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Biomedical subjects

A Braithwaite

Publications and source records attributed to A Braithwaite.

18 recordsLinked to original sources
PubMed2003

Detection of polycyclic aromatic hydrocarbons using quartz crystal microbalances.

A chemically coated piezoelectric sensor has been developed for the determination of PAHs in the liquid phase. An organic monolayer attached to the surface of a gold electrode of a quartz crystal microbalance (QCM) via a covalent thiol-gold link complete with an ionically bound recognition element has been produced. This study has employed the PAH derivative 9-anthracene carboxylic acid which, once bound to the alkane thiol, functions as the recognition element. Binding of anthracene via pi-pi interaction has been observed as a frequency shift in the QCM with a detectability of the target analyte of 2 ppb and a response range of 0-50 ppb. The relative response of the sensor altered for different PAHs despite pi-pi interaction being the sole communication between recognition element and analyte. It is envisaged that such a sensor could be employed in the identification of key marker compounds and, as such, give an indication of total PAH flux in the environment.

Anthracenes↗
PubMed2002

The dopamine D4 receptor and the hyperactivity phenotype: a developmental-epidemiological study.

Attention-deficit hyperactivity disorder (ADHD) affects 2-6% of school-age children and is a precursor of behavioural problems in adolescence and adulthood. Underlying the categorical definition of ADHD are the quantitative traits of activity, impulsivity, and inattention which vary continuously in the population. Both ADHD and quantitative measures of hyperactivity are heritable, and influenced by multiple genes of small effect. Several studies have reported an association between clinically defined ADHD and the seven-repeat allele of a 48-bp tandem repeat polymorphism in the third exon of the dopamine D4 receptor gene (DRD4). We tested this association in a large, unselected birth cohort (n = 1037) using multiple measures of the hyperactivity phenotype taken at multiple assessment ages across 20 years. This longitudinal approach allowed us to ascertain whether or not DRD4 has a general effect on the diagnosed (n = 49) or continuously distributed hyperactivity phenotype, and related personality traits. We found no evidence to support this association.

Adolescent↗
PubMed2002

Molecular imprinted polymer coated QCM for the detection of nandrolone.

An acoustic wave sensor coated with an artificial biomimetic recognition element has been developed to selectively screen for nandrolone in the liquid phase. A highly specific covalently imprinted polymer (MIP) was spin coated onto one electrode of a quartz crystal microbalance (QCM) as a thin permeable film. Selective rebinding of the nandrolone was observed as a frequency shift in the QCM for concentrations up to 0.2 ppm with the sensor binding shown to favour nandrolone over analogous compounds.

Anabolic Agents↗
PubMed2001

Molecular-imprinted, polymer-coated quartz crystal microbalances for the detection of terpenes.

A piezoelectric sensor coated with an artificial biomimetic recognition element has been developed for the determination of L-menthol in the liquid phase. A highly specific noncovalently imprinted polymer (MIP) was cast in situ on to the surface of a gold-coated quartz crystal microbalance (QCM) electrode as a thin permeable film. Selective rebinding of the target analyte was observed as a frequency shift quantified by piezoelectric microgravimetry with the QCM. The detectability of L-menthol was 200 ppb with a response range of 0-1.0 ppm. The response of the MIP-QCM to a range of monoterpenes was investigated with the sensor binding menthol in favor of analogous compounds. The sensor was able to distinguish between the D- and L-enantiomers of menthol owing to the enantioselectivity of the imprinted sites. To our knowledge, this is the first report describing enantiomeric resolution within an MIP utilizing a single monomer-functional moiety interaction. It is envisaged that this technique could be employed to determine the concentration of terpenes in the atmosphere.

Journal Article↗
PubMed1996

Vaccinia virus replication is independent of cellular HSP72 expression which is induced during virus infection.

HSP72 is dramatically induced in the ovaries of vaccinia virus (VV)-infected mice and associates with VV proteins. In order to investigate the role of HSP72 during vaccinia virus replication, we have constructed a recombinant vaccinia virus encoding the major inducible cellular HSP72 (VV-HSP72+) and examined the replication characteristics of this virus. VV-HSP72+ exhibited growth kinetics identical to and peak titers very similar to those of control viruses, both in vitro and in vivo. In particular, replication of VV-HSP72+ was identical to that of control viruses in the HSP72-negative cell line Y3.Ag.1.2.3, and overexpression of HSP72 had no effect on the virulence of VV infection in normal or immunocompromised mice. We conclude that while VV infection results in the induction of the major inducible 72-kDa HSP, VV replication proceeds normally in the absence of this protein. It is unclear whether another celluar chaperone is required to facilitate virus replication in place of HSP72 in Y3.Ag.1.2.3 cells or whether HSP expression plays no role in virus replication, but is simply a component of the generalized stress response to virus infection.

Animals↗
PubMed1995

The transforming oncoproteins determine the mechanism by which p53 suppresses cell transformation: pRb-mediated growth arrest or apoptosis.

To investigate the mechanisms by which p53 suppresses cell transformation, we used the simian virus 40 (SV40) large T antigen (LTag), the adenovirus E1a proteins, and an activated ras protein (EJ-ras), to examine different pathways of transformation for their susceptibility to suppression by p53: While p53 can suppress transformation by various oncoproteins, we have shown that it is unable to suppress the transformation of rat embryo fibroblasts (REFs) by LTag. Interestingly, the function of LTag which enables it to overcome the antiproliferative effects of p53 is not the binding and inactivation of p53, but the binding and inactivation of the pRb family of proteins. This observation indicates that pRb mediates a suppressive effect of p53 on cell transformation. We have also observed that in contrast to LTag, both E1a and EJ-ras cause transformation-related events which are susceptible to suppression by p53. Further studies have revealed that cells expressing E1a are susceptible to p53-mediated apoptosis, while cells expressing EJ-ras are susceptible to p53-induced growth inhibition. We therefore propose that p53 suppresses transformation either by arresting cell growth (mediated by pRb in late G1) or by inducing apoptosis, with the mechanism being determined by the transforming oncoprotein(s).

Adenovirus E1A Proteins↗
PubMed1995

p53 represses SV40 transcription by preventing formation of transcription complexes.

There is now much evidence to suggest that the p53 tumour suppressor protein functions to monitor the integrity of the genome. When DNA damage is detected, p53 suppresses cell growth to allow repair or directs the cell into apoptosis. The mechanism of action of p53 is as yet unclear but recent evidence has accumulated to suggest that p53 might act by regulating gene expression. Consistent with this model, p53 can both activate and repress a number of viral and cellular promoters. p53 has also been shown to bind to the CCAAT-binding Factor and TATA-binding protein (TBP), and there is direct evidence that p53 represses in vitro transcription by preventing TBP from binding DNA. We now provide evidence that p53 can repress transcription from the SV40 promoter by disrupting DNA/protein complexes involving transcription factor Sp1.

Animals↗
PubMed1995

p53-dependent activation of the mouse MCK gene promoter: identification of a novel p53-responsive sequence and evidence for cooperation between distinct p53 binding sites.

Transcriptional activation by p53 is dependent on the presence of a specific p53 binding site within control sequences of the target gene. One such target gene is the mouse muscle-specific creatine kinase (MCK) gene, which contains a p53 binding site between promoter residues -3182 and -3133 relative to the transcription start site. This DNA sequence is reported to be sufficient to confer p53-dependent activation on the MCK promoter. In contrast to this finding, evidence from promoter deletion studies suggests that sequences in the MCK promoter other than this p53 binding site also permit p53-dependent activation. To investigate this possibility, we have further examined sequences in the MCK promoter required for transcriptional activation by mouse p53. We report here identification of a second p53-responsive sequence within the MCK promoter. This novel sequence is situated between residues -177 and -81, and can confer p53-dependent, position- and orientation-independent activation on a heterologous promoter. Moreover, this sequence can specifically bind mouse and human p53. By promoter deletion studies, we provide evidence that these two elements cooperate to provide high-level, p53-dependent activation of the MCK promoter.

Animals↗
PubMed1994

Transcriptional regulation of the PCNA promoter by p53.

We have examined the ability of p53 to affect transcription from the PCNA promoter in a number of cell types. In HeLa cells, p53 activates the PCNA promoter whereas in CV1, CHO, L929, and Saos-2 cells the same promoter is strongly repressed. By using stepwise deletions of the PCNA promoter, we have identified two potential regions of the promoter which are important for the ability of p53 to activate transcription in HeLa cells.

Animals↗
PubMed1993

Prenatal diagnosis of a neurenteric cyst by magnetic resonance imaging.

We report a case of neuroenteric cysts in which the diagnosis was made prenatally by magnetic resonance imaging. These neuroenteric cysts are developmental anomalies of the alimentary tract in connection with midline neural structures that are usually diagnosed in the first decade of life. Magnetic resonance imaging not only helped to make the diagnosis early, but enabled appropriate counseling of the mother and follow-up of the infant so that planning of surgery was optimal.

Adolescent↗
PubMed1990

Transactivation of the p53 oncogene by E1a gene products.

Infection of quiescent rat kidney cells with human adenovirus is shown to transcriptionally stimulate (transactivate) the p53 oncogene. The increased transcription results in an accumulation of p53-specific mRNA in parallel with an increase in p53 protein levels, although there is a considerable delay between transcriptional activation and the detection of stable p53 mRNA and protein. The induction of p53 is detectable with two monoclonal antibodies recognizing different epitopes. The induction of p53 by adenovirus is delayed compared to induction by serum, and it occurs after the onset of adenovirus-induced cellular DNA replication. Thus, adenovirus-induced DNA replication bypasses a G0/G1 control point. Experiments with hydroxyurea show that p53 activation does not require continued cell cycling and thus is likely to be a direct consequence of viral gene expression. Finally, the induction of p53 is shown to be dependent on expression of the 289-residue product encoded by the viral E1a gene.

Adenovirus Early Proteins↗
PubMed1990

Apoptosis induced in macrophages and T blasts by the mycotoxin sporidesmin and protection by Zn2+ salts.

Incubation of 48 h concanavalin A stimulated spleen cells (T blasts) and murine peritoneal macrophages with the mycotoxin sporidesmin results in DNA fragmentation characteristic of apoptosis. Morphological changes, particularly condensed chromatin, observed following incubation of these cells with sporidesmin and the immunotoxin gliotoxin and related epipolythiodioxopiperazines (ETP) also show changes characteristic of apoptosis. The presence of Zn2+ salts in the culture medium at concentrations non toxic to the cells over the time period studied protects against DNA damage and morphological change. Interaction between Zn2+ and the reduced form of a simple ETP compound assessed by spectral changes demonstrated the formation of a weak complex between the two molecules. Complex formation between zinc and thiol however was insufficient to prevent oxidative damage to plasmid DNA in vitro by inhibiting auto-oxidation of the reduced ETP compound because of the looseness of the interaction. Cd2+, which appears to form a tighter complex with the dithiol does inhibit cleavage of plasmid DNA. These results establish that the toxicity of sporidesmin may be due in part to its ability to induce apoptosis or programmed cell death in sensitive cells. In addition the immunotoxin gliotoxin and related compounds have now been shown to induce the same characteristic morphological changes in cells of haemopoietic origin. The inhibition of apoptosis induced by ETP compounds by Zn2+ appears to be due to direct inhibition of apoptosis rather than Zn2+ acting as an antioxidant. These results demonstrate the inhibition of apoptosis induced by ETP compounds by Zn2+ and suggest an alternate explanation for the known prophylactic effect of Zn2+ on sporidesmin induced tissue damage.

Animals↗
PubMed1988

Basal cell carcinoma xenografts in nude mice: studies on epithelial differentiation and stromal relationships.

Thirty-three basal cell carcinomas (BCC) were transplanted into athymic mice, and foci of tumour were identified in 17 grafts recovered after intervals of 2-5 months. Fifteen of these xenografts contained apparently normal differentiated epithelia, considered to derive from elements within the original tumours. The level of differentiation was very close in original and corresponding xenograft BCC. Morphologically recognizable 'specialized' stroma was present in some but not all xenografted BCC, and was also present in some grafts containing only differentiated elements. A monoclonal antibody specific to human type IV collagen showed intact epithelial and also vascular basement membranes within the graft. Surprisingly, mouse cells were found to line these vessels, and the stroma around normal and neoplastic epithelial islands was a mixture of mouse and human cells, with no consistent composition. These observations question the proposed dependence of BCC on its 'specialized' stroma.

Animals↗