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Biomedical subjects

R C Thompson

Publications and source records attributed to R C Thompson.

At least 181 records · Page 10Linked to original sources
PubMed1993

Differences in antigen expression within and between 10 isolates of Giardia duodenalis.

In this study indirect immunofluorescence was performed on both live and fixed trophozoites to determine the level of variability in surface antigen expression between 14 Giardia duodenalis isolates, using a monoclonal antibody raised against the Portland 1 isolate (ATCC No. 30888). Subsets of antigen positive cells were detected in 13 isolates ranging in number from < 1% to 50% of the total population. The differences in antigen expression between 10 uncloned isolates did not correlate with genetic differences determined using isoenzyme analysis. Examination of four clones of the Portland 1 isolate showed that all of the progeny expressed surface antigen at significantly different levels to the parent.

Animals↗
PubMed1993

The efficacy of two electron transport inhibitors (720C80 and 993C76) on murine strongyloidiasis: a comparison with albendazole.

The clinical efficacy of albendazole (ABZ) in the treatment of chronic uncomplicated strongyloidiasis has been reported to be highly variable. In our murine model of strongyloidiasis a single oral dose of 5 and 10 mg kg-1 ABZ reduced (at day 4 post infection) the faecal larval count (FLC) by 54.2 +/- 12.5% and 81.5 +/- 10.2%, respectively. 100 mg kg-1 ABZ reduced the FLC by 100%. Two inhibitors of protozoan and filarial electron transport (720C80 and 993C76) inhibited the endogenous O2 consumption of intact infective (L3) larvae of S. ratti by > 50% at 2 x 10(-5) M in vitro, and reduced the FLC by 72 +/- 9.3% and 62.0 +/- 10.3% respectively in vivo, at a dose of 70 mg kg-1. These results suggest that compounds designed as selective inhibitors of protozoan electron transport have significant efficacy against murine strongyloidiasis and may prove useful in the management of human strongyloidiasis.

Albendazole↗
PubMed1993

Isolation and in vitro translation of messenger RNA encoding allergens of the cat flea, Ctenocephalides felis.

Polyadenylated [poly(A)+] mRNA was isolated from the cat flea, Ctenocephalides felis by oligothymidylic acid-cellulose spin column chromatography and translated in vitro using a cell-free rabbit reticulocyte system. The relative incorporation of 35S-methionine into trichloroacetic acid-precipitable translation products obtained using poly (A+) mRNA was 48.5-fold over control translations performed without added mRNA. SDS-PAGE analysis of the translation products in combination with autoradiography showed that many proteins with apparent molecular weights in the range 14-90 K were synthesized. Immunoprecipitation studies performed using flea-allergic dog sera showed that several of the synthesized proteins corresponded with flea allergens. The allergenicity of the lysates was also confirmed by skin testing.

Allergens↗
PubMed1993

Hydatid disease in Western Australia: a novel approach to education and surveillance.

Hydatid disease (echinococcosis) remains a public health and economic problem of global proportion. Treatment usually requires major surgery and the prognosis for some forms of the disease is poor. The variable transmission patterns exhibited by the causative agents of this complex zoonosis, and inadequate support both internationally and nationally, have resulted in the establishment of control campaigns that are usually organized and funded at a local level. Here, Andrew Thompson, Ian Robertson, Robin Gasser and Clare Constantine describe a novel, targeted campaign of education and surveillance that has recently been initiated in Western Australia, where a totally artificial cycle of transmission for Fchinococcus granulosus has been established as a result of human activity.

Journal Article↗
PubMed1993

Cloning and pharmacological characterization of a rat mu opioid receptor.

We have isolated a rat cDNA clone that displays 75% amino acid homology with the mouse delta and rat kappa opioid receptors. The cDNA (designated pRMuR-12) encodes a protein of 398 amino acids comprising, in part, seven hydrophobic domains similar to those described for other G protein-linked receptors. Data from binding assays conducted with COS-1 cells transiently transfected with a CMV mammalian expression vector containing the full coding region of pRMuR-12 demonstrated mu receptor selectivity. In situ hybridization mRNA analysis revealed an mRNA distribution in rat brain that corresponds well to the distribution of binding sites labeled with mu-selective ligands. Based upon these observations, we conclude that pRMuR-12 encodes a mu opioid receptor.

Amino Acid Sequence↗
PubMed1993

Targets for sepsis therapies: tumor necrosis factor versus interleukin-1.

Clinical testing of therapies for sepsis that target tumor necrosis factor and interleukin-1 is currently in progress. It is now clear from early clinical results that patients display a heterogeneous response to anti-cytokine therapies that may be related to the stage or severity of disease. Experimental results show that either cytokine may contribute to the metabolic derangements that lead to organ dysfunction in severe sepsis. They also provide a physiological basis for understanding the benefits of anti-cytokine therapy in the most severely ill patients.

Animals↗
PubMed1993

Interleukin 1 receptor antagonist (IL-1ra) prevents or cures pulmonary fibrosis elicited in mice by bleomycin or silica.

We explored the role of interleukin 1 (IL-1) in two models of pulmonary fibrosis (PF), elicited in mice by the intra-tracheal instillation of bleomycin or silica. In both models, administration of IL-1 receptor antagonist (IL-1ra) by an osmotic minipump implanted i.p., at a rate of 0.5 microgram/h, completely prevented the collagen deposition, as evaluated by the lung hydroxyproline content on day 15 after instillation. IL-1ra had little or no influence on the number of cells recovered from the broncho-alveolar lavage. Study of histological sections suggests that IL-1ra globally decreased the proportion of damaged lung and particularly in silica the formation of nodules with a rich content in collagen fibrils. IL-1ra was also effective in reducing the lung hydroxyproline content when given on day 25 after instillation of bleomycin or silica, indicating that it may reverse established PF. This study indicates that IL-1ra might be useful for the treatment of incipient or established pulmonary fibrosis.

Animals↗
PubMed1993

Aggressive metastasectomy for pulmonic sarcomatous metastases: a follow-up study.

Pulmonary metastases are the primary cause of death due to bone and soft tissue sarcomas. We have previously shown that an aggressive approach and a new technique of multiple pulmonary metastasectomies have resulted in improved survival for patients with pulmonary metastases. In this follow-up study, an expanded database of patients was retrospectively analyzed to determine survivability as well as to evaluate potential prognostic indicators. Forty-nine patients, 26 of whom had osteogenic sarcoma (OGS), were evaluated. A number of patients had been referred from other institutions where their disease had been considered inoperable because it was extensive or recurrent. Using lateral thoracotomies exclusively, employment of a laser technique, and excision of minimal pulmonary parenchymal tissue, we performed aggressive metastasectomy. A mean of 3.0 thoracotomies was performed, in which an average of 10.2 nodules per thoracotomy were excised. Operative morbidity and mortality were minimal. The disease-free interval, the number of nodules resected, the number of thoracotomies performed, and the size of the nodules were evaluated as potential prognostic indicators. Statistically significant correlation could be established only for the size of the nodules resected. The 5-year survival rate for all patients was 39%; it was 24% for patients with OGS and 71% for those without OGS. Aggressive surgical resection of pulmonary metastases from bone and soft tissue sarcoma should be considered when there is control of local disease, no evidence of extrapulmonary metastasis, and adequate post-resection pulmonary reserve. The presence of bilateral, extensive, or recurrent disease is not a contraindication to thoracotomy. Aggressive resection of multiple nodules and improved chemotherapy appear to prolong survival of these patients when compared with survival rates of historical control subjects.

Adolescent↗
PubMed1993

Characterization of allergens of the cat flea, Ctenocephalides felis: detection and frequency of IgE antibodies in canine sera.

Flea allergens, fractionated by polyacrylamide gel electrophoresis and transferred to nitrocellulose, were identified using 20 flea-allergic dog sera in an enhanced chemiluminescent assay for canine IgE antibodies. At least 15 different flea components in the molecular weight range of 14-150 K bound IgE and every serum demonstrated a different pattern of binding. Three of the components with apparent molecular weights of 25, 40 and 58 K were each bound by at least 40% of the sera. No reactivity was seen when normal dog sera were used. These results demonstrate a greater number of flea allergens and a far greater diversity of the IgE antibody response to flea allergens than has previously been described, and suggest that immediate hypersensitivity may be an important mechanism in the pathogenesis of canine flea allergy.

Allergens↗
PubMed1993

The use of MRI in the diagnosis of benign and malignant bone and soft tissue tumours.

Two hundred and thirty four suspected primary bone and soft tissue tumours were investigated using plain films and MRI. The MR appearance of 200 of these tumours was assessed with respect to the intensity of the lesion, the homogeneity of the tumour, the presence or absence of a capsule or lobulation, whether the tumour was whorled or not and whether it contained either fluid or blood. Apart from benign lipomas and some malignant myxoid liposarcomas, however, it seemed virtually impossible to tell one tumour from another and in many cases to differentiate a benign lesion from a malignant tumour using MRI alone. We recommend that the workup of a suspected soft tissue tumour should be initially by MR scanning and that the workup of a suspected malignant bone tumour should be plain films followed by an MRI scan.

Adult↗
PubMed1993

Activities of several benzimidazoles and tubulin inhibitors against Giardia spp. in vitro.

Previous studies in our laboratory have shown that albendazole is effective against Giardia spp. in vitro and in vivo, prompting an investigation of the effects of several related benzimidazoles (BZs) on the viability of this protozoan parasite. A range of BZs was tested, and their effects were compared with those of a number of microtubule inhibitors. The effects produced by the two types of drugs were markedly similar, namely, trophozoite detachment and distortion of morphology and general structure, indicating a potential antimicrotubule mode of action for BZs. Mebendazole, albendazole, and fenbendazole proved to be among the most effective BZs tested, exhibiting apparent irreversibility. Nocodazole, oxfendazole, and albendazole sulfoxide, among others, produced transient inhibitions only. Further studies are required to evaluate all available BZs and other antigiardial agents to ensure the development of the most effective and safest antigiardial agent possible.

Albendazole↗
PubMed1993

Interleukin-1 (IL-1) receptor antagonist prevents Staphylococcus epidermidis-induced hypotension and reduces circulating levels of tumor necrosis factor and IL-1 beta in rabbits.

Similar to shock in gram-negative sepsis, shock from gram-positive organisms is mediated, in part, by tumor necrosis factor (TNF) and interleukin-1 (IL-1). In the present study, rabbits were infused with IL-1 receptor antagonist (IL-1ra) prior to and during Staphylococcus epidermidis-induced hypotension. After injection of bacteria, a maximal fall in mean arterial pressure to -42% below baseline occurred at 200 min in vehicle-treated animals compared with a nonsignificant decrease of only 7% in the IL-1ra-treated group (P < 0.01, vehicle versus IL-1ra). A similar attenuation was observed in the fall in systemic vascular resistance (P < 0.05). After the injection of S. epidermidis, TNF levels rose to a peak elevation of 475 +/- 160 U/ml in vehicle-treated rabbits, but in rabbits receiving IL-1ra, maximal TNF levels rose only to 85 +/- 23 U/ml (P < 0.01). Plasma IL-1 beta reached maximal concentrations at 180 min of 364 +/- 71 pg/ml in vehicle-treated animals but only 145 +/- 12 pg/ml in rabbits given IL-1ra (P < 0.05). The reductions in TNF and IL-1 were not due to interference by IL-1ra in the respective assays. In vitro, IL-1ra inhibited S. epidermidis-induced TNF from mononuclear cells by 31% +/- 11%, from spleen cells by 17% +/- 4% (P < 0.05), and from whole blood by 42% +/- 17%. Despite the near reversal of the fall in mean arterial pressure and systemic vascular resistance in IL-1ra-treated rabbits, leukopenia and thrombocytopenia were unaffected. These results demonstrate that IL-1ra blocks shock-like hemodynamic parameters and reduces circulating IL-1 and TNF levels in a model of gram-positive sepsis.

Animals↗
PubMed1993

Predicting early and intermediate-term outcome of coronary angioplasty in the elderly.

BACKGROUND: Although the technical success rate of coronary angioplasty in the elderly in high, very old patients have increased risk of procedure-related death and late recurrence of severe angina. We proposed to determine baseline variables that predict early and intermediate-term failure of percutaneous transluminal coronary angioplasty (PTCA) in patients more than 65 so we could effectively stratify risk. METHODS AND RESULTS: We studied 982 patients at least 65 years old who had urgent or elective PTCA (1980 through 1990). Follow-up (mean, 25 months) was obtained for all patients. Multiple baseline variables were analyzed with univariate and multivariate logistic regression to select independent ones to fit predictive models for in-hospital death or myocardial infarction (overall rate, 6.3%), total in-hospital adverse outcome (overall rate, 18.7%), cumulative survival free of myocardial infarction (overall rate, 15% at 3 years), and cumulative survival free of late nonfatal myocardial infarction, bypass surgery, repeat PTCA, or recurrent severe angina (overall rate, 47% at 3 years). The most heavily weighted parameter in the probability regression equation for each end point was the number of diseased coronary artery segments with at least 70% stenosis. Advanced age was less important. The number of concomitant medical illnesses was predictive of late outcome but not early in-hospital events. Lowest risk quintile versus highest risk quintile event rate was 2.9% versus 14% for acute myocardial infarction or death and 17.2% versus 29% for cumulative in-hospital events. For posthospital events at 3 years' follow-up, lowest risk quintile death or myocardial infarction rate was 4% versus 33% for highest risk quintile. For cumulative late adverse events at 3 years, the event rate was 28% versus 63% for the highest risk quintile. CONCLUSIONS: These results stratify patients at high and low risk of early and intermediate-term success after PTCA and identify elderly patients in whom PTCA is most appropriate.

Age Factors↗
PubMed1993

Cytokines contribute to airway dysfunction in antigen-challenged guinea pigs: inhibition of airway hyperreactivity, pulmonary eosinophil accumulation, and tumor necrosis factor generation by pretreatment with an interleukin-1 receptor antagonist.

The role of pro-inflammatory cytokines in an animal model of allergic lung disease was examined by use of an interleukin-1 receptor antagonist (IL-1ra) and a specific bioassay for tumor necrosis factor (TNF). Ovalbumin-sensitized guinea pigs exhibit a marked bronchial hyperreactivity (assessed by airway responsiveness to intravenous histamine) and pulmonary eosinophil accumulation (assessed by bronchoalveolar lavage) 24 h after challenge with aerosolized antigen. Exposure of animals to an aerosol of IL-1ra (50 micrograms over 30 min) immediately before antigen challenge resulted in a marked protection against bronchial hyperreactivity and pulmonary eosinophil accumulation compared with IL-1ra vehicle-pretreated animals. Additionally, we report for the first time generation of TNF bioactivity in the bronchoalveolar lavage of antigen-challenged animals, which was significantly reduced in animals exposed to aerosolized IL-1ra before challenge. These studies point to a key role for the cytokines IL-1 and possibly TNF in the pulmonary changes observed during allergic airway disease.

Aerosols↗
PubMed1993

5'-Heterogeneity of the mineralocorticoid receptor messenger ribonucleic acid: differential expression and regulation of splice variants within the rat hippocampus.

The mineralocorticoid receptor (MR) cDNA we previously isolated from the rat hippocampus differs from the clone isolated from the kidney at the 5'-untranslated (5'UT) region. The kidney clone (alpha MR mRNA) and the hippocampal clone (beta MR mRNA) possess unique 5'UT sequences of 220 and 300 nucleotides, respectively, but share an invariant peptide-coding domain and appear to encode an identical MR protein. The two mRNA variants may represent tissue-specific forms of the MR or may be coexpressed in the rat hippocampus along with other 5'UT variants. Here, we report that three mRNA subtypes were found in the hippocampus; their relative abundance was as follows: alpha = beta >> gamma. The three mRNA variants were differentially distributed within the hippocampal subfields, with the alpha form being highly enriched in CA2, dentate, the fasciculum cinereum, and the indusium griseum, whereas beta and gamma forms were evenly distributed through CA1-4. Adrenalectomy selectively increased alpha MR mRNA content, but the changes were restricted to CA1, CA2, and CA3 regions. We conclude that multiple MR mRNAs are differentially expressed in the rat hippocampus. The expression of alpha MR mRNA is specifically increased during adrenalectomy, suggesting that the increase in total MR mRNA content documented previously arises from a substantial increase in a single MR variant that elevates the total MR mRNA content, with the apparent elevation reflecting the average of regulated and unregulated transcripts. It is suggested from our data that a complex mechanism involving transcription and translation regulates MR expression in the rat hippocampus.

Adrenalectomy↗
PubMed1993

Scanning electron-microscopic and magnetic resonance-imaging studies of injuries to the patellofemoral joint after acute transarticular loading.

To examine the effects of transarticular loading on articular cartilage and subchondral bone, we used a canine model that we had developed previously, in which a standardized load of approximately 2000 newtons is delivered across the patellofemoral joint. The purpose of the study was to define and describe the initial changes, as seen on histopathological and magnetic resonance-imaging studies, that occur in the early stages after injury to the joint by transarticular loading. Scanning electron microscopy was used to define the extent and characteristics of the fractures produced in the subchondral bone of four patellae that were examined on the day of loading. We found multiple, extensive fractures through the zone of calcified cartilage and the subchondral bone, frequently with step-off displacement, and with little or no change in the gross appearance of the articular cartilage. Specimens from four patellae were examined histologically two weeks after loading, and the observed changes were correlated with those that had been demonstrated by scanning electron microscopy. Fractures through the zone of calcified cartilage and the subchondral bone, with step-off displacement, were prominent. Clefts were present in the surface of the articular cartilage and, in some areas, there was a focal loss of proteoglycan from the extracellular matrix, as indicated by the complete absence of staining with safranin O. Six dogs were examined one year after loading. There was healing of the subchondral fractures and restoration of proteoglycan in the extracellular matrix. However, superficial clefts and fissures were still present in the articular cartilage. Sequential magnetic resonance-imaging studies were also carried out on these six dogs, at two, eight, sixteen, thirty-six, and fifty-two weeks after loading. Two weeks after loading, all knees had soft-tissue swelling, effusion, and a decreased marrow signal in the medullary cavity of the patella. The decreased marrow signal and effusion were still present eight weeks after the impact, and then the findings gradually returned to normal. One year after loading, it was found that the histopathological changes had not been progressive; in fact, they had been ameliorated and, to some extent, reversed by repair processes. The early, severe magnetic resonance-imaging changes had also been reversed, so that this study demonstrated normal findings by one year after loading.

Animals↗