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Biomedical subjects

A R Fraser

Publications and source records attributed to A R Fraser.

18 recordsLinked to original sources
PubMed2006

Immature monocytes from G-CSF-mobilized peripheral blood stem cell collections carry surface-bound IL-10 and have the potential to modulate alloreactivity.

Production of the anti-inflammatory cytokine IL-10 by monocytes has been implicated as a probable negative regulator of graft-versus-host disease (GvHD) in patients undergoing allogeneic stem cell transplants (SCT). Monocytes from G-CSF-mobilized peripheral blood stem cell (gmPBSC) collections have been reported to produce more IL-10 than unmobilized monocytes in response to proinflammatory factors such as LPS. Why this should occur is unclear. In this study, monocyte phenotype and IL-10 localization and release were investigated in PB mononuclear cells (MNC) from 27 healthy donors mobilized for allogeneic SCT and from 13 patients with hematological malignancies mobilized for autologous SCT. All isolates contained elevated total percentages of monocytes in comparison with unmobilized PB, a high proportion of which displayed an immature phenotype. Stimulation of gmPB MNC with an inflammatory stimulus [fixed Staphylococcus aureus cells (SAC)] induced rapid up-regulation of CD14, indicating conversion to mature status. Localization studies indicated that IL-10 was predominantly present, bound on the surface of CD64(+)/CD14(low/neg) immature monocytes. Inflammatory stimuli (LPS, polyinosinic:polycytidylic acid, or SAC) induced release of variable quantities of IL-10 from the cell surface. MNC, separated into surface IL-10-positive or -negative fractions, differed in their ability to stimulate alloreactivity in MLR, and IL-10(+) MNC induced significantly lower levels of proliferation than IL-10(-) MNC. Thus, the subset of immature monocytes carrying surface-bound IL-10 in gmPB has the potential to modulate alloreactivity and GvHD after allogeneic SCT through cell-to-cell contact and released IL-10.

Donor Selection↗
PubMed2004

Targeting the silent minority: emerging immunotherapeutic strategies for eradication of malignant stem cells in chronic myeloid leukaemia.

Standard allogeneic stem cell transplantation (alloSCT) has provided a cure for chronic myeloid leukaemia (CML) over the last 25 years, but is only an option for a minority of patients. It was hoped that the introduction of imatinib mesylate (IM), a specific tyrosine kinase inhibitor that targets the Bcr-Abl oncogene product, would provide long-term remission or even cure for those patients without a donor, but studies have shown that IM does not eliminate leukaemic stem cells in CML patients. To overcome this problem of molecular persistence, research is underway to combine reduced intensity stem cell transplant or non-donor-dependent immunotherapies with IM with the aim of increasing cure rate, reducing toxicity and improving quality of life. The alternative approach is to combine IM or second-generation agents with other novel drugs that interrupt key signalling pathways activated by Bcr-Abl. This article will focus on the latest immunotherapy and molecularly targeted therapeutic options in CML and how they may be combined to improve the outcome for CML patients in the future.

Animals↗
PubMed2003

Role of quantitative mineralogical analysis in the investigation of sites contaminated by chromite ore processing residue.

A range of techniques, normally associated with mineralogical studies of soils and sediments, has been used to characterise the solid materials found on sites contaminated with chromite ore processing residue (COPR). The results show that a wide range of minerals are present, many of which are found extensively in high-temperature synthetic systems such as cements and clinkers and their low temperature hydration products. Thus, the minerals in COPR can be divided into three main categories: unreacted feedstock ore (chromite); high temperature phases produced during chromium extraction (brownmillerite, periclase and larnite); and finally, minerals formed under ambient weathering conditions on the disposal sites (brucite, calcite, aragonite, ettringite, hydrocalumite, hydrogarnet). Apart from chromite, chromium occurs in brownmillerite, ettringite, hydrocalumite and hydrogarnet. Detailed study of the chemistry and stoichiometry of chromium-bearing phases in conjunction with phase abundance provides a quantitative description of the solid state speciation of Cr(III) and Cr(VI) in and amongst these minerals and in the COPR as a whole. Of the total chromium present in the samples most, approximately 60-70% is present as Cr(III) in chromite, whilst brownmillerite also represents a significant reservoir of Cr(III) which is approximately 15% of the total. The remaining chromium, between 20 and 25%, is present as Cr(VI) and resides mainly in hydrogarnet, and to a slightly lesser extent in hydrocalumite. In the latter, it is present principally in an exchangeable anionic form. Chromium (VI) is also present in ettringite, but quantitatively ettringite is a much less important reservoir of Cr(VI), accounting for approximately 3% of total chromium in one sample, but less than 1% in the other two. This description provides insight into the processes likely to control the retention and release of Cr(VI) from COPR-contaminated sites. Such information is of particular value in chemical modelling of the system, in risk assessment and in the development of methods of informed remediation.

Journal Article↗
PubMed1990

A double blind trial of moclobemide versus amitriptyline in the treatment of depressive disorders.

The antidepressant efficacy and side-effect profile of amitriptyline were compared to those of moclobemide, a reversible monoamine oxidase inhibitor with selectivity for the type A isozyme. Forty nine patients with DSM-III major depression were randomly assigned to receive either amitriptyline or moclobemide. Thirty seven patients (amitriptyline n = 16, moclobemide n = 21) completed the six week protocol, which was conducted under double blind conditions. The results indicated a comparable antidepressant time course and efficacy for the two treatments. Amitriptyline produced significantly more sedation and antimuscarinic side-effects. Moclobemide appears to be a well tolerated antidepressant without the liability to produce significant postural hypotension and without the need for a tyramine-poor diet.

Adult↗
PubMed1987

Atypical mitochondrial DNA from the deep-sea scallop Placopecten magellanicus.

The mitochondrial DNA of most metazoan animals is highly conserved in size, averaging about 17 kilobase paris (kbp). The mitochondrial DNA from the deep-sea scallop Placopecten magellanicus, in contrast, has been found to be approximately 34 kbp long. It is also highly variable in size from individual to individual and is unusual in the extent of its size variation. Mitochondrial DNAs from individuals collected at the same site differ by as much as 7 kbp. The size variation is due largely to differences in the number of copies of a tandemly repeated 1.2-kbp element.

Journal Article↗
PubMed1983

Choice of antidepressant based on the dexamethasone suppression test.

This retrospective analysis of patients with major depressive disorder correlated response to the dexamethasone suppression test (DST) with clinical response to antidepressants. Nonsuppression on the DST predicted good response to noradrenergic drugs; suppression predicted good response to serotonergic drugs.

Antidepressive Agents↗
PubMed1980

Subacute toxicity of technical fenitrothion in male rats.

Male CD-strain rats (100--125 g) received fenitrothion by oral gavage (2.5, 5.0, 10.0 or 20.0 mg/kg/day) for 30 consecutive days. Control animals received equivalent volumes of taurocholate vehicle. Animals were killed at 8, 15, 22 and 30 days during treatment and at 8, 15, 29, 57 and 85 days after terminating treatment. The brain plasma and erythrocyte cholinesterases, hepatic and renal non-specific carboxylesterases were assayed. Serum biochemical markers of hepatic function were measured. Histologically stained sections of liver were examined by light microscopy. Fenitrothion, at doses between 2.5 and 10 mg/kg body wt, caused few observable deleterious effects to male rats except those effects on tissue esterases associated with organophosphorus esters. Only 8 of 36 animals receiving the 20.0 mg/kg dose died, all in the first week of treatment. A dose-dependent decrease in tissue esterase activity was observed which persisted throughout the entire treatment period. Periodic signs of overt toxicity were observed only in animals receiving 20 mg/kg/day. Tissue esterase activities returned to control levels within 1 or 2 weeks of stopping treatment. No significant treatment-related changes were observed by serum biochemistry or by light microscopy.

Animals↗
PubMed1979

Randomised trial comparing buprenorphine and diamorphine for chest pain in suspected myocardial infarction.

Buprenorphine, a new powerful analgesic agent, was used to treat chest pain in patients with suspected myocardial infarction. Initial studies showed no significant changes in systemic or pulmonary artery blood pressure or in heart rate after intravenous buprenorphine. Sublingual buprenorphine also appeared effective in relieving pain, but its onset of action was considerably delayed compared with the intravenous route. A randomised double-blind controlled trial of equivalent doses of buprenorphine and diamorphine showed no significant difference between the drugs in terms of pain relief and duration of action. The occurrence of nausea, vomiting, and other side effects was similar in the two groups. The onset of action of buprenorphine was slightly but significantly slower than that of diamorphine. Since buprenorphine seems to be comparable with diamorphine in action and is not a controlled drug, it may prove useful in both general and hospital practice.

Buprenorphine↗
PubMed1976

Formation of hybrid concanavalin A molecules by subunit exchange.

Mixing of native concanavalin A (Con A) and its dimeric succinylated derivative (succinyl-Con A) in glycine-HCl buffer, pH 4.5, resulted in the formation of a new chemical species that could be separated as a unique fraction by DEAE-cellulose chromatography or by gel electrophoresis. The molecular weight of this new component, which contained the subunits (Mr= 26,000) of native Con A and its succinyl derivative in equimolar amounts, was 50,000 at both pH 5 and pH 7. These data suggest that subunit exchange between 2 chemically distinct Con A molecules yields a hybrid molecule consisting of one protomer of native Con A and one protomer of succinyl-Con A. Similar exchange reactions and hybrid molecules were also observed after mixing acetyl-Con A and succinyl-Con A. These procedures provide several new chemical variants of the Con A molecule that may be useful for the analysis of lectin-cell surface interactions.

Binding Sites↗
PubMed1976

Monovalent derivatives of concanavalin A.

Monovalent dimers of concanavalin A (Con A) have been prepared by a combination of succinylation and photoaffinity labeling. Partial derivatization of native Con A using the photoaffinity label, p-azidophenyl-alpha-D-mannopyranoside, followed by affinity chromatography yielded a fraction that consisted of dimers with a single saccharide-binding site at pH 5. These monovalent dimers formed divalent tetramers at pH 7. In order to achieve a monovalent dimer at this pH, the divalent tetramers were succinylated by previously developed methods. Ultracentrifugation, equilibrium dialysis, and chromatographic experiments indicated that the resultant preparations consisted mainly of monovalent dimers which showed subunit exchange to yield about 15% divalent dimers after 12 hr at physiological pH. Freshly prepared material failed to agglutinate sheep erythrocytes at concentrations 500-fold higher than native tetravalent Con A. In addition, they showed saturating dose-response curves of mitogenic stimulation of mouse splenic lymphocytes. These curves resembled those of divalent succinyl-Con A but not those of the native molecule. Further development of methods for preparing stable monovalent derivatives of Con A should allow a refined analysis of the effects of lectin valence at the cell surface.

Affinity Labels↗
PubMedDate not supplied

Hindbrain stroke in children caused by extracranial vertebral artery trauma.

Hindbrain transient ischemic attacks (TIAs) culminating in posterior circulation stroke are described in five children. Atlanto-axial subluxation and angiographical documentation of C1 to C2 level arterial pathology are documented in one patient. Four additional patients with nearly identical clinical presentations, posterior fossa TIAs, stroke and basilar angiographical pathology are reviewed. A mechanical traumatic etiology is suggested. Unexplained transient repeated brain stem and/or cerebellar sympotomatology may be due to extracranial vetebral artery stenosis or occlusion by atlanto-axial instability. After appropriate documentation, stabilization may prevent further TIAs or strokes.

Atlanto-Occipital Joint↗