Corticobasal and ataxia syndromes widen the spectrum of C9ORF72 hexanucleotide expansion disease

Recently, a hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72 was reported as the cause of chromosome 9p21‐linked frontotemporal dementia‐amyotrophic lateral sclerosis (FTD‐ALS). We here report the prevalence of the expansion in a hospital‐based cohort and associated clinical features indicating a wider clinical spectrum of C9ORF72 disease than previously described. We studied 280 patients previously screened for mutations in genes involved in early onset autosomal dominant inherited dementia disorders. A repeat‐primed polymerase chain reaction amplification assay was used to identify pathogenic GGGGCC expansions. As a potential modifier, confirmed cases were further investigated for abnormal CAG expansions in ATXN2. A pathogenic GGGGCC expansion was identified in a total of 14 probands. Three of these presented with atypical clinical features and were previously diagnosed with clinical olivopontocerebellar degeneration (OPCD), atypical Parkinsonian syndrome (APS) and a corticobasal syndrome (CBS). Further, the pathogenic expansion was identified in six FTD patients, four patients with FTD‐ALS and one ALS patient. All confirmed cases had normal ATXN2 repeat sizes. Our study widens the clinical spectrum of C9ORF72related disease and confirms the hexanucleotide expansion as a prevalent cause of FTD‐ALS disorders. There was no indication of a modifying effect of the ATXN2 gene.     

The effect of astaxanthin supplementation on performance and fat oxidation during a 40 km cycling time trial

ObjectivesThis study aimed to investigate whether supplementation with 12 mg?day^?1 astaxanthin for 7 days can improve exercise performance and metabolism during a 40 km cycling time trial.DesignA randomised, double-blind, crossover design was employed.MethodsTwelve recreationally trained male cyclists (VO_2peak: 56.5 ± 5.5  mL?kg^?1?min^?1, W_max: 346.8 ± 38.4  W) were recruited. Prior to each experimental trial, participants were supplemented with either 12 mg?day^?1 astaxanthin or an appearance-matched placebo for 7 days (separated by 14 days of washout). On day 7 of supplementation, participants completed a 40 km cycling time trial on a cycle ergometer, with indices of exercise metabolism measured throughout.ResultsTime to complete the 40 km cycling time trial was improved by 1.2 ± 1.7% following astaxanthin supplementation, from 70.76 ± 3.93 min in the placebo condition to 69.90 ± 3.78 min in the astaxanthin condition (mean improvement = 51 ± 71 s, p = 0.029, g = 0.21). Whole-body fat oxidation rates were also greater (+0.09 ± 0.13 g?min^?1, p = 0.044, g = 0.52), and the respiratory exchange ratio lower (?0.03 ± 0.04, p = 0.024, g = 0.60) between 39–40 km in the astaxanthin condition.ConclusionsSupplementation with 12 mg?day^?1 astaxanthin for 7 days provided an ergogenic benefit to 40 km cycling time trial performance in recreationally trained male cyclists and enhanced whole-body fat oxidation rates in the final stages of this endurance-type performance event.     

Nucleotide sequence of immunoglobulin heavy chain joining segments between translocated VH and mu constant regions genes.

To investigate the mechanism of recombination of immunoglobulin heavy chain variable and constant region genes, we have determined the nucleotide sequence of a large portion of the recombination region between an active C mu gene and its associated VH gene, isolated from an IgM-secreting mouse plasmacytoma, HPC76. By comparison with the sequence of the mu mRNA, we determined the exact boundaries of the intervening sequence between the VH76 and C mu genes. The rearranged VH76 gene encodes up to amino acid 116 without interruption, the 3' 39 nucleotides (the JH76 region) being derived from an embryonic JH segment (JH315) whose sequence was recently determined [Early, P., Huang, H., Davis, M., Calame, K. & Hood, L. (1980) Cell 195, 981-992]. The active JH76 does not use the first two codons of the embryonic JH315 from which it is derived. This indicates that V-J recombination is important in generating diversity within the third hypervariable region of heavy chains. We have identified another JH segment (JHA4), located 336 nucleotides 3' to the rearranged JH76 segment. This JH segment is expressed in the heavy chains of anti-levan myeloma proteins, which have truncated third hypervariable regions. We propose that the nucleotide sequence 5' to JHA4 is important for generating V region genes with shortened third hypervariable regions.     

Accuracy of supplementary serologic testing for human T-lymphotropic virus types I and II in US blood donors. Retrovirus Epidemiology Donor Study

Blood donations in the United States have been screened for antibody to human T-lymphotropic virus type I (HTLV-I) by HTLV-I enzyme immunoassay (EIA) since November 1988. Specimens repeatedly found to be reactive by EIA undergo confirmation by supplementary serologic tests. We assessed the accuracy of blood center testing of 994 HTLV-I EIA repeat-reactive specimens in five US blood centers between November 1988 and December 1991. Of 410 confirmed HTLV-I/II donations, 407 (99.3%) were infected with HTLV-I/II, as determined by polymerase chain reaction (PCR) (403 cases) and by repeat serologic testing (4 cases). The three false- positive results occurred in the first year of testing. Of 425 HTLV- indeterminate specimens, 6 (1.4%) were found to be infected by PCR (5 with HTLV-II and 1 with HTLV-I). None of 159 confirmatory test-negative donations was PCR positive. Of HTLV-I/II-seropositive specimens, 80.2% to 95.4% could be typed as HTLV-I or HTLV-II by type-specific serologic assays. These results support recommendations that HTLV-I/II- seropositive donors should be advised that they are infected with HTLV- I, HTLV-II, or HTLV-I/II (depending on results of type-specific assays). HTLV-indeterminate donors should be advised that their results only rarely indicate HTLV infection. HTLV confirmatory test-negative donors should be reassured that they are not infected with HTLV-I or HTLV-II.