Family physicians' perceptions of academic detailing: a quantitative and qualitative study

Background  

The efficacy of academic detailing in changing physicians' knowledge and practice has been the subject of many primary research publications and systematic reviews. However, there is little written about the features of academic detailing that physicians find valuable or that affect their use of it. The goal of our project was to explore family physicians' (FPs) perceptions of academic detailing and the factors that affect their use of it.     

Interleukin 6 Influences Germinal Center Development and Antibody Production via a Contribution of C3 Complement Component

Mice rendered deficient for interleukin (IL) 6 by gene targeting were evaluated for their response to T cell–dependent antigens. Antigen-specific immunoglobulin (Ig)M levels were unaffected whereas all IgG isotypes showed varying degrees of alteration. Germinal center reactions occurred but remained physically smaller in comparison to those in the wild-type mice. This concurred with the observations that molecules involved in initial signaling events leading to germinal center formation were not altered (e.g., B7.2, CD40 and tumor necrosis factor R1). T cell priming was not impaired nor was a gross imbalance of T helper cell (Th) 1 versus Th2 cytokines observed. However, B7.1 molecules, absent from wild-type counterparts, were detected on germinal center B cells isolated from the deficient mice suggesting a modification of costimulatory signaling. A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6–deficient mice. Indeed, C3 provided an essential stimulatory signal for wild-type germinal center cells as both monoclonal antibodies that interrupted C3-CD21 interactions and sheep anti–mouse C3 antibodies caused a significant decrease in antigen-specific antibody production. In addition, germinal center cells isolated from C3–deficient mice produced a similar defect in isotype production. Low density cells with dendritic morphology were the local source of IL-6 and not the germinal center lymphocytes. Adding IL-6 in vitro to IL-6–deficient germinal center cells stimulated cell cycle progression and increased levels of antibody production. These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses.     

Round table conference on clinical trials for the treatment of sepsis Brussels,March 12–14, 1994

The Proceedings of the Round Table Conference will be published as volume 19, in the series Update in Intensive Care and Emergency Medicine (Springer Verlag) in January, 1995.     

A cDNA for the estradiol-regulated 24K protein: Control of mRNA levels in MCF-7 cells

We have previously demonstrated an estradiol-regulated 24 kDa (24K) protein in human breast cancer tissue culture cells and human tumor biopsies. The presence of 24K correlates well with the presence of steroid hormone receptors. In order to further study the hormonal regulation of the 24K protein and gene, we have isolated cDNA clones corresponding to the 24K mRNA.Poly(A)⁺ RNA isolated from the MCF-7 human breast cancer cell line was translated in a cell-free translation system containing [³⁵S]-methionine. The translation products were immunoprecipitated with a 24K monoclonal antibody, and thein vitro synthesis of 24K protein was confirmed by sodium dodecylsulfate (SDS) polyacrylamide gel electrophoresis. The same poly(A)⁺ RNA was used to construct an oligo(dT)-primed cDNA library in thegt11 expression vector system. The library was screened with a highly specific polyclonal antibody raised against 24K protein purified by immunoaffinity chromatography. Four recombinant clones reacting with the antibody by virtue of antigen expression were isolated and three were used in hybridization-selected translation. Three clones were able to hybridize specifically to a messenger RNA (mRNA) that yielded a Mr 24,000 protein when translatedin vitro and analyzed by SDS/polyacrylamide gel electrophoresis. This protein was also immunoprecipitable by the 24K monoclonal antibody. MCF-7 mRNA size fractionated by formaldehyde-agarose gel electrophoresis was transferred to nitrocellulose paper and hybridized to a nick-translated 24K cDNA clone. A single band of hybridization corresponding to a mRNA size of approximately 0.9–1.0 kilobase (kb) was observed. Using this same technique, 24K cDNA was hybridized to mRNA extracted from MCF-7 cells that had been treated for varying periods with either estradiol, nafoxidine, or tamoxifen. The 24K mRNA was elevated by the addition of estradiol, and clearly diminished by nafoxidine and tamoxifen.These results demonstrate that we have isolated cDNA clones for the study of the hormonal regulation of the 24K gene in breast cancer cells, and have shown that the mRNA is regulated by estradiol.     

Reduced cortical noradrenergic neurotransmission is associated with increased neophobia and impaired spatial memory in aged rats

In the present study, young (5-month-old (mo)) and aged (24 mo) adult male Fischer-344 (F344) rats were assigned to experimental groups based upon their performance of a reference memory task in the Morris water maze and reactivity to a novel palatable taste in a gustatory neophobia task. Levels of norepinephrine (NE) and its metabolite 3-methoxy-4-hydroxy-phenylglycol (MHPG) were assayed via high performance liquid chromatography (HPLC) in brain regions associated with the locus coeruleus (LC)-hippocampus-cortex system and A1/A2-hypothalamic system. Binding of ligands specific for alpha-1, alpha-2, beta-1, and beta-2 receptors was assessed in hippocampus and cortex with receptor autoradiography. Impaired acquisition and retention of the water maze task and gustatory neophobia in aged rats was primarily associated with decreased NE activity in cingulate cortex (CC) as indicated by a significant reduction in the MHPG/NE ratio coupled with increased NE content. No significant changes in adrenergic receptor binding were detected in any region sampled. The results suggest that an aging-related reduction in cortical NE neurotransmission is associated with the expression of increased neophobia and deficits in spatial learning and memory performance occurring with advanced age in rats.