Heritability, genetic correlation and linkage to the 9p21.3 region of mixed platelet-leukocyte conjugates in families with and without early myocardial infarction.

BACKGROUND AND AIMS: Variations in mixed platelet-leukocyte conjugate formation in human whole blood could be genetically determined. We quantified platelet and leukocyte activation and interaction in families with or without early myocardial infarction and evaluated their heritability, genetic correlation and linkage to the 9p21.3 region. METHODS AND RESULTS: The study population included 739 subjects (≥ 15 years old) from 54 large pedigrees, 23 with and 31 without familial myocardial infarction. Mixed platelet-leukocyte conjugates and markers of platelet or leukocyte activation (P-selectin, CD11b and L-selectin surface expression) were measured both before and after in vitro blood stimulation with collagen-ADP. All traits had significant genetic components (17.5-65.3% of the phenotypic variability), while shared household effects (0-39.6%) and environmental covariates (0-10.2%) tended to be smaller. Stimulated platelet-polymorphonuclear leukocyte (PMN) and platelet-monocyte conjugates showed the highest linkage to the 9p21.3 region (LOD = 0.94 and 1.33, respectively; empirical p value = 0.017 and 0.009). PMN markers resulted strongly genetically correlated between them in bivariate analysis among pairs of quantitative traits. CONCLUSION: This study supports a genetic regulation of human mixed platelet-leukocyte conjugates.

Incomplete inhibition of platelet function as assessed by the platelet function analyzer (PFA-100) identifies a subset of cardiovascular patients with high residual platelet response while on aspirin.

Sixty-six patients with a history of ischemic events (myocardial infarction, unstable angina, or stroke) on chronic aspirin therapy were studied by different platelet function tests: 37 patients had suffered a recurrent event while on aspirin and 29 were without recurrences. Based on results from light transmission aggregometry (LTA) induced by arachidonic acid (AA) and serum TxB(2) both COX-1-dependent methods, only one patient could be identified as aspirin "resistant". However, when methods only partially-dependent on platelet COX-1 activity were considered, the prevalence of aspirin non-responders ranged, according to the different tests, from 0 to 52%. No difference was observed between patients with recurrences and those without. Among patients with recurrent events, those with an incomplete inhibition of platelet function, as assessed by the PFA-100, had significantly higher residual serum TxB(2) (2.4 ± 2.4 ng/mL vs 0.4 ± 0.1 ng/mL, p = 0.03), residual LTA-AA (9.2 ± 10.6% vs 2.0 ± 1.6%, p = 0.008), LTA-Coll (49.3 ± 14.6% vs 10.2 ± 8.3%, p = 0.007) and LTA-ADP (50.9 ± 16.2% vs 34.3 ± 11.0%, p = 0.04). In conclusion, laboratory tests solely exploring the AA-mediated pathway of platelet function, while being the most appropriate to detect the effect of aspirin on its pharmacologic target (platelet COX-1), may fail to reveal the functional interactions between minimal residual TxA(2) and additional stimuli or primers potentially leading to aspirin-insensitive platelet aggregation. High residual platelet response in platelet function tests only partially dependent on COX-1 may reveal a condition of persistent platelet reactivity in a subset of aspirin-treated patients characterizing them as a subgroup at higher vascular risk.

Relationship between leaf life-span and photosynthetic activity of Quercus ilex in polluted urban areas (Rome).

Anatomical, morphological and physiological leaf traits of Quercus ilex in response to different traffic levels (high traffic level, type A sites; average traffic level, type B sites; control sites, type C sites) were analysed in Rome. Superficial leaf deposits were analysed comparing unwashed and washed leaf samples. Washing lowered Pb 61% in A, 54% in B and 27% in C. Sr, Fe, Cu, Zn and Al showed the same trend as Pb. The higher photosynthetic activity of 1-year-old leaves (Pn=7.0+/-2.9 micromol m(-2 )s(-1), average value) in A sites with respect to B sites (6.7+/-2.4 micromol m(-2 )s(-1)) and C sites (6.7+/-1.8 micromol m(-2 )s(-1)) seems to be related to higher stomatal conductance (g(s)=0.13+/-0.06 mol m(-2 )s(-1)), higher total chlorophyll content (Chl=1.57 mg g(-1)) and higher leaf thickness (L(T)=218.9 microm), particularly palisade parenchyma thickness (109.4 microm). Q. ilex showed, on average, 95% of 1-year-old leaves and rarely 2-year-old leaves in A and B sites; 77% 1-year leaves, 20% previous-year leaves and sporadic 3-year leaves in C sites. The enhanced leaf senescence in A sites is compensated by a stimulated shoot production (18% higher with respect to C sites); 25% increased specific leaf area seems to be compensatory growth occurring in order to increase the size of the assimilatory area. The inverse trend of leaf life-span and Pn seems to be Q. ilex' adaptive strategy in polluted areas.

In vitro activation of heat shock transcription factor by 4-hydroxynonenal.

In the activation of eukaryotic heat shock genes, the acquisition of a binding ability to specific DNA sequence by a transcriptional activator, heat shock factor (HSF), is believed to be a crucial step. The induction of this new DNA binding activity of HSF is also obtained in a cell-free system (in vitro activation) by hyperthermia or at physiological temperature by calcium ions, low pH, urea, or non-ionic detergent. We report here the in vitro activation of HSF by treating at 0 degrees C a HeLa cell-free system with the aldehyde 4-hydroxynonenal (HNE), a highly cytotoxic product of lipid peroxidation. The in vitro activation of HSF by HNE occurred only if some components of the cell-free system were not sedimented at 100,000 x g. The reason for this is unclear but the release of active HSF from nuclei of unshocked cells and the involvement of Ca2+ contained in the mitochondria and ER have been excluded. Although HNE is known to be a sulfhydryl blocking agent, the results obtained with N-ethylmaleimide suggest that different mechanisms might be involved in the in vitro activation of HSF by HNE.

[Vibrio parahaemolyticus in mollusks]. / Ricerca del Vibrio parahaemolyticus in molluschi.

Research on Vibrio parahaemolyticus from mollusks. On 284 samples of edible mollusks from different sources, 12 bacterial strains of Vibrios related to Vibrio parahaemolyticus by cultural and biochemical tests have been isolated; that is 4.3% on the total of the samples examined. The proceeding for isolation and the meaning of this research with reference to microbiological parameters required by the actual legislation on the control of edible mollusks are also discussed.