Analysis of antibody reactivities toward self antigens of IgM of patients with Waldenstrom's macroglobulinemia

By using a quantitative immunoblotting technique, we have analyzed the repertoires of antibody reactivities of IgM directed toward self antigens in the serum of patients with Waldenstrom's macroglobulinemia (WM) and in the serum of healthy adults. Monoclonal IgM of patients with WM expressed various degrees of polyreactivity and a high degree of heterogeneity with regard to the number and the nature of the protein bands that were recognized in homologous tissue extracts. Heterogeneous patterns of reactivity of WM IgM contrasted with the conserved profiles of reactivity of IgM in the serum of healthy blood donors. Protein bands that were recognized by WM IgM belonged to the restricted set of self antigens recognized in homologous tissues by normal polyclonal IgM, indicating the absence of a disease-specific reactivity profile of monoclonal WM IgM. Thus, monoclonal IgM that is present in large amounts in WM distorts the homogeneous pattern of reactivity of natural antibodies with self antigens which characterizes the natural antibody repertoire of healthy individuals.      

Telecommunications access--matching available technologies to people with physical disabilities

People with a disability do not have equitable access to the modern telecommunication medium. Many experience difficulty typing, handling the phone, dialling or answering calls. For those who are unable to speak, the only option is to type messages using whatever functional control site exists on their body. The provision of accessible mobile phones for people with disabilities can significantly improve their quality of life through an increased range of accessible activities, and can improve their independence, safety, security and self-esteem. This research was aimed at providing practical ways for people with a disability to participate in the extensive community of home and mobile phone users. The outcomes of ten participants taking part in the evaluation and trial of off-the-shelf telecommunication options are presented. Nine out of ten participants showed high to very high results in terms of their overall performance and satisfaction with the use of the telecommunication equipment provided. With the right policies, processes and support through equipment matching, education, training and delivery, current off-the-shelf solutions can help people with disabilities to effectively communicate with other members of our society and to access the same range of information systems and services enjoyed by able-bodied members of the community.     

Audience response system technology improves accuracy and reliability of trauma outcome judgments

BACKGROUND: Peer-review judgments are necessary for effective trauma performance improvement (PI), but may be influenced by peer pressure and the tendency to vote with the majority. Incorporation of Audience Response System (ARS) technology into trauma PI should result in improved outcome assessments. METHODS: We compared 30 months of nonanonymous trauma care judgments with 30 months of anonymous judgments obtained with the use of a keypad-based ARS. Statistical methods included the chi2 test and the Wilcoxon rank sum test. RESULTS: Use of the ARS resulted in a 28% reduction in deaths judged nonpreventable and a 24% reduction in trauma care judged to be appropriate (p < 0.0001). Unanimous outcome judgments were also significantly reduced (p < 0.0001). CONCLUSIONS: Outcome judgments obtained anonymously were significantly more divergent and less positive than those obtained nonanonymously. Anonymously derived outcome judgments may provide a better opportunity to identify adverse outcomes and thereby potentially improve trauma PI and trauma care.     

Murine double minute 2 as a modulator of retroviral restrictions mediated by TRIM5α

In human cells, endogenous TRIM5α strongly inhibits N-tropic strains of murine leukemia virus (N-MLV) but does not target the closely related B-MLV. We have used a shRNA-based loss-of-function screen to isolate factors other than TRIM5α involved in the restriction of N-MLV. In one of the isolated clones, the shRNA expressed was found to target the murine double minute-2 mRNA. Knocking down MDM2 increased N-MLV and EIAV infection of human cells by 2- to 5-fold while having little effect on B-MLV. Similarly, knocking down MDM2 in African green monkey cells diminished the restriction of both N-MLV and HIV-1. Dual knockdown experiments showed that MDM2 was involved in the restriction mediated by TRIM5α. Moreover, MDM2 knockdown decreased the sensitivity of N-MLV infection to treatment with MG132 and As₂O₃, two known TRIM5α pharmacological inhibitors. Altogether, our data suggest that MDM2 is a general but nonessential modulator of TRIM5α-mediated antiretroviral functions.