On learning molecular biology in François Gros' lab in the late 1970s and early 1980s.

Although reflection is obviously crucial in molecular biology, experimentation is nonetheless the basis of most major advances. I was lucky to begin my research career at a particularly interesting time, and privileged to have spent a number of years in Francois Gros' laboratory at the Institut Pasteur. His influence, and that of his lab, were crucial in shaping my early career.

Frequency noise stabilisation of a 1550 nm external cavity diode laser with hybrid feedback for next generation gravitational wave interferometry.

Longer wavelength lasers will be needed for future gravitational wave detectors that use cryogenic cooling of silicon based test-mass optics. Diode lasers with a 1550 nm wavelength output are potential seed light sources for such a detector, however diode laser devices have a different spectral profile and higher frequency noise than the solid state lasers used in current detectors. We present a frequency stabilisation system for a 1550 nm external cavity diode laser capable of reducing the laser frequency noise to a level of 0.

A survey of recipient client physician satisfaction with teleoncology services originating from thunder bay regional health sciences centre.

The objective of this work was to investigate end user satisfaction and perceived efficacy on the part of client physicians for teleoncology services in Northwestern Ontario. A survey of 98 referring physicians from 17 remote communities in Northwestern Ontario was undertaken primarily to determine overall client physician satisfaction with the teleoncology process. The survey also investigated perceived problems and explored potential solutions.

End-of-life issues for aboriginal patients: a literature review.

Objective: To understand some of the cross-cultural issues in providing palliative care to aboriginal patients.

Sources Of Information: MEDLINE (1966 to 2005), CINAHL, PsycINFO, Google Scholar, and the Aboriginal Health Collection at the University of Manitoba were searched. Studies were selected based on their focus on both general cross-cultural caregiving and, in particular, end-of-life decision making and treatment.

Single-dose intrathecal analgesia to control labour pain: is it a useful alternative to epidural analgesia?

Objective: To examine the safety and efficacy of single-dose spinal analgesia (intrathecal narcotics [ITN]) during labour.

Quality Of Evidence: MEDLINE was searched and the references of 2 systematic reviews and a meta-analysis were reviewed to find articles on obstetric analgesia and pain measurement. The 33 articles selected included 14 studies, 1 meta-analysis, and 2 systematic reviews, all providing level I evidence.

IL-13 acutely augments HIV-specific and recall responses from HIV-1-infected subjects in vitro by modulating monocytes.

We show in this study that acute exposure of PBMCs derived from HIV-infected subjects to IL-13 results in increased recall T cell lymphoproliferative responses against HIV-1 p24 (n = 30, p < 0.0001) and other recall Ags (influenza, n = 43, p < 0.0001; purified protein derivative tuberculin, n = 6, p = 0.

IL-13 alters mucociliary differentiation and ciliary beating of human respiratory epithelial cells.

In animal models of asthma, interleukin-13 (IL-13) induces goblet cell metaplasia, eosinophil infiltration of the bronchial mucosa, and bronchial hyperreactivity, but the basis of its effects on airway epithelia remain unknown. Lesions of the epithelial barrier, frequently observed in asthma and other chronic lung inflammatory diseases, are repaired through proliferation, migration, and differentiation of epithelial cells. An inflammatory process may then, therefore, influence epithelial regeneration.

Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif.

Two-hybrid screening in yeast with p73alpha isolated SUMO-1 (small ubiquitin-like modifier 1), the enzyme responsible for its conjugation, Ubc-9, and a number of novel SUMO-1-interacting proteins, including thymine DNA glycosylase, PM-Scl75, PIASx, PKY, and CHD3/ZFH. A subset of these proteins contain a common motif, hhXSXS/Taaa, where h is a hydrophobic amino acid and a is an acidic amino acid, that is shown to interact with SUMO-1 in the two-hybrid system. We show here that p73alpha, but not p73beta, can be covalently modified by SUMO-1.

Encapsulation in hollow fibres of xenogeneic cells engineered to secrete IL-4 or IL-13 ameliorates murine collagen-induced arthritis (CIA).

A strategy of gene therapy using IL-4 or IL-13 xenogeneic transfected cells encapsulated into permeable hollow fibres (HF) was used to treat CIA. Hydrogel-based hollow fibres were obtained from AN-69 copolymer, already known for its biocompatibility and tolerance in rodents. Permeability to IL-4 and lack of cell leakage from the fibres were ascertained in vitro and in vivo.

Interleukin-13 prevents autoimmune diabetes in NOD mice.

Interleukin (IL)-13 is a cytokine primarily produced by the T-helper (Th)-2 subset of lymphocytes that possesses powerful anti-inflammatory properties. Here, we have evaluated the impact of IL-13 treatment on development of type 1 diabetes in diabetes-prone nonobese diabetic (NOD) mice. Prolonged treatment with recombinant human IL-13 (hIL-13) markedly diminished the incidence of spontaneous type 1 diabetes in the mice.

Reduced tumorigenicity and augmented leukocyte infiltration after monocyte chemotactic protein-3 (MCP-3) gene transfer: perivascular accumulation of dendritic cells in peritumoral tissue and neutrophil recruitment within the tumor.

Monocyte chemotactic protein-3 (MCP-3) is a C-C chemokine that interacts with the CCR1, CCR2, and CCR3 receptors and has a spectrum of action encompassing T cells, NK cells, eosinophils, and dendritic cells (DC), in addition to mononuclear phagocytes. This broad spectrum of action prompted the present study aimed at assessing the antitumor activity of MCP-3 in a gene transfer approach and at providing information as to the actual in vivo leukocyte recruiting capacity of MCP-3. P815 mastocytoma cells transfected with the gene coding MCP-3 (P815/MCP-3) grew in syngeneic hosts and underwent rejection.

Administration of interleukin 13 to simian immunodeficiency virus-infected macaques: induction of intestinal epithelial atrophy.

Increase Th2 cytokine production may contribute to some clinical manifestations of HIV infection, and studies have suggested that IL-13 rather than IL-4 is involved in these conditions. We directly tested this hypothesis by administrating IL-13 to SIV-infected macaques. SIV-infected rhesus macaques received a daily subcutaneous injection for 21 days of either IL-13 (10 microg/kg/day) or a placebo.

Regulation of interleukin-13 receptor constituents on mature human B lymphocytes.

Human B cells stimulated through both their immunoglobulin and CD40 receptors up-regulate 745 +/- 51 interleukin (IL)-13 ligand binding sites with an affinity of 0.91 +/- 0.08 nM within 24 h.

Stable polarization of peripheral blood T cells towards type 1 or type 2 phenotype after polyclonal activation.

Polarization of T lymphocytes towards type 1 (T1) or type 2 (T2) subsets producing a distinct array of cytokines plays a role in several diseases and could be used for therapeutic intervention. Bearing this purpose in mind, we have established suitable in vitro conditions to drive resting polyclonal human T cells towards stable T1 or T2 polarization profiles. Unselected peripheral lymphocytes from normal donors were primed with soluble anti-CD3 monoclonal antibody in the presence of selected sets of recombinant (r) human cytokines.

Modulation of proinflammatory cytokine production in tumour necrosis factor-alpha (TNF-alpha)-transgenic mice by treatment with cells engineered to secrete IL-4, IL-10 or IL-13.

TNF-alpha is one of the major proinflammatory cytokines involved in the pathogenesis of chronic inflammatory joint disease, in human rheumatoid arthritis as well as in murine models of this disease. It was previously described that a highly destructive chronic spontaneous inflammatory arthritis develops in mice expressing a human TNF-alpha transgene modified with the 3' untranslated region of beta-globin. The present study investigates in this mouse model the effects of the anti-inflammatory cytokines IL-4, IL-10 and IL-13 administered in vivo on proinflammatory cytokine expression.

IL-13 induces CD34+ cells isolated from G-CSF mobilized blood to differentiate in vitro into potent antigen presenting cells.

Dendritic cells (DCs), which are antigen presenting cells of potential use in human antitumor vaccination trials, are presently the subject of intense investigation. Many recent studies have reported the possibility of generating ex vivo large numbers of DCs with high antigen presenting capacity by the culture of bone marrow or blood progenitors. In this study, we examined the differentiation into DCs of CD34+ progenitors isolated from the G-CSF mobilized blood of 3 healthy donors and 5 patients with breast cancer and cultured in the presence of GM-CSF + IL-13.

Monoallelically expressed gene related to p53 at 1p36, a region frequently deleted in neuroblastoma and other human cancers.

We describe a gene encoding p73, a protein that shares considerable homology with the tumor suppressor p53. p73 maps to 1p36, a region frequently deleted in neuroblastoma and other tumors and thought to contain multiple tumor suppressor genes. Our analysis of neuroblastoma cell lines with 1p and p73 loss of heterozygosity failed to detect coding sequence mutations in remaining p73 alleles.

The related cytokines interleukin-13 and interleukin-4 are distinguished by differential production and differential effects on T lymphocytes.

We have compared the production of the related cytokines IL-13 and IL-4 by T lymphocytes, and the effects of the two cytokines on these cells. IL-13 and IL-4 production differ in a number of respects. IL-13 is produced at higher levels than IL-4 by activated T lymphocytes, and its accumulation in the culture medium can be more prolonged, corresponding partly to differential mRNA accumulation and partly to a preferential depletion of IL-4 from the culture medium.

Interleukin-13 effects on activated monocytes lead to novel cytokine secretion profiles intermediate between those induced by interleukin-10 and by interferon-gamma.

We have examined in detail the activities of IL-13 on monokine production in vitro and compared its effects with those of IL-10 and IFN-gamma. IL-13 and IL-10 show qualitatively and quantitatively similar activities on cytokine production by monocytes when administered simultaneously with LPS i.e.

X-SCID B cell responses to interleukin-4 and interleukin-13 are mediated by a receptor complex that includes the interleukin-4 receptor alpha chain (p140) but not the gamma c chain.

This study investigates the effect of interleukin (IL)-4 mutant proteins and a monoclonal antibody to the IL-4 receptor alpha chain on IL-4 and IL-13 response by B cells from X-linked severe combined immunodeficiency (X-SCID) patients in which the common gamma chain (gamma c chain) gene mutations have been fully characterized and no gamma c chain expression was detected. In this gamma c chain gene knockout model, it was confirmed that the gamma c chain is essential for B cell responses to IL-2 but not for IL-4 or IL-13. Dose-response curves for X-SCID and normal B cell responses to IL-4 were indistinguishable, showing that the loss of the gamma c chain did not diminish the sensitivity of B cells to IL-4.

Interleukin-8 production by the human colon epithelial cell line HT-29: modulation by interleukin-13.

1. We have determined which cytokines induce and modulate the production of the chemokine interleukin-8 (IL-8) by the human colonic epithelial cell line HT-29. 2.

Inhibition of proliferation and clonal growth of human breast cancer cells by interleukin 13.

We tested the influence of recombinant human interleukin (rhIL)-l3 and rhIL-4 on clonal growth of human breast cancer cell lines. rhIL-13 and rhIL-4 inhibited clonal growth of three of nine lines to approximately 50% of controls (ED50, 0.5 ng/ml).

Interleukin-13 inhibits interleukin-2-induced proliferation and protects chronic lymphocytic leukemia B cells from in vitro apoptosis.

Human interleukin-13 (IL-13) acts at different stages of the normal B-cell maturation pathway with a spectrum of biologic activities overlapping those of IL-4. B chronic lymphocytic leukemia (B-CLL) is characterized by the accumulation of slow-dividing and long-lived monoclonal B cells, arrested at the intermediate stage of their differentiation. In vitro, B-CLL cells exhibit a spontaneous apoptosis regulated by different cytokines.

Interleukin-13 inhibits inducible nitric oxide synthase expression in human mesangial cells.

The synthesis of nitric oxide in inflammatory situations requires the expression of an inducible isoform of nitric oxide synthase (iNOS). Human mesangial cells (HMC) express an iNOS enzyme after exposure to multiple co-stimuli. In this study we have observed that while tumour necrosis factor-alpha, interleukin (IL)-1 beta, interferon-gamma and bacterial lipopolysaccharide (LPS) were unable to significantly induce NO synthesis when used alone, they induced an evident stimulation of NO synthesis when used in various combinations.