In studying the immune response it is clear that account must be taken of the affinity as well as of the titre of the antibody produced.

Antibody Affinity↗
PubMed1990

Low affinity antibodies against collagen type II are associated with pathology in collagen-induced arthritis in mice.

The relationship between the functional affinity of antibodies against type II collagen (CII) and the development of arthritis was studied in mice with collagen-induced arthritis. The responses of DBA/1 strain mice were compared with those of mice selectively bred to produce antibodies of high functional affinity (HA mice) and low functional affinity (LA mice). HA and LA mice did not develop arthritis in response to immunization with CII whereas 86% of DBA/1 mice did, with 33% showing severe and 53% mild disease. Anti-CII antibodies of the highest titre, the lowest functional affinity, and the greatest affinity heterogeneity were associated with the development of the severest arthritis in DBA/1 mice: even in DBA/1 mice with moderate or no disease the amount of antibody and heterogeneity were higher and functional affinity lower than in either HA or LA mice. Antibodies of the G1, 2a, 2b and 3 subclasses were produced in all mice, and none of these alone accounted for the overall difference in IgG antibody titres or affinity in the groups of mice. Antibodies of the IgG2a subclass showed the closest association with the development of arthritis in the different groups. It is concluded that anti-CII antibodies of low functional affinity, and presumably also of the IgG2a subclass, influence the disease process in collagen arthritis.

Animals↗
PubMed1990

The role of antibody affinity and titre in immunity to Schistosoma mansoni following vaccination with highly irradiated cercariae.

Sera from rabbits and rats vaccinated with highly irradiated cercariae of Schistosoma mansoni (VRabS, VRatS) were found to be of substantially higher affinity than sera from CBA mice vaccinated four times (4 X CVMS), single sex sera (SSS) or chronic infection sera (CIS). In contrast, VRabS and SSS appeared to possess the highest titres of antibody, followed by CIS and VRatS, with 4 X CVMS displaying the lowest titre. Two mouse strains selectively bred for high-affinity (HA) or low-affinity (LA) antibody following vaccination were tested for their ability to resist a challenge infection. LA mice, which produce high titres of low-affinity antibody, manifested significantly more resistance than HA mice, which produce low titres of high-affinity antibody. Immunoprecipitation studies demonstrated that sera from vaccinated LA mice (LVMS) recognized 125I-labelled schistosomular surface antigens more intensely than sera from vaccinated HA mice (HVMS). However, peritoneal macrophages from HA and LA mice in the presence of HVMS, LVMS or 4 X CVMS, and naive macrophages activated in vitro with interferon-gamma (IFN-gamma)/lipopolysaccharide (LPS) mediated comparable levels of schistosomula killing in vitro. The experiments described here provide evidence that the titre of antibody rather than its affinity may be a more critical factor in the development of optimal immunity to S. mansoni.

Animals↗
PubMed1990

Experimental allergic encephalomyelitis (EAE) in mice selectively bred to produce high affinity (HA) or low affinity (LA) antibody responses.

Induction of experimental allergic encephalomyelitis (EAE) in mice genetically selected to produce either high affinity (HA) or low affinity (LA) antibody responses has revealed significant differences in disease susceptibility between the two lines. HA mice were highly susceptible to EAE following subcutaneous sensitization to mouse central nervous system (CNS) tissue emulsified in Freund's complete adjuvant (FCA). Furthermore, of HA mice surviving acute EAE, up to 93% subsequently developed chronic relapsing disease (CREAE) characterized by variable demyelinating inflammatory changes within the spinal cord. In contrast, LA mice, despite having a major histocompatability complex (MHC) haplotype associated with susceptibility to EAE, were highly resistant to the disease and showed no signs of CREAE when observed for up to 100 days post-sensitization. Antibodies to myelin basic protein (MBP) were detected in both lines but rising titres of high functional affinity antibodies were only seen in HA mice. These HA and LA lines of mice provide a new approach to the study of EAE and, in particular, the role of antibody and antibody affinity in the chronic relapsing form of the disease.

Animals↗
PubMed1990

Antibodies of different human IgG subclasses show distinct patterns of affinity maturation after immunization with keyhole limpet haemocyanin.

The functional affinities of antibodies of different IgG subclasses were measured in normal individuals during the primary, secondary and tertiary immune responses to keyhole limpet haemocyanin (KLH). IgG1 responses showed marked affinity maturation between Days 7 and 21 after primary and by Day 7 after secondary and subsequent immunizations, correlating with an expansion of high-affinity antibody populations. When present, IgG2 responses were of low titre but high functional affinity with no change in response to immunization and may represent a T-independent cross-reacting response with a carbohydrate epitope of KLH. IgG3 responses were variable but generally of low titre and low functional affinity, although those of higher titre and affinity were associated with secondary delayed-type hypersensitivity (DTH) and clinical reactions to KLH. In contrast to IgG1, IgG4 antibodies were not detected until 1 year after primary immunization, when they were found at low titre but high functional affinity. Following secondary immunization, IgG4 titres increased rapidly but without any further increase in affinity. The emergence of high-affinity IgG4 antibodies coincided with a loss of the high-affinity IgG1 populations, suggesting a preferential switch with time from high-affinity IgG1 antibodies to IgG4.

Adult↗
PubMed1989

Serial studies on the functional affinity and heterogeneity of antibodies of different IgG subclasses to phospholipase A2 produced in response to bee-venom immunotherapy.

High functional affinity and high titer IgG4 antibodies to phospholipase A2 were produced by allergic patients in response to bee-venom immunotherapy. In contrast, the affinity of IgG1 antibodies decreased after immunotherapy, and both the titer and affinity of IgG1 antiphospholipase A2 remained significantly lower compared to IgG4 1 to 2 years after treatment. Analysis of affinity heterogeneity suggested a loss of IgG1 high-affinity antibody-producing clones during immunotherapy and a preferential expansion of IgG4 clones. High-affinity IgE antibodies were found in untreated allergic patients, and preliminary results suggest that immunotherapy may result in an early marked decrease in the affinity of IgE antibodies.

Adolescent↗
PubMed1989

A human-mouse hybridoma which secretes monoclonal thyroglobulin autoantibody with properties similar to those of the donor patient's serum autoantibody.

Human monoclonal antibodies produced by Epstein Barr (EB) virus transformation and/or cell fusion are frequently IgM antibodies which tend to cross react with a range of antigens and often bear little relationship to the highly specific IgG antibodies associated with human autoimmune disease. By fusing EB virus transformed B lymphocytes from a Hashimoto patient with a mouse myeloma line and selecting for synthesis of IgG class thyroglobulin (Tg) antibody, we have developed a hybridoma (VB/5) secreting Tg antibody of IgG2 subclass and lambda light chain type which has the characteristics of a monoclonal antibody on isoelectric focussing. The antibody has a high affinity for human Tg and recognises Tg from other primates but not non-primate Tg. However, it does not react with human thyroid peroxidase or a panel of other autoantigens. In terms of affinity constant, functional affinity and affinity heterogeneity, the antibody closely resembles the IgG2 lambda Tg antibody present in the serum of the Hashimoto patient whose B lymphocytes were used to develop the hybridoma. In addition to providing a useful reference standard for Tg antibody IgG subclass assays, VB/5 antibody and the hybridoma line provide a valuable starting point for detailed studies of Tg autoantibodies and the genes coding for the variable regions of their heavy and light chains.

Animals↗
PubMed1989

Interferon-gamma as an adjuvant in immunocompromised mice.

We have compared interferon-gamma (IFN-gamma) with saponin and interleukin-1 (IL-1) as adjuvants for a blood-stage malaria vaccine in mice with various immunological abnormalities. IFN-gamma was particularly effective in Biozzi low antibody responder mice, mice selectively bred to produce antibody of low affinity, and mice depleted of CD4+ T cells. IFN-gamma and other cytokines may be safe adjuvants for use in human immunodeficiency states.

Adjuvants, Immunologic↗
PubMed1989

Serial studies on the affinity and heterogeneity of human autoantibodies to thyroglobulin.

The functional affinity and heterogeneity of autoantibodies to thyroglobulin (Tg) were measured by an IgG subclass-specific solid-phase competition ELISA in patients with autoimmune thyroid disease. High-affinity IgG1 and IgG4 antibodies formed the major anti-Tg response. Both titre and affinity of IgG3 and IgG2 anti-Tg were generally low but in some Hashimoto's disease patients high-affinity IgG2 anti-Tg were found and IgG2 anti-Tg, unlike those of other subclasses, showed very restricted heterogeneity. The affinity of IgG4 anti-Tg was similar in patients with thyroid disease and their clinically euthyroid (normal) relatives. In contrast, a progressive increase in IgG1 anti-Tg affinity was seen in clinically euthyroid individuals compared with their relatives with thyroid disease and high titred Hashimoto's disease patients, suggesting that either rising titres of high affinity IgG1 anti-Tg or affinity maturation of IgG1 anti-Tg may be indicative of impending hypothyroidism.

Antibody Affinity↗
PubMed1988

Determination of the functional affinity of IgG1 and IgG4 antibodies to tetanus toxoid by isotype-specific solid-phase assays.

Two solid-phase assays have been used to measure the affinity of IgG1 and IgG4 antibodies to tetanus toxoid (TT) in whole sera. In the first assay, low affinity antibodies were selectively inhibited from binding to solid-phase antigen by a mild chaotropic agent and in the second assay, high affinity antibodies were preferentially inhibited from binding by low concentrations of free antigen. Results from both assays suggest that IgG4 antibodies to TT are of lower functional affinity than IgG1 antibodies and that, in addition, IgG4 responses to TT display a more restricted affinity heterogeneity.

Antibodies, Bacterial↗