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Biomedical subjects

I Fraser

Publications and source records attributed to I Fraser.

At least 19 recordsLinked to original sources
PubMed1996

Involvement of specific macrophage-lineage cells surrounding arterioles in barrier and scavenger function in brain cortex.

The transport of solutes between blood and brain is regulated by a specific barrier. Capillary endothelial cells of brain are known to mediate barrier function and facilitate transport. Here we report that specific cells surrounding arterioles, known as Mato's fluorescent granular perithelial (FGP) cells or perivascular microglial cells, contribute to the barrier function. Immunohistochemical and in situ hybridization studies indicate that, in normal brain cortex, type I and type II macrophage scavenger receptors are expressed only in FGP/perivascular microglial cells, and surface markers of macrophage lineage are also detected on them. These cells mediate the uptake of macromolecules, including modified low density lipoprotein, horseradish peroxidase, and ferritin injected either into the blood or into the cerebral ventricles. Accumulation of scavenged materials with aging or after the administration of a high-fat diet results in the formation of honeycomb-like foam cells and the narrowing of the lumen of arterioles in the brain cortex. These results indicate involvement of FGP/perivascular microglial cells in the barrier and scavenger functions in the central nervous system.

Adult↗
PubMed1996

Inhibition of dihydropyrimidine dehydrogenase by 5-propynyluracil, a metabolite of the anti-varicella zoster virus agent netivudine.

OBJECTIVE: To study the effects of the anti-herpetic drug netivudine on dihydropyrimidine dehydrogenase activity in elderly volunteers and to relate them to concentrations of netivudine and its metabolite 5-propynyluracil. METHODS: Three groups of eight elderly volunteers received 400 or 800 mg netivudine or placebo once daily for 8 days. Plasma netivudine, 5-propynyluracil, and uracil, an indirect measure of dihydropyrimidine dehydrogenase activity, were assayed before the first dose and on days 2, 3, 5, 7 and 8. Full plasma profiles of netivudine and 5-propynyluracil were determined after the last dose. RESULTS: Plasma uracil was unquantifiable in all subjects before the first dose and at all time points in the placebo group. In recipients of netivudine it reached a plateau between days 3 and 5, with mean values of 23.2 and 23.5 mumol/L on day 8 in the subjects who received 400 and 800 mg. Plasma netivudine concentrations were approximately dose proportional, but 5-propynyluracil concentrations were similar in both groups. The half-maximal rise in plasma uracil occurred after a cumulative 5-propynyluracil exposure of 120 mumol/L.hr; such exposures will be achieved even after doses as low as 50 to 100 mg daily. CONCLUSIONS: Netivudine dosing produces complete inhibition of plasma dihydropyrimidine dehydrogenase. Coadministration with the antimetabolite 5-fluorouracil will require a substantial reduction in 5-fluorouracil dose to avoid toxicity but may also improve the therapeutic index of 5-fluorouracil.

Aged↗
PubMed1995

Chondroradionecrosis of the larynx: still a diagnostic dilemma.

Following radiation treatment for carcinoma of the larynx it may be very difficult to differentiate between persistent or recurrent tumour and severe radiation effects particularly chondroradionecrosis. Despite repeated negative biopsy it may be necessary to perform total laryngectomy where the concern about persistent cancer remains and the larynx is non-functioning. We report nine cases presenting as chondroradionecrosis over a five-year period. Two patients settled on medical treatment. Of seven patients treated with laryngectomy the histology on two revealed residual or recurrent carcinoma. We outline the dilemmas in diagnosis and propose management strategies to deal with this condition including recommendations for prevention and treatment.

Adult↗
PubMed1995

The inter-relationship of premenstrual symptoms.

The prospective symptom reports of women seeking treatment for premenstrual symptoms and control subjects was investigated. In order to compare symptom reports from premenstrual symptom sufferers and control subjects a method of combining and analysing prospectively collected menstrual cycle symptom data is required. A technique that uses the time of onset of menses and the time of ovulation (as measured by urinary luteinizing hormone excretion) to standardize each cycle into 14 time points was developed. Summary factors were then empirically derived from data collected prospectively from 30 premenstrual symptom sufferers and 19 control subjects. Twenty-two mood symptoms were summarized into a single factor and the 29 most frequently occurring physical symptoms were summarized into two factors. Factor scores were calculated on the basis of these factors and the effect of time during the menstrual cycle on these scores examined. Both physical symptom factor scores increased significantly in the luteal phase for both the premenstrual symptom sufferer group and the control group. The single mood factor score increased significantly in the luteal phase for the premenstrual sufferer group but not for the control group, suggesting that the only qualitative difference between the groups was the presence of cyclic mood symptoms in the premenstrual symptom sufferer group. The premenstrual symptom sufferer group recorded significantly higher scores on each of the three factors than the control group. The correlation between the scores on each of the factors over three cycles was high both in the follicular and luteal phase suggesting that these factor scores provide a reproducible measure of menstrual cycle symptomatology.

Adult↗
PubMed1994

Use of surface molecules and receptors for studying macrophages and mononuclear phagocytes.

Members of the mononuclear phagocyte system use their extensive repertoire of cell surface receptors to interact with their external environment. A number of different assays are available for the study of these molecules and their many functions. In this paper we describe how monoclonal antibodies may be generated against macrophage molecules, and discuss how screening strategies aimed at producing functionally active reagents may be devised. Using the macrophage mannose and scavenger receptors as examples, we describe assays for determining macrophage adhesion to culture plastic surfaces, endocytosis of soluble ligands and phagocytosis of particles in vitro. These assays may be used in the production of inhibitory monoclonal antibodies, as well as in studies of the regulation of macrophage phenotype and activity.

Animals↗
PubMed1994

Intestinal anastomosis with a skin stapler: a safe and efficient method in humans.

A method of intestinal anastomosis with a skin stapler has been used successfully in 39 patients to form 40 anastomoses. The method has been employed in elective and emergency surgery, in small and large intestine, for a variety of pathological conditions and in the presence of obstruction, sepsis and soiling. Bowel anastomosis with a skin stapler is safe, simple and efficient in time and materials.

Adult↗
PubMed1994

Upregulation of the macrophage scavenger receptor in response to different forms of injury in the CNS.

The monoclonal antibody 2F8 was used to localize the macrophage scavenger receptor by immunohistochemistry. In control adult mice, macrophage scavenger receptor expression in the brain was restricted to stromal and epiplexus macrophages of the choroid plexus, meningeal macrophages and to perivascular sites. Microglia did not express the receptor. In the developing mouse brain, macrophage scavenger receptor expression was high on meningeal macrophages and detectable on immature microglia in the supraventricular corpus callosum, cingulum, cavum septum and the periaqueductal area. In the aged mouse brain, the pattern of macrophage scavenger receptor expression was no different from that in the young adult brain. Macrophage scavenger receptor expression on resident microglia and recruited macrophages was detected 24 h after an intrahippocampal injection of either lipopolysaccharide or kainic acid. Macrophage scavenger receptor expression was also detected in microglia 3 days after optic nerve crush both in the nerve segment distal to the crush site and in the superior colliculus. These studies indicate a potential role for the macrophage scavenger receptor in the CNS in the clearance of debris during acute neuronal degeneration.

Animals↗
PubMed1994

Plasma half-lives and bioavailability of human monoclonal Rh D antibodies BRAD-3 and BRAD-5 following intramuscular injection into Rh D-negative volunteers.

Two human MoAbs, BRAD-3 (an IgG3 anti-D) and BRAD-5 (an IgG1 anti-D), were produced from Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines grown in hollow fibre bioreactors. Six Rh D-negative male volunteers were injected intramuscularly with anti-D; two received BRAD-3 (approx. 1500 micrograms, 2600 IU), two were given BRAD-5 (300 micrograms, 2000 IU), and two had polyclonal anti-D immunoglobulin (500 IU, approx. 100 micrograms anti-D). Levels of anti-D in plasma samples taken up to 42 days later were measured by a sensitive AutoAnalyser method. The half life of BRAD-5 (mean 22.2 days) was greater, and that of BRAD-3 (mean 10.2 days) less than that of polyclonal anti-D (mean 15.6 days). The bioavailability (plasma uptake) of the MoAbs (mean 33.9%) was less than that of the polyclonal anti-D (mean 60.3%). BRAD-3 and BRAD-5 may be suitable for use in antenatal and post-natal prophylaxis against Rh D haemolytic disease of the newborn.

Antibodies, Monoclonal↗
PubMed1993

Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor.

Macrophages interact with other cells and components of the extracellular environment by means of adhesion receptors. Adhesion to artificial substrata in vitro facilitates isolation of macrophages, and has been used to generate antibodies that inhibit their migration in vivo. Unlike other cell types, macrophages attach to tissue culture plastic in the absence of divalent cations. Here we use an adhesion assay exploiting this property to isolate a rat monoclonal antibody, 2F8, which totally inhibits divalent cation-independent adhesion of murine macrophages to tissue culture plastic in the presence of fetal calf serum. Immunoprecipitation from macrophages and stably transfected Chinese hamster ovary cells revealed that the antigen recognized by monoclonal 2F8 is identical to murine macrophage scavenger receptor. We propose a novel function for this molecule, previously described as an endocytic receptor, thus providing a mechanism for mononuclear phagocyte recruitment to and retention in ligand-rich tissues such as in atherosclerotic lesions.

Animals↗