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Biomedical subjects

G Georgiou

Publications and source records attributed to G Georgiou.

At least 19 recordsLinked to original sources
PubMed2007

Polylactic acid-phosphate glass composite foams as scaffolds for bone tissue engineering.

Phosphate glass (PG) of the composition 0.46(CaO)-0.04(Na(2)O)-0.5(P(2)O(5)) was used as filler in poly-L-lactic acid (PLA) foams developed as degradable scaffolds for bone tissue engineering. The effect of PG on PLA was assessed both in bulk and porous composite foams. Composites with various PG content (0, 5, 10, and 20 wt %) were melt-extruded, and either compression-molded or foamed through supercritical CO(2). Dynamic mechanical analysis on the bulk composites showed that incorporating 20 wt % PG resulted in a significant increase in storage modulus. Aging studies in deionized water in terms of weight loss, pH change, and ion release inferred that the degradation was due to PG dissolution, and dependent on the amount of glass in the composites. Foaming was only possible for composites containing 5 and 10 wt % PG, as an increase in PG increased the foam densities; however, the level of porosity was maintained above 75%. PLA-T(g) in the foams was higher than those obtained for the bulk. Compressive moduli showed no significant reinforcement with glass incorporation in either expansion direction, indicating no anisotropy. Biocompatibility showed that proliferation of human fetal bone cells was more rapid for PLA compared to PLA-PG foams. However, the proliferation rate of PLA-PG foams were similar to those obtained for foams of PLA with either hydroxyapatite or beta-tricalcium phosphate.

Biocompatible Materials↗
PubMed2004

Diastolic gradient in hypertrophic cardiomyopathy of the apical type.

Diastolic intracavitary gradient in the left ventricle is a common finding in patients with apical hypertrophy. We report the case of a patient with hypertrophic cardiomyopathy and midventricular obstruction. The paradoxical jet flow in this patient, during diastole, was directed towards the base away from the apex.

Cardiomyopathy, Hypertrophic↗
PubMed2004

The effect of hot pressing on the physical properties of glass reinforced hydroxyapatite.

Hydroxyapatite (HA), being of physiological importance, can be developed synthetically for implant application. A number of avenues have been explored in order to improve the physical and biological properties of a variety of hydroxyapatite composites. However, the fact remains, hydroxyapatite lacks the mechanical properties needed to sustain high loads. This study investigates the advantages of hot pressing on the physical properties of HA and glass reinforced HA (GR-HA). The results show a significant enhancement in the mechanical properties of GR-HA composites compared to HA e.g. flexural bending strength values were given at 91.75 and 88.87 M Nm(-2) for GR-HA (CP15F) and GR-HA (CP20F) respectively, compared to 78.9 M Nm(-2) for HA. The results for other properties such as elastic modulus, fracture toughness, Vicker's hardness, density and porosity also demonstrate the benefit of adding phosphate based glasses as a sintering aid. This is supported by XRD analysis, highlighting the presence of a secondary phase (beta-TCP) in GR-HA systems and the positive effect it has on the physical properties. It must be brought to attention that densification of hot pressed HA and GR-HA composites is reached at a lower temperature compared to a previous study on the same materials that have undergone pressureless sintering.

Biocompatible Materials↗
PubMed2001

Production of correctly folded Fab antibody fragment in the cytoplasm of Escherichia coli trxB gor mutants via the coexpression of molecular chaperones.

Disulfide bonds are normally formed after a polypeptide has been exported from the reducing environment of the cytoplasm into a more oxidizing compartment, such as the bacterial periplasm. Recently, we showed that in Escherichia coli trxB gor mutants, in which the reduction of thioredoxin and glutathione is impaired, the redox potential of the cytoplasm becomes comparable to that of the mammalian endoplasmic reticulum, thus allowing the formation of disulfide bonds in certain complex proteins (P. H. Bessette et al., 1999, Proc. Natl. Acad. Sci. USA 96, 13703-13708]. Here, we investigate the expression of a Fab antibody fragment in the bacterial cytoplasm. The effect of coexpressing cytoplasmic chaperones (GroEL/ES, trigger factor, DnaK/J), as well as signal sequenceless versions of periplasmic chaperones (DsbC and Skp), was examined. Skp coexpression was shown to have the most significant effect (five- to sixfold increase) on the yield of correctly folded Fab. A maximum yield of 0.8 mg Fab/L/OD(600) Fab was obtained, indicating that cytoplasmic expression may be a viable alternative for the preparative production of antibody fragments.

Amino Acid Sequence↗
PubMed2001

Drug and alcohol problems amongst individuals with severe mental health problems in an inner city area of the UK.

BACKGROUND: The extent and impact of drug and alcohol use among those with severe mental health problems has been well documented in the US. However, little is known of the nature of this problem in the UK, particularly in community treatment settings. This paper outlines findings from a large-scale survey conducted across community-based Mental Health and Substance Misuse services, which aimed to ascertain the prevalence of drug and alcohol problems among those with severe mental health problems. METHOD: An assessment instrument was completed by keyworkers for each of their clients, which included mental health diagnosis and an adapted version of the Clinician Rating Scales for Alcohol and Drug Use. RESULTS: From a sample of 3079 clients across services, 1369 clients were identified with a severe mental illness diagnosis. According to their key-workers, 24% of these clients (324/1369) had used alcohol and/or drugs problematically during the past year. These individuals were most likely to have a diagnosis within the schizophrenia cluster, were mainly white males in their mid-30s, and tended to be located within Mental Health services in Assertive Outreach teams and to be higher utilisers of crises/emergency services. CONCLUSIONS: It can be concluded that similar to other studies in inner city areas of the UK, problem substance use is common amongst those with severe mental health problems within Northern Birmingham.

Adolescent↗
PubMed2001

Investigation of thermal parameters and crytallisation in a ternary CaO-Na2O-P2O5-based glass system.

This paper presents the results of a study of the thermal properties of a range of phosphate-based glasses in the system CaO-Na2O-P2O5. The glasses had a fixed P2O5 content of 45 mol% and the CaO:Na2O ratio was varied. The glasses were produced and ground and their thermal properties measured using a Setaram differential thermal analyser (DTA). Initial data showed that for the high Na2O containing glass, NaPO3 forms and a second unidentified phase that is probably calcium rich. In the middle compositional region, multiple phases precipitated out and were identified as NaPO3 and Na4Ca(PO3)6. For the high CaO content glasses, Na4Ca(PO3)6 was the only phase formed. Further studies were carried out to examine whether the phases were bulk or surface nucleating, by grinding the samples to different particle sizes. From this data, it is evident that the NaPO3 forms via a bulk nucleation mechanism and that Na4Ca(PO3)6 forms via surface nucleation. The factors controlling this precipitation process are discussed and ionic radius as a controlling factor is hypothesised.

Calcium Compounds↗
PubMed2001

Glass reinforced hydroxyapatite for hard tissue surgery--part 1: Mechanical properties.

Commercial hydroxyapatite (HA) was reinforced by adding 2.5 and 5 wt% of a Na2O-CaO-P2O5 glass and then sintered. The resulting composites have chemical compositions that are similar to the inorganic constituent of the mineral part of bone, and are closely related to the trace elements that are present, in this case Na. X-ray diffraction showed no decomposition of HA to secondary phases; however, the glass reinforced-HA composites contained a HA phase and variable amounts of tricalcium phosphate phase, depending on the sintering temperature and the amount of glass added. The HA-composite material exhibited higher flexural strength overall compared to sintered HA. The presence of secondary phases beta- and alpha-tricalcium phosphate in the microstructure of the composites has a major influence on the mechanical properties. Additionally, the presence of porosity also has a bearing on the mechanical properties of the material.

Biocompatible Materials↗
PubMed2001

Glass reinforced hydroxyapatite for hard tissue surgery--part II: in vitro evaluation of bone cell growth and function.

Hydroxyapatite (HA)-based materials are considered to be potentially useful as bone implant materials, particularly those reinforced with glass to improve mechanical strength. However, the precise effects of glass-reinforced HA on the growth and functions of bone cells are still unclear. The present study has therefore examined the response of human osteoblast-like cells to HA and HA reinforced with two different proportions of glass, namely 2.5% and 5%. All materials enabled the cells to attach and proliferate during 7 days in culture and, although the growth was less than on control plastic surfaces, there was no deleterious effect of the 5% glass composite compared with HA alone. Flow cytometry analysis showed that there was no effect on cell size and granularity, but there were marked and highly selective changes in the expression of certain connective tissue proteins. Thus, while bone sialoprotein and osteonectin were down-regulated on HA alone, the expression of these antigens was relatively enhanced on the composite materials, and collagen type I was also up-regulated on the glass-reinforced HA. Thus, modulation of the glass composition of HA materials could be used to produce not only improved mechanical strength, but also enhanced biocompatibility.

Biocompatible Materials↗
PubMed2001

High-throughput antibody isolation.

To define the proteome of an organism, there is a need for robust and reproducible methods for the quantitative detection of all the polypeptides in a cell. High-density arrays of receptors specific for each of the polypeptides in a complex sample hold great promise for the analysis of complex protein mixtures. Because of their high affinity, specificity and their ability to bind to virtually any protein, antibodies appear particularly promising as the receptor element in protein-detection arrays. For proteomic-scale analyses, the ability to isolate and produce antibodies en masse to large numbers of target molecules is critical. A variety of systems for the high-throughput isolation of antibodies from combinatorial libraries are being developed and are outlined in this review. However, there are several other important considerations to be borne in mind before such systems can realistically be applied on a large scale.

Antibodies↗
PubMed2001

Isolation of high-affinity ligand-binding proteins by periplasmic expression with cytometric screening (PECS).

Periplasmic expression with cytometric screening (PECS) is a powerful and rapid "display-less" technology for isolating ligand-binding proteins from diverse libraries. Escherichia coli expressing a library of proteins secreted into the periplasmic space are incubated with a fluorescent conjugate of the target ligand. Under the proper conditions, ligands as large as about 10 kDa can equilibrate within the periplasmic space without compromising the cell's integrity or viability. The bacterial cell envelope effectively serves as a dialysis bag to selectively retain receptor-fluorescent probe complexes but not free ligand. Cells displaying increased fluorescence are then isolated by flow cytometry. We demonstrate that scFv antibodies with both very high and low affinity to digoxigenin can be isolated from libraries screened by PECS using a benchtop flow cytometer. We also show that preexisting libraries constructed for display on filamentous bacteriophage can be screened by PECS without the need for subcloning. In fact, PECS was found to select for proteins that could be missed by conventional phage panning and screening methods.

Biochemistry↗
PubMed2001

Tissue characterization using the continuous wavelet transform. Part I: Decomposition method.

In this paper, a novel decomposition of the RF ultrasound signal into its coherent and diffused components is proposed. This decomposition is based on thresholding the energy of the continuous wavelet transform of the RF signal using appropriate wavelets. The two components are modeled separately, and the model parameters are estimated. Previous work [1] required assumptions about the periodicity of the coherent scatterers in the tissue. These assumptions are not necessary in this work. The decomposition algorithm is tested on simulated RF images. The accuracy of the estimated parameters is presented as well as the performance of the algorithm in low coherent-to-diffuse components' energy ratios (SNR).

Algorithms↗
PubMed2001

Tissue characterization using the continuous wavelet transform. Part II: Application on breast RF data.

In the first part of this work [16], a wavelet-based decomposition algorithm of the RF echo into its coherent and diffuse components was introduced. In this paper, the proposed algorithm is used to estimate structural parameters of the breast tissue such as the number and energy of coherent scatterers, the energy of the diffuse scatterers, and the correlation between them. Based on these individual parameters, breast tissue characterization is performed. The database used consists of 155 breast scans from 42 patients. The results are presented in terms of empirical receiver operating characteristics (ROC) curves. The results of this study are discussed in relation to the tissue microstructure. Individual estimated parameters are able to differentiate reliably between normal and fibroadenoma or fibrocystic or cancerous tissue (area under the ROC Az > 0.93). Also, the differentiation between malignant and benign (normal, fibrocystic, and fibroadenoma) tissue was possible (Az > 0.89).

Algorithms↗
PubMed2001

Kinetics of methyl t-butyl ether cometabolism at low concentrations by pure cultures of butane-degrading bacteria.

Butane-oxidizing Arthrobacter (ATCC 27778) bacteria were shown to degrade low concentrations of methyl t-butyl ether (MTBE; range, 100 to 800 microg/liter) with an apparent half-saturation concentration (K(s)) of 2.14 mg/liter and a maximum substrate utilization rate (k(c)) of 0.43 mg/mg of total suspended solids per day. Arthrobacter bacteria demonstrated MTBE degradation activity when grown on butane but not when grown on glucose, butanol, or tryptose phosphate broth. The presence of butane, tert-butyl alcohol, or acetylene had a negative impact on the MTBE degradation rate. Neither Methylosinus trichosporium OB3b nor Streptomyces griseus was able to cometabolize MTBE.

Arthrobacter↗
PubMed2001

Effect of sequences of the active-site dipeptides of DsbA and DsbC on in vivo folding of multidisulfide proteins in Escherichia coli.

We have examined the role of the active-site CXXC central dipeptides of DsbA and DsbC in disulfide bond formation and isomerization in the Escherichia coli periplasm. DsbA active-site mutants with a wide range of redox potentials were expressed either from the trc promoter on a multicopy plasmid or from the endogenous dsbA promoter by integration of the respective alleles into the bacterial chromosome. The dsbA alleles gave significant differences in the yield of active murine urokinase, a protein containing 12 disulfides, including some that significantly enhanced urokinase expression over that allowed by wild-type DsbA. No direct correlation between the in vitro redox potential of dsbA variants and the urokinase yield was observed. These results suggest that the active-site CXXC motif of DsbA can play an important role in determining the folding of multidisulfide proteins, in a way that is independent from DsbA's redox potential. However, under aerobic conditions, there was no significant difference among the DsbA mutants with respect to phenotypes depending on the oxidation of proteins with few disulfide bonds. The effect of active-site mutations in the CXXC motif of DsbC on disulfide isomerization in vivo was also examined. A library of DsbC expression plasmids with the active-site dipeptide randomized was screened for mutants that have increased disulfide isomerization activity. A number of DsbC mutants that showed enhanced expression of a variant of human tissue plasminogen activator as well as mouse urokinase were obtained. These DsbC mutants overwhelmingly contained an aromatic residue at the C-terminal position of the dipeptide, whereas the N-terminal residue was more diverse. Collectively, these data indicate that the active sites of the soluble thiol- disulfide oxidoreductases can be modulated to enhance disulfide isomerization and protein folding in the bacterial periplasmic space.

Catalytic Domain↗
PubMed2000

Flow cytometric screening of cell-based libraries.

Flow cytometry is a powerful, high-throughput library screening tool in numerous applications including the isolation of bioactive molecules from synthetic combinatorial libraries, the identification of virulence genes in microorganisms, and the study and engineering of protein functions. Using flow cytometry, large libraries of protein mutants expressed in microorganisms can be screened quantitatively for desired functions, including ligand binding, catalysis, expression level, and stability. Rare target cells, occurring at frequencies below 10(-6), can be detected and isolated from heterogeneous library populations using one or more cycles of cell sorting and amplification by growth. Flow cytometry is particularly powerful because it provides the unique opportunity to observe and quantitatively optimize the screening process. However, the ability to isolate cells occurring at such low frequencies within a population requires consideration and optimization of screening parameters. With this aim, an analysis of the various parameters involved in screening cell-based libraries for rare target cells possessing a desired trait is presented.

Cell Separation↗
PubMed2000

A hollow-fiber membrane bioreactor for the removal of trichloroethylene from the vapor phase.

A hollow-fiber membrane bioreactor was used to separate trichloroethylene (TCE) from a gaseous waste stream with subsequent cometabolic biodegradation by a pure culture of Methylosinus trichosporium OB3b PP358. The two-stage bioreactor system was successfully operated for 20 days. PP358 was grown in a continuous-flow chemostat and circulated through the fiber lumen of a hollow-fiber membrane module (HFMM), while TCE contaminated air (141 to 191 microg/L) was pumped through the HFMM shell. Between 54% -84% TCE transfer and 92%-96% TCE cometabolism were obtained in the HFMM reactor loop. Short shell-residence times, 1.6 to 5.0 minutes, demonstrated quick throughput of TCE contaminated air. Best-fit computer modeling of the biological experiments estimated mass transfer coefficients between 2.0 x 10(-3) cm/min and 5.6 x 10(-3) cm/min. The average pseudo-first-order biodegradation rate constant for the biological experiments was 0.46 L/mg TSS/d. These results demonstrate that the hollow-fiber membrane bioreactor represents an attractive technology for the bioremediation of gaseous waste streams.

Biodegradation, Environmental↗