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Biomedical subjects

M Wainwright

Publications and source records attributed to M Wainwright.

At least 19 recordsLinked to original sources
PubMed2003

Microorganisms cultured from stratospheric air samples obtained at 41 km.

Samples of air removed from the stratosphere, at an altitude of 41 km, were previously found to contain viable, but non-cultureable bacteria (cocci and rods). Here, we describe experiments aimed at growing these, together with any other organisms, present in these samples. Two bacteria (Bacillus simplex and Staphylococcus pasteuri) and a single fungus, Engyodontium album (Limber) de Hoog were isolated from the samples. Although the possibility of contamination can never be ruled out when space-derived samples are studied on earth, we are confident that the organisms originated from the stratosphere. Possible mechanisms by which these organisms could have attained such a height are discussed.

Altitude↗
PubMed2002

Big bacteria pass through very small holes.

Can normal-sized bacteria pass through small holes, and if so how? We have found that common, potentially pathogenic, bacteria (which are nominally larger than 0.2 microm) can cross a 0.2 microm nylon membrane. All of the bacteria crossed from the upper membrane surface to the solid medium below the membrane; this ability was highly repeatable and did not depend on the make of membrane used. Bacteria growing below the membrane exhibited normal size and morphology. We suggest that the ability of common bacteria to pass through small holes has important implications in relation to their role as pathogens.

Bacterial Physiological Phenomena↗
PubMed2002

Methylene Blue--a therapeutic dye for all seasons?

Since it was first synthesised in 1876, Methylene Blue (MB) has found uses in many different areas of clinical medicine, ranging from dementia to cancer chemotherapy. In addition, MB formed the basis of antimicrobial chemotherapy--particularly in the area of antimalarials--and eventually led to the discovery of the neuroleptic drug families. More recently, the photosensitising potential of MB and its congeners has been recognised, and these are being applied in various antimicrobial fields, especially that of blood disinfection. The range of activities of MB is due to the combination of its simple chemical structure and facility for oxidation-reduction reactions in situ.

Bacterial Infections↗
PubMed2001

Photodynamic therapy and the alimentary tract.

Photodynamic therapy offers the possibility of relatively selective tumour necrosis and normal tissue healing. It has many potential applications but as yet no clear role. Articles, editorials and case reports published primarily in English and listed in Medline/ISI up to April 2000 or identified by a manual search have been reviewed in an attempt to provide a comprehensive overview of the use of photodynamic therapy in the alimentary tract. It is concluded that photodynamic therapy can be an effective treatment for superficial pre-malignant mucosal lesions and early cancers, especially in diffuse disease. Suitable patients include those wishing to avoid surgery, high risk subjects or those in whom other forms of treatment have failed. Superiority over other methods of ablation has not so far been demonstrated. Cheaper and more effective photosensitizers and improved techniques of light delivery are likely to increase the application of photodynamic therapy.

Gastrointestinal Neoplasms↗
PubMed2001

Regional dendritic and spine variation in human cerebral cortex: a quantitative golgi study.

The present study explored differences in dendritic/spine extent across several human cortical regions. Specifically, the basilar dendrites/spines of supragranular pyramidal cells were examined in eight Brodmann's areas (BA) arranged according to Benson's (1993, Behav Neurol 6:75-81) functional hierarchy: primary cortex (somatosensory, BA3-1-2; motor, BA4), unimodal cortex (Wernicke's area, BA22; Broca's area, BA44), heteromodal cortex (supple- mentary motor area, BA6beta; angular gyrus, BA39) and supramodal cortex (superior frontopolar zone, BA10; inferior frontopolar zone, BA11). To capture more general aspects of regional variability, primary and unimodal areas were designated as low integrative regions; heteromodal and supramodal areas were designated as high integrative regions. Tissue was obtained from the left hemisphere of 10 neurologically normal individuals (M(age) = 30 +/- 17 years; five males, five females) and stained with a modified rapid Golgi technique. Ten neurons were sampled from each cortical region (n = 800) and evaluated according to total dendritic length, mean segment length, dendritic segment count, dendritic spine number and dendritic spine density. Despite considerable inter-individual variation, there were significant differences across the eight Brodmann's areas and between the high and low integrative regions for all dendritic and spine measures. Dendritic systems in primary and unimodal regions were consistently less complex than in heteromodal and supramodal areas. The range within these rankings was substantial, with total dendritic length in BA10 being 31% greater than that in BA3-1-2, and dendritic spine number being 69% greater. These findings demonstrate that cortical regions involved in the early stages of processing (e.g. primary sensory areas) generally exhibit less complex dendritic/spine systems than those regions involved in the later stages of information processing (e.g. prefrontal cortex). This dendritic progression appears to reflect significant differences in the nature of cortical processing, with spine-dense neurons at hierarchically higher association levels integrating a broader range of synaptic input than those at lower cortical levels.

Adult↗
PubMed2001

Acridine-a neglected antibacterial chromophore.

The use of acridines as antimicrobial agents was first proposed by Ehrlich and Benda in 1912, and the first clinical use of these agents occurred in 1917. Many compounds containing the acridine chromophore were synthesized and tested, and the aminoacridines found wide use, both as antibacterial agents and as antimalarials, during World War II. The emergence of the penicillins eclipsed the acridines in antisepsis due to the greater therapeutic efficacies of the former. However, with the current massive increases in drug-resistant bacterial infection, new acridine derivatives may be of use. In addition, the topical utilization of aminoacridines in conjunction with directed low-power light offers bactericidal action at much lower doses.

Aminoacridines↗
PubMed2001

Phenothiaziniums as putative photobactericidal agents for red blood cell concentrates.

The antibacterial activities of Methylene Blue and several of its congeners were measured against Yersinia enterocolitica, a gram-negative pathogen known to exhibit significant growth at 4 degrees C and thus constituting a threat to red blood cell concentrates which are stored at this temperature. None of the derivatives was highly active in dark conditions, as expected, but on illumination using a lamp emitting light in the waveband 615-645 nm, considerable bactericidal activity was noted using similar photosensitizer concentrations to those used elsewhere to inactivate blood-borne viruses. Two novel compounds in this area, the phenothiazinium New Methylene Blue N and the phenoxazinium Brilliant Cresyl Blue, exhibited bactericidal activity at lower concentrations than both of the established phenothiaziniums, Methylene Blue and Toluidine Blue O and the recently published blood photovirucidal agent 1,9-Dimethyl Methylene Blue. The photoactivity of these compounds was undiminished in the presence of red blood cells.

Blood Banks↗
PubMed2000

Methylene blue derivatives--suitable photoantimicrobials for blood product disinfection?

Photodynamic antimicrobial agents based on the well-established phenothiazinium biological stain methylene blue offer a simple method for the inactivation or destruction of pathogens contained in donated blood and blood products. The technique is currently concentrated on viruses and the disinfective procedure can be carried out in blood bags using basic low-power light sources. Pathogens of the bacterial, yeast and protozoal classes are also susceptible to phenothiaziniums. The photoantimicrobial mode of action is usually via oxidative damage to cellular components, either due to redox reactions between the agent and a biomolecular target or by the action of reactive oxygen species generated in situ by photodynamic action. The targeting of various microbial species is discussed in relation to the physicochemical make-up of the photosensitizers, and future directions are suggested.

Anti-Infective Agents↗
PubMed2000

Highly pleomorphic staphylococci as a cause of cancer.

An extensive historical literature exists suggesting that bacteria and other non-virus microorganisms cause cancer. Much of this literature stresses the likely involvement of highly pleomorphic bacteria in carcinogenesis. Pleomorphic bacteria exhibit a variety of morphological types, some of which are identical to other bacteria. In particular, bacteria that can express more than one morphology, including that normally associated with common species of Staphylococcus, have frequently been isolated from cancers. Not surprisingly, this has led to considerable confusion and ridicule. The literature linking highly pleomorphic bacteria with carcinogenesis is presented here in an attempt to add weight to the view that bacteria, notably those expressing the morphology of common species of staphylococci, cause cancer.

Humans↗
PubMed2000

Three children with a syndrome of obesity and overgrowth, atypical psychosis, and seizures: a problem in neuropsychopharmacology.

Three children presented with a complex syndrome of atypical psychotic and extremely immature behavior, obesity and overgrowth, borderline retardation, and seizures (prominent in two). Weight overgrowth exceeded height overgrowth and was stratospheric (up to 8 SD above mean). Obesity seemed related to lack of satiety. The cases fit no known condition: hypothalamic damage, Sotos' syndrome, and Prader-Willi syndrome were excluded. Empirical treatment with anticonvulsants (carbamazepine and acetazolamide) together with psychotropic agents (selective serotonin reuptake inhibitors and risperidone) controlled seizures, improved behavior, and stopped weight gain in each patient. We have not found this syndrome previously described. The etiology is unknown: perinatal encephalopathy could be a factor in the two patients with prominent seizures; in the third, familial major affective disorder is implicated. Medication responses suggest a low-serotonin state underlying the lack of satiety, an imbalance of serotonin and noradrenergic modulation in the hypothalamus, and epileptogenic disorders (or affective disorder responsive to anticonvulsants in one case) involving these same systems.

Anticonvulsants↗
PubMed2000

Phenothiazine photosensitizers. III. Activity of methylene blue derivatives against pigmented melanoma cell lines.

The cytotoxicity and photocytotoxicity of methylene blue and several of its derivatives against two pigmented melanoma cell lines (SK-23 murine melanoma and SK-Mel 28 human melanoma) were investigated in culture. The derivatives were all more effective photosensitizers than methylene blue in both cell lines over a range of light doses (3.6-17.6 J cm(-2)). The increased activity correlated with increased cellular uptake and inherent photosensitizing efficacy. The photosensitizers also showed varying levels of interaction with the biopolymer melanin and although this appeared to affect uptake and activity, there was no direct correlation with toxicity.

Animals↗
PubMed2000

Reduced cellular glutathione levels do not affect the cytotoxicity or photocytotoxicity of the cationic photosensitiser Victoria Blue BO.

Victoria Blue BO (VBBO) is thought to exert its photocytotoxic effects via free radical generation. Glutathione and related enzymes are associated with the protection of normal tissues against free-radical damage and have also been implicated in multiple drug resistance. It might, therefore, be expected that cells containing higher levels of glutathione would be resistant to the cytotoxic effects of VBBO. The total glutathione content for a murine mammary tumour cell line, EMT6-S, was found to be lower than in a multi-drug resistant cell line, EMT6-R, 21.84+/-2.54 microg (mg protein)(-1) and 18.79+/-2.7 microg (mg protein)(-1), respectively; however, this was not found to be a significant difference (p > 0.05, Student t-test). Buthionine sulfoximine, a potent inhibitor of gamma-glutamyl cysteine synthetase, brought about a reduction in glutathione levels in both EMT6-S and EMT6-R cell lines in a concentration-dependent manner. Buthionine sulfoximine administration was effective in reducing intracellular glutathione levels by up to 90% in both types of cells. Interestingly, glutathione depletion of EMT6-S and EMT6-R cells did not enhance the photocytotoxic effect of VBBO, suggesting that the primary site of action of VBBO may be at an intracellular site not protected by glutathione or that the mechanism of action is not via the in situ generation of free radical species.

Animals↗
PubMed1999

Morphological changes (including filamentation) in Escherichia coli grown under starvation conditions on silicon wafers and other surfaces.

Using a scanning electron microscope, pleomorphism (notably filamentation) was seen when Escherichia coli was grown under starvation conditions for 14 d on microporous silicon wafers, titanium, glass and plastic discs. Under these conditions, the 'standard', rod shaped cell (1-3 microns) failed to separate after division and filaments developed, some as long as 50 microns, with many showing bulbous tips. Filamentation began to occur 5 d after the imposition of starvation conditions. Dumbbell shaped cells were also observed, although apparent 'Y' and 'V'-shaped cells proved to be artefacts, caused by overlapping rods. The implications of the appearance of pleomorphism in E. coli, when grown under starvation conditions, is discussed in relation to its pathogenicity and growth in the environment.

Escherichia coli↗
PubMed1999

Photobactericidal activity of methylene blue derivatives against vancomycin-resistant Enterococcus spp.

The toxicities and phototoxicities of methylene blue and its two methylated derivatives were measured against one standard and three vancomycin-resistant pathogenic strains of Enterococcus spp. Each of the compounds was bactericidal and the derivatives exhibited photobactericidal activity on illumination at a 'light' dose of 6.3 J/cm(2) against one or more of the strains. Increased bactericidal and photobactericidal activity in the methylated derivatives is thought to be due to their higher hydrophobicities allowing greater interaction with the bacterial cell wall. In addition, the derivatives exhibited higher inherent photosensitizing efficacies.

Enterococcus faecalis↗