Extreme cutaneous histamine sensitivity with hay fever and increased IgE concentrations in an unselected population.

Cutaneous sensitivity to histamine, responses to prick tests with allergens, and serum IgE concentrations were measured and hay fever assessed by questionnaire in an unselected population to determine whether increased sensitivity to histamine is an independent phenomenon contributing to allergic disorders or may be caused by allergic reactions. Increased cutaneous sensitivity to histamine was strongly associated with an increased number of positive responses to prick tests, high serum concentrations of IgE, and hay fever. This new test is simple, cheap, applicable to schoolchildren, and provides useful information.     

Behavioural deprivation: A central problem in animal welfare

A key issue in animal welfare is whether keeping animals in conditions where they cannot or do not perform behaviour typical of more naturally-kept members of their species causes them to suffer. Various measures have been used to resolve this issue. The cost an animal is prepared to pay for the opportunity to perform different behaviour can be used as a measure of the importance of that behaviour to the animal. Manipulation of time-budgets is the most reliable method of measuring such costs and of relating “deprivation” to “suffering”.     

Expression of the alpha 1-proteinase inhibitor gene family during evolution of the genus Mus

alpha 1-Proteinase inhibitors (alpha 1-PIs) are members of the serpin superfamily of proteinase inhibitors, and are important in the maintenance of homeostasis in a wide variety of animal taxa. Previous studies have shown that in mice (genus Mus), evolution of alpha 1-PIs is characterized by gene amplification, region-specific concerted evolution, and rapid accumulation of amino acid substitutions. The latter occurs primarily in the reactive center, which is the region of the alpha 1-PI molecule that determines the inhibitor's specificity for target proteinases. The P1 residue within the reactive center, which is methionine in so-called orthodox alpha 1-PIs and an amino acid other than methionine in unorthodox alpha 1-PIs, is a primary determinant of inhibitor specificity. In the present study, we find that the expression of mRNAs encoding unorthodox alpha 1-PIs is polymorphic within Mus species, i.e., among individuals or inbred strains. This is in striking contrast to mRNAs that encode orthodox alpha 1-PIs, whose concentrations are relatively invariant. The intraspecies variations in mRNA expression represent polymorphisms in the structure of the alpha 1- PI gene family. The results, taken together with previously described aspects of alpha 1-PI evolution, indicate that the dissimilar levels of polymorphism exhibited by orthodox and unorthodox alpha 1-PIs, which likely have distinct physiological functions, may reflect different levels of selective constraint. The significance of this finding to the evolution of gene families is discussed.      

Report of the Working Group on Animal Distress in the Laboratory

Finding ways to minimize pain and distress in research animals is a continuing goal in the laboratory animal research field. Pain and distress, however, are not synonymous, and measures that alleviate one may not affect the other. Here, the authors provide a summary of a meeting held in February 2004 that focused on distress in laboratory animals. They discuss the difficulties associated with defining 'distress,' propose methods to aid in recognizing and alleviating distressful conditions, and provide recommendations for animal research conduct and oversight that would minimize distress experienced by laboratory animals.     

Different allotypes of C3 degrade at different rates

To determine whether different forms of C3 degrade at different rates, we compared two strains of mice with a B10 background. The only difference was that one is C3A, while the other is OR These strains allow comparison of C3A and C3B without the added complication of differing C3 convertases. Sera from the two strains were incubated with zymosan and the degradation products were detected by immunofixation following electrophoresis in agarose. The rate of degradation of mouse C3B was more rapid than that of C3A. Differences in the rates of degradation could not be explained by differing concentrations of C3. We suggest that the genetic differences in C3 determine the decay rate following activation via the alternate pathway.     

Immunoglobulin Deposition in Liver of Patients with Active Chronic Hepatitis and Antibody against Smooth Muscle

Liver biopsies from 33 patients with miscellaneous liver diseases were studied by direct immunofluorescence. Three patients with active chronic hepatitis possessed a distinctive pattern of staining with anti-IgG conjugate. They were relatively young women and all three possessed the anti-smooth-muscle antibody. In addition, all three were untreated at the time of study. It is suggested that direct immunofluorescence on liver biopsies may help in the investigation of liver disease and that humoral immunity may participate in the pathogenesis of active chronic hepatitis.     

Dispelling myths about rare disease registry system development

Rare disease registries (RDRs) are an essential tool to improve knowledge and monitor interventions for rare diseases. If designed appropriately, patient and disease related information captured within them can become the cornerstone for effective diagnosis and new therapies. Surprisingly however, registries possess a diverse range of functionality, operate in different, often-times incompatible, software environments and serve various, and sometimes incongruous, purposes. Given the ambitious goals of the International Rare Diseases Research Consortium (IRDiRC) by 2020 and beyond, RDRs must be designed with the agility to evolve and efficiently interoperate in an ever changing rare disease landscape, as well as to cater for rapid changes in Information Communication Technologies. In this paper, we contend that RDR requirements will also evolve in response to a number of factors such as changing disease definitions and diagnostic criteria, the requirement to integrate patient/disease information from advances in either biotechnology and/or phenotypying approaches, as well as the need to adapt dynamically to security and privacy concerns. We dispel a number of myths in RDR development, outline key criteria for robust and sustainable RDR implementation and introduce the concept of a RDR Checklist to guide future RDR development.