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Biomedical subjects

R Boyd

Publications and source records attributed to R Boyd.

At least 55 records · Page 3Linked to original sources
PubMed1999

Prospective single blinded randomised controlled trial of two orally administered activated charcoal preparations.

OBJECTIVES: To compare two activated charcoal preparations (Carbomix and Actidose-Aqua) in terms of amount ingested and incidence of vomiting after ingestion. METHODS: Single blinded prospective randomised controlled trial. RESULTS: The mean amount of charcoal ingested was Carbomix 26.5 g, Actidose-Aqua 19.5 g. The mean difference was 7 g (95% confidence interval (CI) 1.5 to 12.4 g). The incidence of vomiting was for the Carbomix 6% and the Actidose-Aqua 8%. The mean difference in vomiting was 2% (95% CI -0.8 to 4.8) CONCLUSIONS: Carbomix administration results in an increased amount of activated charcoal ingested after oral administration. Rates of vomiting after activated charcoal administration were low when compared with previously reported rates.

Antidotes↗
PubMed1998

IL-12 regulates VEGF and MMPs in a murine breast cancer model.

In a murine model of breast cancer, IL-12 therapy exerts potent anti-angiogenic effects which contribute to tumor regression. After 7 days of treatment, levels of tumor VEGF protein decline markedly and are undetectable at 14 days. This decline is accompanied by a fall in MMP-9 and, as the tumors regress, an increase in its natural inhibitor, TIMP-1. A cell line established from the primary tumor produced VEGF in vitro. IFN-gamma reduced tumor cell production of VEGF over a 24-hr period in vitro, suggesting that IL-12-induced IFN-gamma may be responsible for the decline in VEGF levels in vivo. There is also in vitro evidence that IL-12 regulates stromal cell interactions, leading to decreased MMP-9 and increased TIMP-1 production. Thus, we suggest that at least 2 mechanisms are involved in IL-12 regulation of angiogenesis, removing the pro-angiogenic stimulus and blocking the release and activity of MMPs.

Animals↗
PubMed1998

Receptor-specific allelic exclusion of TCRV alpha-chains during development.

Expression of a single Ag receptor on lymphocytes is maintained via allelic exclusion that generates cells with a clonal receptor repertoire. We show in normal mice and mice expressing functionally rearranged TCR alphabeta transgenes that allelic exclusion at the TCR alpha locus is not operational in immature thymocytes, whereas most mature T cells express a single TCRV alpha-chain. TCRV alpha allelic exclusion in mature thymocytes is regulated through a CD45 tyrosine phosphatase-mediated signal during positive selection. Using functional and genetic systems for selection of immature double TCRV alpha+ thymocytes, we show that peptide-specific ligand recognition provides the signal for allelic exclusion, i.e., mature T cells maintain expression of the ligand-specific TCRV alpha-chain, but lose the nonfunctional receptor. Whereas activation of TCRV beta-chains or CD3epsilon leads to receptor internalization, TCRV alpha ligation promotes retention of the TCR on the cell surface. Although both TCRV alpha- and TCRV beta-chains trigger phosphotyrosine signaling, only the TCRV beta-chain mediates membrane recruitment of the GTPase dynamin. These data indicate that TCRV alpha-directed signals for positive selection control allelic exclusion in T cells, and that developmental signals can select for single receptor usage.

Alleles↗
PubMed1998

Magnetic resonance assessment of inversion ankle injuries in children.

A cohort of ten children with X-ray negative inversion ankle injuries were studied using Magnetic Resonance Imaging. The images obtained were scored on six pathological criteria. Despite all ten having normal plain radiographs, 50 per cent were found to have direct evidence of growth plate injury. Seventy per cent of the cohort had periosteal elevation including all those with evidence of growth plate injury. This study supports previous work which suggested that children with 'X-ray' negative acute inversion ankle injuries who exhibited the clinical signs of injury to their lower fibular growth plate most probably have an undisplaced Salter-Harris Type 1 fracture of this structure, despite normal radiographs.

Ankle Injuries↗
PubMed1998

Mice lacking the transcription factor CIITA--a second look.

We have generated a second line of mice lacking a transcription factor thought to be a critical regulator of MHC class II gene expression, CIITA (for class II transactivator). Our and the previously published lines differ in the deletion that was engineered and by the fact that we removed the neomycin-resistance promoter and structural gene via the cre-loxP recombination system. Characterization of our line led to two new findings. First, a substantial number of cells can express class II molecules in the absence of CIITA, albeit at 5-fold reduced levels, most notably dendritic cells in s.c. lymph nodes; therefore, the CIITA gene cannot be an absolute 'master gene' controlling the expression of class II molecules, as had been thought. Second, in contrast to recent results on human cell lines, CIITA is not critically involved in the IFN-gamma-induced up-regulation of MHC class I genes.

Animals↗
PubMed1998

Electrical potential difference between exocelomic fluid and maternal blood in early pregnancy.

The forces that drive transfer of solutes between maternal blood and embryo in early human pregnancy are poorly understood. The aim of this study was to determine whether there is an electrical potential difference (PD) between maternal blood and the exocelomic cavity and between maternal blood and the amniotic cavity in the normal human conceptus at or before 10 wk of pregnancy. We measured PD between a saline-filled catheter in a forearm vein of women undergoing termination of pregnancy for psychological reasons in the first trimester and a second saline-filled catheter in the exocelomic cavity or amniotic cavity of their conceptus. The mean (+/- SE) maternal blood/exocelomic cavity PD in eight women was 8.7 +/- 1.0 mV and the mean maternal blood/amniotic cavity PD in four of the women was 6.7 +/- 1.3 mV, embryo side negative for both sets of measurement. These data show that there is a PD between maternal and embryonic extracellular fluid in the first trimester that will directly influence exchange of ions between the two compartments.

Amniotic Fluid↗
PubMed1997

Induction of tolerance with nondepleting anti-CD4 monoclonal antibodies is associated with down-regulation of TH2 cytokines.

BACKGROUND: Induction of tolerance with anti-CD4 has mainly focused on monoclonal antibodies (mAbs) that deplete CD4+ T cells. In this study, the mechanisms by which nondepleting anti-CD4 mAbs induce tolerance in the Dark Agouti to PVG rat heart graft model were examined. METHODS: Five anti-CD4 mAbs were tested. Immunohistology and cytokine mRNA profiles were analyzed within grafts. Effects of combining anti-CD4 therapy with alloantibody (alloAb), interleukin (IL)-4, and anti-IL-4 mAb were also examined. RESULTS: All mAbs tested induced indefinite graft survival (>150 days), with blocking of alloAb production. Exogenous alloAb did not restore rejection. Similar T cell receptor alphabeta+, CD8+, IL-2 receptor+ T cell, macrophage, and natural killer cell infiltration and comparable MHC II and intercellular adhesion molecule-1 levels were seen in rejecting and tolerant grafts. mRNA for IL-2, interferon-gamma, lymphotoxin, tumor necrosis factor-alpha, transforming growth factor-beta, cytolysin, and granzyme-A/B was comparable, although inducible nitric oxide synthase was slightly reduced in tolerant grafts. IL-4 and IL-5 were significantly reduced in tolerant grafts, although IL-6, IL-10, and IL-13 levels were similar; this was consistent with partial T helper (Th)2 response inhibition, which was also manifested by inhibited alloAb. The combination of alloAb, IL-4, or anti-IL-4 mAb with anti-CD4 did not prevent tolerance induction. CONCLUSIONS: This study demonstrated that anti-CD4 mAb therapy did not inhibit activation and infiltration of Th1 and CD8+ effector T cells. Preferential induction of Th2 responses, especially IL-4, was not essential for the induction of tolerance. Our studies also found no evidence to support induction of anergy or transforming growth factor-beta as mechanisms of tolerance induction. These results question whether IL-4 is required for induction of transplantation tolerance.

Animals↗
PubMed1997

Autoantibody production and cytokine profiles of MHC class I (beta2-microglobulin) gene deleted New Zealand black (NZB) mice.

We established a colony of MHC class I deleted (knockout) NZB mice, which lack the beta2 microglobulin gene (NZB.beta2m-/-), to characterize the contribution of MHC class I to the thymic microenvironment abnormalities, autoantibody production and lupus-like disease of NZB mice. Using an extensive panel of well characterized monoclonal antibodies defining thymic epithelial and other stromal elements, we demonstrated that deletion of MHC class I molecules does not change the thymic abnormalities, including the presence of a cortical epithelial cell free region, ectopic expression of medullary epithelial antigens, and the irregular shape of the medullary epithelial network of NZB mice. Moreover, the decreased staining of MTS 33(+) cells, a marker of premature thymocyte maturation, was also seen in NZB.beta2m-/-. However, although NZB.beta2m-/- mice had approximately the same levels of IgM and IgG anti-ss and dsDNA antibodies when compared to control NZB mice, there were significant alterations in the incidence and onset of anti-erythrocyte antibody levels. NZB.beta2m-/- had a lower incidence and a delayed onset of anti-erythrocyte autoantibody production compared to that seen in NZB mice. We also compared constitutive and PHA-P-driven levels of IFN-gamma, IL-4, IL-6, and IL-12 in cells from NZB, NZB.beta-/-2, and control C57BL/6 mice. Mitogen stimulated cells showed a decreased IFN-gamma, and a marked increase in IL-6 and IL-12 in NZB and NZB.beta2m-/- mice.

Animals↗
PubMed1997

Topsoil (0-5 cm) composition in eight arctic catchments in northern Europe (Finland, Norway and Russia).

Frozen topsoil samples (0-5 cm) were collected during March/April 1994 in eight Arctic catchments in northern Europe (four in Russia, three in Finland, one in Norway), at different distances and in different wind directions from the emissions of the Russian mining, roasting and smelting industry on the Kola Peninsula. Between 14 and 25 sites were sampled in each of the eight catchments ranging in size from 12 to 35 km2. Results show that close to the smelters in Monchegorsk and Nikel, topsoil is clearly enriched in Ag, As, Bi, Cd, Co, Cr, Cu, Fe, Ni, Pb, Sb, Se, Te and V. Cu and Ni median contents in topsoils collected close to Monchegorsk are about 600 times higher than in the Finnish catchments. The effect of open-cast mining and waste dumps of alkaline rocks from the nephelinite industry near Kirovsk can be seen in the elevated contents of Al, Ba, K, La, Mn, Na, Sr, Ti, Y and Zn in topsoil collected in a nearby catchment. For many elements, however, variations observed in single catchments are as great as the total regional variation. Several elements (e.g. Cd, Hg, Cu, Ni, Pb, S, Zn) show strong positive correlation between the organic content of the sample and the element content observed. Thus it is necessary to determine the organic content of the samples and correct the element levels when using depth-related soil samples (here, the 0-5 cm topsoil layer) for regional mapping.

Journal Article↗
PubMed1997

The interferon regulatory transcription factor IRF-1 controls positive and negative selection of CD8+ thymocytes.

Little is known about the molecular mechanisms and transcriptional regulation that govern T cell selection processes and the differentiation of CD4+ and CD8+ T cells. Mice lacking the interferon regulatory transcription factor-1 (IRF-1) have reduced numbers of mature CD8+ cells within the thymus and peripheral lymphatic organs. Here we show that positive and negative T cell selection of two MHC class I-restricted TCR alphabeta transgenes, H-Y and P14, are impaired in IRF-1-/- mice. The absence of IRF-1 resulted in decreased expression of LMP2, TAP1, and MHC class I on thymic stromal cells. Despite decreased MHC class I expression on IRF-1-/- thymic stromal cells, the defect in CD8+ T cells development did not reside in the thymic environment, and IRF-1-/- stromal cells can fully support development of CD8+ thymocytes in in vivo bone marrow chimeras and in vitro reaggregation cultures. Moreover, IRF-1-/- thymocytes displayed impaired TCR-mediated signal transduction, and the induction of negative selection in TCR Tg thymocytes from IRF-1-/- mice required a 1000-fold increase in selecting peptide. We also provide evidence that IRF-1 is mainly expressed in mature, but not immature, thymocytes and that expression of IRF-1 in immature thymocytes is induced after peptide-specific TCR activation. These results indicate that IRF-1 regulates gene expression in developing thymocytes required for lineage commitment and selection of CD8+ thymocytes.

Animals↗
PubMed1997

Agonist peptide modulates T cell selection thresholds through qualitative and quantitative shifts in CD8 co-receptor expression.

Engagement of the TCR is a pivotal step in thymocyte development, ultimately resulting in the survival (positive selection) or loss (negative selection) of developing T cells. The roles of peptides and stromal cell interactions necessary for these selection events, however, are still poorly understood. To investigate the effects of agonist peptide in positive selection, we used a novel cell suspension model for in vitro thymic positive selection in adults. Target thymocytes from H-2Db-restricted TCR transgenic mice, specific to the lymphocytic choriomeningitis virus (LCMV) peptide bred on a non-selecting MHC background (H-2d or TAP-1-/-), were co-cultured with freshly isolated H-2b thymic stromal cells. In the presence of selecting stroma the nominal agonist LCMV peptide induced apoptosis at high concentrations and at low concentrations enhanced the efficiency of positive selection both in numbers of cells 'rescued' and kinetics of appearance of selected single-positive cells. We further illustrate down-modulation of CD8 alpha beta or CD8 beta at high but non-deleting concentrations of agonist peptide. This highlights the ability of the T cell, within the window of positive selection, to modify surface co-receptors both qualitatively and quantitatively in response to increasing avidity TCR-peptide-MHC interactions. The direct consequence of this would be to lower the total signaling events below the threshold for apoptosis induction. Hence if self peptide were not presented in sufficient quantities in the thymus, autoreactive cells may escape deletion and may actually be positively selected.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1997

The hip in children with cerebral palsy. Predicting the outcome of soft tissue surgery.

This study reviewed 56 hips in 37 children with cerebral palsy who had undergone an adductor tenotomy alone or in combination with an anterior obturator neurectomy. The mean review period was 5.3 years. At latest review, 25 of 30 (83%) hips with a preoperative migration percentage of less than 40% were reduced, but 20 of 26 (77%) hips with a preoperative migration percentage of 40% or more were subluxated or dislocated. Surgery was unsuccessful for 13 of 15 hips with an acetabular index of more than 27 degrees. Percutaneous adductor tenotomy alone was as effective as the combination of an open procedure with an anterior obturator neurectomy. The age at the time of surgery did not have a significant effect on the outcome. The preoperative migration percentage was the only significant predictor of outcome in this group of children.

Age Factors↗
PubMed1997

Atropine poisoning after drinking Indian tonic water.

Poisoning is one of the most common reasons for acute medical admission to hospital in the UK. However, certain poisons are rarely implicated. Two unusual cases involving poisoning with atropine are presented. The clinical features were classical, but the way in which the patients became poisoned by drinking contaminated Indian tonic water was most unusual.

Adult↗
PubMed1997

Cholecystogastrocolonic fistula with intrahepatic abscess: a rare complication of biliary stone disease.

A 52-year-old woman exhibited both a cholecystogastrocolonic fistula and intrahepatic abscess. Biliary-enteric fistulas are unusual complications of gallstone disease, and multiple, complex fistulas are extremely uncommon. Hepatic abscesses are also unusual complications of gallstone disease. The combination of a complex biliary-enteric fistula and hepatic abscess arising from gallstone disease has not been reported. In our patient, surgery was prompted by the hepatic abscesses; the fistula was not recognized preoperatively. We elected to resect gallbladder, gastric antrum, and transverse colon en bloc with primary closure of the gastric defect and, because the colon had not been "prepped," we created a right transverse colostomy and left mucus fistula. Under ideal circumstances, the anatomy of biliary fistulas is characterized preoperatively and managed definitively with a single procedure.

Biliary Fistula↗
PubMed1997

Gender and ethnic differences in readiness to change smoking behavior.

The Transtheoretical Model has been used extensively to investigate smoking behavior. However, gender and ethnic differences in key constructs of the Transtheoretical Model have not been fully evaluated. This gap in the literature is addressed in this brief report. We examined gender and ethnic differences in stages of change (readiness to quit smoking), perceived pros (benefits) and cons (costs) of smoking, and self-efficacy (confidence) in ability to quit among smokers seeking cessation treatment. Participants were 330 smokers ages 18 to 75, who responded to advertisements for a free minimal-contact smoking cessation program. Thirty percent of women were confident they could quit smoking compared to 53% of men. Women reported more pros of smoking and more cons of smoking than men. White smokers reported more pros of smoking than African smokers. These findings highlight the need to bolster quitting confidence among women and to identify alternatives to the pros of smoking relevant to women smokers.

Adolescent↗