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Biomedical subjects

G M Walton

Publications and source records attributed to G M Walton.

At least 19 recordsLinked to original sources
PubMed2001

Osteomyelitis complicating osteopetrosis--a case report.

Osteomyelitis of the jaws is uncommon but can be a complication of extraction or exposure of teeth in patients who are immunosuppressed or have undergone radiotherapy to the head and neck region. We report a case of osteomyelitis in a patient who has osteopetrosis. The initial clinical presentation was that of an infected retained root, secondary to denture trauma to the supporting tissues. Radiological interpretation was difficult owing to the increased bone density and surgical exploration revealed only a dense region of necrotic bone.

Aged↗
PubMed1999

Tritiated thymidine and bromodeoxyuridine double-labelling studies on growth factors and oral epithelial proliferation in the mouse.

Mouse tongue epithelium is characterized by a circadian variation in the number of cells undergoing DNA synthesis. Groups of male BDF1 mice were followed over 48 h and a double-labelling method with tritiated thymidine and bromodeoxyuridine used to determine S-phase labelling indices, together with cell influx to and cell efflux from S, at 4-hourly time points. Control animals exhibited diurnal peaks in labelling index at 03:00 with trough activity 12 h later at 15:00. Cell influx peaked at 23:00 with troughs occurring between 11:00 to 15:00. Peak cell efflux occurred at 07:00 with trough activity at 19:00. Animals injected with epidermal growth factor at 05:00 demonstrated a significant fall in both influx and efflux throughout the 48-h period (P < 0.001), but with preservation of labelling indices, suggesting a slower transit of cells through S-phase, whereas epidermal growth factor injected at 15:00 only produced a significant rise in cell-efflux values. Adrenergic stimulation by intravenous phenylephrine/isoprenaline injection at both 05:00 and 15:00 resulted in a significant rise in cell efflux (P < 0.001), although there was also a rise in labelling index in the 15:00 group (P < 0.001). Animals injected with calmodulin at 05:00 demonstrated a significant reduction in labelling index throughout the 48-h period (P < 0.001), but maintained control values for cell influx and efflux, suggesting faster transit of cells through S. Calmodulin injection at 15:00 produced only a significant reduction in cell influx (P < 0.001). Administration of exogenous growth factors significantly alters the normal rhythmical proliferation of oral epithelial cells in a mouse model. These effects appear to be both growth factor- and time-dependent, and may have both physiological and pathological implications.

Adrenergic alpha-Agonists↗
PubMed1999

Complications of percutaneous gastrostomy in patients with head and neck cancer--an analysis of 42 consecutive patients.

A total of 42 patients, who underwent insertion of a percutaneous gastrostomy tube prior to resection for oral squamous cell carcinoma, were investigated to examine the incidence and severity of complications associated with use of this technique. The team performing the procedure and the grade of operator was noted together with any subsequent complications and their outcome. Previously reported complication rates were 2.7-2.8% and 6-7.1% for major and minor complications, respectively, but, in this series, a major complication rate of 22.5% and minor complication rate of 17.5% were identified. The findings of this study have led to the introduction of a further prospective audit of this technique in the maxillofacial unit and a more selective policy of PEG prescription for patients undergoing resection for head and neck cancer.

Carcinoma, Squamous Cell↗
PubMed1993

Ketorolac and diclofenac for postoperative pain relief following oral surgery.

A double-blind clinical study was designed to compare the efficacy and safety of intramuscular and oral ketorolac, a new non-steroidal anti-inflammatory analgesic with that of diclofenac and placebo for patients undergoing removal of impacted mandibular third molar teeth. Results showed that both analgesic preparations were more effective than placebo (p = 0.0029) and that ketorolac provided a similar degree of pain relief to that of diclofenac. It is concluded that ketorolac is important new addition to the available intra-muscular NSAID preparations.

Acetaminophen↗
PubMed1992

Cardiopulmonary performance following changes in position and the administration of intravenous Diazemuls.

Twenty healthy volunteers entered a study to assess cardiopulmonary responses, as measured by pulse oximetry, following changes in posture in the dental chair and the administration of Diazemuls (diazepam) in doses sufficient to instill sedation (up to a maximum dose of 20 mg) in the volunteers to a degree such that ptosis was seen. The results indicate that SaO2 values remained above 95 per cent throughout the study. It is concluded that although changes in SaO2 and pulse rate do occur, these differences are not important in healthy individuals, although they may be more serious in patients with pre-existing cardiopulmonary disease.

Adolescent↗
PubMed1992

A nuclear protein is required for thyroid hormone receptor binding to an inhibitory half-site in the epidermal growth factor receptor promoter.

The epidermal growth factor (EGF) receptor (EGFR) promoter is negatively regulated by thyroid hormone and retinoic acid. This regulation can be mapped to a 36-basepair GC-rich region of the promoter (EGFR P/E) that functions autonomously as a promoter and an enhancer when placed in front of the thymidine kinase gene TATA element. Direct high affinity binding of the thyroid hormone receptor (T3R) to this element requires a nuclear protein. Through ion exchange chromatography and gel filtration of HeLa nuclear extract, this activity was identified as a protein of approximately 67 kilodaltons. This protein did not bind to DNA alone, but greatly augmented T3R binding to the EGFR P/E sequence in gel mobility shift and DNA precipitation assays. When combined with the T3R auxillary protein (TRAP), the T3R migrated as a larger complex on the DNA. Chemical cross-linking identified this complex as a heterodimer between T3R and TRAP. T3R-TRAP binds to a 7-basepair site in the EGFR P/E (GGGACTC) that has weak homology to a consensus thyroid response element half-site. Thus, on this element, T3R-TRAP heterodimers contact the DNA primarily on a single site that comprises an inhibitory thyroid response element.

Base Sequence↗
PubMed1991

Structural analysis of the transmembrane domain of the epidermal growth factor receptor.

The ligand-binding domain of the epidermal growth factor (EGF) receptor is separated from the cytoplasmic protein tyrosine kinase domain by a predicted single transmembrane segment. Antipeptide antibodies prepared against the outer portion of the predicted transmembrane segment confirmed this area was exposed only when cells were treated with permeabilizing agents. To investigate structural requirements for signal transduction by the transmembrane domain, three types of mutant EGF receptor were prepared. The first type was designed to shorten the transmembrane domain, the second to place proline substitutions within this domain, and the third to make amino acid substitutions analogous to those present in the transforming c-erbB2/neu oncoprotein. Mutant human receptors were expressed in null recipient mouse B82L and Chinese hamster ovary cells. All receptors bound EGF and exhibited EGF-stimulated protein tyrosine kinase activity in vivo as assayed using a 125I-labeled monoclonal anti-phosphotyrosine antibody. EGF stimulated growth of cells expressing each mutant receptor with similar dose-response characteristics. In contrast to other growth factor receptors, the transmembrane domain of the EGF receptor is tolerant to a variety of changes which neither mimic EGF action by constitutive activation nor interfere with ligand-induced signal transduction.

Amino Acid Sequence↗
PubMed1991

Changes in oxygen saturation using two different sedation techniques.

Pulse oximetry was used to assess the degree of hypoxia observed in patients receiving simple midazolam sedation for removal of lower third molars and compared to that seen in patients receiving a combination sedation technique using nalbuphine and midazolam. Results showed that the degree of hypoxia experienced by patients receiving the combination technique was significantly more profound in both incidence and depth than that seen in the group receiving midazolam alone (p less than 0.05).

Procedural Sedation↗
PubMed1991

Fracture of the mandible in a child.

If unusual injuries to the teeth are present, these should serve as a warning to practitioners that further investigations may be necessary. In the case reported here an undisplaced fracture of the jaw in a young child was only revealed by radiographic investigation.

Child, Preschool↗
PubMed1990

Phosphorylation of the epidermal growth factor receptor at threonine 654 inhibits ligand-induced internalization and down-regulation.

To assess the functional significance of phosphorylation of the epidermal growth factor (EGF) receptor at Thr654, we compared the effects of 12-O-tetradecanoyl-13-acetate (TPA) on ligand-induced internalization and down-regulation between wild-type and mutant receptors that contain an alanine substitution at position 654. Activation of protein kinase C with TPA blocked EGF-induced internalization and down-regulation of Thr654 receptors and inhibited in vivo tyrosine kinase activity by 80%. TPA did not inhibit transferrin receptor internalization or constitutive EGF receptor internalization, suggesting that protein kinase C activation inhibits only the ligand-induced process. Inhibition by TPA of induced internalization, down-regulation, and kinase activity required threonine at position 654 since full-length Ala654 EGF receptors were significantly resistant to TPA inhibition of these ligand-induced activities. However, C'-terminal truncation further enhanced this resistance to TPA inhibition. The EGF-dependent internalization of kinase-inactive receptors truncated at residue 1022 was also impaired by TPA in Thr654 receptors, but not in Ala654 receptors, indicating that phosphorylation at Thr654 also interferes with tyrosine kinase-independent receptor activities. We conclude that the dominant regulatory effect of protein kinase C on the EGF receptor is mediated through phosphorylation at Thr654 which effectively inactivates the receptor. The submembrane region of the EGF receptor appears to regulate transmission of conformational information from the extracellular ligand-binding site to the cytoplasmic kinase and regulatory domains.

Alanine↗
PubMed1990

A comparison of ibuprofen and ibuprofen-codeine combination in the relief of post-operative oral surgery pain.

Non-steroidal anti-inflammatory analgesics are commonly prescribed to out-patients who have undergone oral surgical procedures, since they are said to provide excellent pain relief for mild to moderate pain, allied with minimal side-effects. One hundred patients were entered into a randomised clinical trial to compare the efficacy of a simple non-steroidal analgesic with that of a combination analgesic compound following the removal of lower third molars under local anaesthesia. Pain scores were measured for patients post-operatively by means of a verbal rating scale for 3 days and data were analysed using the Mann-Whitney U-test. Results suggest that this combination product offers no advantages (but shows definite disadvantages) when compared to an effective non-steroidal anti-inflammatory product.

Adolescent↗
PubMed1990

Analysis of deletions of the carboxyl terminus of the epidermal growth factor receptor reveals self-phosphorylation at tyrosine 992 and enhanced in vivo tyrosine phosphorylation of cell substrates.

The human epidermal growth factor receptor (EGFR) contains a large C' terminus distal to the protein tyrosine kinase domain that is conserved among members of its extended gene family. To investigate the C' terminus, a series of mutant EGFR cDNAs encoding progressive C'-terminal deletions were prepared and expressed in null recipient B82L cells. In vivo self-phosphorylation was retained in receptors truncated to residues 1052 and 1022 which lack the three identified sites of tyrosine self-phosphorylation. Receptors truncated to residue 991 did not undergo in vivo self-phosphorylation. Purified 1022 truncated receptor was self-phosphorylated to the extent of 1 mol of phosphate/mol of receptor protein. The deduced additional site of tyrosine self-phosphorylation at residue 992 was confirmed by tryptic phosphopeptide mapping and protein sequencing. EGFRs deleted to give C'-terminal residues 1052, 1022, 991, and 973 exhibited enhanced EGF-stimulated tyrosine phosphorylation of cell substrates in vivo, whereas deletion at residue 944 abolished all detectable EGF-stimulated protein tyrosine phosphorylation. These results indicate that ligand-induced self-phosphorylation is limited to the C' terminus of the EGFR and suggest that this region of the holoreceptor has an inhibitory function.

DNA Mutational Analysis↗
PubMed1989

Functional independence of the epidermal growth factor receptor from a domain required for ligand-induced internalization and calcium regulation.

We have located the distal boundary of the tyrosine kinase domain of the EGF receptor and have identified a distinct sequence in the C' terminus required for EGF-dependent receptor internalization, leading to receptor down-regulation and degradation. Within this receptor domain, an 18 amino acid highly negatively charged region of predicted helical structure is required both for endocytosis via a high-affinity, saturable pathway and for ligand-stimulated increases in cytosolic calcium. In contrast to kinase-inactive, internalization-competent receptors, kinase-active, internalization-defective receptors effectively signaled gene transcription, morphological transformation, and growth. These observations support the hypothesis that mitogenic responses to EGF are mediated by activation of the intrinsic protein tyrosine kinase activity of the membrane-bound receptor, with ligand-induced internalization serving to terminate the signal.

Amino Acid Sequence↗
PubMed1988

Ligand-induced endocytosis of the EGF receptor is blocked by mutational inactivation and by microinjection of anti-phosphotyrosine antibodies.

Early events in ligand-induced endocytosis of the EGF receptor have been examined. A mutant EGF receptor devoid of intrinsic protein-tyrosine kinase activity bound EGF and dimerized normally yet failed to undergo ligand-induced internalization. Immunofluorescence microscopy revealed that receptors lacking kinase activity failed to undergo the ligand-induced internalization characteristic of receptors with kinase activity. Monoclonal anti-phosphotyrosine antibodies effectively inhibited phosphorylation of exogenous substrates in vitro and, when microinjected into cells containing active EGF receptors, prevented internalization of the receptor when cells were subsequently challenged with EGF. These results point to a crucial role for the kinase activity of the EGF receptor in the process of ligand-induced endocytosis of receptors, and imply that a phosphorylated substrate(s) is required.

Antibodies, Monoclonal↗
PubMed1987

A three-step purification procedure for protein kinase C: characterization of the purified enzyme.

An efficient high yield three-step purification procedure for protein kinase C consisting of ion exchange, hydrophobic interaction, and substrate affinity chromatographies is described. Protein which appears homogeneous on sodium dodecyl sulfate-polyacrylamide gel electrophoresis contains amino acid sequences, predicted from cDNA cloning, for both the alpha and beta isoenzyme forms of the bovine brain enzyme. Both forms appear active as indicated by [3H]phorbol dibutyrate binding stoichiometry of approximately 1. Purified enzyme is active as a monomeric species, exhibits high cooperativity between Ca+2 and phosphatidylserine binding for activity, and undergoes intramolecular self-phosphorylation at both serine and threonine residues. Incubation of the enzyme with ATP, which leads to extensive self-phosphorylation, markedly stabilizes phosphotransferase activity without increasing the Vmax of the reaction.

Adenosine Triphosphate↗
PubMed1985

Phosphorylation of high mobility group protein 14 by casein kinase II.

Phosphorylation of chromosomal high mobility group (HMG) protein 14 by casein kinase II has been characterized. Two mol of 32P are incorporated per mol of bovine HMG 14. Kinetic analysis provided evidence for two distinct sites with apparent Km values of 14.5 and 134 microM and respective Vmax values of 0.17 and 0.68 mumol/min/mg casein kinase II. Tryptic peptide mapping identified two phosphorylated products, each with phosphoserine. Amino acid composition and sequence analysis demonstrate that the major high affinity phosphorylation site for casein kinase II is serine 89. This sequence located at the carboxyl-terminal of HMG 14 contains the primary sequence determinants for casein kinase II. On the basis of reverse-phase high performance liquid chromatography and amino acid analysis, HMG 14, serine 99 represents the low affinity phosphorylation site.

Amino Acids↗