Genetic relationship between Streptococcus pneumoniae isolates from nasopharyngeal and cerebrospinal fluid of two infants with Pneumococcal Meningitis

The molecular epidemiology of Streptococcus pneumoniae isolates from carriage and cerebrospinal fluid (CSF) concurrently recovered from the same individual has not yet been reported. By using pulsed-field gel electrophoresis, we demonstrated the genetic linkage among strains from CSF and nasopharynges of two children with pneumococcal meningitis.     

Reducing the time of sperm-oocyte interaction in human in-vitro fertilization improves the implantation rate

Human oocyte development was evaluated after a reduced timeexposure to spermatozoa in vitro. A total of 119 patients wereassigned to two study groups in a randomized prospective studyin which each patient‘s oocytes were exposed to spermatozoafor either 1 h (group 1 – 58 patients) or the standard16 h incubation period (group 2 – 61 patients). The fertilizationrate obtained in group 1 was higher than in group 2 (285/393,73%, and 272/410, 66% respectively), suggesting that the spermatozoa-oocyteinteraction occurs within 1 h. This was confirmed in a studyin vitro using fluorescently labelled spermatozoa and normaloocyte-cumulus complexes. Spermatozoa enter the cumulus complexwithin 15 min, traverse the cumulus layer within 3 h, and firstappear in the oocyte cortex at 4 h post-insemination. The incidenceof polyspermy was higher in oocytes exposed to spermatozoa for16 h (3%) than for 1 h (1%). There was no difference in thecleavage rate or morphological characteristics of embryos fromboth study groups. However, when evaluating the timing of embryodevelopment, group 1 generated a significantly higher percentageof four to five cell embryos when compared to group 2 (55 versus39%; P < 0.001), documented at 40 h post-insemination. Theimplantation and pregnancy rates for group 1 were 11 and 28%,while the corresponding rates for group 2 were 8 and 15%. Thissuggests that a reduced exposure of oocyte to spermatozoa favoursembryo viability, possibly due to a decrease in potential damagefrom sperm metabolic waste products.     

Apolipoprotein(a) phenotypes are reliable biomarkers for familial aggregation of coronary heart disease

Lipoprotein(a) [Lp(a)] is an atherogenic and prothrombotic molecule formed by the covalent binding of the highly polymorphic apolipoprotein(a) [apo(a)] to apoprotein B-100 of LDL. High Lp(a) concentrations are a recognized genetic risk factor for coronary heart disease (CHD) and have been shown to be related with a familial clustering of ischemic cardiac events. Nevertheless, the association between apolipoprotein(a) isoforms and a positive familial history of CHD has received far less attention. In this report, we explored the distribution of apo(a) phenotypes in 127 CHD subjects with a family history of coronary events and in 92 CHD patients without such a history. Twenty-two apo(a) isoforms were detected by a high-resolution immunoblotting method. In univariate analysis, the percentage of subjects with at least one small sized apo(a) isoform was significantly higher in CHD patients with a positive family history than in those without (P<0.01). Multivariate analysis showed that apo(a) isoforms of low molecular weight were the best predictors of familial aggregation of cardiac ischemia. We conclude that apo(a) size polymorphism is strongly associated with a familial history of CHD and is more efficient than Lp(a) plasma concentrations in predicting the familial clustering of coronary disease. When detected by high-resolution techniques, apo(a) phenotypes are objective laboratory markers that can substitute for a knowledge of a positive family history of CHD and should be used, together with Lp(a) levels, to better assess the familial predisposition to coronary events.     

Classification and subtype prediction of adult soft tissue sarcoma by functional genomics

Adult soft tissue sarcomas are a heterogeneous group of tumors, including well-described subtypes by histological and genotypic criteria, and pleomorphic tumors typically characterized by non-recurrent genetic aberrations and karyotypic heterogeneity. The latter pose a diagnostic challenge, even to experienced pathologists. We proposed that gene expression profiling in soft tissue sarcoma would identify a genomic-based classification scheme that is useful in diagnosis. RNA samples from 51 pathologically confirmed cases, representing nine different histological subtypes of adult soft tissue sarcoma, were examined using the Affymetrix U95A GeneChip. Statistical tests were performed on experimental groups identified by cluster analysis, to find discriminating genes that could subsequently be applied in a support vector machine algorithm. Synovial sarcomas, round-cell/myxoid liposarcomas, clear-cell sarcomas and gastrointestinal stromal tumors displayed remarkably distinct and homogenous gene expression profiles. Pleomorphic tumors were heterogeneous. Notably, a subset of malignant fibrous histiocytomas, a controversialhistological subtype, was identified as a distinct genomic group. The support vector machine algorithm supported a genomic basis for diagnosis, with both high sensitivity and specificity. In conclusion, we showed gene expression profiling to be useful in classification and diagnosis, providing insights into pathogenesis and pointing to potential new therapeutic targets of soft tissue sarcoma.     

Control of the cell survival/death decision by cannabinoids

Cannabinoids, the active components of Cannabis sativa (marijuana), and their derivatives produce a wide spectrum of central and peripheral effects, some of which may have clinical application. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to cannabinoids in recent years. One of the most exciting and promising areas of current cannabinoid research is the ability of these compounds to control the cell survival/death decision. Thus cannabinoids may induce proliferation, growth arrest, or apoptosis in a number of cells, including neurons, lymphocytes, and various transformed neural and nonneural cells. The variation in drug effects may depend on experimental factors such as drug concentration, timing of drug delivery, and type of cell examined. Regarding the central nervous system, most of the experimental evidence indicates that cannabinoids may protect neurons from toxic insults such as glutamaergic overstimulation, ischemia and oxidative damage. In contrast, cannabinoids induce apoptosis of glioma cells in culture and regression of malignant gliomas in vivo. Breast and prostate cancer cells are also sensitive to cannabinoid-induced antiproliferation. Regarding the immune system, low doses of cannabinoids may enhance cell proliferation, whereas high doses of cannabinoids usually induce growth arrest or apoptosis. The neuroprotective effect of cannabinoids may have potential clinical relevance for the treatment of neurodegenerative disorders such as multiple sclerosis, Parkinson's disease, and ischemia/stroke, whereas their growth-inhibiting action on transformed cells might be useful for the management of malignant brain tumors. Ongoing investigation is in search for cannabinoid-based therapeutic strategies devoid of nondesired psychotropic effects.     

Mutational analysis of the yeast multidrug resistance ABC transporter Pdr5p with altered drug specificity

Multidrug resistance ABC transporter Pdr5p of Saccharomyces cerevisiae is particularly important due to its ability to export a wide range of unrelated substrates. To clarify its function, we generated Pdr5p mutants by random mutagenesis and screened for mutants with altered drug specificity in vivo by using 5 drug compounds. Nine point mutations that caused significant changes in drug specificity distributed throughout the length of Pdr5p, namely, in the extracellular, transmembrane or cytoplasmic regions of the transporter. We then investigated their effects upon drug resistance, using 36 chemically related or distinct substrates. From this study, overall geometry of the Pdr5p was suggested to contribute in acquiring the enormous range of drug specificity. Based on their ability to inhibit the growth of the mutant strains, the 36 tested drugs were classified into: drugs to which the mutants responded differently (Group 1), drugs to which all the mutants showed sensitivity (Group 2), and drugs to which all the mutants exhibited resistance (Group 3). The ability of the compounds to be partitioned to the plasma membrane seemed an important factor for recognition by Pdr5p.