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Biomedical subjects

H G Thompson

Publications and source records attributed to H G Thompson.

At least 19 recordsLinked to original sources

Rapid detection and identification of biological and chemical agents by immunoassay, gene probe assay and enzyme inhibition using a silicon-based biosensor.

A rapid biosensor assay procedure that utilizes biotin streptavidin mediated filtration capture onto nitrocellulose membrane, in conjunction with a silicon-based light-addressable potentiometric sensor (LAPS) was developed for detection and identification of biological and chemical threat agents. Sandwich immunoassays, nucleic acid hybridization assays and enzyme inhibition assays are described. For immunoassays, the lower limits of detection (LOD) per 100-microl sample were approximately 5 pg/ml for protein (Staphylococcal enterotoxin B), 2 ng/ml for virus (Newcastle disease virus), and 20 ng/ml for vegetative bacteria (Brucella melitensis). In a dual gene probe assay format, the LOD was 0.30 fmol (1.8 x 10(8) copies per 60-microl) of single stranded target DNA. Enzyme inhibition assays on the LAPS using acetylcholinesterase were able to detect soman and sarin in aqueous samples at 2 and 8 pg (100 and 600 pM), respectively. The assays were easy to perform and required a total time equal to the reaction period plus about 15 min for filtering, washing and sensing. The assay format is suitable for detection of a wide range of infectious and toxic substances. New assays can be developed and optimized readily, often within 1 or 2 days.

Biosensing Techniques↗

Rapid immunofiltration assay of Newcastle disease virus using a silicon sensor.

A rapid nonradioactive sandwich immunoassay which utilizes biotin-streptavidin mediated filtration capture of immune complexes in conjunction with a silicon sensor was developed for the detection of virus. Using purified Newcastle disease virus as a model, the lower limits of detection (LOD) were determined for a number of immunoassay configurations employing both monoclonal and polyclonal antibodies. The LODs ranged from 1.3 ng/ml (sample volume of 100 microliter) for an incubation of 60 min to 400 ng/ml for a 1 min incubation. The sandwich immune complexes were formed from one-step incubation of antibody and antigen. No 'hook' effects were observed over a wide range of analyte concentrations. The assays were easy to perform and required a total time equal to the incubation period plus about 5 min. The assay format is suitable for virus, bacteria and protein antigens. New assays can be developed and optimized readily, often within 1 day.

Antibodies, Monoclonal↗

The acetylcholinesterase reactivator HI-6 (1-[[[4-(aminocarbonyl)pyridinio]methoxyl]methyl]- 2-[(hydroxyimino)methyl]-pyridinium dichloride): a comparative study of HI-6 samples from various sources.

A comparison of the chemical purity, toxicology and potency of HI-6 (1-[[[4-(aminocarbonyl)pyridinio]methoxy]methyl]-2- [(hydroxyimino)methyl]-pyridinium dichloride) obtained from various sources (Canada, Israel, Yugoslavia, The Netherlands, United Kingdom) was performed. There were no significant differences between HI-6 obtained from Israel, Yugoslavia, The Netherlands and Canada regarding their potency, when combined with atropine, as an antidote of organophosphate poisoning. HI-6 obtained from the United Kingdom was significantly more toxic and less potent than any of the other HI-6 samples. In addition, the results of this study showed that there was no significant difference between HI-6 prepared as a laboratory batch and HI-6 prepared commercially with regards to chemical purity, toxicology or potency.

Animals↗

Lymphocyte adherence to myelinated tissue in multiple sclerosis: correlation with disease activity.

Human peripheral blood T-lymphocytes adhere to myelinated sections of human and nonhuman brain tissue. No lymphocyte adherence is seen to gray matter. Lymphocytes from patients with MS adhere more than control lymphocytes. Lymphocyte adherence in patients with stable MS and in healthy controls did not vary more than 15%. Lymphocyte adherence in MS patients was decreased significantly during exacerbation. Values rose to pre-exacerbation levels in remissions. Results suggest that T cells that adhere to myelin may migrate from the peripheral blood during exacerbation.

Cell Adhesion↗

Lymphocyte adherence in multiple sclerosis.

It has been reported that peripheral blood lymphocytes from patients with multiple sclerosis (MS) adhere to measles-infected human epithelial cells in significantly greater numbers than do lymphocytes from healthy volunteers or patients with other neurologic diseases. We have confirmed this observation in three separate studies, and have investigated the relationship of lymphocyte adherence to the clinical state. Lymphocyte adherence determination values correlated with the degree of certainty of the clinical diagnosis of MS, and lymphocyte adherence values in individual patients increased during clinical exacerbations. Judicious use of this test may facilitate the diagnosis of MS.

Epithelium↗

Physiological characteristics of free-living and parasitic stages of strains of Haemonchus contortus, susceptible or resistant to benzimidazole anthelmintics.

The effect of changes in genetic constitution (associated with developing benzimidazole resistance) on the physiological characteristics of Haemonchus contortus was investigated. Benzimidazole resistant H contortus were significantly more infective for sheep (20 per cent) than benzimidazole susceptible strains. Pathological changes were more severe in sheep infected with resistant H contortus as measured by packed cell volume, plasma protein concentration and haemoglobin levels. Faecal egg output was significantly higher for resistant strains as was the development and survival of eggs and free-living stages on pasture. Infective third stage larvae of benzimidazole resistant H contortus had a significantly faster exsheathment rate in rumenal fluid than did susceptible strains. These adaptive changes in response to continuing anthelmintic selection of resistant worm populations are discussed and the implications of these findings for worm control programmes indicated.

Animals↗

The effect of route of administration on the anthelmintic efficacy of benzimidazole anthelmintics in sheep infected with strains of Haemonchus contortus and Trichostrongylus colubriformis resistant or susceptible to thiabendazole.

Observations of erratic anthelmintic activity of fenbendazole against known standardised thiabendazole-resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep were investigated. Fenbendazole at a dose rate of 10 mg/kg body weight was administered by oral, intra-ruminal or intra-abomasal routes, and was most effective against both resistant strains following intra-ruminal administration. In addition thiabendazole, oxibendazole, fenbendazole, parbendazole and mebendazole plus two unrelated compounds, levamisole and morantel tartrate, were used at one and a half times their suggested or recommended therapeutic dose rate against thiabendazole-resistant strains of H contortus and T colubriformis in sheep; each drug being administered by the intra-ruminal or intra-abomasal routes. Fenbendazole was more effective against both strains following intra-ruminal administration. Parbendazole was more effective against the resistant strain of T colubriformis following intra-ruminal administration. At the dose rate chosen for the other benzimidazoles used against these resistant strains, there was no difference in anthelmintic efficacy due to route of administration. Levamisole was highly effective against both resistant strains, irrespective of the route of administration. In the groups treated with morantel tartrate, the results obtained were difficult to interpret due to mortalities and a highly variable response in the surviving sheep. Fenbendazole, thiabendazole and mebendazole when used at their suggested or recommended therapeutic dose rate in sheep, were highly effective against known thiabendazole-susceptible strains of H contortus and T colubriformis following both intra-ruminal or intra-abomasal administration.

Abomasum↗

The anthelmintic efficacy of fenbendazole against thiabendazole-resistant strains of Haemonchus contortus and Trichostrongylus colubriformis in sheep.

The anthelmintic efficacy of fenbendazole (methyl 5-(phenylthio)-2-benzimidazole carbamate) was tested in sheep against standardised strains of Hcaemonchus contortus and Trichostrongylus colubriformis, known to be resistant to thiabendazole (LD90 for thiabendazole against H ontortus was 200 mg/kg bodyweight and against T colubriformis was 150 mg/kg). Fenbendazole at dose rates of 5, 10 and 20 mg/kg per os reduced total worm counts in H contortus infected sheep by 66, 90 and 100 per cent respectively, with similar reductions recorded for worm egg outputs. For the thiabendazole resistant strain of T colubriformis, fenbendazole reduced total worm counts in infected sheep by 4, 44 (40-48), 79 (75-83), 96 and 100 per cent at dose rates of 5, 10, 20, 40 and 80 mg/kg per os. Significant suppression of worm-egg production by thiabendazole resistant T colubriformis was obtained with fenbendazole at dose levels of 5 mg/kg and above. The implications of these results are discussed in the light of the increasing occurrence of strains of trichostrongylid nematodes resistant to currently available benzimidazole anthelmintics.

Animals↗