Lateral transmission of natural scrapie to scrapie-free New Zealand sheep placed in an endemically infected UK flock.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
C McKenzie
Publications and source records attributed to C McKenzie.
Derivation of a scrapie-free sheep flock from the progeny of a flock affected by scrapie.
The Cheviot flock at the Institute for Animal Health's Neuropathogenesis Unit (npu) has endemic scrapie, which affects primarily vrq/vrq sheep and at high frequency. A new flock with a full range of PrP genotypes, including the highly susceptible vrq/vrq, has been produced on a separate site, from animals in the npu breeding flock, and it remains scrapie-free after eight years. In contrast, in a parallel flock at the npu farm, scrapie has reappeared after five years, although the animals were kept in separate accommodation from the scrapie-affected sheep. During this time the npu breeding flock continued to have scrapie cases. Although it is known that highly susceptible sheep can remain free of infection in a clean environment, this is the first report of the infection being removed successfully from the bloodlines of scrapie-affected sheep. The results confirm that scrapie is not a genetic disease dependent only on the PrP gene sequence, but requires both genetic susceptibility and an infectious agent.
Animal Husbandry↗
dGEMRIC as a function of BMI.
OBJECTIVE: Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) reflects cartilage glycosaminoglycan (GAG) distribution. The technique assumes that the plasma levels of the contrast agent Gd-DTPA(2-) are the same across individuals after intravenous (IV) injection, when dosing by weight. However, adipose tissue has lower extracellular water (ECW) than lean tissue. The aims of this study were to measure (1) plasma Gd-DTPA(2-) levels vs body mass index (BMI), and (2) dGEMRIC vs BMI after correcting for the dose-BMI effect. METHOD: (1) Plasma Gd-DTPA(2-) levels were analyzed at 3-90 min after IV injection per body weight in 24 individuals with BMI between 21.5 and 46.5. (2) dGEMRIC was compared with BMI in 19 asymptomatic volunteers and 23 with osteoarthritis (OA). RESULTS: (1) Plasma Gd-DTPA(2-) kinetics were similar in obese and non-obese groups, however, overall concentration was higher in the obese group. A very obese subject (BMI 45) would have 1.4 times higher Gd-DTPA(2-) concentration than a lean subject (BMI 20), which translates into a bias in dGEMRIC of up to 20%. (2) With dose bias taken into account, dGEMRIC showed no correlation with BMI in asymptomatic knees. In OA knees, unnarrowed femoral compartments demonstrated a negative correlation between dGEMRIC and BMI (R=0.57, P=0.004). No correlation was seen in radiographically narrowed compartments. CONCLUSION: BMI can be a source of dosing bias in dGEMRIC and a correction factor should be considered in cross-sectional studies with a large range of BMI. There is no correlation between dGEMRIC and BMI in asymptomatic knees, but a negative correlation in OA knees.
Adult↗
In vitro models for oral malodor.
A model is a representation of some real phenomena and contains aspects or elements of the real system to be modeled. The model reflects (or duplicates) the type of behavior (or mechanisms) seen in the real system. The main characteristic of any model is the mapping of elements or parameters found in the system being studied (e.g. tongue dorsum biofilm in situ) on to the model being devised (e.g. laboratory perfusion biofilm). Such parameters include correct physico-chemical (abiotic) conditions as well as biotic conditions that occur in both model and reality. The main purpose of a model is to provide information that better explains the processes observed or thought to occur in the real system. Such models can be abstract (mental, conceptual, theoretical, mathematical or computational) or 'physical', e.g. in the form of a real disaggregated in vitro system or laboratory model. A wide range of different model systems have been used in oral biofilm research. These will be briefly reviewed with special emphasis on those models that have contributed most to knowledge in breath odor research. The different model systems used in breath odor research are compared. Finally, the requirements for developing an overall 'bad breath model' from considering the processes as a whole (real oral cavity, substrates in saliva, biotransformation by tongue microflora, odor gases in the breath) and extending this to the detection of malodor by the human nose will be outlined and discussed.
Biofilms↗
Investigation of health perspectives of those with physical disabilities: the role of spirituality as a determinant of health.
PURPOSE: To identify key determinants of health and the process of health attainment for people with musculoskeletal disabilities. METHOD: Focus groups of people with musculoskeletal disorders, including 30 members and their five trained facilitators, provided data. Discussed were 'What is health for you?' and 'What has helped, or would help you achieve this health?' Delphi-structured analysis identified health themes and a health process model was developed with the facilitators comprising the expert panel. RESULTS: Health was perceived as centred on relationships that required a spiritual awareness for a strong and resilient identity. The Self Attributes Model developed portrays the processes perceived to be required for health. CONCLUSIONS: Although physical, social and psychological interventions are essential aspects of health intervention, by themselves they are not sufficient. Also required for health is a strong resilient self resulting from interaction and connection with other people and the natural world. Moreover, development of such an identity requires a spiritual world-view comprising an acknowledgement of the essence of self and focus upon the nature of the connection of this essence with all other aspects of life. Further research is required to advance understanding of the process by which this occurs for people with chronic disorders.
Adult↗
Maternal transmission studies of BSE in sheep.
If BSE (bovine spongiform encephalopathy) infected the UK sheep population concurrently with cattle, it would only now be maintained by transmission between sheep by routes which could include from mother to lamb either in utero or via perinatal close contact. In this study of experimental BSE, Cheviot ewes challenged orally with BSE cattle brain produced lambs of various PrP genotypes over the next 7 years. Of 72 surviving to >30 months of age, 29 are of the most susceptible PrP genotype (AQ/AQ) and born to mothers that were challenged with BSE. None of the progeny have shown any signs of disease. The results suggest that in these sheep, BSE could only transmit by the maternal route at a frequency of less than one in four (95 % confidence limit) from clinically affected ewes, a rate which if replicated in other breeds may not be sufficient to maintain BSE within the sheep population.
Animals↗
Effect of the oral contraceptive pill on patients undergoing controlled ovarian hyperstimulation.
This is a retrospective analysis of 89 patients who were undergoing controlled ovarian hyperstimulation for in vitro fertilization and embryo transfer in the Fertility Management Unit of the Department of Obstetrics, Gynaecology and Child Health, The University of the West Indies. Twenty-eight patients (Group A), who did not receive oral contraceptive pills prior to controlled ovarian hyperstimulation (COH) were compared with 61 patients in Group B treated with oral contraceptive pills for two months prior to undergoing COH assisted reproduction using the long protocol. The number of follicles, oocytes, estimated oestradiol levels on the day of administration of human chorionic gonadotrophin (hCG), pregnancy rates, miscarriage rates and the incidence of patients who developed ovarian hyperstimulation syndrome (OHSS) were the main outcome measures. The mean age and haematocrit were the same in each group. The number of follicles retrieved tended to be higher in Group A than in Group B (median 8 versus 6, p = 0.06) with significantly more oocytes being retrieved in Group A than Group B (p < 0.05). There were no statistically significant differences between the two groups in oestradiol levels, the proportion of patients with polycystic ovarian disease, the proportion of women who developed ovarian hyper-stimulation syndrome or pregnancy outcomes. There was no difference between the groups in measures of clinical severity of OHSS. In a logistic regression model the significant predictors of OHSS were haematocrit and oestradiol levels. There appeared to be no significant clinical benefit in administering oral contraceptive pills for two months to patients prior to COH.
Adult↗
Endometriosis co-existing with bilateral dermoid cysts of the ovaries treated by laparoscopy.
Endometriosis co-existing with bilateral dermoid cysts of the ovaries is a rare occurrence although both benign conditions are said to be common in women in the reproductive age group. We present a case of a young woman with primary infertility associated with incapacitating dysmenorrhoea. Sonographic evaluation revealed bilateral ovarian cysts. Video-assisted laparoscopy was performed which revealed bilateral dermoid cysts and endometriotic deposits in the pelvis. The ovarian cysts were enucleated and the endometriotic deposits were endo-coagulated. The patient was treated with GnRH agonist for three months. There have been only two reports of benign and malignant teratomas co-existing with endometriomas.
Adult↗
Photoassociation of sodium in a Bose-Einstein condensate.
We form ultracold Na2 molecules by single-photon photoassociation of a Bose-Einstein condensate, measuring the photoassociation rate, linewidth, and light shift of the J = 1, v = 135 vibrational level of the A1 Sigma (+)(u) molecular state. The photoassociation rate constant increases linearly with intensity, even where it is predicted that many-body effects might limit the rate. Our observations are in good agreement with a two-body theory having no free parameters.
Journal Article↗
Patterns of illness and injury encountered in amateur ocean yacht racing: an analysis of the British Telecom Round the World Yacht Race 1996-1997.
OBJECTIVES: To quantify the incidence and type of medical problem arising during an amateur circumnavigation yacht race, the BT Global Challenge. METHODS: All cases from 14 participating yachts in a confidential medical log completed by an appointed medic were reported. RESULTS: A total of 685 cases were reported, of which 299 (43.6%) were injuries and 386 (56.4%) illnesses. The subtype of injury, illness, and three evacuations at sea are described. CONCLUSION: Injury and other forms of medical problem are relatively common in an amateur long distance ocean yacht race. Most can be adequately managed at sea, provided that optimal communication, training, and equipment are provided and maintained.
Adult↗
Dynamical tunnelling of ultracold atoms.
The divergence of quantum and classical descriptions of particle motion is clearly apparent in quantum tunnelling between two regions of classically stable motion. An archetype of such non-classical motion is tunnelling through an energy barrier. In the 1980s, a new process, 'dynamical' tunnelling, was predicted, involving no potential energy barrier; however, a constant of the motion (other than energy) still forbids classically the quantum-allowed motion. This process should occur, for example, in periodically driven, nonlinear hamiltonian systems with one degree of freedom. Such systems may be chaotic, consisting of regions in phase space of stable, regular motion embedded in a sea of chaos. Previous studies predicted dynamical tunnelling between these stable regions. Here we observe dynamical tunnelling of ultracold atoms from a Bose-Einstein condensate in an amplitude-modulated optical standing wave. Atoms coherently tunnel back and forth between their initial state of oscillatory motion (corresponding to an island of regular motion) and the state oscillating 180 degrees out of phase with the initial state.
Journal Article↗
Role of interferon alpha in promoting T helper cell type 1 responses in the small intestine in coeliac disease.
Coeliac disease (CD) is caused by a CD4 T helper cell type 1 (Th1) response in the small intestinal mucosa to dietary gluten. As the major Th1 inducing cytokine, interleukin 12, is undetectable in CD gut mucosa, the mechanism by which Th1 effector cells are generated remains unknown. Interferon (IFN) alpha, a cytokine capable of promoting IFN-gamma synthesis, has been implicated in the development of Th1 mediated immune diseases. Here we report a case of CD-like enteropathy in a patient receiving IFN-alpha for chronic myeloid leukaemia. Morphological assessment of duodenal biopsies taken from the patient showed total villous atrophy, crypt cell hyperplasia, and a high number of CD3+ intraepithelial lymphocytes. Both antigliadin antibodies and antiendomysial antibodies were positive. RNA analysis revealed pronounced expression of IFN-gamma. Withdrawal of gluten from the diet resulted in a patchy improvement in intestinal morphology, normalisation of laboratory parameters, and resolution of clinical symptoms. By western blot analysis, IFN-alpha protein was seen in the duodenal mucosa from untreated CD patients but not in controls. This was associated with marked expression of IFN-gamma protein in CD mucosa. Collectively, these results suggest a role for IFN-alpha in promoting Th1 responses to gluten.
Adolescent↗
Blocking Smad7 restores TGF-beta1 signaling in chronic inflammatory bowel disease.
TGF-beta1 functions as a negative regulator of T cell immune responses, signaling to target cells using the Smad family of proteins. We show here that Smad7, an inhibitor of TGF-beta1 signaling, is overexpressed in inflammatory bowel disease (IBD) mucosa and purified mucosal T cells. Both whole tissue and isolated cells exhibit defective signaling through this pathway, as measured by phospho-Smad3 immunoreactivity. Specific antisense oligonucleotides for Smad7 reduce Smad7 protein expression in cells isolated from patients with IBD, permitting the cells to respond to exogenous TGF-beta1. TGF-beta1 cannot inhibit proinflammatory cytokine production in isolated lamina propria mononuclear cells from patients with Crohn disease (CD), but inhibition of Smad7 restores TGF-beta1 signaling and enables TGF-beta1 to inhibit cytokine production. In inflamed mucosal tissue explants from patients with CD, inhibition of Smad7 also restores p-Smad3 and decreases proinflammatory cytokine production, an effect that is partially blocked by anti-TGF-beta1. These results show that Smad7 blockade of TGF-beta1 signaling helps maintain the chronic production of proinflammatory cytokines that drives the inflammatory process in IBD and that inhibition of Smad7 enables endogenous TGF-beta to downregulate this response.
Activin Receptors, Type I↗
In vitro fertilization. The Jamaican experience.
In June 2000, twenty-eight infertile couples were treated by in vitro fertilization and embryo transfer at our initial assisted reproduction programme carried out in conjunction with Midland Fertility Services, Aldridge, Birmingham, England. A pre-requisite for treatment was that on day 3 of the menstrual cycle the levels of follicle stimulating hormone (FSH) and oestradiol (E2) should be < 10 i mu/l and < 100 pg/ml respectively in the female partner. The ages of the women ranged from 26 to 42 years with a mean age of 35.5 years. Down regulation was carried out by using buserelin acetate 0.5 microgram subcutaneously from day 21 of the cycle for 21 days. This process was completed when the ovaries and pituitary gland were quiescent and the endometrial thickness < 4 mm in diameter. On completion of down regulation the gonadotrophin hormone, pergonal (dosage of 150-450 units) was used for ovarian hyperstimulation. A total of 294 oocytes (mean of 10.5, range 2-45) were retrieved of which 138 were fertilized (mean of 4.9, range of 0-28). Twenty-four patients each received a mean of two embryos. Five patients (20.8%) had positive pregnancy tests. Three patients (0.1%) developed ovarian hyperstimulation syndrome (OHSS), one had the severe, and two, the mild form of the syndrome. All three cases were treated successfully. The success at the initial IVF controlled ovarian hyperstimulation augers well for the future of infertile couples seeking treatment at the Fertility Management Unit, The University of the West Indies, Jamaica.
Adult↗
Human Peyer's patch T cells are sensitized to dietary antigen and display a Th cell type 1 cytokine profile.
Animal studies have demonstrated that feeding Ags induces regulatory (Th2, Th3) cells in Peyer's patches (PP), which migrate to the periphery and produce immunomodulatory cytokines such as IL-4, IL-10, or TGF-beta. In this work we have attempted to extend this paradigm to man by analyzing the response of human PP T cells to in vitro challenge with the common dietary Ag beta-lactoglobulin (betalg) of cow's milk. PP T cells stimulated with betalg showed enhanced proliferation compared with blood T cells from the same patient. Increased expression of CD25 and the Th1-associated chemokine receptor CCR5 was also seen on CD4(+) and CD8(+) PP T cells, but not blood T cells, stimulated with betalg. By enzyme-linked immunospot assay and RT-PCR, the PP T cell recall response to betalg and casein was dominated by IFN-gamma, with negligible IL-4, IL-5, IL-10, or TGF-beta. To help explain the PP T cell response to betalg, we examined IL-12 expression. Both IL-12p40 and -p35 transcripts were abundantly expressed in PP, but not in adjacent normal ileal mucosa. Immunoreactive IL-12p40-containing cells were present below the PP dome epithelium. Furthermore, in culture, PP, but not paired PBMC, spontaneously released IL-12p70. These results suggest that the human response to oral Ags in the gut may be different from that in rodents.
Adolescent↗
Large-scale test of hypothesised associations between the angiotensin-converting-enzyme insertion/deletion polymorphism and myocardial infarction in about 5000 cases and 6000 controls. International Studies of Infarct Survival (ISIS) Collaborators.
BACKGROUND: The original report of a possible association between myocardial infarction and the insertion/deletion (I/D) polymorphism of the gene for the angiotensin-1-converting enzyme (ACE) indicated a risk ratio for myocardial infarction with the DD genotype of 1.34 (95% CI 1.05-1.70), and the association was claimed to be particularly strong in a retrospectively defined low-risk subgroup (3.2 [95% CI 1.7-5.9). Subsequent investigations reached varying conclusions, but all were small, and much larger studies were needed. METHODS: 4629 myocardial infarction cases and 5934 controls were compared. Cases were UK men aged 30-54 years and women aged 30-64 years recruited on presentation to hospital with confirmed myocardial infarction. Controls were aged 30-64 years with no history of cardiovascular disease, but were siblings or children of myocardial infarction survivors, or spouses of such relatives. All risk-ratio calculations allow for this relatedness of some of the controls. An updated meta-analysis of previous studies was also conducted. FINDINGS: The ACE DD genotype was found in 1359 (29.4%) of the myocardial infarction cases and in 1637 (27.6%) of the controls (risk ratio 1.10 [95% CI 1.00-1.21]). The association between myocardial infarction and the DD genotype did not seem to be stronger in the subgroup defined as low risk by previously used criteria (234 [28%] of 836 cases and 911 [28%] of 3253 controls: risk ratio 1.04 [95% CI 0.87-1.24]), or in any other subgroup. Nor was the ACE I/D genotype predictive of subsequent survival. INTERPRETATION: This study involved many more cases than any previously reported study of this question, but did not confirm the existence of any substantial association. In an updated meta-analysis of these results with those of previously published studies, the risk ratio for myocardial infarction with the DD genotype seems to lie in the range 1.0 to about 1.1. Although an increase in risk of up to about 10-15% cannot be ruled out, substantially more extreme risks can be. Moreover, there are not especially strong associations in the subgroups previously selected for emphasis. These findings illustrate the need for some studies of candidate genes to involve much larger populations than is customary, without undue emphasis on retrospectively defined subgroups.
Adult↗
Ligation of alpha4ss1 integrin on human intestinal mucosal mesenchymal cells selectively Up-regulates membrane type-1 matrix metalloproteinase and confers a migratory phenotype.
Human intestinal lamina propria mesenchymal cells show high surface expression of the alpha4ss1 integrin. Ligation of alpha4ss1 on mesenchymal cell lines with an activating monoclonal anti-alpha4 antibody or vascular cell adhesion molecule-immunoglobulin (VCAM-IgG) leads to the appearance of activated forms of gelatinase A in culture supernatants, and the de novo expression of activated membrane type-1-matrix metalloproteinase (MT1-MMP). In functional assays, signaling through alpha4ss1 results in an increased capacity of mesenchymal cells to migrate through an artificial extracellular matrix, an effect inhibitable by excess tissue inhibitor of metalloproteinase-2. In organ cultures of human intestine, VCAM-IgG also up-regulates MT1-MMP, and in mucosal ulcers of inflammatory bowel disease patients, MT1-MMP transcripts are abundant, coincident with expression of VCAM-1 on cells at the ulcer margin. Collectively these results suggest that alpha4ss1-induced up-regulation of MT1-MMP may be a crucial factor in the migration of mesenchymal cells into ulcer beds during restitution of diseased gut mucosa.
Antibodies↗
Topical and intravenous administration of trefoil factors protect the gastric mucosa from ethanol-induced injury in the rat.
BACKGROUND: hTFF2 and pTFF2 (formerly PSP and hSP, respectively) are members of the trefoil factor family (TFF) and are distributed throughout the gastrointestinal tract in both normal and diseased tissue. Trefoil factors have been shown to exert a mucosal protectant and/or healing role in a number of animal models but controversy exists surrounding this property in relation to their dose and route of administration. AIM: To investigate the effects of topically applied and intravenously infused trefoil factors (hTFF2 and pTFF2) and prostaglandin E2 on ethanol-induced gastric mucosal damage in rats. METHOD: A gastric chamber preparation in the anaesthetized rat was used. Injury was caused by exposing the gastric mucosa to absolute ethanol for 1 min. Trefoil factors or prostaglandin E2 were administered either intravenously or topically before and after the introduction of absolute ethanol onto the gastric mucosa. Damage was assessed by measurement of gastric mucosal Na+ leakage and area of macroscopic injury. RESULTS: Like prostaglandin E2, intravenous administration of hTFF2 and pTFF2 reduced both the gastric mucosal Na+ leakage and the mean area of damage caused by ethanol. Similarly, treatment of the gastric mucosa with topical application of hTFF2 at doses of 120 microg/kg and above reduced the Na+ leakage and the area of damage. pTFF2 at 120 microg/kg and 1.2 mg/kg applied topically produced a marked reduction in total area of damage. CONCLUSION: Intravenously infused hTFF2 and pTFF2 protect the gastric mucosa from ethanol-induced damage in the anaesthetized rat. In addition, topical application of trefoil factors also was effective at protecting the gastric mucosa from injury at doses lower than previously reported.
Administration, Topical↗