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Biomedical subjects

C Edwards

Publications and source records attributed to C Edwards.

At least 55 records · Page 3Linked to original sources
PubMed2001

Degenerative alterations of dermal collagen fiber bundles in photodamaged human skin and UV-irradiated hairless mouse skin: possible effect on decreasing skin mechanical properties and appearance of wrinkles.

Dermal collagen fiber bundles (DCFB) are the major constructional element in the dermis. Although degenerative alterations of DCFB have been reported in chronologically aged skin, changes in photodamaged skin have not been fully investigated. We report ultrastructural alterations of DCFB, and their relation to skin elasticity using photodamaged human skin and UV-irradiated hairless mouse skin. The degree to which DCFB were intact and closely packed was evaluated and scored blindly. Exposed skin (outer forearm) exhibited marked ultrastructural degeneration. In UV-irradiated hairless mouse skin, the intact ultrastructural appearance of DCFB was gradually lost with increasing UV dosage; however, marked alterations in DCFB ultrastructure were absent in either human inner upper arm (unexposed) skin or nonirradiated age-matched control mouse skin. Skin mechanical properties were measured using a Cutometer SEM 474 suction extensometer, recording Ue* immediate deformation, Uv* viscous deformation, Uf* final deformation, and Ur* immediate contraction, all normalized for skin thickness. Uf*, Ue*, Uv*, and Ur/Uf were significantly decreased in exposed compared with unexposed skin. Significant positive correlations between degenerative alterations of DCFB and the decrease in Uf*, Ue*, and Uv* were seen. Changes of "% area of wrinkles" in UV-irradiated mouse skin was significantly correlated with degenerative changes of DCFB. Based on these results, we confirm observations made by others that chronic photodamage may have more severe effects on degeneration of DCFB than that of chronologic aging alone. Furthermore, degeneration of DCFB as detected ultrastructurally may, by its effect on skin elasticity, result in an increase in the appearance of wrinkles.

Adult↗
PubMed2001

Surface hygiene monitored using a reporter of fis in Escherichia coli.

AIMS: To examine the value of the fis promoter in monitoring regrowth of a surface-attached bacterial population following exposure to chemical stress using several candidate reporters, beta-galactosidase (lacZYA), bacterial luciferase (luxAB) and enhanced green fluorescent protein (EGFP). METHODS AND RESULTS: The pattern of expression for the reporters within Escherichia coli cells attached to surfaces was determined. Both the bacterial luciferase reporter and EGFP were readily detected, but EGFP was found to overcome problems associated with luciferase and beta-galactosidase. The effect of surface pretreatment, using polymer systems, on bacterial attachment and growth confirmed the usefulness of this approach. CONCLUSION: The fis promoter, combined with EGFP, can be used successfully to study adhesion, biocidal damage and recovery. The stability of the EGFP enabled the magnitude of the total recovery response to be monitored as cells remained fluorescent after the decline in fis expression. SIGNIFICANCE AND IMPACT OF THE STUDY: The E. coli Pfis-egfp reporter system provides a new, versatile and sensitive tool to investigate bacterial adhesion both quantitatively and qualitatively.

Bacterial Adhesion↗
PubMed2001

Prevention and treatment of lethal murine endotoxemia by the novel immunomodulatory agent MFP-14.

Multifunctional protein 14 (MFP-14) is a ubiquitous protein that inhibits the production of tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma), which are involved in the pathogenesis of sepsis. Here, lipopolysaccharide (LPS)-induced lethality in mice was markedly reduced by MFP-14. The treatment also lowered LPS-induced levels of TNF-alpha and IFN-gamma in the blood.

Adjuvants, Immunologic↗
PubMed2001

Making faces: creating three-dimensional parameterized models of facial expression.

Previous studies of the perceptual processing and dynamics of emotional expression in faces have been limited by the lack of realistic yet controlled stimuli. The present work offers researchers a method for creating such stimuli for exploring these phenomena. We describe the creation of the stimuli and a series of experiments testing the validity of these stimuli with respect to emotional expressions in humans. Participants evaluated synthesized facial images and standardized photographs of six basic emotional expressions for intensity and accuracy of perceived emotion. Comparisons of these measures were qualitatively similar for synthesized and photographed faces. A manipulation of the magnitude of the synthesized expressions yielded a significant effect on the perceived intensity of expression. In a subsequent multidimensional scaling study, no systematic differences were uncovered in the derived configurations of the synthesized expressions and the photographs. These results are discussed in the context of possible future research applications.

Emotions↗
PubMed2001

Growth/differentiation factor-5 (GDF-5) and skeletal development.

BACKGROUND: Growth/differentiation factor-5 (GDF-5) has been shown to be essential for normal appendicular skeletal and joint development in humans and mice. In brachypod, a Gdf-5 gene mouse mutant, the defect is first apparent during early chondrogenesis, with the cartilage blastema already reduced in size by E12.5. This defect is associated with changes in the expression of cell surface molecules. METHODS: To understand further how GDF-5 controls cartilage formation, we first mapped the expression of the Gdf-5 gene during skeletal development (please note that the abbreviation for the gene is given in italics and the abbreviation for the protein expressed by the gene is given in capital letters). Subsequently, we over-expressed GDF-5 in the developing chick embryo using a replication competent retrovirus, RCAS(BP). We determined its effects on skeletal development by histological examination and its effects on early growth by autoradiography of proliferating cells. In addition, we examined the effect of GDF-5 on chondrogenic differentiation using micromass and single cell suspension cultures of limb mesenchymal cells, RESULTS: These studies show that the Gdf-5 gene is expressed in the early cartilage condensation, the perichondrium, and the joint interzone. Over-expresSion of GDF-5 in chick limb buds, during the condensation stage or later when the skeletal elements have formed, increased the size of the affected elements. In both cases, the increase in size was associated with an increase in cell number and, at later stages, this was correlated with an increase in S-phase cells. In vitro studies showed that GDF-5 could increase cell adhesiveness, and this may be a mechanism through which GDF-5 initiates condensation formation. CONCLUSION: These studies show that GDF-5 acts at two stages of skeletal development and by two distinct mechanisms. First, GDF-5 promotes the initial stages of chondrogenesis by promoting cell adhesion, which is consistent with the expression of Gdf-5 in the cartilage condensation. Second, GDF-5 can increase the size of the skeletal elements by increasing proliferation within the epiphyseal cartilage adjacent to its expression within the joint interzone.

Animals↗
PubMed2000

Molecular characterization of taurine transport in bovine aortic endothelial cells.

Cultured bovine aortic endothelial (BAE) cells expressed a Na(+)/Cl(-)-dependent taurine uptake activity that saturated with an apparent K(0.5) of approximately 4.9 microM for taurine and was inhibited by beta-alanine, guanidinoethane sulfonate, and homotaurine. We isolated a taurine transporter clone from a BAE cell cDNA library that revealed >91% sequence identity at the amino acid level to the previously cloned high-affinity mammalian taurine transporters. The biochemical and pharmacological properties of the bovine taurine transporter cDNA expressed in Xenopus oocyte was similar to those of the high-affinity taurine transporter. Surprisingly, F(-) blocked taurine uptake in BAE cells with an IC(50) of approximately 17.5 mM. The endogenous taurine uptake was also inhibited by the protein kinase C activator phorbol 12-myristate 13-acetate, but not by its inactive analog, 4 alpha-phorbol 12,13-didecanoate. The endogenous uptake was stimulated, however, by hypertonic stress and the increase was due to an increase in the V(max) of taurine uptake. Our results provide the first description of a molecular mechanism that may be responsible for maintaining the intracellular taurine content in the endothelial cells.

Amino Acid Sequence↗
PubMed2000

Combined molecular ecological and confocal laser scanning microscopic analysis of peat bog methanogen populations.

Confocal laser scanning microscopy, using fluorescently labelled oligonucleotide probes targeting the 16S rRNA of different physiological groups of methanogens, was used to identify which methanogenic genera were present and to describe their in situ spatial locations in samples taken at different depths from blanket peat bog cores. Total bacterial DNA was also extracted and purified from the samples and used as template for amplification of 16S rRNA and regions of methyl CoM reductase-encoding genes using the polymerase chain reaction, as well as for oligonucleotide hybridisation experiments. These techniques, used in concert, demonstrated that methanogens of several physiological groups were present in highest numbers in the mid regions of 25 cm deep peat cores. Some discrepancies were apparent in the findings of the microscopic and molecular methods, though these may be partially accounted for by the different sensitivities of the techniques employed. The combined approaches used in this study gave an insight into the diversity and distribution of methanogens in peat environments not possible using molecular ecological methods alone.

DNA, Archaeal↗
PubMed2000

The induction of EAE is only partially dependent on TNF receptor signaling but requires the IL-1 type I receptor.

Experimental autoimmune encephalomyelitis develops in mice immunized with CNS antigens. To elucidate the role that specific proinflammatory cytokines play in the induction of this process we examined the development of EAE in mice with targeted disruptions of the TNF p55 or p75 or the IL-1 p80 receptors. EAE developed in mice with either one or both TNF receptors deleted although the onset of disease in mice with the p55 receptor deleted was delayed. However, mice with a deletion of the IL-1 p80 receptor failed to develop any inflammatory lesions in the CNS or evidence of clinical EAE. Thus we conclude that TNF or its receptors contribute to, but are not necessary for, the induction of EAE while the IL-1 p80 receptor is absolutely required. The p55 TNF receptor plays a role in determining the onset of disease and its severity.

Animals↗
PubMed2000

Sodium fusidate ameliorates the course of diabetes induced in mice by multiple low doses of streptozotocin.

We studied the effects of the immunosuppressant sodium fusidate (fusidin) on murine immunoinflammatory diabetes mellitus (DM) induced by multiple low doses of streptozotocin (SZ). Fusidin was given by gavage to three strains of mice (C57KsJ, C57BL/6, CD1) at doses 10 or 100 mg/kg body weight every other day. The drug was administered as an early or late prophylactic regime starting either 1 day prior to the first or after the fifth and last injection of SZ. In both situations the largest dose of fusidin successfully reduced the clinical, chemical and histological signs of DM, the treated mice having significantly lower glycaemic values and milder (often absent) insulitis compared with sham-treated animals or controls given SZ alone. The antidiabetogenic effect was long-lasting as it was maintained up to 1 month after cessation of therapy. In contrast, fusidin prophylaxis failed to prevent development of hyperglycaemia acutely induced by one single and high (160 mg/kg) dose of SZ, which is a model of DM primarily due to the toxic action of SZ on the beta cells and does not involve immunopathogenetic mechanisms. On day 14 after SZ, fusidin markedly altered the circulating cytokine profile induced in vivo by ConA, reducing the levels of IFN-gamma, IL-2 and TNF-alpha and augmenting the level of IL-6. However, only the inhibitory effect of the drug on the synthesis/release of IFN-gamma seemed to be causally related to its capacity to counteract the SZ-induced DM. In fact, the disease was prevented by a neutralizing monoclonal antibody (mAb) against IFN-gamma, but not by anti-IL-2 receptor mAb, a soluble form of TNF-receptor type 1 or recombinant human IL-6. The prevention of disease by fusidin was also partly reversed by exogenously administered recombinant mouse IFN-gamma. The data provide further in-vivo evidence for the anti-diabetogenic and immunomodulatory properties of fusidin and indicate that this drug could have a role in prevention and treatment of human type 1 DM.

Animals↗
PubMed2000

Three-dimensional cellular development is essential for ex vivo formation of human bone.

Tissue engineering of human bone is a complex process, as the functional development of bone cells requires that regulatory signals be temporally and spatially ordered. The role of three-dimensional cellular interactions is well understood in embryonic osteogenesis, but in vitro correlates are lacking. Here we report that in vitro serum-free transforming growth factor (TGF)-beta1 stimulation of osteogenic cells immediately after passage results in the formation of three-dimensional cellular condensations (bone cell spheroids) within 24 to 48 hours. In turn, bone cell spheroid formation results in the up-regulation of several bone-related proteins (e.g., alkaline phosphatase, type I collagen, osteonectin) during days 3-7, and the concomitant formation of micro-crystalline bone. This system of ex vivo bone formation should provide important information on the physiological, biological and molecular basis of osteogenesis.

Alkaline Phosphatase↗
PubMed2000

Simple horizontal averaging programme enables shade correction for image analysis in psoriasis.

Computer-assisted area measurement of skin lesions would be useful for the assessment of disease severity. Difficulties can be encountered, however, when lesions cannot simply be separated using the normal threshold tool of an image analyser. Owing to body curvature, peripheral sites are usually shadowed. To obtain a well-fitting curved line to account for body curvature-induced glare and shadow, we devised a simple C-programme for averaging neighbouring pixels on the same horizontal line. An image was captured from a colour slide to the image analysis system. C++ was used for programming. Execution of the averaging programme with the original image resulted in a background brightness image file. When this was subtracted from the original image, the lesions were easily detected using the standard threshold tool and the percentage of area involved was calculated. This method is sufficiently accurate for the assessment of disease severity.

Humans↗
PubMed2000

HBME-1, MOC-31, WT1 and calretinin: an assessment of recently described markers for mesothelioma and adenocarcinoma.

AIMS: To evaluate HBME-1, WT1, calretinin and MOC-31 in the differential diagnosis of pleural mesothelioma and adenocarcinoma of the lung. METHODS AND RESULTS: Paraffin-embedded formalin-fixed blocks from six reactive pleuras, 42 mesotheliomas and 40 adenocarcinomas were used. Sections were stained for Leu-M1, HBME-1, calretinin, WT1 and MOC-31. Leu-M1 was positive or equivocal in 34% of mesotheliomas and in 78% of adenocarcinomas; reactive pleuras were all negative. HBME-1 was positive or equivocal in 76% of mesotheliomas and in 73% of adenocarcinomas; five reactive pleuras were positive. Calretinin was positive or equivocal in 92% of mesotheliomas and in 73% of adenocarcinomas; two reactive pleura were equivocal and four were positive. WT1 was positive or equivocal in 72% of mesotheliomas (excluding autopsy cases) and in 20% of adenocarcinomas; all reactive pleuras were positive. MOC-31 was positive or equivocal in 5% of mesotheliomas and in 90% of adenocarcinomas; all reactive pleuras were negative. The reaction with Leu-M1 was graded as equivocal in 25% of the adenocarcinomas. All 24 of the autopsy cases of mesothelioma were negative for WT1 and in many operative specimens only the periphery was stained. CONCLUSIONS: Neither calretinin nor HBME-1 are sufficiently discriminatory to be of use, even as members of a panel of antibodies. WT1 shows some promise, but it cannot be used on autopsy material. The utility of MOC-31 is confirmed, and outperforms Leu-M1.

Adenocarcinoma↗
PubMed2000

Analysis of denitrification by Pseudomonas stutzeri under nutrient-limited conditions using membrane inlet mass spectrometry.

Membrane inlet mass spectrometry (MIMS) was used to investigate denitrification by Pseudomonas stutzeri in a static lake water column. Continuous real-time measurement of gases enabled the dynamics of the process to be investigated. Concentrations of 17 mmol l-1 nitrate and 10 mmol l-1 nitrite were identified as optimal for denitrification under nutrient-limited conditions (i.e., produced the highest concentrations of N2). Available carbon was the major rate-limiting factor in lake water when nitrate or nitrite was present. No stratification of the process with depth was observed, and aerobic denitrification was apparent under all the conditions employed. The rate of denitrification was dependent on cell concentration, and possible limitations of the usefulness of MIMS under environmentally modelled conditions were identified for environments containing low numbers of bacteria.

Fresh Water↗
PubMed2000

Changes in viability and macromolecular content of long-term batch cultures of Salmonella typhimurium measured by flow cytometry.

Exposure of many Gram-negative bacteria to prolonged starvation induces alternative programmes of gene expression, along with a transition into a dormant condition sometimes referred to as a viable non-culturable (VBNC) state. Knowledge of how pathogenic species respond to nutrient limitation is therefore important for their detection and dissemination. This study used flow cytometry, coupled with fluorescent dyes for viability and macromolecular content, to study the responses of the pathogen Salmonella typhimurium to prolonged batch culture. Statistical analysis of the flow cytometric data, together with total and culturable cell counts, failed to demonstrate a VBNC state in this pathogen, contrary to reports from other workers. Analysis of rRNA and protein content identified a small proportion of cells in 110 day-old cultures that represented an active sub-population. This observation may provide an explanation for the long-term survival properties of this organism during prolonged exposure to nutrient limitation, as well as the high degree of heterogeneity observed in labelled cells.

Bacterial Proteins↗
PubMed2000

Denitrification by indigenous microbial populations of river water measured using membrane inlet mass spectrometry.

The major process that reduces nitrate levels in soils and water is denitrification, which converts nitrate and nitrite into gaseous forms of nitrogen, which are then released into the atmosphere. This study used membrane inlet mass spectrometry (MIMS) to investigate denitrification in river water bacterial isolates supplied with nitrate and succinate as an energy source as well as in the total population by provision of different carbon compounds to untreated river water samples. Substantial variation was observed in the gases detected with nitrogen, nitrous oxide and nitric oxide all being produced by one or more of the isolates. The indigenous river population as a whole was found to respond very differently to the addition of different carbon sources. Peak nitrogen levels differed by nearly 1 mmol 1(-1) and nitrous oxide by approximately 0.5 mmol 1(-1) depending on which carbon source was supplied. Nitric oxide was only detected when glycerol was supplied as the carbon source. These results demonstrate the complex interactions involved in nitrogen cycling and suggest that with careful management it may be possible to stimulate particular consortia of micro-organisms to reduce more nitrate to harmless nitrogen rather than nitrous oxide, a known greenhouse gas.

Aeromonas↗