An inter-laboratory idiotype assay validation study.
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Enzyme-Linked Immunosorbent Assay↗
Biomedical subjects
E Cairns
Publications and source records attributed to E Cairns.
Multilocus and single locus minisatellite analysis in population biological studies.
In this review we describe the situations in which minisatellite analysis is of value to studies of population and evolutionary biology. Evolutionary and population biologists need to be able to quantify genetic relationships among individual organisms at many different levels, from close familial relationships to evolutionarily distant phylogenetic ones. The use of minisatellite markers is put into this context and compared with the other molecular biological techniques. Examples of the use of multilocus minisatellite analysis in population biology are described. The limitations of multilocus fingerprinting are presented, together with the potential advantages of locus-specific probes. The use of locus-specific probes in population biology is now often feasible due to the recent development of a cloning system which allows their efficient isolation. The availability of locus-specific probes should significantly expand the role of minisatellite markers in population biology.
Animals↗
Northern Ireland: political violence and self-reported physical symptoms in a community sample.
In order to investigate the possible relationship between physical health and political violence in Northern Ireland a random sample of residents of four electoral areas (two with relatively high violence and two with relatively low violence) was interviewed at home. Each person was asked to rate their health in terms of common physical symptoms, to indicate their use of family doctor and hospital services, and to rate the level of political violence in their neighbourhood. Analysis of covariance (with a measure of psychological well-being, a measure of trait neuroticism plus age and socioeconomic status as covariates) revealed that women reported more physical symptoms than did men, people in the 'high' violence areas reported more symptoms than did those in the 'low' violence areas, while those who rated their own neighbourhood most highly in terms of perceived violence also reported the greatest number of physical symptoms. However, a series of chi 2 tests revealed no association between political violence or perceived political violence and uptake of services.
Cross-Sectional Studies↗
The development of psychological well-being in late adolescence.
Studies following adolescents from school to work indicate a sharp decrease in psychological symptoms over the 16-17-year period compared to a more gentle decrease subsequently. This could be a genuine developmental phenomenon, related to school leaving, or because anxiety levels are higher at age 16 years due to approaching examinations. The present study examined these hypotheses. GHQ scores for those at school were related to examination candidacy. Eighteen months later such differences had disappeared among those young people now in full-time employment. Similarly, a group who remained in full-time education also showed a significant decline in GHQ scores.
Adaptation, Psychological↗
Comparative study of idiotypes on monoclonal antibodies derived from patients with lupus and leprosy and from normal individuals.
A collaborative study was performed to compare the expression of a series of idiotypes defined on human anti-DNA and other autoantibodies. Three panels of human monoclonal antibodies were tested: eight derived from patients with systemic lupus erythematosus (SLE); 13 from an individual with lepromatous leprosy; and 38 from normal subjects. The following rabbit anti-idiotype sera were used: one (RId16/6) raised against the lupus-derived monoclonal anti-DNA antibody 16/6, four (RId8E7, RId4G7, RId4D5 and RIdTH9) against leprosy-derived monoclonal antibodies of various specificities, and one (anti-4.6.3) against a normal-derived anti-DNA monoclonal (KIM 4.6). In addition, two other anti-idiotypes were used--one a murine monoclonal (3I), the other a rabbit polyclonal (RIdD)--which had been raised against polyclonal anti-DNA antibodies from lupus serum. Further experiments were performed with immunoabsorbed fractions of RId8E7. Direct-binding and competition assays were used. All of the anti-idiotypes produced different patterns of positivity among the three panels of human monoclonal antibodies, with the exception of RId8E7 and RId4G7, which showed considerable concordance. There was a tendency towards anti-idiotypes being disease- or group-specific: thus anti-4.6.3 failed to bind to any of the lupus or leprosy-derived monoclonals, while RId16/6 and RId8E7 bound most strongly to the lupus- and leprosy-derived antibodies respectively. KIM 4.6 itself was bound only weakly by RId16/6, while 16/6 was not recognized by anti-4.6.3; 16/6 was, however, bound by 3I, while KIM 4.6 was not. 3I bound to several other monoclonals but RIdD, which has been shown to be specific for the anti-DNA fraction of lupus serum, did not bind to any of them. These results indicate that the majority of these anti-idiotype preparations recognize largely separate sets of determinants. The monoclonal antibodies which bind to DNA may be only partly representative of anti-DNA antibodies in the serum of lupus patients.
Antibodies, Anti-Idiotypic↗
Impact of television news exposure on children's perceptions of violence in Northern Ireland.
The present study assessed the impact of television news exposure on Irish children's perceptions of the level of violence in their neighborhoods. Estimates from children (N = 570) of the local levels of violence in three areas (high-, low-, and no-violence) were subjected to a four-way analysis of variance (Area x Sex x Age x News Exposure) that showed a main effect for area and sex with respect to the high-violence area and boys. Two two-way interactions also reached statistical significance. The first suggested that the perception of lower levels of violence by girls was confined to the high- and low-violence areas. The second concerned the level of actual violence and the amount of reported news exposure. Only in the high-violence area were these two variables related: Accurate estimates of actual violence levels were associated with more frequent news exposure.
Child↗
The relationship between adolescent perceived self-competence and attendance at single-sex secondary school.
The study examined young people's self-esteem measured using a multidimensional measure of self-esteem, Harter's Perceived Competence Scale, as well as a measure of locus of control, in relation to the type of school they attended--single-sex or co-educational. A sample of students (N = 2295) from both academic and less academic schools was employed. The results indicated that among children (N = 577) attending the more academic grammar schools only, those who attended single-sex schools had higher levels of academic self-esteem and were more inner oriented in terms of locus of control. There were no differential sex effects, however. Additional analyses suggested that this effect was not likely to be due to selection in terms of socio-economic status.
Achievement↗
A human anti-cardiolipin autoantibody is encoded by developementally restricted heavy and light chain variable region genes.
Based on recent structural analyses of monoclonal autoantibodies, it appears that a number of these antibodies express germ-line immunoglobulin variable region (V) genes with little or no somatic mutation. In addition, our group and others have noted the identity or near identity of some autoantibody-associated V genes to V genes apparently expressed preferentially in the fetal pre-B cell repertoire. To extend these data, we now report that the heavy and light chain V genes of an anti-cardiolipin antibody derived from a healthy individual display 99% nucleotide sequence homology with V genes expressed in early B cell ontogeny. Sequence comparisons indicate the likely use of fetal-restricted V genes by this autoantibody. Taken together with other data on autoantibody V gene usage, these findings provide further evidence for overlap between the autoantibody-associated and early ontogeny expressed V gene repertoires and suggest that natural autoreactivity may be instrumental in the development and maintenance of the normal immune repertoire.
Amino Acid Sequence↗
Analysis of variable region genes encoding a human anti-DNA antibody of normal origin. Implications for the molecular basis of human autoimmune responses.
In order to investigate the genetic basis for natural anti-DNA immune responses, we isolated and sequenced the variable gene elements (VH and VL) encoding an anti-DNA antibody expressed by a human hybridoma of normal origin (Kim4.6) and compared these sequences with those reported for four other human anti-DNA antibodies. The Kim4.6 antibody leader and VH segments were identical in nucleotide sequence with the VH1.9III germ-line VH3 gene, and the Kim4.6VL segment showed 98% nucleotide sequence identity with a V lambda I subgroup gene expressed in a Burkitt's lymphoma. Comparative analysis of Kim4.6 and other human hybridoma anti-DNA antibodies indicated that anti-DNA immune responses are diverse in terms of VH and VL gene utilization but may exhibit a bias toward rearrangement of VH genes that are over-represented in the fetal pre-B cell repertoire. Moreover, Kim4.6 and three of four other sequenced human anti-DNA antibodies appear to use a germ-line diversity gene, DXP'1, which may represent a counterpart of the DFL16.1 segment utilized in murine responses to the hapten nitrophenyl. Taken together, our findings indicate that anti-DNA immune responses can be encoded by nonmutated VH genes and that the elements and molecular mechanisms which engender this response are essentially the same among natural and lupus-associated anti-DNA antibodies. Our data also suggest that natural autoimmune responses originate early in B cell ontogeny as is consistent with the hypothesis that autoreactivity plays a major role in shaping the normal immune repertoire.
Amino Acid Sequence↗
Improving the validity of the GHO30 by rescoring for chronicity: a failure to replicate.
To replicate the finding by Goodchild and Duncan-Jones (1985), that rescoring the GHQ30 in order to take account of chronicity would improve its validity, a random sample of 244 people completed the GHQ. Of these 102 also took part in a second interview in which they were administered the PSE. There was no evidence that the new scoring scheme improved correlations between the GHQ and other measures of morbidity nor did this improve its sensitivity or specificity when validated agaist the PSE.
Adult↗
Coping with political violence in Northern Ireland.
Recent community based research, employing a self-assessed measure of psychological distress, has suggested that people in Northern Ireland may be coping relatively well with the stress of continuing political violence. This paper reports a first direct investigation of coping in Northern Ireland. Using two scales from the Folkman and Lazarus Ways of Coping Questionnaire--Distancing and seeking Social Support--an attempt was made to investigate the role of coping in relation to local levels of violence, the appraisal of violence, gender and trait neutoticism. The results indicated that trait neuroticism was not related to the appraisal of levels of violence, but that appraisal was related to both types of coping. In particular, those who perceived the violence to be more serious reported using less distancing, while they also reported seeking the most social support. In addition more women reported seeking social support compared to men. Finally those who lived in a high violence area were more likely to report using distancing than were those from a less violence prone area. These results were taken to support the contention that some form of denial may be the main form of coping in Northern Ireland, and that coping is related more to the appraisal of violence than to actual violence levels, while the appraisal of violence is in turn not related to trait neuroticism.
Adaptation, Psychological↗
Colour naming of violence-related words in Northern Ireland.
To investigate the hypothesis that people in Northern Ireland are using denial to cope with the impact of political violence, a specially designed version of the Stroop test was developed. English students living in Northern Ireland evidenced significantly greater interference on the Violent Stroop compared to either English students living in England or Northern Irish students living in Northern Ireland suggesting that while the Northern Irish natives had habituated to the violence the English students living in Northern Ireland had not yet done so.
Adult↗
Expression in systemic lupus erythematosus of an idiotype common to DNA-binding and nonbinding monoclonal antibodies produced by normal human lymphoid cells.
Rabbit antiserum raised against a normal-derived monoclonal anti-DNA antibody KIM 4.6.3 (IgM lambda) was used for idiotype analyses. This anti-serum (anti-4.6.3 ID) was rendered specific for KIM 4.6.3 idiotype (4.6.3 ID) by absorption with normal human IgM and IgG. The specificity of anti-4.6.3 was shown by its ability to bind to KIM 4.6.3 antibody but not to normal human IgM and IgG, by inhibition of anti-4.6.3 ID reactivity with KIM 4.6.3 antibody by the homologous monoclonal antibody and by the ability of anti-4.6.3 ID to inhibit the binding of single stranded DNA with KIM 4.6.3 antibody. The 4.6.3 ID was found to be commonly expressed since it was detected among 33% (10/30) DNA and 32% (23/72) non-DNA-reactive monoclonal antibodies that were obtained from five different unrelated normal individuals. The binding to ssDNA of the majority of idiotype positive anti-DNA antibodies however was not blocked by anti-4.6.3 ID suggesting that among these other monoclonal antibodies its expression is outside of the antigen binding site. The 4.6.3 ID, which was present among some normal-derived monoclonal IgM molecules was also found at a high frequency (90%) in the sera of patients with systemic lupus erythematosus (SLE) but only at a low frequency (24%) and concentration in normal sera. The level of 4.6.3 ID in SLE did not correlate with serum IgM and IgG nor with anti-DNA antibody concentrations. Idiotypic relatedness between SLE serum antibodies and monoclonal anti-DNA antibodies of normals implies the existence of a cross-reactive idiotype family and implies that a conserved common gene or closely related genes exist in the germ line encoding these 4.6.3 ID positive antibodies some of which are not exclusively associated with nucleic acid reactivity. The expression of these germ line genes in vivo thus distinguishes SLE from normals.
Antibodies, Monoclonal↗
Social class, psychological wellbeing and minority status in Northern Ireland.
The present study sought to evaluate the completing claims of the social stress hypothesis and the social selection hypothesis which both claim to explain the relationship between social class and psychopathology. Scores on a self-report measure of psychological wellbeing, the General Health Questionnaire (GHQ) were obtained from a random sample of 581 respondents in Northern Ireland. An analysis of variance comparing majority (Protestant) and minority (Catholic) group males and females at three socioeconomic levels produced a Religion X Social Status interaction. This was due to a trend of increasing symptoms with decreasing social status among Protestants and the reverse phenomenon among Catholics. It was concluded that the results while similar to those reported earlier by Cochrane and Stopes-Roe, provided no clear support for either the social selection hypothesis or the social stress hypothesis but were possibly related to local factors connected with emigration or the ongoing political violence in Northern Ireland.
Adaptation, Psychological↗
Sex-role attributes, perceived competence and the development of depression in adolescence.
Studies are described which investigated the relationship of sex-role traits to age trends and sex differences in depression in adolescents. Psychological masculinity was negatively related to the level of depression in males and females, and evidence which indicates that this relationship is mediated by a link between masculinity and perceived competence is presented. The level of masculinity was stable across the age ranges studied, but was related to an increasingly higher rate of depression in females than males. It is therefore argued that a sex difference in masculinity arises prior to adolescence, but interacts with other factors which influence vulnerability to depression during the teenage years, thus bringing about the sex difference in depression.
Achievement↗
Antinucleic acid autoantibody responses of normal human origin: antigen specificity and idiotypic characteristics compared to patients with systemic lupus erythematosus and patients with monoclonal IgM.
One idiotype family 4.6.3 derived from a human hybridoma IgML monoclonal anti-DNA antibody of normal origin is commonly expressed (approximately 85%) in the serum of patients with systemic lupus erythematosus but not in normal controls, where its level appears to fluctuate with clinical disease activity. In contrast, the IgM released by normal cultured lymphocytes in vitro expresses this idiotype family but does not bind DNA. Both idiotype 4.6.3 and anti-DNA antibodies are frequently detectable in the serum of patients with monoclonal IgM but not IgG. Therefore, it is likely that idiotype 4.6.3 reflects the expression of a common germ line immunoglobulin gene family. Some of the IgM molecules encoded by these germ line immunoglobulin genes also bind DNA.
Antibodies, Antinuclear↗
Cytoskeletal binding of monoclonal anti-DNA antibodies derived from tonsillar lymphoid cells of a normal subject.
The ability of monoclonal IgM anti-DNA autoantibodies derived from normal human lymphoid cells to bind to cellular constituents of human epithelial cells (HEp-2) was examined by immunofluorescence. Hybridoma supernatants from 10 different clones were studied. Four of them gave a strong fibrillar cytoplasmic staining that resembled cytoskeletal staining, 1 showed strong nuclear staining only, 3 showed weak nucleolar staining only, and 2 showed no staining. The hybridoma supernatants that reacted with HEp-2 cytoskeleton were either polyspecific for various nucleic acid antigens, such as single-stranded DNA, DNA, poly(dA:dT), poly(dG).poly(dC), RNA, and cardiolipin, or were restricted to cardiolipin. Cytoskeletal staining identical to the hybridoma supernatant staining was also seen with mouse monoclonal anti-vimentin antibody B11.5.1. Inhibition of the cytoskeletal staining was accomplished in 3 of the 4 hybridoma supernatants by preabsorption of these hybridoma supernatants with cardiolipin and/or single-stranded DNA, or by preincubation of the HEp-2 cells with the mouse monoclonal anti-vimentin antibody.
Absorption↗
The in vitro production of anti-DNA antibody by cultured peripheral blood or tonsillar lymphoid cells from normal donors and SLE patients.
Anti-DNA antibody responses by cultured circulating lymphocytes from SLE patients and by the tonsillar lymphoid cells of normal donors were detected and enumerated by a sensitive specific ELISA of culture supernatants, or by a hemolytic anti-DNA PFC assay. Although spontaneous IgM and IgG anti-DNA and anti-ssDNA responses were characteristic of SLE lymphocytes and spontaneous IgM anti-ssDNA responses were characteristic of tonsillar lymphocytes, the circulating lymphocytes of normal controls never produced anti-DNA antibodies spontaneously, and rarely after PWM stimulation. The anti-DNA antibody PFC response of tonsil lymphocytes correlated directly with the total number of immunoglobulin-producing cells measured by a reverse hemolytic PFC assay. Mixing experiments in which we employed cultures of comparable numbers of separately enriched autologous circulating and tonsillar B and T cells revealed that tonsillar tissue contained an enriched population of anti-DNA antibody precursor B cells and/or helper T cells.
Adolescent↗