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J Davies

Publications and source records attributed to J Davies.

At least 109 records · Page 6Linked to original sources
PubMed2000

Characterization of the protocatechuic acid catabolic gene cluster from Streptomyces sp. strain 2065.

Protocatechuate 3,4-dioxygenase (EC 1.13.11.3) catalyzes the ring cleavage step in the catabolism of aromatic compounds through the protocatechuate branch of the beta-ketoadipate pathway. A protocatechuate 3,4-dioxygenase was purified from Streptomyces sp. strain 2065 grown in p-hydroxybenzoate, and the N-terminal sequences of the beta- and alpha-subunits were obtained. PCR amplification was used for the cloning of the corresponding genes, and DNA sequencing of the flanking regions showed that the pcaGH genes belonged to a 6. 5-kb protocatechuate catabolic gene cluster; at least seven genes in the order pcaIJFHGBL appear to be transcribed unidirectionally. Analysis of the cluster revealed the presence of a pcaL homologue which encodes a fused gamma-carboxymuconolactone decarboxylase/beta-ketoadipate enol-lactone hydrolase previously identified in the pca gene cluster from Rhodococcus opacus 1CP. The pcaIJ genes encoded proteins with a striking similarity to succinyl-coenzyme A (CoA):3-oxoacid CoA transferases of eukaryotes and contained an indel which is strikingly similar between high-G+C gram-positive bacteria and eukaryotes.

Amino Acid Sequence↗
PubMed2000

Genetic antagonism and hypermutability in Mycobacterium smegmatis.

Multidrug-resistant strains of Mycobacterium tuberculosis are a serious and continuing human health problem. Such strains may contain as many as four or five different mutations, and M. tuberculosis strains that are resistant to both streptomycin and rifampin contain mutations in the rpsL and rpoB genes, respectively. Coexisting mutations of this kind in Escherichia coli have been shown to interact negatively (S. L. Chakrabarti and L. Gorini, Proc. Natl. Acad. Sci. USA 72:2084-2087, 1975; S. L. Chakrabarti and L. Gorini, Proc. Natl. Acad. Sci. USA 74:1157-1161, 1977). We investigated this possibility in Mycobacterium smegmatis by analyzing the frequency and nature of spontaneous mutants that are resistant to either streptomycin or rifampin or to both antibiotics. Mutants resistant to streptomycin were isolated from characterized rifampin-resistant mutants of M. smegmatis under selection either for one or for both antibiotics. Similarly, mutants resistant to rifampin were isolated from streptomycin-resistant strains. The second antibiotic resistance mutation occurred at a lower frequency in both cases. Surprisingly, in both cases a very high rate of reversion of the initial antibiotic resistance allele was detected when single antibiotic selection was used; the majority of strains resistant to only one antibiotic were isolated by this process. Determinations of rates of mutation to antibiotic resistance in M. smegmatis showed that the frequencies were enhanced up to 10(4)-fold during stationary phase. If such behavior is also typical of slow-growing pathogenic mycobacteria, these studies suggest that the generation of multiply drug-resistant strains by successive mutations may be a more complex genetic phenomenon than suspected.

Alcohol Oxidoreductases↗
PubMed2000

Efficacy of an inactivated vaccine for equine herpesvirus type 1 in a novel hamster model.

A vaccine designated F.EHV1(S(-))BHK, which was prepared by formaldehyde treatment of equine herpesvirus type 1 (EHV1)-infected baby hamster kidney cells, stimulated neutralising antibodies in hamsters and rabbits and protected new-born hamsters against a lethal challenge with EHV1 by vaccination of their pregnant mothers. The preparative method was then modified to eliminate virus particles and intraparticulate DNA, producing a vaccine designated Bg.F.EHV1(S(-))BHK. this modification stimulated neutralising antibodies with evidence of in vivo inactivation of the virus above non-specific levels in a mouse model. There were no adverse effects from these vaccines in rodent or rabbit species.

Animals↗
PubMed2000

Issues in effective pain control. 1: Assessment and education.

Pain is a complex phenomenon to which an individual's response is determined by the interactions of physical, psychological, cultural and social factors (Melzack and Wall, 1988; Woodward, 1995; Horn and Munafo, 1997). It cannot be measured, and self-assessment by patients is increasingly recognized as the most accurate means of evaluating their pain. However, research indicates that even self-assessment remains problematic because nurses frequently either do not use pain tools effectively, or do not always accept the self-assessment. Reasons for this seem to be rooted in the attitudes and beliefs of nurses, and inadequate communication. The latter problem could be improved by more effective use of pain tools, but attitudinal problems are more difficult to address once the barriers have become established. This article suggests that the most effective way to prevent such barriers arising is to ensure that nurses receive a focused, substantive input on pain assessment and pain control within their preregistration studies. Referring to proposals put forward several years ago by the Royal College of Nursing (Davis and Seers, 1991), the authors suggest that the process should begin very early in preregistration studies, preferably within the first 6 months, and involve teaching and learning strategies that encourage personal exploration and so are conducive to personal growth and development. In this way, postregistration studies could realistically focus on specialist aspects of pain care more appropriate to 'continuing education'.

Attitude of Health Personnel↗
PubMed2000

Issues in effective pain control. 2: From assessment to management.

In the first of these two articles, Davies and McVicar (2000) reviewed issues regarding pain assessment and examined the best means of providing the underpinning education. In the second article, pain management issues are considered while focusing on the factors that influence the translation of planned care into action. The literature identifies that inadequate pain control continues to be a problem and, assessment issues apart, suggests that a lack of knowledge of analgesic pharmacology, and resultant misconceptions among both health professionals and patients, are major factors. This article provides an overview of the rationale for the use of analgesics by considering their biological actions, how the drugs fit into the analgesic 'ladder' (World Health Organization (WHO), 1994), and how they relate to the principles of managing chronic pain. The most common misconceptions concern the use of morphine and arise as a consequence of a lack of understanding of this drug. Further issues relating to the multidimensional aspects of pain and the need for psychosocial care and sound re-evaluations of the continuing effectiveness of pain control are identified. Finally, some of the professional issues that affect the transference of assessment and knowledge are examined. Nurses have a pivotal role in pain assessment and it is suggested that education must play a role in the development of genuine interprofessional working which will allow nurses to have more influence in formulating the care strategy and subsequent action.

Humans↗
PubMed2000

Allograft rejection results from a failed attempt by the immune system to protect foreign tissue.

The focus of our research is to understand the immune response to foreign tissue. We believe that a dichotomy exists within the immune response to an allograft such that part of the response is dedicated to the protection of the graft. Nevertheless, in a dominantly graft-aggressive environment, rejection typically ensues. In this article, we describe models that have been set up to test directly the ability of potentially protective aspects of the immune response to prevent allograft rejection. We discuss our data in the context of a growing body of exciting and often controversial literature.

Animals↗
PubMed2000

Enhanced production of microbial metabolites in the presence of dimethyl sulfoxide.

Bacterial strains grown in the presence of low concentrations of dimethyl sulfoxide (DMSO) exhibit significant qualitative and quantitative alterations in the production of secondary metabolites. This effect was confirmed for a variety of biosynthetic families, including chloramphenicol (chorismate), thiostrepton (peptide) and tetracenomycin (polyketide), and for natural and recombinant strains of streptomycetes; a similar effect was seen with antibiotic-producing bacilli such as B. circulans. Increase in antibiotic production was not the result of a change in the growth rate of these organisms, since yields of biomass were similar in media with and without DMSO (up to 3%). We suggest that the addition of compounds such as DMSO provides a means of examining the full biosynthetic potential of microbes and might be used to promote secondary metabolite production. The mode of action of DMSO is not known, but in the cases studied it may act at the level of translation.

Anti-Bacterial Agents↗
PubMed2000

DNase I induced DNA degradation is inhibited by neomycin.

Preparations of antimicrobials from biotechnological sources containing nucleic acids may serve as vector for the dissemination of resistance genes. An essential prerequisite for the acquisition of a new resistance phenotype in a transformational scenario is the availability of physically intact DNA molecules capable of transforming competent microorganisms. DNA is thought to be an easy target for catabolic processes when present in the natural habitat of bacteria (e.g. gastrointestinal tract, soil) due to the overall presence of nucleolytic enzymes. Aminoglycoside antibiotics are known to display a strong affinity to nucleic acids rendering these compounds to be primary candidates for exerting DNA protective functions in the gastrointestinal tract when applied orally during antibiotic chemotherapy. Using a DNase I protection assay it could be demonstrated that neomycin B at a concentration of 2 mM completely inhibited degradation of plasmid DNA in vitro. No inhibition of degradation was observed with streptomycin and kanamycin and the non-aminoglycoside antibiotics oxytetracycline and ampicillin under identical assay conditions. Thus, neomycin preparations may be able to promote structural integrity of contaminating DNA-fragments in DNase-rich environments.

Ampicillin↗
PubMed2000

The oral health of South Asian five-year-old children in deprived areas of Dudley compared with White children of equal deprivation and fluoridation status.

OBJECTIVE: To investigate the oral health of five-year-old children from South Asian ethnic groups and compare this with White children of equal deprivation and fluoridation status. DESIGN: An epidemiological survey of five-year-old children in Dudley was carried out as part of the 1996 BASCD co-ordinated programme but with the collection of additional variables (ethnic classification and postcode of residence). CLINICAL SETTING: The examinations were carried out in schools in Dudley, England. PARTICIPANTS: Five hundred and fifty-four five-year-old children living in neighbourhoods with an ACORN code F (striving) and attending schools in the fluoridated part of Dudley. MAIN OUTCOME MEASURES: Disease levels were measured using the dmft index. Caries was diagnosed at the caries into dentine (d3) threshold using a visual method without radiography or fibre-optic transillumination. RESULTS: The prevalence of dental caries, particularly untreated caries, was higher in South Asian children. There was no difference in the intensity or pattern of disease between the two groups when comparing those children with disease experience. CONCLUSIONS: Dental caries experience in young children continues to be associated with ethnicity once the data are controlled for deprivation and fluoridation status.

Bangladesh↗
PubMed1999

Antibiotic resistance in microbes.

The treatment of infectious disease is compromised by the development of antibiotic-resistant strains of microbial pathogens. A variety of biochemical processes are involved that may keep antibiotics out of the cell, alter the target of the drug, or disable the antibiotic. Studies have shown that resistance determinants arise by either of two genetic mechanisms: mutation and acquisition. Antibiotic resistance genes can be disseminated among bacterial populations by several processes, but principally by conjugation. Thus the overall problem of antibiotic resistance is one of genetic ecology and a better understanding of the contributing parameters is necessary to devise rational approaches to reduce the development and spread of antibiotic resistance and so avoid a critical situation in therapy--a return to a pre-antibiotic era.

Animals↗
PubMed1999

Trisomy 20p resulting from inverted duplication and neocentromere formation.

Normal human centromeres contain large tandem arrays of alpha-satellite DNA of varying composition and complexity. However, a new class of mitotically stable marker chromosomes which contain neocentromeres formed from genomic regions previously devoid of centromere activity was described recently. These neocentromeres are fully functional yet lack the repeat sequences traditionally associated with normal centromere function. We report here a supernumerary marker chromosome derived from the short arm of chromosome 20 in a patient with manifestations of dup(20p) syndrome. Detailed cytogenetic, FISH, and polymorphic microsatellite analyses indicate the de novo formation of the marker chromosome during meiosis or early postzygotically, involving an initial chromosome breakage at 20p11.2, followed by an inverted duplication of the distal 20p segment due to rejoining of sister chromatids and the activation of a neocentromere within 20p12. This inv dup(20p) marker chromosome lacks detectable centromeric alpha-satellite and pericentric satellite III sequences, or centromere protein CENP-B. Functional activity of the neocentromere is evidenced by its association with 5 different, functionally critical centromere proteins: CENP-A, CENP-C, CENP-E, CENP-F, and INCENP. Formation of a neocentromere on human chromosome 20 has not been reported previously and in this context represents a new mechanism for the origin of dup(20p) syndrome.

Centromere↗
PubMed1999

The influence of epitope availability on atomic-force microscope studies of antigen-antibody interactions.

The ability of the atomic-force microscope (AFM) to detect interaction forces between individual biological molecules has recently been demonstrated. In this study, force measurements have been obtained between AFM probes functionalized with the beta-subunit of human chorionic gonadotrophin (betahCG) and surfaces functionalized with anti-betahCG antibody. A comparison of the obtained results with previous anti-ferritin antibody-binding data identifies differences when the antigen molecule expresses only a single epitope (betahCG), rather than multiple epitopes (ferritin), for the monoclonal antibodies employed. Specifically, the probability of observing probe-sample adhesion is found to be higher when the antigen expresses multiple epitopes. However, the periodic force observed in the adhesive-force distribution, due to the rupture of single antigen-antibody interactions, is found to be larger and more clearly observed for the mono-epitopic system. Hence, these findings indicate the potential of the AFM to distinguish between multivalent and monovalent antibody-antigen interactions, and demonstrate the influence of the number of expressed epitopes upon such binding studies.

Adhesiveness↗
PubMed1999

Cooperation of Myb and Myc proteins in T cell lymphomagenesis.

The v-Myb oncogene causes late onset T cell lymphomas when expressed in the T cell lineage of transgenic mice. In order to define the cellular mutations cooperating with s-Myb to cause lymphomas, we have infected v-Myb transgenic mice with Moloney murine leukemia virus (M-MuLV). Tumor formation is significantly accelerated from a mean age of onset of 60 weeks in uninfected vMyb transgenics to 13 weeks in infected vMyb transgenics. We studied the loci into which the M-MuLV had inserted, and found that in 73% of animals, either the c-myc or the N-myc genes had been disrupted and deregulated. Therefore, v-myb and c-myb can cooperate to induce T cell lymphomas.

Age of Onset↗
PubMed1999

Molecular dissection of mitogillin reveals that the fungal ribotoxins are a family of natural genetically engineered ribonucleases.

Mitogillin and the related fungal ribotoxins are highly specific ribonucleases which inactivate the ribosome enzymatically by cleaving the 23-28 S RNA of the large ribosomal subunit at a single phosphodiester bond. The site of cleavage occurs between G4325 and A4326 (rat ribosome numbering) which are present in one of the most conserved sequences (the alpha-sarcin loop) among the large subunit ribosomal RNAs of all living species. Amino acid sequence comparison of ribotoxins and guanyl/purine ribonucleases have identified domains or residues likely involved in ribonucleolytic activity or cleavage specificity. Fifteen deletion mutants (each 4 to 8 amino acid deletions) in motifs of mitogillin showing little amino acid sequence homology with guanyl/purine ribonucleases were constructed by site-directed mutagenesis. Analyses of the purified mutant proteins identified those regions in fungal ribotoxins contributing to ribosome targeting and modulating the catalytic activity of the toxin; some of the identified motifs are homologous to sequences in ribosomal proteins and elongation factors. This mutational study of mitogillin together with the recently published x-ray structure of restrictocin (a close relative of mitogillin) supports the hypothesis that the specific cleavage properties of ribotoxins are the result of natural genetic engineering in which the ribosomal targeting elements of ribosome-associated proteins were inserted into nonessential regions of T1-like ribonucleases.

Allergens↗