Activation of the B Cell Antigen Receptor Triggers Reactivation of Latent Kaposi's Sarcoma-Associated Herpesvirus in B Cells

Kaposi''s sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus and the cause of Kaposi''s sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman''s disease. Latently infected B cells are the main reservoir of this virus in vivo, but the nature of the stimuli that lead to its reactivation in B cells is only partially understood. We established stable BJAB cell lines harboring latent KSHV by cell-free infection with recombinant virus carrying a puromycin resistance marker. Our latently infected B cell lines, termed BrK.219, can be reactivated by triggering the B cell receptor (BCR) with antibodies to surface IgM, a stimulus imitating antigen recognition. Using this B cell model system we studied the mechanisms that mediate the reactivation of KSHV in B cells following the stimulation of the BCR and could identify phosphatidylinositol 3-kinase (PI3K) and X-box binding protein 1 (XBP-1) as proteins that play an important role in the BCR-mediated reactivation of latent KSHV.     

Do kinesiologic activities change aberrant behavior in preschool children?

An experimental treatment was carried out in a sample of 117 preschool children by applying kinesiologic activities. The treatment lasting for 60 minutes was applied for a period of 9 months, twice a week. Control group of 139 children were trained according to the program for preschool institutions. Treatment effects were assessed by 7 motor ability tests, one intellectual test (Raven's Colored Progressive Matrices) and 36-item questionnaire for assessing aberrant behavior, which was filled out by parents. Aberrant behavior reduced significantly when motor abilities improved through systematic exercise. These findings point to the importance of motor exercise and applying additional kinesiologic activities with various modalities to reduce aberrant behavior in preschool children.     

Impact of game elements on tennis match outcome in Wimbledon and Roland Garros 2009

The aim of the study was to assess the correlation among particular tennis game elements and match outcomes specifically at Wimbledon and Roland Garros tournaments 2009. Study results showed the winners to differ statistically significantly from the losers in total sample including players from both tournaments in all variables except for those describing service speed. Like the sample in total, the winners at Wimbledon were superior in all variables, which was most pronounced in the percentage of points won to the opponent's service, percentage of points won by first and second service, percentage of break points, percentage of net points, and number of aces and winners. The winners at Roland Garros may be efficient due to the high quality of play to their own and the opponent's service. In conclusion, Wimbledon winners are characterized by the variables related to service which the players rely on, while Roland Garros winners are characterized by baseline play predominated by basic strokes.     

Broad TCR usage in functional HIV-1-specific CD8+ T cell expansions driven by vaccination during highly active antiretroviral therapy

During chronic HIV-1 infection, continuing viral replication is associated with impaired proliferative capacity of virus-specific CD8+ T cells and with the expansion and persistence of oligoclonal T cell populations. TCR usage may significantly influence CD8+ T cell-mediated control of AIDS viruses; however, the potential to modulate the repertoire of functional virus-specific T cells by immunotherapy has not been explored. To investigate this, we analyzed the TCR Vbeta usage of CD8+ T cells populations which were expanded following vaccination with modified vaccinia virus Ankara expressing a HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected patients receiving highly active antiretroviral therapy. Vaccinations induced the re-expansion of HIV-1-specific CD8+ T cells and these showed broad TCR Vbeta usage which was maintained for at least 1 year in some individuals. By contrast, virus-specific CD8+ T cell populations in the same donors which failed to expand after vaccination and in unvaccinated controls were oligoclonal. Simultaneously, we observed that CD8+ T cells recognizing vaccine-derived HIV-1 epitopes displayed enhanced capacity to proliferate and to inhibit HIV-1 replication in vitro, following MVA.HIVA immunizations. Taken together, these data indicate that an attenuated viral-vectored vaccine can modulate adaptive CD8+ T cell responses to HIV-1 and improve their antiviral functional capacity. The potential therapeutic benefit of this vaccination approach warrants further investigation.     

Tissue-specific changes in the hydroxylysine content and cross-links of collagens and alterations in fibril morphology in lysyl hydroxylase 1 knock-out mice

We have generated mice with targeted inactivation of the Plod1 gene for lysyl hydroxylase 1 (LH1). Its human mutations cause Ehlers-Danlos syndrome VIA (EDS VIA) characterized by muscular hypotonia, joint laxity, and kyphoscoliosis. The Plod1(-/-) mice are flaccid and have gait abnormalities. About 15% of them died because of aortic rupture and smooth muscle cells in non-ruptured Plod1(-/-) aortas showed degenerative changes. Collagen fibrils in the Plod1(-/-) aorta and skin had an abnormal morphology. The LH activity level in the Plod1(-/-) skin and aorta samples was 35-45% of that in the wild type. The hydroxylysine content was decreased in all the Plod1(-/-) tissues, ranging from 22% of that in the wild type in the skin to 75 and 86% in the femur and lung. The hydroxylysylpyridinoline crosslinks likewise showed decreases in all the Plod1(-/-) tissues, ranging from 28 and 33% of that in the wild type in the aorta and cornea to 47 and 59% in femur and tendon, while lysylpyridinolines were increased. The hydroxylysines found in the Plod1(-/-) collagens and their cross-links were evidently synthesized by the other two LH isoenzymes. Few data are available on abnormalities in EDS VIA tissues other than the skin. Plod1(-/-) mice offer an in vivo model for systematic analysis of the tissue-specific consequences of the lack of LH1 activity and may also provide a tool for analyzing the roles of connective tissue in muscle function and the complex interactions occurring in the proper assembly of the extracellular matrix.     

Utility of plasma apelin and other indices of cardiac dysfunction in the clinical assessment of patients with dilated cardiomyopathy

Apelin is a recently discovered peptide ligand reported to be involved in the regulation of cardiovascular homeostasis. The exact role of apelin in the pathophysiology of congestive heart failure has remained obscure, and the reported circulating levels of apelin in patients with heart failure have been contradictory. To establish the role of apelin in the assessment of cardiac dysfunction we measured plasma apelin levels in 65 patients with congestive heart failure caused by idiopathic dilated cardiomyopathy (IDC) and 14 healthy volunteers by specific radioimmunoassay. IDC patients were carefully examined including echocardiography, both-sided cardiac catheterization and cardiopulmonary exercise test. In addition, plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), N-terminal pro-atrial natriuretic peptide (NT-proANP), interleukin (IL)-6, tumor necrosis factor alpha (TNF-), epinephrine and norepinephrine were determined. Plasma apelin levels were similar in IDC patients (median 26.5 pg/ml, range < 3.40–97.6 pg/ml) and in control subjects (median 24.1 pg/ml, range 19.0–28.7 pg/ml; p = NS). Unlike the levels of NT-proBNP, IL-6, TNF-, and norepinephrine, plasma apelin levels did not reflect the severity of heart failure. Our study demonstrates that although disturbed apelin–APJ signalling in heart may play a role in the pathophysiology of heart failure, circulating apelin levels cannot be applied in the clinical assessment of patients with chronic left ventricular dysfunction.     

Interlaboratory comparison of Taq Nuclease Assays for the quantification of the toxic cyanobacteria Microcystis sp

The application of quantitative real-time PCR has been proposed for the quantification of toxic genotypes of cyanobacteria. We have compared the Taq Nuclease Assay (TNA) in quantifying the toxic cyanobacteria Microcystis sp. via the intergenic spacer region of the phycocyanin operon (PC) and mcyB indicative of the production of the toxic heptapeptide microcystin between three research groups employing three instruments (ABI7300, GeneAmp5700, ABI7500). The estimates of mcyB genotypes were compared using (i) DNA of a mcyB containing strain and a non-mcyB containing strain supplied in different mixtures across a low range of variation (0-10% of mcyB) and across a high range of variation (20-100%), and (ii) DNA from field samples containing Microcystis sp. For all three instruments highly significant linear regression curves between the proportion of the mcyB containing strain and the percentage of mcyB genotypes both within the low range and within the high range of mcyB variation were obtained. The regression curves derived from the three instruments differed in slope and within the high range of mcyB variation mcyB proportions were either underestimated (0-50%) or overestimated (0-72%). For field samples cell numbers estimated via both TNAs as well as mcyB proportions showed significant linear relationships between the instruments. For all instruments a linear relationship between the cell numbers estimated as PC genotypes and the cell numbers estimated as mcyB genotypes was observed. The proportions of mcyB varied from 2 to 28% and did not differ between the instruments. It is concluded that the TNA is able to provide quantitative estimates on mcyB genotype numbers that are reproducible between research groups and is useful to follow variation in mcyB genotype proportion occurring within weeks to months.     

Effects of biomotor structures on performance of competitive gymnastics elements in elementary school female sixth-graders

In order to identify biomotor systems that determine performance of competitive gymnastics elements in elementary school female sixth-graders, factor structures of morphological characteristics and basic motor abilities were determined first, followed by relations of the morphological-motor system factors obtained with a set of criterion variables evaluating specific motor skills in competitive gymnastics in 126 female children aged 12 years +/- 3 months. Factor analysis of 17 morphological measures yielded three morphological factors: factor of mesoendomorphy and/or adipose body voluminosity; factor of longitudinal body dimensionality; and factor of transverse arm dimensionality. Factor analysis of 16 motor variables produced four motor factors: general motoricity factor (motor system); general speed factor; factor of explosive strength of throwing type (arm explosiveness); and factor of arm and leg flexibility. Three significant canonical correlations, i.e. linear combinations, explained the association between the set of seven latent variables of the morphological and basic motor system, and five variables evaluating the knowledge in competitive gymnastics. The first canonical linear combination was based on a favorable and predominant impact of the general motor factor (a system integrating whole body coordination, leg explosiveness, relative arm strength, arm movement frequency and body flexibility) on performance of gymnastics elements, cartwheel, handstand and backward pullover mount in particular, and to a lesser extent front scale and double leg pirouette for 180 degrees. The relation of the second pair of canonical factors additionally explained the role of transverse dimensionality of arm skeleton, arm flexibility and explosiveness in performing cartwheel and squat vault, whereas the relation of the third pair of canonical factors explained the unfavorable impact of adipose voluminosity on the performance of squat vault and backward pullover mount.     

Chronic patients--persons with diabetes frequent attenders in Croatian family practice

Chronic diseases cause high frequency visits and generate the long-term frequent attenders (FAs). The connection between frequent attendance and specific morbidities in the health care systems in transitional Europe has been underestimated. We investigated whether frequent visits of chronic patients in primary care are related to characteristic of chronic disease (diabetes mellitus) and whether this is influenced by the family practice in the transitional health care. We analyzed the number of visits a day time work for 490 persons with diabetes in the period 1997 to 2000. As the cut-off points between frequent attenders and non frequent attenders (NFAs) we used the value of the third quartile (Q3) of visits determined for the sex and age groups in the parallel study in the whole population. The analysis was performed for 23 variables: demographic characteristics of patients, disease characteristic and variables of physician. Logistic regressions were employed to identify the predictors of FAs/NFAs. 56.9% (in 1997) to 62.4% (in 2000) persons with diabetes were FAs, compared to 22.4% to 24.3% FAs patients in the whole population. Logistic regression analysis significantly differentiated the two group of visits with 68% accuracy. 4 variables are significant predictors for FAs/NFAs: diabetes as the main disease (p = 0.0005), diet-only-treatment (p = 0.0062), treatment by secondary care (p = 0.0116), and if glycated hemoglobin test (HbA1c) is determined (p = 0.0272). Understanding the similarities and differences of FAs/NFAs persons with diabetes may be important in improving the care and management of chronic diseases in family medicine in transitional health care systems.