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Biomedical subjects

J Armour

Publications and source records attributed to J Armour.

At least 19 recordsLinked to original sources

Allelic imbalance on chromosome 1 in human breast cancer. I. Minisatellite and RFLP analysis.

In order to characterise the role of chromosome 1 more fully in breast cancer, polymorphic markers mapping along the length of the whole chromosome were used to assess a panel of 71 tumour-lymphocyte pairs for allelic imbalance. Complex patterns of alterations were established that are consistent with cytogenetic data in the literature. Deletion mapping of individuals with loss of heterozygosity identified five independent smallest common regions of deletion, two of which are novel. There are also three discrete regions showing a gain in copy number of one homologue. The two arms of the chromosome may be subject to different events; the short arm primarily undergoes interstitial deletions, whereas the long arm is subject to whole arm events (as both gains and losses) as well as regional deletions.

Alleles

Establishment and pathogenicity of two strains of Ostertagia ostertagi and Cooperia oncophora in calves in different locations.

An experiment was carried out simultaneously in Glasgow and in Wageningen to investigate possible differences between the local strains of Ostertagia ostertagi and Cooperia oncophora. In each location calves of the local Friesian breed were infected with 100,000 larvae of either the Glasgow or Wageningen strain of O ostertagi or C oncophora. At both locations the calves received the same diet. The Glasgow strain of O ostertagi was more pathogenic than the Wageningen strain and a larger proportion of the worm burden was found in the abomasal mucosa. The number of ova per female was greater in the Wageningen strain. For C oncophora the Wageningen strain gave rise to higher worm burdens and longer worms. Differences were also present between locations. The British Friesians had higher worm burdens of C oncophora and the worms of this species were longer in this host. Compared with the Dutch Friesians the British calves had a higher proportion of O ostertagi in the mucosa. This experiment showed how difficult it is to compare data from the literature because of differences in parasite and host strains and laboratory techniques.

Abomasum

Response to ivermectin treatment of parasitic stages of Haemonchus contortus resistant or susceptible to ivermectin.

Two groups of 33 helminth-naive lambs were infected with 5,000 L3 of an ivermectin-resistant or -susceptible strain of Haemonchus contortus (groups R and S). On days 6, 10, 16, and 21 postinfection, 5 animals from each group were chosen at random and orally treated with 0.2 mg/kg of ivermectin. On each occasion, 2 randomly selected lambs from each group were also killed to determine the number and stage of development of the worms present at the time of treatment. These necropsies revealed that by day 6 early and late fourth-stage larvae were present, whereas on day 10 the early fifth stage had been reached; by days 16 and 21 all worms had reached the adult stage. Necropsies on day 28 postinfection revealed that although animals treated at day 6 had 26.3% fewer worms than the controls, there was no significant difference (P greater than 0.05) between worm burdens from any of the animals infected with the R strain and treated at different times after infection when compared with the untreated controls. With ivermectin significant reductions were obtained in the worm burdens of the animals infected with the susceptible strain; these were reduced by 96% when treatment was given on day 6 against fourth-stage larvae and 98.9% when the drug was given on day 21 against adult stages. From these results it is clear that resistance to ivermectin in this strain of H. contortus is present as early as the fourth larval stage.

Animals

Effect of development of resistance to benzimidazoles, salicylanilides and ivermectin on the pathogenicity and survival of Haemonchus contortus.

Two groups of six lambs were infected either with an anthelmintic-susceptible strain of Haemonchus contortus or with a strain resistant to benzimidazoles, ivermectin and salicylanilides. The pathogenicity of the two strains of parasite was compared by monitoring the development of anaemia, changes in plasma proteins and abomasal damage in the two groups of lambs. There were no significant differences between the groups, suggesting that the development of resistance to several anthelmintics did not correlate with an increase in the pathogenicity of the parasites. Furthermore, the establishment rates and egg production of the susceptible and resistant parasites were similar. However, fewer of the eggs of the resistant parasites survived and developed at a variety of temperatures.

Animals

Fecundity of anthelmintic resistant adult Haemonchus contortus after exposure to ivermectin or benzimidazoles in vivo.

A strain of Haemonchus contortus resistant to the benzimidazoles, ivermectin and salicylanilides was used to study the effect of exposure to ivermectin or oxfendazole on the number of eggs produced by adult female parasites. After anthelmintic administration there was a reduction in the faecal egg count of the infected lambs. Ivermectin caused a reduction in the number of eggs within adult parasites for up to 72 hours but this returned to higher than pre-treatment levels at 168 hours after treatment. After oxfendazole treatment there was an increase in the number of eggs stored in the adult parasites at 24 hours and then a significant reduction in the number of eggs for over 168 hours. This suggested that both ivermectin and oxfendazole have a deleterious effect on the reproductive potential of female H contortus although the parasites are resistant to these drugs. These results confirm the importance of allowing up to 10 days to elapse between the time of administration of an anthelmintic and the collecting of faecal samples when using the faecal egg count reduction test to identify anthelmintic resistance, especially when using benzimidazoles. The more prolonged effect on fecundity produced by oxfendazole may reflect the antimitotic action of the benzimidazole anthelmintics.

Animals

Efficacy of some anthelmintics on an ivermectin-resistant strain of Haemonchus contortus in sheep.

Following evidence of reduced efficacy of ivermectin in a field population of Haemonchus contortus in Brazil, this strain of the parasite was submitted to a controlled anthelmintic test. Eighty worm-free lambs were randomly split into two groups of 40. Each lamb in the first group was infected with 5000 third stage larvae (L3) of the ivermectin-resistant strain; the remaining 40 lambs were each infected with 5000 L3 of a H. contortus strain of known susceptibility to the major groups of anthelmintic compounds used in sheep. On Day 28 post-infection, each group was subdivided according to egg counts and at random into four sub-groups of ten lambs, each of which was treated with albendazole (ABZ) at 3.8 mg kg-1, levamisole (LEV) at 7.5 mg kg-1 or ivermectin (IVM) at 0.2 mg kg-1, or was left as untreated control. At slaughter, 7 days later, all the anthelmintics reduced worm burdens in animals infected with the susceptible strain (ABZ 98.9%, LEV and IVM 100%). By contrast, in the lambs infected with the ivermectin-resistant strain, LEV was 99.8% effective, but ABZ reduced worm counts by only 14.7% and IVM by only 10.4%. Interestingly at necropsy on Day 7 post-treatment, the egg counts in the resistant strain treated with ABZ had been reduced by 92.5%, although worm counts were reduced by only 14.7%.(ABSTRACT TRUNCATED AT 250 WORDS)

Albendazole

Pathophysiological and parasitological studies on a concurrent infection of Ostertagia ostertagi and Cooperia oncophora in calves.

Calves which had received daily concurrent infections of 2000 Ostertagia ostertagi and 10,000 Cooperia oncophora infective larvae over a 42-day period displayed a range of clinical signs typical of acute parasitic gastroenteritis including inappetence, weight loss, hypoalbuminaemia and diarrhoea. There were consistent and significant depressions in both digestive efficiency and nitrogen retention. Radioisotopic studies revealed marked disturbances in protein metabolism which were associated with high losses of plasma proteins into the gastrointestinal tract. On post mortem examination larval establishment of O ostertagi was seen to be high. The adverse changes were prevented by the prior administration of a morantel bolus.

Animals

Pathophysiology of the periparturient egg rise in sheep: the role of prolactin.

The involvement of prolactin in the periparturient rise in the faecal nematode egg count in sheep was investigated. Ostertagia circumcincta larvae (5000 third stage larvae three times weekly) were administered to adult immune ewes from three weeks before parturition to three weeks afterwards. Ten ewes were injected twice daily with 2-bromo-alpha-ergocryptine (bromocriptine), an antagonist of prolactin secretion, for two weeks starting two days after lambing while 10 ewes remained untreated. Bromocriptine treatment was initiated approximately two weeks pre partum in three other ewes. Plasma pepsinogen concentrations rose significantly by one week after the start of O circumcincta larval challenge in all the ewes but faecal egg counts remained negative until approximately one week post partum. Plasma prolactin concentration was reduced to a very low level in all bromocriptine treated ewes but this did not alter the dynamics of the periparturient rise in faecal egg counts. Neither cell-mediated nor humoral immunity of the ewes, as assessed by their sensitivity to BCG inoculation and by antibody titre raised against horse red blood cells, respectively, were impaired during the rise in faecal egg count, nor were these parameters altered by manipulation of plasma prolactin concentration. Lamb growth rate was not retarded by low plasma prolactin concentration in the bromocriptine treated ewes. These results are not consistent with the generally held hypothesis that elevated plasma prolactin concentration is directly associated with the periparturient rise.

Animals

The influence of host immunity on the epidemiology of trichostrongyle infections in cattle.

The acquisition of immunity to the important trichostrongyles of cattle is reviewed and the subsequent effect on the epidemiology of trichostrongylosis is discussed. Examples of factors which can delay or impair the development of immunity to these nematode infections are presented. These include the interactions with anthelmintic prophylactic programmes, nutrition, intercurrent infections, pregnancy and lactation.

Animal Nutritional Physiological Phenomena

Anthelmintic resistance and the control of ovine ostertagiasis: a drug action model for genetic selection.

A site-specific genetic prediction model is presented, which examines the influences of different anthelmintic treatment regimens on selecting for drug resistance within a sheep management system. The model exploits the power of modern microcomputers to integrate factors such as parasite strain, geographic location, management practice and genetic fitness to identify effective control regimens which do not lead to resistant Ostertagia circumcincta strains over a 30-year horizon. The potential use of the model as a farm level management-support tool is discussed.

Animals

Level of benzimidazole resistance in a strain of Ostertagia circumcincta studied over several infections in lambs.

A benzimidazole-resistant strain of Ostertagia circumcincta (HFRO) was used experimentally to infect lambs. The level of resistance, measured by an egg hatch assay, was studied throughout each infection and also after treatment of the lambs with fenbendazole. The HFRO strain was highly resistant to benzimidazoles. There was day-to-day variation in the level of resistance throughout a single infection with a high level of resistance in the early part of the infection, around Day 27 post-inoculation of infective larvae, falling to a lower level later in the infection. Egg hatch assays on the 3 days immediately post-treatment with fenbendazole showed the resistance level was high then resistance fell to the pre-treatment level after 7 days. Selection for benzimidazole resistance using fenbendazole treatment at the normal dose rate of 5 mg kg-1 over five passages of the HFRO strain in lambs failed to increase the resistance level. Storage of larvae over a 5-month period at 4 degrees C, prior to infection of lambs, did not produce any alteration in the resistance level. The possible reasons for the variations in resistance found with the HFRO strain are discussed along with the implications for sheep parasite control and further development of benzimidazole resistance.

Albendazole

The retinoblastoma gene is frequently altered leading to loss of expression in primary breast tumours.

We have analysed the organisation of the retinoblastoma (RB1) gene in 77 primary breast carcinomas, in metastatic tissue derived from 16 of those primary tumours, and in a variety of benign breast lesions. Expression of RB1 was also assessed in most samples by immunohistochemical detection of the RB1 protein in tissue sections. Structural abnormalities to RB1 were detected in DNA from 15/77 (19%) of primary breast carcinomas examined. Where DNA was available from metastatic tissue derived from such primary tumours, the same aberration could be detected. No alterations were seen in benign breast lesions. 16/56 (29%) of tumours examined for expression by immunohistochemical methods showed a proportion of tumour cells to be completely negative for the RB1 protein. All tumours in which a structural alteration to RB1 was detected had a proportion of negative cells, except for one case where all cells were positive. Several primary tumour samples were identified where there was no detectable structural change to the gene, but there was loss of expression in some tumour cells. The data presented here demonstrate that changes to the RB1 gene leading to loss of expression of both alleles are frequent in primary human breast tumours.

Amino Acid Sequence

Pathophysiological and parasitological studies on Ostertagia ostertagi infections in calves.

Friesian calves given a low level infection of the abomasal parasite Ostertagia ostertagi over a six week period displayed a mild diarrhoea with high faecal egg counts and elevated plasma pepsinogen values. At necropsy on day 23 abomasal lesions characteristic of ostertagiasis were widespread. At 42 and 84 days oedema and congestion were also prominent. Total worm burdens on days 23 and 42 were similar but a marked decrease had occurred by day 84. Feed digestibility and nitrogen economy were not markedly affected but radioisotopic measurements demonstrated an increase in albumin disappearance and catabolic rates, and plasma faecal clearance during the course of the infection. Prior administration of a morantel sustained release bolus to a group of similarly infected calves reduced the total worm burdens to less than 50 per cent of those recorded in the infected calves on days 23 and 42 and this fell to 3 per cent on day 84. Abomasal damage and the adverse pathophysiological changes associated with infection were prevented in this group.

Abomasum

Control of naturally acquired bovine parasitic bronchitis and gastroenteritis with an oxfendazole pulse release device.

Four groups, each of six male Friesian calves, were set-stocked on separate 0.66 ha paddocks from May 7 until October 23 1986. Each of the animals in groups 1 and 4 was dosed with an oxfendazole pulse release bolus at turn out whereas the animals in groups 2 and 3 were left untreated. Parasite-free naive tracer calves were introduced into each paddock for a limited period 12 days after turn out and again at the end of the trial. No adverse reactions or clinical signs were observed in either of the groups of calves which received boluses. The development of clinical parasitic gastroenteritis in both the untreated groups necessitated the humane slaughter of two animals and emergency anthelmintic treatment of the remainder. The lower plasma pepsinogen concentrations, and lower faecal egg and larval counts and worm burdens post mortem, together with the absence of clinical signs of parasitic gastroenteritis and bronchitis in the treated calves, confirmed the high efficacy of the bolus treatment.

Animals

Immunity of ivermectin treated cattle to challenge from helminth parasites in the following season.

Two groups of yearling cattle which had been treated with ivermectin either three and eight, or three, eight and 13 weeks after turn out to trichostrongyle contaminated pasture in their first grazing season were exposed in the following season to natural challenge with helminth parasites. To assess their immunity to this challenge each group shared a pasture with parasite naive first season calves. No anthelmintic treatments were administered at any time during the year. Throughout the grazing period the yearlings showed normal respiratory rates, negative faecal lungworm larval counts, and, relative to the calves, low faecal trichostrongyle egg counts. All the first season calves developed patent lungworm infections and on one occasion the mean respiratory rates of each group of calves were significantly greater than those of the yearling cattle. At the end of the grazing period, from early May until late September or October 1986, the cattle were removed from pasture and together with parasite naive controls challenged with either 10 or 22 third stage larvae of Dictyocaulus viviparus/kg bodyweight and necropsied between 18 and 23 days later. Although the experimental challenge resulted in relatively heavy lungworm infection of the naive controls, none of the yearlings and only three of the 11 calves which had been at pasture were found to be infected. However, large numbers of arrested fourth stage larvae of Ostertagia ostertagi were present in all the naturally infected yearlings and calves.

Animals