Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.     

Effect of aminoglutethimide on murine fetal hepatic erythroid colony formation

Pretreatment of pregnant mice with aminoglutethimide phosphate, an inhibitor of glucocorticoid synthesis, increases the content of fetal liver erythroid colony-forming cells (CFU-E), as assessed by the formation of erythroid colonies in vitro by fetal liver cells in plasma clots containing exogenous erythropoietin. In addition, the inability of aminoglutethimide to influence erythroid colony formation in vitro suggests that endogenous glucocorticoids exert a suppressive effect on the number of functional CFU-E in the fetal liver.     

Antibodies against metal chelates

Because monoclonal antibodies can recognize and bind to specific groups of atoms such as tumour antigens, they have promise for use in vivo as carriers of radionuclides, drugs or other appended molecules for diagnosis and treatment of disease. Attachment of metal ions to antibodies by means of bifunctional chelating agents can add the diverse nuclear, physical and chemical properties of the metallic elements to these specific binding proteins (ref. 4 and refs therein). With the ultimate aim of engineering probe-binding properties into the antibodies themselves, we have now prepared monoclonal antibodies against the EDTA chelate of indium. These antibodies show a remarkable preference for indium chelates; changing to another metal such as scandium or gallium can decrease the antibody-binding constant by more than three orders of magnitude. These antibodies also introduce a new degree of control over the biological distributions of chelated radionuclides, markedly altering their uptake in tumours and normal organs.     

A STUDY OF SEAM STRENGTH AND EXTENSIBILITY FOR PRESSURE GARMENTS

Pressure garments are functional garments designed for medical purposes and arc normally used under prolonged stress. The stress across seams is related to the size of the wearer and the fit and the garment, the more close fitting a garment, the greater stress is put on the seam. Since pressure garments are subjected to appreciable stress during wear, seams with the required strength and extensiblity are particular important. The seam type, stitch type, stitch density and thread strength are the main factors determining the strength and extensibility of a seam. In this paper, investigation of seam strength and extensibility are made on four types of seams which have been used for making pressure garments. Five different types of stitch densities and two sizes of sewing thread are used on each type of scam to be tested. The seaming conditions of the selected fabric are also examined.     

A primary determinant for lipoxygenase positional specificity

The three mammalian lipoxygenases are named according to the carbon position (5, 12 or 15) at which they catalyse the oxygenation of arachidonic acid; they are implicated in inflammatory disorders, for example 15-lipoxygenase is induced in atherosclerosis and can oxidize low-density lipoprotein to its atherogenic form. To identify what determines this positional specificity, we have exchanged conserved differences in the isoforms of 12- and 15-lipoxygenases. Substitution of methionine with valine at position 418 of human 15-lipoxygenase results in an enzyme that performs 12- and 15-lipoxygenation equally. This effect can be mimicked by incubating wild-type 15-lipoxygenase with a synthetically altered substrate which has its doubly allylic methylene carbons shifted by one carbon relative to arachidonic acid. Other mutations at the neighbouring amino acids 416 and 417 give an enzyme which performs 12- and 15-lipoxygenation in a ratio of 15:1. These results indicate that this region might position the substrate in the active site.     

Thomas Clifford Allbutt and Comparative Pathology

This paper reconceptualizes Thomas Clifford Allbutt's contributions to the making of scientific medicine in late nineteenth-century England. Existing literature on Allbutt usually describes his achievements, such as his design of the pocket thermometer and his advocacy of the use of the ophthalmoscope in general medicine, as independent events; and his work on the development of comparative pathology is largely overlooked. In this paper I focus on this latter aspect. I examine Allbutt's books and addresses and claim that Allbutt argued for the centrality of comparative pathology in the advancement of medical knowledge. He held that diseases should be studied as biological phenomena and that medicine should be made a biological science. He also argued that comparative pathology should be based upon the idea of evolution, and its study should embrace other nineteenth-century sciences including neurology, embryology and bacteriology. Allbutt's writings reveal that his endorsement of comparative pathology (1880s to 1920s), his promotion of the use of the ophthalmoscope and the thermometer in clinical medicine (early 1870s), and his support of the hospital unit system (1910s to 1920s) were part of a single programme. All were grounded in his scientific vision of medicine which emphasized a research culture, a stringent nosological attitude and an integration of laboratory sciences and clinical medicine.     

The Allocation of Production orders to offshore Plants in the Clothing Industry: Part 2-Prototype System Supporting Order Allocation Decisions

This part demonstrates a prototype system which has been constructed to enable the allocation of orders of different product types to different manufacturing locations . ' What - if' experiments using this system show that different allocation rules would provide different outcomes in terms of the number of unallocated orders. A high number of unallocated orders will have a direct Impact on workload. Further research effort is necessary to channel into the exercbe of production order allocation with particular reference to allocation rules.     

Metallothionein expression by NG2 glial cells following CNS injury

Metallothionein (MT) expression is rapidly up-regulated following CNS injury, and there is a strong correlation between the presence or absence of MTand improved or impaired (respectively) recovery from such trauma.We now report that a distinct subset of NG2-positive, GFAP-negative glial cells bordering the injury tract express MT following focal injury to the adult rat neocortex. To confirm the ability of these NG2 glial cells to express MT, we have isolated and cultured them and identified that they can express MT following stimulation with zinc. To investigate the functional importance of MT expression by NG2 glial cells, we plated cortical neurons onto these cells and found that expression of MT enhanced the permissivity of NG2 glial cells to neurite outgrowth. Our data suggest that expression of MT by NG2 glial cells may contribute to the overall permissiveness of these cells to axon regeneration.