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Biomedical subjects

T Sweeney

Publications and source records attributed to T Sweeney.

At least 19 recordsLinked to original sources

Is there a relationship between prion protein genotype and ovulation rate and litter size in sheep?

The identification of an association between polymorphisms of the prion protein (PrP) gene and susceptibility to scrapie has enabled the development of breeding programmes to increase natural resistance to scrapie. It is, however, imperative to identify if such selection would affect important reproduction and production traits. The objective of this study was to determine if there is a relationship between polymorphisms at codons 136, 154 and 171 of the PrP gene and ovulation rate or litter size in sheep. Data were collected from a mixed-aged flock of Belclare ewes, over a 9-year period. Ovulation rate was determined annually using laparoscopy by counting the number of corpora lutea at each of two consecutive oestrous cycles, one immediately before and one after mating (2418 records from 366 ewes). Litter size was recorded at parturition (875 records from 353 ewes). The five common PrP alleles were present in the population and 14 PrP genotypes were represented among the animals studied. There was no significant overall effect of PrP genotype on ovulation rate or litter size and pairwise comparisons among genotypes did not reveal any significant differences for either trait. These data suggest that breeding programmes based on selection for specific polymorphisms of the PrP gene will not influence ovulation rate or litter size, at least in the breed studied.

Animals↗

Effect of carprofen administration during banding or burdizzo castration of bulls on plasma cortisol, in vitro interferon-gamma production, acute-phase proteins, feed intake, and growth.

The objective of this study was to determine the effect of carprofen (C) administration before banding or burdizzo castration of bulls on cortisol, in vitro interferon-gamma (IFN-gamma) production, acute-phase proteins, feed intake, and growth. Fifty Holstein Friesian bulls (5.5 mo old; 191 +/- 3.7 kg) were blocked by weight and assigned randomly to 1 of 5 treatments (n = 10/treatment): 1) untreated control (2) banding castration at 0 min (Band); 3) Band following an i.v. injection of 1.4 mg/kg of BW of C at -20 min (Band+C); 4) Burdizzo castration at 0 min (Burd); or 5) Burd following 1.4 mg/kg of BW of C at -20 min (Burd+C). Castration acutely increased plasma cortisol concentrations compared with control; no significant differences occurred in peak and interval to peak cortisol responses between Band and Band+C or Burd and Burd+C groups. The administration of C in Band+C reduced (P < 0.05) the cortisol concentration between 6 and 12 h postcastration compared with Band animals. Overall, the integrated cortisol response was greater (P < 0.05) in the castrates than in control, whereas C treatments tended to reduce this response compared with Band (P = 0.08) and Burd (P = 0.07), respectively. Plasma fibrinogen was elevated in Band animals on d 14 and in Burd animals on d 3 and 14. Carprofen administration reduced Band- and Burd-induced fibrinogen production on d 14 and 3, respectively. Plasma haptoglobin was elevated in Band animals on d 3 and 35 compared with control, and C administration was effective in reducing the haptoglobin elevation on d 35 in Band+C compared with Band. There were no differences among treatments in in vitro IFN-gamma production induced by concanavalin A and phytohemagglutinin on d 1 and 2. Overall from d -1 to 16, there were no DMI differences among treatments. From d -1 to 35, there were no ADG differences among treatments. In conclusion, banding and burdizzo castration increased plasma cortisol with no change in in vitro IFN-gamma production. Carprofen (1.4 mg/kg of BW) tended to reduce the integrated cortisol response, and it reduced cortisol secretion in banded animals between 6 and 12 h postcastration. There was an increased acute-phase protein production following castration; this response was effectively moderated by the administration of C before castration.

Acute-Phase Proteins↗

Short communication: A potential antiapoptotic phenotype in neutrophils of cows milked once daily in early lactation.

The objectives of this experiment were to compare the circulating concentrations of cortisol and determine whether these correlated with the expression profiles of a set of candidate apoptosis genes in neutrophils of Holstein-Friesian cows milked once vs. 3 times daily for 28 d postpartum. Cows on the once-daily milking regimen had significantly higher plasma cortisol concentrations on d 3, 14, and 28 postpartum than did those milked 3 times daily. On d 3 postpartum, when differences in cortisol and neutrophil counts were highest between the groups, mean mRNA abundance of nuclear factor kappaB p65 subunit, IkappaBalpha, X-linked inhibitor of apoptosis; and heat shock protein 70 were higher in neutrophils of the cows milked once daily than in cows milked 3 times daily. However, no correlations were detected among plasma cortisol concentration, neutrophil count, or neutrophil gene expression in this study. Results suggest that the modest neutrophilia associated with once daily milking of cows immediately postpartum may be related to modifications in the cells' apoptotic program by factors other than cortisol.

Animals↗

Clinical and pathological features of experimental scrapie in Irish Blackface Mountain sheep.

There have been no reports of natural scrapie in Irish Blackface Mountain (BM) sheep which account for approximately 16% of the Irish national sheep flock. The aim of this study was to determine if Irish BM sheep had unusual clinical and/or pathological features of scrapie which would account for failure to diagnose the disease in this breed. BM (n=7), Texel (n=3) and Suffolk sheep (n=1) of scrapie-susceptible PrP genotypes (ARQ/ARQ and VRQ/ARQ) were orally challenged with scrapie-infected brain inoculum. The incubation period, clinical signs, pathology and distribution of disease specific prion protein (PrP(d)) in scrapie-affected BM sheep were similar to scrapie in the Texel and Suffolk sheep. It was concluded that there was no evidence to suggest that scrapie in BM sheep differs clinicopathologically from scrapie in other breeds of sheep.

Animals↗

Intron 1 of the interferon gamma gene: Its role in nematode resistance in Suffolk and Texel sheep breeds.

Genetic variation at intron 1 of the interferon gamma gene has recently been associated with variation in faecal egg count in Romney, Merino and Soay breeds of sheep. The Texel breed is more resistant to gastrointestinal nematode infection than the Suffolk breed, based on faecal egg count. Hence, the objective of this experiment was to characterise the polymorphisms of intron 1 of the interferon gammagene in Suffolk and Texel sheep, and to determine if the characterised haplotype variants were associated with faecal egg count variation in these breeds. Intron 1 haplotypes and faecal egg measurements were determined for Suffolks (n=113) and Texels (n=135). Four haplotypes were identified in Suffolks (A, B, C and D), two haplotypes as previously described, and two previously unknown haplotypes. However, there was no association between interferon gamma intron 1 haplotype and faecal egg count in Suffolks. In contrast, two previously identified haplotypes (A and B) were present in the Texel breed, and the B haplotype was associated with resistance to nematode infection (P=0.02). These results suggest that intron 1 of the interferon gamma gene has an important role in resistance to nematode infection in the Texel breed.

Animals↗

Immunohistochemical distinction between preclinical bovine spongiform encephalopathy and scrapie infection in sheep.

Sheep are susceptible experimentally to bovine spongiform encephalopathy (BSE), the clinical signs being indistinguishable from those of scrapie. Because of the possibility of natural ovine BSE infection, laboratory tests are needed to distinguish between scrapie and BSE infection. The objectives of this study were to determine whether (1) PrPSc accumulates in biopsy samples of the tonsil or third eyelid, or both, of BSE-infected sheep before the appearance of clinical disease, and (2) such samples from BSE- and scrapie-infected sheep differ in respect of PrPSc accumulations. Homozygous ARQ sheep (n = 10) were dosed orally at 4-5 months of age with a brain homogenate from BSE-infected cattle. Third eyelid and tonsillar biopsy samples were taken at < or = 6 monthly intervals post-infection and examined immunohistochemically for PrPSc. Third eyelid protuberances were difficult to identify, resulting in many unsuitable samples; however, third eyelid samples shown to contain lymphoid follicles were invariably negative for PrPSc. In contrast, tonsillar biopsy samples became positive for PrPSc from 11 to 20 months post-infection. Consistent differences in the morphology of PrPSc granules in tingible body macrophages (TBMs) between BSE- and scrapie-infected sheep were detected with anti-peptide antibodies directed towards amino acids 93-106 of the ovine prion protein: thus, PrPSc appeared as single granules in TBMs of tonsillar sections from BSE-infected sheep, whereas clusters of PrPSc granules were observed within TBMs in the tonsils of scrapie-infected sheep. In contrast, antibodies against epitopes situated N- and C-terminally from the 93-106 region of the ovine prion protein revealed no differences between BSE- and scrapie-infected sheep in terms of PrPSc granules in TBMs.

Animals↗

Major histocompatibility complex DRB1 gene: its role in nematode resistance in Suffolk and Texel sheep breeds.

A potential control strategy for nematode infection in sheep is the implementation of a breeding programme to select for genes associated with resistance. The Texel breed is more resistant to gastrointestinal nematode infection than the Suffolk breed, based on faecal egg count, and this difference should enable the identification of some of the genes responsible for resistance. The objective of this study was to determine if variation at the ovine MHC-DRB1 locus was associated with variation in faecal egg count in Suffolk and Texel sheep. Ovar-DRB1 alleles and faecal egg count were determined for Texel (n = 105) and Suffolk (n = 71) lambs. Eight Ovar-DRB1 alleles, including 1 previously unknown allele, were identified in the Texel breed by sequence-base-typing. Seven Ovar-DRB1 alleles were identified in the Suffolk breed. Two Ovar-DRB1 alleles were common to both breeds, but were among the least frequent in the Suffolk population. In the Suffolk breed 1 Ovar-DRB1 allele was associated with a decrease in faecal egg count and 2 alleles with an increase in faecal egg count. This locus accounted for 14% of the natural variation in faecal egg count in Suffolks. There was no evidence for an association between Ovar-DRB1 alleles and faecal egg count in the Texel breed and the Ovar-DRB1 locus accounted for only 3% of the phenotypic variation in faecal egg count. These results suggest that the Ovar-DRB1 gene plays an important role in resistance to nematode infection in the Suffolk breed. The difference in faecal egg counts between these breeds may be attributable in part to the different allele profile at the Ovar-DRB1 locus.

Alleles↗

Gastrointestinal nematode infection in sheep--a review of the alternatives to anthelmintics in parasite control.

Efforts to curb production losses caused by nematode parasitism in sheep have led to the development of a number of control methods to complement or replace anthelmintics. The need for alternative control measures stems from the emergence of anthelmintic-resistant parasitic nematodes with reports of multi-class resistance to these drugs now emerging. A number of these control methods such as predacious microfungi, protein supplementation, plant extracts in feed and vaccines have demonstrated potential to control infection but require development and examination under natural conditions. Breeding for natural resistance to nematode infection has already shown success in controlling the disease under natural conditions. Selection for resistance is currently based on fecal egg count measurements but identification of genetic indicators of resistance will provide a more efficient method of selection. Current quantitative trait loci for nematode resistance include the MHC genes, interferon gamma gene, IgE gene and microsatellites on chromosome 1, 5 and 6. This paper reviews the current alternatives to anthelmintics to control infection, with an emphasis on breeding for host resistance and identification of genetic indicators of resistance.

Animals↗

Immunohistochemical studies of scrapie archival material from Irish ARQ/ARQ sheep for evidence of bovine spongiform encephalopathy-derived disease.

Since scrapie and bovine spongiform encephalopathy (BSE) in sheep are clinicopathologically indistinguishable, BSE in sheep may have been misdiagnosed as scrapie. Disease-specific prion protein (PrP(d)) patterns in archival tissues of 38 Irish ARQ/ARQ sheep diagnosed as scrapie-affected were compared to those in four Dutch BSE-challenged sheep. When medulla oblongata was immunolabelled with an antibody directed against amino acids 93-99 of ovine prion protein (ovPrP), intraneuronal PrP(d) was apparent in all 38 Irish sheep but was absent in BSE-challenged sheep. When lymphoid follicles were immunolabelled with antibodies directed against amino acids 93-106 of ovPrP, granule clusters of PrP(d) were seen in 34 of the 38 Irish sheep. Follicles of the remaining four archive sheep contained either no PrP(d) or single PrP(d) granules, similar to follicles from BSE-challenged sheep. Based on the medulla results, none of the archival cases had BSE-derived disease. The identification of some scrapie sheep with little or no intrafollicular PrP(d) suggests that this technique may be limited in discriminating between the two diseases.

Animals↗

Discrimination between scrapie and bovine spongiform encephalopathy in sheep by molecular size, immunoreactivity, and glycoprofile of prion protein.

A procedure for discrimination between scrapie and bovine spongiform encephalopathy (BSE) in sheep is of importance for establishing whether BSE has entered the sheep population. Since BSE has not yet been found in sheep at the farm level, such discrimination procedures can be developed only with experimental sheep BSE. Two distinctive molecular features of the prion protein (PrP)-molecular size and glycosylation profile-in proteinase K digests of brain stem tissue from sheep were used here; upon Western blotting, these features led to an unequivocal discrimination among natural scrapie, experimental scrapie, and experimental BSE. The higher electrophoretic mobility of PrP in sheep BSE could be best observed after deglycosylation treatment with N-glycosidase F. A simpler method for confirmation of this size difference involved comparison of the ratios for the binding of two monoclonal antibodies: P4 and 66.94b4. Based on epitope mapping studies with P4 and peptides, it appeared that N-terminal amino acid sequence WGQGGSH was intact only in sheep scrapie digests. Another feature typical for PrP in sheep BSE was the large fraction of diglycosylated PrP (70% or more). These data were obtained for a large group of positive sheep, consisting of 7 sheep with experimental BSE infection (genotypes: six ARQ/ARQ and one AHQ/AHQ), 48 sheep naturally infected with scrapie (six different genotypes), and 3 sheep with primary experimental scrapie infection. Routine tests of slaughter material serve well for the initial detection of both BSE and scrapie. With Western blotting as a rapid follow-up test, a 66.94b4/P4 antibody binding ratio above 1.5 is a practical indicator for serious suspicion of BSE infection in sheep.

Amino Acid Sequence↗

Effects of endocrine disrupting compounds on the pathology and oestrogen receptor alpha and beta distribution in the uterus and cervix of ewe lambs.

A number of chemicals have been classed as endocrine disrupting compounds due to their ability to mimic the actions of endogenous hormones in vivo and in vitro. The objective of this experiment was to determine the pathological changes and oestrogen receptor (ER) distribution in the cervix and uterus of prepubertal ovariectomised ewe lambs following exposure to a range of compounds with a predominantly oestrogenic effect. Lambs were exposed to diethylstilbestrol (0.175 mg/kg biweekly), bisphenol-A (3.5mg/kg biweekly) or octylphenol (3.5mg/kg biweekly) for 6 weeks. Following sacrifice, uterine and cervical tissue pathology was assessed. The endometrial and myometrial areas were quantified and the distribution of ERalpha and ERbeta assessed by immunohistochemistry. No differences were observed between control and octylphenol-exposed lambs in uterine gross pathology and histopathology. Uteri from bisphenol-A- and diethylstilbestrol-exposed lambs were heavier than both control and octylphenol-exposed lambs. In the bisphenol-A-exposed lambs, endometrial oedema accounted for a significant increase in the endometrial cross-sectional area over the other groups. Uteri from animals exposed to diethylstilbestrol showed variable pathology including oedema and cellular proliferation. Keratinisation of the cervical epithelium was observed in both bisphenol-A- and diethylstilbestrol-exposed lambs. Exposure to diethylstilbestrol and bisphenol-A was associated with a diffuse intracellular distribution of ERalpha and ERbeta in the uterine endometrium. This was in addition to the strong cytoplasmic staining of uterine epithelial cells and nuclear staining of specific sub-epithelial cells observed in all groups. We conclude that a 6-week exposure of lambs to bisphenol-A and diethylstilbestrol altered the uterocervical environment and has the potential to disrupt subsequent reproductive function. Pathological changes could not be detected in the uterus or cervix of lambs exposed to octylphenol.

Animals↗

Evaluation of peripheral lymphoreticular biopsy techniques and their clinical side effects in sheep.

Tissue samples were collected postmortem from 126 sheep at five lymphoreticular sites by different techniques. The three most successful combinations of sites and techniques were: the third eyelids, using a forceps and scissors, which provided a mean (se) of 5.32 (0.70) lymphoid follicles per 5 microm tissue section, a mandibular lymph node, using a Biopty gun, which gave 1.19 (0.26) lymphoid follicles per 5 microm tissue section, and tonsil, using a biopsy forceps, which gave 1.14 (0.27) lymphoid follicles per 5 microm tissue section. These three techniques were repeated once a month for five months on five sheep under general anaesthesia, and their clinical effects were compared with five control sheep which were restrained and anaesthetised in the same way but from which no biopsies were taken. Most lymphoid follicles (3.47 [0.58] per 5 pm tissue section) were obtained by using the third eyelid biopsy technique. There were no clinical side effects associated with the biopsy procedure. There were increases in the plasma concentration of cortisol in all the animals, suggesting that the restraint and anaesthesia were more stressful than the biopsy procedure.

Animals↗

Prion protein (PrP) gene polymorphisms associated with natural scrapie cases and their flock-mates in Ireland.

The PrP genotypes associated with natural scrapie in Ireland were determined and a comparison was made between genotypes found in scrapie-infected sheep and those found in healthy animals from scrapie-infected flocks. Seven PrP genotypes were identified in scrapie-infected animals: VV(136)RR(154)QQ(171),VA(136)RR(154)QQ(171),VA(136)RR(154)QR(171),VA(136)RR(154)QH(171),AA(136)RR(154)QQ(171),AA(136)RR(154)QH(171) and AA(136)RR(154)HH(171). Of 11 scrapie-infected flocks, 15 genotypes were identified in the healthy flock-mates. The genotypes identified in scrapie-affected animals were also all identified in healthy flock-mates. In 9 of the 11 flocks studied, the genotype frequencies among scrapie-infected animals were significantly different from those among healthy flock-mates. The results show that there is a significant risk of developing the clinical signs of scrapie associated with particular PrP genotypes in the Irish sheep population. The association between the V(136)R(154)Q(171) allele and scrapie was evident, as was the association between A(136)R(154)R(171) and resistance to developing the clinical signs of scrapie. The presence of the A(136)H(154)Q(171) allele in the flocks examined resulted in a decreased risk of developing scrapie compared to the presence of the A(136)R(154)Q(171).

Alleles↗

Effect of maternal exposure to the environmental estrogen, octylphenol, during fetal and/or postnatal life on onset of puberty, endocrine status, and ovarian follicular dynamics in ewe lambs.

Octylphenol (OP) is one of a number of compounds found in the environment that has estrogen-mimicking actions in vivo. Our objective was to determine if maternal exposure to octylphenol during fetal and/or postnatal life would affect the onset of puberty, endocrine status, and subsequent ovarian follicular dynamics of ewe lambs. Lambs were born in March to ewes that received twice weekly s.c. injections of octylphenol (1000 micro g/kg/day) from Day 70 of gestation to weaning (n = 6); Day 70 of gestation to birth (n = 3); birth to weaning (n = 5; gestation = 145 days); or corn oil from Day 70 of gestation to weaning (control; n = 5). Blood samples were collected twice weekly to determine progesterone and FSH concentrations from 20 wk of age throughout the first breeding season. Onset of puberty and interestrous intervals were determined from 20 wk of age by twice daily observation for estrus in the presence of a vasectomized ram. During January the ovaries of each lamb were examined using transrectal ultrasonography from the day of estrus for 15 days. Blood samples were collected every 8 h to examine FSH concentrations and every 2 h to detect the preovulatory gonadotropin surge throughout this estrous cycle. The onset of puberty and first progesterone rise was advanced and the FSH preovulatory surge was elevated for longer in the OP-treated lambs compared with the control lambs (P < 0.05). Interestrous intervals, FSH profiles, and ovarian follicular dynamics were not affected (P > 0.05) by exposure to octylphenol. In conclusion, octylphenol exposure advanced the onset of puberty but it did not disrupt FSH concentrations or the dynamics of ovarian follicular growth.

Animals↗

Robotically assisted minimally invasive biliary surgery in a porcine model.

BACKGROUND: A robotic surgery system has the potential both to reduce the effects of tremor and fatigue and to enhance dexterity in the performance of complex, fine endosurgical tasks. We report a prospective study of robotically assisted minimally invasive biliary surgery in a porcine model using the Zeus robotic surgical system (Computer Motion, Goleta, Ca, USA). METHODS: For this study, 50-kg domestic swine were used. Minimally invasive robotically assisted cholecystectomy was performed in 16 animals, either longitudinal or transverse common bile duct incision, T-tube placement, and suture repair of the common bile duct. Retrieval of 12 simulated bile duct calculi was attempted. Eight animals were monitored for 6 weeks postoperatively. Liver function tests and cholangiography were performed 2 and 6 weeks after surgery. RESULTS: The median setup time for the robotic system was 45 min (range, 10-120 min). The median operative time was 40 min (range, 25-60 min) for cholecystectomy and 80 min (range, 40-165 min) for bile duct dissection, exploration, and repair. Of 12 bile duct calculi, 11 were retrieved successfully. Cholangiography demonstrated no leaks, and the anastomotic stenotic index (diameter of the proximal bile duct divided by the diameter of distal bile duct) at 6 weeks was 0.98. The results of the liver function tests remained normal in all animals. One postoperative death unrelated to operative technique occurred. Complications included one minor splenic laceration and two intraoperative gallbladder perforations. CONCLUSIONS: Robotically assisted minimally invasive biliary surgery in this animal model is both feasible and safe. The Zeus system provides enhanced dexterity, which facilitates precise laparoscopic suture repair of small bile ducts.

Animals↗

Prion protein gene polymorphisms in pedigree sheep in Ireland.

The development of clinical signs of scrapie in sheep has been linked to polymorphisms in the prion protein (PrP) gene. The most important polymorphisms appear to be at codons 136, 154 and 171. The objective of this study was to investigate polymorphisms at these codons in five native (Belclare, Galway, Wicklow Cheviot, Donegal Blackface Mountain and Mayo Blackface Mountain) and five imported (Texel, Bleu du Maine, Rouge de l'Ouest, Vendéen and Charollais) sheep breeds in Ireland. A total of 13 genotypes were found. The percentage of the most resistant genotype AA(136)RR(154)RR(171)varied from 1.8 per cent in the Vendéen breed, 3.1 per cent in Donegal Blackface Mountain, 10.0 per cent in Texel, 11.1 per cent in Wicklow Cheviot, 12.9 per cent in Belclare, 22.0 per cent in Charollais, 25.6 per cent in Mayo Blackface Mountain, 33.3 per cent in Galway, 46.4 per cent in Bleu du Maine to 62.5 per cent in Rouge de l'Ouest. The results indicate that a significant amount of variation exists between the breeds analysed in this study.

Animals↗

Petrolatum versus Resurfix ointment in the treatment of pressure ulcers.

This study compares the therapeutic effects of a new topically applied, nonprescription medication that has been introduced for re-epithelialization of ulcers and erosions of the skin, with petrolatum in treating pressure ulcers of shallow depth (Stage I and Stage II). A 6-week, randomized, double-blind study was performed on 19 patients with Stage I or Stage II pressure ulcers. The patients received either the new nonprescription medication or petrolatum, which served as a control. After the course of the study, the study ointment effected resolution in a majority of pressure ulcers (9 out of 10), while only one out of three ulcers treated with petrolatum resolved in the same time period. These preliminary results show that the study ointment is a safe and effective treatment for Stage I and II pressure ulcers.

Aged↗