PubMed Health⌕ Search

Biomedical subjects

C Edmonds

Publications and source records attributed to C Edmonds.

16 recordsLinked to original sources
PubMed1992

Graves' ophthalmopathy in relation to cigarette smoking and ethnic origin.

OBJECTIVE: We aimed to study the effect of cigarette smoking on the prevalence and severity of Graves' ophthalmopathy (GO). PATIENTS: One hundred and fifty-five newly diagnosed patients with Graves' disease (GD) were diagnosed clinically and by routine biochemical methods. Twenty-five per cent (39) were of Asian origin. METHODS: Eye signs were classified according to the American Thyroid Association Classification. A detailed smoking questionnaire and data from hospital notes were used to calculate an index of cigarette consumption. RESULTS: Thirty-four per cent of all patients had Graves' ophthalmopathy, and the prevalence in males (26%) and females (36%) did not differ significantly. There was a prevalence of 42% among Europeans compared to 7.7% in Asians (P = 0.0002). The overall risk for Europeans for developing Graves' ophthalmopathy was 6.4 (1.78-22.7 confidence interval) times higher than for Asians. Corrected for the ethnic factor the increased risk from smoking for Europeans was 2.4 (1.12-5.18, 95% confidence interval) times higher. There was a significant dose effect (P = 0.008). CONCLUSIONS: The present findings confirm an effect of cigarette smoking on Graves' ophthalmopathy and in addition show that Europeans have a substantially greater risk of developing Graves' ophthalmopathy than have Asians.

Adolescent↗
PubMed1991

Croup. A common cause of airway obstruction in children.

Although viral croup is usually a self-limiting disease, its signs and symptoms are distressing enough to make parents seek immediate medical advice. This is fortunate because a much more serious disorder may be present. Indeed, morbidity requiring hospitalization may occur, as may a true emergency. Drs Thomsen and Edmonds discuss the epidemiology and current management of croup and related conditions.

Airway Obstruction↗
PubMed1990

The region of the HPV E7 oncoprotein homologous to adenovirus E1a and Sv40 large T antigen contains separate domains for Rb binding and casein kinase II phosphorylation.

Some genital human papillomavirus (HPV) types, such as 16 and 18, are highly associated with malignant cervical tumors while others, such as HPV 6, are only rarely found in these malignancies. The E7 oncoproteins of HPV 6, 16 and 18 each have a 17 amino acid region with striking homology to adenovirus E1a and SV40 LT. E1a, LT and the E7 oncoprotein of HPV16 all bind the cellular Rb protein in vitro, and for E1a and LT this region of homology contains sequences essential for interaction with Rb. We have now found that in HPV 16 E7 this region (amino acids 21-37) contains two separate biochemical activities, each of which contributes to E7-mediated transformation. Rb binding was localized to the N terminus of this region, while the C terminus was shown to serve as a substrate for casein kinase (CK) II, which phosphorylated serine-31 and serine-32. Replacement of the two serines by non-phosphorylatable amino acids led to a reduction in transforming activity and abolished phosphorylation but did not affect Rb binding. Rb binding and CK II phosphorylation were also examined for the E7 proteins of HPV 6 and HPV 18. HPV 16 and 18 E7 bound similar amounts of Rb, but HPV 6 E7 consistently bound less. Phosphorylation rates also varied, with HPV 18 E7 being 2-fold faster than HPV 16 E7, which in turn was 2-fold faster than HPV 6 E7. We conclude that Rb binding and phosphorylation of E7 by CKII are independent activities which are required for efficient transformation by E7 and that these activities correlate directly with the relative oncogenic potential of these viruses.

Adenovirus Early Proteins↗
PubMed1990

Analysis of human papillomavirus type 16 open reading frame E7 immortalizing function in rat embryo fibroblast cells.

The E7 open reading frame of human papillomavirus type 16 (HPV-16) encodes a protein that can immortalize primary rat cells, cooperate with the ras oncoprotein to transform low passage rat cells and transform established rodent cells to anchorage independence. The immortalizing and cooperation functions have been investigated using a series of point mutations that introduce single amino acid changes into the E7 protein in two distinct regions. Certain mutations altering amino acids conserved between the E7 protein of genital HPV types, the adenovirus E1a protein and simian virus 40 large T antigen abolished the ability of the E7 protein to immortalize or cooperate with ras in a focus forming assay. Mutations in a consensus sequence for a casein kinase II recognition site, which is also shared by E1a and large T, reduced immortalizing activity, but did not affect the ability to cooperate with ras. Single mutations disrupting cysteine motifs, which form putative zinc-binding sites in the second region, reduced the activity of the E7 protein, whereas double mutants, in which neither of the cysteine motifs remained intact, showed no or very low activity. The activity of the mutants in immortalization and cooperation assays was essentially the same as their transforming activities in NIH 3T3 cells. This indicates that these three functions of E7 map to overlapping domains which cannot be separated by these mutations in the region of E1a/large T homology or the cysteine motifs.

Amino Acid Sequence↗
PubMed1990

Ability of the HPV16 E7 protein to bind RB and induce DNA synthesis is not sufficient for efficient transforming activity in NIH3T3 cells.

Previous studies have demonstrated that the HPV-16 E7 gene product encodes the major transforming activity of the virus in rodent cell systems. In this study we have generated a series of point mutations affecting the region of HPV-16 E7, which shows homology to adenovirus E1a conserved domain (CD)1. In conjunction with previously described mutants in the region of E7 with similarity to E1a CD2 and SV40 LT, we have investigated three known activities of the E7 protein; transformation, association with the cellular RB protein and induction of cellular DNA synthesis. The results show that RB binding correlates with the ability of E7 to induce cellular DNA synthesis and mediate cell transformation. In addition an unidentified function of E7, which is necessary for transformation of NIH3T3 cells, but does not affect RB binding or the ability to induce cellular DNA synthesis, has also been demonstrated. This study therefore identifies two separate regions of the E7 gene necessary for transformation of established cells. One of these, in the region of E7 which shows similarity to E1a CD2 and LT, is required for RB binding and DNA synthesis. The other region important for transformation, in the N-terminus of E7, is separable from the RB binding/DNA synthesis function.

Amino Acid Sequence↗
PubMed1989

Demonstration and partial characterization of ADP-ribosylation in Pseudomonas maltophilia.

ADP-ribosylation of proteins occurs in many eukaryotes, and it is also the mechanism of action of a growing number of important bacterial toxins. To date, however, there is only one well-characterized ADP-ribosylation system where the ADP-ribosyltransferase and the substrate protein are both bacterial in origin, namely within the nitrogen-fixing bacterium Rhodospirillum rubrum. The present paper demonstrates the endogenous ADP-ribosylation of two proteins of Mr 32,000 and 20,000 within Pseudomonas maltophilia, a Gram-negative aerobe. The proteins have been partially purified: two apparently separate species of modified protein can be separated by ion-exchange chromatography and gel filtration (V0 and Mr 158,000 - Vi). The substrate protein(s) either has, or is co-eluted with, NAD+ glycohydrolase activity. The modification is mono-ADP-ribosyl in nature. The linkage between the acceptor amino acid and the ADP-ribose moiety is alkali-labile and stable to hydroxylamine, possibly indicating an S-glycosidic bond. The activity appears to be a true ADP-ribosylation reaction and not an NAD+ glycohydrolase activity followed by non-enzymic addition of ADP-ribose to protein. The results presented here indicate that ADP-ribosylation may have a wider significance within prokaryotic systems than previously thought.

ADP Ribose Transferases↗
PubMed1989

A point mutational analysis of human papillomavirus type 16 E7 protein.

The E7 open reading frame of human papillomavirus type 16 (HPV16) has been shown to be selectively retained in cervical tumors and to encode both transforming and trans-activating functions in murine cells, supporting the notion that expression of E7 contributes towards the progression of premalignant cervical lesions. A comparison among E7 sequences of different HPV types reveals some homology at the amino acid level. Of particular interest are two regions, one which contains significant homology to a region of adenovirus E1a and simian virus 40 large T (LT), and a second region which contains two conserved Cys-X-X-Cys motifs. To determine the importance of these domains to the function of the E7 protein, a series of mutants carrying substitutions at amino acids in the region of E1a-LT homology and at the Cys-X-X-Cys motifs were constructed. The mutated E7 sequences were placed under the control of a strong heterologous promoter (Moloney long terminal repeat), and the activity of the mutants was assayed in NIH 3T3 cells, a cell line in which both the transforming function and the trans-activating function of E7 could be determined. A single amino acid substitution analogous to a mutation in E1a which destroys the transforming ability of this protein abolished both transformation and trans-activation by E7. Mutations at the Cys-X-X-Cys motifs demonstrated that this region contributes to the transforming potential of E7, although proteins in which both motifs were interrupted retained a low level of transforming activity. Mutations in the region of E1a-LT homology which occur within a recognition sequence for casein kinase II did not markedly affect transforming activity of E7 but severely reduced trans-activating ability. This indicates that efficient trans-activation is not required for transformation by HPV16 E7 in these cells.

Amino Acid Sequence↗
PubMed1987

Quantitative cell-adhesion assay for Clostridium difficile cytotoxin.

A quantitative assay for Clostridium difficile cytotoxin has been developed, based on the observation that suspended fibroblasts exposed to cytotoxin fail to adhere to plastic. A dye-binding technique was used to quantitate adherent cells, in order to obviate microscopy. Adherent BHK cells were fixed with glutaraldehyde and cell protein was stained with Coomassie blue R-250. Cell-bound dye was eluted and estimated spectrophotometrically. The amount of eluted dye was proportional to the number of adherent cells and cell staining was time dependent. Cytotoxin was purified by gel-permeation and ion-exchange chromatography and migrated as a single band on SDS-PAGE. After exposure of suspended BHK cells to purified cytotoxin, their adhesion to plastic was inhibited in a manner which depended on concentration of cytotoxin and on time and temperature of exposure. This study provides the basis for a C. difficile cytotoxin assay that is quantitative, rapid and reproducible and may have wider applicability in the study of other toxins or agents that inhibit cell adhesion.

Animals↗
PubMed1987

Neurobehavioural effects of professional abalone diving.

In a study of 33 commercial abalone divers from the Port Lincoln area of South Australia nervous system function was examined using a battery of neurobehavioural tests. Their performance was compared with that of non-diver controls matched for age, sex, education level, job type, language abilities, and cigarette and alcohol consumption. Abalone divers showed significantly poorer vision, learning, and short term memory performance and increased tremor relative to their controls. The reaction time of abalone divers, however, was as fast as or significantly faster than that of controls but their error rates were much higher, indicating that abalone divers were sacrificing speed for accuracy. Despite their apparent risk taking approach to these tests, the performance of abalone divers suggests some impairment of nervous system function.

Adult↗
PubMed1976

Dangerous marine animals.

Tales of dangerous marine animals have flourished, entwining history, legend and imagination. Man is now demonstrating his remarkable adaptability in returning to the aquatic environment, from which he had his origins, and factual knowledge of marine creatures is surplanting mystery, folklore and fear. There is still cause to fear certain aspects of the underwater world, and the one aspect that still holds sway over public interest is that of dangerous marine animals. There is little justification for this top priority. The kelp beds of San Diego will claim more diving victims than all the marine animals around the United States of America. The cold seas off the English coastline, the tidal currents of Hawaii and the multitude of drowning accidents in water caves of Florida and Australia belittle the relatively few fatalities caused by marine animals. Nevertheless, the latter do cause injury and death, especially in the tropical, subtropical and temperate regions. The Indo-Pacific area seems particularly well endowed with a variety of potentially lethal species, and some of these will be dealt with in this paper.

Animals↗
PubMed1975

Disorientation with middle ear barotrauma of descent.

Disorientation and vertigo, which develops in divers during descent, is objectively demonstrated with dysbaric electronystagmographic tracings. Middle ear barotrauma of descent is verified as a valid etiology in the classification of vertigo associated with diving and may present as either a transitory or a more persistent disorder.

Diving↗
PubMedDate not supplied

Sinus barotrauma in divers.

Sinus barotrauma is a common occupational disease of divers, with the incidence of descent barotrauma approximately double that of ascent. Pain chronologically associated with the change of pressure is the most dominant symptom and is seen in 92% of the cases presented for treatment. The majority complain of a frontal distribution of pain, with ethmoidal and maxillary being much less significant. Epistaxis is the second commonest symptom, and may be the sole symptom in some ascent cases. A history of recent or past sinus barotrauma or upper respiratory tract pathology is very common. Clinical examination supports the evidence of upper respiratory tract pathology in many cases. The radiological signs of abnormality were present in over three quarters of the cases examined. Of these the maxillary sinus was affected in most cases, the frontal in approximately one quarter and the ethmoidal in less than a fifth. The pathology was more commonly that of mucosal thickening, but in 12% of cases there was a fluid level. It is noted that although symptoms were predominantly frontal, x-ray changes were most often present in the maxillary sinuses.

Diving↗