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Biomedical subjects

F Houston

Publications and source records attributed to F Houston.

At least 19 recordsLinked to original sources
PubMed2005

Use of a new immunoassay to measure PrP Sc levels in scrapie-infected sheep brains reveals PrP genotype-specific differences.

The diagnosis of prion diseases, such as scrapie and BSE, has traditionally relied upon the identification of the disease-associated form of the prion protein, PrP(Sc), based on its resistance to digestion by proteinase K (PK). A more recent development is the conformation-dependent immunoassay (CDI), which distinguishes between PrP Sc and normal PrP (PrP C) based on their differing solubility in guanidine hydrochloride rather than resistance or sensitivity to PK. We have developed a CDI-formatted sandwich immunoassay for the measurement of PrP Sc in sheep brain, which discriminates between clinically affected scrapie cases (natural or experimental) and uninfected controls of the same PrP genotype. Using this method, we have shown for the first time that, in sheep, the PrP genotype has a significant influence on the amount of PrP Sc deposited in the brains of animals experimentally infected with scrapie.

Animals↗
PubMed2005

Expression of PrPC on cellular components of sheep blood.

PrP(C), a glycosylphosphatidylinositol-linked glycoprotein, plays a central role in the pathogenesis of transmissible spongiform encephalopathies (TSEs), undergoing a conformational alteration to the disease-associated isoform, commonly designated PrP(Sc). PrP(C) is expressed in many tissues other than the nervous system, although its precise function(s) remains unclear. It has previously been demonstrated that TSEs can be transmitted by blood transfusion in sheep. The aim of this work was to identify which components of blood carried the infection. As an initial step, the distribution of PrP(C) on cellular components of sheep blood was examined to identify potential targets for infection. Cell-surface expression of PrP(C) was found only on peripheral blood mononuclear cells (PBMCs); however, platelets also contained significant amounts of intracellular PrP(C). The level of PrP(C) expressed on the cell surface of PBMCs was influenced by PrP genotype, with the highest levels found in scrapie-susceptible VRQ/VRQ sheep and the lowest levels in scrapie-resistant ARR/ARR sheep. In susceptible sheep, PrP(C) was expressed at varying levels on all major subsets of PBMCs, with the highest levels on the CD21(+) subset of B cells, and PrP expression was upregulated dramatically on CD21(+) B cells in some scrapie-infected sheep.

Animals↗
PubMed2003

Epidemiological implications of the susceptibility to BSE of putatively resistant sheep.

The experimental infection of sheep with bovine spongiform encephalopathy (BSE) by the oral route and the likelihood that sheep were fed BSE-infected meat and bone meal has led to extensive speculation as to whether or not sheep are naturally infected with BSE. In response, the UK government has initiated the National Scrapie Plan (NSP), an ambitious pound 120 million per year project to create a BSE- and scrapie-resistant national sheep flock, by selectively breeding for a genotype of sheep believed to be resistant to both diseases. This genotype has recently been shown to be susceptible to BSE by intracerebral (i.c.) inoculation. Should these sheep be sufficiently susceptible to BSE via natural transmission, the NSP might fail. Here we estimate the susceptibility of this genotype to horizontal (sheep-to-sheep) transmission of BSE by comparison with more extensive oral and i.c. exposure data for other sheep genotypes. We show that a previous estimate of the risk of BSE transmission to sheep via the feedborne route remains robust. However, using a mathematical model for the within-flock transmission of BSE, we show that, while the best estimate indicates that the NSP should be successful, current data cannot exclude the failure of the NSP.

Animals↗
PubMed2002

Effects of agent strain and host genotype on PrP accumulation in the brain of sheep naturally and experimentally affected with scrapie.

Different cellular and neuroanatomical types of disease-specific prion protein (PrP(d)) accumulation in the brain were identified in sheep of different breeds and PrP genotypes exposed to experimental or natural scrapie infection. Immunohistochemical examination of the brains of 43 sheep with clinical signs compatible with scrapie revealed 12 different PrP(d)types, which were subjectively quantified in eight different brain regions. The PrP(d)types were grouped into four PrP(d)patterns, the relative magnitude of which provided the PrP(d)profile of each sheep examined. The analysis of the differences in magnitude and relative proportion of each of these PrP(d)types and patterns indicated (1) an effect of the scrapie strain on the PrP(d)profile, and (2) a possible effect of the host genotype on the magnitude of PrP(d)accumulation in the brain, apparently related to the incubation period. Furthermore, intraneuronal deposition of PrP(d)was the type most closely associated with the development of clinical disease. We conclude that different scrapie strains can be distinguished by PrP immunohistochemical examination of brains of affected animals.

Animals↗
PubMed2002

Vacuolar lesion profile in sheep scrapie: factors influencing its variation and relationship to disease-specific PrP accumulation.

Detailed neuropathological examination for vacuolar lesions was performed on the brains of 42 sheep with clinical signs compatible with scrapie. The sheep were grouped according to their breed (Poll-Dorset, Cheviot, Welsh Mountain, Shetland and Suffolk), their PrP genotype at codons 136, 154 and 171 (VRQ/VRQ, VRQ/ARQ, VRQ/ARR and ARQ/ARQ) and the type of infection (experimental infection with SSBP/1, or natural disease). Twenty-two neuroanatomical sites from seven brain regions were examined for vacuolation in the neuropil and five sites at the level of the obex were examined for intraneuronal vacuolation. In 36 sheep, immunohistochemical examination for disease-specific PrP (PrP(d)) accumulation had also been performed in the same brain regions in an earlier study. The magnitude of total neuropil vacuolation was highest in the naturally affected ARQ/ARQ Suffolk sheep and lowest in the experimentally infected VRQ/VRQ Cheviot sheep and VRQ/ARR Poll-Dorset sheep. The severity of neuropil vacuolation at nine of the 22 neuroanatomical sites examined was used to generate a vacuolar lesion profile, which showed variations between the different sheep groups. These variations could be attributed to both PrP genotype and sheep breed and also possibly to scrapie agent; there was, however, considerable individual variation in lesion profile within sheep groups. All groups showed a similar ratio of neuropil vacuolation to neuronal vacuolation at the level of the obex. Although a positive correlation between neuropil vacuolation and PrP(d) deposition was generally observed, it was low except for the astrocyte-associated pattern of PrP(d) accumulation. The study suggests that vacuolar lesion profiles in sheep are affected by several factors and, by comparison with lesion profiles in mice, are of no more than limited value for discriminating between scrapie strains.

Animals↗
PubMed2002

Scrapie epidemic in a fully PrP-genotyped sheep flock.

In scrapie-affected sheep flocks, host PrP genotype plays a vital role in determining which sheep will succumb to scrapie and the incubation period. Consequently, within-flock scrapie dynamics is best understood within the context of the genotype profile of the flock. Here we describe a 17 month epidemic of scrapie in a commercially farmed flock of 230 genotyped Texel sheep. At the start of the study, 70% of the sheep were of three genotypes only: ARR/ARQ, ARH/ARQ and ARQ/ARQ. Only 15% of sheep encoded the disease-associated VRQ allele and only a single sheep (0.4%) was of the most susceptible VRQ/VRQ genotype. For susceptible genotypes there was a marked deficit (P<0.025) of older animals (> or =3 years), implying that some cases of scrapie had occurred previously. In the ensuing 17 months, 18 sheep of known genotype were confirmed positive for the disease: seven VRQ/ARQ, six VRQ/ARH, two VRQ/ARR, three ARQ/ARQ. Median ages at death were 2.7, 2.8, 4.2 and 3.8 years respectively. Mortality rates were 55, 86, 13 and 3% respectively. Survival analysis revealed a highly significant effect of genotype on survivorship, but no difference between VRQ/ARQ and VRQ/ARH, or between VRQ/ARR and ARQ/ARQ. There was no difference in the survivorship of middle- and older-age cohorts of susceptible sheep. Scrapie risk group (as defined by PrP genotype) was not associated with submission as a scrapie suspect but later found to be negative, or with dying of unknown causes on the farm.

Age Factors↗
PubMed2002

Can prion diseases be transmitted between individuals via blood transfusion: evidence from sheep experiments.

We have shown that it is possible to transmit bovine spongiform encephalitis (BSE) to a sheep by transfusion with whole blood taken from another sheep during the pre-clinical phase of an experimental BSE infection when the donor animal appears healthy. BSE and new variant Creutzfeld-Jakob disease (vCJD) in humans are caused by the same infectious agent and the sheep-BSE experimental model has similar pathogenesis, with involvement of the lymphoreticular system, to that of human vCJD. Although we have had only one case of positive transmission of BSE out of a total of 21 transfusions, our studies remain incomplete and further cases could occur. Our studies, however, reinforce the possibility that whole blood donated by pre-clinical vCJD-infected humans may represent a risk of spreading vCJD infection among the human population of the U.K.

Animals↗
PubMed2000

The signature of scrapie: differences in the PrP genotype profile of scrapie-affected and scrapie-free UK sheep flocks.

The amino-acid sequence of the PrP protein plays an important role in determining whether sheep are susceptible to scrapie. Although the genetics of scrapie susceptibility are now well understood, there have been few studies of the PrP gene at the population level, especially in commercially farmed sheep. Here we describe the PrP genetic profiles of the breeding stock of four UK sheep flocks, comprising nearly 650 animals in total. Two flocks had been scrapie affected for about eight years and two were scrapie free. Scrapie-resistant PrP genotypes predominated in all flocks but highly susceptible genotypes were present in each case. The distribution of PrP genotypes was similar in the scrapie-affected and scrapie-free flocks. The former, however, showed a slight but significant skew towards more susceptible genotypes despite their previous losses of susceptible sheep. Surprisingly, this skew was apparent in younger, but not older, sheep. We suggest that these patterns may occur if sheep flocks destined to become scrapie affected are predisposed by a genetic profile skewed towards susceptibility. The age structure of the scrapie-affected flocks suggests that the number of losses attributable directly or indirectly to scrapie considerably exceeds that recognized by the farmers, and also that significant losses may occur even in sheep of a moderately susceptible genotype. Similar patterns were not detected in the scrapie-free flocks, indicating that these losses are associated with scrapie infection as well as genotype.

Age Factors↗
PubMed2000

Transmission of BSE by blood transfusion in sheep.

We have shown that it is possible to transmit bovine spongiform encephalopathy (BSE) to a sheep by transfusion with whole blood taken from another sheep during the symptom-free phase of an experimental BSE infection. BSE and variant Creutzfeldt-Jakob disease (vCJD) In human beings are caused by the same infectious agent, and the sheep-BSE experimental model has a similar pathogenesis to that of human vCJD. Although UK blood transfusions are leucodepleted--a possible protective measure against any risk from blood transmission--this report suggests that blood donated by symptom-free vCJD-infected human beings may represent a risk of spread of vCJD infection among the human population of the UK.

Animals↗
PubMed2000

Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors.

The function of the cholinergic system is known to change during normal aging and in pathological conditions such as Alzheimer's disease. The present study was designed to assess, within the same group of old animals, the behavioral, electrophysiological and neurochemical effects of chronic treatment with agents that increase the function of the cholinergic system through both muscarinic and nicotinic mechanisms. Doses were determined that produced 60% cholinesterase inhibition by donepezil and galantamine for the old rats. This was chosen to be analogous to therapeutic levels achieved for treatment of human Alzheimer's disease patients with these agents. Because of the well-known age-related changes in spatial memory and hippocampal synaptic plasticity, spatial working memory in the radial eight-arm maze and hippocampal long-term potentiation induction and decay, as well as nicotinic receptor density and affinity, were measured in old rats implanted with minipumps that delivered donepezil, galantamine or saline. There was no effect of drug treatment on baseline synaptic transmission or on the threshold or magnitude of long-term potentiation induction. Both drug treatment groups, however, showed significantly extended long-term potentiation decay times at the perforant path-granule cell synapse over the saline control animals, as measured during the week following induction. Both drugs also elevated the number of nicotinic receptors within the hippocampus and neocortex. This is the first demonstration of cholinergic modulation of synaptic plasticity over the time-course of days. Furthermore, the durability of long-term potentiation was significantly, positively correlated with nicotinic receptor binding in the hippocampus. Chronic treatment with donepezil or galantamine had no significant effect on a well-learned spatial working memory task on the radial maze. These data suggest that the therapeutic doses of cholinesterase inhibitors used to treat patients with Alzheimer's disease may have effects on neurophysiology and neurochemistry that are close to the threshold for producing detectable behavioral improvements.

Acetylcholinesterase↗
PubMed1998

Cost-saving implant training aids.

This article describes a simple step-by-step procedure that uses inexpensive materials to enable those who wish to learn procedures used in the construction of a screw-type implant overdenture to practice these procedures before they use expensive precious metal components. The use of this procedure will result in considerable savings in training costs and affords a greater opportunity to provide practical experience before making this type of an overdenture for patients. It could also provide for a rapid expansion in the number of trained personnel who could make this form of treatment available to a larger number of patients.

Dental Alloys↗
PubMed1998

The fit of cast and premachined implant abutments.

STATEMENT OF PROBLEM: There is insufficient information regarding the adaptation of abutments to implants. PURPOSE: This study assessed the adaptation of premachined, cast, and laboratory modified premachined abutments to implants at two sites: abutment/implant interface and screw to screw seat. MATERIAL AND METHODS: Six combinations of abutments and implants were studied: CeraOne abutments joined to Nobel Biocare implants; STR (Implant Innovations Inc.) abutments joined to 31 implants; Cast UCLA (31) abutments subjected to porcelain firing cycles and joined to 31 implants; Cast UCLA abutments subjected to porcelain firing cycles and joined to Nobel Biocare implants; UCLA premachined abutments cast with gold palladium alloy and subjected to porcelain firing cycles (later joined to 31 implants); and UCLA premachined abutments joined to 31 implants. Each group contained five assemblies. RESULTS: The adaptation of abutments to implants was closer and the amounts of contact larger for assemblies with premachined and laboratory modified premachined abutments than for those with cast abutments. CONCLUSION: The finishing of custom-made abutments requires further refinement.

Analysis of Variance↗
PubMed1997

A comparison of the dimensional accuracy of the splinted and unsplinted impression techniques for the Bone-Lock implant system.

STATEMENT OF PROBLEM: The precise transfer of intraoral relationships of implants to laboratory working models is central to the success of implant prostheses. PURPOSE: In this study a stone master model incorporating five implants (Bone-Lock) was used to compare the dimensional accuracy of a splinted impression technique with an unsplinted impression technique. METHODS: A three-factor analysis of variance was used to examine the effect of technique, relative position of the implant on the cast, and plane of measurement. RESULTS: All three factors had a significant effect on dimensional accuracy. CONCLUSIONS: The splinted technique exhibited more deviation from the master model than the unsplinted technique did. This was primarily associated with rotational discrepancies around the long axes of the implants for the splinted technique.

Analysis of Variance↗
PubMed1995

Comparison of the dimensional accuracy of one- and two-step techniques with the use of putty/wash addition silicone impression materials.

This study compared the putty/wash one-step and two-step techniques for making addition silicone impressions. For each technique 15 impressions were made of a stainless steel base to which three tapered posts were attached. Stone models were made of all impressions. The results indicated that the interabutment distances increased slightly compared with the stainless steel model for both techniques, but the differences between techniques were not considered to be clinically important. The intraabutment measurements for the abutment without undercut increased, whereas abutments with undercuts decreased. These variations from the stainless steel model were also clinically insignificant.

Calcium Sulfate↗
PubMed1987

Periodontal status and bruxism. A comparative study of patients with periodontal disease and occlusal parafunctions.

This study investigated a possible association between bruxism and severity of periodontal disease. Subjects consisted of 51 patients (mean age 47.3 years) referred to the Department of Periodontology for treatment of moderate to severe periodontal disease (Perio-group) and 40 patients (mean age 48.9 years) referred to the Department of Stomatognathic Physiology for treatment of symptoms related to bruxism (Bruxism-group). Examination of the two groups included measurements of the alveolar bone height, probing attachment level, tooth mobility, and attrition of teeth. A questionnaire was also used to gain information on the patient's awareness of bruxism and tooth mobility. Awareness of clenching and/or grinding was reported by 57% of patients in the Bruxism-group and 24% of patients in the Perio-group. The perio-patients reported significantly higher frequency of tooth mobility than did the bruxism-patients. Alveolar bone loss, attachment loss, and tooth mobility were significantly more pronounced in the Perio-group than in the Bruxism-group. The Bruxism-group showed a higher frequency of tooth attrition than the Perio-group. Periodontal disease and bruxism seldom occurred in the same individual, and the results indicate that the two phenomena are in general not closely associated.

Adult↗
PubMed1987

Mandibular dysfunction and periodontitis. A comparative study of patients with periodontal disease and occlusal parafunctions.

Fifty-one patients (mean age, 47.3 years) with moderate to severe periodontal disease and 40 patients (mean age, 48.9 years) with symptoms related to bruxism (occlusal parafunctions such as grinding and/or clenching of the teeth) were compared with regard to periodontal conditions and signs and symptoms of mandibular dysfunction. The bruxists reported more symptoms of pain and dysfunction of the masticatory system than the periodontal patients. The clinical dysfunction index was significantly higher among the bruxists, while there was a similarity between the groups in the variation of occlusal conditions, except for occlusal wear, which was more pronounced in the bruxist group. Attrition was in general positively correlated to alveolar bone height. This correlation was stronger (and statistically significant) for the canines than for other teeth. Attrition was negatively correlated to tooth mobility. It is concluded that patients with moderate to severe periodontal disease and patients with bruxism/occlusal parafunctions are distinctly different with regard to signs and symptoms of mandibular dysfunction. The results support the opinions that there is no or only weak correlation between periodontal disease and bruxism, and between bruxism and occlusal status.

Adult↗