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Biomedical subjects

M Wainwright

Publications and source records attributed to M Wainwright.

At least 37 records · Page 2Linked to original sources
PubMed1999

Cytotoxicity and adjuvant activity of cationic photosensitizers in a multidrug resistant cell line.

The toxicities and phototoxicities of methylene blue (MB), toluidine blue O (TBO) and Victoria blue BO (VBBO) in a murine mammary tumour cell line (EMT6-S) and a multidrug resistant (MDR) sub-line (EMT6-R) were measured and their efficacy against the resistant sub-line was compared to that of doxorubicin and cis-platinum. The MDR cell line was considerably more susceptible to VBBO than to the conventional agent doxorubicin. VBBO was also phototoxic whereas illumination did not alter the activity of doxorubicin or of cisplatin. Both TBO and MB showed limited light activation (2-fold) in both the sensitive and resistant cell lines. Pre-treatment with VBBO prior to exposure to doxorubicin caused a two-fold increase in doxorubicin toxicity in both cell lines. MB and TBO, however, increased doxorubicin toxicity in EMT6-R cells x2 and x3 respectively, but had less effect on the sensitive cell line (increase x1.4 and x2 respectively). Thus MB and TBO may act on the MDR cell line via a different mechanism to that of VBBO.

Animals↗
PubMed1998

Apoptosis induction by different pathways with methylene blue derivative and light from mitochondrial sites in V79 cells.

The importance of mitochondria for the induction of apoptosis by photodynamic therapy (PDT) was studied with a new photosensitizing dye, methylene blue derivative (MBD), and light. By using fluorescence microscopy and by measuring the MBD-PDT-induced inhibition of specifically subcellularly localized marker enzymes, we show that MBD is localized in mitochondria and not in lysosomes, endoplasmic reticulum or Golgi apparatus of V79 Chinese hamster fibroblasts. Cellular uptake kinetics and fluorescence properties of the dye in cells were characterized. Cell death was studied by a cell survival assay and by flow cytometry of cells stained using the terminal deoxynucleotidyl transferase (TdT) assay. MBD with light induced cell death by apoptosis via 2 different pathways, one rapid and one delayed, depending on the amount of dye in the cells. Cells treated with an MBD concentration higher than 0.05 microg/ml died by apoptosis within 3 hr after light exposure. At a concentration of 0.05 microg/ml MBD, cell death was induced slowly, and apoptotic cells appeared increasingly from the second day after PDT. Combination studies with 2-deoxyglucose (2-DOG) and carbonylcyanide-m-chlorophenylhydrazone (CCCP), inhibitors of glycolysis and oxidative phosphorylation, respectively, indicated that MBD and light inhibited mitochondrial oxidative phosphorylation. Abolishment of both energy sources led to cell death by necrosis within 6 hr. Inhibition of glycolysis alone induced apoptosis between 3 and 6 hr, while inhibition of mitochondrial oxidative phosphorylation alone led to delayed apoptosis within days.

Animals↗
PubMed1998

Photobactericidal activity of phenothiazinium dyes against methicillin-resistant strains of Staphylococcus aureus.

The photodynamic antibacterial properties of a closely related series of phenothiazinium dyes were tested against several pathogenic strains of Staphylococcus aureus, four of which were methicillin-resistant. Illumination of the photosensitisers at a fluence rate of 1.75 mW cm-2 generally resulted in the enhancement of antibacterial activity in liquid culture and in greater efficacy than the methicillin analogue flucloxacillin. For methylene blue, dimethyl methylene blue and new methylene blue illumination led to increases in bactericidal activity < or = 16-fold, typically 4-fold. In addition dimethyl methylene blue and new methylene blue were active against epidemic strains of methicillin-resistant Staphylococcus aureus at concentrations lower than that of vancomycin (> or = 0.5 microM).

Anti-Bacterial Agents↗
PubMed1998

A comparison of the bactericidal and photobactericidal activities of aminoacridines and bis(aminoacridines).

An attempt was made to increase the activity of some antibacterial acridines in two ways: (a) via the use of bis-aminacrines (analogues of 1,6-bis-[9-acridinamino]hexane), in order to increase the potential for DNA intercalation and (b) via photoactivation, as several acridines are known to produce the cytotoxin singlet oxygen on irradiation. The bactericidal activity of the simple aminoacridines was much higher than that of the corresponding bis-acridine compounds. In addition, on low-power illumination of the compounds in liquid culture, many of the monomeric compounds exhibited marked increases in activity against both Gram-negative and Gram-positive bacteria, whereas the bis-acridines showed little or no increase.

Aminoacridines↗
PubMed1998

Photodynamic antimicrobial chemotherapy (PACT).

Whereas the photodynamic therapy (PDT) of cancer has recently shown rapid clinical acceptance, photodynamic antimicrobial chemotherapy (PACT)--which predates the related cancer regimen--is not widely appreciated. Like PDT, PACT utilizes photosensitizers and visible or ultraviolet light in order to give a phototoxic response, normally via oxidative damage. Currently, the major use of PACT is in the disinfection of blood products, particularly for viral inactivation, although more clinically-based protocols are being developed, e.g. in the treatment of oral infection. The technique has been shown to be effective in vitro against bacteria (including drug-resistant strains), yeasts, viruses and parasites. A wide range of photosensitizers, both natural and synthetic, is available with differing physicochemical make-up and light-absorption properties. PACT is proposed as a potential, low-cost approach to the treatment of locally occurring infection.

Animals↗
PubMed1997

Increased cytotoxicity and phototoxicity in the methylene blue series via chromophore methylation.

The cytotoxic and photodynamic activities of the commercially-available biological stains methylene blue (MB), 1,9-dimethyl MB (Taylor's Blue) and a newly synthesised compound, 1-methyl MB, were measured against the murine mammary tumour cell line, EMT-6. Both 1-methyl MB and 1,9-dimethyl MB exhibited increased dark toxicity with concomitant higher phototoxicity compared to MB at a light dose of 7.2 J cm-2. While increasing the light dose as a function of the fluence rate increased the photocytotoxicity of MB, this had little effect on the methylated derivatives. In vitro chemical testing proved that successive methylation rendered the phenothiazinium chromophore both more resistant to reduction to its inactive leuco form, and also led to increased levels of singlet-oxygen production, thus providing a possible explanation for the increased toxicities of the methylated derivatives. Comparisons are made with the benzo[a]phenothiazinium photosensitizer, EtNBS.

Animals↗
PubMed1997

In-vitro photobactericidal activity of aminoacridines.

The toxicities of several aminoacridines were measured against pathogenic strains of both Gram-positive (Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus) and Gram-negative (Escherichia coli, Pseudomonas aeruginosa) organisms. In several cases, illumination at a light dose of 6.3 J/cm2 resulted in considerable decreases in the minimum lethal drug concentrations required, giving up to 50-fold increases in bactericidal activity. Derivatives of 9-aminoacridine (aminacrine) exhibited phototoxicity against one or more of the test organisms, but the established photosensitizing acridines proflavine and acridine orange were photobactericidal against all strains.

Aminoacridines↗
PubMed1997

A study of photobactericidal activity in the phenothiazinium series.

The photodynamic antibacterial properties of a closely related series of commercially available phenothiazinium dyes were tested against a range of pathogenic strains of Gram-positive (Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus) and Gram-negative organisms (Escherichia coli, Pseudomonas aeruginosa). The photosensitisers were illuminated using a non-laser light source at a fluence of 1.75 mW cm-2 and this resulted in the enhancement of antibacterial activity in liquid culture. In several cases, illumination resulted in considerable decreases in the minimum lethal concentrations required, giving up to 100-fold increases in bactericidal activity.

Acridine Orange↗
PubMed1995

Nitrification in vitro by a range of filamentous fungi and yeasts.

A wide range of fungi including yeasts, growing on Czapek Dox medium, nitrified added ammonium and the ammonium released by urea hydrolysis. Phanerochaete chrysosporium and Hymenoscyphus ericiae were the only fungi tested which failed to nitrify. A soil yeast (isolate 1) was the most active nitrifier of ammonium in vitro, forming 0.80 microgram nitrate mg-1 biomass over the 7 d incubation period.

Biomass↗
PubMed1994

Primary structure of the human platelet serotonin 5-HT2A receptor: identify with frontal cortex serotonin 5-HT2A receptor.

Previous radioligand binding studies have demonstrated human platelet serotonin2A (5-HT2A) receptor binding sites. Pharmacological similarities between platelet and frontal cortex 5-HT2A receptor binding parameters have been demonstrated. However, it is not clear whether the platelet 5-HT2A receptor primary structure is identical to that of the brain receptor. Three overlapping cDNAs were obtained to span completely the coding region of the 5-HT2A receptor. These clones were sequenced with external and internal primers. The nucleotide sequence of human platelet 5-HT2A cDNA was identical to that reported for the human frontal cortex 5-HT2A receptor, except for nucleotide 102 (T-->C), which has been reported to represent a normal DNA polymorphism that does not alter the amino acid sequence. This finding may have implications in the study of neuropsychiatric disorders for which altered platelet 5-HT2A receptor binding has been demonstrated.

Adult↗
PubMed1993

William Arthur Johnson--a postgraduate's contribution to the Krebs cycle.

Anyone wishing to find out more about William Arthur Johnson will find little of relevance in the history of the Krebs cycle. Although Krebs makes fleeting reference to Johnson in his autobiography, no mention is made of Johnson's contribution in the Nobel Prize oration. Who was William Johnson and what role did he play in this crucially important work?

Biochemistry↗