The response to Salmonella typhimurium antigens by two different strains of mice

A technique is described for the detection and enumeration of cells producing antibody to O-somatic antigen specificities 1, 4, 5 and 12 of Salmonella typhimurium. Using this technique, a difference in the immune response has been demonstrated between Swiss White and the BALB/c strain mice, when both these strains are injected with a standard dose of acetone-killed S. typhimurium C5 vaccine. BALB/c mice fail to respond to antigen 5 and their response to the 1, 4 and 12 O-somatic antigens, while reaching the same magnitude, is less prolonged than that in Swiss White mice.     

Specific, functional effector/memory CD8+ T cells are found in the liver post-vaccination

BACKGROUND: The liver efficiently eliminates activated CD8+ T blasts. It is unknown if vaccine-primed CD8+ T blasts migrate to and establish functional CD8+ T cell immunity in the liver post-immunization. AIMS: We tested, if functional CD8+ T cell populations can be detected in the liver post-vaccination. METHODS: Murine CD8+ T cells with different epitope/restriction specificities were primed by intramuscular injection of protein- or DNA-based vaccines. The kinetics of appearance in the liver, as well as the surface phenotype and functional competence of intrahepatic, specific CD8+ T cell populations was tested. RESULTS: High numbers of specific CD8+ T cells appear in the liver after vaccination that are activated (CD69+ CD44+), express effector functions (CD27lo/CD28lo phenotype, interferon gamma secretion, specific cytolytic reactivity), but show no evidence of apoptosis (annexin V-, B220lo, similar numbers/kinetics in primed, congenic lpr/lpr mice). Specific CD8+ T cells from the liver adoptively transferred into a na?ve, syngeneic host successfully reconstitute specific CD8+ T cell immunity. CONCLUSIONS: Specific, functionally competent CD8+ effector/memory T cell populations are established in the liver for months post-vaccination.     

A novel mutation in human ether-a-go-go-related gene, alanine to proline at position 490, found in a large family with autosomal dominant long QT syndrome

Long-QT syndrome is a rare disease characterized by prolonged ventricular repolarization. The clinical presentation of long-QT syndrome is the occurrence of syncope, seizures, or cardiac arrest in young patients. Previous studies have demonstrated locus heterogeneity, with causative mutations reported in >or=8 different genes, including the human ether-a-go-go-related gene. This study was conducted in 26 members of a 4-generation family with long-QT syndrome. The proband was a 14-year-old female patient referred to the emergency department for the evaluation of recurrent syncope associated with a prolonged QT interval on electrocardiography at rest. There was a family history of sudden death in a 27-year-old woman. Sequencing of the entire coding regions of the human ether-a-go-go-related gene and the intron and exon boundaries of the proband identified a single base-pair substitution (guanine to cytosine at nucleotide 1468). This mutation resulted in a novel missense mutation, alanine to proline at position 490 (Ala490Pro), in the inner loop of the S2 and S3 domains. The proband was heterozygous for the Ala490Pro mutation. To address whether the mutational change detected in the patient would be a polymorphism, 100 control subjects from the same ethnical background were investigated. None showed the Ala490Pro substitution. Of 26 family members, 9 were mutation carriers, and none had normal electrocardiographic results. The penetrance of this pedigree was assumed to be 100%. In conclusion, the Ala490Pro mutation of the human ether-a-go-go-related gene is a rare, novel mutation that was inherited in this family, leading to Romano-Ward syndrome with complete penetrance.     

European School of Internal Medicine (ESIM) in Brighton: experiences and reflections

The European School of Internal Medicine (ESIM) is a meeting aimed at young physicians training in internal medicine throughout Europe. Since 1998 the school has been held annually, and in this report we reflect on our experiences during the recent school in Brighton in July 2010. The school combined a broad mix of lectures, workshops and case presentations covering a variety of rare diseases, and both faculty and residents participated with noticeable enthusiasm, making this a special experience for all of us. The school also provided an opportunity to compare and discuss topical professional issues in internal medicine in Europe and was a memorable social gathering for physicians who share a strong interest in internal medicine.     

Direct oral anticoagulants more effective than low-molecular-weight heparin for venous thrombo-embolism in cancer: an updated meta-analysis of randomized trials

Journal of Thrombosis and Thrombolysis - In the recent past, low-molecular-weight heparin (LMWH) was the first choice in the treatment of cancer related venous thrombo-embolism (VTE). Evidence...