Immunoglobulin M. Specific for Measles and Mumps in Multiple Sclerosis

Sera from 43 patients with multiple sclerosis were tested by immunofluorescence. Sera from patients with active multiple sclerosis included four with measles virus-specific immunoglobulin M (measles IgM) and two with mumps virus-specific IgM (mumps IgM). In one case each mumps IgM and measles IgM seem to have persisted for two and a half years and three years respectively. In a comparable group of 43 patients with other nervous diseases measles IgM was found in only one serum, and among 43 normal patients no measles or mumps IgM was found.Herpes simplex virus-specific IgM (herpes simplex IgM) was distributed among all three groups. Anticellular IgM was also found, predominantly in active multiple sclerosis, and persisted in two sera for two and a half years.     

Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2

The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected phosphopeptide motif reveals the determinants of binding specificity and shows that both mutations are remote from the peptide binding site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1 through either or both of two structurally distinct mechanisms. Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions.     

Debating Ethics in HIV Research: Gaps between Policy and Practice in Nigeria

HIV prevention is a critical health issue in Nigeria; a country that has one of the worst HIV epidemic profiles in the world. With 270,000 new infections in 2012, Nigeria is a prime site for HIV prevention research. One effect of the HIV epidemic has been to revolutionalise ethical norms for the conduct of research: it is now considered unethical to design and implement HIV related studies without community engagement. Unfortunately, there is very little commensurate effort in building the capacity of local persons to engage actively with researchers, and there is no existing platform to facilitate dialogue between researchers and communities engaged in research in Nigeria. In an effort to address this gap, we undertook a series of three community dialogues (Phase One) and two community‐researcher interface meetings (Phase Two) in Nigeria. This paper aims to give an empirical account of the dialogue from these community engagement processes and provide a resulting critique of the implementation of research ethics practices in Nigeria. It is anticipated that the outputs will: (i) support researchers in designing community‐based research protocols; (ii) inform ethics committees of key considerations during research protocol reviews from a community perspective; and (iii) inform policy makers and research sponsors about issues of primary concern to communities with respect to HIV research.     

Measles Immunoglobulins in Subacute Sclerosing Panencephalitis

Normal responses of measles specific immunoglobulins M and G (IgM and IgG) were defined in 10 children with measles. Abnormal responses of measles IgM and IgG were found in both sera and cerebrospinal fluids from three cases of subacute sclerosing panencephalitis. In two patients the serum titres of measles IgM and IgG were abnormally high. The measles IgM was present during prolonged illnesses in serum and cerebrospinal fluid, which suggested a correlation with the known persistence of measles virus antigen in the brain of the three patients. It was concluded that both measles IgM and IgG may be produced within the central nervous system in subacute sclerosing panencephalitis.     

Mitogen-induced preferential synthesis of proteins during the G0 to S phase transition in human lymphocytes

We have followed the induction of protein synthesis in mitogen-activated human peripheral blood mononuclear cells during the transition from quiescence, or G0, through the prereplicative phase and into first S phase. Doses of mitogens optimal for proliferative response preferentially enhance the synthesis of a subset of intracellular proteins during the approximately 24-h lag interval. The mitogenic lectin phytohemagglutinin (PHA) and OKT3, a mitogenic monoclonal antibody to the CD3 component of the T cell antigen receptor, preferentially enhance bands of the same molecular weight in one-dimensional SDS-PAGE. The proteins are low detergent soluble (0.1% Triton X-100) "cytoplasmic" cellular components and some have been identified as single spots on two-dimensional gels. Bands of 51 and 66 kDa are induced early in lag phase (4 h after stimulation) but are transiently synthesized, decreasing later in lag phase. The majority of the mitogen-induced proteins, 39, 51, 55, 60, 73, and 95 kDa are enhanced by mid lag phase (12 h after stimulation). With the exception of the 55-kDa band, five of these proteins are clearly enhanced in T cells purified after mitogen stimulation. The same five bands show sustained synthesis in actively cycling cells 42-48 h after stimulation and are major synthesized proteins, and corresponding bands are synthesized in a transformed T cell line, MOLT-4. Two of the proteins in this group that are most prominently synthesized during the lag interval have been previously identified as the heat shock proteins, HSP 90 (95-kDa band) and HSC 70 (73-kDa band). We speculate that this group of five proteins, including HSP 90 and HSC 70, may be coordinately expressed in actively replicating T cells and may have some common structural or functional role in sustaining the replicative state.     

Monitoring access to nationally commissioned services in England

Background

Deficiency of complex II (succinate dehydrogenase, SDH) represents a rare cause of mitochondrial disease and is associated with a wide range of clinical symptoms. Recently, mutations of SDHAF1, the gene encoding for the SDH assembly factor 1, were reported in SDH-defective infantile leukoencephalopathy. Our goal was to identify SDHAF1 mutations in further patients and to delineate the clinical phenotype.

Methods

In a retrospective data collection study we identified nine children with biochemically proven complex II deficiency among our cohorts of patients with mitochondrial disorders. The cohort comprised five patients from three families affected by SDH-defective infantile leukoencephalopathy with accumulation of succinate in disordered cerebral white matter, as detected by in vivo proton MR spectroscopy. One of these patients had neuropathological features of Leigh syndrome. Four further unrelated patients of the cohort showed diverse clinical phenotypes without leukoencephalopathy. SDHAF1 was sequenced in all nine patients.

Results

Homozygous mutations of SDHAF1 were detected in all five patients affected by leukoencephalopathy with accumulated succinate, but not in any of the four patients with other, diverse clinical phenotypes. Two sisters had a mutation reported previously, in three patients two novel mutations were found.

Conclusion

Leukoencephalopathy with accumulated succinate is a key symptom of defective complex II assembly due to SDHAF1 mutations.