Spontaneous mutation during fetal development and post-natal growth

Somatic mutations seem to accumulate slowly with age duringadult life in both mice and men. There is, however, a substantialmutant frequency at birth, suggesting that the rate of accumulationis much higher before birth. This suggests that DNA replicationplays an important role in the generation of spontaneous mutations.Since most cell division and accompanying DNA replication occursearly in development, more mutations would arise during growthand development. Indeed, if the mutations are genetically neutral,the mutant frequency would rise very rapidly during early fetalgrowth, more slowly during later fetal growth and developmentand still more slowly after birth. To test this hypothesis,we have assayed the mutant frequencies from before birth to28 days after birth, by which time most growth has occurred.We have used the F₁ mice generated by crossing SWR females andMuta^TMMouse males. The Muta^TMMouse has a rescuable lacZ/     

A retrospective study to determine the risk of red cell alloimmunization and transfusion during pregnancy

A retrospective review of post-delivery antibody records was performed at a teaching hospital and a community hospital to determine the frequency of new red cell alloantibody production and transfusion during pregnancy. If alloantibody was undetected at delivery, it was assumed that alloimmunization had not occurred. When antibody was detected, a chart review was performed to determine if the antibody was present at the beginning of the pregnancy or was newly produced during the pregnancy. A total of 17,568 pregnancies were reviewed. Antibody was detected at delivery in 948 (5.4%) cases, of which 89.5 percent (848/948) involved passive anti-D or clinically insignificant antibodies. The remaining 100 pregnancies involved clinically significant IgG antibodies. In 58 pregnancies, the antibody was detected in the first trimester, and in 42, new antibody production occurred during the pregnancy. Thus, the prevalence of new antibody production during pregnancy was 0.24 percent (95% confidence interval [CI], 0.17-0.32). Transfusion records indicated that the prevalence of transfusions during pregnancy was 0.09 percent (95% CI, 0.04-0.14). None of the women with new alloantibody formation during their pregnancies required transfusion; hence, new alloantibody production and the need for transfusion appear to be independent events. The probability of these events occurring together was 2.1 × 10(-6), or 1 in 500,000 deliveries.     

Development of monoclonal mouse antibodies specific for allergenic components in ryegrass (Lolium perenne) pollen

The development of monoclonal mouse antibodies against ryegrass (Lolium perenne) pollen allergens is described. Hybridoma colonies secreting antibodies specific for allergenic components were detected using an enzyme-linked immunosorbent assay. Positive colonies were cloned and expanded. The pollen components with which the monoclonal antibodies interact were identified and characterised following sodium dodecyl sulphate polyacrylamide gel electrophoresis and electrophoretic transfer to nitrocellulose. In this paper six monoclonal mouse antibodies are described. Three antibodies interact with a single molecule of between 30,000 and 35,000 daltons. One antibody interacts with a component of 16,000 daltons whereas the remaining two antibodies react with more than one component, one reacting with two components at 28,000 and 30,000, and the other with five components having molecular weights between 18,000 and 71,000 daltons.     

Dog immunoglobulins. I. immunochemical characterization of dog serum, parotid saliva, colostrum, milk and small bowel fluid.

The levels of immunoglobulins A, M and G were measured in dog serum, colostrum, milk, parotid saliva and small bowel fluid using the single radial immunodiffusion method. All the external secretions except early colostrum, by contrast with serum, were found to be rich in IgA with small quantities of IgM and IgG. Exocrine immunoglobulins were partially characterized by gel filtration.     

The effect of lysozyme on the complement-dependent bactericidal action of different antibody classes.

Preparations of rabbit, dog and sheep IgA, IgA and IgM were examined for their antibacterial effects using a complement-dependent bactericidal assay. IgM and IgG were effecient bactericidal antibodies in the presence of complement; IgA, however, contained negligible activity. Except for sheep IgG no enhancement of bactericidal activity was observed in the presence of added lysozyme.     

Risks,benefits and the role of stakeholders in pathogen reduction technology

While Canada’s blood supply is currently very safe, risks remain, prompting blood suppliers to develop a more effective strategy to minimise the risk of transmitting infectious agents through blood transfusion. Pathogen reduction technology provides an additional way to protect the blood supply from new threats. However, the uptake of this new technology has been slow, reflecting the safety of the current system, the success of surveillance and screening methods, the lack of knowledge regarding pathogen reduction technology and the impact of pathogen reduction on blood quality and recipient safety. In the absence of public debate, the legacy of previous adverse events and the challenges of negotiating perceptions of risk, our objective in this article is to explore stakeholder perceptions of the challenges of introducing pathogen reduction technology in Canada. In this article, we provide a debate about risk communication and assessment drawing on data from a study of 2010 that used focus groups and interviews with key stakeholders, including media, blood suppliers, blood or blood product recipients and implementers of pathogen reduction technologies to examine stakeholders’ perceptions of risk assessment and communication. We found that there was a broad understanding among stakeholders of the need to effectively communicate the risks and benefits of pathogen reduction technology and to provide accurate information. Consequently, we predict that public acceptance of the new technology will be largely based on its perception of the risk of pathogen reduction technology.     

Sinus node sequences after atrial stimulation: similarities of effects of different methods

Sinoatrial conduction is commonly assessed from features of the initial cycle after a single atrial extrastimulus or eight beats atrial pacing. In contrast, sinus node automaticity is assessed by the duration of the first interval after prolonged atrial pacing. The return cycle and initial sequences after these different methods were compared in 10 subjects with normal sinus node function and 30 patients with sick sinus syndrome. Typically, sequences after all three methods showed a maximally prolonged first interval with a progressive decrease over five or more cycles. A model of recovery from overdrive suppression was used to compute the elements of conduction time and automaticity in the first interval. The sequences which followed a single extrastimulus and pacing were similar, the only index which increased significantly with prolonged pacing was associated with the degree of suppression of automaticity. The computed component of sinoatrial conduction in the return cycle was similar for all three methods. Thus all three conventional methods which consider only the initial post-stimulation interval measure both sinoatrial conduction and sinus node automaticity. The separate components of automaticity and conduction may be assessed by analysis of the total sequence.     

Role of the proximal and distal stomach in mixed solid and liquid meal emptying.

The role of the proximal and distal stomach in the emptying of solids and liquids from the stomach remains unclear. We have used a dual isotope technique to quantify proximal and distal stomach emptying of a solid (100 g of 99mTc labelled liver/ground beef) liquid (either 200 ml of normal saline (eight subjects) or 25% dextrose (seven subjects) labelled with 113mIn-diethylenetriaminepenta-acetic acid) mixed meal. A manometric catheter simultaneously measured antral, pyloric, and duodenal motor activity. The liquid component dispersed rapidly throughout the stomach and emptied after a minimal lag period. The emptying of the 25% dextrose was delayed compared with the saline. This delay was associated with increased retention of the liquid in the distal stomach, a significant increase in localised phasic pyloric contractions, and a suppression of antral contractions. The solid component initially resided wholly within a proximal stomach reservoir area. Solids then redistributed from proximal to distal stomach during the emptying of liquid from the stomach. Dextrose delayed gastric emptying of solids compared with saline by increasing the solid lag period and retention in the proximal stomach. There was no significant difference between saline and dextrose meals in the distal stomach retention of solid or in the linear rate of emptying after the lag period. We conclude that, contrary to general opinion, the proximal stomach plays an important role in the control of gastric emptying of solids while the distal stomach is important in the emptying of nutrient liquids.