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Biomedical subjects

C Gibbs

Publications and source records attributed to C Gibbs.

At least 19 recordsLinked to original sources
PubMed2001

The tethered agonist approach to mapping ion channel proteins--toward a structural model for the agonist binding site of the nicotinic acetylcholine receptor.

BACKGROUND: The integral membrane proteins of neurons and other excitable cells are generally resistant to high resolution structural tools. Structure-function studies, especially those enhanced by the nonsense suppression methodology for unnatural amino acid incorporation, constitute one of the most powerful probes of ion channels and related structures. The nonsense suppression methodology can also be used to incorporate functional side chains designed to deliver novel structural probes to membrane proteins. In this vein, we sought to generalize a potentially powerful tool - the tethered agonist approach - for mapping the agonist binding site of ligand-gated ion channels. RESULTS: Using the in vivo nonsense suppression method for unnatural amino acid incorporation, a series of tethered quaternary ammonium derivatives of tyrosine have been incorporated into the nicotinic acetylcholine receptor. At three sites a constitutively active receptor results, but the pattern of activation as a function of chain length is different. At position alpha149, there is a clear preference for a three-carbon tether, while at position alpha93 tethers of 2-5 carbons are comparably effective. At position gamma55/delta57 all tethers except the shortest one can activate the receptor. Based on these and other data, a model for the receptor binding site can be developed by analogy to the acetylcholine esterase crystal structure. CONCLUSION: Through the use of nonsense suppression techniques, the tethered agonist approach has been made into a general tool for probing receptor structures. When applied to the nicotinic receptor, the method places new restrictions on developing models for the agonist binding site.

Animals↗
PubMed2001

Antiviral efficacy and pharmacokinetics of oral adefovir dipivoxil in chronically woodchuck hepatitis virus-infected woodchucks.

The antiviral efficacy of orally administered adefovir dipivoxil was evaluated in an 18-week study (12 weeks of treatment and 6 weeks of recovery) conducted with woodchucks chronically infected with woodchuck hepatitis virus (WHV). Adefovir dipivoxil is a prodrug of adefovir designed to enhance its oral bioavailability. Following administration of 15 mg of adefovir dipivoxil per kg of body weight in four WHV-infected animals, the mean maximum concentration of adefovir in serum was 0.462 microg/ml, with an elimination half-life of 10.2 h, and the oral bioavailability of adefovir was estimated to be 22.9% (+/-11.2%). To study antiviral efficacy, the animals were divided into three groups. There were six animals each in a high-dose group (15 mg/kg/day) and a low-dose group (5 mg/kg/day). A vehicle control group consisted of five animals because WHV DNA was detectable only by PCR at the time of the study in one of the original six animals. Efficacy was evaluated by determining the levels of WHV DNA in serum. The geometric mean WHV DNA level for the high-dose group diminished by >40-fold (>1.6 log(10)) after 2 weeks of treatment and >300-fold (>2.5 log(10)) at 12 weeks. There was a >10-fold reduction in five of six low-dose animals by 2 weeks, but levels were unchanged in one animal. By 12 weeks of treatment there was a >45-fold (>1.6 log(10)) reduction of WHV DNA levels, and serum WHV DNA levels were below the limit of quantification in three of six animals. Viral DNA levels returned to pretreatment levels during the 6-week recovery period. There were no clinically significant changes in body weight, hematology, or serum chemistry values, including bicarbonate or lactate, in any of the treated animals. No histologic evidence of liver injury was apparent in the biopsies. Under the conditions of this study, adefovir dipivoxil was an effective antihepadnaviral agent.

Adenine↗
PubMed2000

Radial carpal bone fractures in 15 dogs.

Between 1977 and 1992, 15 adult dogs were presented to the Universities of Bristol, Glasgow, Liverpool and London with fractures of the radial carpal bone which had occurred without a known episode of violent trauma. Eleven of the dogs were boxers and the other breeds affected were a Pharaoh hound, rottweiler, springer spaniel and a greyhound. The condition was bilateral in three cases. Eleven dogs were treated surgically by cast immobilisation (four cases), fragment removal (one case), lag screw fixation (three cases), pan-carpal arthrodesis (one case) and lag screw reduction followed by pan-carpal arthrodesis (two cases). The remaining four dogs were treated conservatively with rest and tactical use of non-steroidal anti-inflammatory drugs. Follow-up periods ranged from two months to 11 years. Varying degrees of lameness, which tended to be exacerbated by exercise, persisted in all cases. The radial carpal bone appears to have at least three separate centres of ossification which eventually fuse; their planes of fusion correspond approximately to the two main fracture lines. These areas of fusion could be weak points within the radial carpal bone.

Animals↗
PubMed1998

When staff training isn't enough: an evaluation of a collaborative approach.

This paper describes an evaluation of a training workshop for staff working with people who have severe physical and learning disabilities and who need extensive support with eating and drinking. Training involved joint input from speech and language therapy, dietetics, occupational therapy and physiotherapy and was evaluated at three levels: participants' satisfaction, gains in knowledge and video-tapes of mealtimes pre- and post-training to assess changes in practice. Results indicated very positive staff perceptions of the workshops and highly significant increases in knowledge, both immediately (p < 0.001) and after six months (p < 0.001). However there was no evidence of significant change in practice. Results are discussed in the context of bringing about changes in staff behaviour.

Caregivers↗
PubMed1995

Echocardiographic measurements of cardiac dimensions and indices of cardiac function in normal adult thoroughbred horses.

Cardiac dimensions and indices of cardiac function were measured in 29 clinically normal adult Thoroughbreds (TB) which performed minimal exercise using guided M-mode and two-dimensional (2-D) echocardiography, from a variety of image planes and measurement methods, and standardised imaging planes based on intracardiac anatomical landmarks. The different methods of measuring these variables were compared. The variables which were considered to be most valuable for quantitative echocardiography were measured in a further 9 horses. Comparable measurements of cardiac dimensions can be obtained from a variety of different imaging planes, using either 2-D or guided M-mode echocardiography from the left or right side of the chest, although differences in measurement methods must be taken into account. The results of this study give a useful range of dimensions and indices of cardiac function in normal adult TBs for comparison with those recorded from horses with suspected cardiac disease. Comparisons are only valid if there is meticulous attention to correct orientation of imaging planes with regard to internal landmarks and that comparable measurement locations and timing are used.

Animals↗
PubMed1995

Effects of sedation with detomidine hydrochloride on echocardiographic measurements of cardiac dimensions and indices of cardiac function in horses.

Twenty-six horses were sedated with detomidine hydrochloride (Domosedan, SmithKline Beecham Animal Health, Tadworth, Surrey, UK) at a dose of 10 micrograms/kg bwt, administered i.v. Echocardiograms were recorded before and after sedation, measurements of cardiac dimensions were made and functional indices were calculated. The pre- and post sedation values were compared. No significant change was detected following sedation in the ejection time (ET), left ventricular dimension, left atrial diameter at the sinotubular junction at end-systole or end-diastole or at the sinus of Valsalva at end-diastole. Sedation was found to result in a statistically significant increase in end-systolic left ventricular diameter and internal area and aortic diameter measured at the sinus of Valsalva. Left ventricular free-wall thickness and interventricular septal thickness at end-systole, fractional shortening, fractional area change and heart rate were significantly reduced following sedation. A significant increase in pre-ejection period (PEP), duration of electromechanical systole (EMS) and PEP/ET (ejection time) was detected.

Animals↗
PubMed1994

Hamartomatous polyps in the intestine of two dogs.

Partly obstructing, proliferative mucosal masses in the small intestine of two dogs were shown histologically to be hamartomatous polyps. They were characterized by an extension of smooth muscle from the muscularis mucosae into the lamina propria of the lesion. This is the first report of such lesions in domestic animals. In one of the dogs the lesion had become malignant.

Adenocarcinoma↗
PubMed1993

Angiostrongylus vasorum infection in seven dogs.

Angiostrongylus vasorum infection was diagnosed in six dogs by the identification of larvae in sputum or faeces, or by the identification of adult worms post mortem. In another dog strong evidence of the condition was obtained but no parasites were identified. In four cases the main clinical signs were coughing and dyspnoea, but one dog had exercise intolerance and no history of coughing. One dog in which larvae were found in the faeces had no clinical signs that were related to the infection. Another dog had flaccid hindlimb paralysis and forelimb hypermetria-clinical signs of the disease which have not been reported previously. Four of the cases came from south Wales, one of them being the first case of the infection to be reported from this area.

Angiostrongylus↗
PubMed1993

Temporal analysis in children.

This study investigated the development of temporal resolution as a function of frequency region using a modified masking period pattern paradigm. This paradigm also allowed age-dependent comparisons of within-channel (temporal resolution) versus across-channel (comodulation masking release [CMR]) processing of temporal information to be made in the same listeners. The results indicated that temporal resolution improves with age. At low frequencies, this improvement continues beyond 10 years of age, whereas at high frequencies performance approaches adult levels by about age 6. Although it is reasonable to expect an association between CMR and temporal acuity, the measure of CMR did not show a significant age effect. The possibility was raised that the poorer temporal resolution of children may not reflect simply a deficiency in peripheral processing of temporal information.

Adult↗
PubMed1993

Molecular cloning and characterization of a cDNA encoding feline interleukin-6.

With the discovery that the cat is susceptible to infection by a lentivirus quite similar to the virus that causes the human acquired immune deficiency syndrome, the cat has become an important animal model with which the interactions between host and immunodeficiency virus can be studied. To facilitate investigation of the feline immune response and the response of cytokine expression to infection by feline immunodeficiency virus, our laboratory has focused on the isolation and molecular cloning of cDNA representative of feline lymphokines, cytokines, and monokines. Herein, we describe the molecular cloning and characterization of a cDNA encoding feline interleukin (IL)-6. The nucleotide sequence of feline IL-6 was found to exhibit 81%, 76%, 63%, and 61% homology with pig, human, rat, and mouse IL-6, respectively, while the predicted amino acid sequence exhibits 66%, 53%, 37%, and 30% homology with pig, human, rat, and mouse IL-6, respectively.

Amino Acid Sequence↗
PubMed1993

Radiographic assessment of gastric mucosal fold thickness in dogs.

One hundred two dogs without known gastric lesions were evaluated to establish a reference range of gastric rugal fold thickness (millimeters). Mucosal folds were measurable for 63 examinations, and the length of the second lumbar vertebra was measured for 61 of the 63 (centimeters). Body weight was available in the case records of 29 dogs. Measurements of the mucosal folds were related to body weight (n = 29) and length of the second lumbar vertebra (n = 61) by use of linear regression analysis. Reference range of normal gastric mucosal fold thickness, 1 to 8 mm, was defined by this study for dogs of any breed weighing between 2 and 50 kg.

Animals↗
PubMed1992

A review of the usefulness of myelography in 50 dogs.

Fifty dogs showing clinical signs of spinal disease were investigated by myelography, using iopamidol. In 27 cases the technique was considered worthwhile. Of the 19 dogs not subjected to surgery or euthanasia as a result of the findings, three suffered seizures during recovery from anaesthesia, eight deteriorated in neurological condition and one suffered permanent respiratory arrest as a result of extensive subarachnoid haemorrhage.

Animals↗
PubMed1992

Congenital urinary incontinence in cats: a review of 19 cases.

Nineteen cases of feline congenital urinary incontinence (10 cats with ureteral ectopia and nine with incompetence of the urethral sphincter mechanism) are reviewed. The 10 cats with ureteral ectopia are considered together with 13 from previous reports. There was no apparent breed predisposition. Most of the 23 cats were presented for urinary incontinence but two of them were continent. Thirteen were females and ectopia was unilateral in 13 and bilateral in 10. Twenty-eight of 31 ectopic ureters terminated in the urethra. The commonest complication was hydroureter/hydronephrosis (10 cases). Eighteen of the cats were treated surgically, 13 by ureteral transplantation, four by ureteronephrectomy and one by ligation of the renal blood vessels; 16 of them were cured by surgery. Congenital urethral sphincter mechanism incompetence has not been reported previously in the cat. Nine cases are presented and the urethras of all were markedly hypoplastic. A common concomitant abnormality was vaginal aplasia, with the uterine horns terminating in the dorsum of the bladder. Bacteriuria was more common in this group than in the cats with ureteral ectopia.

Animals↗
PubMed1992

Characterization of the immune response to a secondary encephalitogenic epitope of basic protein in Lewis rats. II. Biased T cell receptor V beta expression predominates in spinal cord infiltrating T cells.

The immune response of Lewis rat lymph node T cells to guinea pig myelin basic protein (GP-BP) in experimental allergic encephalomyelitis is directed primarily against a region of basic protein encompassed by residues 72-89. T cells that respond to this epitope are restricted by the RT1.B class II molecule of the MHC and use V beta 8.2 exclusively in their TCR. A second region of GP-BP, residues 87-99, also induces experimental allergic encephalomyelitis in Lewis rats but this response is restricted primarily by RT1.D. Elsewhere we describe the biologic characteristics of T cell clones responding to the synthetic peptide, s87-99, and to a related peptide, s85-99. We present a detailed analysis of TCR V beta gene expression among these clones, derived from the lymph node and spinal cord of immunized animals, and among spinal cord derived T cell clones reactive to GP-BP 72-89. We find that spinal cord-derived clones, reactive to s85-99 and to s87-99, use V beta 6 predominantly. In contrast, T cell clones derived from lymph nodes and reactive to the same peptides express multiple V beta genes including V beta 6. This difference in heterogeneity of V beta usage at the clonal level is also seen in T cell lines derived from spinal cord and immune lymph node. DNA sequence comparison of the CDR3 regions in V beta 6+ spinal cord clones revealed a conserved amino acid motif also found in the majority of V beta 6 sequences from the spinal cord anti-s85-99 line. Although V beta 6 was expressed in some lymph node-derived clones, only one contained a CDR3 region similar to that seen in spinal cord isolates. All spinal cord-derived T cell clones reactive to GP-BP 72-89 used V beta 8.2 and most (five of six) contained the AspSer residues in CDR3 previously shown to be associated with V beta 8.2 receptors expressed by the majority of lymph node T cells responding to GP-BP 72-89. These data indicate that TCR V beta usage in peripheral T cells responding to an autoantigen does not always predict the V beta usage among T cells at the site of an autoimmune attack. Possible explantations for the relative homogeneity in TCR V beta expression seen in T cell clones derived from the spinal cord are discussed.

Amino Acid Sequence↗