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Biomedical subjects

D R Taylor

Publications and source records attributed to D R Taylor.

At least 19 recordsLinked to original sources
PubMed1996

Immunoglobulin switch transcript production in vivo related to the site and time of antigen-specific B cell activation.

Immunoglobulin (Ig) class switch recombination is associated with the production and splicing of germline IgCH messenger RNA transcripts. Levels of gamma 1 transcripts in mouse spleen sections were assessed by semiquantitative analysis of reverse transcriptase polymerase chain reaction (PCR) products during primary and secondary antibody responses to chicken gamma globulin (CGG). This was correlated with the appearance of CGG-specific B cells and their growth and differentiation to plasma cells. After primary immunization with CGG, gamma 1 switch transcripts appeared after 4 d, peaked at a median of six times starting levels between 10 and 18 d after immunization, and returned to background levels before secondary immunization at 5 wk. By contrast, after secondary challenge with CGG, a sevenfold increase in transcripts occurs during the first d. The level again doubles by day 3, when it is six times that which is seen at the peak of the primary response. After day 4, there was a gradual decline over the next 2-3 wk. Within 12 h of secondary immunization, antigen-specific memory B cells appeared in the outer I zone and by 24 h entered S phase, presumably as a result of cognate interaction with primed T cells. Over the next few hours, they migrated to the edge of the red pulp, where they grew exponentially until the fourth day, when they synchronously differentiated to become plasma cells. The same pattern was seen for the migration, growth, and differentiation of virgin hapten-specific B cells when CGG-primed mice were challenged with hapten protein. The continued production of transcripts after day 3 indicates that switching also occurs in germinal centers, but in a relatively small proportion of their B cells. The impressive early production of switch transcripts during T cell-dependent antibody responses occurs in cells that are about to undergo massive clonal expansion. It is argued that Ig class switching at this time, which is associated with cognate T cell-B cell interaction in the T zone, has a major impact on the class and subclasses of Ig produced during the response.

Animals↗
PubMed1996

The beta-agonist controversy.

After many years of increasing morbidity and mortality, several avenues of scientific investigation now appear to be converging to offer an explanation for the asthma paradox and indicate that regular or long-term use of short-acting inhaled beta-agonist drugs is inappropriate. Pharmacoepidemiologic studies indicate a strong association between increased beta-agonist use and asthma deaths, which does not appear entirely related to confounding by severity. Clinical data, although still limited, show little evidence for symptomatic or functional improvement during long-term beta-agonist therapy and, in many instances, reveal significant adverse effects. Related investigations offer evidence of potential plausible mechanisms, notably increased bronchial responsiveness to inhaled allergen, to explain these findings. A radical revision of the therapeutic use of these drugs in asthma has been prompted by these findings. Beta-agonist drugs remain essential for the management of acute severe attacks. They are also useful on demand for the relief of breakthrough symptoms and for prophylaxis of exercise-induced symptoms. In chronic asthma, however, adequate anti-inflammatory therapy is the treatment of choice. Long-term treatment with short-acting beta-agonist, even in the presence of seemingly adequate anti-inflammatory therapy, may be associated with deterioration of asthma over the long-term. The effects of long-acting beta-agonists remain under review. To date, there are no data that clearly indicate a deleterious effect, and many clinical trials show benefits in symptom control and improved lung function associated with their regular use. The significance of tachyphylaxis remains to be defined. Their current role is still somewhat unclear, but they have been successfully used in subjects in whom, despite the use of moderate doses of inhaled corticosteroid, short-acting bronchodilator is still frequently required. The use of twice-daily long-acting beta-agonist appears preferable to frequent use of short-acting beta-agonists.

Adrenergic beta-Agonists↗
PubMed1995

Functional characterization of the RNA-binding domain and motif of the double-stranded RNA-dependent protein kinase DAI (PKR).

The double-stranded (ds) RNA-activated protein kinase, DAI (also known as PKR), contains an RNA-binding domain comprising two tandem repeats of a motif, the dsRBM, which is shared with a number of other proteins that interact with structured RNAs. We have expressed the entire domain and the first copy of the motif in Escherichia coli and purified the two proteins, p20 and p10, to apparent homogeneity in order to study their interactions with RNA and with the intact kinase enzyme. Both p20 and p10 bound preferentially to structured RNA molecules. Competition assays showed that in both cases the order of affinity is dsRNA > VA RNA > tRNA, but the isolated motif bound much less tightly than the entire domain. Measurement of the dissociation constants for dsRNA by quantitative gel mobility shift analysis gave apparent Kd values of 4 x 10(-9) M and 3.8 x 10(-7) M for p20 and p10, respectively. The binding of p20 molecules to dsRNA appeared to be cooperative. Multiple complexes were formed between the intact domain and dsRNA, saturating at a density of about one p20 molecule/11.25 base-pairs (or one turn) of duplex, whereas p10 achieved only about half of this packing density. The apparent Kd for the p20-VA RNA interaction was estimated as 3.5 x 10(-7) M and at least three complexes were detected, but no distinct complexes were visualized for the interaction between p10 and VA RNA. Both p20 and p10 inhibited autophosphorylation of intact DAI, probably by binding the dsRNA activator. Once activated, DAI could phosphorylate both p10 and p20, suggesting that intermolecular phosphorylation can occur.

Amino Acid Sequence↗
PubMed1995

The opiate addiction test: a clinical evaluation of a quick test for physical dependence on opiate drugs.

1. Mydriasis (pupil dilation) in response to conjunctivally applied naloxone hydrochloride has been demonstrated using an innovative electronic binocular pupillometer in 40 opiate dependent patients, on maintenance methadone treatment. 2. No pupillary response to naloxone was seen when an identical procedure was carried out in a control population of 12 healthy volunteers. 3. After a baseline measurement of pupil size, two drops of naloxone hydrochloride were instilled into the conjunctival sac of one eye. Serial binocular pupillometry was then carried out at 5, 10, 15, 20, 25, 30, 35, 40 and 45 min post-instillation. 4. Discriminant analysis between the control and patient groups showed that the false negative rate (error of misclassification to the wrong population) was lowest (20%) at 40 min post-eyedrop instillation, with no false positives in the control group. 5. The study has therefore shown an improvement in the previously reported false negative rate (25%) [1,2], of the conjunctival naloxone test of opiate dependence, with the use of our innovative electronic binocular pupillometer.

Adult↗
PubMed1995

Calcium carbonate in cholesterol gallstones: polymorphism, distribution, and hypotheses about pathogenesis.

This study of sets of cholesterol gallstones collected consecutively from 222 patients in La Paz, Bolivia, and Mexico City, Mexico, has developed a reliable infrared (IR) spectroscopic method for the detection of calcium carbonate in cholesterol gallstones and provided the basis for simultaneous identification of each of its three polymorphs: calcite, vaterite, and aragonite. The peaks in the 854 to 876 cm-1 region demonstrated 98% sensitivity and specificity for carbonate detection. As little as 3% carbonate by weight could be detected using these peaks. The overall incidence of carbonate was 19% in these populations containing a high proportion of Amerinds. Infrared microspectroscopy of 10 to 50 microns particles, dissected from stones, allowed a ring-by-ring examination of 11 carbonate-containing stones. It was determined that different carbonate polymorphs, when present in the same gallstone, almost always occurred in separate rings. In approximately half of the gallstones, different polymorphs were present in successive layers in the same stone, indicating that conditions governing stone growth changed cyclically. Carbonates were usually precipitated in peripheral layers rather than in the center, supporting the theory that formation of calcium carbonates may be related to episodes of intermittent obstruction of the cystic duct, as opposed to being a major factor in stone nidation.

Calcium Carbonate↗
PubMed1994

Asthma control.

Explore the source record for details and available documents.

Albuterol↗
PubMed1994

Sex ratio in hybrids between Silene alba and Silene dioica: evidence for Y-linked restorers.

Sex ratio in Silene alba is generally female biased, and the bias is influenced by Y-linked alleles that are polymorphic in natural populations. One interpretation of these alleles is that they enhance the production of males in female-biased populations, i.e. they are restorers. Two Silene species, S. alba and S. dioica, and their reciprocal hybrids were used to investigate the inheritance of sex ratio and the relationship between sex ratio and male fertility. Sex ratio was paternally inherited (i.e. Y-linked), but was also strongly influenced by the maternal parent through an interaction with the Y chromosome. These results corroborate previous work on the inheritance of sex ratio within S. alba, and suggest that sex ratio in S. alba and S. dioica has a similar genetic basis. Examination of the maternal by Y chromosome interaction revealed that the Y chromosome of each species produced a more severe female bias in crosses with females of the opposite species. This is consistent with the hypothesis that the alleles expressed in the maternal parent cause the female bias, while the Y-linked alleles tend to restore sex ratio toward equality.

Crosses, Genetic↗
PubMed1994

The genetic basis of sex ratio in Silene alba (= S. latifolia).

A survey of maternal families collected from natural populations showed that the sex ratio in Silene alba was slightly female biased. Sex ratio varied among populations and among families within a female biased population. Crosses among plants from the most female biased population and the most male biased population showed that the sex ratio polymorphism was inherited through or expressed in the male parent. Males from one family in particular exhibited a severe female bias, characterized by less than 20% male progeny. The inheritance of sex ratio was investigated using a reciprocal crossing design. Sex ratios from reciprocal crosses were significantly different, indicating either sex-linkage or cytoplasmic inheritance of sex ratio. The sex ratios produced by males generally resembled the sex ratios produced by their male parents, indicating that the sex ratio modifier was Y linked. The maternal parent also significantly influenced sex ratio through an interaction with the genotype of the paternal parent. Sex ratio, therefore, is apparently controlled by several loci. Although sex ratio bias in this species may be due to deleterious alleles on the Y chromosome, it is more likely to involve an interaction between loci that cause the female bias and a Y-linked locus that enhances the proportion of males in the progeny.

Crosses, Genetic↗
PubMed1994

Chronic interstitial lung disease in a welder of galvanized steel.

A 32-year-old man who took pride in his skill and speed as a welder suffered two relatively brief intense exposures (three months each) to welding fumes under relatively confined space conditions. He developed shortness of breath within 18 months of beginning work, with severe impairment of his diffusion capacity. This remains some months later despite discontinuing his welding activities.

Adult↗
PubMed1994

The beta 2-agonist controversy. Observations, explanations and relationship to asthma epidemiology.

Links between frequent use of inhaled beta 2-agonists and morbidity and mortality from asthma appear probable. Two mortality epidemics followed the marketing of potent inhaled adrenergic agents. Case-control studies in New Zealand linked mortality with prescription of fenoterol, especially in severe asthma. A Saskatchewan case-control study confirmed an association of mortality with fenoterol, and also with frequent use of salbutamol (albuterol). Cardiac effects of beta 2-agonists do not cause mortality, but frequent use of these agents may increase the chronic severity of asthma, hence increasing the number of asthmatic patients at risk of death in an acute attack. Frequent use of beta 2-agonists may reduce lung function, increasing airway responsiveness, and impair control of asthma, despite use of inhaled corticosteroids. Mechanisms for this effect may include tachyphylaxis to nonbronchodilator effects, increased responsiveness to allergen, interaction with corticosteroid receptors, altered mucociliary function, differential effects of enantiomers, and masking of symptoms by beta 2-agonist use. The withdrawal of fenoterol from New Zealand in 1990 was associated with a substantial decline in morbidity and mortality. Overall, the evidence suggests that frequent use of inhaled beta 2-agonists has a deleterious effect on the control of asthma. Epidemics of mortality are explained by an increase in chronic severity of asthma following introduction of more potent beta 2-agonists. While beta 2-agonists remain essential for relief of breakthrough symptoms, long term use, particularly with high doses of potent agents, appears to be detrimental.

Adrenergic beta-Agonists↗
PubMed1993

Methotrexate in the management of severe steroid dependent asthma.

AIMS: This study was designed to assess the efficacy of low dose methotrexate, 15 mg weekly, as a steroid-sparing agent in asthmatic patients requiring long-term oral prednisone treatment. METHODS: The study was a randomised, double blind, placebo controlled, cross over study of 48 weeks duration. Eleven patients with severe steroid-dependent asthma were included. A successful outcome was defined as a reduction in mean prednisone requirements of 7 mg daily compared to baseline requirements, during active treatment. RESULTS: Two patients were required to be withdrawn owing to methotrexate-related adverse effects. The mean prednisone dose for patients who completed the study was 14.4 mg per day (95% CI; 13.6, 15.1) during active treatment, and 12.9 mg per day (95% CI: 12.2, 13.6) during placebo treatment (NS). Only one patient reduced his individual dose requirements by more than 7 mg per day, whereas in three patients prednisone requirements actually increased during active treatment. There were no significant differences in symptom scores, pulmonary function data, and exacerbations between active and placebo treatments. CONCLUSION: No significant steroid-sparing effect was obtained using low dose methotrexate in this study. This negative outcome may be attributable to the small population of patients studied, low baseline FEV1, and the omission of a steroid minimisation run-in period. Our results highlight the importance of careful patient selection and a painstaking approach in the management of patients with steroid-dependent asthma.

Administration, Inhalation↗