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M C Edwards

Publications and source records attributed to M C Edwards.

At least 37 records · Page 2Linked to original sources
PubMed1992

RNA recombination in the genome of barley stripe mosaic virus.

Barley stripe mosaic Hordeivirus (BSMV) is a positive-strand RNA virus requiring three single-stranded RNAs (alpha, beta, and gamma) for infectivity. A terminal-sequence-dependent cloning strategy was used to clone the entire genome of the CV17 strain. Full-length gamma cDNA clones were obtained when oligonucleotides specific for the 5'-terminal sequence of RNA alpha were used in the cloning procedure, but not when RNA gamma-specific oligonucleotides were used. Sequence analysis of six putative gamma cDNA clones revealed that nucleotides 1-70 possess 89% homology with the first 70 nucleotides of RNA alpha. This leader region is separated from the gamma-specific coding region by an eight-base intervening sequence common to both CV17 RNAs alpha and gamma. Northern and Southern hybridization with oligonucleotide probes specific for either alpha or gamma leader sequences indicated that CV17 gamma cDNA clones are representative of native CV17 gamma RNAs. Furthermore, bioassays indicated that in vitro transcripts derived from these gamma cDNA clones were infectious when coinoculated with in vitro transcripts of full-length alpha and beta cDNA clones. Thus, the evidence suggests that RNA gamma of BSMV strain CV17 is a recombinant molecule which may have arisen as a result of natural recombination between RNAs alpha and gamma.

Base Sequence↗
PubMed1992

A human dimorphism resulting from loss of an Alu.

The molecular phylogeny of Alu and other repeated sequences in the human genome provides clues to events during primate evolution. A subclass of human Alu's has been previously identified as dimorphic insertions within members of the medium reiteration frequency (mer) class of repeats, reflecting the complicated sequence of insertion and radiation events leading to the current human genome structure. One dimorphic Alu is located within a previously unidentified mer family member, in the first intron of the human T4 (CD4) gene. The insertion (Alu+ allele) has a frequency of approximately 70% in Europeans and Africans and is homozygous in 20 Asian samples. Polymerase chain reaction amplification, direct DNA sequencing, and Southern analysis using oligonucleotide probes revealed that the Alu- allele was derived from the Alu+ allele by loss of part of the inserted sequence. Comparison with a tightly linked marker within the human genome and studies of baboon DNA samples revealed that the original insertion was a relatively early event in primate evolution, but that the Alu sequence loss leading to the dimorphism has occurred much more recently. Loss of Alu insertions therefore represents one mechanism for the generation of human Alu dimorphisms.

Animals↗
PubMed1990

Systemic movement of an RNA plant virus determined by a point substitution in a 5' leader sequence.

The ability of viruses to move through infected plants is an important determinant of host range and pathogenicity. We have investigated the genetic basis for the inability of the Type strain of barley stripe mosaic hordeivirus to undergo long-range systemic movement in the tobacco Nicotiana benthamiana. We show that, in this model system, a short open reading frame in the 5' leader of the smallest viral genomic RNA prevents long-range vascular movement. As predicted by the ribosome scanning model, the leader open reading frame decreases the efficiency with which the 5'-proximal gene is translated in vitro. Thus, systemic pathogenicity in this system may be determined by the efficiency of translation of a viral gene in vivo and is not determined by the primary sequence of the encoded protein.

Amino Acid Sequence↗
PubMed1990

Expression of resistance to barley stripe mosaic virus in barley and oat protoplasts.

Mesophyll protoplasts from both susceptible and resistant hosts were inoculated with RNA purified from barley stripe mosaic virus (BSMV) strains CV52 and CV42 using the polyethylene glycol (PEG) method. Protoplasts derived from the susceptible Hordeum vulgare L. cv. Black Hulless were susceptible to both BSMV strains, as indicated by fluorescein isothiocyanate staining and ELISA. More than 80% of protoplasts derived from an oat cultivar resistant to CV52, but not to CV42, were readily infected by either CV52 or CV42. Protoplasts from 10 barley lines resistant to CV42 remained resistant to CV42, although a limited number of protoplasts were infected. Functional resistance in the cultured barley protoplasts, but not in those from oat plants, suggests that resistance in these barley lines may be the result of restriction of replication, whereas resistance in oat plants is more likely due to restriction of cell-to-cell movement.

Edible Grain↗
PubMed1989

Phorbol esters of different biological activities may preferentially act as mitogens of human suppressor T-cells and are equi-effective mitogens of IL-2 dependent cells.

The actions of tetradecanoylphorbolacetate (TPA) and 12-deoxyphorbolphenylacetate-20-acetate (DPPAA) together with a phytohaemagglutinin (PHA) have been examined on the proliferative responses of human mononuclear cells (MNC) depleted of specific cell subsets by the use of monoclonal antibodies. PHA-induced proliferation was found to be reduced when monocytes/macrophages and T-helper cells were depleted from MNC, but enhanced compared with MNC responses when T-suppressor cells were depleted. In contrast, TPA- and DPPAA-induced proliferation was unchanged or slightly enhanced following macrophage/monocyte depletion, and whereas TPA-induced proliferation was largely independent of subtype constitution, the non-tumour promoting DPPAA appeared to selectively enhance proliferation of the T8+ suppressor subset. Indomethacin increased the proliferative MNC responses of phorbol esters whilst having little effect upon the PHA response, an effect antagonized by addition of PGE2. The addition of interleukin-2 (IL-2) increased the proliferative response, as well as resistance to inhibition induced by cyclosporin A and dexamethasone and partially abolished the selective actions of DPPAA and PHA. In IL-2 dependent cultures PHA induced stimulation was more sensitive to inhibition by cyclosporin than were the phorbol esters. The results suggest that, although induction of lymphocyte proliferation by phorbol esters is not a correlate for tumour promotion itself, non-promoting phorbol esters may have a more restricted ability to induce proliferation than TPA.

Antibodies, Monoclonal↗
PubMed1989

Cluster of Malassezia furfur pulmonary infections in infants in a neonatal intensive-care unit.

Between 23 and 27 July 1987, three infants at one hospital developed severe bronchopneumonia associated with respiratory failure, thrombocytopenia, and leukocytosis. Two infants died; at postmortem examination, Malassezia furfur was identified in their lung tissues. M. furfur was isolated from cultures of blood, urine, and stool samples from the infant who survived. All documented M. furfur infections occurred in infants with a birth weight of less than 1,000 g; the attack rate was 42.9% (three of seven infants). A case-control study comparing the three cases and nine infants randomly selected from infants in the neonatal intensive care unit during the outbreak showed the following variables to be significantly associated with case-infants: younger gestational age (less than 26 weeks), hyaline membrane disease, duration of ventilation, duration of antimicrobial therapy, and the presence of a Broviac catheter. In a second case-control study, in which case-infants were compared with birth weight-matched controls, only the duration of antimicrobial therapy was significantly associated with case-infants. A point prevalence culture survey showed that 2 of 10 infants and 2 of 11 personnel were colonized with M. furfur. This cluster suggests that M. furfur can be transmitted from an infected or colonized infant to other infants. Infection control practices should be aimed at (i) identifying high-risk infants and (ii) reemphasizing the importance of hand washing.

Birth Weight↗
PubMed1988

Blood pressure reactivity and bias vary with age in a comparison of traditional and automated methods of measurement.

This study examined the effects of initial-reading reactivity and measurement methods of blood pressure across different age groups. Subjects were men and women (n = 132), 17 to 96 years of age. Two measurements were obtained from each subject, with a 1-min interval between trials. Each trial consisted of concurrent measurements from each arm, using a standard mercury manometer and an automated blood pressure monitor for use at home. A double-blind control procedure was used. Significant effects were obtained for age (younger, middle, and older age groups), method by trial and age by trial. The blood pressure reactivity and the effect of observer bias varied across age groups. The results support the hypotheses that blood pressure readings decline across trials; that observer bias using traditional methods is sufficient to mask this decline; and that the extent of reactivity and subsequent decline is dependent on age or an age-related increase in blood pressure. Implications of these findings for the use of automated monitoring instruments designed for use at home are discussed.

Adolescent↗
PubMed1987

The potentiation of phorbol ester-induced aggregation of human platelets by the prostaglandin endoperoxide analogue, U46619.

It was not possible to desensitize human blood platelets to 12-deoxyphorbol-phenylacetate (DOPP) stimulation in a manner analogous with that to platelet aggregating factor (PAF), prostaglandin-endoperoxide analogue (U46619) or adenosine diphosphate (ADP). Platelets previously desensitized to U46619, when challenged with DOPP and ADP, showed an increased aggregation and release of 5-HT. Sub-threshold aggregating doses of U46619 also caused a potentiation of the platelet response and release reaction to DOPP. The concentration of U46619 used to pretreat platelets affected the extent of potentiation of platelet stimulation induced by DOPP. The degree of potentiation was also affected by the time interval between addition of U46619 and DOPP. U46619 did not potentiate the aggregating effects of PAF, or ionophore A23187. The stimulus potentiation of DOPP by U46619 was abolished by prostacyclin (PGI2) and an antibody to U46619, but was unaffected by indomethacin and CP/CPK.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1985

Structural correlations of phorbol-ester-induced stimulation of PGE2 production by human rheumatoid synovial cells.

Eight phorbol esters were studied for their ability to stimulate prostaglandin production in human rheumatoid synovial cells over the dose range 0.1 ng to 1.0 micrograms. These derivatives were based upon phorbol, 4-deoxyphorbol, and 12-deoxyphorbol nuclei. This activity was structurally dependent and, although it did not correlate with the actions of the same compounds to induce erythema in vivo, it did correlate with their ability to stimulate human lymphocyte mitogenesis. Stimulation of PGE2 production by a phorbol and a 12-deoxyphorbol analog was inhibited in this system by both indomethacin and dexamethasone.

Arthritis, Rheumatoid↗
PubMed1984

An autoradiographic method for determining nutrient competition between leaf epiphytes and plant pathogens.

A method is described for the study of nutrient competition between leaf surface microorganisms and plant pathogenic fungi. Autoradiography was used to investigate the uptake of water-soluble 14C-labelled nutrients by applying a dry pre-formed layer of emulsion to the specimen. The method was adapted for use on both leaf and artificial surfaces. A photometric method was used for rapid examination of autoradiographs.

Autoradiography↗
PubMed1983

New phorbol and deoxyphorbol esters: isolation and relative potencies in inducing platelet aggregation and erythema of skin.

Diester diterpenes based upon phorbol, 4-deoxyphorbol, 4 alpha-deoxyphorbol, 4-deoxy-5-hydroxyphorbol and 4,20-dideoxy-5-hydroxyphorbol were isolated from the fruit oil of Sapium indicum. Corresponding tri- and tetra-esters were produced by acetylation and mono-esters by selective hydrolysis. Twenty-six compounds were tested for production of erythema in vivo and induction of human and rabbit platelet aggregation in vitro. The flatter shape of the AB-ring trans compounds is necessary for interaction of phorbolesters at their receptor in that the cis analogues were inactive. The tertiary C-4 hydroxy group of phorbol was not necessary for activity although the 4-deoxy derivatives were less potent than the 4-hydroxy diterpenes. A primary hydroxy group at C-20 was essential for biological activity because the methyl and aldehyde derivatives of this position were inactive. The C-20 acetates were also inactive on platelets, but they did produce erythema, possibly because of the removal of the ester due to lipase activity in the skin. 5-hydroxy-analogues which undergo intramolecular hydrogen bonding had greatly reduced activities in both systems. Membrane stabilisers, phospholipase A2 and calmodulin inhibitors were antagonists for phorbol esters in platelet aggregation tests, whilst cyclo-oxygenase inhibitors and free radical scavengers had no inhibitory effects. Consequently, one electron withdrawal and free radical formation plays no part in the biological activity of these compounds.

Animals↗
PubMed1983

Tumor-promoting and nonpromoting proinflammatory esters act as human lymphocyte mitogens with different sensitivities to inhibition by cyclosporin A.

Ten closely related tumor-promoting and nonpromoting, proinflammatory phorbol derivatives were tested for stimulation of [3H]thymidine ( [3H]TdR) incorporation into human mononuclear cells. Co-mitogenic activity was assessed with maximally effective concentrations of phytohemagglutinin (PHA) or mixed-lymphocyte reactions (MLR) in the presence of phorbol esters. Tetradecanoyl phorbol acetate (TPA), two 4-deoxyphorbol esters, and two 12-deoxyphorbol monoesters stimulated [3H]TdR incorporation in a dose-related manner. Two established nonpromoting 12-deoxyphorbol diesters were also mitogenic, although less effective than TPA, and produced lower maximal responses. TPA, the 4-deoxyphorbol esters, the 12-deoxyphorbol monoesters, and the two nonpromoting diesters were able to increase MLR-induced incorporation to the same level. When conditions were used where PHA and phorbol esters were optimally mitogenic, inhibition resulted. With the exception of co-mitogenic activity of the nonpromoting diesters, the mitogenic, co-mitogenic, and PHA-inhibiting activities were correlatable. Phorbol, a 4 alpha-deoxyphorbol ester, and resiniferatoxin had no effects. Mitogenic activity of the phorbol esters was inhibited by dexamethasone, chloroquine, and p-bromophenacyl bromide. TPA, the 4-deoxyphorbol esters, and the 12-deoxyphorbol monoesters were resistant to inhibition of activity by cyclosporin A, whereas the noncorrelating diesters exhibited sensitivity to cyclosporin A inhibition comparable to that of PHA. MLR-induced [3H] TdR incorporation was susceptible to cyclosporin A, but the phorbol ester-enhanced responses were cyclosporin A-resistant.

Carcinogens↗
PubMed1979

Randomized controlled trial of cefuroxime for established postoperative respiratory infection.

A randomized controlled trial has investigated the value of cefuroxime (a new antibiotic resistant to beta-lactamase) in 80 patients with established postoperative respiratory infection. Although the majority of respiratory isolates were sensitive to cefuroxime, there was no significant advantage in the antibiotic group compared with the controls with respect to duration of fever, radiological abnormality or infected sputum. We conclude that antibiotics are rarely necessary for the majority of patients who develop postoperative respiratory infections.

Cephalosporins↗