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To study pathogenic T helper cells in myasthenia gravis (MG) reacting against the acetylcholine receptor (AChR), we have previously selected five CD4+ T cell lines/clones from MG patients (or healthy controls) against full-length recombinant human AChR alpha subunit (alpha 1-437); these can all recognize AChR solubilized from human muscle. Recently, T cells selected with pooled AChR subunit synthetic peptides have shown greater heterogeneity than above. Hoping to validate that, we have characterized three MG and six control T cell lines selected with pooled peptides (averaging 33 residues long) covering the alpha subunit sequence; recurring responses to three particular peptides each showed preferred HLA class II restrictions--p75-115/DR4, p138-167/DR4, and p309-344/DR3 (or DR52a). However, none of three lines from MG patients recognized p138-167--even one from a previous responder to this epitope in full-length alpha 1-437; otherwise they resembled those from controls. Moreover, no peptide-selected line responded significantly to whole AChR, alpha 1-437, or even to shorter polypeptides sharing one terminus with the peptide, suggesting specificity for epitopes not naturally processed by APCs from blood. Of 20 sublines maintained with individual peptides, at least 10 responded to independently synthesized overlapping sequences, but four others depended on contaminants in the original peptides. A single line did recognize one longer polypeptide, but only after tryptic digestion; the processing of this cryptic epitope was evidently the limiting factor here rather than its concentration or the T cell sensitivity. Therefore, while synthetic peptides are essential for mapping epitopes, assessment of the pathogenic MG T cell repertoire requires full-length Ag processed naturally.

Background Whether people living with HIV who have not received antiretroviral therapy (ART) and have high CD4 cell counts have higher mortality than the general population is unknown. We aimed to examine this by analysis of pooled data from industrialised countries. Methods We merged data on demographics, CD4 cell counts, viral-load measurements, hepatitis C co-infection status, smoking status, date of death, and whether death was AIDS-related or not from 23 European and North American cohorts. We calculated standardised mortality ratios (SMRs) standardised by age, sex, and year, stratifying by risk group. Data were included for patients aged 20-59 years who had at least one CD4 count greater than 350 cells per mu L while ART naive. All pre-ART CD4 counts greater than 350 cells per mu L from January, 1990, to December, 2004, were included. We investigated mortality for four risk groups men who have sex with men, heterosexual people, injecting drug users, and those at other or unknown risk. The association between CD4 cell count and death rate was investigated by use of Poisson regression methods. Findings Data were analysed for 40 830 patients contributing 80 682 person-years of follow-up. Of 419 deaths, 401 were used in the SMR analysis: 100 men who have sex with men (SMR 1.30 , 95% CI 1.06-1 58); 68 heterosexual people (2.94, 2.28-3.73); 203 injecting drug users (9.37, 8.13-10.75); and 30 in the other or unknown risk category (4.57, 3.09-6.53). Compared with CD4 counts of 350-499 cells per mu L, death rate was lower in patients with counts of 500-699 cells per mu L (adjusted rate ratio 0-77, 95% CI 0.61-0.95) and counts of 700 cells per mu L (0.66, 0.52-0.85). Interpretation In HIV-infected ART-naive patients with high CD4 cell counts, death rates were raised compared with the general population. In men who have sex with men this was modest, suggesting that a substantial proportion of the increased risk in other groups is due to confounding by other factors. Even though the increased risk is small, new studies of potential benefits of ART in this group are merited.

Usual questions that may require analytical work in rock art relate to investigations that seek correlations between archaeological deposits and the rock wall and human activities within the site, the relationships between sites (material sourcing, landscape use), dating (direct or relative chronology), and conservation studies (nature and causes of alterations). From early works to recent research in archaeology, South Africand France have had many fruitful interactions (e.g. Breuil 1930; Clottes 1996; Henshilwood 2002; Parkington 2005; Hœrlé 2007; Tournié 2010). Today, under the aegis of two international and interdisciplinary programmes linking South Africand France - GDRI-STAR "Science, Technologies, Art Rupestre" and ARCUS le-de-France/South Africa "Rock Art" - the aim, among other topics, is to foster the use of materials microanalytical tools in rock art studies. GDRI-STAR is an international research network gathering together teams of South African and French researchers from backgrounds as diverse as archaeology, linguistics, conservation, materialscience and geosciences, with a common interest in rock art studies. GDRI-STAR is jointly funded by the French Centre National de la Recherche Scientifique (CNRS) and the South African National Research Foundation (NRF). The ARCUS le-deFrance/South Africa "Rock Art" project aims at fostering research in the field of rock art by bringing together a cluster of analytical laboratories and archaeological teams in Région le-de-France, France, and leading South African academic centres. It is funded by the French Ministry of Foreign and European Affairs and the le-de-France provincial council, and managed through the CNRS and the Agence Française de Développement (AFD).

Work in swine and poultry units is associated with exposure to significant levels of organic dust and endotoxins with the highest concentrations found in poultry houses, whereas values found in dairy and in cattle farming are much lower. Corresponding to this is an excess of work-related respiratory symptoms in swine farmers. A dose-response relationship exists between symptoms and number of working hours. Longitudinal studies have demonstrated an accelerated decline of lung function in swine farmers large enough to cause clinically significant disease in some farmers. Because of the large number of people needed in swine farming and the long working hours, swine farming has emerged as the major respiratory problem in farming. Experimental studies indicate that exposure has to be lowered substantially to avoid acute effects and longitudinal studies demonstrate that loss of lung function occurs in non-smoking swine farmers without respiratory symptoms and that accelerated decline in lung function occurs below endotoxin concentrations in dust (100 ng/m3 ) proposed as a safe threshold.

A flock of Rambouillet sheep experienced unexpected lamb mortality associated with excessive bleeding at the time of parturition. Most lambs died of blood loss through the umbilicus or into subcutaneous tissues. Subsequently, nine ewes which had previously delivered lambs that bled to death were bred to the suspected sire of the previous bleeding lambs. Fifteen lambs were born alive the following Spring, and three males and one female bled clinically. These lambs had markedly decreased factor IX (< 16%) and factor X (< 4%) activities, with variably decreased factor II (11-36%) and factor VII (20-37%) activities. Protein C chromogenic activity was also markedly decreased (< 1%) in these lambs. The results from crossed immunoelectrophoresis and 'protein-induced-in-vitamin-K-absence' determination of the plasma of affected lambs, with antiserum directed against coagulation factor X, protein C or proteins S, suggested that these proteins were not carboxylated normally. Examination of liver from one lamb in the first batch and the four subsequent lambs did not reveal a known vitamin K antagonist. The breeding data suggested that the coagulopathy in these sheep was inherited as an autosomal recessive trait. The genetic or molecular defect that exists in these lambs is unknown, but possibilities include abnormal gamma-glutamyl carboxylase activity or abnormal metabolism of vitamin K.

Are taking an overdose and undergoing termination of pregnancy linked? In one practice this study has identified a significant association between the two events. If this finding is supported more widely, could one event act as a risk marker for the second?