Rapid turnover of the recirculating lymphocyte pool in vivo

Lymphocytes are unique among blood cells in their capacity to continually recirculate between blood and the tissues via the lymph. Previous estimates of lymphocyte lifespan in vivo and the turnover of the recirculating lymphocyte pool have been deduced from indirect labeling techniques. Using the fluorescent dye PKH-26, individual labeled cells have been tracked in sheep for periods >2 months. By direct measurement their lifespan was calculated. This label was found to be stable in vivo, allowing long-term analysis of the characteristics of the recirculating lymphocyte pool. It Is possible to calculate the rate of turnover of cells of the recirculating pool based on the rate at which labeled cells disappear from the lymphatic circulation. The recirculating lymphocyte pool was found to repopulate itself every 16.5 ± 3.0 days. Using this label, it was estimated that recirculating lymphocytes divide on average once every 29.8 ± 6.8 days. Labeled erythrocytes were also examined and found to have an average lifespan of 153 days, demonstrating no dye loss over the 2 month period of observation. These data suggest that the recirculating lymphocyte pool is a highly dynamic compartment, with a high rate of turnover and peripheral cell division in vivo. This is the first report of the direct measurement of the in vivo turnover of recirculating lymphocyte pools, and this method may now be used to further analyze the lifespan of individual lymphocyte subsets and the in vivo lifespan of other cell types in viv

Tracking dendritic cells: use of an in situ method to label all blood leukocytes

Here we describe an in situ procedure with a labeling index (percent of labeled blood leukocytes) >98%, which is high enough to permit the direct tracking of dendritic cell (DC) precursors from blood into lymphoid tissues, while circumventing the pitfalls associated with in vitro labeling. DC and lymphocytes have similar blood to afferent lymph migratory capabilities. This method has additional applications in tracking other rare cell populations in both normal and pathological state

Influenza Virus Infection in Travelers to Tropical and Subtropical Countries

Background. Influenza outbreaks have been reported among travelers, but attack rates and incidence are unknown. Methods. A cohort study was conducted. Travelers to subtropical and tropical countries recruited at the University of Zurich Travel Clinic (Switzerland), January 1998 to March 2000, were investigated with pre- and posttravel assessment of hemagglutination inhibition and by questionnaire. Results. Among 1450 travelers recruited who completed questionnaires and provided serum samples before departure, 289 (19.9%) reported febrile illness during or after traveling abroad; of these, 211 (73.0%) provided paired serum samples. Additionally, paired serum samples were collected from 321 frequency-matched afebrile control subjects among the remaining 1161 subjects of the study population. Seroconversion for influenza virus infection was demonstrated in 40 (2.8%) of all travelers; 18 participants (1.2%) had a ⩾4-fold increase in antibody titers. This corresponds to an incidence of 1.0 influenza-associated events per 100 person-months abroad. Among the 211 febrile participants, 27 (12.8%) had seroconversion, 13 (6.2%) with a ⩾4-fold increase; among the 321 afebrile control subjects, 13 (4.0%) had seroconversion, 5 (1.6%) with a ⩾4-fold increase. Twenty-five seroconverters (62.5%; P = .747) acquired influenza outside of the European epidemic season. Sixteen patients (40.0%) sought medical attention either abroad or at home, and 32 (80.0%) were asymptomatic at the time of completion of the survey. Conclusions. This survey indicates that influenza is the most frequent vaccine-preventable infection among travelers to subtropical and tropical countries. Infections occur mainly outside the domestic epidemic season, and they have a considerable impact. Pretravel vaccination should be considered for travelers to subtropical and tropical countrie

Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): economic evaluation of a randomised controlled trial

Objective To estimate the cost to the NHS and to parents and carers of treating febrile preschool children with paracetamol, ibuprofen, or both, and to compare these costs with the benefits of each treatment regimen

Medicine dosing by weight in the home: Can parents accurately weigh preschool children? A method comparison study

Objective: To determine the accuracy with which parents can estimate preschool children's weight using home scales in order to calculate antipyretic dose. Design: Cross-sectional, method comparison study. Setting and participants: 156 preschool children aged 6 months to 6 years recruited from primary care and the community to an antipyretic strategies trial and managed at home. Comparison and outcome measures: Research nurse weight estimate using Seca 835-2 digital paediatric scales compared with parental weight estimate using usual home scales. Results: Parents of 62 (40%) preschool children had home scales. Research scale estimated weights were heavier than home scale weight estimates, with a mean difference of 0.41 kg (95% CI -0.24 to 0.74 kg), with 95% limits of agreement of -2.44 to 1.47 kg. Conclusion: Weight can be estimated accurately enough to calculate antipyretic medicine doses by the minority of parents having scales that can be used to estimate their child's weight

Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial

Objective To investigate whether paracetamol (acetaminophen) plus ibuprofen are superior to either drug alone for increasing time without fever and the relief of fever associated discomfort in febrile children managed at home

Identifying the genetic basis of antigenic change in influenza A(H1N1)

Determining phenotype from genetic data is a fundamental challenge. Influenza A viruses undergo rapid antigenic drift and identification of emerging antigenic variants is critical to the vaccine selection process. Using former seasonal influenza A(H1N1) viruses, hemagglutinin sequence and corresponding antigenic data were analyzed in combination with 3-D structural information. We attributed variation in hemagglutination inhibition to individual amino acid substitutions and quantified their antigenic impact, validating a subset experimentally using reverse genetics. Substitutions identified as low-impact were shown to be a critical component of influenza antigenic evolution and by including these, as well as the high-impact substitutions often focused on, the accuracy of predicting antigenic phenotypes of emerging viruses from genotype was doubled. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine techniques that predict the fitness and evolutionary success of variant viruses, leading to stronger theoretical foundations for selection of candidate vaccine viruses

APC2 is critical for ovarian WNT signalling control, fertility and tumour suppression

Background Canonical WNT signalling plays a critical role in the regulation of ovarian development; mis-regulation of this key pathway in the adult ovary is associated with subfertility and tumourigenesis. The roles of Adenomatous polyposis coli 2 (APC2), a little-studied WNT signalling pathway regulator, in ovarian homeostasis, fertility and tumourigenesis have not previously been explored. Here, we demonstrate essential roles of APC2 in regulating ovarian WNT signalling and ovarian homeostasis. Methods A detailed analysis of ovarian histology, gene expression, ovulation and hormone levels was carried out in 10 week old and in aged constitutive APC2-knockout (Apc2−/−) mice (mixed background). Statistical significance for qRT-PCR data was determined from 95% confidence intervals. Significance testing was performed using 2-tailed Student’s t-test, when 2 experimental cohorts were compared. When more were compared, ANOVA test was used, followed by a post-hoc test (LSD or Games-Howell). P-values of < 0.05 were considered statistically significant. Results APC2-deficiency resulted in activation of ovarian WNT signalling and sub-fertility driven by intra-ovarian defects. Follicular growth was perturbed, resulting in a reduced rate of ovulation and corpora lutea formation, which could not be rescued by administration of gonadotrophins. Defects in steroidogenesis and follicular vascularity contributed to the subfertility phenotype. Tumour incidence was assessed in aged APC2-deficient mice, which also carried a hypomorphic Apc allele. APC2-deficiency in these mice resulted in predisposition to granulosa cell tumour (GCT) formation, accompanied by acute tumour-associated WNT-signalling activation and a histologic pattern and molecular signature seen in human adult GCTs. Conclusions Our work adds APC2 to the growing list of WNT-signalling members that regulate ovarian homeostasis, fertility and suppress GCT formation. Importantly, given that the APC2-deficient mouse develops tumours that recapitulate the molecular signature and histological features of human adult GCTs, this mouse has excellent potential as a pre-clinical model to study ovarian subfertility and transitioning to GCT, tumour biology and for therapeutic testing