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Biomedical subjects

R C Thompson

Publications and source records attributed to R C Thompson.

At least 253 records · Page 14Linked to original sources
PubMed1990

Heterogeneity of helper/inducer T lymphocytes. III. Responses of IL-2- and IL-4-producing (Th1 and Th2) clones to antigens presented by different accessory cells.

Murine CD4+ T cell clones have been classified into at least two subsets, Th1 and Th2, on the basis of their distinct lymphokine secretion profiles and functions. In the present study, we compared the functional responses of Th1 and Th2 clones to Ag presentation by splenic B cells and peritoneal macrophages. Th2 clones secreted IL-4 in response to Ag presented by resting B cells, but their optimal proliferation required the addition of IL-1 or a source of IL-1. The degree of IL-1 dependence varied among the four Th2 clones examined. In contrast, Th1 clones secreted IL-2 and proliferated in response to Ag presented by both B cells and macrophages, without any requirement for exogenous IL-1. Furthermore, the proliferation of Th2 clones in response to Ag presented by splenocytes or macrophages was inhibited by an IL-1R antagonist. These results indicate that IL-1 is an important costimulator for the expansion of the Th2 subset of CD4+ T cells. The different requirements for the proliferation of Th1 and Th2 cells may be responsible for the preferential expansion of one or the other subset under different conditions of immunization.

Animals↗
PubMed1990

Location of the protease-inhibitory region of secretory leukocyte protease inhibitor.

Secretory leukocyte protease inhibitor (SLPI) is a two-domain protein that inhibits a wide range of proteases including chymotrypsin, leukocyte elastase, and trypsin. Based on its homology to other protease inhibitors and on x-ray crystallography of an SLPI-chymotrypsin complex it has been proposed that the elastase and chymotrypsin-inhibitory site is in the COOH-terminal domain and that the trypsin-inhibitory site is in the NH2-terminal domain. We have prepared muteins of SLPI by site-directed mutagenesis of a synthetic gene for the protein, followed by expression in Escherichia coli. The protease-inhibitory activities of these muteins indicate that leucine 72 in the COOH-terminal domain is at the inhibitory site for elastase and chymotrypsin. Unexpectedly, our measurements indicate that the trypsin-inhibitory site is not in the NH2-terminal domain. Instead they suggest that leucine 72 is also the inhibitory site for trypsin, even though the amino acid residues at the inhibitory sites of other trypsin inhibitors are almost always either lysine or arginine.

Amino Acid Sequence↗
PubMed1990

Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor.

Three interleukin-1 inhibitors have been purified to homogeneity from medium conditioned by human monocytes. Partial sequence analysis and digestion with N-glycanase indicate that these are glycosylation forms of a single protein. The protein binds to the interleukin-1 receptor but has no interleukin-1-like activity, even at very high concentrations, and is therefore a pure receptor antagonist.

Amidohydrolases↗
PubMed1990

Primary structure and functional expression from complementary DNA of a human interleukin-1 receptor antagonist.

Human monocytes induced with adherent IgG secrete an interleukin-1 receptor antagonist which could be important for the in vivo regulation of IL-1 activity. A complementary DNA for this molecule has been isolated from a human monocyte library. Analysis of monocyte RNA indicates that the gene is transcriptionally regulated. The sequence of the receptor antagonist indicates that it is structurally similar to IL-1 beta. Expression of the cDNA in Escherichia coli yields IL-1 receptor antagonist activity.

Amino Acid Sequence↗
PubMed1990

Echinococcus: biology and strain variation.

Biology and strain variation in the causative agent of hydatid disease is reviewed with emphasis on developmental and genetic aspects. In vitro cultivation experiments have made a significant contribution to current knowledge of the developmental plasticity of Echinococcus. However, the mechanisms which regulate and determine developmental strategies in the parasite, as well as the characteristics, source and cytodifferentiation of germinal cells, are not understood. The nature, significance and origin of strain variation in Echinococcus are examined. Before we can fully appreciate the phenotypic consequences of genetic differentiation between populations, we need to know something about the genetic and environmental components of variation in traits such as development rate, host preference, host specificity, virulence and drug resistance. There is an urgent need for research on the developmental pathways by which genetic differences within and between strains of E. granulosus are translated to phenotypic differences in these traits.

Animals↗
PubMed1990

Intraspecific variation in parasites- what is a strain?

The use of molecular techniques in parasitology has revealed a startling degree of diversity within species of parasite. These discoveries have emphasized the need for parasitologists to define and describe accurately the organisms with which they work. Andrew Thompson and Alan Lymbery propose that parasite strains be described by a combination of genetic and biological characteristics since reliance on the genotype alone may confer significance on a feature of little biological relevance.

Journal Article↗
PubMed1990

Streptokinase therapy for extensive venous thromboses in a patient with severe ulcerative colitis.

Thromboembolic disease is a known complication of patients with inflammatory bowel disease and often is associated with increased morbidity and mortality. In a patient with severe ulcerative colitis, extensive venous thromboses developed in three extremities. Despite active bleeding in the lower gastrointestinal tract, he was successfully managed preoperatively with infusions of streptokinase followed by full-dose heparinization. During the 48 hours he received streptokinase, his venous thromboses resolved dramatically. Within 2 weeks after admission, he underwent an uneventful proctocolectomy in conjunction with an ileoanal anastomosis.

Adult↗
PubMed1990

Rostellar hook morphology of Echinococcus granulosus (Batsch, 1786) from natural and experimental Australian hosts, and its implications for strain recognition.

An analysis of the rostellar hooks of Australian isolates of Echinococcus granulosus revealed that there was less variation in larval (metacestode) than adult characters and that metacestode characters could be measured directly from adult worms. A factor analysis indicated that two factors, one representing a contrast between number of hooks and their length, and the other representing blade lengths, were sufficient to account for 87.5% of the variance in metacestode hook measurements. These results indicate that rostellar hook morphology is not useful for discriminating strains of E. granulosus in Australia. The Tasmanian and mainland domestic strains were found to be indistinguishable using rostellar morphology. Although many of the isolates from sylvatic hosts differed from those from domestic hosts, there was not a clear separation as would be expected if two distinct strains existed. Evidence was presented to show that the morphological differences seen in sylvatic hosts could be attributed to host-induced effects, and that the previously accepted existence of two mainland strains should be investigated further.

Animals↗
PubMed1990

Genetic diversity and genetic differentiation in Echinococcus granulosus (Batsch, 1786) from domestic and sylvatic hosts on the mainland of Australia.

Enzyme electrophoresis was used to examine genetic variation within and between populations of Echinococcus granulosus from domestic and sylvatic hosts in western and eastern Australia. Substantial genetic diversity was found within all populations. There was no evidence, however, of genetic differentiation between populations from different hosts or geographic areas. When isolates were grouped into previously described domestic or sylvatic strains on the basis of rostellar hook morphology, most (94%) of the genetic variation occurred within, rather than between strains. These results conflict with the currently accepted theory of separate domestic and sylvatic strains of E. granulosus on the mainland of Australia.

Alleles↗
PubMed1990

A second tumor necrosis factor receptor gene product can shed a naturally occurring tumor necrosis factor inhibitor.

An inhibitor of tumor necrosis factor (TNF) has been isolated from the human histiocytic lymphoma cell line U-937 that is capable of inhibiting both TNF-alpha and TNF-beta. Protein sequencing has verified that it is distinct from a previously described TNF inhibitor that is a soluble fragment of a TNF receptor molecule (TNFrI). The cDNA sequence of this second TNF inhibitor clone suggests that it is also a soluble fragment of a TNF receptor. Expression of this cDNA sequence in COS-7 cells verified that it encodes a receptor for TNF-alpha (TNFrII) that can give rise to a soluble inhibitor of TNF-alpha, presumably through proteolytic cleavage. The extracellular domain of TNFrII has significant homology with that of TNFrI and these two receptors share a striking conservation of cysteine residue alignment with the extracellular domain of the nerve growth factor receptor. These three receptor molecules are therefore members of a family of polypeptide hormone receptors.

Amino Acid Sequence↗
PubMed1990

Nucleotide sequence and tissue-specific expression of the rat melanin concentrating hormone gene.

Melanin concentrating hormone (MCH) is a key neuroendocrine peptide which is involved in the regulation of body color in teleost fish. Antigenically similar peptides exist in higher vertebrates including rodents and man. The precise function(s) of these peptides in these higher vertebrates has yet to be fully elucidated, although regulatory roles in stress-induced or corticotropin-releasing hormone-stimulated ACTH release and/or water balance have been proposed. The salmon, rat, and human MCH cDNA clones have been isolated and sequenced. We isolated and characterized the structure of the rat MCH gene. In addition to providing the complete nucleotide sequence of this gene, we demonstrate that there is a single copy of this gene in the rat genome. The structure of the rat MCH gene indicates that the MCH mRNA is encoded by three exons. Using primer extension and RNase protection assays, the transcriptional start sites of hypothalamic MCH mRNA were determined, allowing us to define the promoter region of this gene. We also characterize the central nervous system distribution of expression of the MCH gene by Northern blot analysis, demonstrating that the MCH mRNA is found predominantly if not exclusively within the hypothalamus.

Amino Acid Sequence↗
PubMed1990

Aerosolization of recombinant SLPI to augment antineutrophil elastase protection of pulmonary epithelium.

In a variety of lung diseases the respiratory epithelial surface must contend with an increased burden of neutrophil elastase (NE). One candidate for augmenting epithelial anti-NE protection is the secretory leukoprotease inhibitor (SLPI). In vitro evaluation demonstrated that 96 +/- 1% of the recombinant SLPI (rSLPI) molecules were capable of inhibiting NE, with an association rate constant of 7.1 +/- 0.1 X 10(6) M-1.s-1. Evaluation of rSLPI after in vitro and in vivo aerosolization showed that aerosolization did not alter rSLPI. Aerosolization of a single dose of 50 mg rSLPI to sheep resulted in a fourfold increase of the anti-NE capacity in epithelial lining fluid (ELF) at 3 h, with a half-life in ELF of 12 h. After aerosolization some rSLPI appeared in lung lymph. Simultaneous aerosolization of rSLPI and recombinant alpha 1-antitrypsin (rAAT) demonstrated a molar ratio of the concentration in lymph to the concentration in ELF 3 h after the aerosol eightfold higher for rAAT than for rSLPI. Overall, these observations demonstrate that it is feasible to use aerosolized rSLPI to directly augment the anti-NE capacity of the lung, particularly on the pulmonary epithelial surface.

Aerosols↗
PubMed1990

Pharmacokinetics and distribution of recombinant secretory leukocyte proteinase inhibitor in rats.

Secretory leukocyte proteinase inhibitor (SLPI) is a potent elastase, trypsin, and chymotrypsin inhibitor occurring in all mucous secretions. Its inhibitory potency and profile suggested that it may become a therapeutic adjuvant in diseases where proteinases play a pathogenetic role. In the course of developing recombinant SLPI for therapeutic purposes, we studied its pharmacokinetics after intravenous, intraperitoneal, and intratracheal application to rats. In plasma, SLPI was determined with an ELISA or by following a radiotracer [( 35S]SLPI). In bronchoalveolar lavage fluid (BALF), SLPI was determined additionally by a functional assay (elastase inhibitory capacity). Intravenously applied SLPI (2 mg/kg) was rapidly cleared, with half-times of distribution of 6 min and half-times of elimination of 50 min. Very little (less than 5%) appeared in the urine even after 24 h. Approximately 80% of intraperitoneally injected SLPI (12 mg/kg) was absorbed and generated maximal plasma concentration of 6 to 10 micrograms/ml 30 to 120 min after administration. When given intratracheally (8.6 mg/kg), SLPI disappeared from the lungs, with a half-time of 4 to 5 h. This value was the same whether the remaining SLPI in BALF was determined radiometrically, by ELISA or by the functional assay, indicating minimal metabolism in the lung. As in the case of intraperitoneal application, SLPI was absorbed systemically, resulting in a maximal plasma level of about 2 micrograms/ml 1 to 2 h after application. In contrast to the measurements in BALF, the ELISA and radiotracer measurements in plasma correlated only for the first 2 h after application and diverged progressively after that, suggesting breakdown of the molecule once it reaches the plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Biological properties of recombinant human monocyte-derived interleukin 1 receptor antagonist.

Human monocytes cultured on adherent IgG produce a specific IL-1 inhibitor that functions as a receptor antagonist (IL-1ra). This molecular has been purified, sequenced, cloned as a cDNA, and expressed in Escherichia coli. Recombinant IL-1ra has 17,000 mol wt and binds to IL-1 receptors on T lymphocytes, synovial cells, and chondrocytes with an affinity nearly equal to that of IL-1. These studies have examined some biological properties of purified recombinant human IL-1ra. This protein exhibits a dose-responsive inhibition of Il-1 alpha and Il-1 beta augmentation of PHA-induced murine thymocyte proliferation. The recombinant IL-1ra also blocks IL-1 alpha and IL-1 beta stimulation of PGE2 production in human synovial cells and rabbit articular chondrocytes, and of collagenase production by the synovial cells. A 50% inhibition of these IL-1-induced biological responses requires amounts of IL-1ra up to 100-fold in excess of the amounts of IL-1 alpha or IL-1 beta present. IL-1ra may play an important role in normal physiology or in pathophysiological states by functioning as a natural IL-1 receptor antagonist in the cell microenvironment.

Animals↗
PubMed1990

Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis.

Interleukin 1 (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-1 alpha and beta mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-1 alpha was significantly elevated at 4 h (9.4 +/- 1.5 ng/g colon), progressively increased at 48 h (31 +/- 5.8 ng/g) and then decreased by 96 h (11.5 +/- 3.4 ng/g). IL-1 beta levels were 2.0 +/- 0.5 ng/g colon at 4 h, 5.0 +/- 1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-1 alpha levels were highly correlated with inflammation (r = 0.885, P less than 0.0001), edema (r = 0.789, P less than 0.0001) and necrosis (r = 0.752, P less than 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-1 ra) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2 +/- 0.4 to 1.4 +/- 0.3, P less than 0.02), edema (from 2.2 +/- 0.4 to 0.6 +/- 0.3, P less than 0.01) and necrosis (from 43 +/- 10% to 6.6 +/- 3.2%, P less than 0.03) compared to vehicle-matched colitis animals. These studies demonstrate that (a) IL-1 gene expression and synthesis occur early in the course of immune complex-induced colitis; (b) are significantly elevated for 12 h before the appearance of PGE2 and LTB4; (c) tissue levels of IL-1 correlate with the degree of tissue inflammation and; (d) specific blockade of IL-1 receptors reduces the inflammatory responses associated with experimental colitis.

Antigen-Antibody Complex↗