Biomedical subjects

T Charles

Publications and source records attributed to T Charles.

7 recordsLinked to original sources

PubMed2003

Should HIV discordant couples have access to assisted reproductive technologies?

In this paper we identify and evaluate arguments for and against offering assisted reproductive technologies (ART), specifically IVF, to HIV discordant couples (male partner HIV positive, female partner HIV negative). The idea of offering ART to HIV discordant couples generates concerns about safety and public health and raises questions such as: what is an acceptable level of risk to offspring and should couples who want this assistance be subject to selection criteria; should they undergo scrutiny about their suitability as parents when those who are able to conceive naturally face no such scrutiny and people with other illnesses are given access to ART? We conclude that offering ART to HIV discordant couples is likely to produce more benefit than harm and violates no ethical principles. Nevertheless, a decision to deny treatment need not constitute unjustified discrimination.

Child↗

PubMed2001

Genetic transformation of Trametes versicolor to phleomycin resistance with the dominant selectable marker shble.

We have developed a stable, DNA-mediated transformation system for the white-rot basidiomycete Trametes versicolor based on the dominant selectable marker shble (phleomycin resistance). We employed a vector containing the selectable marker under control of expression sequences from the basidiomycete Schizophyllum commune and a polyethylene glycol/ CaCl2 protoplast-fusion technique to introduce the transforming DNA. This transformation system generated stable phleomycin-resistant transformants at a frequency of four to seven transformants/microg of transforming DNA.

Anti-Bacterial Agents↗

PubMed2001

Amyotrophic lateral sclerosis: current understanding.

Amyotrophic lateral sclerosis (ALS), or motor neuron disease (MND) as it is usually termed in the United Kingdom, is a fatal degenerative disease resulting in progressive weakness and wasting of voluntary muscles. The disease is caused by degeneration of upper motor neurons in the motor cortex and of lower motor neurons in the brainstem and spinal cord. This combined loss of function causes spastic paralysis, flaccid muscle weakness, wasting, and fasciculations. The disease process spares the sensory, autonomic, and oculomotor neurons. ALS is the most common of the MND syndromes in adults. Although the cause of ALS is unknown, there is evidence that the excitatory neurotransmitter glutamate plays an important role in neuronal cell death in the disease. Several risk factors, such as exposure to welding and soldering, inhalation of lead vapor, exposure to chemicals, and electrical trauma are postulated as contributing to the pathogenesis of ALS. About 90% of all ALS patients have the sporadic form. Approximately 20% of all familial ALS cases are associated with mutations of the copper/zinc superoxide dismutase-1 gene. What is not clear is what factors contribute to the causation of the more common sporadic cases. The drug riluzole has neuroprotective effects in ALS and is the only disease-specific treatment available to date. Riluzole has been approved by the National Institute for Clinical Excellence for use in the National Health Service of the United Kingdom. Other treatments are aimed at managing the devastating symptoms of ALS.

Drug Approval↗

PubMed2000

Polyphasic microbial community analysis of petroleum hydrocarbon-contaminated soils from two northern Canadian communities.

The cold-adapted bacterial communities in petroleum hydrocarbon-contaminated and non-impacted soils from two northern Canadian environments, Kuujjuaq, Que., and Alert, Nunavut, were analyzed using a polyphasic approach. Denaturing gradient gel electrophoresis (DGGE) separation of 16S rDNA PCR fragments from soil total community DNA revealed a high level of bacterial diversity, as estimated by the total number of bands visualized. Dendrogram analysis clustered the sample sites on the basis of geographical location. Comparison of the overall microbial molecular diversity suggested that in the Kuujjuaq sites, contamination negatively impacted diversity whereas in the Alert samples, diversity was maintained or increased as compared to uncontaminated controls. Extraction and sequencing analysis of selected 16S rDNA bands demonstrated a range of similarity of 86-100% to reference organisms, with 63.6% of the bands representing high G+C Gram-positive organisms in the order Actinomycetales and 36.4% in the class Proteobacteria. Community level physiological profiles generated using Biolog GN plates were analyzed by cluster analysis. Based on substrate oxidation rates, the samples clustered into groups similar to those of the DGGE dendrograms, i.e. separation based upon geographic origin. The coinciding results reached using culture-independent and -dependent analyses reinforces the conclusion that geographical origin of the samples, rather than petroleum contamination level, was more important in determining species diversity within these cold-adapted bacterial communities.

Journal Article↗

PubMed1993

Preformed dimeric state of the sensor protein VirA is involved in plant--Agrobacterium signal transduction.

Plant signal molecules such as acetosyringone and certain monosaccharides induce the expression of Agrobacterium tumefaciens virulence (vir) genes, which are required for the processing, transfer, and possibly integration of a piece of the bacterial plasmid DNA (T-DNA) into the plant genome. Two fo the vir genes, virA and virG, belonging to the bacterial two-component regulatory system family, control the induction of vir genes by plant signals. virA encodes a membrane-bound sensor kinase protein and virG encodes a cytoplasmic regulator protein. Although it is well established from in vitro studies that the signal transduction process involves VirA autophosphorylation and subsequent phosphate transfer to VirG, the structural state of the VirA protein involved in signal transduction is not understood. In this communication, we describe an in vivo crosslinking approach which provides physical evidence that VirA exists as a homodimer in its native configuration. The dimerization of VirA neither requires nor is stimulated by the plant signal molecule acetosyringone. We also present genetic data which support the hypothesis that VirA exists as a homodimer which is the functional state transducing the plant signal in an intersubunit mechanism. To our knowledge, this report provides the first evidence that a bacterial membrane-bound sensor kinase exists and functions as a homodimer in vivo.

Agrobacterium tumefaciens↗

PubMed1992

Characterization of a tumor necrosis factor-alpha inhibitor activity in cancer patients.

To evaluate the feasibility of tumor necrosis factor-alpha (TNF-alpha) treatment of lung cancer patients, we chose the malignant cells contained in their pleural effusions as a first convenient target. We found, however, that a TNF-alpha inhibitor (TNF-alpha I) activity was present in both patient sera and pleural fluids. We therefore compared the TNF-alpha I activity present in patients with benign or malignant pleural effusions using a bioassay of TNF-alpha inhibition and partially characterized it. A high TNF-alpha I activity characterizes cancer patients with sera levels twice as high as the control level measured for blood bank donors (2.54 +/- 1.28 versus 1.19 +/- 0.38) and with even higher levels in pleural fluids (3.75 +/- 1.83). In contrast, patients with benign pleural effusions present similar levels of TNF-alpha I activity, at about the control level, in both their sera and pleural fluids (1.37 +/- 0.98 versus 1.16 +/- 0.85). A high TNF-alpha I activity is consistently found in cancer patients but is only released in vitro by leukocytes. It is most likely related to recently purified TNF-alpha inhibitors that, as soluble shed fragments of TNF receptors, may function as traps for TNF molecules. This study suggests that tumors may evade TNF cytotoxic action by modulating systemic levels of TNF and implies a reassessment of TNF therapy in cancer patients.

Adult↗

PubMed1992

Dexamethasone modulation of tumour necrosis factor-alpha (cachectin) release by activated normal human alveolar macrophages.

Recurrent infections of the lower respiratory tract are a frequent and serious side-effect of chronic corticosteroid treatment. Since alveolar macrophages (AM) are currently thought to play a central role in the protection of the lower respiratory tract against infectious agents, it is likely that a steroid-induced deficiency of AM is involved in this process. In this respect, when activated, AM are major producers of tumour necrosis factor-alpha (TNF or cachectin), a versatile cytokine with several biological properties including antiviral and anti-infectious activities. A deficit of TNF production induced by corticosteroid may be one mechanism of the sensitivity to infections. Thus normal human AM obtained by bronchoalveolar lavage were pretreated with dexamethasone (DXM) before activation with lipopolysaccharides (LPS) and the amounts of TNF released in culture were quantified. Pretreatment with DXM resulted in a marked decrease of TNF release in a dose-dependent fashion. In contrast, when AM were activated with LPS before DXM treatment, TNF release by AM was suppressed in a more limited fashion. Thus DXM suppression of LPS-activated AM ability to release TNF may play a role in the susceptibility to infections of patients chronically treated with corticosteroids.

Adult↗