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Biomedical subjects

M Finney

Publications and source records attributed to M Finney.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of the efficacies of disinfectants to control microbial contamination in dental unit water systems in general dental practices across the European Union.

Water delivered by dental unit water systems (DUWS) in general dental practices can harbor high numbers of bacteria, including opportunistic pathogens. Biofilms on tubing within DUWS provide a reservoir for microorganisms and should be controlled. This study compared disinfection products for their ability to meet the American Dental Association's guideline of <200 CFU x ml(-1) for DUWS water. Alpron, BioBlue, Dentosept, Oxygenal, Sanosil, Sterilex Ultra, and Ster4Spray were tested in DUWS (n = 134) in Denmark, Germany, Greece, Ireland, The Netherlands, Spain, and the United Kingdom. Weekly water samples were tested for total viable counts (TVCs) on yeast extract agar, and, where possible, the effects of products on established biofilm (TVCs) were measured. A 4- to 5-week baseline measurement period was followed by 6 to 8 weeks of disinfection (intermittent or continuous product application). DUWS water TVCs before disinfection ranged from 0 to 5.41 log CFU x ml(-1). Disinfectants achieved reductions in the median water TVC ranging from 0.69 (Ster4Spray) to 3.11 (Dentosept) log CFU x ml(-1), although occasional high values (up to 4.88 log CFU x ml(-1)) occurred with all products. Before treatment, 64% of all baseline samples exceeded American Dental Association guidelines, compared to only 17% following commencement of treatment; where tested, biofilm TVCs were reduced to below detectable levels. The antimicrobial efficacies of products varied (e.g., 91% of water samples from DUWS treated with Dentosept or Oxygenal met American Dental Association guidelines, compared to 60% of those treated with Ster4Spray). Overall, the continuously applied products performed better than those applied intermittently. The most effective products were Dentosept and Oxygenal, although Dentosept gave the most consistent and sustained antimicrobial effect over time.

Biofilms↗
PubMed2004

Microbiological evaluation of dental unit water systems in general dental practice in Europe.

A range of opportunistic pathogens have been associated with dental unit water systems (DUWS), particularly in the biofilms that can line the tubing. This study therefore aimed to assess the microbiology of DUWS and biofilms in general dental practices across seven European countries, including the United Kingdom (UK), Ireland (IRL), Greece (GR), Spain (ES), Germany (D), Denmark (DK) and the Netherlands (NL). Water supplied by 51% of 237 dental unit water lines exceeded current American Dental Association recommendations of < or = 200 colony-forming units (CFU) ml(-1). Microbiological loading of the source waters was between 0 (Denmark, the Netherlands and Spain) and 4.67 (IRL) log CFU ml(-1); water line samples from the DUWS ranged from 1.52 (ES) to 2.79 (GR) log CFU ml(-1); and biofilm counts ranged from 1.49 (GR) to 3.22 (DK) log CFU.cm(-2). Opportunistic pathogens such as legionellae (DK and ES), including Legionella pneumophila SG1 (DK and GR), and Mycobacterium spp. (DK, NL, GR, D and ES) were recovered occasionally. Presumptive oral streptococci (ES and NL), oral anaerobes (GR), Candida spp. (UK, NL and ES) and blood (GR and IRL) were detected at relatively low frequencies, but their presence indicated a failure of the 3-in-1 antiretraction valve, leading to back siphonage of oral fluids into the water and biofilm phase. These findings confirm that a substantial proportion of DUWS have high levels of microbial contamination, irrespective of country, type of equipment and source water. The study emphasizes the need for effective mechanisms to reduce the microbial burden within DUWS, and highlights the risk of occupational exposure and cross-infection in general dental practice.

Bacteria↗
PubMed2003

Evaluation of Chromocult coliform agar for the detection and enumeration of Enterobacteriaceae from faecal samples from healthy subjects.

The purpose of this study was to examine the use of Chromocult agar medium for isolation and enumeration of Enterobacteriaceae from human faecal samples, to compare it to MacConkey agar and to evaluate its usefulness as a possible alternative selective medium in human faecal studies. The medium was shown to be effective in identifying Escherichia coli and coliforms in faeces without the need for extensive accompanying biochemical tests for confirmation of identity. A positive correlation (r=0.86) was found between the recovery of Enterobacteriaceae on the two media, and no significant difference (P>0.05) between overall mean bacterial counts for the whole study group or at different intervals of faecal collection were observed. Chromocult agar is an effective replacement for MacConkey agar in human faecal studies and has the advantage of differentiating E. coli from other coliforms.

Agar↗
PubMed2001

Using wound fluid analyses to identify trace element requirements for efficient healing.

A series of wound fluid and blood plasma samples from 20 patients with breast cancer were analysed by Potentiometric Stripping Analysis and computer-aided chemical speciation to quantify the concentrations of the trace elements of copper and zinc in the samples and to investigate the individual species of copper and zinc present. Comparisons were made between total concentrations of copper and zinc in wound fluid, pre-operative blood plasma levels and reference values. A wound fluid model constructed using JESS identified the main copper and zinc species present. It was also used to investigate the effects of a change in pH and changes in the total concentrations of certain components on their predominance. The clinical significance of the research is discussed, together with suggestions for a continuation in the research.

Breast Neoplasms↗
PubMed1997

Self-seal reagent: evaporation control for molecular histology procedures without chambers, clips or fingernail polish.

Sensitive nucleic acid based detection methods such as in situ PCR, in situ RT-PCR and PRINS have great potential in the areas of developmental biology, pathogenesis and diagnostics. However, control of evaporation from in situ reactions is critical to ensure reliable data. Self-Seal Reagent, a component added directly to the in situ reaction mixture, effectively controls evaporation during in situ procedures by creating an evaporation-limiting barrier around the periphery of a standard cover glass as the reaction proceeds. At the end of the procedure, the cover glass is easily removed by soaking in an aqueous solution. A model is presented for how Self-Seal Reagent controls evaporation while maintaining reagent concentrations. Self-Seal Reagent is shown to be effective in the detection of HIV sequences in cells by in situ PCR.

Cosmetics↗
PubMed1995

Regulation of neurite outgrowth from differentiated human neuroepithelial cells: a comparison of the activities of prothrombin and thrombin.

The mechanism by which thrombin and prothrombin control neurite retraction was studied in Ad12E1HER10 human neuroepithelial cells. Morphological changes in differentiated cells were apparent within minutes of the addition of very low concentrations of thrombin (3 pM). Higher concentrations (2 nM) of prothrombin were required to elicit a similar response. Doses of thrombin and prothrombin sufficient to cause neurite retraction stimulated protein tyrosine kinase activity. Protein tyrosine kinase activation also correlated positively with thrombin- and prothrombin-induced phosphoinositide 3-kinase activation and InsP6 dephosphorylation. However, thrombin-stimulated Ins(1,4,5)P3 generation and intracellular Ca2+ mobilization only occurred at concentrations in excess of those needed to induce retraction. No fluctuations in Ins(1,4,5)P3 were detected after stimulation with prothrombin, and no rapid synchronized release of Ca2+ was observed, even at very high concentrations. Prothrombin did, however, cause small oscillations in the intracellular Ca2+ concentration, similar to those produced by low concentrations of thrombin, after approximately 30 min. We conclude that prothrombin- and thrombin-induced neurite retractions are not dependent on PtdIns(4,5)P2 and Ca2+ mobilization, but are more probably mediated through an effector mechanism involving protein tyrosine kinase activation. No intracellular Ca2+ mobilization, protein tyrosine kinase activity or neurite retraction was observed after treatment of cells with proteolytically inactive mutant thrombin (S205-->A). Prothrombin-mediated intracellular Ca2+ mobilization and neurite retraction were inhibited by hirudin, which was shown to interact with thrombin but not prothrombin. It is concluded that cleavage of prothrombin to thrombin is a necessary prerequisite for biological activity on differentiated Ad12E1HER10 cells and that differences in agonist concentration are capable of coupling the thrombin receptor to different pathways within the cell.

Blotting, Western↗
PubMed1995

Engagement of CD20 suppresses apoptosis in germinal center B cells.

In a screen of 67 monoclonal antibodies (mAb) included in the Blind Panel of B cell antibodies for the 5th International Workshop on Human Leukocyte Differentiation Antigens, only the CD20 mAb--included as a positive control for immunophenotyping studies--was found to suppress the spontaneous apoptosis which occurs in human germinal center (GC) B cells when placed in tissue culture at 37 degrees C. Further detailed study using the 1F5 mAb confirmed this observation, showing that rescue from apoptosis via CD20, while not as efficient as that obtained on ligating CD40, was of similar magnitude to that achieved on engagement of surface immunoglobulin (sIg) by immobilized antibody. Also similar to anti-Ig, the CD20 mAb rescued from apoptosis without priming for the proliferation of GC B cells: this was quite different to its action on resting, non-GC B cells, where it provides a potent priming signal for cell cycle progression in response to IL-4 or anti-CD40. Unlike the survival signal engendered via sIg, CD20 engagement neither mobilized Ca2+ from intracellular stores or opening of a Ca2+ channel with 1F5, nor did it affect the ability of anti-Ig to open a Ca2+ gate in GC B cells. An unexpected feature of CD20-mediated rescue of GC B cells from apoptosis was a failure to turn on Bcl-2 expression.

Antibodies, Monoclonal↗
PubMed1994

Targeted mutations in the Caenorhabditis elegans POU homeo box gene ceh-18 cause defects in oocyte cell cycle arrest, gonad migration, and epidermal differentiation.

We used targeted gene inactivation to analyze the function of a Caenorhabditis elegans POU gene, ceh-18, and to dissect its functional domains in vivo. In ceh-18 mutants, oocytes exhibit an incompletely penetrant failure to arrest in diakinesis of meiotic prophase I and instead undergo multiple rounds of DNA replication without cytokinesis. ceh-18 is expressed in the gonadal sheath cells that signal the oocyte, but not in the oocyte. This suggests that ceh-18 affects, directly or indirectly, a sheath cell signal that causes oocytes to maintain diakinesis arrest. ceh-18 also participates in directing gonad migration and in specifying the differentiated phenotypes of epidermal cells during postembryonic development. Analysis of targeted deletions that disrupt half of the POU domain selectively by deleting either the POUhd or the POUsp alone, indicates that each CEH-18 POU subdomain is sufficient for partial activity in vivo.

Amino Acid Sequence↗
PubMed1993

Stimulation of tyrosine phosphorylation without inositol lipid hydrolysis in human B lymphocytes on engaging CD72.

Occupancy of CD72 on resting tonsillar B cells by monoclonal antibodies (mAb) promotes entry into the G1 phase of the cell cycle with an accompanying increase in MHC Class II expression and provides a co-stimulus to immobilized anti-mu for driving DNA synthesis. We now report that engagement of CD72 by mAb stimulates tyrosine phosphorylation in B cells with a peak of activity seen at 5-10 min. Two major substrates of 29 and 57 kDa showed a basal level of phosphorylation which increased with time, while a 40 kDa protein and several other minor components were phosphorylated de novo on the addition of mAb to CD72. Inositol lipid hydrolysis was found to be unperturbed, although a shallow rise in the basal level of intracellular free Ca2+ was provoked on engaging CD72. Receptor cross-linking was not a requirement for signaling human B cells through CD72: simple occupancy by univalent antibody was sufficient both to trigger the rise in basal [Ca2+]i and to promote DNA synthesis.

Antigens, CD↗
PubMed1993

Inhibition by glucocorticoid and staurosporine of IL-4-dependent CD23 production in B lymphocytes is reversed on engaging CD40.

IL-4 synergizes with signals delivered through CD40 both for the induction of CD23/Fc epsilon RII expression and for IgE synthesis. Moreover, engagement of CD40 on the B cell surface by MoAb overcomes the ability of interferons, transforming growth factor-beta, or anti-CD19 to inhibit IL-4-dependent change. We now report that occupancy of CD40 relieves potent suppression of IL-4-induced CD23 production by glucocorticoid or the relatively broad-acting kinase inhibitor staurosporine. Interruption of the IL-4 signal was observed with concentrations of staurosporine considered to be selective for protein kinase C (PKC) inhibition (IC50 = 10 nM) but not with genistein or tyrphostins, effective inhibitors of tyrosine kinase activity. On ligation of CD40, staurosporine no longer inhibited the IL-4 signal: at concentrations of between 1 and 20 nM, staurosporine actually increased by as much as 100% the rate of CD23 production stimulated on simultaneous activation through CD40 and IL-4R. Such augmentation was not observed when the more specific PKC inhibitor RO-31-8220 was used; indeed, CD40 engagement was unable to overcome the ability of this inhibitor to block IL-4-promoted CD23 induction (IC50 = 10 microM). Occupancy of CD40 did, however, thwart completely the usual ability of prednisolone to inhibit the IL-4 signal leading to CD23 induction. Activation through CD40 left inhibition of phorbol ester-induced CD23 expression by staurosporine, RO-31-8220, or glucocorticoid unchecked. These findings further highlight the intimate level of cross-talk existing between CD40 and IL-4R on resting B lymphocytes to promote CD23 expression, a phenotypic change which preludes IgE synthesis.

Alkaloids↗
PubMed1992

Second-messenger pathways involved in the regulation of survival in germinal-centre B cells and in Burkitt lymphoma lines.

Spontaneous apoptosis in germinal-centre (GC) B cells can be prevented by treatment with anti-immunoglobulin (Ig). By contrast, susceptible group-I Burkitt lymphoma (BL) cells can be driven to apoptosis by anti-Ig. The second-messenger pathways involved in the regulation of apoptosis in GC B lymphocytes and in BL cell lines were studied using pharmacological agonists or inhibitors of intracellular calcium ([Ca2+]i) and protein kinase C (PKC). Anti-Ig was found to mobilize Ca2+ in group-I cells. Pre-incubation with the Ca2+ chelator EGTA partially reduced apoptosis induced by anti-Ig or by Ca2+ ionophore in group-I BL cells. Activation of PKC with phorbol ester reduced such Ca(2+)-driven programmed cell death (PCD) to control levels of apoptosis. Apoptosis in group-I BL cell lines could also be triggered by the kinase inhibitors staurosporine and Ro-31-8220 at concentrations selective for PKC activity. Expression of the bcl-2 protein in BL group-I cells following gene transfer affords protection from apoptosis induced by ionomycin or anti-Ig. In the present study, bcl-2 was additionally found to protect from apoptosis driven by staurosporine. The high levels of spontaneous apoptosis exhibited by normal GC B cells were reduced, but not abrogated, by co-culture with phorbol ester. These results indicate that, in group-I BL cells, imbalance in the phosphoinositide pathway of signalling, in favour of [Ca2+]i and away from PKC, results in apoptosis: constitutive phosphorylation of key proteins by PKC may therefore suppress apoptosis in BL as well as in GC B cells.

Apoptosis↗
PubMed1992

Inositol lipids and phosphates in the proliferation and differentiation of lymphocytes and myeloid cells.

It is established that receptor-stimulated hydrolysis of phosphatidylinositol 4,5-bisphosphate is an essential signalling reaction in the responses of many haemopoietic cells to stimuli: examples include platelet activation, antigen-driven initiation of cell proliferation in mature B and T lymphocytes and histamine release by mast cells, and chemotaxis and oxygen radical generation by neutrophils. However, the roles of inositol lipids and phosphates in the development of haemopoietic and immune cells are less well understood. This paper discusses three such situations: the sequential employment of phosphatidylinositol 4,5-bisphosphate hydrolysis and cyclic AMP accumulation as two signals essential to the action of the B lymphocyte-stimulatory cytokine interleukin 4; the involvement of antigen receptor-triggered inositol lipid hydrolysis in apoptotic elimination of immature anti-self T lymphocytes in the fetal mouse thymus; and the possible role of changes in the levels of abundant inositol polyphosphates in the differentiation of HL-60 promyelocytic cells and of normal human myeloid blast cells.

Bone Marrow Cells↗
PubMed1992

Regulation of the mec-3 gene by the C.elegans homeoproteins UNC-86 and MEC-3.

The mec-3 gene encodes a homeodomain protein with LIM repeats that is required for the specification of touch cell fate in Caenorhabditis elegans. Previous experiments suggested that mec-3 expression requires the product of the unc-86 gene, a POU-type homeoprotein, and mec-3 itself. We have analyzed the control of mec-3 expression by identifying potential cis regulatory elements in the mec-3 gene (by conservation in a related nematode and by DNase I footprinting using unc-86 and mec-3 proteins) and testing their importance by transforming C.elegans with mec-3lacZ fusions in which these sites have been mutagenized in vitro. Both unc-86 and mec-3 proteins bind specifically to the promoter of the mec-3 gene, suggesting that both proteins may be directly involved in the regulation of the mec-3 gene. In addition, the footprint pattern with mec-3 protein is altered in the presence of unc-86 protein. In vivo transformation experiments reveal that some of the binding regions of the two proteins are needed for general positive control and maintenance of mec-3 expression while others have no detectable, unique function. Interestingly, the unc-86 gene appears to be required not only to initiate mec-3 expression but also to maintain it.

Amino Acid Sequence↗
PubMed1991

Tc4, a Caenorhabditis elegans transposable element with an unusual fold-back structure.

We have identified and characterized a family of transposable elements in the nematode Caenorhabditis elegans. The Tc4 transposable element family is present at about 20 copies per haploid genome in the C. elegans Bristol and Bergerac strains. Although Tc4 transposition events have not been observed in these wild-type strains, we have identified Tc4 transposition events in the mut-2 mutant strain TR679, in which the elements Tc1 and Tc3 also transpose at a higher frequency than in the wild type. We determined the sequence of one Tc4 element. This 1.6-kilobase element contains almost perfect inverted terminal repeats of 774 base pairs (bp) with a 57-bp unique internal sequence. Tc4 is a fold-back element, but its long inverted terminal repeats, unlike those of the fold-back elements of other organisms, do not consist of multiple short repeats. In the two cases studied, Tc4 insertion resulted in duplication of a TNA trinucleotide target site. The family of Tc4 elements differs from other C. elegans transposable element families in structure, degree of structural heterogeneity, and target-site specificity.

Animals↗
PubMed1990

The unc-86 gene product couples cell lineage and cell identity in C. elegans.

The C. elegans gene unc-86 is required in several distinct neuroblast lineages for daughter cells to become different from their mothers, and is also required for the specification of particular neural identities. Consistent with the fact that unc-86 encodes a POU domain protein, we find that the unc-86 protein is localized to the nucleus. In the affected lineages, unc-86 protein appears within a few minutes after cell division in the nuclei of those daughter cells that are transformed by unc-86 mutations. Thus, expression of unc-86 protein is dependent on cell lineage. unc-86 protein is not asymmetrically segregated at further divisions. unc-86 protein also appears shortly after cell division in the nuclei of particular identified differentiating neurons; at least some of these neurons are nonfunctional in unc-86 mutants.

Animals↗