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Biomedical subjects

A M King

Publications and source records attributed to A M King.

At least 19 recordsLinked to original sources
PubMed2006

Anatomy and ultrasonographic appearance of the tympanic bulla and associated structures in the rabbit.

Otitis media is a relatively common condition in the rabbit although it can be difficult to evaluate clinically. Diagnostic imaging of the rabbit has traditionally involved radiography and there are few reports regarding the use of ultrasound. The aim of this study was to determine if the tympanic bulla (TB) and associated structures could be evaluated in the rabbit using currently available ultrasound equipment. The normal anatomy of the region was established using gross dissection and emascerated specimens and compared with the dog and cat. Ten New Zealand white rabbit cadavers were examined using two ultrasound machines and four transducers from a variety of locations. A 12 MHz linear transducer was found to be most appropriate. From a lateral approach the external ear canal could be visualized to the level of the external acoustic meatus while the TB itself could only be visualized from a ventral approach. The jugular and mastoid processes in the rabbit are very prominent and interfered with imaging of the TB from all approaches. Water-soluble lubricant introduced into the TB could be identified through the ventral bone wall of the TB and allowed the lumen and far wall to be visualised. Further work is required to determine whether ultrasound examination of the TB can be performed in live rabbits and to evaluate its benefits in the evaluation of clinical cases of otitis media.

Animals↗
PubMed2006

Comparison of ultrasonography, radiography and a single computed tomography slice for fluid identification within the feline tympanic bulla.

Evaluation of the tympanic bulla (TB) in cases of acute feline otitis media can be a diagnostic challenge, although a feature often associated with this condition is the accumulation of fluid or material within the middle ear cavity. A technique is reported allowing optimum imaging of the feline TB using ultrasound (US) and recording of the appearance of gas and fluid-filled TB. A random number of bullae in 42 feline cadavers were filled with lubricant and rostroventral-caudodorsal oblique radiographs, single slice computed tomography (CT) images and US images were created and interpreted by blinded operators. The content (fluid or gas) of each TB was determined using each technique and the cadavers were then frozen and sectioned for confirmation. CT remained the most accurate diagnostic method, but US produced better results than radiology. Given the advantages of US over other imaging techniques, these results suggest that further work is warranted to determine applications of this modality in the evaluation of clinical cases of feline otitis media.

Animals↗
PubMed2005

Development, advances and applications of diagnostic ultrasound in animals.

Ultrasound has many industrial applications but it was first introduced as a medical diagnostic aid in the 1940s with its first veterinary application, the detection of ovine pregnancy, being reported in 1966. Since then, improvements in equipment quality combined with an increased awareness of the benefits of ultrasound as an imaging technique have led to its widespread use in the veterinary field. Recent advances in computer technology have significantly influenced equipment design and the miniaturization of transducers allows intra-operative and intra-vascular applications. Software advances have improved the ability to manipulate and process data, leading to an increased amount of information being obtained from each examination and the advent of 'remote diagnosis'. Ultrasound guided interventional techniques can now be used for diagnostic or therapeutic purposes. Many of these developments have been introduced by equipment manufacturers but have found specific applications in the veterinary field. Ultrasound is currently employed in a very diverse range of situations, not just as a diagnostic tool in the routine clinical workup of a range of species, but also for disease screening, conservation projects, commercial services, herd management and clinical research.

Animals↗
PubMed2001

A randomised prospective study to evaluate a rapid HIV-antibody assay in the management of cases of percutaneous exposure amongst health care workers.

A rapid start of post-exposure prophylaxis with an antiretroviral regime is recommended after percutaneous exposure to blood from an HIV-positive source. Since the HIV-antibody status of the source is usually not known at the time of injury, antiretroviral treatment is started pending the results of HIV testing of the source. A randomised prospective study was designed to compare the use of a rapid-screening assay in the management of cases of percutaneous exposure with the conventional procedure. Prior to the comparative study, the accuracy of a rapid-screening assay performed by non-laboratory trained personnel was evaluated. 123 blinded HIV-positive and HIV-negative samples were correctly identified. In a randomised comparison with the conventional procedure, the application of the rapid-screening assay resulted in a significant reduction of psychological stress, drug use and cost. The estimated net benefit per case was CHF 93.-(62 US$). This study strongly supports the use of the rapid-screening assay in the management of post-exposure prophylaxis for HIV after percutaneous exposure in health care workers.

Anti-HIV Agents↗
PubMed2001

Role of the cytoplasmic domain of the beta-subunit of integrin alpha(v)beta6 in infection by foot-and-mouth disease virus.

Field isolates of foot-and-mouth disease virus (FMDV) are believed to use RGD-dependent integrins as cellular receptors in vivo. Using SW480 cell transfectants, we have recently established that one such integrin, alpha(v)beta6, functions as a receptor for FMDV. This integrin was shown to function as a receptor for virus attachment. However, it was not known if the alpha(v)beta6 receptor itself participated in the events that follow virus binding to the host cell. In the present study, we investigated the effects of various deletion mutations in the beta6 cytoplasmic domain on infection. Our results show that although loss of the beta6 cytoplasmic domain has little effect on virus binding, this domain is essential for infection, indicating a critical role in postattachment events. The importance of endosomal acidification in alpha(v)beta6-mediated infection was confirmed by experiments showing that infection could be blocked by concanamycin A, a specific inhibitor of the vacuolar ATPase.

Acids↗
PubMed2000

The reduced expression of surrogate light chains in B cell precursors from senescent BALB/c mice is associated with decreased E2A proteins.

Senescent mice exhibit decreased numbers of pre-B cells in the bone marrow. Herein, we show that the molecules, lambda5 and VpreB, which comprise the surrogate light chain component of the pre-B cell receptor, are reduced in pro-B/early pre-B cells derived in vitro from the bone marrow of 18-27 months old BALB/c mice after stimulation with IL-7. Both lambda5 and VpreB expression were decreased at the mRNA level as indicated by semi-quantitative RT-PCR; this suggests that the reduced surrogate light chains seen in senescent B cell precursors result from dysfunctional transcriptional regulation. The transcription of surrogate light chains is regulated, in part, by E2A (E47) gene products. Levels of E2A proteins, including E47, were decreased in senescent B cell precursors by up to 90%. Reduced E2A (E47) expression and subsequent reduced transcription of the surrogate light chain components lambda5 and VpreB may, in part, explain the diminished production of B lineage cells observed in senescence.

Aging↗
PubMed2000

Functional discovery via a compendium of expression profiles.

Ascertaining the impact of uncharacterized perturbations on the cell is a fundamental problem in biology. Here, we describe how a single assay can be used to monitor hundreds of different cellular functions simultaneously. We constructed a reference database or "compendium" of expression profiles corresponding to 300 diverse mutations and chemical treatments in S. cerevisiae, and we show that the cellular pathways affected can be determined by pattern matching, even among very subtle profiles. The utility of this approach is validated by examining profiles caused by deletions of uncharacterized genes: we identify and experimentally confirm that eight uncharacterized open reading frames encode proteins required for sterol metabolism, cell wall function, mitochondrial respiration, or protein synthesis. We also show that the compendium can be used to characterize pharmacological perturbations by identifying a novel target of the commonly used drug dyclonine.

Cell Wall↗
PubMed2000

Foot-and-mouth disease virus is a ligand for the high-affinity binding conformation of integrin alpha5beta1: influence of the leucine residue within the RGDL motif on selectivity of integrin binding.

Field isolates of foot-and-mouth disease virus (FMDV) use RGD-dependent integrins as receptors for internalization, whereas strains that are adapted for growth in cultured cell lines appear to be able to use alternative receptors like heparan sulphate proteoglycans (HSPG). The ligand-binding potential of integrins is regulated by changes in the conformation of their ectodomains and the ligand-binding state would be expected to be an important determinant of tropism for viruses that use integrins as cellular receptors. Currently, alphavbeta3 is the only integrin that has been shown to act as a receptor for FMDV. In this study, a solid-phase receptor-binding assay has been used to characterize the binding of FMDV to purified preparations of the human integrin alpha5beta1, in the absence of HSPG and other RGD-binding integrins. In this assay, binding of FMDV resembled authentic ligand binding to alpha5beta1 in its dependence on divalent cations and specific inhibition by RGD peptides. Most importantly, binding was found to be critically dependent on the conformation of the integrin, as virus bound only after induction of the high-affinity ligand-binding state. In addition, the identity of the amino acid residue immediately following the RGD motif is shown to influence differentially the ability of FMDV to bind integrins alpha5beta1 and alphavbeta3 and evidence is provided that alpha5beta1 might be an important FMDV receptor in vivo.

Amino Acid Motifs↗
PubMed2000

Replication-competent foot-and-mouth disease virus RNAs lacking capsid coding sequences.

RNA transcripts were prepared from plasmids encoding an infectious cDNA of foot-and-mouth disease virus (FMDV) or derivatives in which the leader (Lab and Lb) and capsid protein coding sequences were deleted or replaced by sequences encoding chloramphenicol acetyltransferase (CAT). The transcripts were electroporated into BHK cells and the expression of CAT and the FMDV 3C protease was monitored. Detection of CAT and 3C was dependent on the ability of the transcript to replicate. All of the Lb coding sequence and 94% of P1 (the capsid protein precursor) coding sequence could be deleted without any apparent effect on the ability of the RNA to replicate. Thus, no cis-acting replication element is present within this region of the FMDV genome. TRANS:-encapsidation of these FMDV replicons was very inefficient, which may explain the lack of production of defective-interfering particles in FMDV-infected cells.

Aphthovirus↗
PubMed2000

The epithelial integrin alphavbeta6 is a receptor for foot-and-mouth disease virus.

Field isolates of foot-and-mouth disease virus (FMDV) have been shown to use the RGD-dependent integrin alphavbeta3 as a cellular receptor on cultured cells. However, several other RGD-dependent integrins may have the potential to act as receptors for FMDV in vivo. Of these, alphavbeta6 is a likely candidate for use as a receptor by FMDV as it is expressed on epithelial cells, which correlates with the tissue tropism of the virus. In this report, we show that human colon carcinoma cells (SW480) that are normally nonpermissive for FMDV become susceptible to infection as a result of transfection with the integrin beta6 subunit and expression of alphavbeta6 at the cell surface. Integrin alphavbeta6 is the major site for virus attachment on the beta6-transfected cells, and binding to alphavbeta6 serves to increase the rate of virus entry into these cells. In addition, we show that virus binding and infection of the beta6-transfected cells is mediated through an RGD-dependent interaction that is specifically inhibited by a monoclonal antibody (10D5) that recognizes alphavbeta6. These studies establish a role for alphavbeta6 as a cellular receptor for FMDV.

Animals↗
PubMed1999

The structure and function of a foot-and-mouth disease virus-oligosaccharide receptor complex.

Heparan sulfate has an important role in cell entry by foot-and-mouth disease virus (FMDV). We find that subtype O1 FMDV binds this glycosaminoglycan with a high affinity by immobilizing a specific highly abundant motif of sulfated sugars. The binding site is a shallow depression on the virion surface, located at the junction of the three major capsid proteins, VP1, VP2 and VP3. Two pre-formed sulfate-binding sites control receptor specificity. Residue 56 of VP3, an arginine in this virus, is critical to this recognition, forming a key component of both sites. This residue is a histidine in field isolates of the virus, switching to an arginine in adaptation to tissue culture, forming the high affinity heparan sulfate-binding site. We postulate that this site is a conserved feature of FMDVs, such that in the infected animal there is a biological advantage to low affinity, or more selective, interactions with glycosaminoglycan receptors.

Adaptation, Physiological↗
PubMed1999

The performance of foreign medical graduates on the National Board of Medical Examiners (NBME) standardized patient examination prototype: a collaborative study of the NBME and the Educational Commission for Foreign Medical Graduates (ECFMG).

OBJECTIVES: The purpose of the study was to explore foreign medical graduates' (FMGs) performance on a clinical skills (SPX) examination. The National Board of Medical Examiners (NBME) is in the process of developing an SPX for potential use in the United States Medical Licensing Examination (USMLE). The Educational Commission for Foreign Medical Graduates (ECFMG) is developing the Clinical Skills Assessment (CSA) as an additional requirement for FMGs who wish to be certified by ECFMG. DESIGN: Thirty-three FMGs and 151 United States medical students (USMSs) took the SPX during the winter of 1996 as part of the ongoing pilot studies conducted by the NBME. Four clinical skill areas were assessed: history-taking, physical examination, communication and interpersonal skills. The examination used in this research consisted of 12 cases. The examination utilizes standardized patients (SPs) who are trained to document examinee behaviours and evaluate the communication component of the test. The SPs were also trained to evaluate the English proficiency of the candidates. Candidates were also administered the Test of Spoken English developed by the Educational Testing Services (ETS). SETTING: The examination was conducted in one medical school which served as an SPX centre for NBME pilot studies. SUBJECTS: Thirty-three foreign medical students and 151 US medical students. RESULTS: The indications were that the majority of candidates in both groups felt the examination was moderately fair but 78% of FMGs felt moderately pressed for time, vs. 80% of the USMSs who did not feel pressed for time. Reliabilities obtained for the various SPX components were somewhat higher for the FMGs reflecting the heterogeneity of this group. CONCLUSIONS: The NBME-ECFMG collaborative study yielded important information regarding the NBME SPX prototype as a performance measure for FMGs.

Clinical Competence↗
PubMed1999

Clinical findings for a group of infants and young children with auditory neuropathy.

OBJECTIVE: To examine the prevalence of auditory neuropathy in a group of infants at risk for hearing impairment and to present an overview of the clinical findings for affected children. DESIGN: Results for 20 subjects who showed repeatable cochlear microphonic potentials in the absence of click-evoked auditory brain stem responses are included in this study. Behavioral and steady state evoked potential thresholds were established in each case. Where possible, otoacoustic emission and speech perception results (unaided and aided) also were obtained. RESULTS: One in 433 (0.23%) of the children in our series had evidence of auditory neuropathy. The audiometric findings for these subjects varied significantly, with behavioral thresholds ranging from normal to profound levels. Discrimination skills were also variable. Approximately half of the subjects showed little understanding, or even awareness, of speech inputs in both the unaided and aided conditions. There were, however, a number of children who could score at significant levels on speech discrimination tasks and who benefited from the provision of amplification. CONCLUSION: The results suggest that auditory neuropathy is more common in the infant population than previously suspected. The effects of neuropathy on auditory function appear to be idiosyncratic, producing significant variations in both the detection and discrimination of auditory signals. As such, the management of children with this disorder must allow for individual differences.

Audiometry, Evoked Response↗
PubMed1998

Aicardi syndrome.

Explore the source record for details and available documents.

Agenesis of Corpus Callosum↗
PubMed1997

Arginine-glycine-aspartic acid-specific binding by foot-and-mouth disease viruses to the purified integrin alpha(v)beta3 in vitro.

The integrin alpha(v)beta3 has been shown to act as the receptor for internalization of foot-and-mouth disease virus (FMDV) (A12), with attachment being through a highly conserved RGD motif located on the G-H loop of viral capsid protein VP1. In addition, however, we have recently shown that efficient infection of culture-grown cells by FMDV (O1BFS) requires binding to cell surface heparan sulfate. In this study, we have used a solid-phase receptor binding assay to characterize the binding by FMDV to purified alpha(v)beta3 in the absence of heparan sulfate and other cell surface components. In this assay, FMDV (O1BFS) successfully replicated authentic ligand binding by cellular alpha(v)beta3 in terms of its high affinity, dependence on divalent cations, and activation by manganese ions. Virus binding to this preparation of alpha(v)beta3 was exquisitely sensitive to competition by short RGD-containing peptides (50% inhibition at < 10(-8) M peptide), and this inhibition was highly sequence specific, with the equivalent RGE peptide being at least 10(4) fold less effective as a competitor. Representative viruses of the other six serotypes of FMDV bound to alpha(v)beta3 in a similar RGD-specific manner, although significant differences in sensitivity to RGD peptides suggest that the affinity of the different FMDV serotypes for alpha(v)beta3 is influenced, in part, by the variable amino acid residues in the VP1 G-H loop on either side of the RGD.

Aphthovirus↗
PubMed1996

Efficient infection of cells in culture by type O foot-and-mouth disease virus requires binding to cell surface heparan sulfate.

Foot-and-mouth disease virus (FMDV) enters cells by attaching to cellular receptor molecules of the integrin family, one of which has been identified as the RGD-binding integrin alpha(v)beta3. Here we report that, in addition to an integrin binding site, type O strains of FMDV share with natural ligands of alpha(v)beta3 (i.e., vitronectin and fibronectin) a specific affinity for heparin and that binding to the cellular form of this sulfated glycan, heparan sulfate, is required for efficient infection of cells in culture. Binding of the virus to paraformaldehyde-fixed cells was powerfully inhibited by agents such as heparin, that compete with heparan sulfate or by agents that compete for heparan sulfate (platelet factor 4) or that inactivate it (heparinase). Neither chondroitin sulfate, a structurally related component of the extracellular matrix, nor dextran sulfate appreciably inhibited binding. The functional importance of heparan sulfate binding was demonstrated by the facts that (i) infection of live cells by FMDV could also be blocked specifically by heparin, albeit at a much higher concentration of inhibitor; (ii) pretreatment of cells with heparinase reduced the number of plaques formed compared with that for untreated cells; and (iii) mutant cell lines deficient in heparan sulfate expression were unable to support plaque formation by FMDV, even though they remained equally susceptible to another picornavirus, bovine enterovirus. The results show that entry of type O FMDV into cells is a complex process and suggest that the initial contact with the cell surface is made through heparan sulfate.

Animals↗