Metrical Venn diagrams.
A type of Venn diagram is described which enables the observed frequencies in a 2x2x2 contingency table to be compared with their expectations on the hypothesis of no associations.
Gene Frequency↗
Biomedical subjects
J H Edwards
Publications and source records attributed to J H Edwards.
The need for care in the use of linkage analysis for genetic diagnosis in small families, with particular reference to uniparental disomy.
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Aneuploidy↗
Doubt about evidence for a schizophrenia gene on chromosome 5.
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Chromosomes, Human, Pair 5↗
Pigeon breeders' lung--the effect of loft litter materials on airborne particles and antigens.
An Andersen sampler was used to collect different sized fractions of airborne dust within pigeon lofts. Antigens associated with pigeon breeders' lung were then measured using an ELISA technique. Levels of soluble antigen in the 0.5-5 microns range correlated significantly with airborne particle concentrations in the same range, determined by particle size analysis. However, antigenic material was not soley confined to the 0.5-5 microns fraction and was detected in particles up to 11 microns in diameter. Using both particle size analysis and ELISA in local pigeon lofts revealed significantly increased particles (up to x 50) and antigens (up to x 10) in some lofts employing litter materials to dehydrate voided pigeon droppings, compared with lofts cleaned regularly with no litter agent. Paradoxically, ventilation did not influence particle or antigen concentrations under static conditions or during loft cleaning. The settling rate of loft dusts correlated significantly with that of the litter used, suggesting litter particles were a carrier for soluble pigeon dropping components, but differences in particle numbers generated from the litters and litter/dropping combinations showed that an interaction between voided droppings and litter agents had occurred. A change from litter systems to regular cleaning was undertaken in two lofts, resulting in a marked decrease in respirable particles and antigens.
Air Pollutants↗
Measurement of interleukin-6 in bronchoalveolar lavage fluid by radioimmunoassay: differences between patients with interstitial lung disease and control subjects.
Bronchoalveolar lavage fluid (BALF) from subjects with a variety of interstitial lung diseases (active sarcoidosis, pigeon breeders' disease (PBD), asymptomatic pigeon breeders, patients with idiopathic pulmonary fibrosis) and from control subjects were assayed for interleukin-6 (IL-6) using a novel radioimmunoassay system. IL-6 was detectable in BALF from all groups, with disease groups showing significantly increased IL-6 levels compared with controls (P less than 0.01 in all cases). When these results were standardized, using urea to compensate for dilution effects in the BALF, only the asymptomatic pigeon breeders had significantly higher IL-6 levels than the controls (P less than 0.025), with all other groups showing no difference. When albumin was used for standardization, both the PBD group (P less than 0.001) and the sarcoidosis patients (P less than 0.01) had considerably lower levels of IL-6 than the control subjects. Using either albumin or urea for standardization, the PBD patients had significantly lower levels of IL-6 than do their asymptomatic counterparts (P less than 0.001 in both cases). This is contrasted by the finding of greatly elevated levels of IgG in the BALF of the PBD patients compared with asymptomatics (P less than 0.001). There was, however, no relation between IL-6 and IgG in any patient group, although the PBD patients had the lowest IL-6 and highest IgG as a group. These findings may suggest a mechanism by which asymptomatic subjects remain free from clinical complaints.
Albumins↗
Immunoglobulin and antibody levels in bronchoalveolar lavage fluid from symptomatic and asymptomatic pigeon breeders.
Twenty-one symptomatic subjects with pigeon breeders' lung (PBL) and 10 asymptomatic pigeon breeders, with a similar exposure to pigeon antigens, underwent bronchoalveolar lavage. Total IgG, IgM and IgA in lavage fluid were determined as were specific antibody levels against antigens in pigeon serum and droppings. Results were converted to levels in epithelial lining fluid (ELF) using lavage and serum urea ratios. It was found that symptomatics represent a group that is hyperreactive to pigeon antigens compared with the asymptomatic group with significantly higher IgG, IgM, IgA levels as well as specific antibody levels against pigeon serum and droppings. Paired serum and ELF samples from 12 symptomatic subjects showed significantly elevated IgG, IgM and IgA levels in ELF compared with serum when values were expressed in terms of albumin. This strongly supports the concept of local production of immunoglobulins within the lung after inhaling immunogens as opposed to their diffusion from the vasculature. Results for IgA indicate that any putative protective role for this immunoglobulin is not valid in relation to the prevention of extrinsic allergic alveolitis. Analysis of smoking habits, lung immunoglobulins and response to inhalation challenge confirm the negative influence of smoking on total and functional lung immunoglobulins; however, levels in the ELF of ex-smokers suggest that the effect of smoking is not permanent. Smoking did not prevent responses to inhalation challenge.
Allergens↗
The Oxford Grid.
The 'Oxford Grid' is a term used to denote a method of displaying homologous loci from two species. It may also be used as a basis for historical inferences relating to co-ancestry. These uses are discussed with special reference to man and mouse. It is inferred that as few as 30 reciprocal translocations are sufficient to explain the differences defined by the present grid and that the telocentric karyotype, through which the mouse differs from both man and many closely related rodents, including the rat, must have evolved mainly through the formation and suppression of centromeres rather than through pericentric inversions. Mouse and man share the widest distribution of any mammal and their success appears to be related to being omnivorous with behavioural modifications allowing a wide range of habitat.
Animals↗
The reliability of locus orderings.
Locus orders are frequently presented in graphical form, supported by likelihood statements relating to less likely orders. Many imply genetic distances which are inconsistent with the meiotic evidence, usually by a factor of about 2. While such orders may be the best possible on the data available, measures of their reliability are difficult: the common assumption that an order is correct because changes lead to less likely orders only relates to the subset of orders tested. It is only possible to deduce the order of any set of loci if a recombinant separates every pair. This usually requires a number of recombinants substantially exceeding the number of loci. Orders may be inferred from distance in the absence of consistent separation. However, if reasonable reliability is to be achieved, the number of meioses necessary to define distances with sufficient precision will be many times the number of loci. Some estimates of the minimum number of recombinants necessary for a correct ordering to achieve a probability of a half, the 'half-right' solution, would be helpful. As a first approximation to this we use the probability of no 'null gap', i.e. no pair of adjacent loci with no recombination between them. Where the number of recombinant events is not available from counting, rough guidance can be given by estimating the number of equivalent meioses from lod scores. Where data are not available from homologies from other mammals or from pulsed-field studies, deductive methods of family analysis should be used, followed by pairwise optimizing methods for positioning.(ABSTRACT TRUNCATED AT 250 WORDS)
Chromosome Mapping↗
An attempt to map two genes for tuberous sclerosis using novel two-point methods.
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Adult↗
Challenging the amphetamine challenge test: report of an antidepressant treatment study.
The primary goal of this study was to determine whether the amphetamine challenge test (ACT) response, as measured by a subjective rating scale, the How I Feel Scale (HIF), could predict antidepressant treatment outcome. Following a 1-day non-blind ACT with dextroamphetamine (d-AMPH), patients were treated double-blind for 6 weeks with either desipramine, alprazolam, or a desipramine-alprazolam combination. Regression (true score) analyses were carried out on pre- and post-ACT HIF scores and on baseline and end of study Hamilton Depression Rating Scale (HDRS) scores to determine the magnitudes of improvement measured in response to the ACT and antidepressant treatment, respectively. Regression analyses were performed on the residuals (true scores of improvement) to determine the best fitting (linear) prediction equation. Improvement in the HIF total score predicted HDRS improvement for the whole sample. Possible sources of error contributing to the outcome are identified and the results are discussed in relation to previous clinical investigations of the potential usefulness of the ACT as a predictor of antidepressant response.
Adult↗
Down regulation in hypersensitivity pneumonitis.
Levels of soluble interleukin-2 receptor (sol-IL-2R) in the bronchoalveolar lavage fluid (BALF) of pigeon breeders with hypersensitivity pneumonitis were compared with BALF levels in asymptomatic pigeon breeders who had been exposed to pigeon allergens for an equivalent length of time. No mean difference in sol-IL-2R levels was detected when these levels were expressed per milliliter BALF, epithelial lining fluid, or per T-lymphocyte. In sarcoidosis, the availability of sol-IL-2R per T cell was significantly higher for the group with inactive sarcoidosis compared with the group with active sarcoidosis. The results do not support the hypothesis that down regulation, in subjects exposed to allergens causing hypersensitivity pneumonitis, is a function of cell-free sol-IL-2R levels in BALF. In the dynamic situation, however, the hypothesis appears tenable.
Adult↗
Ispaghula sensitization in workers manufacturing a bulk laxative.
Exposure to ispaghula dust in a pharmaceutical factory resulted in chest tightness/wheeze, nasal, and ocular or skin symptoms in 48 of 92 exposed workers. Whilst symptoms were not incapacitating in the majority (44) of these, one worker required antihistamines and three others experienced severe respiratory symptoms when exposed to the dust. These three were atopic, had a positive RAST and skin test to ispaghula; a combination unique to them. There was a significant relationship between work-related symptoms and atopic status, however, smoking did not influence symptoms, total serum IgE and specific anti-ispaghula IgE. We conclude that handling ispaghula produces an irritant effect in most exposed people, however, sensitization to the dust can occur with severe respiratory symptoms.
Adult↗
Sequential serological responses to Aspergillus fumigatus in patients with cystic fibrosis. Use of antigen 'stretching' to delineate IgG and IgE activity.
Immunogens from Aspergillus fumigatus were fractionated on the basis of molecular weight. Nine fractions ranging from 900 to 10 kDa were used in ELISA and in a radioallergosorbent test (RAST) with sera from cases of allergic bronchopulmonary aspergillosis (ABPA) and from cystic fibrosis (CF) patients with ABPA or other Aspergillus involvement and compared with control subjects. The profile of IgG reactivity to the nine fractions did not vary substantially for all Aspergillus-involved groups producing peaks at greater than 900 kD and 170 kD whereas the profile for control subjects had a peak at greater than 900 kD only. The IgE profile for CF patients with ABPA did not differ from the profile of the RAST-positive CF patients without ABPA and provided only one peak of activity at 24 kD. Recovery from an episode of ABPA in CF patients was accompanied by a fall in both IgG and IgE antibody levels to all nine fractions, whereas increases in IgG and IgE to all fractions were seen during an episode of ABPA. Although there was an exaggerated IgG increase to antigens in the 43-170 kD range during ABPA, a meaningful increase was also observed to unfractionated A. fumigatus antigen preparations. With IgE in one detailed study the 24-kD fraction provided a better indication of Aspergillus involvement than the unfractionated A. fumigatus antigens. Sequential studies of IgG and IgE levels were not able to predict an episode of ABPA but were useful in conjunction with clinical assessment in following the course of the illness.
Adolescent↗
The linkage detection problem.
Linkage data in man are usually analysed on families lacking a full set of grandparents on the assumption that there is one locus relating to an abnormal phenotype, the test locus. The basic problems of establishing linkage of this locus to another locus, the marker locus, with a defined likelihood and of estimating the recombination fraction were resolved by Morton (1955). However, the likelihood ratio derived after estimating the most likely recombination fraction is widely misunderstood to be a direct measure of the likelihood of linkage while the bias of estimates conditional on some likelihood criterion derived from the same data is usually ignored. Since data are limited this tolerance of excessive confidence in detecting linkages and a consistent tendency to underestimate recombination fractions is justified but the expected errors are not small and they are readily magnified when multiple loci are involved. Multiple markers provide further opportunities for detecting false linkages although the corrections required are known. The problems imposed by multiple loci at which mutations lead to a common phenotype have so far had little consideration. As most proteins are multimers whose units are not necessarily coded for by neighbouring loci, and as disturbances to any of several enzymes acting in series may lead to similar consequences, the assumption of a one-to-one relationship between a locus and a phenotype will usually be wrong.
Animals↗
The slash sheet: a simple procedure for risk analysis in cystic fibrosis.
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Cystic Fibrosis↗
A comparison of albumin and urea as reference markers in bronchoalveolar lavage fluid from patients with interstitial lung disease.
Lavage fluids were investigated for 67 subjects in 6 groups: 12 with active sarcoidosis, 8 with inactive sarcoidosis, 17 with pigeon breeder's disease, 10 asymptomatic pigeon breeders, 12 with idiopathic pulmonary fibrosis (IPF) and 8 normal subjects. Albumin and urea per ml of bronchoalveolar lavage fluid (BALF) were determined for each subject together with percentage return of fluid (BAL%). Novel assay systems were employed to measure urea and albumin and these were compared with existing analytical techniques. When compared with the control group, we found that urea per ml of BALF was not statistically different for all other groups, except those with pigeon breeder's disease who had significantly raised levels. For albumin, however, three groups had significantly higher levels than the controls, namely those with active sarcoidosis, pigeon breeder's disease and IPF. BAL% return showed no significant differences for any group when compared with the controls. We conclude that since albumin is significantly raised in most patients with interstitial lung disease it does not represent a suitable marker for the quantitation of reactive proteins in BALF. Urea shows much less variability between groups than does albumin, and hence in the absence of a proven alternative represents the most reliable estimate available of epithelial lining fluid dilution during the lavage procedure, providing dwell time is kept to a minimum.
Albumins↗
Detecting maternal cell contamination in prenatal diagnosis.
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Chorionic Villi Sampling↗