A wide range of baroreflex stimulation does not alter forearm blood flow

The contribution to the regulation of forearm blood flow (FBF) by different baroreceptor populations has previously only been studied over a limited range of stimuli. Therefore, FBF and R-R interval were recorded during neck suctions and neck pressures ranging from –60 to +40 mmHg. The change in R-R interval (R-R) during neck suction was significantly increased at each stage when compared to the control (P<0.05). R-R did not show any significant change during any of the neck pressure stages (P>0.05). Suction or pressure applied to the neck did not elicit any significant changes in FBF when compared to the control (P>0.05). These data show that widening the range of applied stimuli to carotid sinus baroreceptors does not induce a change in FBF. However, the small transient changes reported previously cannot be discounted.     

Linkage disequilibrium in young genetically isolated Dutch population

The design and feasibility of genetic studies of complex diseases are critically dependent on the extent and distribution of linkage disequilibrium (LD) across the genome and between different populations. We have examined genomewide and region-specific LD in a young genetically isolated population identified in the Netherlands by genotyping approximately 800 Short Tandem Repeat markers distributed genomewide across 58 individuals. Several regions were analyzed further using a denser marker map. The permutation-corrected measure of LD was used for analysis. A significant (P<0.0004) relation between LD and genetic distance on a genomewide scale was found. Distance explained 4% of the total LD variation. For fine-mapping data, distance accounted for a larger proportion of LD variation (up to 39%). A notable similarity in the genomewide distribution of LD was revealed between this population and other young genetically isolated populations from Micronesia and Costa Rica. Our study population and experiment was simulated in silico to confirm our knowledge of the history of the population. High agreement was observed between results of analysis of simulated and empirical data. We conclude that our population shows a high level of LD similar to that demonstrated previously in other young genetic isolates. In Europe, there may be a large number of young genetically isolated populations that are similar in history to ours. In these populations, a similar degree of LD is expected and thus they may be effectively used for linkage or LD mapping.     

The economic costs associated with physical inactivity and obesity in Canada: an update.

The purpose of this analytical review was to estimate the direct and indirect economic costs of physical inactivity and obesity in Canada in 2001. The relative risks of diseases associated with physical inactivity and obesity were determined from a meta-analysis of existing prospective studies and applied to the health care costs of these diseases in Canada. Estimates were derived for both the direct health care expenditures and the indirect costs, which included the value of economic output lost because of illness, injury-related work disability, or premature death. The economic burden of physical inactivity was $5.3 billion ($1.6 billion in direct costs and $3.7 billion in indirect costs) while the cost associated with obesity was $4.3 billion ($1.6 billion of direct costs and $2.7 billion of indirect costs). The total economic costs of physical inactivity and obesity represented 2.6% and 2.2%, respectively, of the total health care costs in Canada. The results underscore the importance of public health efforts aimed at combating the current epidemics of physical inactivity and obesity in Canada.     

A novel means of identifying the neuraminidase type of currently circulating human A(H1) influenza viruses

With the recent emergence and spread of influenza A(H1N2) viruses which appear to have arisen by reassortment of circulating A(H1N1) and A(H3N2) strains, there is a need in epidemiological studies to determine the neuraminidase type in order to differentiate between influenza A(H1N2) and A(H1N1) strains. A fluorescence-based neuraminidase enzyme inhibition assay that has been developed to screen influenza viruses for potential resistance to the neuraminidase inhibitor drugs appears to be suitable for this purpose. When used with the neuraminidase inhibitor zanamivir the assay was able to provide a positive predictive value of 93.5% for the identification of neuraminidase type N1 or N2. This assay enables a large number of influenza A viruses to be screened at low cost to determine relative levels of A(H1N2) or A(H1N1) viruses circulating in the population.     

Sperm proteome mapping of a patient who experienced failed fertilization at IVF reveals altered expression of at least 20 proteins compared with fertile donors: case report

The aim of this study was to compare the sperm protein expression profile (proteome map) from a patient who experienced failed fertilization at IVF with fertile controls. One patient and three fertile donor sperm samples were characterized using two-dimensional electrophoresis. Differences in protein expression were established using gel analysis software before attempted protein identification. Gel analysis of the fertile donor proteome maps revealed excellent reproducibility as well as very low intra-donor and inter-donor variability in the presence of protein spots. In the patient samples, we have noted 20 consistent differences in protein expression (six spots missing, three additional spots, four less abundant, seven more abundant) compared with the controls. Two proteins that were more intense in the patient have been conclusively identified as secretory actin-binding protein and outer dense fibre protein 2/2. In conclusion proteome variation between different fertile donors was very low. In contrast, the patient proteome exhibited 20 differences compared with controls, which we believe is an underestimate. These proteins merit further investigation to determine whether failed fertilization at IVF might be caused by abnormalities in their expression. This case report represents a proof of principle that proteomics may be useful to study defects in sperm function.     

The comparative metabolism of triclabendazole sulphoxide by triclabendazole-susceptible and triclabendazole-resistant<Emphasis Type="Italic"> Fasciola hepatica</Emphasis>

Benzimidazole anthelmintics are widely used against nematode, cestode and trematode parasites. The drugs undergo several enzyme-mediated reactions within the host animal that produce a number of metabolites. Although it has been shown that certain helminths, including Fasciola hepatica, can metabolise albendazole, nothing is known regarding the ability of the liver fluke to metabolise triclabendazole, which is the major flukicidal compound currently on the market. In the current study, adult triclabendazole-susceptible flukes were treated with triclabendazole sulphoxide in vitro, and the metabolism of the drug was monitored by high performance liquid chromatography. The data show that F. hepatica can metabolise triclabendazole sulphoxide into its relatively inert sulphone metabolite. Parallel experiments using triclabendazole-resistant flukes showed that the conversion of triclabendazole sulphoxide to triclabendazole sulphone was on average 20.29% greater in the resistant flukes compared with the susceptible flukes. The results are discussed with regard to the mechanism of triclabendazole resistance in F. hepatica.     

B cell chronic lymphocytic leukaemia cells have reduced capacity to upregulate expression of MHC class I in response to interferon-gamma

AIMS: An important consideration in the design of a tumour vaccine is the ability of tumour-specific cytotoxic T lymphocytes (CTL) to recognise unmanipulated tumour cells in vivo. To determine whether B-CLL might use an escape strategy, the current studies compared B-CLL and normal B cell MHC class I expression. METHODS: Flow cytometry, TAP allele PCR and MHC class I PCR were used. RESULTS: While baseline expression of MHC class I did not differ, upregulation of MHC class I expression by B-CLL cells in response to IFN-gamma was reduced. No deletions or mutations of TAP 1 or 2 genes were detected. B-CLL cells upregulated TAP protein expression in response to IFN-gamma. Responsiveness of B-CLL MHC class I mRNA to IFN-gamma was not impaired. CONCLUSIONS: The data suggest that MHC class I molecules might be less stable at the cell surface in B-CLL than normal B cells, as a result of the described release of beta(2)m and beta(2)m-free class I heavy chains from the membrane. This relative MHC class I expression defect of B-CLL cells may reduce their susceptibility to CTL lysis in response to immunotherapeutic approaches.     

The expression of early resistance to an infection with Mycobacterium tuberculosis by old mice is dependent on IFN type II (IFN-gamma) but not IFN type I

Old mice can express a transient early resistance to infection with M. tuberculosis that requires the presence of CD8 T cells within the lungs. Further characterization of those CD8 T cells within the aged lung established that the majority of CD8 T cells from old mice expressed the IL-15 receptor (CD122) in combination with bright expression of CD44 (CD44(hi)), and were capable of producing IFN-gamma after T cell receptor cross-linking. It has been previously described that CD8 CD44(hi) T cells proliferate in response to IFN-I, acting via IL-15, and therefore we determined whether IFN-I signaling could be a participant in the response of CD8 T cells within the lungs of old mice infected with M. tuberculosis. We demonstrate here that IFN-I signaling was required for the expansion of CD8 T cells within the aging lung in response to infection with M. tuberculosis, but that IFN-I signaling had no influence on the capacity of old mice to express early resistance to an infection with M. tuberculosis. Resident CD8 T cells were still however capable of producing IFN-gamma, which we demonstrate here to be critical in the expression of early resistance, suggesting that the expression of early resistance requires the participation, but not expansion, of the CD8 T cell pool within the aging lung.     

Response of guinea pig vestibular nucleus neurons to clicks

Responses of single neurons in the vestibular nuclei to clicks were studied by extracellular recording in anaesthetised guinea pigs. Eighty-four neurons in the ipsilateral vestibular nuclei were activated with an average latency of 1.75±0.30 ms, which is about 0.9 ms longer than the mean latency of activation of click-sensitive vestibular afferents to intense clicks. The threshold of clicks for evoking the response of these neurons was around 70 dB above the auditory brainstem response threshold. Earlier studies have indicated that click-sensitive vestibular afferents are tilt-sensitive and likely to originate from saccular receptors, and in the present study nine of the click-sensitive vestibular nucleus neurons were tilt-sensitive, suggesting that these central neurons receive monosynaptic input from the corresponding saccular afferents. Recording sites were marked by means of iontophoretic injection of FCF green dye; they were located in the lateral portion of the descending vestibular nucleus and the caudal and ventral regions of the lateral vestibular nucleus.