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Biomedical subjects

T Parsons

Publications and source records attributed to T Parsons.

At least 19 recordsLinked to original sources
PubMed2005

Effect of medium type, age and aeration on the MICs of tigecycline and classical tetracyclines.

BACKGROUND: Tigecycline is a minocycline derivative, belonging to a chemical class prone to oxidation and to medium-related effects on susceptibility. We therefore studied the effect of medium type and age on the tigecycline MICs found in broth and on agar by the Clinical Laboratory Standards Institute and British Society for Applied Chemotherapy methods. METHODS: MICs of tigecycline, minocycline and tetracycline were determined for 96 non-fastidious bacteria and 20 streptococci using Mueller-Hinton broth (MHB), Mueller-Hinton agar (MHA), Iso-Sensitest broth (ISB) and Iso-Sensitest agar (ISA) as: (i) freshly-prepared media; (ii) fresh media but with the antibiotic added 1 day before inoculation and (iii) media stored for 7 days before antibiotic addition and use. RESULTS: MICs of tigecycline in fresh MHB were up to two doubling dilutions higher than on or in MHA, ISA or ISB. Media with tigecycline or classical tetracyclines added a day before use gave raised MICs, though rarely by more than one dilution. MICs of tigecycline (less so classical tetracyclines) were increased in 7-day-old MHB or ISB, even though the antibiotic was freshly added. This latter effect was greatest for the most susceptible strains and was absent or much reduced for organisms with MICs > or = 8 mg/L; it did not occur in the corresponding agar dilution tests. Addition of blood to MHB largely abrogated the effect, as did steaming the broth before adding the antibiotic. CONCLUSIONS: The raised MICs of tigecycline in aged broth probably reflect inactivation by dissolved oxygen. This accords with the lack of any MIC increase in newly-steamed (i.e. degassed) MHB or on aged agar (which is melted at 100 degrees C before use). Blood, which also abrogated the effect, may increase reducing capacity, protecting the tigecycline. At a practical level, broth MIC determinations for tigecycline should always employ fresh media.

Anti-Bacterial Agents↗
PubMed2004

A novel CEA vaccine stimulates T cell proliferation, gammaIFN secretion and CEA specific CTL responses.

Carcinoembryonic antigen (CEA) is a cell surface protein over-expressed by a wide range of tumours. The mouse anti-idiotypic antibody, 708, mimics CEA and can induce both antibody and T cell responses that specifically recognise this antigen. Sequence analysis of 708 revealed homology with a previously identified HLA-A3 T cell epitope in CEA but not to other closely related molecules. 708 was chimerised to a human IgG1 to allow Fc targeting of APCs and was deimmunised to remove unwanted T cell epitopes. The chimerised and deimmunised, but not the mouse 708, could stimulate CTL, proliferation and gammaIFN responses in vitro in normal (HLA-A3, DR1) individuals. Furthermore, the CTLs killed tumour cells expressing CEA suggesting that this deimmunised antibody could be a useful vaccine for solid tumours.

Algorithms↗
PubMed2001

Human anti-idiotypic antibodies can be good immunogens as they target FC receptors on antigen-presenting cells allowing efficient stimulation of both helper and cytotoxic T-cell responses.

Anti-idiotypic antibodies that mimic tumour-associated antigens can stimulate anti-tumour T-cell responses. In this article, we have studied the role of Fc in the presentation of T-cell epitopes by 2 anti-idiotypic antibodies, 105AD7 and 708. The human monoclonal antibody 105AD7, which mimics CD55, stimulated strong in vitro T-cell proliferation, gammaIFN secretion and redirected cytotoxicity in unprimed T cells from healthy donors. However, removal of the Fc region of the anti-idiotype reduced the sensitivity of the assay 1,000-fold, as did inhibiting Fc uptake of the anti-idiotype by an excess of human IgG. The mouse anti-idiotype 708, which mimics CEA, failed to stimulate in vitro T-cell responses on unprimed T cells from healthy donors. However, when a human IgG1 Fc region replaced its mouse Fc region, the anti-idiotype induced T-cell proliferation, gammaIFN secretion and redirected cytotoxicity in lymphocytes from unimmunised donors. Human anti-idiotypes are therefore good immunogens since they target Fc receptors on antigen-presenting cells, allowing efficient stimulation of both helper and cytotoxic T-cell responses. The immunogenicity of other anti-idiotypes may therefore be enhanced by human Fc targeting of antigen-presenting cells.

Animals↗
PubMed2001

Dietary advice for illness-related malnutrition in adults.

BACKGROUND: Illness-related malnutrition has been reported in 10-55% of people in hospital and in ill people in the community in areas of food sufficiency. It has been suggested that dietary counseling to encourage the use of energy- and protein-rich foods should be used in preference to oral nutritional supplements in the management of illness-related malnutrition. OBJECTIVES: To examine the evidence that dietary advice, to improve nutritional intake, in adults with illness-related malnutrition can improve survival, weight and anthropometry and to estimate the size of any additional effect of whole protein nutritional supplements when given in combination with dietary advice. SEARCH STRATEGY: Six electronic databases were searched (Cochrane Library, Medline, EMBASE, CINAHL, ERIC and Dissertation Abstracts). Additional studies were sought by contacting dietitians, clinicians and the manufacturers of nutritional supplements. SELECTION CRITERIA: All randomised controlled trials of dietary advice compared with no advice, oral nutritional supplements and dietary advice plus oral nutritional supplements in people with illness-related malnutrition. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trial eligibility, methodological quality and extracted the data. MAIN RESULTS: Fifteen trials (16 comparisons) met the inclusion criteria. An additional group of six trials were identified during searching which compared dietary advice plus supplements if required with no advice. These trials have been included in the review as an additional comparison. The review includes 1185 randomised participants from a variety of clinical backgrounds. The duration of follow-up was from six weeks to 12 months. Nine trials reported clearly concealed randomisation and allocation and two trials reported blinding of outcome assessment. Nine trials reported outcomes in an unusable format. Gain in weight was significantly higher for groups consuming supplements with or without advice, compared with advice alone. Energy intake was significantly improved in those consuming supplements compared with those receiving advice alone. There was insufficient data on group differences in functional outcomes and mortality. REVIEWER'S CONCLUSIONS: This review highlights the lack of evidence for the provision of dietary advice in the management of illness-related malnutrition. The available data suggest that oral nutritional supplements have a greater role than dietary advice in the improvement of body weight and energy intake. A large adequately powered randomised controlled trial is needed to compare the efficacy of different forms of therapy to increase dietary intake in people with illness-related malnutrition and to examine the impact of this on clinical function and survival.

Adult↗
PubMed2001

Herbal therapy for treating osteoarthritis.

BACKGROUND: The increasing popularity of complementary and alternative medicine appears to be particularly evident amongst people with chronic disease. In the treatment of osteoarthritis, one therapy that has been identified as having potential benefit, is herbal medicine (phytotherapy). OBJECTIVES: To determine the effectiveness of herbal therapies in treating osteoarthritis. SEARCH STRATEGY: Databases for mainstream and complementary medicine were searched using terms to include all forms of arthritis combined with herbal medicine. We searched the following electronic databases: MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane Controlled Trials Register (CCTR), Cochrane Musculoskeletal specialized register, Dissertation Abstracts, BIDS ISI and the Cochrane Complementary Medicine Fields Specialized Register. We also searched the reference lists from retrieved trials. SELECTION CRITERIA: All randomized trials of herbal interventions in osteoarthritis, compared to placebo. Studies were included according to the a priori protocol and agreement between two reviewers who independently read each selected paper for content and for assessment of quality. Papers of any language were included. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the same two reviewers. MAIN RESULTS: Five studies (four different herbal interventions) met the review criteria. Two studies were suitable for data pooling. It was not possible to draw firm conclusions from the single studies but two studies of avocado/soybean unsaponifiables showed beneficial effects on functional index, pain, intake of NSAIDs and global evaluation. No serious side effects were reported. REVIEWER'S CONCLUSIONS: The evidence for avocado-soybean unsaponifiables in the treatment of osteoarthritis is convincing but evidence for the other herbal interventions is insufficient to either recommend or discourage their use.

Chronic Disease↗
PubMed2001

Herbal therapy for treating rheumatoid arthritis.

BACKGROUND: The increasing popularity of the use of complementary and alternative interventions or treatments appears to be particularly evident amongst people with chronic disease. In the treatment of rheumatoid arthritis, one therapy that has been identified as having potential benefit, is herbal medicine (phytotherapy). OBJECTIVES: To assess the effectiveness of herbal therapies in the treatment of rheumatoid arthritis. SEARCH STRATEGY: We developed a search strategy using terms to include all forms of arthritis combined with herbal medicine. We searched the following electronic databases from 1966 to 2000: MEDLINE, EMBASE, CISCOM, AMED, CINAHL, Cochrane Controlled Trials Register (CCTR), Cochrane Musculoskeletal specialized register, Dissertation Abstracts, BIDS ISI and the Cochrane Complementary Medicine Fields Specialized Register. This was supplemented by searching the reference lists from retrieved trials. SELECTION CRITERIA: All randomized trials of herbal interventions in rheumatoid arthritis, compared to placebo. Two reviewers independently read and selected each potential study according to the criteria published in an a priori protocol. Papers of any language were included. DATA COLLECTION AND ANALYSIS: Data were extracted independently by the same two reviewers and an assessment of methodological quality was conducted. MAIN RESULTS: Eleven studies met the inclusion criteria. Seven of the studies compared gamma-linolenic acid (GLA) to placebo although three of these were not suitable for data pooling. The remaining studies considered four different herbal interventions and were assessed individually. All of the GLA studies found some improvement in clinical outcomes but methodology and study quality was variable, making it difficult to draw conclusive results. However, the better quality studies suggest potential relief of pain, morning stiffness and joint tenderness. With the exception of one intervention (Tripterygium wilfordii hook F), no serious side effects were reported. REVIEWER'S CONCLUSIONS: There appears to be some potential benefit for the use of GLA in rheumatoid arthritis although further studies are required to establish optimum dosage and duration of treatment. The single studies are inconclusive.

Arthritis, Rheumatoid↗
PubMed2000

SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha catalyzed by Ubc3 and Ubc4.

NF kappa B is an important transcriptional regulator of multiple pro-inflammatory genes. In non-stimulated cells NF kappa B is anchored in the cytoplasm via the inhibitory protein I kappa B alpha. Following exposure to diverse pro-inflammatory signals (e.g. TNF alpha, IL1, LPS) various signal transduction cascades are initiated converging on the I kappa B kinase (IKK). IKK phosphorylates I kappa B alpha on serines 32 and 36 signaling the inhibitory protein for ubiquitin-mediated degradation. The SCF beta-TRCP complex is the ubiquitin ligase responsible for mediating phosphorylation dependent ubiquitination of I kappa B alpha. Here we reconstitute phosphorylation dependent ubiquitination of I kappa B alpha using recombinant components. Our results suggest that the cullin specificity of the SCF complex may reflect its ability to associate with Rbx1. We demonstrate specific ubiquitination of I kappa B alpha by Ubc3 and Ubc4 in a phosphorylation and SCF beta-TRCP dependent manner and that both are capable of associating with the SCF beta-TRCP complex isolated from human cells. Finally, we show that Ubc4 is in excess to Ubc3 in THP.1 cells and 19 times more efficient in catalyzing the reaction, suggesting that Ubc4 is the preferentially used Ubc in this reaction in vivo. Our results also suggest that ubiquitin is transferred directly from the Ubc to phospho-I kappa B alpha in a SCF beta-TRCP dependent reaction. Oncogene (2000) 19, 3529 - 3536

Amino Acid Sequence↗
PubMed2000

Vanadium-catalyzed asymmetric cyanohydrin synthesis

Based on a mechanistic understanding of asymmetric cyanohydrin synthesis catalyzed by chiral titanium-salen complexes, a new catalyst based on vanadium(IV) has been developed. The chiral (salen)VO catalyst is more enantioselective than the titanium-based systems, 0.1 mol % of the catalyst being sufficient to convert aromatic and aliphatic aldehydes into the corresponding trimethylsilyl ethers of cyanohydrins with 68-95% enantiomeric excess at room temperature.

Journal Article↗
PubMed2000

Heightened odds of large earthquakes near istanbul: An interaction-based probability calculation

We calculate the probability of strong shaking in Istanbul, an urban center of 10 million people, from the description of earthquakes on the North Anatolian fault system in the Marmara Sea during the past 500 years and test the resulting catalog against the frequency of damage in Istanbul during the preceding millennium. Departing from current practice, we include the time-dependent effect of stress transferred by the 1999 moment magnitude M = 7.4 Izmit earthquake to faults nearer to Istanbul. We find a 62 +/- 15% probability (one standard deviation) of strong shaking during the next 30 years and 32 +/- 12% during the next decade.

Journal Article↗
PubMed2000

Nutritional and other influences in childhood as predictors of adult obesity.

It has been proposed that there are critical periods during childhood that influence the development of obesity, including gestation and early infancy, the period of adiposity rebound that occurs between ages 5 and 7 years, and adolescence. Despite an extensive literature, there is to date only modest evidence for most of the factors such as nutrition, physical activity and other behavioural factors that are suspected as playing a role in the development of obesity. A recent review of this evidence (Parsons et al. 1999) showed, however, a consistent relationship between socio-economic status (SES) of origin and adult obesity, whereby those from lower SES backgrounds were fatter subsequently in adulthood. This association appeared to apply to both men and women, a finding that contrasts with the trends observed in cross-sectional studies, of an association with SES for women only. There are several potential explanations for the SES of origin-adult obesity relationship. SES of origin may be confounded by parental body size; studies to date provide insufficient evidence of an independent association with SES after allowing for parental body size. Alternatively, environment in early life (for which SES of origin is a proxy measure) may have a long-term impact on obesity later in adulthood, through one or more of several processes. Three major potential explanations can be identified: (1) nutrition in infancy and childhood, either over- or undenutrition, followed subsequently by overnutrition; (2) psychological factors, possibly involving emotional deprivation in childhood; (3) cultural or social norms regarding dietary restraint and attitudes to fatness that may be acquired during childhood.

Adolescent↗
PubMed1996

A mechanism for regulation of the adhesion-associated proteintyrosine kinase pp125FAK.

Focal adhesion kinase (pp125FAK) is a member of a growing family of structurally distinct protein tyrosine kinases that includes the recently identified FakB and PYK2/CAKbeta/RAFTK. Activation of pp125FAK has been functionally linked to the formation of focal adhesions, integrin-mediated sites of contact between the cell and the extracellular matrix. The carboxy-terminal domain of pp125FAK is also expressed as a separate protein called pp41/43FRNK (where FRNK represents pp125FAK-related non-kinase). Here we show that pp41/43FRNK acts as an inhibitor of pp125FAK by transiently blocking the formation of focal adhesions on fibronectin and constitutively reducing tyrosine phosphorylation of both pp125FAK and two focal adhesion proteins, tensin and paxillin. These inhibitory effects of pp41/43FRNK are reversed by co-expression of pp125FAK, suggesting that pp125FAK and pp41/43 FRNK compete for a common binding protein(s) whose association with pp125FAK is necessary for signalling by pp125FAK. We propose that pp41/43FRNK functions as an endogenous regulator of pp125FAK, thus providing an unusual means to regulate both tyrosine kinase activity and cellular adhesion to the extracellular matrix.

Animals↗
PubMed1996

Association of phosphatidylinositol 3-kinase, via the SH2 domains of p85, with focal adhesion kinase in polyoma middle t-transformed fibroblasts.

Focal adhesion kinase (FAK), a non-receptor protein tyrosine kinase, becomes activated and phosphorylated on tyrosine in cells transformed with v-src. By cytoimmunofluorescence a sub-fraction of the p85 subunit of phosphoinositide 3-kinase (PI 3-kinase) localized in focal adhesion plaques. We examined the possibility that FAK associates with PI 3-kinase. In fibroblasts transformed with polyoma middle t, PI 3-kinase activity co-immunoprecipitated with pp125FAK using two different antibodies against this protein. PP125FAK from middle t-transformed cells associated with a glutathione-S-transferase fusion protein containing the 85-kDa subunit of phosphatidylinositol 3-kinase. Both of the SH2 domains and the SH3 domain of p85 also formed complexes with pp125FAK in vitro. Phosphopeptides that bind to the SH2 domains completely blocked the binding of full-length p85 to pp125FAK, while a peptide that binds to the SH3 domain was ineffective, indicating that the association between p85 and pp125FAK is mediated by the SH2 domains of p85.

3T3 Cells↗
PubMed1996

Psychosis and genes with trinucleotide repeat polymorphism.

Abnormal expansion of genes with trinucleotide repeat (TNR) polymorphism has been found in a number of neuropsychiatric disorders. These disorders and the major psychoses, schizophrenia and bipolar affective disorder, appear to share an interesting phenomenon: genetic anticipation. Because TNR expansion correlates with anticipation, these unstable DNA sites are considered important candidate loci for the major psychoses. We investigated genes with TNR polymorphisms, including B1, B33, B37, and the N-cadherin gene, in unrelated Caucasian North American and Italian schizophrenics (n = 53 to 74), and matched controls. Also, unrelated Caucasian North American patients with bipolar I affective disorder were screened for the B33 and N-cadherin genes (n = 49 and 63, respectively). No unusually long alleles that would suggest abnormal expansion of the TNR were observed for any of these genes. Also, no statistically significant results were found in tests for genetic association between any of these genes and schizophrenia. For B37, a trend toward a difference in allele counts between schizophrenics and controls was observed. However, no clear evidence for a role of these TNR-containing genes in schizophrenia or bipolar affective disorders was found.

Bipolar Disorder↗
PubMed1994

Identification and characterization of an iron-regulated hemopexin receptor in Haemophilus influenzae type b.

Heme can serve Haemophilus influenzae as a source of both essential porphyrin and iron. In extracellular mammalian body fluids neither free heme nor free iron is available, since they are tightly bound to hemopexin and transferrin, respectively. Since H. influenzae grows in the presence of iron-transferrin and heme-hemopexin and is known to express a saturable receptor for transferrin, we investigated the process by which this pathogen acquired heme from hemopexin for use as an iron source. The ability of human and rabbit hemopexin to donate heme as a source of iron to H. influenzae type b strains was demonstrated by plate bioassays. With a dot enzyme assay with biotinylated hemopexin as ligand, H. influenzae bound heme-hemopexin and apo-hemopexin following growth in iron-restricted, but not in iron-sufficient, medium. Competitive binding studies with heme-hemopexin and apo-hemopexin demonstrated saturability of binding. Neither heme, protoporphyrin IX, hemoglobin, nor transferrin blocked the binding of hemopexin to whole cells, demonstrating the specificity of binding. Treatment of whole H. influenzae cells with trypsin abolished binding. Taken together, these observations suggest that H. influenzae type b expresses an outer membrane protein(s) which acts as a receptor for hemopexin and which is regulated by the availability of iron in the growth medium. In iron-restricted media, H. influenzae 706705 and DL42 did not express the 100-kDa hemopexin-binding protein previously reported (M.S. Hanson, S.E. Pelzel, J. Latimer, U. Muller-Eberhard, and E.J. Hansen, Proc. Natl. Acad. Sci. USA 89:1973-1977, 1992). The putative iron-regulated hemopexin receptor was solubilized from cell envelopes of H. influenzae 706705, DL42, and Eagan with the detergent CHAPS (3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propanesulfonate) and isolated by affinity chromatography on heme-hemopexin-Sepharose 4B. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the proteins bound to the affinity resin revealed three proteins of 29, 38, and 57 kDa, of which the 57- and 29-kDa proteins bound hemopexin after Western blotting (immunoblotting). A monoclonal antibody to the 57-kDa hemopexin-binding protein of 706705 recognized a 57-kDa protein on Western blots of the cell envelope proteins of 706705, DL42, and Eagan; no reaction was observed with the 100-kDa hemopexin-binding protein of DL42. These data suggest that some H. influenzae strains possess at least two hemopexin receptors, the expression of which is determined by the prevailing growth environment.

Aerobiosis↗
PubMed1993

Antigenic relationships of transferrin-binding proteins from Neisseria meningitidis, N. gonorrhoeae and Haemophilus influenzae: cross-reactivity of antibodies to NH2-terminal peptides.

The NH2-terminal amino sequence through the first 20 amino acids was obtained for transferrin-binding protein (TBP)1 from three strains of Neisseria meningitidis. These were identical except for a glutamine to a glycine substitution at residue 6 in one case. The sequences of the NH2-terminal 20 amino acids of TBP2 from the same three strains were also determined; one TBP2 had a M(r) of 68,000 and the other two of 78,000. Sequences were identical up to residue 13 in all three proteins. Peptides based on the NH2-terminal sequences of TBP1 and 2 were synthesized, linked to Keyhole Limpet haemocyanin and used to raise antibodies in rabbits. Anti-peptide antibodies cross-reacted on immunoblotting with the respective TBPs from all meningococcal strains tested, as well as with those from N. gonorrhoeae, suggesting that the NH2-terminals of these proteins are well conserved in the Neisseria. Neither anti-peptide serum reacted with the analogous TBP1 and 2 from Haemophilus influenzae, although common epitopes have previously been shown to exist.

Amino Acid Sequence↗
PubMed1993

A recombinant amino terminal fragment of bactericidal/permeability-increasing protein inhibits the induction of leukocyte responses by LPS.

Bactericidal/permeability-increasing protein (BPI) is a major component of the granules of polymorphonuclear neutrophils (PMNs) and is involved in the killing of gram-negative bacteria. A 23-kd recombinant protein, corresponding to the NH2-terminal fragment of human BPI (rBPI23), has been shown to bind lipid A and antagonize some lipopolysaccharide (LPS)-mediated effects. In this study the ability of rBPI23 to prevent a wide range of cellular responses to LPS was investigated. In vitro assays were carried out using human blood to more closely approximate in vivo conditions. The release of proinflammatory cytokines [tumor necrosis factor (TNF), interleukin-1 beta (IL-1 beta), IL-6, IL-8], induced by E. coli O113 LPS, was markedly reduced by rBPI23 in a concentration-dependent fashion. The production of the anti-inflammatory protein IL-1ra (IL-1 receptor antagonist) was triggered by lower LPS concentrations than those necessary for the other cytokines. Furthermore, prevention of IL-1ra release required higher rBPI23 concentrations than for other cytokines. The LPS-induced production of oxygen-derived free radicals by phagocytic cells (resulting in chemiluminescence) was also prevented by rBPI23. The inhibition was specific for LPS because the activation of leukocytes by phorbol myristate acetate, zymosan, or TNF was unaffected by BPI. The ability of rBPI23 to antagonize specifically the effects of endotoxin in the complex environment of human blood along with its bactericidal activity suggests that rBPI23 may be a novel therapeutic agent in the treatment of gram-negative infections.

Antimicrobial Cationic Peptides↗