Sera from patients with heparin-induced thrombocytopenia generate platelet-derived microparticles with procoagulant activity: an explanation for the thrombotic complications of heparin-induced thrombocytopenia

Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia.     

A humanised tissue‐engineered bone model allows species‐specific breast cancer‐related bone metastasis in vivo

Bone metastases frequently occur in the advanced stages of breast cancer. At this stage, the disease is deemed incurable. To date, the mechanisms of breast cancer‐related metastasis to bone are poorly understood. This may be attributed to the lack of appropriate animal models to investigate the complex cancer cell–bone interactions. In this study, two established tissue‐engineered bone constructs (TEBCs) were applied to a breast cancer‐related metastasis model. A cylindrical medical‐grade polycaprolactone‐tricalcium phosphate scaffold produced by fused deposition modelling (scaffold 1) was compared with a tubular calcium phosphate‐coated polycaprolactone scaffold fabricated by solution electrospinning (scaffold 2) for their potential to generate ectopic humanised bone in NOD/SCID mice. While scaffold 1 was found not suitable to generate a sufficient amount of ectopic bone tissue due to poor ectopic integration, scaffold 2 showed excellent integration into the host tissue, leading to bone formation. To mimic breast cancer cell colonisation to the bone, MDA‐MB‐231, SUM1315, and MDA‐MB‐231BO breast cancer cells were cultured in polyethylene glycol‐based hydrogels and implanted adjacent to the TEBCs. Histological analysis indicated that the breast cancer cells induced an osteoclastic reaction in the TEBCs, demonstrating analogies to breast cancer‐related bone metastasis seen in patients.     

Humoral immune response of BALB/c mice immunized with chimer HBcAg proteins carrying the epitopes of surface hepatic B virus protein

Chimeric HBcAg proteins carrying epitopes from surface hepatitis B virus (HBV) protein (regions 137-147 a.o. HBsAg, 27-37 a.a. region preS1 and 131-145 a.a. region preS2) have been early constructed. This paper presents the data of an investigation of a humoral immune response in mice immunized with obtained by chimeric HBcAg proteins. The findings suggest that the chimeric HBcAg proteins carrying the epitopes of surface HBV protein are able to induce an immune response to both inserted epitopes and carrying protein (HBcAg). Immunization with a mixture of chimeric proteins taken in equivalent quantities induces the synthesis of antibodies to hybrid proteins. The use of aluminum hydroxide considerably enhances a humoral immune response during immunization with chimeric bovine proteins.     

Molecular characterization of a high A2 beta thalassemia by direct sequencing of single strand enriched amplified genomic DNA

Two families, one of Anglo-Saxon-Dutch descent, and the other, West Indian black, have an atypical beta thalassemia characterized by an unusually high level of Hb A2 in the heterozygous state. Restriction endonuclease mapping showed a deletion of about 1.35 kilobase (kb) in the 5' region of the beta globin gene. Direct sequencing of a specific region of genomic DNA amplified by a new modification of the polymerase chain reaction defined the deletion to be 1,393 base pairs (bp) and to be the same in both families. The deletion extends from 485 bp 5' to the mRNA CAP site to the middle of the second intervening sequence. This deletion, together with three others previously described that remove the 5' end of the beta gene but leave the delta gene intact, are all associated with unusually high levels of Hb A2 in the heterozygous state.     

Clinically significant symptom change in children with attention‐deficit/hyperactivity disorder: does it correspond with reliable improvement in functioning?

This study examined the relation between clinically significant (CS) change in symptoms of attention‐deficit/hyperactivity disorder (ADHD) and of oppositional defiant disorder (ODD), and reliable change in multiple domains of functioning in children who participated in the Multimodal Treatment Study of Children with ADHD. Children with CS change in symptoms were significantly more likely than children without CS change to have reliable change across five domains of functioning. Interestingly, however, depending on the measure of functioning, 14 to 52% of children who did not achieve CS change in symptoms showed reliable improvement in functional domains. The results have implications for the definition and measurement of CS change in child treatment‐outcome studies. © 2008 Wiley Periodicals, Inc. J Clin Psychol 65:1–18, 2009.     

Hygienic assessment of ambient air pollution in rural localities in the area exposed to effluents of the Orenburg gas-field complex

A complex analysis suggests that there has been an increase in airogenic load on the population living in an area exposed to gas waste from the Orenburg gas-field complex at the expense of nitrogen dioxide, which may be associated with its higher levels in the waste from 1058.3 tons/year in 1996 to 2084.89 tons/year in 2000 and with the maximum effluent of 2550.79 tons/year in 1999. The study has revealed that the rural locality with the greatest aerogenic load is the village of Dedurovka.