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Objective: To synthesize the literature on the effect of provision of personalised cancer risk information to individuals at population level risk on accuracy of risk perception and psychological responses., Methods: A systematic review and random effects meta-analysis of articles published from 01/01/2000 to 01/07/2017., Results: We included 23 studies. Immediately after provision of risk information 87% of individuals were able to recall the absolute risk estimate. Less than half believed that to be their risk, with up to 71% believing their risk to be higher than the estimate. Provision of risk information increased accuracy of perceived absolute risk immediately after risk information compared with no information (pooled RR 4.16 (95%CI 1.28-13.49), 3 studies). There was no significant effect on comparative risk accuracy (pooled RR 1.39 (0.72-2.69), 2 studies) and either no change or a reduction in cancer worry, anxiety and fear., Conclusion: These findings highlight the complex cognitive processes involved in the conceptualisation of risk., Practice Implications: Individuals who appear to understand and are able to recall risk information most likely do not believe it reflects their own risk., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Rituximab is a chimeric anti-CD20 monoclonal antibody that has revolutionised the treatment of many B-cell malignancies, and is now increasingly being used in non-malignant conditions such as auto-immune disorders. Serum rituximab levels are highly variable in patients receiving similar 'standard' approved doses. Little is known regarding the factors that affect serum rituximab concentration and that in turn may influence clinical outcome. In order to provide a tool that may ultimately enable patient specific dosing of rituximab therapy, we have validated a reliable, robust ELISA for the quantitation of serum rituximab levels to provide accurate pharmacokinetic (PK) data that will guide the optimisation of rituximab dosing regimes. Extensive validation of the assay was performed in order to utilise the assay for clinical applications. The within and between day plate coating reproducibility was tested and proved a robust starting platform for the assay. The within day precision for the assay was determined using spiked serum samples and was shown to have a coefficient of variation (CV) of <10% with an accuracy between 91 and 125%. The between day precision (CV) was <25% with an accuracy between 95 and 109%. Dilution linearity and parallelism were demonstrated. Spike recovery for all concentrations and donors was shown to be within +/-15% on average, with a CV below 10%. This assay is highly accurate and reproducible in determining the levels of rituximab in spiked serum samples. It meets stringent acceptance criteria, is fit for purpose, and is currently being applied to several clinical trials incorporating rituximab in the treatment of lymphoma. This assay represents a useful tool for clinical application of this widely used therapeutic., (2010 Elsevier B.V. All rights reserved.)

The effect of induction therapy with multiple doses of rituximab on the subsequent efficacy and toxicity of anti-CD20 radioimmunotherapy is unknown. We evaluated a novel protocol using 4 weekly infusions of 375 mg/m(2) rituximab followed by 2 fractions of (131)I-rituximab, preceded by a 100-mg/m(2) predose of rituximab, in relapsed indolent B-cell lymphoma. Induction therapy with rituximab significantly increased the effective half-life of (131)I-rituximab (P = .003) and high serum levels of rituximab after induction therapy correlated with increased effective half-life of the radioimmunoconjugate (P = .009). Patients with large tumor burdens experienced significant increases in the effective half-life of (131)I-rituximab between delivery of the first and second fractions (P = .007). Induction therapy with multiple doses of rituximab did not appear to compromise the clinical efficacy or increase toxicity of subsequent (131)I-rituximab radioimmunotherapy. The overall response rate was 94%, with complete response rate 50%. The median time to progression was 20 months, significantly longer than for the last qualifying chemotherapy (P = .001). Fractionation of (131)I-rituximab allowed cumulative whole-body doses of more than 120 cGy, approximately 60% greater than those previously achieved with a single administration of a murine radioimmunconjugate, to be delivered without significant hematologic toxicity.

Radioimmunotherapy (RIT) has emerged as an effective treatment for lymphoma, however the underlying mechanisms are poorly understood. We therefore investigated the relative contributions of antibody and targeted radiation to the clearance of tumor in vivo, using 2 different syngeneic murine B-cell lymphoma models. Although RIT with (131)I-anti-major histocompatibility complex class II (MHCII) was effective in targeting radiation to tumor, no improvement in survival was seen by escalating the radiation dose alone and there were no long-term survivors. In contrast, using the combination of (131)I anti-MHCII in the presence of unlabeled anti-idiotype (anti-Id), 100% prolonged disease-free survival was seen in both B-cell lymphoma models at the higher radiation dose. Using in vivo tracking we show that treatment with radiation plus anti-Id monoclonal antibody (mAb) results in a substantially greater reduction of splenic tumor cells than with either treatment alone. Prolonged survival could also be achieved using (131)I anti-MHCII plus the signaling anti-CD19 mAb. Furthermore, the ability of these anti-B-cell mAbs to improve survival with targeted radiotherapy appeared to correlate with their ability to initiate intracellular signal transduction. Together these data illustrate that using 1 mAb to target radiation to tumor and a second to induce cell signaling is an effective new strategy in RIT.

The three human alpha adrenergic receptor subtypes, alpha 1a, alpha 1b, and alpha 1c, have been cloned, expressed in COS-7 cells, and characterized pharmacologically. Competition binding studies of several adrenergic ligands with the three human receptor subtypes reveals a distinct pharmacological profile for each receptor subtype. RNase protection analysis demonstrates that the three receptor subtypes have different patterns of distribution in human tissue. The availability of the three human alpha 1 receptor subtypes will facilitate the development of subtype-selective alpha 1 antagonists for a variety of therapeutic indications.

The role of certain amino acids, dipeptides and organic acids as ligands to facilitate the intestinal absorption of zinc was investigated by using an in vivo procedure on ileal segments of adult rats. Ligand:zinc ratios equal to or less than 3:1 were optimal for amino acids and dipeptides such as L-glutamate, glycine, L-histidine, L-tryptophan and glycylglycine. An excess of ligand reduced zinc absorption. At a 130:1 L-histidine:zinc ratio the absorption of zinc was less than one-fourth that obtained at a 3:1 ratio. Picolinate was a less effective ligand. The kinetics of the complex L-histidine:zinc at a 2:1 ratio and at pH 7.5 were determined in the absence and presence of a 20 mM excess of amino acid in a zinc concentration range between 0.038 mM and 6.00 mM. In both cases the Vmax was 2200 pmol/(minute . cm), but the Kt increased from 0.54 mM to 1.46 mM in the presence of the L-histidine excess. These data suggest a competitive inhibition of the L-histidine:zinc complex by the amino acid. Such an effect was dependent on the stereoisomerism of histidine, since the unnatural D-isomer was far less effective than the natural L-isomer in facilitating zinc absorption. The presence of an intact protein (bovine serum albumin) sharply decreased the ileal absorption of the L-histidine:zinc complex.

A general method has been developed for the large scale isolation of intact, circular, single-stranded DNA molecules of each strand from supercoiled duplex DNA. The method involves the conversion of the supercoiled duplex DNA to singly nicked, relaxed duplex DNA; denaturation of the duplex DNA; separation of circular DNA molecules from linear DNA molecules; and separation of circular plus and minus strands. All separations involve zone sedimentation. No isopycnic gradient centrifugation is required. The last step in the purification, the separation of plus and minus strands, can be easily adapted for small scale analytical measurements of the amounts of plus and minus strand DNA.

Zinc status was studied in 30 patients with chronic inflammatory bowel disease (CIBD) as well as in 17 normal children, 13 primordial short stature, and 17 anorexia nervosa patients. Basal serum and urinary excretion levels of zinc were measured in all patients. In addition, a zinc loading test was performed in 16 CIBD patients, 21 normal and/or short stature children, and nine patients with anorexia nervosa. Eleven of 30 patients with CIBD had serum zinc values less than 0.7 microgram/ml, whereas none of the other patients had hypozincemia. In addition, the mean urinary zinc excretion of CIBD patients was significantly lower than that of patients with primordial short stature and with anorexia nervosa. An altered response to oral zinc load was the most frequent abnormality in CIBD patients. Those with moderate and severe clinical disease activity had a decreased serum rise of zinc after the oral load of this ion. Urinary excretion of zinc after oral load was also marked by deficiency in all CIBD patients. The abnormalities of zinc metabolism were more frequent among the CIBD patients with growth abnormalities, although they were also found in patients who had normal growth. Among the 14 patients with CIBD and growth abnormalities, seven were hypozincemic and four hypozincuric. Hypozincemia was only found in four patients who had normal height; however, the growth velocity was not known. The zinc tolerance test revealed abnormalities in four of five CIBD patients with short stature and in two of three patients with slow growth. On the other hand, similar alterations in zinc tolerance tests were seen in three of seven CIBD patients with normal height and growth.

Four distinct DNA polymerase activities were isolated from ovaries of the frog Xenopus laevis. Specific assays for each activity were established. The isolated activities were characterized by molecular weight, template-primer preferences, and sensitivity to specific inhibitors as Xenopus laevis ovarian DNA polymerases-alpha 1, -alpha 2, -beta, and -gamma. All previously described Xenopus laevis DNA polymerases were classified using these properties.

The combined stress of protein-energy malnutrition (PEM) and exposure of the jejunum to pathophysiological (0.5 mM) levels of a bacterial metabolite, deconjugated bile salts, led to alterations not apparent with either stress alone. Perfusion of the jejunum of PEM rats with 0.5 mM deoxycholate (DCh) and a 40,000 dalton macromolecular tracer, horseradish peroxidase, led to higher serum horseradish peroxidase levels than were seen in PEM rats not exposed to DCh or in well-nourished controls treated with DCh. Semiquantitative cytochemical analysis indicated an increased number of villi with horseradish peroxidase penetration in PEM rats treated with 0.5 mM DCh. DCh perfusion of PEM rats also produced fine structural damage to epithelial cells not apparent in other preparations. And, perfusion with 0.5 mM cholate only produced sodium secretion in PEM rats. These observations in an animal model of PEM suggest that malnourished children with a colonic type of bacterial overgrowth of the small bowel may attain increased levels of foreign antigens or toxins from the intestinal lumen.

A soluble extract of Xenopus laevis ovaries catalyzed ATP-dependent concatenation of linear duplex DNA molecules. DNA ligase and a unique X. laevis DNA binding protein were required for the formation of concatemers. A linear DNA concatenation system was reconstituted using T4 DNA ligase and homogeneous X. laevis DNA binding protein. This system catalyzed intermolecular ligation of DNA molecules into linear concatemers of up to ten or more times monomer length.