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Biomedical subjects

A P Taylor

Publications and source records attributed to A P Taylor.

14 recordsLinked to original sources
PubMed2004

Magnetosomal matrix: ultrafine structure may template biomineralization of magnetosomes.

The organic matrix surrounding bullet-shaped, cubo-octahedral, D-shaped, irregular arrowhead-shaped, and truncated hexa-octahedral magnetosomes was analysed in a variety of uncultured magnetotactic bacteria. The matrix was examined using low- (80 kV) and intermediate- (400 kV) voltage TEM. It encapsulated magnetosomes in dehydrated cells, ultraviolet-B-irradiated dehydrated cells and stained resin-embedded fixed cells, so the apparent structure of the matrix does not appear to be an artefact of specimen preparation. High-resolution images revealed lattice fringes in the matrix surrounding magnetite and greigite magnetosomes that were aligned with lattice fringes in the encapsulated magnetosomes. In all except one case, the lattice fringes had widths equal to or twice the width of the corresponding lattice fringes in the magnetosomes. The lattice fringes in the matrix were aligned with the [311], [220], [331], [111] and [391] related lattice planes of magnetite and the [222] lattice plane of greigite. An unidentified material, possibly an iron hydroxide, was detected in two immature magnetosomes containing magnetite. The unidentified phase had a structure similar to that of the matrix as it contained [311], [220] and [111] lattice fringes, which indicates that the matrix acts as a template for the spatially controlled biomineralization of the unidentified phase, which itself transforms into magnetite. The unidentified phase was thus called pre-magnetite. The presence of the magnetosomal matrix explains all of the five properties of the biosignature of the magnetosomal chain proposed previously by Friedmann et al. and supports their claim that some of the magnetite particles in the carbonate globules in the Martian meteorite ALH84001 are biogenic. Two new morphologies of magnetite magnetosomes are also reported here (i.e. tooth-shaped and hexa-octahedral magnetosomes). Tooth-shaped magnetite magnetosomes elongated in the [110] direction are reported, and are distinct from arrowhead-shaped and bullet-shaped magnetosomes. Elongation of magnetite magnetosomes in the [110] direction has not been reported previously. A Martian hexa-octahedral magnetite particle was previously characterized by Thomas-Keptra et al. and compared with truncated hexa-octahedral magnetite magnetosomes. Hexa-octahedral magnetite magnetosomes with the same morphology and similar sizes and axial ratios as those reported by Thomas-Keptra et al. are characterized here. These observations support their claim that ALH84001 contains evidence for a past Martian biota.

Bacteria↗
PubMed2001

Structural and morphological anomalies in magnetosomes: possible biogenic origin for magnetite in ALH84001.

We report biogenic magnetite whiskers, with axial ratios of 6 : 1, elongated in the [1 1 1], [1 1 2] and [1 0 0] directions, resembling the magnetite whiskers detected in the Martian meteorite ALH84001 by Bradley et al., and interpreted by those authors as evidence of vapour-phase (abiogenic) growth. Magnetosomal whiskers with extended defects consistent with screw dislocations and magnetosomes resembling flattened twinned platelets, as well as other twinning phenomena and other structural defects, are also reported here. Magnetosomes with teardrop-shaped, cuboidal, irregular and jagged structures similar to those detected in ALH84001 by McKay et al., coprecipitation of magnetite possibly with amorphous calcium carbonate, coprecipitation of magnetite possibly with amorphous silica, the incorporation of titanium in volutin inclusions and disoriented arrays of magnetosomes are also described. These observations demonstrate that the structures of the magnetite particles in ALH84001, their spatial arrangement and coprecipitation with carbonates and proximity to silicates are consistent with being biogenic. Electron-beam-induced flash-melting of magnetosomes produced numerous screw dislocations in the [1 1 1], [1 0 0], and [1 1 0] lattice planes and induced fusion of platelets. From this, the lack of screw dislocations reported in the magnetite particles in ALH84001 (McKay et al., and Bradley et al.) indicates that they have a low-temperature origin.

Bacteria↗
PubMed2000

Degranulating eosinophils in human endometriosis.

Degranulating eosinophils have been described in most endometrial cancers. We hypothesized that endometriosis (ectopic, nonneoplastic endometrial tissue) would be an appropriate model system for determining whether eosinophil degranulation is part of a specific immune response to endometrial cancer or if it is related to the more general phenomenon of tissue remodeling (wound healing) that is common to both disorders. To test this hypothesis, we performed immunohistochemistry and Western blotting to evaluate the presence of eosinophil peroxidase (a marker of eosinophil degranulation) in normal endometrium (n = 20) and endometriosis samples (n = 24) and to define the coexpression of three eosinophil chemoattractants: interleukin-5 (IL-5), eotaxin, and regulated on activator-normal T cell expressed and secreted (RANTES). There was focally intense deposition of eosinophil peroxidase in the fibrotic connective tissue and blood vessels of 21 of 24 human endometriosis specimens; two samples showed weak staining, and only one tissue was negative for eosinophil degranulation. None of the 10 normal proliferative endometrial specimens had evidence of eosinophil degranulation, and four of 10 secretory tissues stained only weakly for eosinophil peroxidase. The presence of degranulating eosinophils was also associated with the presence of eotaxin and IL-5 in some samples and with RANTES in others. We conclude that the abundant presence of degranulating eosinophils in the fibrous regions of endometriosis supports the interpretation that eosinophils are involved in general tissue remodeling and wound healing rather than a tissue-directed immune response.

Blotting, Western↗
PubMed2000

Adhesion of microbes using 3-aminopropyl triethoxy silane and specimen stabilisation techniques for analytical transmission electron microscopy.

A variety of adhesive support-films were tested for their ability to adhere various biological specimens for transmission electron microscopy. Support films primed with 3-amino-propyl triethoxy silane (APTES), poly-L-lysine, carbon and ultraviolet-B (UV-B)-irradiated carbon were tested for their ability to adhere a variety of biological specimens including axenic cultures of Bacillus subtilis and Escherichia coli and wild-type magnetotactic bacteria. The effects of UV-B irradiation on the support film in the presence of air and electrostatic charge on primer deposition were tested and the stability of adhered specimens on various surfaces was also compared. APTES-primed UV-B-irradiated Pioloform was consistently the best adhesive, especially for large cells, and when adhered specimens were UV-B irradiated they became remarkably stable under an electron beam. This assisted the acquisition of in situ phase-contrast lattice images from a variety of biominerals in magnetotactic bacteria, in particular metastable greigite magnetosomes. Washing tests indicated that specimens adhering to APTES-primed UV-B-irradiated Pioloform were covalently coupled. The electron beam stability was hypothesised to be the result of mechanical strengthening of the specimen and support film and the reduced electrical resistance in the specimen and support film due to their polymerization and covalent coupling.

Bacillus subtilis↗
PubMed1998

Therapeutic effect of interferon-gamma gene transfer in experimental visceral leishmaniasis.

Interferon (IFN)-gamma, in both natural endogenous form and administered as exogenous protein, induces control over visceral Leishmania donovani in experimentally infected BALB/c mice. To further characterize the therapeutic role of IFN-gamma in host defense against intracellular L. donovani, the efficacy of IFN-gamma delivered by gene transfer was tested. One week after infection, normal and IFN-gamma gene-disrupted (GKO) BALB/c mice were injected with an IFN-gamma gene-bearing mammalian expression plasmid (pIFN). Plasmid-specific IFN-gamma transcripts were detected in liver and spleen. Whereas liver parasite burdens more than doubled in untreated and mock-treated normal and GKO mice during the subsequent 2 weeks, animals injected with pIFN had controlled visceral infection and reduced parasite burden. These results indicate that, in infected tissues, IFN-gamma delivered by gene transfer enhances control over disseminated intracellular infection.

Animals↗
PubMed1997

Intracellular antimicrobial activity in the absence of interferon-gamma: effect of interleukin-12 in experimental visceral leishmaniasis in interferon-gamma gene-disrupted mice.

Despite permitting uncontrolled intracellular visceral infection for 8 wk, interferon-gamma (IFN-gamma) gene knockout (GKO) mice infected with Leishmania donovani proceeded to reduce liver parasite burdens by 50% by week 12. This late-developing IFN-gamma-independent antileishmanial mechanism appeared to be dependent largely on endogenous tumor necrosis factor-alpha (TNF-alpha): L. donovani infection induced TNF-alpha mRNA expression in parasitized GKO livers and neutralization of TNF-alpha reversed control at week 12.7 d of treatment of infected GKO mice with interleukin-12 (IL-12) readily induced leishmanicidal activity and also partially restored the near-absent tissue granulomatous response, observations that for the first time expand the antimicrobial repertoire of IL-12 to include IFN-gamma-independent effects. The action of IL-12 against L. donovani was TNF-alpha dependent and required the activity of inducible nitric oxide synthase. These results point to the presence of an IFN-gamma-independent antimicrobial mechanism, mediated by TNF-alpha, which remains quiescent until activated late in the course of experimental visceral leishmaniasis. However, as judged by the effect of exogenous IL-12 this quiescent mechanism can readily be induced to rapidly yield enhanced intracellular antimicrobial activity.

Animals↗
PubMed1997

Cyclospora.

Explore the source record for details and available documents.

Animals↗
PubMed1995

Effect of granulocyte-macrophage colony-stimulating factor in experimental visceral leishmaniasis.

GM-CSF induces three effects potentially beneficial in visceral leishmaniasis: blood monocyte mobilization, macrophage activation, and amelioration of granulocytopenia. To determine the experimental role and effect of GM-CSF in this intracellular infection, livers from Leishmania donovani-infected BALB/c mice were tested for GM-CSF mRNA expression and mice were treated with anti-GM-CSF antiserum or GM-CSF. L. donovani infection upregulated hepatic GM-CSF mRNA expression by 10-fold, and anti-GM-CSF treatment exacerbated visceral infection and tripled liver parasite burdens 4 wk after challenge. In euthymic mice with established infection, treatment with 1-5 micrograms/d murine GM-CSF induced three dose-related effects: peripheral blood leukocytosis, preferential accumulation of myelomonocytic cells at visceral foci of infection, and leishmanicidal activity comparable to that achieved by IFN-gamma. These effects were either largely or entirely T cell dependent. Treatment with human GM-CSF also induced anti-leishmanial activity but with little effect on peripheral leukocyte number or tissue myelomonocytic cell influx; human G-CSF stimulated marked peripheral granulocytosis and neutrophil tissue accumulation but induced little antileishmanial effect. These results identify a role for endogenous GM-CSF in the initial host defense response to L. donovani, reemphasize the influxing monocyte as an effector cell, and indicate that GM-CSF can be used as an antileishmanial treatment.

Animals↗
PubMed1993

Camelford water poisoning accident: serial neuropsychological assessments and further observations on bone aluminium.

The serial cognitive assessment of ten individuals made between 8 and 26 months after the water at Camelford in Cornwall was accidentally contaminated with aluminium sulphate, showed consistent evidence of impairment of information processing and memory. There was no obvious relationship between these impairments and measurements of anxiety and depression. Serial bone biopsies in two individuals showed that the aluminium which was present 6 and 7 months after the accident had disappeared by 19 months. In the eight individuals biopsied 12-17 months after the accident the bone showed no stainable aluminium. Thus, aluminium deposited in the bone of normal individuals can disappear within 18 months. After an accident such as that at Camelford important evidence of toxicity is likely to be missed if an investigation is delayed. The abnormal neuropsychological findings indicate cognitive impairment, but whether this was caused by an acute episode of brain damage, or other causes such as the psychological effects of stress resulting from the accident, is uncertain.

Accidents↗
PubMed1992

A co-stimulatory role for CD28 in the activation of CD4+ T lymphocytes by staphylococcal enterotoxin B.

In this study we investigated the differential effect of the co-stimulatory receptor ligand molecules CD2/LFA-3, LFA-1/ICAM-1, and CD28/B7 on microbial superantigen mediated activation of CD4+ T cells. Highly purified CD4+ T cells, depleted of antigen presenting cells (APCs), do not proliferate in response to the superantigen, staphylococcal enterotoxin B (SEB). However, CD4+ T cells do respond to SEB in the presence of the LFA-3, ICAM-1, and B7 positive erythroleukemic cell line K562, murine L cells, human B7 transfected L cells or CD28 mAb. The K562 plus SEB induced response can be inhibited by combinations of mAbs to CD2 and LFA-1, and to LFA-3, ICAM-1, and B7. Addition of CD28 mAb to the CD2 and LFA-1 inhibited cultures could restore the response. Furthermore, soluble CD28 mAb alone is able to synergize with SEB to induce a proliferative CD4+ T cell response. CD4+ T cells depleted of APCs could also be activated by a pool of four mAbs directed to the V beta 5, V beta 6, V beta 8, and V beta 12 region of the TCR when a co-stimulatory signal was provided by the CD28 mAb, while the V beta mAbs alone or in combination are unable to activate CD4+ T cells in the absence of APCs. In contrast, addition of soluble mAbs to CD2 and LFA-1 molecules failed to co-stimulate SEB activated CD4+ T lymphocytes. The kinetics of the different modes of activation are distinct. SEB induced proliferation is most efficient in the presence of autologous APCs with maximal proliferation at a log4 lower SEB concentration than when CD28 mAbs were used. SEB plus K562 activation peaks on day 7, while SEB plus CD28 mAb induced proliferative responses do not peak until day 9. Thus, superantigen mediated activation of CD4+ T cells requires co-stimulatory signals, among which CD28 has distinct and unique effects.

Adult↗
PubMed1990

Aluminium deposition in bone after contamination of drinking water supply.

Two healthy individuals who drank water accidentally contaminated at source with aluminium sulphate solution were investigated 6-7 months later. Bone biopsy specimens showed discrete lines of positive staining for aluminium, the distribution being compatible with acute exposure some months previously. These findings show that under certain conditions normal individuals can absorb aluminium via the gut, and that such aluminium can be deposited in bone.

Adult↗