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S W Reid

Publications and source records attributed to S W Reid.

At least 73 records · Page 4Linked to original sources

An altered position of the alpha 2 helix of MHC class I is revealed by the crystal structure of HLA-B*3501.

The crystal structure of the human major histocompatibility complex class I B allele HLA B*3501 complexed with the 8-mer peptide epitope HIV1 Nef 75-82 (VPLRPMTY) has been determined at 2.0 angstrom resolution. Comparison with the crystal structure of the closely related allele HLA B*5301 reveals the structural basis for the tyrosine specificity of the B*3501 F pocket. The structure also reveals a novel conformation of the 8-mer peptide within the binding groove. The positions of the peptide N and C termini are nonstandard, but the classic pattern of hydrogen bonding to nonpolymorphic MHC class I residues is maintained, at the N terminus by addition of a water molecule, and at the C terminus by a substantial shift in the alpha 2 helix.

Alleles↗

Bound water structure and polymorphic amino acids act together to allow the binding of different peptides to MHC class I HLA-B53.

The structure of the human MHC class I molecule HLA-B53 complexed to two nonameric peptide epitopes (from the malaria parasite P. falciparum and the HIV2 gag protein) has been determined by X-ray crystallography at 2.3 angstrom resolution. The structures reveal the architecture of a Pro-specific B pocket common to many HLA-B alleles. Relative to other alleles, the B53 peptide-binding groove is widened by a significant (up to 1.25 angstrom) shift in the position of the alpha 1 helix. Within this groove, bound water molecules, acting in concert with the side chains of polymorphic residues, provide the functional malleability of the MHC, which enables the high affinity/low specificity binding of multiple peptide epitopes.

Amino Acid Sequence↗

Epidemiological risk factors associated with a diagnosis of clinical cyathostomiasis in the horse.

Multiple logistic regression was used to assess epidemiological risk factors associated with the diagnosis of cyathostomiasis in 87 cases of chronic diarrhoea in the horse. Age, season and the period since last receiving anthelmintics were identified as important risk factors using chi-square and two-sample t test analyses, whereas access to grazing, shared grazing with other horses and recurrence of signs were only weakly associated with a diagnosis of cyathostomiasis. Multivariate analysis of the parameters using logistic regression was performed. The final model included age, season and time since last deworming. At a predicted probability of cyathostomiasis of 0.5, the model had a specificity of 86.0%, sensitivity of 66.7%, overall correct classification of 79.3%, a positive predictive value of 71.4% and a negative predictive value of 83.1%. The results of this study indicated that the specified variables and factors may be useful in the differentiation of clinical cyathostomiasis from other causes of chronic diarrhoea, based on case history alone.

Animals↗

Nucleotide sequence of exons 5 to 9 of the p53 tumour-suppressor gene of the donkey (Equus asinus).

The evolutionary conserved region of the equine homologue of the p53 gene from the donkey genome was PCR amplified and cloned. The 1380 bp fragment consisted of exons 5 to 9 and the intervening introns. The exonic and intronic DNA sequences showed a variable but high level of homology with previously published human sequences. The aminoacid sequences corresponding to the evolutionary conserved domains II, III, and V were identical to the human regions, whilst domain IV was 96% homologous.

Amino Acid Sequence↗

Targeted mutation in the neurotrophin-3 gene results in loss of muscle sensory neurons.

Neurotrophin 3 (NT-3) is one of four related polypeptide growth factors that share structural and functional homology to nerve growth factor (NGF). NT-3 and its receptor, called neurotrophic tyrosine kinase receptor type 3 (Ntrk3; also called TrkC), are expressed early and throughout embryogenesis. We have inactivated the NT-3 gene in embryonic stem (ES) cells by homologous recombination. The mutated allele has been transmitted through the mouse germ line, and heterozygote intercrosses have yielded homozygous mutant newborn pups. The NT-3-deficient mutants fail to thrive and exhibit severe neurological dysfunction. Analysis of mutant embryos uncovers loss of Ntrk3/TrkC-expressing sensory neurons and abnormalities at early stages of sensory neuronal development. NT-3-deficient mice will permit further study of the role of this neurotrophin in neural development.

Animals↗

Detection, cloning and characterisation of papillomaviral DNA present in sarcoid tumours of Equus asinus.

Molecular investigations on 18 naturally occurring sarcoid tumors removed from donkeys identified papillomaviral DNA homologous to bovine papillomavirus (BPV)-2 DNA under stringent conditions, in all the samples. Restriction endonuclease analysis of 15 of the tumours demonstrated papillomaviral DNA similar to BPV-1 and BPV-2. The type of DNA was not specific to either the site or the type of lesion. The analysis of the nucleotide base sequence of a cloned papillomaviral element from a sarcoid showed that the isolate was 96 and 98 per cent homologous to BPV-1 in the L1 and E5 open reading frames, respectively. It was concluded that the disease in the donkey is similar to that in the horse and that the E5 open reading frame may be involved in oncogenesis in the sarcoid.

Animals↗

Targeted disruption of the neurofibromatosis type-1 gene leads to developmental abnormalities in heart and various neural crest-derived tissues.

The neurofibromatosis (NF1) gene shows significant homology to mammalian GAP and is an important regulator of the ras signal transduction pathway. To study the function of NF1 in normal development and to try and develop a mouse model of NF1 disease, we have used gene targeting in ES cells to generate mice carrying a null mutation at the mouse Nf1 locus. Although heterozygous mutant mice, aged up to 10 months, likely attributable to a severe malformation of the heart. Interestingly, mutant embryos also display hyperplasia of neural crest-derived sympathetic ganglia. These results identify new roles for NF1 in development and indicate that some of the abnormal growth phenomena observed in NF1 patients can be recapitulated in neurofibromin-deficient mice.

Alleles↗

Epidemiological observations on sarcoids in a population of donkeys (Equus asinus).

An epidemiological study of equine sarcoid in a population of 4126 donkeys showed that the peak incidence of the disease was 15.2 cases per 100 animal-years and occurred in animals in their fourth year of life. The crude incidence of the disease was 0.6 cases per 100 animal-years. The disease occurred most frequently in younger, male animals during their first five years in the population. The lesions were observed most commonly in the paragenital region. Pre-entry quarantine procedures did not appear to play a significant role in the spread of the disease but there was an indication that close in-contact animals were more likely to have sarcoids than animals in the general population. This suggested that a transmissible agent might have been involved in the aetiopathogenesis or that the animals had encountered some event that had predisposed them to the disease.

Age Factors↗

Fluorescent responses of acrylodan-labeled plasma gelsolin.

Under nondenaturing conditions, 1 mol of horse plasma gelsolin reacts with 1.9 +/- 0.5 mol (mean +/- SD, n = 6) of the sulfhydryl-specific fluorescent reagent 6-acryloyl-2-dimethylaminonaphthalene (acrylodan). The degree of labeling in 6 M guanidine-HCl increases to about 3 mol of acrylodan per mole of gelsolin. Viscosity studies show that the modified gelsolin retains its ability to sever F-actin filaments. Circular dichroism spectra in the peptide bond absorption region are indistinguishable for labeled and unmodified gelsolin at room temperature. The thermal stability of gelsolin, as monitored by circular dichroism, is unaffected by reaction with acrylodan. While circular dichroism spectra of acrylodan-labeled gelsolin recorded at room temperature are not influenced significantly by Ca2+, fluorescence studies reveal a number of Ca(2+)-dependent changes in the protein. Ca2+ causes a decrease and red-shift in fluorescence emission, an increase in sensitivity to quenching by I-, and a decrease in polarization of the fluorescence of acrylodan-labeled gelsolin. Together, these changes in fluorescence properties indicate there to be an increased exposure of the label to the solvent when gelsolin binds Ca2+. Fluorescence polarization experiments in which acrylodan-labeled gelsolin is titrated with actin emphasize that Ca2+ is required for these two proteins to interact.

2-Naphthylamine↗

The Trk family of tyrosine kinases: receptors for NGF-related neurotrophins.

Neurotrophins are known to have important functions in the survival of embryonic and adult subpopulations of neurons. The identification of Trk family RTKs as receptors for NGF-related neurotrophins indicates phosphotyrosine-mediated signal transduction as a principal mechanism for neurotrophin signaling. Previous trk and trkB expression studies (Klein et al. 1989, 1990b; Martin-Zanca et al. 1990) and more recent studies with trkC (L. Tessarollo et al., in prep.) provide important clues about function. Thus, trkB and trkC expression in motor neurons and in many nonneuronal cells suggests that these cells are targets for neurotrophin action in vivo, even though this has not been demonstrated in the classic in vitro survival assays. Expression of trkB and trkC in nonneuronal cells implies that these receptors may act in additional aspects of organogenesis and development. Current approaches to assay Trk receptor and neurotrophin function will be complemented by further studies in the living organism. Transgenic approaches aimed at ectopic expression and at interfering with normal receptor function should provide additional insights. Finally, reverse genetic approaches using targeted mutation of Trk receptors in embryonic stem cells (Stanton et al. 1992) will allow assessment of critical receptor requirements and provide powerful reagents for studying nervous system development and function.

Animals↗

The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor.

Neurotrophic factors are essential for neuronal survival and function. Recent data have demonstrated that the product of the tyrosine kinase trk proto-oncogene binds NGF and is a component of the high affinity NGF receptor. Analysis of the trkB gene product, gp145trkB, in NIH 3T3 cells indicates that this tyrosine kinase receptor is rapidly phosphorylated on tyrosine residues upon exposure to the NGF-related neurotrophic factors BDNF and NT-3. Furthermore, gp145trkB specifically binds BDNF and NT-3 in NIH 3T3 cells and in hippocampal cells, but does not bind NGF. Thus, the trk family of receptors are likely to be important signal transducers of NGF-related trophic signals in the formation and maintenance of neuronal circuits.

Animals↗

Germ line transmission of an inactive N-myc allele generated by homologous recombination in mouse embryonic stem cells.

We have disrupted one allele of the N-myc locus in mouse embryonic stem (ES) cells by using homologous recombination techniques and have obtained germ line transmission of null N-myc ES cell lines with transmission of the null N-myc allele to the offspring. The creation of mice with a deficient N-myc allele will allow the generation of offspring bearing null N-myc alleles in both chromosomes and permit study of the role that this proto-oncogene plays in embryonic development.

Alleles↗

Fructosamine measurement in ponies: validation and response following experimental cyathostome infection.

Validation of an assay for measurement of fructosamine in equine serum and plasma utilised blood samples collected from 24 British native breed ponies. The results indicated that fructosamine can be measured easily using an assay which is precise and accurate. Paired plasma and serum fructosamine measurements were highly correlated, however, greater variations were observed within serum compared with those in plasma. A reference range for fructosamine in plasma was calculated to be 256.9 +/- 60.6 mumol litre-1 (mean +/- 2 SD). In order to assess the fructosamine response following experimental cyathostome infection, nine British native breed ponies were allocated to one of three groups: Group 1 (3.9 million third-stage cyathostome larvae (L3) over a nine-week-period), Group 2 (3.15 million L3 over seven weeks) and Group 3 (uninfected controls). From four weeks prior to infection, blood was obtained, once weekly, from all animals for measurement of plasma fructosamine, plasma albumin and serum globulin concentrations. Plasma fructosamine concentrations decreased in all infected ponies post-infection due to enteric protein loss and/or altered protein composition and/or increased protein turnover.

Aging↗

Screening for bovine papillomavirus in peripheral blood cells of donkeys with and without sarcoids.

Papillomaviral DNA has been identified in peripheral blood cells of both cattle and humans with and without associated disease and it has been suggested that such cells may act as sites of viral latency. In order to investigate the possibility of latent papillomaviral infection in the aetiopathogenesis of the equine sarcoid, peripheral blood derived DNA samples from 20 healthy and 34 sarcoid-affected donkeys were subject to polymerase chain reaction (PCR) using papillomaviral specific primers. Analysis of blood derived DNA samples failed to demonstrate the presence of papillomaviral DNA in any animal. Screening of 37 matched sarcoid derived DNA samples confirmed the presence of BPV in 34 diseased donkeys. This study supports the hypothesis of BPV as an aetiological agent in the equine sarcoid and suggests that latent virus in circulating peripheral blood cells does not play a role in the pathogenesis and epidemiology of the equine sarcoid.

Animals↗

Breath hydrogen measurement in ponies: a preliminary study.

The aim of this study was to establish the normal patterns of breath hydrogen excretion in adult ponies following either voluntary consumption or administration per stomach tube of a test meal/carbohydrate substrate. After an overnight fast, the ponies (n = 7) received either no test meal (ie fasted), glucose, xylose, lactose, lactulose, wheat flour or oats. Exhaled breath samples were collected in duplicate at 0 minutes and at 30-minute intervals thereafter for eight hours. Analysis of duplicate breath hydrogen measurements (n = 714) indicated that the breath hydrogen collection/storage method was reliable. Fasting resulted in negligible levels of breath hydrogen excretion. Increases in breath hydrogen concentration greater than 10 ppm, sustained for at least 30 minutes, were regarded as being biologically significantly different than fasting data and were observed for all ponies following the ingestion of oats or the administration of wheat flour, for three ponies following the administration of glucose and xylose and for two ponies following the administration of lactulose and lactose. The pattern of breath hydrogen excretion was subject to variation between animals following the ingestion of identical test meals. This study provides evidence of incomplete glucose absorption in healthy ponies and indicates that ingestion of non-absorbable carbohydrates do not always result in hydrogen excretion.

Animals↗

Oropharyngeal penetrating injuries in 50 dogs: a retrospective study.

OBJECTIVES: To summarize the presenting complaints and clinical signs associated with traumatic penetrating injuries to the canine oropharynx. To determine how the site of injury, causative agent, and duration of disease affect the presentation and clinical outcome of treatment. STUDY DESIGN: Retrospective study. SAMPLE POPULATION: 50 client-owned dogs. METHODS: The medical records of 50 dogs with oropharyngeal penetrating injuries referred to Glasgow University Veterinary Hospital (GUVH) between 1979-1999 were reviewed. Data regarding signalment, owners' presenting complaint, history, physical examination, radiographic and endoscopic findings, surgical findings, and outcome were recorded and compared with the GUVH population. Estimates of individual breed-specific odds ratios were calculated. Outcome was evaluated by reexamination 6 weeks after surgery with recurrence of disease recorded as failure. RESULTS: Oropharyngeal injuries occurred most often in medium to large breed dogs. The majority of dogs presented with chronic disease (82%). The common findings on clinical examination were discharging sinus (72%) and swelling (70%). Acute cases typically presented with dysphagia and oral pain. The original site of injury was evident in only 34% of dogs, with the sublingual area the most frequently traumatized. The apparent cause of injury to the oropharynx was most commonly a piece of wood (72%). Other causes were metallic foreign bodies (3 dogs) and bones (2 dogs). In the remaining 9 dogs, the cause was not determined. The clinical signs resolved in all dogs that presented acutely compared with only 62% in dogs with chronic signs. CONCLUSION: Medium to large breed dogs appear to be prone to oropharyngeal injuries caused mainly by wooden foreign bodies. This may be attributable to stick chewing or retrieving behavior in these animals. CLINICAL RELEVANCE: History of trauma, stick retrieval, submandibular/cervical swelling, and discharging sinus are commonly encountered in the presentation of this condition. The sublingual area was the most frequent portal of entry recorded, although in chronic cases the initial site of injury was often unclear. Radiography and endoscopy, while offering definitive diagnosis with positive findings, often provide false negative findings. Aggressive surgical debridement of all sinus tracts is essential in obtaining a successful result, but recovery of a foreign body is not necessarily a determinant of success.

Animals↗

A comparison of the effects of unilateral thyroarytenoid lateralization versus cricoarytenoid laryngoplasty on the area of the rima glottidis and clinical outcome in dogs with laryngeal paralysis.

OBJECTIVE: To compare the clinical effects of unilateral thyroarytenoid lateralization versus unilateral cricoarytenoid laryngoplasty for the treatment of canine laryngeal paralysis. Study Design-A prospective, clinical trial. ANIMALS: Twenty client-owned dogs admitted to Glasgow University Veterinary Hospital (GUVH) between 1997 and 1999 with a diagnosis of laryngeal paralysis. METHODS: A thorough evaluation of each dog was undertaken that included history, physical and neurologic examinations, complete blood count, serum biochemistry profile, serum thyroxine (T4) level, and thyroid-stimulating hormone (TSH) assay. The exercise tolerance of each dog was investigated by assessing respiratory rate and arterial blood gas analysis at rest and after 5 minutes of mild exercise. Animals were included in the study on the basis of a definitive diagnosis of laryngeal paralysis made by endoscopic observation of the larynx in the lightly anesthetized patient. The animals were randomly assigned to 1 of 2 treatment groups: unilateral thyroarytenoid lateralization or unilateral cricoarytenoid laryngoplasty, with all procedures being performed by the same surgeon. Video images of the rima glottidis were recorded pre- and postoperatively using video endoscopy. Video images were digitized and the area of the rima glottidis measured using image-analysis software. An increase in the area of the rima glottidis was expressed as a percentage of the preoperative area. All animals were reassessed 6 weeks' postoperatively, and exercise tolerance tests were repeated. RESULTS: The mean increase in the area of the rima glottidis postoperatively when compared with the preoperative area was 140% for those animals undergoing unilateral thyroarytenoid lateralization (range, 120%-158%) and 207% for those animals undergoing unilateral cricoarytenoid laryngoplasty (range, 183%-228%). This difference was statistically significant (P < .0001). At the 6-week postoperative examination, there was no significant difference in improvement between the 2 groups when compared on either a clinical basis or exercise tolerance tests. The mean surgical time in the 2 groups was 25 minutes for thyroarytenoid lateralization and 43 minutes for cricoarytenoid laryngoplasty. This was a statistically significant difference (P = .002). CONCLUSION: Although increase in area of the rima glottidis was significantly greater after unilateral cricoarytenoid laryngoplasty compared with unilateral thyroarytenoid lateralization, no difference in clinical outcome could be detected. However, the cricoarytenoid laryngoplasty procedure required significantly more surgical time. CLINICAL RELEVANCE: Both unilateral cricoarytenoid laryngoplasty and unilateral thyroarytenoid lateralization are successful methods for the treatment of laryngeal paralysis; however, thyroarytenoid lateralization requires less surgical time to perform.

Animals↗